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Molecules, Volume 19, Issue 2 (February 2014), Pages 1378-2706

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Open AccessArticle Antileishmanial Lead Structures from Nature: Analysis of Structure-Activity Relationships of a Compound Library Derived from Caffeic Acid Bornyl Ester
Molecules 2014, 19(2), 1394-1410; doi:10.3390/molecules19021394
Received: 23 December 2013 / Revised: 13 January 2014 / Accepted: 13 January 2014 / Published: 27 January 2014
Cited by 10 | PDF Full-text (451 KB) | HTML Full-text | XML Full-text
Abstract
Bioassay-guided fractionation of a chloroform extract of Valeriana wallichii (V. wallichii) rhizomes lead to the isolation and identification of caffeic acid bornyl ester (1) as the active component against Leishmania major (L. major) promastigotes (IC
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Bioassay-guided fractionation of a chloroform extract of Valeriana wallichii (V. wallichii) rhizomes lead to the isolation and identification of caffeic acid bornyl ester (1) as the active component against Leishmania major (L. major) promastigotes (IC50 = 48.8 µM). To investigate the structure-activity relationship (SAR), a library of compounds based on 1 was synthesized and tested in vitro against L. major and L. donovani promastigotes, and L. major amastigotes. Cytotoxicity was determined using a murine J774.1 cell line and bone marrow derived macrophages (BMDM). Some compounds showed antileishmanial activity in the concentration range of pentamidine and miltefosine which are the standard drugs in use. In the L. major amastigote assay compounds 15, 19 and 20 showed good activity with relatively low cytotoxicity against BMDM, resulting in acceptable selectivity indices. Molecules with adjacent phenolic hydroxyl groups exhibited elevated cytotoxicity against murine cell lines J774.1 and BMDM. The Michael system seems not to be essential for antileishmanial activity. Based on the results compound 27 can be regarded as new lead structure for further structure optimization. Full article
Open AccessArticle Ultrasound-Assisted Extraction of Mangiferin from Mango (Mangifera indica L.) Leaves Using Response Surface Methodology
Molecules 2014, 19(2), 1411-1421; doi:10.3390/molecules19021411
Received: 29 December 2013 / Revised: 20 January 2014 / Accepted: 20 January 2014 / Published: 27 January 2014
Cited by 9 | PDF Full-text (602 KB) | HTML Full-text | XML Full-text
Abstract
Mangiferin is a xanthone widely distributed in higher plants showing antioxidative, antiviral, anticancer, antidiabetic, immunomodulatory, hepatoprotective and analgesic effects. In the present study, an ultrasonic-assisted extraction method was developed for the effective extraction of mangiferin from mango leaves. Some parameters such as ethanol
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Mangiferin is a xanthone widely distributed in higher plants showing antioxidative, antiviral, anticancer, antidiabetic, immunomodulatory, hepatoprotective and analgesic effects. In the present study, an ultrasonic-assisted extraction method was developed for the effective extraction of mangiferin from mango leaves. Some parameters such as ethanol concentration, liquid-to-solid ratio, extraction temperature, and extraction time were optimized by single-factor experiment and response surface methodology. The optimal extraction conditions were 44% ethanol, the liquid-to-solid ratio was 38:1, and extraction for 19.2 min at 60 °C under ultrasound irradiation of 200 W. Under optimal conditions, the yield of mangiferin was 58.46 ± 1.27 mg/g. The results obtained are helpful for the full utilization of mango leaves, and also indicated that ultrasonic-assisted extraction is a very useful method for the extraction of mangiferin from plant materials. Full article
Open AccessArticle Griffipavixanthone from Garcinia oblongifolia Champ Induces Cell Apoptosis in Human Non-Small-Cell Lung Cancer H520 Cells in Vitro
Molecules 2014, 19(2), 1422-1431; doi:10.3390/molecules19021422
Received: 9 December 2013 / Revised: 14 January 2014 / Accepted: 18 January 2014 / Published: 27 January 2014
Cited by 3 | PDF Full-text (1092 KB) | HTML Full-text | XML Full-text
Abstract
Griffipavixanthone (GPX) is a dimeric xanthone which was isolated in a systematic investigation of Garcinia oblongifolia Champ. In this study, we investigate the effect of GPX on cell proliferation and apoptosis on human Non-small-cell lung cancer (NSCLC) cells in vitro and determine the
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Griffipavixanthone (GPX) is a dimeric xanthone which was isolated in a systematic investigation of Garcinia oblongifolia Champ. In this study, we investigate the effect of GPX on cell proliferation and apoptosis on human Non-small-cell lung cancer (NSCLC) cells in vitro and determine the mechanisms of its action. GPX inhibited the growth of H520 cells in dose- and time-dependent manners, with IC50 values of 3.03 ± 0.21 μM at 48 h. The morphologic characteristics of apoptosis and apoptotic bodies were observed by fluorescence microscope and transmission electron microscope. In addition, Annexin V/PI double staining assay revealed that cells in early stage of apoptosis were significantly increased upon GPX treatment dose-dependently. Rh123 staining assay indicated that GPX reduced the mitochondrial membrane potential. DCFH-DA staining revealed that intracellular ROS increased with GPX treatment. Moreover, GPX cleaved and activated caspase-3. In summary, this study showed that GPX inhibited H520 cell proliferation in dose- and time-dependent manner. Further mechanistic study indicated that GPX induced cell apoptosis through mitochondrial apoptotic pathway accompanying with ROS production. Our results demonstrate the potential application of GPX as an anti-non-small cell lung cancer agent. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of Linear Geranylphenols and Their Effect on Mycelial Growth of Plant Pathogen Botrytis cinerea
Molecules 2014, 19(2), 1512-1526; doi:10.3390/molecules19021512
Received: 9 December 2013 / Revised: 4 January 2014 / Accepted: 15 January 2014 / Published: 27 January 2014
Cited by 6 | PDF Full-text (526 KB) | HTML Full-text | XML Full-text
Abstract
Natural geranyl compounds are known to exhibit important biological activities. In this work a series of geranylphenols were synthesized to evaluate their effect on the mycelial growth of Botrytis cinerea. Geranyl derivatives were synthesized by direct geranylation reactions between the corresponding phenol
[...] Read more.
Natural geranyl compounds are known to exhibit important biological activities. In this work a series of geranylphenols were synthesized to evaluate their effect on the mycelial growth of Botrytis cinerea. Geranyl derivatives were synthesized by direct geranylation reactions between the corresponding phenol derivatives and geraniol, using BF3.OEt2 as catalyst and AgNO3 as secondary catalyst. Previously reported molecules [geranylhydroquinone (2), geranylhydroquinone diacetate (6) and geranylphloroglucinol (9)], and new substances [(E)-4-(3,7-dimethylocta-2,6-dienyl)benzene-1,2,3-triol (geranyl-pyrogallol, 7), (E)-4-(3,7-dimethylocta-2,6-dienyl)benzene-1,2,3-triyl triacetate (8), (E)-2-(3,7-dimethylocta-2,6-dienyl)benzene-1,3,5-triyl triacetate geranylphloroglucinol triacetate (10), 2,4-bis((E)-3,7-dimethylocta-2,6-dienyl)benzene-1,3,5-triyl triacetate (11), 2,6-bis((E)-3,7-dimethylocta-2,6-dienyl)-3,5-dihydroxyphenyl acetate (12)], were obtained. All compounds were characterized by IR, HRMS and NMR spectroscopic data. The inhibitory effect of the synthesized compounds on the mycelial growth of Botrytis cinerea was tested in vitro. Excepting compound 11, all substances constrained the mycelial growth of Botrytis cinerea. The antifungal activity depends on the chemical structure of geranylphenol derivatives. Compounds 2 and 9 were the more effective substances showing inhibition degrees higher than those obtained with the commercial fungicide Captan, even at lower concentrations. Monosubstitution on the aromatic nucleus by a geranyl chain seems to be more effective for the inhibition of mycelial growth than a double substitution. These results suggest that the new derivatives of geranylphenols have the ability to block the mycelial development of the plant pathogen B. cinerea and that this capacity depends strongly on the structural features and lipophilicity of the compounds. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Gas Phase Thermal Reactions of exo-8-Cyclopropyl-bicyclo[4.2.0]oct-2-ene (1-exo)
Molecules 2014, 19(2), 1527-1543; doi:10.3390/molecules19021527
Received: 19 December 2013 / Revised: 10 January 2014 / Accepted: 15 January 2014 / Published: 27 January 2014
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Abstract
The title compound 1-exo (with minor amounts of its C8 epimer 1-endo) was prepared by Wolff-Kishner reduction of the cycloadduct of 1,3-cyclohexadiene and cyclopropylketene. The [1,3]-migration product 2-endo was synthesized by efficient selective cyclopropanation of endo-5-vinylbicyclo[2.2.2]oct-2-ene at the
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The title compound 1-exo (with minor amounts of its C8 epimer 1-endo) was prepared by Wolff-Kishner reduction of the cycloadduct of 1,3-cyclohexadiene and cyclopropylketene. The [1,3]-migration product 2-endo was synthesized by efficient selective cyclopropanation of endo-5-vinylbicyclo[2.2.2]oct-2-ene at the exocyclic π-bond. Gas phase thermal reactions of 1-exo afforded C8 epimerization to 1-endo, [1,3]- migrations to 2-exo and 2-endo, direct fragmentation to cyclohexadiene and vinylcyclopropane, and CPC rearrangement in the following relative kinetic order: kep > k13 > kf > kCPC. Full article
(This article belongs to the Special Issue Gas Phase Reactions)
Open AccessArticle miRNA in Plasma Exosome is Stable under Different Storage Conditions
Molecules 2014, 19(2), 1568-1575; doi:10.3390/molecules19021568
Received: 11 December 2013 / Revised: 21 January 2014 / Accepted: 23 January 2014 / Published: 27 January 2014
Cited by 44 | PDF Full-text (726 KB) | HTML Full-text | XML Full-text
Abstract
Exosomes are small membrane-bound vesicles secreted by most cell types. Exosomes contain various functional proteins, mRNAs and microRNAs (miRNAs) that could be used for diagnostic and therapeutic purposes. How we should store the samples before RNA isolation and whether those long term stored
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Exosomes are small membrane-bound vesicles secreted by most cell types. Exosomes contain various functional proteins, mRNAs and microRNAs (miRNAs) that could be used for diagnostic and therapeutic purposes. How we should store the samples before RNA isolation and whether those long term stored samples could be used for circulating RNA investigation because of RNase is unknown. The aim of the study was to determine the stability of circulating miRNA in exosomes and plasma. Exosomes were isolated from plasma samples by using ExoQuick Precipitation methods. RNA was extracted from exosomes and the corresponding plasma samples with a Qiagen miRNeasy Mini kit. The concentration of RNA was measured by a Qubit® RNA HS Assay Kit, and quantitative PCR was used for individual miRNA expression level detection. Results showed that exosomal miRNA showed extra stability under different storage conditions and no significant influence on plasma miRNA, except for short term storage at 4 °C. It is thus indicated that exosome miRNAs can be good biomarkers based on their stability under various storage conditions. Full article
Open AccessArticle Ursolic Acid-Enriched Herba Cynomorii Extract Induces Mitochondrial Uncoupling and Glutathione Redox Cycling Through Mitochondrial Reactive Oxygen Species Generation: Protection Against Menadione Cytotoxicity in H9c2 Cells
Molecules 2014, 19(2), 1576-1591; doi:10.3390/molecules19021576
Received: 2 December 2013 / Revised: 19 January 2014 / Accepted: 21 January 2014 / Published: 27 January 2014
Cited by 5 | PDF Full-text (536 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Herba Cynomorii (Cynomorium songaricum Rupr., Cynomoriaceae) is one of the most commonly used ‘Yang-invigorating’ tonic herbs in Traditional Chinese Medicine (TCM). An earlier study in our laboratory has demonstrated that HCY2, an ursolic acid-enriched fraction derived from Herba Cynomorii, increased mitochondrial ATP
[...] Read more.
Herba Cynomorii (Cynomorium songaricum Rupr., Cynomoriaceae) is one of the most commonly used ‘Yang-invigorating’ tonic herbs in Traditional Chinese Medicine (TCM). An earlier study in our laboratory has demonstrated that HCY2, an ursolic acid-enriched fraction derived from Herba Cynomorii, increased mitochondrial ATP generation capacity (ATP-GC) and induced mitochondrial uncoupling as well as a cellular glutathione response, thereby protecting against oxidant injury in H9c2 cells. In this study, we demonstrated that pre-incubation of H9c2 cells with HCY2 increased mitochondrial reactive oxygen species (ROS) generation in these cells, which is likely an event secondary to the stimulation of the mitochondrial electron transport chain. The suppression of mitochondrial ROS by the antioxidant dimethylthiourea abrogated the HCY2-induced enhancement of mitochondrial uncoupling and glutathione reductase (GR)-mediated glutathione redox cycling, and also protected against menadione-induced cytotoxicity. Studies using specific inhibitors of uncoupling protein and GR suggested that the HCY2-induced mitochondrial uncoupling and glutathione redox cycling play a determining role in the cytoprotection against menadione-induced oxidant injury in H9c2 cells. Experimental evidence obtained thus far supports the causal role of HCY2-induced mitochondrial ROS production in eliciting mitochondrial uncoupling and glutathione antioxidant responses, which offer cytoprotection against oxidant injury in H9c2 cells. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
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Open AccessArticle Resveratrol-4-O-D-(2'-galloyl)-glucopyranoside Isolated from Polygonum cuspidatum Exhibits Anti-Hepatocellular Carcinoma Viability by Inducing Apoptosis via the JNK and ERK Pathway
Molecules 2014, 19(2), 1592-1602; doi:10.3390/molecules19021592
Received: 6 November 2013 / Revised: 21 January 2014 / Accepted: 23 January 2014 / Published: 27 January 2014
Cited by 5 | PDF Full-text (505 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol-4-O-D-(2'-galloyl)-glucopyranoside (RESG) is one of the active compounds isolated from Polygonum cuspidatum. The purpose of our present study was to investigate the anti-hepatocellular carcinoma effect of RESG in vitro and in vivo, and the possible mechanisms in vitro.
[...] Read more.
