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Molecules, Volume 19, Issue 1 (January 2014), Pages 1-1377

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Editorial

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Open AccessEditorial Molecules Best Paper Award 2014
Molecules 2014, 19(1), 1375-1377; doi:10.3390/molecules19011375
Received: 6 December 2013 / Revised: 11 December 2013 / Accepted: 17 December 2013 / Published: 22 January 2014
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Abstract
Molecules instituted some years ago a “Best Paper” award to recognize the most outstanding papers in the area of natural products, medicinal chemistry and molecular diversity published each year in Molecules. We are pleased to announce the third “Molecules Best Paper
[...] Read more.
Molecules instituted some years ago a “Best Paper” award to recognize the most outstanding papers in the area of natural products, medicinal chemistry and molecular diversity published each year in Molecules. We are pleased to announce the third “Molecules Best Paper Award” for 2014. The winners were chosen by the Editor-in-Chief and selected editorial board members from among all the papers published in 2010. Reviews and research papers were evaluated separately. [...] Full article
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Research

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Open AccessArticle Two New Phenolic Compounds from the Heartwood of Caesalpinia sappan L.
Molecules 2014, 19(1), 1-8; doi:10.3390/molecules19010001
Received: 18 November 2013 / Revised: 9 December 2013 / Accepted: 10 December 2013 / Published: 19 December 2013
Cited by 2 | PDF Full-text (322 KB) | HTML Full-text | XML Full-text
Abstract
Two new phenolic compounds, epicaesalpin J and 7,10,11-trihydroxydracaenone, were isolated from the heartwood of Caesalpinia sappan L. Their structures were identified by spectroscopic analysis methods, such as 1D and 2D NMR, along with the high resolution mass spectral data. The NO inhibition activities
[...] Read more.
Two new phenolic compounds, epicaesalpin J and 7,10,11-trihydroxydracaenone, were isolated from the heartwood of Caesalpinia sappan L. Their structures were identified by spectroscopic analysis methods, such as 1D and 2D NMR, along with the high resolution mass spectral data. The NO inhibition activities of two new compounds and six known compounds were tested. Full article
Open AccessArticle Influence of Temperature on the Enantioselectivity of Koga Tetraamines on Amylose Chiral Stationary Phases
Molecules 2014, 19(1), 9-21; doi:10.3390/molecules19010009
Received: 25 October 2013 / Revised: 4 December 2013 / Accepted: 10 December 2013 / Published: 19 December 2013
Cited by 2 | PDF Full-text (1261 KB) | HTML Full-text | XML Full-text
Abstract
Enantioseparation is largely based on the formation of transitional complexes, the solvation species, the stationary phase configurations or the diastereomeric complexes formed by analytes and the chiral stationary phase. Temperature and the chemical nature and composition of the eluent play significant roles during
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Enantioseparation is largely based on the formation of transitional complexes, the solvation species, the stationary phase configurations or the diastereomeric complexes formed by analytes and the chiral stationary phase. Temperature and the chemical nature and composition of the eluent play significant roles during that process. In this study; unique temperature-induced behaviors were observed during the enantioseparation of Koga tetraamines, also known as Koga bases, on polysaccharide chiral stationary phases, in which van’t Hoff plots were acquired over a temperature range of 10 °C to 40 °C with 5 °C increments. Koga bases were eluted by a mixture of methanol and 2-propanol with 0.03% triethylamine as a modifier. The van’t Hoff plots are linear in the case of eluent containing equal volumes of methanol and 2-propanol. Increasing 2-propanol concentration from 50% to 85% in volume led to non-linear van’t Hoff plots over the entire temperature range studied. Examination of the individual non-linear plots revealed two linear regions of 10 °C–20 °C and 20 °C–40 °C. Transition from one linear region to the other at 20 °C indicates alterations of chiral stationary phase conformation and/or enantioseparation mechanism as a result of temperature changes. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Open AccessArticle Physicochemical Characteristics and Anti-Inflammatory Activities of Antrodan, a Novel Glycoprotein Isolated from Antrodia cinnamomea Mycelia
Molecules 2014, 19(1), 22-40; doi:10.3390/molecules19010022
Received: 11 October 2013 / Revised: 5 December 2013 / Accepted: 6 December 2013 / Published: 19 December 2013
Cited by 4 | PDF Full-text (4143 KB) | HTML Full-text | XML Full-text
Abstract
Antrodia cinnamomea (AC) is a unique fungus found inhabiting the rotten wood of Cinnamomum kanehirai. A submerged liquid culture of AC has been developed and its bioproducts have been used to meet the market demand for natural fruiting bodies. AC exhibits anti-inflammatory, antitumor,
[...] Read more.
Antrodia cinnamomea (AC) is a unique fungus found inhabiting the rotten wood of Cinnamomum kanehirai. A submerged liquid culture of AC has been developed and its bioproducts have been used to meet the market demand for natural fruiting bodies. AC exhibits anti-inflammatory, antitumor, antioxidant, and immunomodulatory effects. Previously, we isolated polysaccharide AC-2 from AC mycelia by means of alkali extraction with subsequent acid precipitation and found it had a pronounced anti-inflammatory effect. In this study, a novel polysaccharide named “antrodan” was obtained by further purification of AC-2 using Sepharose CL-6B column chromatography. Antrodan exhibited a molecular weight of 442 kD and contained a particularly high content of uronic acid (152.6 ± 0.8 mg/g). The protein content was 71.0%, apparently, higher than the carbohydrate content (14.1%), and thus antrodan was characterized as a glycoprotein. Its total glucan content was 15.65%, in which β-glucan (14.20%) was prominently higher than α-glucan (1.45%). Its FTIR confirmed the presence of β-linkages between sugars, and intramolecular amide bonds between sugars and amino acids. Its 1H-NMR spectrum showed that antrodan was a complex union of α- and β-glucans, which had (1→ 4)-linked α-Glcp and (1→ 3)-linked β-Glcp linkages to the carbohydrate chains via asparagine linked to protein site. Biologically, antrodan was confirmed to be totally non-detrimental to RAW 264.7 cell line even at dose as high as 400 μg/mL. It showed potent suppressing effect on the lipopolysaccharide-induced inflammatory responses in RAW 264.7 cell line. Moreover, antrodan significantly reduced the nitrogen oxide production at doses as low as 18.75 μg/mL. Full article
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Open AccessArticle Three-Component Reaction of Tautomeric Amidines with 3-Ferrocenylmethylidene-2,4-pentanedione. Formation of Polymeric Coordination Complexes of Potassium Ferrocenyl-(hexahydro)pyrimidoxides
Molecules 2014, 19(1), 41-54; doi:10.3390/molecules19010041
Received: 8 October 2013 / Revised: 5 December 2013 / Accepted: 9 December 2013 / Published: 20 December 2013
Cited by 1 | PDF Full-text (1228 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Acetamidine hydrochloride and p-aminobenzamidine dihydrochloride interact with 3-ferrocenylmethylidene-2,4-pentanedione at 80–82 °C in the presence of K2CO3 in the water–alcohol medium in two tautomeric forms (the amidoimine and enediamine ones) with formation of mixtures of pyrimidine and piperidone derivatives and
[...] Read more.
Acetamidine hydrochloride and p-aminobenzamidine dihydrochloride interact with 3-ferrocenylmethylidene-2,4-pentanedione at 80–82 °C in the presence of K2CO3 in the water–alcohol medium in two tautomeric forms (the amidoimine and enediamine ones) with formation of mixtures of pyrimidine and piperidone derivatives and polymeric coordination complexes of potassium ferrocenyl(hexahydro)pyrimidoxides. The structure of the resultant compounds is elucidated on the basis of IR, 1H- and 13C-NMR spectroscopy, mass spectrometry and elemental analysis data. The crystal structures of 6-ferrocenyl-4-hydroxy-4-methyl-2-piperidone, potassium 6-ferrocenyl-4-methyl-2-methylidene(hexahydro)pyrimidin-4-oxide and 2-(4-aminophenyl)-4-ferrocenyl-6-methyl-pyrimidine were determined by X-ray analysis of suitable single crystals. Full article
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Open AccessCommunication Pseudo-Four Component Synthesis of Mono- and Di-Benzylated-1,2,3-Triazoles Derived from Aniline
Molecules 2014, 19(1), 55-66; doi:10.3390/molecules19010055
Received: 30 October 2013 / Revised: 16 December 2013 / Accepted: 16 December 2013 / Published: 20 December 2013
Cited by 2 | PDF Full-text (250 KB) | HTML Full-text | XML Full-text
Abstract
The pseudo-four component click synthesis of dibenzylated 1,2,3-triazoles derived from aniline is reported. The cycloaddition of sodium azide to N-(prop-2-ynyl)-benzenamine (I) in the presence of equimolar amounts of p-substituted benzyl derivatives, yields a mixture of mono- and dibenzylated 1,2,3-triazoles.
[...] Read more.
The pseudo-four component click synthesis of dibenzylated 1,2,3-triazoles derived from aniline is reported. The cycloaddition of sodium azide to N-(prop-2-ynyl)-benzenamine (I) in the presence of equimolar amounts of p-substituted benzyl derivatives, yields a mixture of mono- and dibenzylated 1,2,3-triazoles. When two equivalents of the benzyl derivative are added to the multicomponent reaction, the selective preparation of the dibenzylated compounds is achieved. The reactivity of the aniline N-H bond in monobenzylated 1,2,3-triazoles was tested by treatment with one equivalent of a p-substituted benzyl chloride at 40 °C, rendering the dibenzylated derivatives quantitatively. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Optimized Ultrasound-Assisted Extraction of Phenolic Compounds from Polygonum cuspidatum
Molecules 2014, 19(1), 67-77; doi:10.3390/molecules19010067
Received: 23 October 2013 / Revised: 14 November 2013 / Accepted: 26 November 2013 / Published: 20 December 2013
Cited by 10 | PDF Full-text (1875 KB) | HTML Full-text | XML Full-text
Abstract
In this study the phenolic compounds piceid, resveratrol and emodin were extracted from P. cuspidatum roots using ultrasound-assisted extraction. Multiple response surface methodology was used to optimize the extraction conditions of these phenolic compounds. A three-factor and three-level Box-Behnken experimental design was employed
[...] Read more.
In this study the phenolic compounds piceid, resveratrol and emodin were extracted from P. cuspidatum roots using ultrasound-assisted extraction. Multiple response surface methodology was used to optimize the extraction conditions of these phenolic compounds. A three-factor and three-level Box-Behnken experimental design was employed to evaluate the effects of the operation parameters, including extraction temperature (30–70 °C), ethanol concentration (40%–80%), and ultrasonic power (90–150 W), on the extraction yields of piceid, resveratrol, and emodin. The statistical models built from multiple response surface methodology were developed for the estimation of the extraction yields of multi-phenolic components. Based on the model, the extraction yields of piceid, resveratrol, and emodin can be improved by controlling the extraction parameters. Under the optimum conditions, the extraction yields of piceid, resveratrol and emodin were 10.77 mg/g, 3.82 mg/g and 11.72 mg/g, respectively. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle 1H-2,3-Dihydroperimidine Derivatives: A New Class of Potent Protein Tyrosine Phosphatase 1B Inhibitors
Molecules 2014, 19(1), 102-121; doi:10.3390/molecules19010102
Received: 31 October 2013 / Revised: 12 December 2013 / Accepted: 13 December 2013 / Published: 23 December 2013
Cited by 3 | PDF Full-text (693 KB) | HTML Full-text | XML Full-text
Abstract
A series of 1H-2,3-dihydroperimidine derivatives was designed, synthesized, and evaluated as a new class of inhibitors of protein tyrosine phosphatase 1B (PTP1B) with IC50 values in the micromolar range. Compounds 46 and 49 showed submicromolar inhibitory activity against PTP1B,
[...] Read more.
A series of 1H-2,3-dihydroperimidine derivatives was designed, synthesized, and evaluated as a new class of inhibitors of protein tyrosine phosphatase 1B (PTP1B) with IC50 values in the micromolar range. Compounds 46 and 49 showed submicromolar inhibitory activity against PTP1B, and good selectivity (3.48-fold and 2.10-fold respectively) over T-cell protein tyrosine phosphatases (TCPTP). These results have provided novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Bioactive Compounds from the Roots of Asiasarum heterotropoides
Molecules 2014, 19(1), 122-138; doi:10.3390/molecules19010122
Received: 14 November 2013 / Revised: 13 December 2013 / Accepted: 16 December 2013 / Published: 23 December 2013
Cited by 1 | PDF Full-text (538 KB) | HTML Full-text | XML Full-text
Abstract
A new tetrahydrofuran lignan, (7S,8R,7'S,8'S)-3-methoxy-3',4'-methylenedioxy-7,9'-epoxylignane-4,7',9-triol (1), and 21 known compounds 222 were isolated from the roots of Asiasarum heterotropoides by chromatographic separation methods. The structures of all compounds 122
[...] Read more.
A new tetrahydrofuran lignan, (7S,8R,7'S,8'S)-3-methoxy-3',4'-methylenedioxy-7,9'-epoxylignane-4,7',9-triol (1), and 21 known compounds 222 were isolated from the roots of Asiasarum heterotropoides by chromatographic separation methods. The structures of all compounds 122 were elucidated by spectroscopic analysis including 1D- and 2D-NMR. Fourteen of these compounds (13, 7, 10, 1217, 19, 21, and 22) were isolated from this species in this study for the first time. All of the isolates were evaluated for their anticancer activities using in vitro assays. Among the 22 tested compounds, two (compounds 5 and 7) induced the downregulation of NO production, FOXP3 expression, and HIF-1α transcriptional activity. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Asymmetric Synthesis of 4,1-Benzoxazepine-2,5-Diones — Effect of the Halogen of (2S)-α-Haloacids
Molecules 2014, 19(1), 139-148; doi:10.3390/molecules19010139
Received: 28 November 2013 / Revised: 12 December 2013 / Accepted: 16 December 2013 / Published: 23 December 2013
Cited by 3 | PDF Full-text (307 KB) | HTML Full-text | XML Full-text
Abstract Novel chiral 4,1-benzoxazepine-2,5-diones have been unusually synthesized in a single step by exploiting the chiral pool methodology. Substituted anthranilic acids afford N-acylanthranilic acids and (3R)-3-alkyl-4,1-benzoxazepines-2,5-dione upon coupling with α-chloroacids or α-bromoacids, respectively. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Molecular Docking Characterization of a Four-Domain Segment of Human Fibronectin Encompassing the RGD Loop with Hydroxyapatite
Molecules 2014, 19(1), 149-158; doi:10.3390/molecules19010149
Received: 24 October 2013 / Revised: 2 December 2013 / Accepted: 11 December 2013 / Published: 23 December 2013
Cited by 2 | PDF Full-text (1106 KB) | HTML Full-text | XML Full-text
Abstract
Fibronectin adsorption on biomaterial surfaces plays a key role in the biocompatibility of biomedical implants. In the current study, the adsorption behavior of the 7–10th type III modules of fibronectin (FN-III7–10) in the presence of hydroxyapatite (HAP) was systematically investigated by
[...] Read more.
Fibronectin adsorption on biomaterial surfaces plays a key role in the biocompatibility of biomedical implants. In the current study, the adsorption behavior of the 7–10th type III modules of fibronectin (FN-III7–10) in the presence of hydroxyapatite (HAP) was systematically investigated by using molecular docking approach. It was revealed that the FN-III10 is the most important module among FN-III7–10 in promoting fibronectin binding to HAP by optimizing the interaction energy; the arginine residues were observed to directly interact with the hydroxyl group of HAP through electrostatic forces and hydrogen bonding. Moreover, it was found that the HAP-binding sites on FN-III10 are mainly located at the RGD loop region, which does not affect the interaction between the fibronectin protein and its cognate receptors on the cell surface. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Involvement of CUL4A in Regulation of Multidrug Resistance to P-gp Substrate Drugs in Breast Cancer Cells
Molecules 2014, 19(1), 159-176; doi:10.3390/molecules19010159
Received: 14 September 2013 / Revised: 15 December 2013 / Accepted: 17 December 2013 / Published: 24 December 2013
Cited by 20 | PDF Full-text (2422 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
CUL4A encodes a core component of a cullin-based E3 ubiquitin ligase complex that regulates many critical processes such as cell cycle progression, DNA replication, DNA repair and chromatin remodeling by targeting a variety of proteins for ubiquitination and degradation. In the research described
[...] Read more.
