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Molecules, Volume 19, Issue 3 (March 2014), Pages 2707-3850

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Editorial

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Open AccessEditorial Acknowledgement to Reviewers of Molecules in 2013
Molecules 2014, 19(3), 2707-2732; doi:10.3390/molecules19032707
Received: 25 February 2014 / Accepted: 25 February 2014 / Published: 25 February 2014
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Abstract The editors of Molecules would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2013. [...] Full article

Research

Jump to: Editorial, Review, Other

Open AccessArticle Chemical Composition, Biological and Cytotoxic Activities of Plant Extracts and Compounds Isolated from Ferula lutea
Molecules 2014, 19(3), 2733-2747; doi:10.3390/molecules19032733
Received: 24 December 2013 / Revised: 14 February 2014 / Accepted: 18 February 2014 / Published: 26 February 2014
Cited by 6 | PDF Full-text (323 KB) | HTML Full-text | XML Full-text
Abstract
The present work describes the phytochemical study on Ferula lutea flowers. Total phenolics and flavonoids of the n-butanol and ethyl acetate extracts were quantified (phenolics [40.68–52.29 mg gallic acid equivalent/g of dry weight], flavonoids [12.38–14.72 mg quercitin/g dry weight]). Two diastereoisomers were
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The present work describes the phytochemical study on Ferula lutea flowers. Total phenolics and flavonoids of the n-butanol and ethyl acetate extracts were quantified (phenolics [40.68–52.29 mg gallic acid equivalent/g of dry weight], flavonoids [12.38–14.72 mg quercitin/g dry weight]). Two diastereoisomers were isolated and identified using spectroscopic techniques (1D, 2D NMR and GC-MS). The extracts and diastereoisomers were tested for antioxidant, antiacetylcholinesterase, antimicrobial, antidiabectic, cytotoxic (leukemia cell line) activities and allelopathic potentialities. The strongest antioxidant activity was obtained for the ethyl acetate extract (IC50 = 12.8 ± 1.29 µg/mL). The two extracts exhibited high antidiabetic activity (54.1 and 52.1% at 40 µg/mL). Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Polyolefin Backbone Substitution in Binders for Low Temperature Powder Injection Moulding Feedstocks
Molecules 2014, 19(3), 2748-2760; doi:10.3390/molecules19032748
Received: 3 January 2014 / Revised: 20 February 2014 / Accepted: 21 February 2014 / Published: 27 February 2014
Cited by 5 | PDF Full-text (704 KB) | HTML Full-text | XML Full-text
Abstract
This paper reports the substitution of polyolefin backbone binder components with low melting temperature carnauba wax for powder injection moulding applications. The effect of various binder compositions of Al2O3 feedstock on thermal degradation parameters is investigated by thermogravimetric analysis. Within
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This paper reports the substitution of polyolefin backbone binder components with low melting temperature carnauba wax for powder injection moulding applications. The effect of various binder compositions of Al2O3 feedstock on thermal degradation parameters is investigated by thermogravimetric analysis. Within the experimental framework 29 original feedstock compositions were prepared and the superiority of carnauba wax over the polyethylene binder backbone was demonstrated in compositions containing polyethylene glycol as the initial opening agent and governing the proper mechanism of the degradation process. Moreover, the replacement of synthetic polymer by the natural wax contributes to an increase of environmental sustainability of modern industrial technologies. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Biomolecule-Mediated Synthesis of Selenium Nanoparticles using Dried Vitis vinifera (Raisin) Extract
Molecules 2014, 19(3), 2761-2770; doi:10.3390/molecules19032761
Received: 10 January 2014 / Revised: 4 February 2014 / Accepted: 24 February 2014 / Published: 27 February 2014
Cited by 16 | PDF Full-text (1225 KB) | HTML Full-text | XML Full-text
Abstract
Biomolecule-mediated nanoparticle synthesis has recently gained the attention of researchers due to its ecofriendly and non-toxic nature. Metabolites from plant extracts represent a better alternative to chemical methods to fulfill the growing demand for non-hazardous nanoparticle synthesis routes. Selenium and its nanoparticles have
[...] Read more.
Biomolecule-mediated nanoparticle synthesis has recently gained the attention of researchers due to its ecofriendly and non-toxic nature. Metabolites from plant extracts represent a better alternative to chemical methods to fulfill the growing demand for non-hazardous nanoparticle synthesis routes. Selenium and its nanoparticles have an extensive range of applications. Thus, biofabrication of selenium nanoparticles can be potentially useful in various fields. This study reports a green approach to biosynthesize selenium nanoparticles (Se-np) using dried Vitis vinifera (raisin) extracts. The biosynthesized selenium nanoparticles were characterized using transmission electron microscope (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), energy dispersive X-ray (EDX) spectroscopy and Fourier transform infrared spectroscopy (FTIR). Transmission electron microscopic images revealed the spherical shape of biosynthesized selenium nanoparticles and a size range of 3–18 nm. Dynamic light scattering also confirmed the average particle size of 8.12 ± 2.5 nm with 0.212 PDI. The crystalline nature of selenium nanoparticles was confirmed by the X-ray diffraction study. Moreover, as inferred from the FTIR spectrum, the presence of highly stable lignin biopolymer on the surface of selenium nanoballs suggests a possible role as capping agent. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Effect of Corn Steep Liquor (CSL) and Cassava Wastewater (CW) on Chitin and Chitosan Production by Cunninghamella elegans and Their Physicochemical Characteristics and Cytotoxicity
Molecules 2014, 19(3), 2771-2792; doi:10.3390/molecules19032771
Received: 2 December 2013 / Revised: 14 February 2014 / Accepted: 17 February 2014 / Published: 28 February 2014
Cited by 4 | PDF Full-text (2065 KB) | HTML Full-text | XML Full-text
Abstract
Microbiological processes were used for chitin and chitosan production with Cunninghamella elegans UCP/WFCC 0542 grown in different concentrations of two agro-industrial wastes, corn steep liquor (CSL) and cassava wastewater (CW) established using a 22 full factorial design. The polysaccharides were extracted by
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Microbiological processes were used for chitin and chitosan production with Cunninghamella elegans UCP/WFCC 0542 grown in different concentrations of two agro-industrial wastes, corn steep liquor (CSL) and cassava wastewater (CW) established using a 22 full factorial design. The polysaccharides were extracted by alkali-acid treatment and characterized by infrared spectroscopy, viscosity, thermal analysis, elemental analysis, scanning electron microscopy and X-ray diffraction. The cytotoxicity of chitosan was evaluated for signs of vascular change on the chorioallantoic membrane of chicken eggs. The highest biomass (9.93 g/L) was obtained in trial 3 (5% CW, 8% CSL), the greatest chitin and chitosan yields were 89.39 mg/g and 57.82 mg/g, respectively, and both were obtained in trial 2 (10% CW, 4% CSL). Chitin and chitosan showed a degree of deacetylation of 40.98% and 88.24%, and a crystalline index of 35.80% and 23.82%, respectively, and chitosan showed low molecular weight (LMW 5.2 × 103 Da). Chitin and chitosan can be considered non-irritating, due to the fact they do not promote vascular change. It was demonstrated that CSL and CW are effective renewable agroindustrial alternative substrates for the production of chitin and chitosan. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Astragalus membranaceus Improves Exercise Performance and Ameliorates Exercise-Induced Fatigue in Trained Mice
Molecules 2014, 19(3), 2793-2807; doi:10.3390/molecules19032793
Received: 15 February 2014 / Revised: 24 February 2014 / Accepted: 24 February 2014 / Published: 3 March 2014
Cited by 14 | PDF Full-text (8355 KB) | HTML Full-text | XML Full-text
Abstract
Astragalus membranaceus (AM) is a popular “Qi-tonifying” herb with a long history of use as a Traditional Chinese Medicine with multiple biological functions. However, evidence for the effects of AM on exercise performance and physical fatigue is limited. We evaluated the potential beneficial
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Astragalus membranaceus (AM) is a popular “Qi-tonifying” herb with a long history of use as a Traditional Chinese Medicine with multiple biological functions. However, evidence for the effects of AM on exercise performance and physical fatigue is limited. We evaluated the potential beneficial effects of AM on ergogenic and anti-fatigue functions following physiological challenge. Male ICR strain mice were randomly assigned to four groups (n = 10 per group) for treatment: (1) sedentary control and vehicle treatment (vehicle control); (2) exercise training with vehicle treatment (exercise control); and (3) exercise training with AM treatment at 0.615 g/kg/day (Ex-AM1) or (4) 3.075 g/kg/day (Ex-AM5). Both the vehicle and AM were orally administered for 6 weeks. Exercise performance and anti-fatigue function were evaluated by forelimb grip strength, exhaustive swimming time, and levels of serum lactate, ammonia, glucose, and creatine kinase after 15-min swimming exercise. Exercise training combined with AM supplementation increased endurance exercise capacity and increased hepatic and muscle glycogen content. AM reduced exercise-induced accumulation of the byproducts blood lactate and ammonia with acute exercise challenge. Moreover, we found no deleterious effects from AM treatment. Therefore, AM supplementation improved exercise performance and had anti-fatigue effects in mice. It may be an effective ergogenic aid in exercise training. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Inhibitory Effect of Corn Silk on Skin Pigmentation
Molecules 2014, 19(3), 2808-2818; doi:10.3390/molecules19032808
Received: 27 December 2013 / Revised: 21 February 2014 / Accepted: 25 February 2014 / Published: 3 March 2014
PDF Full-text (737 KB) | HTML Full-text | XML Full-text
Abstract
In this study, the inhibitory effect of corn silk on melanin production was evaluated. This study was performed to investigate the inhibitory effect of corn silk on melanin production in Melan-A cells by measuring melanin production and protein expression. The corn silk extract
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In this study, the inhibitory effect of corn silk on melanin production was evaluated. This study was performed to investigate the inhibitory effect of corn silk on melanin production in Melan-A cells by measuring melanin production and protein expression. The corn silk extract applied on Melan-A cells at a concentration of 100 ppm decreased melanin production by 37.2% without cytotoxicity. This was a better result than arbutin, a positive whitening agent, which exhibited a 26.8% melanin production inhibitory effect at the same concentration. The corn silk extract did not suppress tyrosinase activity but greatly reduced the expression of tyrosinase in Melan-A cells. In addition, corn silk extract was applied to the human face with hyperpigmentation, and skin color was measured to examine the degree of skin pigment reduction. The application of corn silk extract on faces with hyperpigmentation significantly reduced skin pigmentation without abnormal reactions. Based on the results above, corn silk has good prospects for use as a material for suppressing skin pigmentation. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle New Thiophene and Flavonoid from Tagetes minuta Leaves Growing in Saudi Arabia
Molecules 2014, 19(3), 2819-2828; doi:10.3390/molecules19032819
Received: 28 January 2014 / Revised: 25 February 2014 / Accepted: 25 February 2014 / Published: 4 March 2014
Cited by 12 | PDF Full-text (262 KB) | HTML Full-text | XML Full-text
Abstract
Phytochemical investigation of the methanolic extract of Tagetes minuta L. (Asteraceae) leaves resulted in the isolation and identification of two new compounds: 5-methyl-2,2',5',2'',5'',2''',5''',2''''-quinquethiophene (1) and quercetagetin-6-O-(6-O-caffeoyl-β-D-glucopyranoside) (9), in addition to seven known compounds: quercetin-3,6-dimethyl ether
[...] Read more.
