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Molecules, Volume 19, Issue 7 (July 2014), Pages 8707-10669

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Open AccessArticle Determination of Volatile Organic Compounds (VOCs) from Wrapping Films and Wrapped PDO Italian Cheeses by Using HS-SPME and GC/MS
Molecules 2014, 19(7), 8707-8724; doi:10.3390/molecules19078707
Received: 30 April 2014 / Revised: 18 June 2014 / Accepted: 19 June 2014 / Published: 25 June 2014
Cited by 2 | PDF Full-text (709 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nowadays food wrapping assures attractive presentation and simplifies self-service shopping. Polyvinylchloride (PVC)- and polyethylene (PE)-based cling-films are widely used worldwide for wrapping cheeses. For this purpose, films used in retail possess suitable technical properties such as clinginess and unrolling capacity, that are achieved
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Nowadays food wrapping assures attractive presentation and simplifies self-service shopping. Polyvinylchloride (PVC)- and polyethylene (PE)-based cling-films are widely used worldwide for wrapping cheeses. For this purpose, films used in retail possess suitable technical properties such as clinginess and unrolling capacity, that are achieved by using specific plasticizers during their manufacturing process. In the present study, the main VOCs of three cling-films (either PVC-based or PE-based) for retail use were characterized by means of Solid-Phase Micro-Extraction and GC/MS. In addition, the effects of cling film type and contact time on the migration of VOCs from the films to four different PDO Italian cheeses during cold storage under light or dark were also investigated. Among the VOCs isolated from cling-films, PVC released 2-ethylhexanol and triacetin. These compounds can likely be considered as a “non-intentionally added substance”. These same compounds were also detected in cheeses wrapped in PVC films with the highest concentration found after 20 days storage. The PE cling-film was shown to possess a simpler VOC profile, lacking some molecules peculiar to PVC films. The same conclusions can be drawn for cheeses wrapped in the PE cling-film. Other VOCs found in wrapped cheeses were likely to have been released either by direct transfer from the materials used for the manufacture of cling-films or from contamination of the films. Overall, HS-SPME is shown to be a rapid and solvent free technique to screen the VOCs profile of cling-films, and to detect VOCs migration from cling-films to cheese under real retail storage conditions. Full article
(This article belongs to the Special Issue Microextraction)
Open AccessArticle Synthesis, Anti-microbial and Molecular Docking Studies of Quinazolin-4(3H)-one Derivatives
Molecules 2014, 19(7), 8725-8739; doi:10.3390/molecules19078725
Received: 15 April 2014 / Revised: 6 June 2014 / Accepted: 9 June 2014 / Published: 25 June 2014
Cited by 7 | PDF Full-text (1029 KB) | HTML Full-text | XML Full-text
Abstract
In this work, synthesis, antimicrobial activities and molecular docking studies of some new series of substituted quinazolinone 2ah and 3ad were described. Starting form 2-aminobenzamide derivatives 1, a new series of quinazolinone derivatives has been synthesized, in high
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In this work, synthesis, antimicrobial activities and molecular docking studies of some new series of substituted quinazolinone 2ah and 3ad were described. Starting form 2-aminobenzamide derivatives 1, a new series of quinazolinone derivatives has been synthesized, in high yields, assisted by microwave and classical methods. Some of these substituted quinazolinones were tested for their antimicrobial activity against Gram-negative bacteria (Pseudomonas aeruginosa and Esherichia coli) and Gram-positive bacteria (Staphylococcus aureus, and Bacillus subtilis), and anti-fungal activity against (Aspergillus fumigatus, Saccharomyces cervevisiae, and Candida albicans) using agar well diffusion method. Among the prepared products, 3-benzyl-2-(4-chlorophenyl)quinazolin-4(3H)-one (3a) was found to exhibits the most potent in vitro anti-microbial activity with MICs of 25.6 ± 0.5, 24.3 ± 0.4, 30.1 ± 0.6, and 25.1 ± 0.5 µg/mL against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Esherichia coli, respectively. Compound 3a was found to exhibits the most potent in vitro anti-fungal activity with MICs of 18.3 ± 0.6, 23.1 ± 0.4, and 26.1 ± 0. 5 µg/mL against Aspergillus fumigatus, Saccharomyces cervevisiae, and Candidaal bicans, respectively. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle In Vitro and in Vivo Antitumor Activity of Scutebarbatine A on Human Lung Carcinoma A549 Cell Lines
Molecules 2014, 19(7), 8740-8751; doi:10.3390/molecules19078740
Received: 10 May 2014 / Revised: 30 May 2014 / Accepted: 16 June 2014 / Published: 25 June 2014
Cited by 7 | PDF Full-text (366 KB) | HTML Full-text | XML Full-text
Abstract
During our systematic study on the anticancer activities of Scutellaria barbata, scutebarbatine A (SBT-A), one of the major alkaloids in S. barbata, was found to have antitumor effects on A549 cells. Thus, we designed the present study to investigate in detail
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During our systematic study on the anticancer activities of Scutellaria barbata, scutebarbatine A (SBT-A), one of the major alkaloids in S. barbata, was found to have antitumor effects on A549 cells. Thus, we designed the present study to investigate in detail the antitumor effects of SBT-A. The cytotoxic effect of SBT-A on A549 in vitro were determined by an MTT assay and evaluated by IC50 values. Furthermore, results of Hoechst 33258 and Annexin V/PI staining assays demonstrated that SBT-A had significant antitumor effects on A549 cells via apoptosis, in a concentration-dependent manner. What’s more, the mechanism was explored by western blotting, and our study revealed that SBT-A can up-regulate the expressions of cytochrome c, caspase-3 and 9, and down-regulate the levels of Bcl-2 in A549 cells. Finally, the antitumor effects of SBT-A were evaluated in vivo by using transplanted tumor nude mice, and the results confirmed that SBT-A has a notable antitumor effect on A549 cancer via mitochondria-mediated apoptosis. Collectively, our results demonstrated that SBT-A showed significant antitumor effects on A549 cells in vivo and in vitro via mitochondria-mediated apoptosis by up-regulating expressions of caspase-3 and 9, and down-regulating Bcl-2. Full article
Open AccessArticle Preparative Separation of Alkaloids from Picrasma quassioides (D. Don) Benn. by Conventional and pH-Zone-Refining Countercurrent Chromatography
Molecules 2014, 19(7), 8752-8761; doi:10.3390/molecules19078752
Received: 22 May 2014 / Revised: 12 June 2014 / Accepted: 18 June 2014 / Published: 25 June 2014
Cited by 6 | PDF Full-text (425 KB) | HTML Full-text | XML Full-text
Abstract
Two high-speed countercurrent chromatography (HSCCC) modes were compared by separation of major alkaloids from crude extract of Picrasma quassioides. The conventional HSCCC separation was performed with a two-phase solvent system composed of petroleum ether–ethyl acetate–methanol–water (5:5:4.5:5.5, v/v/v/v) with 200 mg loading. pH-Zone-refining
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Two high-speed countercurrent chromatography (HSCCC) modes were compared by separation of major alkaloids from crude extract of Picrasma quassioides. The conventional HSCCC separation was performed with a two-phase solvent system composed of petroleum ether–ethyl acetate–methanol–water (5:5:4.5:5.5, v/v/v/v) with 200 mg loading. pH-Zone-refining CCC was performed with two-phase solvent system composed of petroleum ether–ethyl acetate–n-butanol–water (3:2:7:9, v/v/v/v) where triethylamine (10 mM) was added to the upper organic stationary phase and hydrochloric acid (5 mM) was added to the lower aqueous phase with 2 g loading. From 2 g of crude extract, 87 mg of 5-methoxycanthin-6-one (a), 38 mg of 1-methoxy-β-carboline (b), 134 mg of 1-ethyl-4,8-dimethoxy-β-carboline (c), 74 mg of 1-ethoxycarbonyl-β-carboline (d), 56 mg of 1-vinyl-4,8-dimethoxy-β-carboline (e) and 26 mg of 1-vinyl-4-dimethoxy-β-carboline (f) were obtained with purities of over 97.0%. The results indicated that pH-zone-refining CCC is an excellent separations tool at the multigram level. Full article
Open AccessArticle Cytotoxic Aporphine Alkaloids from Leaves and Twigs of Pseuduvaria trimera (Craib)
Molecules 2014, 19(7), 8762-8772; doi:10.3390/molecules19078762
Received: 21 May 2014 / Revised: 17 June 2014 / Accepted: 19 June 2014 / Published: 25 June 2014
PDF Full-text (334 KB) | HTML Full-text | XML Full-text
Abstract
From ethyl acetate-methanol extracts of leaves and twigs of Pseuduvaria trimera a new aporphine alkaloid; 8-hydroxy-1,4,5-trimethoxy-7-oxoaporphine or 8-hydroxyartabonatine C (1) was isolated, together with the known 1,2,3-trimethoxy-4,5-dioxo-6a,7-dehydroaporphine (ouregidione, 2). Their structures were elucidated by a combination of spectral methods; mainly
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From ethyl acetate-methanol extracts of leaves and twigs of Pseuduvaria trimera a new aporphine alkaloid; 8-hydroxy-1,4,5-trimethoxy-7-oxoaporphine or 8-hydroxyartabonatine C (1) was isolated, together with the known 1,2,3-trimethoxy-4,5-dioxo-6a,7-dehydroaporphine (ouregidione, 2). Their structures were elucidated by a combination of spectral methods; mainly 2D NMR; IR and MS. Compounds 1 and 2 exhibited cytotoxic activity with IC50 values of 26.36 ± 5.18 μM and 12.88 ± 2.49 μM, respectively, for human hepatocellular carcinoma HepG2 cells, and 64.75 ± 4.45 and 67.06 ± 3.5 μM, respectively, for human breast cancer MDA-MB231 cells. Both compounds displayed anti-cancer activity but less than that of doxorubicin; a conventional chemotherapeutic drug, the IC50 levels of which were 2.21 ± 1.72 and 1.83 ± 0.09 μM for HepG2 and MDA-MB231 cells, respectively. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle Two-Step Separation of Nostotrebin 6 from Cultivated Soil Cyanobacterium (Nostoc sp.) by High Performance Countercurrent Chromatography
Molecules 2014, 19(7), 8773-8787; doi:10.3390/molecules19078773
Received: 7 May 2014 / Revised: 17 June 2014 / Accepted: 18 June 2014 / Published: 25 June 2014
Cited by 2 | PDF Full-text (676 KB) | HTML Full-text | XML Full-text
Abstract
High performance countercurrent chromatography (HPCCC) was successfully applied for the separation of nostotrebin 6 from cultivated soil cyanobacteria in a two-step operation. A two-phase solvent system composed of n-hexane–ethyl acetate–methanol–water (4:5:4:5, v/v/v/v) was employed for the HPCCC separation. In the first-step operation,
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High performance countercurrent chromatography (HPCCC) was successfully applied for the separation of nostotrebin 6 from cultivated soil cyanobacteria in a two-step operation. A two-phase solvent system composed of n-hexane–ethyl acetate–methanol–water (4:5:4:5, v/v/v/v) was employed for the HPCCC separation. In the first-step operation, its neutral upper phase was used as stationary phase and its basic lower phase (1% NH3 in lower phase) was employed as mobile phase at a flow rate of 1 mL/min. In the second operation step, its neutral upper phase was used as stationary phase, whereas both its neutral lower phase and basic lower phase were employed as mobile phase with a linear gradient elution at a flow rate of 0.8 mL/min. The revolution speed and temperature of the separation column were 1,000 rpm and 30 °C, respectively. Using HPCCC followed by clean-up on Sephadex LH-20 gel, 4 mg of nostotrebin 6 with a purity of 99% as determined by HPLC/DAD-ESI-HRMS was obtained from 100 mg of crude extract. The chemical identity of the isolated compound was confirmed by comparing its spectroscopic data (UV, ESI-HRMS, ESI-HRMS2) with those of an authentic standard and data available in the literature. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Phenoxyacetohydrazide Schiff Bases: β-Glucuronidase Inhibitors
Molecules 2014, 19(7), 8788-8802; doi:10.3390/molecules19078788
Received: 7 May 2014 / Revised: 6 June 2014 / Accepted: 11 June 2014 / Published: 25 June 2014
Cited by 16 | PDF Full-text (332 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phenoxyacetohydrazide Schiff base analogs 128 have been synthesized and their in vitro β-glucouoronidase inhibition potential studied. Compounds 1 (IC50 = 9.20 ± 0.32 µM), 5 (IC50 = 9.47 ± 0.16 µM), 7 (IC50 = 14.7 ± 0.19
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Phenoxyacetohydrazide Schiff base analogs 128 have been synthesized and their in vitro β-glucouoronidase inhibition potential studied. Compounds 1 (IC50 = 9.20 ± 0.32 µM), 5 (IC50 = 9.47 ± 0.16 µM), 7 (IC50 = 14.7 ± 0.19 µM), 8 (IC50 = 15.4 ± 1.56 µM), 11 (IC50 = 19.6 ± 0.62 µM), 12 (IC50 = 30.7 ± 1.49 µM), 15 (IC50 = 12.0 ± 0.16 µM), 21 (IC50 = 13.7 ± 0.40 µM) and 22 (IC50 = 22.0 ± 0.14 µM) showed promising β-glucuronidase inhibition activity, better than the standard (D-saccharic acid-1,4-lactone, IC50 = 48.4 ± 1.25 µM). Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synthesis and Cytotoxicity Evaluation of Naphthalimide Derived N-Mustards
Molecules 2014, 19(7), 8803-8819; doi:10.3390/molecules19078803
Received: 21 May 2014 / Revised: 10 June 2014 / Accepted: 17 June 2014 / Published: 25 June 2014
Cited by 1 | PDF Full-text (1097 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of N-mustards, which was conjugated to mono- or bis-naphthalimides with a flexible amine link, were synthesized and evaluated for cytotoxicity against five cancer cell lines (HCT-116, PC-3, U87 MG, Hep G2 and SK-OV-3). Several compounds displayed better activities than the
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A series of N-mustards, which was conjugated to mono- or bis-naphthalimides with a flexible amine link, were synthesized and evaluated for cytotoxicity against five cancer cell lines (HCT-116, PC-3, U87 MG, Hep G2 and SK-OV-3). Several compounds displayed better activities than the control compound amonafide. Further evaluations by fluorescence spectroscopy studies and DNA-interstrand cross-linking assays revealed that the derivatives showed both alkylating and intercalating properties. Among the derivatives, the bis-naphthalimide N-mustard derivative 11b was found to exhibit the highest cytotoxic activity and DNA cross-linking ability. Both 11b and 7b induce HCT-116 cell apoptosis by S phase arrest. Full article
Open AccessArticle Regulatory Effects of Fisetin on Microglial Activation
Molecules 2014, 19(7), 8820-8839; doi:10.3390/molecules19078820
Received: 30 April 2014 / Revised: 13 June 2014 / Accepted: 18 June 2014 / Published: 26 June 2014
Cited by 11 | PDF Full-text (2770 KB) | HTML Full-text | XML Full-text
Abstract
Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant
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Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant properties. In the present study, treatment with fisetin inhibited microglial cell migration and ROS (reactive oxygen species) production. Treatment with fisetin also effectively inhibited LPS plus IFN-γ-induced nitric oxide (NO) production, and inducible nitric oxide synthase (iNOS) expression in microglial cells. Furthermore, fisetin also reduced expressions of iNOS and NO by stimulation of peptidoglycan, the major component of the Gram-positive bacterium cell wall. Fisetin also inhibited the enhancement of LPS/IFN-γ- or peptidoglycan-induced inflammatory mediator IL (interlukin)-1 β expression. Besides the antioxidative and anti-inflammatory effects of fisetin, our study also elucidates the manner in fisetin-induced an endogenous anti-oxidative enzyme HO (heme oxygenase)-1 expression. Moreover, the regulatory molecular mechanism of fisetin-induced HO-1 expression operates through the PI-3 kinase/AKT and p38 signaling pathways in microglia. Notably, fisetin also significantly attenuated inflammation-related microglial activation and coordination deficit in mice in vivo. These findings suggest that fisetin may be a candidate agent for the development of therapies for inflammation-related neurodegenerative diseases. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
Open AccessCommunication A New Xanthone from Moutabea guianensis Aubl
Molecules 2014, 19(7), 8885-8889; doi:10.3390/molecules19078885
Received: 22 May 2014 / Revised: 18 June 2014 / Accepted: 19 June 2014 / Published: 26 June 2014
Cited by 1 | PDF Full-text (192 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The ethyl acetate extract of the roots of Moutabea guianensis gave 1,6-dihydroxy-4,7,8-trimethoxy-9H-xanthen-9-one (1), a new xanthone. The isolation was accomplished by column chromatography on silica gel and the structural elucidation of this compound was established by spectroscopic analyses including
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The ethyl acetate extract of the roots of Moutabea guianensis gave 1,6-dihydroxy-4,7,8-trimethoxy-9H-xanthen-9-one (1), a new xanthone. The isolation was accomplished by column chromatography on silica gel and the structural elucidation of this compound was established by spectroscopic analyses including 1D and 2D NMR and HRESIMS. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Using MUSIC and CC(CO)NH for Backbone Assignment of Two Medium-Sized Proteins Not Fully Accessible to Standard 3D NMR
Molecules 2014, 19(7), 8890-8903; doi:10.3390/molecules19078890
Received: 5 May 2014 / Revised: 5 June 2014 / Accepted: 12 June 2014 / Published: 26 June 2014
Cited by 1 | PDF Full-text (306 KB) | HTML Full-text | XML Full-text
Abstract
The backbone assignment of medium-sized proteins is rarely as straightforward as that of small proteins, and thus often requires creative solutions. Here, we describe the application of a combination of standard 3D heteronuclear methods with CC(CO)NH and a variety of MUltiplicity Selective In-phase
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The backbone assignment of medium-sized proteins is rarely as straightforward as that of small proteins, and thus often requires creative solutions. Here, we describe the application of a combination of standard 3D heteronuclear methods with CC(CO)NH and a variety of MUltiplicity Selective In-phase Coherence transfer (MUSIC) experiments. Both CC(CO)NH and MUSIC are, in theory, very powerful methods for the backbone assignment of proteins. Due to low sensitivity, their use has usually been linked to small proteins only. However, we found that combining CC(CO)NH and MUSIC experiments simplified the assignment of two challenging medium-sized proteins of 13 and 19.5 kDa, respectively. These methods are to some extent complementary to each other: CC(CO)NH acquired with a long isotropic mixing time can identify amino acids with large aliphatic side chains. Whereas the most sensitive MUSIC experiments identify amino acid types that cannot be detected by CC(CO)NH, comprising the residues with acid and amide groups, and aromatic rings in their side chains. Together these methods provide a means of identifying the majority of peaks in the 2D 15N HSQC spectrum which simplifies the backbone assignment work even for proteins, e.g., small kinases, whose standard spectra resulted in little spectral resolution and low signal intensities. Full article
(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)
Open AccessArticle Mulberry Fruit Extract Protects Pancreatic β-Cells against Hydrogen Peroxide-Induced Apoptosis via Antioxidative Activity
Molecules 2014, 19(7), 8904-8915; doi:10.3390/molecules19078904
Received: 20 May 2014 / Revised: 7 June 2014 / Accepted: 18 June 2014 / Published: 26 June 2014
Cited by 6 | PDF Full-text (1193 KB) | HTML Full-text | XML Full-text
Abstract
Among the many environmental stresses, excessive production of reactive oxygen species (ROS) and the ensuring oxidative stress are known to cause significant cellular damage. This has clinical implications in the onset of type 1 diabetes, which is triggered by the destruction of pancreatic
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Among the many environmental stresses, excessive production of reactive oxygen species (ROS) and the ensuring oxidative stress are known to cause significant cellular damage. This has clinical implications in the onset of type 1 diabetes, which is triggered by the destruction of pancreatic β-cells and is associated with oxidative stress. In this study, we investigated the protective and antioxidative effects of mulberry extract (ME) in insulin-producing pancreatic β-cells. We found that ME protects pancreatic β-cells against hydrogen peroxide (H2O2)-induced oxidative stress and the associated apoptotic cell death. ME treatment significantly reduced the levels of H2O2-induced 2-diphenyl-1-picrylhydrazyl (DPPH) radicals, and lipid peroxidation and intracellular ROS accumulation. In addition, ME inhibited DNA condensation and/or fragmentation induced by H2O2. These results suggest that ME protects pancreatic β-cells against hydrogen peroxide-induced oxidative stress. Full article
Open AccessArticle Synthesis and Evaluation of 2,4-Disubstituted Quinazoline Derivatives with Potent Anti-Angiogenesis Activities
Molecules 2014, 19(7), 8916-8932; doi:10.3390/molecules19078916
Received: 23 April 2014 / Revised: 15 June 2014 / Accepted: 18 June 2014 / Published: 26 June 2014
Cited by 5 | PDF Full-text (947 KB) | HTML Full-text | XML Full-text
Abstract
A series of 2,4-disubstituted quinazoline derivatives were designed and synthesized. The biological results showed that most of quinazoline derivatives exhibited potent antiproliferative activities against a panel of three tumor cell lines and a good inhibitory effect against the adhesion and migration of human
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A series of 2,4-disubstituted quinazoline derivatives were designed and synthesized. The biological results showed that most of quinazoline derivatives exhibited potent antiproliferative activities against a panel of three tumor cell lines and a good inhibitory effect against the adhesion and migration of human umbilical vein endothelial cells (HUVECs). Among these compounds, 11d was the most potent agent, that also exhibited the highest anti-angiogenesis activities in the chick embryo chorioallantoic membrane (CAM) assay. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Flavonoids with M1 Muscarinic Acetylcholine Receptor Binding Activity
Molecules 2014, 19(7), 8933-8948; doi:10.3390/molecules19078933
Received: 27 February 2014 / Revised: 20 June 2014 / Accepted: 23 June 2014 / Published: 27 June 2014
PDF Full-text (4490 KB) | HTML Full-text | XML Full-text
Abstract
Muscarinic acetylcholine receptor-active compounds have potential for the treatment of Alzheimer’s disease. In this study, a series of natural and synthetic flavones and flavonols was assayed in vitro for their ability to inhibit radioligand binding at human cloned M1 muscarinic receptors. Several
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Muscarinic acetylcholine receptor-active compounds have potential for the treatment of Alzheimer’s disease. In this study, a series of natural and synthetic flavones and flavonols was assayed in vitro for their ability to inhibit radioligand binding at human cloned M1 muscarinic receptors. Several compounds were found to possess competitive binding affinity (Ki = 40–110 µM), comparable to that of acetylcholine (Ki = 59 µM). Despite the fact that these compounds lack a positively-charged ammonium group under physiological conditions, molecular modelling studies suggested that they bind to the orthosteric site of the receptor, mainly through non-polar interactions. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Discovery of Gramine Derivatives That Inhibit the Early Stage of EV71 Replication in Vitro
Molecules 2014, 19(7), 8949-8964; doi:10.3390/molecules19078949
Received: 14 April 2014 / Revised: 19 June 2014 / Accepted: 20 June 2014 / Published: 27 June 2014
Cited by 3 | PDF Full-text (658 KB) | HTML Full-text | XML Full-text
Abstract
Enterovirus 71 (EV71) is a notable causative agent of hand, foot, and mouth disease in children, which is associated with an increased incidence of severe neurological disease and death, yet there is no specific treatment or vaccine for EV71 infections. In this study,
[...] Read more.
Enterovirus 71 (EV71) is a notable causative agent of hand, foot, and mouth disease in children, which is associated with an increased incidence of severe neurological disease and death, yet there is no specific treatment or vaccine for EV71 infections. In this study, the antiviral activity of gramine and 21 gramine derivatives against EV71 was investigated in cell-based assays. Eighteen derivatives displayed some degree of inhibitory effects against EV71, in that they could effectively inhibit virus-induced cytopathic effects (CPEs), but the anti-EV71 activity of the lead compound gramine was not observed. Studies on the preliminary modes of action showed that these compounds functioned by targeting the early stage of the EV71 lifecycle after viral entry, rather than inactivating the virus directly, inhibiting virus adsorption or affecting viral release from the cells. Among these derivatives, one (compound 4s) containing pyridine and benzothiazole units showed the most potency against EV71. Further studies demonstrated that derivative 4s could profoundly inhibit viral RNA replication, protein synthesis, and virus-induced apoptosis in RD cells. These results indicate that derivative 4s might be a feasible therapeutic agent against EV71 infection and that these gramine derivatives may provide promising lead scaffolds for the further design and synthesis of potential antiviral agents. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Volatile Organic Compound Emissions from Different Stages of Cananga odorata Flower Development
Molecules 2014, 19(7), 8965-8980; doi:10.3390/molecules19078965
Received: 14 April 2014 / Revised: 15 June 2014 / Accepted: 17 June 2014 / Published: 27 June 2014
Cited by 2 | PDF Full-text (696 KB) | HTML Full-text | XML Full-text
Abstract
Headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) was used to identify the volatile organic compounds (VOCs) of the different flower development stages of Cananga odorata for the evaluation of floral volatile polymorphism as a basis to determine the best time of harvest. Electronic nose
[...] Read more.
Headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) was used to identify the volatile organic compounds (VOCs) of the different flower development stages of Cananga odorata for the evaluation of floral volatile polymorphism as a basis to determine the best time of harvest. Electronic nose results, coupled with discriminant factor analysis, suggested that emitted odors varied in different C. odorata flower development stages, including the bud, display-petal, initial-flowering, full-flowering, end-flowering, wilted-flower, and dried flower stages. The first two discriminant factors explained 97.52% of total system variance. Ninety-two compounds were detected over the flower life, and the mean Bray–Curtis similarity value was 52.45% among different flower development stages. A high level of volatile polymorphism was observed during flower development. The VOCs were largely grouped as hydrocarbons, esters, alcohols, aldehydes, phenols, acids, ketones, and ethers, and the main compound was β-caryophyllene (15.05%–33.30%). Other identified compounds were β-cubebene, D-germacrene, benzyl benzoate, and α-cubebene. Moreover, large numbers of VOCs were detected at intermediate times of flower development, and more hydrocarbons, esters, and alcohols were identified in the full-flowering stage. The full-flowering stage may be the most suitable period for C. odorata flower harvest. Full article
Open AccessArticle MAPLE Fabricated Fe3O4@Cinnamomum verum Antimicrobial Surfaces for Improved Gastrostomy Tubes
Molecules 2014, 19(7), 8981-8994; doi:10.3390/molecules19078981
Received: 20 May 2014 / Revised: 14 June 2014 / Accepted: 23 June 2014 / Published: 27 June 2014
Cited by 7 | PDF Full-text (1996 KB) | HTML Full-text | XML Full-text
Abstract
Cinnamomum verum-functionalized Fe3O4 nanoparticles of 9.4 nm in size were laser transferred by matrix assisted pulsed laser evaporation (MAPLE) technique onto gastrostomy tubes (G-tubes) for antibacterial activity evaluation toward Gram positive and Gram negative microbial colonization. X-ray diffraction analysis
[...] Read more.
Cinnamomum verum-functionalized Fe3O4 nanoparticles of 9.4 nm in size were laser transferred by matrix assisted pulsed laser evaporation (MAPLE) technique onto gastrostomy tubes (G-tubes) for antibacterial activity evaluation toward Gram positive and Gram negative microbial colonization. X-ray diffraction analysis of the nanoparticle powder showed a polycrystalline magnetite structure, whereas infrared mapping confirmed the integrity of C. verum (CV) functional groups after the laser transfer. The specific topography of the deposited films involved a uniform thin coating together with several aggregates of bio-functionalized magnetite particles covering the G-tubes. Cytotoxicity assays showed an increase of the G-tube surface biocompatibility after Fe3O4@CV treatment, allowing a normal development of endothelial cells up to five days of incubation. Microbiological assays on nanoparticle-modified G-tube surfaces have proved an improvement of anti-adherent properties, significantly reducing both Gram negative and Gram positive bacteria colonization. Full article
(This article belongs to the Special Issue Bio and Nanomaterials Based on Fe3O4)
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Open AccessArticle Ultrasonic Extraction of Antioxidants from Chinese Sumac (Rhus typhina L.) Fruit Using Response Surface Methodology and Their Characterization
Molecules 2014, 19(7), 9019-9032; doi:10.3390/molecules19079019
Received: 23 April 2014 / Revised: 9 June 2014 / Accepted: 23 June 2014 / Published: 27 June 2014
Cited by 7 | PDF Full-text (383 KB) | HTML Full-text | XML Full-text
Abstract
For the first time, response surface methodology (RSM) using a Box-Behnken Design (BBD) was employed to optimize the conditions for ultrasonic assisted extraction (UAE) of antioxidants from Chinese sumac (Rhus typhina L.) fruits. Initially, influencing factors such as liquid-solid ratio, duration of
[...] Read more.
For the first time, response surface methodology (RSM) using a Box-Behnken Design (BBD) was employed to optimize the conditions for ultrasonic assisted extraction (UAE) of antioxidants from Chinese sumac (Rhus typhina L.) fruits. Initially, influencing factors such as liquid-solid ratio, duration of ultrasonic assisted extraction, pH range, extraction temperature and ethanol concentration were identified using single-factor experiments. Then, with respect to the three most significant influencing factors, the extraction process focusing on the DPPH· scavenging capacity of antioxidants was optimized using RSM. Results showed that the optimal conditions for antioxidant extraction were 13.03:1 (mL/g) liquid-solid ratio, 16.86 min extraction time and 40.51% (v/v) ethanol, and the desirability was 0.681. The UPLC-ESI-MS analysis results revealed eleven kinds of phenolic compounds, including four major rare anthocyanins, among the antioxidants. All these results suggest that UAE is efficient at extracting antioxidants and has the potential to be used in industry for this purpose. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Comparison of the Apoptotic Effects of Supercritical Fluid Extracts of Antrodia cinnamomea Mycelia on Hepatocellular Carcinoma Cells
Molecules 2014, 19(7), 9033-9050; doi:10.3390/molecules19079033
Received: 30 April 2014 / Revised: 19 June 2014 / Accepted: 19 June 2014 / Published: 27 June 2014
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Abstract
Antrodia cinnamomea (AC) has been widely used as a folk medicine in the prevention and treatment of liver diseases, such as hepatitis, hepatic fibrosis, and hepatocellular carcinoma. Previous studies have indicated that triterpenoids and benzenoids show selective cytotoxicity against human hepatoma cell lines.
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Antrodia cinnamomea (AC) has been widely used as a folk medicine in the prevention and treatment of liver diseases, such as hepatitis, hepatic fibrosis, and hepatocellular carcinoma. Previous studies have indicated that triterpenoids and benzenoids show selective cytotoxicity against human hepatoma cell lines. The aim of the study was to compare the triterpenoid content of extract and the extract-induced cytotoxicity in HepG2 cells from mycelia extracts of solid state cultured AC obtained by supercritical fluid extraction (SFE) and the conventional solvent extraction method. SFE with CO2 mixed with a constant amount of ethanol co-solvent (10% of CO2 volume) applied at different temperatures and pressures (40, 60 and 80 °C and, 20.7, 27.6 and 34.5 Mpa) was also compared in the study. Although the extraction yield of triterpenoids (59.7 mg/g) under the optimal extraction conditions of 34.5 MPa (5000 psi)/60 °C (designated as sample S-5000-60) was equivalent to the extraction yield using conventional liquid solvent extraction with ethanol (ETOH-E) at room temperature (60.33 mg/g), the cytotoxicity of the former against the proliferation of HepG2 cell line measured as the inhibition of 50% of cell growth activity (IC50) at dosages of 116.15, 57.82 and 43.96 µg/mL was superior to that of EtOH-E at 131.09, 80.04 and 48.30 µg/mL at 24, 48 and 72 h, respectively. Additionally, we further proved that the apoptotic effect of S-5000-60 presented a higher apoptosis ratio (21.5%) than ETOH-E (10.5%) according to annexin V-FITC and propidium iodide double staining assay results. The high affinity and selectivity of SFE on bioactive components resulted in a higher extraction efficiency than conventional solvent extraction. The chemical profile of the obtained extracts from solid state cultivated mycelium of AC was also determined by high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS), whereby three benzenoids and four triterpenoids were found for the first time in SFE extracts with 4,7-dimethoxy-5-methyl-l,3-benzodioxole (5.78 mg/g) being the most abundant component, followed by 2,4-dimethoxy-6-methylbenzene-1,3-diol (3.03 mg/g) and dehydroeburicoic acid (0.40 mg/g). Full article
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Open AccessArticle Targeted Lipid Analysis of Haemolytic Mycelial Extracts of Aspergillus niger
Molecules 2014, 19(7), 9051-9069; doi:10.3390/molecules19079051
Received: 28 February 2014 / Revised: 19 June 2014 / Accepted: 23 June 2014 / Published: 30 June 2014
Cited by 1 | PDF Full-text (1144 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ethanolic extracts of mycelia from Aspergillus niger (strain N402) grown in liquid media were observed to have haemolytic activity on bovine erythrocytes. This haemolytic activity decreased significantly during the time of growth (1–3 days). Moreover, when A. niger was grown on carbon-deprived medium,
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Ethanolic extracts of mycelia from Aspergillus niger (strain N402) grown in liquid media were observed to have haemolytic activity on bovine erythrocytes. This haemolytic activity decreased significantly during the time of growth (1–3 days). Moreover, when A. niger was grown on carbon-deprived medium, the efficiency of this haemolytic activity in the ethanolic extracts was much lower than when grown in carbon-enriched medium, and became almost undetectable after 3 days of growth in carbon-deprived medium. The lipid composition of these ethanolic extracts was analysed by liquid chromatography–electrospray ionisation tandem mass spectrometry. This haemolytic activity can be mainly linked to the relative levels of the molar ratios of the unsaturated fatty acids and lysophosphatidylcholines. Full article
(This article belongs to the Special Issue Fatty Acids)
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Open AccessArticle Characterization of Intact Neo-Glycoproteins by Hydrophilic Interaction Liquid Chromatography
Molecules 2014, 19(7), 9070-9088; doi:10.3390/molecules19079070
Received: 12 May 2014 / Revised: 18 June 2014 / Accepted: 19 June 2014 / Published: 30 June 2014
Cited by 5 | PDF Full-text (2269 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, an HPLC HILIC-UV method was developed for the analysis of intact neo-glycoproteins. During method development the experimental conditions evaluated involved different HILIC columns (TSKgel Amide-80 and ZIC-pHILIC), and water-acetonitrile mixtures containing various types of acids and salts.
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In this study, an HPLC HILIC-UV method was developed for the analysis of intact neo-glycoproteins. During method development the experimental conditions evaluated involved different HILIC columns (TSKgel Amide-80 and ZIC-pHILIC), and water-acetonitrile mixtures containing various types of acids and salts. The final selected method was based on a TSKgel Amide-80 column and a mobile phase composed of acetonitrile and water both containing 10 mM HClO4. The influence of temperature and sample preparation on the chromatographic performances of the HILIC method was also investigated. The method was applied to the separation of neo-glycoproteins prepared starting from the model protein RNase A by chemical conjugation of different glycans. Using the method here reported it was possible to monitor by UV detection the glycosylation reaction and assess the distribution of neo-glycoprotein isoforms without laborious sample workup prior to analysis. Full article
(This article belongs to the Special Issue Oligosaccharides and Glyco-Conjugates)
Open AccessArticle Cholesteryl-Modification of a Glucomannan from Bletilla striata and Its Hydrogel Properties
Molecules 2014, 19(7), 9089-9100; doi:10.3390/molecules19079089
Received: 25 May 2014 / Revised: 21 June 2014 / Accepted: 24 June 2014 / Published: 30 June 2014
Cited by 4 | PDF Full-text (671 KB) | HTML Full-text | XML Full-text
Abstract
A glucomannan-type polysaccharide, named BSP, was obtained from the tubers of Bletilla striata by ultrasonic-assisted extraction, ethanol precipitation, deproteination and gel-permeation chromatography. HPLC analysis revealed that BSP contained mannose and glucose in the molar ratio of 3.5:1. Its molecular weight (Mw) was estimated
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A glucomannan-type polysaccharide, named BSP, was obtained from the tubers of Bletilla striata by ultrasonic-assisted extraction, ethanol precipitation, deproteination and gel-permeation chromatography. HPLC analysis revealed that BSP contained mannose and glucose in the molar ratio of 3.5:1. Its molecular weight (Mw) was estimated to be 20 kDa. Methylation analysis, FT-IR and NMR analyses indicated that BSP consisted of (1→4)-linked β-D-glucopyranosyl residues and (1→4)-linked β-D-mannopyranosyl residues. Cholesteryl succinate was linked to BSP to make it more amphiphilic and the degree of substitution of cholesteryl succinate-BSP was 3.2%. The critical micelle concentration of modified BSP was 0.001 mg/mL, suggesting it could self-assemble into nanoparticles in aqueous solution. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Bioactive Profiles, Antioxidant Activities, Nitrite Scavenging Capacities and Protective Effects on H2O2-Injured PC12 Cells of Glycyrrhiza Glabra L. Leaf and Root Extracts
Molecules 2014, 19(7), 9101-9113; doi:10.3390/molecules19079101
Received: 15 May 2014 / Revised: 24 June 2014 / Accepted: 25 June 2014 / Published: 30 June 2014
Cited by 6 | PDF Full-text (572 KB) | HTML Full-text | XML Full-text
Abstract
This study compared the total flavonoid content of Glycyrrhiza glabra L. leaf and root extracts. Results suggested that the total flavonoid content in the leaf extract was obviously higher than that in the root extract. Pinocembrin, the main compound in the leaf extract
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This study compared the total flavonoid content of Glycyrrhiza glabra L. leaf and root extracts. Results suggested that the total flavonoid content in the leaf extract was obviously higher than that in the root extract. Pinocembrin, the main compound in the leaf extract after purification by column chromatography, showed good antioxidant activity and nitrite scavenging capacity, but moderate inhibitory effect on mushroom tyrosinase. Liquiritin was the main compound in root extract and possessed strong inhibitory effect on mushroom tyrosinase. Both compounds exhibited significant protection effect on H2O2-injured PC12 cells at a low concentration. These results indicate that Glycyrrhiza glabra L. leaf is potential as an important raw material for functional food. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Investigation of the Flexibility of Protein Kinases Implicated in the Pathology of Alzheimer’s Disease
Molecules 2014, 19(7), 9134-9159; doi:10.3390/molecules19079134
Received: 4 May 2014 / Revised: 16 June 2014 / Accepted: 19 June 2014 / Published: 30 June 2014
Cited by 2 | PDF Full-text (7383 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The pathological characteristics of Alzheimer’s Disease (AD) have been linked to the activity of three particular kinases—Glycogen Synthase Kinase 3β (GSK3β), Cyclin-Dependent Kinase 5 (CDK5) and Extracellular-signal Regulated Kinase 2 (ERK2). As a consequence, the design of selective, potent and drug-like inhibitors of
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The pathological characteristics of Alzheimer’s Disease (AD) have been linked to the activity of three particular kinases—Glycogen Synthase Kinase 3β (GSK3β), Cyclin-Dependent Kinase 5 (CDK5) and Extracellular-signal Regulated Kinase 2 (ERK2). As a consequence, the design of selective, potent and drug-like inhibitors of these kinases is of particular interest. Structure-based design methods are well-established in the development of kinase inhibitors. However, progress in this field is limited by the difficulty in obtaining X-ray crystal structures suitable for drug design and by the inability of this method to resolve highly flexible regions of the protein that are crucial for ligand binding. To address this issue, we have undertaken a study of human protein kinases CDK5/p25, CDK5, ERK2 and GSK3β using both conventional molecular dynamics (MD) and the new Active Site Pressurisation (ASP) methodology, to look for kinase-specific patterns of flexibility that could be leveraged for the design of selective inhibitors. ASP was used to examine the intrinsic flexibility of the ATP-binding pocket for CDK5/p25, CDK5 and GSK3β where it is shown to be capable of inducing significant conformational changes when compared with X-ray crystal structures. The results from these experiments were used to quantify the dynamics of each protein, which supported the observations made from the conventional MD simulations. Additional information was also derived from the ASP simulations, including the shape of the ATP-binding site and the rigidity of the ATP-binding pocket. These observations may be exploited in the design of selective inhibitors of GSK3β, CDK5 and ERK2. Full article
(This article belongs to the Special Issue In-Silico Drug Design and In-Silico Screening)
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Open AccessArticle Adsorption Characteristics of Sol Gel-Derived Zirconia for Cesium Ions from Aqueous Solutions
Molecules 2014, 19(7), 9160-9172; doi:10.3390/molecules19079160
Received: 19 April 2014 / Revised: 1 June 2014 / Accepted: 9 June 2014 / Published: 1 July 2014
Cited by 7 | PDF Full-text (372 KB) | HTML Full-text | XML Full-text
Abstract
Zirconia powder was synthesized via a sol gel method and placed in a batch reactor for cesium removal investigation. X-ray analysis and Fourier transform infrared spectroscopy were utilized for the evaluation of the developed adsorbent. The adsorption process has been investigated as a
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Zirconia powder was synthesized via a sol gel method and placed in a batch reactor for cesium removal investigation. X-ray analysis and Fourier transform infrared spectroscopy were utilized for the evaluation of the developed adsorbent. The adsorption process has been investigated as a function of pH, contact time and temperature. The adsorption is strongly dependent on the pH of the medium whereby the removal efficiency increases as the pH turns to the alkaline range. The process was initially very fast and the maximum adsorption was attained within 60 min of contact. A pseudo-second-order model and homogeneous particle diffusion model (HPDM) were found to be the best to correlate the diffusion of cesium into the zirconia particles. Furthermore, adsorption thermodynamic parameters, namely the standard enthalpy, entropy, and Gibbs free energy, were calculated. The results indicate that cesium adsorption by zirconia is an endothermic (ΔH > 0) process and good affinity of cesium ions towards the sorbent (ΔS > 0) was observed. Full article
Open AccessArticle Quantitative Analysis of Major Constituents in Green Tea with Different Plucking Periods and Their Antioxidant Activity
Molecules 2014, 19(7), 9173-9186; doi:10.3390/molecules19079173
Received: 27 April 2014 / Revised: 19 June 2014 / Accepted: 23 June 2014 / Published: 1 July 2014
Cited by 13 | PDF Full-text (750 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this study was to determine the relationship between the plucking periods and the major constituents and the antioxidant activity in green tea. Green tea was prepared from leaves plucked from the end of April 2013 to the end of May
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The objective of this study was to determine the relationship between the plucking periods and the major constituents and the antioxidant activity in green tea. Green tea was prepared from leaves plucked from the end of April 2013 to the end of May 2013 at intervals of one week or longer. The contents of theanine, theobromine, caffeine, catechin (C), and gallocatechin gallate (GCg) were significantly decreased, whereas those of epicatechin (EC), epigallocatechin gallate (EGCg) and epigallocatechin (EGC) were significantly increased along with the period of tea leaf plucking. In addition, antioxidant activity of green tea and standard catechins was investigated using ABTS, FRAP and DPPH assays. The highest antioxidant activity was observed in relatively the oldest leaf, regardless of the assay methods used. Additionally, the order of antioxidant activity of standard catechins was as follows: EGCg ³ GCg ³ ECg > EGC ³ GC ³ EC ³ C. Moreover, the cis-catechins contents were the key factor affecting the antioxidant activity of green tea in all assays employed (ABTS, r = 0.731, p < 0.01; FRAP, r = 0.886, p < 0.01; DPPH, r = 0.778, p < 0.01). Full article
Open AccessArticle A Comparative Study of the Physicochemical Properties of a Virgin Coconut Oil Emulsion and Commercial Food Supplement Emulsions
Molecules 2014, 19(7), 9187-9202; doi:10.3390/molecules19079187
Received: 14 April 2014 / Revised: 19 June 2014 / Accepted: 23 June 2014 / Published: 1 July 2014
PDF Full-text (820 KB) | HTML Full-text | XML Full-text
Abstract
Food manufacturers are interested in developing emulsion-based products into nutritional foods by using beneficial oils, such as fish oil and virgin coconut oil (VCO). In this study, the physicochemical properties of a VCO oil-in-water emulsion was investigated and compared to other commercial oil-in-water
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Food manufacturers are interested in developing emulsion-based products into nutritional foods by using beneficial oils, such as fish oil and virgin coconut oil (VCO). In this study, the physicochemical properties of a VCO oil-in-water emulsion was investigated and compared to other commercial oil-in-water emulsion products (C1, C2, C3, and C4). C3 exhibited the smallest droplet size of 3.25 µm. The pH for the emulsion samples ranged from 2.52 to 4.38 and thus were categorised as acidic. In a texture analysis, C2 was described as the most firm, very adhesive and cohesive, as well as having high compressibility properties. From a rheological viewpoint, all the emulsion samples exhibited non-Newtonian behaviour, which manifested as a shear-thinning property. The G'G'' crossover illustrated by the VCO emulsion in the amplitude sweep graph but not the other commercial samples illustrated that the VCO emulsion had a better mouthfeel. In this context, the VCO emulsion yielded the highest zeta potential (64.86 mV), which was attributed to its strong repulsive forces, leading to a good dispersion system. C2 comprised the highest percentage of fat among all emulsion samples, followed by the VCO emulsion, with 18.44% and 6.59%, respectively. Full article
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Open AccessArticle Microwave-Assisted Kinetic Resolution of Homochiral (Z)-Cyclooct-5-ene-1,2-diol and (Z)-2-Acetoxycyclooct-4-enyl Acetate Using Lipases
Molecules 2014, 19(7), 9215-9227; doi:10.3390/molecules19079215
Received: 30 May 2014 / Revised: 21 June 2014 / Accepted: 30 June 2014 / Published: 2 July 2014
Cited by 2 | PDF Full-text (333 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Over the last decade, the use of biocatalysts has become an attractive alternative to conventional chemical methods, especially for organic synthesis, due to their unusual properties. Among these enzymes, lipases are the most widely used, because they are cheap, easily available, cofactor-free, and
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Over the last decade, the use of biocatalysts has become an attractive alternative to conventional chemical methods, especially for organic synthesis, due to their unusual properties. Among these enzymes, lipases are the most widely used, because they are cheap, easily available, cofactor-free, and have broad substrate specificity. Combined to microwave heating in non-aqueous medium, recent results suggest that irradiation may influence the enzyme activity. This Communication reports the benefits of lipases and the microwave irradiation on the kinetic resolution of racemic homochiral (Z)-cyclooct-5-ene-1,2-diol and (Z)-2-acetoxycyclooct-4-enyl acetate. In order to best achieve the kinetic resolution, different parameters were studied including the type of lipase, the temperature, the impact of microwave power compared to conventional heating. Optimization of the reaction parameters lead to the obtainment of highly enriched or enantiopure diols and diesters in a clean, efficient and safe way. Full article
(This article belongs to the Special Issue ECSOC-17)
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Open AccessCommunication Mechanistic Insight into CM18-Tat11 Peptide Membrane-Perturbing Action by Whole-Cell Patch-Clamp Recording
Molecules 2014, 19(7), 9228-9239; doi:10.3390/molecules19079228
Received: 30 April 2014 / Revised: 25 June 2014 / Accepted: 30 June 2014 / Published: 2 July 2014
PDF Full-text (5317 KB) | HTML Full-text | XML Full-text
Abstract
The membrane-destabilization properties of the recently-introduced endosomolytic CM18-Tat11 hybrid peptide (KWKLFKKIGAVLKVLTTG-YGRKKRRQRRR, residues 1–7 of cecropin-A, 2–12 of melittin, and 47–57 of HIV-1 Tat protein) are investigated in CHO-K1 cells by using the whole-cell configuration of the patch-clamp technique. CM18
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The membrane-destabilization properties of the recently-introduced endosomolytic CM18-Tat11 hybrid peptide (KWKLFKKIGAVLKVLTTG-YGRKKRRQRRR, residues 1–7 of cecropin-A, 2–12 of melittin, and 47–57 of HIV-1 Tat protein) are investigated in CHO-K1 cells by using the whole-cell configuration of the patch-clamp technique. CM18-Tat11, CM18, and Tat11 peptides are administered to the cell membrane with a computer-controlled micro-perfusion system. CM18-Tat11 induces irreversible cell-membrane permeabilization at concentrations (≥4 µM) at which CM18 triggers transient pore formation, and Tat11 does not affect membrane integrity. We argue that the addition of the Tat11 module to CM18 is able to trigger a shift in the mechanism of membrane destabilization from “toroidal” to “carpet”, promoting a detergent-like membrane disruption. Collectively, these results rationalize previous observations on CM18-Tat11 delivery properties that we believe can guide the engineering of new modular peptides tailored to specific cargo-delivery applications. Full article
