Next Issue
Previous Issue

E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Table of Contents

Molecules, Volume 20, Issue 12 (December 2015), Pages 20967-22907

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-137
Export citation of selected articles as:

Research

Jump to: Review, Other

Open AccessArticle Pyranocoumarins from Root Extracts of Peucedanum praeruptorum Dunn with Multidrug Resistance Reversal and Anti-Inflammatory Activities
Molecules 2015, 20(12), 20967-20978; doi:10.3390/molecules201219738
Received: 18 September 2015 / Revised: 10 November 2015 / Accepted: 17 November 2015 / Published: 25 November 2015
Cited by 5 | PDF Full-text (1766 KB) | HTML Full-text | XML Full-text
Abstract
In the search for novel herbal-based anticancer agents, we isolated a new angular-type pyranocoumarin, (+)-cis-(3′S,4′S)-3′-angeloyl-4′-tigloylkhellactone (1) along with 12 pyranocoumarins (213), two furanocoumarins (14, 15), and a polyacetylene
[...] Read more.
In the search for novel herbal-based anticancer agents, we isolated a new angular-type pyranocoumarin, (+)-cis-(3′S,4′S)-3′-angeloyl-4′-tigloylkhellactone (1) along with 12 pyranocoumarins (213), two furanocoumarins (14, 15), and a polyacetylene (16) were isolated from the roots of Peucedanum praeruptorum using chromatographic separation methods. The structures of the compounds were determined using spectroscopic analysis with nuclear magnetic resonance (NMR) and high-resolution-electrospray ionization-mass spectrometry (HR-ESI-MS). The multidrug-resistance (MDR) reversal and anti-inflammatory effects of all the isolated compounds were evaluated in human sarcoma MES-SA/Dx5 and lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among the 16 tested compounds, two (2 and 16) downregulated nitric oxide (NO) production and five (1, 7, 8, 11, and 13) inhibited the efflux of drugs by MDR protein, indicating the reversal of MDR. Therefore, these compounds may be potential candidates for the development of effective agents against MDR forms of cancer. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Algae Undaria pinnatifida Protects Hypothalamic Neurons against Endoplasmic Reticulum Stress through Akt/mTOR Signaling
Molecules 2015, 20(12), 20998-21009; doi:10.3390/molecules201219744
Received: 5 October 2015 / Revised: 13 November 2015 / Accepted: 20 November 2015 / Published: 25 November 2015
Cited by 2 | PDF Full-text (2288 KB) | HTML Full-text | XML Full-text
Abstract
Increased endoplasmic reticulum (ER) stress is known to be one of the causes of hypothalamic neuronal damage, as well as a cause of metabolic disorders such as obesity and diabetes. Recent evidence has suggested that Undaria pinnatifida (UP), an edible brown algae, has
[...] Read more.
Increased endoplasmic reticulum (ER) stress is known to be one of the causes of hypothalamic neuronal damage, as well as a cause of metabolic disorders such as obesity and diabetes. Recent evidence has suggested that Undaria pinnatifida (UP), an edible brown algae, has antioxidant activity. However, the neuroprotective effect of UP has yet to be examined. In this study, to investigate the neuroprotective effect of UP on ER stress-induced neuronal damage in mouse hypothalamic neurons, mice immortal hypothalamic neurons (GT1-7) were incubated with extract of UP. ER stress was induced by treating with tunicamycin. Tunicamycin induced apoptotic cell death was compared with the vehicle treatment through excessive ER stress. However UP protected GT1-7 cells from cell death, occurring after treatment with tunicamycin by reducing ER stress. Treatment with UP resulted in reduced increment of ATF6 and CHOP, and recovered the decrease of phosphorylation of Akt/mTOR by tunicamycin and the increment of autophagy. These results show that UP protects GT1-7 cells from ER stress induced cell death through the Akt/mTOR pathway. The current study suggests that UP may have a beneficial effect on cerebral neuronal degeneration in metabolic diseases with elevated ER stress. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Development and Evaluation of Liquid and Solid Self-Emulsifying Drug Delivery Systems for Atorvastatin
Molecules 2015, 20(12), 21010-21022; doi:10.3390/molecules201219745
Received: 27 August 2015 / Revised: 17 October 2015 / Accepted: 20 November 2015 / Published: 25 November 2015
Cited by 3 | PDF Full-text (3279 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this work was to design and characterize liquid and solid self-emulsifying drug delivery systems (SEDDS) for poorly soluble atorvastatin. To optimize the composition of liquid atorvastatin-SEDDS, solubility tests, pseudoternary phase diagrams, emulsification studies and other in vitro examinations (thermodynamic stability,
[...] Read more.
The objective of this work was to design and characterize liquid and solid self-emulsifying drug delivery systems (SEDDS) for poorly soluble atorvastatin. To optimize the composition of liquid atorvastatin-SEDDS, solubility tests, pseudoternary phase diagrams, emulsification studies and other in vitro examinations (thermodynamic stability, droplet size and zeta potential analysis) were performed. Due to the disadvantages of liquid SEDDS (few choices for dosage forms, low stability and portability during the manufacturing process), attempts were also made to obtain solid SEDDS. Solid SEDDS were successfully obtained using the spray drying technique from two optimized liquid formulations, CF3 and OF2. Despite liquid SEDDS formulation, CF3 was characterized by lower turbidity, higher percentage transmittance and better self-emulsifying properties, and based on the in vitro dissolution study it can be concluded that better solubilization properties were exhibited by solid formulation OF2. Overall, the studies demonstrated the possibility of formulating liquid and solid SEEDS as promising carriers of atorvastatin. SEDDS, with their unique solubilization properties, provide the opportunity to deliver lipophilic drugs to the gastrointestinal tract in a solubilized state, avoiding dissolution—a restricting factor in absorption rate of BCS Class 2 drugs, including atorvastatin. Full article
(This article belongs to the collection Poorly Soluble Drugs)
Open AccessArticle Synthesis and Fungicidal Activities of (Z/E)-3,7-Dimethyl-2,6-octadienamide and Its 6,7-Epoxy Analogues
Molecules 2015, 20(12), 21023-21036; doi:10.3390/molecules201219743
Received: 10 October 2015 / Revised: 17 November 2015 / Accepted: 17 November 2015 / Published: 25 November 2015
PDF Full-text (710 KB) | HTML Full-text | XML Full-text
Abstract
In order to find new lead compounds with high fungicidal activity, (Z/E)-3,7-dimethyl-2,6-octadienoic acids were synthesized via selective two-step oxidation using the commercially available geraniol/nerol as raw materials. Twenty-eight different (Z/E)-3,7-dimethyl-2,6-octadienamide derivatives were prepared by reactions
[...] Read more.
In order to find new lead compounds with high fungicidal activity, (Z/E)-3,7-dimethyl-2,6-octadienoic acids were synthesized via selective two-step oxidation using the commercially available geraniol/nerol as raw materials. Twenty-eight different (Z/E)-3,7-dimethyl-2,6-octadienamide derivatives were prepared by reactions of (Z/E)-carboxylic acid with various aromatic and aliphatic amines, followed by oxidation of peroxyacetic acid to afford their 6,7-epoxy analogues. All of the compounds were characterized by HR-ESI-MS and 1H-NMR spectral data. The preliminary bioassays showed that some of these compounds exhibited good fungicidal activities against Rhizoctonia solani (R. solani) at a concentration of 50 µg/mL. For example, 5C, 5I and 6b had 94.0%, 93.4% and 91.5% inhibition rates against R. solani, respectively. Compound 5f displayed EC50 values of 4.3 and 9.7 µM against Fusahum graminearum and R. Solani, respectively. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Optical and Electrical Properties of TTF-MPcs (M = Cu, Zn) Interfaces for Optoelectronic Applications
Molecules 2015, 20(12), 21037-21049; doi:10.3390/molecules201219742
Received: 9 November 2015 / Accepted: 17 November 2015 / Published: 25 November 2015
Cited by 3 | PDF Full-text (1374 KB) | HTML Full-text | XML Full-text
Abstract
Sandwich structures were fabricated by a vacuum deposition method using MPc (M = Cu, Zn), with a Tetrathiafulvalene (TTF) derivative, and Indium Tin Oxide (ITO) and aluminum electrodes. The structure and morphology of the deposited films were studied by IR spectroscopy, scanning electron
[...] Read more.
Sandwich structures were fabricated by a vacuum deposition method using MPc (M = Cu, Zn), with a Tetrathiafulvalene (TTF) derivative, and Indium Tin Oxide (ITO) and aluminum electrodes. The structure and morphology of the deposited films were studied by IR spectroscopy, scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). The absorption spectra of TTF derivative-MPc (M = Cu, Zn) thin films deposited at room temperature were recorded in the spectral range 200–1000 nm. The optical band gap of the thin films was determined from the (αhν)1/2 vs. plot. The direct-current (DC) electrical properties of the glass/ITO/TTFderiv-MPc (M = Cu, Zn)/Al structures were also investigated. Changes in conductivity of the derivative-TTF-enriched Pc compounds suggest the formation of alternative paths for carrier conduction. At low voltages, forward current density obeys an ohmic I-V relationship; at higher voltages, conduction is mostly due to a space-charge-limited conduction (SCLC) mechanism. Full article
(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)
Figures

Open AccessArticle Towards the Synthesis of Graphene Azide from Graphene Oxide
Molecules 2015, 20(12), 21050-21057; doi:10.3390/molecules201219747
Received: 30 October 2015 / Revised: 17 November 2015 / Accepted: 18 November 2015 / Published: 26 November 2015
Cited by 3 | PDF Full-text (2039 KB) | HTML Full-text | XML Full-text
Abstract
In the last decades, organic azides haven proven to be very useful precursors in organic chemistry, for example in 1,3-dipolar cycloaddition reactions (click-chemistry). Likewise, azides can be introduced into graphene oxide with an almost intact carbon framework, namely oxo-functionalized graphene (oxo-G1),
[...] Read more.
In the last decades, organic azides haven proven to be very useful precursors in organic chemistry, for example in 1,3-dipolar cycloaddition reactions (click-chemistry). Likewise, azides can be introduced into graphene oxide with an almost intact carbon framework, namely oxo-functionalized graphene (oxo-G1), which is a highly oxidized graphene derivative and a powerful precursor for graphene that is suitable for electronic devices. The synthesis of a graphene derivative with exclusively azide groups (graphene azide) is however still a challenge. In comparison also hydrogenated graphene, called graphene or halogenated graphene remain challenging to synthesize. A route to graphene azide would be the desoxygenation of azide functionalized oxo-G1. Here we show how treatment of azide functionalized oxo-G1 with HCl enlarges the π-system and removes strongly adsorbed water and some oxo-functional groups. This development reflects one step towards graphene azide. Full article
(This article belongs to the Special Issue Organic Azides)
Open AccessArticle The Effect of Replacing Fish Meal in the Diet with Enzyme-Treated Soybean Meal (HP310) on Growth and Body Composition of Rainbow Trout Fry
Molecules 2015, 20(12), 21058-21066; doi:10.3390/molecules201219751
Received: 4 August 2015 / Revised: 13 October 2015 / Accepted: 23 October 2015 / Published: 26 November 2015
PDF Full-text (190 KB) | HTML Full-text | XML Full-text
Abstract
The potential of enzyme-treated soybean meal powder (HP310) as fish meal alternative in diets for rainbow trout weighing 1.17 ± 0.3 g was evaluated for 60 days. Fish meal was replaced with HP310 at 25%, 50%, 75% and 100% of experimental diets. A
[...] Read more.
The potential of enzyme-treated soybean meal powder (HP310) as fish meal alternative in diets for rainbow trout weighing 1.17 ± 0.3 g was evaluated for 60 days. Fish meal was replaced with HP310 at 25%, 50%, 75% and 100% of experimental diets. A control group was also considered. The results showed that diets containing 75% and 100% HP310 had significantly higher feed conversion ratio and lower feed intake, weight gain and specific growth rate compared to fish feed diets containing higher levels of fish protein ingredients (p < 0.05). Results suggested use of 50% HP310 in trout diet had a positive effect on growth performance (p < 0.05). All fish feed diets with HP310 had lower hematocrit, hemoglobin and red blood cells compared to the control group, but the differences between the control and the other treatments up to 75% HP310 replacement levels of diet (p > 0.05). However increasing in level of HP310 in the diet caused a significant increase of the white blood cells (p < 0.05). The fish fed with a diet totally replaced by HP310 showed the highest values of ash and moisture content among the diets and showed significantly different levels when compared with the control and other feeding treatments (p < 0.05). Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Technological Application of Maltodextrins According to the Degree of Polymerization
Molecules 2015, 20(12), 21067-21081; doi:10.3390/molecules201219746
Received: 24 October 2015 / Revised: 17 November 2015 / Accepted: 19 November 2015 / Published: 27 November 2015
Cited by 6 | PDF Full-text (2225 KB) | HTML Full-text | XML Full-text
Abstract
Maltodextrin (MX) is an ingredient in high demand in the food industry, mainly for its useful physical properties which depend on the dextrose equivalent (DE). The DE has however been shown to be an inaccurate parameter for predicting the performance of the MXs
[...] Read more.
Maltodextrin (MX) is an ingredient in high demand in the food industry, mainly for its useful physical properties which depend on the dextrose equivalent (DE). The DE has however been shown to be an inaccurate parameter for predicting the performance of the MXs in technological applications, hence commercial MXs were characterized by mass spectrometry (MS) to determine their molecular weight distribution (MWD) and degree of polymerization (DP). Samples were subjected to different water activities (aw). Water adsorption was similar at low aw, but radically increased with the DP at higher aw. The decomposition temperature (Td) showed some variations attributed to the thermal hydrolysis induced by the large amount of adsorbed water and the supplied heat. The glass transition temperature (Tg) linearly decreased with both, aw and DP. The microstructural analysis by X-ray diffraction showed that MXs did not crystallize with the adsorption of water, preserving their amorphous structure. The optical micrographs showed radical changes in the overall appearance of the MXs, indicating a transition from a glassy to a rubbery state. Based on these characterizations, different technological applications for the MXs were suggested. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle When Phosphosugars Meet Gold: Synthesis and Catalytic Activities of Phostones and Polyhydroxylated Phosphonite Au(I) Complexes
Molecules 2015, 20(12), 21082-21093; doi:10.3390/molecules201219755
Received: 23 September 2015 / Revised: 29 October 2015 / Accepted: 20 November 2015 / Published: 27 November 2015
PDF Full-text (1335 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The synthesis and characterization of P-chiral phosphonite-, phosphonate- and thiophosphonate-Au(I) complexes are reported. These novel ligands for Au(I) are based on glycomimetic phosphorus scaffolds, obtained from the chiral pool. The catalytic activities of these complexes are shown in the cyclization of allenols and
[...] Read more.
The synthesis and characterization of P-chiral phosphonite-, phosphonate- and thiophosphonate-Au(I) complexes are reported. These novel ligands for Au(I) are based on glycomimetic phosphorus scaffolds, obtained from the chiral pool. The catalytic activities of these complexes are shown in the cyclization of allenols and the hydroamination of 2-(2-propynyl)aniline combined with an organocatalyzed reduction to the corresponding 2-phenyl tetrahydroquinoline. All described gold complexes present excellent catalytic activities. Full article
(This article belongs to the Section Organometallic Chemistry)
Figures

Open AccessArticle Stereo- and Regiocontrolled Syntheses of Exomethylenic Cyclohexane β-Amino Acid Derivatives
Molecules 2015, 20(12), 21094-21102; doi:10.3390/molecules201219749
Received: 15 October 2015 / Revised: 12 November 2015 / Accepted: 19 November 2015 / Published: 27 November 2015
Cited by 2 | PDF Full-text (2855 KB) | HTML Full-text | XML Full-text
Abstract
Cyclohexane analogues of the antifungal icofungipen [(1R,2S)-2-amino-4-methylenecyclopentanecarboxylic acid] were selectively synthesized from unsaturated bicyclic β-lactams by transformation of the ring olefinic bond through three different regio- and stereocontrolled hydroxylation techniques, followed by hydroxy group oxidation and oxo-methylene interconversion with
[...] Read more.
Cyclohexane analogues of the antifungal icofungipen [(1R,2S)-2-amino-4-methylenecyclopentanecarboxylic acid] were selectively synthesized from unsaturated bicyclic β-lactams by transformation of the ring olefinic bond through three different regio- and stereocontrolled hydroxylation techniques, followed by hydroxy group oxidation and oxo-methylene interconversion with a phosphorane. Starting from an enantiomerically pure bicyclic β-lactam obtained by enzymatic resolution of the racemic compound, an enantiodivergent procedure led to the preparation of both dextro- and levorotatory cyclohexane analogues of icofungipen. Full article
(This article belongs to the Section Organic Synthesis)
Figures

Open AccessArticle Iridium-Catalyzed Asymmetric Ring-Opening of Oxabenzonorbornadienes with N-Substituted Piperazine Nucleophiles
Molecules 2015, 20(12), 21103-21124; doi:10.3390/molecules201219748
Received: 5 October 2015 / Revised: 17 November 2015 / Accepted: 19 November 2015 / Published: 27 November 2015
Cited by 4 | PDF Full-text (6880 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Iridium-catalyzed asymmetric ring-opening of oxabenzonorbornadienes with N-substituted piperazines was described. The reaction afforded the corresponding ring-opening products in high yields and moderate enantioselectivities in the presence of 2.5 mol % [Ir(COD)Cl]2 and 5.0 mol % (S)-p-Tol-BINAP. The
[...] Read more.
Iridium-catalyzed asymmetric ring-opening of oxabenzonorbornadienes with N-substituted piperazines was described. The reaction afforded the corresponding ring-opening products in high yields and moderate enantioselectivities in the presence of 2.5 mol % [Ir(COD)Cl]2 and 5.0 mol % (S)-p-Tol-BINAP. The effects of various chiral bidentate ligands, catalyst loading, solvent, and temperature on the yield and enantioselectivity were also investigated. A plausible mechanism was proposed to account for the formation of the corresponding trans-ring opened products based on the X-ray structure of product 2i. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Argentatin B Inhibits Proliferation of Prostate and Colon Cancer Cells by Inducing Cell Senescence
Molecules 2015, 20(12), 21125-21137; doi:10.3390/molecules201219757
Received: 2 September 2015 / Revised: 13 November 2015 / Accepted: 17 November 2015 / Published: 27 November 2015
PDF Full-text (2769 KB) | HTML Full-text | XML Full-text
Abstract
Argentatin B has been shown to inhibit the growth of colon HCT-15, and prostate PC-3 cancer cells. However, the mechanism by which argentatin B inhibits cell proliferation is still unknown. We aimed to investigate the mechanism by which argentatin B inhibits cell proliferation.
[...] Read more.
Argentatin B has been shown to inhibit the growth of colon HCT-15, and prostate PC-3 cancer cells. However, the mechanism by which argentatin B inhibits cell proliferation is still unknown. We aimed to investigate the mechanism by which argentatin B inhibits cell proliferation. The cell cycle was studied by flow cytometry. Apoptosis was evaluated by Annexin-V-Fluos, and Hoechst 33342 dye staining. Cell senescence was evaluated by proliferation tests, and staining for SA-β-galactosidase. Senescence-related proteins (PCNA, p21, and p27) were analyzed by Western blotting. Potential toxicity of argentatin B was evaluated in CD-1 mice. Its effect on tumor growth was tested in a HCT-15 and PC-3 xenograft model. Argentatin B induced an increment of cells in sub G1, but did not produce apoptosis. Proliferation of both cell lines was inhibited by argentatin B. Forty-three percent HCT-15, and 66% PC-3 cells showed positive SA-β-galactosidase staining. The expression of PCNA was decreased, p21 expression was increased in both cell lines, but p27 expression increased only in PC-3 cells after treatment. Administration of argentatin B to healthy mice did not produce treatment-associated pathologies. However, it restricted the growth of HCT-15 and PC-3 tumors. These results indicate that treatment with argentatin B induces cell senescence. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Apigenin Attenuates Melanoma Cell Migration by Inducing Anoikis through Integrin and Focal Adhesion Kinase Inhibition
Molecules 2015, 20(12), 21157-21166; doi:10.3390/molecules201219752
Received: 10 November 2015 / Revised: 20 November 2015 / Accepted: 20 November 2015 / Published: 27 November 2015
Cited by 6 | PDF Full-text (1267 KB) | HTML Full-text | XML Full-text
Abstract
Apigenin, a nonmutagenic flavonoid, has been found to have antitumor properties and is therefore particularly relevant for the development of chemotherapeutic agents for cancers. In this study, time- and dose-dependent cell viability and cytotoxicity were assessed to determine the effects of apigenin on
[...] Read more.
Apigenin, a nonmutagenic flavonoid, has been found to have antitumor properties and is therefore particularly relevant for the development of chemotherapeutic agents for cancers. In this study, time- and dose-dependent cell viability and cytotoxicity were assessed to determine the effects of apigenin on A2058 and A375 melanoma cells. Melanoma cells were pretreated with different concentrations of apigenin and analyzed for morphological changes, anoikis induction, cell migration, and levels of proteins associated with apoptosis. Apigenin reduced integrin protein levels and inhibited the phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK1/2), which induce anoikis in human cutaneous melanoma cells. Apigenin exhibited dose-dependent inhibition of melanoma cell migration, unlike untreated controls. Furthermore, apigenin treatment increased apoptotic factors such as caspase-3 and cleaved poly(ADP-ribose) polymerase in a dose-dependent manner, demonstrating the metastasis of melanoma cells. Our results provide a new insight into the mechanisms by which apigenin prevents melanoma metastasis by sensitizing anoikis induced by the loss of integrin proteins in the FAK/ERK1/2 signaling pathway. These findings elucidate the related mechanisms and suggest the potential of apigenin in developing clinical treatment strategies against malignant melanoma. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Improved Antioxidant Capacity of Optimization of a Self-Microemulsifying Drug Delivery System for Resveratrol
Molecules 2015, 20(12), 21167-21177; doi:10.3390/molecules201219750
Received: 16 September 2015 / Revised: 13 November 2015 / Accepted: 17 November 2015 / Published: 27 November 2015
Cited by 2 | PDF Full-text (6183 KB) | HTML Full-text | XML Full-text
Abstract
The use of nano-encapsulated resveratrol (RSV) in self-micro-emulsified drug delivery systems (SMEDDS) formulations was investigated. Self-emulsifying grading tests were used to establish the optimal ratio of oil, surfactant, and co-surfactant. The optimized system was further investigated for the droplet size and zeta potential
[...] Read more.
The use of nano-encapsulated resveratrol (RSV) in self-micro-emulsified drug delivery systems (SMEDDS) formulations was investigated. Self-emulsifying grading tests were used to establish the optimal ratio of oil, surfactant, and co-surfactant. The optimized system was further investigated for the droplet size and zeta potential at the different medium pH values by a Malvern Zetasizer and transmission electron microscopy (TEM). The antioxidant capacity and cytotoxicity of the formulation were detected by DCFH-DA and a CCK-8 assays. The results showed that the nano-emulsion based on ethyl oleate, Tween-80, and PEG-400 (35:40:25, w/w/w) was the most stable formulation due to the small droplet size (approximately 50 nm) and high zeta potential in a neutral environment. Furthermore, this formulation also exhibited a greater antioxidant capacity with less toxicity than free RSV. Taken together, considering these results and the simple fabrication process, this formulation could be used to deliver nutritional food supplements in a stable, efficient, and safe manner. Full article
(This article belongs to the collection Poorly Soluble Drugs)
Open AccessArticle A Copper-Based Metal-Organic Framework as an Efficient and Reusable Heterogeneous Catalyst for Ullmann and Goldberg Type C–N Coupling Reactions
Molecules 2015, 20(12), 21178-21192; doi:10.3390/molecules201219756
Received: 30 October 2015 / Revised: 13 November 2015 / Accepted: 17 November 2015 / Published: 27 November 2015
Cited by 4 | PDF Full-text (2946 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A highly porous metal-organic framework (Cu-TDPAT), constructed from a paddle-wheel type dinuclear copper cluster and 2,4,6-tris(3,5-dicarboxylphenylamino)-1,3,5-triazine (H6TDPAT), has been tested in Ullmann and Goldberg type C–N coupling reactions of a wide range of primary and secondary amines with halobenzenes, affording the
[...] Read more.
A highly porous metal-organic framework (Cu-TDPAT), constructed from a paddle-wheel type dinuclear copper cluster and 2,4,6-tris(3,5-dicarboxylphenylamino)-1,3,5-triazine (H6TDPAT), has been tested in Ullmann and Goldberg type C–N coupling reactions of a wide range of primary and secondary amines with halobenzenes, affording the corresponding N-arylation compounds in moderate to excellent yields. The Cu-TDPAT catalyst could be easily separated from the reaction mixtures by simple filtration, and could be reused at least five times without any significant degradation in catalytic activity. Full article
(This article belongs to the Special Issue Metal Mediated Activation of Small Molecules)
Figures

Open AccessArticle Dihydrochalcone Compounds Isolated from Crabapple Leaves Showed Anticancer Effects on Human Cancer Cell Lines
Molecules 2015, 20(12), 21193-21203; doi:10.3390/molecules201219754
Received: 6 October 2015 / Revised: 9 November 2015 / Accepted: 10 November 2015 / Published: 27 November 2015
Cited by 6 | PDF Full-text (1370 KB) | HTML Full-text | XML Full-text
Abstract
Seven dihydrochalcone compounds were isolated from the leaves of Malus crabapples, cv. “Radiant”, and their chemical structures were elucidated by UV, IR, ESI-MS, 1H-NMR and 13C-NMR analyses. These compounds, which include trilobatin (A1), phloretin (A2), 3-hydroxyphloretin (
[...] Read more.
Seven dihydrochalcone compounds were isolated from the leaves of Malus crabapples, cv. “Radiant”, and their chemical structures were elucidated by UV, IR, ESI-MS, 1H-NMR and 13C-NMR analyses. These compounds, which include trilobatin (A1), phloretin (A2), 3-hydroxyphloretin (A3), phloretin rutinoside (A4), phlorizin (A5), 6′′-O-coumaroyl-4′-O-glucopyranosylphloretin (A6), and 3′′′-methoxy-6′′-O-feruloy-4′-O-glucopyranosyl-phloretin (A7), all belong to the phloretin class and its derivatives. Compounds A6 and A7 are two new rare dihydrochalcone compounds. The results of a MTT cancer cell growth inhibition assay demonstrated that phloretin and these derivatives showed significant positive anticancer activities against several human cancer cell lines, including the A549 human lung cancer cell line, Bel 7402 liver cancer cell line, HepG2 human ileocecal cancer cell line, and HT-29 human colon cancer cell line. A7 had significant effects on all cancer cell lines, suggesting potential applications for phloretin and its derivatives. Adding a methoxyl group to phloretin dramatically increases phloretin’s anticancer activity. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Metabolic Characteristics in Meal of Black Rapeseed and Yellow-Seeded Progeny of Brassica napusSinapis alba Hybrids
Molecules 2015, 20(12), 21204-21213; doi:10.3390/molecules201219761
Received: 18 September 2015 / Revised: 5 November 2015 / Accepted: 23 November 2015 / Published: 30 November 2015
Cited by 2 | PDF Full-text (208 KB) | HTML Full-text | XML Full-text
Abstract
Breeding of yellow-seeded rapeseed (Brassica napus) is preferred over black-seeded rapeseed for the desirable properties of the former. This study evaluated the metabolites and nutritive values of black-seeded rapeseed meal and yellow-seeded meal from the progeny of a B. napus
[...] Read more.
Breeding of yellow-seeded rapeseed (Brassica napus) is preferred over black-seeded rapeseed for the desirable properties of the former. This study evaluated the metabolites and nutritive values of black-seeded rapeseed meal and yellow-seeded meal from the progeny of a B. napusSinapis alba hybrid. Yellow-seed meal presented higher protein (35.46% vs. 30.29%), higher sucrose (7.85% vs. 7.29%), less dietary fiber (26.19% vs. 34.63%) and crude fiber (4.56% vs. 8.86%), and less glucosinolates (22.18 vs. 28.19 μmol/g) than black-seeded one. Amounts of ash (3.65% vs. 4.55%), phytic acid (4.98% vs. 5.60%), and total polyphenols (2.67% vs. 2.82%) were decreased slightly in yellow-seeded meal compared with black-seeded meal. Yellow-seeded meal contained more essential amino acids than black-seeded meal. Levels of the mineral elements Fe, Mn, and Zn in yellow-seeded meal were higher than black-seeded meal. By contrast, levels of P, Ca, and Mg were lower in yellow-seeded meal. Moreover, yellow-seeded meal showed lower flavonol (kaempferol, quercetin, isorhamnetin, and their derivatives) content than black-seeded meal. Comparison of metabolites between yellow and black rapeseed confirmed the improved nutritional value of meal from yellow-seeded B. napus, and this would be helpful to the breeding and improvement of rapeseed for animal feeding. Full article
(This article belongs to the Section Metabolites)
Figures