Phytochemical investigation of the methanolic extract of Tagetes minuta L. (Asteraceae) leaves resulted in the isolation and identification of two new compounds: 5-methyl-2,2',5',2'',5'',2''',5''',2''''-quinquethiophene (1) and quercetagetin-6-O-(6-O-caffeoyl-β-D-glucopyranoside) (9), in addition to seven known compounds: quercetin-3,6-dimethyl ether (2), quercetin-3-methyl ether (3), quercetin (4), axillarin-7-O-β-D-glucopyranoside (5), quercetagetin-3,7-dimethoxy-6-O-β-D-glucopyranoside (6), quercetagetin-7-methoxy-6-O-β-D-glucopyranoside (7), and quercetagetin-6-O-β-D-glucopyranoside (8). The compounds were identified by UV, IR, 1D, 2D NMR, and HRESIMS spectral data. They showed significant antioxidant activity, comparable with that of propyl gallate. Compounds 8 and 3 showed weak to moderate antileishmanial and antimalarial activities, with IC50 values of 31.0 μg/mL and 4.37 μg/mL, respectively. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Chiroptical Properties and the Racemization of Pyrene and Tetrathiafulvalene-Substituted Allene: Substitution and Solvent Effects on Racemization in Tetrathiafulvalenylallene
Molecules 2014, 19(3), 2829-2841; doi:10.3390/molecules19032829
Received: 21 January 2014 / Revised: 21 February 2014 / Accepted: 23 February 2014 / Published: 4 March 2014
Cited by 4 | PDF Full-text (818 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Dissymmetric 1,3-diphenylallene derivative 3 connected with 4,5-bis(methyl-thio)tetrathiafulvalenyl and 1-pyrenyl substituents was prepared and characterized. The molecular structure was determined by X-ray crystallographic analysis. Optical resolution was accomplished using a recycling chiral HPLC, and its chiroptical properties were examined with optical rotation and electronic
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Dissymmetric 1,3-diphenylallene derivative 3 connected with 4,5-bis(methyl-thio)tetrathiafulvalenyl and 1-pyrenyl substituents was prepared and characterized. The molecular structure was determined by X-ray crystallographic analysis. Optical resolution was accomplished using a recycling chiral HPLC, and its chiroptical properties were examined with optical rotation and electronic circular dichroism (ECD) spectra. The title compound underwent photoracemization under daylight. This behavior was investigated in various solvents and compared with that of 1,3-bis(tetrathiafulvalenyl)allene (bis-TTF-allene) derivative 2. The first-order rate plot of the intensity of the ECD spectra at a given time interval gave the rate of racemization. Mild racemization was observed in polar solvents, whereas a relatively fast rate was obtained in less polar solvents. In addition, the TTF groups of the allene also accelerate the racemization rate. These results suggest that the racemization mechanism occurs via a non-polar diradical structure. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
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Open AccessArticle 3D-QSAR/CoMFA-Based Structure-Affinity/Selectivity Relationships of Aminoalkylindoles in the Cannabinoid CB1 and CB2 Receptors
Molecules 2014, 19(3), 2842-2861; doi:10.3390/molecules19032842
Received: 15 January 2014 / Revised: 25 February 2014 / Accepted: 25 February 2014 / Published: 5 March 2014
Cited by 4 | PDF Full-text (695 KB) | HTML Full-text | XML Full-text
Abstract
A 3D-QSAR (CoMFA) study was performed in an extensive series of aminoalkylindoles derivatives with affinity for the cannabinoid receptors CB1 and CB2. The aim of the present work was to obtain structure-activity relationships of the aminoalkylindole family in order to explain the affinity
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A 3D-QSAR (CoMFA) study was performed in an extensive series of aminoalkylindoles derivatives with affinity for the cannabinoid receptors CB1 and CB2. The aim of the present work was to obtain structure-activity relationships of the aminoalkylindole family in order to explain the affinity and selectivity of the molecules for these receptors. Major differences in both, steric and electrostatic fields were found in the CB1 and CB2 CoMFA models. The steric field accounts for the principal contribution to biological activity. These results provide a foundation for the future development of new heterocyclic compounds with high affinity and selectivity for the cannabinoid receptors with applications in several pathological conditions such as pain treatment, cancer, obesity and immune disorders, among others. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Telmisartan Exerts Anti-Tumor Effects by Activating Peroxisome Proliferator-Activated Receptor-γ in Human Lung Adenocarcinoma A549 Cells
Molecules 2014, 19(3), 2862-2876; doi:10.3390/molecules19032862
Received: 6 January 2014 / Revised: 25 February 2014 / Accepted: 26 February 2014 / Published: 5 March 2014
Cited by 7 | PDF Full-text (1375 KB) | HTML Full-text | XML Full-text
Abstract
Telmisartan, a member of the angiotensin II type 1 receptor blockers, is usually used for cardiovascular diseases. Recent studies have showed that telmisartan has the property of PPARγ activation. Meanwhile, PPARγ is essential for tumor proliferation, invasion and metastasis. In this work we
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Telmisartan, a member of the angiotensin II type 1 receptor blockers, is usually used for cardiovascular diseases. Recent studies have showed that telmisartan has the property of PPARγ activation. Meanwhile, PPARγ is essential for tumor proliferation, invasion and metastasis. In this work we explore whether telmisartan could exert anti-tumor effects through PPARγ activation in A549 cells. MTT and trypan blue exclusion assays were included to determine the survival rates and cell viabilities. RT-PCR and western blotting were used to analyze the expression of ICAM-1, MMP-9 and PPARγ. DNA binding activity of PPARγ was evaluated by EMSA. Our data showed that the survival rates and cell viabilities of A549 cells were all reduced by telmisartan in a time- and concentration-dependent manner. Meanwhile, our results also demonstrated that telmisartan dose-dependently inhibited the expression of ICAM-1 and MMP-9. Moreover, the cytotoxic and anti-proliferative effects, ICAM-1 and MMP-9 inhibitive properties of telmisartan were totally blunted by the PPARγ antagonist GW9662. Our findings also showed that the expression of PPARγ was up-regulated by telmisartan in a dose dependent manner. And, the EMSA results also figured out that DNA binding activity of PPARγ was dose-dependently increased by telmisartan. Additionally, our data also revealed that telmisartan-induced PPARγ activation was abrogated by GW9662. Taken together, our results indicated that telmisartan inhibited the expression of ICAM-1 and MMP-9 in A549 cells, very likely through the up-regulation of PPARγ synthesis. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Unravelling the Complex Antimicrobial Interactions of Essential Oils — The Case of Thymus vulgaris (Thyme)
Molecules 2014, 19(3), 2896-2910; doi:10.3390/molecules19032896
Received: 7 February 2014 / Revised: 22 February 2014 / Accepted: 26 February 2014 / Published: 6 March 2014
Cited by 9 | PDF Full-text (371 KB) | HTML Full-text | XML Full-text
Abstract
Thymus vulgaris has gained tremendous popularity as an ornamental, culinary herb and its use in phytotherapy is well established and supported in the literature. The objective of this study was to explore possible interactions between selected molecules within Thymus vulgaris essential oil (TvEO)
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Thymus vulgaris has gained tremendous popularity as an ornamental, culinary herb and its use in phytotherapy is well established and supported in the literature. The objective of this study was to explore possible interactions between selected molecules within Thymus vulgaris essential oil (TvEO) to gain a better understanding of how this complex essential oil exerts its antimicrobial activity. Evaluation of the antimicrobial efficacy and interactions were assessed on the essential oil and volatile constituents against various pathogens. Interactions between molecules at various ratios were graphically observed through the construction of isobolograms. Gas chromatography-mass spectrometry (GC-MS) analysis revealed 22 compounds which collectively represent >95% of the oil composition. Based on their minimum inhibitory concentration (MIC) values, they were categorised into weak (≥4 mg mL−1), moderate (2–4 mg mL−1) and noteworthy active (≤2 mg mL−1) compounds. For the combination study, 21% synergistic, 42% additive, 36% indifferent and 1% antagonistic interactions were observed. Most of the interactions were observed between the weak and highly active molecules, and interestingly, no synergistic interaction was observed between the highly active compounds. Synergistic and additive interactions between the strong and weaker antimicrobial constituents present in TvEO enhance the antimicrobial efficacy of this commercially important essential oil. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Determination of Pesticide Residues in Honeybees using Modified QUEChERS Sample Work-Up and Liquid Chromatography-Tandem Mass Spectrometry
Molecules 2014, 19(3), 2911-2924; doi:10.3390/molecules19032911
Received: 3 December 2013 / Revised: 24 February 2014 / Accepted: 26 February 2014 / Published: 6 March 2014
Cited by 8 | PDF Full-text (917 KB) | HTML Full-text | XML Full-text
Abstract
Increasing emissions of chemical compounds to the environment, especially of pesticides, is one of factors that may explain present honeybee colony losses. In this work, an analytical method employing liquid chromatography-tandem mass spectrometry (LC-MS/MS) was optimized for the simultaneous screening of 19 pesticides
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Increasing emissions of chemical compounds to the environment, especially of pesticides, is one of factors that may explain present honeybee colony losses. In this work, an analytical method employing liquid chromatography-tandem mass spectrometry (LC-MS/MS) was optimized for the simultaneous screening of 19 pesticides which have not been yet determined in honeybee samples from northern Poland (Pomerania). The sample preparation, based on the QuEChERS method combining salting-out liquid-liquid extraction to acetonitrile and a dispersive-SPE clean-up, was adjusted to honeybee samples by adding a small amount of hexane to eliminate beeswax. The recovery of analytes ranged from 70% to 120% with relative standard deviation ≤20%. The limits of detection were in the range of 0.91–25 ng/g. A total of 19 samples of honeybees from suspected pesticide poisoning incidents were analyzed, in which 19 different pesticides were determined. Full article
(This article belongs to the Special Issue Microextraction)
Open AccessArticle The Influence of Chemical Surface Modification of Kenaf Fiber using Hydrogen Peroxide on the Mechanical Properties of Biodegradable Kenaf Fiber/Poly(Lactic Acid) Composites
Molecules 2014, 19(3), 2957-2968; doi:10.3390/molecules19032957
Received: 4 November 2013 / Revised: 20 February 2014 / Accepted: 21 February 2014 / Published: 7 March 2014
Cited by 11 | PDF Full-text (1759 KB) | HTML Full-text | XML Full-text
Abstract
Bleaching treatment of kenaf fiber was performed in alkaline medium containing hydrogen peroxide solution maintained at pH 11 and 80 °C for 60 min. The bleached kenaf fiber was analyzed using Fourier Transform Infrared (FTIR) and X-ray Diffraction (XRD) analysis. The bleached kenaf
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Bleaching treatment of kenaf fiber was performed in alkaline medium containing hydrogen peroxide solution maintained at pH 11 and 80 °C for 60 min. The bleached kenaf fiber was analyzed using Fourier Transform Infrared (FTIR) and X-ray Diffraction (XRD) analysis. The bleached kenaf fiber was then compounded with poly-(lactic acid) (PLA) via a melt blending method. The mechanical (tensile, flexural and impact) performance of the product was tested. The fiber treatment improved the mechanical properties of PLA/bleached kenaf fiber composites. Scanning electron micrograph (SEM) morphological analysis showed improvement of the interfacial adhesion between the fiber surface and polymer matrix. Full article
Open AccessArticle Understanding the Adsorption of CuPc and ZnPc on Noble Metal Surfaces by Combining Quantum-Mechanical Modelling and Photoelectron Spectroscopy
Molecules 2014, 19(3), 2969-2992; doi:10.3390/molecules19032969
Received: 16 January 2014 / Revised: 24 February 2014 / Accepted: 26 February 2014 / Published: 7 March 2014
Cited by 26 | PDF Full-text (2113 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phthalocyanines are an important class of organic semiconductors and, thus, their interfaces with metals are both of fundamental and practical relevance. In the present contribution we provide a combined theoretical and experimental study, in which we show that state-of-the-art quantum-mechanical simulations are nowadays
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Phthalocyanines are an important class of organic semiconductors and, thus, their interfaces with metals are both of fundamental and practical relevance. In the present contribution we provide a combined theoretical and experimental study, in which we show that state-of-the-art quantum-mechanical simulations are nowadays capable of treating most properties of such interfaces in a quantitatively reliable manner. This is shown for Cu-phthalocyanine (CuPc) and Zn-phthalocyanine (ZnPc) on Au(111) and Ag(111) surfaces. Using a recently developed approach for efficiently treating van der Waals (vdW) interactions at metal/organic interfaces, we calculate adsorption geometries in excellent agreement with experiments. With these geometries available, we are then able to accurately describe the interfacial electronic structure arising from molecular adsorption. We find that bonding is dominated by vdW forces for all studied interfaces. Concomitantly, charge rearrangements on Au(111) are exclusively due to Pauli pushback. On Ag(111), we additionally observe charge transfer from the metal to one of the spin-channels associated with the lowest unoccupied π-states of the molecules. Comparing the interfacial density of states with our ultraviolet photoelectron spectroscopy (UPS) experiments, we find that the use of a hybrid functionals is necessary to obtain the correct order of the electronic states. Full article
(This article belongs to the Special Issue Photoelectron Spectroscopy)
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Open AccessArticle Synthesis and Spectroscopic Properties of New Azo Dyes Derived from 3-Ethylthio-5-cyanomethyl-4-phenyl-1,2,4-triazole
Molecules 2014, 19(3), 2993-3003; doi:10.3390/molecules19032993
Received: 31 December 2013 / Revised: 10 February 2014 / Accepted: 10 February 2014 / Published: 7 March 2014
Cited by 1 | PDF Full-text (290 KB) | HTML Full-text | XML Full-text
Abstract
New 1,2,4-triazole colorants were obtained, in high yields, by coupling 3-ethylthio-5-cyanomethyl-4-phenyl-1,2,4-triazole (1) with diazotized aniline derivatives 2, 4 and 6. The azo dyes prepared in this work may exist in three tautomeric forms. We found that the tautomerism is
[...] Read more.
New 1,2,4-triazole colorants were obtained, in high yields, by coupling 3-ethylthio-5-cyanomethyl-4-phenyl-1,2,4-triazole (1) with diazotized aniline derivatives 2, 4 and 6. The azo dyes prepared in this work may exist in three tautomeric forms. We found that the tautomerism is influenced mainly by the nature of substituent at the para position of the aniline coupling component. This tautomerisation was observed in the NMR spectra of the dyes. The dyes were characterized by IR, 1H-NMR, 13C-NMR and MS spectroscopic techniques. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Limonoids from the Fruits of Khaya ivorensis
Molecules 2014, 19(3), 3004-3011; doi:10.3390/molecules19033004
Received: 22 January 2014 / Revised: 27 February 2014 / Accepted: 28 February 2014 / Published: 7 March 2014
Cited by 1 | PDF Full-text (415 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new limonoids, namely 14,15-didehydroruageanin A (1) and 3-O-methyl- butyrylseneganolide A (2), were isolated from the fruits of Khaya ivorensis along with six known limonoids: seneganolide A (3), 1,3-dideacetylkhivorin (4), 7-deacetylkhivorin (5
[...] Read more.
Two new limonoids, namely 14,15-didehydroruageanin A (1) and 3-O-methyl- butyrylseneganolide A (2), were isolated from the fruits of Khaya ivorensis along with six known limonoids: seneganolide A (3), 1,3-dideacetylkhivorin (4), 7-deacetylkhivorin (5), 3-deacetylkhivorin (6), 1-deacetylkhivorin (7), and 3-deacetyl-7-oxokhivorin (8). All the compounds were evaluated for their cytotoxicity against five tumor cell lines. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Ginsenoside Rb1 Protects Rat Neural Progenitor Cells against Oxidative Injury
Molecules 2014, 19(3), 3012-3024; doi:10.3390/molecules19033012
Received: 6 January 2014 / Revised: 13 February 2014 / Accepted: 3 March 2014 / Published: 7 March 2014
Cited by 12 | PDF Full-text (2516 KB) | HTML Full-text | XML Full-text
Abstract
Ginseng, the root of Panax ginseng C.A. Meyer, has been used as a tonic to enhance bodily functions against various ailments for hundreds of years in Far Eastern countries without apparent adverse effects. Ginsenoside Rb1, one of the most active ingredients of ginseng,