Resveratrol-4-O-D-(2'-galloyl)-glucopyranoside (RESG) is one of the active compounds isolated from Polygonum cuspidatum. The purpose of our present study was to investigate the anti-hepatocellular carcinoma effect of RESG in vitro and in vivo, and the possible mechanisms in vitro. In vitro, our results showed that RESG could significantly inhibit the human hepatocellular carcinoma viability in the MTT assay, in a dose- and time-dependent manner. Furthermore, our results demonstrated that RESG could induce SMMC-7721 cell apoptosis and activate caspases 3 and caspases 9 by using Annexin V-FITC staining and western blot, respectively. In vivo, RESG also showed efficacy in SMMC-7721 xenograft model in nude mice, and further molecule mechanisms were investigated in vitro. The results showed that RESG up-regulated the p-JNK expressions, whereas it down-regulated the p-ERK expressions. Above results demonstrated that RESG is a potential therapeutic agent for hepatocellular carcinoma via JNK and ERK pathway to induce apoptosis. Our finding provided a basis for further development of RESG as an anticancer agent. Full article
Open AccessCommunication A New Dicoumarinyl Ether from the Roots of Stellera chamaejasme L
Molecules 2014, 19(2), 1603-1607; doi:10.3390/molecules19021603
Received: 8 January 2014 / Revised: 22 January 2014 / Accepted: 22 January 2014 / Published: 27 January 2014
PDF Full-text (190 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract A new dicoumarinyl ether, 3-hydroxy-6-methoxy-7,7'-dicoumarinyl ether (1), was isolated from the roots of Stellera chamaejasme L, together with the known compound umbelliferone (2). Their structures were determined on the basis of spectroscopic techniques, including IR, NMR, and HR-ESI-MS. Full article
Open AccessArticle Molecular Cloning and Yeast Expression of Cinnamate 4-Hydroxylase from Ornithogalum saundersiae Baker
Molecules 2014, 19(2), 1608-1621; doi:10.3390/molecules19021608
Received: 26 November 2013 / Revised: 18 January 2014 / Accepted: 21 January 2014 / Published: 28 January 2014
Cited by 11 | PDF Full-text (443 KB) | HTML Full-text | XML Full-text
Abstract
OSW-1, isolated from the bulbs of Ornithogalum saundersiae Baker, is a steroidal saponin endowed with considerable antitumor properties. Biosynthesis of the 4-methoxybenzoyl group on the disaccharide moiety of OSW-1 is known to take place biochemically via the phenylpropanoid biosynthetic pathway, but molecular biological
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OSW-1, isolated from the bulbs of Ornithogalum saundersiae Baker, is a steroidal saponin endowed with considerable antitumor properties. Biosynthesis of the 4-methoxybenzoyl group on the disaccharide moiety of OSW-1 is known to take place biochemically via the phenylpropanoid biosynthetic pathway, but molecular biological characterization of the related genes has been insufficient. Cinnamic acid 4-hydroxylase (C4H, EC 1.14.13.11), catalyzing the hydroxylation of trans-cinnamic acid to p-coumaric acid, plays a key role in the ability of phenylpropanoid metabolism to channel carbon to produce the 4-methoxybenzoyl group on the disaccharide moiety of OSW-1. Molecular isolation and functional characterization of the C4H genes, therefore, is an important step for pathway characterization of 4-methoxybenzoyl group biosynthesis. In this study, a gene coding for C4H, designated as OsaC4H, was isolated according to the transcriptome sequencing results of Ornithogalum saundersiae. The full-length OsaC4H cDNA is 1,608-bp long, with a 1,518-bp open reading frame encoding a protein of 505 amino acids, a 55-bp 5′ non-coding region and a 35-bp 3'-untranslated region. OsaC4H was functionally characterized by expression in Saccharomyces cerevisiae and shown to catalyze the oxidation of trans-cinnamic acid to p-coumaric acid, which was identified by high performance liquid chromatography with diode array detection (HPLC-DAD), HPLC-MS and nuclear magnetic resonance (NMR) analysis. The identification of the OsaC4H gene was expected to open the way to clarification of the biosynthetic pathway of OSW-1. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle 4-Aminobenzoic Acid-Coated Maghemite Nanoparticles as Potential Anticancer Drug Magnetic Carriers: A Case Study on Highly Cytotoxic Cisplatin-Like Complexes Involving 7-Azaindoles
Molecules 2014, 19(2), 1622-1634; doi:10.3390/molecules19021622
Received: 23 December 2013 / Revised: 17 January 2014 / Accepted: 23 January 2014 / Published: 28 January 2014
Cited by 3 | PDF Full-text (2646 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This study describes a one-pot synthesis of superparamagnetic maghemite-based 4-aminobenzoic acid-coated spherical core-shell nanoparticles (PABA@FeNPs) as suitable nanocomposites potentially usable as magnetic carriers for drug delivery. The PABA@FeNPs system was subsequently functionalized by the activated species (1* and 2*) of highly
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This study describes a one-pot synthesis of superparamagnetic maghemite-based 4-aminobenzoic acid-coated spherical core-shell nanoparticles (PABA@FeNPs) as suitable nanocomposites potentially usable as magnetic carriers for drug delivery. The PABA@FeNPs system was subsequently functionalized by the activated species (1* and 2*) of highly in vitro cytotoxic cis-[PtCl2(3Claza)2] (1; 3Claza stands for 3-chloro-7-azaindole) or cis-[PtCl2(5Braza)2] (2; 5Braza stands for 5-bromo-7-azaindole), which were prepared by a silver(I) ion assisted dechlorination of the parent dichlorido complexes. The products 1*@PABA@FeNPs and 2*@PABA@FeNPs, as well as an intermediate PABA@FeNPs, were characterized by a combination of various techniques, such as Mössbauer, FTIR and EDS spectroscopy, thermal analysis, SEM and TEM. The results showed that the products consist of well-dispersed maghemite-based nanoparticles of 13 nm average size that represent an easily obtainable system for delivery of highly cytotoxic cisplatin-like complexes in oncological practice. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Simultaneous Determination of Fifteen Constituents of Jitai Tablet Using Ultra High-Performance Liquid Chromatography Coupled with Triple Quadrupole Electrospray Tandem Mass Spectrometry
Molecules 2014, 19(2), 1635-1650; doi:10.3390/molecules19021635
Received: 30 November 2013 / Revised: 24 January 2014 / Accepted: 24 January 2014 / Published: 28 January 2014
Cited by 3 | PDF Full-text (406 KB) | HTML Full-text | XML Full-text
Abstract
An ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method was developed for simultaneous determination of fifteen constituents in Jitai tablet (JTT), a complex Traditional Chinese Medicine prescription (TCMP) used in treating opiate addiction. Benefitting from a small particle size (1.8 µm) C18
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An ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method was developed for simultaneous determination of fifteen constituents in Jitai tablet (JTT), a complex Traditional Chinese Medicine prescription (TCMP) used in treating opiate addiction. Benefitting from a small particle size (1.8 µm) C18 column, accelerated analysis with satisfactory resolution, sensitivity and selectivity were achieved in a single run within 7 min with linear gradient elution of acetonitrile-0.1% (v/v) formic acid in water. The analytical signal was obtained by multiple reaction monitoring transitions via electrospray ionization source operating in both positive and negative ionization mode. The approach was validated for linearity, sensitivity, precision, repeatability, stability and recovery. All analytes showed good linearity over a wide concentration range (r > 0.99). The method limits ranged from 0.03 ng/mL to 19.35 ng/mL which are sensitive enough for quality control studies. The developed method was successfully applied to the simultaneous determination of fifteen constituents in JTT. In conclusion, our experimental results demonstrate that UHPLC-ESI-MS/MS is a useful approach for the overall quality assessment of complex TCMPs. Full article
Open AccessArticle Correlation between Inflammatory Markers of Atherosclerosis and Carotid Intima-Media Thickness in Obstructive Sleep Apnea
Molecules 2014, 19(2), 1651-1662; doi:10.3390/molecules19021651
Received: 23 December 2013 / Revised: 21 January 2014 / Accepted: 21 January 2014 / Published: 29 January 2014
Cited by 22 | PDF Full-text (253 KB) | HTML Full-text | XML Full-text
Abstract
Obstructive Sleep Apnea (OSA) is a sleep-related breathing disorder associated with the development of cardiovascular diseases and atherosclerosis. Systemic inflammation plays an important role in the development of cardiovascular complications in OSA patients. The aim of the study was to evaluate the relationship
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Obstructive Sleep Apnea (OSA) is a sleep-related breathing disorder associated with the development of cardiovascular diseases and atherosclerosis. Systemic inflammation plays an important role in the development of cardiovascular complications in OSA patients. The aim of the study was to evaluate the relationship between carotid intima-media thickness (cIMT) and inflammatory markers plasma levels in OSA patients. We enrolled 80 OSA patients and 40 controls matched for age and body mass index (BMI). The presence and severity of sleep apnea was determined by in-laboratory portable monitoring (PM). Demographic data, blood pressure, heart rate, and cIMT were measured. High-sensitive C-Reactive Protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α and pentraxin (PTX)-3 serum concentrations were detected. cIMT was higher in OSA patients than controls (0.89 ± 0.13 mm vs. 0.65 ± 0.1 mm, p < 0.01). Moderate-severe OSA patients (0.95 ± 0.09 mm) had significantly increased cIMT than mild OSA (0.76 ± 0.1 mm; p < 0.01) and control (0.65 ± 0.1 mm; p < 0.01). hsCRP, IL-6, TNF-α, and PTX-3 in patients with OSA (1.67 ± 0.66 mg/L, 2.86 ± 1.39 pg/mL, 20.09 ± 5.39 pg/mL, 2.1 ± 0.59 ng/mL, respectively) were significantly higher than in controls (1.08 ± 0.53 mg/L, p < 0.01; 1.5 ± 0.67 pg/mL, p < 0.01; 12.53 ± 3.48 pg/mL, p < 0.01; 1.45 ± 0.41 ng/mL, p < 0.01, respectively). Carotid IMT was significantly correlated to CRP (r = 0.44; p < 0.01), IL-6 (r = 0.42; p < 0.01), TNF-α (r = 0.53; p < 0.01), and PTX-3 (r = 0.49; p < 0.01). OSA patients showed increased cIMT, CRP, IL-6, TNF-α, and PTX-3 levels. Inflammatory markers levels are correlated to cIMT in OSA patients. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Penostatin Derivatives, a Novel Kind of Protein Phosphatase 1B Inhibitors Isolated from Solid Cultures of the Entomogenous Fungus Isaria tenuipes
Molecules 2014, 19(2), 1663-1671; doi:10.3390/molecules19021663
Received: 20 December 2013 / Revised: 22 January 2014 / Accepted: 23 January 2014 / Published: 29 January 2014
Cited by 2 | PDF Full-text (233 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Protein tyrosine phosphatase 1B (PTP1B) is implicated as a negative regulator of insulin receptor (IR) signaling and a potential drug target for the treatment of type II diabetes and other associated metabolic syndromes. Therefore, small molecular inhibitors of PTP1B can be considered as
[...] Read more.
Protein tyrosine phosphatase 1B (PTP1B) is implicated as a negative regulator of insulin receptor (IR) signaling and a potential drug target for the treatment of type II diabetes and other associated metabolic syndromes. Therefore, small molecular inhibitors of PTP1B can be considered as an attractive approach for the design of new therapeutic agents of type II diabetes diseases. In a continuing search for new protein phosphatase inhibitors from fungi, we have isolated a new compound, named penostatin J (1), together with three known ones, penostatin C (2), penostatin A (3), and penostatin B (4), from cultures of the entomogenous fungus Isaria tenuipes. The structure of penostatin J (1) was elucidated by extensive spectroscopic analysis. We also demonstrate for the first time that penostatin derivatives exhibit the best PTP1B inhibitory action. These findings suggest that penostatin derivatives are a potential novel kind of PTP1B inhibitors. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Docking Studies in Target Proteins Involved in Antibacterial Action Mechanisms: Extending the Knowledge on Standard Antibiotics to Antimicrobial Mushroom Compounds
Molecules 2014, 19(2), 1672-1684; doi:10.3390/molecules19021672
Received: 7 January 2014 / Revised: 22 January 2014 / Accepted: 26 January 2014 / Published: 29 January 2014
Cited by 4 | PDF Full-text (381 KB) | HTML Full-text | XML Full-text
Abstract
In the present work, the knowledge on target proteins of standard antibiotics was extended to antimicrobial mushroom compounds. Docking studies were performed for 34 compounds in order to evaluate their affinity to bacterial proteins that are known targets for some antibiotics with different
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In the present work, the knowledge on target proteins of standard antibiotics was extended to antimicrobial mushroom compounds. Docking studies were performed for 34 compounds in order to evaluate their affinity to bacterial proteins that are known targets for some antibiotics with different mechanism of action: inhibitors of cell wall synthesis, inhibitors of protein synthesis, inhibitors of nucleic acids synthesis and antimetabolites. After validation of the molecular docking approach, virtual screening of all the compounds was performed against penicillin binding protein 1a (PBP1a), alanine racemase (Alr), d-alanyl-d-alanine synthetase (Ddl), isoleucyl-tRNA sinthetase (IARS), DNA gyrase subunit B, topoisomerase IV (TopoIV), dihydropteroate synthetase (DHPS) and dihydrofolate reductase (DHFR) using AutoDock4. Overall, it seems that for the selected mushroom compounds (namely, enokipodins, ganomycins and austrocortiluteins) the main mechanism of the action is the inhibition of cell wall synthesis, being Alr and Ddl probable protein targets. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Synthesis and Evaluation of Poly(Sodium 2-Acrylamido-2-Methylpropane Sulfonate-co-Styrene)/Magnetite Nanoparticle Composites as Corrosion Inhibitors for Steel
Molecules 2014, 19(2), 1713-1731; doi:10.3390/molecules19021713
Received: 9 January 2014 / Revised: 21 January 2014 / Accepted: 27 January 2014 / Published: 30 January 2014
Cited by 13 | PDF Full-text (814 KB) | HTML Full-text | XML Full-text
Abstract
Self-stabilized magnetic polymeric composite nanoparticles of coated poly-(sodium 2-acrylamido-2-methylpropane sulfonate-co-styrene)/magnetite (PAMPS-Na-co-St/Fe3O4) were prepared by emulsifier-free miniemulsion polymerization using styrene (St) as a monomer, 2-acrylamido-2-methylpropane sulfonic acid sodium salt (AMPS-Na) as an ionic comonomer, N,N-methylenebisacrylamide (MBA) as crosslinker, hexadecane
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Self-stabilized magnetic polymeric composite nanoparticles of coated poly-(sodium 2-acrylamido-2-methylpropane sulfonate-co-styrene)/magnetite (PAMPS-Na-co-St/Fe3O4) were prepared by emulsifier-free miniemulsion polymerization using styrene (St) as a monomer, 2-acrylamido-2-methylpropane sulfonic acid sodium salt (AMPS-Na) as an ionic comonomer, N,N-methylenebisacrylamide (MBA) as crosslinker, hexadecane (HD) as a hydrophobic solvent, and 2,2-azodiisobutyronitrile (AIBN) as an initiator in the presence of hydrophobic oleic acid coated magnetite particles. Hydrophobic oleic acid coated magnetite particles with an average size of about 7-10 nm were prepared with the new modified water-based magnetite ferrofluid, synthesized by a chemical modified coprecipitation method. The morphology and the particle size distributions of the crosslinked PAMPS-Na-co-St/Fe3O4 composite were observed and analyzed by transmission electron microscopy (TEM). The average Fe3O4 content of PAMPS-Na-co-St/Fe3O4 was determined by thermogravimetric analysis (TGA). The inhibitory action of PAMPS-Na-co-St/Fe3O4 towards steel corrosion in 1 M HCl solutions has been investigated by polarization and electrochemical impedance spectroscopy (EIS) methods. Polarization measurements indicate that PAMPS-Na-co-St/Fe3O4 acts as a mixed type-inhibitor and the inhibition efficiency increases with inhibitor concentration. The results of potentiodynamic polarization and EIS measurements clearly showed that the inhibition mechanism involves blocking of the steel surface by inhibitor molecules via adsorption. Full article
Open AccessArticle Kingianic Acids A–G, Endiandric Acid Analogues from Endiandra kingiana
Molecules 2014, 19(2), 1732-1747; doi:10.3390/molecules19021732
Received: 14 November 2013 / Revised: 3 January 2014 / Accepted: 23 January 2014 / Published: 31 January 2014
Cited by 8 | PDF Full-text (335 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A phytochemical investigation of the methanolic extract of the bark of Endiandra kingiana led to the isolation of seven new tetracyclic endiandric acid analogues, kingianic acids A–G (17), together with endiandric acid M (8), tsangibeilin B (
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A phytochemical investigation of the methanolic extract of the bark of Endiandra kingiana led to the isolation of seven new tetracyclic endiandric acid analogues, kingianic acids A–G (17), together with endiandric acid M (8), tsangibeilin B (9) and endiandric acid (10). Their structures were determined by 1D- and 2D-NMR analysis in combination with HRMS experiments. The structure of compounds 9 and 10 were confirmed by single-crystal X-ray diffraction analysis. These compounds were screened for Bcl-xL and Mcl-1 binding affinities and cytotoxic activity on various cancer cell lines. Compound 5 showed moderate cytotoxic activity against human colorectal adeno-carcinoma (HT-29) and lung adenocarcinoma epithelial (A549) cell lines, with IC50 values in the range 15–17 µM, and compounds 3, 6 and 9 exhibited weak binding affinity for the anti-apoptotic protein Mcl-1. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Easy Access to a Cyclic Key Intermediate for the Synthesis of Trisporic Acids and Related Compounds
Molecules 2014, 19(2), 1748-1762; doi:10.3390/molecules19021748
Received: 19 December 2013 / Revised: 22 January 2014 / Accepted: 23 January 2014 / Published: 3 February 2014
Cited by 2 | PDF Full-text (420 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The synthesis of a cyclohexane skeleton possessing different oxygenated functional groups at C–3, C–8 and C–9, and a D1,6-double bond has been accomplished in 10 steps with an overall 17% yield. This compound is a key intermediate for access to a
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The synthesis of a cyclohexane skeleton possessing different oxygenated functional groups at C–3, C–8 and C–9, and a D1,6-double bond has been accomplished in 10 steps with an overall 17% yield. This compound is a key intermediate for access to a wide range of compounds of the bioactive trisporoid family. The synthetic sequence consists of the preparation of a properly functionalized epoxygeraniol derivative, and its subsequent stereoselective cyclization mediated by Ti(III). This last step implies a domino process that starts with a homolytic epoxide opening followed by a radical cyclization and regioselective elimination. This concerted process gives access to the cyclohexane moiety with stereochemical control of five of its six carbon atoms. Full article
(This article belongs to the Special Issue Domino Reactions)
Open AccessArticle Pauson-Khand Reaction of Internal Dissymmetric Trifluoromethyl Alkynes. Influence of the Alkene on the Regioselectivity
Molecules 2014, 19(2), 1763-1774; doi:10.3390/molecules19021763
Received: 2 January 2014 / Revised: 15 January 2014 / Accepted: 27 January 2014 / Published: 3 February 2014
Cited by 4 | PDF Full-text (237 KB) | HTML Full-text | XML Full-text
Abstract
The scope of the Pauson-Khand reaction (PKR) of internal trifluoromethyl alkynes, previously described with norbornadiene, is expanded to norbornene and ethylene. A thorough structural analysis of the resulting PK adducts has been carried out to unveil that α-trifluoromethylcyclopentenones are preferred in all cases,
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The scope of the Pauson-Khand reaction (PKR) of internal trifluoromethyl alkynes, previously described with norbornadiene, is expanded to norbornene and ethylene. A thorough structural analysis of the resulting PK adducts has been carried out to unveil that α-trifluoromethylcyclopentenones are preferred in all cases, independently of the electronic properties of the alkyne. The regioselectivity observed with norbornadiene and ethylene is higher than in the case of norbornene. Full article