Open AccessArticle Characterization of Global Transcriptome Using Illumina Paired-End Sequencing and Development of EST-SSR Markers in Two Species of Gynostemma (Cucurbitaceae)
Molecules 2015, 20(12), 21214-21231; doi:10.3390/molecules201219758
Received: 8 October 2015 / Revised: 5 November 2015 / Accepted: 9 November 2015 / Published: 30 November 2015
Cited by 3 | PDF Full-text (1774 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Gynostemma pentaphyllum is an important medicinal herb of the Cucurbitaceae family, but limited genomic data have hindered genetic studies. In this study, transcriptomes of two closely-related Gynostemma species, Gynostemma cardiospermum and G. pentaphyllum, were sequenced using Illumina paired-end sequencing technology. A total
[...] Read more.
Gynostemma pentaphyllum is an important medicinal herb of the Cucurbitaceae family, but limited genomic data have hindered genetic studies. In this study, transcriptomes of two closely-related Gynostemma species, Gynostemma cardiospermum and G. pentaphyllum, were sequenced using Illumina paired-end sequencing technology. A total of 71,607 nonredundant unigenes were assembled. Of these unigenes, 60.45% (43,288) were annotated based on sequence similarity search with known proteins. A total of 11,059 unigenes were identified in the Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG) database. A total of 3891 simple sequence repeats (SSRs) were detected in 3526 nonredundant unigenes, 2596 primer pairs were designed and 360 of them were randomly selected for validation. Of these, 268 primer pairs yielded clear products among six G. pentaphyllum samples. Thirty polymorphic SSR markers were used to test polymorphism and transferability in Gynostemma. Finally, 15 SSR makers that amplified in all 12 Gynostemma species were used to assess genetic diversity. Our results generated a comprehensive sequence resource for Gynostemma research. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Hydrothermal Conversion of Giant Reed to Furfural and Levulinic Acid: Optimization of the Process under Microwave Irradiation and Investigation of Distinctive Agronomic Parameters
Molecules 2015, 20(12), 21232-21253; doi:10.3390/molecules201219760
Received: 12 October 2015 / Revised: 16 November 2015 / Accepted: 23 November 2015 / Published: 30 November 2015
Cited by 13 | PDF Full-text (3667 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The hydrothermal conversion of giant reed (Arundo donax L.) to furfural (FA) and levulinic acid (LA) was investigated in the presence of dilute hydrochloric acid. FA and LA yields were improved by univariate optimization of the main reaction parameters: concentration of the
[...] Read more.
The hydrothermal conversion of giant reed (Arundo donax L.) to furfural (FA) and levulinic acid (LA) was investigated in the presence of dilute hydrochloric acid. FA and LA yields were improved by univariate optimization of the main reaction parameters: concentration of the acid catalyst, solid/liquid ratio of the reaction mixture, hydrolysis temperature, and reaction time. The catalytic performances were investigated adopting the efficient microwave (MW) irradiation, allowing significant energy and time savings. The best FA and LA yields were further confirmed using a traditionally heated autoclave reactor, giving very high results, when compared with the literature. Hydrolysis temperature and time were the main reaction variables to be carefully optimized: FA formation needed milder reaction conditions, while LA more severe ones. The effect of the crop management (e.g., harvest time) on FA/LA production was discussed, revealing that harvest time was not a discriminating parameter for the further optimization of both FA and LA production, due to the very high productivity of the giant reed throughout the year. The promising results demonstrate that giant reed represents a very interesting candidate for a very high contemporary production of FA and LA of up to about 70% and 90% of the theoretical yields, respectively. Full article
Figures

Open AccessArticle Factors Influencing Oral Bioavailability of Thai Mango Seed Kernel Extract and Its Key Phenolic Principles
Molecules 2015, 20(12), 21254-21273; doi:10.3390/molecules201219759
Received: 16 October 2015 / Revised: 17 November 2015 / Accepted: 19 November 2015 / Published: 30 November 2015
Cited by 5 | PDF Full-text (3943 KB) | HTML Full-text | XML Full-text
Abstract
Mango seed kernel extract (MSKE) and its key components (gallic acid, GA; methyl gallate, MG; and pentagalloyl glucopyranose, PGG) have generated interest because of their pharmacological activities. To develop the potential use of the key components in MSKE as natural therapeutic agents, their
[...] Read more.
Mango seed kernel extract (MSKE) and its key components (gallic acid, GA; methyl gallate, MG; and pentagalloyl glucopyranose, PGG) have generated interest because of their pharmacological activities. To develop the potential use of the key components in MSKE as natural therapeutic agents, their pharmacokinetic data are necessary. Therefore, this study was performed to evaluate the factors affecting their oral bioavailability as pure compounds and as components in MSKE. The in vitro chemical stability, biological stability, and absorption were evaluated in Hanks’ Balanced Salt Solution, Caco-2 cell and rat fecal lysates, and the Caco-2 cell model, respectively. The in vivo oral pharmacokinetic behavior was elucidated in Sprague-Dawley rats. The key components were unstable under alkaline conditions and in Caco-2 cell lysates or rat fecal lysates. The absorptive permeability coefficient followed the order MG > GA > PGG. The in vivo results exhibited similar pharmacokinetic trends to the in vitro studies. Additionally, the co-components in MSKE may affect the pharmacokinetic behaviors of the key components in MSKE. In conclusion, chemical degradation under alkaline conditions, biological degradation by intestinal cell and colonic microflora enzymes, and low absorptive permeability could be important factors underlying the oral bioavailability of these polyphenols. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Comparative Pharmacokinetics Study of Icariin and Icariside II in Rats
Molecules 2015, 20(12), 21274-21286; doi:10.3390/molecules201219763
Received: 5 October 2015 / Revised: 18 November 2015 / Accepted: 19 November 2015 / Published: 1 December 2015
Cited by 8 | PDF Full-text (1699 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
To explore the pharmacokinetic properties of icariin (ICA) and icariside II (ICA II) following intragastric and intravenous administration in rats, a rapid and sensitive method by using ultra-performance liquid chromatography–tandem mass spectroscopy (UPLC-MS/MS) was developed and validated for the simultaneous quantification of ICA
[...] Read more.
To explore the pharmacokinetic properties of icariin (ICA) and icariside II (ICA II) following intragastric and intravenous administration in rats, a rapid and sensitive method by using ultra-performance liquid chromatography–tandem mass spectroscopy (UPLC-MS/MS) was developed and validated for the simultaneous quantification of ICA and ICA II in rat plasma. The quantification was performed by using multiple reaction monitoring of the transitions m/z 677.1/531.1 for ICA, 515.1/369.1 for ICA II and 463.1/301.1 for diosmetin-7-O-β-d-glucopyranoside (IS). The assay showed linearity over the concentration range of 1.03–1032 ng/mL, with correlation coefficients of 0.9983 and 0.9977. Intra- and inter-day precision and accuracy were within 15%. The lower limit of quantification for both ICA and ICA II was 1.03 ng/mL, respectively. The recovery of ICA and ICA II was more than 86.2%. The LC-MS/MS method has been successfully used in the pharmacokinetic studies of ICA and ICA II in rats. The results indicated that 91.2% of ICA was transformed into ICA II after oral administration by rats, whereas only 0.4% of ICA was transformed into ICA II after intravenous administration. A comparison of the pharmacokinetics of ICA and ICA II after oral administration revealed that the Cmax and AUC0–t of ICA II were 3.8 and 13.0 times higher, respectively, than those of ICA. However, after intravenous administration, the Cmax and AUC0–t of ICA II were about only 12.1% and 4.2% of those of ICA. These results suggest that ICA and ICA II have distinct pharmacokinetic properties, and the insights obtained facilitate future pharmacological action studies. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells
Molecules 2015, 20(12), 21287-21297; doi:10.3390/molecules201219764
Received: 25 September 2015 / Revised: 11 November 2015 / Accepted: 20 November 2015 / Published: 1 December 2015
Cited by 6 | PDF Full-text (2881 KB) | HTML Full-text | XML Full-text
Abstract
Foam cell formation as a result of imbalance of modified cholesterol influx and efflux by macrophages is a key to the occurrence and development of atherosclerosis. Oxidative stress is thought to be involved in the pathogenesis of atherosclerosis. SS-31 is a member of
[...] Read more.
Foam cell formation as a result of imbalance of modified cholesterol influx and efflux by macrophages is a key to the occurrence and development of atherosclerosis. Oxidative stress is thought to be involved in the pathogenesis of atherosclerosis. SS-31 is a member of the Szeto-Schiller (SS) peptides shown to specifically target the inner mitochondrial membrane to scavenge reactive oxygen species. In this study, we investigated whether SS-31 may provide protective effect on macrophage from foam cell formation in RAW264.7 cells. The results showed that SS-31 inhibited oxidized low-density lipoproteins (ox-LDL)-induced foam cell formation and cholesterol accumulation, demonstrated by intracellular oil red O staining and measurement of cholesterol content. The mechanism was revealed that SS-31 did not only significantly attenuated ox-LDL-induced generation of reactive oxygen species (ROS) and increased the activities of superoxide dismutases, but also dose-dependently inhibited the expression of CD36 and LOX-1, two scavenger receptors of ox-LDL, while the expression of ATP-binding cassette A1 and G1, playing a pivotal role in cholesterol efflux, was not affected. As a result, SS-31 decreased pro-inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha, suggesting the prevention of inflammatory responses. In conclusion, our results demonstrate that SS-31 provides a beneficial effect on macrophages from foam cell formation, likely, through both ROS scavenging and inhibition of cholesterol influx. Therefore, SS-31 may potentially be of therapeutic relevance in prevention of human atherogenesis. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Evaluation of Antimicrobial Efficiency of New Polymers Comprised by Covalently Attached and/or Electrostatically Bound Bacteriostatic Species, Based on Quaternary Ammonium Compounds
Molecules 2015, 20(12), 21313-21327; doi:10.3390/molecules201219768
Received: 2 October 2015 / Revised: 22 November 2015 / Accepted: 24 November 2015 / Published: 1 December 2015
Cited by 6 | PDF Full-text (2704 KB) | HTML Full-text | XML Full-text
Abstract
In the present work a detailed study of new bacteriostatic copolymers with quaternized ammonium groups introduced in the polymer chain through covalent attachment or electrostatic interaction, was performed. Different copolymers have been considered since beside the active species, the hydrophobic/hydrophilic nature of the
[...] Read more.
In the present work a detailed study of new bacteriostatic copolymers with quaternized ammonium groups introduced in the polymer chain through covalent attachment or electrostatic interaction, was performed. Different copolymers have been considered since beside the active species, the hydrophobic/hydrophilic nature of the co-monomer was also evaluated in the case of covalently attached bacteriostatic groups, aiming at achieving permanent antibacterial activity. Homopolymers with quaternized ammonium/phosphonium groups were also tested for comparison reasons. The antimicrobial activity of the synthesized polymers after 3 and 24 h of exposure at 4 and 22 °C was investigated on cultures of Gram-negative (P. aeruginosa, E. coli) and Gram-positive (S. aureus, E. faecalis) bacteria. It was found that the combination of the hydrophilic monomer acrylic acid (AA), at low contents, with the covalently attached bacteriostatic group vinyl benzyl dimethylhexadecylammonium chloride (VBCHAM) in the copolymer P(AA-co-VBCHAM88), resulted in a high bacteriostatic activity against P. aeruginosa and E. faecalis (6 log reduction in certain cases). Moreover, the combination of covalently attached VBCHAM units with electrostatically bound cetyltrimethylammonium 4-styrene sulfonate (SSAmC16) units in the P(SSAmC16-co-VBCHAMx) copolymers led to efficient antimicrobial materials, especially against Gram-positive bacteria, where a log reduction between 4.9 and 6.2 was verified. These materials remain remarkably efficient even when they are incorporated in polysulfone membranes. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessCommunication Synthesis, Characterization and Reactions of (Azidoethynyl)trimethylsilane
Molecules 2015, 20(12), 21328-21335; doi:10.3390/molecules201219770
Received: 9 November 2015 / Revised: 20 November 2015 / Accepted: 23 November 2015 / Published: 1 December 2015
Cited by 3 | PDF Full-text (1240 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Synthesis of azido(trimethylsilyl)acetylene (6) was performed by treating the iodonium salt 5 with highly soluble hexadecyltributylphosphonium azide (QN3) at −40 °C. Although this product is very unstable, it can nevertheless be trapped by the click reaction with cyclooctyne to
[...] Read more.
Synthesis of azido(trimethylsilyl)acetylene (6) was performed by treating the iodonium salt 5 with highly soluble hexadecyltributylphosphonium azide (QN3) at −40 °C. Although this product is very unstable, it can nevertheless be trapped by the click reaction with cyclooctyne to give the corresponding 1,2,3-triazole, and also directly characterized by 1H- and 13C-NMR data as well as IR-spectra, which were measured in solution at low temperature and in the gas phase. The thermal or photochemical decay of azide 6 leads to cyano(trimethylsilyl)carbene. This is demonstrated not only by quantum chemical calculations, but also by the trapping reactions with the help of isobutene. Full article
(This article belongs to the Special Issue Organic Azides)
Figures

Open AccessArticle Isoeugenin, a Novel Nitric Oxide Synthase Inhibitor Isolated from the Rhizomes of Imperata cylindrica
Molecules 2015, 20(12), 21336-21345; doi:10.3390/molecules201219767
Received: 28 October 2015 / Revised: 20 November 2015 / Accepted: 24 November 2015 / Published: 1 December 2015
Cited by 2 | PDF Full-text (1165 KB) | HTML Full-text | XML Full-text
Abstract
Phytochemical studies on the constituents of the rhizomes of Imperata cylindrica (Gramineae) were performed using high-performance liquid chromatography (HPLC). We also aimed to search for any biologically active substance capable of inhibiting nitric oxide (NO) formation in lipopolysaccharide (LPS)-activated macrophage 264.7
[...] Read more.
Phytochemical studies on the constituents of the rhizomes of Imperata cylindrica (Gramineae) were performed using high-performance liquid chromatography (HPLC). We also aimed to search for any biologically active substance capable of inhibiting nitric oxide (NO) formation in lipopolysaccharide (LPS)-activated macrophage 264.7 cells, by testing four compounds isolated from this plant. Four compounds, including a new chromone, isoeugenin, along with ferulic acid, p-coumaric acid, and caffeic acid were isolated and identified by NMR spectroscopy. The structure of isoeugenin was determined as 7-hydroxy-5-methoxy-2-methylchromone by the 2D-NMR technique. Among the four compounds, isoeugenin has the lowest IC50 value on the inhibition of NO production in LPS-activated macrophage RAW264.7 cells (IC50, 9.33 μg/mL). In addition, isoeugenin significantly suppressed the LPS-induced expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory cytokines mRNA levels. Taken together, these results suggest that the anti-inflammatory activity of isoeugenin is associated with the down-regulation of iNOS, COX-2, and pro-inflammatory cytokines in RAW264.7 cells. Accordingly, our results suggest that the new chromone isoegenin should be considered a potential treatment for inflammatory disease. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Synthesis and Physicochemical Characterization of the Process-Related Impurities of Olmesartan Medoxomil. Do 5-(Biphenyl-2-yl)-1-triphenylmethyltetrazole Intermediates in Sartan Syntheses Exist?
Molecules 2015, 20(12), 21346-21363; doi:10.3390/molecules201219762
Received: 23 October 2015 / Revised: 18 November 2015 / Accepted: 19 November 2015 / Published: 1 December 2015
Cited by 4 | PDF Full-text (2595 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
During the process development for multigram-scale synthesis of olmesartan medoxomil (OM), two principal regioisomeric process-related impurities were observed along with the final active pharmaceutical ingredient (API). The impurities were identified as N-1- and N-2-(5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl derivatives of OM. Both compounds, of which
[...] Read more.
During the process development for multigram-scale synthesis of olmesartan medoxomil (OM), two principal regioisomeric process-related impurities were observed along with the final active pharmaceutical ingredient (API). The impurities were identified as N-1- and N-2-(5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl derivatives of OM. Both compounds, of which N-2 isomer of olmesartan dimedoxomil is a novel impurity of OM, were synthesized and fully characterized by differential scanning calorimetry (DSC), infrared spectroscopy (IR), nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrometry/electrospray ionization (HRMS/ESI). Their 1H, 13C and 15N nuclear magnetic resonance signals were fully assigned. The molecular structures of N-triphenylmethylolmesartan ethyl (N-tritylolmesartan ethyl) and N-tritylolmesartan medoxomil, the key intermediates in OM synthesis, were solved and refined using single-crystal X-ray diffraction (SCXRD). The SCXRD study revealed that N-tritylated intermediates of OM exist exclusively as one of the two possible regioisomers. In molecular structures of these regioisomers, the trityl substituent is attached to the N-2 nitrogen atom of the tetrazole ring, and not to the N-1 nitrogen, as has been widely reported up to the present. This finding indicates that the reported structural formula of N-tritylolmesartan ethyl and N-tritylolmesartan medoxomil, as well as their systematic chemical names, must be revised. The careful analysis of literature spectroscopic data for other sartan intermediates and their analogs with 5-(biphenyl-2-yl)tetrazole moiety showed that they also exist exclusively as N-2-trityl regioisomers. Full article
(This article belongs to the Special Issue Prodrugs)
Figures

Open AccessArticle A GC-MS Based Metabonomics Study of Rheumatoid Arthritis and the Interventional Effects of the Simiaowan in Rats
Molecules 2015, 20(12), 21364-21372; doi:10.3390/molecules201219776
Received: 7 October 2015 / Revised: 18 November 2015 / Accepted: 19 November 2015 / Published: 1 December 2015
PDF Full-text (747 KB) | HTML Full-text | XML Full-text
Abstract
Simiaowan (SMW) is a famous Chinese prescription widely used in clinical treatment of rheumatoid arthritis (RA). The aim of the present study is to determine novel biomarkers to increase the current understanding of RA mechanisms, as well as the underlying therapeutic mechanism of
[...] Read more.
Simiaowan (SMW) is a famous Chinese prescription widely used in clinical treatment of rheumatoid arthritis (RA). The aim of the present study is to determine novel biomarkers to increase the current understanding of RA mechanisms, as well as the underlying therapeutic mechanism of SMW, in RA-model rats. Plasma extracts from control, RA model, and SMW-treated rats were analyzed by gas chromatography coupled with mass spectrometry (GC-MS). An orthogonal partial least-square discriminant analysis (OPLS-DA) model was created to detect metabolites that were expressed in significantly different amounts between the RA model and the control rats and investigate the therapeutic effect of SMW. Metabonomics may prove to be a valuable tool for determining the efficacy of complex traditional prescriptions. Full article
(This article belongs to the Section Metabolites)
Figures

Open AccessArticle Analysis of Chemical Constituents in Wuzi-Yanzong-Wan by UPLC-ESI-LTQ-Orbitrap-MS
Molecules 2015, 20(12), 21373-21404; doi:10.3390/molecules201219765
Received: 21 October 2015 / Revised: 20 November 2015 / Accepted: 23 November 2015 / Published: 1 December 2015
Cited by 3 | PDF Full-text (1728 KB) | HTML Full-text | XML Full-text
Abstract
Wuzi-Yanzong-Wan (WZYZW), a classical traditional Chinese medicine (TCM) prescription containing Fructus Lych, Semen Cuscutae (fried), Fructus Rubi, Fructus Schisandrae chinensis (steamed) and Semen Plantaginis (fried with salt), is widely used to treat impotence, sterility, spermatorrhea, premature ejaculation, lumbago and post-micturation dribble.
[...] Read more.
Wuzi-Yanzong-Wan (WZYZW), a classical traditional Chinese medicine (TCM) prescription containing Fructus Lych, Semen Cuscutae (fried), Fructus Rubi, Fructus Schisandrae chinensis (steamed) and Semen Plantaginis (fried with salt), is widely used to treat impotence, sterility, spermatorrhea, premature ejaculation, lumbago and post-micturation dribble. However, the chemical profile of WZYZW has not been established yet. In this work, a rapid and sensitive method for systematically screening and identifying the chemical constituents of WZYZW in both positive and negative ion modes using Ultra-Performance LC coupled with ESI-linear ion trap-Orbitrap tandem mass spectrometry (UPLC-ESI-LTQ-Orbitrap-MS) has been developed. Based on the chromatographic and spectrometric data, and referring to the literature, we could tentatively identify 106 compounds, including organic acids, flavonoids, phenylpropanoids, alkaloids and terpenoids. Fourteen ingredients from Fructus Lych were identified, while 10 ingredients were from Semen Cuscutae (fried), 33 ingredients were from Fructus Rubi, 37 ingredients were from Fructus Schisandrae chinensis (steamed), and 20 ingredients were from Semen Plantaginis (fried with salt). The results may provide essential data for further quality control, pharmacological research and clinical evaluation of WZYZW. Furthermore, this study indicates the developed approach based on UPLC-ESI-LTQ-Orbitrap-MS is suitable for characterizing the chemical profiles of TCM prescriptions. This is the first report to provide a comprehensive analysis of the chemical constituents of WZYZW. Full article
(This article belongs to the collection Herbal Medicine Research)
Open AccessArticle Soluble Epoxide Hydrolase Inhibitory Activity of Selaginellin Derivatives from Selaginella tamariscina
Molecules 2015, 20(12), 21405-21414; doi:10.3390/molecules201219774
Received: 23 October 2015 / Revised: 23 November 2015 / Accepted: 26 November 2015 / Published: 2 December 2015
Cited by 9 | PDF Full-text (1900 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Selaginellin derivatives 13 isolated from Selaginella tamariscina were evaluated for their inhibition of soluble epoxide hydrolase (sEH) to demonstrate their potential for the treatment of cardiovascular disease. All selaginellin derivatives (13) inhibited sEH enzymatic activity and PHOME
[...] Read more.
Selaginellin derivatives 13 isolated from Selaginella tamariscina were evaluated for their inhibition of soluble epoxide hydrolase (sEH) to demonstrate their potential for the treatment of cardiovascular disease. All selaginellin derivatives (13) inhibited sEH enzymatic activity and PHOME hydrolysis, in a dose-dependent manner, with IC50 values of 3.1 ± 0.1, 8.2 ± 2.2, and 4.2 ± 0.2 μM, respectively. We further determined that the derivatives function as non-competitive inhibitors. Moreover, the predicted that binding sites and interaction between 13 and sEH were solved by docking simulations. According to quantitative analysis, 13 were confirmed to have high content in the roots of S. tamariscina; among them, selaginellin 3 exhibited the highest content of 189.3 ± 0.0 μg/g. Full article
(This article belongs to the Section Bioorganic Chemistry)
Figures

Open AccessCommunication Synthesis of a Stable Primary-Alkyl-Substituted Selenenyl Iodide and Its Hydrolytic Conversion to the Corresponding Selenenic Acid
Molecules 2015, 20(12), 21415-21420; doi:10.3390/molecules201219773
Received: 1 November 2015 / Revised: 18 November 2015 / Accepted: 25 November 2015 / Published: 2 December 2015
Cited by 1 | PDF Full-text (1375 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A primary-alkyl-substituted selenenyl iodide was successfully synthesized through oxidative iodination of a selenol with N-iodosuccinimide by taking advantage of a cavity-shaped steric protection group. The selenenyl iodide exhibited high thermal stability and remained unchanged upon heating at 100 °C for 3 h
[...] Read more.
A primary-alkyl-substituted selenenyl iodide was successfully synthesized through oxidative iodination of a selenol with N-iodosuccinimide by taking advantage of a cavity-shaped steric protection group. The selenenyl iodide exhibited high thermal stability and remained unchanged upon heating at 100 °C for 3 h in [D8]toluene. The selenenyl iodide was reduced to the corresponding selenol by treatment with dithiothreitol. Hydrolysis of the selenenyl iodide under alkaline conditions afforded the corresponding selenenic acid almost quantitatively, corroborating the chemical validity of the recent proposal that hydrolysis of a selenenyl iodide to a selenenic acid is potentially involved in the catalytic mechanism of an iodothyronine deiodinase. Full article
(This article belongs to the Special Issue Selenium Catalysts and Antioxidants)
Open AccessArticle Accurate Mass GC/LC-Quadrupole Time of Flight Mass Spectrometry Analysis of Fatty Acids and Triacylglycerols of Spicy Fruits from the Apiaceae Family
Molecules 2015, 20(12), 21421-21432; doi:10.3390/molecules201219779
Received: 3 October 2015 / Revised: 23 November 2015 / Accepted: 26 November 2015 / Published: 2 December 2015
Cited by 3 | PDF Full-text (6747 KB) | HTML Full-text | XML Full-text
Abstract
The triacylglycerol (TAG) structure and the regio-stereospecific distribution of fatty acids (FA) of seed oils from most of the Apiaceae family are not well documented. The TAG structure ultimately determines the final physical properties of the oils and the position of FAs in
[...] Read more.
The triacylglycerol (TAG) structure and the regio-stereospecific distribution of fatty acids (FA) of seed oils from most of the Apiaceae family are not well documented. The TAG structure ultimately determines the final physical properties of the oils and the position of FAs in the TAG molecule affects the digestion; absorption and metabolism; and physical and technological properties of TAGs. Fixed oils from the fruits of dill (Anethum graveolens), caraway (Carum carvi), cumin (Cuminum cyminum), coriander (Coriandrum sativum), anise (Pimpinella anisum), carrot (Daucus carota), celery (Apium graveolens), fennel (Foeniculum vulgare), and Khella (Ammi visnaga), all from the Apiaceae family, were extracted at room temperature in chloroform/methanol (2:1 v/v) using percolators. Crude lipids were fractionated by solid phase extraction to separate neutral triacylglycerols (TAGs) from other lipids components. Neutral TAGs were subjected to transesterification process to convert them to their corresponding fatty acids methyl esters (FAMES) using 1% boron trifluoride (BF3) in methanol. FAMES were analyzed by gas chromatography-quadrupole time of flight (GC-QTOF) mass spectrometry. Triglycerides were analyzed using high performance liquid chromatography-quadrupole time of flight (LC-QTOF) mass spectrometry. Petroselinic acid was the major fatty acid in all samples ranging from 57% of the total fatty acids in caraway up to 82% in fennel. All samples contained palmitic (16:0), palmitoleic (C16:1n-9), stearic (C18:0), petroselinic (C18:1n-12), linoleic (C18:2n-6), linolinic (18:3n-3), and arachidic (C20:0) acids. TAG were analyzed using LC-QTOF for accurate mass identification and mass spectrometry/mass spectrometry (MS/MS) techniques for regiospesific elucidation of the identified TAGs. Five major TAGs were detected in all samples but with different relative concentrations in all of the tested samples. Several other TAGs were detected as minor components and were present in some samples and absence in the others. Regiospecific analysis showed a non-random fatty acids distribution. Petroselinic acid was predominantly located at the sn-1 and sn-3 positions. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessCommunication DFT Studies on the Stereoselectivity of α-Silyloxy Diazoalkane Cycloadditions
Molecules 2015, 20(12), 21433-21441; doi:10.3390/molecules201219783
Received: 14 October 2015 / Revised: 18 November 2015 / Accepted: 26 November 2015 / Published: 2 December 2015
PDF Full-text (2433 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The intramolecular [3+2] cycloaddition (32CA) of alkene-tethered α-silyloxydiazoalkanes provides variable stereoselectivity in generating bicyclic pyrazolines where the silyloxy group is either syn or anti to the newly formed pyrazoline ring. To elucidate the origin of the stereoselectivity, density functional theory (DFT) calculations were
[...] Read more.
The intramolecular [3+2] cycloaddition (32CA) of alkene-tethered α-silyloxydiazoalkanes provides variable stereoselectivity in generating bicyclic pyrazolines where the silyloxy group is either syn or anti to the newly formed pyrazoline ring. To elucidate the origin of the stereoselectivity, density functional theory (DFT) calculations were carried out for the energy of each transition state structure (TSs) and product. Steric effects were identified as the major determining factors in the diastereoselectivity of the 32CA reaction with regards to substrate structure (cyclic or acyclic α-silyloxydiazoalkanes). Full article
(This article belongs to the Special Issue Pericyclic Reactions)
Figures

Open AccessArticle Enrichment and Purification of Polyphenol Extract from Sphallerocarpus gracilis Stems and Leaves and in Vitro Evaluation of DNA Damage-Protective Activity and Inhibitory Effects of α-Amylase and α-Glucosidase
Molecules 2015, 20(12), 21442-21457; doi:10.3390/molecules201219780
Received: 6 November 2015 / Revised: 24 November 2015 / Accepted: 26 November 2015 / Published: 2 December 2015
Cited by 1 | PDF Full-text (1270 KB) | HTML Full-text | XML Full-text
Abstract
An efficient preparative separation method for Sphallerocarpus gracilis stems and leaves polyphenols (SGslP) was established in this study. An X-5 macroporous adsorption resin was selected for the purification of the SGslP, and the polyphenol content of the purified SGslP (PSGslP) was increased 5.11-fold
[...] Read more.
An efficient preparative separation method for Sphallerocarpus gracilis stems and leaves polyphenols (SGslP) was established in this study. An X-5 macroporous adsorption resin was selected for the purification of the SGslP, and the polyphenol content of the purified SGslP (PSGslP) was increased 5.11-fold from 8.29% to 42.38% after one treatment run. The chemical composition of the PSGslP was analyzed by HPLC-MS/MS, and the predominant compounds were found to be luteolin-7-glucoside, acacetin-7-acetyglycoside and its isomers. In addition, the PSGslP was evaluated in vitro to determine the DNA damage-protective activity and inhibitory effects of α-amylase and α-glucosidase. The results indicated that the PSGslP exhibited significant protective activities against both ROO• and •OH radical-induced DNA damage. Moreover, the PSGslP exerted a dose-dependent inhibition effect on α-glucosidase but no inhibitory effect on α-amylase. These findings indicate that the Sphallerocarpus gracilis stems and leaves are good natural sources of antioxidants and are potent inhibitors of α-glucosidase activity and are potential anti-diabetic inhibitor. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication An Effective Synthesis Method for Tilorone Dihydrochloride with Obvious IFN-α Inducing Activity
Molecules 2015, 20(12), 21458-21463; doi:10.3390/molecules201219781
Received: 9 October 2015 / Revised: 18 November 2015 / Accepted: 26 November 2015 / Published: 2 December 2015
Cited by 2 | PDF Full-text (805 KB) | HTML Full-text | XML Full-text
Abstract
Tilorone dihydrochloride (1) has great potential for inducing interferon against pathogenic infection. In this paper, we describe a convenient preparation method for 2,7-dihydroxyfluoren-9-one (2), which is a usual pharmaceutical intermediate for preparing tilorone dihydrochloride (1). In the
[...] Read more.
Tilorone dihydrochloride (1) has great potential for inducing interferon against pathogenic infection. In this paper, we describe a convenient preparation method for 2,7-dihydroxyfluoren-9-one (2), which is a usual pharmaceutical intermediate for preparing tilorone dihydrochloride (1). In the novel method, methyl esterification of 4,4′-dihydroxy-[1,1′-biphenyl]-2-carboxylic acid (4) was carried out under milder conditions with higher yield and played an important role in the preparation of compound 2. The structures of the relative intermediates and target compound were characterized by melting point, IR, MS, and 1H-NMR. Furthermore, the synthesized tilorone dihydrochloride exhibited an obvious effect on induction of interferon-α (IFN-α) in mice within 12 h, and the peak level was observed until 24 h. This fruitful work has resulted in tilorone dihydrochloride becoming available in large-scale and wide application in clinics, which has a good pharmaceutical development prospects. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synthesis and Biological Evaluation of Norcantharidin Derivatives Possessing an Aromatic Amine Moiety as Antifungal Agents
Molecules 2015, 20(12), 21464-21480; doi:10.3390/molecules201219782
Received: 11 November 2015 / Revised: 26 November 2015 / Accepted: 30 November 2015 / Published: 2 December 2015
Cited by 2 | PDF Full-text (895 KB) | HTML Full-text | XML Full-text
Abstract
Based on the structure of naturally produced cantharidin, different arylamine groups were linked to the norcantharidin scaffold to provide thirty six compounds. Their structures were confirmed by melting point, 1H-NMR, 13C-NMR and HRMS-ESI studies. These synthetic compounds were tested as fungistatic
[...] Read more.
Based on the structure of naturally produced cantharidin, different arylamine groups were linked to the norcantharidin scaffold to provide thirty six compounds. Their structures were confirmed by melting point, 1H-NMR, 13C-NMR and HRMS-ESI studies. These synthetic compounds were tested as fungistatic agents against eight phytopathogenic fungi using the mycelium growth rate method. Of these thirty six derivatives, seven displayed stronger antifungal activity than did norcantharidin, seven showed higher activity than did cantharidin and three exhibited more significant activity than that of thiabendazole. In particular, 3-(3′-chloro-phenyl)carbamoyl norcantharidate II-8 showed the most significant fungicidal activity against Sclerotinia fructigena and S. sclerotiorum, with IC50 values of 0.88 and 0.97 μg/mL, respectively. The preliminary structure-activity relationship data of these compounds revealed that: (1) the benzene ring is critical for the improvement of the spectrum of antifungal activity (3-phenylcarbamoyl norcantharidate II-1 vs norcantharidin and cantharidin); (2) among the three sites, including the C-2′, C-3′ and C-4′ positions of the phenyl ring, the presence of a halogen atom at the C-3′position of the benzene ring caused the most significant increase in antifungal activity; (3) compounds with strongly electron-drawing or electron-donating groups substitutions were found to have a poor antifungal activity; and (4) compared with fluorine, bromine and iodine, chlorine substituted at the C-3′ position of the benzene ring most greatly promoted fungistatic activity. Thus, compound II-8 has emerged as new lead structure for the development of new fungicides. Full article
(This article belongs to the Section Bioorganic Chemistry)
Figures