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Ginseng, the root of Panax ginseng C.A. Meyer, has been used as a tonic to enhance bodily functions against various ailments for hundreds of years in Far Eastern countries without apparent adverse effects. Ginsenoside Rb1, one of the most active ingredients of ginseng, has been shown to possess various pharmacological activities. Here we report that Rb1 exhibits potent neuroprotective effects against oxidative injury induced by tert-butylhydroperoxide (t-BHP). Lactate dehydrogenase (LDH) assay demonstrated that incubation with 300 µm t-BHP for 2.5 h led to a significant cell loss of cultured rat embryonic cortex-derived neural progenitor cells (NPCs) and the cell viability was pronouncedly increased by 24 h pretreatment of 10 µm Rb1. TUNEL staining further confirmed that pretreatment of Rb1 significantly reduced the cell apoptosis in t-BHP-induced oxidative injury. Real time PCR revealed that pretreatment with Rb1 activated Nrf2 pathway in cultured NPCs and led to an elevated expression of HO-1. The results of the present study demonstrate that Rb1 shows a potent anti-oxidative effect on cultured NPCs by activating Nrf2 pathway. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
Open AccessArticle Microwave-Assisted Extraction of Herbacetin Diglucoside from Flax (Linum usitatissimum L.) Seed Cakes and Its Quantification using an RP-HPLC-UV System
Molecules 2014, 19(3), 3025-3037; doi:10.3390/molecules19033025
Received: 9 January 2014 / Revised: 26 February 2014 / Accepted: 28 February 2014 / Published: 10 March 2014
Cited by 8 | PDF Full-text (385 KB) | HTML Full-text | XML Full-text
Abstract
Flax (Linum usitatissimum L.) seeds are widely used for oil extraction and the cold-pressed flaxseed (or linseed) cakes obtained during this process constitute a valuable by-product. The flavonol herbacetin diglucoside (HDG) has been previously reported as a constituent of the flaxseed lignan
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Flax (Linum usitatissimum L.) seeds are widely used for oil extraction and the cold-pressed flaxseed (or linseed) cakes obtained during this process constitute a valuable by-product. The flavonol herbacetin diglucoside (HDG) has been previously reported as a constituent of the flaxseed lignan macromolecule linked through ester bonds to the linker molecule hydroxymethylglutaric acid. In this context, the development and validation of a new approach using microwave-assisted extraction (MAE) of HDG from flaxseed cakes followed by quantification with a reverse-phase HPLC system with UV detection was purposed. The experimental parameters affecting the HDG extraction yield, such as microwave power, extraction time and sodium hydroxide concentration, from the lignan macromolecule were optimized. A maximum HDG concentration of 5.76 mg/g DW in flaxseed cakes was measured following an irradiation time of 6 min, for a microwave power of 150 W using a direct extraction in 0.1 M NaOH in 70% (v/v) aqueous methanol. The optimized method was proven to be rapid and reliable in terms of precision, repeatability, stability and accuracy for the extraction of HDG. Comparison with a conventional extraction method demonstrated that MAE is more effective and less time-consuming. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Assessment of Circulating microRNAs in Plasma of Lung Cancer Patients
Molecules 2014, 19(3), 3038-3054; doi:10.3390/molecules19033038
Received: 17 February 2014 / Revised: 28 February 2014 / Accepted: 4 March 2014 / Published: 10 March 2014
Cited by 18 | PDF Full-text (481 KB) | HTML Full-text | XML Full-text
Abstract
Lung cancer is the most common cause of cancer deaths worldwide and numerous ongoing research efforts are directed to identify new strategies for its early detection. The development of non-invasive blood-based biomarkers for cancer detection in its preclinical phases is crucial to improve
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Lung cancer is the most common cause of cancer deaths worldwide and numerous ongoing research efforts are directed to identify new strategies for its early detection. The development of non-invasive blood-based biomarkers for cancer detection in its preclinical phases is crucial to improve the outcome of this deadly disease. MicroRNAs (miRNAs) are a new promising class of circulating biomarkers for cancer detection and prognosis definition, but lack of consensus on data normalization methods for circulating miRNAs and the critical issue of haemolysis, has affected the identification of circulating miRNAs with diagnostic potential. We describe here an interesting approach for profiling circulating miRNAs in plasma samples based on the evaluation of reciprocal miRNA levels measured by quantitative Real-Time PCR. By monitoring changes of plasma miRNA-ratios, it is possible to assess the deregulation of tumor-related miRNAs and identify signatures with diagnostic and prognostic value. In addition, to avoid bias due to the release of miRNAs from blood cells, a miRNA-ratios signature distinguishing haemolyzed samples was identified. The method described was validated in plasma samples of lung cancer patients, but given its reproducibility and reliability, could be potentially applied for the identification of diagnostic circulating miRNAs in other diseases. Full article
(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)
Open AccessArticle Five New Alkaloids from the Stem Bark of Daphniphyllum macropodum
Molecules 2014, 19(3), 3055-3067; doi:10.3390/molecules19033055
Received: 11 February 2014 / Revised: 25 February 2014 / Accepted: 26 February 2014 / Published: 10 March 2014
Cited by 1 | PDF Full-text (414 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Five new alkaloids, daphnicyclidins M and N (compounds 1 and 2) and calyciphyllines Q–S (compounds 35), along with four known ones, paxiphylline C (6), macropodumine B (7), macropodumine C (8) and daphnicyclidin A
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Five new alkaloids, daphnicyclidins M and N (compounds 1 and 2) and calyciphyllines Q–S (compounds 35), along with four known ones, paxiphylline C (6), macropodumine B (7), macropodumine C (8) and daphnicyclidin A (9) were isolated from the stem bark of Daphniphyllum macropodum. Calyciphylline Q (3) is the first calyciphylline A derivative possessing a double bond between C-18 and C-19. Their structures and relative configurations were elucidated on the basis of spectroscopic methods, especially 2D NMR techniques. Compounds 1, 2, 8 and 9 exhibited cytotoxic activity against P-388 cells with IC50 values of 5.7, 6.5, 10.3 and 13.8 µM, respectively. Compounds 1 and 2 also showed cytotoxic activity against SGC-7901 cells with IC50 values of 22.4 and 25.6 µM. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Synthesis of Novel Highly Functionalized 4-Thiazolidinone Derivatives from 4-Phenyl-3-thiosemicarbazones
Molecules 2014, 19(3), 3068-3083; doi:10.3390/molecules19033068
Received: 7 February 2014 / Revised: 27 February 2014 / Accepted: 4 March 2014 / Published: 11 March 2014
Cited by 3 | PDF Full-text (595 KB) | HTML Full-text | XML Full-text
Abstract We present herein the synthesis in good yields of two series of highly functionalized thiazolidinone derivatives from the reactions of various 4-phenyl-3-thio-semicarbazones with ethyl 2-bromoacetate and diethyl acetylenedicarboxylate, respectively. Full article
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Open AccessArticle Nutraceutical Value of Yellow- and Red-Fleshed South African Plums (Prunus salicina Lindl.): Evaluation of Total Antioxidant Capacity and Phenolic Composition
Molecules 2014, 19(3), 3084-3109; doi:10.3390/molecules19033084
Received: 6 February 2014 / Revised: 27 February 2014 / Accepted: 4 March 2014 / Published: 11 March 2014
Cited by 2 | PDF Full-text (402 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ten South African plum cultivars and selections, including yellow- and red-fleshed plums from two harvest seasons were evaluated in terms of nutraceutical value (phenolic composition, total polyphenol content (TPC) and total antioxidant capacity (TAC)) and fruit attributes (colour, fruit mass, etc.). Plums
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Ten South African plum cultivars and selections, including yellow- and red-fleshed plums from two harvest seasons were evaluated in terms of nutraceutical value (phenolic composition, total polyphenol content (TPC) and total antioxidant capacity (TAC)) and fruit attributes (colour, fruit mass, etc.). Plums were evaluated at two maturity stages, i.e., directly after harvest (unripe) and after a commercial cold storage and ripening regime (ripe). The phenolic composition of South African plums varied greatly, both qualitatively and quantitatively, between cultivars and selections. Neochlorogenic acid, cyanidin-3-O-glucoside and quercetin-3-O-glucoside were the predominant hydroxycinnamic acid, anthocyanin and flavonol, respectively, although not present in all plums. The flavan-3-ols, (+)-catechin, (−)-epicatechin and procyanidins B1 and B2, were present in all plums. Red-fleshed plums tended to display higher TAC and TPC than yellow-fleshed plums. The flavan-3-ol content was highly correlated with TAC. The effect of harvest season was cultivar-dependent, but cultivar differences were not obscured. In terms of maturity stage, the ripe fruits tended to contain higher levels of anthocyanins and some flavonol compounds, although the TPC and TAC were not affected in most cases. South African plums, especially the red-fleshed selections PR04-32 and PR04-35, were shown to provide generally high TAC and TPC compared to literature values. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Antioxidant Activity of Co-Products from Guava, Mango and Barbados Cherry Produced in the Brazilian Northeast
Molecules 2014, 19(3), 3110-3119; doi:10.3390/molecules19033110
Received: 20 January 2014 / Revised: 25 February 2014 / Accepted: 5 March 2014 / Published: 11 March 2014
Cited by 4 | PDF Full-text (219 KB) | HTML Full-text | XML Full-text
Abstract
Co-products from the juice processing of guava (CG), mango (CM) and barbados cherry (CB) were investigated with a view to their exploitation as a potential source of natural antioxidants. The ethanolic extracts were analyzed for total extractable phenolic content (TEP), DPPH radical scavenging
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Co-products from the juice processing of guava (CG), mango (CM) and barbados cherry (CB) were investigated with a view to their exploitation as a potential source of natural antioxidants. The ethanolic extracts were analyzed for total extractable phenolic content (TEP), DPPH radical scavenging activity (RSA-DPPH), ferric reducing antioxidant power (FRAP) and antioxidant activity in relation to the β-carotene/ linoleic acid system. The TEP levels in the CG, CM and CB extracts were (24.15 ± 1.59), (44.18 ± 1.73) and (49.21 ± 3.70) mg GAE/g extract, respectively. The CM extract showed higher DPPH, FRAP and antioxidant activity in the β-carotene/linoleic acid system. The data revealed a positive linear correlation between TEP, RSA-DPPH and FRAP (r2 = 0.85 − 0.98); however, the β-carotene/linoleic acid system (r2 = 0.01 − 0.26) shows low correlation with the TEP levels and other assessment systems. The results suggest that co-products generated from the juice processing of the studied fruit have promising use as a natural source of antioxidants. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Pharmacokinetic Study in Mice of Galphimine-A, an Anxiolytic Compound from Galphimia glauca
Molecules 2014, 19(3), 3120-3134; doi:10.3390/molecules19033120
Received: 28 January 2014 / Revised: 25 February 2014 / Accepted: 25 February 2014 / Published: 12 March 2014
PDF Full-text (260 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to obtain pharmacokinetic data for the anxiolytic compound galphimine-A (G–A) from Galphimia glauca. G–A is the most abundant anxiolytic compound in this plant, while Galphimine-E (G–E) is the most abundant galphimine, but inactive. G–E was transformed
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The aim of this study was to obtain pharmacokinetic data for the anxiolytic compound galphimine-A (G–A) from Galphimia glauca. G–A is the most abundant anxiolytic compound in this plant, while Galphimine-E (G–E) is the most abundant galphimine, but inactive. G–E was transformed chemically into G–A. The pharmacokinetic study was carried out in ICR mice, which were orally administered a single 200 mg/kg dose of G–A. Samples of blood and brain were taken at different times after administration of G–A. Previously, we established the validation of methods for determining the concentration of G–A. The G–A was detected in plasma 5 min after oral administration, and its concentration reached 2.47 μg/mL. Data from concentration-time curves allowed us to establish the main pharmacokinetic parameters in two models: one- and/or two-compartment. Cmax values were 3.33 and 3.42 μg/mL respectively, likewise AUC0→1440 min were 1,951.58 and 1,824.95 μg/mL·min. The G–A in brain tissue was noted to cross the blood-brain barrier, reaching Cmax 2.74 μg/mL, Tmax 81.6 min, and then drop gradually to 0.32 μg/mL detected at 24 h. The presence of G–A in brain tissue, confirmed that this anxiolytic compound can access the target organ and acts directly on the CNS. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of PNA Oligoether Conjugates
Molecules 2014, 19(3), 3135-3148; doi:10.3390/molecules19033135
Received: 21 January 2014 / Revised: 1 March 2014 / Accepted: 4 March 2014 / Published: 13 March 2014
Cited by 2 | PDF Full-text (346 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Several different approaches have been explored for conjugation of oligoethers to PNA with internally or N-terminal placed diaminopropionic acid residues. Single and double conjugation of 2-(2-(2-aminoethoxy)ethoxy)ethanol was obtained using carbonyldimidazole. Using a post PNA-assembly coupling procedure the building block 2-(2-(2-(benzoyloxy)ethoxy)ethoxy)acetic acid multiple attachment
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Several different approaches have been explored for conjugation of oligoethers to PNA with internally or N-terminal placed diaminopropionic acid residues. Single and double conjugation of 2-(2-(2-aminoethoxy)ethoxy)ethanol was obtained using carbonyldimidazole. Using a post PNA-assembly coupling procedure the building block 2-(2-(2-(benzoyloxy)ethoxy)ethoxy)acetic acid multiple attachment of 2-(2-(2-hydroxyethoxy)ethoxy)acetyl groups to both N-terminal and β-amino groups of inserted diaminopropionic acids residues was achieved. Use of a new oligoether functionalized amino acid allows inclusion of oligoether conjugates during on-line machine assisted synthesis which also allowed combination of methods for attachment of different oligoethers and co-conjugation of neocuproine as well as conjugation of an aminosugar. Full article
(This article belongs to the Special Issue Bioconjugations)
Open AccessArticle 5-Azacytidine Induces Anoikis, Inhibits Mammosphere Formation and Reduces Metalloproteinase 9 Activity in MCF-7 Human Breast Cancer Cells
Molecules 2014, 19(3), 3149-3159; doi:10.3390/molecules19033149
Received: 24 January 2014 / Revised: 7 March 2014 / Accepted: 7 March 2014 / Published: 13 March 2014
Cited by 10 | PDF Full-text (2348 KB) | HTML Full-text | XML Full-text
Abstract
Cancer stem cells are a subset of cancer cells that initiate the growth of tumors. Low levels of cancer stem cells also exist in established cancer cell lines, and can be enriched in serum-free tumorsphere cultures. Since cancer stem cells have been reported
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Cancer stem cells are a subset of cancer cells that initiate the growth of tumors. Low levels of cancer stem cells also exist in established cancer cell lines, and can be enriched in serum-free tumorsphere cultures. Since cancer stem cells have been reported to be resilient to common chemotherapeutic drugs in comparison to regular cancer cells, screening for compounds selectively targeting cancer stem cells may provide an effective therapeutic strategy. We found that 5-azacytidine (5-AzaC) selectively induced anoikis of MCF-7 in suspension cultures with an EC50 of 8.014 µM, and effectively inhibited tumorsphere formation, as well as the migration and matrix metalloproteinases-9 (MMP-9) activity of MCF-7 cells. Furthermore, 5-AzaC and radiation collaboratively inhibited MCF-7 tumorsphere formation at clinically relevant radiation doses. Investigating the underlying mechanism may provide insight into signaling pathways crucial for cancer stem cell survival and pave the way to novel potential therapeutic targets. Full article
Open AccessArticle Extract from Armoracia rusticana and Its Flavonoid Components Protect Human Lymphocytes against Oxidative Damage Induced by Hydrogen Peroxide
Molecules 2014, 19(3), 3160-3172; doi:10.3390/molecules19033160
Received: 14 January 2014 / Revised: 27 February 2014 / Accepted: 4 March 2014 / Published: 14 March 2014
Cited by 6 | PDF Full-text (274 KB) | HTML Full-text | XML Full-text
Abstract
DNA damage prevention is an important mechanism involved in cancer prevention by dietary compounds. Armoracia rusticana is cultivated mainly for its roots that are used in the human diet as a pungent spice. The roots represent rich sources of biologically active phytocompounds, which