CUL4A encodes a core component of a cullin-based E3 ubiquitin ligase complex that regulates many critical processes such as cell cycle progression, DNA replication, DNA repair and chromatin remodeling by targeting a variety of proteins for ubiquitination and degradation. In the research described in this report we aimed to clarify whether CUL4A participates in multiple drug resistance (MDR) in breast cancer cells. We first transfected vectors carrying CUL4A and specific shCUL4A into breast cancer cells and corresponding Adr cells respectively. Using reverse transcription polymerase chain reactions and western blots, we found that overexpression of CUL4A in MCF7 and MDA-MB-468 cells up-regulated MDR1/P-gp expression on both the transcription and protein levels, which conferred multidrug resistance to P-gp substrate drugs, as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. On the other hand, silencing CUL4A in MCF7/Adr and MDA-MB-468/Adr cells led to the opposite effect. Moreover, ERK1/2 in CUL4A-overexpressing cells was highly activated and after treatment with PD98059, an ERK1/2-specific inhibitor, CUL4A-induced expression of MDR1/P-gp was decreased significantly. Lastly, immunohistochemistry in breast cancer tissues showed that P-gp expression had a positive correlation with the expression of CUL4A and ERK1/2. Thus, these results implied that CUL4A and ERK1/2 participated in multi-drug resistance in breast cancer through regulation of MDR1/P-gp expression. Full article
Open AccessArticle A Comparative Study on the Metabolism of Epimedium koreanum Nakai-Prenylated Flavonoids in Rats by an Intestinal Enzyme (Lactase Phlorizin Hydrolase) and Intestinal Flora
Molecules 2014, 19(1), 177-203; doi:10.3390/molecules19010177
Received: 6 November 2013 / Revised: 11 December 2013 / Accepted: 17 December 2013 / Published: 24 December 2013
Cited by 9 | PDF Full-text (5759 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to compare the significance of the intestinal hydrolysis of prenylated flavonoids in Herba Epimedii by an intestinal enzyme and flora. Flavonoids were incubated at 37 °C with rat intestinal enzyme and intestinal flora. HPLC-UV was used to
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The aim of this study was to compare the significance of the intestinal hydrolysis of prenylated flavonoids in Herba Epimedii by an intestinal enzyme and flora. Flavonoids were incubated at 37 °C with rat intestinal enzyme and intestinal flora. HPLC-UV was used to calculate the metabolic rates of the parent drug in the incubation and LC/MS/MS was used to determine the chemical structures of metabolites generated by different flavonoid glycosides. Rates of flavonoid metabolism by rat intestinal enzyme were quicker than those of intestinal flora. The sequence of intestinal flora metabolic rates was icariin > epimedin B > epimedin A > epimedin C > baohuoside I, whereas the order of intestinal enzyme metabolic rates was icariin > epimedin A > epimedin C > epimedin B > baohuoside I. Meanwhile, the LC/MS/MS graphs showed that icariin produced three products, epimedin A/B/C had four and baohuoside I yielded one product in incubations of both intestinal enzyme and flora, which were more than the results of HPLC-UV due to the fact LC/MS/MS has lower detectability and higher sensitivity. Moreover, the outcomes indicated that the rate of metabolization of flavonoids by intestinal enzyme were faster than those of intestinal flora, which was consistent with the HPLC-UV results. In conclusion, the metabolic pathways of the same components by intestinal flora and enzyme were the same. What’s more, an intestinal enzyme such as lactase phlorizin hydrolase exhibited a more significant metabolic role in prenylated flavonoids of Herba Epimedi compared with intestinal flora. Full article
Open AccessArticle Unfolding Studies of the Cysteine Protease Baupain, a Papain-Like Enzyme from Leaves of Bauhinia forficata: Effect of pH, Guanidine Hydrochloride and Temperature
Molecules 2014, 19(1), 233-246; doi:10.3390/molecules19010233
Received: 8 October 2013 / Revised: 12 December 2013 / Accepted: 13 December 2013 / Published: 24 December 2013
Cited by 3 | PDF Full-text (731 KB) | HTML Full-text | XML Full-text
Abstract
Baupain belongs to the α+β class of proteins with a secondary structure-content of 44% α-helix, 16% β-sheet and 12% β-turn. The structural transition induced by pH was found to be noncooperative, with no important differences observed in the pH range from 3.0 to
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Baupain belongs to the α+β class of proteins with a secondary structure-content of 44% α-helix, 16% β-sheet and 12% β-turn. The structural transition induced by pH was found to be noncooperative, with no important differences observed in the pH range from 3.0 to 10.5. At pH 2.0 the protein presented substantial non-native structure with strong ANS binding. Guanidine hydrochloride (GdnHCl)-induced unfolding did not change the protein structure significantly until 4.0 M, indicating the high rigidity of the molecule. The unfolding was cooperative, as seen by the sigmoidal transition curves with midpoints at 4.7 ± 0.2 M and 5.0 ± 0.2 M GdnHCl, as measured by CD and fluorescence spectroscopy. A red shift of 7 nm in intrinsic fluorescence was observed with 6.0 M GdnHCl. Temperature-induced unfolding of baupain was incomplete, and at least 35% of the native structure of the protein was retained, even at high temperature (90 °C). Baupain showed characteristics of a molten globule state, due to preferential ANS binding at pH 2.0 in comparison to the native form (pH 7.0) and completely unfolded (6.0 M GdnHCl) state. Combined with information about N-terminal sequence similarity, these results allow us to include baupain in the papain superfamily. Full article
(This article belongs to the Special Issue Enzyme Chemistry)
Open AccessArticle Organically Modified Silica with Pyrazole-3-carbaldehyde as a New Sorbent for Solid-Liquid Extraction of Heavy Metals
Molecules 2014, 19(1), 247-262; doi:10.3390/molecules19010247
Received: 3 December 2013 / Revised: 17 December 2013 / Accepted: 19 December 2013 / Published: 24 December 2013
Cited by 9 | PDF Full-text (569 KB) | HTML Full-text | XML Full-text
Abstract
A new chelating matrix, SiNP, has been prepared by immobilizing 1.5-dimethyl-1H-pyrazole-3-carbaldehyde on silica gel modified with 3-aminopropyl-trimethoxysilane. This new chelating material was well characterized by elemental analysis, FT-IR spectroscopy, cross polarization magic angle spinning solid state 13C-NMR, nitrogen adsorption-desorption isotherm,
[...] Read more.
A new chelating matrix, SiNP, has been prepared by immobilizing 1.5-dimethyl-1H-pyrazole-3-carbaldehyde on silica gel modified with 3-aminopropyl-trimethoxysilane. This new chelating material was well characterized by elemental analysis, FT-IR spectroscopy, cross polarization magic angle spinning solid state 13C-NMR, nitrogen adsorption-desorption isotherm, BET surface area, BJH pore size, and scanning electron microscopy (SEM). The new product exhibits good chemical and thermal stability as determined by thermogravimetry curves (TGA). The new prepared material was used as an adsorbent for the solid-phase extraction (SPE) of Pb(II), Cd(II), Cu(II) and Zn(II) from aqueous solutions using a batch method, prior to their determination by flame atomic adsorption spectrometry. The adsorption capacity was investigated using kinetics and pH effects. Common coexisting ions did not interfere with separation and determination. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle The Phenolics from the Roots of Livistona chinensis Show Antioxidative and Obsteoblast Differentiation Promoting Activity
Molecules 2014, 19(1), 263-278; doi:10.3390/molecules19010263
Received: 13 November 2013 / Revised: 10 December 2013 / Accepted: 13 December 2013 / Published: 27 December 2013
Cited by 2 | PDF Full-text (1053 KB) | HTML Full-text | XML Full-text
Abstract
This study investigated the antioxidative and obsteoblast differentiation promoting activity of the phenolics isolated from the 70% ethanol extract of the roots of Livistona chinensis. Two new phenolics, (2R,3R)-3,5,6,7,3',4'-hexahydroxyflavane (1), and phenanthrene-2,4,9-triol (2), together
[...] Read more.
This study investigated the antioxidative and obsteoblast differentiation promoting activity of the phenolics isolated from the 70% ethanol extract of the roots of Livistona chinensis. Two new phenolics, (2R,3R)-3,5,6,7,3',4'-hexahydroxyflavane (1), and phenanthrene-2,4,9-triol (2), together with six known phenolics 38, were isolated and identified on the basis of extensive spectroscopic analysis. The antioxidative and obsteoblast differentiation promoting abilities of the compounds 13, 78 were tested, the phenolics 13, 7 showed effects on proliferation of osteoblastic cells and antioxidative activity of 3.125–50 µg/mL. In addition, the phenolics 13 observably increased alkaline phosphatase activity, osteocalcin content and hydroxyproline content in osteoblastic cells. Phenolic 1 at 12.5 µg/mL concentration significantly increased the area of nodules by about 9.35-fold. The antioxidative activity results indicated that the anti-osteoporosis effects of these phenolics may be linked to a reduction of oxidative stress. The observed effects of these phenolics on bone formation by rat osteoblastic cells suggest that these phenolics may have beneficial effects on bone health. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of Novel 2-(Substituted amino)alkylthiopyrimidin-4(3H)-ones as Potential Antimicrobial Agents
Molecules 2014, 19(1), 279-290; doi:10.3390/molecules19010279
Received: 29 November 2013 / Revised: 13 December 2013 / Accepted: 16 December 2013 / Published: 27 December 2013
Cited by 4 | PDF Full-text (249 KB) | HTML Full-text | XML Full-text
Abstract
5-Alkyl-6-(substituted benzyl)-2-thiouracils 3a,c were reacted with (2-chloroethyl) diethylamine hydrochloride to afford the corresponding 2-(2-diethylamino)ethylthiopyrimidin- 4(3H)-ones 4a,b. Reaction of 3ac with N-(2-chloroethyl)pyrrolidine hydrochloride and/or N-(2-chloroethyl)piperidine hydrochloride gave the corresponding 2-[2-(pyrrolidin-1-yl)ethyl]-thiopyrimidin-4(3H)-ones 5a
[...] Read more.
5-Alkyl-6-(substituted benzyl)-2-thiouracils 3a,c were reacted with (2-chloroethyl) diethylamine hydrochloride to afford the corresponding 2-(2-diethylamino)ethylthiopyrimidin- 4(3H)-ones 4a,b. Reaction of 3ac with N-(2-chloroethyl)pyrrolidine hydrochloride and/or N-(2-chloroethyl)piperidine hydrochloride gave the corresponding 2-[2-(pyrrolidin-1-yl)ethyl]-thiopyrimidin-4(3H)-ones 5ac and 2-[2-(piperidin-1-yl)ethyl]thiopyrimidin-4(3H)-ones 6a,b, respectively. Treatment of 3ad with N-(2-chloroethyl)morpholine hydrochloride under the same reaction conditions formed the corresponding 2-[2-(morpholin-4-yl)ethyl]thiopyrimidines 6cf. On the other hand, 3a,b were reacted with N-(2-bromoethyl)phthalimide and/or N-(3-bromopropyl)phthalimide to furnish the corresponding 2-[2-(N-phthalimido)ethyl]-pyrimidines 7a,b and 2-[3-(N-phthalimido)-propyl]pyrimidines 7c,d, respectively. Compounds 3ad, 4a,b, 5ac, 6af and 7ad were screened against Gram-positive bacteria (Staphylococcus aureus ATCC 29213, Bacillus subtilis NRRL 4219 and Bacillus cereus), yeast-like pathogenic fungus (Candida albicans ATCC 10231) and a fungus (Aspergillusniger NRRL 599). The best antibacterial activity was displayed by compounds 3a, 3b, 4a, 5a, 5b, 6d, 6f, 7b and 7d, whereas compounds 4b, 5b, 5c, 6a, 6b and 6f exhibited the best antifungal activity. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Protective Effects of Quercetin and Quercetin-5',8-Disulfonate against Carbon Tetrachloride-Caused Oxidative Liver Injury in Mice
Molecules 2014, 19(1), 291-305; doi:10.3390/molecules19010291
Received: 22 November 2013 / Revised: 5 December 2013 / Accepted: 12 December 2013 / Published: 27 December 2013
Cited by 8 | PDF Full-text (1226 KB) | HTML Full-text | XML Full-text
Abstract
Oxidative stress is one of the major factors in the pathogenesis of liver disease. Quercetin is a plant-based antioxidant traditionally used as a treatment for hepatic injury, but its poor solubility affects its bioavailability. We here report the regulative effects on hepatoprotection and
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Oxidative stress is one of the major factors in the pathogenesis of liver disease. Quercetin is a plant-based antioxidant traditionally used as a treatment for hepatic injury, but its poor solubility affects its bioavailability. We here report the regulative effects on hepatoprotection and absorption in mice of quercetin sulfation to form quercetin-5',8-disulfonate (QS), a novel synthetic compound. Oral administration of both QS and the parent quercetin at 100, 200 and 500 mg/kg·bw prior to acute CCl4 oxidative damage in mice, effectively attenuated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities and hepatic malondialdehyde (MDA) levels (p < 0.05), and suppressed the CCl4-induced depletion of glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD). Selective 5',8-sulfation of quercetin increased the hepatoprotective effect, and its relative absorption relative to quercetin (p < 0.05) as indicated by an improved 24-hour urinary excretion and a decreased fecal excretion determined by HPLC. These results and histopathological observations collectively demonstrate that quercetin sulfation increases its hepatoprotective effects and absorption in mice, and QS has potential as a chemopreventive and chemotherapeutic agent for liver diseases. Full article
Open AccessCommunication Nucleophilic Trapping Nitrilimine Generated by Photolysis of Diaryltetrazole in Aqueous Phase
Molecules 2014, 19(1), 306-315; doi:10.3390/molecules19010306
Received: 1 October 2013 / Revised: 6 December 2013 / Accepted: 18 December 2013 / Published: 27 December 2013
Cited by 8 | PDF Full-text (493 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nitrilimine generated by photolysis of diaryltetrazole in aqueous phase under mild conditions was trapped by nucleophiles including amines and thioalcohols. The representative products were characterized, while products with all 20 natural amino acids and a peptide were observed by MALDI-TOF mass spectroscopy. Competitive
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Nitrilimine generated by photolysis of diaryltetrazole in aqueous phase under mild conditions was trapped by nucleophiles including amines and thioalcohols. The representative products were characterized, while products with all 20 natural amino acids and a peptide were observed by MALDI-TOF mass spectroscopy. Competitive studies showed that this reaction also occurred in the presence of acrylamide. These results provided new information for understanding the potential side reactions when tetrazole-alkene pairs were used as a bioorthogonal reaction in labeling proteins and related studies in buffered systems. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Cytoprotective Effect of American Ginseng in a Rat Ethanol Gastric Ulcer Model
Molecules 2014, 19(1), 316-326; doi:10.3390/molecules19010316
Received: 4 November 2013 / Revised: 14 December 2013 / Accepted: 23 December 2013 / Published: 27 December 2013
Cited by 7 | PDF Full-text (1896 KB) | HTML Full-text | XML Full-text
Abstract
Panax quinquefolium L. (American Ginseng, AG) is one of the most popular herbal medicines in the World. We aimed to investigate whether chronic (28-day) supplementation with AG could protect against ethanol-induced ulcer in gastric tissue. Furthermore, we investigated the possible molecular mechanisms leading
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Panax quinquefolium L. (American Ginseng, AG) is one of the most popular herbal medicines in the World. We aimed to investigate whether chronic (28-day) supplementation with AG could protect against ethanol-induced ulcer in gastric tissue. Furthermore, we investigated the possible molecular mechanisms leading to AG-mediated gastric mucosal protection. We randomized 32 male Wistar rats into four groups for treatment (n = 8 per group): supplementation with water (vehicle) and low-dose (AG-1X), medium-dose (AG-2X) and high-dose (AG-5X) AG at 0, 250, 500, and 1250 mg/kg, respectively. In the first experiment, animals were fed vehicle or AG treatments for 4 weeks. At day 29, 75% ethanol was given orally to each animal at 10 mL/kg to induce gastric ulceration for 2 h. In a second experiment, animals were pretreated orally with each treatment for 1 hr before a single oral administration of ethanol (70%, 10 mL/kg). Trend analysis revealed that AG treatments inhibited ethanol-induced gastric mucosal damage. AG supplementation dose-dependently decreased the pro-inflammatory levels of interleukin 1β and cyclooxygenase 2 and the expression of pro-apoptotic proteins tBid, cytochrome C, and caspases-9 and -3 and increased the levels of anti-apoptotic proteins Bcl-2, Bcl-xL and p-Bad. AG could have pharmacological potential for treating gastric ulcer. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle 1,6- and 1,7-Regioisomers of Asymmetric and Symmetric Perylene Bisimides: Synthesis, Characterization and Optical Properties
Molecules 2014, 19(1), 327-341; doi:10.3390/molecules19010327
Received: 25 November 2013 / Revised: 10 December 2013 / Accepted: 11 December 2013 / Published: 27 December 2013
Cited by 6 | PDF Full-text (1661 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The 1,6- and 1,7-regioisomers of dinitro- (1,6-A and 1,7-A) and diamino-substituted perylene bisimides (1,6-B and 1,7-B), and 1-amino-6-nitro- and 1-amino-7-nitroperylene bisimides (1,6-C and 1,7-C) were synthesized. The 1,6-A and 1,7-A regioisomers were
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The 1,6- and 1,7-regioisomers of dinitro- (1,6-A and 1,7-A) and diamino-substituted perylene bisimides (1,6-B and 1,7-B), and 1-amino-6-nitro- and 1-amino-7-nitroperylene bisimides (1,6-C and 1,7-C) were synthesized. The 1,6-A and 1,7-A regioisomers were successfully separated by high performance liquid chromatography and characterized by 500 MHz 1H-NMR spectroscopy, and subsequently, their reduction which afforded the corresponding diaminoperylene bisimides 1,6-B and 1,7-B, respectively. On the other hand, the monoreduction of 1,6-A and 1,7-A, giving the asymmetric 1-amino-6-nitro (1,6-C) and 1-amino-7-nitroperylene bisimides (1,7-C), respectively, can be performed by shortening the reaction time from 6 h to 1 h. This is the first time the asymmetric 1,6-disubstituted perylene bisimide 1,6-C is obtained in pure form. The photophysical properties of 1,6-A and 1,7-A were found to be almost the same. However, the regioisomers 1,6-C and 1,7-C, as well as 1,6-B and 1,7-B, exhibit significant differences in their optical characteristics. Time-dependent density functional theory calculations performed on these dyes are reported in order to rationalize their electronic structure and absorption spectra. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Development of a Supercritical Fluid Chromatography-Tandem Mass Spectrometry Method for the Determination of Azacitidine in Rat Plasma and Its Application to a Bioavailability Study
Molecules 2014, 19(1), 342-351; doi:10.3390/molecules19010342
Received: 29 October 2013 / Revised: 18 December 2013 / Accepted: 19 December 2013 / Published: 27 December 2013
Cited by 3 | PDF Full-text (480 KB) | HTML Full-text | XML Full-text
Abstract
Azacitidine is widely used for the treatment of myelodysplastic syndromes (MDS) and acute myelogenous leukaemia (AML). The analysis of azacitidine in biological samples is subject to interference by endogenous compounds. Previously reported high-performance liquid chromatography/tandem mass spectrometric (HPLC-MS/MS) bioanalytical assays for azacitidine suffer
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Azacitidine is widely used for the treatment of myelodysplastic syndromes (MDS) and acute myelogenous leukaemia (AML). The analysis of azacitidine in biological samples is subject to interference by endogenous compounds. Previously reported high-performance liquid chromatography/tandem mass spectrometric (HPLC-MS/MS) bioanalytical assays for azacitidine suffer from expensive sample preparation procedures or from long separation times to achieve the required selectivity. Herein, supercritical fluid chromatography with tandem mass spectrometry (SFC-MS/MS) was explored as a more promising technique for the selective analysis of structure-like or chiral drugs in biological matrices. In this study, a simple, rapid and specific SFC/MS/MS analytical method was developed for the determination of azacitidine levels in rat plasma. Azacitidine was completely separated from the endogenous compounds on an ACQUITY UPLC™ BEH C18 column (100 mm × 3.0 mm, 1.7 μm; Waters Corp., Milford, MA, USA) using isocratic elution with CO2/methanol as the mobile phase. The single-run analysis time was as short as 3.5 min. The sample preparation for protein removal was accomplished using a simple methanol precipitation method. The lower limit of quantification (LLOQ) of azacitidine was 20 ng/mL. The intra-day and inter-day precisions were less than 15%, and the relative error (RE) was within ±15% for the medium- and high-concentration quality control (QC) samples and within ±20% for the low-concentration QC samples. Finally, the developed method was successfully applied to a pharmacokinetic study in rats following the intravenous administration of azacitidine. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Pyrene-Fullerene C60 Dyads as Light-Harvesting Antennas