Open AccessArticle Two New Flavonol Glycosides from Polygala sibirica L. var megalopha Fr.
Molecules 2015, 20(12), 21494-21500; doi:10.3390/molecules201219775
Received: 21 October 2015 / Revised: 11 November 2015 / Accepted: 16 November 2015 / Published: 2 December 2015
PDF Full-text (522 KB) | HTML Full-text | XML Full-text
Abstract
Two new flavonol glycosides, named polygalin H (1) and polygalin I (2), as well as the known compound polygalin D (3), were isolated from the whole plant of Polygala sibirica L. var megalopha Fr. Their structures were
[...] Read more.
Two new flavonol glycosides, named polygalin H (1) and polygalin I (2), as well as the known compound polygalin D (3), were isolated from the whole plant of Polygala sibirica L. var megalopha Fr. Their structures were elucidated on the basis of spectroscopic data analysis. These flavonol glycosides exhibited strong inhibitory activities against xanthine oxidase in vitro. Their half-maximal inhibitory concentrations (IC50) were calculated, which were 9.48, 8.31, 16.00 μM, respectively. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Biological Evaluation of Curcumin Derivatives with Water-Soluble Groups as Potential Antitumor Agents: An in Vitro Investigation Using Tumor Cell Lines
Molecules 2015, 20(12), 21501-21514; doi:10.3390/molecules201219772
Received: 26 October 2015 / Revised: 24 November 2015 / Accepted: 26 November 2015 / Published: 2 December 2015
Cited by 3 | PDF Full-text (1791 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three series of curcumin derivatives including phosphorylated, etherified, and esterified products of curcumin were synthesized, and their anti-tumor activities were assessed against human breast cancer MCF-7, hepatocellular carcinoma Hep-G2, and human cervical carcinoma HeLa cells. Compared with curcumin, compounds 3, 8,
[...] Read more.
Three series of curcumin derivatives including phosphorylated, etherified, and esterified products of curcumin were synthesized, and their anti-tumor activities were assessed against human breast cancer MCF-7, hepatocellular carcinoma Hep-G2, and human cervical carcinoma HeLa cells. Compared with curcumin, compounds 3, 8, and 9 exhibited stronger antitumor cell line growth activities against HeLa cells. Compound 12 also showed higher antitumor cell line growth activities on MCF-7 cells than curcumin. Among them, 4-((1E,6E)-7-(4-Hydroxy-3-methoxyphenyl)-3,5-dioxohepta-1,6-dienyl)-2-methoxyphenyl dihydrogen phosphate(3) showed the strongest activity with an half maximal inhibitory concentration (IC50) of 6.78 µM against HeLa cells compared with curcumin with an IC50 of 17.67 µM. Stabilities of representatives of the three series were tested in rabbit plasma in vitro, and compounds 3 and 4 slowly released curcumin in plasma. The effect of compound 3 on HeLa cell apoptosis was determined by examining morphological changes by DAPI (4′,6-diamidino-2-phenylindole) staining as well as Annexin V-FITC/ Propidium Iodide (PI) double staining and flow cytometry. The results showed that 3 induced cellular apoptosis in a dose-dependent manner. Together our findings show that 3 merits further investigation as a new potential antitumor drug candidate. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle The Novel Multiple Inner Primers-Loop-Mediated Isothermal Amplification (MIP-LAMP) for Rapid Detection and Differentiation of Listeria monocytogenes
Molecules 2015, 20(12), 21515-21531; doi:10.3390/molecules201219787
Received: 9 September 2015 / Revised: 16 November 2015 / Accepted: 16 November 2015 / Published: 3 December 2015
Cited by 5 | PDF Full-text (12030 KB) | HTML Full-text | XML Full-text
Abstract
Here, a novel model of loop-mediated isothermal amplification (LAMP), termed multiple inner primers-LAMP (MIP-LAMP), was devised and successfully applied to detect Listeria monocytogenes. A set of 10 specific MIP-LAMP primers, which recognized 14 different regions of target gene, was designed to target
[...] Read more.
Here, a novel model of loop-mediated isothermal amplification (LAMP), termed multiple inner primers-LAMP (MIP-LAMP), was devised and successfully applied to detect Listeria monocytogenes. A set of 10 specific MIP-LAMP primers, which recognized 14 different regions of target gene, was designed to target a sequence in the hlyA gene. The MIP-LAMP assay efficiently amplified the target element within 35 min at 63 °C and was evaluated for sensitivity and specificity. The templates were specially amplified in the presence of the genomic DNA from L. monocytogenes. The limit of detection (LoD) of MIP-LAMP assay was 62.5 fg/reaction using purified L. monocytogenes DNA. The LoD for DNA isolated from serial dilutions of L. monocytogenes cells in buffer and in milk corresponded to 2.4 CFU and 24 CFU, respectively. The amplified products were analyzed by real-time monitoring of changes in turbidity, and visualized by adding Loop Fluorescent Detection Reagent (FD), or as a ladder-like banding pattern on gel electrophoresis. A total of 48 pork samples were investigated for L. monocytogenes by the novel MIP-LAMP method, and the diagnostic accuracy was shown to be 100% when compared to the culture-biotechnical method. In conclusion, the MIP-LAMP methodology was demonstrated to be a reliable, sensitive and specific tool for rapid detection of L. monocytogenes strains. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Characterization of Amorphous and Co-Amorphous Simvastatin Formulations Prepared by Spray Drying
Molecules 2015, 20(12), 21532-21548; doi:10.3390/molecules201219784
Received: 25 August 2015 / Revised: 24 November 2015 / Accepted: 25 November 2015 / Published: 3 December 2015
Cited by 4 | PDF Full-text (5780 KB) | HTML Full-text | XML Full-text
Abstract
In this study, spray drying from aqueous solutions, using the surface-active agent sodium lauryl sulfate (SLS) as a solubilizer, was explored as a production method for co-amorphous simvastatin–lysine (SVS-LYS) at 1:1 molar mixtures, which previously have been observed to form a co-amorphous mixture
[...] Read more.
In this study, spray drying from aqueous solutions, using the surface-active agent sodium lauryl sulfate (SLS) as a solubilizer, was explored as a production method for co-amorphous simvastatin–lysine (SVS-LYS) at 1:1 molar mixtures, which previously have been observed to form a co-amorphous mixture upon ball milling. In addition, a spray-dried formulation of SVS without LYS was prepared. Energy-dispersive X-ray spectroscopy (EDS) revealed that SLS coated the SVS and SVS-LYS particles upon spray drying. X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) showed that in the spray-dried formulations the remaining crystallinity originated from SLS only. The best dissolution properties and a “spring and parachute” effect were found for SVS spray-dried from a 5% SLS solution without LYS. Despite the presence of at least partially crystalline SLS in the mixtures, all the studied formulations were able to significantly extend the stability of amorphous SVS compared to previous co-amorphous formulations of SVS. The best stability (at least 12 months in dry conditions) was observed when SLS was spray-dried with SVS (and LYS). In conclusion, spray drying of SVS and LYS from aqueous surfactant solutions was able to produce formulations with improved physical stability for amorphous SVS. Full article
(This article belongs to the collection Poorly Soluble Drugs)
Figures

Open AccessArticle Determination of Solubility Parameters of Ibuprofen and Ibuprofen Lysinate
Molecules 2015, 20(12), 21549-21568; doi:10.3390/molecules201219777
Received: 30 September 2015 / Revised: 23 October 2015 / Accepted: 28 October 2015 / Published: 3 December 2015
Cited by 8 | PDF Full-text (3430 KB) | HTML Full-text | XML Full-text
Abstract
In recent years there has been a growing interest in formulating solid dispersions, which purposes mainly include solubility enhancement, sustained drug release and taste masking. The most notable problem by these dispersions is drug-carrier (in)solubility. Here we focus on solubility parameters as a
[...] Read more.
In recent years there has been a growing interest in formulating solid dispersions, which purposes mainly include solubility enhancement, sustained drug release and taste masking. The most notable problem by these dispersions is drug-carrier (in)solubility. Here we focus on solubility parameters as a tool for predicting the solubility of a drug in certain carriers. Solubility parameters were determined in two different ways: solely by using calculation methods, and by experimental approaches. Six different calculation methods were applied in order to calculate the solubility parameters of the drug ibuprofen and several excipients. However, we were not able to do so in the case of ibuprofen lysinate, as calculation models for salts are still not defined. Therefore, the extended Hansen’s approach and inverse gas chromatography (IGC) were used for evaluating of solubility parameters for ibuprofen lysinate. The obtained values of the total solubility parameter did not differ much between the two methods: by the extended Hansen’s approach it was δt = 31.15 MPa0.5 and with IGC it was δt = 35.17 MPa0.5. However, the values of partial solubility parameters, i.e., δd, δp and δh, did differ from each other, what might be due to the complex behaviour of a salt in the presence of various solvents. Full article
(This article belongs to the collection Poorly Soluble Drugs)
Figures

Open AccessArticle Amphiphilic Lipopeptide-Mediated Transport of Insulin and Cell Membrane Penetration Mechanism
Molecules 2015, 20(12), 21569-21583; doi:10.3390/molecules201219771
Received: 22 September 2015 / Revised: 25 October 2015 / Accepted: 12 November 2015 / Published: 3 December 2015
Cited by 3 | PDF Full-text (2868 KB) | HTML Full-text | XML Full-text
Abstract
Arginine octamer (R8) and its derivatives were developed in this study for the enhanced mucosal permeation of insulin. R8 was substituted with different aminos, then modified with stearic acid (SA). We found that the SAR6EW-insulin complex had stronger intermolecular interactions and higher complex
[...] Read more.
Arginine octamer (R8) and its derivatives were developed in this study for the enhanced mucosal permeation of insulin. R8 was substituted with different aminos, then modified with stearic acid (SA). We found that the SAR6EW-insulin complex had stronger intermolecular interactions and higher complex stability. The amphiphilic lipopeptide (SAR6EW) was significantly more efficient for the permeation of insulin than R8 and R6EW both in vitro and in vivo. Interestingly, different cellular internalization mechanisms were observed for the complexes. When the effectiveness of the complexes in delivering insulin in vivo was examined, it was found that the SAR6EW-insulin complex provided a significant and sustained (six hours) reduction in the blood glucose levels of diabetic rats. The improved absorption could be the comprehensive result of stronger intermolecular interactions, better enzymatic stability, altered internalization pathways, and increased transportation efficacy. In addition, no sign of toxicity was observed after consecutive administrations of SAR6EW. These results demonstrate that SAR6EW is a promising epithelium permeation enhancer for insulin and suggest that the chemical modification of cell-penetrating peptides is a feasible strategy to enhance their potential. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Oral Administration of Achyranthis radix Extract Prevents TMA-induced Allergic Contact Dermatitis by Regulating Th2 Cytokine and Chemokine Production in Vivo
Molecules 2015, 20(12), 21584-21596; doi:10.3390/molecules201219788
Received: 25 August 2015 / Revised: 16 November 2015 / Accepted: 26 November 2015 / Published: 3 December 2015
PDF Full-text (2411 KB) | HTML Full-text | XML Full-text
Abstract
Allergic contact dermatitis (ACD) remains a major skin disease in many countries, necessitating the discovery of novel and effective anti-ACD agents. In this study, we investigated the preventive effects of Achyranthis radix extract (AcRE) on trimellitic anhydride (TMA)-induced dermatitis and the potential mechanism
[...] Read more.
Allergic contact dermatitis (ACD) remains a major skin disease in many countries, necessitating the discovery of novel and effective anti-ACD agents. In this study, we investigated the preventive effects of Achyranthis radix extract (AcRE) on trimellitic anhydride (TMA)-induced dermatitis and the potential mechanism of action involved. Oral administration of AcRE and prednisolone (PS) significantly suppressed TMA-induced increases in ear and epidermal thickness, and IgE expression. In addition, abnormal expression of IL-1β and TNF-α protein and mRNA was also significantly attenuated by oral administration of AcRE. Treatment with AcRE also significantly suppressed TMA-induced IL-4 and IL-13 cytokines and mRNA expression in vivo. Moreover, AcRE strongly suppressed TMA-induced IL-4 and IL-5 production in draining lymph nodes, as well as OVA-induced IL-4 and IL-5 expression in primary cultured splenocytes. Interestingly, AcRE suppressed IL-4-induced STAT6 phosphorylation in both primary cultured splenocytes and HaCaT cells, and TMA-induced GATA3 mRNA expression ex vivo. AcRE also suppressed TMA-mediated CCL11 and IL-4-induced CCL26 mRNA expression and infiltration of CCR3 positive cells. The major compounds from AcRE were identified as gentisic acid (0.64 ± 0.2 μg/g dry weight of AcRE), protocatechuic acid (2.69 ± 0.1 μg/g dry weight of AcRE), 4-hydroxybenzoic acid (5.59 ± 0.3 μg/g dry weight of AcRE), caffeic acid (4.21 ± 0.1 μg/g dry weight of AcRE), and ferulic acid (14.78 ± 0.4 ± 0.3 μg/g dry weight of AcRE). Taken together, these results suggest that AcRE has potential for development as an agent to prevent and treat allergic contact dermatitis. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Simultaneous Determination of Eight Ginsenosides in Rat Plasma by Liquid Chromatography–Electrospray Ionization Tandem Mass Spectrometry: Application to Their Pharmacokinetics
Molecules 2015, 20(12), 21597-21608; doi:10.3390/molecules201219790
Received: 31 October 2015 / Revised: 26 November 2015 / Accepted: 27 November 2015 / Published: 3 December 2015
Cited by 7 | PDF Full-text (5614 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A high-performance liquid chromatography–electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was successfully developed and validated for the identification and determination of eight ginsenosides: ginsenoside Rg1 (1); 20(S)-ginsenoside Rh1 (2); 20(S)-ginsenoside Rg2 (
[...] Read more.
A high-performance liquid chromatography–electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was successfully developed and validated for the identification and determination of eight ginsenosides: ginsenoside Rg1 (1); 20(S)-ginsenoside Rh1 (2); 20(S)-ginsenoside Rg2 (3); 20(R)-ginsenoside Rh1 (4); 20(R)-ginsenoside Rg2 (5); ginsenoside Rd (6); 20(S)-ginsenoside Rg3 (7); and 20(R)-ginsenoside Rg3 (8) in rat plasma. The established rapid method had high linearity, selectivity, sensitivity, accuracy, and precision. The method has been used successfully to study the pharmacokinetics of abovementioned eight ginsenosides for the first time. After an oral administration of total saponins in the stems-leaves of Panax ginseng C. A. Meyer (GTSSL) at a dose of 400 mg/kg, the ginsenosides 6, 7, and 8, belonging to protopanaxadiol-type saponins, exhibited relatively long tmax values, suggesting that they were slowly absorbed, while the ginsenosides 15, belonging to protopanaxatriol-type saponins, had different tmax values, which should be due to their differences in the substituted groups. Compounds 2 and 4, 3 and 5, 7 and 8 were three pairs of R/S epimerics at C-20, which was interesting that the t1/2 of 20(S)-epimers were always longer than those of 20(R)-epimers. This pharmacokinetic identification of multiple ginsenosides of GTSSL in rat plasma provides a significant basis for better understanding the clinical application of GTSSL. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Influence of Pre-Fermentation Treatments on Wine Volatile and Sensory Profile of the New Disease Tolerant Cultivar Solaris
Molecules 2015, 20(12), 21609-21625; doi:10.3390/molecules201219791
Received: 6 October 2015 / Revised: 22 November 2015 / Accepted: 27 November 2015 / Published: 3 December 2015
Cited by 6 | PDF Full-text (1686 KB) | HTML Full-text | XML Full-text
Abstract
Solaris is a new disease tolerant cultivar increasingly cultivated in cool climate regions. In order to explore the winemaking processes’ potential to make different styles of Solaris wines, the effects of different pre-fermentation treatments (direct press after crushing, whole cluster press, cold maceration,
[...] Read more.
Solaris is a new disease tolerant cultivar increasingly cultivated in cool climate regions. In order to explore the winemaking processes’ potential to make different styles of Solaris wines, the effects of different pre-fermentation treatments (direct press after crushing, whole cluster press, cold maceration, and skin fermentation) on the volatile profile, chemical, and sensory properties of Solaris wines were investigated. Cold maceration treatment for 24 h and fermentation on skin led to wines with lower acidity and higher glycerol and total polyphenol indexes. Sensory analysis showed that cold maceration enhanced “apricot” and “apple” flavor while skin fermentation gave rise to increased “rose” and “elderflower” flavor. The PLS regression model revealed that fruity flavor of cold macerated wines was related to a combination of esters while β-damascenone and linalool were correlated to the “rose” and “elderflower” flavor. This study provides information about pre-fermentation techniques that allowed the possibility of obtaining wines with different styles. Full article
(This article belongs to the collection Wine Chemistry)
Figures

Open AccessArticle Influence of Excipients and Spray Drying on the Physical and Chemical Properties of Nutraceutical Capsules Containing Phytochemicals from Black Bean Extract
Molecules 2015, 20(12), 21626-21635; doi:10.3390/molecules201219792
Received: 6 October 2015 / Revised: 20 October 2015 / Accepted: 19 November 2015 / Published: 3 December 2015
Cited by 4 | PDF Full-text (610 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Black beans (Phaseolus vulgaris L.) are a rich source of flavonoids and saponins with proven health benefits. Spray dried black bean extract powders were used in different formulations for the production of nutraceutical capsules with reduced batch-to-batch weight variability. Factorial designs were
[...] Read more.
Black beans (Phaseolus vulgaris L.) are a rich source of flavonoids and saponins with proven health benefits. Spray dried black bean extract powders were used in different formulations for the production of nutraceutical capsules with reduced batch-to-batch weight variability. Factorial designs were used to find an adequate maltodextrin-extract ratio for the spray-drying process to produce black bean extract powders. Several flowability properties were used to determine composite flow index of produced powders. Powder containing 6% maltodextrin had the highest yield (78.6%) and the best recovery of flavonoids and saponins (>56% and >73%, respectively). The new complexes formed by the interaction of black bean powder with maltodextrin, microcrystalline cellulose 50 and starch exhibited not only bigger particles, but also a rougher structure than using only maltodextrin and starch as excipients. A drying process prior to capsule production improved powder flowability, increasing capsule weight and reducing variability. The formulation containing 25.0% of maltodextrin, 24.1% of microcrystalline cellulose 50, 50% of starch and 0.9% of magnesium stearate produced capsules with less than 2.5% weight variability. The spray drying technique is a feasible technique to produce good flow extract powders containing valuable phytochemicals and low cost excipients to reduce the end-product variability. Full article
(This article belongs to the Special Issue Recent Advances in Plant Phenolics)
Open AccessArticle Symmetry Breaking of B2N(−, 0, +): An Aspect of the Electric Potential and Atomic Charges
Molecules 2015, 20(12), 21636-21657; doi:10.3390/molecules201219769
Received: 6 August 2015 / Revised: 16 October 2015 / Accepted: 29 October 2015 / Published: 3 December 2015
Cited by 35 | PDF Full-text (2118 KB) | HTML Full-text | XML Full-text
Abstract
In this study, the three forms of B2N(−, 0, +)—radical, anion and cation—have been compared in terms of electric potential and atomic charges, ESP, rather than the well-known cut of the potential energy surface (PES). We have realized that
[...] Read more.
In this study, the three forms of B2N(−, 0, +)—radical, anion and cation—have been compared in terms of electric potential and atomic charges, ESP, rather than the well-known cut of the potential energy surface (PES). We have realized that the double minimum of the BNB radical is related to the lack of the correct permutational symmetry of the wave function and charge distribution. The symmetry breaking (SB) for B2N(0, +) exhibits energy barrier in the region of (5–150) cm−1. The SB barrier goes through a dynamic change with no centrosymmetric form which depends on the wave function or charge distribution. In spite of A ˜ 2 Σ g + exited state, the B ˜ 2 ∏ g excited configuration contributes to the ground state ( B ˜ 2 ∏ g − X ˜ 2 Σ u + ) for forming radicals. The SB did not occur for the anion form (B2N(−)) in any electrostatic potential and charges distribution. Finally, we have modified the Columbic term of the Schrödinger equation to define the parameters “αα' and ββ'” in order to investigate the SBs subject. Full article
(This article belongs to the Special Issue Boron Nitride: Synthesis and Application)
Open AccessCommunication Microwave-Assisted Superheating and/or Microwave-Specific Superboiling (Nucleation-Limited Boiling) of Liquids Occurs under Certain Conditions but is Mitigated by Stirring
Molecules 2015, 20(12), 21672-21680; doi:10.3390/molecules201219793
Received: 28 October 2015 / Revised: 17 November 2015 / Accepted: 20 November 2015 / Published: 4 December 2015
Cited by 4 | PDF Full-text (2519 KB) | HTML Full-text | XML Full-text
Abstract
Temporary superheating and sustained nucleation-limited “superboiling” of unstirred liquids above the normal atmospheric boiling point have been documented during microwave heating. These phenomena are reliably observed under prescribed conditions, although the duration (of superheating) and magnitude (of superheating and superboiling) vary according to
[...] Read more.
Temporary superheating and sustained nucleation-limited “superboiling” of unstirred liquids above the normal atmospheric boiling point have been documented during microwave heating. These phenomena are reliably observed under prescribed conditions, although the duration (of superheating) and magnitude (of superheating and superboiling) vary according to system parameters such as volume of the liquid and the size and shape of the vessel. Both phenomena are mitigated by rapid stirring with an appropriate stir bar and/or with the addition of boiling chips, which provide nucleation sites to support the phase-change from liquid to gas. With proper experimental design and especially proper stirring, the measured temperature of typical organic reaction mixtures heated at reflux will be close to the normal boiling point temperature of the solvent, whether heated using microwave radiation or conventional convective heat transfer. These observations are important to take into consideration when comparing reaction rates under conventional and microwave heating. Full article
(This article belongs to the Special Issue Microwave-Assisted Organic Synthesis)
Figures

Open AccessArticle An Improved Helferich Method for the α/β-Stereoselective Synthesis of 4-Methylumbelliferyl Glycosides for the Detection of Microorganisms
Molecules 2015, 20(12), 21681-21699; doi:10.3390/molecules201219789
Received: 15 September 2015 / Revised: 26 November 2015 / Accepted: 26 November 2015 / Published: 4 December 2015
Cited by 1 | PDF Full-text (3723 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An improved Helferich method is presented. It involves the glycosylation of 4-methyl-umbelliferone with glycosyl acetates in the presence of boron trifluoride etherate combined with triethylamine, pyridine, or 4-dimethylaminopyridine under mild conditions, followed by deprotection to give fluorogenic 4-methylumbelliferyl glycoside substrates. Due to the
[...] Read more.
An improved Helferich method is presented. It involves the glycosylation of 4-methyl-umbelliferone with glycosyl acetates in the presence of boron trifluoride etherate combined with triethylamine, pyridine, or 4-dimethylaminopyridine under mild conditions, followed by deprotection to give fluorogenic 4-methylumbelliferyl glycoside substrates. Due to the use of base, the glycosylation reaction proceeds more easily, is uncommonly α- or β-stereoselective, and affords the corresponding products in moderate to excellent yields (51%–94%) under appropriate conditions. Full article
Figures