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DNA damage prevention is an important mechanism involved in cancer prevention by dietary compounds. Armoracia rusticana is cultivated mainly for its roots that are used in the human diet as a pungent spice. The roots represent rich sources of biologically active phytocompounds, which are beneficial for humans. In this study we investigated the modulation of H2O2 genotoxicity using the A. rusticana root aqueous extract (AE) and two flavonoids (kaempferol or quercetin). Human lymphocytes pre-treated with AE, kaempferol and quercetin were challenged with H2O2 and the DNA damage was assessed by the comet assay. At first we assessed a non-genotoxic concentration of AE and flavonoids, respectively. In lymphocytes challenged with H2O2 we proved that the 0.0025 mg·mL−1 concentration of AE protected human DNA. It significantly reduced H2O2-induced oxidative damage (from 78% to 35.75%). Similarly, a non-genotoxic concentration of kaempferol (5 μg·mL−1) significantly diminished oxidative DNA damage (from 83.3% to 19.4%), and the same concentration of quercetin also reduced the genotoxic effect of H2O2 (from 83.3% to 16.2%). We conclude that AE, kaempferol and quercetin probably act as antimutagens. The molecular mechanisms underlying their antimutagenic activity might be explained by their antioxidant properties. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Antibacterial Effects of Afzelin Isolated from Cornus macrophylla on Pseudomonas aeruginosa, A Leading Cause of Illness in Immunocompromised Individuals
Molecules 2014, 19(3), 3173-3180; doi:10.3390/molecules19033173
Received: 7 February 2014 / Revised: 10 March 2014 / Accepted: 10 March 2014 / Published: 17 March 2014
Cited by 9 | PDF Full-text (466 KB) | HTML Full-text | XML Full-text
Abstract
The crude ethyl acetate extract of the leaves of Cornus macrophylla showed antibacterial activity against Pseudomonas aeruginosa, a leading cause of illness in immunocompromised individuals. Bioactivity-guided separation led to the isolation of kaempferol 3-O-α-L-rhamnopyranoside (afzelin). The structure was determined based
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The crude ethyl acetate extract of the leaves of Cornus macrophylla showed antibacterial activity against Pseudomonas aeruginosa, a leading cause of illness in immunocompromised individuals. Bioactivity-guided separation led to the isolation of kaempferol 3-O-α-L-rhamnopyranoside (afzelin). The structure was determined based on evaluation of its spectroscopic (UV, MS, and NMR) data. The minimum inhibitory concentration (MIC) of afzelin against Pseudomonas aeruginosa was found to be 31 µg/mL. In addition, the results indicated that a hydroxyl group at C3 of the C-ring of the flavone skeleton and the rhamnose group may act as a negative factor and an enhancing factor, respectively, in the antibacterial activities of afzelin. Full article
Open AccessArticle Sesquiterpenes from the Brazilian Red Alga Laurencia dendroidea J. Agardh
Molecules 2014, 19(3), 3181-3192; doi:10.3390/molecules19033181
Received: 15 January 2014 / Revised: 3 March 2014 / Accepted: 5 March 2014 / Published: 17 March 2014
Cited by 3 | PDF Full-text (541 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new chamigrane sesquiterpenes 12 and three known compounds 35 were isolated from a lipophilic extract of the red alga Laurencia dendroidea collected from the Southeastern Brazilian coast. Dendroidone (1) and dendroidiol (2) were isolated
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Two new chamigrane sesquiterpenes 12 and three known compounds 35 were isolated from a lipophilic extract of the red alga Laurencia dendroidea collected from the Southeastern Brazilian coast. Dendroidone (1) and dendroidiol (2) were isolated from samples collected at Biscaia Inlet, Angra dos Reis, Rio de Janeiro and at Manguinhos Beach, Serra, Espírito Santo, respectively. Debromoelatol (3), obtusane (4) and (1S*,2S*,3S*,5S*,8S*,9S*)-2,3,5,9-tetramethyltricyclo[6.3.0.01.5]undecan-2-ol (5) were obtained from specimens collected at Vermelha Beach, Parati, Rio de Janeiro. The structures of new compounds were elucidated by extensive NMR (1H-, 13C-, COSY, HSQC, HMBC and NOESY) and high resolution mass spectrometry analysis. Additionally, the absolute configuration of compound 2 was assigned by X-ray analysis. Full spectroscopic data is described for the first time for compound 3. Anti-inflammatory and antimycobacterial activities of compounds 25 were evaluated. Compounds 35 inhibited the release of inflammatory mediator NO while TNF-α levels were only affected by 3. All compounds tested displayed moderate antimycobacterial action. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Biological Evaluation of 2,4-Diaminopyrimidine-Based Antifolate Drugs against Bacillus anthracis
Molecules 2014, 19(3), 3231-3246; doi:10.3390/molecules19033231
Received: 11 January 2014 / Revised: 8 March 2014 / Accepted: 10 March 2014 / Published: 17 March 2014
Cited by 4 | PDF Full-text (528 KB) | HTML Full-text | XML Full-text
Abstract
Due to the innate ability of bacteria to develop resistance to available antibiotics, there is a critical need to develop new agents to treat more resilient strains. As a continuation of our research in this area, we have synthesized a series of racemic
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Due to the innate ability of bacteria to develop resistance to available antibiotics, there is a critical need to develop new agents to treat more resilient strains. As a continuation of our research in this area, we have synthesized a series of racemic 2,4-diaminopyrimidine-based drug candidates, and evaluated them against Bacillus anthracis. The structures are comprised of a 2,4-diaminopyrimidine ring, a 3,4-dimethoxybenzyl ring, and an N-acryloyl-substituted 1,2-dihydrophthalazine ring. Various changes were made at the C1 stereocenter of the dihydrophthalazine moiety in the structure, and the biological activity was assessed by measurement of the MIC and Ki values to identify the most potent drug candidate. Full article
(This article belongs to the Special Issue Heterocyclic and Medicinal Chemistry)
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Open AccessArticle Omega-3 Fatty Acids Protect Renal Functions by Increasing Docosahexaenoic Acid-Derived Metabolite Levels in SHR.Cg-Leprcp/NDmcr Rats, a Metabolic Syndrome Model
Molecules 2014, 19(3), 3247-3263; doi:10.3390/molecules19033247
Received: 30 December 2013 / Revised: 7 March 2014 / Accepted: 7 March 2014 / Published: 17 March 2014
Cited by 7 | PDF Full-text (647 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The omega-3 polyunsaturated fatty acids (ω-3 PUFAs) docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) protect against diabetic nephropathy by inhibiting inflammation. The aim of this study was to assess the effects of highly purified DHA and EPA or EPA only administration on renal
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The omega-3 polyunsaturated fatty acids (ω-3 PUFAs) docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) protect against diabetic nephropathy by inhibiting inflammation. The aim of this study was to assess the effects of highly purified DHA and EPA or EPA only administration on renal function and renal eicosanoid and docosanoid levels in an animal model of metabolic syndrome, SHR.Cg-Leprcp/NDmcr (SHRcp) rats. Male SHRcp rats were divided into 3 groups. Control (5% arabic gum), TAK-085 (300 mg/kg/day, containing 467 mg/g EPA and 365 mg/g DHA), or EPA (300 mg/kg/day) was orally administered for 20 weeks. The urinary albumin to creatinine ratio in the TAK-085-administered group was significantly lower than that in other groups. The glomerular sclerosis score in the TAK-085-administered group was significantly lower than that in the other groups. Although DHA levels were increased in total kidney fatty acids, the levels of nonesterified DHA were not significantly different among the 3 groups, whereas the levels of protectin D1, resolvin D1, and resolvin D2 were significantly increased in the TAK-085-administered group. The results show that the use of combination therapy with DHA and EPA in SHRcp rats improved or prevented renal failure associate with metabolic syndrome with decreasing triglyceride levels and increasing ω-3 PUFA lipid mediators. Full article
(This article belongs to the Special Issue Fatty Acids)
Open AccessArticle Cytotoxic Quinones from the Roots of Aloe dawei
Molecules 2014, 19(3), 3264-3273; doi:10.3390/molecules19033264
Received: 24 January 2014 / Revised: 5 March 2014 / Accepted: 10 March 2014 / Published: 17 March 2014
Cited by 5 | PDF Full-text (230 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Seven naphthoquinones and nine anthraquinones were isolated from the roots of Aloe dawei by chromatographic separation. The purified metabolites were identified by NMR and MS analyses. Out of the sixteen quinones, 6-hydroxy-3,5-dimethoxy-2-methyl-1,4-naphthoquinone is a new compound. Two of the isolates, 5,8-dihydroxy-3-methoxy-2-methylnaphthalene-1,4-dione and 1-hydroxy-8-methoxy-3-methylanthraquinone
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Seven naphthoquinones and nine anthraquinones were isolated from the roots of Aloe dawei by chromatographic separation. The purified metabolites were identified by NMR and MS analyses. Out of the sixteen quinones, 6-hydroxy-3,5-dimethoxy-2-methyl-1,4-naphthoquinone is a new compound. Two of the isolates, 5,8-dihydroxy-3-methoxy-2-methylnaphthalene-1,4-dione and 1-hydroxy-8-methoxy-3-methylanthraquinone showed high cytotoxic activity (IC50 1.15 and 4.85 µM) on MCF-7 breast cancer cells, whereas the others showed moderate to low cytotoxic activity against MDA-MB-231 (ER Negative) and MCF-7 (ER Positive) cancer cells. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Computational Study of Electron Delocalization in Hexaarylbenzenes
Molecules 2014, 19(3), 3274-3296; doi:10.3390/molecules19033274
Received: 28 November 2013 / Revised: 7 March 2014 / Accepted: 7 March 2014 / Published: 17 March 2014
Cited by 5 | PDF Full-text (2026 KB) | HTML Full-text | XML Full-text
Abstract
A number of hexaarylbenzene compounds were studied theoretically, in order to compare energy changes as a result of the toroidal delocalization effect that is characteristic of all these species. The energy was studied taking advantage of locally designed isodesmic reactions. Results indicate that
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A number of hexaarylbenzene compounds were studied theoretically, in order to compare energy changes as a result of the toroidal delocalization effect that is characteristic of all these species. The energy was studied taking advantage of locally designed isodesmic reactions. Results indicate that the amount of aromaticity manifested by each substituent is a factor that should be considered when assessing the quantity of energy dissipated from each aromatic center. The influence of different substituents on electronic delocalization is also analyzed, as well as the role played by their frontier molecular orbitals. Full article
Open AccessArticle Synthesis and Anticancer Activity of Some New Pyrazolo[3,4-d]pyrimidin-4-one Derivatives
Molecules 2014, 19(3), 3297-3309; doi:10.3390/molecules19033297
Received: 31 December 2013 / Revised: 27 February 2014 / Accepted: 5 March 2014 / Published: 18 March 2014
Cited by 5 | PDF Full-text (273 KB) | HTML Full-text | XML Full-text
Abstract
3,6-Dimethyl-1-phenyl-1H-pyrazolo[3,4-d][1,3]oxazin-4-one (3) was prepared by hydrolysis of ethyl 5-amino-3-methyl-1-phenyl-1H-pyrazole-4-carboxylate (1) to afford the corresponding carboxylic acid 2, which was reacted with acetic anhydride to give 3. The pyrazolo[3,4-d][1,3]oxazin-4-one 3
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3,6-Dimethyl-1-phenyl-1H-pyrazolo[3,4-d][1,3]oxazin-4-one (3) was prepared by hydrolysis of ethyl 5-amino-3-methyl-1-phenyl-1H-pyrazole-4-carboxylate (1) to afford the corresponding carboxylic acid 2, which was reacted with acetic anhydride to give 3. The pyrazolo[3,4-d][1,3]oxazin-4-one 3 was reacted with hydroxylamine hydrochloride, urea, thiourea, thiosemicarbazide, phenylhydrazine and aromatic amines to afford the corresponding pyrazolo[3,4-d]pyrimidin-4-ones 4, 5a,b, 6, 7, 8ae, respectively. Condensation of pyrazoloxazine derivative 3 with 99% hydrazine hydrate afforded the 5-aminopyrazolo[3,4-d] pyrimidine derivative 9. Coupling of 9 with aromatic aldehydes yielded a series of 3,6-dimethyl-5-(4-substitutedbenzylideneamino)-1-phenyl-1,5-dihydropyrazolo[3,4-d]pyrimidin- 4-ones 10ae. The new compounds were tested for their antitumor activity on the MCF-7 human breast adenocarcinoma cell line. Almost all the tested compounds revealed antitumor activity, especially 3,6-dimethyl-5-(4-nitrobenzylideneamino)-1-phenyl-1,5-dihydropyrazolo[3,4-d]pyrimidin-4-one (10e) which displayed the most potent inhibitory activity with a half maximal inhibitory concentration (IC50) of 11 µM. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Appraisal of Antioxidant and Anti-Inflammatory Activities of Various Extracts from the Fruiting Bodies of Pleurotus florida
Molecules 2014, 19(3), 3310-3326; doi:10.3390/molecules19033310
Received: 25 December 2013 / Revised: 28 February 2014 / Accepted: 12 March 2014 / Published: 18 March 2014
Cited by 6 | PDF Full-text (1035 KB) | HTML Full-text | XML Full-text
Abstract
Pleurotus florida has been widely used for nutritional and medicinal purposes. The present study was conducted to evaluate the antioxidant and anti-inflammatory effects of the fruiting bodies of P. florida extracted with acetone, methanol, and hot water. The antioxidant activities of the
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Pleurotus florida has been widely used for nutritional and medicinal purposes. The present study was conducted to evaluate the antioxidant and anti-inflammatory effects of the fruiting bodies of P. florida extracted with acetone, methanol, and hot water. The antioxidant activities of the acetone and methanol extracts of P. florida showed stronger inhibition of β-carotene-linoleic acid compared to that of the hot water extract. The acetone extract (8 mg/mL) showed a high reducing power of 1.86. The acetone and methanol extracts showed more effective DPPH radical scavenging activities than the hot water extract. The chelating effect of the extracts at lower concentrations was significantly effective compared to that of the positive control. Thirteen phenolic compounds were detected from acetonitrile and hydrochloric acid solvent extracts. Nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in lipolysaccahride (LPS) stimulated RAW 264.7 cells, a murine macrophage cell line, were inhibited significantly by the mushroom extracts in a concentration dependent manner. The anti-inflammatory activity on carrageenan-induced edema in the rat hind-paw reduced significantly by the mushroom extracts. Therefore, we have demonstrated that P. florida fruiting bodies possess antioxidant and anti-inflammatory activites related to their inhibitory activities on NO production, iNOS protein expression, and carrageenan-induced paw edema in rats. The results suggest that the fruiting bodies of P. florida are a good source of natural antioxidant and anti-inflammatory agents. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Intracellular Glutathione Depletion by Oridonin Leads to Apoptosis in Hepatic Stellate Cells
Molecules 2014, 19(3), 3327-3344; doi:10.3390/molecules19033327
Received: 17 February 2014 / Revised: 4 March 2014 / Accepted: 13 March 2014 / Published: 18 March 2014
Cited by 15 | PDF Full-text (1785 KB) | HTML Full-text | XML Full-text
Abstract
Proliferation of hepatic stellate cells (HSCs) plays a key role in the pathogenesis of liver fibrosis. Induction of HSC apoptosis by natural products is considered an effective strategy for treating liver fibrosis. Herein, the apoptotic effects of 7,20-epoxy-ent-kaurane (oridonin), a diterpenoid
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Proliferation of hepatic stellate cells (HSCs) plays a key role in the pathogenesis of liver fibrosis. Induction of HSC apoptosis by natural products is considered an effective strategy for treating liver fibrosis. Herein, the apoptotic effects of 7,20-epoxy-ent-kaurane (oridonin), a diterpenoid isolated from Rabdosia rubescens, and its underlying mechanisms were investigated in rat HSC cell line, HSC-T6. We found that oridonin inhibited cell viability of HSC-T6 in a concentration-dependent manner. Oridonin induced a reduction in mitochondrial membrane potential and increases in caspase 3 activation, subG1 phase, and DNA fragmentation. These apoptotic effects of oridonin were completely reversed by thiol antioxidants, N-acetylcysteine (NAC) and glutathione monoethyl ester. Moreover, oridonin increased production of reactive oxygen species (ROS), which was also inhibited by NAC. Significantly, oridonin reduced intracellular glutathione (GSH) level in a concentration- and time-dependent fashion. Additionally, oridonin induced phosphorylations of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK). NAC prevented the activation of MAPKs in oridonin-induced cells. However, selective inhibitors of MAPKs failed to alter oridonin-induced cell death. In summary, these results demonstrate that induction of apoptosis in HSC-T6 by oridonin is associated with a decrease in cellular GSH level and increase in ROS production. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Compounds from Dryopteris Fragrans (L.) Schott with Cytotoxic Activity
Molecules 2014, 19(3), 3345-3355; doi:10.3390/molecules19033345
Received: 7 February 2014 / Revised: 12 March 2014 / Accepted: 13 March 2014 / Published: 18 March 2014
Cited by 3 | PDF Full-text (409 KB) | HTML Full-text | XML Full-text
Abstract