(This article belongs to the Special Issue Fluorine Chemistry 2016)
Open AccessArticle Inhibitory Activity of Synthesized Acetylated Procyanidin B1 Analogs against HeLa S3 Cells Proliferation
Molecules 2014, 19(2), 1775-1785; doi:10.3390/molecules19021775
Received: 19 November 2013 / Revised: 22 January 2014 / Accepted: 28 January 2014 / Published: 4 February 2014
Cited by 3 | PDF Full-text (334 KB) | HTML Full-text | XML Full-text
Abstract
Proanthocyanidins, also known as condensed tannins and/or oligomeric flavonoids, occur in many edible plants and have various interesting biological activities. Previously, we reported a synthetic method for the preparation of various procyanidins in pure form and described their biological activities. Here, we describe
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Proanthocyanidins, also known as condensed tannins and/or oligomeric flavonoids, occur in many edible plants and have various interesting biological activities. Previously, we reported a synthetic method for the preparation of various procyanidins in pure form and described their biological activities. Here, we describe the synthesis of procyanidin B1 acetylated analogs and discuss their inhibition activities against HeLa S3 cell proliferation. Surprisingly, the lower-unit acetylated procyanidin B1 strongly inhibited the proliferation of HeLa S3 cells. This molecule showed much stronger inhibitory activity than did epigallocatechin-3-O-gallate (EGCG), green tea polyphenol, and dimeric compounds that included EGCG as a unit. This result suggests that the phenolic hydroxyl groups of the upper-units in flavan-3-ols are important for their inhibitory activity against cancer cell proliferation and that a hydrophobic lower unit dimer enhances this activity. Full article
(This article belongs to the Special Issue Structure-Activity Relationship of Flavonoids)
Open AccessArticle A Pair of New Antioxidant Phenolic Acid Stereoisomers Isolated from Danshen Injection (Lyophilized Powder)
Molecules 2014, 19(2), 1786-1794; doi:10.3390/molecules19021786
Received: 17 December 2013 / Revised: 27 January 2014 / Accepted: 29 January 2014 / Published: 4 February 2014
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Abstract
A pair of new phenolic acid stereoisomers, (R)-norsalvianolic acid L (1) and (S)-norsalvianolic acid L (2), was isolated from the Danshen Injection (lyophilized powder). The structural elucidation and stereochemistry determination were achieved by spectroscopic and
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A pair of new phenolic acid stereoisomers, (R)-norsalvianolic acid L (1) and (S)-norsalvianolic acid L (2), was isolated from the Danshen Injection (lyophilized powder). The structural elucidation and stereochemistry determination were achieved by spectroscopic and chemical methods including 1D, 2D NMR (1H-1H COSY, HSQC and HMBC) and circular dichroism experiments. Their antioxidant activities were assessed by the DPPH· and ABTS·+ scavenging methods in vitro with microplate assay. The IC50 values of 1 were 6.9 and 9.7 μM respectively, which was close to the control salvianolic acid B (7.8 and 7.1 μM respectively), while the IC50 values of isomer 2 were 27.1 and 25.3 μM, respectively. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Alleviation of Water Stress Effects on MR220 Rice by Application of Periodical Water Stress and Potassium Fertilization
Molecules 2014, 19(2), 1795-1819; doi:10.3390/molecules19021795
Received: 3 December 2013 / Revised: 21 January 2014 / Accepted: 23 January 2014 / Published: 5 February 2014
Cited by 4 | PDF Full-text (459 KB) | HTML Full-text | XML Full-text
Abstract
The use of periodical water stress and potassium fertilization may enhance rice tolerance to drought stress and improve the crop’s instantaneous water use efficiency without much yield reduction. This study was conducted to assess the effects of different periodical water stress combined with
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The use of periodical water stress and potassium fertilization may enhance rice tolerance to drought stress and improve the crop’s instantaneous water use efficiency without much yield reduction. This study was conducted to assess the effects of different periodical water stress combined with potassium fertilization regimes on growth, yield, leaf gas exchanges and biochemical changes in rice grown in pots and compare them with standard local rice grower practices. Five treatments including (1) standard local grower’s practice (control, 80CF = 80 kg K2O/ha + control flooding); (2) 120PW15 = 120 kg K2O/ha + periodical water stress for 15 days; (3) 120DS15V = 120 kg K2O/ha + drought stress for 15 days during the vegetative stage; (4) 120DS25V = 120 kg K2O/ha + drought stress for 25 days and (5) 120DS15R = 120 kg K2O/ha + drought stress for 15 days during the reproductive stage, were evaluated in this experiment. Control and 120PW15 treatments were stopped at 100 DAS, and continuously saturated conditions were applied until harvest. It was found that rice under 120PW15 treatment showed tolerance to drought stress evidenced by increased water use efficiency, peroxidase (POX), catalase (CAT) and proline levels, maximum efficiency of photosystem II (fv/fm) and lower minimal fluorescence (fo), compared to other treatments. Path coefficient analysis revealed that most of parameters contribute directly rather than indirectly to rice yield. In this experiment, there were four factors that are directly involved with rice yield: grain soluble sugar, photosynthesis, water use efficiency and total chlorophyll content. The residual factors affecting rice yield are observed to be quite low in the experiment (0.350), confirming that rice yield was mostly influenced by the parameters measured during the study. Full article
Open AccessArticle Cytotoxic Prenylated Xanthones from the Pericarps of Garcinia mangostana
Molecules 2014, 19(2), 1820-1827; doi:10.3390/molecules19021820
Received: 30 December 2013 / Revised: 21 January 2014 / Accepted: 27 January 2014 / Published: 6 February 2014
Cited by 9 | PDF Full-text (252 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Bioassay-guided fractionation of an ethanol extract of the pericarps of Garcinia mangostana led to the isolation of two new prenylated xanthones, named 1,3,7-trihydroxy-2-(3-methyl-2-butenyl)-8-(3-hydroxy-3-methylbutyl)-xanthone (1) and 1,3,8-trihydroxy-2-(3-methyl-2-butenyl)-4-(3-hydroxy-3-methylbutanoyl)-xanthone (2), together with the five known compounds garcinones C (3) and
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Bioassay-guided fractionation of an ethanol extract of the pericarps of Garcinia mangostana led to the isolation of two new prenylated xanthones, named 1,3,7-trihydroxy-2-(3-methyl-2-butenyl)-8-(3-hydroxy-3-methylbutyl)-xanthone (1) and 1,3,8-trihydroxy-2-(3-methyl-2-butenyl)-4-(3-hydroxy-3-methylbutanoyl)-xanthone (2), together with the five known compounds garcinones C (3) and D (4), gartanin (5), xanthone I (6), and γ-mangostin (7). Their structures were elucidated primarily based on MS and NMR data. Compounds 17 showed significant cytotoxic activities against various human cancer cell lines. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Theoretical Study on the Allosteric Regulation of an Oligomeric Protease from Pyrococcus horikoshii by Cl Ion
Molecules 2014, 19(2), 1828-1842; doi:10.3390/molecules19021828
Received: 19 December 2013 / Revised: 23 January 2014 / Accepted: 27 January 2014 / Published: 7 February 2014
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Abstract
The thermophilic intracellular protease (PH1704) from Pyrococcus horikoshii that functions as an oligomer (hexamer or higher forms) has proteolytic activity and remarkable stability. PH1704 is classified as a member of the C56 family of peptidases. This study is the first to observe that
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The thermophilic intracellular protease (PH1704) from Pyrococcus horikoshii that functions as an oligomer (hexamer or higher forms) has proteolytic activity and remarkable stability. PH1704 is classified as a member of the C56 family of peptidases. This study is the first to observe that the use of Cl as an allosteric inhibitor causes appreciable changes in the catalytic activity of the protease. Theoretical methods were used for further study. Quantum mechanical calculations indicated the binding mode of Cl with Arg113. A molecular dynamics simulation explained how Cl stabilized distinct contact species and how it controls the enzyme activity. The new structural insights obtained from this study are expected to stimulate further biochemical studies on the structures and mechanisms of allosteric proteases. It is clear that the discovery of new allosteric sites of the C56 family of peptidases may generate opportunities for pharmaceutical development and increases our understanding of the basic biological processes of this peptidase family. Full article
(This article belongs to the Special Issue In-Silico Drug Design and In-Silico Screening)
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Open AccessArticle Antiproliferative Activity and Induction of Apoptosis in PC-3 Cells by the Chalcone Cardamonin from Campomanesia adamantium (Myrtaceae) in a Bioactivity-Guided Study
Molecules 2014, 19(2), 1843-1855; doi:10.3390/molecules19021843
Received: 3 January 2014 / Revised: 31 January 2014 / Accepted: 3 February 2014 / Published: 7 February 2014
Cited by 11 | PDF Full-text (437 KB) | HTML Full-text | XML Full-text
Abstract
The Myrtaceae family is a common source of medicines used in the treatment of numerous diseases in South America. In Brazil, fruits of the Campomanesia species are widely used to make liqueurs, juices and sweets, whereas leaves are traditionally employed as a medicine
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The Myrtaceae family is a common source of medicines used in the treatment of numerous diseases in South America. In Brazil, fruits of the Campomanesia species are widely used to make liqueurs, juices and sweets, whereas leaves are traditionally employed as a medicine for dysentery, stomach problems, diarrhea, cystitis and urethritis. Ethanol extracts of Campomanesia adamantium (Myrtaceae) leaves and fruits were evaluated against prostate cancer cells (PC-3). The compound (2E)-1-(2,4-dihydroxy-6-methoxyphenyl)-3-phenylprop-2-en-1-one, cardamonin) was isolated from ethanol extracts of C. adamantium leaves in a bioactivity-guided study and quantified by UPLC-MS/MS. In vitro studies showed that the isolated chalcone cardamonin inhibited prostate cancer cell proliferation and decreased the expression of NFkB1. Moreover, analysis by flow cytometry showed that this compound induced DNA fragmentation, suggesting an effect on apoptosis induction in the PC-3 cell line. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Optimization of High-Pressure Ultrasonic-Assisted Simultaneous Extraction of Six Major Constituents from Ligusticum chuanxiong Rhizome using Response Surface Methodology
Molecules 2014, 19(2), 1887-1911; doi:10.3390/molecules19021887
Received: 19 December 2013 / Revised: 24 January 2014 / Accepted: 3 February 2014 / Published: 10 February 2014
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Abstract
High-pressure ultrasound-assisted extraction technology was applied to extract ferulic acid, senkyunolide I, senkyunolide H, senkyunolide A, ligustilide and levistolide A from Ligusticum chuanxiong rhizomes. Seven independent variables, including solvent type, pressure, particle size, liquid-to-solid ratio, extraction temperature, ultrasound power, and extraction time were
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High-pressure ultrasound-assisted extraction technology was applied to extract ferulic acid, senkyunolide I, senkyunolide H, senkyunolide A, ligustilide and levistolide A from Ligusticum chuanxiong rhizomes. Seven independent variables, including solvent type, pressure, particle size, liquid-to-solid ratio, extraction temperature, ultrasound power, and extraction time were examined. Response Surface Methodology (RSM) using a Central Composite Design (CCD) was employed to optimize the experimental conditions (extraction temperature, ultrasonic power, and extraction time) on the basis of the results of single factor tests for the extraction of these six major components in L. chuanxiong rhizomes. The experimental data were fitted to a second-order polynomial equation using multiple regression analysis and were also examined using appropriate statistical methods. The best extraction conditions were as follows: extraction solvent: 40% ethanol; pressure: 10 MPa; particle size: 80 mesh; liquid-to-solid ratio: 100:1; extraction temperature: 70 °C; ultrasonic power, 180 W; and extraction time, 74 min. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Use of EST-SSR Markers for Evaluating Genetic Diversity and Fingerprinting Celery (Apium graveolens L.) Cultivars
Molecules 2014, 19(2), 1939-1955; doi:10.3390/molecules19021939
Received: 23 December 2013 / Revised: 5 February 2014 / Accepted: 7 February 2014 / Published: 10 February 2014
Cited by 3 | PDF Full-text (333 KB) | HTML Full-text | XML Full-text
Abstract
Celery (Apium graveolens L.) is one of the most economically important vegetables worldwide, but genetic and genomic resources supporting celery molecular breeding are quite limited, thus few studies on celery have been conducted so far. In this study we made use of
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Celery (Apium graveolens L.) is one of the most economically important vegetables worldwide, but genetic and genomic resources supporting celery molecular breeding are quite limited, thus few studies on celery have been conducted so far. In this study we made use of simple sequence repeat (SSR) markers generated from previous celery transcriptome sequencing and attempted to detect the genetic diversity and relationships of commonly used celery accessions and explore the efficiency of the primers used for cultivars identification. Analysis of molecular variance (AMOVA) of Apium graveolens L. var. dulce showed that approximately 43% of genetic diversity was within accessions, 45% among accessions, and 22% among horticultural types. The neighbor-joining tree generated by unweighted pair group method with arithmetic mean (UPGMA), and population structure analysis, as well as principal components analysis (PCA), separated the cultivars into clusters corresponding to the geographical areas where they originated. Genetic distance analysis suggested that genetic variation within Apium graveolens was quite limited. Genotypic diversity showed any combinations of 55 genic SSRs were able to distinguish the genotypes of all 30 accessions. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle A Variable Temperature X-ray Diffraction Investigation of [PPN+][S4N5]: Supramolecular Interactions Governing an Order/Disorder Transformation and the First High Resolution X-ray Structure of the Anion
Molecules 2014, 19(2), 1956-1975; doi:10.3390/molecules19021956
Received: 14 January 2014 / Revised: 29 January 2014 / Accepted: 30 January 2014 / Published: 12 February 2014
Cited by 1 | PDF Full-text (1433 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The title salt, triphenyl(P,P,P-triphenylphosphineimidato-kN)-phosphorus(1+) 1,3,5,7-tetrathia(1,5-SIV)-2,4,6,8,9-pentaazabicyclo[3.3.1]nona-1,4,6,7-tetraene(1−), CAS [48236-06-2], prepared by the literature method, is found by crystallography to be a 1:1 CH3CN solvate. Disorder exists for the N atoms of the anion. A VT crystal
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The title salt, triphenyl(P,P,P-triphenylphosphineimidato-kN)-phosphorus(1+) 1,3,5,7-tetrathia(1,5-SIV)-2,4,6,8,9-pentaazabicyclo[3.3.1]nona-1,4,6,7-tetraene(1−), CAS [48236-06-2], prepared by the literature method, is found by crystallography to be a 1:1 CH3CN solvate. Disorder exists for the N atoms of the anion. A VT crystal structure study was conducted at 100 K, 120 K, 140 K, 172 K, 200 K, 240 K and 280 K. The 100 K structure is superior, with only 10% of a second anion position oppositely-oriented w.r.t the diad axis of point group 2mm. At 120 K, an adjacent two-site disorder is encountered, but at higher temperatures three-site disorder with both opposite and adjacent placements of S4N5 ions is required w.r.t. the primary component. At 240 and especially 280 K, the anion nitrogen atoms appear fully scrambled amongst the six possible sites on the edges of an S4 tetrahedron with 83.3% occupancy for each. The PPN+ geometry does not show strong cation-cation interactions. However, there are numerous supramolecular contacts corresponding mostly to non-classical H-bonds between PPN+ ions and S4N5 as well as CH3CN. The geometry of the anion is corroborated from B3LYP/6-311++G(3df) DFT calculations, and the infra-red spectrum was assigned with excellent agreement between experimental and calculated frequencies. Full article
(This article belongs to the Special Issue Chalcogen-Nitrogen Chemistry)
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Open AccessArticle Pyrrolidine-Mediated Direct Preparation of (E)-Monoarylidene Derivatives of Homo- and Heterocyclic Ketones with Various Aldehydes
Molecules 2014, 19(2), 1976-1989; doi:10.3390/molecules19021976
Received: 18 December 2013 / Revised: 21 January 2014 / Accepted: 26 January 2014 / Published: 12 February 2014
Cited by 1 | PDF Full-text (435 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An efficient method for the facile synthesis of (E)-monoarylidene derivatives of homo- and heterocyclic ketones with various aldehydes in the presence of a pyrrolidine organocatalyst has been achieved. A range of α,β-unsaturated ketones were obtained in moderate to high yields (up
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An efficient method for the facile synthesis of (E)-monoarylidene derivatives of homo- and heterocyclic ketones with various aldehydes in the presence of a pyrrolidine organocatalyst has been achieved. A range of α,β-unsaturated ketones were obtained in moderate to high yields (up to 99%). Unlike the Claisen-Schmidt condensation process, the formation of undesired bisarylidene byproducts is not observed. The possible reaction mechanism suggests that the reaction proceeds via a Mannich-elimination sequence. Full article
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Open AccessArticle Synthesis, Molecular and Crystal Structure Analysis of 1-(4-Methylbenzenesulfonyl)indole-3-carbaldehyde and DFT Investigation of Its Rotational Conformers
Molecules 2014, 19(2), 1990-2003; doi:10.3390/molecules19021990
Received: 13 November 2013 / Revised: 25 January 2014 / Accepted: 28 January 2014 / Published: 13 February 2014
PDF Full-text (825 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two independent molecules that differ in terms of rotation about the central S-N bond comprise the asymmetric unit of the title compound 1. The molecules have a V-shape with the dihedral angles between the fused ring system and benzene ring being 79.08(6)°
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Two independent molecules that differ in terms of rotation about the central S-N bond comprise the asymmetric unit of the title compound 1. The molecules have a V-shape with the dihedral angles between the fused ring system and benzene ring being 79.08(6)° and 72.83(5)°, respectively. The packing is mostly driven by p···p interactions occurring between the tolyl ring of one molecule and the C6 ring of the indole fused ring system of the other. DFT and IRC calculations for these and related 1-(arylsulfonyl)indole molecules showed that the rotational barrier about the S-N bond between conformers is within the 2.5–5.5 kcal/mol range. Crystal data for C16H13NO3S (1): Mr = 299.33, space group Pna21, a = 19.6152(4) Å, b = 11.2736(4) Å, c = 12.6334(3) Å, V = 2793.67(13) Å3, Z = 8, Z' = 2, R = 0.034. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Synthesis and Biological Evaluation of Chromenylurea and Chromanylurea Derivatives as Anti-TNF-α agents that Target the p38 MAPK Pathway
Molecules 2014, 19(2), 2004-2028; doi:10.3390/molecules19022004
Received: 17 December 2013 / Revised: 28 January 2014 / Accepted: 28 January 2014 / Published: 13 February 2014
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Abstract
A series of 1-aryl-3-(2H-chromen-5-yl)urea and 1-aryl-3-(chroman-5-yl)urea derivatives were designed, synthesized and evaluated for their inhibitory activities towards TNF-α production in lipopolysaccharide-stimulated THP-1 cells. The most active compound, 40g, inhibited TNF-α release with an IC50 value of 0.033 μM, which