Molecules 2014, 19(1), 352-366; doi:10.3390/molecules19010352
Received: 4 December 2013 / Revised: 19 December 2013 / Accepted: 20 December 2013 / Published: 30 December 2013
PDF Full-text (1240 KB) | HTML Full-text | XML Full-text
Abstract
A series of pyrene-fullerene C60 dyads bearing pyrene units (PyFC12, PyFPy, Py2FC12 and PyFN) were synthesized and characterized. Their optical properties were studied by absorption and fluorescence spectroscopies. Dyads were designed in this way because
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A series of pyrene-fullerene C60 dyads bearing pyrene units (PyFC12, PyFPy, Py2FC12 and PyFN) were synthesized and characterized. Their optical properties were studied by absorption and fluorescence spectroscopies. Dyads were designed in this way because the pyrene moeities act as light-harvesting molecules and are able to produce “monomer” (PyFC12) or excimer emission (PyFPy, Py2FC12 and PyFN). The fluorescence spectra of the dyads exhibited a significant decrease in the amount of pyrene monomer and excimer emission, without the appearance of a new emission band due to fullerene C60. The pyrene fluorescence quenching was found to be almost quantitative, ranging between 96%–99% depending on the construct, which is an indication that energy transfer occurred from one of the excited pyrene species to the fullerene C60. Full article
Open AccessArticle A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial Activity
Molecules 2014, 19(1), 367-399; doi:10.3390/molecules19010367
Received: 21 October 2013 / Revised: 19 November 2013 / Accepted: 19 November 2013 / Published: 30 December 2013
Cited by 7 | PDF Full-text (2262 KB) | HTML Full-text | XML Full-text
Abstract
The Hartree-Fock method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with antimalarial activity. Maps of molecular electrostatic potential (MEPs) and molecular docking were used to investigate the interaction between ligands and the receptor
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The Hartree-Fock method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with antimalarial activity. Maps of molecular electrostatic potential (MEPs) and molecular docking were used to investigate the interaction between ligands and the receptor (heme). Principal component analysis and hierarchical cluster analysis were employed to select the most important descriptors related to activity. The correlation between biological activity and molecular properties was obtained using the partial least squares and principal component regression methods. The regression PLS and PCR models built in this study were also used to predict the antimalarial activity of 30 new artemisinin compounds with unknown activity. The models obtained showed not only statistical significance but also predictive ability. The significant molecular descriptors related to the compounds with antimalarial activity were the hydration energy (HE), the charge on the O11 oxygen atom (QO11), the torsion angle O1-O2-Fe-N2 (D2) and the maximum rate of R/Sanderson Electronegativity (RTe+). These variables led to a physical and structural explanation of the molecular properties that should be selected for when designing new ligands to be used as antimalarial agents. Full article
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Open AccessArticle Synthesis, Anticancer Activity and UPLC Analysis of the Stability of Some New Benzimidazole-4,7-dione Derivatives
Molecules 2014, 19(1), 400-413; doi:10.3390/molecules19010400
Received: 21 October 2013 / Revised: 9 December 2013 / Accepted: 16 December 2013 / Published: 31 December 2013
Cited by 6 | PDF Full-text (347 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this work, a sensitive analytical method to study the stability of two new series of synthesized heterocyclic compounds, the benzimidazole-4,7-diones 5 and N-oxide benzimidazole-4,7-dione derivatives 6 was established and validated. These derivatives were developed as potential anticancer substances to be activated
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In this work, a sensitive analytical method to study the stability of two new series of synthesized heterocyclic compounds, the benzimidazole-4,7-diones 5 and N-oxide benzimidazole-4,7-dione derivatives 6 was established and validated. These derivatives were developed as potential anticancer substances to be activated under hypoxic conditions. At this point we were concerned with establishing their stability in some specific environments for further biological studies. For that, we developed and validated an RP-UPLC method. Next, selected compounds were tested in vitro for possible anticancer activity. Their effect on A549 tumour cell lines under normoxia and hypoxia conditions was determined by a WST-1 test. Four of the examined compounds (compounds 5ac and 6c) showed very good antiproliferative effects and three of them (compounds 6a, 6b and 6d) were specific for hypoxia conditions. The hypoxia/normoxia cytotoxic coefficient of compound 6b is close to that of tirapazamine—a reference compound in our experiments—and this parameter locates it between mitomycin C and 2-nitroimidazole (misonidazole). Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle A New Chemical Approach to Human ABO Histo-Blood Group Type 2 Antigens
Molecules 2014, 19(1), 414-437; doi:10.3390/molecules19010414
Received: 13 December 2013 / Revised: 24 December 2013 / Accepted: 25 December 2013 / Published: 31 December 2013
Cited by 9 | PDF Full-text (402 KB) | HTML Full-text | XML Full-text
Abstract
A new chemical approach to synthesizing human ABO histo-blood type 2 antigenic determinants was developed. N-Phthaloyl-protected lactosaminyl thioglycoside derived from lactulose via the Heyns rearrangement was employed to obtain a type 2 core disaccharide. Use of this scheme lowered the overall number
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A new chemical approach to synthesizing human ABO histo-blood type 2 antigenic determinants was developed. N-Phthaloyl-protected lactosaminyl thioglycoside derived from lactulose via the Heyns rearrangement was employed to obtain a type 2 core disaccharide. Use of this scheme lowered the overall number of reaction steps. Stereoselective construction of the α-galactosaminide/galactoside found in A- and B-antigens, respectively, was achieved by using a unique di-tert-butylsilylene-directed α-glycosylation method. The proposed synthetic scheme provides an alternative to existing procedures for preparing ABO blood group antigens. Full article
(This article belongs to the Special Issue Oligosaccharides and Glyco-Conjugates)
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Open AccessArticle Antioxidant Properties and Hyphenated HPLC-PDA-MS Profiling of Chilean Pica Mango Fruits (Mangifera indica L. Cv. piqueño)
Molecules 2014, 19(1), 438-458; doi:10.3390/molecules19010438
Received: 12 November 2013 / Revised: 22 December 2013 / Accepted: 23 December 2013 / Published: 31 December 2013
Cited by 10 | PDF Full-text (744 KB) | HTML Full-text | XML Full-text
Abstract
Antioxidant capacities and polyphenolic contents of two mango cultivars from northern Chile, one of them endemic of an oasis in the Atacama Desert, were compared for the first time. Twenty one phenolic compounds were detected in peel and pulp of mango fruits varieties
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Antioxidant capacities and polyphenolic contents of two mango cultivars from northern Chile, one of them endemic of an oasis in the Atacama Desert, were compared for the first time. Twenty one phenolic compounds were detected in peel and pulp of mango fruits varieties Pica and Tommy Atkins by HPLC-PDA-MS and tentatively characterized. Eighteen compounds were present in Pica pulp (ppu), 13 in Pica peel (ppe) 11 in Tommy Atkins pulp (tpu) and 12 in Tommy Atkins peel (tpe). Three procyanidin dimers (peaks 6, 9 and 10), seven acid derivatives (peaks 14, 11, 20 and 21) and four xanthones were identified, mainly mangiferin (peak 12) and mangiferin gallate, (peak 7), which were present in both peel and pulp of the two studied species from northern Chile. Homomangiferin (peak 13) was also present in both fruit pulps and dimethylmangiferin (peak 14) was present only in Tommy pulp. Pica fruits showed better antioxidant capacities and higher polyphenolic content (73.76/32.23 µg/mL in the DPPH assay and 32.49/72.01 mg GAE/100 g fresh material in the TPC assay, for edible pulp and peel, respectively) than Tommy Atkins fruits (127.22/46.39 µg/mL in the DPPH assay and 25.03/72.01 mg GAE/100 g fresh material in the TPC assay for pulp and peel, respectively). The peel of Pica mangoes showed also the highest content of phenolics (66.02 mg/100 g FW) measured by HPLC-PDA. The HPLC generated fingerprint can be used to authenticate Pica mango fruits and Pica mango food products. Full article
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Open AccessArticle NMR Structural Study of the Prototropic Equilibrium in Solution of Schiff Bases as Model Compounds
Molecules 2014, 19(1), 459-481; doi:10.3390/molecules19010459
Received: 28 October 2013 / Revised: 12 December 2013 / Accepted: 13 December 2013 / Published: 31 December 2013
Cited by 2 | PDF Full-text (2860 KB) | HTML Full-text | XML Full-text
Abstract
An NMR titration method has been used to simultaneously measure the acid dissociation constant (pKa) and the intramolecular NHO prototropic constant ΔKNHOon a set of Schiff bases. The model compounds were synthesized from benzylamine and substituted ortho
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An NMR titration method has been used to simultaneously measure the acid dissociation constant (pKa) and the intramolecular NHO prototropic constant ΔKNHO on a set of Schiff bases. The model compounds were synthesized from benzylamine and substituted ortho-hydroxyaldehydes, appropriately substituted with electron-donating and electron-withdrawing groups to modulate the acidity of the intramolecular NHO hydrogen bond. The structure in solution was established by 1H-, 13C- and 15N-NMR spectroscopy. The physicochemical parameters of the intramolecular NHO hydrogen bond (pKa, ΔKNHO and ΔΔG°) were obtained from 1H-NMR titration data and pH measurements. The Henderson–Hasselbalch data analysis indicated that the systems are weakly acidic, and the predominant NHO equilibrium was established using Polster–Lachmann δ-diagram analysis and Perrin model data linearization. Full article
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Open AccessArticle Wine by-Products: Phenolic Characterization and Antioxidant Activity Evaluation of Grapes and Grape Pomaces from Six Different French Grape Varieties
Molecules 2014, 19(1), 482-506; doi:10.3390/molecules19010482
Received: 22 November 2013 / Revised: 21 December 2013 / Accepted: 25 December 2013 / Published: 2 January 2014
Cited by 24 | PDF Full-text (350 KB) | HTML Full-text | XML Full-text
Abstract
Grenache, Syrah, Carignan Noir, Mourvèdre, Counoise and Alicante Bouchet grape seeds and skins, harvested in 2009 and 2010 in the Rhône valley area of France, and their respective pomaces remaining after vinification, were analyzed for their phenolic composition and antioxidant activity. The polyphenol
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Grenache, Syrah, Carignan Noir, Mourvèdre, Counoise and Alicante Bouchet grape seeds and skins, harvested in 2009 and 2010 in the Rhône valley area of France, and their respective pomaces remaining after vinification, were analyzed for their phenolic composition and antioxidant activity. The polyphenol content was quantified by HPLC and the Folin-Ciocalteu assay. The antioxidant potential was measured with four different assays: ORAC, FRAP, ABTS and DPPH. Seeds contained higher amounts of total polyphenols, up to 44.5 mg of gallic acid equivalent [GAE]/g dry weight in Alicante pomace, than skin extracts. The maximum total phenolic in skins was 31.6 mg GAE/g dry weight detected in 2010 Alicante pomace. Seeds also had the highest antioxidant capacity. HPLC analysis revealed that, despite the vinification process, pomaces still contained an appreciable amount of proanthocyanidins as well as several anthocyanin glycosides. Alicante and Syrah proved to be the varieties of most interest in terms of their potential development for nutraceutical purposes. Full article
Open AccessArticle Characterization of a New Sesquiterpene and Antifungal Activities of Chemical Constituents from Dryopteris fragrans (L.) Schott
Molecules 2014, 19(1), 507-513; doi:10.3390/molecules19010507
Received: 14 October 2013 / Revised: 25 November 2013 / Accepted: 28 November 2013 / Published: 2 January 2014
Cited by 9 | PDF Full-text (275 KB) | HTML Full-text | XML Full-text
Abstract
One new sesquiterpene and six known compounds were isolated from Dryopteris fragrans (L.) Schot. They were identified as 3-O-β-D-glucopyranosylalbicanol- 11-O-β-D-glucopyranoside (1), dihydroconiferylalcohol (2), (E)-3-(4-hydroxyphenyl)acrylic acid (3), esculetin
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One new sesquiterpene and six known compounds were isolated from Dryopteris fragrans (L.) Schot. They were identified as 3-O-β-D-glucopyranosylalbicanol- 11-O-β-D-glucopyranoside (1), dihydroconiferylalcohol (2), (E)-3-(4-hydroxyphenyl)acrylic acid (3), esculetin (4), 5,7-dihydroxy-2-hydroxymethylchromone (5), eriodictyol (6) and isoorientin (7) by UV, MS, 1D-NMR and 2D-NMR spectroscopy. The antifungal activities of the seven isolated compounds were screened. Compounds 2, 3, 4 and 5 showed obvious activities against Microsporum canis and Epidermophyton floccosum. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle New Natural Diterpene-Type Abietane from Tetradenia riparia Essential Oil with Cytotoxic and Antioxidant Activities
Molecules 2014, 19(1), 514-524; doi:10.3390/molecules19010514
Received: 12 December 2013 / Revised: 24 December 2013 / Accepted: 25 December 2013 / Published: 3 January 2014
Cited by 7 | PDF Full-text (283 KB) | HTML Full-text | XML Full-text
Abstract
Tetradenia riparia (Hochstetter) Codd belongs to the Lamiaceae family and it was introduced in Brazil as an exotic ornamental plant. A previous study showed its antimicrobial, acaricidal and analgesic activities. Two compounds were isolated from essential oil of T. riparia leaves and identified
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Tetradenia riparia (Hochstetter) Codd belongs to the Lamiaceae family and it was introduced in Brazil as an exotic ornamental plant. A previous study showed its antimicrobial, acaricidal and analgesic activities. Two compounds were isolated from essential oil of T. riparia leaves and identified as 9β,13β-epoxy-7-abietene (1), a new one, and 6,7-dehydroroyleanone (2), already reported for another plant. The structure of these compounds was determined by spectroscopic analysis and by comparison with literature data. The cytotoxic activities of the essential oil and compounds 1 and 2 were determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, and by tumor cells MDA-MB-435 (human breast carcinoma), HCT-8 (human colon), SF-295 (human nervous system) and HL-60 (human promyelocytic leukemia). The essential oil and compound 1 showed high cytotoxic potential of the cell lines SF-295 (78.06% and 94.80%, respectively), HCT-8 (85.00% and 86.54%, respectively) and MDA-MB-435 (59.48% and 45.43%, respectively). Compound 2 had no cytotoxic activity. The antioxidant activity was determined by 2,2-diphenyl-1-picryl-hydrazyl (DPPH), β-carotene-linoleic acid system and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. The inhibitory concentration (IC50 in µg mL−1) for essential oil and compound 2 was, respectively 15.63 and 0.01 for DPPH; 130.1 and 109.6 for β-carotene-linoleic acid and 1524 and 1024 for ABTS. Compound 1 had no antioxidant activity. By fractioning the oil, it was possible to identify two unpublished compounds: 1 with high cytotoxic potential and 2 with high antioxidant potential. Full article
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Open AccessCommunication Saccharide Substituted Zinc Phthalocyanines: Optical Properties, Interaction with Bovine Serum Albumin and Near Infrared Fluorescence Imaging for Sentinel Lymph Nodes
Molecules 2014, 19(1), 525-537; doi:10.3390/molecules19010525
Received: 20 November 2013 / Revised: 24 December 2013 / Accepted: 24 December 2013 / Published: 3 January 2014
Cited by 4 | PDF Full-text (1986 KB) | HTML Full-text | XML Full-text
Abstract
Saccharide-substituted zinc phthalocyanines, [2,9(10),16(17),23(24)-tetrakis((1-(β-D-glucose-2-yl)-1H-1,2,3-triazol-4-yl)methoxy)phthalocyaninato]zinc(II) and [2,9(10), 16(17),23(24)-tetrakis((1-(β-D-lactose-2-yl)-1H-1,2,3-triazol-4-yl)methoxy)phthalocyaninato] zinc(II), were evaluated as novel near infrared fluorescence agents. Their interaction with bovine serum albumin was investigated by fluorescence and circular dichroism spectroscopy and isothermal titration calorimetry. Near infrared imaging for sentinel
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Saccharide-substituted zinc phthalocyanines, [2,9(10),16(17),23(24)-tetrakis((1-(β-D-glucose-2-yl)-1H-1,2,3-triazol-4-yl)methoxy)phthalocyaninato]zinc(II) and [2,9(10), 16(17),23(24)-tetrakis((1-(β-D-lactose-2-yl)-1H-1,2,3-triazol-4-yl)methoxy)phthalocyaninato] zinc(II), were evaluated as novel near infrared fluorescence agents. Their interaction with bovine serum albumin was investigated by fluorescence and circular dichroism spectroscopy and isothermal titration calorimetry. Near infrared imaging for sentinel lymph nodes in vivo was performed using nude mice as models. Results show that saccharide- substituted zinc phthalocyanines have favourable water solubility, good optical stability and high emission ability in the near infrared region. The interaction of lactose-substituted phthalocyanine with bovine serum albumin displays obvious differences to that of glucose- substituted phthalocyanine. Moreover, lactose-substituted phthalocyanine possesses obvious imaging effects for sentinel lymph nodes in vivo. Full article
(This article belongs to the Special Issue Fluorescent Probes)
Open AccessArticle Pharmacokinetics of BMEDA after Intravenous Administration in Beagle Dogs
Molecules 2014, 19(1), 538-549; doi:10.3390/molecules19010538
Received: 14 October 2013 / Revised: 2 December 2013 / Accepted: 3 December 2013 / Published: 3 January 2014
PDF Full-text (200 KB) | HTML Full-text | XML Full-text
Abstract
The pharmacokinetics of N,N-bis(2-mercapatoethly)-N',N'-diethylenediamine (BMEDA), a molecule that can form a chelate with rhenium-188 (188Re) to produce the 188Re-BMEDA-liposomes, was studied. In this work, beagles received a single injection of BMEDA, at doses
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The pharmacokinetics of N,N-bis(2-mercapatoethly)-N',N'-diethylenediamine (BMEDA), a molecule that can form a chelate with rhenium-188 (188Re) to produce the 188Re-BMEDA-liposomes, was studied. In this work, beagles received a single injection of BMEDA, at doses of 1, 2, or 5 mg/kg; the concentration of BMEDA in the beagles’ plasma was then analyzed and determined by liquid chromatography-mass spectrometry/mass spectrometry. Based on the pharmacokinetic parameters of BMEDA, we found that male and female animals shared similar patterns indicating that the pharmacokinetics of BMEDA is independent of gender differences. In addition, the pharmacokinetics of BMEDA was seen to be non-linear because the increase of mean AUC0–t and AUC0–∞ values tend to be greater than dose proportional while the mean Vss and CL values of BMEDA appeared to be dose dependent. The information on the pharmacokinetics of BMEDA generated from this study will serve as a basis to design appropriate pharmacology and toxicology studies for future human use. Full article
Open AccessArticle [15]aneN4S: Synthesis, Thermodynamic Studies and Potential Applications in Chelation Therapy
Molecules 2014, 19(1), 550-567; doi:10.3390/molecules19010550
Received: 2 December 2013 / Revised: 23 December 2013 / Accepted: 24 December 2013 / Published: 3 January 2014
PDF Full-text (765 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The purpose of this work was to synthesize and characterize the thiatetraaza macrocycle 1-thia-4,7,10,13-tetraazacyclopentadecane ([15]aneN4S). Its acid-base behaviour was studied by potentiometry at 25 °C and ionic strength 0.10 M in KNO3. The protonation sequence of this ligand was