One new coumarin, dryofracoumarin A (1), and eight known compounds 29 were isolated from Dryopteris fragrans (L.) Schott. Their structures were established on the basis of extensive spectroscopic data analyses and comparison with reported spectroscopic data. The new compound
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One new coumarin, dryofracoumarin A (1), and eight known compounds 29 were isolated from Dryopteris fragrans (L.) Schott. Their structures were established on the basis of extensive spectroscopic data analyses and comparison with reported spectroscopic data. The new compound 1 was determined to be 8-hydroxyl-4-isopropyl-7-methyl-6-methyl-2H-benzopyran-2-one. Two dimers, trans- and cis-3-(3,4-dimethoxyphen-yl)-4-[(E)-3,4-dimethoxystyryl]cyclohex-1-ene (compounds 8 and 9), were isolated from the Dryopteris genus for the first time. The other six were esculetin (2), isoscopoletin (3), methylphlorbutyrophenone (4), aspidinol (5), albicanol (6) and (E)-4-(3,4-dimethoxyphen-yl)but-3-en-1-ol (7). All compounds were evaluated for their cytotoxic effects by the MTT assay. Compounds 2, 3, 8 and 9 showed significantly cytotoxic effects against three cell lines (A549, MCF7 and HepG2), 1 and 5 against two cell lines (A549 and MCF7), and 6 against one cell line (MCF7). Their IC50 values ranged between 2.73 ± 0.86 μM and 24.14 ± 3.12 μM. These active compounds might be promising lead compounds for the treatment of cancer. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Nilotinib Enhances the Efficacy of Conventional Chemotherapeutic Drugs in CD34+CD38 Stem Cells and ABC Transporter Overexpressing Leukemia Cells
Molecules 2014, 19(3), 3356-3375; doi:10.3390/molecules19033356
Received: 21 October 2013 / Revised: 11 March 2014 / Accepted: 11 March 2014 / Published: 19 March 2014
Cited by 8 | PDF Full-text (1311 KB) | HTML Full-text | XML Full-text
Abstract
Incomplete chemotherapeutic eradication of leukemic CD34+CD38 stem cells is likely to result in disease relapse. The purpose of this study was to evaluate the effect of nilotinib on eradicating leukemia stem cells and enhancing the efficacy of chemotherapeutic agents. Our
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Incomplete chemotherapeutic eradication of leukemic CD34+CD38 stem cells is likely to result in disease relapse. The purpose of this study was to evaluate the effect of nilotinib on eradicating leukemia stem cells and enhancing the efficacy of chemotherapeutic agents. Our results showed that ABCB1 and ABCG2 were preferentially expressed in leukemic CD34+CD38 cells. Nilotinib significantly enhanced the cytotoxicity of doxorubicin and mitoxantrone in CD34+CD38 cells and led to increased apoptosis. Moreover, nilotinib strongly reversed multidrug resistance and increased the intracellular accumulation of rhodamine 123 in primary leukemic blasts overexpressing ABCB1 and/or ABCG2. Studies with ABC transporter-overexpressing carcinoma cell models confirmed that nilotinib effectively reversed ABCB1- and ABCG2-mediated drug resistance, while showed no significant reversal effect on ABCC1- and ABCC4-mediated drug resistance. Results from cytotoxicity assays showed that CD34+CD38 cells exhibited moderate resistance (2.41-fold) to nilotinib, compared with parental K562 cells. Furthermore, nilotinib was less effective in blocking the phosphorylation of Bcr-Abl and CrkL (a substrate of Bcr-Abl kinase) in CD34+CD38 cells. Taken together, these data suggest that nilotinib particularly targets CD34+CD38 stem cells and MDR leukemia cells, and effectively enhances the efficacy of chemotherapeutic drugs by blocking the efflux function of ABC transporters. Full article
Open AccessArticle Laccase Immobilized on a PAN/Adsorbents Composite Nanofibrous Membrane for Catechol Treatment by a Biocatalysis/Adsorption Process
Molecules 2014, 19(3), 3376-3388; doi:10.3390/molecules19033376
Received: 20 January 2014 / Revised: 6 March 2014 / Accepted: 6 March 2014 / Published: 19 March 2014
Cited by 12 | PDF Full-text (1930 KB) | HTML Full-text | XML Full-text
Abstract
The treatment of catechol via biocatalysis and adsorption with a commercial laccase immobilized on polyacrylonitrile/montmorillonite/graphene oxide (PAN/MMT/GO) composite nanofibers was evaluated with a homemade nanofibrous membrane reactor. The properties in this process of the immobilized laccase on PAN, PAN/MMT as well as PAN/MMT/GO
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The treatment of catechol via biocatalysis and adsorption with a commercial laccase immobilized on polyacrylonitrile/montmorillonite/graphene oxide (PAN/MMT/GO) composite nanofibers was evaluated with a homemade nanofibrous membrane reactor. The properties in this process of the immobilized laccase on PAN, PAN/MMT as well as PAN/MMT/GO with different weight ratios of MMT and GO were investigated. These membranes were successfully applied for removal of catechol from an aqueous solution. Scanning electron microscope images revealed different morphologies of the enzyme aggregates on different supports. After incorporation of MMT or MMT/GO, the optimum pH showed an alkaline shift to 4, compared to 3.5 for laccase immobilized on pure PAN nanofibers. The optimum temperature was at 55 °C for all the immobilized enzymes. Besides, the addition of GO improved the operational stability and storage stability. A 39% ± 2.23% chemical oxygen demand (COD) removal from the catechol aqueous solution was achieved. Experimental results suggested that laccase, PAN, adsorbent nanoparticles (MMT/GO) can be combined together for catechol treatment in industrial applications. Full article
(This article belongs to the Special Issue Enzyme Immobilization)
Open AccessArticle An Unusual 2,3-Secotaraxerene and Other Cytotoxic Triterpenoids from Pleiocarpa pycnantha (Apocynaceae) Leaves Collected from Nigeria
Molecules 2014, 19(3), 3389-3400; doi:10.3390/molecules19033389
Received: 18 January 2014 / Revised: 26 February 2014 / Accepted: 11 March 2014 / Published: 20 March 2014
Cited by 3 | PDF Full-text (670 KB) | HTML Full-text | XML Full-text
Abstract
Three known triterpenoids, namely ursolic acid (1), and the 27-E- and 27-Z-p-coumaric esters of ursolic acid (compounds 2, 3), were isolated together with a new triterpene 2,3-seco-taraxer-14-en-2,3-lactone [pycanocarpine (4)] from an ethanolic
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Three known triterpenoids, namely ursolic acid (1), and the 27-E- and 27-Z-p-coumaric esters of ursolic acid (compounds 2, 3), were isolated together with a new triterpene 2,3-seco-taraxer-14-en-2,3-lactone [pycanocarpine (4)] from an ethanolic extract of Pleiocarpa pycnantha leaves. The structure of 4 was unambiguously assigned using NMR, HREIMS and X-ray crystallography. The cytotoxic activities of the compounds were evaluated against HeLa, MCF-7, KMST-6 and HT-29 cells using the WST-1 assay. Ursolic acid (1) displayed potent cytotoxic activity against HeLa, HT-29 and MCF-7 cells with IC50 values of 10, 10 and 20 µM respectively. The new compound 4 and its hydrolysed derivative 5 were selectively cytotoxic to the breast cancer cell line, MCF-7 with IC50 values 20 and 10 µM respectively. This is the first report on isolation of a 2,3-seco-taraxerene derivative from the Apocynaceae family and cytotoxic activityof P. pycnantha constituents. Full article
Open AccessArticle Regioselective Electrophilic Aromatic Bromination: Theoretical Analysis and Experimental Verification
Molecules 2014, 19(3), 3401-3416; doi:10.3390/molecules19033401
Received: 24 February 2014 / Revised: 10 March 2014 / Accepted: 13 March 2014 / Published: 20 March 2014
Cited by 3 | PDF Full-text (352 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Electrophilic aromatic bromination is the most common synthetic method used to prepare aryl bromides, which are very useful intermediates in organic synthesis. To understand the experimental results in electrophilic aromatic brominations, ab initio calculations are used here for a tentative analysis of the
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Electrophilic aromatic bromination is the most common synthetic method used to prepare aryl bromides, which are very useful intermediates in organic synthesis. To understand the experimental results in electrophilic aromatic brominations, ab initio calculations are used here for a tentative analysis of the positional selectivity. The calculated results agree well with the corresponding experimental data, and the reliability of the resulting positional selectivity was verified by the corresponding experimental data. Full article
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Open AccessArticle Synthesis, Docking Study and β-Adrenoceptor Activity of Some New Oxime Ether Derivatives
Molecules 2014, 19(3), 3417-3435; doi:10.3390/molecules19033417
Received: 17 February 2014 / Revised: 5 March 2014 / Accepted: 11 March 2014 / Published: 20 March 2014
Cited by 3 | PDF Full-text (481 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new series of oxime ethers 4az was designed and synthesized to test the blocking activity against β1 and β2-adrenergic receptors. Docking of these ether derivatives into the active site of the identified 3D structures of β1 and β2-adrenergic receptors showed MolDock scores comparable
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A new series of oxime ethers 4az was designed and synthesized to test the blocking activity against β1 and β2-adrenergic receptors. Docking of these ether derivatives into the active site of the identified 3D structures of β1 and β2-adrenergic receptors showed MolDock scores comparable to those of reference compounds. Biological results revealed that the inhibition effects on the heart rate and contractility are less than those of propranolol. Nevertheless, the two compounds 4p and 4q that displayed the highest negative MolDock score with β2-adrenergic receptors showed β2-antagonistic activity by decreasing salbutamol relaxation of precontracted tracheal strips, which indicates the importance of a chlorothiophene moiety in the hydrophobic region for best complementarity with β2 receptors. On other hand, the presence of a homoveratryl moiety increases the MolDock score of the tested compounds with the β1 receptor. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synthesis of New 2,5-Di-substituted 1,3,4-Oxadiazoles Bearing 2,6-Di-tert-butylphenol Moieties and Evaluation of Their Antioxidant Activity
Molecules 2014, 19(3), 3436-3449; doi:10.3390/molecules19033436
Received: 7 February 2014 / Revised: 11 March 2014 / Accepted: 12 March 2014 / Published: 20 March 2014
Cited by 6 | PDF Full-text (469 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Eleven new 2,6-di-tert-butyl-4-(5-aryl-1,3,4-oxadiazol-2-yl)phenols 5ak were synthesized by reacting aryl hydrazides with 3,5-di-tert butyl 4-hydroxybenzoic acid in the presence of phosphorus oxychloride. The resulting compounds were characterized based on their IR, 1H-NMR, 13C-NMR, and HRMS data. 2,2-Diphenyl-1-picrylhydrazide
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Eleven new 2,6-di-tert-butyl-4-(5-aryl-1,3,4-oxadiazol-2-yl)phenols 5ak were synthesized by reacting aryl hydrazides with 3,5-di-tert butyl 4-hydroxybenzoic acid in the presence of phosphorus oxychloride. The resulting compounds were characterized based on their IR, 1H-NMR, 13C-NMR, and HRMS data. 2,2-Diphenyl-1-picrylhydrazide (DPPH) and ferric reducing antioxidant power (FRAP) assays were used to test the antioxidant properties of the compounds. Compounds 5f and 5j exhibited significant free-radical scavenging ability in both assays. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Authentication of Bulbus Fritillariae Cirrhosae by RAPD-Derived DNA Markers
Molecules 2014, 19(3), 3450-3459; doi:10.3390/molecules19033450
Received: 17 January 2014 / Revised: 14 March 2014 / Accepted: 17 March 2014 / Published: 20 March 2014
Cited by 10 | PDF Full-text (571 KB) | HTML Full-text | XML Full-text
Abstract
Bulbus Fritillariae is the most commonly used antitussive herb in China. Eleven species of Fritillaria are recorded as Bulbus Fritillariae in the Chinese Pharmacopoeia. Bulbus Fritillariae Cirrhosae is a group of six Fritillaria species with higher efficiency and lower toxicity derived mainly from
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Bulbus Fritillariae is the most commonly used antitussive herb in China. Eleven species of Fritillaria are recorded as Bulbus Fritillariae in the Chinese Pharmacopoeia. Bulbus Fritillariae Cirrhosae is a group of six Fritillaria species with higher efficiency and lower toxicity derived mainly from wild sources. Because of their higher market price, five other Fritillaria species are often sold deceptively as Bulbus Fritillariae Cirrhosae in the herbal market. To ensure the efficacy and safety of medicinal herbs, the authentication of botanical resources is the first step in quality control. Here, a DNA based identification method was developed to authenticate the commercial sources of Bulbus Fritillariae Cirrhosae. A putative DNA marker (0.65 kb) specific for Bulbus Fritillariae Cirrhosae was identified using the Random Amplified Polymorphic DNA (RAPD) technique. A DNA marker representing a Sequence Characterized Amplified Region (SCAR) was developed from a RAPD amplicon. The SCAR marker was successfully applied to differentiate Bulbus Fritillariae Cirrhosae from different species of Fritillaria. Additionally, the SCAR marker was also useful in identifying the commercial samples of Bulbus Fritillariae Cirrhosae. Our results indicated that the RAPD-SCAR method was rapid, accurate and applicable in identifying Bulbus Fritillariae Cirrhosae at the DNA level. Full article
(This article belongs to the Special Issue Phytochemicals: Analytical and Medicinal Chemistry)
Open AccessArticle Metabonomic Analysis of Water Extracts from Different Angelica Roots by 1H-Nuclear Magnetic Resonance Spectroscopy
Molecules 2014, 19(3), 3460-3470; doi:10.3390/molecules19033460
Received: 20 December 2013 / Revised: 25 February 2014 / Accepted: 13 March 2014 / Published: 20 March 2014
Cited by 4 | PDF Full-text (1538 KB) | HTML Full-text | XML Full-text
Abstract
Angelica Radix, the roots of the genus Angelica, has been used for more than 2,000 years as a traditional medicine in Eastern Asia. The Chinese Pharmacopoeia records more than 100 herbal formulae containing Angelica roots. There are two common sources of Angelica
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Angelica Radix, the roots of the genus Angelica, has been used for more than 2,000 years as a traditional medicine in Eastern Asia. The Chinese Pharmacopoeia records more than 100 herbal formulae containing Angelica roots. There are two common sources of Angelica roots, Angelica sinensis from China and A. gigas from Korea. The two species of Angelica roots differ in their chemical compositions, pharmacological properties and clinical efficacy. 1H-NMR metabolic profiling has recently emerged as a promising quality control method for food and herbal chemistry. We explored the use of 1H-NMR metabolic profiling for the quality control of Angelica Radix. Unlike previous work, we performed the metabolic profiling on hot water extracts, so as to mimic the clinically relevant preparation method. Unsupervised principle component analyses of both the full spectral profile and a selection of targeted molecules revealed a clear differentiation of three types of Angelica roots. In addition, the levels of 13 common metabolites were measured. Statistically significant differences in the levels of glucose, fructose and threonine were found between different sources of Angelica. Ferulic acid, a marker commonly used to evaluate Angelica root, was detected in our samples, but the difference in ferulic acid levels between the samples was not statistically significant. Overall, we successfully applied 1H-NMR metabolic profiling with water extraction to discriminate all three sources of Angelica roots, and obtained quantitative information of many common metabolites. Full article
(This article belongs to the Special Issue Phytochemicals: Analytical and Medicinal Chemistry)
Open AccessArticle Inhibition of GlcNAc-Processing Glycosidases by C-6-Azido-NAG-Thiazoline and Its Derivatives
Molecules 2014, 19(3), 3471-3488; doi:10.3390/molecules19033471
Received: 4 February 2014 / Revised: 6 March 2014 / Accepted: 13 March 2014 / Published: 20 March 2014
Cited by 4 | PDF Full-text (1057 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
NAG-thiazoline is a strong competitive inhibitor of GH20 β-N-acetyl- hexosaminidases and GH84 β-N-acetylglucosaminidases. Here, we focused on the design, synthesis and inhibition potency of a series of new derivatives of NAG-thiazoline modified at the C-6 position. Dimerization of NAG-thiazoline
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NAG-thiazoline is a strong competitive inhibitor of GH20 β-N-acetyl- hexosaminidases and GH84 β-N-acetylglucosaminidases. Here, we focused on the design, synthesis and inhibition potency of a series of new derivatives of NAG-thiazoline modified at the C-6 position. Dimerization of NAG-thiazoline via C-6 attached triazole linkers prepared by click chemistry was employed to make use of multivalency in the inhibition. Novel compounds were tested as potential inhibitors of β-N-acetylhexosaminidases from Talaromyces flavus, Streptomyces plicatus (both GH20) and β-N-acetylglucosaminidases from Bacteroides thetaiotaomicron and humans (both GH84). From the set of newly prepared NAG-thiazoline derivatives, only C-6-azido-NAG-thiazoline displayed inhibition activity towards these enzymes; C-6 triazole-substituted NAG-thiazolines lacked inhibition activity against the enzymes used. Docking of C-6-azido-NAG-thiazoline into the active site of the tested enzymes was performed. Moreover, a stability study with GlcNAc-thiazoline confirmed its decomposition at pH < 6 yielding 2-acetamido-2-deoxy-1-thio-α/β-D-glucopyranoses, which presumably dimerize oxidatively into S-S linked dimers; decomposition products of NAG-thiazoline are void of inhibitory activity. Full article