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A series of 1-aryl-3-(2H-chromen-5-yl)urea and 1-aryl-3-(chroman-5-yl)urea derivatives were designed, synthesized and evaluated for their inhibitory activities towards TNF-α production in lipopolysaccharide-stimulated THP-1 cells. The most active compound, 40g, inhibited TNF-α release with an IC50 value of 0.033 μM, which is equipotent to that of BIRB796 (IC50 = 0.032 μM). Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Effects of Danshensu and Salvianolic Acid B from Salvia miltiorrhiza Bunge (Lamiaceae) on Cell Proliferation and Collagen and Melanin Production
Molecules 2014, 19(2), 2029-2041; doi:10.3390/molecules19022029
Received: 4 December 2013 / Revised: 1 February 2014 / Accepted: 8 February 2014 / Published: 13 February 2014
Cited by 7 | PDF Full-text (1011 KB) | HTML Full-text | XML Full-text
Abstract
Danshensu (DSU) and salvianolic acid B (SAB) are the primary water-soluble compounds of Salvia miltiorrhiza Bunge (Lamiaceae). In this study, we analyzed the effects of DSU, SAB and a S. miltiorrhiza extract (SME) on cell proliferation. Additionally, the effects of DSU
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Danshensu (DSU) and salvianolic acid B (SAB) are the primary water-soluble compounds of Salvia miltiorrhiza Bunge (Lamiaceae). In this study, we analyzed the effects of DSU, SAB and a S. miltiorrhiza extract (SME) on cell proliferation. Additionally, the effects of DSU and SAB on collagen synthesis in Detroit 551 human normal fibroblast cells and on melanin production in B16 melanoma cells were verified. The results demonstrated that SME can enhance the proliferation of Detroit 551 cells and that this boost may be caused by DSU and SAB. This research showed that SME, DSU and SAB all have the ability to increase the production of collagen in Detroit 551 cells. The results also confirmed that DSU and SAB can attenuate the α-MSH-stimulated melanin production of B16 cells by inhibiting tyrosinase activity. Therefore, SME, DSU and SAB each have the potential to be utilized as active ingredients in wound healing or cosmetic treatments. In the future, DSU and SAB could also be used as functional components for treating hyperpigmentation. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Coumarins from Edgeworthia chrysantha
Molecules 2014, 19(2), 2042-2048; doi:10.3390/molecules19022042
Received: 9 January 2014 / Revised: 23 January 2014 / Accepted: 23 January 2014 / Published: 13 February 2014
Cited by 1 | PDF Full-text (238 KB) | HTML Full-text | XML Full-text
Abstract
A new coumarin, edgeworic acid (1), was isolated from the flower buds of Edgeworthia chrysantha, together with the five known coumarins umbelliferone (2), 5,7-dimethoxycoumarin (3), daphnoretin (4), edgeworoside C (5), and edgeworoside
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A new coumarin, edgeworic acid (1), was isolated from the flower buds of Edgeworthia chrysantha, together with the five known coumarins umbelliferone (2), 5,7-dimethoxycoumarin (3), daphnoretin (4), edgeworoside C (5), and edgeworoside A (6). Their structures were established on the basis of spectral data, particularly by the use of 1D NMR and several 2D shift-correlated NMR pulse sequences (1H-1H COSY, HSQC and HMBC), in combination with acetylation reactions. Full article
Open AccessArticle Three New Clerodane Diterpenes from Polyalthia longifolia var. pendula
Molecules 2014, 19(2), 2049-2060; doi:10.3390/molecules19022049
Received: 10 January 2014 / Revised: 30 January 2014 / Accepted: 3 February 2014 / Published: 13 February 2014
Cited by 5 | PDF Full-text (349 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three new clerodane diterpenes, (4→2)-abeo-cleroda-2,13E-dien-2,14-dioic acid (1), (4→2)-abeo-2,13-diformyl-cleroda-2,13E-dien-14-oic acid (2), and 16(R&S)- methoxycleroda-4(18),13-dien-15,16-olide (3), were isolated from the unripe fruit of Polyalthia longifolia var. pendula
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Three new clerodane diterpenes, (4→2)-abeo-cleroda-2,13E-dien-2,14-dioic acid (1), (4→2)-abeo-2,13-diformyl-cleroda-2,13E-dien-14-oic acid (2), and 16(R&S)- methoxycleroda-4(18),13-dien-15,16-olide (3), were isolated from the unripe fruit of Polyalthia longifolia var. pendula (Annonaceae) together with five known compounds (48). The structures of all isolates were determined by spectroscopic analysis. The anti-inflammatory activity of the isolates was evaluated by testing their inhibitory effect on NO production in LPS-stimulated RAW 264.7 macrophages. Among the isolated compounds, 16-hydroxycleroda-3,13-dien-15,16-olide (6) and 16-oxocleroda-3,13-dien-15-oic acid (7) showed promising NO inhibitory activity at 10 µg/mL, with 81.1% and 86.3%, inhibition, respectively. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Anticancer and Multidrug Resistance-Reversal Effects of Solanidine Analogs Synthetized from Pregnadienolone Acetate
Molecules 2014, 19(2), 2061-2076; doi:10.3390/molecules19022061
Received: 9 December 2013 / Revised: 29 January 2014 / Accepted: 6 February 2014 / Published: 17 February 2014
Cited by 9 | PDF Full-text (453 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A set of solanidine analogs with antiproliferative properties were recently synthetized from pregnadienolone acetate, which occurs in Nature. The aim of the present study was an in vitro characterization of their antiproliferative action and an investigation of their multidrug resistance-reversal activity on cancer
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A set of solanidine analogs with antiproliferative properties were recently synthetized from pregnadienolone acetate, which occurs in Nature. The aim of the present study was an in vitro characterization of their antiproliferative action and an investigation of their multidrug resistance-reversal activity on cancer cells. Six of the compounds elicited the accumulation of a hypodiploid population of HeLa cells, indicating their apoptosis-inducing character, and another one caused cell cycle arrest at the G2/M phase. The most effective agents inhibited the activity of topoisomerase I, as evidenced by plasmid supercoil relaxation assays. One of the most potent analogs down-regulated the expression of cell-cycle related genes at the mRNA level, including tumor necrosis factor alpha and S-phase kinase-associated protein 2, and induced growth arrest and DNA damage protein 45 alpha. Some of the investigated compounds inhibited the ABCB1 transporter and caused rhodamine-123 accumulation in murine lymphoma cells transfected by human MDR1 gene, expressing the efflux pump (L5178). One of the most active agents in this aspect potentiated the antiproliferative action of doxorubicin without substantial intrinsic cytostatic capacity. The current results indicate that the modified solanidine skeleton is a suitable substrate for the rational design and synthesis of further innovative drug candidates with anticancer activities. Full article
(This article belongs to the Special Issue Bioactivity-focused Semi-synthesis in Drug Discovery)
Open AccessArticle Synergism of Cyclin-Dependent Kinase Inhibitors with Camptothecin Derivatives in Small Cell Lung Cancer Cell Lines
Molecules 2014, 19(2), 2077-2088; doi:10.3390/molecules19022077
Received: 31 October 2013 / Revised: 21 January 2014 / Accepted: 29 January 2014 / Published: 17 February 2014
Cited by 8 | PDF Full-text (506 KB) | HTML Full-text | XML Full-text
Abstract
Advanced small cell lung cancer (SCLC) has a dismal prognosis. Modulation of the camptothecin topotecan, approved for second-line therapy, may improve response. Our recent finding of synergistic enhancement of the cytotoxic activity of camptothecin (CPT) by cyclin-dependent kinase 4 inhibitors is extended here
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Advanced small cell lung cancer (SCLC) has a dismal prognosis. Modulation of the camptothecin topotecan, approved for second-line therapy, may improve response. Our recent finding of synergistic enhancement of the cytotoxic activity of camptothecin (CPT) by cyclin-dependent kinase 4 inhibitors is extended here to a panel of camptothecin analogs comprising 10-hydroxy-CPT (HOCPT), topotecan (TPT; 9-[(dimethylamino)-methyl]-10-hydroxy-CPT), 9-amino-CPT (9AC), 9-nitrocamptothecin (rubitecan), SN38 (7-ethyl-10-hydroxycamptothecin) and 10-hydroxy-9-nitrocamptothecin (CPT109) in combination with PD0332991, CDK4I, roscovitine and olomoucine. SCLC cell lines employed are chemoresistant NCI-H417 and DMS153 and the chemosensitive SCLC26A line established at our institution. The CPT analogs exhibiting highest cytotoxicity towards the three SCLC lines tested were SN38 and 9AC, followed by rubitecan, HOCPT, TPT and CPT109. NCI-H417 and DMS153 revealed an approximately 25-fold and 7-fold higher resistance compared to the chemosensitive SCLC26A cell line. Whereas the CDK4/6 inhibitor PD0332991 proved less effective to chemosensitize SCLC cells to CPT analogs, the CDK inhibitors CDK4I, roscovitine and olomoucine gave comparable chemosensitization effects in combination with 9AC, SN38, rubitecan and to a lesser extent with TPT and CPT109, not directly related with topoisomerase mRNA expression. In conclusion, small chemical modifications of the parent CPT structure result in differing cytotoxicities and chemomodulatory effects in combination with CDKIs of the resulting analogs. Full article
(This article belongs to the Special Issue Bioactivity-focused Semi-synthesis in Drug Discovery)
Open AccessArticle Antiplatelet and Antithrombotic Activities of Non-Steroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit
Molecules 2014, 19(2), 2089-2099; doi:10.3390/molecules19022089
Received: 8 November 2013 / Revised: 30 January 2014 / Accepted: 10 February 2014 / Published: 17 February 2014
Cited by 8 | PDF Full-text (277 KB) | HTML Full-text | XML Full-text
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) 15 containing an N-acyl hydrazone subunit were prepared and their antiplatelet and antithrombotic activities assessed in vitro and in vivo. Compounds 15 inhibited the platelet aggregation induced by adenosine diphosphate and/or arachidonic acid, with
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Nonsteroidal anti-inflammatory drugs (NSAIDs) 15 containing an N-acyl hydrazone subunit were prepared and their antiplatelet and antithrombotic activities assessed in vitro and in vivo. Compounds 15 inhibited the platelet aggregation induced by adenosine diphosphate and/or arachidonic acid, with inhibition rates of 18.0%–61.1% and 65.9%–87.3%, respectively. Compounds 1 and 5 were the most active compounds, inhibiting adenosine-diphosphate-induced platelet aggregation by 57.2% and 61.1%, respectively. The inhibitory rates for arachidonic-acid-induced platelet aggregation were similar for compound 2 (80.8%) and acetylsalicylic acid (ASA, 80%). After their oral administration to mice, compounds 1, 3, and 5 showed shorter mean bleeding times than ASA. Compounds 1 and 5 also protected against thromboembolic events, with survival rates of 40% and 33%, respectively, compared with 30% for ASA. In conclusion, these results indicate that these novel NSAIDs containing an NAH subunit may offer better antiplatelet and antithrombotic activities than ASA. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Comparative Evaluation of the Radical-Scavenging Activities of Fucoxanthin and Its Stereoisomers
Molecules 2014, 19(2), 2100-2113; doi:10.3390/molecules19022100
Received: 6 November 2013 / Revised: 7 January 2014 / Accepted: 8 February 2014 / Published: 17 February 2014
Cited by 7 | PDF Full-text (265 KB) | HTML Full-text | XML Full-text
Abstract
Fucoxanthin (Fuco) is a characteristic carotenoid of brown seaweeds. In the present study, Fuco and its stereoisomers 9'Z-Fuco, 13Z- and 13'Z-Fuco were extracted from Laminaria japonica Aresch. They were isolated and purified by silica gel column
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Fucoxanthin (Fuco) is a characteristic carotenoid of brown seaweeds. In the present study, Fuco and its stereoisomers 9'Z-Fuco, 13Z- and 13'Z-Fuco were extracted from Laminaria japonica Aresch. They were isolated and purified by silica gel column chromatography, Sephadex LH-20, and reversed-phase HPLC. The radical-scavenging activities of the three stereoisomers were evaluated toward 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 2-2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical, hydroxyl radical, and superoxide radical. The order of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity was 13Z- and 13'Z-Fuco > (all-E)-Fuco > 9'Z-Fuco. The order of 2-2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydroxyl radical-scavenging activities were 9'Z-Fuco > (all-E)-Fuco > 13Z-and 13'Z-Fuco. The order of superoxide radical-scavenging activity was 13Z- and 13'Z-Fuco > (all-E)-Fuco > 9'Z-Fuco. The scavenging activities of Fuco and its stereoisomers toward the four radical types were all dose-dependent. The ABTS, DPPH, and superoxide radical-scavenging activities were all weaker than that of tocopherol (VE), while their hydroxyl radical-scavenging activities were stronger than that of VE. The results confirmed that Fuco and its stereoisomers have potent antioxidant activities. Full article
Open AccessCommunication The Suppressive Activities of Six Sources of Medicinal Ferns Known as Gusuibu on Heat-Labile Enterotoxin-Induced Diarrhea
Molecules 2014, 19(2), 2114-2120; doi:10.3390/molecules19022114
Received: 6 January 2014 / Revised: 24 January 2014 / Accepted: 7 February 2014 / Published: 18 February 2014
PDF Full-text (285 KB) | HTML Full-text | XML Full-text
Abstract
Diarrheal disease is one of the most important worldwide health problems. Enterotoxigenic Escherichia coli (ETEC) is the most frequently isolated enteropathogen in diarrheal diseases. In developing countries, a very large number of people, especially children, suffer from diarrhea. To combat this problem, World
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Diarrheal disease is one of the most important worldwide health problems. Enterotoxigenic Escherichia coli (ETEC) is the most frequently isolated enteropathogen in diarrheal diseases. In developing countries, a very large number of people, especially children, suffer from diarrhea. To combat this problem, World Health Organization has constituted the Diarrhea Diseases Control Program which guides studies on traditional medicinal practices and preventive measures. Gusuibu, a traditional folk medicine, has been claimed to heal certain types of diarrhea. However, so far no scientific study has been carried out on the anti-diarrheal mechanism of Gusiubu. The present study was performed to examine the suppressive activities of ethanol extracts of six sources of folk medicinal ferns used as Gusuibu on heat-labile enterotoxin (LT)-induced diarrhea. Inhibitory effects of six sources were evaluated on the ETEC LT subunit B (LTB) and monosialotetrahexosylganglioside (GMI) interaction by GM1-enzyme linked immunosorbent assay and patent mouse gut assay. Our results indicated that Drynaria fortunei had no anti-diarrheal effect, while, among the remaining five folk medicinal ferns, four belonging to family Davalliaceae had significant abilities on both the blocking of LTB and GM1 interaction and the inhibition of LT-induced diarrhea. In conclusion, these findings suggested the potential application of Gusuibu as an anti-diarrheal remedy. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Cytotoxic Oleanane-Type Triterpenoid Saponins from the Rhizomes of Anemone rivularis var. flore-minore
Molecules 2014, 19(2), 2121-2134; doi:10.3390/molecules19022121
Received: 20 January 2014 / Revised: 6 February 2014 / Accepted: 10 February 2014 / Published: 18 February 2014
Cited by 5 | PDF Full-text (492 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phytochemical investigation of the n-BuOH extract of the rhizomes of Anemone rivularis var. flore-minore led to the isolation of five new oleanane-type triterpenoid saponins 15, together with five known saponins 610. Their structures were determined by
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Phytochemical investigation of the n-BuOH extract of the rhizomes of Anemone rivularis var. flore-minore led to the isolation of five new oleanane-type triterpenoid saponins 15, together with five known saponins 610. Their structures were determined by the extensive use of 1D and 2D NMR experiments, along with ESIMS analyses and acid hydrolysis. The aglycone of 4 and 5 was determined as 21α-hydroxyoleanolic acid, which was reported in this genus for the first time. The cytotoxicity of these compounds was evaluated against four human cancer cell line, including HL-60 (promyelocytic leukemia), HepG2 (hepatocellular carcinoma), A549 (lung carcinoma) and HeLa (cervical carcinoma). The monodesmosidic saponins 68 exhibited cytotoxic activity toward all tested cancer cell lines, with IC50 values in the 7.25–22.38 μM range. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Synthesis, Biological Evaluation and Structure-Activity Relationships of New Quinoxaline Derivatives as Anti-Plasmodium falciparum Agents
Molecules 2014, 19(2), 2166-2180; doi:10.3390/molecules19022166
Received: 10 January 2014 / Revised: 8 February 2014 / Accepted: 10 February 2014 / Published: 18 February 2014
Cited by 8 | PDF Full-text (267 KB) | HTML Full-text | XML Full-text
Abstract
We report the synthesis and antimalarial activities of eighteen quinoxaline and quinoxaline 1,4-di-N-oxide derivatives, eight of which are completely novel. Compounds 1a and 2a were the most active against Plasmodium falciparum strains. Structure-activity relationships demonstrated the importance of an enone moiety
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We report the synthesis and antimalarial activities of eighteen quinoxaline and quinoxaline 1,4-di-N-oxide derivatives, eight of which are completely novel. Compounds 1a and 2a were the most active against Plasmodium falciparum strains. Structure-activity relationships demonstrated the importance of an enone moiety linked to the quinoxaline ring. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Optimized Production of Vanillin from Green Vanilla Pods by Enzyme-Assisted Extraction Combined with Pre-Freezing and Thawing
Molecules 2014, 19(2), 2181-2198; doi:10.3390/molecules19022181
Received: 3 January 2014 / Revised: 10 February 2014 / Accepted: 11 February 2014 / Published: 19 February 2014
Cited by 3 | PDF Full-text (1975 KB) | HTML Full-text | XML Full-text
Abstract
Production of vanillin from natural green vanilla pods was carried out by enzyme-assisted extraction combined with pre-freezing and thawing. In the first step the green vanilla pods were pre-frozen and then thawed to destroy cellular compartmentation. In the second step pectinase from Aspergillus
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Production of vanillin from natural green vanilla pods was carried out by enzyme-assisted extraction combined with pre-freezing and thawing. In the first step the green vanilla pods were pre-frozen and then thawed to destroy cellular compartmentation. In the second step pectinase from Aspergillus niger was used to hydrolyze the pectin between the glucovanillin substrate and β-glucosidase. Four main variables, including enzyme amount, reaction temperature, time and pH, which were of significance for the vanillin content were studied and a central composite design (CCD) based on the results of a single-factor tests was used. Response surface methodology based on CCD was employed to optimize the combination of enzyme amount, reaction temperature, time, and pH for maximum vanillin production. This resulted in the optimal condition in regards of the enzyme amount, reaction temperature, time, and pH at 84.2 mg, 49.5 °C, 7.1 h, and 4.2, respectively. Under the optimal condition, the experimental yield of vanillin was 4.63% ± 0.11% (dwb), which was in good agreement with the value predicted by the model. Compared to the traditional curing process (1.98%) and viscozyme extract (2.36%), the optimized method for the vanillin production significantly increased the yield by 133.85% and 96%, respectively. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Biological Properties of Novel Triazole-Thiol and Thiadiazole Derivatives of the 1,2,4-Triazole-3(5)-one Class
Molecules 2014, 19(2), 2199-2212; doi:10.3390/molecules19022199
Received: 28 November 2013 / Revised: 7 January 2014 / Accepted: 8 January 2014 / Published: 19 February 2014
Cited by 8 | PDF Full-text (271 KB) | HTML Full-text | XML Full-text
Abstract