(This article belongs to the Special Issue Peptide Chemistry)
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Open AccessArticle The Effect of Some 4,2 and 5,2 Bisthiazole Derivatives on Nitro-Oxidative Stress and Phagocytosis in Acute Experimental Inflammation
Molecules 2014, 19(7), 9240-9256; doi:10.3390/molecules19079240
Received: 12 May 2014 / Revised: 24 June 2014 / Accepted: 27 June 2014 / Published: 2 July 2014
Cited by 1 | PDF Full-text (645 KB) | HTML Full-text | XML Full-text
Abstract
Nineteen bisthiazoles were tested in order to assess their anti-inflammatory and antioxidant properties. First, we evaluated the in vitro direct antioxidant capacity of the bisthiazoles using the DPPH radical scavenging method. Then, the anti-inflammatory effect was tested in acute rat experimental inflammation by
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Nineteen bisthiazoles were tested in order to assess their anti-inflammatory and antioxidant properties. First, we evaluated the in vitro direct antioxidant capacity of the bisthiazoles using the DPPH radical scavenging method. Then, the anti-inflammatory effect was tested in acute rat experimental inflammation by measuring the acute phase bone marrow response, the phagocytic capacity and the serum nitro-oxidative stress status. Although none of the substances showed significant direct antioxidant potential in the DPPH assay, most of them improved serum oxidative status, when administered to rats with inflammation. Four of the bisthiazoles proved to have good anti-inflammatory properties, similar or superior to that of equal doses meloxicam. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Protective Effects of Baccharis dracunculifolia Leaves Extract against Carbon Tetrachloride- and Acetaminophen-Induced Hepatotoxicity in Experimental Animals
Molecules 2014, 19(7), 9257-9272; doi:10.3390/molecules19079257
Received: 14 May 2014 / Revised: 25 June 2014 / Accepted: 26 June 2014 / Published: 2 July 2014
Cited by 5 | PDF Full-text (576 KB) | HTML Full-text | XML Full-text
Abstract
In this work we investigated the in vivo protective effects of Baccharis dracunculifolia leaves extract (BdE) against carbon tetrachloride (CCl4)- and acetaminophen (APAP)-induced hepatotoxicity. Total phenolic content, total flavonoid content, antioxidant DPPH radical scavenging activity, and HPLC analysis were performed. Our
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In this work we investigated the in vivo protective effects of Baccharis dracunculifolia leaves extract (BdE) against carbon tetrachloride (CCl4)- and acetaminophen (APAP)-induced hepatotoxicity. Total phenolic content, total flavonoid content, antioxidant DPPH radical scavenging activity, and HPLC analysis were performed. Our results showed that pretreatment with BdE significantly reduced the damage caused by CCl4 and APAP on the serum markers of hepatic injury, AST, ALT, and ALP. Results were confirmed by histopathological analysis. Phytochemical analysis, performed by HPLC, showed that BdE was rich in p-coumaric acid derivatives, caffeoylquinic acids and flavonoids. BdE also showed DPPH antioxidant activity (EC50 of 15.75 ± 0.43 μg/mL), and high total phenolic (142.90 ± 0.77 mg GAE/g) and flavonoid (51.47 ± 0.60 mg RE/g) contents. This study indicated that B. dracunculifolia leaves extract has relevant in vivo hepatoprotective properties. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Chitosan-Coated Magnetic Nanoparticles Prepared in One-Step by Precipitation in a High-Aqueous Phase Content Reverse Microemulsion
Molecules 2014, 19(7), 9273-9287; doi:10.3390/molecules19079273
Received: 27 May 2014 / Revised: 25 June 2014 / Accepted: 25 June 2014 / Published: 2 July 2014
Cited by 4 | PDF Full-text (849 KB) | HTML Full-text | XML Full-text
Abstract
Chitosan-coated magnetic nanoparticles (CMNP) were prepared in one-step by precipitation in a high-aqueous phase content reverse microemulsion in the presence of chitosan. The high-aqueous phase concentration led to productivities close to 0.49 g CMNP/100 g microemulsion; much higher than those characteristic of precipitation
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Chitosan-coated magnetic nanoparticles (CMNP) were prepared in one-step by precipitation in a high-aqueous phase content reverse microemulsion in the presence of chitosan. The high-aqueous phase concentration led to productivities close to 0.49 g CMNP/100 g microemulsion; much higher than those characteristic of precipitation in reverse microemulsions for preparing magnetic nanoparticles. The obtained nanoparticles present a narrow particle size distribution with an average diameter of 4.5 nm; appearing to be formed of a single crystallite; furthermore they present superparamagnetism and high magnetization values; close to 49 emu/g. Characterization of CMNP suggests that chitosan is present as a non-homogeneous very thin layer; which explains the slight reduction in the magnetization value of CMNP in comparison with that of uncoated magnetic nanoparticles. The prepared nanoparticles show high heavy ion removal capability; as demonstrated by their use in the treatment of Pb2+ aqueous solutions; from which lead ions were completely removed within 10 min. Full article
(This article belongs to the Special Issue Bio and Nanomaterials Based on Fe3O4)
Open AccessArticle Ni-Catalyzed Homoallylation of Polyhydroxy N,O-Acetals with Conjugated Dienes Promoted by Triethylborane
Molecules 2014, 19(7), 9288-9306; doi:10.3390/molecules19079288
Received: 4 April 2014 / Revised: 13 June 2014 / Accepted: 23 June 2014 / Published: 2 July 2014
PDF Full-text (299 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the presence of Ni-catalyst and triethylborane, N,O-acetals prepared from glycolaldehyde and glyceraldehyde with primary amines in situ underwent homoallylation with conjugated dienes to provide 2-amino-5-hexenols in high regio- and stereoselectivity. Under similar reaction conditions, N,O-acetals from
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In the presence of Ni-catalyst and triethylborane, N,O-acetals prepared from glycolaldehyde and glyceraldehyde with primary amines in situ underwent homoallylation with conjugated dienes to provide 2-amino-5-hexenols in high regio- and stereoselectivity. Under similar reaction conditions, N,O-acetals from carbohydrates with primary amines provided the corresponding polyhydroxy-bishomoallylamines in good to reasonable yields. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Open AccessArticle N-Alkyl Carbazole Derivatives as New Tools for Alzheimer’s Disease: Preliminary Studies
Molecules 2014, 19(7), 9307-9317; doi:10.3390/molecules19079307
Received: 8 May 2014 / Revised: 12 June 2014 / Accepted: 24 June 2014 / Published: 2 July 2014
Cited by 6 | PDF Full-text (555 KB) | HTML Full-text | XML Full-text
Abstract
Alzheimer’s disease (AD) is a progressive and age-related neurodegenerative disorder affecting brain cells and is the most common form of “dementia”, because of the cognitive detriment which takes place. Neuronal disruption represents its major feature, due to the cytosolic accumulation of amyloid β-peptide
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Alzheimer’s disease (AD) is a progressive and age-related neurodegenerative disorder affecting brain cells and is the most common form of “dementia”, because of the cognitive detriment which takes place. Neuronal disruption represents its major feature, due to the cytosolic accumulation of amyloid β-peptide (Aβ) which leads to senile plaques formation and intracellular neurofibrillary tangles. Many studies have focused on the design and therapeutic use of new molecules able to inhibit Aβ aggregation. In this context, we evaluated the ability of two recently synthesized series of N-alkyl carbazole derivatives to increase the Aβ soluble forms, through molecular docking simulations and in vitro experiments. Our data evidenced that two carbazole derivatives, the most active, adopt distinct binding modes involving key residues for Aβ fibrillization. They exhibit a good interfering activity on Aβ aggregation in mouse (N2a) cells, stably expressing wild-type human amyloid precursor protein (APP) 695. These preliminary results are promising and we are confident that the N-alkyl carbazole derivatives may encourage next future studies needed for enlarging the knowledge about the AD disease approach. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle New Potentially Active Pyrazinamide Derivatives Synthesized Under Microwave Conditions
Molecules 2014, 19(7), 9318-9338; doi:10.3390/molecules19079318
Received: 30 May 2014 / Revised: 17 June 2014 / Accepted: 26 June 2014 / Published: 3 July 2014
Cited by 2 | PDF Full-text (419 KB) | HTML Full-text | XML Full-text
Abstract
A series of 18 N-alkyl substituted 3-aminopyrazine-2-carboxamides was prepared in this work according to previously experimentally set and proven conditions using microwave assisted synthesis methodology. This approach for the aminodehalogenation reaction was chosen due to higher yields and shorter reaction times compared
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A series of 18 N-alkyl substituted 3-aminopyrazine-2-carboxamides was prepared in this work according to previously experimentally set and proven conditions using microwave assisted synthesis methodology. This approach for the aminodehalogenation reaction was chosen due to higher yields and shorter reaction times compared to organic reactions with conventional heating. Antimycobacterial, antibacterial, antifungal and photosynthetic electron transport (PET) inhibiting in vitro activities of these compounds were investigated. Experiments for the determination of lipophilicity were also performed. Only a small number of substances with alicyclic side chain showed activity against fungi which was the same or higher than standards and the biological efficacy of the compounds increased with rising lipophilicity. Nine pyrazinamide derivatives also inhibited PET in spinach chloroplasts and the IC50 values of these compounds varied in the range from 14.3 to 1590.0 μmol/L. The inhibitory activity was connected not only with the lipophilicity, but also with the presence of secondary amine fragment bounded to the pyrazine ring. Structure-activity relationships are discussed as well. Full article
(This article belongs to the Special Issue ECSOC-17)
Open AccessArticle Synthesis and Pharmacological Evaluation of Modified Adenosines Joined to Mono-Functional Platinum Moieties
Molecules 2014, 19(7), 9339-9353; doi:10.3390/molecules19079339
Received: 26 March 2014 / Revised: 23 June 2014 / Accepted: 25 June 2014 / Published: 3 July 2014
Cited by 5 | PDF Full-text (392 KB) | HTML Full-text | XML Full-text
Abstract
The synthesis of four novel platinum complexes, bearing N6-(6-amino-hexyl)adenosine or a 1,6-di(adenosin-N6-yl)-hexane respectively, as ligands of mono-functional cisplatin or monochloro(ethylendiamine)platinum(II), is reported. The chemistry exploits the high affinity of the charged platinum centres towards the N7 position of
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The synthesis of four novel platinum complexes, bearing N6-(6-amino-hexyl)adenosine or a 1,6-di(adenosin-N6-yl)-hexane respectively, as ligands of mono-functional cisplatin or monochloro(ethylendiamine)platinum(II), is reported. The chemistry exploits the high affinity of the charged platinum centres towards the N7 position of the adenosine base system and a primary amine of an alkyl chain installed on the C6 position of the purine. The cytotoxic behaviour of the synthesized complexes has been studied in A549 adenocarcinomic human alveolar basal epithelial and MCF7 human breast adenocarcinomic cancer cell lines, in order to investigate their effects on cell viability and proliferation. Full article
(This article belongs to the Special Issue Practical Applications of Metal Complexes)
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Open AccessArticle Intramolecular Hydrogen Bond in Biologically Active o-Carbonyl Hydroquinones
Molecules 2014, 19(7), 9354-9368; doi:10.3390/molecules19079354
Received: 9 May 2014 / Revised: 18 June 2014 / Accepted: 27 June 2014 / Published: 3 July 2014
Cited by 10 | PDF Full-text (1081 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Intramolecular hydrogen bonds (IHBs) play a central role in the molecular structure, chemical reactivity and interactions of biologically active molecules. Here, we study the IHBs of seven related o-carbonyl hydroquinones and one structurally-related aromatic lactone, some of which have shown anticancer and
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Intramolecular hydrogen bonds (IHBs) play a central role in the molecular structure, chemical reactivity and interactions of biologically active molecules. Here, we study the IHBs of seven related o-carbonyl hydroquinones and one structurally-related aromatic lactone, some of which have shown anticancer and antioxidant activity. Experimental NMR data were correlated with theoretical calculations at the DFT and ab initio levels. Natural bond orbital (NBO) and molecular electrostatic potential (MEP) calculations were used to study the electronic characteristics of these IHB. As expected, our results show that NBO calculations are better than MEP to describe the strength of the IHBs. NBO energies (∆Eij(2)) show that the main contributions to energy stabilization correspond to LPàσ* interactions for IHBs, O1O2-H2 and the delocalization LPàπ* for O2-C2 = Cα(β). For the O1O2-H2 interaction, the values of ∆Eij(2) can be attributed to the difference in the overlap ability between orbitals i and j (Fij), instead of the energy difference between them. The large energy for the LP O2àπ* C2 = Cα(β) interaction in the compounds 9-Hydroxy-5-oxo-4,8, 8-trimethyl-l,9(8H)-anthracenecarbolactone (VIII) and 9,10-dihydroxy-4,4-dimethylanthracen-1(4H)-one (VII) (55.49 and 60.70 kcal/mol, respectively) when compared with the remaining molecules (all less than 50 kcal/mol), suggests that the IHBs in VIII and VII are strongly resonance assisted. Full article
(This article belongs to the Special Issue Intramolecular Hydrogen Bonding)
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Open AccessArticle Determination of Phenol Compounds In Surface Water Matrices by Bar Adsorptive Microextraction-High Performance Liquid Chromatography-Diode Array Detection
Molecules 2014, 19(7), 9369-9379; doi:10.3390/molecules19079369
Received: 13 March 2014 / Revised: 26 June 2014 / Accepted: 27 June 2014 / Published: 3 July 2014
Cited by 3 | PDF Full-text (277 KB) | HTML Full-text | XML Full-text
Abstract
Bar adsorptive microextraction combined with liquid desorption followed by high performance liquid chromatography with diode array detection (BAµE-LD/HPLC-DAD) is proposed for the determination of trace levels of five phenol compounds (3-nitrophenol, 4-nitrophenol, bisphenol-A, 4-n-octylphenol and 4-n-nonylphenol) in surface water
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Bar adsorptive microextraction combined with liquid desorption followed by high performance liquid chromatography with diode array detection (BAµE-LD/HPLC-DAD) is proposed for the determination of trace levels of five phenol compounds (3-nitrophenol, 4-nitrophenol, bisphenol-A, 4-n-octylphenol and 4-n-nonylphenol) in surface water matrices. By using a polystyrene-divinylbenzene copolymer (PS-DVB) sorbent phase, high selectivity and efficiency is achieved even against polydimethylsiloxane through stir bar sorptive extraction. Assays performed by BAµE(PS-DVB)-LD/HPLC-DAD on 25 mL water samples spiked at the 10.0 µg/L levels yielded recoveries over 88.0% ± 5.7% for all five analytes, under optimized experimental conditions. The analytical performance showed good precision (RSD < 15%), detection limits of 0.25 µg/L and linear dynamic ranges (1.0–25.0 μg/L) with determination coefficient higher than 0.9904. By using the standard addition method, the application of the present method to surface water matrices allowed very good performances at the trace level. The proposed methodology proved to be a suitable alternative to monitor phenol compounds in surface water matrices, showing to be easy to implement, reliable, sensitive and requiring a low sample volume. Full article
(This article belongs to the Special Issue Microextraction)
Open AccessArticle Antioxidant Activity and Acetylcholinesterase Inhibition of Grape Skin Anthocyanin (GSA)
Molecules 2014, 19(7), 9403-9418; doi:10.3390/molecules19079403
Received: 25 April 2014 / Revised: 18 June 2014 / Accepted: 28 June 2014 / Published: 3 July 2014
Cited by 6 | PDF Full-text (421 KB) | HTML Full-text | XML Full-text
Abstract
We aimed to investigate the antioxidant and acetylcholinesterase inhibitory activities of the anthocyanin rich extract of grape skin. Grape skin anthocyanin (GSA) neutralized free radicals in different test systems, such as 2,-2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, to form complexes with Fe
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We aimed to investigate the antioxidant and acetylcholinesterase inhibitory activities of the anthocyanin rich extract of grape skin. Grape skin anthocyanin (GSA) neutralized free radicals in different test systems, such as 2,-2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, to form complexes with Fe2+ preventing 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced erythrocyte hemolysis and oxidative DNA damage. Moreover, GSA decreased reactive oxygen species (ROS) generation in isolated mitochondria thus inhibiting 2',-7'-dichlorofluorescin (DCFH) oxidation. In an in vivo study, female BALB/c mice were administered GSA, at 12.5, 25, and 50 mg per kg per day orally for 30 consecutive days. Herein, we demonstrate that GSA administration significantly elevated the level of antioxidant enzymes in mice sera, livers, and brains. Furthermore, GSA inhibited acetylcholinesterase (AChE) in the in vitro assay with an IC50 value of 363.61 µg/mL. Therefore, GSA could be an excellent source of antioxidants and its inhibition of cholinesterase is of interest with regard to neurodegenerative disorders such as Alzheimer’s disease. Full article
(This article belongs to the Special Issue Anthocyanins) Print Edition available
Open AccessArticle Synthesis, Spectroscopic and Theoretical Studies of New Dimeric Quaternary Alkylammonium Conjugates of Sterols
Molecules 2014, 19(7), 9419-9434; doi:10.3390/molecules19079419
Received: 10 June 2014 / Revised: 30 June 2014 / Accepted: 1 July 2014 / Published: 3 July 2014
Cited by 3 | PDF Full-text (704 KB) | HTML Full-text | XML Full-text
Abstract
New dimeric quaternary alkylammonium conjugates of sterols were obtained by two step reactions of ergosterol, cholesterol and cholestanol with bromoacetic acid bromide, followed by bimolecular nucleophilic substitution with N,N,N',N'-tetramethyl-1,3-propanediamine, N,N,N',N''
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New dimeric quaternary alkylammonium conjugates of sterols were obtained by two step reactions of ergosterol, cholesterol and cholestanol with bromoacetic acid bromide, followed by bimolecular nucleophilic substitution with N,N,N',N'-tetramethyl-1,3-propanediamine, N,N,N',N'',N''-pentamethyldiethylenetriamine and 3,3'-iminobis- (N,N-dimethylpropylamine). The product structures were confirmed by spectral (1H-NMR, 13C-NMR, FT-IR) analysis, mass spectrometry (ESI-MS) and PM5 semiempirical methods. Additionally in silico studies have been conducted for the synthesized compounds on the basis of Prediction of Activity Spectra for Substances (PASS). Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle GSK3β Regulates Milk Synthesis in and Proliferation of Dairy Cow Mammary Epithelial Cells via the mTOR/S6K1 Signaling Pathway
Molecules 2014, 19(7), 9435-9452; doi:10.3390/molecules19079435
Received: 16 May 2014 / Revised: 22 June 2014 / Accepted: 27 June 2014 / Published: 3 July 2014
Cited by 12 | PDF Full-text (502 KB) | HTML Full-text | XML Full-text
Abstract
Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase, whose activity is inhibited by AKT phosphorylation. This inhibitory phosphorylation of GSK3β can in turn play a regulatory role through phosphorylation of several proteins (such as mTOR, elF2B) to promote protein synthesis. mTOR is
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Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase, whose activity is inhibited by AKT phosphorylation. This inhibitory phosphorylation of GSK3β can in turn play a regulatory role through phosphorylation of several proteins (such as mTOR, elF2B) to promote protein synthesis. mTOR is a key regulator in protein synthesis and cell proliferation, and recent studies have shown that both GSK3β and mTORC1 can regulate SREBP1 to promote fat synthesis. Thus far, however, the cross talk between GSK3β and the mTOR pathway in the regulation of milk synthesis and associated cell proliferation is not well understood. In this study the interrelationship between GSK3β and the mTOR/S6K1 signaling pathway leading to milk synthesis and proliferation of dairy cow mammary epithelial cells (DCMECs) was analyzed using techniques including GSK3β overexpression by transfection, GSK3β inhibition, mTOR inhibition and methionine stimulation. The analyses revealed that GSK3β represses the mTOR/S6K1 pathway leading to milk synthesis and cell proliferation of DCMECs, whereas GSK3β phosphorylation enhances this pathway. Conversely, the activated mTOR/S6K1 signaling pathway downregulates GSK3β expression but enhances GSK3β phosphorylation to increase milk synthesis and cell proliferation, whereas inhibition of mTOR leads to upregulation of GSK3β and repression of GSK3β phosphorylation, which in turn decreases milk synthesis, and cell proliferation. These findings indicate that GSK3β and phosphorylated GSK3β regulate milk synthesis and proliferation of DCMECs via the mTOR/S6K1 signaling pathway. These findings provide new insight into the mechanisms of milk synthesis. Full article
Open AccessArticle Tanacetum polycephalum (L.) Schultz-Bip. Induces Mitochondrial-Mediated Apoptosis and Inhibits Migration and Invasion in MCF7 Cells
Molecules 2014, 19(7), 9478-9501; doi:10.3390/molecules19079478
Received: 13 May 2014 / Revised: 6 June 2014 / Accepted: 23 June 2014 / Published: 3 July 2014
Cited by 8 | PDF Full-text (4893 KB) | HTML Full-text | XML Full-text
Abstract
Tanacetum polycephalum (L.) Schultz-Bip (Mokhaleseh) has been traditionally used in the treatment of headaches, migraines, hyperlipidemia and diabetes. The present study aimed to evaluate its anticancer properties and possible mechanism of action using MCF7 as an in vitro model. T. polycephalum leaves were
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Tanacetum polycephalum (L.) Schultz-Bip (Mokhaleseh) has been traditionally used in the treatment of headaches, migraines, hyperlipidemia and diabetes. The present study aimed to evaluate its anticancer properties and possible mechanism of action using MCF7 as an in vitro model. T. polycephalum leaves were extracted using hexane, chloroform and methanol solvents and the cytotoxicity was evaluated using the MTT assay. Detection of the early apoptotic cells was investigated using acridine orange/propidium iodide staining. An Annexin-V-FITC assay was carried out to observe the phosphatidylserine externalization as a marker for apoptotic cells. High content screening was applied to analyze the cell membrane permeability, nuclear condensation, mitochondrial membrane potential (MMP) and cytochrome c release. Apoptosis was confirmed by using caspase-8, caspase-9 and DNA laddering assays. In addition, Bax/Bcl-2 expressions and cell cycle arrest also have been investigated. MTT assay revealed significant cytotoxicity of T. Polycephalum hexane extract (TPHE) on MCF7 cells with the IC50 value of 6.42 ± 0.35 µg/mL. Significant increase in chromatin condensation was also observed via fluorescence analysis. Treatment of MCF7 cells with TPHE encouraged apoptosis through reduction of MMP by down-regulation of Bcl-2 and up-regulation of Bax, triggering the cytochrome c leakage from mitochondria to the cytosol. The treated MCF7 cells significantly arrested at G1 phase. The chromatographic analysis elicited that the major active compound in this extract is 8β-hydroxy-4β,15-dihydrozaluzanin C. Taken together, the results presented in this study demonstrated that the hexane extract of T. Polycephalum inhibits the proliferation of MCF7 cells, resulting in the cell cycle arrest and apoptosis, which was explained to be through the mitochondrial pathway. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Effects of Icariin on Reproductive Functions in Male Rats
Molecules 2014, 19(7), 9502-9514; doi:10.3390/molecules19079502
Received: 25 April 2014 / Revised: 18 June 2014 / Accepted: 24 June 2014 / Published: 3 July 2014
Cited by 5 | PDF Full-text (1728 KB) | HTML Full-text | XML Full-text
Abstract
The present study investigated the effects and potential mechanism(s) of action of icariin on the reproductive functions of male rats. Adult rats were treated orally with icariin at doses of 0 (control), 50, 100, or 200 mg/kg body weight for 35 consecutive days.