Open AccessArticle Antioxidant Activity of Hispidin Oligomers from Medicinal Fungi: A DFT Study
Molecules 2014, 19(3), 3489-3507; doi:10.3390/molecules19033489
Received: 30 January 2014 / Revised: 17 March 2014 / Accepted: 17 March 2014 / Published: 21 March 2014
Cited by 6 | PDF Full-text (853 KB) | HTML Full-text | XML Full-text
Abstract
Hispidin oligomers are styrylpyrone pigments isolated from the medicinal fungi Inonotus xeranticus and Phellinus linteus. They exhibit diverse biological activities and strong free radical scavenging activity. To rationalize the antioxidant activity of a series of four hispidin oligomers and determine the favored
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Hispidin oligomers are styrylpyrone pigments isolated from the medicinal fungi Inonotus xeranticus and Phellinus linteus. They exhibit diverse biological activities and strong free radical scavenging activity. To rationalize the antioxidant activity of a series of four hispidin oligomers and determine the favored mechanism involved in free radical scavenging, DFT calculations were carried out at the B3P86/6-31+G (d, p) level of theory in gas and solvent. The results showed that bond dissociation enthalpies of OH groups of hispidin oligomers (ArOH) and spin density delocalization of related radicals (ArO) are the appropriate parameters to clarify the differences between the observed antioxidant activities for the four oligomers. The effect of the number of hydroxyl groups and presence of a catechol moiety conjugated to a double bond on the antioxidant activity were determined. Thermodynamic and kinetic studies showed that the PC-ET mechanism is the main mechanism involved in free radical scavenging. The spin density distribution over phenoxyl radicals allows a better understanding of the hispidin oligomers formation. Full article
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Open AccessArticle Celastrol Induces Apoptosis in Gefitinib-Resistant Non-Small Cell Lung Cancer Cells via Caspases-Dependent Pathways and Hsp90 Client Protein Degradation
Molecules 2014, 19(3), 3508-3522; doi:10.3390/molecules19033508
Received: 9 January 2014 / Revised: 26 February 2014 / Accepted: 12 March 2014 / Published: 21 March 2014
Cited by 11 | PDF Full-text (4835 KB) | HTML Full-text | XML Full-text
Abstract
Celastrol, a triterpene extracted from the Chinese herb Tripterygium wilfordii, has been shown to have multiple bioactivities. Although among these activities, its anti-cancer effects have attracted the most attention, the effect of celastrol on gefitinib-resistant non-small cell lung cancer (NSCLC) cells is
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Celastrol, a triterpene extracted from the Chinese herb Tripterygium wilfordii, has been shown to have multiple bioactivities. Although among these activities, its anti-cancer effects have attracted the most attention, the effect of celastrol on gefitinib-resistant non-small cell lung cancer (NSCLC) cells is not clearly known. Here, we examined the potency of celastrol in three different NSCLC cell lines. We explored its treatment mechanism in two gefitinib-resistant NSCLC cell lines (H1650 and H1975). Our data demonstrated that celastrol exerted its apoptotic effect in a dose- and time-dependent manner. Also, the mitochondria membrane potential was gradually lost and the ratio of Bax/Bcl-2 increased after the treatment of celastrol, both of which are indicators of mitochondria membrane integrity. Although the caspases were activated, the treatment with pan-caspase inhibitor could partially inhibit the level of apoptosis. Moreover, the protein level of Hsp90 client proteins, EGFR and AKT, was measured. Interestingly, both client proteins were remarkably down-regulated after the treatment of celastrol. Taken together, our data showed that celastrol may be developed as a promising agent for treating gefitinib-resistant NSCLCs by inducing apoptosis through caspase-dependent pathways and Hsp90 client protein degradation. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Structure-Activity Relationship Study of Sesquiterpene Lactones and Their Semi-Synthetic Amino Derivatives as Potential Antitrypanosomal Products
Molecules 2014, 19(3), 3523-3538; doi:10.3390/molecules19033523
Received: 12 November 2013 / Revised: 13 March 2014 / Accepted: 13 March 2014 / Published: 21 March 2014
Cited by 6 | PDF Full-text (294 KB) | HTML Full-text | XML Full-text
Abstract
Sesquiterpene lactones (STLs) are natural products that have potent antitrypanosomal activity in vitro and, in the case of cynaropicrin, also reduce parasitemia in the murine model of trypanosomiasis. To explore their structure-antitrypanosomal activity relationships, a set of 34 natural and semi-synthetic STLs and
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Sesquiterpene lactones (STLs) are natural products that have potent antitrypanosomal activity in vitro and, in the case of cynaropicrin, also reduce parasitemia in the murine model of trypanosomiasis. To explore their structure-antitrypanosomal activity relationships, a set of 34 natural and semi-synthetic STLs and amino-STLs was tested in vitro against T. b. rhodesiense (which causes East African sleeping sickness) and mammalian cancer cells (rat bone myoblast L6 cells). It was found that the α-methylene-γ-lactone moiety is necessary for both antitrypanosomal effects and cytotoxicity. Antitrypanosomal selectivity is facilitated by 2-(hydroxymethyl)acrylate or 3,4-dihydroxy-2-methylenebutylate side chains, and by the presence of cyclopentenone rings. Semi-synthetic STL amines with morpholino and dimethylamino groups showed improved in vitro activity over the native STLs. The dimethylamino derivative of cynaropicrin was prepared and tested orally in the T. b. rhodesiense acute mouse model, where it showed reduced toxicity over cynaropicrin, but also lost antitrypanosomal activity. Full article
Open AccessArticle Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists
Molecules 2014, 19(3), 3539-3551; doi:10.3390/molecules19033539
Received: 26 January 2014 / Revised: 17 March 2014 / Accepted: 18 March 2014 / Published: 21 March 2014
Cited by 1 | PDF Full-text (274 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The design, synthesis and structure-activity relationship studies of some novel trisubstituted pyrimidine amide derivatives prepared as CCR4 antagonists are described. The activities of these compounds were evaluated by the CCR4-MDC chemotaxis inhibition assay. Compound 1, which we have previously reported as a
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The design, synthesis and structure-activity relationship studies of some novel trisubstituted pyrimidine amide derivatives prepared as CCR4 antagonists are described. The activities of these compounds were evaluated by the CCR4-MDC chemotaxis inhibition assay. Compound 1, which we have previously reported as a potent antagonist of CCR4, was employed as the positive control. The results indicated that most of the synthesized compounds exhibited some chemotaxis inhibition activity against CCR4. Of these new compounds, compounds 6c, 12a and 12b, with IC50 values of 0.064, 0.077 and 0.069 μM, respectively, showed higher or similar activity compared with compound 1 (IC50 of 0.078 μM). These compounds provide a basis for further structural modifications. The systematic structure-activity relationship of these trisubstituted pyrimidine amide derivatives was discussed based on the obtained experimental data. The results from the SAR study may be useful for identifying more potent CCR4 antagonists. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Protein-Rich Fraction of Cnidoscolus urens (L.) Arthur Leaves: Enzymatic Characterization and Procoagulant and Fibrinogenolytic Activities
Molecules 2014, 19(3), 3552-3569; doi:10.3390/molecules19033552
Received: 20 December 2013 / Revised: 13 March 2014 / Accepted: 14 March 2014 / Published: 21 March 2014
Cited by 2 | PDF Full-text (808 KB) | HTML Full-text | XML Full-text
Abstract
Proteolytic enzymes are important macromolecules in the regulation of biochemical processes in living organisms. Additionally, these versatile biomolecules have numerous applications in the industrial segment. In this study we have characterized a protein-rich fraction of Cnidoscolus urens (L.) Arthur leaves, rich in proteolytic
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Proteolytic enzymes are important macromolecules in the regulation of biochemical processes in living organisms. Additionally, these versatile biomolecules have numerous applications in the industrial segment. In this study we have characterized a protein-rich fraction of Cnidoscolus urens (L.) Arthur leaves, rich in proteolytic enzymes, and evaluated its effects on the coagulation cascade. Three protein-rich fractions were obtained from the crude extract of C. urens leaves by precipitation with acetone. Fraction F1.0 showed higher proteolytic activity upon azocasein, and thus, was chosen for subsequent tests. The proteolytic activity of F1.0 on fibrinogen was dose-dependent and time-dependent. The extract demonstrated procoagulant activity on citrated plasma and reduced the APTT, not exerting effects on PT. Despite the fibrin(ogen)olytic activity, F1.0 showed no defibrinogenating activity in vivo. The fraction F1.0 did not express hemorrhagic nor hemolytic activities. The proteolytic activity was inhibited by E-64, EDTA and in the presence of metal ions, and increased when pretreated with reducing agents, suggesting that the observed activity was mostly due to cysteine proteases. Several bands with proteolytic activity were detected by zymography with gelatin, albumin and fibrinogen. The optimal enzymatic activity was observed in temperature of 60 °C and pH 5.0, demonstrating the presence of acidic proteases. In conclusion, these results could provide basis for the pharmacological application of C. urens proteases as a new source of bioactive molecules to treat bleeding and thrombotic disorders. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Properties of a Lacquer Wax-Based Quarternary Ammonium Gemini Surfactant
Molecules 2014, 19(3), 3596-3606; doi:10.3390/molecules19033596
Received: 4 November 2013 / Revised: 11 March 2014 / Accepted: 14 March 2014 / Published: 24 March 2014
Cited by 1 | PDF Full-text (265 KB) | HTML Full-text | XML Full-text
Abstract
Lacquer wax is an important fatty resource obtained from the mesocarp of the berries of Toxicodendron vernicifluum. In order to expand the applications of lacquer wax, we hydrolyzed it after establishing the best conditions for the acid-catalyzed hydrolysis using a Box-Behnken design.
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Lacquer wax is an important fatty resource obtained from the mesocarp of the berries of Toxicodendron vernicifluum. In order to expand the applications of lacquer wax, we hydrolyzed it after establishing the best conditions for the acid-catalyzed hydrolysis using a Box-Behnken design. Then we synthesized a quarternary ammonium gemini surfactant by a three-step reaction. The surface properties of an aqueous solution of the final product were investigated. The optimum conditions were 9% catalyst, 100 °C of reaction temperature and 14 h of reaction time, while the maximum free fatty acids (FFA)% was 99.67%. From the gas chromatography, the main fatty acids of the lacquer wax were palmitic, oleic and octadecanoic acid. The lacquer wax gemini surfactant was synthesized, and its structure was confirmed by IR and NMR. The experiments showed that the critical micelle concentration (CMC) is 5 × 10−4 mol·L−1, the surface tension is 33.6 mN·m−1. When the content of surfactant was 0.1%, the separation time of 5 mL water was 10 min. Full article
Open AccessArticle Antimicrobial Activities against Periodontopathic Bacteria of Pittosporum tobira and Its Active Compound
Molecules 2014, 19(3), 3607-3616; doi:10.3390/molecules19033607
Received: 23 December 2013 / Revised: 18 March 2014 / Accepted: 18 March 2014 / Published: 24 March 2014
Cited by 4 | PDF Full-text (525 KB) | HTML Full-text | XML Full-text
Abstract
The study of medicinal plants for treatment of periodontitis is of great value to establish their efficacy as sources of new antimicrobial drugs. Five hundred and fifty eight Korean local plant extracts were screened for antibacterial activity against representative periodontopathic bacteria such as
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The study of medicinal plants for treatment of periodontitis is of great value to establish their efficacy as sources of new antimicrobial drugs. Five hundred and fifty eight Korean local plant extracts were screened for antibacterial activity against representative periodontopathic bacteria such as Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum. Among the various medicinal plants, the alcohol extract of Pittosporum tobira, which significantly exhibited antibacterial effect for all tested strains, showed the highest activity in the antimicrobial assays. NMR analyses revealed that R1-barrigenol, a triterpene sapogenin, was the most effective compound in P. tobira. These results demonstrated that P. tobira possesses antimicrobial properties and would be beneficial for the prevention and treatment of periodontitis. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Trigocherrierin A, a Potent Inhibitor of Chikungunya Virus Replication
Molecules 2014, 19(3), 3617-3627; doi:10.3390/molecules19033617
Received: 21 February 2014 / Revised: 12 March 2014 / Accepted: 17 March 2014 / Published: 24 March 2014
Cited by 14 | PDF Full-text (454 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Trigocherrierin A (1) and trigocherriolide E (2), two new daphnane diterpenoid orthoesters (DDOs), and six chlorinated analogues, trigocherrins A, B, F and trigocherriolides A–C, were isolated from the leaves of Trigonostemon cherrieri. Their structures were identified by mass
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Trigocherrierin A (1) and trigocherriolide E (2), two new daphnane diterpenoid orthoesters (DDOs), and six chlorinated analogues, trigocherrins A, B, F and trigocherriolides A–C, were isolated from the leaves of Trigonostemon cherrieri. Their structures were identified by mass spectrometry, extensive one- and two-dimensional NMR spectroscopy and through comparison with data reported in the literature. These compounds are potent and selective inhibitors of chikungunya virus (CHIKV) replication. Among the DDOs isolated, compound 1 exhibited the strongest anti-CHIKV activity (EC50 = 0.6 ± 0.1 µM, SI = 71.7). Full article
(This article belongs to the Section Natural Products)
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Open AccessCommunication Entrapment of Probiotics in Water Extractable Arabinoxylan Gels: Rheological and Microstructural Characterization
Molecules 2014, 19(3), 3628-3637; doi:10.3390/molecules19033628
Received: 16 January 2014 / Revised: 13 March 2014 / Accepted: 14 March 2014 / Published: 24 March 2014
Cited by 3 | PDF Full-text (870 KB) | HTML Full-text | XML Full-text
Abstract
Due to their porous structure, aqueous environment and dietary fiber nature arabinoxylan (AX) gels could have potential applications for colon-specific therapeutic molecule delivery. In addition, prebiotic and health related effects of AX have been previously demonstrated. It has been also reported that cross-linked
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Due to their porous structure, aqueous environment and dietary fiber nature arabinoxylan (AX) gels could have potential applications for colon-specific therapeutic molecule delivery. In addition, prebiotic and health related effects of AX have been previously demonstrated. It has been also reported that cross-linked AX can be degraded by bacteria from the intestinal microbiota. However, AX gels have not been abundantly studied as carrier systems and there is no information available concerning their capability to entrap cells. In this regard, probiotic bacteria such as Bifidobacterium longum have been the focus of intense research activity lately. The objective of this research was to investigate the entrapment of probiotic B. longum in AX gels. AX solution at 2% (w/v) containing B. longum (1 × 107 CFU/cm) formed gels induced by laccase as cross-linking agent. The entrapment of B. longum decreased gel elasticity from 31 to 23 Pa, probably by affecting the physical interactions taking place between WEAX chains. Images of AX gels containing B. longum viewed under a scanning electron microscope show the gel network with the bacterial cells entrapped inside. The microstructure of these gels resembles that of an imperfect honeycomb. The results suggest that AX gels can be potential candidates for the entrapment of probiotics. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of New 1,2,3-Triazol-4-yl-quinazoline Nucleoside and Acyclonucleoside Analogues
Molecules 2014, 19(3), 3638-3653; doi:10.3390/molecules19033638
Received: 13 January 2014 / Revised: 6 March 2014 / Accepted: 17 March 2014 / Published: 24 March 2014
Cited by 4 | PDF Full-text (565 KB) | HTML Full-text | XML Full-text
Abstract
In this study, we describe the synthesis of 1,4-disustituted-1,2,3-triazolo-quinazoline ribonucleosides or acyclonucleosides by means of 1,3-dipolar cycloaddition between various O or N-alkylated propargyl-quinazoline and 1'-azido-2',3',5'-tri-O-benzoylribose or activated alkylating agents under microwave conditions. None of the compounds selected showed significant anti-HCV