2,2'-(4,4'(Butane-1,4-diyl/hexane-1,6-diyl)bis(3-methyl-5-oxo-4,5-dihydro-1,2,4- triazole-4,1-diyl)) diacetohydrazides 3a,b were obtained via the formation of diethyl 2,2'-(4,4'(butane-1,4-diyl/hexane-1,6-diyl)bis(3-methyl-5-oxo-4,5-dihydro-1,2,4-triazole-4,1- diyl))diacetates 2a,b, obtained starting from di-[3(methyl-2-yl-methyl)-4,5-dihydro-1H-[1,2,4]-triazole-5-one-4yl]-n-alkanes 1a,b in two steps. The synthesis of the compounds 7a,b9a
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2,2'-(4,4'(Butane-1,4-diyl/hexane-1,6-diyl)bis(3-methyl-5-oxo-4,5-dihydro-1,2,4- triazole-4,1-diyl)) diacetohydrazides 3a,b were obtained via the formation of diethyl 2,2'-(4,4'(butane-1,4-diyl/hexane-1,6-diyl)bis(3-methyl-5-oxo-4,5-dihydro-1,2,4-triazole-4,1- diyl))diacetates 2a,b, obtained starting from di-[3(methyl-2-yl-methyl)-4,5-dihydro-1H-[1,2,4]-triazole-5-one-4yl]-n-alkanes 1a,b in two steps. The synthesis of the compounds 7a,b9a,b incorporating the 1,3,4-thiadiazole, and 10a,b11a,b with a 1,2,4-triazole-thiol nucleus as the second heterocycle, was performed by the acidic or basic treatment of compounds 4a,b6a,b which were obtained from the reaction of 3a,b with several isothiocyanates. Newly synthesized compounds were screened for antimicrobial activities and their antioxidant properties by the 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging method. Compounds 4a,b, 5a,b, and 6a,b were found to possess good antioxidant properties. Almost all compounds have significant antimicrobial activities. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Synthesis of ∆3-2-Hydroxybakuchiol Analogues and Their Growth Inhibitory Activity against Rat UMR106 Cells
Molecules 2014, 19(2), 2213-2225; doi:10.3390/molecules19022213
Received: 17 January 2014 / Revised: 9 February 2014 / Accepted: 11 February 2014 / Published: 20 February 2014
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Abstract
A series of ∆3-2-hydroxybakuchiol analogues have been synthesized and tested for their growth inhibitory activity against rat UMR106 cells by using the MTT method. Some of them exhibit enhanced activities compared with the natural product, and the preliminary SAR profile shows
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A series of ∆3-2-hydroxybakuchiol analogues have been synthesized and tested for their growth inhibitory activity against rat UMR106 cells by using the MTT method. Some of them exhibit enhanced activities compared with the natural product, and the preliminary SAR profile shows that the chain tail on the natural product could be subtly modified to enhance the activity and the aromatic moiety or the terminal olefin on the main chain can also be modified without any evident loss of activity. The stereo-configuration of the quaternary chiral center has an important influence on the activity. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Structure and Antioxidant Activity Relationships of Isoflavonoids from Dalbergia parviflora
Molecules 2014, 19(2), 2226-2237; doi:10.3390/molecules19022226
Received: 13 January 2014 / Revised: 5 February 2014 / Accepted: 11 February 2014 / Published: 20 February 2014
Cited by 3 | PDF Full-text (620 KB) | HTML Full-text | XML Full-text
Abstract
The antioxidant activities of 24 isoflavonoids that were previously isolated as pure compounds from Dalbergia parviflora were evaluated using three different in vitro antioxidant-based assay systems: xanthine/xanthine oxidase (X/XO), ORAC, and DPPH. The isolates consisted of three subgroups, namely isoflavones, isoflavanones, and isoflavans,
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The antioxidant activities of 24 isoflavonoids that were previously isolated as pure compounds from Dalbergia parviflora were evaluated using three different in vitro antioxidant-based assay systems: xanthine/xanthine oxidase (X/XO), ORAC, and DPPH. The isolates consisted of three subgroups, namely isoflavones, isoflavanones, and isoflavans, each of which appeared to have diversified substituents, and were thus ideal for the study of their structure-activity relationships (SARs). The SAR analysis was performed using the results obtained from both the inter-subgroup isoflavonoids with the same substitution pattern and the intra-subgroup compounds with different substitution patterns. The inter-subgroup comparison showed that the isoflavones exhibited the highest antioxidant activities based on all three assays. The intra-subgroup analysis showed that the additional presence of an OH group in Ring B at either R3′ or R5′ from the basic common structure of the R7-OH of Ring A and the R4′-OH (or -OMe) of Ring B greatly increased the antioxidant activities of all of the isoflavonoid subgroups and that other positions of OH and OMe substitutions exerted different effects on the activities depending on the subgroup and assay type. Therefore, based on the structural diversity of the isoflavonoids in D. parviflora, the present study provides the first clarification of the detailed antioxidant SARs of isoflavonoids. Full article
(This article belongs to the Special Issue Structure-Activity Relationship of Flavonoids)
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Open AccessArticle Two New Bidesmoside Triterpenoid Saponins from the Seeds of Momordica charantia L.
Molecules 2014, 19(2), 2238-2246; doi:10.3390/molecules19022238
Received: 29 December 2013 / Revised: 7 February 2014 / Accepted: 10 February 2014 / Published: 21 February 2014
PDF Full-text (244 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new bidesmoside triterpenoid saponins which were identifed as 28-O-β-D-xylopyranosyl(1→3)-β-D-xylopyranosyl(1→4)-α-L-rhamnopyranosyl(1→2)-[α-L-rhamno-pyranosyl(1→3)]-β-D-fucopyranosyl gypsogenin 3-O-β-D-glucopyranosyl (1→2)-β-D-glucopyranosiduronic acid (C1) and 28-O-β-D-xylopyranosyl(1→4)-α-L-rhamnopyranosyl
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Two new bidesmoside triterpenoid saponins which were identifed as 28-O-β-D-xylopyranosyl(1→3)-β-D-xylopyranosyl(1→4)-α-L-rhamnopyranosyl(1→2)-[α-L-rhamno-pyranosyl(1→3)]-β-D-fucopyranosyl gypsogenin 3-O-β-D-glucopyranosyl (1→2)-β-D-glucopyranosiduronic acid (C1) and 28-O-β-D-xylopyranosyl(1→4)-α-L-rhamnopyranosyl (1→2)-[α-L-rhamnopyranosyl(1→3)]-β-D-fucopyranosyl gypsogenin 3-O-β-D-gluco-pyranosyl(1→2)-β-D-glucopyranosiduronic acid (C2) were isolated together with two known compounds from the seeds of Momordica charantia L. Their structures were elucidated by the combination of mass spectrometry (MS), one and two-dimensional NMR experiments and chemical reactions. Full article
Open AccessArticle In Silico Studies of Quinoxaline-2-Carboxamide 1,4-di-N-Oxide Derivatives as Antimycobacterial Agents
Molecules 2014, 19(2), 2247-2260; doi:10.3390/molecules19022247
Received: 31 December 2013 / Revised: 8 February 2014 / Accepted: 10 February 2014 / Published: 21 February 2014
Cited by 2 | PDF Full-text (1632 KB) | HTML Full-text | XML Full-text
Abstract
Molecular modelling studies were performed on some previously reported novel quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives (series 1–9). Using the LigandScout program, a pharmacophore model was developed to further optimize the antimycobacterial activity of this series of compounds. Using the Dock6 program, docking studies
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Molecular modelling studies were performed on some previously reported novel quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives (series 1–9). Using the LigandScout program, a pharmacophore model was developed to further optimize the antimycobacterial activity of this series of compounds. Using the Dock6 program, docking studies were performed in order to investigate the mode of binding of these compounds. The molecular modeling study allowed us to confirm the preferential binding mode of these quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives inside the active site. The obtained binding mode was as same as that of the novobiocin X-ray structure. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle On Tuning the Fluorescence Emission of Porphyrin Free Bases Bonded to the Pore Walls of Organo-Modified Silica
Molecules 2014, 19(2), 2261-2285; doi:10.3390/molecules19022261
Received: 24 December 2013 / Revised: 29 January 2014 / Accepted: 7 February 2014 / Published: 21 February 2014
Cited by 6 | PDF Full-text (1628 KB) | HTML Full-text | XML Full-text
Abstract
A sol-gel methodology has been duly developed in order to perform a controlled covalent coupling of tetrapyrrole macrocycles (e.g., porphyrins, phthalocyanines, naphthalocyanines, chlorophyll, etc.) to the pores of metal oxide networks. The resulting absorption and emission spectra intensities in the UV-VIS-NIR range
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A sol-gel methodology has been duly developed in order to perform a controlled covalent coupling of tetrapyrrole macrocycles (e.g., porphyrins, phthalocyanines, naphthalocyanines, chlorophyll, etc.) to the pores of metal oxide networks. The resulting absorption and emission spectra intensities in the UV-VIS-NIR range have been found to depend on the polarity existing inside the pores of the network; in turn, this polarization can be tuned through the attachment of organic substituents to the tetrapyrrrole macrocycles before bonding them to the pore network. The paper shows clear evidence of the real possibility of maximizing fluorescence emissions from metal-free bases of substituted tetraphenylporphyrins, especially when these molecules are bonded to the walls of functionalized silica surfaces via the attachment of alkyl or aryl groups arising from the addition of organo-modified alkoxides. Full article
(This article belongs to the Special Issue Macrocyclic Chemistry)
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Open AccessArticle Addition of Bases to the 5'-end of Human Telomeric DNA: Influences on Thermal Stability and Energetics of Unfolding
Molecules 2014, 19(2), 2286-2298; doi:10.3390/molecules19022286
Received: 29 September 2013 / Revised: 24 January 2014 / Accepted: 7 February 2014 / Published: 21 February 2014
Cited by 3 | PDF Full-text (710 KB) | HTML Full-text | XML Full-text
Abstract
Telomeric DNA has been intensely investigated for its role in chromosome protection, aging, cell death, and disease. In humans the telomeric tandem repeat (TTAGGG)n is found at the ends of chromosomes and provides a novel target for the development of new drugs
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Telomeric DNA has been intensely investigated for its role in chromosome protection, aging, cell death, and disease. In humans the telomeric tandem repeat (TTAGGG)n is found at the ends of chromosomes and provides a novel target for the development of new drugs in the treatment of age related diseases such as cancer. These telomeric sequences show slight sequence variations from species to species; however, each contains repeats of 3 to 4 guanines allowing the G-rich strands to fold into compact and stable nuclease resistant conformations referred to as G-quadruplexes. The focus of this manuscript is to examine the effects of 5'-nucleotides flanking the human telomeric core sequence 5'-AGGG(TTAGGG) 3-3' (h-Tel22). Our studies reveal that the addition of the 5'-flanking nucleotides (5'-T, and 5'-TT) results in significant changes to the thermodynamic stability of the G-quadruplex structure. Our data indicate that the observed changes in stability are associated with changes in the number of bound waters resulting from the addition of 5'-flanking nucleotides to the h-Tel22 sequence as well as possible intermolecular interactions of the 5' overhang with the core structure. Full article
(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)
Open AccessArticle Fatty Acids from Pool Lipids as Possible Precursors of the Male Marking Pheromone in Bumblebees
Molecules 2014, 19(2), 2330-2343; doi:10.3390/molecules19022330
Received: 31 December 2013 / Revised: 14 February 2014 / Accepted: 14 February 2014 / Published: 21 February 2014
Cited by 1 | PDF Full-text (284 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Triacylglycerols (TGs) stored in the fat bodies of bumblebee males have a species-specific composition. The striking structural similarities between TG fatty acids (FAs) and components of the male marking pheromone in certain species led to the hypothesis that FAs may serve as precursors
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Triacylglycerols (TGs) stored in the fat bodies of bumblebee males have a species-specific composition. The striking structural similarities between TG fatty acids (FAs) and components of the male marking pheromone in certain species led to the hypothesis that FAs may serve as precursors in pheromone biosynthesis. Here, we analysed TGs from B. ruderatus, B. bohemicus, and B. campestris. Nonadec-9-ene and icos-15-en-1-ol are the main components of B. ruderatus labial gland secretion, forming up to 92% of the gland extract. The corresponding icos-11-enic and icos-15-enic acids were found in TGs at levels higher than usual for bumblebee species. We found similar relationships in B. campestris and B. bohemicus. These results suggest that FAs might be precursors of aliphatic compounds in the male pheromones. Furthermore, we report for the first time the pheromone structure of B. ruderatus males. Full article
(This article belongs to the Special Issue Fatty Acids)
Open AccessArticle Influence of Extractive Solvents on Lipid and Fatty Acids Content of Edible Freshwater Algal and Seaweed Products, the Green Microalga Chlorella kessleri and the Cyanobacterium Spirulina platensis
Molecules 2014, 19(2), 2344-2360; doi:10.3390/molecules19022344
Received: 6 December 2013 / Revised: 5 February 2014 / Accepted: 7 February 2014 / Published: 21 February 2014
Cited by 7 | PDF Full-text (325 KB) | HTML Full-text | XML Full-text
Abstract
Total lipid contents of green (Chlorella pyrenoidosa, C), red (Porphyra tenera, N; Palmaria palmata, D), and brown (Laminaria japonica, K; Eisenia bicyclis, A; Undaria pinnatifida, W, WI; Hizikia fusiformis, H) commercial edible algal
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Total lipid contents of green (Chlorella pyrenoidosa, C), red (Porphyra tenera, N; Palmaria palmata, D), and brown (Laminaria japonica, K; Eisenia bicyclis, A; Undaria pinnatifida, W, WI; Hizikia fusiformis, H) commercial edible algal and cyanobacterial (Spirulina platensis, S) products, and autotrophically cultivated samples of the green microalga Chlorella kessleri (CK) and the cyanobacterium Spirulina platensis (SP) were determined using a solvent mixture of methanol/chloroform/water (1:2:1, v/v/v, solvent I) and n-hexane (solvent II). Total lipid contents ranged from 0.64% (II) to 18.02% (I) by dry weight and the highest total lipid content was observed in the autotrophically cultivated cyanobacterium Spirulina platensis. Solvent mixture I was found to be more effective than solvent II. Fatty acids were determined by gas chromatography of their methyl esters (% of total FAMEs). Generally, the predominant fatty acids (all results for extractions with solvent mixture I) were saturated palmitic acid (C16:0; 24.64%–65.49%), monounsaturated oleic acid (C18:1(n-9); 2.79%–26.45%), polyunsaturated linoleic acid (C18:2(n-6); 0.71%–36.38%), α-linolenic acid (C18:3(n-3); 0.00%–21.29%), γ-linolenic acid (C18:3(n-6); 1.94%–17.36%), and arachidonic acid (C20:4(n-6); 0.00%–15.37%). The highest content of ω-3 fatty acids (21.29%) was determined in Chlorella pyrenoidosa using solvent I, while conversely, the highest content of ω-6 fatty acids (41.42%) was observed in Chlorella kessleri using the same solvent. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Edge-Termination and Core-Modification Effects of Hexagonal Nanosheet Graphene
Molecules 2014, 19(2), 2361-2373; doi:10.3390/molecules19022361
Received: 9 December 2013 / Revised: 29 January 2014 / Accepted: 10 February 2014 / Published: 21 February 2014
Cited by 5 | PDF Full-text (1284 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Optimized geometries and electronic structures of two different hexagonal grapheme nanosheets (HGNSs), with armchair (n-A-HGNS, n = 3–11) and zigzag (n-Z-HGNS, n = 1–8) edges have been calculated by using the GGA/PBE method implemented in the SIESTA package, with
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Optimized geometries and electronic structures of two different hexagonal grapheme nanosheets (HGNSs), with armchair (n-A-HGNS, n = 3–11) and zigzag (n-Z-HGNS, n = 1–8) edges have been calculated by using the GGA/PBE method implemented in the SIESTA package, with the DZP basis set, where n represents the number of peripheral rings. The computed HOMO-LUMO energy gap (Eg = ELUMO − EHOMO) decreases for fully H-terminated A- and Z-HGNSs with increasing n, i.e., with increasing nanosheet size and pπ-orbitals being widely delocalized over the sheet surface. The full terminations, calculated with various functional groups, including the electron-withdrawing (F-, Cl-, and CN-) and -donating (OH-, and SH-) substitutions, were addressed. Significant lowering of EHOMO and ELUMO was obtained for CN-terminated HGNS as compared to those for H-terminated ones due to the mesomeric effect. The calculated Eg value decreases with increasing n for all terminations, whereby for the SH-termination in HGNS, the termination effect becomes less significant with increasing n. Further, the calculation results for stabilities of HGNS oxides support the tendency toward the oxidative reactivity at the edge site of the sheet, which shows most pronounced C-C bond length alternation, by chemical modification. Physical properties of HGNSs with various numbers of the core-defects, which can be obtained by strong oxidation, were also investigated. Their structures can change drastically from planar to saddle-like shapes. These conformations could be used as stationary phases with controlled interaction in the separation methods such as HPLC and the other chemical analysis techniques. Full article
Open AccessArticle Functional Properties of a Cysteine Proteinase from Pineapple Fruit with Improved Resistance to Fungal Pathogens in Arabidopsis thaliana
Molecules 2014, 19(2), 2374-2389; doi:10.3390/molecules19022374
Received: 3 December 2013 / Revised: 19 January 2014 / Accepted: 13 February 2014 / Published: 21 February 2014
Cited by 3 | PDF Full-text (1033 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In plant cells, many cysteine proteinases (CPs) are synthesized as precursors in the endoplasmic reticulum, and then are subject to post-translational modifications to form the active mature proteinases. They participate in various cellular and physiological functions. Here, AcCP2, a CP from pineapple fruit
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In plant cells, many cysteine proteinases (CPs) are synthesized as precursors in the endoplasmic reticulum, and then are subject to post-translational modifications to form the active mature proteinases. They participate in various cellular and physiological functions. Here, AcCP2, a CP from pineapple fruit (Ananas comosus L.) belonging to the C1A subfamily is analyzed based on the molecular modeling and homology alignment. Transcripts of AcCP2 can be detected in the different parts of fruits (particularly outer sarcocarps), and gradually increased during fruit development until maturity. To analyze the substrate specificity of AcCP2, the recombinant protein was overexpressed and purified from Pichia pastoris. The precursor of purified AcCP2 can be processed to a 25 kDa active form after acid treatment (pH 4.3). Its optimum proteolytic activity to Bz-Phe-Val-Arg-NH-Mec is at neutral pH. In addition, the overexpression of AcCP2 gene in Arabidopsis thaliana can improve the resistance to fungal pathogen of Botrytis cinerea. These data indicate that AcCP2 is a multifunctional proteinase, and its expression could cause fruit developmental characteristics of pineapple and resistance responses in transgenic Arabidopsis plants. Full article
Open AccessArticle Endotoxin Molecule Lipopolysaccharide-Induced Zebrafish Inflammation Model: A Novel Screening Method for Anti-Inflammatory Drugs
Molecules 2014, 19(2), 2390-2409; doi:10.3390/molecules19022390
Received: 11 January 2014 / Revised: 7 February 2014 / Accepted: 10 February 2014 / Published: 21 February 2014
Cited by 11 | PDF Full-text (2333 KB) | HTML Full-text | XML Full-text
Abstract
Lipopolysaccharide (LPS), an endotoxin molecule, has been used to induce inflammatory responses. In this study, LPS was used to establish an in vivo inflammation model in zebrafish for drug screening. We present an experimental method that conveniently and rapidly assesses the anti-inflammatory properties