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The present study investigated the effects and potential mechanism(s) of action of icariin on the reproductive functions of male rats. Adult rats were treated orally with icariin at doses of 0 (control), 50, 100, or 200 mg/kg body weight for 35 consecutive days. The results show that icariin had virtually no effect on the body weight or organ coefficients of the testes or epididymides. However, 100 mg/kg icariin significantly increased epididymal sperm counts. In addition, 50 and 100 mg/kg icariin significantly increased testosterone levels. Real-time PCR suggests icariin may be involved in testosterone production via mRNA expression regulation of genes such as peripheral type benzodiazepine receptor (PBR) and steroidogenic acute regulatory protein (StAR). Furthermore, 100 mg/kg icariin treatment also affected follicle stimulating hormone receptor (FSHR) and claudin-11 mRNA expression in Sertoli cells. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were measured in the testes; 50 and 100 mg/kg icariin treatment improved antioxidative capacity, while 200 mg/kg icariin treatment upregulated oxidative stress. These results collectively suggest that icariin within a certain dose range is beneficial to male reproductive functions; meanwhile, higher doses of icariin may damage reproductive functions by increasing oxidative stress in the testes. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Studies on Cytotoxic Constituents from the Leaves of Elaeagnus oldhamii Maxim. in Non-Small Cell Lung Cancer A549 Cells
Molecules 2014, 19(7), 9515-9534; doi:10.3390/molecules19079515
Received: 29 April 2014 / Revised: 15 June 2014 / Accepted: 25 June 2014 / Published: 4 July 2014
Cited by 13 | PDF Full-text (314 KB) | HTML Full-text | XML Full-text
Abstract
Elaeagnus oldhamii Maxim. is a commonly used traditional herbal medicine. In Taiwan the leaves of E. oldhamii Maxim. are mainly used for treating lung disorders. Twenty five compounds were isolated from the leaves of E. oldhamii Maxim. in the present study. These
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Elaeagnus oldhamii Maxim. is a commonly used traditional herbal medicine. In Taiwan the leaves of E. oldhamii Maxim. are mainly used for treating lung disorders. Twenty five compounds were isolated from the leaves of E. oldhamii Maxim. in the present study. These included oleanolic acid (1), 3-O-(Z)-coumaroyl oleanolic acid (2), 3-O-(E)-coumaroyl oleanolic acid (3), 3-O-caffeoyl oleanolic acid (4), ursolic acid (5), 3-O-(Z)-coumaroyl ursolic acid (6), 3-O-(E)-coumaroyl ursolic acid (7), 3-O-caffeoyl ursolic acid (8), 3β, 13β-dihydroxyolean-11-en-28-oic acid (9), 3β, 13β-dihydroxyurs-11-en-28-oic acid (10), uvaol (11), betulin (12), lupeol (13), kaempferol (14), aromadendrin (15), epigallocatechin (16), cis-tiliroside (17), trans-tiliroside (18), isoamericanol B (19), trans-p-coumaric acid (20), protocatechuic acid (21), salicylic acid (22), trans-ferulic acid (23), syringic acid (24) and 3-O-methylgallic acid (25). Of the 25 isolated compounds, 21 compounds were identified for the first time in E. oldhamii Maxim. These included compounds 1, 4, 5 and 825. These 25 compounds were evaluated for their inhibitory activity against the growth of non-small cell lung cancer A549 cells by the MTT assay, and the corresponding structure-activity relationships were discussed. Among these 25 compounds, compound 6 displayed the best activity against the A549 cell line in vitro (CC50 = 8.56 ± 0.57 μg/mL, at 48 h of MTT asssay). Furthermore, compound 2, 4, 8 and 18 exhibited in vitro cytotoxicity against the A549 cell line with the CC50 values of less than 20 μg/mL at 48 h of MTT asssay. These five compounds 2, 4, 6, 8 and 18 exhibited better cytotoxic activity compared with cisplatin (positive control, CC50 value of 14.87 ± 1.94 μg/mL, at 48 h of MTT asssay). The result suggested that the five compounds might be responsible for its clinical anti-lung cancer effect. Full article
Open AccessArticle Secondary Metabolite Profiling of Curcuma Species Grown at Different Locations Using GC/TOF and UPLC/Q-TOF MS
Molecules 2014, 19(7), 9535-9551; doi:10.3390/molecules19079535
Received: 16 April 2014 / Revised: 26 June 2014 / Accepted: 30 June 2014 / Published: 4 July 2014
Cited by 9 | PDF Full-text (686 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Curcuma, a genus of rhizomatous herbaceous species, has been used as a spice, traditional medicine, and natural dye. In this study, the metabolite profile of Curcuma extracts was determined using gas chromatography-time of flight mass spectrometry (GC/TOF MS) and ultrahigh-performance liquid chromatography–quadrupole
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Curcuma, a genus of rhizomatous herbaceous species, has been used as a spice, traditional medicine, and natural dye. In this study, the metabolite profile of Curcuma extracts was determined using gas chromatography-time of flight mass spectrometry (GC/TOF MS) and ultrahigh-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) to characterize differences between Curcuma aromatica and Curcuma longa grown on the Jeju-do or Jin-do islands, South Korea. Previous studies have performed primary metabolite profiling of Curcuma species grown in different regions using NMR-based metabolomics. This study focused on profiling of secondary metabolites from the hexane extract of Curcuma species. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) plots showed significant differences between the C. aromatica and C. longa metabolite profiles, whereas geographical location had little effect. A t-test was performed to identify statistically significant metabolites, such as terpenoids. Additionally, targeted profiling using UPLC/Q-TOF MS showed that the concentration of curcuminoids differed depending on the plant origin. Based on these results, a combination of GC- and LC-MS allowed us to analyze curcuminoids and terpenoids, the typical bioactive compounds of Curcuma, which can be used to discriminate Curcuma samples according to species or geographical origin. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle Formation of a Flavin-Linked Peptide
Molecules 2014, 19(7), 9552-9561; doi:10.3390/molecules19079552
Received: 27 May 2014 / Revised: 2 July 2014 / Accepted: 2 July 2014 / Published: 4 July 2014
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Abstract
In a previous study, we showed that formylmethylflavin (FMF) can bind to cysteine. In this study, FMF was reacted with native peptides (CG and CKLVFF) containing an N-terminal cysteine. The formation of flavin-CG and flavin-CKLVFF was confirmed using HPLC and ESI-MS. Storage of
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In a previous study, we showed that formylmethylflavin (FMF) can bind to cysteine. In this study, FMF was reacted with native peptides (CG and CKLVFF) containing an N-terminal cysteine. The formation of flavin-CG and flavin-CKLVFF was confirmed using HPLC and ESI-MS. Storage of flavin-CKLVFF in DMSO at −30 °C for 7 days resulted in no detectable deposition. In contrast, flavin-CKLVFF formed deposits when stored in water at −30 °C for 1 day, but no deposit was observed in the aqueous solution of flavin-CKLVFF after 7 days storage in the presence of 0.1% Triton X-100. Full article
(This article belongs to the Special Issue ECSOC-17)
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Open AccessArticle Combined Effects of Ultrasound and Immobilization Protocol on Butyl Acetate Synthesis Catalyzed by CALB
Molecules 2014, 19(7), 9562-9576; doi:10.3390/molecules19079562
Received: 26 May 2014 / Revised: 30 June 2014 / Accepted: 1 July 2014 / Published: 7 July 2014
Cited by 8 | PDF Full-text (457 KB) | HTML Full-text | XML Full-text
Abstract
It is well established that the performance of lipase B from Candida antarctica (CALB) as catalyst for esterification reactions may be improved by the use of ultrasound technology or by its immobilization on styrene-divinylbenzene beads (MCI-CALB). The present research evaluated the synthesis of
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It is well established that the performance of lipase B from Candida antarctica (CALB) as catalyst for esterification reactions may be improved by the use of ultrasound technology or by its immobilization on styrene-divinylbenzene beads (MCI-CALB). The present research evaluated the synthesis of butyl acetate using MCI-CALB under ultrasonic energy, comparing the results against those obtained using the commercial preparation, Novozym 435. The optimal conditions were determined using response surface methodology (RSM) evaluating the following parameters: reaction temperature, substrate molar ratio, amount of biocatalyst, and added water. The optimal conditions for butyl acetate synthesis catalyzed by MCI-CALB were: temperature, 48.8 °C; substrate molar ratio, 3.46:1 alcohol:acid; amount of biocatalyst, 7.5%; and added water 0.28%, both as substrate mass. Under these conditions, 90% of conversion was reached in 1.5 h. In terms of operational stability, MCI-CALB was reused in seven cycles while keeping 70% of its initial activity under ultrasonic energy. The support pore size and resistance are key points for the enzyme activity and stability under mechanical stirring. The use of ultrasound improved both activity and stability because of better homogeneity and reduced mechanical stress to the immobilized system. Full article
(This article belongs to the Special Issue Enzyme Immobilization)
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Open AccessArticle Quantification of the Resveratrol Analogs trans-2,3-Dimethoxy-stilbene and trans-3,4-Dimethoxystilbene in Rat Plasma: Application to Pre-Clinical Pharmacokinetic Studies
Molecules 2014, 19(7), 9577-9590; doi:10.3390/molecules19079577
Received: 4 May 2014 / Revised: 26 June 2014 / Accepted: 28 June 2014 / Published: 7 July 2014
Cited by 1 | PDF Full-text (821 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
trans-2,3-Dimethoxystilbene (2,3-DMS) and trans-3,4-dimethoxystilbene (3,4-DMS) are two synthetic resveratrol (trans-3,5,4'-trihydroxystilbene) analogs. In this study, a simple HPLC method was developed and validated to determine 2,3-DMS and 3,4-DMS in rat plasma. Chromatographic separation was obtained with a reversed-phase HPLC column
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trans-2,3-Dimethoxystilbene (2,3-DMS) and trans-3,4-dimethoxystilbene (3,4-DMS) are two synthetic resveratrol (trans-3,5,4'-trihydroxystilbene) analogs. In this study, a simple HPLC method was developed and validated to determine 2,3-DMS and 3,4-DMS in rat plasma. Chromatographic separation was obtained with a reversed-phase HPLC column through a 12.5-min gradient delivery of a mixture of acetonitrile and water at the flow rate of 1.5 mL/min at 50 °C. The lower limit of quantification was 10 ng/mL. After successful validation, the pharmacokinetic profiles of 2,3-DMS and 3,4-DMS were subsequently studied in Sprague-Dawley rats. Upon single intravenous administration (4 mg/kg), 2,3-DMS had a medium volume of distribution of the central compartment (Vc = 2.71 ± 0.51 L/kg), quite rapid clearance (Cl = 52.0 ± 7.0 mL/min/kg), moderate mean transit time (MTT0→last = 131.0 ± 4.5 min) but a fairly long terminal elimination half-life (t1/2 λZ = 288.9 ± 92.9 min). Interestingly, 3,4-DMS displayed a pharmacokinetic profile apparently distinct from 2,3-DMS and it had more extensive distribution (Vc = 5.58 ± 1.73 L/kg), faster clearance (Cl = 143.4 ± 40.5 mL/min/kg) and shorter residence (MTT0→last = 61.4 ± 27.1 min). Following single oral administration (10 mg/kg), 2,3-DMS had low and erratic plasma exposure (Cmax = 37.5 ± 23.7 ng/mL) and poor oral bioavailability (2.22% ± 2.13%) while the oral bioavailability of 3,4-DMS was even poorer than 2,3-DMS. Clearly, the location of the methoxy groups had a significant impact on the pharmacokinetics of resveratrol analogs. This study provided useful information for the design of resveratrol derivatives in future study. Full article
(This article belongs to the Special Issue Resveratrol)
Open AccessArticle Combined Kinetic Studies and Computational Analysis on Kojic Acid Analogs as Tyrosinase Inhibitors
Molecules 2014, 19(7), 9591-9605; doi:10.3390/molecules19079591
Received: 6 June 2014 / Revised: 1 July 2014 / Accepted: 2 July 2014 / Published: 7 July 2014
Cited by 4 | PDF Full-text (623 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Tyrosinase is a key enzyme in melanin synthesis and widely distributed in plants and animals tissues. In mammals, this enzyme is related to pigment production, involved in wound healing, primary immune response and it can also contribute to catecholamines synthesis in the brain.
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Tyrosinase is a key enzyme in melanin synthesis and widely distributed in plants and animals tissues. In mammals, this enzyme is related to pigment production, involved in wound healing, primary immune response and it can also contribute to catecholamines synthesis in the brain. Consequently, tyrosinase enzyme represents an attractive and selective target in the field of the medicine, cosmetics and bio-insecticides. In this paper, experimental kinetics and computational analysis were used to study the inhibition of tyrosinase by analogous of Kojic acid. The main interactions occurring between inhibitors-tyrosinase complexes and the influence of divalent cation (Cu2+) in enzymatic inhibition were investigated by using molecular docking, molecular dynamic simulations and electrostatic binding free energy by using the Linear Interaction Energy (LIE) method. The results showed that the electrostatic binding free energy are correlated with values of constant inhibition (r2 = 0.97).Thus, the model obtained here could contribute to future studies of this important system and, therefore, eventually facilitate development of tyrosinase inhibitors. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Cytotoxic and Antiproliferative Effect of Tepary Bean Lectins on C33-A, MCF-7, SKNSH, and SW480 Cell Lines
Molecules 2014, 19(7), 9610-9627; doi:10.3390/molecules19079610
Received: 4 May 2014 / Revised: 2 July 2014 / Accepted: 2 July 2014 / Published: 7 July 2014
PDF Full-text (630 KB) | HTML Full-text | XML Full-text
Abstract
For many years, several studies have been employing lectin from vegetables in order to prove its toxic effect on various cell lines. In this work, we analyzed the cytotoxic, antiproliferative, and post-incubatory effect of pure tepary bean lectins on four lines of malignant
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For many years, several studies have been employing lectin from vegetables in order to prove its toxic effect on various cell lines. In this work, we analyzed the cytotoxic, antiproliferative, and post-incubatory effect of pure tepary bean lectins on four lines of malignant cells: C33-A; MCF-7; SKNSH, and SW480. The tests were carried out employing MTT and 3[H]-thymidine assays. The results showed that after 24 h of lectin exposure, the cells lines showed a dose-dependent cytotoxic effect, the effect being higher on MCF-7, while C33-A showed the highest resistance. Cell proliferation studies showed that the toxic effect induced by lectins is higher even when lectins are removed, and in fact, the inhibition of proliferation continues after 48 h. Due to the use of two techniques to analyze the cytotoxic and antiproliferative effect, differences were observed in the results, which can be explained by the fact that one technique is based on metabolic reactions, while the other is based on the 3[H]-thymidine incorporated in DNA by cells under division. These results allow concluding that lectins exert a cytotoxic effect after 24 h of exposure, exhibiting a dose-dependent effect. In some cases, the cytotoxic effect is higher even when the lectins are eliminated, however, in other cases, the cells showed a proliferative effect. Full article
Open AccessArticle Novel Cinnamic Acid Derivatives as Antioxidant and Anticancer Agents: Design, Synthesis and Modeling Studies
Molecules 2014, 19(7), 9655-9674; doi:10.3390/molecules19079655
Received: 5 May 2014 / Revised: 13 June 2014 / Accepted: 17 June 2014 / Published: 7 July 2014
Cited by 8 | PDF Full-text (507 KB) | HTML Full-text | XML Full-text
Abstract
Cinnamic acids have been identified as interesting compounds with antioxidant, anti-inflammatory and cytotoxic properties. In the present study, simple cinnamic acids were synthesized by Knoevenagel condensation reactions and evaluated for the above biological activities. Compound 4ii proved to be the most potent LOX
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Cinnamic acids have been identified as interesting compounds with antioxidant, anti-inflammatory and cytotoxic properties. In the present study, simple cinnamic acids were synthesized by Knoevenagel condensation reactions and evaluated for the above biological activities. Compound 4ii proved to be the most potent LOX inhibitor. Phenyl- substituted acids showed better inhibitory activity against soybean LOX, and it must be noted that compounds 4i and 3i with higher lipophilicity values resulted less active than compounds 2i and 1i. The compounds have shown very good activity in different antioxidant assays. The antitumor properties of these derivatives have been assessed by their 1/IC50 inhibitory values in the proliferation of HT-29, A-549, OAW-42, MDA-MB-231, HeLa and MRC-5 normal cell lines. The compounds presented low antitumor activity considering the IC50 values attained for the cell lines, with the exception of compound 4ii. Molecular docking studies were carried out on cinnamic acid derivative 4ii and were found to be in accordance with our experimental biological results. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
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Open AccessArticle Characterization of Phytochemicals and Antioxidant Activities of Red Radish Brines during Lactic Acid Fermentation
Molecules 2014, 19(7), 9675-9688; doi:10.3390/molecules19079675
Received: 30 May 2014 / Revised: 24 June 2014 / Accepted: 27 June 2014 / Published: 7 July 2014
Cited by 4 | PDF Full-text (637 KB) | HTML Full-text | XML Full-text
Abstract
Red radish (Raphanus L.) pickles are popular appetizers or spices in Asian-style cuisine. However, tons of radish brines are generated as wastes from industrial radish pickle production. In this study, we evaluated the dynamic changes in colour properties, phenolics, anthocyanin profiles, phenolic
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Red radish (Raphanus L.) pickles are popular appetizers or spices in Asian-style cuisine. However, tons of radish brines are generated as wastes from industrial radish pickle production. In this study, we evaluated the dynamic changes in colour properties, phenolics, anthocyanin profiles, phenolic acid composition, flavonoids, and antioxidant properties in radish brines during lactic acid fermentation. The results showed that five flavonoids detected were four anthocyanins and one kaempferol derivative, including pelargonidin-3-digluoside-5-glucoside derivatives acylated with p-coumaric acid, ferulic acid, p-coumaric and manolic acids, or ferulic and malonic acids. Amounts ranged from 15.5–19.3 µg/mL in total monomeric anthocyanins, and kaempferol-3,7-diglycoside (15–30 µg/mL). 4-Hydroxy-benzoic, gentisic, vanillic, syringic, p-coumaric, ferulic, sinapic and salicylic acids were detected in amounts that varied from 70.2–92.2 µg/mL, whereas the total phenolic content was 206–220 µg/mL. The change in colour of the brine was associated with the accumulation of lactic acid and anthocyanins. The ORAC and Fe2+ chelation capacity of radish brines generally decreased, whereas the reducing power measured as FRAP values was increased during the fermentation from day 5 to day 14. This study provided information on the phytochemicals and the antioxidative activities of red radish fermentation waste that might lead to further utilization as nutraceuticals or natural colorants. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Ionic Liquid-Based Vacuum Microwave-Assisted Extraction Followed by Macroporous Resin Enrichment for the Separation of the Three Glycosides Salicin, Hyperin and Rutin from Populus Bark
Molecules 2014, 19(7), 9689-9711; doi:10.3390/molecules19079689
Received: 16 May 2014 / Revised: 23 June 2014 / Accepted: 1 July 2014 / Published: 7 July 2014
Cited by 14 | PDF Full-text (2136 KB) | HTML Full-text | XML Full-text
Abstract
An effective ionic liquid vacuum microwave-assisted method was developed for extraction of the thermo- and oxygen-sensitive glycosides salicin, hyperin and rutin from Populus bark due to the strong solvating effects of ionic liquids on plant cell walls. In this study, [C4mim]BF
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An effective ionic liquid vacuum microwave-assisted method was developed for extraction of the thermo- and oxygen-sensitive glycosides salicin, hyperin and rutin from Populus bark due to the strong solvating effects of ionic liquids on plant cell walls. In this study, [C4mim]BF4 solution was selected as the extracting solution for extraction of the target analytes. After optimization by single factor experiments and response surface methodology, the optimum condition parameters were achieved, which included 1.0 M [C4mim]BF4, 2 h soaking time, −0.08 MPa vacuum, 20 min microwave irradiation time, 400 W microwave irradiation power and 25 mL/g liquid/solid ratio. Under the optimum conditions, higher extraction yields of salicin (35.53 mg/g), hyperin (1.32 mg/g) and rutin (2.40 mg/g) were obtained. Compared with other extraction methods, the developed method provided higher yields of the three target components after a relatively shorter extraction time (20 min). No obvious degradation of the target analytes was observed under the optimum conditions in performed stability studies and the proposed method had a high reproducibility. Meanwhile, after adsorption and desorption on macroporous D101 resin, the target analytes can be effectively separated from the [C4mim]BF4 ionic liquid extraction solution and the yields of salicin, hyperin and rutin were 89%, 82% and 84%, respectively. The recovered [C4mim]BF4 ionic liquid presented a good extraction effect on the three analytes after recycling five times. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Photophysical Properties of the 2-(3-(2-Alkyl-6,8-diaryl-4-oxo-1,2,3,4-tetrahydroquinazolin-2-yl)propyl)-6,8-diarylquinazolin-4(3H)-ones
Molecules 2014, 19(7), 9712-9735; doi:10.3390/molecules19079712
Received: 6 June 2014 / Revised: 30 June 2014 / Accepted: 1 July 2014 / Published: 8 July 2014
Cited by 1 | PDF Full-text (1587 KB) | HTML Full-text | XML Full-text
Abstract
Iodine-catalyzed condensation of 2-amino-3,5-dibromobenzamide with cyclohexane-1,3-dione derivatives in refluxing toluene afforded the corresponding bisquinazolinones. Suzuki-Miyaura cross-coupling of the latter with arylboronic acids afforded tetraarylbisquinazolinones. The electronic absorption and emission properties of these tetraarylbisquinazolinones were measured in dimethylsulfoxide (DMSO) and acetic acid by means
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Iodine-catalyzed condensation of 2-amino-3,5-dibromobenzamide with cyclohexane-1,3-dione derivatives in refluxing toluene afforded the corresponding bisquinazolinones. Suzuki-Miyaura cross-coupling of the latter with arylboronic acids afforded tetraarylbisquinazolinones. The electronic absorption and emission properties of these tetraarylbisquinazolinones were measured in dimethylsulfoxide (DMSO) and acetic acid by means of UV-Vis and fluorescence spectroscopic techniques in conjunction with quantum chemical methods to understand the influence of substituents on intramolecular charge transfer (ICT). Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Synthesis of Riboflavines, Quinoxalinones and Benzodiazepines through Chemoselective Flow Based Hydrogenations
Molecules 2014, 19(7), 9736-9759; doi:10.3390/molecules19079736
Received: 4 June 2014 / Revised: 25 June 2014 / Accepted: 2 July 2014 / Published: 8 July 2014
Cited by 11 | PDF Full-text (708 KB) | HTML Full-text | XML Full-text
Abstract
Robust chemical routes towards valuable bioactive entities such as riboflavines, quinoxalinones and benzodiazepines are described. These make use of modern flow hydrogenation protocols enabling the chemoselective reduction of nitro group containing building blocks in order to rapidly generate the desired amine intermediates in
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Robust chemical routes towards valuable bioactive entities such as riboflavines, quinoxalinones and benzodiazepines are described. These make use of modern flow hydrogenation protocols enabling the chemoselective reduction of nitro group containing building blocks in order to rapidly generate the desired amine intermediates in situ. In order to exploit the benefits of continuous processing the individual steps were transformed into a telescoped flow process delivering selected benzodiazepine products on scales of 50 mmol and 120 mmol respectively. Full article
(This article belongs to the Special Issue Heterocycles in Supramolecular Chemistry)
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Open AccessArticle A Novel Fungal Metabolite with Beneficial Properties for Agricultural Applications
Molecules 2014, 19(7), 9760-9772; doi:10.3390/molecules19079760
Received: 5 March 2014 / Revised: 26 June 2014 / Accepted: 1 July 2014 / Published: 8 July 2014
Cited by 9 | PDF Full-text (1020 KB) | HTML Full-text | XML Full-text
Abstract
Trichoderma are ubiquitous soil fungi that include species widely used as biocontrol agents in agriculture. Many isolates are known to secrete several secondary metabolites with different biological activities towards plants and other microbes. Harzianic acid (HA) is a T. harzianum metabolite able to
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Trichoderma are ubiquitous soil fungi that include species widely used as biocontrol agents in agriculture. Many isolates are known to secrete several secondary metabolites with different biological activities towards plants and other microbes. Harzianic acid (HA) is a T. harzianum metabolite able to promote plant growth and strongly bind iron. In this work, we isolated from the culture filtrate of a T. harzianum strain a new metabolite, named isoharzianic acid (iso-HA), a stereoisomer of HA. The structure and absolute configuration of this compound has been determined by spectroscopic methods, including UV-Vis, MS, 1D and 2D NMR analyses. In vitro applications of iso-HA inhibited the mycelium radial growth of Sclerotinia sclerotiorum and Rhizoctonia solani. Moreover, iso HA improved the germination of tomato seeds and induced disease resistance. HPLC-DAD experiments showed that the production of HA and iso HA was affected by the presence of plant tissue in the liquid medium. In particular, tomato tissue elicited the production of HA but negatively modulated the biosynthesis of its analogue iso-HA, suggesting that different forms of the same Trichoderma secondary metabolite have specific roles in the molecular mechanism regulating the Trichoderma plant interaction. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Vasorelaxation Induced by a New Naphthoquinone-Oxime is Mediated by NO-sGC-cGMP Pathway
Molecules 2014, 19(7), 9773-9785; doi:10.3390/molecules19079773
Received: 19 May 2014 / Revised: 21 June 2014 / Accepted: 23 June 2014 / Published: 8 July 2014
Cited by 5 | PDF Full-text (408 KB) | HTML Full-text | XML Full-text
Abstract
It has been established that oximes cause endothelium-independent relaxation in blood vessels. In the present study, the cardiovascular effects of the new oxime 3-hydroxy-4–(hydroxyimino)-2-(3-methylbut-2-enylnaphtalen-1(4H)-one (Oxime S1) derived from lapachol were evaluated. In normotensive rats, administration of Oxime S1 (10,
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It has been established that oximes cause endothelium-independent relaxation in blood vessels. In the present study, the cardiovascular effects of the new oxime 3-hydroxy-4–(hydroxyimino)-2-(3-methylbut-2-enylnaphtalen-1(4H)-one (Oxime S1) derived from lapachol were evaluated. In normotensive rats, administration of Oxime S1 (10, 15, 20 and 30 mg/Kg, i.v.) produced dose-dependent reduction in blood pressure. In isolated aorta and superior mesenteric artery rings, Oxime S1 induced endothelium-independent and concentration-dependent relaxations (10−8 M to 10−4 M). In addition, Oxime S1-induced vasorelaxations were attenuated by hydroxocobalamin or methylene blue in aorta and by PTIO or ODQ in mesenteric artery rings, suggesting a role for the nitric oxide (NO) pathway. Additionally, Oxime S1 (30 and 100 µM) significantly increased NO concentrations (13.9 ± 1.6 nM and 17.9 ± 4.1 nM, respectively) measured by nitric oxide microsensors. Furthermore, pre-contraction with KCl (80 mM) prevented Oxime S1-derived vasorelaxation in endothelium-denuded aortic rings. Of note, combined treatment with potassium channel inhibitors also reduced Oxime S1-mediated vasorelaxation suggesting a role for potassium channels, more precisely Kir, Kv and KATP channels. We observed the involvement of BKCa channels in Oxime S1-induced relaxation in mesenteric artery rings. In conclusion, these data suggest that the Oxime S1 induces hypotension and vasorelaxation via NO pathway by activating soluble guanylate cyclase (sGC) and K+ channels. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Isolation, Structural Analyses and Biological Activity Assays against Chronic Lymphocytic Leukemia of Two Novel Cytochalasins — Sclerotionigrin A and B