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The purpose of this work was to synthesize and characterize the thiatetraaza macrocycle 1-thia-4,7,10,13-tetraazacyclopentadecane ([15]aneN4S). Its acid-base behaviour was studied by potentiometry at 25 °C and ionic strength 0.10 M in KNO3. The protonation sequence of this ligand was investigated by 1H-NMR titration that also allowed the determination of protonation constants in D2O. Binding studies of [15]aneN4S with Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+ and Pb2+ metal ions were further performed under the same experimental conditions. The results demonstrated that this compound has a higher selectivity and thermodynamic stability for Hg2+ and Cu2+, followed by Ni2+. The UV-visible-near IR spectroscopies and magnetic moment data for the Co(II) and Ni(II) complexes indicated a tetragonal distorted coordination geometry for both metal centres. The value of magnetic moment and the X-band EPR spectra of the Cu(II) complex are consistent with a distorted square pyramidal geometry. Full article
(This article belongs to the Special Issue Macrocyclic Chemistry)
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Open AccessArticle Hormesis of Glyceollin I, an Induced Phytoalexin from Soybean, on Budding Yeast Chronological Lifespan Extension
Molecules 2014, 19(1), 568-580; doi:10.3390/molecules19010568
Received: 25 November 2013 / Revised: 19 December 2013 / Accepted: 20 December 2013 / Published: 6 January 2014
Cited by 1 | PDF Full-text (477 KB) | HTML Full-text | XML Full-text
Abstract
Glyceollin I, an induced phytoalexin isolated from soybean, has been reported to have various bioactivities, including anti-bacterial, anti-nematode, anti-fungal, anti-estrogenic and anti-cancer, anti-oxidant, anti-inflammatory, insulin sensitivity enhancing, and attenuation of vascular contractions. Here we show that glyceollin I has hormesis and extends yeast
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Glyceollin I, an induced phytoalexin isolated from soybean, has been reported to have various bioactivities, including anti-bacterial, anti-nematode, anti-fungal, anti-estrogenic and anti-cancer, anti-oxidant, anti-inflammatory, insulin sensitivity enhancing, and attenuation of vascular contractions. Here we show that glyceollin I has hormesis and extends yeast life span at low (nM) doses in a calorie restriction (CR)-dependent manner, while it reduces life span and inhibits yeast cell proliferation at higher (μM) doses. In contrast, the other two isomers (glyceollin II and III) cannot extend yeast life span and only show life span reduction and antiproliferation at higher doses. Our results in anti-aging activity indicate that glyceollin I might be a promising calorie restriction mimetic candidate, and the high content of glyceollins could improve the bioactivity of soybean as functional food ingredients. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Gastroprotective Mechanisms of Action of Semisynthetic Carnosic Acid Derivatives in Human Cells
Molecules 2014, 19(1), 581-594; doi:10.3390/molecules19010581
Received: 2 December 2013 / Revised: 30 December 2013 / Accepted: 30 December 2013 / Published: 6 January 2014
Cited by 3 | PDF Full-text (234 KB) | HTML Full-text | XML Full-text
Abstract
Carnosic acid (CA) and its semisynthetic derivatives display relevant gastroprotective effects on HCl/ethanol induced gastric lesions in mice. However, little is known on the mechanisms of action of the new compounds. The aim of the present work was to assess the gastroprotective action
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Carnosic acid (CA) and its semisynthetic derivatives display relevant gastroprotective effects on HCl/ethanol induced gastric lesions in mice. However, little is known on the mechanisms of action of the new compounds. The aim of the present work was to assess the gastroprotective action mechanisms of CA and its derivatives using human cell culture models. A human gastric adenocarcinoma cell line (AGS) and lung fibroblasts (MRC-5) were used to reveal the possible mechanisms involved. The ability of the compounds to protect cells against sodium taurocholate (NaT)-induced damage, and to increase the cellular reduced glutathione (GSH) and prostaglandin E2 (PGE2) content was determined using AGS cells. Stimulation of cell proliferation was studied employing MRC-5 fibroblasts. Carnosic acid and its derivatives 1018 raised GSH levels in AGS cells. While CA did not increase the PGE2 content in AGS cells, all derivatives significantly stimulated PGE2 synthesis, the best effect being found for the 12-O-indolebutyrylmethylcarnosate 13. A significant increase in MRC-5 fibroblast proliferation was observed for the derivatives 7 and 1618. The antioxidant effect of the compounds was assessed by the inhibition of lipid peroxidation in human erythrocyte membranes, scavenging of superoxide anion and DPPH discoloration assay. The new CA derivatives showed gastroprotective effects by different mechanisms, including protection against cell damage induced by NaT, increase in GSH content, stimulation of PGE2 synthesis and cell proliferation. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle The Human Telomere Sequence, (TTAGGG)4, in the Absence and Presence of Cosolutes: A Spectroscopic Investigation
Molecules 2014, 19(1), 595-608; doi:10.3390/molecules19010595
Received: 6 November 2013 / Revised: 13 December 2013 / Accepted: 18 December 2013 / Published: 6 January 2014
Cited by 3 | PDF Full-text (321 KB) | HTML Full-text | XML Full-text
Abstract
Historically, biophysical studies of nucleic acids have been carried out under near ideal conditions, i.e., low buffer concentration (e.g., 10 mM phosphate), pH 7, low ionic strength (e.g., 100 mM) and, for optical studies, low concentrations of DNA (e.g., 1 × 10
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Historically, biophysical studies of nucleic acids have been carried out under near ideal conditions, i.e., low buffer concentration (e.g., 10 mM phosphate), pH 7, low ionic strength (e.g., 100 mM) and, for optical studies, low concentrations of DNA (e.g., 1 × 10−6 M). Although valuable structural and thermodynamic data have come out of these studies, the conditions, for the most, part, are inadequate to simulate realistic cellular conditions. The increasing interest in studying biomolecules under more cellular-like conditions prompted us to investigate the effect of osmotic stress on the structural and thermodynamic properties of DNA oligomers containing the human telomere sequence (TTAGGG). Here, we report the characterization of (TTAGGG)4 in potassium phosphate buffer with increasing percent PEG (polyethylene glycol) or acetonitrile. In general, the presence of these cosolutes induces a conformational change from a unimolecular hybrid structure to a multimolecular parallel stranded structure. Hence, the structural change is accompanied with a change in the molecularity of quadruplex formation. Full article
(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)
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Open AccessArticle Toxicity Assessments of Chalcone and Some Synthetic Chalcone Analogues in a Zebrafish Model
Molecules 2014, 19(1), 641-650; doi:10.3390/molecules19010641
Received: 31 October 2013 / Revised: 4 December 2013 / Accepted: 17 December 2013 / Published: 7 January 2014
Cited by 5 | PDF Full-text (1089 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to investigate the in vivo toxicities of some novel synthetic chalcones. Chalcone and four chalcone analogues 1ad were evaluated using zebrafish embryos following antibody staining to visualize their morphological changes and muscle fiber alignment. Results
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The aim of this study was to investigate the in vivo toxicities of some novel synthetic chalcones. Chalcone and four chalcone analogues 1ad were evaluated using zebrafish embryos following antibody staining to visualize their morphological changes and muscle fiber alignment. Results showed that embryos treated with 3'-hydroxychalcone (compound 1b) displayed a high percentage of muscle defects (96.6%), especially myofibril misalignment. Ultrastructural analysis revealed that compound 1b-treated embryos displayed many muscle defect phenotypes, including breakage and collapse of myofibrils, reduced cell numbers, and disorganized thick (myosin) and thin (actin) filaments. Taken together, our results provide in vivo evidence of the myotoxic effects of the synthesized chalcone analogues on developing zebrafish embryos. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties
Molecules 2014, 19(1), 651-671; doi:10.3390/molecules19010651
Received: 2 December 2013 / Revised: 29 December 2013 / Accepted: 31 December 2013 / Published: 7 January 2014
Cited by 6 | PDF Full-text (392 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this work a series of 15 N-benzylamine substituted 5-amino-6-methyl-pyrazine-2,3-dicarbonitriles was prepared by the aminodehalogenation reactions using microwave assisted synthesis with experimentally set and proven conditions. This approach for the aminodehalogenation reaction was chosen due to its higher yields and shorter reaction
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In this work a series of 15 N-benzylamine substituted 5-amino-6-methyl-pyrazine-2,3-dicarbonitriles was prepared by the aminodehalogenation reactions using microwave assisted synthesis with experimentally set and proven conditions. This approach for the aminodehalogenation reaction was chosen due to its higher yields and shorter reaction times. The products of this reaction were characterized by IR, NMR and other analytical data. The compounds were evaluated for their antibacterial, antifungal and herbicidal activity. Compounds 3 (R = 3,4-Cl), 9 (R = 2-Cl) and 11 (R = 4-CF3) showed good antimycobacterial activity against Mycobacterium tuberculosis (MIC = 6.25 µg/mL). It was found that the lipophilicity is important for antimycobacterial activity and the best substitution on the benzyl moiety of the compounds is a halogen or trifluoromethyl group according to Craig’s plot. The activities against bacteria or fungi were insignificant. The presented compounds also inhibited photosynthetic electron transport in spinach chloroplasts and the IC50 values of the active compounds varied in the range from 16.4 to 487.0 µmol/L. The most active substances were 2 (R = 3-CF3), 3 (R = 3,4-Cl) and 11 (R = 4-CF3). A linear dependence between lipophilicity and herbicidal activity was observed. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle A STD-NMR Study of the Interaction of the Anabaena Ferredoxin-NADP+ Reductase with the Coenzyme
Molecules 2014, 19(1), 672-685; doi:10.3390/molecules19010672
Received: 24 September 2013 / Revised: 17 December 2013 / Accepted: 18 December 2013 / Published: 7 January 2014
PDF Full-text (686 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ferredoxin-NADP+ reductase (FNR) catalyzes the electron transfer from ferredoxin to NADP+ via its flavin FAD cofactor. To get further insights in the architecture of the transient complexes produced during the hydride transfer event between the enzyme and the NADP+ coenzyme
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Ferredoxin-NADP+ reductase (FNR) catalyzes the electron transfer from ferredoxin to NADP+ via its flavin FAD cofactor. To get further insights in the architecture of the transient complexes produced during the hydride transfer event between the enzyme and the NADP+ coenzyme we have applied NMR spectroscopy using Saturation Transfer Difference (STD) techniques to analyze the interaction between FNRox and the oxidized state of its NADP+ coenzyme. We have found that STD NMR, together with the use of selected mutations on FNR and of the non-FNR reacting coenzyme analogue NAD+, are appropriate tools to provide further information about the the interaction epitope. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
Open AccessArticle Study on the Mechanism of Intestinal Absorption of Epimedins A, B and C in the Caco-2 Cell Model
Molecules 2014, 19(1), 686-698; doi:10.3390/molecules19010686
Received: 6 November 2013 / Revised: 27 December 2013 / Accepted: 30 December 2013 / Published: 7 January 2014
Cited by 5 | PDF Full-text (580 KB) | HTML Full-text | XML Full-text
Abstract
Epimedium spp. is commonly used in Traditional Chinese Medicine. Epimedins A, B, and C are three major bioactive flavonoids found in Epimedium spp. that share similar chemical structures. In this study, the intestinal absorption mechanism of these three compounds was investigated using the
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Epimedium spp. is commonly used in Traditional Chinese Medicine. Epimedins A, B, and C are three major bioactive flavonoids found in Epimedium spp. that share similar chemical structures. In this study, the intestinal absorption mechanism of these three compounds was investigated using the Caco-2 cell monolayer model in both the apical-to-basolateral (A-B) and the basolateral-to-apical (B-A) direction. The absorption permeability (PAB) of epimedins A, B, and C were extremely low and increased as the concentration of the epimedins increased from 5 to 20 μM, but, at 40 μM, the PAB values were reduced. Meanwhile, the amount of transported compounds increased in a time-dependent manner. The PAB of epimedins A and C were significantly increased and efflux ratios decreased in the presence of verapamil (an inhibitor of P-glycoprotein) and dipyridamole (an inhibitor of breast cancer resistance protein) while, in the presence of MK571 (an inhibitor of multidrug resistance proteins), the absorption of epimedins A and C did not change significantly, indicating that P-gp and BCRP might be involved in the transport of epimedins A and C. The PAB of epimedin B significantly increased while its secretory permeability (PBA) significantly decreased in the presence of dipyridamole, indicating that BCRP might be involved in the transport of epimedin B. No obvious changes in the transport of epimedin B were observed in the presence of verapamil and MK571. In summary, our results clearly demonstrate, for the first time, that poor bioavailability of these three prenylated flavonoids is the result of poor intrinsic permeability and efflux by apical efflux transporters. Full article
Open AccessArticle Magnetically Separable and Recyclable Fe3O4-Supported Ag Nanocatalysts for Reduction of Nitro Compounds and Selective Hydration of Nitriles to Amides in Water
Molecules 2014, 19(1), 699-712; doi:10.3390/molecules19010699
Received: 28 November 2013 / Revised: 27 December 2013 / Accepted: 30 December 2013 / Published: 7 January 2014
Cited by 11 | PDF Full-text (870 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
As hybrid nanostructures have become more important in many fields of chemistry, Ag nanoparticles (NPs) are being increasingly immobilized onto Fe3O4 microspheres in situ. Structural characterization reveals that the Ag NPs are uniformly immobilized in the Fe3O
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As hybrid nanostructures have become more important in many fields of chemistry, Ag nanoparticles (NPs) are being increasingly immobilized onto Fe3O4 microspheres in situ. Structural characterization reveals that the Ag NPs are uniformly immobilized in the Fe3O4 microsphere-based supports. Moreover, Ag NPs are more stable in the hybrid structure than in the naked state and show high catalytic activity for the reduction of nitro compounds and hydration of nitriles to amides in water. The Fe3O4 microspheres were recycled several times using an external magnet. Full article
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Open AccessArticle Trifolium pratense L. as a Potential Natural Antioxidant
Molecules 2014, 19(1), 713-725; doi:10.3390/molecules19010713
Received: 2 December 2013 / Revised: 20 December 2013 / Accepted: 2 January 2014 / Published: 7 January 2014
Cited by 9 | PDF Full-text (220 KB) | HTML Full-text | XML Full-text
Abstract
The essential oils of three different growth stages of Trifolium pratense L. (TP1, TP2 and TP3) were investigated by gas chromatography-mass spectrometry and tested for their antioxidant and antimicrobial activities. The highest content of volatile compounds was found in the essential oil sample
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The essential oils of three different growth stages of Trifolium pratense L. (TP1, TP2 and TP3) were investigated by gas chromatography-mass spectrometry and tested for their antioxidant and antimicrobial activities. The highest content of volatile compounds was found in the essential oil sample TP1, where terpenes such as β-myrcene (4.55%), p-cymene (3.59%), limonene (0.86%), tetrahydroionone (1.56%) were highlighted due to their biological activity. The antioxidant activity was determined by following the scavenging capacity of the essential oils for the free radicals DPPH·, NO· and O2·-, as well as effects of the investigated oils on lipid peroxidation (LP). In all three cases, the sample TP1 showed the best radical-capturing capacity for DPPH· (27.61 ± 0.12 µg/mL), NO· (16.03 ± 0.11 µg/mL), O2·− (16.62 ± 0.29 µg/mL) and also had the best lipid peroxidation effects in the Fe2+/ascorbate induction system (9.35 ± 0.11 µg/mL). Antimicrobial activity was evaluated against the following bacteria cultures: Escherichia coli (ATCC10526), Salmonella typhimurium (ATCC 14028), Staphylococcus aureus (ATCC 11632) and Bacillus cereus (ATCC 10876). None of the examined essential oil samples showed inhibitory effects on the tested bacterial strains. Full article
Open AccessArticle Synthesis, Half-Wave Potentials and Antiproliferative Activity of 1-Aryl-substituted Aminoisoquinolinequinones
Molecules 2014, 19(1), 726-739; doi:10.3390/molecules19010726
Received: 29 November 2013 / Revised: 30 December 2013 / Accepted: 31 December 2013 / Published: 8 January 2014
Cited by 2 | PDF Full-text (331 KB) | HTML Full-text | XML Full-text
Abstract
The synthesis of a variety of 1-aryl-7-phenylaminoisoquinolinequinones from 1,4-benzoquinone and arylaldehydes via the respective 1-arylisoquinolinequinones is reported. The cyclic voltammograms of the new compounds exhibit two one-electron reduction waves to the corresponding radical-anion and dianion and two quasi-reversible oxidation peaks. The half-wave potential
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The synthesis of a variety of 1-aryl-7-phenylaminoisoquinolinequinones from 1,4-benzoquinone and arylaldehydes via the respective 1-arylisoquinolinequinones is reported. The cyclic voltammograms of the new compounds exhibit two one-electron reduction waves to the corresponding radical-anion and dianion and two quasi-reversible oxidation peaks. The half-wave potential values (EI½) of the members of the series have proven sensitive to the electron-donor effect of the aryl group (phenyl, 2-thienyl, 2-furyl) at the 1-position as well as to the phenylamino groups (anilino, p-anisidino) at the 7-position. The antiproliferative activity of the new compounds was evaluated in vitro using the MTT colorimetric method against one normal cell line (MRC-5 lung fibroblasts) and two human cancer cell lines: AGS human gastric adenocarcinoma and HL-60 human promyelocytic leukemia cells in 72-h drug exposure assays. Among the series, compounds 5a, 5b, 5g, 5h, 6a and 6d exhibited interesting antiproliferative activities against human gastric adenocarcinoma. The 1-arylisoquinolinequinone 6a was found to be the most promising active compound against the tested cancer cell lines in terms of IC50 values (1.19; 1.24 µM) and selectivity index (IS: 3.08; 2.96), respect to the anti-cancer agent etoposide used as reference (IS: 0.57; 0.14). Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Synthesis of 2-Phenylazonaphtho[1,8-ef][1,4]diazepines and 9-(3-Arylhydrazono)pyrrolo[1,2-a]perimidines as Antitumor Agents
Molecules 2014, 19(1), 740-755; doi:10.3390/molecules19010740
Received: 17 November 2013 / Revised: 16 December 2013 / Accepted: 17 December 2013 / Published: 8 January 2014
Cited by 9 | PDF Full-text (270 KB) | HTML Full-text | XML Full-text
Abstract
Two series of naphtho[1,8-ef][1,4]diazepines and pyrrolo[1,2-a]perimidines were prepared starting from 1,8-diaminonaphthalene and hydrazonoyl chlorides. The structures of the products were determined on the basis of their spectral data and elemental analyses. The mechanism of formation of such products was
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Two series of naphtho[1,8-ef][1,4]diazepines and pyrrolo[1,2-a]perimidines were prepared starting from 1,8-diaminonaphthalene and hydrazonoyl chlorides. The structures of the products were determined on the basis of their spectral data and elemental analyses. The mechanism of formation of such products was also discussed. The prepared compounds were screened for their antitumor activity against three cell lines, namely, MCF-7, TK-10 and UACC-62, and some derivatives showed promising activity. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Antimalarial Evaluation of the Chemical Constituents of Hairy Root Culture of Bixa orellana L.