Open AccessArticle 1-Deoxynojirimycin Alleviates Insulin Resistance via Activation of Insulin Signaling PI3K/AKT Pathway in Skeletal Muscle of db/db Mice
Molecules 2015, 20(12), 21700-21714; doi:10.3390/molecules201219794
Received: 28 September 2015 / Revised: 25 November 2015 / Accepted: 27 November 2015 / Published: 4 December 2015
Cited by 8 | PDF Full-text (3314 KB) | HTML Full-text | XML Full-text
Abstract
1-Deoxynojirimycin (DNJ) is widely used for the treatment of diabetes mellitus as an inhibitor of intestinal α-glucosidase. However, there are few reports about its effect on insulin sensitivity improvement. The aim of the present study was to investigate whether DNJ decreased hyperglycemia by
[...] Read more.
1-Deoxynojirimycin (DNJ) is widely used for the treatment of diabetes mellitus as an inhibitor of intestinal α-glucosidase. However, there are few reports about its effect on insulin sensitivity improvement. The aim of the present study was to investigate whether DNJ decreased hyperglycemia by improving insulin sensitivity. An economical method was established to prepare large amounts of DNJ. Then, db/db mice were treated with DNJ intravenously (20, 40 and 80 mg·kg−1·day−1) for four weeks. Blood glucose and biochemical analyses were conducted to evaluate the therapeutic effects on hyperglycemia and the related molecular mechanisms in skeletal muscle were explored. DNJ significantly reduced body weight, blood glucose and serum insulin levels. DNJ treatment also improved glucose tolerance and insulin tolerance. Moreover, although expressions of total protein kinase B (AKT), phosphatidylinositol 3 kinase (PI3K), insulin receptor beta (IR-β), insulin receptor substrate-1 (IRS1) and glucose transporter 4 (GLUT4) in skeletal muscle were not affected, GLUT4 translocation and phosphorylation of Ser473-AKT, p85-PI3K, Tyr1361-IR-β and Tyr612-IRS1 were significantly increased by DNJ treatment. These results indicate that DNJ significantly improved insulin sensitivity via activating insulin signaling PI3K/AKT pathway in skeletal muscle of db/db mice. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Seapolynol Extracted from Ecklonia cava Inhibits Adipocyte Differentiation in Vitro and Decreases Fat Accumulation in Vivo
Molecules 2015, 20(12), 21715-21731; doi:10.3390/molecules201219796
Received: 22 October 2015 / Revised: 25 November 2015 / Accepted: 26 November 2015 / Published: 4 December 2015
Cited by 3 | PDF Full-text (3751 KB) | HTML Full-text | XML Full-text
Abstract
Seapolynol (SN) is a polyphenol mixture derived from Ecklonia cava. We evaluated the effects of SN on lipid accumulation in adipocytes, zebrafish, and mice. SN effectively inhibited lipid accumulation in three experimental models by suppressing adipogenic factors. Triglyceride synthetic enzymes such as diacylglycerol
[...] Read more.
Seapolynol (SN) is a polyphenol mixture derived from Ecklonia cava. We evaluated the effects of SN on lipid accumulation in adipocytes, zebrafish, and mice. SN effectively inhibited lipid accumulation in three experimental models by suppressing adipogenic factors. Triglyceride synthetic enzymes such as diacylglycerol acyltransferase 1 (DGAT1) and GPAT3 were also downregulated by SN. This SN-induced inhibition of adipogenic factors was shown to be due to the regulatory effect of SN on early adipogenic factors; SN downregulated the expression of Krueppel-like factor 4 (KLF4), KLF5, CCAAT-enhancer-binding protein β (C/EBPβ), C/EBPδ, and Protein C-ets-2 (ETS2), while KLF2, an anti-early adipogenic factor, was upregulated by SN. SN-mediated inhibition in early adipogenesis was closely correlated with the inhibition of mitotic clonal expansion via cell cycle arrest. SN inhibited cell cycle progression by suppressing cell cycle regulators, such as cyclin A, cyclinD, and pRb but increased p27, a cell cycle inhibitor. In a mouse study, SN effectively reduced body weight and plasma lipid increases induced by a high-fat diet; triglycerides, total cholesterol, and low-density lipoprotein (LDL) levels were markedly reduced by SN. Moreover, SN remarkably improved high-fat-diet-induced hepatic lipid accumulation. Furthermore, SN activated AMP-activated protein kinase-α (AMPKα), an energy sensor, to suppress acetyl-coA carboxylase (ACC), inhibiting lipid synthesis. Our study suggests that SN may be an edible agent that can play a positive role in prevention of metabolic disorders. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle In Vivo Effects of Quercetin in Association with Moderate Exercise Training in Improving Streptozotocin-Induced Aortic Tissue Injuries
Molecules 2015, 20(12), 21770-21786; doi:10.3390/molecules201219802
Received: 24 October 2015 / Revised: 26 November 2015 / Accepted: 30 November 2015 / Published: 4 December 2015
Cited by 1 | PDF Full-text (1883 KB) | HTML Full-text | XML Full-text
Abstract
Background: Diabetes mellitus (DM) is a chronic endocrine-metabolic disorder associated with endothelial dysfunction. Hyperglycemia, dyslipidemia and abnormal nitric oxide-mediated vasodilatation are the major causal factors in the development of endothelial dysfunction in DM. The prevention of endothelial dysfunction may be a first target
[...] Read more.
Background: Diabetes mellitus (DM) is a chronic endocrine-metabolic disorder associated with endothelial dysfunction. Hyperglycemia, dyslipidemia and abnormal nitric oxide-mediated vasodilatation are the major causal factors in the development of endothelial dysfunction in DM. The prevention of endothelial dysfunction may be a first target against the appearance of atherosclerosis and cardiovascular diseases. We have investigated the synergistic protective effects of quercetin administration and moderate exercise training on thoracic aorta injuries induced by diabetes. Methods: Diabetic rats that performed exercise training were subjected to a swimming training program (1 h/day, 5 days/week, 4 weeks). The diabetic rats received quercetin (30 mg/kg body weight/day) for 4 weeks. At the end of the study, the thoracic aorta was isolated and divided into two parts; one part was immersed in 10% formalin for histopathological evaluations and the other was frozen for the assessment of oxidative stress markers (malondialdehyde, MDA and protein carbonyls groups, PC), the activity of antioxidant enzymes (superoxide dismutase, SOD and catalase, CAT), nitrite plus nitrate (NOx) production and inducible nitric oxide synthase (iNOS) protein expression. Results: Diabetic rats showed significantly increased MDA and PC levels, NOx production and iNOS expression and a reduction of SOD and CAT activity in aortic tissues. A decrease in the levels of oxidative stress markers, NOx production and iNOS expression associated with elevated activity of antioxidant enzymes in the aortic tissue were observed in quercetin-treated diabetic trained rats. Conclusions: These findings suggest that quercetin administration in association with moderate exercise training reduces vascular complications and tissue injuries induced by diabetes in rat aorta by decreasing oxidative stress and restoring NO bioavailability. Full article
Open AccessArticle Significant Improvement of Optoelectronic and Photovoltaic Properties by Incorporating Thiophene in a Solution-Processable D–A–D Modular Chromophore
Molecules 2015, 20(12), 21787-21801; doi:10.3390/molecules201219798
Received: 6 October 2015 / Revised: 24 November 2015 / Accepted: 25 November 2015 / Published: 4 December 2015
Cited by 4 | PDF Full-text (2574 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Through the incorporation of a thiophene functionality, a novel solution-processable small organic chromophore was designed, synthesized and characterized for application in bulk-heterojunction solar cells. The new chromophore, (2Z,2′Z)-2,2′-(1,4-phenylene)bis(3-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)acrylonitrile) (coded as AS2), was based on a donor–acceptor–donor (D–A–D) module
[...] Read more.
Through the incorporation of a thiophene functionality, a novel solution-processable small organic chromophore was designed, synthesized and characterized for application in bulk-heterojunction solar cells. The new chromophore, (2Z,2′Z)-2,2′-(1,4-phenylene)bis(3-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)acrylonitrile) (coded as AS2), was based on a donor–acceptor–donor (D–A–D) module where a simple triphenylamine unit served as an electron donor, 1,4-phenylenediacetonitrile as an electron acceptor, and a thiophene ring as the π-bridge embedded between the donor and acceptor functionalities. AS2 was isolated as brick-red, needle-shaped crystals, and was fully characterized by 1H- and 13C-NMR, IR, mass spectrometry and single crystal X-ray diffraction. The optoelectronic and photovoltaic properties of AS2 were compared with those of a structural analogue, (2Z,2′Z)-2,2′-(1,4-phenylene)bis(3-(4-(diphenylamino)phenyl)-acrylonitrile) (AS1). Benefiting from the covalent thiophene bridges, compared to AS1 thin solid film, the AS2 film showed: (1) an enhancement of light-harvesting ability by 20%; (2) an increase in wavelength of the longest wavelength absorption maximum (497 nm vs. 470 nm) and (3) a narrower optical band-gap (1.93 eV vs. 2.17 eV). Studies on the photovoltaic properties revealed that the best AS2-[6,6]-phenyl-C61-butyric acid methyl ester (PC61BM)-based device showed an impressive enhanced power conversion efficiency of 4.10%, an approx. 3-fold increase with respect to the efficiency of the best AS1-based device (1.23%). These results clearly indicated that embodiment of thiophene functionality extended the molecular conjugation, thus enhancing the light-harvesting ability and short-circuit current density, while further improving the bulk-heterojunction device performance. To our knowledge, AS2 is the first example in the literature where a thiophene unit has been used in conjunction with a 1,4-phenylenediacetonitrile accepting functionality to extend the π-conjugation in a given D–A–D motif for bulk-heterojunction solar cell applications. Full article
(This article belongs to the Special Issue Molecular Engineering for Electrochemical Power Sources)
Open AccessArticle In Vitro Metabolic Pathways of the New Anti-Diabetic Drug Evogliptin in Human Liver Preparations
Molecules 2015, 20(12), 21802-21815; doi:10.3390/molecules201219808
Received: 3 November 2015 / Revised: 19 November 2015 / Accepted: 25 November 2015 / Published: 4 December 2015
Cited by 2 | PDF Full-text (1434 KB) | HTML Full-text | XML Full-text
Abstract
Evogliptin ((R)-4-((R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl)-piperazin-2-one), is a new dipeptidyl peptidase IV inhibitor used for the treatment of type II diabetes mellitus. The in vitro metabolic pathways of evogliptin were identified in human hepatocytes, liver microsomes, and liver S9 fractions using
[...] Read more.
Evogliptin ((R)-4-((R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl)-piperazin-2-one), is a new dipeptidyl peptidase IV inhibitor used for the treatment of type II diabetes mellitus. The in vitro metabolic pathways of evogliptin were identified in human hepatocytes, liver microsomes, and liver S9 fractions using liquid chromatography-Orbitrap mass spectrometry (LC-HRMS). Five metabolites of evogliptin-4-oxoevogliptin (M1), 4(S)-hydroxyevogliptin (M2), 4(R)-hydroxyevogliptin (M3), 4(S)-hydroxyevogliptin glucuronide (M4), and evogliptin N-sulfate (M5)—were identified in human liver preparations by comparison with authentic standards. We characterized the cytochrome P450 (CYP) enzymes responsible for evogliptin hydroxylation to 4(S)-hydroxyevogliptin (M2) and 4(R)-hydroxyevogliptin (M3) and the UGT enzymes responsible for glucuronidation of 4(S)-hydroxyevogliptin (M2) to 4(S)-hydroxy-evogliptin glucuronide (M4). CYP3A4/5 played the major role in the hydroxylation of evogliptin to 4(S)-hydroxyevogliptin (M2) and 4(R)-hydroxyevogliptin (M3). Glucuronidation of 4(S)-hydroxy-evogliptin (M2) to 4(S)-hydroxyevogliptin glucuronide (M4) was catalyzed by the enzymes UGT2B4 and UGT2B7. These results suggest that the interindividual variability in the metabolism of evogliptin in humans is a result of the genetic polymorphism of the CYP and UGT enzymes responsible for evogliptin metabolism. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Fast Simultaneous Determination of 13 Nucleosides and Nucleobases in Cordyceps sinensis by UHPLC–ESI–MS/MS
Molecules 2015, 20(12), 21816-21825; doi:10.3390/molecules201219807
Received: 4 November 2015 / Revised: 29 November 2015 / Accepted: 1 December 2015 / Published: 4 December 2015
Cited by 2 | PDF Full-text (910 KB) | HTML Full-text | XML Full-text
Abstract
A reliable ultra-high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UHPLC–ESI–MS/MS) method for the fast simultaneous determination of 13 nucleosides and nucleobases in Cordyceps sinensis (C. sinensis) with 2-chloroadenosine as internal standard was developed and validated. Samples were ultrasonically extracted in an ice
[...] Read more.
A reliable ultra-high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UHPLC–ESI–MS/MS) method for the fast simultaneous determination of 13 nucleosides and nucleobases in Cordyceps sinensis (C. sinensis) with 2-chloroadenosine as internal standard was developed and validated. Samples were ultrasonically extracted in an ice bath thrice, and the optimum analyte separation was performed on an ACQUITY UPLCTM HSS C18 column (100 mm × 2.1 mm, 1.8 μm) with gradient elution. All targeted analytes were separated in 5.5 min. Furthermore, all calibration curves showed good linear regression (r > 0.9970) within the test ranges, and the limits of quantitation and detection of the 13 analytes were less than 150 and 75 ng/mL, respectively. The relative standard deviations (RSDs) of intra- and inter-day precisions were <6.23%. Recoveries of the quantified analytes ranged within 85.3%–117.3%, with RSD < 6.18%. The developed UHPLC–ESI–MS/MS method was successfully applied to determine nucleosides and nucleobases in 11 batches of C. sinensis samples from different regions in China. The range for the total content in the analyzed samples was 1329–2057 µg/g. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Utility of 3-Acetyl-6-bromo-2H-chromen-2-one for the Synthesis of New Heterocycles as Potential Antiproliferative Agents
Molecules 2015, 20(12), 21826-21839; doi:10.3390/molecules201219803
Received: 27 August 2015 / Revised: 25 November 2015 / Accepted: 26 November 2015 / Published: 4 December 2015
Cited by 9 | PDF Full-text (900 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Coumarin derivatives containing pyrazolo[1,5-a]pyrimidine, tetrazolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrimidine, pyrazolo[3,4-d]pyrimidine, 1,3,4-thiadiazoles and thiazoles were synthesized from 6-bromo-3-(3-(dimethylamino)acryloyl)-2H-chromen-2-one, methyl 2-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene)hydrazine carbodithioate, 2-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene) hydrazine carbothioamide and each of heterocyclic amine, hydrazonoyl chlorides and hydroximoyl
[...] Read more.
Coumarin derivatives containing pyrazolo[1,5-a]pyrimidine, tetrazolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrimidine, pyrazolo[3,4-d]pyrimidine, 1,3,4-thiadiazoles and thiazoles were synthesized from 6-bromo-3-(3-(dimethylamino)acryloyl)-2H-chromen-2-one, methyl 2-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene)hydrazine carbodithioate, 2-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene) hydrazine carbothioamide and each of heterocyclic amine, hydrazonoyl chlorides and hydroximoyl chlorides. The structures of the newly synthesized compounds were elucidated on the basis of elemental analysis, spectral data, and alternative synthetic routes whenever possible. Moreover, selected newly synthesized products were evaluated for their antitumor activity against a liver carcinoma cancer cell line (HEPG2-1). The results revealed that pyrazolo[1,5-a]pyrimidine 7c, thiazole 23g and 1,3,4-thiadiazole 18a (IC50 = 2.70 ± 0.28, 3.50 ± 0.23 and 4.90 ± 0.69 µM, respectively) have promising antitumor activity against liver carcinoma (HEPG2-1) while most of the tested compounds showed moderate activity. Full article
(This article belongs to the collection Heterocyclic Compounds)
Figures

Open AccessArticle Alkylation of Methyl Linoleate with Propene in Ionic Liquids in the Presence of Metal Salts
Molecules 2015, 20(12), 21840-21853; doi:10.3390/molecules201219805
Received: 5 November 2015 / Revised: 20 November 2015 / Accepted: 27 November 2015 / Published: 7 December 2015
Cited by 1 | PDF Full-text (3586 KB) | HTML Full-text | XML Full-text
Abstract
Vegetable oils and fatty acid esters are suitable precursor molecules for the production of a variety of bio-based products and materials, such as paints and coatings, plastics, soaps, lubricants, cosmetics, pharmaceuticals, printing inks, surfactants, and biofuels. Here, we report the possibility of using
[...] Read more.
Vegetable oils and fatty acid esters are suitable precursor molecules for the production of a variety of bio-based products and materials, such as paints and coatings, plastics, soaps, lubricants, cosmetics, pharmaceuticals, printing inks, surfactants, and biofuels. Here, we report the possibility of using Lewis acidic ionic liquids (ILs) to obtain polyunsaturated ester dimerization-oligomerization and/or, in the presence of another terminal alkene (propene), co-polymerization. In particular, we have tested the Lewis acidic mixtures arising from the addition of a proper amount of GaCl3 (Χ > 0.5) to two chloride-based (1-butyl-3-methylimidazolium chloride, [bmim]Cl, and 1-butylisoquinolium chloride, [BuIsoq]Cl) or by dissolution of a smaller amount of Al(Tf2N)3 (Χ = 0.1) in 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [bmim][Tf2N]. On the basis of product distribution studies, [bmim][Tf2N]/Al(Tf2N)3 appears the most suitable medium in which methyl linoleate alkylation with propene can compete with methyl linoleate or propene oligomerization. Full article
(This article belongs to the Special Issue Ionic Liquids in Organic Synthesis)
Open AccessArticle Comparative Analysis of Amaryllidaceae Alkaloids from Three Lycoris Species
Molecules 2015, 20(12), 21854-21869; doi:10.3390/molecules201219806
Received: 8 November 2015 / Revised: 29 November 2015 / Accepted: 30 November 2015 / Published: 7 December 2015
Cited by 4 | PDF Full-text (1446 KB) | HTML Full-text | XML Full-text
Abstract
The major active constituents from Amaryllidaceae family were reported to be Amaryllidaceae alkaloids (AAs), which exhibited a wide spectrum of biological activities, such as anti-tumor, anti-viral, and acetyl-cholinesterase-inhibitory activities. In order to better understand their potential as a source of bioactive AAs and
[...] Read more.
The major active constituents from Amaryllidaceae family were reported to be Amaryllidaceae alkaloids (AAs), which exhibited a wide spectrum of biological activities, such as anti-tumor, anti-viral, and acetyl-cholinesterase-inhibitory activities. In order to better understand their potential as a source of bioactive AAs and the phytochemical variations among three different species of Lycoris herbs, the HPLC fingerprint profiles of Lycoris aurea (L. aurea), L. radiata, and L. guangxiensis were firstly determined and compared using LC-UV and LC-MS/MS. As a result, 39 peaks were resolved and identified as AAs, of which nine peaks were found in common for all these three species, while the other 30 peaks could be revealed as characteristic AAs for L. aurea, L. radiata and L. guangxiensis, respectively. Thus, these AAs can be used as chemical markers for the identification and quality control of these plant species. To further reveal correlations between chemical components and their pharmaceutical activities of these species at the molecular level, the bioactivities of the total AAs from the three plant species were also tested against HepG2 cells with the inhibitory rate at 78.02%, 84.91% and 66.81% for L. aurea, L. radiata and L. guangxiensis, respectively. This study firstly revealed that the three species under investigation were different not only in the types of AAs, but also in their contents, and both contributed to their pharmacological distinctions. To the best of our knowledge, the current research provides the most detailed phytochemical profiles of AAs in these species, and offers valuable information for future valuation and exploitation of these medicinal plants. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Design, Synthesis and Bioactivities of Novel Dichloro-Allyloxy-Phenol-Containing Pyrazole Oxime Derivatives
Molecules 2015, 20(12), 21870-21880; doi:10.3390/molecules201219811
Received: 10 November 2015 / Revised: 27 November 2015 / Accepted: 2 December 2015 / Published: 8 December 2015
PDF Full-text (556 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, in order to find novel biologically active pyrazole oxime compounds, a number of dichloro-allyloxy-phenol-containing pyrazole oximes were designed and synthesized according to the method of active group combination. All of the target compounds were confirmed by 1H-NMR, 13C-NMR
[...] Read more.
In this study, in order to find novel biologically active pyrazole oxime compounds, a number of dichloro-allyloxy-phenol-containing pyrazole oximes were designed and synthesized according to the method of active group combination. All of the target compounds were confirmed by 1H-NMR, 13C-NMR and elemental analysis. In addition, bioassays showed that all of the newly synthesized compounds had no acaricidal activity against Tetranychus cinnabarinus and low insecticidal activity against Aphis craccivora at tested concentrations. However, most of them displayed excellent insecticidal activity against Oriental armyworm at a concentration of 500 μg/mL, and some designed compounds still exhibited potent insecticidal activity against Oriental armyworm even at the dose of 20 μg/mL, especially compounds 7f, 7n and 7p had 100%, 90% and 90% inhibition rates, respectively, which were comparable to that of the control pyridalyl. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Nanocasting of Periodic Mesoporous Materials as an Effective Strategy to Prepare Mixed Phases of Titania
Molecules 2015, 20(12), 21881-21895; doi:10.3390/molecules201219812
Received: 17 November 2015 / Revised: 1 December 2015 / Accepted: 3 December 2015 / Published: 8 December 2015
PDF Full-text (7909 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mesoporous titanium dioxide materials were prepared using a nanocasting technique involving silica SBA-15 as the hard-template. At an optimal loading of titanium precursor, the hexagonal periodic array of pores in SBA-15 was retained. The phases of titanium dioxide could be easily varied by
[...] Read more.
Mesoporous titanium dioxide materials were prepared using a nanocasting technique involving silica SBA-15 as the hard-template. At an optimal loading of titanium precursor, the hexagonal periodic array of pores in SBA-15 was retained. The phases of titanium dioxide could be easily varied by the number of impregnation cycles and the nature of titanium alkoxide employed. Low number of impregnation cycles produced mixed phases of anatase and TiO2(B). The mesoporous TiO2 materials were tested for solar hydrogen production, and the material consisting of 98% anatase and 2% TiO2(B) exhibited the highest yield of hydrogen from the photocatalytic splitting of water. The periodicity of the pores was an important factor that influenced the photocatalytic activity. This study indicates that mixed phases of titania containing ordered array of pores can be prepared by using the nanocasting strategy. Full article
Open AccessArticle Exploring the Reactivity of Na[W2(μ-Cl)3Cl4(THF)2]∙(THF)3 towards the Polymerization of Selected Cycloolefins
Molecules 2015, 20(12), 21896-21908; doi:10.3390/molecules201219810
Received: 19 October 2015 / Revised: 24 November 2015 / Accepted: 30 November 2015 / Published: 8 December 2015
Cited by 5 | PDF Full-text (2310 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The bimetallic compound Na[W2(μ-Cl)3Cl4(THF)2]·(THF)3 (1, {W 3 W}6+, a′2e′4) is a highly efficient room-temperature initiator for ring opening metathesis polymerization (ROMP) of norbornene (NBE)
[...] Read more.
The bimetallic compound Na[W2(μ-Cl)3Cl4(THF)2]·(THF)3 (1, {W 3 W}6+, a′2e′4) is a highly efficient room-temperature initiator for ring opening metathesis polymerization (ROMP) of norbornene (NBE) and some of its derivatives. In most cases, addition of phenylacetylene (PA) as co-initiator improves the catalytic activity and retains the high cis-stereoselectivity. On the other hand, 1 can polymerize cyclopentadiene (CPD), not via a metathetic, but rather, via a cationic mechanism. Here, we present a comparison of the reactivity of the two catalytic systems (1 and 1/PA) between themselves and with other systems reported in the literature, the characterization of the polymers formed and mechanistic aspects of the corresponding reactions. Full article
(This article belongs to the Special Issue Olefin Metathesis)
Figures

Open AccessArticle Efficient Diethylzinc/Gallic Acid and Diethylzinc/Gallic Acid Ester Catalytic Systems for the Ring-Opening Polymerization of rac-Lactide
Molecules 2015, 20(12), 21909-21923; doi:10.3390/molecules201219815
Received: 5 November 2015 / Revised: 23 November 2015 / Accepted: 30 November 2015 / Published: 8 December 2015
Cited by 3 | PDF Full-text (2221 KB) | HTML Full-text | XML Full-text
Abstract
Polylactide (PLA) represents one of the most promising biomedical polymers due to its biodegradability, bioresorbability and good biocompatibility. This work highlights the synthesis and characterization of PLAs using novel diethylzinc/gallic acid (ZnEt2/GAc) and diethylzinc/propyl gallate (ZnEt2/PGAc) catalytic systems that
[...] Read more.
Polylactide (PLA) represents one of the most promising biomedical polymers due to its biodegradability, bioresorbability and good biocompatibility. This work highlights the synthesis and characterization of PLAs using novel diethylzinc/gallic acid (ZnEt2/GAc) and diethylzinc/propyl gallate (ZnEt2/PGAc) catalytic systems that are safe for human body. The results of the ring-opening polymerization (ROP) of rac-lactide (rac-LA) in the presence of zinc-based catalytic systems have shown that, depending on the reaction conditions, “predominantly isotactic”, disyndiotactic or atactic PLA can be obtained. Therefore, the controlled and stereoselective ROP of rac-LA is discussed in detail in this paper. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle New 1H-Benzo[f]indazole-4,9-diones Conjugated with C-Protected Amino Acids and Other Derivatives: Synthesis and in Vitro Antiproliferative Evaluation
Molecules 2015, 20(12), 21924-21938; doi:10.3390/molecules201219809
Received: 4 November 2015 / Revised: 30 November 2015 / Accepted: 1 December 2015 / Published: 8 December 2015
PDF Full-text (1275 KB) | HTML Full-text | XML Full-text
Abstract
1H-Benzo[f]indazole-4,9-dione derivatives conjugated with C-protected amino acids (glycine, l-alanine, l-phenylalanine and l-glutamic acid) 6al were prepared by chemically modifying the prenyl substituent of 3-methyl-7-(4-methylpent-3-enyl)-1H-benzo[f]indazole-4,9-dione 2 through epoxidation, degradative oxidation, oxidation and N-acyl condensation
[...] Read more.
1H-Benzo[f]indazole-4,9-dione derivatives conjugated with C-protected amino acids (glycine, l-alanine, l-phenylalanine and l-glutamic acid) 6al were prepared by chemically modifying the prenyl substituent of 3-methyl-7-(4-methylpent-3-enyl)-1H-benzo[f]indazole-4,9-dione 2 through epoxidation, degradative oxidation, oxidation and N-acyl condensation reactions. The chemical structures of the synthesized compounds were elucidated by analyzing their IR, 1H-NMR and 13C-NMR spectral data together with elemental analysis for carbon, hydrogen and nitrogen. The preliminary in vitro antiproliferative activity of the synthesized derivatives was evaluated on KATO-III and MCF-7 cell lines using a cell proliferation assay. The majority of the derivatives exhibited significant antiproliferative activity with IC50 values ranging from 25.5 to 432.5 μM. These results suggest that 1H-benzo[f]indazole-4,9-dione derivatives are promising molecules to be researched for developing new anticancer agents. Full article
Figures

Open AccessArticle Chemical Compositions and Insecticidal Activities of Alpinia kwangsiensis Essential Oil against Lasioderma serricorne
Molecules 2015, 20(12), 21939-21945; doi:10.3390/molecules201219818
Received: 16 November 2015 / Revised: 28 November 2015 / Accepted: 1 December 2015 / Published: 8 December 2015
Cited by 3 | PDF Full-text (193 KB) | HTML Full-text | XML Full-text
Abstract
The essential oil obtained by hydrodistillation from Alpinia kwangsiensis rhizomes was investigated by GC-MS. A total of 31 components representing 92.45% of the oil were identified and the main compounds in the oil were found to be camphor (17.59%), eucalyptol (15.16%), β-pinene (11.15%)
[...] Read more.
The essential oil obtained by hydrodistillation from Alpinia kwangsiensis rhizomes was investigated by GC-MS. A total of 31 components representing 92.45% of the oil were identified and the main compounds in the oil were found to be camphor (17.59%), eucalyptol (15.16%), β-pinene (11.15%) and α-pinene (10.50%). These four compounds were subsequently isolated and the essential oil and four isolated compounds exhibited potent insecticidal activity against Lasioderma serricorne adults. During the assay, it was shown that the essential oil exhibited both potential contact (LD50 = of 24.59 μg/adult) and fumigant (LC50 = of 9.91 mg/L air) toxicity against Lasioderma serricorne. The study revealed that the insecticidal activity of the essential oil can be attributed to the synergistic effects of its diverse major components, which indicates that oil of Alpinia kwangsiensis and its isolated compounds have potential to be developed into natural insecticides to control insects in stored grains and traditional Chinese medicinal materials. Full article
(This article belongs to the collection Herbal Medicine Research)
Open AccessArticle Bioactive Constituents from the Aerial Parts of Lippia triphylla
Molecules 2015, 20(12), 21946-21959; doi:10.3390/molecules201219814
Received: 27 September 2015 / Revised: 27 November 2015 / Accepted: 4 December 2015 / Published: 8 December 2015
Cited by 2 | PDF Full-text (1958 KB) | HTML Full-text | XML Full-text
Abstract
Five new compounds, lippianosides A (1), B (2), C (3), D (4), and E (5), along with 26 (631) known ones were obtained from the 95% EtOH extract of
[...] Read more.
Five new compounds, lippianosides A (1), B (2), C (3), D (4), and E (5), along with 26 (631) known ones were obtained from the 95% EtOH extract of Lippia triphylla (L. triphylla) aerial parts collected from Rwanda, Africa. Among the known compounds, 11 and 1730 were isolated from the Lippia genus for the first time. In addition, 12, 13, and 16 were firstly obtained from this species. The structures of them were elucidated by chemical and spectroscopic methods. The antioxidant and triglyceride accumulation inhibition effects of the 31 compounds were examined in L6 cells and HepG2 cells, respectively. Full article
(This article belongs to the collection Herbal Medicine Research)
Open AccessArticle Novel 3-Amino-6-chloro-7-(azol-2 or 5-yl)-1,1-dioxo-1,4,2-benzodithiazine Derivatives with Anticancer Activity: Synthesis and QSAR Study
Molecules 2015, 20(12), 21960-21970; doi:10.3390/molecules201219821
Received: 30 October 2015 / Revised: 20 November 2015 / Accepted: 1 December 2015 / Published: 9 December 2015
Cited by 4 | PDF Full-text (958 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of new 3-amino-6-chloro-7-(azol-2 or 5-yl)-1,1-dioxo-1,4,2-benzodithiazine derivatives 5aj have been synthesized and evaluated in vitro for their antiproliferative activity at the U.S. National Cancer Institute. The most active compound 5h showed significant cytotoxic effects against ovarian (OVCAR-3) and breast (MDA-MB-468)
[...] Read more.
A series of new 3-amino-6-chloro-7-(azol-2 or 5-yl)-1,1-dioxo-1,4,2-benzodithiazine derivatives 5aj have been synthesized and evaluated in vitro for their antiproliferative activity at the U.S. National Cancer Institute. The most active compound 5h showed significant cytotoxic effects against ovarian (OVCAR-3) and breast (MDA-MB-468) cancer (10% and 47% cancer cell death, respectively) as well as a good selectivity toward prostate (DU-145), colon (SW-620) and renal (TK-10) cancer cell lines. To obtain a deeper insight into the structure-activity relationships of the new compounds 5aj QSAR studies have been applied. Theoretical calculations allowed the identification of molecular descriptors belonging to the RDF (RDF055p and RDF145m in the MOLT-4 and UO-31 QSAR models, respectively) and 3D-MorSE (Mor32m and Mor16e for MOLT-4 and UO-31 QSAR models) descriptor classes. Based on these data, QSAR models with good robustness and predictive ability have been obtained. Full article
Figures

Open AccessArticle The Restorative Effects of Eucommia ulmoides Oliver Leaf Extract on Vascular Function in Spontaneously Hypertensive Rats
Molecules 2015, 20(12), 21971-21981; doi:10.3390/molecules201219826
Received: 13 October 2015 / Revised: 24 November 2015 / Accepted: 2 December 2015 / Published: 9 December 2015
Cited by 5 | PDF Full-text (2322 KB) | HTML Full-text | XML Full-text
Abstract
Eucommia ulmoides Oliv. leaf is a traditional Chinese antihypertensive and antidiabetic medicine. We examined the effects of chronic Eucommia leaf extract (ELE) administration on artery function and morphology in spontaneously hypertensive rats (SHRs). ELE was orally administered via normal diet ad libitum to
[...] Read more.
Eucommia ulmoides Oliv. leaf is a traditional Chinese antihypertensive and antidiabetic medicine. We examined the effects of chronic Eucommia leaf extract (ELE) administration on artery function and morphology in spontaneously hypertensive rats (SHRs). ELE was orally administered via normal diet ad libitum to six-week-old male SHRs at a concentration of 5% for seven weeks. Acetylcholine (ACh)-induced endothelium-dependent relaxation, sodium nitroprusside (SNP)-induced endothelium-independent relaxation, plasma nitric oxide (NO) levels, and media thickness were assessed. ELE significantly improved ACh-induced aortic endothelium-dependent relaxation but did not affect SNP-induced endothelium-independent relaxation in the SHRs, as compared to the animals receiving normal diet. Plasma NO levels and media thickness were significantly increased and decreased, respectively, in the ELE-treated SHRs. Therefore, long-term ELE administration may effectively improve vascular function by increasing plasma NO levels and bioavailability, and by preventing vascular hypertrophy in the SHR aorta. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Eco-Friendly Synthesis of Some Thiosemicarbazones and Their Applications as Intermediates for 5-Arylazothiazole Disperse Dyes
Molecules 2015, 20(12), 21982-21991; doi:10.3390/molecules201219820
Received: 13 November 2015 / Revised: 30 November 2015 / Accepted: 3 December 2015 / Published: 9 December 2015
PDF Full-text (1088 KB) | HTML Full-text | XML Full-text
Abstract
The solid-solid reactions of thiosemicarbazide with 4-formylantipyrine, 2-acetylpyrrole and camphor were performed to afford the thiosemicarbazones 13 which underwent hetero-cyclization with phenacyl bromide to furnish the corresponding thiazole derivatives 46. The yields of the reactions are quantitative in
[...] Read more.
The solid-solid reactions of thiosemicarbazide with 4-formylantipyrine, 2-acetylpyrrole and camphor were performed to afford the thiosemicarbazones 13 which underwent hetero-cyclization with phenacyl bromide to furnish the corresponding thiazole derivatives 46. The yields of the reactions are quantitative in all cases and the products do not require further purification. A series of 5-arylazo-2-(substituted ylidene-hydrazinyl)-thiazole dyes 79 was then prepared by diazo coupling of thiazole derivatives 46 with several diazonium chlorides. The synthesized dyes were applied as disperse dyes for dyeing polyester fabric. The dyed fabrics exhibit good washing, perspiration, sublimation and light fastness properties, with little variation in their moderate to good rubbing fastness. Full article
(This article belongs to the collection Heterocyclic Compounds)
Figures