Molecules 2014, 19(7), 9786-9797; doi:10.3390/molecules19079786
Received: 21 March 2014 / Revised: 24 June 2014 / Accepted: 2 July 2014 / Published: 8 July 2014
Cited by 3 | PDF Full-text (281 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new cytochalasins, sclerotionigrin A (1) and B (2) were isolated together with the known proxiphomin (3) from the filamentous fungus Aspergillus sclerotioniger. The structures and relative stereochemistry of 1 and 2 were determined based on
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Two new cytochalasins, sclerotionigrin A (1) and B (2) were isolated together with the known proxiphomin (3) from the filamentous fungus Aspergillus sclerotioniger. The structures and relative stereochemistry of 1 and 2 were determined based on comparison with 3, and from extensive 1D and 2D NMR spectroscopic analysis, supported by high resolution mass spectrometry (HRMS). Compounds 2 and 3 displayed cytotoxic activity towards chronic lymphocytic leukemia cells in vitro, with 3 being the most active. Full article
(This article belongs to the Special Issue Bioassay-Guided Isolation of Natural Products)
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Open AccessArticle The Hydractinia echinata Test-System. III: Structure-Toxicity Relationship Study of Some Azo-, Azo-Anilide, and Diazonium Salt Derivatives
Molecules 2014, 19(7), 9798-9817; doi:10.3390/molecules19079798
Received: 17 April 2014 / Revised: 29 June 2014 / Accepted: 3 July 2014 / Published: 8 July 2014
Cited by 1 | PDF Full-text (205 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Structure-toxicity relationships for a series of 75 azo and azo-anilide dyes and five diazonium salts were developed using Hydractinia echinata (H. echinata) as model species. In addition, based on these relationships, predictions for 58 other azo-dyes were made. The experimental
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Structure-toxicity relationships for a series of 75 azo and azo-anilide dyes and five diazonium salts were developed using Hydractinia echinata (H. echinata) as model species. In addition, based on these relationships, predictions for 58 other azo-dyes were made. The experimental results showed that the measured effectiveness Mlog(1/MRC50) does not depend on the number of azo groups or the ones corresponding to metobolites, but it is influenced by the number of anilide groups, as well as by the substituents’ positions within molecules. The conformational analysis pointed out the intramolecular hydrogen bonds, especially the simple tautomerization of quinoidic (STOH) or aminoidic (STNH2) type. The effectiveness is strongly influenced by the “push-pull” electronic effect, specific to two hydroxy or amino groups separated by an azo moiety (double alternate tautomery, (DAT), to the –COOH or –SO3H groups which are located in ortho or para position with respect to the azo group. The levels of the lipophylic/hydrophilic, electronic and steric equilibriums, pointed out by the Mlog(1/MRC50) values, enabled the calculation of their average values Clog(1/MRC50) (“Köln model”), characteristic to one derivative class (class isotoxicity). The azo group reduction and the hydrolysis of the amido/peptidic group are two concurrent enzymatic reactions, which occur with different reaction rates and mechanisms. The products of the partial biodegradation are aromatic amines. No additive or synergic effects are noticed among them. Full article
Open AccessArticle Additives Enhancing the Catalytic Properties of Lipase from Burkholderia cepacia Immobilized on Mixed-Function-Grafted Mesoporous Silica Gel
Molecules 2014, 19(7), 9818-9837; doi:10.3390/molecules19079818
Received: 16 May 2014 / Revised: 23 June 2014 / Accepted: 2 July 2014 / Published: 8 July 2014
Cited by 10 | PDF Full-text (517 KB) | HTML Full-text | XML Full-text
Abstract
Effects of various additives on the lipase from Burkholderia cepacia (BcL) immobilized on mixed-function-grafted mesoporous silica gel support by hydrophobic adsorption and covalent attachment were investigated. Catalytic properties of the immobilized biocatalysts were characterized in kinetic resolution of racemic 1-phenylethanol (
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Effects of various additives on the lipase from Burkholderia cepacia (BcL) immobilized on mixed-function-grafted mesoporous silica gel support by hydrophobic adsorption and covalent attachment were investigated. Catalytic properties of the immobilized biocatalysts were characterized in kinetic resolution of racemic 1-phenylethanol (rac-1a) and 1-(thiophen-2-yl)ethan-1-ol (rac-1b). Screening of more than 40 additives showed significantly enhanced productivity of immobilized BcL with several additives such as PEGs, oleic acid and polyvinyl alcohol. Effects of substrate concentration and temperature between 0–100 °C on kinetic resolution of rac-1a were studied with the best adsorbed BcLs containing PEG 20 k or PVA 18–88 additives in continuous-flow packed-bed reactor. The optimum temperature of lipase activity for BcL co-immobilized with PEG 20k found at around 30 °C determined in the continuous-flow system increased remarkably to around 80 °C for BcL co-immobilized with PVA 18–88. Full article
(This article belongs to the Special Issue Enzyme Immobilization)
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Open AccessArticle Glutaraldehyde Cross-Linking of Immobilized Thermophilic Esterase on Hydrophobic Macroporous Resin for Application in Poly(ε-caprolactone) Synthesis
Molecules 2014, 19(7), 9838-9849; doi:10.3390/molecules19079838
Received: 21 May 2014 / Revised: 3 July 2014 / Accepted: 4 July 2014 / Published: 8 July 2014
Cited by 3 | PDF Full-text (330 KB) | HTML Full-text | XML Full-text
Abstract
The immobilized thermophilic esterase from Archaeoglobus fulgidus was successfully constructed through the glutaraldehyde-mediated covalent coupling after its physical adsorption on a hydrophobic macroporous resin, Sepabeads EC-OD. Through 0.05% glutaraldehyde treatment, the prevention of enzyme leaching and the maintenance of catalytic activity could be
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The immobilized thermophilic esterase from Archaeoglobus fulgidus was successfully constructed through the glutaraldehyde-mediated covalent coupling after its physical adsorption on a hydrophobic macroporous resin, Sepabeads EC-OD. Through 0.05% glutaraldehyde treatment, the prevention of enzyme leaching and the maintenance of catalytic activity could be simultaneously realized. Using the enzymatic ring-opening polymerization of ε-caprolactone as a model, effects of organic solvents and reaction temperature on the monomer conversion and product molecular weight were systematically investigated. After the optimization of reaction conditions, products were obtained with 100% monomer conversion and Mn values lower than 1010 g/mol. Furthermore, the cross‑linked immobilized thermophilic esterase exhibited an excellent operational stability, with monomer conversion values exceeding 90% over the course of 12 batch reactions, still more than 80% after 16 batch reactions. Full article
(This article belongs to the Special Issue Enzyme Immobilization)
Open AccessArticle Preparation of Polyphosphazene Hydrogels for Enzyme Immobilization
Molecules 2014, 19(7), 9850-9863; doi:10.3390/molecules19079850
Received: 19 May 2014 / Revised: 23 June 2014 / Accepted: 24 June 2014 / Published: 8 July 2014
Cited by 4 | PDF Full-text (490 KB) | HTML Full-text | XML Full-text
Abstract
We report on the synthesis and application of a new hydrogel based on a methacrylate substituted polyphosphazene. Through ring-opening polymerization and nucleophilic substitution, poly[bis(methacrylate)phosphazene] (PBMAP) was successfully synthesized from hexachlorocyclotriphosphazene. By adding PBMAP to methacrylic acid solution and then treating with UV light,
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We report on the synthesis and application of a new hydrogel based on a methacrylate substituted polyphosphazene. Through ring-opening polymerization and nucleophilic substitution, poly[bis(methacrylate)phosphazene] (PBMAP) was successfully synthesized from hexachlorocyclotriphosphazene. By adding PBMAP to methacrylic acid solution and then treating with UV light, we could obtain a cross-linked polyphosphazene network, which showed an ultra-high absorbency for distilled water. Lipase from Candida rugosa was used as the model lipase for entrapment immobilization in the hydrogel. The influence of methacrylic acid concentration on immobilization efficiency was studied. Results showed that enzyme loading reached a maximum of 24.02 mg/g with an activity retention of 67.25% when the methacrylic acid concentration was 20% (w/w). Full article
(This article belongs to the Special Issue Enzyme Immobilization)
Open AccessArticle T-Type Ca2+ Channel Blocker, KYS05090 Induces Autophagy and Apoptosis in A549 Cells through Inhibiting Glucose Uptake
Molecules 2014, 19(7), 9864-9875; doi:10.3390/molecules19079864
Received: 27 May 2014 / Revised: 27 June 2014 / Accepted: 3 July 2014 / Published: 8 July 2014
Cited by 7 | PDF Full-text (384 KB) | HTML Full-text | XML Full-text
Abstract
It has been reported that [3-(1,1'-biphenyl-4-yl)-2-(1-methyl-5-dimethylamino-pentylamino)-3,4-dihydroquinazolin-4-yl]-N-benzylacetamide 2hydrochloride (KYS05090), a selective T-type Ca2+ channel blocker, reduces tumor volume and weight in the A549 xenograft model, but the molecular mechanism of cell death has not yet been elucidated. In this study, KYS05090
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It has been reported that [3-(1,1'-biphenyl-4-yl)-2-(1-methyl-5-dimethylamino-pentylamino)-3,4-dihydroquinazolin-4-yl]-N-benzylacetamide 2hydrochloride (KYS05090), a selective T-type Ca2+ channel blocker, reduces tumor volume and weight in the A549 xenograft model, but the molecular mechanism of cell death has not yet been elucidated. In this study, KYS05090 induced autophagy- and apoptosis-mediated cell death in human lung adenocarcinoma A549 cells. Although KYS05090 decreased intracellular Ca2+ levels, it was not directly related with KYS05090-induced cell death. In addition, KYS05090 generated intracellular reactive oxygen species (ROS) and reduced glucose uptake, and catalase and methyl pyruvate prevented KYS05090-induced cell death. These results indicate that KYS05090 can lead to autophagy and apoptosis in A549 cells through ROS generation by inhibiting glucose uptake. Our findings suggest that KYS05090 has potential chemotherapeutic value for the treatment of lung cancer. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Fluorescent Lectins for Local in Vivo Visualization of Peripheral Nerves
Molecules 2014, 19(7), 9876-9892; doi:10.3390/molecules19079876
Received: 7 May 2014 / Revised: 19 June 2014 / Accepted: 1 July 2014 / Published: 8 July 2014
Cited by 2 | PDF Full-text (1944 KB) | HTML Full-text | XML Full-text
Abstract
Damage to peripheral nerves caused during a surgical intervention often results in function loss. Fluorescence imaging has the potential to improve intraoperative identification and preservation of these structures. However, only very few nerve targeting agents are available. This study describes the in vivo
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Damage to peripheral nerves caused during a surgical intervention often results in function loss. Fluorescence imaging has the potential to improve intraoperative identification and preservation of these structures. However, only very few nerve targeting agents are available. This study describes the in vivo nerve staining capabilities of locally administered fluorescent lectin-analogues. To this end WGA, PNA, PHA-L and LEL were functionalized with Cy5 (λex max 640 nm; λem max 680 nm). Transfer of these imaging agents along the sciatic nerve was evaluated in Thy1-YFP mice (n = 12) after intramuscular injection. Migration from the injection site was assessed in vivo using a laboratory fluorescence scanner and ex vivo via fluorescence confocal microscopy. All four lectins showed retrograde movement and staining of the epineurium with a signal-to-muscle ratio of around two. On average, the longest transfer distance was obtained with WGA-Cy5 (0.95 cm). Since WGA also gave minimal uptake in the lymphatic system, this lectin type revealed the highest potential as a migration imaging agent to visualize nerves. Full article
(This article belongs to the Special Issue Fluorescent Probes)
Open AccessArticle Homoconjugation vs. Exciton Coupling in Chiral α,β-Unsaturated Bicyclo[3.3.1]nonane Dinitrile and Carboxylic Acids
Molecules 2014, 19(7), 9893-9906; doi:10.3390/molecules19079893
Received: 4 May 2014 / Revised: 3 June 2014 / Accepted: 5 June 2014 / Published: 8 July 2014
PDF Full-text (606 KB) | HTML Full-text | XML Full-text
Abstract
The chiroptical properties of enantiomerically pure bicyclo[3.3.1]nona-2,6-diene-2,6-dicarbonitrile and related acids were studied by circular dichroism spectroscopy and theoretical computations. A consideration of the molecular structure of the synthesized difunctional compounds revealed that chromophores are predisposed to transannular through-space interaction due to a favourable
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The chiroptical properties of enantiomerically pure bicyclo[3.3.1]nona-2,6-diene-2,6-dicarbonitrile and related acids were studied by circular dichroism spectroscopy and theoretical computations. A consideration of the molecular structure of the synthesized difunctional compounds revealed that chromophores are predisposed to transannular through-space interaction due to a favourable conformation of the bicyclic skeleton and a rather small interchromophoric distance. Evidence for non-exciton-type coupling between the two acrylonitrile and acrylate moieties in 3 and 4, respectively, was obtained by chiroptical spectroscopy and DFT calculations. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Open AccessArticle Stability of Sunscreens Containing CePO4: Proposal for a New Inorganic UV Filter
Molecules 2014, 19(7), 9907-9925; doi:10.3390/molecules19079907
Received: 1 May 2014 / Revised: 30 June 2014 / Accepted: 1 July 2014 / Published: 9 July 2014
Cited by 3 | PDF Full-text (932 KB) | HTML Full-text | XML Full-text
Abstract
Inorganic UV filters have become attractive because of their role in protecting the skin from the damage caused by continuous exposure to the sun. However, their large refractive index and high photocatalytic activity have led to the development of alternative inorganic materials such
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Inorganic UV filters have become attractive because of their role in protecting the skin from the damage caused by continuous exposure to the sun. However, their large refractive index and high photocatalytic activity have led to the development of alternative inorganic materials such as CePO4 for application as UV filters. This compound leaves a low amount of white residue on the skin and is highly stable. The aim of this study was to evaluate the physical and chemical stability of a cosmetic formulation containing ordinary organic UV filters combined with 5% CePO4, and, to compare it with other formulations containing the same vehicle with 5% TiO2 or ZnO as inorganic materials. The rheological behavior and chemical stability of the formulations containing these different UV filters were investigated. Results showed that the formulation containing CePO4 is a promising innovative UV filter due to its low interaction with organic filters, which culminates in longer shelf life when compared with traditional formulations containing ZnO or TiO2 filters. Moreover, the recognized ability of CePO4 to leave a low amount of white residue on the skin combined with great stability, suggests that CePO4 can be used as inorganic filter in high concentrations, affording formulations with high SPF values. Full article
Open AccessArticle 1,4-Disubstituted Thiosemicarbazide Derivatives are Potent Inhibitors of Toxoplasma gondii Proliferation
Molecules 2014, 19(7), 9926-9943; doi:10.3390/molecules19079926
Received: 11 June 2014 / Revised: 27 June 2014 / Accepted: 27 June 2014 / Published: 9 July 2014
Cited by 7 | PDF Full-text (605 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of 4-arylthiosemicarbazides substituted at the N1 position with a 5-membered heteroaryl ring was synthesized and evaluated in vitro for T. gondii inhibition proliferation and host cell cytotoxicity. At non-toxic concentrations for the host cells all studied compounds displayed excellent
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A series of 4-arylthiosemicarbazides substituted at the N1 position with a 5-membered heteroaryl ring was synthesized and evaluated in vitro for T. gondii inhibition proliferation and host cell cytotoxicity. At non-toxic concentrations for the host cells all studied compounds displayed excellent anti-parasitic effects when compared to sulfadiazine, indicating a high selectivity of their anti-T. gondii activity. The differences in bioactivity investigated by DFT calculations suggest that the inhibitory activity of 4-aryl-thiosemicarbazides towards T. gondii proliferation is connected with the electronic structure of the molecule. Further, these compounds were tested as potential antibacterial agents. No growth-inhibiting effect on any of the test microorganisms was observed for all the compounds, even at high concentrations. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Relative Quantitation of Glycopeptides Based on Stable Isotope Labeling Using MALDI-TOF MS
Molecules 2014, 19(7), 9944-9961; doi:10.3390/molecules19079944
Received: 31 March 2014 / Revised: 1 July 2014 / Accepted: 7 July 2014 / Published: 9 July 2014
Cited by 3 | PDF Full-text (572 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We have developed an effective, sensitive method for quantitative glycopeptide profiling using stable isotope labeling and MALDI-TOF mass spectrometry (MS). In this study, we synthesized benzoic acid-d0 N-succinimidyl ester (BzOSu) and benzoic acid-d5 N-succinimidyl ester (d-BzOSu) as light and heavy isotope reagents for
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We have developed an effective, sensitive method for quantitative glycopeptide profiling using stable isotope labeling and MALDI-TOF mass spectrometry (MS). In this study, we synthesized benzoic acid-d0 N-succinimidyl ester (BzOSu) and benzoic acid-d5 N-succinimidyl ester (d-BzOSu) as light and heavy isotope reagents for stable isotope quantification for the comparative analysis of glycopeptides. Using this approach provided enhanced ionization efficiency in both positive and negative modes by MALDI-TOF MS. These reagents were quantitatively reacted with glycopeptides from human serum IgG (hIgG) at a wide range of concentrations; the labeling efficiency of the glycopeptides showed high reproducibility and a good calibration curve was obtained. To demonstrate the practical utility of this approach, we characterized the structures of glycopeptides from hIgG and from IgG1 produced by myeloma plasma. The glycopeptides were quantitatively analyzed by mixing Bz-labeled IgG1 glycopeptides with d-Bz-labeled hIgG glycopeptides. Glycan structural identification of the hIgG glycopeptides was demonstrated by combining the highly specific recognition of endo-β-N-acetyl glucosaminidases from Streptococcus pyogenes (endoS) or from Streptococcus pneumoniae (endo-D) with MALDI-TOF MS analysis. The obtained data revealed the glycan profile and the ratio of glycan structural isomers containing a galactosylated extension on IgG1, IgG2 and IgG3 glycopetides. Full article
(This article belongs to the Special Issue Oligosaccharides and Glyco-Conjugates)
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Open AccessArticle A Comparative Study on the Electrochemical Corrosion Behavior of Iron and X-65 Steel in 4.0 wt % Sodium Chloride Solution after Different Exposure Intervals
Molecules 2014, 19(7), 9962-9974; doi:10.3390/molecules19079962
Received: 13 May 2014 / Revised: 30 June 2014 / Accepted: 3 July 2014 / Published: 9 July 2014
Cited by 11 | PDF Full-text (295 KB) | HTML Full-text | XML Full-text
Abstract
In this work, the results obtained from studying the anodic dissolution of pure iron and API X-65 5L pipeline steel after 40 min and 12 h exposure period in 4.0 wt % NaCl solutions at room temperature were reported. Potential-time, electrochemical impedance spectroscopy,
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In this work, the results obtained from studying the anodic dissolution of pure iron and API X-65 5L pipeline steel after 40 min and 12 h exposure period in 4.0 wt % NaCl solutions at room temperature were reported. Potential-time, electrochemical impedance spectroscopy, potentiodynamic polarization, and chronoamperometric current-time at constant potential techniques were employed. It has been found that the iron electrode corrodes in the chloride test solutions faster than the API X-65 5L steel does under the same conditions. Increasing the exposure period for the electrodes from 40 min to 12 h showed a significant reduction in the corrosion parameters for both iron and steel in the 4.0 wt % NaCl solution. Results together confirmed clearly that the X-65 steel is superior to iron against corrosion in sodium chloride solutions. Full article
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Open AccessArticle Susceptibility of Opportunistic Burkholderia glumae to Copper Surfaces Following Wet or Dry Surface Contact
Molecules 2014, 19(7), 9975-9985; doi:10.3390/molecules19079975
Received: 21 March 2014 / Revised: 3 July 2014 / Accepted: 4 July 2014 / Published: 9 July 2014
Cited by 5 | PDF Full-text (929 KB) | HTML Full-text | XML Full-text
Abstract
Burkholderia glumae has been proposed to have a potential risk to vulnerable communities. In this work, we investigated the antibacterial activity and mechanism of copper surfaces against multi-drug resistant B. glumae from both patients and rice plants. The susceptibility of B
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Burkholderia glumae has been proposed to have a potential risk to vulnerable communities. In this work, we investigated the antibacterial activity and mechanism of copper surfaces against multi-drug resistant B. glumae from both patients and rice plants. The susceptibility of B. glumae to copper surfaces was noted by a significant decline in viable bacterial counts, relative to the slight reduction of stainless steel and polyvinylchloride, both of which were used as control surfaces. The mode of action of bacterial killing was determined by examing the mutagenicity, DNA damage, copper ions accumulation, and membrane damage in bacterial cells. The results indicated that the cells exposed to copper surfaces did not cause severe DNA lesions or increase the mutation frequencies, but resulted in a loss of cell membrane integrity within minutes. Furthermore, bacterial cells exposed to copper surfaces accumulated significantly higher amounts of copper compared to control surfaces. Overall, this study showed that metallic copper had strong antibacterial effect against B. glumae by causing DNA and membrane damage, cellular accumulation of copper, and cell death following DNA degradation, which could be utilized to reduce the risk of bacterial contamination and infection. Full article
(This article belongs to the Special Issue Practical Applications of Metal Complexes)
Open AccessArticle Batch and Continuous Flow Preparation of Hantzsch 1,4-Dihydropyridines under Microwave Heating and Simultaneous Real-time Monitoring by Raman Spectroscopy. An Exploratory Study
Molecules 2014, 19(7), 9986-9998; doi:10.3390/molecules19079986
Received: 23 May 2014 / Revised: 19 June 2014 / Accepted: 26 June 2014 / Published: 9 July 2014
Cited by 1 | PDF Full-text (2294 KB) | HTML Full-text | XML Full-text
Abstract
Dialkyl 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates have been prepared in a batch mode under conventional heating as well as under continuous flow conditions in the Miniflow 200SS, Sairem’s microwave-assisted batch and continuous flow equipment. Real-time monitoring of the reactions by Raman spectroscopy enabled to compare both heating
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Dialkyl 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates have been prepared in a batch mode under conventional heating as well as under continuous flow conditions in the Miniflow 200SS, Sairem’s microwave-assisted batch and continuous flow equipment. Real-time monitoring of the reactions by Raman spectroscopy enabled to compare both heating modes and to determine (optimized) reaction times. Full article
(This article belongs to the Special Issue ECSOC-17)
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Open AccessArticle Lycodine-Type Alkaloids from Lycopodiastrum casuarinoides and Their Acetylcholinesterase Inhibitory Activity
Molecules 2014, 19(7), 9999-10010; doi:10.3390/molecules19079999
Received: 23 May 2014 / Revised: 18 June 2014 / Accepted: 27 June 2014 / Published: 10 July 2014
Cited by 6 | PDF Full-text (379 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four new lycodine-type alkaloids, namely 16-hydroxyhuperzine B (1), N-methyl-11-acetoxyhuperzine B (2), 8,15-dihydrolycoparin A (3) and (7S,12S,13R)-huperzine D-16-O-β-d-glucopyranoside (4), along with ten known analogues 514
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Four new lycodine-type alkaloids, namely 16-hydroxyhuperzine B (1), N-methyl-11-acetoxyhuperzine B (2), 8,15-dihydrolycoparin A (3) and (7S,12S,13R)-huperzine D-16-O-β-d-glucopyranoside (4), along with ten known analogues 514, were isolated from the whole plant of Lycopodiastrum casuarinoides. The structures of the new compounds were elucidated by means of spectroscopic techniques (IR, MS, NMR, and CD) and chemical methods. Compounds 1 and 2 possessed four connected six-membered rings, while compounds 3 and 4 were piperidine ring cleavage products. In particular, compound 4 was a lycopodium alkaloidal glycoside which is reported for the first time. Among the isolated compounds N-demethylhuperzinine (7), huperzine C (8), huperzine B (9) and lycoparin C (13) possessed significant inhibitory activity against acetylcholinesterase, and the new compound 1 showed moderate inhibitory activity. The structure activity relationships were discussed. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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Open AccessArticle Plumbagin Modulates Leukemia Cell Redox Status
Molecules 2014, 19(7), 10011-10032; doi:10.3390/molecules190710011
Received: 3 June 2014 / Revised: 20 June 2014 / Accepted: 25 June 2014 / Published: 10 July 2014
Cited by 8 | PDF Full-text (1235 KB) | HTML Full-text | XML Full-text
Abstract
Plumbagin is a plant naphtoquinone exerting anti-cancer properties including apoptotic cell death induction and generation of reactive oxygen species (ROS). The aim of this study was to elucidate parameters explaining the differential leukemia cell sensitivity towards this compound. Among several leukemia cell lines,
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Plumbagin is a plant naphtoquinone exerting anti-cancer properties including apoptotic cell death induction and generation of reactive oxygen species (ROS). The aim of this study was to elucidate parameters explaining the differential leukemia cell sensitivity towards this compound. Among several leukemia cell lines, U937 monocytic leukemia cells appeared more sensitive to plumbagin treatment in terms of cytotoxicity and level of apoptotic cell death compared to more resistant Raji Burkitt lymphoma cells. Moreover, U937 cells exhibited a ten-fold higher ROS production compared to Raji. Neither differential incorporation, nor efflux of plumbagin was detected. Pre-treatment with thiol-containing antioxidants prevented ROS production and subsequent induction of cell death by apoptosis whereas non-thiol-containing antioxidants remained ineffective in both cellular models. We conclude that the anticancer potential of plumbagin is driven by pro-oxidant activities related to the cellular thiolstat. Full article
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Open AccessArticle Facile, Regio- and Diastereoselective Synthesis of Spiro-Pyrrolidine and Pyrrolizine Derivatives and Evaluation of Their Antiproliferative Activities
Molecules 2014, 19(7), 10033-10055; doi:10.3390/molecules190710033
Received: 29 May 2014 / Revised: 24 June 2014 / Accepted: 1 July 2014 / Published: 10 July 2014
Cited by 11 | PDF Full-text (594 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A number of novel spiro-pyrrolidines/pyrrolizines derivatives were synthesized through [3+2]-cycloaddition of azomethine ylides with 3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones 2an. Azomethine ylides were generated in situ from the reaction of 1H-indole-2,3-dione (isatin, 3) with N-methylglycine (sarcosine),