Molecules 2014, 19(1), 756-766; doi:10.3390/molecules19010756
Received: 3 December 2013 / Revised: 18 December 2013 / Accepted: 19 December 2013 / Published: 8 January 2014
Cited by 5 | PDF Full-text (428 KB) | HTML Full-text | XML Full-text
Abstract
Over 216 million malaria cases are reported annually worldwide and about a third of these cases, primarily children under the age of five years old, will not survive the infection. Despite this significant world health impact, only a limited number of therapeutic agents
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Over 216 million malaria cases are reported annually worldwide and about a third of these cases, primarily children under the age of five years old, will not survive the infection. Despite this significant world health impact, only a limited number of therapeutic agents are currently available. The lack of scaffold diversity poses a threat in the event that multi-drug–resistant strains emerge. Terrestrial natural products have provided a major source of chemical diversity for starting materials in many FDA approved drugs over the past century. Bixa orellana L. is a popular plant used in South America for the treatment of malaria. In search of new potential therapeutic agents, the chemical constituents of a selected hairy root culture line of Bixa orellana L. were characterized utilizing NMR and mass spectrometry methods, followed by its biological evaluation against malaria strains 3D7 and K1. The crude extract and its isolated compounds demonstrated EC50 values in the micromolar range. Herein, we report our findings on the chemical constituents of Bixa orellana L. from hairy roots responsible for the observed antimalarial activity. Full article
Open AccessArticle Acetylcholinesterase Inhibitory, Antioxidant and Phytochemical Properties of Selected Medicinal Plants of the Lamiaceae Family
Molecules 2014, 19(1), 767-782; doi:10.3390/molecules19010767
Received: 6 November 2013 / Revised: 31 December 2013 / Accepted: 2 January 2014 / Published: 9 January 2014
Cited by 25 | PDF Full-text (536 KB) | HTML Full-text | XML Full-text
Abstract
The present study aimed to evaluate acetylcholinesterase (AChE) inhibitory and antioxidant activities of Lamiaceae medicinal plants growing wild in Croatia. Using Ellman’s colorimetric assay all tested ethanolic extracts and their hydroxycinnamic acid constituents demonstrated in vitro AChE inhibitory properties in a dose dependent
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The present study aimed to evaluate acetylcholinesterase (AChE) inhibitory and antioxidant activities of Lamiaceae medicinal plants growing wild in Croatia. Using Ellman’s colorimetric assay all tested ethanolic extracts and their hydroxycinnamic acid constituents demonstrated in vitro AChE inhibitory properties in a dose dependent manner. The extracts of Mentha x piperita, M. longifolia, Salvia officinalis, Satureja montana, Teucrium arduini, T. chamaedrys, T. montanum, T. polium and Thymus vulgaris at 1 mg/mL showed strong inhibitory activity against AChE. The antioxidant potential of the investigated Lamiaceae species was assessed by DPPH scavenging activity and total antioxidant capacity assays, in comparison with hydroxycinnamic acids and trolox. The extracts differed greatly in their total hydroxycinnamic derivatives content, determined spectrophotometrically. Rosmarinic acid was found to be the predominant constituent in most of the investigated medicinal plants (by RP-HPLC) and had a substantial influence on their AChE inhibitory and antioxidant properties, with the exception of Teucrium species. These findings indicate that Lamiaceae species are a rich source of various natural AChE inhibitors and antioxidants that could be useful in the prevention and treatment of Alzheimer’s and other related diseases. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Preventive Effects of Citrus unshiu Peel Extracts on Bone and Lipid Metabolism in OVX Rats
Molecules 2014, 19(1), 783-794; doi:10.3390/molecules19010783
Received: 18 November 2013 / Revised: 6 January 2014 / Accepted: 7 January 2014 / Published: 9 January 2014
Cited by 9 | PDF Full-text (700 KB) | HTML Full-text | XML Full-text
Abstract
Dried Citrus unshiu peel has been widely used for various medicinal purposes in Oriental Medicine. This study evaluated the metabolic effects of dried C. unshiu peel in ovariectomized (OVX) rats. The OVX rats were divided into five groups treated with distilled water, 17β-estradiol
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Dried Citrus unshiu peel has been widely used for various medicinal purposes in Oriental Medicine. This study evaluated the metabolic effects of dried C. unshiu peel in ovariectomized (OVX) rats. The OVX rats were divided into five groups treated with distilled water, 17β-estradiol (E2 10 μg/kg, once daily, i.p.) and dried C. unshiu peel extracts (DCPE 30, 100 and 300 mg/kg, once daily, p.o.) for eight weeks. The treatments with high-dose DCPE significantly decreased the bone mineral density (BMD) loss in the femur, which was reflected by the decrease in alkaline phosphatase (ALP), telopeptides of collagen type I (CTx) and osteocalcin (OC) serum levels. It also inhibited the increase in lipoprotein levels compared to the OVX-control group without elevating the serum levels of estradiol, aspartate aminotransferase (AST) and alanine transaminase (ALT). Furthermore, DCPE exhibits a hepatoprotective effect in OVX-induced hepatic steatosis, indicated by reduced hepatic lipid contents. Taken together, our findings suggest that DCPE has the potential to improve both lipid and bone metabolism without influencing hormones such as estrogen in OVX rats. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Photophysical Property Studies of the 2,6,8-Triaryl-4-(phenylethynyl)quinazolines
Molecules 2014, 19(1), 795-818; doi:10.3390/molecules19010795
Received: 29 October 2013 / Revised: 30 December 2013 / Accepted: 6 January 2014 / Published: 10 January 2014
Cited by 12 | PDF Full-text (1432 KB) | HTML Full-text | XML Full-text
Abstract
The 2-aryl-6,8-dibromo-4-chloroquinazolines derived from the 2-aryl-6,8-dibromoquinazolin-4(3H)-ones were subjected to the Sonogashira cross-coupling with terminal acetylenes at room temperature to afford novel 2-aryl-6,8-dibromo-4-(alkynyl)quinazoline derivatives. Further transformation of the 2-aryl-6,8-dibromo-4-(phenylethynyl)quinazolines via Suzuki-Miyaura cross-coupling with arylboronic acids occurred without selectivity to afford the corresponding
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The 2-aryl-6,8-dibromo-4-chloroquinazolines derived from the 2-aryl-6,8-dibromoquinazolin-4(3H)-ones were subjected to the Sonogashira cross-coupling with terminal acetylenes at room temperature to afford novel 2-aryl-6,8-dibromo-4-(alkynyl)quinazoline derivatives. Further transformation of the 2-aryl-6,8-dibromo-4-(phenylethynyl)quinazolines via Suzuki-Miyaura cross-coupling with arylboronic acids occurred without selectivity to afford the corresponding 2,6,8-triaryl-4-(phenylethynyl)quinazolines. The absorption and emission properties of these polysubstituted quinazolines were also determined. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Pestalafuranones F–J, Five New Furanone Analogues from the Endophytic Fungus Nigrospora sp. BM-2
Molecules 2014, 19(1), 819-825; doi:10.3390/molecules19010819
Received: 9 December 2013 / Revised: 3 January 2014 / Accepted: 3 January 2014 / Published: 10 January 2014
Cited by 3 | PDF Full-text (216 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Five new 2(5H)-furanone-type derivatives, pestalafuranones F–J (compounds 37), together with two known compounds, pestalafuranones A (1) and B (2), were isolated from the ethyl acetate extract from the fermentation broth of the endophytic fungus
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Five new 2(5H)-furanone-type derivatives, pestalafuranones F–J (compounds 37), together with two known compounds, pestalafuranones A (1) and B (2), were isolated from the ethyl acetate extract from the fermentation broth of the endophytic fungus Nigrospora sp. BM-2 in a hypersaline medium. The structures of these metabolites were elucidated by EIMS, HREIMS and NMR spectroscopic data. Compounds 17 exhibited no cytotoxic activities against the MDA-MB-231 and Caski cancer cell lines. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Diastereoselective Three-Component Reactions of Chiral Nickel(II) Glycinate for Convenient Synthesis of Novel α-Amino-β-Substituted-γ,γ-Disubstituted Butyric Acids
Molecules 2014, 19(1), 826-845; doi:10.3390/molecules19010826
Received: 9 December 2013 / Revised: 20 December 2013 / Accepted: 25 December 2013 / Published: 10 January 2014
PDF Full-text (588 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The convenient, high yielding and diastereoselective synthesis of α-amino-β-substituted-γ,γ-disubstituted butyric acid derivatives was carried out by a three-component tandem reaction of a chiral equivalent of nucleophilic glycine. The reaction was performed smoothly under mild conditions and enabled the construction of two or three
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The convenient, high yielding and diastereoselective synthesis of α-amino-β-substituted-γ,γ-disubstituted butyric acid derivatives was carried out by a three-component tandem reaction of a chiral equivalent of nucleophilic glycine. The reaction was performed smoothly under mild conditions and enabled the construction of two or three adjacent chiral centers in one step, thus affording a novel and convenient route to α-amino-β-substituted-γ,γ-disubstituted butyric acid derivatives. Full article
Open AccessArticle Three-Component Coupling Reactions of Arynes for the Synthesis of Benzofurans and Coumarins
Molecules 2014, 19(1), 863-880; doi:10.3390/molecules19010863
Received: 16 December 2013 / Revised: 7 January 2014 / Accepted: 8 January 2014 / Published: 13 January 2014
Cited by 7 | PDF Full-text (514 KB) | HTML Full-text | XML Full-text
Abstract
The domino three-component coupling reaction of arynes with DMF and active methylenes or methines was studied as a highly efficient method for preparing heterocycles. Coumarin derivative 5 was formed when diethyl malonate (2) or α-bromomalonate (3) were used as
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The domino three-component coupling reaction of arynes with DMF and active methylenes or methines was studied as a highly efficient method for preparing heterocycles. Coumarin derivative 5 was formed when diethyl malonate (2) or α-bromomalonate (3) were used as a C2-unit. In contrast, dihydrobenzofurans 7a and 7b were obtained by using α-chloroenolates generated from α-chloromalonates 4a and 4b and Et2Zn. The benzofuran 15a could be obtained by using ethyl iodoacetate (14) as a C1-unit. The one-pot conversion of dihydrobenzofurans 7a, 7b and 8a into benzofurans 15a and 15b was also studied. The direct synthesis of benzofuran 15b was achieved by using the active methine 18 having ketone and ester groups. Full article
(This article belongs to the Special Issue Domino Reactions)
Open AccessArticle Volatile Profile, Phytochemicals and Antioxidant Activity of Virgin Olive Oils from Croatian Autochthonous Varieties Mašnjača and Krvavica in Comparison with Italian Variety Leccino
Molecules 2014, 19(1), 881-895; doi:10.3390/molecules19010881
Received: 14 November 2013 / Revised: 3 January 2014 / Accepted: 8 January 2014 / Published: 14 January 2014
Cited by 9 | PDF Full-text (329 KB) | HTML Full-text | XML Full-text
Abstract
Virgin olive oils (VOOs) obtained from the fruits of Croatian autochthonous varieties Mašnjača and Krvavica were extensively characterized for the first time. Investigated oils were compared with the oil obtained from Italian variety Leccino, grown and processed under the same conditions. Headspace
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Virgin olive oils (VOOs) obtained from the fruits of Croatian autochthonous varieties Mašnjača and Krvavica were extensively characterized for the first time. Investigated oils were compared with the oil obtained from Italian variety Leccino, grown and processed under the same conditions. Headspace volatile profile, tocopherols, chlorophylls, carotenoids and total phenolic content, peroxide value, % acidity, K232, K270 as well as antioxidant activity (DPPH) of the oils’ hydrophilic fractions (HFs) including their phenolic composition were assessed by means of HS-SPME/GC-MS, HPLC-FL, HPLC-DAD and spectrophotometric methods, respectively. Most of the studied quality parameters varied between the cultivars. The main volatile compounds detected in all tested olive oils were the C6 compounds derived from polyunsaturated fatty acids through the lipoxygenase pathway. Krvavica oil was characterized by hexanal (8.8%–9.4%). Leccino oil contained the highest percentage of (E)-hex-2-enal (73.4%–74.0%), whereas (Z)-hex-3-enal (21.9%–25.0%) and (E)-hex-2-enal (27.6%–28.9%) dominated in Mašnjača oil. Leccino oil contained the highest amount of tocopherols (312.4 mg/kg), chlorophylls (7.3 mg/kg), carotenoids (4.2 mg/kg) and total phenols (246.6 mg/kg). The HF of Leccino oil showed the highest antioxidant capacity (1.3 mmol TEAC/kg), while the HFs of Mašnjača and Krvavica oils exhibited the activity of 0.5 mmol TEAC/kg. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Amination of Nitroazoles — A Comparative Study of Structural and Energetic Properties
Molecules 2014, 19(1), 896-910; doi:10.3390/molecules19010896
Received: 12 November 2013 / Revised: 6 January 2014 / Accepted: 8 January 2014 / Published: 14 January 2014
Cited by 10 | PDF Full-text (687 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this work, 3-nitro-1H-1,2,4-triazole (1) and 3,5-dinitro-1H-pyrazole (2) were C-aminated and N-aminated using different amination agents, yielding their respective C-amino and N-amino products. All compounds were fully characterized by NMR (
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In this work, 3-nitro-1H-1,2,4-triazole (1) and 3,5-dinitro-1H-pyrazole (2) were C-aminated and N-aminated using different amination agents, yielding their respective C-amino and N-amino products. All compounds were fully characterized by NMR (1H, 13C, 15N), IR spectroscopy, differential scanning calorimetry (DSC). X-ray crystallographic measurements were performed and delivered insight into structural characteristics as well as inter- and intramolecular interactions of the products. Their impact sensitivities were measured by using standard BAM fallhammer techniques and their explosive performances were computed using the EXPLO 5.05 program. A comparative study on the influence of those different amino substituents on the structural and energetic properties (such as density, stability, heat of formation, detonation performance) is presented. The results showed that the incorporation of an N-amino group into a nitroazole ring can improve nitrogen content, heat of formation and impact sensitivity, while the introduction of a C-amino group can enhance density, detonation velocity and pressure. The potential of N-amino and C-amino moieties for the design of next generation energetic materials is explored. Full article
(This article belongs to the Special Issue Heterocyclic and Medicinal Chemistry)
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Open AccessArticle A New and Efficient Method for the Synthesis of Novel 3-Acetyl Coumarins Oxadiazoles Derivatives with Expected Biological Activity
Molecules 2014, 19(1), 911-924; doi:10.3390/molecules19010911
Received: 2 December 2013 / Revised: 30 December 2013 / Accepted: 30 December 2013 / Published: 14 January 2014
Cited by 4 | PDF Full-text (308 KB) | HTML Full-text | XML Full-text
Abstract
This paper presents the design of some novel 3-acetylcoumarin derivatives, based on minimal inhibitory concentration values (MICs) previously obtained against some microorganism cultures, Gram positive and negative bacteria and fungi. Some of these molecules exhibited antibacterial activity against S. aureus, comparable to
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This paper presents the design of some novel 3-acetylcoumarin derivatives, based on minimal inhibitory concentration values (MICs) previously obtained against some microorganism cultures, Gram positive and negative bacteria and fungi. Some of these molecules exhibited antibacterial activity against S. aureus, comparable to that of the standard used (impinem). The in vitro antioxidant activities of the novel 3-acetylcoumarin oxadiazoles were assayed by the quantitative 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity method. The compounds 5c,d proved to be the most active, showing the highest capacity to deplete the DPPH radicals. Structure elucidation of the products has been accomplished on the basis of IR, 1H-NMR, 13C-NMR, NOESY and HMBC NMR data. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synthesis and Broad-Spectrum Antiviral Activity of Some Novel Benzo-Heterocyclic Amine Compounds
Molecules 2014, 19(1), 925-939; doi:10.3390/molecules19010925
Received: 28 November 2013 / Revised: 8 January 2014 / Accepted: 9 January 2014 / Published: 15 January 2014
PDF Full-text (281 KB) | HTML Full-text | XML Full-text
Abstract
A series of novel unsaturated five-membered benzo-heterocyclic amine derivatives were synthesized and assayed to determine their in vitro broad-spectrum antiviral activities. The biological results showed that most of our synthesized compounds exhibited potent broad-spectrum antiviral activity. Notably, compounds 3f (IC50 = 3.21–5.06
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A series of novel unsaturated five-membered benzo-heterocyclic amine derivatives were synthesized and assayed to determine their in vitro broad-spectrum antiviral activities. The biological results showed that most of our synthesized compounds exhibited potent broad-spectrum antiviral activity. Notably, compounds 3f (IC50 = 3.21–5.06 μM) and 3g (IC50 = 0.71–34.87 μM) showed potent activity towards both RNA viruses (influenza A, HCV and Cox B3 virus) and a DNA virus (HBV) at low micromolar concentrations. An SAR study showed that electron-withdrawing substituents located on the aromatic or heteroaromatic ring favored antiviral activity towards RNA viruses. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Pd-Catalyzed Amination in the Synthesis of a New Family of Macropolycyclic Compounds Comprising Diazacrown Ether Moieties
Molecules 2014, 19(1), 940-965; doi:10.3390/molecules19010940
Received: 5 December 2013 / Revised: 26 December 2013 / Accepted: 27 December 2013 / Published: 15 January 2014
Cited by 3 | PDF Full-text (484 KB) | HTML Full-text | XML Full-text
Abstract
N,N'-bis(bromobenzyl) and N,N'-bis(halopyridinyl) derivatives of diaza-12-crown-4, diaza-15-crown-5 and diaza-18-crown-6 ethers were synthesized in high yields. The Pd-catalyzed macrocyclization reactions of these compounds were carried out using a variety of polyamines and oxadiamines were carried out to give
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N,N'-bis(bromobenzyl) and N,N'-bis(halopyridinyl) derivatives of diaza-12-crown-4, diaza-15-crown-5 and diaza-18-crown-6 ethers were synthesized in high yields. The Pd-catalyzed macrocyclization reactions of these compounds were carried out using a variety of polyamines and oxadiamines were carried out to give novel macrobicyclic and macrotricyclic compounds of the cryptand type. The dependence of the yields of macropolycycles on the nature of the starting diazacrown derivatives and polyamines was established. Generally N,N'-bis(3-bromobenzyl)-substituted diazacrown ethers and oxadiamines provided better yields of the target products. The highest yield of the macrobicyclic products reached 57%. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Influence of Disulfide Connectivity on Structure and Bioactivity of α-Conotoxin TxIA
Molecules 2014, 19(1), 966-979; doi:10.3390/molecules19010966
Received: 8 November 2013 / Revised: 7 January 2014 / Accepted: 9 January 2014 / Published: 15 January 2014