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Lipopolysaccharide (LPS), an endotoxin molecule, has been used to induce inflammatory responses. In this study, LPS was used to establish an in vivo inflammation model in zebrafish for drug screening. We present an experimental method that conveniently and rapidly assesses the anti-inflammatory properties of drugs. The yolks of 3-day post-fertilization (dpf) larvae were injected with 0.5 mg/mL LPS to induce fatal inflammation. After LPS stimulation, macrophages were tracked by NR and SB staining and neutrophil migration was observed using the MPO:GFP line. Larval mortality was used as the primary end-point. Expression levels of key cytokines involved in the inflammatory response including IL-1β, IL-6, and TNF-α, were measured using quantitative reverse transcription polymerase chain reaction (RT-PCR). Macrophages and neutrophils were both recruited to the LPS-injected site during the inflammatory response. Mortality was increased by LPS in a dose-dependent manner within 48 h. Analyses of IL-1β, IL-6, and TNF-α expression levels revealed the upregulation of the inflammatory response in the LPS-injected larvae. Further, the anti-inflammatory activity of chlorogenic acid (CA) was evaluated in this zebrafish model to screen for anti-inflammatory drugs. A preliminary result showed that CA revealed a similar effect as the corticosteroid dexamethasone (DEX), which was used as a positive control, by inhibiting macrophage and neutrophil recruitment to the LPS site and improving survival. Our results suggest that this zebrafish screening model could be applied to study inflammation-mediated diseases. Moreover, the Traditional Chinese Medicine CA displays potential anti-inflammatory activity. Full article
Open AccessArticle A Tractable and Efficient One-Pot Synthesis of 5'-Azido-5'-deoxyribonucleosides
Molecules 2014, 19(2), 2434-2444; doi:10.3390/molecules19022434
Received: 11 September 2013 / Revised: 11 February 2014 / Accepted: 12 February 2014 / Published: 21 February 2014
Cited by 2 | PDF Full-text (251 KB) | HTML Full-text | XML Full-text
Abstract
Synthetic routes to 5'-azidoribonucleosides are reported for adenosine, cytidine, guanosine, and uridine, resulting in a widely applicable one-pot methodology for the synthesis of these and related compounds. The target compounds are appropriate as precursors in a variety of purposive syntheses, as the synthetic
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Synthetic routes to 5'-azidoribonucleosides are reported for adenosine, cytidine, guanosine, and uridine, resulting in a widely applicable one-pot methodology for the synthesis of these and related compounds. The target compounds are appropriate as precursors in a variety of purposive syntheses, as the synthetic and therapeutic relevance of azido- and amino-modified nucleosides is expansive. Furthermore, in the conversion of alcohols to azides, these methods offer a tractable alternative to the Mitsunobu and other more difficult reactions. Full article
(This article belongs to the Special Issue Synthesis of Nucleosides, Nucleotides and Their Derivatives)
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Open AccessArticle Preparation and In Vitro Evaluation of Glycyrrhetinic Acid-Modified Curcumin-Loaded Nanostructured Lipid Carriers
Molecules 2014, 19(2), 2445-2457; doi:10.3390/molecules19022445
Received: 14 November 2013 / Revised: 11 February 2014 / Accepted: 17 February 2014 / Published: 21 February 2014
Cited by 9 | PDF Full-text (1134 KB) | HTML Full-text | XML Full-text
Abstract
Curcumin, a phenolic antioxidant compound derived from the rhizome of the turmeric plant Curcuma longa, has proven to be a modulator of intracellular signaling pathways that control cancer cell growth, inflammation, invasion and apoptosis, revealing its anticancer potential. In this study, a
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Curcumin, a phenolic antioxidant compound derived from the rhizome of the turmeric plant Curcuma longa, has proven to be a modulator of intracellular signaling pathways that control cancer cell growth, inflammation, invasion and apoptosis, revealing its anticancer potential. In this study, a Glycyrrhetinic Acid-Modified Curcumin-Loaded Nanostructured Lipid Carrier (Cur-GA-PEG-NLC) was prepared by the film ultrasound method to improve the tumor-targeting ability. The drug content was detected by an UV spectrophotometry method. The encapsulation efficiency of curcumin in the nanostructured lipid carriers (NLCs) was determined using a mini-column centrifugation method. The encapsulation efficiency for various Cur-GA-PEG-NLC was within the range of 90.06%–95.31% and particle size was between 123.1 nm and 132.7 nm. An in vitro MTT assay showed that Cur-GA10%-PEG-NLC had significantly high cellular uptake and cytotoxicity against HepG2 cells compared with other groups. Full article
Open AccessArticle Novel Lycorine Derivatives as Anticancer Agents: Synthesis and In Vitro Biological Evaluation
Molecules 2014, 19(2), 2469-2480; doi:10.3390/molecules19022469
Received: 29 January 2014 / Revised: 13 February 2014 / Accepted: 13 February 2014 / Published: 21 February 2014
Cited by 10 | PDF Full-text (299 KB) | HTML Full-text | XML Full-text
Abstract
Lycorine, which is the most abundant alkaloid isolated from the Amaryllidaceae family of plants, reportedly exhibits promising anticancer activities. Herein, a series of novel lycorine derivatives were synthesized and evaluated for their in vitro inhibitory activities against seven different cancer cell lines, including
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Lycorine, which is the most abundant alkaloid isolated from the Amaryllidaceae family of plants, reportedly exhibits promising anticancer activities. Herein, a series of novel lycorine derivatives were synthesized and evaluated for their in vitro inhibitory activities against seven different cancer cell lines, including A549, HCT116, SK-OV-3, NCI-H460, K562, MCF-7 and HL-60. The results indicated that compounds bearing diverse amine substituents at the C-2 position demonstrated good anticancer activities. The selectivity towards different cancer cell lines of the synthesized derivatives is discussed. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Pharmacophore Generation from a Drug-like Core Molecule Surrounded by a Library Peptide via the 10BASEd-T on Bacteriophage T7
Molecules 2014, 19(2), 2481-2496; doi:10.3390/molecules19022481
Received: 30 December 2013 / Revised: 10 February 2014 / Accepted: 12 February 2014 / Published: 21 February 2014
Cited by 3 | PDF Full-text (1983 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We have achieved site-specific conjugation of several haloacetamide derivatives into designated cysteines on bacteriophage T7-displayed peptides, which are fused to T7 capsid protein gp10. This easiest gp10 based-thioetherification (10BASEd-T) undergoes almost quantitatively like a click reaction without side reaction or loss
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We have achieved site-specific conjugation of several haloacetamide derivatives into designated cysteines on bacteriophage T7-displayed peptides, which are fused to T7 capsid protein gp10. This easiest gp10 based-thioetherification (10BASEd-T) undergoes almost quantitatively like a click reaction without side reaction or loss of phage infectivity. The post-translational modification yield, as well as the site-specificity, is quantitatively analyzed by a fluorescent densitometric analysis after gel electrophoresis. The detailed structure of the modified peptide on phage is identified with tandem mass spectrometry. Construction of such a peptide-fused phage library possessing non-natural core structures will be useful for future drug discovery. For this aim, we propose a novel concept of pharmacophore generation from a drug-like molecule (i.e., salicylic acid) conjugated with surrounding randomized peptides. By using the hybrid library, streptavidin-specific binders are isolated through four rounds of biopanning. Full article
(This article belongs to the Special Issue Bioorthogonal Chemistry)
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Open AccessArticle Synthesis and Antiproliferative Activity of Some Novel Triazole Derivatives from Dehydroabietic Acid
Molecules 2014, 19(2), 2523-2535; doi:10.3390/molecules19022523
Received: 24 January 2014 / Revised: 18 February 2014 / Accepted: 18 February 2014 / Published: 21 February 2014
Cited by 10 | PDF Full-text (231 KB) | HTML Full-text | XML Full-text
Abstract
Dehydroabietic acid (DHA) is a naturally occurring diterpene with different and relevant biological activities. Previous studies have shown that some DHA derivatives display antiproliferative activity. However, the reported compounds did not include triazole derivatives. Starting from DHA (8,11,13-abietatrien-18-oic acid), and its alcohol dehydroabietinol
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Dehydroabietic acid (DHA) is a naturally occurring diterpene with different and relevant biological activities. Previous studies have shown that some DHA derivatives display antiproliferative activity. However, the reported compounds did not include triazole derivatives. Starting from DHA (8,11,13-abietatrien-18-oic acid), and its alcohol dehydroabietinol (8,11,13-abietatrien-18-ol), four alkyl esters were prepared. The alkyl terpenes were treated with different aromatic azides to synthesize hybrid compounds using click chemistry. Some 16 new DHA hybrids were thus synthesized and their structures were confirmed by spectroscopic and spectrometric means. The antiproliferative activity of the new compounds was assessed towards human cell lines, namely normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), lung cancer (SK-MES-1) and bladder carcinoma (J82) cells. Better antiproliferative effect was found for compound 5, with an IC50 of 6.1 μM and selectivity on SK-MES-1 cells. Under the same experimental conditions, the IC50 of etoposide, was 1.83 µM. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Skullcap (Scutellaria baicalensis) Extract and Its Active Compound, Wogonin, Inhibit Ovalbumin-Induced Th2-Mediated Response
Molecules 2014, 19(2), 2536-2545; doi:10.3390/molecules19022536
Received: 3 January 2014 / Revised: 10 February 2014 / Accepted: 18 February 2014 / Published: 21 February 2014
Cited by 4 | PDF Full-text (499 KB) | HTML Full-text | XML Full-text
Abstract
Skullcap (Scutellaria baicalensis) has been widely used as a dietary ingredient and traditional herbal medicine owing to its anti-inflammatory and anticancer properties. In this study, we investigated the anti-allergic effects of skullcap and its active compounds, focusing on T cell-mediated responses ex
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Skullcap (Scutellaria baicalensis) has been widely used as a dietary ingredient and traditional herbal medicine owing to its anti-inflammatory and anticancer properties. In this study, we investigated the anti-allergic effects of skullcap and its active compounds, focusing on T cell-mediated responses ex vivo and in vivo. Splenocytes from mice sensitized with ovalbumin (OVA) were isolated for analyses of cytokine production and cell viability. Mice sensitized with OVA were orally administered skullcap or wogonin for 16 days, and then immunoglobulin (Ig) and cytokine levels were measured by enzyme-linked immunosorbent assays. Treatment with skullcap significantly inhibited interleukin (IL)-4 production without reduction of cell viability. Moreover, wogonin, but not baicalin and baicalein, suppressed IL-4 and interferon-gamma production. In vivo, skullcap and wogonin downregulated OVA-induced Th2 immune responses, especially IgE and IL-5 prediction. Wogonin as an active component of skullcap may be applied as a therapeutic agent for IgE- and IL-5-mediated allergic disorders. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle In Vivo and In Vitro Anti-Tumor Effects of Fungal Extracts
Molecules 2014, 19(2), 2546-2556; doi:10.3390/molecules19022546
Received: 7 January 2014 / Revised: 6 February 2014 / Accepted: 20 February 2014 / Published: 21 February 2014
Cited by 3 | PDF Full-text (714 KB) | HTML Full-text | XML Full-text
Abstract
Fungal extracts are extensively used as nutritional supplements in Far-Eastern Asia. In this study, we aimed to evaluate the anti-cancer activities of some different fungal species against different cancer cell lines. The water or ethanol extracts of Fomitopsis pinicola (F. pinicola),
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Fungal extracts are extensively used as nutritional supplements in Far-Eastern Asia. In this study, we aimed to evaluate the anti-cancer activities of some different fungal species against different cancer cell lines. The water or ethanol extracts of Fomitopsis pinicola (F. pinicola), Ganoderma sinense, Fomitopsis officinalis, Polyporus melanopus, and Taiwanofungus camphorates were used to evaluate the anti-cancer activities in various cancer cells. We found that all of the fungi ethanol extracts used in this study exert anti-cancer activities in vitro, whereas water extracts show lower inhibitory activities as determined by 3-(4,5-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Among the tested fungi species, F. pinicola ethanol extract exerts the most significant anti-cancer activity (growth inhibitory ratio 82.8%, p < 0.001) by increasing cell apoptosis. Moreover, F. pinicola ethanol extract significantly decreased tumor size (tumor growth inhibitory ratio 54%, p < 0.05) and increased the lifespan in mice bearing sarcoma-180 tumors. Taken together, this is the first study indicating the anti-tumor effect of F. pinicola in vivo and in vitro. F. pinicola ethanol extract induces cell apoptosis to exert a significant anti-tumor activity, with potential to be a new alternative anti-tumor medicine. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synthesis, Spectroscopic and Theoretical Studies of New Quasi-Podands from Bile Acid Derivatives Linked by 1,2,3-Triazole Rings
Molecules 2014, 19(2), 2557-2570; doi:10.3390/molecules19022557
Received: 17 December 2013 / Revised: 19 February 2014 / Accepted: 20 February 2014 / Published: 24 February 2014
Cited by 5 | PDF Full-text (467 KB) | HTML Full-text | XML Full-text
Abstract
A novel method for the synthesis of bile acid derivatives has been developed using “click chemistry”. Intermolecular 1,3-dipolar cycloaddition of the propargyl ester of bile acids and azide groups of 1,3,5-tris(azidomethyl)benzene gave a new quasi-podands with 1,2,3-triazole rings. The structures of the products
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A novel method for the synthesis of bile acid derivatives has been developed using “click chemistry”. Intermolecular 1,3-dipolar cycloaddition of the propargyl ester of bile acids and azide groups of 1,3,5-tris(azidomethyl)benzene gave a new quasi-podands with 1,2,3-triazole rings. The structures of the products were confirmed by spectral (1H-NMR, 13C-NMR, and FT-IR) analysis, mass spectrometry and PM5 semiempirical methods. Estimation of the pharmacotherapeutic potential has been accomplished for synthesized compounds on the basis of Prediction of Activity Spectra for Substances (PASS). Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Synthetic Fosmidomycin Analogues with Altered Chelating Moieties Do Not Inhibit 1-Deoxy-D-xylulose 5-phosphate Reductoisomerase or Plasmodium falciparum Growth In Vitro
Molecules 2014, 19(2), 2571-2587; doi:10.3390/molecules19022571
Received: 6 February 2014 / Revised: 18 February 2014 / Accepted: 19 February 2014 / Published: 24 February 2014
Cited by 5 | PDF Full-text (387 KB) | HTML Full-text | XML Full-text
Abstract
Fourteen new fosmidomycin analogues with altered metal chelating groups were prepared and evaluated for inhibition of E. coli Dxr, M. tuberculosis Dxr and the growth of P. falciparum K1 in human erythrocytes. None of the synthesized compounds showed activity against either enzyme or
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Fourteen new fosmidomycin analogues with altered metal chelating groups were prepared and evaluated for inhibition of E. coli Dxr, M. tuberculosis Dxr and the growth of P. falciparum K1 in human erythrocytes. None of the synthesized compounds showed activity against either enzyme or the Plasmodia. This study further underlines the importance of the hydroxamate functionality and illustrates that identifying effective alternative bidentate ligands for this target enzyme is challenging. Full article
Open AccessArticle Inhibition of Human Cytochrome P450 Enzymes by Bacopa monnieri Standardized Extract and Constituents
Molecules 2014, 19(2), 2588-2601; doi:10.3390/molecules19022588
Received: 21 January 2014 / Revised: 19 February 2014 / Accepted: 19 February 2014 / Published: 24 February 2014
Cited by 11 | PDF Full-text (1637 KB) | HTML Full-text | XML Full-text
Abstract
Bacopa monnieri and the constituents of this plant, especially bacosides, possess various neuropharmacological properties. Like drugs, some herbal extracts and the constituents of their extracts alter cytochrome P450 (CYP) enzymes, causing potential herb-drug interactions. The effects of Bacopa monnieri standardized extract and the
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Bacopa monnieri and the constituents of this plant, especially bacosides, possess various neuropharmacological properties. Like drugs, some herbal extracts and the constituents of their extracts alter cytochrome P450 (CYP) enzymes, causing potential herb-drug interactions. The effects of Bacopa monnieri standardized extract and the bacosides from the extract on five major CYP isoforms in vitro were analyzed using a luminescent CYP recombinant human enzyme assay. B. monnieri extract exhibited non-competitive inhibition of CYP2C19 (IC50/Ki = 23.67/9.5 µg/mL), CYP2C9 (36.49/12.5 µg/mL), CYP1A2 (52.20/25.1 µg/mL); competitive inhibition of CYP3A4 (83.95/14.5 µg/mL) and weak inhibition of CYP2D6 (IC50 = 2061.50 µg/mL). However, the bacosides showed negligible inhibition of the same isoforms. B. monnieri, which is orally administered, has a higher concentration in the gut than the liver; therefore, this herb could exhibit stronger inhibition of intestinal CYPs than hepatic CYPs. At an estimated gut concentration of 600 µg/mL (based on a daily dosage of 300 mg/day), B. monnieri reduced the catalytic activities of CYP3A4, CYP2C9 and CYP2C19 to less than 10% compared to the total activity (without inhibitor = 100%). These findings suggest that B. monnieri extract could contribute to herb-drug interactions when orally co-administered with drugs metabolized by CYP1A2, CYP3A4, CYP2C9 and CYP2C19. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Glycosylation of a Newly Functionalized Orthoester Derivative
Molecules 2014, 19(2), 2602-2611; doi:10.3390/molecules19022602
Received: 26 January 2014 / Revised: 20 February 2014 / Accepted: 21 February 2014 / Published: 24 February 2014
PDF Full-text (250 KB) | HTML Full-text | XML Full-text
Abstract Tandem glycosylation of the 6-O-Fmoc-substituted benzyl orthoester derivative 2a was carried out in moderate yields by electrogenerated acid (EGA). The Fmoc group was effectively removed under mild basic conditions, and the product was submitted to the subsequent glycosylation. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Triptolide Induces S Phase Arrest and Apoptosis in Gallbladder Cancer Cells
Molecules 2014, 19(2), 2612-2628; doi:10.3390/molecules19022612
Received: 31 December 2013 / Revised: 13 February 2014 / Accepted: 13 February 2014 / Published: 24 February 2014
Cited by 11 | PDF Full-text (5918 KB) | HTML Full-text | XML Full-text
Abstract
Gallbladder carcinoma is the most common malignancy of the biliary tract, with a very low 5-year survival rate and extremely poor prognosis. Thus, new effective treatments and drugs are urgently needed for the treatment of this malignancy. In this study, for the first
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Gallbladder carcinoma is the most common malignancy of the biliary tract, with a very low 5-year survival rate and extremely poor prognosis. Thus, new effective treatments and drugs are urgently needed for the treatment of this malignancy. In this study, for the first time we investigated the effects of triptolide on gallbladder cancer cells and identified the mechanisms underlying its potential anticancer effects. The MTT assay showed that triptolide decreased cell viability in a dose- and time-dependent manner. The results of the colony formation assay indicated that triptolide strongly suppressed colony formation ability in GBC-SD and SGC-996 cells. Flow cytometric analysis revealed that triptolide induced S phase arrest in gallbladder cancer cells. In addition, triptolide induced apoptosis, as shown by the results of annexin V/propidium iodide double-staining and Hoechst 33342 staining. Furthermore, triptolide decreased mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Finally, western blot analysis of triptolide-treated cells revealed the activation of caspase-3, caspase-9, PARP, and Bcl-2; this result demonstrated that triptolide induced apoptosis in gallbladder cancer cells by regulating apoptosis-related protein expression, and suggests that triptolide may be a promising drug to treat gallbladder carcinoma. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Three New Tetranorditerpenes from Aerial Parts of Acerola Cherry (Malpighia emarginata)