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A number of novel spiro-pyrrolidines/pyrrolizines derivatives were synthesized through [3+2]-cycloaddition of azomethine ylides with 3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones 2an. Azomethine ylides were generated in situ from the reaction of 1H-indole-2,3-dione (isatin, 3) with N-methylglycine (sarcosine), phenylglycine, or proline. All compounds (50 μM) were evaluated for their antiproliferative activity against human breast carcinoma (MDA-MB-231), leukemia lymphoblastic (CCRF-CEM), and ovarian carcinoma (SK-OV-3) cells. N-α-Phenyl substituted spiro-pyrrolidine derivatives (5an) showed higher antiproliferative activity in MDA-MB-231 than other cancer cell lines. Among spiro-pyrrolizines 6an, a number of derivatives including 6ac and 6im showed a comparable activity with doxorubicin in all three cell lines. Among all compounds in three classes, 6a, 6b, and 6m, were found to be the most potent derivatives showing 64%, 87%, and 74% antiproliferative activity in MDA-MB-231, SK-OV-3, and CCRF-CEM cells, respectively. Compound 6b showed an IC50 value of 3.6 mM in CCRF-CEM cells. These data suggest the potential antiproliferative activity of spiro-pyrrolidines/pyrrolizines. Full article
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Open AccessArticle Polyphenolic Content, Antioxidant and Antimicrobial Activities of Lycium barbarum L. and Lycium chinense Mill. Leaves
Molecules 2014, 19(7), 10056-10073; doi:10.3390/molecules190710056
Received: 26 May 2014 / Revised: 16 June 2014 / Accepted: 4 July 2014 / Published: 10 July 2014
Cited by 27 | PDF Full-text (289 KB) | HTML Full-text | XML Full-text
Abstract
This study was performed to evaluate the in vitro antioxidant and antimicrobial activities and the polyphenolic content of Lycium barbarum L. and L. chinense Mill. leaves. The different leave extracts contain important amounts of flavonoids (43.73 ± 1.43 and 61.65 ± 0.95 mg/g,
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This study was performed to evaluate the in vitro antioxidant and antimicrobial activities and the polyphenolic content of Lycium barbarum L. and L. chinense Mill. leaves. The different leave extracts contain important amounts of flavonoids (43.73 ± 1.43 and 61.65 ± 0.95 mg/g, respectively) and showed relevant antioxidant activity, as witnessed by the quoted methods. Qualitative and quantitative analyses of target phenolic compounds were achieved using a HPLC-UV-MS method. Rutin was the dominant flavonoid in both analysed species, the highest amount being registered for L. chinense. An important amount of chlorogenic acid was determined in L. chinense and L. barbarum extracts, being more than twice as high in L. chinense than in L. barbarum. Gentisic and caffeic acids were identified only in L. barbarum, whereas kaempferol was only detected in L. chinense. The antioxidant activity was evaluated by DPPH, TEAC, hemoglobin ascorbate peroxidase activity inhibition (HAPX) and inhibition of lipid peroxidation catalyzed by cytochrome c assays revealing a better antioxidant activity for the L. chinense extract. Results obtained in the antimicrobial tests revealed that L. chinense extract was more active than L. barbarum against both Gram-positive and Gram-negative bacterial strains. The results suggest that these species are valuable sources of flavonoids with relevant antioxidant and antimicrobial activities. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of a 2ꞌꞌ-Deoxy-β-GalCer
Molecules 2014, 19(7), 10090-10102; doi:10.3390/molecules190710090
Received: 29 May 2014 / Revised: 25 June 2014 / Accepted: 30 June 2014 / Published: 10 July 2014
PDF Full-text (320 KB) | HTML Full-text | XML Full-text
Abstract
Structural studies of ternary complexes of CD1d/glycosyl ceramides/iNKT cells and CD1d/sulfatide/sulfatide reactive Type II NKT cells have shown how the polar moieties on the glycolipids interact with both the antigen presenting protein (CD1d) and the T cell receptors. However, these structures
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Structural studies of ternary complexes of CD1d/glycosyl ceramides/iNKT cells and CD1d/sulfatide/sulfatide reactive Type II NKT cells have shown how the polar moieties on the glycolipids interact with both the antigen presenting protein (CD1d) and the T cell receptors. However, these structures alone do not reveal the relative importance of these interactions. This study focuses on the synthesis of the previously unknown 2ꞌꞌ-deoxy-β-galactosyl ceramide 2. This glycolipid is also evaluated for its ability to stimulate iNKT cells and sulfatide-reactive Type II NKT cells. Full article
(This article belongs to the Special Issue Synthesis, Structure, Analysis and Properties of Glycolipids)
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Open AccessArticle Capsaicin: A Potent Inhibitor of Carbonic Anhydrase Isoenzymes
Molecules 2014, 19(7), 10103-10114; doi:10.3390/molecules190710103
Received: 6 May 2014 / Revised: 19 June 2014 / Accepted: 3 July 2014 / Published: 10 July 2014
Cited by 37 | PDF Full-text (271 KB) | HTML Full-text | XML Full-text
Abstract
Carbonic anhydrase (CA, EC 4.2.1.1) is a zinc containing metalloenzyme that catalyzes the rapid and reversible conversion of carbon dioxide (CO2) and water (H2O) into a proton (H+) and bicarbonate (HCO3) ion. On the
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Carbonic anhydrase (CA, EC 4.2.1.1) is a zinc containing metalloenzyme that catalyzes the rapid and reversible conversion of carbon dioxide (CO2) and water (H2O) into a proton (H+) and bicarbonate (HCO3) ion. On the other hand, capsaicin is the main component in hot chili peppers and is used extensively used in spices, food additives and drugs; it is responsible for their spicy flavor and pungent taste. There are sixteen known CA isoforms in humans. Human CA isoenzymes I, and II (hCA I and hCA II) are ubiquitous cytosolic isoforms. In this study, the inhibition properties of capsaicin against the slow cytosolic isoform hCA I, and the ubiquitous and dominant rapid cytosolic isozymes hCA II were studied. Both CA isozymes were inhibited by capsaicin in the micromolar range. This naturally bioactive compound has a Ki of 696.15 µM against hCA I, and of 208.37 µM against hCA II. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Computer Aided Screening of Secreted Frizzled-Related Protein 4 (SFRP4): A Potential Control for Diabetes Mellitus
Molecules 2014, 19(7), 10129-10136; doi:10.3390/molecules190710129
Received: 21 April 2014 / Revised: 8 June 2014 / Accepted: 30 June 2014 / Published: 11 July 2014
Cited by 6 | PDF Full-text (820 KB) | HTML Full-text | XML Full-text
Abstract
Diabetes mellitus is a life threatening disease and scientists are doing their best to find a cost effective and permanent treatment of this malady. The recent trend is to control the disease by target base inhibiting of enzymes or proteins. Secreted frizzled-related protein
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Diabetes mellitus is a life threatening disease and scientists are doing their best to find a cost effective and permanent treatment of this malady. The recent trend is to control the disease by target base inhibiting of enzymes or proteins. Secreted frizzled-related protein 4 (SFRP4) is found to cause five times more risk of diabetes when expressed above average levels. This study was therefore designed to analyze the SFRP4 and to find its potential inhibitors. SFRP4 was analyzed by bio-informatics tools of sequence tool and structure tool. A total of three potential inhibitors of SFRP4 were found, namely cyclothiazide, clopamide and perindopril. These inhibitors showed significant interactions with SFRP4 as compared to other inhibitors as well as control (acetohexamide). The findings suggest the possible treatment of diabetes mellitus type 2 by inhibiting the SFRP4 using the inhibitors cyclothiazide, clopamide and perindopril. Full article
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Open AccessArticle First Order Temperature Dependent Phase Transition in a Monoclinic Polymorph Crystal of 1,6-Hexanedioic Acid: An Interpretation Based on the Landau Theory Approach
Molecules 2014, 19(7), 10137-10149; doi:10.3390/molecules190710137
Received: 28 May 2014 / Revised: 1 July 2014 / Accepted: 8 July 2014 / Published: 11 July 2014
Cited by 1 | PDF Full-text (553 KB) | HTML Full-text | XML Full-text
Abstract
Crystals of 1,6-hexanedioic acid (I) undergo a temperature-dependent reversible phase transition from monoclinic P21/c at a temperature higher than the critical temperature (Tc) 130 K to another monoclinic P21/c at temperature lower
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Crystals of 1,6-hexanedioic acid (I) undergo a temperature-dependent reversible phase transition from monoclinic P21/c at a temperature higher than the critical temperature (Tc) 130 K to another monoclinic P21/c at temperature lower than Tc. The phase transition is of first order, involving a discontinuity and a tripling of the b-axis at Tc whereas the other unit cell parameters vary continuously. The transition is described by the phenomenological Landau theory. The crystal structure analyses for data collected at 297(2) K and 120.0(1) K show that there is half of a molecule of (I) in the asymmetric unit at 297(2) K whereas there are one and a half molecules of (I) in the asymmetric unit at 120.0(1) K. At both temperatures, 297(2) and 120.0(1) K, intermolecular O-H···O hydrogen bonds link the molecules of I into infinite 1D chains along [101] direction. However there are significantly more O-H···O hydrogen bonds presented in the 120.0(1) K polymorph, thereby indicating this phase transition is negotiated via hydrogen bonds. The relationship of the conformational changes and hydrogen bonding for these two polymorphs are explained in detail. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Design, Synthesis and Biological Evaluation of C(6)-Modified Celastrol Derivatives as Potential Antitumor Agents
Molecules 2014, 19(7), 10177-10188; doi:10.3390/molecules190710177
Received: 7 May 2014 / Revised: 2 July 2014 / Accepted: 4 July 2014 / Published: 14 July 2014
Cited by 6 | PDF Full-text (691 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
New six C6-celastrol derivatives were designed, synthesized, and evaluated for their in vitro cytotoxic activities against nine human cancer cell lines (BGC-823, H4, Bel7402, H522, Colo 205, HepG2 and MDA-MB-468). The results showed that most of the compounds displayed
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New six C6-celastrol derivatives were designed, synthesized, and evaluated for their in vitro cytotoxic activities against nine human cancer cell lines (BGC-823, H4, Bel7402, H522, Colo 205, HepG2 and MDA-MB-468). The results showed that most of the compounds displayed potent inhibition against BGC823, H4, and Bel7402, with IC50s of 1.84–0.39 μM. The best compound NST001A was tested in an in vivo antitumor assay on nude mice bearing Colo 205 xenografts, and showed significant inhibition of tumor growth at low concentrations. Therefore, celastrol C-6 derivatives are potential drug candidates for treating cancer. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Phenolic Profiles and Antioxidant Properties of Young Wines Made from Yan73 (Vitis vinifera L.) and Cabernet Sauvignon (Vitis vinifera L.) Grapes Treated by 24-Epibrassinolide
Molecules 2014, 19(7), 10189-10207; doi:10.3390/molecules190710189
Received: 20 April 2014 / Revised: 2 July 2014 / Accepted: 10 July 2014 / Published: 14 July 2014
Cited by 4 | PDF Full-text (777 KB) | HTML Full-text | XML Full-text
Abstract
The grape berries of two varieties, Yan73 (Vitis vinifera L.) and Cabernet Sauvignon (CS) (Vitis vinifera L.) were treated with 0.40 mg/L 24-epibrassinolide (EBR), 1.00 mg/L brassinazole (Brz), and deionized water (control), at the veraison period. The
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The grape berries of two varieties, Yan73 (Vitis vinifera L.) and Cabernet Sauvignon (CS) (Vitis vinifera L.) were treated with 0.40 mg/L 24-epibrassinolide (EBR), 1.00 mg/L brassinazole (Brz), and deionized water (control), at the veraison period. The EBR treatment significantly increased total phenolic content (TPC), total tannin content (TTC) and total anthocyanin content (TAC) of Yan73 and CS wines, whereas Brz treatment decreased TPC, total flavonoid content (TFC), TAC in the two wines. Moreover, the content of most of the phenolic compounds identified by HPLC-DAD/ESI-MS in EBR-treated wines was significantly higher than that in control. The antioxidant capacities, which determined using DPPH, ABTS and HRSA methods, of the wines were increased by EBR treatment as well. There was a good correlation between the antioxidant capacity and phenolic content. The results demonstrated that EBR could enhance the phenolic compounds and antioxidant capacity of Yan73 and CS wines, but the effects may vary by different cultivars. Full article
Open AccessArticle Identification of Catechol as a New Marker for Detecting Propolis Adulteration
Molecules 2014, 19(7), 10208-10217; doi:10.3390/molecules190710208
Received: 18 June 2014 / Revised: 2 July 2014 / Accepted: 10 July 2014 / Published: 14 July 2014
Cited by 4 | PDF Full-text (1351 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Adulteration of propolis with poplar extract is a serious issue in the bee products market. The aim of this study was to identify marker compounds in adulterated propolis, and examine the transformation of chemical components from poplar buds to propolis. The chemical profiles
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Adulteration of propolis with poplar extract is a serious issue in the bee products market. The aim of this study was to identify marker compounds in adulterated propolis, and examine the transformation of chemical components from poplar buds to propolis. The chemical profiles of poplar extracts and propolis were compared, and a new marker compound, catechol, was isolated and identified from the extracts of poplar buds. The polyphenol oxidase, catechol oxidase, responsible for catalyzing oxidation of catechol was detected in poplar buds and propolis. The results indicate catechol can be used as a marker to detect propolis adulterated with poplar extract. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
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Open AccessArticle An Erbium-Based Bifuctional Heterogeneous Catalyst: A Cooperative Route Towards C-C Bond Formation
Molecules 2014, 19(7), 10218-10229; doi:10.3390/molecules190710218
Received: 28 May 2014 / Revised: 2 July 2014 / Accepted: 4 July 2014 / Published: 15 July 2014
Cited by 1 | PDF Full-text (686 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Heterogeneous bifuctional catalysts are multifunctional synthetic catalysts enabling efficient organic transformations by exploiting two opposite functionalities without mutual destruction. In this paper we report the first Er(III)-based metallorganic heterogeneous catalyst, synthesized by post-calcination MW-assisted grafting and modification of the natural aminoacid L-cysteine. The
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Heterogeneous bifuctional catalysts are multifunctional synthetic catalysts enabling efficient organic transformations by exploiting two opposite functionalities without mutual destruction. In this paper we report the first Er(III)-based metallorganic heterogeneous catalyst, synthesized by post-calcination MW-assisted grafting and modification of the natural aminoacid L-cysteine. The natural acid–base distance between sites was maintained to assure the cooperation. The applicability of this new bifunctional heterogeneous catalyst to C-C bond formation and the supposed mechanisms of action are discussed as well. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle QM/MM Studies of Contemporary and Novel Membrane Raft Fluorescent Probes
Molecules 2014, 19(7), 10230-10241; doi:10.3390/molecules190710230
Received: 16 June 2014 / Revised: 9 July 2014 / Accepted: 10 July 2014 / Published: 15 July 2014
Cited by 1 | PDF Full-text (640 KB) | HTML Full-text | XML Full-text
Abstract
We have studied a number of contemporary and novel membrane probes, selected for their structural similarity to membrane raft components, in order to properly anchor themselves within a sphingolipid/cholesterol rich region. A QM/MM approach was adopted in order to understand the structural and
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We have studied a number of contemporary and novel membrane probes, selected for their structural similarity to membrane raft components, in order to properly anchor themselves within a sphingolipid/cholesterol rich region. A QM/MM approach was adopted in order to understand the structural and electrostatic influences of fluorescence emission shifts of the probes in different lipid and solvation environments. The proposed modifications to the membrane probes have shown encouraging data relating not only to emission shifts within the membrane, but also their ability to anchor within a membrane raft domain and the stability to internalization within a membrane system. Full article
Open AccessArticle Jasmonic Acid Effect on the Fatty Acid and Terpenoid Indole Alkaloid Accumulation in Cell Suspension Cultures of Catharanthus roseus
Molecules 2014, 19(7), 10242-10260; doi:10.3390/molecules190710242
Received: 4 May 2014 / Revised: 23 June 2014 / Accepted: 10 July 2014 / Published: 15 July 2014
Cited by 7 | PDF Full-text (1637 KB) | HTML Full-text | XML Full-text
Abstract
The stress response after jasmonic acid (JA) treatment was studied in cell suspension cultures of Catharanthus roseus. The effect of JA on the primary and secondary metabolism was based on changes in profiles of fatty acids (FA) and terpenoid indole alkaloids (TIA).
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The stress response after jasmonic acid (JA) treatment was studied in cell suspension cultures of Catharanthus roseus. The effect of JA on the primary and secondary metabolism was based on changes in profiles of fatty acids (FA) and terpenoid indole alkaloids (TIA). According to multivariate data analyses (MVDA), three major time events were observed and characterized according to the variations of specific FA and TIA: after 0–30 min of induction FA such as C18:1, C20:0, C22:0 and C24:0 were highly induced by JA; 90–360 min after treatment was characterized by variations of C14:0 and C15:0; and 1440 min after induction JA had the largest effect on both group of metabolites were C18:1, C18:2, C18:3, C16:0, C20:0, C22:0, C24:0, catharanthine, tabersonine-like 1, serpentine, tabersonine and ajmalicine-like had the most significant variations. These results unambiguously demonstrate the profound effect of JA particularly on the accumulation of its own precursor, C18:3 and the accumulation of TIA, which can be considered as late stress response events to JA since they occurred only after 1440 min. These observations show that the early events in the JA response do not involve the de novo biosynthesis of neither its own precursor nor TIA, but is due to an already present biochemical system. Full article
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Open AccessArticle Bioassay-Guided Chemical Study of the Anti-Inflammatory Effect of Senna villosa (Miller) H.S. Irwin & Barneby (Leguminosae) in TPA-Induced Ear Edema
Molecules 2014, 19(7), 10261-10278; doi:10.3390/molecules190710261
Received: 23 March 2014 / Revised: 9 July 2014 / Accepted: 10 July 2014 / Published: 15 July 2014
Cited by 2 | PDF Full-text (566 KB) | HTML Full-text | XML Full-text
Abstract
Senna villosa (Miller) is a plant that grows in México. In traditional Mexican medicine, it is used topically to treat skin infections, pustules and eruptions and to heal wounds by scar formation. However, studies of its potential anti-inflammatory effects have not been performed.
[...] Read more.
Senna villosa (Miller) is a plant that grows in México. In traditional Mexican medicine, it is used topically to treat skin infections, pustules and eruptions and to heal wounds by scar formation. However, studies of its potential anti-inflammatory effects have not been performed. The aim of the present study was to determine the anti-inflammatory effect of extracts from the leaves of Senna villosa and to perform a bioassay-guided chemical study of the extract with major activity in a model of ear edema induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). The results reveal that the chloroform extract from Senna villosa leaves has anti-inflammatory and anti-proliferative properties. Nine fractions were obtained from the bioassay-guided chemical study, including a white precipitate from fractions 2 and 3. Although none of the nine fractions presented anti-inflammatory activity, the white precipitate exhibited pharmacological activity. It was chemically characterized using mass spectrometry and infrared and nuclear magnetic resonance spectroscopy, resulting in a mixture of three aliphatic esters, which were identified as the principal constituents: hexyl tetradecanoate (C20H40O2), heptyl tetradecanoate (C21H42O2) and octyl tetradecanoate (C22H44O2). This research provides, for the first time, evidence of the anti-inflammatory and anti-proliferative properties of compounds isolated from Senna villosa. Full article
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Open AccessArticle The Natural Product Citral Can Cause Significant Damage to the Hyphal Cell Walls of Magnaporthe grisea
Molecules 2014, 19(7), 10279-10290; doi:10.3390/molecules190710279
Received: 19 June 2014 / Revised: 1 July 2014 / Accepted: 10 July 2014 / Published: 15 July 2014
Cited by 7 | PDF Full-text (1094 KB) | HTML Full-text | XML Full-text
Abstract
In order to find a natural alternative to the synthetic fungicides currently used against the devastating rice blast fungus, Magnaporthe grisea, this study explored the antifungal potential of citral and its mechanism of action. It was found that citral not only inhibited
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In order to find a natural alternative to the synthetic fungicides currently used against the devastating rice blast fungus, Magnaporthe grisea, this study explored the antifungal potential of citral and its mechanism of action. It was found that citral not only inhibited hyphal growth of M. grisea, but also caused a series of marked hyphal morphological and structural alterations. Specifically, citral was tested for antifungal activity against M. grisea in vitro and was found to significantly inhibit colony development and mycelial growth with IC50 and IC90 values of 40.71 and 203.75 μg/mL, respectively. Furthermore, citral reduced spore germination and germ tube length in a concentration-dependent manner. Following exposure to citral, the hyphal cell surface became wrinkled with folds and cell breakage that were observed under scanning electron microscopy (SEM). There was damage to hyphal cell walls and membrane structures, loss of villous-like material outside of the cell wall, thinning of the cell wall, and discontinuities formed in the cell membrane following treatment based on transmission electron microscopy (TEM). This increase in chitinase activity both supports the morphological changes seen in the hyphae, and also suggests a mechanism of action. In conclusion, citral has strong antifungal properties, and treatment with this compound is capable of causing significant damage to the hyphal cell walls of M. grisea. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Biotransformation and in Vitro Metabolic Profile of Bioactive Extracts from a Traditional Miao-Nationality Herbal Medicine, Polygonum capitatum
Molecules 2014, 19(7), 10291-10308; doi:10.3390/molecules190710291
Received: 23 May 2014 / Revised: 7 July 2014 / Accepted: 8 July 2014 / Published: 16 July 2014
Cited by 2 | PDF Full-text (1219 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Polygonum capitatum Buch.-Ham.ex D. Don, a traditional Miao-nationality herbal medicine, has been widely used in the treatment of various urologic disorders. Recent pharmacological studies demonstrated that a pure compound, FR429, isolated from the ethanol extracts of P. capitatum could selectively inhibit the growth
[...] Read more.
Polygonum capitatum Buch.-Ham.ex D. Don, a traditional Miao-nationality herbal medicine, has been widely used in the treatment of various urologic disorders. Recent pharmacological studies demonstrated that a pure compound, FR429, isolated from the ethanol extracts of P. capitatum could selectively inhibit the growth of four hepatocellular carcinoma (HCC) cell lines in a dose-dependent manner. Thus, P. capitatum probably exhibits potential antitumor activity. However, there is very little information on the metabolism of substances present in P. capitatum extracts. In this study, gallic acid, quercetrin, ethanol extracts and ethyl acetate fraction of ethnolic extract (EtOAc fraction) of P. capitatum were cultured anaerobically with rat intestinal bacteria. A highly sensitive and selective liquid chromatography electrospray ionization-ion trap-time of fight mass spectrometry (LC/MSn-IT-TOF) technique was employed to identify and characterize the resulting metabolites. A total of 22 metabolites (M1–M22), including tannins, phenolic acids and flavonoids, were detected and characterized. The overall results demonstrated that the intestinal bacteria played an important role in the metabolism of P. capitatum, and the main metabolic pathways were hydrolysis, reduction and oxidation reactions. Our results provided a basis for the estimation of the metabolic transformation of P. capitatum in vivo. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Simultaneous Quantitation and Validation of Triterpenoids and Phytosteroids in Phaseolus angularis Seeds
Molecules 2014, 19(7), 10309-10319; doi:10.3390/molecules190710309
Received: 22 May 2014 / Revised: 30 June 2014 / Accepted: 4 July 2014 / Published: 16 July 2014
Cited by 4 | PDF Full-text (256 KB) | HTML Full-text | XML Full-text
Abstract
A reproducible analytical method using reverse-phase high liquid performance chromatography combined with UV detecting was developed for the quantitative determination of four compounds isolated from the ethanol extract of Phaseolus angularis seeds (PASE): oleanolic acid (1), oleanolic acid acetate (2
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A reproducible analytical method using reverse-phase high liquid performance chromatography combined with UV detecting was developed for the quantitative determination of four compounds isolated from the ethanol extract of Phaseolus angularis seeds (PASE): oleanolic acid (1), oleanolic acid acetate (2), stigmasterol (3) and β-sitosterol (4). This method was fully validated in terms of linearity (r2 > 0.999), accuracy (98.5%–100.8%), precision (<0.92%), LOD (<0.0035 mg/mL), and LOQ (<0.0115 mg/mL). The effects of the PASE and isolated compounds 14 on TLR4 activation were tested in THP1-Blue cells. Among the tested substances, compound 2 showed potent inhibitory activity with an IC50 value of 3.89 ± 0.17 µM. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Atypical McMurry Cross-Coupling Reactions Leading to a New Series of Potent Antiproliferative Compounds Bearing the Key [Ferrocenyl-Ene-Phenol] Motif
Molecules 2014, 19(7), 10350-10369; doi:10.3390/molecules190710350
Received: 12 June 2014 / Revised: 3 July 2014 / Accepted: 7 July 2014 / Published: 17 July 2014
Cited by 7 | PDF Full-text (658 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the course of the preparation of a series of ferrocenyl derivatives of diethylstilbestrol (DES), in which one of the 4-hydroxyphenyl moieties was replaced by a ferrocenyl group, the McMurry reaction of chloropropionylferrocene with a number of mono-aryl ketones unexpectedly yielded the hydroxylated
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In the course of the preparation of a series of ferrocenyl derivatives of diethylstilbestrol (DES), in which one of the 4-hydroxyphenyl moieties was replaced by a ferrocenyl group, the McMurry reaction of chloropropionylferrocene with a number of mono-aryl ketones unexpectedly yielded the hydroxylated ferrocenyl DES derivatives, 5ac, in poor yields (10%–16%). These compounds showed high activity on the hormone-independent breast cancer cell line MDA-MB-231 with IC50 values ranging from 0.14 to 0.36 µM. Surprisingly, non-hydroxylated ferrocenyl DES, 4, showed only an IC50 value of 1.14 µM, illustrating the importance of the hydroxyethyl function in this promising new series. For comparison, McMurry reactions of the shorter chain analogue chloroacetylferrocene were carried out to see the difference in behaviour with mono-aryl ketones versus a diaryl ketone. The effect of changing the length of the alkyl chain adjacent to the phenolic substituent of the hydroxylated ferrocenyl DES was studied, a mechanistic rationale to account for the unexpected products is proposed, and the antiproliferative activities of all of these compounds on MDA-MB-231 cells lines were measured and compared. X-ray crystal structures of cross-coupled products and of pinacol-pinacolone rearrangements are reported. Full article
(This article belongs to the Special Issue Practical Applications of Metal Complexes)
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Open AccessArticle Variation in the Bioactive Compound Content at Three Ripening Stages of Strawberry Fruit
Molecules 2014, 19(7), 10370-10385; doi:10.3390/molecules190710370
Received: 27 May 2014 / Revised: 7 July 2014 / Accepted: 8 July 2014 / Published: 17 July 2014
Cited by 6 | PDF Full-text (348 KB) | HTML Full-text | XML Full-text
Abstract
During the harvest season of two consecutive years, five strawberry cultivars (‘Arosa’, ‘Elsanta’, ‘Marmolada’, ‘Miss’ and ‘Raurica’), grown in the continental part of the Republic of Croatia, were examined. Strawberry fruits quality was evaluated by individual phenol compounds, individual anthocyanins and fruit color.