Open AccessArticle Identification of Hydrophobic Interfaces in Protein-Ligand Complexes by Selective Saturation Transfer NMR Spectroscopy
Molecules 2015, 20(12), 21992-21999; doi:10.3390/molecules201219824
Received: 6 May 2015 / Revised: 17 September 2015 / Accepted: 26 November 2015 / Published: 9 December 2015
PDF Full-text (3299 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The proper characterization of protein-ligand interfaces is essential for structural biology, with implications ranging from the fundamental understanding of biological processes to pharmacology. Nuclear magnetic resonance is a powerful technique for such studies. We propose a novel approach to the direct determination of
[...] Read more.
The proper characterization of protein-ligand interfaces is essential for structural biology, with implications ranging from the fundamental understanding of biological processes to pharmacology. Nuclear magnetic resonance is a powerful technique for such studies. We propose a novel approach to the direct determination of the likely pose of a peptide ligand onto a protein partner, by using frequency-selective cross-saturation with a low stringency isotopic labeling methods. Our method illustrates a complex of the Src homology 3 domain of C-terminal Src kinase with a peptide from the proline-enriched tyrosine phosphatase. Full article
(This article belongs to the Special Issue Molecular Docking in Drug Design)
Figures

Open AccessArticle Efficient Synthesis of β-Aryl-γ-lactams and Their Resolution with (S)-Naproxen: Preparation of (R)- and (S)-Baclofen
Molecules 2015, 20(12), 22028-22043; doi:10.3390/molecules201219830
Received: 31 October 2015 / Revised: 24 November 2015 / Accepted: 2 December 2015 / Published: 10 December 2015
Cited by 4 | PDF Full-text (1986 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An efficient synthesis of enantiomerically-pure β-aryl-γ-lactams is described. The principal feature of this synthesis is the practical resolution of β-aryl-γ-lactams with (S)-Naproxen. The procedure is based on the Michael addition of nitromethane to benzylidenemalonates, which was easily obtained, followed by the
[...] Read more.
An efficient synthesis of enantiomerically-pure β-aryl-γ-lactams is described. The principal feature of this synthesis is the practical resolution of β-aryl-γ-lactams with (S)-Naproxen. The procedure is based on the Michael addition of nitromethane to benzylidenemalonates, which was easily obtained, followed by the reduction of the γ-nitroester in the presence of Raney nickel and the subsequent saponification/decarboxylation reaction. The utility of this methodology was highlighted by the preparation of enantiomerically-pure (R)- and (S)-Baclofen hydrochloride. Full article
(This article belongs to the Section Organic Synthesis)
Figures

Open AccessArticle Novel Penicillin-Type Analogues Bearing a Variable Substituted 2-Azetidinone Ring at Position 6: Synthesis and Biological Evaluation
Molecules 2015, 20(12), 22044-22057; doi:10.3390/molecules201219828
Received: 28 September 2015 / Revised: 20 November 2015 / Accepted: 2 December 2015 / Published: 10 December 2015
Cited by 4 | PDF Full-text (1048 KB) | HTML Full-text | XML Full-text
Abstract
The synthesis and the biological activity of novel semi-synthetic β-lactam compounds containing an azetidinone moiety joined to the amino-nitrogen of the (+)-6-aminopenicillanic acid (6-APA) as new antibacterial agents is reported. The synthesized compounds were screened for their in vitro antimicrobial activity against a
[...] Read more.
The synthesis and the biological activity of novel semi-synthetic β-lactam compounds containing an azetidinone moiety joined to the amino-nitrogen of the (+)-6-aminopenicillanic acid (6-APA) as new antibacterial agents is reported. The synthesized compounds were screened for their in vitro antimicrobial activity against a panel of Gram positive and Gram negative pathogens and environmental bacteria. Tested compounds displayed good antimicrobial activity against all tested Gram positive bacteria and for Staphylococcus aureus and Staphylococcus epidermidis antimicrobial activity resulted higher than that of the reference antibiotic. Additionally, in vitro cytotoxic screening was also carried out indicating that the compounds do not cause a cell vitality reduction effective at concentration next to and above those shown to be antimicrobial. Full article
Figures

Open AccessArticle Adsorption Kinetics at Silica Gel/Ionic Liquid Solution Interface
Molecules 2015, 20(12), 22058-22068; doi:10.3390/molecules201219833
Received: 3 September 2015 / Revised: 30 October 2015 / Accepted: 19 November 2015 / Published: 10 December 2015
PDF Full-text (2451 KB) | HTML Full-text | XML Full-text
Abstract
A series of imidazolium and pyridinium ionic liquids with different anions (Cl, Br, BF4, PF6) has been evaluated for their adsorption activity on silica gel. Quantification of the ionic liquids has been performed
[...] Read more.
A series of imidazolium and pyridinium ionic liquids with different anions (Cl, Br, BF4, PF6) has been evaluated for their adsorption activity on silica gel. Quantification of the ionic liquids has been performed by the use of RP-HPLC with organic-aqueous eluents containing an acidic buffer and a chaotropic salt. Pseudo-second order kinetic models were applied to the experimental data in order to investigate the kinetics of the adsorption process. The experimental data showed good fitting with this model, confirmed by considerably high correlation coefficients. The adsorption kinetic parameters were determined and analyzed. The relative error between the calculated and experimental amount of ionic liquid adsorbed at equilibrium was within 7%. The effect of various factors such as initial ionic liquid concentration, temperature, kind of solvent, kind of ionic liquid anion and cation on adsorption efficiency were all examined in a lab-scale study. Consequently, silica gel showed better adsorptive characteristics for imidazolium-based ionic liquids with chaotropic anions from aqueous solutions in comparison to pyridinium ionic liquids. The adsorption was found to decrease with the addition of organic solvents (methanol, acetonitrile) but it was not sensitive to the change of temperature in the range of 5–40 °C. Full article
(This article belongs to the Special Issue Ionic Liquids in Organic Synthesis)
Figures

Open AccessArticle Synthesis and Regioselective Reaction of Some Unsymmetrical Heterocyclic Chalcone Derivatives and Spiro Heterocyclic Compounds as Antibacterial Agents
Molecules 2015, 20(12), 22069-22083; doi:10.3390/molecules201219827
Received: 19 October 2015 / Revised: 26 November 2015 / Accepted: 3 December 2015 / Published: 10 December 2015
Cited by 9 | PDF Full-text (4157 KB) | HTML Full-text | XML Full-text
Abstract
A number of novel heterocyclic chalcone derivatives can be synthesized by thermal and microwave tools. Treatment of 4-(4-Acetylamino- and/or 4-bromo-phenyl)-4-oxobut-2-enoic acids with hydrogen peroxide in alkaline medium were afforded oxirane derivatives 2. Reaction of the epoxide 2 with 2-amino-5-aryl-1,3,4-thiadiazole derivatives yielded chalcone
[...] Read more.
A number of novel heterocyclic chalcone derivatives can be synthesized by thermal and microwave tools. Treatment of 4-(4-Acetylamino- and/or 4-bromo-phenyl)-4-oxobut-2-enoic acids with hydrogen peroxide in alkaline medium were afforded oxirane derivatives 2. Reaction of the epoxide 2 with 2-amino-5-aryl-1,3,4-thiadiazole derivatives yielded chalcone of imidazo[2,1-b]thiadiazole derivative 4 via two thermal routes. In one pot reaction of 4-bromoacetophenone, diethyloxalate, and 2-amino-5-aryl-1,3,4-thiadiazole derivatives in MW irradiation (W 250 and T 150 °C) under eco-friendly conditions afforded an unsuitable yield of the desired chalcone 4d. The chalcone derivatives 4 were used as a key starting material to synthesize some new spiroheterocyclic compounds via Michael and aza-Michael adducts. The chalcone 4f was similar to the aryl-oxo-vinylamide derivatives for the inhibition of tyrosine kinase and cancer cell growth. The electron-withdrawing substituents, such as halogens, and 2-amino-1,3,4-thiadiazole moeity decreasing the electron density, thereby decreasing the energy of HOMO, and the presence of imidazothiadiazole moiety should improve the antibacterial activity. Thus, the newly synthesized compounds were evaluated for their anti-bacterial activity against (ATCC 25923), (ATCC 10987), (ATCC 274,) and (SM514). The structure of the newly synthesized compounds was confirmed by elemental analysis and spectroscopic data. Full article
(This article belongs to the collection Heterocyclic Compounds)
Figures

Open AccessArticle 7-Methoxytacrine-p-Anisidine Hybrids as Novel Dual Binding Site Acetylcholinesterase Inhibitors for Alzheimer’s Disease Treatment
Molecules 2015, 20(12), 22084-22101; doi:10.3390/molecules201219836
Received: 2 November 2015 / Revised: 2 December 2015 / Accepted: 4 December 2015 / Published: 10 December 2015
Cited by 14 | PDF Full-text (2739 KB) | HTML Full-text | XML Full-text
Abstract
Alzheimer’s disease (AD) is a debilitating progressive neurodegenerative disorder that ultimately leads to the patient’s death. Despite the fact that novel pharmacological approaches endeavoring to block the neurodegenerative process are still emerging, none of them have reached use in clinical practice yet. Thus,
[...] Read more.
Alzheimer’s disease (AD) is a debilitating progressive neurodegenerative disorder that ultimately leads to the patient’s death. Despite the fact that novel pharmacological approaches endeavoring to block the neurodegenerative process are still emerging, none of them have reached use in clinical practice yet. Thus, palliative treatment represented by acetylcholinesterase inhibitors (AChEIs) and memantine are still the only therapeutics used. Following the multi-target directed ligands (MTDLs) strategy, herein we describe the synthesis, biological evaluation and docking studies for novel 7-methoxytacrine-p-anisidine hybrids designed to purposely target both cholinesterases and the amyloid cascade. Indeed, the novel derivatives proved to be effective non-specific cholinesterase inhibitors showing non-competitive AChE inhibition patterns. This compounds’ behavior was confirmed in the subsequent molecular modeling studies. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle Safety Evaluation, in Vitro and in Vivo Antioxidant Activity of the Flavonoid-Rich Extract from Maydis stigma
Molecules 2015, 20(12), 22102-22112; doi:10.3390/molecules201219835
Received: 29 October 2015 / Revised: 4 December 2015 / Accepted: 7 December 2015 / Published: 10 December 2015
Cited by 4 | PDF Full-text (1099 KB) | HTML Full-text | XML Full-text
Abstract
This study aimed to assess the acute toxicity and safety of flavonoid-rich extract from Maydis stigma (FMS) in mice. The in vitro antioxidant activity of FMS was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethyl-benzthiazoline-6-sulphonate) (ABTS) scavenging assays. Furthermore, the in vivo antioxidant of FMS
[...] Read more.
This study aimed to assess the acute toxicity and safety of flavonoid-rich extract from Maydis stigma (FMS) in mice. The in vitro antioxidant activity of FMS was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethyl-benzthiazoline-6-sulphonate) (ABTS) scavenging assays. Furthermore, the in vivo antioxidant of FMS against ethanol-induced oxidative damage in mice was determined by analysis of the serum total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA) content, liver tissue glutathione (GSH) content, and protein carbonyl (PC) content in liver tissue. The oral administration of FMS at doses of 30 g/kg did not cause death in mice, and there were no significant biologically adverse effects in mice. These results indicated that the median lethal dose (LD50) is higher than this dose. The IC50 values of FMS for the DPPH and ABTS scavenging activity were 50.73 and 0.23 mg/mL, respectively. Meanwhile, FMS could significantly enhance T-SOD activity, reduce MDA content in the serum, increase GSH content, and decrease PC content in the liver tissue at the tested doses (25, 50, 100, 200 mg/kg·day). These results indicate that FMS can be generally regarded as safe and used potentially as a bioactive source of natural antioxidants. Full article
(This article belongs to the collection Herbal Medicine Research)
Open AccessArticle Herb-Drug Pharmacokinetic Interactions: Transport and Metabolism of Indinavir in the Presence of Selected Herbal Products
Molecules 2015, 20(12), 22113-22127; doi:10.3390/molecules201219838
Received: 19 October 2015 / Revised: 2 December 2015 / Accepted: 7 December 2015 / Published: 10 December 2015
PDF Full-text (751 KB) | HTML Full-text | XML Full-text
Abstract
Patients receiving anti-retroviral drug treatment are sometimes simultaneously taking herbal remedies, which may result in pharmacokinetic herb-drug interactions. This study aimed to determine if pharmacokinetic interactions exist between selected commercially available herbal products (i.e., Linctagon Forte®, Viral Choice®
[...] Read more.
Patients receiving anti-retroviral drug treatment are sometimes simultaneously taking herbal remedies, which may result in pharmacokinetic herb-drug interactions. This study aimed to determine if pharmacokinetic interactions exist between selected commercially available herbal products (i.e., Linctagon Forte®, Viral Choice® and Canova®) and indinavir in terms of in vitro transport and metabolism. Bi-directional transport of indinavir was evaluated across Caco-2 cell monolayers in the presence and absence of the selected herbal products and verapamil (positive control). Metabolism of indinavir was determined in LS180 cells in the presence and absence of the selected herbal products as well as ketoconazole (positive control). The secretory transport of indinavir increased in a concentration dependent way in the presence of Linctagon Forte® and Viral Choice® when compared to that of indinavir alone. Canova® only slightly affected the efflux of indinavir compared to that of the control group. There was a pronounced inhibition of the metabolism of indinavir in LS180 cells over the entire concentration range for all the herbal products investigated in this study. These in vitro pharmacokinetic interactions indicate the selected herbal products may affect indinavir’s bioavailability, but the clinical significance needs to be confirmed with in vivo studies before final conclusions can be made. Full article
(This article belongs to the collection Herbal Medicine Research)
Open AccessArticle Limonin, a Component of Dictamni Radicis Cortex, Inhibits Eugenol-Induced Calcium and cAMP Levels and PKA/CREB Signaling Pathway in Non-Neuronal 3T3-L1 Cells
Molecules 2015, 20(12), 22128-22136; doi:10.3390/molecules201219840
Received: 16 October 2015 / Revised: 30 November 2015 / Accepted: 2 December 2015 / Published: 10 December 2015
PDF Full-text (1900 KB) | HTML Full-text | XML Full-text
Abstract
Limonin, one of the major components in dictamni radicis cortex (DRC), has been shown to play various biological roles in cancer, inflammation, and obesity in many different cell types and tissues. Recently, the odorant-induced signal transduction pathway (OST) has gained attention not only
[...] Read more.
Limonin, one of the major components in dictamni radicis cortex (DRC), has been shown to play various biological roles in cancer, inflammation, and obesity in many different cell types and tissues. Recently, the odorant-induced signal transduction pathway (OST) has gained attention not only because of its function in the perception of smell but also because of its numerous physiological functions in non-neuronal cells. However, little is known about the effects of limonin and DRC on the OST pathway in non-neuronal cells. We investigated odorant-stimulated increases in Ca2+ and cAMP, major second messengers in the OST pathway, in non-neuronal 3T3-L1 cells pretreated with limonin and ethanol extracts of DRC. Limonin and the extracts significantly decreased eugenol-induced Ca2+ and cAMP levels and upregulated phosphorylation of CREB and PKA. Our results demonstrated that limonin and DRC extract inhibit the OST pathway in non-neuronal cells by modulating Ca2+ and cAMP levels and phosphorylation of CREB. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Development of an Analytical Method Based on Temperature Controlled Solid-Liquid Extraction Using an Ionic Liquid as Solid Solvent
Molecules 2015, 20(12), 22137-22145; doi:10.3390/molecules201219842
Received: 5 August 2015 / Revised: 29 October 2015 / Accepted: 19 November 2015 / Published: 10 December 2015
Cited by 1 | PDF Full-text (1292 KB) | HTML Full-text | XML Full-text
Abstract
At the present paper, an analytical method based on temperature controlled solid-liquid extraction (TC-SLE) utilizing a synthesized ionic liquid, (N-butylpyridinium hexafluorophosphate, [BPy]PF6), as solid solvent and phenanthroline (PT) as an extractant was developed to determine micro levels of Fe
[...] Read more.
At the present paper, an analytical method based on temperature controlled solid-liquid extraction (TC-SLE) utilizing a synthesized ionic liquid, (N-butylpyridinium hexafluorophosphate, [BPy]PF6), as solid solvent and phenanthroline (PT) as an extractant was developed to determine micro levels of Fe2+ in tea by PT spectrophotometry. TC-SLE was carried out in two continuous steps: Fe2+ can be completely extracted by PT-[BPy]PF6 or back-extracted at 80 °C and the two phases were separated automatically by cooling to room temperature. Fe2+, after back-extraction, needs 2 mol/L HNO3 as stripping agent and the whole process was determined by PT spectrophotometry at room temperature. The extracted species was neutral Fe(PT)mCl2 (m = 1) according to slope analysis in the Fe2+-[BPy]PF6-PT TC-SLE system. The calibration curve was Y = 0.20856X − 0.000775 (correlation coefficient = 0.99991). The linear calibration range was 0.10–4.50 μg/mL and the limit of detection for Fe2+ is 7.0 × 10−2 μg/mL. In this method, the contents of Fe2+ in Tieguanyin tea were determined with RSDs (n = 5) 3.05% and recoveries in range of 90.6%–108.6%. Full article
(This article belongs to the Special Issue Ionic Liquids in Organic Synthesis)
Open AccessArticle Impact of Natural Juice Consumption on Plasma Antioxidant Status: A Systematic Review and Meta-Analysis
Molecules 2015, 20(12), 22146-22156; doi:10.3390/molecules201219834
Received: 27 October 2015 / Revised: 13 November 2015 / Accepted: 17 November 2015 / Published: 10 December 2015
Cited by 5 | PDF Full-text (1757 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Background: Oxidative stress may lead to overproduction of reactive species and a decrease in antioxidant defenses, resulting in chronic diseases such as diabetes and cancer. The consumption of natural compounds with an antioxidant profile may be a preventive alternative. Therefore, we aimed to
[...] Read more.
Background: Oxidative stress may lead to overproduction of reactive species and a decrease in antioxidant defenses, resulting in chronic diseases such as diabetes and cancer. The consumption of natural compounds with an antioxidant profile may be a preventive alternative. Therefore, we aimed to obtain evidence regarding the potential antioxidant activity of juices in human plasma. Methods: A systematic review and meta-analysis was performed, which included randomized controlled trials that compared the use of fruit or vegetable juices vs. placebo or other beverages. An electronic search was conducted in PubMed, Scopus, International Pharmaceutical Abstracts, and SciELO. The outcome measures extracted were related to antioxidant status, e.g., vitamin C, superoxide dismutase (SOD), and catalase (CAT) levels and reduction in malondialdehyde (MDA) and antioxidant capacity measured as TEAC. Results: Twenty-eight trials were identified (n = 1089), of which 16 were used for meta-analysis. No significant differences were observed between juices and placebo with regard to TEAC, SOD, and CAT. However, juices were superior to control in enhancing vitamin C and reducing MDA. Conclusions: Natural juices are possible candidates for the management of oxidative stress. The effects of juices should be further investigated by conducting larger and well-defined trials of longer duration. Full article
(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)
Open AccessArticle Leishmanicidal Activity of (+)-Phyllanthidine and the Phytochemical Profile of Margaritaria nobilis (Phyllanthaceae)
Molecules 2015, 20(12), 22157-22169; doi:10.3390/molecules201219829
Received: 7 October 2015 / Revised: 26 November 2015 / Accepted: 27 November 2015 / Published: 11 December 2015
Cited by 2 | PDF Full-text (3628 KB) | HTML Full-text | XML Full-text
Abstract
The effects of the Securinega alkaloid (+)-phyllanthidine on Leishmania (L.) amazonensis and the first chemical investigation of Margaritaria nobilis L.f. (Phyllanthaceae) are described. Treating the parasites with this alkaloid caused a dose-dependent reduction in promastigote growth of 67.68% (IC50 82.37 μg/mL or
[...] Read more.
The effects of the Securinega alkaloid (+)-phyllanthidine on Leishmania (L.) amazonensis and the first chemical investigation of Margaritaria nobilis L.f. (Phyllanthaceae) are described. Treating the parasites with this alkaloid caused a dose-dependent reduction in promastigote growth of 67.68% (IC50 82.37 μg/mL or 353 µM) and in amastigote growth of 83.96% (IC50 49.11 μg/mL or 210 µM), together with ultrastructural alterations in the promastigotes. No cytotoxic effect was detected in mammalian cells (CC50 1727.48 µg/mL or CC50 5268 µM). Classical chromatographic techniques and spectral methods led to the isolation and identification of betulinic acid, kaempferol, corilagin, gallic acid and its methyl ester, besides (+)-phyllanthidine from M. nobilis leaves and stems. Margaritaria nobilis is another source of the small group of Securinega alkaloids, together with other Phyllanthaceae (Euphorbiaceae s.l.) species. The low toxicity to macrophages and the effects against promastigotes and amastigotes are suggestive that (+)-phyllanthidine could be a promising antileishmanial agent for treating cutaneous leishmaniasis. Full article
Figures

Open AccessArticle Helleborus purpurascens—Amino Acid and Peptide Analysis Linked to the Chemical and Antiproliferative Properties of the Extracted Compounds
Molecules 2015, 20(12), 22170-22187; doi:10.3390/molecules201219819
Received: 1 October 2015 / Revised: 27 November 2015 / Accepted: 27 November 2015 / Published: 11 December 2015
Cited by 2 | PDF Full-text (5107 KB) | HTML Full-text | XML Full-text
Abstract
There is a strong drive worldwide to discover and exploit the therapeutic potential of a large variety of plants. In this work, an alcoholic extract of Helleborus purpurascens (family Ranunculaceae) was investigated for the identification of amino acids and peptides with putative
[...] Read more.
There is a strong drive worldwide to discover and exploit the therapeutic potential of a large variety of plants. In this work, an alcoholic extract of Helleborus purpurascens (family Ranunculaceae) was investigated for the identification of amino acids and peptides with putative antiproliferative effects. In our work, a separation strategy was developed using solvents of different polarity in order to obtain active compounds. Biochemical components were characterized through spectroscopic (mass spectroscopy) and chromatographic techniques (RP-HPLC and GC-MS). The biological activity of the obtained fractions was investigated in terms of their antiproliferative effects on HeLa cells. Through this study, we report an efficient separation of bioactive compounds (amino acids and peptides) from a plant extract dependent on solvent polarity, affording fractions with unaffected antiproliferative activities. Moreover, the two biologically tested fractions exerted a major antiproliferative effect, thereby suggesting potential anticancer therapeutic activity. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Study of the Relationships between the Structure, Lipophilicity and Biological Activity of Some Thiazolyl-carbonyl-thiosemicarbazides and Thiazolyl-azoles
Molecules 2015, 20(12), 22188-22201; doi:10.3390/molecules201219841
Received: 20 October 2015 / Revised: 20 November 2015 / Accepted: 3 December 2015 / Published: 11 December 2015
Cited by 1 | PDF Full-text (3186 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Lipophilicity, as one of the most important physicochemical parameters of bioactive molecules, was investigated for twenty-two thiazolyl-carbonyl-thiosemicarbazides and thiazolyl-azoles. The determination was carried out by reversed-phase thin-layer chromatography, using a binary isopropanol-water mobile phase. Chromatographically obtained lipophilicity parameters were correlated with calculated log
[...] Read more.
Lipophilicity, as one of the most important physicochemical parameters of bioactive molecules, was investigated for twenty-two thiazolyl-carbonyl-thiosemicarbazides and thiazolyl-azoles. The determination was carried out by reversed-phase thin-layer chromatography, using a binary isopropanol-water mobile phase. Chromatographically obtained lipophilicity parameters were correlated with calculated log P and log D and with some biological parameters, determined in order to evaluate the anti-inflammatory and antioxidant potential of the investigated compounds, by using principal component analysis (PCA). The PCA grouped the compounds based on the nature of their substituents (X, R and Y), indicating that their nature, electronic effects and molar volumes influence the lipophilicity parameters and their anti-inflammatory and antioxidant effects. Also, the results of the PCA analysis applied on all the experimental and computed parameters show that the best anti-inflammatory and antioxidant compounds were correlated with medium values of the lipophilicity parameters. On the other hand, the knowledge of the grouping patterns of the tested variables allows the reduction of the number of parameters, determined in order to establish the biological activity. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle Targeted and Untargeted Metabolomics to Explore the Bioavailability of the Secoiridoids from a Seed/Fruit Extract (Fraxinus angustifolia Vahl) in Human Healthy Volunteers: A Preliminary Study
Molecules 2015, 20(12), 22202-22219; doi:10.3390/molecules201219845
Received: 9 November 2015 / Revised: 30 November 2015 / Accepted: 4 December 2015 / Published: 11 December 2015
Cited by 2 | PDF Full-text (2969 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The bark, seeds, fruits and leaves of the genus Fraxinus (Oleaceae) which contain a wide range of phytochemicals, mostly secoiridoid glucosides, have been widely used in folk medicine against a number of ailments, yet little is known about the metabolism and uptake of
[...] Read more.
The bark, seeds, fruits and leaves of the genus Fraxinus (Oleaceae) which contain a wide range of phytochemicals, mostly secoiridoid glucosides, have been widely used in folk medicine against a number of ailments, yet little is known about the metabolism and uptake of the major Fraxinus components. The aim of this work was to advance in the knowledge on the bioavailability of the secoiridoids present in a Fraxinus angustifolia Vahl seed/fruit extract using both targeted and untargeted metabolomic analyses. Plasma and urine samples from nine healthy volunteers were taken at specific time intervals following the intake of the extract and analyzed by UPLC-ESI-QTOF. Predicted metabolites such as tyrosol and ligstroside-aglycone glucuronides and sulfates were detected at low intensity. These compounds reached peak plasma levels 2 h after the intake and exhibited high variability among the participants. The ligstroside-aglycone conjugates may be considered as potential biomarkers of the Fraxinus secoiridoids intake. Using the untargeted approach we additionally detected phenolic conjugates identified as ferulic acid and caffeic acid sulfates, as well as hydroxybenzyl and hydroxyphenylacetaldehyde sulfate derivatives which support further metabolism of the secoiridoids by phase I and (or) microbial enzymes. Overall, the results of this study suggest low uptake of intact secoiridoids from a Fraxinus angustifolia Vahl extract in healthy human volunteers and metabolic conversion by esterases, glycosidases, and phase II sulfo- and glucuronosyl transferases to form smaller conjugated derivatives. Full article
Figures