Molecules 2014, 19(2), 2629-2636; doi:10.3390/molecules19022629
Received: 15 January 2014 / Revised: 19 February 2014 / Accepted: 20 February 2014 / Published: 24 February 2014
Cited by 1 | PDF Full-text (267 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Acerola cherry is a world famous fruit which contains abundant antioxidants such as vitamin C, anthocyanins, flavonoids, and phenolics. However, studies concerning bioactivity components from aerial parts of acerola (Malpighia emarginata) are scarce. In view of this, we have examined the
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Acerola cherry is a world famous fruit which contains abundant antioxidants such as vitamin C, anthocyanins, flavonoids, and phenolics. However, studies concerning bioactivity components from aerial parts of acerola (Malpighia emarginata) are scarce. In view of this, we have examined the constituents of aerial parts of acerola, and three new tetranorditerpenes acerolanins A–C (13) with a rare 2H-benz[e]inden-2-one substructure were isolated. Their structures were determined on the basis of spectral studies and acerolanin C was confirmed by X-ray crystallographic analysis. Furthermore, three new compounds have been studied for their cytotoxic activity. Full article
Open AccessArticle Synthesis of A New Class of Pyridazin-3-one and 2-Amino-5-arylazopyridine Derivatives and Their Utility in the Synthesis of Fused Azines
Molecules 2014, 19(2), 2637-2654; doi:10.3390/molecules19022637
Received: 27 January 2014 / Revised: 11 February 2014 / Accepted: 17 February 2014 / Published: 24 February 2014
Cited by 2 | PDF Full-text (516 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A general route for the synthesis of a novel class of pyridazin-3-one derivatives 3 by the reaction in acetic anhydride between 3-oxo-2-arylhydrazonopropanals 1 and some active methylene compounds like p-nitrophenylacetic acid and cyanoacetic acid was established. Under these conditions the pyridazin-3-one derivatives
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A general route for the synthesis of a novel class of pyridazin-3-one derivatives 3 by the reaction in acetic anhydride between 3-oxo-2-arylhydrazonopropanals 1 and some active methylene compounds like p-nitrophenylacetic acid and cyanoacetic acid was established. Under these conditions the pyridazin-3-one derivatives 3 were formed as the sole isolable products in excellent yield. The 6-acetyl-3-oxopyridazine derivative 3l was reacted with DMF-DMA to afford the corresponding enaminone derivative 4, which reacts with a variety of aminoazoles to afford the corresponding azolo[1,5-a]pyrimidine derivatives 57. Also, in order to explore the viability and generality of a recently uncovered reaction between 3-oxo-2-arylhydrazonopropanals and active methylene compounds, a variety of 2-amino-6-aryl-5-arylazo-3-aroylpyridines 1619 were prepared by reacting 3-oxo-2-arylhydrazonopropanals with miscellaneous active methylene compounds like 3-oxo-3-phenylpropionitrile, hetaroylacetonitriles and cyanoacetamides. These 2-aminopyridine derivatives undergo smooth reactions with cyanoacetic acid that led to the formation in high yield of a new class of 1,8-naphthyridine derivatives 24. The structures of all new substances prepared in this investigation were determined by the different analytical spectroscopic methods, in addition to the X-ray crystallographic analysis. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Discovery of Novel c-Met Inhibitors Bearing a 3-Carboxyl Piperidin-2-one Scaffold
Molecules 2014, 19(2), 2655-2673; doi:10.3390/molecules19022655
Received: 21 January 2014 / Revised: 13 February 2014 / Accepted: 14 February 2014 / Published: 24 February 2014
Cited by 3 | PDF Full-text (528 KB) | HTML Full-text | XML Full-text
Abstract
A series of compounds containing a novel 3-carboxypiperidin-2-one scaffold based on the lead structure BMS-777607 were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against MKN45 cancer cell lines. The results indicated that five compounds exhibited significant inhibitory effect on
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A series of compounds containing a novel 3-carboxypiperidin-2-one scaffold based on the lead structure BMS-777607 were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against MKN45 cancer cell lines. The results indicated that five compounds exhibited significant inhibitory effect on c-Met with IC50 values of 8.6−81 nM and four compounds showed potent inhibitory activity against MKN45 cell proliferation, with IC50s ranging from 0.57−16 μM. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Comparative Diagnostic Techniques for Cryptosporidium Infection
Molecules 2014, 19(2), 2674-2683; doi:10.3390/molecules19022674
Received: 25 December 2013 / Revised: 20 January 2014 / Accepted: 21 January 2014 / Published: 24 February 2014
Cited by 6 | PDF Full-text (302 KB) | HTML Full-text | XML Full-text
Abstract
Diarrhoea caused by Cryptosporidium is usually mild in immune competent individuals but severe in the young and those with underlying disease leading to compromised immunity. The conventional diagnosis of Cryptosporidium requires observation of the infective oocysts however, their tiny size yields indistinct results,
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Diarrhoea caused by Cryptosporidium is usually mild in immune competent individuals but severe in the young and those with underlying disease leading to compromised immunity. The conventional diagnosis of Cryptosporidium requires observation of the infective oocysts however, their tiny size yields indistinct results, thus limiting the effectiveness of the conventional diagnostic technique, modified Ziehl-Neelsen (ZN) differential staining. Consequent to the abovementioned limitation, ZN staining, sandwich antigen detection enzyme linked immunosorbent assay (sad-ELISA) and a direct polymerase chain reaction (PCR) assay techniques were evaluated for diagnostic efficacy. Stool samples were collected from 180 consenting adult patients attending outpatient and inpatient clinics at Victoria Hospital, Alice, Eastern Cape Province of South Africa. Subjects were stratified as; 35 HIV-positive and diarrhoeagenic, 125 HIV-negative diarrhoeagenic and 20 apparently healthy controls. Cryptosporidium incidence following diagnostic techniques were 13 (37.1%; ZN staining), 26 (74.3%; sad-ELISA) and 23 (65.7%; PCR), respectively, among HIV-positive diarrhoeagenic patients and 34 (27.2%; ZN staining), 96 (76.8%; sad-ELISA) and 89 (71.2%; PCR) among HIV-negative diarrhoeagenic patients. Sensitivity, specificity and predictive values of the diagnostic techniques’ efficiency were: sensitivity: 46.2% (HIV-positive) and 32.3% (HIV-negative) against the ZN technique and 96.9% against sad-ELISA and PCR, respectively, for both HIV-positive and -negative patients; specificity was 88.9% (HIV-positive) and 96.6% (HIV-negative) against the ZN technique. Lastly, the predictive values were 92.3% (HIV-positive) and 96.9% (HIV-negative), respectively, following ZN staining. The sad-ELISA technique proved more suitable for the determination of the presence of Cryptosporidium oocysts. The high incidence of Cryptosporidium in HIV-positive subjects as compared to the HIV-negative population accentuates the significance of cryptosporidiosis diagnosis in the treatment and management of HIV cases. Full article
Open AccessArticle Characteristics, Composition and Oxidative Stability of Lannea microcarpa Seed and Seed Oil
Molecules 2014, 19(2), 2684-2693; doi:10.3390/molecules19022684
Received: 13 November 2013 / Revised: 6 December 2013 / Accepted: 9 December 2013 / Published: 24 February 2014
Cited by 1 | PDF Full-text (202 KB) | HTML Full-text | XML Full-text
Abstract
The proximate composition of seeds and main physicochemical properties and thermal stability of oil extracted from Lannea microcarpa seeds were evaluated. The percentage composition of the seeds was: ash (3.11%), crude oil (64.90%), protein (21.14%), total carbohydrate (10.85%) and moisture (3.24%). Physicochemical properties
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The proximate composition of seeds and main physicochemical properties and thermal stability of oil extracted from Lannea microcarpa seeds were evaluated. The percentage composition of the seeds was: ash (3.11%), crude oil (64.90%), protein (21.14%), total carbohydrate (10.85%) and moisture (3.24%). Physicochemical properties of the oil were: refractive index, 1.473; melting point, 22.60°C; saponification value, 194.23 mg of KOH/g of oil; iodine value, 61.33 g of I2/100 g of oil; acid value, 1.21 mg of KOH/g of oil; peroxide value, 1.48 meq of O2/kg of oil and oxidative stability index, 43.20 h. Oleic (43.45%), palmitic (34.45%), linoleic (11.20%) and stearic (8.35%) acids were the most dominant fatty acids. Triacylglycerols with equivalent carbon number (ECN) 48 and ECN 46 were dominant (46.96% and 37.31%, respectively). The major triacylglycerol constituents were palmitoyl diolein (POO) (21.23%), followed by dipalmitoyl olein (POP) (16.47%), palmitoyl linoleyl olein (PLO) (12.03%), dipalmitoyl linolein (PLP) (10.85%) and dioleoyl linolein (LOO) (9.30%). The total polyphenol and tocopherol contents were 1.39 mg GAE g−1 DW and 578.56 ppm, respectively. γ-Tocopherol was the major tocopherol (437.23 ppm). These analytical results indicated that the L. microcarpa seed oil could be used as a frying oil and in the cosmetic industry. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Biological Evaluation of Substituted Desloratadines as Potent Arginine Vasopressin V2 Receptor Antagonists
Molecules 2014, 19(2), 2694-2706; doi:10.3390/molecules19022694
Received: 2 December 2013 / Revised: 14 January 2014 / Accepted: 26 January 2014 / Published: 24 February 2014
Cited by 2 | PDF Full-text (268 KB) | HTML Full-text | XML Full-text
Abstract
Twenty-one non-peptide substituted desloratadine class compounds were synthesized as novel arginine vasopressin receptor antagonists from desloratadine via successive acylation, reduction and acylation reactions. Their structures were characterized by 1H-NMR and HRMS, their biological activity was evaluated by in vitro and in vivo
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Twenty-one non-peptide substituted desloratadine class compounds were synthesized as novel arginine vasopressin receptor antagonists from desloratadine via successive acylation, reduction and acylation reactions. Their structures were characterized by 1H-NMR and HRMS, their biological activity was evaluated by in vitro and in vivo studies. The in vitro binding assay and cAMP accumulation assay indicated that these compounds are potent selective V2 receptor antagonists. Among them compounds 1n, 1t and 1v exhibited both high affinity and promising selectivity for V2 receptors. The in vivo diuretic assay demonstrated that 1t presented remarkable diuretic activity. In conclusion, 1t is a potent novel AVP V2 receptor antagonist candidate. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessReview Applications of Copper-Catalyzed Click Chemistry in Activity-Based Protein Profiling
Molecules 2014, 19(2), 1378-1393; doi:10.3390/molecules19021378
Received: 23 December 2013 / Revised: 9 January 2014 / Accepted: 17 January 2014 / Published: 27 January 2014
Cited by 17 | PDF Full-text (390 KB) | HTML Full-text | XML Full-text
Abstract
Activity-based protein profiling (ABPP) is a chemical proteomic technique that enables the interrogation of protein activity directly within complex proteomes. Given the dominant role of posttranslational modifications in regulating protein function in vivo, ABPP provides a direct readout of activity that is
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Activity-based protein profiling (ABPP) is a chemical proteomic technique that enables the interrogation of protein activity directly within complex proteomes. Given the dominant role of posttranslational modifications in regulating protein function in vivo, ABPP provides a direct readout of activity that is not attained through traditional proteomic methods. ABPP relies on the design of covalent binding probes that either target a specific enzyme or a class of enzymes with related function. These covalent warheads are coupled to either fluorophores or biotin groups for visualization and enrichment of these active proteins. The advent of bioorthogonal chemistries, in particular, the copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC), has benefitted the field of ABPP by achieving the following: (1) replacing bulky reporter groups with smaller alkyne or azide groups to promote cell permeability; (2) adding modularity to the system such that a single probe can be diversified with a variety of reporter groups without the need to develop new synthetic routes; and (3) enabling the conjugation of complex linkers to facilitate quantitative proteomic analyses. Here, we summarize recent examples of CuAAC in ABPP that serve to illustrate the contribution of bioorthogonal chemistry to advancing discoveries in this field. Full article
(This article belongs to the Special Issue Bioorthogonal Chemistry)
Open AccessReview Natural Products from the Genus Tephrosia
Molecules 2014, 19(2), 1432-1458; doi:10.3390/molecules19021432
Received: 10 December 2013 / Revised: 2 January 2014 / Accepted: 13 January 2014 / Published: 27 January 2014
Cited by 8 | PDF Full-text (541 KB) | HTML Full-text | XML Full-text
Abstract
The genus Tephrosia, belonging to the Leguminosae family, is a large pantropical genus of more than 350 species, many of which have important traditional uses in agriculture. This review not only outlines the source, chemistry and biological evaluations of natural products from
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The genus Tephrosia, belonging to the Leguminosae family, is a large pantropical genus of more than 350 species, many of which have important traditional uses in agriculture. This review not only outlines the source, chemistry and biological evaluations of natural products from the genus Tephrosia worldwide that have appeared in literature from 1910 to December 2013, but also covers work related to proposed biosynthetic pathways and synthesis of some natural products from the genus Tephrosia, with 105 citations and 168 new compounds. Full article
Open AccessReview A Review on Anti-Inflammatory Activity of Phenylpropanoids Found in Essential Oils
Molecules 2014, 19(2), 1459-1480; doi:10.3390/molecules19021459
Received: 3 December 2013 / Revised: 27 December 2013 / Accepted: 30 December 2013 / Published: 27 January 2014
Cited by 24 | PDF Full-text (294 KB) | HTML Full-text | XML Full-text
Abstract
The search for alternative drugs capable of disrupting the inflammatory process has become an important issue in scientific research, especially with reference to the use of natural substances and the reduction of undesirable side effects. Essential oils represent an important source of such
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The search for alternative drugs capable of disrupting the inflammatory process has become an important issue in scientific research, especially with reference to the use of natural substances and the reduction of undesirable side effects. Essential oils represent an important source of such substances, since their active constituents often exhibit an array of pharmacological properties, including anti-inflammatory activity. This review presents an overview of the anti-inflammatory action exerted by phenylpropanoids from essential oils and discusses possible mechanisms of action involved in the anti-inflammatory response, assessed through specific experimental models. Full article
(This article belongs to the Section Natural Products)
Open AccessReview Cross-Talk of Phosphorylation and Prolyl Isomerization of the C-terminal Domain of RNA Polymerase II
Molecules 2014, 19(2), 1481-1511; doi:10.3390/molecules19021481
Received: 26 October 2013 / Revised: 6 January 2014 / Accepted: 21 January 2014 / Published: 27 January 2014
Cited by 4 | PDF Full-text (2631 KB) | HTML Full-text | XML Full-text
Abstract
Post-translational modifications of the heptad repeat sequences in the C-terminal domain (CTD) of RNA polymerase II (Pol II) are well recognized for their roles in coordinating transcription with other nuclear processes that impinge upon transcription by the Pol II machinery; and this is
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Post-translational modifications of the heptad repeat sequences in the C-terminal domain (CTD) of RNA polymerase II (Pol II) are well recognized for their roles in coordinating transcription with other nuclear processes that impinge upon transcription by the Pol II machinery; and this is primarily achieved through CTD interactions with the various nuclear factors. The identification of novel modifications on new regulatory sites of the CTD suggests that, instead of an independent action for all modifications on CTD, a combinatorial effect is in operation. In this review we focus on two well-characterized modifications of the CTD, namely serine phosphorylation and prolyl isomerization, and discuss the complex interplay between the enzymes modifying their respective regulatory sites. We summarize the current understanding of how the prolyl isomerization state of the CTD dictates the specificity of writers (CTD kinases), erasers (CTD phosphatases) and readers (CTD binding proteins) and how that correlates to transcription status. Subtle changes in prolyl isomerization states cannot be detected at the primary sequence level, we describe the methods that have been utilized to investigate this mode of regulation. Finally, a general model of how prolyl isomerization regulates the phosphorylation state of CTD, and therefore transcription-coupled processes, is proposed. Full article
(This article belongs to the Special Issue RNA Polymerases as Molecular Machines)
Open AccessReview Pharmacological Importance of Optically Active Tetrahydro-β-carbolines and Synthetic Approaches to Create the C1 Stereocenter
Molecules 2014, 19(2), 1544-1567; doi:10.3390/molecules19021544
Received: 19 December 2013 / Revised: 17 January 2014 / Accepted: 20 January 2014 / Published: 27 January 2014
Cited by 12 | PDF Full-text (984 KB) | HTML Full-text | XML Full-text
Abstract
1,2,3,4-Tetrahydro-β-carbolines (THβCs) are a pharmacologically important group of compounds belonging to the indole alkaloids. C1-Substituted optically active THβCs have been the target of extensive synthetic efforts due to the presence of the scaffold in numerous natural products and synthetic targets. This review briefly
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1,2,3,4-Tetrahydro-β-carbolines (THβCs) are a pharmacologically important group of compounds belonging to the indole alkaloids. C1-Substituted optically active THβCs have been the target of extensive synthetic efforts due to the presence of the scaffold in numerous natural products and synthetic targets. This review briefly summarizes the methods to obtain the C1 stereocenter and concentrates on evaluating the pharmacological importance of optically active C1-substituted THβCs, including their PDE5-inhibitory, antimalarial, antiviral and antitumor activities. Full article
(This article belongs to the Section Natural Products)
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Open AccessReview Crataegus pinnatifida: Chemical Constituents, Pharmacology, and Potential Applications
Molecules 2014, 19(2), 1685-1712; doi:10.3390/molecules19021685
Received: 30 December 2013 / Revised: 22 January 2014 / Accepted: 22 January 2014 / Published: 30 January 2014
Cited by 20 | PDF Full-text (537 KB) | HTML Full-text | XML Full-text
Abstract
Crataegus pinnatifida (Hawthorn) is widely distributed in China and has a long history of use as a traditional medicine. The fruit of C. pinnatifida has been used for the treatment of cardiodynia, hernia, dyspepsia, postpartum blood stasis, and hemafecia and thus increasing interest
[...] Read more.