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During the harvest season of two consecutive years, five strawberry cultivars (‘Arosa’, ‘Elsanta’, ‘Marmolada’, ‘Miss’ and ‘Raurica’), grown in the continental part of the Republic of Croatia, were examined. Strawberry fruits quality was evaluated by individual phenol compounds, individual anthocyanins and fruit color. Fruits were harvested in three different periods. Analyzed strawberry cultivars show very good average values of the studied phenolic acids and flavonoids with predominant caffeic acid and epicatechin content in all researched strawberry cultivars. Considering the content of individual anthocyanins, pelargonidin 3-glucoside is predominant in strawberry extract followed by cyanidin-3-glucoside and pelargonidin 3-rutinoside. The correlation between individual anthocyanin content and chromaticity parameters was detected in all strawberry cultivars, additionally correlation coefficients and statistical significance were much lower. The results show a positive association between cultivar and harvest time on strawberry pulp color, with each of the color variables, a, b, a/b ratio, C, L and values. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Preparation and Biological Properties of Ring-Substituted Naphthalene-1-Carboxanilides
Molecules 2014, 19(7), 10386-10409; doi:10.3390/molecules190710386
Received: 10 May 2014 / Revised: 13 July 2014 / Accepted: 14 July 2014 / Published: 17 July 2014
Cited by 6 | PDF Full-text (438 KB) | HTML Full-text | XML Full-text
Abstract
In this study, a series of twenty-two ring-substituted naphthalene-1-carboxanilides were prepared and characterized. Primary in vitro screening of the synthesized carboxanilides was performed against Mycobacterium avium subsp. paratuberculosis. N-(2-Methoxyphenyl)naphthalene-1-carboxamide, N-(3-methoxy-phenyl)naphthalene-1-carboxamide, N-(3-methylphenyl)naphthalene-1-carboxamide, N-(4-methylphenyl)naphthalene-1-carboxamide and N-(3-fluorophenyl)naphthalene-1-carboxamide showed against M.
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In this study, a series of twenty-two ring-substituted naphthalene-1-carboxanilides were prepared and characterized. Primary in vitro screening of the synthesized carboxanilides was performed against Mycobacterium avium subsp. paratuberculosis. N-(2-Methoxyphenyl)naphthalene-1-carboxamide, N-(3-methoxy-phenyl)naphthalene-1-carboxamide, N-(3-methylphenyl)naphthalene-1-carboxamide, N-(4-methylphenyl)naphthalene-1-carboxamide and N-(3-fluorophenyl)naphthalene-1-carboxamide showed against M. avium subsp. paratuberculosis two-fold higher activity than rifampicin and three-fold higher activity than ciprofloxacin. The most effective antimycobacterial compounds demonstrated insignificant toxicity against the human monocytic leukemia THP-1 cell line. The testing of biological activity of the compounds was completed with the study of photosynthetic electron transport (PET) inhibition in isolated spinach (Spinacia oleracea L.) chloroplasts. The PET-inhibiting activity expressed by IC50 value of the most active compound N-[4-(trifluoromethyl)phenyl]naphthalene-1-carboxamide was 59 μmol/L. The structure-activity relationships are discussed. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Preparation of Crosslinked Amphiphilic Silver Nanogel as Thin Film Corrosion Protective Layer for Steel
Molecules 2014, 19(7), 10410-10426; doi:10.3390/molecules190710410
Received: 6 June 2014 / Revised: 9 July 2014 / Accepted: 14 July 2014 / Published: 17 July 2014
Cited by 6 | PDF Full-text (884 KB) | HTML Full-text | XML Full-text
Abstract
Monodisperse silver nanoparticles were synthesized by a new developed method via reaction of AgNO3 and oleic acid with the addition of a trace amount of Fe3+ ions. Emulsion polymerization at room temperature was employed to prepare a core-shell silver nanoparticle with
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Monodisperse silver nanoparticles were synthesized by a new developed method via reaction of AgNO3 and oleic acid with the addition of a trace amount of Fe3+ ions. Emulsion polymerization at room temperature was employed to prepare a core-shell silver nanoparticle with controllable particle size. N,N'-methylenebisacrylamide (MBA) and potassium peroxydisulfate (KPS) were used as a crosslinker, and as redox initiator system, respectively for crosslinking polymerization. The structure and morphology of the silver nanogels were characterized by Fourier transform infrared spectroscopy (FTIR), transmission and scanning electron microscopy (TEM and SEM). The effectiveness of the synthesized compounds as corrosion inhibitors for steel in 1 M HCl was investigated by various electrochemical techniques such as potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). Monolayers of silver nanoparticle were self-assembled on the fresh active surface of the steel electrode and have been tested as a corrosion inhibitor for steel in 1 M HCl solution. The results of polarization measurements showed that nanogel particles act as a mixed type inhibitor. Full article
Open AccessArticle Qualitative and Quantitative Analysis of Rhizoma Smilacis glabrae by Ultra High Performance Liquid Chromatography Coupled with LTQ OrbitrapXL Hybrid Mass Spectrometry
Molecules 2014, 19(7), 10427-10439; doi:10.3390/molecules190710427
Received: 3 June 2014 / Revised: 10 July 2014 / Accepted: 11 July 2014 / Published: 17 July 2014
Cited by 10 | PDF Full-text (300 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Rhizoma Smilacis glabrae, a traditional Chinese medicine (TCM) as well as a functional food, has been commonly used for detoxification treatments, relieving dampness and as a diuretic. In order to quickly define the chemical profiles and control the quality of
[...] Read more.
Rhizoma Smilacis glabrae, a traditional Chinese medicine (TCM) as well as a functional food, has been commonly used for detoxification treatments, relieving dampness and as a diuretic. In order to quickly define the chemical profiles and control the quality of Smilacis glabrae, ultra high performance liquid chromatography coupled with electrospray ionization hybrid linear trap quadrupole orbitrap mass spectrometry (UHPLC-ESI/LTQ-Orbitrap-MS) was applied for simultaneous identification and quantification of its bioactive constituents. A total of 56 compounds, including six new compounds, were identified or tentatively deduced on the basis of their retention behaviors, mass spectra, or by comparison with reference substances and literature data. The identified compounds belonged to flavonoids, phenolic acids and phenylpropanoid glycosides. In addition, an optimized UHPLC-ESI/LTQ-Orbitrap-MS method was established for quantitative determination of six marker compounds from five batches. The validation of the method, including linearity, sensitivity (LOQ), precision, repeatability and spike recoveries, was carried out and demonstrated to be satisfied the requirements of quantitative analysis. The results suggested that the established method would be a powerful and reliable analytical tool for the characterization of multi-constituent in complex chemical system and quality control of TCM. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Dynamic Changes of Flavonoids Contents in the Different Parts of Rhizome of Belamcanda chinensis During the Thermal Drying Process
Molecules 2014, 19(7), 10440-10454; doi:10.3390/molecules190710440
Received: 16 April 2014 / Revised: 24 June 2014 / Accepted: 10 July 2014 / Published: 17 July 2014
Cited by 4 | PDF Full-text (602 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The dried rhizome of Belamcanda. chinensis (L.) DC. is an important traditional Chinese medicine. Previous chemical and pharmacological investigations indicated that flavonoids may be responsible for the bioactivity of the herb. In this paper, the effects on the contents of twelve flavonoids in
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The dried rhizome of Belamcanda. chinensis (L.) DC. is an important traditional Chinese medicine. Previous chemical and pharmacological investigations indicated that flavonoids may be responsible for the bioactivity of the herb. In this paper, the effects on the contents of twelve flavonoids in the three subunit parts of the rhizome of B. chinensis during the thermal drying process under treatment temperatures ranging from 40 °C to 120 °C at 10 °C intervals were investigated. The results showed that the content of most of the individual flavonoids except that of tectorigenin in the fresh eldest parts of the rhizome that originate directly from the seedling was higher than those of the other junior parts. The change trends of flavonoids contents were similar for three subunit parts of the rhizome during the drying process under the same treatment temperature. Most of the individual flavonoid contents in the rhizome increased in the early stages of the drying processes and decreased as the process was prolonged. The durations required to reaching the points of the maximal amounts of flavonoids revealed a significant negative correlation with the temperature. The variation of the content of mangiferin, iristectorigenin A, irigenin, irilone and dichotomitin was positively correlated with irisflorentin that is the chemical marker used for the quality control of this herb. Taking into account of the production effectiveness and flavonoid yields, the appropriate drying temperature for this herb was suggested to be 100 °C. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle The Effect of Mini-PEG-Based Spacer Length on Binding and Pharmacokinetic Properties of a 68Ga-Labeled NOTA-Conjugated Antagonistic Analog of Bombesin
Molecules 2014, 19(7), 10455-10472; doi:10.3390/molecules190710455
Received: 3 June 2014 / Revised: 10 July 2014 / Accepted: 11 July 2014 / Published: 17 July 2014
Cited by 14 | PDF Full-text (560 KB) | HTML Full-text | XML Full-text
Abstract
The overexpression of gastrin-releasing peptide receptor (GRPR) in cancer can be used for peptide-receptor mediated radionuclide imaging and therapy. We have previously shown that an antagonist analog of bombesin RM26 conjugated to 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) via a
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The overexpression of gastrin-releasing peptide receptor (GRPR) in cancer can be used for peptide-receptor mediated radionuclide imaging and therapy. We have previously shown that an antagonist analog of bombesin RM26 conjugated to 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) via a diethyleneglycol (PEG2) spacer (NOTA-PEG2-RM26) and labeled with 68Ga can be used for imaging of GRPR-expressing tumors. In this study, we evaluated if a variation of mini-PEG spacer length can be used for optimization of targeting properties of the NOTA-conjugated RM26. A series of analogs with different PEG-length (n = 2, 3, 4, 6) was synthesized, radiolabeled and evaluated in vitro and in vivo. The IC50 values of natGa-NOTA-PEGn-RM26 (n = 2, 3, 4, 6) were 3.1 ± 0.2, 3.9 ± 0.3, 5.4 ± 0.4 and 5.8 ± 0.3 nM, respectively. In normal mice all conjugates demonstrated similar biodistribution pattern, however 68Ga-NOTA-PEG3-RM26 showed lower liver uptake. Biodistribution of 68Ga-NOTA-PEG3-RM26 was evaluated in nude mice bearing PC-3 (prostate cancer) and BT-474 (breast cancer) xenografts. High uptake in tumors (4.6 ± 0.6%ID/g and 2.8 ± 0.4%ID/g for PC-3 and BT-474 xenografts, respectively) and high tumor-to-background ratios (tumor/blood of 44 ± 12 and 42 ± 5 for PC-3 and BT-474 xenografts, respectively) were found already at 2 h p.i. of 68Ga-NOTA-PEG3-RM26. Results of this study suggest that variation in the length of the PEG spacer can be used for optimization of targeting properties of peptide-chelator conjugates. However, the influence of the mini-PEG length on biodistribution is minor when di-, tri-, tetra- and hexaethylene glycol are compared. Full article
(This article belongs to the Special Issue Peptide Chemistry)
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Open AccessArticle Two New Iridoids from Verbena officinalis L.
Molecules 2014, 19(7), 10473-10479; doi:10.3390/molecules190710473
Received: 16 June 2014 / Revised: 6 July 2014 / Accepted: 15 July 2014 / Published: 18 July 2014
Cited by 4 | PDF Full-text (287 KB) | HTML Full-text | XML Full-text
Abstract
Two new iridoids, 3-(5-(methoxycarbonyl)-2-oxo-2H-pyran-3-yl)butanoic acid, named verbeofflin I (1), and 7-hydroxydehydrohastatoside (2), were isolated from the aerial part of Verbena officinalis L, along with three known iridoids, verbenalin (3), 3,4-dihydroverbenalin (4), hastatoside (
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Two new iridoids, 3-(5-(methoxycarbonyl)-2-oxo-2H-pyran-3-yl)butanoic acid, named verbeofflin I (1), and 7-hydroxydehydrohastatoside (2), were isolated from the aerial part of Verbena officinalis L, along with three known iridoids, verbenalin (3), 3,4-dihydroverbenalin (4), hastatoside (5) by means of various column chromatography steps. The structures of these compounds were elucidated through analysis of their spectroscopic data obtained using 1D and 2D NMR and MS techniques. Verbeofflin I (1) is the new class of secoiridoid in the family Verbenaceae. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Antioxidant, Antimicrobial and Phytochemical Variations in Thirteen Moringa oleifera Lam. Cultivars
Molecules 2014, 19(7), 10480-10494; doi:10.3390/molecules190710480
Received: 13 June 2014 / Revised: 2 July 2014 / Accepted: 9 July 2014 / Published: 18 July 2014
Cited by 11 | PDF Full-text (276 KB) | HTML Full-text | XML Full-text
Abstract
A study was undertaken to assess variation in antioxidant, antimicrobial and phytochemical properties of thirteen Moringa oleifera cultivars obtained from different locations across the globe. Standard antioxidant methods including the DPPH scavenging, ferric reducing power (FRAP) and β-carotene-linoleic acid model were used
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A study was undertaken to assess variation in antioxidant, antimicrobial and phytochemical properties of thirteen Moringa oleifera cultivars obtained from different locations across the globe. Standard antioxidant methods including the DPPH scavenging, ferric reducing power (FRAP) and β-carotene-linoleic acid model were used to evaluate the activity. Variation in the antioxidant activity was observed, with TOT4951 from Thailand being the most active, with activity five times higher than that of ascorbic acid (reference compound). A different trend was observed for the activity in the FRAP and β-carotene-linoleic acid assays. Antimicrobial activity was tested against Gram-positive (Staphylococcus aureus) and Gram-negative (Klebsiella pneumoniae) strains using the microdilution method. Acetone extracts of all cultivars exhibited good antibacterial activity against K. pneumoniae (MIC values of 0.78 mg/mL). The remaining extracts exhibited weak activity against the two microorganisms. For the antifungal activity, all the extracts exhibited low activity. Variations were observed in the total phenolic and flavonoid contents. Cultivars TOT5169 (Thailand) and SH (South Africa) exhibited highest amounts of total phenolic compounds while TOT5028 (Thailand) exhibited the lowest amounts of five times lower than the highest. The information offer an understanding on variations between cultivars from different geographical locations and is important in the search for antioxidant supplementation and anti-ageing products. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
Open AccessArticle Thioctic Acid Derivatives as Building Blocks to Incorporate DNA Oligonucleotides onto Gold Nanoparticles
Molecules 2014, 19(7), 10495-10523; doi:10.3390/molecules190710495
Received: 11 June 2014 / Revised: 4 July 2014 / Accepted: 4 July 2014 / Published: 18 July 2014
Cited by 7 | PDF Full-text (1382 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Oligonucleotide gold nanoparticle conjugates are being used as diagnostic tools and gene silencing experiments. Thiol-chemistry is mostly used to functionalize gold nanoparticles with oligonucleotides and to incorporate DNA or RNA molecules onto gold surfaces. However, the stability of such nucleic acid–gold nanoparticle conjugates
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Oligonucleotide gold nanoparticle conjugates are being used as diagnostic tools and gene silencing experiments. Thiol-chemistry is mostly used to functionalize gold nanoparticles with oligonucleotides and to incorporate DNA or RNA molecules onto gold surfaces. However, the stability of such nucleic acid–gold nanoparticle conjugates in certain conditions may be a limitation due to premature break of the thiol-gold bonds followed by aggregation processes. Here, we describe a straightforward synthesis of oligonucleotides carrying thioctic acid moiety based on the use of several thioctic acid-L-threoninol derivatives containing different spacers, including triglycine, short polyethyleneglycol, or aliphatic spacers. The novel thioctic-oligonucleotides were used for the functionalization of gold nanoparticles and the surface coverage and stability of the resulting thioctic-oligonucleotide gold nanoparticles were assessed. In all cases gold nanoparticles functionalized with thioctic-oligonucleotides had higher loadings and higher stability in the presence of thiols than gold nanoparticles prepared with commercially available thiol-oligonucleotides. Furthermore, the thioctic derivative carrying the triglycine linker is sensitive to cathepsin B present in endosomes. In this way this derivative may be interesting for the cellular delivery of therapeutic oligonucleotides as these results provides the basis for a potential endosomal escape. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessCommunication Reduction of Adhesion Molecule Production and Alteration of eNOS and Endothelin-1 mRNA Expression in Endothelium by Euphorbia hirta L. through Its Beneficial β-Amyrin Molecule
Molecules 2014, 19(7), 10534-10545; doi:10.3390/molecules190710534
Received: 6 June 2014 / Revised: 3 July 2014 / Accepted: 11 July 2014 / Published: 18 July 2014
Cited by 3 | PDF Full-text (519 KB) | HTML Full-text | XML Full-text
Abstract
The inflammatory reaction in large blood vessels involves up-regulation of vascular adhesion molecules such as endothelial cell selectin (E-selectin), soluble vascular cell adhesion molecule (sVCAM)-1, and soluble intercellular adhesion molecule (sICAM)-1. These vascular dysfunctions are associated with the development of atherosclerosis. β-Amyrin, an
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The inflammatory reaction in large blood vessels involves up-regulation of vascular adhesion molecules such as endothelial cell selectin (E-selectin), soluble vascular cell adhesion molecule (sVCAM)-1, and soluble intercellular adhesion molecule (sICAM)-1. These vascular dysfunctions are associated with the development of atherosclerosis. β-Amyrin, an active component of Euphorbia hirta L., has potent anti-inflammatory effects. So far, its preventive effects against the expression of inflammatory mediator-induced adhesion molecules have not been investigated. Endothelial cells (SVEC4-10 cell line) were treated with 50% RAW conditioned media (i.e., normal SVEC4-10 culture media contains 50% of lipopolysaccharide-activated macrophage culture media) without or with β-amyrin (0.6 and 0.3 µM). The production levels of E-selectin, sICAM-1, and sVCAM-1 in the SVEC4-10 cells were measured with ELISA assay kits. Under the same treatment conditions, expression of endothelin (ET)-1 and endothelial type of NO synthase (eNOS) mRNA were analyzed by RT-PCR and agarose gel. With β-amyrin, the 50% RAW conditioned media-induced E-selectin, sICAM-1, and sVCAM-1 levels as well as ET-1 gene expression were all suppressed. β-Amyrin treatment also restored the 50% RAW conditioned media-suppressed eNOS mRNA expression. These data indicate that β-amyrin is potentially useful in preventing chronic inflammation-related vascular diseases. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Hologram QSAR Studies of Antiprotozoal Activities of Sesquiterpene Lactones
Molecules 2014, 19(7), 10546-10562; doi:10.3390/molecules190710546
Received: 4 April 2014 / Revised: 8 July 2014 / Accepted: 9 July 2014 / Published: 18 July 2014
Cited by 4 | PDF Full-text (995 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Infectious diseases such as trypanosomiasis and leishmaniasis are considered neglected tropical diseases due the lack for many years of research and development into new drug treatments besides the high incidence of mortality and the lack of current safe and effective drug therapies. Natural
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Infectious diseases such as trypanosomiasis and leishmaniasis are considered neglected tropical diseases due the lack for many years of research and development into new drug treatments besides the high incidence of mortality and the lack of current safe and effective drug therapies. Natural products such as sesquiterpene lactones have shown activity against T. brucei and L. donovani, the parasites responsible for these neglected diseases. To evaluate structure activity relationships, HQSAR models were constructed to relate a series of 40 sesquiterpene lactones (STLs) with activity against T. brucei, T. cruzi, L. donovani and P. falciparum and also with their cytotoxicity. All constructed models showed good internal (leave-one-out q2 values ranging from 0.637 to 0.775) and external validation coefficients (r2test values ranging from 0.653 to 0.944). From HQSAR contribution maps, several differences between the most and least potent compounds were found. The fragment contribution of PLS-generated models confirmed the results of previous QSAR studies that the presence of α,β-unsatured carbonyl groups is fundamental to biological activity. QSAR models for the activity of these compounds against T. cruzi, L. donovani and P. falciparum are reported here for the first time. The constructed HQSAR models are suitable to predict the activity of untested STLs. Full article
Open AccessArticle Isolation and Characterization of an α-Glucosidase Inhibitor from Musa spp. (Baxijiao) Flowers
Molecules 2014, 19(7), 10563-10573; doi:10.3390/molecules190710563
Received: 3 June 2014 / Revised: 15 July 2014 / Accepted: 15 July 2014 / Published: 18 July 2014
Cited by 10 | PDF Full-text (292 KB) | HTML Full-text | XML Full-text
Abstract
The use of α-glucosidase inhibitors is considered to be an effective strategy in the treatment of diabetes. Using a bioassay-guided fractionation technique, five Bacillus stearothermophilus α-glucosidase inhibitors were isolated from the flowers of Musa spp. (Baxijiao). Using NMR spectroscopy analysis they were identified
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The use of α-glucosidase inhibitors is considered to be an effective strategy in the treatment of diabetes. Using a bioassay-guided fractionation technique, five Bacillus stearothermophilus α-glucosidase inhibitors were isolated from the flowers of Musa spp. (Baxijiao). Using NMR spectroscopy analysis they were identified as vanillic acid (1), ferulic acid (2), β-sitosterol (3), daucosterol (4) and 9-(4′-hydroxyphenyl)-2-methoxyphenalen-1-one (5). The half maximal inhibitory concentration (IC50) values of compounds 15 were 2004.58, 1258.35, 283.67, 247.35 and 3.86 mg/L, respectively. Compared to a known α-glucosidase inhibitor (acarbose, IC50 = 999.31 mg/L), compounds 3, 4 and 5 showed a strong α-glucosidase inhibitory effect. A Lineweaver-Burk plot indicated that compound 5 is a mixed-competitive inhibitor, while compounds 3 and 4 are competitive inhibitors. The inhibition constants (Ki) of compounds 3, 4 and 5 were 20.09, 2.34 and 4.40 mg/L, respectively. Taken together, these data show that the compounds 3, 4 and 5 are potent α-glucosidase inhibitors. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Nonlinear Optical Molecular Switches for Alkali Ion Identification
Molecules 2014, 19(7), 10574-10586; doi:10.3390/molecules190710574
Received: 6 May 2014 / Revised: 23 June 2014 / Accepted: 7 July 2014 / Published: 21 July 2014
Cited by 4 | PDF Full-text (1307 KB) | HTML Full-text | XML Full-text
Abstract
This work demonstrates by means of DFT and ab initio calculations that recognition of alkali cations can be achieved by probing the variations of the second-order nonlinear optical properties along the commutation process in spiropyran/merocyanine systems. Due to the ability of the merocyanine
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This work demonstrates by means of DFT and ab initio calculations that recognition of alkali cations can be achieved by probing the variations of the second-order nonlinear optical properties along the commutation process in spiropyran/merocyanine systems. Due to the ability of the merocyanine isomer to complex metal cations, the switching between the two forms is accompanied by large contrasts in the quadratic hyperpolarizability that strongly depend on the size of the cation in presence. Exploiting the nonlinear optical responses of molecular switches should therefore provide powerful analytical tools for detecting and identifying metal cations in solution. Full article
(This article belongs to the Special Issue Molecular Switches)
Open AccessArticle MALDI Mass Spectrometry Imaging for the Simultaneous Location of Resveratrol, Pterostilbene and Viniferins on Grapevine Leaves
Molecules 2014, 19(7), 10587-10600; doi:10.3390/molecules190710587
Received: 4 May 2014 / Revised: 1 July 2014 / Accepted: 16 July 2014 / Published: 21 July 2014
Cited by 8 | PDF Full-text (739 KB) | HTML Full-text | XML Full-text
Abstract
To investigate the in-situ response to a stress, grapevine leaves have been subjected to mass spectrometry imaging (MSI) experiments. The Matrix Assisted Laser Desorption/Ionisation (MALDI) approach using different matrices has been evaluated. Among all the tested matrices, the 2,5-dihydroxybenzoic acid (DHB) was found
[...] Read more.