Cited by 4 | PDF Full-text (1336 KB) | HTML Full-text | XML Full-text
Abstract
Cone snails express a sophisticated arsenal of small bioactive peptides known as conopeptides or conotoxins (CTxs). Through evolutionary selection, these peptides have gained the ability to interact with a range of ion channels and receptors, such as nicotinic acetylcholine receptors (nAChRs). Here, we
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Cone snails express a sophisticated arsenal of small bioactive peptides known as conopeptides or conotoxins (CTxs). Through evolutionary selection, these peptides have gained the ability to interact with a range of ion channels and receptors, such as nicotinic acetylcholine receptors (nAChRs). Here, we used reversed-phase high performance liquid chromatography (RP-HPLC) and electrospray ionization-mass spectrometry (ESI-MS) to explore the venom peptide diversity of Conus textile, a species of cone snail native to Hainan, China. One fraction of C. textile crude venom potently blocked α3β2 nAChRs. Subsequent purification, synthesis, and tandem mass spectrometric analysis demonstrated that the most active compound in this fraction was identical to α-CTx TxIA, an antagonist of α3β2 nAChRs. Then three disulfide isoforms of α-CTx TxIA were synthesized and their activities were investigated systematically for the first time. As we observed, disulfide isomerisation was particularly important for α-CTx TxIA potency. Although both globular and ribbon isomers showed similar retention times in RP-HPLC, globular TxIA potently inhibited α3β2 nAChRs with an IC50 of 5.4 nM, while ribbon TxIA had an IC50 of 430 nM. In contrast, beads isomer had little activity towards α3β2 nAChRs. Two-step oxidation synthesis produced the highest yield of α-CTx TxIA native globular isomer, while a one-step production process based on random oxidation folding was not suitable. In summary, this study demonstrated the relationship between conotoxin activity and disulfide connectivity on α-CTx TxIA. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle EPR Spectroscopy of a Clinically Active (1:2) Copper(II)-Histidine Complex Used in the Treatment of Menkes Disease: A Fourier Transform Analysis of a Fluid CW-EPR Spectrum
Molecules 2014, 19(1), 980-991; doi:10.3390/molecules19010980
Received: 27 November 2013 / Revised: 23 December 2013 / Accepted: 26 December 2013 / Published: 15 January 2014
Cited by 7 | PDF Full-text (249 KB) | HTML Full-text | XML Full-text
Abstract
Redox active transition metal ions (e.g., iron and copper) have been implicated in the etiology of many oxidative stress-related diseases including also neurodegenerative disorders. Unbound copper can catalyze formation of reactive oxygen species (hydroxyl radicals) via Fenton reaction/Haber–Weiss chemistry and therefore, under physiological
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Redox active transition metal ions (e.g., iron and copper) have been implicated in the etiology of many oxidative stress-related diseases including also neurodegenerative disorders. Unbound copper can catalyze formation of reactive oxygen species (hydroxyl radicals) via Fenton reaction/Haber–Weiss chemistry and therefore, under physiological conditions, free copper is potentially toxic and very rarely exists inside cells. Copper(II) bound to the aminoacid L-histidine represents a species discovered in blood in the mid 60s and since then extensive research on this complex was carried out. Copper bound to L-histidine represents an exchangeable pool of copper(II) in equilibrium with the most abundant blood plasma protein, human serum albumin. The structure of this complex, in aqueous solution, has been a subject of many studies and reviews, however without convincing success. The significance of the (1:2) copper(II)-L-histidine complex at physiological pH documents its therapeutic applications in the treatment of Menkes disease and more recently in the treatment of infantile hypertrophic cardioencephalomyopathy. While recently the (1:2) Cu(II)-L-His complex has been successfully crystallized and the crystal structure was solved by X-ray diffraction, the structure of the complex in fluid solution at physiological pH is not satisfactorily known. The aim of this paper is to study the (1:2) Cu(II)-L-histidine complex at low temperatures by X-band and S-band EPR spectroscopy and at physiological pH at room temperature by Fourier transform CW-EPR spectroscopy. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Fatty Acid Profile of Cheese from Dairy Goats Fed a Diet Enriched with Castor, Sesame and Faveleira Vegetable Oils
Molecules 2014, 19(1), 992-1003; doi:10.3390/molecules19010992
Received: 18 November 2013 / Revised: 7 January 2014 / Accepted: 8 January 2014 / Published: 15 January 2014
Cited by 4 | PDF Full-text (221 KB) | HTML Full-text | XML Full-text
Abstract
The addition of vegetable oils to the diets of dairy goats is an alternative to supplemental feeding during the dry period and improves the lipid profile of milk and by-products. Cheeses were produced using milk from cross bred goats (Saanen × Alpina) fed
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The addition of vegetable oils to the diets of dairy goats is an alternative to supplemental feeding during the dry period and improves the lipid profile of milk and by-products. Cheeses were produced using milk from cross bred goats (Saanen × Alpina) fed diets enriched with 4% vegetable oil (faveleira, sesame or castor), the fatty acid profile of cheeses was studied. Supplementation with vegetable oils did not increase the total fat percentage of the cheese (p ≥ 0.05) but did increase the percentage of CLA isomers, long-chain fatty acids (LCFA) and polyunsaturated fatty acids (PUFA); in addition, the index of desirable fatty acids (DFA - expressed as the sum of unsaturated fatty acids plus stearic acid) was increased for cheese made from milk from goats fed sesame or faveleira oil. Cheeses may have had increased percentages of cis-9,trans-11-CLA due to the supplementation of animal diets with vegetable oils rich in C18:2, such as faveleira and sesame oils. The fatty acid profile of goat cheese did not change significantly in response to the use of castor oil. Thus, the addition of sesame and faveleira oils to goat diets positively altered the fatty acid profile, which improved the nutritional characteristics of the fat present in goat cheese. Full article
(This article belongs to the Special Issue Fatty Acids)
Open AccessArticle Coupling Bioorthogonal Chemistries with Artificial Metabolism: Intracellular Biosynthesis of Azidohomoalanine and Its Incorporation into Recombinant Proteins
Molecules 2014, 19(1), 1004-1022; doi:10.3390/molecules19011004
Received: 4 December 2013 / Revised: 7 January 2014 / Accepted: 9 January 2014 / Published: 15 January 2014
Cited by 11 | PDF Full-text (735 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this paper, we present a novel, “single experiment” methodology based on genetic engineering of metabolic pathways for direct intracellular production of non-canonical amino acids from simple precursors, coupled with expanded genetic code. In particular, we engineered the intracellular biosynthesis of L-azidohomoalanine from
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In this paper, we present a novel, “single experiment” methodology based on genetic engineering of metabolic pathways for direct intracellular production of non-canonical amino acids from simple precursors, coupled with expanded genetic code. In particular, we engineered the intracellular biosynthesis of L-azidohomoalanine from O-acetyl-L-homoserine and NaN3, and achieved its direct incorporation into recombinant target proteins by AUG codon reassignment in a methionine-auxotroph E. coli strain. In our system, the host’s methionine biosynthetic pathway was first diverted towards the production of the desired non-canonical amino acid by exploiting the broad reaction specificity of recombinant pyridoxal phosphate-dependent O-acetylhomoserine sulfhydrylase from Corynebacterium glutamicum. Then, the expression of the target protein barstar, accompanied with efficient L-azidohomoalanine incorporation in place of L-methionine, was accomplished. This work stands as proof-of-principle and paves the way for additional work towards intracellular production and site-specific incorporation of biotechnologically relevant non-canonical amino acids directly from common fermentable sources. Full article
(This article belongs to the Special Issue Bioorthogonal Chemistry)
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Open AccessArticle Preparation of 2'-13C-L-Histidine Starting from 13C-Thiocyanate: Synthetic Access to Any Site-Directed Stable Isotope Enriched L-Histidine
Molecules 2014, 19(1), 1023-1033; doi:10.3390/molecules19011023
Received: 14 November 2013 / Revised: 19 December 2013 / Accepted: 20 December 2013 / Published: 15 January 2014
Cited by 1 | PDF Full-text (205 KB) | HTML Full-text | XML Full-text
Abstract
1-Benzyl-2-(methylthio)-imidazole-5-ketone is obtained in a few simple steps starting from thiocyanate and glycine amide (glycin). Subsequent treatment with diethyl phosphorocyanidate and functional group manipulations gives 1-benzyl-5-chloromethyl-imidazolium chloride. This compound is converted under mild O’Donnell conditions into the corresponding L-histidine derivative. After deprotection L-histidine
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1-Benzyl-2-(methylthio)-imidazole-5-ketone is obtained in a few simple steps starting from thiocyanate and glycine amide (glycin). Subsequent treatment with diethyl phosphorocyanidate and functional group manipulations gives 1-benzyl-5-chloromethyl-imidazolium chloride. This compound is converted under mild O’Donnell conditions into the corresponding L-histidine derivative. After deprotection L-histidine is obtained in good yield and 99% enantiomeric excess. 2'-13C-L-Histidine has been obtained via this new scheme with high (99%) 13C incorporation starting with commercially available 13C- thiocyanate. This synthetic scheme allows access to any isotopomer of L-histidine and many other biologically important imidazole derivatives. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Synthesis, Crystal Structure and Anti-Fatigue Effects of Some Benzamide Derivatives
Molecules 2014, 19(1), 1034-1046; doi:10.3390/molecules19011034
Received: 4 December 2013 / Revised: 10 January 2014 / Accepted: 10 January 2014 / Published: 16 January 2014
PDF Full-text (1269 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of benzamide derivatives such as 1-(1,3-benzodioxol-5-ylcarbonyl) piperidine (1-BCP) were synthesized by the reaction of substituted benzoic acids with piperidine, morpholine or pyrrolidine using a novel method. The crystals of these benzamide derivatives were obtained by recrystallization. Structures of target and intermediate
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A series of benzamide derivatives such as 1-(1,3-benzodioxol-5-ylcarbonyl) piperidine (1-BCP) were synthesized by the reaction of substituted benzoic acids with piperidine, morpholine or pyrrolidine using a novel method. The crystals of these benzamide derivatives were obtained by recrystallization. Structures of target and intermediate compounds were determined via FT-IR, 1H-NMR and elemental analysis and X-ray crystallography of select examples. The crystal structures of these compounds have potential applications to identify the binding site for allosteric modulators of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor. The anti-fatigue effects of the benzamide derivatives in weight-loaded forced swimming mice were investigated in a swimming endurance capacity test used as an indicator of fatigue. The swimming times to exhaustion were longer in the b3, d3, and e3 groups than in the caffeine group (p < 0.05). In conclusion, b3, d3 and e3 enhanced the forced swimming capacity of mice. The mechanism of the anti-fatigue effects will be studied in the future. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Microbiological and Nutritional Quality of the Goat Meat by-Product “Sarapatel”
Molecules 2014, 19(1), 1047-1059; doi:10.3390/molecules19011047
Received: 11 December 2013 / Revised: 31 December 2013 / Accepted: 2 January 2014 / Published: 16 January 2014
Cited by 4 | PDF Full-text (232 KB) | HTML Full-text | XML Full-text
Abstract
Goat “sarapatel” is a product made from blood and viscera. For the first time, the microbiological and nutritional quality of “sarapatel” samples (n = 48) sold under different conditions (in street markets, butcher shops, and supermarkets under refrigeration, frozen or at room
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Goat “sarapatel” is a product made from blood and viscera. For the first time, the microbiological and nutritional quality of “sarapatel” samples (n = 48) sold under different conditions (in street markets, butcher shops, and supermarkets under refrigeration, frozen or at room temperature) was evaluated. Goat “sarapatel” is a nutritive food, with each 100 g providing, on average, 72 g of moisture, 2 g of ash, 18 g of protein, 9 g of lipids, 2 g of carbohydrates, 282 mg of cholesterol, and high amounts of unsaturated fatty acids and essential amino acids. The analysis of the “sarapatel” samples shows that none of them contain Salmonella spp. or L. monocytogenes. High counts (>104) of total coliforms, thermotolerant coliforms, and sulfite-reducing Clostridium were detected, and coagulase-positive Staphylococcus was found in 31.25% of samples. The storage conditions evaluated (refrigeration, frozen or at room temperature) did not affect the physicochemical quality of the “sarapatel”; however, the unsatisfactory microbiological quality indicates that it is necessary to improve the health-sanitary aspects of the processing and sale of this product. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessCommunication Analgesic Effect of Harpagophytum procumbens on Postoperative and Neuropathic Pain in Rats
Molecules 2014, 19(1), 1060-1068; doi:10.3390/molecules19011060
Received: 12 December 2013 / Revised: 10 January 2014 / Accepted: 13 January 2014 / Published: 16 January 2014
Cited by 7 | PDF Full-text (894 KB) | HTML Full-text | XML Full-text
Abstract
Harpagophytum procumbens, also known as Devil’s Claw, has historically been used to treat a wide range of conditions, including pain and arthritis. The study was designed to investigate whether H. procumbens extracts exhibit analgesic effects in plantar incision and spared nerve injury
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Harpagophytum procumbens, also known as Devil’s Claw, has historically been used to treat a wide range of conditions, including pain and arthritis. The study was designed to investigate whether H. procumbens extracts exhibit analgesic effects in plantar incision and spared nerve injury (SNI) rats. The whole procedure was performed on male SD rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT) test measured by von Frey filaments. Pain-related behavior was also determined through analysis of ultrasonic vocalization (USVs). The results of experiments showed MWT values of the group that was treated with 300 mg/kg H. procumbens extract increased significantly; on the contrary, the number of 22–27 kHz USVs of the treated group was reduced at 6 h and 24 h after plantar incision operation. After 21 days of continuous treatment with H. procumbens extracts at 300 mg/kg, the treated group showed significantly alleviated SNI-induced hypersensitivity responses by MWT, compared with the control group. These results suggest that H. procumbens extracts have potential analgesic effects in the case of acute postoperative pain and chronic neuropathic pain in rats. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Concerted Halogen Bonding and Orthogonal Metal-Halogen Interactions in Dimers of Lithium Formamidinate and Halogenated Formamidines: An ab Initio Study
Molecules 2014, 19(1), 1069-1084; doi:10.3390/molecules19011069
Received: 11 December 2013 / Revised: 6 January 2014 / Accepted: 14 January 2014 / Published: 17 January 2014
Cited by 4 | PDF Full-text (1026 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Dimers of lithium formamidinate, CH(NH)2Li, and halogenated formamidines, HN=CHNHX, (X=Cl, Br, or I) are used as model systems to investigate simultaneous N-X···N and N-Li···N interactions, in tandem with orthogonal Li···X interactions. Geometry optimizations and energy calculations for the dimers are examined
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Dimers of lithium formamidinate, CH(NH)2Li, and halogenated formamidines, HN=CHNHX, (X=Cl, Br, or I) are used as model systems to investigate simultaneous N-X···N and N-Li···N interactions, in tandem with orthogonal Li···X interactions. Geometry optimizations and energy calculations for the dimers are examined with the MP2 method and the M06-2X hybrid functional and the aug-cc-pVTZ basis set (the aug-cc-pVTZ-PP basis set is used for the iodine atom). Both methods predict the formation of a planar structure of C2v symmetry, regardless of the identity of the halogen atom. In this structure, the identities of the constituent monomers are essentially lost. Accordingly, the N-X···N interactions emerge as a rather symmetric quasi-linear N···X···N, where the covalent N-X bond in the halogenated formamidine is replaced by a partly covalent N···X interaction. Formation of the C2v structure is also driven by a fairly linear N···Li···N interaction parallel to the N···X···N interaction, and a Li···X interaction orthogonal to both the N···X···N and N···Li···N interactions. The strength of the interactions increases with the size of the halogen. The robustness of the interactions suggests that the dimers studied here or suitable analogues may find diverse applications including their use as novel polymeric synthons. Full article
(This article belongs to the Special Issue Computational Chemistry)
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Open AccessArticle Gold Nanoparticles Decorated with Mannose-6-phosphate Analogues
Molecules 2014, 19(1), 1120-1149; doi:10.3390/molecules19011120
Received: 25 November 2013 / Revised: 7 January 2014 / Accepted: 10 January 2014 / Published: 17 January 2014
Cited by 3 | PDF Full-text (715 KB) | HTML Full-text | XML Full-text
Abstract
Herein, the preparation of neoglycoconjugates bearing mannose-6-phosphate analogues is described by: (a) synthesis of a cyclic sulfate precursor to access the carbohydrate head-group by nucleophilic displacement with an appropriate nucleophile; (b) introduction of spacers on the mannose-6-phosphate analogues via Huisgen’s cycloaddition, the Julia
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Herein, the preparation of neoglycoconjugates bearing mannose-6-phosphate analogues is described by: (a) synthesis of a cyclic sulfate precursor to access the carbohydrate head-group by nucleophilic displacement with an appropriate nucleophile; (b) introduction of spacers on the mannose-6-phosphate analogues via Huisgen’s cycloaddition, the Julia reaction, or the thiol-ene reaction under ultrasound activation. With the resulting compounds in hand, gold nanoparticles could be functionalized with various carbohydrate derivatives (glycoconjugates) and then tested for angiogenic activity. It was observed that the length and flexibility of the spacer separating the sugar analogue from the nanoparticle have little influence on the biological response. One particular nanoparticle system substantially inhibits blood vessel growth in contrast to activation by the corresponding monomeric glycoconjugate, thereby demonstrating the importance of multivalency in angiogenic activity. Full article
(This article belongs to the Special Issue Synthesis, Structure, Analysis and Properties of Glycolipids)
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Open AccessArticle A Greener, Efficient Approach to Michael Addition of Barbituric Acid to Nitroalkene in Aqueous Diethylamine Medium
Molecules 2014, 19(1), 1150-1162; doi:10.3390/molecules19011150