Open AccessArticle Multi-Optimization of Ultrasonic-Assisted Enzymatic Extraction of Atratylodes macrocephala Polysaccharides and Antioxidants Using Response Surface Methodology and Desirability Function Approach
Molecules 2015, 20(12), 22220-22235; doi:10.3390/molecules201219837
Received: 14 October 2015 / Revised: 30 November 2015 / Accepted: 4 December 2015 / Published: 11 December 2015
Cited by 4 | PDF Full-text (3955 KB) | HTML Full-text | XML Full-text
Abstract
Rhizoma Atractylodes macrocephala polysaccharides (RAMP) have been reported to have a variety of important biological activities. In this study, an ultrasonic-assisted enzymatic extraction (UAEE) was employed to obtain the highest extraction yield and strongest antioxidant activity of RAMP and optimized by a multi-response
[...] Read more.
Rhizoma Atractylodes macrocephala polysaccharides (RAMP) have been reported to have a variety of important biological activities. In this study, an ultrasonic-assisted enzymatic extraction (UAEE) was employed to obtain the highest extraction yield and strongest antioxidant activity of RAMP and optimized by a multi-response optimization process. A three-level four-factor Box-Behnken design (BBD) was performed as response surface methodology (RSM) with desirability function (DF) to attain the optimal extraction parameters. The DPPH scavenging percentage was used to represent the antioxidant ability of RAMP. The maximum D value (0.328), along with the maximum yield (59.92%) and DPPH scavenging percentage (13.28%) were achieved at 90.54 min, 57.99 °C, 1.95% cellulase and 225.29 W. These values were further validated and found to be in good agreement with the predicted values. Compared to the other extraction methods, both the yield and scavenging percentage of RAMP obtained by UAEE was favorable and the method appeared to be time-saving and of high efficiency. These results demostrated that UAEE is an appropriate and effective extraction technique. Moreover, RSM with DF approach has been proved to be adequate for the design and optimization of the extraction parameters for RAMP. This work has a wide range of implications for the design and operation of polysaccharide extraction processes. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Studies on the Low-Temp Oxidation of Coal Containing Organic Sulfur and the Corresponding Model Compounds
Molecules 2015, 20(12), 22241-22256; doi:10.3390/molecules201219843
Received: 19 October 2015 / Revised: 2 December 2015 / Accepted: 3 December 2015 / Published: 11 December 2015
Cited by 2 | PDF Full-text (4298 KB) | HTML Full-text | XML Full-text
Abstract
This paper selects two typical compounds containing organic sulfur as model compounds. Then, by analyzing the chromatograms of gaseous low-temp oxidation products and GC/MS of the extractable matter of the oxidation residue, we summarizing the mechanism of low-temp sulfur model compound oxidation. The
[...] Read more.
This paper selects two typical compounds containing organic sulfur as model compounds. Then, by analyzing the chromatograms of gaseous low-temp oxidation products and GC/MS of the extractable matter of the oxidation residue, we summarizing the mechanism of low-temp sulfur model compound oxidation. The results show that between 30 °C to 80 °C, the interaction between diphenyl sulfide and oxygen is mainly one of physical adsorption. After 80 °C, chemical adsorption and chemical reactions begin. The main reaction mechanism in the low-temp oxidation of the model compound diphenyl sulfide is diphenyl sulfide generates diphenyl sulfoxide, and then this sulfoxide is further oxidized to diphenyl sulphone. A small amount of free radicals is generated in the process. The model compound cysteine behaves differently from diphenyl sulfide. The main reaction low-temp oxidation mechanism involves the thiol being oxidized into a disulphide and finally evolving to sulfonic acid, along with SO2 being released at 130 °C and also a small amount of free radicals. We also conducted an experiment on coal from Xingcheng using X-ray photoelectron spectroscopy (XPS). The results show that the major forms of organic sulfur in the original coal sample are thiophene and sulfone. Therefore, it can be inferred that there is none or little mercaptan and thiophenol in the original coal. After low-temp oxidation, the form of organic sulfur changes. The sulfide sulfur is oxidized to the sulfoxide, and then the sulfoxide is further oxidized to a sulfone, and these steps can be easily carried out under experimental conditions. What’s more, the results illustrate that oxidation promotes sulfur element enrichment on the surface of coal. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle In Vivo and In Vitro Toxicity Evaluation of Polyprenols Extracted from Ginkgo biloba L. Leaves
Molecules 2015, 20(12), 22257-22271; doi:10.3390/molecules201219839
Received: 14 September 2015 / Revised: 27 November 2015 / Accepted: 7 December 2015 / Published: 11 December 2015
Cited by 4 | PDF Full-text (2147 KB) | HTML Full-text | XML Full-text
Abstract
Polyprenols of Ginkgo biloba L. leaves (GBP) are a new type of lipid with 14–24 isoprenyl units, which in humans have strong bioactivity like the dolichols. A large amount of work showed that GBP had good antibacterial activity and powerful protective effects against
[...] Read more.
Polyprenols of Ginkgo biloba L. leaves (GBP) are a new type of lipid with 14–24 isoprenyl units, which in humans have strong bioactivity like the dolichols. A large amount of work showed that GBP had good antibacterial activity and powerful protective effects against acute hepatic injury induced by carbon tetrachloride and alcohol, as well as antitumor activity, but the safety of GBP was not considered. The current study was designed to evaluate the toxicity of these polyprenols. Acute toxicity in mice was observed for 14 days after GBP oral dosing with 5, 7.5, 10, 15 and 21.5 g/kg body weight (b. wt.) Further, an Ames toxicity assessment was carried out by plate incorporation assay on spontaneous revertant colonies of TA97, TA98, TA100 and TA102, with GBP doses designed as 8, 40, 200, 1000 and 5000 μg/dish, and subchronic toxicity was evaluated in rats for 91 days at GBP doses of 500, 1000 and 2000 mg/kg b. wt./day. The weight, food intake, hematological and biochemical indexes, the ratio of viscera/body weight, and histopathological examinations of tissue slices of organs were all investigated. The results showed that no animal behavior and appearance changes and mortality were seen during the observation period with 21.5 g/kg GBP dose in the acute toxicity test. Also, no mutagenicity effects were produced by GBP (mutation rate < 2) on the four standard Salmonella strains (p > 0.05) in the Ames toxicity test. Furthermore, the no observed adverse effect level (NOAEL) of GBP was 2000 mg/kg for 91 days feeding of rats in the subchronic toxicity tests. Results also showed the hematological and biochemical indexes as well as histopathological examination changed within a small range, and all clinical observation indexes were normal. No other distinct impacts on cumulative growth of body weight, food intake and food utilization rate were discovered with GBP. No significant difference was discovered for the rats’ organ weight and the ratio of viscera to body weight (p > 0.05). Reversible pathological changes in the histopathological examinations of tissue slices of organs were not observed. GBP could therefore be considered as a safe material with minor side effects. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle Asymmetric Synthesis and Absolute Configuration Assignment of a New Type of Bedaquiline Analogue
Molecules 2015, 20(12), 22272-22285; doi:10.3390/molecules201219846
Received: 3 November 2015 / Revised: 4 December 2015 / Accepted: 7 December 2015 / Published: 11 December 2015
Cited by 4 | PDF Full-text (2003 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Bedaquiline is the first FDA-approved new chemical entity to fight multidrug-resistant tuberculosis in the last forty years. Our group replaced the quinoline ring with a naphthalene ring, leading to a new type of triarylbutanol skeleton. An asymmetric synthetic route was established for our
[...] Read more.
Bedaquiline is the first FDA-approved new chemical entity to fight multidrug-resistant tuberculosis in the last forty years. Our group replaced the quinoline ring with a naphthalene ring, leading to a new type of triarylbutanol skeleton. An asymmetric synthetic route was established for our bedaquiline analogues, and the goal of assigning their absolute configurations was achieved by comparison of experimental and calculated electronic circular dichroism spectra, and was confirmed by the combined use of circular dichroism and NMR spectroscopy. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle Potent PPARγ Ligands from Swietenia macrophylla Are Capable of Stimulating Glucose Uptake in Muscle Cells
Molecules 2015, 20(12), 22301-22314; doi:10.3390/molecules201219847
Received: 22 October 2015 / Revised: 27 November 2015 / Accepted: 1 December 2015 / Published: 12 December 2015
Cited by 4 | PDF Full-text (3982 KB) | HTML Full-text | XML Full-text
Abstract
Numerous documented ethnopharmacological properties have been associated with Swietenia macrophylla (Meliaceae), with its seed extract reported to display anti-hypoglycemic activities in diabetic rats. In the present study, three compounds isolated from the seeds of S. macrophylla were tested on a modified ELISA binding
[...] Read more.
Numerous documented ethnopharmacological properties have been associated with Swietenia macrophylla (Meliaceae), with its seed extract reported to display anti-hypoglycemic activities in diabetic rats. In the present study, three compounds isolated from the seeds of S. macrophylla were tested on a modified ELISA binding assay and showed to possess PPARγ ligand activity. They were corresponded to PPARγ-mediated cellular response, stimulated adipocyte differentiation but produced lower amount of fat droplets compared to a conventional anti-diabetic agent, rosiglitazone. The up-regulation of adipocytes was followed by increased adipocyte-related gene expressions such as adiponectin, adipsin, and PPARγ. The S. macrophylla compounds also promoted cellular glucose uptake via the translocation of GLUT4 glucose transporter. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Mechanism of Breast Cancer Preventive Action of Pomegranate: Disruption of Estrogen Receptor and Wnt/β-Catenin Signaling Pathways
Molecules 2015, 20(12), 22315-22328; doi:10.3390/molecules201219853
Received: 10 November 2015 / Revised: 2 December 2015 / Accepted: 8 December 2015 / Published: 12 December 2015
Cited by 8 | PDF Full-text (7773 KB) | HTML Full-text | XML Full-text
Abstract
A pomegranate emulsion (PE), containing various bioactive phytochemicals, has recently been found to exert substantial chemopreventive effect against 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumorigenesis in rats via antiproliferative and proapoptotic actions. Nevertheless, the underlying mechanisms of action are not completely understood. The present
[...] Read more.
A pomegranate emulsion (PE), containing various bioactive phytochemicals, has recently been found to exert substantial chemopreventive effect against 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumorigenesis in rats via antiproliferative and proapoptotic actions. Nevertheless, the underlying mechanisms of action are not completely understood. The present study was designed to investigate the effects of PE treatment on intratumor expression of estrogen receptor (ER)-α, ER-β,β-catenin and cyclin D1 during DMBA rat mammary carcinogenesis. Mammary tumor sections were harvested from a chemopreventive study in which PE (0.2, 1.0 and 5.0 g/kg) exhibited inhibition of mammary tumorigenesis in a dose-response manner. The expressions of ER-α, ER-β, β-catenin and cyclin D1 were analyzed by immunohistochemical techniques. PE downregulated the expression of intratumor ER-α and ER-β and lowered ER-α:ER-β ratio. PE also decreased the expression, cytoplasmic accumulation, and nuclear translocation of β-catenin, an essential transcriptional cofactor for Wnt signaling. Moreover, PE suppressed the expression of cell growth regulatory protein cyclin D1, which is a downstream target for both ER and Wnt signaling. Our current results in conjunction with our previous findings indicate that concurrent disruption of ER and Wnt/β-catenin signaling pathways possibly contributes to antiproliferative and proapoptotic effects involved in PE-mediated chemoprevention of DMBA-inflicted rat mammary tumorigenesis. Full article
(This article belongs to the collection Herbal Medicine Research)
Figures

Open AccessArticle Contents Changes of Triterpenic Acids, Nucleosides, Nucleobases, and Saccharides in Jujube (Ziziphus jujuba) Fruit During the Drying and Steaming Process
Molecules 2015, 20(12), 22329-22340; doi:10.3390/molecules201219852
Received: 8 October 2015 / Revised: 23 November 2015 / Accepted: 24 November 2015 / Published: 12 December 2015
Cited by 2 | PDF Full-text (679 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chinese jujube (Ziziphus jujuba), a medicinal and edible plant, is widely consumed in Asian countries owing to the remarkable health activities of its fruits. To facilitate selection of the suitable processing method for jujube fruits, in this study their contents of
[...] Read more.
Chinese jujube (Ziziphus jujuba), a medicinal and edible plant, is widely consumed in Asian countries owing to the remarkable health activities of its fruits. To facilitate selection of the suitable processing method for jujube fruits, in this study their contents of triterpenic acids, nucleosides, nucleobases and saccharides after drying and steaming treatment were determined using ultra-high performance liquid chromatography and high performance liquid chromatography coupled with evaporative light scattering detector methods. The results showed that except for sucrose, the content levels of most analytes were increasing in the jujube fruits during drying treatment at 45 °C. The levels of cyclic nucleotides such as adenosine 3′,5′-cyclic monophosphate and guanosine 3′,5′-cyclic monophosphate, were significantly decreased after the fruits were steamed. Therefore, owing to the bioactivities of these components for human health, the dried fruits would be the better choice as medicinal material or functional food, and dried jujube fruit should not be further steamed. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Protective Effects of Red Guava on Inflammation and Oxidative Stress in Streptozotocin-Induced Diabetic Mice
Molecules 2015, 20(12), 22341-22350; doi:10.3390/molecules201219831
Received: 13 November 2015 / Revised: 2 December 2015 / Accepted: 3 December 2015 / Published: 12 December 2015
Cited by 2 | PDF Full-text (1281 KB) | HTML Full-text | XML Full-text
Abstract
Diabetes is an important chronic disease and the 4th leading cause of death in Taiwan. Hyperglycemia-induced oxidative and inflammatory damage are the main causes of chronic complications in diabetic patients. The red guava (red-fleshed guava cultivar of Psidium guajava L.) is a tropical
[...] Read more.
Diabetes is an important chronic disease and the 4th leading cause of death in Taiwan. Hyperglycemia-induced oxidative and inflammatory damage are the main causes of chronic complications in diabetic patients. The red guava (red-fleshed guava cultivar of Psidium guajava L.) is a tropical fruit belonging to the Myrtaceae family and an important commercial crop in Taiwan. In this study, the protective effects of a diet containing red guava on inflammation and oxidative stress in streptozotocin (STZ)-induced diabetic mice were examined. The experimental group was divided into seven subgroups: normal (N), diabetes mellitus (DM), diabetes + red guava 1% (L), 2% (M), and 5% (H), diabetes + 5% red guava + anti-diabetic rosiglitazone (HR), and diabetes + anti-diabetic rosiglitazone (R). The mice were fed for 8 weeks and sacrificed by decapitation. Compared with the DM group, the experimental groups with diets containing red guava as well as rosiglitazone all showed significant improvements in blood glucose control, insulin resistance, creatinine, blood urea nitrogen, triglycerides, non-esterified fatty acids, cholesterol, c-reactive protein, TNF-α, and IL-10. Furthermore, the expression of inflammatory proteins, such as iNOS and NF-κB, was suppressed via activated PPARγ, and the expression levels of GPx3 and ACO increased. In summary, red guava can significantly suppress inflammatory and oxidative damage caused by diabetes and alleviate diabetic symptoms; thus, it exerts protective effects and has potential applications for the development of a dietary supplement. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of New 2-Halo-2-(1H-tetrazol-5-yl)-2H-azirines via a Non-Classical Wittig Reaction
Molecules 2015, 20(12), 22351-22363; doi:10.3390/molecules201219848
Received: 30 October 2015 / Revised: 30 November 2015 / Accepted: 8 December 2015 / Published: 12 December 2015
Cited by 6 | PDF Full-text (2315 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The synthesis and reactivity of tetrazol-5-yl-phosphorus ylides towards N-halosuccinimide/TMSN3 reagent systems was explored, opening the way to new haloazidoalkenes bearing a tetrazol-5-yl substituent. These compounds were obtained as single isomers, except in one case. X-ray crystal structures were determined for three
[...] Read more.
The synthesis and reactivity of tetrazol-5-yl-phosphorus ylides towards N-halosuccinimide/TMSN3 reagent systems was explored, opening the way to new haloazidoalkenes bearing a tetrazol-5-yl substituent. These compounds were obtained as single isomers, except in one case. X-ray crystal structures were determined for three derivatives, establishing that the non-classical Wittig reaction leads to the selective synthesis of haloazidoalkenes with (Z)-configuration. The thermolysis of the haloazidoalkenes afforded new 2-halo-2-(tetrazol-5-yl)-2H-azirines in high yields. Thus, the reported synthetic methodologies gave access to important building blocks in organic synthesis, vinyl tetrazoles and 2-halo-2-(tetrazol-5-yl)-2H-azirine derivatives. Full article
(This article belongs to the Special Issue Organic Azides)
Figures

Open AccessArticle Role of Polymeric Excipients in the Stabilization of Olanzapine when Exposed to Aqueous Environments
Molecules 2015, 20(12), 22364-22382; doi:10.3390/molecules201219832
Received: 5 October 2015 / Revised: 25 November 2015 / Accepted: 2 December 2015 / Published: 12 December 2015
Cited by 2 | PDF Full-text (7011 KB) | HTML Full-text | XML Full-text
Abstract
Hydrate formation is a phase transition which can occur during manufacturing processes involving water. This work considers the prevention of hydration of anhydrous olanzapine and hydrate conversions in the presence of water and polymers (polyethyleneglycol; hydroxypropylcellulose; polyvinylpyrrolidone) in forming pellets by wet extrusion
[...] Read more.
Hydrate formation is a phase transition which can occur during manufacturing processes involving water. This work considers the prevention of hydration of anhydrous olanzapine and hydrate conversions in the presence of water and polymers (polyethyleneglycol; hydroxypropylcellulose; polyvinylpyrrolidone) in forming pellets by wet extrusion and spheronisation. Anhydrous olanzapine was added to water with or without those polymers prior to extrusion with microcrystalline cellulose. Assessment of olanzapine conversion was made by XRP-Diffraction; FTIR spectroscopy; calorimetry (DSC) and microscopy (SEM for crystal size and shape). The addition of water converted the anhydrous form into dihydrate B and higher hydrate; whereas polyethyleneglycol promoted a selective hydrate conversion into the higher hydrate olanzapine form. Both polyvinylpyrrolidone and hydroxypropylcellulose prevented the hydrate transformations of the anhydrous drug; the latter even in the presence of hydrate seeds. This may be explained by the higher H-bond ability; higher network association and higher hydrophobicity of hydroxypropylcellulose by comparison with polyethyleneglycol and polyvinylpyrrolidone; which could contribute to its higher affinity to the crystal surfaces of the hydrate nuclei/initial crystals and promoting steric hindrance to the incorporation of other drug molecules into the crystal lattice; thus, preventing the crystal growth. The addition of microcrystalline cellulose needed for the pellets production (final product) did not eliminate the protector effect of both hydroxypropylcellulose and polyvinylpyrrolidone during pellets’ processing and dissolution evaluation. Full article
(This article belongs to the collection Poorly Soluble Drugs)
Figures

Open AccessArticle Retinoprotective Effects of Bilberry Anthocyanins via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms in a Visible Light-Induced Retinal Degeneration Model in Pigmented Rabbits
Molecules 2015, 20(12), 22395-22410; doi:10.3390/molecules201219785
Received: 6 September 2015 / Revised: 27 October 2015 / Accepted: 11 November 2015 / Published: 14 December 2015
Cited by 5 | PDF Full-text (4068 KB) | HTML Full-text | XML Full-text
Abstract
Excessive visible light exposure can induce damage to retinal cells and contribute to the development or progression of age-related macular degeneration. In this study we created a model of phototoxicity in pigmented rabbits. Furthermore, we investigated the protective effect of bilberry anthocyanin extract
[...] Read more.
Excessive visible light exposure can induce damage to retinal cells and contribute to the development or progression of age-related macular degeneration. In this study we created a model of phototoxicity in pigmented rabbits. Furthermore, we investigated the protective effect of bilberry anthocyanin extract (BAE, Table A1) and explored the possible mechanisms of action in this model. The model of light-induced retinal damage was established by the pigmented rabbits exposed to light at 18,000 lx for 2 h, and they were sacrificed on day 7. After administration of BAE at dosages of 250 and 500 mg/kg/day, retinal dysfunction was significantly inhibited in terms of electroretinograms, and the decreased thicknesses of retinal outer nuclear layer and lengths of the outer segments of the photoreceptor cells were suppressed in rabbits with retinal degeneration. BAE attenuated the changes caused by light to certain apoptotic proteins (Bax, Bcl-2, and caspase-3). The extract increased the levels of superoxide dismutase, glutathione peroxidase, and catalase, as well as the total antioxidant capacity, but decreased the malondialdehyde level in the retinal cells. BAE inhibited the light-induced elevation in the levels of proinflammatory cytokines and angiogenic parameters (IL-1β and VEGF). Results showed that visible light-induced retinal degeneration model in pigmented rabbits was successfully established and BAE exhibited protective effects by increasing the antioxidant defense mechanisms, suppressing lipid peroxidation and proinflammatory cytokines, and inhibiting retinal cells apoptosis. Full article
(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)
Figures

Open AccessArticle A Comprehensive Study of the Use of Cu(I)/4,4’-Dicarboxy-2,2’-biquinoline Complexes to Measure the Total Reducing Capacity: Application in Herbal Extracts
Molecules 2015, 20(12), 22411-22421; doi:10.3390/molecules201219855
Received: 26 September 2015 / Revised: 20 November 2015 / Accepted: 8 December 2015 / Published: 14 December 2015
PDF Full-text (1613 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A method for the determination of total reducing capacity (TRC) based on the reduction of Cu(II) to Cu(I) by antioxidants in a buffered solution (pH 7.0) containing 4,4′-dicarboxy-2,2′-biquinoline acid (BCA) was developed. Absorbance values at 558 nm characteristic of the Cu(I)/BCA complexes formed
[...] Read more.
A method for the determination of total reducing capacity (TRC) based on the reduction of Cu(II) to Cu(I) by antioxidants in a buffered solution (pH 7.0) containing 4,4′-dicarboxy-2,2′-biquinoline acid (BCA) was developed. Absorbance values at 558 nm characteristic of the Cu(I)/BCA complexes formed were used to determine the TRC of aqueous extracts of twelve Brazilian plants. The TRC values obtained with the suggested method correlated well with values obtained using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method (r2 = 0.959). They were also compared with the total polyphenol content (using the Folin-Ciocalteu reagent) and the good agreement (r2 = 0.919) indicates that the polyphenols should be responsible for this reducing capacity. The method proposed here (and successfully applied in plant extracts) can be used to measure the TRC of aqueous samples derived from other plants (e.g., teas, juices, beers and wines) and even in biological samples (e.g., serum, urine and follicular fluid). To achieve a structure-activity relationship of the proposed reaction, the reduction capability of 25 standard antioxidants (phenolic derivatives, flavonoids, stilbenoids, vitamins, etc.) was individually evaluated and the apparent molar absorptivity values (at 558 nm) obtained were compared and discussed. Full article
(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)
Figures

Open AccessArticle Use of Modified Phenolic Thyme Extracts (Thymus vulgaris) with Reduced Polyphenol Oxidase Substrates as Anthocyanin Color and Stability Enhancing Agents
Molecules 2015, 20(12), 22422-22434; doi:10.3390/molecules201219854
Received: 16 October 2015 / Revised: 6 November 2015 / Accepted: 18 November 2015 / Published: 14 December 2015
Cited by 4 | PDF Full-text (1167 KB) | HTML Full-text | XML Full-text
Abstract
Residual enzymatic activity in certain foods, particularly of polyphenoloxidase (PPO), is responsible for the majority of anthocyanin degradation in food systems, causing also parallel losses of other relevant nutrients. The present work explored the feasibility of modifying phenolic profiles of thyme extracts, by
[...] Read more.
Residual enzymatic activity in certain foods, particularly of polyphenoloxidase (PPO), is responsible for the majority of anthocyanin degradation in food systems, causing also parallel losses of other relevant nutrients. The present work explored the feasibility of modifying phenolic profiles of thyme extracts, by use of chromatographic resins, to obtain phenolic extracts capable of enhancing anthocyanin colour and stability in the presence of PPO activity. Results indicated that pretreatment of thyme extracts with strong-anion exchange resins (SAE) enhanced their copigmentation abilities with strawberry juice anthocyanins. Phenolic chromatographic profiles, by HPLC-PDA, also demonstrated that thyme extracts subjected to SAE treatments had significantly lower concentrations of certain phenolic compounds, but extracts retained their colour enhancing and anthocyanin stabilization capacities though copigmentation. Additional testing also indicated that SAE modified extract had a lower ability (73% decrease) to serve as PPO substrate, when compared to the unmodified extract. Phenolic profile modification process, reported herein, could be potentially used to manufacture modified anthocyanin-copigmentation food and cosmetic additives for colour-stabilizing applications with lower secondary degradation reactions in matrixes that contain PPO activity. Full article
(This article belongs to the Special Issue Recent Advances in Plant Phenolics)
Open AccessArticle The Antileishmanial Potential of C-3 Functionalized Isobenzofuranones against Leishmania (Leishmania) Infantum Chagasi
Molecules 2015, 20(12), 22435-22444; doi:10.3390/molecules201219857
Received: 5 November 2015 / Revised: 3 December 2015 / Accepted: 8 December 2015 / Published: 14 December 2015
PDF Full-text (2319 KB) | HTML Full-text | XML Full-text
Abstract
Leishmaniases are diseases caused by protozoan parasites of the genus Leishmania. Clinically, leishmaniases range from cutaneous to visceral forms, with estimated global incidences of 1.2 and 0.4 million cases per year, respectively. The treatment of these diseases relies on multiple parenteral injections
[...] Read more.
Leishmaniases are diseases caused by protozoan parasites of the genus Leishmania. Clinically, leishmaniases range from cutaneous to visceral forms, with estimated global incidences of 1.2 and 0.4 million cases per year, respectively. The treatment of these diseases relies on multiple parenteral injections with pentavalent antimonials or amphotericin B. However, these pharmaceuticals are either too toxic or expensive for routine use in developing countries. These facts call for safer, cheaper, and more effective new antileishmanial drugs. In this investigation, we describe the results of the assessment of the activities of a series of isobenzofuran-1(3H)-ones (phtalides) against Leishmania (Leishmania) infantum chagasi, which is the main causative agent of visceral leishmaniasis in the New World. The compounds were tested at concentrations of 100, 75, 50, 25 and 6.25 µM over 24, 48, and 72 h. After 48 h of treatment at the 100 µM concentration, compounds 7 and 8 decreased parasite viability to 4% and 6%, respectively. The concentration that gives half-maximal responses (LC50) for the antileishmanial activities of compounds 7 and 8 against promastigotes after 24 h were 60.48 and 65.93 µM, respectively. Additionally, compounds 7 and 8 significantly reduced parasite infection in macrophages. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle New Ent-Kaurane-Type Diterpene Glycosides and Benzophenone from Ranunculus muricatus Linn.
Molecules 2015, 20(12), 22445-22453; doi:10.3390/molecules201219801
Received: 21 October 2015 / Revised: 16 November 2015 / Accepted: 21 November 2015 / Published: 15 December 2015
Cited by 2 | PDF Full-text (1186 KB) | HTML Full-text | XML Full-text
Abstract
Two new ent-kaurane diterpene glycosides, ranunculosides A (1) and B (2), and a new benzophenone, ranunculone C (3), were isolated from the aerial part of Ranunculus muricatus Linn. The chemical structures of compounds 13
[...] Read more.
Two new ent-kaurane diterpene glycosides, ranunculosides A (1) and B (2), and a new benzophenone, ranunculone C (3), were isolated from the aerial part of Ranunculus muricatus Linn. The chemical structures of compounds 13 were established to be (2S)-ent-kauran-2β-ol-15-en-14-O-β-d-glucopyranoside, (2S,4S)-ent-kauran-2β,18-diol-15-en-14-O-β-d-glucopyranoside, and (R)-3-[2-(3,4-dihydroxybenzoyl)-4,5-dihydroxy-phenyl]-2-hydroxylpropanoic acid, respectively, by spectroscopic data and chemical methods. The absolute configuration of 1 was determined by the combinational application of RP-HPLC analysis and Mosher’s method. Full article
(This article belongs to the Section Molecular Diversity)
Figures

Open AccessArticle Authentication of Cordyceps sinensis by DNA Analyses: Comparison of ITS Sequence Analysis and RAPD-Derived Molecular Markers
Molecules 2015, 20(12), 22454-22462; doi:10.3390/molecules201219861
Received: 27 November 2015 / Revised: 8 December 2015 / Accepted: 10 December 2015 / Published: 15 December 2015
Cited by 6 | PDF Full-text (2963 KB) | HTML Full-text | XML Full-text
Abstract
Cordyceps sinensis is an endoparasitic fungus widely used as a tonic and medicinal food in the practice of traditional Chinese medicine (TCM). In historical usage, Cordyceps specifically is referring to the species of C. sinensis. However, a number of closely related species
[...] Read more.
Cordyceps sinensis is an endoparasitic fungus widely used as a tonic and medicinal food in the practice of traditional Chinese medicine (TCM). In historical usage, Cordyceps specifically is referring to the species of C. sinensis. However, a number of closely related species are named themselves as Cordyceps, and they are sold commonly as C. sinensis. The substitutes and adulterants of C. sinensis are often introduced either intentionally or accidentally in the herbal market, which seriously affects the therapeutic effects or even leads to life-threatening poisoning. Here, we aim to identify Cordyceps by DNA sequencing technology. Two different DNA-based approaches were compared. The internal transcribed spacer (ITS) sequences and the random amplified polymorphic DNA (RAPD)-sequence characterized amplified region (SCAR) were developed here to authenticate different species of Cordyceps. Both approaches generally enabled discrimination of C. sinensis from others. The application of the two methods, supporting each other, increases the security of identification. For better reproducibility and faster analysis, the SCAR markers derived from the RAPD results provide a new method for quick authentication of Cordyceps. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Phenolic Profiling of Duchesnea indica Combining Macroporous Resin Chromatography (MRC) with HPLC-ESI-MS/MS and ESI-IT-MS
Molecules 2015, 20(12), 22463-22475; doi:10.3390/molecules201219859
Received: 14 October 2015 / Revised: 20 November 2015 / Accepted: 10 December 2015 / Published: 15 December 2015
Cited by 4 | PDF Full-text (775 KB) | HTML Full-text | XML Full-text
Abstract
Duchesnea indica (D. indica) is an important traditional Chinese medicine, and has long been clinically used to treat cancer in Asian countries. It has been described previously as a rich source of phenolic compounds with a broad array of diversified structures,
[...] Read more.
Duchesnea indica (D. indica) is an important traditional Chinese medicine, and has long been clinically used to treat cancer in Asian countries. It has been described previously as a rich source of phenolic compounds with a broad array of diversified structures, which are the major active ingredients. However, an accurate and complete phenolic profiling has not been determined yet. In the present work, the total phenolic compounds in crude extracts from D. indica were enriched and fractionated over a macroporous resin column, then identified by HPLC-ESI-MS/MS and ESI-IT-MS (ion trap MS). A total of 27 phenolic compounds were identified in D. indica, of which 21 compounds were identified for the first time. These 27 phenolic compounds encompassing four phenolic groups, including ellagitannins, ellagic acid and ellagic acid glycosides, hydroxybenzoic acid and hydroxycinnamic acid derivatives, and flavonols, were then successfully quantified using peak areas against those of the corresponding standards with good linearity (R2 > 0.998) in the range of the tested concentrations. As a result, the contents of individual phenolic compounds varied from 6.69 mg per 100 g dry weight (DW) for ellagic acid to 71.36 mg per 100 g DW for brevifolin carboxylate. Not only did this study provide the first phenolic profiling of D. indica, but both the qualitative identification and the subsequent quantitative analysis of 27 phenolic compounds from D. indica should provide a good basis for future exploration of this valuable medicinal plant. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Green Chemistry Approach for Synthesis of Effective Anticancer Palladium Nanoparticles
Molecules 2015, 20(12), 22476-22498; doi:10.3390/molecules201219860
Received: 26 November 2015 / Revised: 9 December 2015 / Accepted: 10 December 2015 / Published: 15 December 2015
Cited by 12 | PDF Full-text (5589 KB) | HTML Full-text | XML Full-text
Abstract
The purpose of this study was to design and synthesize Palladium nanoparticles (PdNPs) using an environmentally friendly approach and evaluate the in vitro efficacy of PdNPs in human ovarian cancer A2780 cells. Ultraviolet-Visible (UV-Vis) spectroscopy was used to monitor the conversion of Pd(II)
[...] Read more.
The purpose of this study was to design and synthesize Palladium nanoparticles (PdNPs) using an environmentally friendly approach and evaluate the in vitro efficacy of PdNPs in human ovarian cancer A2780 cells. Ultraviolet-Visible (UV-Vis) spectroscopy was used to monitor the conversion of Pd(II) ions to Pd(0)NPs. X-ray diffraction (XRD) revealed the crystallinity of the as-synthesized PdNPs and Fourier transform infrared spectroscopy (FTIR) further confirmed the role of the leaf extract of Evolvulus alsinoides as a reducing and stabilizing agent for the synthesis of PdNPs. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) showed that the average size of the NPs was 5 nm. After a 24-h exposure to PdNPs, cell viability and light microscopy assays revealed the dose-dependent toxicity of the PdNPs. Furthermore, the dose-dependent cytotoxicity of the PdNPs was confirmed by lactate dehydrogenase (LDH), increased reactive oxygen species (ROS) generation, activation of PdNPs-induced autophagy, impairment of mitochondrial membrane potential (MMP), enhanced caspase-3 activity, and detection of TUNEL-positive cells. Our study demonstrates a single, simple, dependable and green approach for the synthesis of PdNPs using leaf extracts of Evolvulus alsinoides. Furthermore, the in vitro efficacy of PdNPs in human ovarian cancer cells suggests that it could be an effective therapeutic agent for cancer therapy. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)
Open AccessArticle Syntheses of 4-Indolylquinoline Derivatives via Reductive Cyclization of Indolylnitrochalcone Derivatives by Fe/HCl
Molecules 2015, 20(12), 22499-22519; doi:10.3390/molecules201219862
Received: 23 November 2015 / Revised: 7 December 2015 / Accepted: 8 December 2015 / Published: 15 December 2015
PDF Full-text (17734 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An easy and efficient procedure for the synthesis of 4-indolylquinoline derivatives is described. This process involves two steps, the first of which is the Michael addition of indole to nitrochalcones promoted by sulfamic acid under solvent free conditions and the second step is
[...] Read more.
An easy and efficient procedure for the synthesis of 4-indolylquinoline derivatives is described. This process involves two steps, the first of which is the Michael addition of indole to nitrochalcones promoted by sulfamic acid under solvent free conditions and the second step is a reductive cyclization of the indolylnitrochalcone intermediates to 4-indolylquinoline derivatives by Fe/HCl in ethanol. In both steps, the reactions are clean and the yields of products are high. Full article
(This article belongs to the collection Heterocyclic Compounds)
Open AccessArticle Novel Polycarbo-Substituted Imidazo[1,2-c]quinazolines: Synthesis and Cytotoxicity Study
Molecules 2015, 20(12), 22520-22533; doi:10.3390/molecules201219863
Received: 9 November 2015 / Revised: 30 November 2015 / Accepted: 1 December 2015 / Published: 15 December 2015
Cited by 2 | PDF Full-text (1226 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Amination of the 2-aryl-6-bromo-4-chloro-8-iodoquinazolines with 2-aminoethanol followed by acid-promoted cyclodehydration of the incipient 2-((6,8-dihalo-2-phenylquinazolin-4-yl)amino)ethanols afforded the corresponding novel 5-aryl-9-bromo-7-iodo-2,3-dihydro-2H-imidazo[1,2-c]quinazolines. The latter were, in turn, subjected to sequential (Sonogashira and Suzuki-Miyaura) and one-pot two-step (Sonogashira/Stille) cross-coupling reactions to afford diversely
[...] Read more.
Amination of the 2-aryl-6-bromo-4-chloro-8-iodoquinazolines with 2-aminoethanol followed by acid-promoted cyclodehydration of the incipient 2-((6,8-dihalo-2-phenylquinazolin-4-yl)amino)ethanols afforded the corresponding novel 5-aryl-9-bromo-7-iodo-2,3-dihydro-2H-imidazo[1,2-c]quinazolines. The latter were, in turn, subjected to sequential (Sonogashira and Suzuki-Miyaura) and one-pot two-step (Sonogashira/Stille) cross-coupling reactions to afford diversely functionalized polycarbo-substituted 2H-imidazo[1,2-c]quinazolines. The imidazoquinazolines were screened for in vitro cytotoxicity against human breast adenocarcinoma (MCF-7) cells and human cervical cancer (HeLa) cells. Full article
(This article belongs to the Section Bioorganic Chemistry)
Figures