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In this study, we describe the synthesis of 1,4-disustituted-1,2,3-triazolo-quinazoline ribonucleosides or acyclonucleosides by means of 1,3-dipolar cycloaddition between various O or N-alkylated propargyl-quinazoline and 1'-azido-2',3',5'-tri-O-benzoylribose or activated alkylating agents under microwave conditions. None of the compounds selected showed significant anti-HCV activity in vitro. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Artichoke, Cynarin and Cyanidin Downregulate the Expression of Inducible Nitric Oxide Synthase in Human Coronary Smooth Muscle Cells
Molecules 2014, 19(3), 3654-3668; doi:10.3390/molecules19033654
Received: 13 January 2014 / Revised: 17 March 2014 / Accepted: 18 March 2014 / Published: 24 March 2014
Cited by 2 | PDF Full-text (439 KB) | HTML Full-text | XML Full-text
Abstract
Artichoke (Cynara scolymus L.) is one of the world’s oldest medicinal plants with multiple health benefits. We have previously shown that artichoke leaf extracts and artichoke flavonoids upregulate the gene expression of endothelial-type nitric oxide synthase (eNOS) in human endothelial cells. Whereas
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Artichoke (Cynara scolymus L.) is one of the world’s oldest medicinal plants with multiple health benefits. We have previously shown that artichoke leaf extracts and artichoke flavonoids upregulate the gene expression of endothelial-type nitric oxide synthase (eNOS) in human endothelial cells. Whereas NO produced by the eNOS is a vasoprotective molecule, NO derived from the inducible iNOS plays a pro-inflammatory role in the vasculature. The present study was aimed to investigate the effects of artichoke on iNOS expression in human coronary artery smooth muscle cells (HCASMC). Incubation of HCASMC with a cytokine mixture led to an induction of iNOS mRNA expression. This iNOS induction was concentration- and time-dependently inhibited by an artichoke leaf extract (1–100 µg/mL, 6 h or 24 h). Consistently, the artichoke leaf extract also reduced cytokine-induced iNOS promoter activation and iNOS protein expression. In addition, treatment of HCASMC with four well-known artichoke compounds (cynarin > cyanidin > luteolin ≈ cynaroside) led to a downregulation iNOS mRNA and protein expression, with cynarin being the most potent one. In conclusion, artichoke contains both eNOS-upregulating and iNOS-downregulating compounds. Such compounds may contribute to the beneficial effects of artichoke and may per se have therapeutic potentials. Full article
(This article belongs to the Special Issue Biosynthesis and Biotransformation)
Open AccessArticle Additional New Minor Cucurbitane Glycosides from Siraitia grosvenorii
Molecules 2014, 19(3), 3669-3680; doi:10.3390/molecules19033669
Received: 25 February 2014 / Revised: 14 March 2014 / Accepted: 17 March 2014 / Published: 24 March 2014
Cited by 4 | PDF Full-text (251 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Continuous phytochemical studies of the crude extract of Luo Han Guo (Siraitia grosvenorii) furnished three additional new cucurbitane triterpene glycosides, namely 11-deoxymogroside V, 11-deoxyisomogroside V, and 11-deoxymogroside VI. The structures of all the isolated compounds were characterized on the basis of
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Continuous phytochemical studies of the crude extract of Luo Han Guo (Siraitia grosvenorii) furnished three additional new cucurbitane triterpene glycosides, namely 11-deoxymogroside V, 11-deoxyisomogroside V, and 11-deoxymogroside VI. The structures of all the isolated compounds were characterized on the basis of extensive NMR and mass spectral data as well as hydrolysis studies. The complete 1H- and 13C-NMR spectral assignments of the three unknown compounds are reported for the first time based on COSY, TOCSY, HSQC, and HMBC spectroscopic data. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Rooibos Flavonoids Inhibit the Activity of Key Adrenal Steroidogenic Enzymes, Modulating Steroid Hormone Levels in H295R Cells
Molecules 2014, 19(3), 3681-3695; doi:10.3390/molecules19033681
Received: 15 January 2014 / Revised: 15 March 2014 / Accepted: 19 March 2014 / Published: 24 March 2014
Cited by 4 | PDF Full-text (826 KB) | HTML Full-text | XML Full-text
Abstract
Major rooibos flavonoids—dihydrochalcones, aspalathin and nothofagin, flavones—orientin and vitexin, and a flavonol, rutin, were investigated to determine their influence on the activity of adrenal steroidogenic enzymes, 3β-hydroxysteroid dehydrogenase (3βHSD2) and cytochrome P450 (P450) enzymes, P450 17α-hydroxylase/17,20-lyase (CYP17A1), P450 21-hydroxylase (CYP21A2) and P450 11β-hydroxylase
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Major rooibos flavonoids—dihydrochalcones, aspalathin and nothofagin, flavones—orientin and vitexin, and a flavonol, rutin, were investigated to determine their influence on the activity of adrenal steroidogenic enzymes, 3β-hydroxysteroid dehydrogenase (3βHSD2) and cytochrome P450 (P450) enzymes, P450 17α-hydroxylase/17,20-lyase (CYP17A1), P450 21-hydroxylase (CYP21A2) and P450 11β-hydroxylase (CYP11B1). All the flavonoids inhibited 3βHSD2 and CYP17A1 significantly, while the inhibition of downstream enzymes, CYP21A2 and CYP11B1, was both substrate and flavonoid specific. The dihydrochalcones inhibited the activity of CYP21A2, but not that of CYP11B1. Although rutin, orientin and vitexin inhibited deoxycortisol conversion by CYP11B1 significantly, inhibition of deoxycorticosterone was <20%. These three flavonoids were unable to inhibit CYP21A2, with negligible inhibition of deoxycortisol biosynthesis only. Rooibos inhibited substrate conversion by CYP17A1 and CYP21A2, while the inhibition of other enzyme activities was <20%. In H295R cells, rutin had the greatest inhibitory effect on steroid production upon forskolin stimulation, reducing total steroid output 2.3-fold, while no effect was detected under basal conditions. Nothofagin and vitexin had a greater inhibitory effect on overall steroid production compared to aspalathin and orientin, respectively. The latter compounds contain two hydroxyl groups on the B ring, while nothofagin and vitexin contain a single hydroxyl group. In addition, all of the flavonoids are glycosylated, albeit at different positions—dihydrochalcones at C3' and flavones at C8 on ring A, while rutin, a larger molecule, has a rutinosyl moiety at C3 on ring C. Structural differences regarding the number and position of hydroxyl and glucose moieties as well as structural flexibility could indicate different mechanisms by which these flavonoids influence the activity of adrenal steroidogenic enzymes. Full article
(This article belongs to the Special Issue Structure-Activity Relationship of Flavonoids)
Open AccessArticle Antiadhesive Properties of Arabinogalactan Protein from Ribes nigrum Seeds against Bacterial Adhesion of Helicobacter pylori
Molecules 2014, 19(3), 3696-3717; doi:10.3390/molecules19033696
Received: 4 February 2014 / Revised: 7 March 2014 / Accepted: 15 March 2014 / Published: 24 March 2014
Cited by 7 | PDF Full-text (1425 KB) | HTML Full-text | XML Full-text
Abstract
Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized
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Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. Bacterial adhesins affected were identified by overlay assay with immobilized ligands. 125I-radiolabeled F2 served for binding studies to H. pylori and interaction experiments with BabA and SabA. F2 had no cytotoxic effects against H. pylori and AGS cells; but inhibited bacterial binding to human gastric cells. F2 inhibited the binding of BabA and fibronectin-binding adhesin to its specific ligands. Radiolabeled F2 bound non-specifically to different strains of H. pylori; and to BabA deficient mutant. F2 did not lead to subsequent feedback regulation or increased expression of adhesins or virulence factors. From these data the non-specific interactions between F2 and the H. pylori lead to moderate antiadhesive effects. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Discrimination of Dendrobium officinale and Its Common Adulterants by Combination of Normal Light and Fluorescence Microscopy
Molecules 2014, 19(3), 3718-3730; doi:10.3390/molecules19033718
Received: 16 January 2014 / Revised: 13 March 2014 / Accepted: 14 March 2014 / Published: 24 March 2014
Cited by 1 | PDF Full-text (3985 KB) | HTML Full-text | XML Full-text
Abstract
The stems of Dendrobium officinale Kimura et Migo, named Tie-pi-shi-hu, is one of the most endangered and precious species in China. Because of its various pharmacodynamic effects, D. officinale is widely recognized as a high-quality health food in China and other countries
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The stems of Dendrobium officinale Kimura et Migo, named Tie-pi-shi-hu, is one of the most endangered and precious species in China. Because of its various pharmacodynamic effects, D. officinale is widely recognized as a high-quality health food in China and other countries in south and south-east Asia. With the rising interest of D. officinale, its products have a high price due to a limited supply. This high price has led to the proliferation of adulterants in the market. To ensure the safe use of D. officinale, a fast and convenient method combining normal and fluorescence microscopy was applied in the present study to distinguish D. officinale from three commonly used adulterants including Zi-pi-shi-hu (D. devonianum), Shui-cao-shi-hu (D. aphyllum), Guang-jie-shi-hu (D. gratiosissimum). The result demonstrated that D. officinale could be identified by the characteristic “two hat-shaped” vascular bundle sheath observed under the fluorescence microscopy and the distribution of raphides under normal light microscopy. The other three adulterants could be discriminated by the vascular bundle differences and the distribution of raphides under normal light microscopy. This work indicated that combination of normal light and fluorescence microscopy is a fast and efficient technique to scientifically distinguish D. officinale from the commonly confused species. Full article
Open AccessArticle Microencapsulation of Purified Amylase Enzyme from Pitaya (Hylocereus polyrhizus) Peel in Arabic Gum-Chitosan using Freeze Drying
Molecules 2014, 19(3), 3731-3743; doi:10.3390/molecules19033731
Received: 15 January 2014 / Revised: 10 March 2014 / Accepted: 11 March 2014 / Published: 24 March 2014
Cited by 5 | PDF Full-text (425 KB) | HTML Full-text | XML Full-text
Abstract
Amylase is one of the most important enzymes in the world due to its wide application in various industries and biotechnological processes. In this study, amylase enzyme from Hylocereus polyrhizus was encapsulated for the first time in an Arabic gum-chitosan matrix using freeze
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Amylase is one of the most important enzymes in the world due to its wide application in various industries and biotechnological processes. In this study, amylase enzyme from Hylocereus polyrhizus was encapsulated for the first time in an Arabic gum-chitosan matrix using freeze drying. The encapsulated amylase retained complete biocatalytic activity and exhibited a shift in the optimum temperature and considerable increase in the pH and temperature stabilities compared to the free enzyme. Encapsulation of the enzyme protected the activity in the presence of ionic and non-ionic surfactants and oxidizing agents (H2O2) and enhanced the shelf life. The storage stability of amylase is found to markedly increase after immobilization and the freeze dried amylase exhibited maximum encapsulation efficiency value (96.2%) after the encapsulation process. Therefore, the present study demonstrated that the encapsulation of the enzyme in a coating agent using freeze drying is an efficient method to keep the enzyme active and stable until required in industry. Full article
Open AccessArticle Atomic Model and Micelle Dynamics of QS-21 Saponin
Molecules 2014, 19(3), 3744-3760; doi:10.3390/molecules19033744
Received: 27 January 2014 / Revised: 28 February 2014 / Accepted: 5 March 2014 / Published: 24 March 2014
Cited by 2 | PDF Full-text (2340 KB) | HTML Full-text | XML Full-text
Abstract
QS-21 is a saponin extracted from Quillaja saponaria, widely investigated as a vaccine immunoadjuvant. However, QS-21 use is mainly limited by its chemical instability, significant variety in molecular composition and low tolerance dose in mammals. Also, this compound tends to form micelles
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QS-21 is a saponin extracted from Quillaja saponaria, widely investigated as a vaccine immunoadjuvant. However, QS-21 use is mainly limited by its chemical instability, significant variety in molecular composition and low tolerance dose in mammals. Also, this compound tends to form micelles in a concentration-dependent manner. Here, we aimed to characterize its conformation and the process of micelle formation, both experimentally and computationally. Therefore, molecular dynamics (MD) simulations were performed in systems containing different numbers of QS-21 molecules in aqueous solution, in order to evaluate the spontaneous micelle formation. The applied methodology allowed the generation of micelles whose sizes were shown to be in high agreement with small-angle X-ray scattering (SAXS). Furthermore, the ester linkage between fucose and acyl chain was less solvated in the micellar form, suggesting a reduction in hydrolysis. This is the first atomistic interpretation of previous experimental data, the first micellar characterization of saponin micelles by SAXS and first tridimensional model of a micelle constituted of saponins, contributing to the understanding of the molecular basis of these compounds. Full article
(This article belongs to the Special Issue Oligosaccharides and Glyco-Conjugates)
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Open AccessArticle Synthesis and Biological Activity of Some Bile Acid-Based Camptothecin Analogues
Molecules 2014, 19(3), 3761-3776; doi:10.3390/molecules19033761
Received: 16 January 2014 / Revised: 17 March 2014 / Accepted: 18 March 2014 / Published: 24 March 2014
Cited by 3 | PDF Full-text (717 KB) | HTML Full-text | XML Full-text
Abstract
In an effort to decrease the toxicity of camptothecin (CPT) and improve selectivity for hepatoma and colon cancer cells, bile acid groups were introduced into the CPT 20 or 10 positions, resulting in the preparation of sixteen novel CPT-bile acid analogues. The compounds
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In an effort to decrease the toxicity of camptothecin (CPT) and improve selectivity for hepatoma and colon cancer cells, bile acid groups were introduced into the CPT 20 or 10 positions, resulting in the preparation of sixteen novel CPT-bile acid analogues. The compounds in which a bile acid group was introduced at the 20-hydroxyl group of CPT showed better cytotoxic selectivity for human hepatoma and colon cancer cells than for human breast cancer cells. Fluorescence microscopy analysis demonstrated that one compound (E2) entered human hepatoma cells more effectively than it did human breast cancer cells. Compound G4 exhibited the best anti-tumour activity in vivo. These results suggested that introduction of a bile acid group at the 20-position of CPT could decrease toxicity in vivo and improve selectivity for hepatoma cells. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synthesis, Cytotoxic Activity and 2D-QSAR Study of Some Imidazoquinazoline Derivatives
Molecules 2014, 19(3), 3777-3792; doi:10.3390/molecules19033777
Received: 14 January 2014 / Revised: 17 March 2014 / Accepted: 19 March 2014 / Published: 24 March 2014
Cited by 1 | PDF Full-text (339 KB) | HTML Full-text | XML Full-text
Abstract
A novel series of 4-substituted amino-7,8-dimethoxy-1-phenylimidazo[1,5-a]quinazolin-5(4H)-one derivatives was designed, synthesized and tested for their antitumor activity against a human mammary carcinoma cell line (MCF7). Compound 5a was found to be the most active derivative. Physico-chemical parameters were also determined
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A novel series of 4-substituted amino-7,8-dimethoxy-1-phenylimidazo[1,5-a]quinazolin-5(4H)-one derivatives was designed, synthesized and tested for their antitumor activity against a human mammary carcinoma cell line (MCF7). Compound 5a was found to be the most active derivative. Physico-chemical parameters were also determined and revealed that most of the compounds obeyed the “rule of five” properties with good absorption percentages. 2D-QSAR studies revealed a well predictive and statistically significant and cross validated QSAR model that helps to explore some expectedly potent compounds. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Antischistosomal Activity of the Terpene Nerolidol
Molecules 2014, 19(3), 3793-3803; doi:10.3390/molecules19033793
Received: 7 January 2014 / Revised: 13 March 2014 / Accepted: 19 March 2014 / Published: 24 March 2014
Cited by 15 | PDF Full-text (1080 KB) | HTML Full-text | XML Full-text
Abstract
Schistosomiasis is a neglected tropical disease that affects hundreds of millions of people worldwide. Since the treatment of this disease currently relies on a single drug, praziquantel, new and safe schistosomicidal agents are urgently required. Nerolidol, a sesquiterpene present in the essential oils
[...] Read more.