To investigate the in-situ response to a stress, grapevine leaves have been subjected to mass spectrometry imaging (MSI) experiments. The Matrix Assisted Laser Desorption/Ionisation (MALDI) approach using different matrices has been evaluated. Among all the tested matrices, the 2,5-dihydroxybenzoic acid (DHB) was found to be the most efficient matrix allowing a broader range of detected stilbene phytoalexins. Resveratrol, but also more toxic compounds against fungi such as pterostilbene and viniferins, were identified and mapped. Their spatial distributions on grapevine leaves irradiated by UV show their specific colocation around the veins. Moreover, MALDI MSI reveals that resveratrol (and piceids) and viniferins are not specifically located on the same area when leaves are infected by Plasmopara viticola. Results obtained by MALDI mass spectrometry imaging demonstrate that this technique would be essential to improve the level of knowledge concerning the role of the stilbene phytoalexins involved in a stress event. Full article
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Open AccessArticle Saponins of Trifolium spp. Aerial Parts as Modulators of Candida Albicans Virulence Attributes
Molecules 2014, 19(7), 10601-10617; doi:10.3390/molecules190710601
Received: 9 June 2014 / Revised: 10 July 2014 / Accepted: 14 July 2014 / Published: 21 July 2014
Cited by 4 | PDF Full-text (5320 KB) | HTML Full-text | XML Full-text
Abstract
The aim was to provide the insight into the biology of C. albicans influenced by undescribed yet properties of saponin-rich (80%–98%) fractions (SAPFs), isolated from extracts of Trifolium alexandrinum, T. incarnatum, T. resupinatum var. resupinatum aerial parts. Their concentrations below 0.5
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The aim was to provide the insight into the biology of C. albicans influenced by undescribed yet properties of saponin-rich (80%–98%) fractions (SAPFs), isolated from extracts of Trifolium alexandrinum, T. incarnatum, T. resupinatum var. resupinatum aerial parts. Their concentrations below 0.5 mg/mL were arbitrarily considered as subMICs for C. albicans ATCC 10231 and were further used. SAPFs affected yeast enzymatic activity, lowered tolerance to the oxidative stress, to the osmotic stress and to the action of the cell wall disrupting agent. In their presence, germ tubes formation was significantly and irreversibly inhibited, as well as Candida invasive capacity. The evaluation of SAPFs interactions with anti-mycotics showed synergistic activity, mainly with azoles. Fluconazole MIC was lowered—susceptible C. albicans ATCC 10231 was more susceptible, and resistant C. glabrata (clinical strain) become more susceptible (eightfold). Moreover, the tested samples showed no hemolytic activity and at the concentrations up to 0.5 mg/mL did not reduce viability of fibroblasts L929. This study provided the original evidence that SAPFs of Trifolium spp. aerial part exhibit significant antimicrobial activity, by reduce the expression/quantity of important Candida virulence factors and have good potential for the development of novel antifungal products supporting classic drugs. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle A Combinatorial Approach to Biophysically Characterise Chemokine-Glycan Binding Affinities for Drug Development
Molecules 2014, 19(7), 10618-10634; doi:10.3390/molecules190710618
Received: 22 May 2014 / Revised: 7 July 2014 / Accepted: 16 July 2014 / Published: 22 July 2014
Cited by 12 | PDF Full-text (439 KB) | HTML Full-text | XML Full-text
Abstract
Chemokine binding to glycosaminoglycans (GAGs) is recognised to be an important step in inflammation and other pathological disorders like tumor growth and metastasis. Although different ways and strategies to interfere with these interactions are being pursued, no major breakthrough in the development of
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Chemokine binding to glycosaminoglycans (GAGs) is recognised to be an important step in inflammation and other pathological disorders like tumor growth and metastasis. Although different ways and strategies to interfere with these interactions are being pursued, no major breakthrough in the development of glycan-targeting drugs has been reported so far. We have engineered CXCL8 towards a dominant-negative form of this chemokine (dnCXCL8) which was shown to be highly active in various inflammatory animal models due to its inability to bind/activate the cognate CXCL8 GPC receptors on neutrophils in combination with its significantly increased GAG-binding affinity [1]. For the development of GAG-targeting chemokine-based biopharmaceuticals, we have established a repertoire of methods which allow the quantification of protein-GAG interactions. Isothermal fluorescence titration (IFT), surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), and a novel ELISA-like competition assay (ELICO) have been used to determine Kd and IC50 values for CXCL8 and dnCXCL8 interacting with heparin and heparan sulfate (HS), the proto-typical members of the GAG family. Although the different methods gave different absolute affinities for the four protein-ligand pairs, the relative increase in GAG-binding affinity of dnCXCL8 compared to the wild type chemokine was found by all methods. In combination, these biophysical methods allow to discriminate between unspecific and specific protein-GAG interactions. Full article
(This article belongs to the Special Issue Oligosaccharides and Glyco-Conjugates)
Open AccessArticle Effects of Echium plantagineum L. Bee Pollen on Basophil Degranulation: Relationship with Metabolic Profile
Molecules 2014, 19(7), 10635-10649; doi:10.3390/molecules190710635
Received: 7 May 2014 / Revised: 10 July 2014 / Accepted: 14 July 2014 / Published: 22 July 2014
Cited by 5 | PDF Full-text (951 KB) | HTML Full-text | XML Full-text
Abstract
This study aimed to evaluate the anti-allergic potential of Echium plantagineum L. bee pollen and to characterize its primary metabolites. The activity of E. plantagineum hydromethanolic extract, devoid of alkaloids, was tested against β-hexosaminidase release in rat basophilic leukemic cells (RBL-2H3). Two different
[...] Read more.
This study aimed to evaluate the anti-allergic potential of Echium plantagineum L. bee pollen and to characterize its primary metabolites. The activity of E. plantagineum hydromethanolic extract, devoid of alkaloids, was tested against β-hexosaminidase release in rat basophilic leukemic cells (RBL-2H3). Two different stimuli were used: calcium ionophore A23187 and IgE/antigen. Lipoxygenase inhibitory activity was evaluated in a cell-free system using soybean lipoxygenase. Additionally, the extract was analysed by HPLC-UV for organic acids and by GC-IT/MS for fatty acids. In RBL-2H3 cells stimulated either with calcium ionophore or IgE/antigen, the hydromethanolic extract significantly decreased β-hexosaminidase release until the concentration of 2.08 mg/mL, without compromising cellular viability. No effect was found on lipoxygenase. Concerning extract composition, eight organic acids and five fatty acids were determined for the first time. Malonic acid (80%) and α-linolenic acid (27%) were the main compounds in each class. Overall, this study shows promising results, substantiating for the first time the utility of intake of E. plantagineum bee pollen to prevent allergy and ameliorate allergy symptoms, although a potentiation of an allergic response can occur, depending on the dose used. Full article

Review

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Open AccessReview The Use of Supported Acidic Ionic Liquids in Organic Synthesis
Molecules 2014, 19(7), 8840-8884; doi:10.3390/molecules19078840
Received: 30 April 2014 / Revised: 30 May 2014 / Accepted: 16 June 2014 / Published: 26 June 2014
Cited by 14 | PDF Full-text (463 KB) | HTML Full-text | XML Full-text
Abstract
Catalysts obtained by the immobilisation of acidic ionic liquids (ILs) on solid supports offer several advantages compared to the use of catalytically active ILs themselves. Immobilisation may result in an increase in the number of accessible active sites of the catalyst and a
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Catalysts obtained by the immobilisation of acidic ionic liquids (ILs) on solid supports offer several advantages compared to the use of catalytically active ILs themselves. Immobilisation may result in an increase in the number of accessible active sites of the catalyst and a reduction of the amount of the IL required. The ionic liquid films on the carrier surfaces provide a homogeneous environment for catalytic reactions but the catalyst appears macroscopically as a dry solid, so it can simply be separated from the reaction mixture. As another advantage, it can easily be applied in a continuous fixed bed reactor. In the present review the main synthetic strategies towards the preparation of supported Lewis acidic and Brønsted acidic ILs are summarised. The most important characterisation methods and structural features of the supported ionic liquids are presented. Their efficiency in catalytic reactions is discussed with special emphasis on their recyclability. Full article
(This article belongs to the Special Issue Heterogeneous Acid Catalysts)
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Open AccessReview Immobilization as a Strategy for Improving Enzyme Properties-Application to Oxidoreductases
Molecules 2014, 19(7), 8995-9018; doi:10.3390/molecules19078995
Received: 12 May 2014 / Revised: 13 June 2014 / Accepted: 16 June 2014 / Published: 27 June 2014
Cited by 72 | PDF Full-text (858 KB) | HTML Full-text | XML Full-text
Abstract
The main objective of the immobilization of enzymes is to enhance the economics of biocatalytic processes. Immobilization allows one to re-use the enzyme for an extended period of time and enables easier separation of the catalyst from the product. Additionally, immobilization improves many
[...] Read more.
The main objective of the immobilization of enzymes is to enhance the economics of biocatalytic processes. Immobilization allows one to re-use the enzyme for an extended period of time and enables easier separation of the catalyst from the product. Additionally, immobilization improves many properties of enzymes such as performance in organic solvents, pH tolerance, heat stability or the functional stability. Increasing the structural rigidity of the protein and stabilization of multimeric enzymes which prevents dissociation-related inactivation. In the last decade, several papers about immobilization methods have been published. In our work, we present a relation between the influence of immobilization on the improvement of the properties of selected oxidoreductases and their commercial value. We also present our view on the role that different immobilization methods play in the reduction of enzyme inhibition during biotechnological processes. Full article
(This article belongs to the Special Issue Enzyme Immobilization)
Open AccessReview Red Card for Pathogens: Phytoalexins in Sorghum and Maize
Molecules 2014, 19(7), 9114-9133; doi:10.3390/molecules19079114
Received: 19 May 2014 / Revised: 26 June 2014 / Accepted: 26 June 2014 / Published: 30 June 2014
Cited by 8 | PDF Full-text (1077 KB) | HTML Full-text | XML Full-text
Abstract
Cereal crop plants such as maize and sorghum are constantly being attacked by a great variety of pathogens that cause large economic losses. Plants protect themselves against pathogens by synthesizing antimicrobial compounds, which include phytoalexins. In this review we summarize the current knowledge
[...] Read more.
Cereal crop plants such as maize and sorghum are constantly being attacked by a great variety of pathogens that cause large economic losses. Plants protect themselves against pathogens by synthesizing antimicrobial compounds, which include phytoalexins. In this review we summarize the current knowledge on phytoalexins produced by sorghum (luteolinidin, apigeninidin) and maize (zealexin, kauralexin, DIMBOA and HDMBOA). For these molecules, we highlight biosynthetic pathways, known intermediates, proposed enzymes, and mechanisms of elicitation. Finally, we discuss the involvement of phytoalexins in plant resistance and their possible application in technology, medicine and agriculture. For those whose world is round we tried to set the scene in the context of a hypothetical football game in which pathogens fight with phytoalexins on the different playing fields provided by maize and sorghum. Full article
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Open AccessReview Tuning of Essential Oil Properties by Enzymatic Treatment: Towards Sustainable Processes for the Generation of New Fragrance Ingredients
Molecules 2014, 19(7), 9203-9214; doi:10.3390/molecules19079203
Received: 22 May 2014 / Revised: 18 June 2014 / Accepted: 23 June 2014 / Published: 1 July 2014
Cited by 3 | PDF Full-text (343 KB) | HTML Full-text | XML Full-text
Abstract
In this review, several strategies of modification of essential oils by enzymatic treatment are presented. Being either applied before or after the production of the essential oil, enzymatic methods are shown to be particularly adapted to attain the required selectivity, specificity and efficiency
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In this review, several strategies of modification of essential oils by enzymatic treatment are presented. Being either applied before or after the production of the essential oil, enzymatic methods are shown to be particularly adapted to attain the required selectivity, specificity and efficiency in sustainable processes delivering products eligible for the natural grade. Examples dealing with the optimization of the properties of essential oils in terms of biological activity, odor and safety are provided, and it is likely that these strategies will address other type of properties in the future, such as the physico-chemical properties, for example. Full article
(This article belongs to the Section Natural Products)
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Open AccessReview Fluorescent Probes for Exploring Plant Cell Wall Deconstruction: A Review
Molecules 2014, 19(7), 9380-9402; doi:10.3390/molecules19079380
Received: 25 April 2014 / Revised: 27 June 2014 / Accepted: 27 June 2014 / Published: 3 July 2014
Cited by 7 | PDF Full-text (2403 KB) | HTML Full-text | XML Full-text
Abstract
Plant biomass is a potential resource of chemicals, new materials and biofuels that could reduce our dependency on fossil carbon, thus decreasing the greenhouse effect. However, due to its chemical and structural complexity, plant biomass is recalcitrant to green biological transformation by enzymes,
[...] Read more.
Plant biomass is a potential resource of chemicals, new materials and biofuels that could reduce our dependency on fossil carbon, thus decreasing the greenhouse effect. However, due to its chemical and structural complexity, plant biomass is recalcitrant to green biological transformation by enzymes, preventing the establishment of integrated bio-refineries. In order to gain more knowledge in the architecture of plant cell wall to facilitate their deconstruction, many fluorescent probes bearing various fluorophores have been devised and used successfully to reveal the changes in structural motifs during plant biomass deconstruction, and the molecular interactions between enzymes and plant cell wall polymers. Fluorescent probes are thus relevant tools to explore plant cell wall deconstruction. Full article
(This article belongs to the Special Issue Fluorescent Probes)
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Open AccessReview Blumea balsamifera—A Phytochemical and Pharmacological Review
Molecules 2014, 19(7), 9453-9477; doi:10.3390/molecules19079453
Received: 30 May 2014 / Revised: 27 June 2014 / Accepted: 2 July 2014 / Published: 3 July 2014
Cited by 9 | PDF Full-text (797 KB) | HTML Full-text | XML Full-text
Abstract
The main components of sambong (Blumea balsamifera) are listed in this article. The whole plant and its crude extracts, as well as its isolated constituents, display numerous biological activities, such as antitumor, hepatoprotective, superoxide radical scavenging, antioxidant, antimicrobial and anti-inflammation, anti-plasmodial,
[...] Read more.
The main components of sambong (Blumea balsamifera) are listed in this article. The whole plant and its crude extracts, as well as its isolated constituents, display numerous biological activities, such as antitumor, hepatoprotective, superoxide radical scavenging, antioxidant, antimicrobial and anti-inflammation, anti-plasmodial, anti-tyrosinase, platelet aggregation, enhancing percutaneous penetration, wound healing, anti-obesity, along with disease and insect resistant activities. Although many experimental and biological studies have been carried out, some traditional uses such as rheumatism healing still need to be verified by scientific pharmacological studies, and further studies including phytochemical standardization and bioactivity authentication would be beneficial. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessReview Ruthenium Complexes as NO Donors for Vascular Relaxation Induction
Molecules 2014, 19(7), 9628-9654; doi:10.3390/molecules19079628
Received: 8 April 2014 / Revised: 9 June 2014 / Accepted: 26 June 2014 / Published: 7 July 2014
Cited by 10 | PDF Full-text (1534 KB) | HTML Full-text | XML Full-text
Abstract
Nitric oxide (NO) donors are substances that can release NO. Vascular relaxation induction is among the several functions of NO, and the administration of NO donors is a pharmacological alternative to treat hypertension. This review will focus on the physicochemical description of ruthenium-derived
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Nitric oxide (NO) donors are substances that can release NO. Vascular relaxation induction is among the several functions of NO, and the administration of NO donors is a pharmacological alternative to treat hypertension. This review will focus on the physicochemical description of ruthenium-derived NO donor complexes that release NO via reduction and light stimulation. In particular, we will discuss the complexes synthesized by our research group over the last ten years, and we will focus on the vasodilation and arterial pressure control elicited by these complexes. Soluble guanylyl cyclase (sGC) and potassium channels are the main targets of the NO species released from the inorganic compounds. We will consider the importance of the chemical structure of the ruthenium complexes and their vascular effects. Full article
(This article belongs to the Special Issue Ruthenium Complex)
Open AccessReview Molecular and Chemical Regulation of the Keap1-Nrf2 Signaling Pathway
Molecules 2014, 19(7), 10074-10089; doi:10.3390/molecules190710074
Received: 11 May 2014 / Revised: 2 June 2014 / Accepted: 2 July 2014 / Published: 10 July 2014
Cited by 28 | PDF Full-text (260 KB) | HTML Full-text | XML Full-text
Abstract
Extracellular and intracellular oxidants or electrophiles are key contributors to the damages in cellular macromolecules, such as DNA, proteins and lipids. Nrf2 is a master transcription factor that modulates a cellular antioxidant response program and plays an important role in the protection against
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Extracellular and intracellular oxidants or electrophiles are key contributors to the damages in cellular macromolecules, such as DNA, proteins and lipids. Nrf2 is a master transcription factor that modulates a cellular antioxidant response program and plays an important role in the protection against oxidants and electrophiles. Keap1 is a regulator of Nrf2 by serving as a substrate adaptor for Cullin3-dependent E3 ubiquitin ligase. While Nrf2 activation is a feasible strategy for treatment of age-related diseases, aberrant Nrf2 activation also confers a selective growth advantage of tumor cells during chemotherapy or radiotherapy. In the present review, we provide an overview of the Keap1-Nrf2-ARE system, the domain organization of Nrf2 and Keap1, and the regulatory mechanisms of Nrf2 proteolysis by Keap1. We also discuss how Nrf2 prevents tumor promotion, hampers the sensitivity of selected tumors against chemotherapy or radiotherapy, and reprograms the metabolism to facilitate the tumor proliferation. Finally, we illustrate the current status in the development of Nrf2 chemical activators and inhibitors for the use of potential chemopreventive agents and chemotherapeutic adjuvants, respectively. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
Open AccessReview MicroRNAs and Bone Metastasis: A New Challenge
Molecules 2014, 19(7), 10115-10128; doi:10.3390/molecules190710115
Received: 4 April 2014 / Revised: 16 June 2014 / Accepted: 19 June 2014 / Published: 11 July 2014
Cited by 10 | PDF Full-text (204 KB) | HTML Full-text | XML Full-text
Abstract
The development of bone metastases requires multistep and multicellular machinery consisting not only of processes shared with any type of metastases (formation of a pre-metastatic niche, chemotaxis of tumor cells into the host tissue, tumor cells escape from the microvasculature), but also biological
[...] Read more.
The development of bone metastases requires multistep and multicellular machinery consisting not only of processes shared with any type of metastases (formation of a pre-metastatic niche, chemotaxis of tumor cells into the host tissue, tumor cells escape from the microvasculature), but also biological interactions that are strictly related to the particular bone microenvironment (bone marrow colonization by cancer cells, osteomimicry, deregulation of bone homeostasis). MiRNAs are highly conserved, small RNAs molecules that regulate gene expression. The functional consequence of miRNA deregulation lies in the mRNA targets whose expression is altered. MiRNA networks acting as upstream regulators of these genes interfere with the initial steps of tumor local invasion and cancer cell intravasation, mainly by regulating the epithelial-mesenchymal transition, the motility, invasiveness and survival abilities of these cells. The miRNA-mediated regulation on the steps of bone tropism, anchorage, homing and finally bone colonization is more tissue specific, being dependent on the expression pattern of target miRNAs in bone marrow sinusoids, bone cells and microenvironment. In that, miRNA specific expression signatures that can distinguish between primary tumors from their corresponding bone metastases might be determinants of clinical aggressiveness. In this review, we focus on the current advances on functions and molecular mechanisms by which miRNAs exert their biological roles in regulating bone metastases development. Full article
(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)
Open AccessReview Challenges, Applications, and Recent Advances of Protein-Ligand Docking in Structure-Based Drug Design
Molecules 2014, 19(7), 10150-10176; doi:10.3390/molecules190710150
Received: 23 April 2014 / Revised: 13 June 2014 / Accepted: 2 July 2014 / Published: 11 July 2014
Cited by 21 | PDF Full-text (238 KB) | HTML Full-text | XML Full-text
Abstract
The docking methods used in structure-based virtual database screening offer the ability to quickly and cheaply estimate the affinity and binding mode of a ligand for the protein receptor of interest, such as a drug target. These methods can be used to enrich
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The docking methods used in structure-based virtual database screening offer the ability to quickly and cheaply estimate the affinity and binding mode of a ligand for the protein receptor of interest, such as a drug target. These methods can be used to enrich a database of compounds, so that more compounds that are subsequently experimentally tested are found to be pharmaceutically interesting. In addition, like all virtual screening methods used for drug design, structure-based virtual screening can focus on curated libraries of synthesizable compounds, helping to reduce the expense of subsequent experimental verification. In this review, we introduce the protein-ligand docking methods used for structure-based drug design and other biological applications. We discuss the fundamental challenges facing these methods and some of the current methodological topics of interest. We also discuss the main approaches for applying protein-ligand docking methods. We end with a discussion of the challenging aspects of evaluating or benchmarking the accuracy of docking methods for their improvement, and discuss future directions. Full article
(This article belongs to the Special Issue In-Silico Drug Design and In-Silico Screening)
Open AccessReview Microextraction Techniques Coupled to Liquid Chromatography with Mass Spectrometry for the Determination of Organic Micropollutants in Environmental Water Samples
Molecules 2014, 19(7), 10320-10349; doi:10.3390/molecules190710320
Received: 13 May 2014 / Revised: 2 July 2014 / Accepted: 10 July 2014 / Published: 16 July 2014
Cited by 10 | PDF Full-text (541 KB) | HTML Full-text | XML Full-text
Abstract
Until recently, sample preparation was carried out using traditional techniques, such as liquid–liquid extraction (LLE), that use large volumes of organic solvents. Solid-phase extraction (SPE) uses much less solvent than LLE, although the volume can still be significant. These preparation methods are expensive,
[...] Read more.
Until recently, sample preparation was carried out using traditional techniques, such as liquid–liquid extraction (LLE), that use large volumes of organic solvents. Solid-phase extraction (SPE) uses much less solvent than LLE, although the volume can still be significant. These preparation methods are expensive, time-consuming and environmentally unfriendly. Recently, a great effort has been made to develop new analytical methodologies able to perform direct analyses using miniaturised equipment, thereby achieving high enrichment factors, minimising solvent consumption and reducing waste. These microextraction techniques improve the performance during sample preparation, particularly in complex water environmental samples, such as wastewaters, surface and ground waters, tap waters, sea and river waters. Liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) and time-of-flight mass spectrometric (TOF/MS) techniques can be used when analysing a broad range of organic micropollutants. Before separating and detecting these compounds in environmental samples, the target analytes must be extracted and pre-concentrated to make them detectable. In this work, we review the most recent applications of microextraction preparation techniques in different water environmental matrices to determine organic micropollutants: solid-phase microextraction SPME, in-tube solid-phase microextraction (IT-SPME), stir bar sorptive extraction (SBSE) and liquid-phase microextraction (LPME). Several groups of compounds are considered organic micropollutants because these are being released continuously into the environment. Many of these compounds are considered emerging contaminants. These analytes are generally compounds that are not covered by the existing regulations and are now detected more frequently in different environmental compartments. Pharmaceuticals, surfactants, personal care products and other chemicals are considered micropollutants. These compounds must be monitored because, although they are detected in low concentrations, they might be harmful toward ecosystems. Full article
(This article belongs to the Special Issue Microextraction)
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Open AccessReview Mistaken Identity: Clarification of Rubus coreanus Miquel (Bokbunja)
Molecules 2014, 19(7), 10524-10533; doi:10.3390/molecules190710524
Received: 5 May 2014 / Revised: 3 July 2014 / Accepted: 15 July 2014 / Published: 18 July 2014
Cited by 4 | PDF Full-text (625 KB) | HTML Full-text | XML Full-text
Abstract
In the U.S., there has been a recent surge in Korean black raspberry products available and in the number of reports about this species appearing in the scientific literature. Despite this, the majority of products sold and the work carried out has been
[...] Read more.
In the U.S., there has been a recent surge in Korean black raspberry products available and in the number of reports about this species appearing in the scientific literature. Despite this, the majority of products sold and the work carried out has been on Rubus occidentalis L., not R. coreanus Miquel. The importance of accurate recognition of all starting material is multiplied for research downstream, including genetics/genomics, plant breeding, phenolic identification, food processing improvements and pharmacokinetic investigations. An overview of distinguishing characteristics separating R. coreanus from R. occidentalis will be presented. Research conducted on correctly identified fruit will also be summarized to aid future studies that might showcase the unique qualities that bokbunja can offer. Full article
(This article belongs to the Special Issue Anthocyanins) Print Edition available
Open AccessReview A Systematic Review of the Botanical, Phytochemical and Pharmacological Profile of Dracaena cochinchinensis, a Plant Source of the Ethnomedicine “Dragon’s Blood”
Molecules 2014, 19(7), 10650-10669; doi:10.3390/molecules190710650
Received: 26 May 2014 / Revised: 8 July 2014 / Accepted: 15 July 2014 / Published: 22 July 2014
Cited by 5 | PDF Full-text (875 KB) | HTML Full-text | XML Full-text
Abstract
“Dragon’s blood” is the name given to a deep red resin obtained from a variety of plant sources. The resin extracted from stems of Dracaena cochinchinensis is one such source of “dragon’s blood”. It has a reputation for facilitating blood circulation and dispersing
[...] Read more.
“Dragon’s blood” is the name given to a deep red resin obtained from a variety of plant sources. The resin extracted from stems of Dracaena cochinchinensis is one such source of “dragon’s blood”. It has a reputation for facilitating blood circulation and dispersing blood stasis. In traditional Chinese medicine, this resinous medicine is commonly prescribed to invigorate blood circulation for the treatment of traumatic injuries, blood stasis and pain. Modern pharmacological studies have found that this resinous medicine has anti-bacterial, anti-spasmodic, anti-inflammatory, analgesic, anti-diabetic, and anti-tumor activities, while it is also known to enhance immune function, promote skin repair, stop bleeding and enhance blood circulation. Various compounds have been isolated from the plant, including loureirin A, loureirin B, loureirin C, cochinchinenin, socotrin-4'-ol, 4',7-dihydroxyflavan, 4-methylcholest-7-ene-3-ol, ethylparaben, resveratrol, and hydroxyphenol. The present review summarizes current knowledge concerning the botany, phytochemistry, pharmacological effects, toxicology studies and clinical applications of this resinous medicine as derived from D. cochinchinenesis. Full article

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Open AccessComment Is a Highly Linear Relationship Between the Dose of Quercetin and the Pharmacological Effect Possible? — A Comment on Liu, et al. Evaluation of Antioxidant and Immunity Activities of Quercetin in Isoproterenol-Treated Rats. Molecules 2012, 17, 4281–4291
Molecules 2014, 19(7), 9606-9609; doi:10.3390/molecules19079606
Received: 19 March 2014 / Accepted: 1 July 2014 / Published: 7 July 2014
Cited by 1 | PDF Full-text (257 KB) | HTML Full-text | XML Full-text
Abstract We wish to offer some comments on the article by H. Liu et al. entitled “Evaluation of antioxidant and immunity activities of quercetin in isoproterenol-treated rats”, published in Molecules in 2012 [1]. [...] Full article
(This article belongs to the Section Natural Products)

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