Open AccessArticle A Nanostructured Lipid System as a Strategy to Improve the in Vitro Antibacterial Activity of Copper(II) Complexes
Molecules 2015, 20(12), 22534-22545; doi:10.3390/molecules201219822
Received: 30 October 2015 / Revised: 23 November 2015 / Accepted: 24 November 2015 / Published: 16 December 2015
Cited by 5 | PDF Full-text (1097 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to construct a nanostructured lipid system as a strategy to improve the in vitro antibacterial activity of copper(II) complexes. New compounds with the general formulae [CuX2(INH)2]·nH2O (X = Cl and
[...] Read more.
The aim of this study was to construct a nanostructured lipid system as a strategy to improve the in vitro antibacterial activity of copper(II) complexes. New compounds with the general formulae [CuX2(INH)2]·nH2O (X = Cl and n = 1 (1); X = NCS and n = 5 (2); X = NCO and n = 4 (3); INH = isoniazid, a drug widely used to treat tuberculosis) derived from the reaction between the copper(II) chloride and isoniazid in the presence or absence of pseudohalide ions (NCS or NCO) were synthesized and characterized by infrared spectrometry, electronic absorption spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, elemental analysis, melting points and complexometry with 2,2′,2′′,2′′′-(Ethane-1,2-diyldinitrilo)tetraacetic acid (EDTA). The characterization techniques allowed us to confirm the formation of the copper(II) complexes. The Cu(II) complexes were loaded into microemulsion (MEs) composed of 10% phase oil (cholesterol), 10% surfactant [soy oleate and Brij® 58 (1:2)] and 80% aqueous phase (phosphate buffer pH = 7.4) prepared by sonication. The Cu(II) complex-loaded MEs displayed sizes ranging from 158.0 ± 1.060 to 212.6 ± 1.539 nm, whereas the polydispersity index (PDI) ranged from 0.218 ± 0.007 to 0.284 ± 0.034. The antibacterial activity of the free compounds and those that were loaded into the MEs against Staphylococcus aureus ATCC® 25923 and Escherichia coli ATCC® 25922, as evaluated by a microdilution technique, and the cytotoxicity index (IC50) against the Vero cell line (ATCC® CCL-81TM) were used to calculate the selectivity index (SI). Among the free compounds, only compound 2 (MIC 500 μg/mL) showed activity for S. aureus. After loading the compounds into the MEs, the antibacterial activity of compounds 1, 2 and 3 was significantly increased against E. coli (MIC’s 125, 125 and 500 μg/mL, respectively) and S. aureus (MICs 250, 500 and 125 μg/mL, respectively). The loaded compounds were less toxic against the Vero cell line, especially compound 1 (IC50 from 109.5 to 319.3 μg/mL). The compound 2- and 3-loaded MEs displayed the best SI for E. coli and S. aureus, respectively. These results indicated that the Cu(II) complex-loaded MEs were considerably more selective than the free compounds, in some cases, up to 40 times higher. Full article
Figures

Open AccessCommunication Antiproliferative Activities of Water Infusions from Leaves of Five Cornus L. Species
Molecules 2015, 20(12), 22546-22552; doi:10.3390/molecules201219786
Received: 27 October 2015 / Revised: 20 November 2015 / Accepted: 24 November 2015 / Published: 16 December 2015
Cited by 4 | PDF Full-text (394 KB) | HTML Full-text | XML Full-text
Abstract
Cornaceae plants are known for their edible berries, and their leaves are used as tea. In the present study aqueous leaf extracts from Cornus mas (CM), C. alba (CA), C. flaviramea (CF), C. kousa (CK), and C. officinalis (CO) were tested for their
[...] Read more.
Cornaceae plants are known for their edible berries, and their leaves are used as tea. In the present study aqueous leaf extracts from Cornus mas (CM), C. alba (CA), C. flaviramea (CF), C. kousa (CK), and C. officinalis (CO) were tested for their antiproliferative activity in human breast cancer cells (MCF-7). Dose- (50–750 µg/mL) and time (24, 48, 72 h)-dependent antiproliferative effects were measured by WST-1, and correlated with the content of flavonoids (FL), total hydroxycinnamic derivatives (THD), total polyphenols (TP) and tannins (T). Extracts induced time dependent decreases in cell survival; CA, CO and CM were the most effective (11.2%, 10.3% and 11.1%, after 72 h). The ED50 (effective dose) values were similar for all extracts and times tested. The THD and TP were identical in all samples, while a two-fold higher T content was present in CK and CO, and of FL in CF. The maximal effects (% of surviving cells) negatively correlated with the T and TP levels, and positively with FL and THD. The results demonstrate the significant antiproliferative effects of the tested water extracts in MCF-7 cells, in which CA, CO and CM are the most effective; and the effectiveness is related to the T and TP contents. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Anti-Ulcerogenic Properties of Lycium chinense Mill Extracts against Ethanol-Induced Acute Gastric Lesion in Animal Models and Its Active Constituents
Molecules 2015, 20(12), 22553-22564; doi:10.3390/molecules201219867
Received: 29 October 2015 / Revised: 10 December 2015 / Accepted: 10 December 2015 / Published: 16 December 2015
Cited by 7 | PDF Full-text (3810 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this study was to explore the gastroprotective properties of the aerial part of Lycium chinense Mill (LCA) against ethanol-induced gastric mucosa lesions in mice models. Administration of LCA at doses of 50, 100, 200 and 400 mg/kg body weight prior
[...] Read more.
The objective of this study was to explore the gastroprotective properties of the aerial part of Lycium chinense Mill (LCA) against ethanol-induced gastric mucosa lesions in mice models. Administration of LCA at doses of 50, 100, 200 and 400 mg/kg body weight prior to ethanol consumption dose dependently inhibited gastric ulcers. The gastric mucosal injury was analyzed by gastric juice acidity, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO) activities. Furthermore, the levels of the inflammatory mediators, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in serum were also analyzed using ELISA. Pathological changes were also observed with the aid of hematoxylin-eosin (HE) staining. Our results indicated that LCA significantly reduced the levels of MPO, MDA and increased SOD and GSH activities. Furthermore, LCA also significantly inhibited the levels of TNF-α, IL-6, and IL-1β in the serum of ulcerated mice in a dose dependent manner. Immunohistological analysis indicated that LCA also significantly attenuated the overexpression of nuclear factor-κB in pretreated mice models. This findings suggests Lycium chinense Mill possesses gastroprotective properties against ethanol-induced gastric injury and could be a possible therapeutic intervention in the treatment and management of gastric ulcers. Full article
(This article belongs to the collection Bioactive Compounds)
Figures

Open AccessCommunication Seven New Tetrahydroanthraquinones from the Root of Prismatomeris connata and Their Cytotoxicity against Lung Tumor Cell Growth
Molecules 2015, 20(12), 22565-22577; doi:10.3390/molecules201219856
Received: 11 November 2015 / Revised: 6 December 2015 / Accepted: 7 December 2015 / Published: 17 December 2015
Cited by 1 | PDF Full-text (2402 KB) | HTML Full-text | XML Full-text
Abstract
The root of Prismatomeris connata has been used in China for centuries as the medicinal herb “Huang Gen” (HG), but its phytochemicals or active ingredients are not well understood. In this study, we performed chemical analysis of the ethyl acetate fraction
[...] Read more.
The root of Prismatomeris connata has been used in China for centuries as the medicinal herb “Huang Gen” (HG), but its phytochemicals or active ingredients are not well understood. In this study, we performed chemical analysis of the ethyl acetate fraction of a HG ethanol extract. We thus isolated seven new tetrahydroanthraquinones, prisconnatanones C–I (compounds 17) from the root of P. connata and identified their structures using spectroscopic analyses. Their absolute configurations were established by both modified Mosher’s and Mo2OAc4 methods, and ORD techniques. Their cytotoxicity was tested in a panel of human lung tumor cells (H1229, HTB179, A549 and H520 cell lines). Prisconnatanone I (7) showed the highest activity, with an IC50 value ranging from 2.7 µM to 3.9 µM in the suppression of tumor cell growth, and the others with chelated phenolic hydroxyls exhibited relatively lower activity (IC50: 8–20 µM). In conclusion, these data suggest that some of the natural tetrahydroanthraquinones in HG are bioactive, and hydroxylation at C-1 significantly increases the cytotoxicity of these compounds against lung tumor cell growth. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Analysis of Indole Alkaloids from Rhazya stricta Hairy Roots by Ultra-Performance Liquid Chromatography-Mass Spectrometry
Molecules 2015, 20(12), 22621-22634; doi:10.3390/molecules201219873
Received: 28 October 2015 / Revised: 10 December 2015 / Accepted: 11 December 2015 / Published: 17 December 2015
Cited by 2 | PDF Full-text (1367 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Rhazya stricta Decne. (Apocynaceae) contains a large number of terpenoid indole alkaloids (TIAs). This study focused on the composition of alkaloids obtained from transformed hairy root cultures of R. stricta employing ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). In the UPLC-MS analyses, a total of
[...] Read more.
Rhazya stricta Decne. (Apocynaceae) contains a large number of terpenoid indole alkaloids (TIAs). This study focused on the composition of alkaloids obtained from transformed hairy root cultures of R. stricta employing ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). In the UPLC-MS analyses, a total of 20 TIAs were identified from crude extracts. Eburenine and vincanine were the main alkaloids followed by polar glucoalkaloids, strictosidine lactam and strictosidine. Secodine-type alkaloids, tetrahydrosecodinol, tetrahydro- and dihydrosecodine were detected too. The occurrence of tetrahydrosecodinol was confirmed for the first time for R. stricta. Furthermore, two isomers of yohimbine, serpentine and vallesiachotamine were identified. The study shows that a characteristic pattern of biosynthetically related TIAs can be monitored in Rhazya hairy root crude extract by this chromatographic method. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Metathetical Redox Reaction of (Diacetoxyiodo)arenes and Iodoarenes
Molecules 2015, 20(12), 22635-22644; doi:10.3390/molecules201219874
Received: 25 November 2015 / Revised: 10 December 2015 / Accepted: 15 December 2015 / Published: 17 December 2015
Cited by 4 | PDF Full-text (2718 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The oxidation of iodoarenes is central to the field of hypervalent iodine chemistry. It was found that the metathetical redox reaction between (diacetoxyiodo)arenes and iodoarenes is possible in the presence of a catalytic amount of Lewis acid. This discovery opens a new strategy
[...] Read more.
The oxidation of iodoarenes is central to the field of hypervalent iodine chemistry. It was found that the metathetical redox reaction between (diacetoxyiodo)arenes and iodoarenes is possible in the presence of a catalytic amount of Lewis acid. This discovery opens a new strategy to access (diacetoxyiodo)arenes. A computational study is provided to rationalize the results observed. Full article
(This article belongs to the Special Issue Hypervalent Iodine Chemistry)
Figures

Open AccessArticle Storage Stability of Kinnow Fruit (Citrus reticulata) as Affected by CMC and Guar Gum-Based Silver Nanoparticle Coatings
Molecules 2015, 20(12), 22645-22661; doi:10.3390/molecules201219870
Received: 6 November 2015 / Revised: 4 December 2015 / Accepted: 11 December 2015 / Published: 18 December 2015
Cited by 4 | PDF Full-text (4799 KB) | HTML Full-text | XML Full-text
Abstract
The influence of carboxy methyl cellulose (CMC) and guargum-based coatings containing silver nanoparticles was studied on the postharvest storage stability of the kinnow mandarin (Citrus reticulata cv. Blanco) for a period of 120 days (85%–90% relative humidity) at 4 °C and 10
[...] Read more.
The influence of carboxy methyl cellulose (CMC) and guargum-based coatings containing silver nanoparticles was studied on the postharvest storage stability of the kinnow mandarin (Citrus reticulata cv. Blanco) for a period of 120 days (85%–90% relative humidity) at 4 °C and 10 °C. Physicochemical and microbiological qualities were monitored after every 15 days of storage. Overall results revealed an increase in total soluble solid (TSS), total sugars, reducing sugars and weight loss but this increase was comparatively less significant in coated fruits stored at 4 °C. Ascorbic acid, total phenolics, and antioxidant activity was significantly enhanced in coated fruits stored at 4 °C. Titratable acidity significantly decreased during storage except for coated kinnow stored at 4 °C. In control samples stored at 10 °C, high intensity of fruit rotting and no chilling injury was observed. Total aerobic psychrotrophic bacteria and yeast and molds were noticed in all treatments during storage but the growth was not significant in coated fruits at 4 °C. Kinnow fruit can be kept in good quality after coating for four months at 4 °C and for 2 months at 10 °C. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)
Figures

Open AccessArticle Potassium Hexacyanoferrate (III)-Catalyzed Dimerization of Hydroxystilbene: Biomimetic Synthesis of Indane Stilbene Dimers
Molecules 2015, 20(12), 22662-22673; doi:10.3390/molecules201219872
Received: 16 November 2015 / Revised: 7 December 2015 / Accepted: 9 December 2015 / Published: 18 December 2015
Cited by 2 | PDF Full-text (1885 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Using potassium hexacyanoferrate (III)–sodium acetate as oxidant, the oxidative coupling reaction of isorhapontigenin and resveratrol in aqueous acetone resulted in the isolation of three new indane dimers 4, 6, and 7, together with six known stilbene dimers. Indane dimer 5
[...] Read more.
Using potassium hexacyanoferrate (III)–sodium acetate as oxidant, the oxidative coupling reaction of isorhapontigenin and resveratrol in aqueous acetone resulted in the isolation of three new indane dimers 4, 6, and 7, together with six known stilbene dimers. Indane dimer 5 was obtained for the first time by direct transformation from isorhapontigenin. The structures and relative configurations of the dimers were elucidated using spectral analysis, and their possible formation mechanisms were discussed. The results indicate that this reaction could be used as a convenient method for the semi-synthesis of indane dimers because of the mild conditions and simple reaction products. Full article
(This article belongs to the Section Bioorganic Chemistry)
Figures

Open AccessArticle Short-Term and Sub-Chronic Dietary Exposure to Aspalathin-Enriched Green Rooibos (Aspalathus linearis) Extract Affects Rat Liver Function and Antioxidant Status
Molecules 2015, 20(12), 22674-22690; doi:10.3390/molecules201219868
Received: 9 November 2015 / Revised: 9 December 2015 / Accepted: 11 December 2015 / Published: 18 December 2015
Cited by 4 | PDF Full-text (1075 KB) | HTML Full-text | XML Full-text | Correction
Abstract
An aspalathin-enriched green rooibos (Aspalathus linearis) extract (GRE) was fed to male Fischer rats in two independent studies for 28 and 90 days. The average dietary total polyphenol (TP) intake was 756 and 627 mg Gallic acid equivalents (GAE)/kg body weight
[...] Read more.
An aspalathin-enriched green rooibos (Aspalathus linearis) extract (GRE) was fed to male Fischer rats in two independent studies for 28 and 90 days. The average dietary total polyphenol (TP) intake was 756 and 627 mg Gallic acid equivalents (GAE)/kg body weight (bw)/day over 28 and 90 days, respectively, equaling human equivalent doses (HEDs) of 123 and 102 GAE mg/kg bw/day. Aspalathin intake of 295 mg/kg bw/day represents a HED of 48 mg/kg bw/day (90 day study). Consumption of GRE increased feed intake significantly (p < 0.05) compared to the control after 90 days, but no effect on body and organ weight parameters was observed. GRE significantly (p < 0.05) reduced serum total cholesterol and iron levels, whilst significantly (p < 0.05) increasing alkaline phosphatase enzyme activity after 90 days. Endogenous antioxidant enzyme activity in the liver, i.e., catalase and superoxide dismutase activity, was not adversely affected. Glutathione reductase activity significantly (p < 0.05) increased after 28 days, while glutathione (GSH) content was decreased after 90 days, suggesting an altered glutathione redox cycle. Quantitative Real Time polymerase chain reaction (PCR) analysis showed altered expression of certain antioxidant defense and oxidative stress related genes, indicative, among others, of an underlying oxidative stress related to changes in the GSH redox pathway and possible biliary dysfunction. Full article
(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)
Open AccessArticle Solid-State Characterization and Biological Activity of Betulonic Acid Derivatives
Molecules 2015, 20(12), 22691-22702; doi:10.3390/molecules201219876
Received: 1 November 2015 / Revised: 4 December 2015 / Accepted: 7 December 2015 / Published: 18 December 2015
PDF Full-text (2263 KB) | HTML Full-text | XML Full-text
Abstract
Betulonic acid belongs to the pentacyclic triterpenic derivative class and can be obtained through the selective oxidation of betulin. In this study we set obtaining several functionalized derivatives of this compound by its condensation with several amino compounds such as aminoguanidine, hydroxylamine, n
[...] Read more.
Betulonic acid belongs to the pentacyclic triterpenic derivative class and can be obtained through the selective oxidation of betulin. In this study we set obtaining several functionalized derivatives of this compound by its condensation with several amino compounds such as aminoguanidine, hydroxylamine, n-butylamine and thiosemicarbazide as our goal. The functionalization of the parent compound led to several molecules with antiproliferative potential, the most promising being 3–2-carbamothioylhydrazonolup-20(29)-en-28-oic acid. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Phenolic Assesment of Uncaria tomentosa L. (Cat’s Claw): Leaves, Stem, Bark and Wood Extracts
Molecules 2015, 20(12), 22703-22717; doi:10.3390/molecules201219875
Received: 14 October 2015 / Revised: 7 December 2015 / Accepted: 10 December 2015 / Published: 18 December 2015
Cited by 5 | PDF Full-text (2451 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The phenolic composition of extracts from Uncaria tomentosa L. from different regions of Costa Rica was studied using advanced analytical techniques such as UPLC/TQ-ESI-MS and 13C-NMR. Samples from leaves, stems, bark and wood (n = 22) were subjected to extraction to
[...] Read more.
The phenolic composition of extracts from Uncaria tomentosa L. from different regions of Costa Rica was studied using advanced analytical techniques such as UPLC/TQ-ESI-MS and 13C-NMR. Samples from leaves, stems, bark and wood (n = 22) were subjected to extraction to obtain phenolic and alkaloid extracts, separately. Comparatively, higher values of total phenolic content were observed for leaves, stems and bark (225–494 gallic acid equivalents/g) than for wood extracts (40–167 gallic acid equivalents/g). A total of 32 non-flavonoid and flavonoid compounds were identified in the phenolic extracts: hydroxybenzoic acids (benzoic, salicylic, 4-hydroxybenzoic, prochatechuic, gallic, syringic and vanillic acids), hydroxycinnamic acids (p-coumaric, caffeic, ferulic and isoferulic acids), flavan-3-ols monomers [(+)-catechin and (−)-epicatechin)], procyanidin dimers (B1, B2, B3, B4, B5, B7 and two other of unknown structure) and trimers (C1, T2 and one of unknown structure), flavalignans (four unknown structures pertaining to the cinchonain family) and propelargonidin dimers (four unknown structures, reported for the first time in U. tomentosa). Additionally, alkaloid extracts obtained from the plant residue after phenolic extraction exhibited a content of tetracyclic and pentacyclic alkaloids ranging between 95 and 275 mg/100 g of dry material for bark extracts, and between 30 and 704 mg/100 g for leaves extracts. In addition, a minor alkaloid was isolated and characterized, namely 18,19-dehydrocorynoxinoic acid. Our results confirmed the feasibility of U. tomentosa as a suitable raw material for obtaining phenolic- and alkaloid-rich extracts of potential interest. Full article
(This article belongs to the Special Issue Recent Advances in Plant Phenolics)
Figures

Open AccessFeature PaperArticle OSU-6: A Highly Efficient, Metal-Free, Heterogeneous Catalyst for the Click Synthesis of 5-Benzyl and 5-Aryl-1H-tetrazoles
Molecules 2015, 20(12), 22757-22766; doi:10.3390/molecules201219881
Received: 18 November 2015 / Revised: 7 December 2015 / Accepted: 11 December 2015 / Published: 19 December 2015
Cited by 3 | PDF Full-text (2132 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
OSU-6, an MCM-41 type hexagonal mesoporous silica with mild Brönsted acid properties, has been used as an efficient, metal-free, heterogeneous catalyst for the click synthesis of 5-benzyl and 5-aryl-1H-tetrazoles from nitriles in DMF at 90 °C. This catalyst offers advantages including
[...] Read more.
OSU-6, an MCM-41 type hexagonal mesoporous silica with mild Brönsted acid properties, has been used as an efficient, metal-free, heterogeneous catalyst for the click synthesis of 5-benzyl and 5-aryl-1H-tetrazoles from nitriles in DMF at 90 °C. This catalyst offers advantages including ease of operation, milder conditions, high yields, and reusability. Studies are presented that demonstrate the robust nature of the catalyst under the optimized reaction conditions. OSU-6 promotes the 1,3-dipolar addition of azides to nitriles without significant degradation or clogging of the nanoporous structure. The catalyst can be reused up to five times without a significant reduction in yield, and it does not require treatment with acid between reactions. Full article
(This article belongs to the Section Organic Synthesis)
Figures

Open AccessArticle Tissue- Specific Expression Analysis of Anthocyanin Biosynthetic Genes in White- and Red-Fleshed Grape Cultivars
Molecules 2015, 20(12), 22767-22780; doi:10.3390/molecules201219883
Received: 18 October 2015 / Revised: 11 December 2015 / Accepted: 15 December 2015 / Published: 19 December 2015
Cited by 3 | PDF Full-text (1858 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Yan73, a teinturier (dyer) grape variety in China, is one of the few Vitis vinifera cultivars with red-coloured berry flesh. To examine the tissue-specific expression of genes associated with berry colour in Yan73, we analysed the differential accumulation of anthocyanins in the skin
[...] Read more.
Yan73, a teinturier (dyer) grape variety in China, is one of the few Vitis vinifera cultivars with red-coloured berry flesh. To examine the tissue-specific expression of genes associated with berry colour in Yan73, we analysed the differential accumulation of anthocyanins in the skin and flesh tissues of two red-skinned grape varieties with either red (Yan73) or white flesh (Muscat Hamburg) based on HPLC-MS analysis, as well as the differential expression of 18 anthocyanin biosynthesis genes in both varieties by quantitative RT-PCR. The results revealed that the transcripts of GST, OMT, AM3, CHS3, UFGT, MYBA1, F3′5′H, F3H1 and LDOX were barely detectable in the white flesh of Muscat Hamburg. In particular, GST, OMT, AM3, CHS3 and F3H1 showed approximately 50-fold downregulation in the white flesh of Muscat Hamburg compared to the red flesh of Yan73. A correlation analysis between the accumulation of different types of anthocyanins and gene expression indicated that the cumulative expression of GST, F3′5′H, LDOX and MYBA1 was more closely associated with the acylated anthocyanins and the 3′5′-OH anthocyanins, while OMT and AM3 were more closely associated with the total anthocyanins and methoxylated anthocyanins. Therefore, the transcripts of OMT, AM3, GST, F3′5′H, LDOX and MYBA1 explained most of the variation in the amount and composition of anthocyanins in skin and flesh of Yan73. The data suggest that the specific localization of anthocyanins in the flesh tissue of Yan73 is most likely due to the tissue-specific expression of OMT, AM3, GST, F3′5′H, LDOX and MYBA1 in the flesh. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Studies on Chromatographic Fingerprint and Fingerprinting Profile-Efficacy Relationship of Saxifraga stolonifera Meerb.
Molecules 2015, 20(12), 22781-22798; doi:10.3390/molecules201219882
Received: 28 September 2015 / Revised: 15 December 2015 / Accepted: 15 December 2015 / Published: 19 December 2015
Cited by 5 | PDF Full-text (1538 KB) | HTML Full-text | XML Full-text
Abstract
This work investigated the spectrum-effect relationships between high performance liquid chromatography (HPLC) fingerprints and the anti-benign prostatic hyperplasia activities of aqueous extracts from Saxifraga stolonifera. The fingerprints of S. stolonifera from various sources were established by HPLC and evaluated by similarity analysis
[...] Read more.
This work investigated the spectrum-effect relationships between high performance liquid chromatography (HPLC) fingerprints and the anti-benign prostatic hyperplasia activities of aqueous extracts from Saxifraga stolonifera. The fingerprints of S. stolonifera from various sources were established by HPLC and evaluated by similarity analysis (SA), hierarchical clustering analysis (HCA) and principal component analysis (PCA). Nine samples were obtained from these 24 batches of different origins, according to the results of SA, HCA and the common chromatographic peaks area. A testosterone-induced mouse model of benign prostatic hyperplasia (BPH) was used to establish the anti-benign prostatic hyperplasia activities of these nine S. stolonifera samples. The model was evaluated by analyzing prostatic index (PI), serum acid phosphatase (ACP) activity, concentrations of serum dihydrotestosterone (DHT), prostatic acid phosphatase (PACP) and type II 5α-reductase (SRD5A2). The spectrum-effect relationships between HPLC fingerprints and anti-benign prostatic hyperplasia activities were investigated using Grey Correlation Analysis (GRA) and partial least squares regression (PLSR). The results showed that a close correlation existed between the fingerprints and anti-benign prostatic hyperplasia activities, and peak 14 (chlorogenic acid), peak 17 (quercetin 5-O-β-d-glucopyranoside) and peak 18 (quercetin 3-O-β-l-rhamno-pyranoside) in the HPLC fingerprints might be the main active components against anti-benign prostatic hyperplasia. This work provides a general model for the study of spectrum-effect relationships of S. stolonifera by combing HPLC fingerprints with a testosterone-induced mouse model of BPH, which can be employed to discover the principle components of anti-benign prostatic hyperplasia bioactivity. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Ellagitannins and Flavan-3-ols from Raspberry Pomace Modulate Caecal Fermentation Processes and Plasma Lipid Parameters in Rats
Molecules 2015, 20(12), 22848-22862; doi:10.3390/molecules201219878
Received: 5 October 2015 / Revised: 25 November 2015 / Accepted: 14 December 2015 / Published: 21 December 2015
Cited by 4 | PDF Full-text (478 KB) | HTML Full-text | XML Full-text
Abstract
Raspberry pomace is a source of polyphenols, which nutritional and health promoting properties are not sufficiently known. The aim of this 8-weeks study was to scrutinize if raspberry extracts (REs) with different ellagitannins to flavan-3-ols ratios might favorably affect the caecal fermentation processes
[...] Read more.
Raspberry pomace is a source of polyphenols, which nutritional and health promoting properties are not sufficiently known. The aim of this 8-weeks study was to scrutinize if raspberry extracts (REs) with different ellagitannins to flavan-3-ols ratios might favorably affect the caecal fermentation processes and blood lipid profile in rats. Forty male Wistar rats were fed with a standard diet or its modification with two types of REs (E1 and E2) characterized by different ratios of ellagitannins to flavan-3-ols (7.7 and 3.1 for E1 and E2, respectively) and added to a diet at two dosages of polyphenolic compounds (0.15 and 0.30% of a diet; L and H treatments, respectively). Irrespective of polyphenols dietary level, both REs reduced the activity of bacterial β-glucuronidase, increased production of butyric acid in the caecum and reduced triacylglycerols in blood plasma. The E1 treatment at both dosages caused more effective reduction in the concentration of ammonia and elevated acetate level in the caecal digesta than E2. On the other hand, only the E2 treatment lowered value of the atherogenic index when compared with control group. When comparing dosages of REs, a higher one was more potent to reduce the activity of bacterial β-glucosidase, β-, α-galactosidase and lowered value of the HDL profile in plasma. To conclude, REs may favorably modulate the activity of the caecal microbiota and blood lipid profile in rats; however, the intensity of these effects may be related to the dosages of dietary polyphenols and to their profile, e.g., ellagitannins to flavan-3-ols ratio. Full article
Figures