Crataegus pinnatifida (Hawthorn) is widely distributed in China and has a long history of use as a traditional medicine. The fruit of C. pinnatifida has been used for the treatment of cardiodynia, hernia, dyspepsia, postpartum blood stasis, and hemafecia and thus increasing interest in this plant has emerged in recent years. Between 1966 and 2013, numerous articles have been published on the chemical constituents, pharmacology or pharmacologic effects and toxicology of C. pinnatifida. To review the pharmacologic advances and to discuss the potential perspective for future investigation, we have summarized the main literature findings of these publications. So far, over 150 compounds including flavonoids, triterpenoids, steroids, monoterpenoids, sesquiterpenoids, lignans, hydroxycinnamic acids, organic acids and nitrogen-containing compounds have been isolated and identified from C. pinnatifida. It has been found that these constituents and extracts of C. pinnatifida have broad pharmacological effects with low toxicity on, for example, the cardiovascular, digestive, and endocrine systems, and pathogenic microorganisms, supporting the view that C. pinnatifida has favorable therapeutic effects. Thus, although C. pinnatifida has already been widely used as pharmacological therapy, due to its various active compounds, further research is warranted to develop new drugs. Full article
Open AccessReview The Remarkable Structural Diversity Achieved in ent-Kaurane Diterpenes by Fungal Biotransformations
Molecules 2014, 19(2), 1856-1886; doi:10.3390/molecules19021856
Received: 24 December 2013 / Revised: 5 February 2014 / Accepted: 6 February 2014 / Published: 10 February 2014
Cited by 2 | PDF Full-text (423 KB) | HTML Full-text | XML Full-text
Abstract
The use of biotransformations in organic chemistry is widespread, with highlights of interesting applications in the functionalization of natural products containing unactivated carbons, like the kaurane diterpenes. A number of compounds with kaurane skeletons can be isolated in large amounts from several plant
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The use of biotransformations in organic chemistry is widespread, with highlights of interesting applications in the functionalization of natural products containing unactivated carbons, like the kaurane diterpenes. A number of compounds with kaurane skeletons can be isolated in large amounts from several plant species and a myriad of biological activities has been related to these compounds. Studies on structure versus activity have showed that, in most cases, in kaurane diterpenes, activity increases with the increase of functionalization. Since naturally occurring kaurane diterpenes usually have limited functional groups to be used as targets for semi-synthetic modifications, production of more polar derivatives from kaurane diterpenes have been achieved mostly through the use of fungal biotransformations. In this review, selected examples the wonderful chemical diversity produced by fungi in kaurane diterpenes is presented. This diversity includes mainly hydroxylation of nearly all carbon atoms of the kaurane molecule, many of them carried out stereoselectively, as well as ring rearrangements, among other chemical modifications. Sources of starting materials, general biotransformation protocols employed, fungi with most consistent regioselectivity towards kaurane skeleton, as well as biological activities associated with starting materials and products are also described. Full article
(This article belongs to the Special Issue Biosynthesis and Biotransformation)
Open AccessReview Tumor-Associated Circulating MicroRNAs as Biomarkers of Cancer
Molecules 2014, 19(2), 1912-1938; doi:10.3390/molecules19021912
Received: 10 December 2013 / Revised: 24 January 2014 / Accepted: 29 January 2014 / Published: 10 February 2014
Cited by 54 | PDF Full-text (308 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs), the 17- to 25-nucleotide long noncoding RNAs that modulate the expression of mRNAs and proteins, have emerged as critical players in cancer initiation and progression processes. Deregulation of tissue miRNA expression levels associated with specific genetic alterations has been demonstrated in
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MicroRNAs (miRNAs), the 17- to 25-nucleotide long noncoding RNAs that modulate the expression of mRNAs and proteins, have emerged as critical players in cancer initiation and progression processes. Deregulation of tissue miRNA expression levels associated with specific genetic alterations has been demonstrated in cancer, where miRNAs function either as oncogenes or as tumor-suppressor genes and are shed from cancer cells into circulation. The present review summarizes and evaluates recent advances in our understanding of the characteristics of tumor tissue miRNAs, circulating miRNAs, and the stability of miRNAs in tissues and their varying expression profiles in circulating tumor cells, and body fluids including blood plasma. These advances in knowledge have led to intense efforts towards discovery and validation of differentially expressing tumor-associated miRNAs as biomarkers and therapeutic targets of cancer. The development of tumor-specific miRNA signatures as cancer biomarkers detectable in malignant cells and body fluids should help with early detection and more effective therapeutic intervention for individual patients. Full article
(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)
Open AccessReview Radiolabeling Strategies for Tumor-Targeting Proteinaceous Drugs
Molecules 2014, 19(2), 2135-2165; doi:10.3390/molecules19022135
Received: 6 September 2013 / Revised: 16 January 2014 / Accepted: 1 February 2014 / Published: 18 February 2014
Cited by 7 | PDF Full-text (432 KB) | HTML Full-text | XML Full-text
Abstract
Owing to their large size proteinaceous drugs offer higher operative information content compared to the small molecules that correspond to the traditional understanding of druglikeness. As a consequence these drugs allow developing patient-specific therapies that provide the means to go beyond the possibilities
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Owing to their large size proteinaceous drugs offer higher operative information content compared to the small molecules that correspond to the traditional understanding of druglikeness. As a consequence these drugs allow developing patient-specific therapies that provide the means to go beyond the possibilities of current drug therapy. However, the efficacy of these strategies, in particular “personalized medicine”, depends on precise information about individual target expression rates. Molecular imaging combines non-invasive imaging methods with tools of molecular and cellular biology and thus bridges current knowledge to the clinical use. Moreover, nuclear medicine techniques provide therapeutic applications with tracers that behave like the diagnostic tracer. The advantages of radioiodination, still the most versatile radiolabeling strategy, and other labeled compounds comprising covalently attached radioisotopes are compared to the use of chelator-protein conjugates that are complexed with metallic radioisotopes. With the techniques using radioactive isotopes as a reporting unit or even the therapeutic principle, care has to be taken to avoid cleavage of the radionuclide from the protein it is linked to. The tracers used in molecular imaging require labeling techniques that provide site specific conjugation and metabolic stability. Appropriate choice of the radionuclide allows tailoring the properties of the labeled protein to the application required. Until the event of positron emission tomography the spectrum of nuclides used to visualize cellular and biochemical processes was largely restricted to iodine isotopes and 99m-technetium. Today, several nuclides such as 18-fluorine, 68-gallium and 86-yttrium have fundamentally extended the possibilities of tracer design and in turn caused the need for the development of chemical methods for their conjugation. Full article
(This article belongs to the Special Issue Reagents and Methods for Protein Target Identification)
Open AccessReview Carnosinases, Their Substrates and Diseases
Molecules 2014, 19(2), 2299-2329; doi:10.3390/molecules19022299
Received: 25 October 2013 / Revised: 7 January 2014 / Accepted: 28 January 2014 / Published: 21 February 2014
Cited by 8 | PDF Full-text (1717 KB) | HTML Full-text | XML Full-text
Abstract
Carnosinases are Xaa-His dipeptidases that play diverse functions throughout all kingdoms of life. Human isoforms of carnosinase (CN1 and CN2) under appropriate conditions catalyze the hydrolysis of the dipeptides carnosine (β-alanyl-L-histidine) and homocarnosine (γ-aminobutyryl-L-histidine). Alterations of serum carnosinase (CN1) activity has been associated
[...] Read more.
Carnosinases are Xaa-His dipeptidases that play diverse functions throughout all kingdoms of life. Human isoforms of carnosinase (CN1 and CN2) under appropriate conditions catalyze the hydrolysis of the dipeptides carnosine (β-alanyl-L-histidine) and homocarnosine (γ-aminobutyryl-L-histidine). Alterations of serum carnosinase (CN1) activity has been associated with several pathological conditions, such as neurological disorders, chronic diseases and cancer. For this reason the use of carnosinase levels as a biomarker in cerebrospinal fluid (CSF) has been questioned. The hydrolysis of imidazole-related dipeptides in prokaryotes and eukaryotes is also catalyzed by aminoacyl-histidine dipeptidases like PepD (EC 3.4.13.3), PepV (EC 3.4.13.19) and anserinase (EC 3.4.13.5). The review deals with the structure and function of this class of enzymes in physiological and pathological conditions. The main substrates of these enzymes, i.e., carnosine, homocarnosine and anserine (β-alanyl-3-methyl-L-histidine) will also be described. Full article
(This article belongs to the Special Issue Enzyme Chemistry)
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Open AccessReview Ultrafast Internal Conversion of Aromatic Molecules Studied by Photoelectron Spectroscopy using Sub-20 fs Laser Pulses
Molecules 2014, 19(2), 2410-2433; doi:10.3390/molecules19022410
Received: 5 December 2013 / Revised: 8 February 2014 / Accepted: 12 February 2014 / Published: 21 February 2014
Cited by 1 | PDF Full-text (2665 KB) | HTML Full-text | XML Full-text
Abstract
This article describes our recent experimental studies on internal conversion via a conical intersection using photoelectron spectroscopy. Ultrafast S2(ππ*)–S1(*) internal conversion in pyrazine is observed in real time using sub-20 fs deep ultraviolet pulses
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This article describes our recent experimental studies on internal conversion via a conical intersection using photoelectron spectroscopy. Ultrafast S2(ππ*)–S1(*) internal conversion in pyrazine is observed in real time using sub-20 fs deep ultraviolet pulses (264 and 198 nm). While the photoelectron kinetic energy distribution does not exhibit a clear signature of internal conversion, the photoelectron angular anisotropy unambiguously reveals the sudden change of electron configuration upon internal conversion. An explanation is presented as to why these two observables have different sensitivities to internal conversion. The 198 nm probe photon energy is insufficient for covering the entire Franck-Condon envelopes upon photoionization from S2/S1 to D1/D0. A vacuum ultraviolet free electron laser (SCSS) producing 161 nm radiation is employed to solve this problem, while its pulse-to-pulse timing jitter limits the time resolution to about 1 ps. The S2S1 internal conversion is revisited using the sub-20 fs 159 nm pulse created by filamentation four-wave mixing. Conical intersections between D1(π−1) and D0(n−1) and also between the Rydberg state with a D1 ion core and that with a D0 ion core of pyrazine are studied by He(I) photoelectron spectroscopy, pulsed field ionization photoelectron spectroscopy and one-color resonance-enhanced multiphoton ionization spectroscopy. Finally, ultrafast S2(ππ*)–S1(ππ*) internal conversion in benzene and toluene are compared with pyrazine. Full article
(This article belongs to the Special Issue Photoelectron Spectroscopy)
Open AccessReview Clinical Application of MicroRNA Testing in Neuroendocrine Tumors of the Gastrointestinal Tract
Molecules 2014, 19(2), 2458-2468; doi:10.3390/molecules19022458
Received: 16 January 2014 / Revised: 17 February 2014 / Accepted: 17 February 2014 / Published: 21 February 2014
Cited by 13 | PDF Full-text (588 KB) | HTML Full-text | XML Full-text
Abstract
It is well documented that dysregulation of microRNAs is a hallmark of human cancers. Thus, this family of small non-coding regulatory molecules represents an excellent source of sensitive biomarkers. Unique microRNAs expression profiles have been associated with different types and subsets of gastrointestinal
[...] Read more.
It is well documented that dysregulation of microRNAs is a hallmark of human cancers. Thus, this family of small non-coding regulatory molecules represents an excellent source of sensitive biomarkers. Unique microRNAs expression profiles have been associated with different types and subsets of gastrointestinal tumors including gastroenteropancreatic neuroendocrine tumors (GEP-NETs). GEP-NETs are a heterogeneous group of epithelial neoplasms with neuroendocrine differentiation. At present, early detection and surgical resection of GEP-NETs represent the best chance for a cure. Thus, clinically useful biomarkers for GEP-NETs that strongly correlate with early detection are urgently needed. The purpose of this review is to summarize the role of miRNAs in GEP-NET carcinogenesis and their possible use as novel diagnostic, prognostic and predictive biomarkers. Full article
(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)
Open AccessReview Effects of Honey and Its Mechanisms of Action on the Development and Progression of Cancer
Molecules 2014, 19(2), 2497-2522; doi:10.3390/molecules19022497
Received: 28 November 2013 / Revised: 6 February 2014 / Accepted: 10 February 2014 / Published: 21 February 2014
Cited by 15 | PDF Full-text (517 KB) | HTML Full-text | XML Full-text
Abstract
Honey is a natural product known for its varied biological or pharmacological activities—ranging from anti-inflammatory, antioxidant, antibacterial, antihypertensive to hypoglycemic effects. This review article focuses on the role of honey in modulating the development and progression of tumors or cancers. It reviews available
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Honey is a natural product known for its varied biological or pharmacological activities—ranging from anti-inflammatory, antioxidant, antibacterial, antihypertensive to hypoglycemic effects. This review article focuses on the role of honey in modulating the development and progression of tumors or cancers. It reviews available evidence (some of which is very recent) with regards to the antimetastatic, antiproliferative and anticancer effects of honey in various forms of cancer. These effects of honey have been thoroughly investigated in certain cancers such as breast, liver and colorectal cancer cell lines. In contrast, limited but promising data are available for other forms of cancers including prostate, bladder, endometrial, kidney, skin, cervical, oral and bone cancer cells. The article also underscores the various possible mechanisms by which honey may inhibit growth and proliferation of tumors or cancers. These include regulation of cell cycle, activation of mitochondrial pathway, induction of mitochondrial outer membrane permeabilization, induction of apoptosis, modulation of oxidative stress, amelioration of inflammation, modulation of insulin signaling and inhibition of angiogenesis. Honey is highly cytotoxic against tumor or cancer cells while it is non-cytotoxic to normal cells. The data indicate that honey can inhibit carcinogenesis by modulating the molecular processes of initiation, promotion, and progression stages. Thus, it may serve as a potential and promising anticancer agent which warrants further experimental and clinical studies. Full article
(This article belongs to the Section Natural Products)

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