Received: 5 December 2013 / Revised: 7 January 2014 / Accepted: 10 January 2014 / Published: 17 January 2014
Cited by 13 | PDF Full-text (317 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An efficient method for the synthesis of a variety of pyrimidine derivatives 3at by reaction of barbituric acids 1a,b as Michael donor with nitroalkenes 2ak as Michael acceptor using an aqueous medium and diethylamine is described. This
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An efficient method for the synthesis of a variety of pyrimidine derivatives 3at by reaction of barbituric acids 1a,b as Michael donor with nitroalkenes 2ak as Michael acceptor using an aqueous medium and diethylamine is described. This 1,4-addition strategy offers several advantages, such as using an economic and environmentally benign reaction media, high yields, versatility, and shorter reaction times. The synthesized compounds were identified by 1H-NMR, 13C-NMR, CHN, IR, and MS. The structure of compound 3a was further confirmed by single crystal X-ray structure determination. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Design and Synthesis of Some New 1,3,4-Thiadiazines with Coumarin Moieties and Their Antioxidative and Antifungal Activity
Molecules 2014, 19(1), 1163-1177; doi:10.3390/molecules19011163
Received: 12 December 2013 / Revised: 13 January 2014 / Accepted: 14 January 2014 / Published: 17 January 2014
Cited by 4 | PDF Full-text (332 KB) | HTML Full-text | XML Full-text
Abstract
A series of newly disubstituted (compounds 4a,b) and trisubstituted 1,3,4-thiadiazines 5al with various substituents was prepared utilizing different thiosemicarbazides and 3-α-bromoacetylcoumarins as starting compounds. The structures of the synthesized 1,3,4-thiadiazines are elucidated and confirmed utilizing the corresponding analytical
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A series of newly disubstituted (compounds 4a,b) and trisubstituted 1,3,4-thiadiazines 5al with various substituents was prepared utilizing different thiosemicarbazides and 3-α-bromoacetylcoumarins as starting compounds. The structures of the synthesized 1,3,4-thiadiazines are elucidated and confirmed utilizing the corresponding analytical and spectroscopic data. All of the new thiadiazine derivatives were tested for their antioxidant activity, employing different antioxidant assays (DPPH scavenging activity, iron chelating activity, power reducing activity). Compounds 5b, 5f, 5j and 4b were proven to be the best DPPH radical scavengers, while compounds 5h and 5j have shown the best iron chelating activity. Thiadiazine derivatives were also tested on their antifungal activity against four mycotoxicogenic fungi, Aspergillus flavus, A. ochraceus, Fusarium graminearum and F. verticillioides. The best antifungal against A. flavus was proven to be compound 5e, while compounds 4a and 5c were the best antifungals on A. ochraceus, and compound 5g showed the best antifungal activity on F. verticillioides. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle A New Sesquilignan Glucoside from Uraria sinensis
Molecules 2014, 19(1), 1178-1188; doi:10.3390/molecules19011178
Received: 26 November 2013 / Revised: 7 January 2014 / Accepted: 13 January 2014 / Published: 17 January 2014
Cited by 1 | PDF Full-text (315 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new sesquilignan glucoside, urariasinoside A (1), together with eight known compounds, including two lignans, a sesquilignan, a dilignan, and four flavonoid derivatives were isolated from the aerial parts of Uraria sinensis. Their structures were determined on the basis of
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A new sesquilignan glucoside, urariasinoside A (1), together with eight known compounds, including two lignans, a sesquilignan, a dilignan, and four flavonoid derivatives were isolated from the aerial parts of Uraria sinensis. Their structures were determined on the basis of extensive spectroscopic analyses and comparison with literature data. Compound 1 was evaluated for in vitro cytotoxicity activity against HL-60, SMMC-7721, A549, MCF-7, SW480, and BEAS-2B cell lines. Full article
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Open AccessArticle Validation of a Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry Method for Determination of All-Trans Retinoic Acid in Human Plasma and Its Application to a Bioequivalence Study
Molecules 2014, 19(1), 1189-1200; doi:10.3390/molecules19011189
Received: 29 November 2013 / Revised: 25 December 2013 / Accepted: 7 January 2014 / Published: 17 January 2014
Cited by 1 | PDF Full-text (576 KB) | HTML Full-text | XML Full-text
Abstract
A sensitive, reliable and specific LC-MS-MS method was developed and validated for the identification and quantitation of all-trans retinoic acid (ATRA) in human plasma. Acitretin was used as the internal standard (IS). After liquid-liquid extraction of 500 μL plasma with methyl tert
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A sensitive, reliable and specific LC-MS-MS method was developed and validated for the identification and quantitation of all-trans retinoic acid (ATRA) in human plasma. Acitretin was used as the internal standard (IS). After liquid-liquid extraction of 500 μL plasma with methyl tert-butyl ether (MTBE), ATRA and the IS were chromatographed on a HyPURITY C18 column (150 mm × 2.1 mm, 5 μm) with the column temperature set at 40 °C. The mobile phase was consisted of 40% phase A (MTBE–methanol–acetic acid, 50:50:0.5, v/v) and 60% phase B (water–methanol–acetic acid, 50:50:0.5, v/v) with a flow rate of 0.3 mL/min. The API 4000 triple quadrupole mass spectrometer was operated in multiple reaction monitoring (MRM) mode via the positive electrospray ionization interface using the transition m/z 301.4 → 123.1 for ATRA and m/z 326.9 → 177.1 for IS, respectively. The calibration curve was linear over the range of 0.45–217.00 ng/mL (r ≥ 0.999) with a lower limit of quantitation (LLOQ) of 0.45 ng/mL. The intra- and inter-day precisions values were below 8% relative standard deviation and the accuracy was from 98.98% to 106.19% in terms of relative error. The validated method was successfully applied in a bioequivalence study of ATRA in Chinese healthy volunteers. Full article
Open AccessCommunication Anticholinesterase Inhibitory Activity of Quaternary Alkaloids from Tinospora crispa
Molecules 2014, 19(1), 1201-1211; doi:10.3390/molecules19011201
Received: 1 December 2013 / Revised: 14 January 2014 / Accepted: 15 January 2014 / Published: 20 January 2014
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Abstract
Quaternary alkaloids are the major alkaloids isolated from Tinospora species. A previous study pointed to the necessary presence of quaternary nitrogens for strong acetylcholinesterase (AChE) inhibitory activity in such alkaloids. Repeated column chromatography of the vine of Tinospora crispa extract led to the
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Quaternary alkaloids are the major alkaloids isolated from Tinospora species. A previous study pointed to the necessary presence of quaternary nitrogens for strong acetylcholinesterase (AChE) inhibitory activity in such alkaloids. Repeated column chromatography of the vine of Tinospora crispa extract led to the isolation of one new protoberberine alkaloid, 4,13-dihydroxy-2,8,9-trimethoxydibenzo[a,g]quinolizinium (1), along with six known alkaloids—dihydrodiscretamine (2), columbamine (3), magnoflorine (4), N-formylannonaine (5), N-formylnornuciferine (6), and N-trans-feruloyltyramine (7). The seven compounds were isolated and structurally elucidated by spectroscopic analysis. Two known alkaloids, namely, dihydrodiscretamine and columbamine are reported for the first time for this plant. The compounds were tested for AChE inhibitory activity using Ellman’s method. In the AChE inhibition assay, only columbamine (3) showed strong activity with IC50 48.1 µM. The structure–activity relationships derived from these results suggest that the quaternary nitrogen in the skeleton has some effect, but that a high degree of methoxylation is more important for acetylcholinesterase inhibition. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Simultaneous Determination of 24 Antidepressant Drugs and Their Metabolites in Wastewater by Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry
Molecules 2014, 19(1), 1212-1222; doi:10.3390/molecules19011212
Received: 7 November 2013 / Revised: 14 January 2014 / Accepted: 15 January 2014 / Published: 20 January 2014
Cited by 8 | PDF Full-text (913 KB) | HTML Full-text | XML Full-text
Abstract
Antidepressants are a new kind of pollutants being increasingly found in wastewater. In this study, a fast and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry method was developed and validated for the analysis of 24 antidepressant drugs and six of their metabolites in
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Antidepressants are a new kind of pollutants being increasingly found in wastewater. In this study, a fast and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry method was developed and validated for the analysis of 24 antidepressant drugs and six of their metabolites in wastewater. This is the first time that the antidepressant residues in wastewater of Beijing (China) were systematically reported. A solid-phase extraction process was performed with 3 M cation disk, followed by ultra-high performance liquid chromatography–tandem mass spectrometry measurements. The chromatographic separation and mass parameters were optimized in order to achieve suitable retention time and good resolution for analytes. All compounds were satisfactorily determined in one single injection within 20 min. The limit of quantification (LOQ), linearity, and extraction recovery were validated. The LOQ for analytes were ranged from 0.02 to 0.51 ng/mL. The determination coefficients were more than 0.99 within the tested concentration range (0.1–25 ng/mL), and the recovery rate for each target compound was ranged from 81.2% to 118% at 1 ng/mL. This new developed method was successfully applied to analysis the samples collected from Beijing municipal wastewater treatment plants. At least ten target antidepressants were found in all samples and the highest mean concentration of desmethylvenlafaxin was up to 415.6 ng/L. Full article
Open AccessArticle Synthesis of Tetrahydrohonokiol Derivates and Their Evaluation for Cytotoxic Activity against CCRF-CEM Leukemia, U251 Glioblastoma and HCT-116 Colon Cancer Cells
Molecules 2014, 19(1), 1223-1237; doi:10.3390/molecules19011223
Received: 9 December 2013 / Revised: 9 January 2014 / Accepted: 13 January 2014 / Published: 20 January 2014
Cited by 9 | PDF Full-text (280 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Biphenyl neolignans such as honokiol and magnolol, which are the major active constituents of the Asian medicinal plant Magnolia officinalis, are known to exert a multitude of pharmacological and biological activities. Among these, cytotoxic and tumor growth inhibitory activity against various tumour
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Biphenyl neolignans such as honokiol and magnolol, which are the major active constituents of the Asian medicinal plant Magnolia officinalis, are known to exert a multitude of pharmacological and biological activities. Among these, cytotoxic and tumor growth inhibitory activity against various tumour cell lines are well-documented. To further elucidate the cytotoxic effects of honokiol derivatives, derivatizations were performed using tetrahydrohonokiol as a scaffold. The derivatizations comprised the introduction of functional groups, e.g., nitro and amino groups, as well as alkylation. This way, 18 derivatives, of which 13 were previously undescribed compounds, were evaluated against CCRF-CEM leukemia cells, U251 glioblastoma and HCT-116 colon cancer cells. The results revealed no significant cytotoxic effects in any of the three tested cell lines at a test concentration of 10 µM. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Construction of the 1,2-Dialkenylcyclohexane Framework via Ireland-Claisen Rearrangement and Intramolecular Barbier Reaction: Application to the Synthesis of (±)-Geijerone and a Diastereoisomeric Mixture with Its 5-Epimer
Molecules 2014, 19(1), 1238-1249; doi:10.3390/molecules19011238
Received: 17 December 2013 / Revised: 14 January 2014 / Accepted: 15 January 2014 / Published: 20 January 2014
Cited by 2 | PDF Full-text (255 KB) | HTML Full-text | XML Full-text
Abstract
The elemene-type terpenoids, which possess various biological activities, contain a syn- or anti-1,2-dialkenylcyclohexane framework. An efficient synthetic route to the syn- and anti-1,2-dialkenylcyclohexane core and its application in the synthesis of (±)-geijerone and its diastereomer is reported. Construction of
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The elemene-type terpenoids, which possess various biological activities, contain a syn- or anti-1,2-dialkenylcyclohexane framework. An efficient synthetic route to the syn- and anti-1,2-dialkenylcyclohexane core and its application in the synthesis of (±)-geijerone and its diastereomer is reported. Construction of the syn- and anti-1,2-dialkenyl moiety was achieved via Ireland-Claisen rearrangement of the (E)-allylic ester, and the cyclohexanone moiety was derived from the iodoaldehyde via intramolecular Barbier reaction. The synthetic strategy allows rapid access to various epimers and analogues of elemene-type products. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Two New Secondary Metabolites from Xylaria sp. cfcc 87468
Molecules 2014, 19(1), 1250-1257; doi:10.3390/molecules19011250
Received: 5 December 2013 / Revised: 15 January 2014 / Accepted: 15 January 2014 / Published: 20 January 2014
Cited by 1 | PDF Full-text (286 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new isocoumarin glycoside, 3R-(+)-5-O-[6'-O-acetyl]-α-D-glucopyranosyl-5-hydroxymellein (1), and a new phenylethanol glycoside, (−)-phenylethyl-8-O-α-L-rhamno-pyranoside (2), were isolated from the ethyl acetate extract of the fungus Xylaria sp. cfcc 87468,
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A new isocoumarin glycoside, 3R-(+)-5-O-[6'-O-acetyl]-α-D-glucopyranosyl-5-hydroxymellein (1), and a new phenylethanol glycoside, (−)-phenylethyl-8-O-α-L-rhamno-pyranoside (2), were isolated from the ethyl acetate extract of the fungus Xylaria sp. cfcc 87468, together with five known steroids, β-sitosterol (3), stigmast-4-en-3-one (4), ergosterol (5), (22E)-cholesta-4,6,8(14),22-tetraen-3-one (6), and 4α-methyl- ergosta-8(14),24(28)-dien-3β-ol (7). The structures of compounds 1 and 2 were elucidated by MS, extensive 1D and 2D NMR spectroscopy, and the circular dichroism (CD) spectroscopy. Full article
Open AccessArticle Inhibition of Epstein-Barr Virus Lytic Cycle by an Ethyl Acetate Subfraction Separated from Polygonum cuspidatum Root and Its Major Component, Emodin
Molecules 2014, 19(1), 1258-1272; doi:10.3390/molecules19011258
Received: 11 December 2013 / Revised: 9 January 2014 / Accepted: 14 January 2014 / Published: 20 January 2014
Cited by 5 | PDF Full-text (1623 KB) | HTML Full-text | XML Full-text
Abstract
Polygonum cuspidatum is widely used as a medicinal herb in Asia. In this study, we examined the ethyl acetate subfraction F3 obtained from P. cuspidatum root and its major component, emodin, for their capacity to inhibit the Epstein-Barr virus (EBV) lytic cycle. The
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Polygonum cuspidatum is widely used as a medicinal herb in Asia. In this study, we examined the ethyl acetate subfraction F3 obtained from P. cuspidatum root and its major component, emodin, for their capacity to inhibit the Epstein-Barr virus (EBV) lytic cycle. The cell viability was determined by the MTT [3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide] method. The expression of EBV lytic proteins was analyzed by immunoblot, indirect immunofluorescence and flow cytometric assays. Real-time quantitative PCR was used to assess the EBV DNA replication and the transcription of lytic genes, including BRLF1 and BZLF1. Results showed that the F3 and its major component emodin inhibit the transcription of EBV immediate early genes, the expression of EBV lytic proteins, including Rta, Zta, and EA-D and reduces EBV DNA replication, showing that F3 and emodin are potentially useful as an anti-EBV drug. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of 4-Methoxybenzoylhydrazones and Evaluation of Their Antiglycation Activity
Molecules 2014, 19(1), 1286-1301; doi:10.3390/molecules19011286
Received: 17 December 2013 / Revised: 31 December 2013 / Accepted: 2 January 2014 / Published: 21 January 2014
Cited by 15 | PDF Full-text (295 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of 4-methoxybenzoylhydrazones 130 was synthesized and the structures of the synthetic derivatives elucidated by spectroscopic methods. The compounds showed a varying degree of antiglycation activity, with IC50 values ranging between 216.52 and 748.71 µM, when compared to a
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A series of 4-methoxybenzoylhydrazones 130 was synthesized and the structures of the synthetic derivatives elucidated by spectroscopic methods. The compounds showed a varying degree of antiglycation activity, with IC50 values ranging between 216.52 and 748.71 µM, when compared to a rutin standard (IC50 = 294.46 ± 1.50 µM). Compounds 1 (IC50 = 216.52 ± 4.2 µM), 3 (IC50 = 289.58 ± 2.64 µM), 6 (IC50 = 227.75 ± 0.53 µM), 7 (IC50 = 242.53 ± 6.1) and 11 (IC50 = 287.79 ± 1.59) all showed more activity that the standard, and these compounds have the potential to serve as possible leads for drugs to inhibit protein glycation in diabetic patients. A preliminary SAR study was performed. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Crystal Structures, Vibrational Spectra, and Fungicidal Activity of 1,5-Diaryl-3-oxypyrazoles
Molecules 2014, 19(1), 1302-1316; doi:10.3390/molecules19011302
Received: 4 November 2013 / Revised: 9 January 2014 / Accepted: 14 January 2014 / Published: 21 January 2014
PDF Full-text (1824 KB) | HTML Full-text | XML Full-text
Abstract
The aryloxypyrazole structure is present in a number of bioactive molecules. Four 1,5-diaryl-3-oxypyrazoles containing benzoyl (I), thiazolidinethione (II and III) or per-O-acetylated glucopyranosyl (IV) moieties were characterized by single-crystal X-ray diffraction. Compounds I and
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The aryloxypyrazole structure is present in a number of bioactive molecules. Four 1,5-diaryl-3-oxypyrazoles containing benzoyl (I), thiazolidinethione (II and III) or per-O-acetylated glucopyranosyl (IV) moieties were characterized by single-crystal X-ray diffraction. Compounds I and II crystallize in a triclinic P-1 system, whereas III and IV crystallize in an orthorhombic Pbca and a monoclinic P21 space groups, respectively. The dihedral angles between the two benzene rings of the pyrazole are 61.33° (I), 62.87° (II), 57.09° (III) and 70.25° (IV). The structures were stabilized by classical intra- (C-H···S for II and III, C-H···O for IV) and intermolecular (C-H···O for I and IV) H-bonds, as well as intermolecular C-H···π stacking interactions. The theoretical FTIR results showed good agreement with the experimental data. Compounds IV, II and III showed moderate fungicidal activity against Sclerotinia sclerotiorum and Gibberella zeae. The structure-activity relationships were discussed. Full article
Open AccessCommunication Antibacterial and Antioxidant Activities of Ursolic Acid and Derivatives
Molecules 2014, 19(1), 1317-1327; doi:10.3390/molecules19011317
Received: 7 November 2013 / Revised: 11 December 2013 / Accepted: 20 December 2013 / Published: 21 January 2014
Cited by 22 | PDF Full-text (212 KB) | HTML Full-text | XML Full-text
Abstract
Ursolic acid, an important bioactive compound, was isolated from ethanol extract of aerial parts of Sambucus australis. In order to develop bioactive ursolic acid derivatives, two semi-synthetic compounds were obtained through modification at C-3. The antibacterial activity of the ursolic acid and