Open AccessArticle Bioactive Properties of Tabebuia impetiginosa-Based Phytopreparations and Phytoformulations: A Comparison between Extracts and Dietary Supplements
Molecules 2015, 20(12), 22863-22871; doi:10.3390/molecules201219885
Received: 12 November 2015 / Revised: 15 December 2015 / Accepted: 17 December 2015 / Published: 21 December 2015
PDF Full-text (207 KB) | HTML Full-text | XML Full-text
Abstract
Tabebuia impetiginosa (Mart. ex DC.) Standl. has been used in traditional medicine for many centuries, being nowadays marketed as dried plant material (inner bark) for infusions, pills, and syrups. The main objective of the present work was to validate its popular use through
[...] Read more.
Tabebuia impetiginosa (Mart. ex DC.) Standl. has been used in traditional medicine for many centuries, being nowadays marketed as dried plant material (inner bark) for infusions, pills, and syrups. The main objective of the present work was to validate its popular use through the bioactivity evaluation of the inner bark (methanolic extract and infusion) and of two different formulations (pills and syrup) also based on the same plant-material. The antioxidant activity was evaluated by in vitro assays testing free radical scavenging activity, reducing power and inhibition of lipid peroxidation in brain homogenates. The cytotoxicity was determined in four human tumor cell lines (MCF-7, NCI-H460, HeLa and HepG2, and also in non-tumor cells (porcine liver primary cells, PLP2)). Furthermore, the sample was chemically characterized regarding free sugars, organic acids, fatty acids, and tocopherols. Syrup and methanolic extract showed the highest antioxidant activity, related to their highest amount of phenolics and flavonoids. Methanolic extract was the only sample showing cytotoxic effects on the tested human tumor cell lines, but none of the samples showed toxicity in PLP2. Glucose and oxalic acid were, respectively, the most abundant sugar and organic acid in the sample. Unsaturated predominated over the saturated fatty acids, due to oleic, linoleic, and linolenic acids expression. α- and γ-Tocopherols were also identified and quantified. Overall, T. impetiginosa might be used in different phytoformulations, taking advantage of its interesting bioactive properties and chemical composition. Full article
(This article belongs to the collection Bioactive Compounds)
Figures

Open AccessCommunication Fatty Acid Profile and Biological Activities of Linseed and Rapeseed Oils
Molecules 2015, 20(12), 22872-22880; doi:10.3390/molecules201219887
Received: 2 November 2015 / Revised: 13 December 2015 / Accepted: 16 December 2015 / Published: 21 December 2015
Cited by 6 | PDF Full-text (907 KB) | HTML Full-text | XML Full-text
Abstract
It has been postulated that fatty acids found in edible oils may exert beneficial health effects by the modulation of signaling pathways regulating cell differentiation and proliferation, especially in the treatment of cardiovascular diseases. In the present study, the biological effects of selected
[...] Read more.
It has been postulated that fatty acids found in edible oils may exert beneficial health effects by the modulation of signaling pathways regulating cell differentiation and proliferation, especially in the treatment of cardiovascular diseases. In the present study, the biological effects of selected edible oils—linseed (LO) and rapeseed (RO) oils—were tested in vitro on fibroblast cells. The fatty acid profile of the oils was determined using gas chromatography and FTIR spectroscopy. LO was found to be rich in α-linolenic acid (ALA), whereas oleic acid was the most abundant species in RO. Fatty acids were taken up by the cells and promoted cell proliferation. No oxidative stress-mediated cytotoxic or genotoxic effects were observed after oil stimulation. Oils ameliorated the process of wound healing as judged by improved migration of fibroblasts to the wounding area. As ALA-rich LO exhibited the most potent wound healing activity, ALA may be considered a candidate for promoting the observed effect. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle The Sensitivity of Endodontic Enterococcus spp. Strains to Geranium Essential Oil
Molecules 2015, 20(12), 22881-22889; doi:10.3390/molecules201219888
Received: 18 September 2015 / Revised: 7 December 2015 / Accepted: 14 December 2015 / Published: 21 December 2015
Cited by 1 | PDF Full-text (199 KB) | HTML Full-text | XML Full-text
Abstract
Enterococci are able to survive endodontic procedures and contribute to the failure of endodontic therapy. Thus, it is essential to identify novel ways of eradicating them from infected root canals. One such approach may be the use of antimicrobials such as plant essential
[...] Read more.
Enterococci are able to survive endodontic procedures and contribute to the failure of endodontic therapy. Thus, it is essential to identify novel ways of eradicating them from infected root canals. One such approach may be the use of antimicrobials such as plant essential oils. Enterococcal strains were isolated from endodontically treated teeth by standard microbiological methods. Susceptibility to antibiotics was evaluated by the disc-diffusion method. The minimal inhibitory concentration (MIC) of geranium essential oil was investigated by microdilution in 96-well microplates in Mueller Hinton Broth II. Biofilm eradication concentrations were checked in dentin tests. Geranium essential oil inhibited enterococcal strains at concentrations ranging from 1.8–4.5 mg/mL. No correlation was shown between resistance to antibiotics and the MICs of the test antimicrobials. The MICs of the test oil were lower than those found to show cytotoxic effects on the HMEC-1 cell line. Geranium essential oil eradicated enterococcal biofilm at concentrations of 150 mg/mL. Geranium essential oil inhibits the growth of endodontic enterococcal species at lower concentrations than those required to reach IC50 against the HMEC-1 cell line, and is effective against bacteria protected in biofilm at higher concentrations. In addition, bacteria do not develop resistance to essential oils. Hence, geranium essential oil represents a possible alternative to other antimicrobials during endodontic procedures. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Cross-Coupling Synthesis of Methylallyl Alkenes: Scope Extension and Mechanistic Study
Molecules 2015, 20(12), 22890-22899; doi:10.3390/molecules201219886
Received: 20 November 2015 / Revised: 9 December 2015 / Accepted: 14 December 2015 / Published: 21 December 2015
Cited by 2 | PDF Full-text (5257 KB) | HTML Full-text | XML Full-text
Abstract
Cross-coupling reactions between 2-methyl-2-propen-1-ol and various boronic acids are used to obtain aromatic-(2-methylallyl) derivatives. However, deboronation or isomerization side reactions may occur for several boronic acids. We describe herein the synthesis of original alkenes with good yields under mild reaction conditions that decrease
[...] Read more.
Cross-coupling reactions between 2-methyl-2-propen-1-ol and various boronic acids are used to obtain aromatic-(2-methylallyl) derivatives. However, deboronation or isomerization side reactions may occur for several boronic acids. We describe herein the synthesis of original alkenes with good yields under mild reaction conditions that decrease these side reactions. The scope of this environmentally benign reaction is thereby extended to a wide variety of boronic acids. A mechanistic study was conducted and suggested a plausible catalytic cycle mechanism, pointing to the importance of the Lewis acidity of the boronic acid used. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessCommunication Guignardones P–S, New Meroterpenoids from the Endophytic Fungus Guignardia mangiferae A348 Derived from the Medicinal Plant Smilax glabra
Molecules 2015, 20(12), 22900-22907; doi:10.3390/molecules201219890
Received: 23 November 2015 / Revised: 15 December 2015 / Accepted: 17 December 2015 / Published: 21 December 2015
Cited by 7 | PDF Full-text (3618 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four new meroterpenoids, guignardones P–S (14), and three known analogues (57) were isolated from the endophytic fungal strain Guignardia mangiferae A348. Their structures were elucidated on the basis of spectroscopic analysis and single crystal X-ray
[...] Read more.
Four new meroterpenoids, guignardones P–S (14), and three known analogues (57) were isolated from the endophytic fungal strain Guignardia mangiferae A348. Their structures were elucidated on the basis of spectroscopic analysis and single crystal X-ray diffraction. All the isolated compounds were evaluated for their inhibitory effects on SF-268, MCF-7, and NCI-H460 human cancer cell lines. Compounds 2 and 4 exhibited weak inhibitions of cell proliferation against MCF-7 cell line. Full article
(This article belongs to the collection Bioactive Compounds)
Figures

Review

Jump to: Research, Other

Open AccessReview DNA Aptamers in the Diagnosis and Treatment of Human Diseases
Molecules 2015, 20(12), 20979-20997; doi:10.3390/molecules201219739
Received: 15 September 2015 / Revised: 16 November 2015 / Accepted: 16 November 2015 / Published: 25 November 2015
Cited by 4 | PDF Full-text (787 KB) | HTML Full-text | XML Full-text
Abstract
Aptamers have a promising role in the field of life science and have been extensively researched for application as analytical tools, therapeutic agents and as vehicles for targeted drug delivery. Compared with RNA aptamers, DNA aptamers have inherent advantages in stability and facility
[...] Read more.
Aptamers have a promising role in the field of life science and have been extensively researched for application as analytical tools, therapeutic agents and as vehicles for targeted drug delivery. Compared with RNA aptamers, DNA aptamers have inherent advantages in stability and facility of generation and synthesis. To better understand the specific potential of DNA aptamers, an overview of the progress in the generation and application of DNA aptamers in human disease diagnosis and therapy are presented in this review. Special attention is given to researches that are relatively close to practical application. DNA aptamers are expected to have great potential in the diagnosis and treatment of human diseases. Full article
(This article belongs to the Special Issue Aptamers: Past, Present, and Future)
Open AccessReview Antioxidant Phytochemicals for the Prevention and Treatment of Chronic Diseases
Molecules 2015, 20(12), 21138-21156; doi:10.3390/molecules201219753
Received: 19 August 2015 / Revised: 10 November 2015 / Accepted: 20 November 2015 / Published: 27 November 2015
Cited by 60 | PDF Full-text (254 KB) | HTML Full-text | XML Full-text
Abstract
Overproduction of oxidants (reactive oxygen species and reactive nitrogen species) in the human body is responsible for the pathogenesis of some diseases. The scavenging of these oxidants is thought to be an effective measure to depress the level of oxidative stress of organisms.
[...] Read more.
Overproduction of oxidants (reactive oxygen species and reactive nitrogen species) in the human body is responsible for the pathogenesis of some diseases. The scavenging of these oxidants is thought to be an effective measure to depress the level of oxidative stress of organisms. It has been reported that intake of vegetables and fruits is inversely associated with the risk of many chronic diseases, and antioxidant phytochemicals in vegetables and fruits are considered to be responsible for these health benefits. Antioxidant phytochemicals can be found in many foods and medicinal plants, and play an important role in the prevention and treatment of chronic diseases caused by oxidative stress. They often possess strong antioxidant and free radical scavenging abilities, as well as anti-inflammatory action, which are also the basis of other bioactivities and health benefits, such as anticancer, anti-aging, and protective action for cardiovascular diseases, diabetes mellitus, obesity and neurodegenerative diseases. This review summarizes recent progress on the health benefits of antioxidant phytochemicals, and discusses their potential mechanisms in the prevention and treatment of chronic diseases. Full article
(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)
Open AccessReview Oligonucleotide Functionalised Microbeads: Indispensable Tools for High-Throughput Aptamer Selection
Molecules 2015, 20(12), 21298-21312; doi:10.3390/molecules201219766
Received: 22 September 2015 / Revised: 21 October 2015 / Accepted: 12 November 2015 / Published: 1 December 2015
Cited by 4 | PDF Full-text (1479 KB) | HTML Full-text | XML Full-text
Abstract
The functionalisation of microbeads with oligonucleotides has become an indispensable technique for high-throughput aptamer selection in SELEX protocols. In addition to simplifying the separation of binding and non-binding aptamer candidates, microbeads have facilitated the integration of other technologies such as emulsion PCR (ePCR)
[...] Read more.
The functionalisation of microbeads with oligonucleotides has become an indispensable technique for high-throughput aptamer selection in SELEX protocols. In addition to simplifying the separation of binding and non-binding aptamer candidates, microbeads have facilitated the integration of other technologies such as emulsion PCR (ePCR) and Fluorescence Activated Cell Sorting (FACS) to high-throughput selection techniques. Within these systems, monoclonal aptamer microbeads can be individually generated and assayed to assess aptamer candidate fitness thereby helping eliminate stochastic effects which are common to classical SELEX techniques. Such techniques have given rise to aptamers with 1000 times greater binding affinities when compared to traditional SELEX. Another emerging technique is Fluorescence Activated Droplet Sorting (FADS) whereby selection does not rely on binding capture allowing evolution of a greater diversity of aptamer properties such as fluorescence or enzymatic activity. Within this review we explore examples and applications of oligonucleotide functionalised microbeads in aptamer selection and reflect upon new opportunities arising for aptamer science. Full article
(This article belongs to the Special Issue Aptamers: Past, Present, and Future)
Figures

Open AccessReview Technological Aspects of Chemoenzymatic Epoxidation of Fatty Acids, Fatty Acid Esters and Vegetable Oils: A Review
Molecules 2015, 20(12), 21481-21493; doi:10.3390/molecules201219778
Received: 9 October 2015 / Revised: 10 November 2015 / Accepted: 17 November 2015 / Published: 2 December 2015
Cited by 11 | PDF Full-text (823 KB) | HTML Full-text | XML Full-text
Abstract
The general subject of the review is analysis of the effect of technological parameters on the chemoenzymatic epoxidation processes of vegetable oils, fatty acids and alkyl esters of fatty acids. The technological parameters considered include temperature, concentration, amount of hydrogen peroxide relative to
[...] Read more.
The general subject of the review is analysis of the effect of technological parameters on the chemoenzymatic epoxidation processes of vegetable oils, fatty acids and alkyl esters of fatty acids. The technological parameters considered include temperature, concentration, amount of hydrogen peroxide relative to the number of unsaturated bonds, the amounts of enzyme catalysts, presence of solvent and amount of free fatty acids. Also chemical reactions accompanying the technological processes are discussed together with different technological options and significance of the products obtained. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessReview Pharmaceutical Potential of Synthetic and Natural Pyrrolomycins
Molecules 2015, 20(12), 21658-21671; doi:10.3390/molecules201219797
Received: 16 October 2015 / Revised: 19 November 2015 / Accepted: 24 November 2015 / Published: 4 December 2015
Cited by 6 | PDF Full-text (1550 KB) | HTML Full-text | XML Full-text
Abstract
The emergence of antibiotic resistance is currently considered one of the most important global health problem. The continuous onset of multidrug-resistant Gram-positive and Gram-negative bacterial strains limits the clinical efficacy of most of the marketed antibiotics. Therefore, there is an urgent need for
[...] Read more.
The emergence of antibiotic resistance is currently considered one of the most important global health problem. The continuous onset of multidrug-resistant Gram-positive and Gram-negative bacterial strains limits the clinical efficacy of most of the marketed antibiotics. Therefore, there is an urgent need for new antibiotics. Pyrrolomycins are a class of biologically active compounds that exhibit a broad spectrum of biological activities, including antibacterial, antifungal, anthelmintic, antiproliferative, insecticidal, and acaricidal activities. In this review we focus on the antibacterial activity and antibiofilm activity of pyrrolomycins against Gram-positive and Gram-negative pathogens. Their efficacy, combined in some cases with a low toxicity, confers to these molecules a great potential for the development of new antimicrobial agents to face the antibiotic crisis. Full article
Figures

Open AccessReview Polyphenols from Bee Pollen: Structure, Absorption, Metabolism and Biological Activity
Molecules 2015, 20(12), 21732-21749; doi:10.3390/molecules201219800
Received: 20 October 2015 / Revised: 17 November 2015 / Accepted: 27 November 2015 / Published: 4 December 2015
Cited by 11 | PDF Full-text (829 KB) | HTML Full-text | XML Full-text | Correction
Abstract
Bee pollen constitutes a natural source of antioxidants such as phenolic acids and flavonoids, which are responsible for its biological activity. Research has indicated the correlation between dietary polyphenols and cardioprotective, hepatoprotective, anti-inflammatory, antibacterial, anticancerogenic, immunostimulating, antianaemic effects, as well as their beneficial
[...] Read more.
Bee pollen constitutes a natural source of antioxidants such as phenolic acids and flavonoids, which are responsible for its biological activity. Research has indicated the correlation between dietary polyphenols and cardioprotective, hepatoprotective, anti-inflammatory, antibacterial, anticancerogenic, immunostimulating, antianaemic effects, as well as their beneficial influence on osseous tissue. The beneficial effects of bee pollen on health result from the presence of phenolic acids and flavonoids which possess anti-inflammatory properties, phytosterol and linolenic acid which play an anticancerogenic role, and polysaccharides which stimulate immunological activity. Polyphenols are absorbed in the alimentary tract, metabolised by CYP450 enzymes, and excreted with urine and faeces. Flavonoids and phenolic acids are characterised by high antioxidative potential, which is closely related to their chemical structure. The high antioxidant potential of phenolic acids is due to the presence and location of hydroxyl groups, a carboxyl group in the immediate vicinity of ortho-diphenolic substituents, and the ethylene group between the phenyl ring and the carboxyl group. As regards flavonoids, essential structural elements are hydroxyl groups at the C5 and C7 positions in the A ring, and at the C3′ and C4′ positions in the B ring, and a hydroxyl group at the C3 position in the C ring. Furthermore, both, the double bond between C2 and C3, and a ketone group at the C4 position in the C ring enhance the antioxidative potential of these compounds. Polyphenols have an ideal chemical structure for scavenging free radicals and for creating chelates with metal ions, which makes them effective antioxidants in vivo. Full article
(This article belongs to the Section Metabolites)
Open AccessReview Polymer-Based Prodrugs: Improving Tumor Targeting and the Solubility of Small Molecule Drugs in Cancer Therapy
Molecules 2015, 20(12), 21750-21769; doi:10.3390/molecules201219804
Received: 25 September 2015 / Revised: 5 November 2015 / Accepted: 17 November 2015 / Published: 4 December 2015
Cited by 14 | PDF Full-text (1505 KB) | HTML Full-text | XML Full-text
Abstract
The majority of anticancer drugs have poor aqueous solubility, produce adverse effects in healthy tissue, and thus impose major limitations on both clinical efficacy and therapeutic safety of cancer chemotherapy. To help circumvent problems associated with solubility, most cancer drugs are now formulated
[...] Read more.
The majority of anticancer drugs have poor aqueous solubility, produce adverse effects in healthy tissue, and thus impose major limitations on both clinical efficacy and therapeutic safety of cancer chemotherapy. To help circumvent problems associated with solubility, most cancer drugs are now formulated with co-solubilizers. However, these agents often also introduce severe side effects, thereby restricting effective treatment and patient quality of life. A promising approach to addressing problems in anticancer drug solubility and selectivity is their conjugation with polymeric carriers to form polymer-based prodrugs. These polymer-based prodrugs are macromolecular carriers, designed to increase the aqueous solubility of antitumor drugs, can enhance bioavailability. Additionally, polymer-based prodrugs approach exploits unique features of tumor physiology to passively facilitate intratumoral accumulation, and so improve chemodrug pharmacokinetics and pharmacological properties. This review introduces basic concepts of polymer-based prodrugs, provides an overview of currently emerging synthetic, natural, and genetically engineered polymers that now deliver anticancer drugs in preclinical or clinical trials, and highlights their major anticipated applications in anticancer therapies. Full article
(This article belongs to the collection Poorly Soluble Drugs)
Figures

Open AccessReview Recent Advances in the Development and Application of Radiolabeled Kinase Inhibitors for PET Imaging
Molecules 2015, 20(12), 22000-22027; doi:10.3390/molecules201219816
Received: 22 October 2015 / Revised: 18 November 2015 / Accepted: 1 December 2015 / Published: 9 December 2015
Cited by 4 | PDF Full-text (7839 KB) | HTML Full-text | XML Full-text
Abstract
Over the last 20 years, intensive investigation and multiple clinical successes targeting protein kinases, mostly for cancer treatment, have identified small molecule kinase inhibitors as a prominent therapeutic class. In the course of those investigations, radiolabeled kinase inhibitors for positron emission tomography (PET)
[...] Read more.
Over the last 20 years, intensive investigation and multiple clinical successes targeting protein kinases, mostly for cancer treatment, have identified small molecule kinase inhibitors as a prominent therapeutic class. In the course of those investigations, radiolabeled kinase inhibitors for positron emission tomography (PET) imaging have been synthesized and evaluated as diagnostic imaging probes for cancer characterization. Given that inhibitor coverage of the kinome is continuously expanding, in vivo PET imaging will likely find increasing applications for therapy monitoring and receptor density studies both in- and outside of oncological conditions. Early investigated radiolabeled inhibitors, which are mostly based on clinically approved tyrosine kinase inhibitor (TKI) isotopologues, have now entered clinical trials. Novel radioligands for cancer and PET neuroimaging originating from novel but relevant target kinases are currently being explored in preclinical studies. This article reviews the literature involving radiotracer design, radiochemistry approaches, biological tracer evaluation and nuclear imaging results of radiolabeled kinase inhibitors for PET reported between 2010 and mid-2015. Aspects regarding the usefulness of pursuing selective vs. promiscuous inhibitor scaffolds and the inherent challenges associated with intracellular enzyme imaging will be discussed. Full article
(This article belongs to the Special Issue Kinase Inhibitor Chemistry)
Figures

Open AccessReview Understanding Critical Quality Attributes for Nanocrystals from Preparation to Delivery
Molecules 2015, 20(12), 22286-22300; doi:10.3390/molecules201219851
Received: 6 October 2015 / Revised: 8 December 2015 / Accepted: 8 December 2015 / Published: 12 December 2015
Cited by 5 | PDF Full-text (1740 KB) | HTML Full-text | XML Full-text
Abstract
Poor solubility of active pharmaceutical ingredients (APIs) is a great challenge for the pharmaceutical industry and, hence, drug nanocrystals are widely studied as one solution to overcome these solubility problems. Drug nanocrystals have comparatively simple structures which make them attractive for the formulation
[...] Read more.
Poor solubility of active pharmaceutical ingredients (APIs) is a great challenge for the pharmaceutical industry and, hence, drug nanocrystals are widely studied as one solution to overcome these solubility problems. Drug nanocrystals have comparatively simple structures which make them attractive for the formulation for poorly soluble drugs, and their capability to improve the dissolution in vitro is easily demonstrated, but turning the in vitro superior properties of nanocrystals to success in vivo, is often demanding: controlled (including enhanced) drug dissolution followed by successful permeation is not guaranteed, if for example, the dissolved drug precipitates before it is absorbed. In this review critical quality attributes related to nanocrystal formulations from production to final product performance in vivo are considered. Many important parameters exist, but here physical stability (aggregation tendency and solid state form), solubility properties influencing dissolution and supersaturation, excipient use to promote the maintenance of supersaturation, and finally the fate of nanocrystals in vivo are the main subjects of our focus. Full article
(This article belongs to the collection Poorly Soluble Drugs)
Open AccessReview Chemical Composition and Biological Activities of Fragrant Mexican Copal (Bursera spp.)
Molecules 2015, 20(12), 22383-22394; doi:10.3390/molecules201219849
Received: 15 October 2015 / Revised: 9 December 2015 / Accepted: 9 December 2015 / Published: 12 December 2015
Cited by 1 | PDF Full-text (1527 KB) | HTML Full-text | XML Full-text
Abstract
Copal is the Spanish word used to describe aromatic resins from several genera of plants. Mexican copal derives from several Bursera spp., Protium copal, some Pinus spp. (e.g., P. pseudostrobus) and a few Fabaceae spp. It has been used for centuries
[...] Read more.
Copal is the Spanish word used to describe aromatic resins from several genera of plants. Mexican copal derives from several Bursera spp., Protium copal, some Pinus spp. (e.g., P. pseudostrobus) and a few Fabaceae spp. It has been used for centuries as incense for religious ceremonies, as a food preservative, and as a treatment for several illnesses. The aim of this review is to analyze the chemical composition and biological activity of commercial Mexican Bursera copal. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
Figures

Open AccessReview Chemoprevention of Breast Cancer by Dietary Polyphenols
Molecules 2015, 20(12), 22578-22620; doi:10.3390/molecules201219864
Received: 2 October 2015 / Revised: 4 December 2015 / Accepted: 8 December 2015 / Published: 17 December 2015
Cited by 13 | PDF Full-text (9006 KB) | HTML Full-text | XML Full-text
Abstract
The review will discuss in detail the effects of polyphenols on breast cancer, including both the advantages and disadvantages of the applications of these natural compounds. First, we focus on the characterization of the main classes of polyphenols and then on in vitro
[...] Read more.
The review will discuss in detail the effects of polyphenols on breast cancer, including both the advantages and disadvantages of the applications of these natural compounds. First, we focus on the characterization of the main classes of polyphenols and then on in vitro and in vivo experiments carried out in breast cancer models. Since the therapeutic effects of the administration of a single type of polyphenol might be limited because of the reduced bioavailability of these drugs, investigations on combination of several polyphenols or polyphenols with conventional therapy will also be discussed. In addition, we present recent data focusing on clinical trials with polyphenols and new approaches with nanoparticles in breast cancer. Besides the clinical and translational findings this review systematically summarizes our current knowledge about the molecular mechanisms of anti-cancer effects of polyphenols, which are related to apoptosis, cell cycle regulation, plasma membrane receptors, signaling pathways and epigenetic mechanisms. At the same time the effects of polyphenols on primary tumor, metastasis and angiogenesis in breast cancer are discussed. The increasing enthusiasm regarding the combination of polyphenols and conventional therapy in breast cancer might lead to additional efforts to motivate further research in this field. Full article
Figures

Open AccessReview Unfolded Protein Response and Macroautophagy in Alzheimer’s, Parkinson’s and Prion Diseases
Molecules 2015, 20(12), 22718-22756; doi:10.3390/molecules201219865
Received: 30 October 2015 / Revised: 30 November 2015 / Accepted: 9 December 2015 / Published: 18 December 2015
Cited by 6 | PDF Full-text (2421 KB) | HTML Full-text | XML Full-text
Abstract
Proteostasis are integrated biological pathways within cells that control synthesis, folding, trafficking and degradation of proteins. The absence of cell division makes brain proteostasis susceptible to age-related changes and neurodegeneration. Two key processes involved in sustaining normal brain proteostasis are the unfolded protein
[...] Read more.
Proteostasis are integrated biological pathways within cells that control synthesis, folding, trafficking and degradation of proteins. The absence of cell division makes brain proteostasis susceptible to age-related changes and neurodegeneration. Two key processes involved in sustaining normal brain proteostasis are the unfolded protein response and autophagy. Alzheimer’s disease (AD), Parkinson’s disease (PD) and prion diseases (PrDs) have different clinical manifestations of neurodegeneration, however, all share an accumulation of misfolded pathological proteins associated with perturbations in unfolded protein response and macroautophagy. While both the unfolded protein response and macroautophagy play an important role in the prevention and attenuation of AD and PD progression, only macroautophagy seems to play an important role in the development of PrDs. Macroautophagy and unfolded protein response can be modulated by pharmacological interventions. However, further research is necessary to better understand the regulatory pathways of both processes in health and neurodegeneration to be able to develop new therapeutic interventions. Full article
Open AccessFeature PaperReview Pharmacophore Models and Pharmacophore-Based Virtual Screening: Concepts and Applications Exemplified on Hydroxysteroid Dehydrogenases
Molecules 2015, 20(12), 22799-22832; doi:10.3390/molecules201219880
Received: 19 November 2015 / Revised: 3 December 2015 / Accepted: 9 December 2015 / Published: 19 December 2015
Cited by 12 | PDF Full-text (6349 KB) | HTML Full-text | XML Full-text
Abstract
Computational methods are well-established tools in the drug discovery process and can be employed for a variety of tasks. Common applications include lead identification and scaffold hopping, as well as lead optimization by structure-activity relationship analysis and selectivity profiling. In addition, compound-target interactions
[...] Read more.
Computational methods are well-established tools in the drug discovery process and can be employed for a variety of tasks. Common applications include lead identification and scaffold hopping, as well as lead optimization by structure-activity relationship analysis and selectivity profiling. In addition, compound-target interactions associated with potentially harmful effects can be identified and investigated. This review focuses on pharmacophore-based virtual screening campaigns specifically addressing the target class of hydroxysteroid dehydrogenases. Many members of this enzyme family are associated with specific pathological conditions, and pharmacological modulation of their activity may represent promising therapeutic strategies. On the other hand, unintended interference with their biological functions, e.g., upon inhibition by xenobiotics, can disrupt steroid hormone-mediated effects, thereby contributing to the development and progression of major diseases. Besides a general introduction to pharmacophore modeling and pharmacophore-based virtual screening, exemplary case studies from the field of short-chain dehydrogenase/reductase (SDR) research are presented. These success stories highlight the suitability of pharmacophore modeling for the various application fields and suggest its application also in futures studies. Full article
(This article belongs to the Special Issue Chemoinformatics)
Open AccessReview Properties and Applications of Polyvinyl Alcohol, Halloysite Nanotubes and Their Nanocomposites
Molecules 2015, 20(12), 22833-22847; doi:10.3390/molecules201219884
Received: 15 October 2015 / Revised: 27 November 2015 / Accepted: 11 December 2015 / Published: 19 December 2015
Cited by 27 | PDF Full-text (3289 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this review was to analyze/investigate the synthesis, properties, and applications of polyvinyl alcohol–halloysite nanotubes (PVA–HNT), and their nanocomposites. Different polymers with versatile properties are attractive because of their introduction and potential uses in many fields. Synthetic polymers, such as PVA,
[...] Read more.
The aim of this review was to analyze/investigate the synthesis, properties, and applications of polyvinyl alcohol–halloysite nanotubes (PVA–HNT), and their nanocomposites. Different polymers with versatile properties are attractive because of their introduction and potential uses in many fields. Synthetic polymers, such as PVA, natural polymers like alginate, starch, chitosan, or any material with these components have prominent status as important and degradable materials with biocompatibility properties. These materials have been developed in the 1980s and are remarkable because of their recyclability and consideration of the natural continuation of their physical and chemical properties. The fabrication of PVA–HNT nanocomposites can be a potential way to address some of PVA’s limitations. Such nanocomposites have excellent mechanical properties and thermal stability. PVA–HNT nanocomposites have been reported earlier, but without proper HNT individualization and PVA modifications. The properties of PVA–HNT for medicinal and biomedical use are attracting an increasing amount of attention for medical applications, such as wound dressings, drug delivery, targeted-tissue transportation systems, and soft biomaterial implants. The demand for alternative polymeric medical devices has also increased substantially around the world. This paper reviews individualized HNT addition along with crosslinking of PVA for various biomedical applications that have been previously reported in literature, thereby showing the attainability, modification of characteristics, and goals underlying the blending process with PVA. Full article
(This article belongs to the Section Molecular Diversity)

Other

Jump to: Research, Review

Open AccessCorrection Correction: Zhang, Y., et al. 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, 20939–20954
Molecules 2015, 20(12), 22236-22240; doi:10.3390/molecules201219850
Received: 27 November 2015 / Accepted: 30 November 2015 / Published: 11 December 2015
PDF Full-text (3297 KB) | HTML Full-text | XML Full-text
Abstract
The authors wish to make the following correction to this paper [1]. Due to mislabeling, the following figures: [...] Full article
(This article belongs to the Section Bioorganic Chemistry)
Figures

Figure 1

Journal Contact

MDPI AG
Molecules Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
E-Mail: 
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Molecules Edit a special issue Review for Molecules
logo
loading...
Back to Top