Schistosomiasis is a neglected tropical disease that affects hundreds of millions of people worldwide. Since the treatment of this disease currently relies on a single drug, praziquantel, new and safe schistosomicidal agents are urgently required. Nerolidol, a sesquiterpene present in the essential oils of several plants, is found in many foods and was approved by the U.S. Food and Drug Administration. In this study we analysed the in vitro antiparasitic effect of nerolidol on Schistosoma mansoni adult worms. Nerolidol at concentrations of 31.2 and 62.5 μM reduced the worm motor activity and caused the death of all male and female schistosomes, respectively. In addition, confocal laser scanning microscopy revealed morphological alterations on the tegument of worms such as disintegration, sloughing and erosion of the surface, and a correlation between viability and tegumental damage was observed. In conclusion, nerolidol may be a promising lead compound for the development of antischistosomal natural agents. Full article
Open AccessArticle Synthesis of All-Z-1,6,9,12,15-Octadecapenten-3-one, A Vinyl Ketone Polyunsaturated Marine Natural Product Isolated from Callysponga sp.
Molecules 2014, 19(3), 3804-3812; doi:10.3390/molecules19033804
Received: 31 December 2013 / Revised: 7 March 2014 / Accepted: 10 March 2014 / Published: 24 March 2014
Cited by 5 | PDF Full-text (212 KB) | HTML Full-text | XML Full-text
Abstract
The synthesis of the marine natural product 1,6Z,9Z,12Z,15Z-octadecapentaen-3-one (1) has been achieved by two different routes starting from the ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. Using EPA ethyl
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The synthesis of the marine natural product 1,6Z,9Z,12Z,15Z-octadecapentaen-3-one (1) has been achieved by two different routes starting from the ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. Using EPA ethyl ester as starting material the polyunsaturated vinyl ketone lipid 1 was obtained in 17% overall yield. Full article
(This article belongs to the Special Issue Fatty Acids)
Open AccessArticle Isolation and Characterization of Microsatellite Markers for Cotinus coggygria Scop. (Anacardiaceae) by 454 Pyrosequencing
Molecules 2014, 19(3), 3813-3819; doi:10.3390/molecules19033813
Received: 7 February 2014 / Revised: 20 March 2014 / Accepted: 21 March 2014 / Published: 24 March 2014
Cited by 7 | PDF Full-text (181 KB) | HTML Full-text | XML Full-text
Abstract
Cotinus coggygria Scop. (Anacardiaceae) is a deciduous shrub or small tree that is native to a large area covering from southern Europe, east across central Asia, and the Himalayas in northern China. Shotgun 454 pyrosequencing was used to develop microsatellite markers from the
[...] Read more.
Cotinus coggygria Scop. (Anacardiaceae) is a deciduous shrub or small tree that is native to a large area covering from southern Europe, east across central Asia, and the Himalayas in northern China. Shotgun 454 pyrosequencing was used to develop microsatellite markers from the genome of C. coggygria. In this study, 349 microsatellite loci were identified from 40,074 individual sequence reads produced by one-sixteenth run, and primer pairs were designed for these loci. To test the primer amplification efficiency, 50 microsatellite primer pairs were tested across 12 individuals from two C. coggygria populations (Wuzhi Mountain: 36°30'N, 113°39'E; Tianlong Mountain: 37°42'N, 112°26'E). Among the 50 tested primer pairs, eight were found to be polymorphic. The average allele number of the microsatellites was 3.5 per locus, with a range from two to five. The inbreeding coefficient ranged from −0.478 to 0.222. The observed and expected heterozygosities varied from 0.167 to 0.750 and from 0.163 to 0.743, respectively. This set of markers is potentially useful for assessing the genetic diversity, as well as for understanding the population structure and phylogeographical and landscape genetic patterns, of C. coggygria. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Goat Milk Fat Naturally Enriched with Conjugated Linoleic Acid Increased Lipoproteins and Reduced Triacylglycerol in Rats
Molecules 2014, 19(3), 3820-3831; doi:10.3390/molecules19033820
Received: 30 December 2013 / Revised: 16 March 2014 / Accepted: 17 March 2014 / Published: 24 March 2014
Cited by 2 | PDF Full-text (594 KB) | HTML Full-text | XML Full-text
Abstract
Goat milk is source of different lipids, including conjugated linoleic acid (CLA). CLA reduces body fat and protect against cardiovascular diseases. In the present study fat from goat milk naturally enriched with CLA was used. Male Wistar rats were divided into three groups
[...] Read more.
Goat milk is source of different lipids, including conjugated linoleic acid (CLA). CLA reduces body fat and protect against cardiovascular diseases. In the present study fat from goat milk naturally enriched with CLA was used. Male Wistar rats were divided into three groups that received during a 10 week diet with different lipid sources: soybean oil (CON), coconut oil (CO) and goat milk fat naturally enriched with CLA (GM-CLA). We evaluated the effects of a GM-CLA on biochemistry parameters - high density lipoprotein (HDL), triacylglycerol (TAG), TAG/HDL ratio, total cholesterol and glucose -, body weight and histopathological aspects of the intestine and liver. GM-CLA increased body weight from the second to the fifth week of the experiment compared to CON. Feed intake differed between the CON group and GM-CLA early in the first to third week of the experiments and later between the ninth and tenth week. The CLA-diet group showed increased levels of HDL, reduced levels of TAG and TAG/HDL ratio and no effect on LDL, but enhanced total cholesterol. Serum glucose of the GM-CLA group showed no difference from the control group. Thus, a GM-CLA diet promoted growth in young rats and acted as protector of cardiovascular function, but further studies are still needed to clarify these effects. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Platinum(II) Oxalato Complexes Involving Adenosine-Based N-Donor Ligands: Synthesis, Characterization and Cytotoxicity Evaluation
Molecules 2014, 19(3), 3832-3847; doi:10.3390/molecules19033832
Received: 31 January 2014 / Revised: 11 March 2014 / Accepted: 21 March 2014 / Published: 24 March 2014
Cited by 7 | PDF Full-text (643 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A one-step synthetic procedure using the reaction of potassium bis(oxalato)platinate(II) with the corresponding N6-benzyladenosine derivative (nL) provided the [Pt(ox)(nL)2]∙1.5H2O oxalato (ox) complexes 15, involving the nL molecules as monodentate coordinated
[...] Read more.
A one-step synthetic procedure using the reaction of potassium bis(oxalato)platinate(II) with the corresponding N6-benzyladenosine derivative (nL) provided the [Pt(ox)(nL)2]∙1.5H2O oxalato (ox) complexes 15, involving the nL molecules as monodentate coordinated N-donor ligands. The complexes were thoroughly characterized by elemental analysis, multinuclear (1H, 13C, 15N, 195Pt) and two dimensional NMR, infrared and Raman spectroscopy, and mass spectrometry, proving their composition and purity as well as coordination of nL through the N7 atom of the purine moiety. Geometry of [Pt(ox)(4FL)2] (5) was optimized at the B3LYP/LANLTZ/6-311G** level of theory. The complexes were screened for their in vitro cytotoxicity against two human cancer cell lines (HOS osteosarcoma and MCF7 breast adenocarcinoma), but they did not show any effect up to the concentration of 50.0 µM (compounds 1, 2) or 20.0 µM (compounds 35). Full article
(This article belongs to the Section Medicinal Chemistry)

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Open AccessReview Use of Natural Compounds in the Management of Diabetic Peripheral Neuropathy
Molecules 2014, 19(3), 2877-2895; doi:10.3390/molecules19032877
Received: 20 December 2013 / Revised: 20 February 2014 / Accepted: 26 February 2014 / Published: 5 March 2014
Cited by 9 | PDF Full-text (249 KB) | HTML Full-text | XML Full-text
Abstract
Nephropathy, retinopathy cardiomyopathy and peripheral neuropathy are all recognized as important complications in about 50% of diabetes mellitus (DM) patients, mostly related to a poor glycemic control or to an improper management of this pathology. In any case, amongst others, diabetic peripheral neuropathy
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Nephropathy, retinopathy cardiomyopathy and peripheral neuropathy are all recognized as important complications in about 50% of diabetes mellitus (DM) patients, mostly related to a poor glycemic control or to an improper management of this pathology. In any case, amongst others, diabetic peripheral neuropathy (DPN) seems the leading and most painful complication usually affecting many DM patients. For this reason, this work was conceived to review the large variety of strategies adopted for management of DPN, starting from the most conventional therapies to arrive at alternative approaches. From this perspective, both the most popular pharmacological treatments used to respond to the poorly effect of common analgesics—non-steroidal anti-inflammatory drugs (NSAIDS) and opioids—understood as gabapentin vs. pregabalin clinical use, and the guidelines provided by Oriental Medicine as well as by a long list of natural compounds that many authors identify as possible therapeutic or alternative agents to replace or to combine with the existing therapies will be included. Moreover, in the effort to provide the widest panel of remedies, the most antique techniques of acupuncture and electrostimulation will be considered as alternative, which are useful approaches to take into account in any non-pharmacological strategy for DPN management. Full article
(This article belongs to the Section Natural Products)
Open AccessReview Early State Research on Antifungal Natural Products
Molecules 2014, 19(3), 2925-2956; doi:10.3390/molecules19032925
Received: 2 December 2013 / Revised: 1 January 2014 / Accepted: 9 January 2014 / Published: 7 March 2014
Cited by 13 | PDF Full-text (663 KB) | HTML Full-text | XML Full-text
Abstract
Nosocomial infections caused by fungi have increased greatly in recent years, mainly due to the rising number of immunocompromised patients. However, the available antifungal therapeutic arsenal is limited, and the development of new drugs has been slow. Therefore, the search for alternative drugs
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Nosocomial infections caused by fungi have increased greatly in recent years, mainly due to the rising number of immunocompromised patients. However, the available antifungal therapeutic arsenal is limited, and the development of new drugs has been slow. Therefore, the search for alternative drugs with low resistance rates and fewer side effects remains a major challenge. Plants produce a variety of medicinal components that can inhibit pathogen growth. Studies of plant species have been conducted to evaluate the characteristics of natural drug products, including their sustainability, affordability, and antimicrobial activity. A considerable number of studies of medicinal plants and alternative compounds, such as secondary metabolites, phenolic compounds, essential oils and extracts, have been performed. Thus, this review discusses the history of the antifungal arsenal, surveys natural products with potential antifungal activity, discusses strategies to develop derivatives of natural products, and presents perspectives on the development of novel antifungal drug candidates. Full article
(This article belongs to the Special Issue Advances in Medicinal Chemistry of Antifungals)
Open AccessReview Hyaluronic Acid Conjugates as Vectors for the Active Targeting of Drugs, Genes and Nanocomposites in Cancer Treatment
Molecules 2014, 19(3), 3193-3230; doi:10.3390/molecules19033193
Received: 20 January 2014 / Revised: 7 March 2014 / Accepted: 11 March 2014 / Published: 17 March 2014
Cited by 26 | PDF Full-text (583 KB) | HTML Full-text | XML Full-text
Abstract
Hyaluronic acid (HA) is a naturally-occurring glycosaminoglycan and a major component of the extracellular matrix. Low levels of the hyaluronic acid receptor CD44 are found on the surface of epithelial, hematopoietic, and neuronal cells; it is overexpressed in many cancer cells, and in
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Hyaluronic acid (HA) is a naturally-occurring glycosaminoglycan and a major component of the extracellular matrix. Low levels of the hyaluronic acid receptor CD44 are found on the surface of epithelial, hematopoietic, and neuronal cells; it is overexpressed in many cancer cells, and in particular in tumor-initiating cells. HA has recently attracted considerable interest in the field of developing drug delivery systems, having been used, as such or encapsulated in different types of nanoassembly, as ligand to prepare nano-platforms for actively targeting drugs, genes, and diagnostic agents. This review describes recent progress made with the several chemical strategies adopted to synthesize conjugates and prepare novel delivery systems with improved behaviors. Full article
(This article belongs to the Special Issue Bioconjugations)
Open AccessReview Structure-Activity Association of Flavonoids in Lung Diseases
Molecules 2014, 19(3), 3570-3595; doi:10.3390/molecules19033570
Received: 16 October 2013 / Revised: 13 March 2014 / Accepted: 17 March 2014 / Published: 24 March 2014
Cited by 18 | PDF Full-text (966 KB) | HTML Full-text | XML Full-text
Abstract
Flavonoids are polyphenolic compounds classified into flavonols, flavones, flavanones, isoflavones, catechins, anthocyanidins, and chalcones according to their chemical structures. They are abundantly found in Nature and over 8,000 flavonoids have from different sources, mainly plant materials, have been described. Recently reports have shown
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Flavonoids are polyphenolic compounds classified into flavonols, flavones, flavanones, isoflavones, catechins, anthocyanidins, and chalcones according to their chemical structures. They are abundantly found in Nature and over 8,000 flavonoids have from different sources, mainly plant materials, have been described. Recently reports have shown the valuable effects of flavonoids as antiviral, anti-allergic, antiplatelet, antitumor, antioxidant, and anti-inflammatory agents and interest in these compounds has been increasing since they can be helpful to human health. Several mechanisms of action are involved in the biological properties of flavonoids such as free radical scavenging, transition metal ion chelation, activation of survival genes and signaling pathways, regulation of mitochondrial function and modulation of inflammatory responses. The anti-inflammatory effects of flavonoids have been described in a number of studies in the literature, but not frequently associated to respiratory disease. Thus, this review aims to discuss the effects of different flavonoids in the control of lung inflammation in some disorders such as asthma, lung emphysema and acute respiratory distress syndrome and the possible mechanisms of action, as well as establish some structure-activity relationships between this biological potential and chemical profile of these compounds. Full article
(This article belongs to the Special Issue Structure-Activity Relationship of Flavonoids)
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Open AccessCorrection Correction: Moharam et al., Inhibitory Effects of Phylligenin and Quebrachitol Isolated from Mitrephora vulpina on Platelet Activating Factor Receptor Binding and Platelet Aggregation. Molecules 2010, 15, 7840-7848
Molecules 2014, 19(3), 3848-3849; doi:10.3390/molecules19033848
Received: 4 March 2014 / Accepted: 11 March 2014 / Published: 24 March 2014
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Abstract The authors wish to inform readers that there are several minor errors and omissions in the chemical structures shown in Figure 1 of this paper [1]. [...] Full article
Open AccessRetraction Retraction: Agarwal et al. Dynamic Action of Carotenoids in Cardioprotection and Maintenance of Cardiac Health, Molecules 2012, 17, 4755-4769
Molecules 2014, 19(3), 3850; doi:10.3390/molecules19033850
Received: 20 March 2014 / Accepted: 25 March 2014 / Published: 25 March 2014
PDF Full-text (114 KB) | HTML Full-text | XML Full-text
Abstract
We were recently alerted by an anonymous tip that at least two paragraphs in the title review [1] appeared to be copied verbatim from papers by other authors without attribution. Upon checking these facts we have established that in addition to the parts
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We were recently alerted by an anonymous tip that at least two paragraphs in the title review [1] appeared to be copied verbatim from papers by other authors without attribution. Upon checking these facts we have established that in addition to the parts brought to our attention, large portions of the review are made up of paragraphs copied verbatim from other reviews or books, sometimes cited, but mostly presented without any references other than to the corresponding original primary literature. Full article

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