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Ursolic acid, an important bioactive compound, was isolated from ethanol extract of aerial parts of Sambucus australis. In order to develop bioactive ursolic acid derivatives, two semi-synthetic compounds were obtained through modification at C-3. The antibacterial activity of the ursolic acid and its derivatives was investigated. The microdilution method was used for determination of the minimal inhibitory concentration (MIC), against twelve bacterial strains. The influence of ursolic acid and its derivatives on the susceptibility of some bacterial pathogens to the aminoglycosides antibiotics neomycin, amikacin, kanamycin and gentamicin was evaluated. The most representative synergistic effect was observed by 3β-formyloxy-urs-12-en-28-oic acid at the concentration of 64 μg/mL in combination with kanamycin against Escherichia coli (27), a multidrug-resistant clinical isolate from sputum, with reduction of MIC value from 128 μg/mL to 8 μg/mL. Ursolic acid and its derivatives were examined for their radical scavenger activity using the DPPH assay, and showed significant activity. Full article
Open AccessArticle EGF Receptor-Dependent Mechanism May be Involved in the Tamm–Horsfall Glycoprotein-Enhanced PMN Phagocytosis via Activating Rho Family and MAPK Signaling Pathway
Molecules 2014, 19(1), 1328-1343; doi:10.3390/molecules19011328
Received: 3 December 2013 / Revised: 13 January 2014 / Accepted: 16 January 2014 / Published: 21 January 2014
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Abstract
Our previous studies showed that urinary Tamm–Horsfall glycoprotein (THP) potently enhanced polymorphonuclear neutrophil (PMN) phagocytosis. However, the domain structure(s), signaling pathway and the intracellular events responsible for THP-enhanced PMN phagocytosis remain to be elucidated. THP was purified from normal human urine. The human
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Our previous studies showed that urinary Tamm–Horsfall glycoprotein (THP) potently enhanced polymorphonuclear neutrophil (PMN) phagocytosis. However, the domain structure(s), signaling pathway and the intracellular events responsible for THP-enhanced PMN phagocytosis remain to be elucidated. THP was purified from normal human urine. The human promyelocytic leukemia cell line HL-60 was induced to differentiate into PMNs by all-trans retinoid acid. Pretreatment with different MAPK and PI3K inhibitors was used to delineate signaling pathways in THP-enhanced PMN phagocytosis. Phosphorylation of molecules responsible for PMN phagocytosis induced by bacterial lipopolysaccharide (LPS), THP, or human recombinant epidermal growth factor (EGF) was evaluated by western blot. A p38 MAPK inhibitor, SB203580, effectively inhibited both spontaneous and LPS- and THP-induced PMN phagocytosis. Both THP and LPS enhanced the expression of the Rho family proteins Cdc42 and Rac that may lead to F-actin re-arrangement. Further studies suggested that THP and EGF enhance PMN and differentiated HL-60 cell phagocytosis in a similar pattern. Furthermore, the EGF receptor inhibitor GW2974 significantly suppressed THP- and EGF-enhanced PMN phagocytosis and p38 and ERK1/2 phosphorylation in differentiated HL-60 cells. We conclude that EGF receptor-dependent signaling may be involved in THP-enhanced PMN phagocytosis by activating Rho family and MAP kinase. Full article
(This article belongs to the Special Issue Oligosaccharides and Glyco-Conjugates)
Open AccessArticle Synthesis and Characterization of Impurities of Barnidipine Hydrochloride, an Antihypertensive Drug Substance
Molecules 2014, 19(1), 1344-1352; doi:10.3390/molecules19011344
Received: 11 December 2013 / Revised: 15 January 2014 / Accepted: 15 January 2014 / Published: 21 January 2014
Cited by 2 | PDF Full-text (265 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Barnidipine hydrochloride is a long term dihydropyridine calcium channel blocker used for the treatment of hypertension. During the process development of barnidipine hydrochloride, four barnidipine impurities were detected by high-performance liquid chromatography (HPLC) with an ordinary column (Agilent ZORBAX Eclipse XDB-C18, 150 mm
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Barnidipine hydrochloride is a long term dihydropyridine calcium channel blocker used for the treatment of hypertension. During the process development of barnidipine hydrochloride, four barnidipine impurities were detected by high-performance liquid chromatography (HPLC) with an ordinary column (Agilent ZORBAX Eclipse XDB-C18, 150 mm × 4.6 mm, 5 µm). All these impurities were identified, synthesized, and subsequently characterized by their respective spectral data (MS, 1H-NMR, and 13C-NMR). The identification of these impurities should be useful for quality control in the manufacture of barnidipine. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Molecular Dynamics of Neutral Polymer Bonding Agent (NPBA) as Revealed by Solid-State NMR Spectroscopy
Molecules 2014, 19(1), 1353-1366; doi:10.3390/molecules19011353
Received: 12 October 2013 / Revised: 3 January 2014 / Accepted: 16 January 2014 / Published: 22 January 2014
Cited by 1 | PDF Full-text (441 KB) | HTML Full-text | XML Full-text
Abstract
Neutral polymer bonding agent (NPBA) is one of the most promising polymeric materials, widely used in nitrate ester plasticized polyether (NEPE) propellant as bonding agent. The structure and dynamics of NPBA under different conditions of temperatures and sample processing are comprehensively investigated by
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Neutral polymer bonding agent (NPBA) is one of the most promising polymeric materials, widely used in nitrate ester plasticized polyether (NEPE) propellant as bonding agent. The structure and dynamics of NPBA under different conditions of temperatures and sample processing are comprehensively investigated by solid state NMR (SSNMR). The results indicate that both the main chain and side chain of NPBA are quite rigid below its glass transition temperature (Tg). In contrast, above the Tg, the main chain remains relatively immobilized, while the side chains become highly flexible, which presumably weakens the interaction between bonding agent and the binder or oxidant fillers and in turn destabilizes the high modulus layer formed around the oxidant fillers. In addition, no obvious variation is found for the microstructure of NPBA upon aging treatment or soaking with acetone. These experimental results provide useful insights for understanding the structural properties of NPBA and its interaction with other constituents of solid composite propellants under different processing and working conditions. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)

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Open AccessReview Structure and Antioxidant Activity of Polyphenols Derived from Propolis
Molecules 2014, 19(1), 78-101; doi:10.3390/molecules19010078
Received: 13 October 2013 / Revised: 11 December 2013 / Accepted: 12 December 2013 / Published: 20 December 2013
Cited by 26 | PDF Full-text (499 KB) | HTML Full-text | XML Full-text
Abstract
Propolis is a potential source of natural antioxidants such as phenolic acids and flavonoids. Its wide biological effects have been known and used since antiquity. In the modern world natural substances are sought which would be able to counteract the effects of antioxidative
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Propolis is a potential source of natural antioxidants such as phenolic acids and flavonoids. Its wide biological effects have been known and used since antiquity. In the modern world natural substances are sought which would be able to counteract the effects of antioxidative stress, which underlies many diseases, such as cancer, diabetes and atherosclerosis. This paper aims to present the antioxidative activity of phenolic acids and flavonoids present in Polish propolis and the relationship between their chemical structure and antioxidative activity influencing its medicinal properties. Data concerning the biological activity of propolis are summarized here, including its antibacterial, anti-inflammatory, anticarcinogenic, antiatherogenic, estrogenic effects, as well as AIDS- counteracting and reparative-regenerative function. Full article
Open AccessReview Recent Syntheses of 1,2,3,4-Tetrahydroquinolines, 2,3-Dihydro-4(1H)-quinolinones and 4(1H)-Quinolinones using Domino Reactions
Molecules 2014, 19(1), 204-232; doi:10.3390/molecules19010204
Received: 2 December 2013 / Accepted: 20 December 2013 / Published: 24 December 2013
Cited by 26 | PDF Full-text (725 KB) | HTML Full-text | XML Full-text
Abstract
A review of the recent literature is given focusing on synthetic approaches to 1,2,3,4-tetrahydroquinolines, 2,3-dihydro-4(1H)-quinolinones and 4(1H)-quinolinones using domino reactions. These syntheses involve: (1) reduction or oxidation followed by cyclization; (2) SNAr-terminated sequences; (3) acid-catalyzed ring closures
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A review of the recent literature is given focusing on synthetic approaches to 1,2,3,4-tetrahydroquinolines, 2,3-dihydro-4(1H)-quinolinones and 4(1H)-quinolinones using domino reactions. These syntheses involve: (1) reduction or oxidation followed by cyclization; (2) SNAr-terminated sequences; (3) acid-catalyzed ring closures or rearrangements; (4) high temperature cyclizations and (5) metal-promoted processes as well as several less thoroughly studied reactions. Each domino method is presented with a brief discussion of mechanism, scope, yields, simplicity and potential utility. Full article
(This article belongs to the Special Issue Domino Reactions)
Open AccessReview Transition Metal Complexes and Radical Anion Salts of 1,10-Phenanthroline Derivatives Annulated with a 1,2,5-Tiadiazole and 1,2,5-Tiadiazole 1,1-Dioxide Moiety: Multidimensional Crystal Structures and Various Magnetic Properties
Molecules 2014, 19(1), 609-640; doi:10.3390/molecules19010609
Received: 8 November 2013 / Revised: 26 December 2013 / Accepted: 27 December 2013 / Published: 7 January 2014
Cited by 2 | PDF Full-text (1299 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Advances in the molecular variety and the elucidation of the physical properties of 1,10-phenanthroline annulated with 1,2,5-thiadiazole and 1,2,5-thiadiazole 1,1-dioxide moieties have been achieved, and are described herein. A 1,2,5-thiadiazole compound, [1,2,5]thiadiazolo[3,4-f][1,10]phenanthroline (tdap), was used as a ligand to create multidimensional
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Advances in the molecular variety and the elucidation of the physical properties of 1,10-phenanthroline annulated with 1,2,5-thiadiazole and 1,2,5-thiadiazole 1,1-dioxide moieties have been achieved, and are described herein. A 1,2,5-thiadiazole compound, [1,2,5]thiadiazolo[3,4-f][1,10]phenanthroline (tdap), was used as a ligand to create multidimensional network structures based on S•••S and S•••N intermolecular interactions. A 1,2,5-thiadiazole 1,1-dioxide compound, [1,2,5] thiadiazolo[3,4-f][1,10]phenanthroline, 1,1-dioxide (tdapO2), was designed to create a stable radical anion, as well as good network structures. Single crystal X-ray structure analyses revealed that transition metal complexes of tdap, and radical anion salts of tdapO2 formed multidimensional network structures, as expected. Two kinds of tdap iron complexes, namely [Fe(tdap)2(NCS)2] and [Fe(tdap)2(NCS)2]•MeCN exhibited spin crossover transitions, and their transition temperatures showed a difference of 150 K, despite their similar molecular structures. Magnetic measurements for the tdapO2 radical anion salts revealed that the magnetic coupling constants between neighboring radical species vary from strongly antiferromagnetic (J = −320 K) to ferromagnetic (J = 24 K), reflecting the differences in their π overlap motifs. Full article
(This article belongs to the Special Issue Chalcogen-Nitrogen Chemistry)
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Open AccessReview A Systematic Review of the Wound-Healing Effects of Monoterpenes and Iridoid Derivatives
Molecules 2014, 19(1), 846-862; doi:10.3390/molecules19010846
Received: 30 October 2013 / Revised: 9 December 2013 / Accepted: 17 December 2013 / Published: 13 January 2014
Cited by 8 | PDF Full-text (263 KB) | HTML Full-text | XML Full-text
Abstract
The search for more effective and lower cost therapeutic approaches for wound healing remains a challenge for modern medicine. In the search for new therapeutic options, plants and their metabolites are a great source of novel biomolecules. Among their constituents, the monoterpenes represent
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The search for more effective and lower cost therapeutic approaches for wound healing remains a challenge for modern medicine. In the search for new therapeutic options, plants and their metabolites are a great source of novel biomolecules. Among their constituents, the monoterpenes represent 90% of essential oils, and have a variety of structures with several activities such as antimicrobial, anti-inflammatory, antioxidant and wound healing. Based on that, and also due to the lack of reviews concerning the wound-healing activity of monoterpenes, we performed this systematic review—which provides an overview of their characteristics and mechanisms of action. In this search, the terms “terpenes”, “monoterpenes”, “wound healing” and “wound closure techniques” were used to retrieve articles published in LILACS, PUBMED and EMBASE until May 2013. Seven papers were found concerning the potential wound healing effect of five compouds (three monoterpenes and two iridoid derivatives) in preclinical studies. Among the products used for wound care, the films were the most studied pharmaceutical form. Monoterpenes are a class of compounds of great diversity of biological activities and therapeutic potential. The data reviewed here suggest that monoterpenes, although poorly studied in this context, are promising compounds for the treatment of chronic wound conditions. Full article
(This article belongs to the Section Metabolites)
Open AccessReview Invasive Fungal Infections in the ICU: How to Approach, How to Treat
Molecules 2014, 19(1), 1085-1119; doi:10.3390/molecules19011085
Received: 1 November 2013 / Revised: 3 January 2014 / Accepted: 9 January 2014 / Published: 17 January 2014
Cited by 28 | PDF Full-text (381 KB) | HTML Full-text | XML Full-text
Abstract
Invasive fungal infections are a growing problem in critically ill patients and are associated with increased morbidity and mortality. Most of them are due to Candida species, especially Candida albicans. Invasive candidiasis includes candidaemia, disseminated candidiasis with deep organ involvement and chronic disseminated
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Invasive fungal infections are a growing problem in critically ill patients and are associated with increased morbidity and mortality. Most of them are due to Candida species, especially Candida albicans. Invasive candidiasis includes candidaemia, disseminated candidiasis with deep organ involvement and chronic disseminated candidiasis. During the last decades rare pathogenic fungi, such as Aspergillus species, Zygomycetes, Fusarium species and Scedosporium have also emerged. Timely diagnosis and proper treatment are of paramount importance for a favorable outcome. Besides blood cultures, several laboratory tests have been developed in the hope of facilitating an earlier detection of infection. The antifungal armamentarium has also been expanded allowing a treatment choice tailored to individual patients’ needs. The physician can choose among the old class of polyenes, the older and newer azoles and the echinocandins. Factors related to patient’s clinical situation and present co-morbidities, local epidemiology data and purpose of treatment (prophylactic, pre-emptive, empiric or definitive) should be taken into account for the appropriate choice of antifungal agent. Full article
(This article belongs to the Special Issue Advances in Medicinal Chemistry of Antifungals)
Open AccessReview Oxidized Fatty Acids as Inter-Kingdom Signaling Molecules
Molecules 2014, 19(1), 1273-1285; doi:10.3390/molecules19011273
Received: 26 December 2013 / Revised: 16 January 2014 / Accepted: 16 January 2014 / Published: 20 January 2014
Cited by 8 | PDF Full-text (1196 KB) | HTML Full-text | XML Full-text
Abstract
Oxylipins or oxidized fatty acids are a group of molecules found to play a role in signaling in many different cell types. These fatty acid derivatives have ancient evolutionary origins as signaling molecules and are ideal candidates for inter-kingdom communication. This review discusses
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Oxylipins or oxidized fatty acids are a group of molecules found to play a role in signaling in many different cell types. These fatty acid derivatives have ancient evolutionary origins as signaling molecules and are ideal candidates for inter-kingdom communication. This review discusses examples of the ability of organisms from different kingdoms to “listen” and respond to oxylipin signals during interactions. The interactions that will be looked at are signaling between animals and plants; between animals and fungi; between animals and bacteria and between plants and fungi. This will aid in understanding these interactions, which often have implications in ecology, agriculture as well as human and animal health. Full article
(This article belongs to the Section Natural Products)

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Open AccessLetter Comment on Gao, W., et al. “Efficient One-Pot Synthesis of 5-Chloromethylfurfural (CMF) from Carbohydrates in Mild Biphasic Systems”, Molecules 2013, 18, 7675-7685
Molecules 2014, 19(1), 1367-1369; doi:10.3390/molecules19011367
Received: 19 August 2013 / Revised: 2 January 2014 / Accepted: 2 January 2014 / Published: 22 January 2014
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Abstract
In a recent paper entitled “Efficient One-Pot Synthesis of 5-Chloromethylfurfural (CMF) from Carbohydrates in Mild Biphasic Systems,” published in Molecules [1], Gao and coworkers describe the use of a biphasic aq. HCl-H3PO4/CHCl3 reagent for the preparation of CMF
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In a recent paper entitled “Efficient One-Pot Synthesis of 5-Chloromethylfurfural (CMF) from Carbohydrates in Mild Biphasic Systems,” published in Molecules [1], Gao and coworkers describe the use of a biphasic aq. HCl-H3PO4/CHCl3 reagent for the preparation of CMF from various feedstocks. The maximum yield (46.8%) was obtained from fructose by reaction at 45 °C for 20 h. While sucrose gave a similar yield, the same reaction with glucose and cellulose gave 7.3% and 7.8% yields, respectively. Remarkably, the same process applied to Kraft pulp and powdered wood samples gave between 16.0% and 31.4% CMF, based on sugar content. Looking to the Experimental section for insight into this unusual outcome, the statement, “the procedure of treating lignocellulose sample (Table 6) was almost the same as the carbohydrate, except adding the selected simple 1.0 mg each trial [sic] appears, which is difficult to interpret. Full article
Open AccessCorrection Correction: Gao, W., et al. Efficient One-Pot Synthesis of 5-Chloromethyl-furfural (CMF) from Carbohydrates in Mild Biphasic Systems. Molecules 2013, 18, 7675-7685
Molecules 2014, 19(1), 1370-1374; doi:10.3390/molecules19011370
Received: 12 November 2013 / Revised: 13 January 2014 / Accepted: 13 January 2014 / Published: 22 January 2014
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Abstract We have recently been made aware by Prof. Mark Mascal (University of California Davis) and the Molecules Editorial Offices of some errors and omissions in the Introduction section of our recent paper. [...] Full article

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