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Molecules, Volume 21, Issue 11 (November 2016)

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Cover Story Hypervalent pentacoordinated phosphoranes are an interesting class of organophosphorus compounds [...] Read more.
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Editorial

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Open AccessEditorial Special Issue “Molecular Engineering for Electrochemical Power Sources”
Molecules 2016, 21(11), 1524; doi:10.3390/molecules21111524
Received: 9 November 2016 / Revised: 10 November 2016 / Accepted: 10 November 2016 / Published: 12 November 2016
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(This article belongs to the Special Issue Molecular Engineering for Electrochemical Power Sources)
Open AccessEditorial Special Issue: “Organic Reactions in Green Solvents”
Molecules 2016, 21(11), 1527; doi:10.3390/molecules21111527
Received: 3 November 2016 / Accepted: 9 November 2016 / Published: 15 November 2016
Cited by 3 | PDF Full-text (154 KB) | HTML Full-text | XML Full-text
Abstract
To overcome the well-established drawbacks of conventional organic solvents (toxicity, non-biodegradability, flammability, accumulation in the atmosphere) remarkable research efforts have been recently devoted to the replacement of traditional organic reaction media by the so-called Green Solvents. In this sense, the choice of
[...] Read more.
To overcome the well-established drawbacks of conventional organic solvents (toxicity, non-biodegradability, flammability, accumulation in the atmosphere) remarkable research efforts have been recently devoted to the replacement of traditional organic reaction media by the so-called Green Solvents. In this sense, the choice of a safe, non-toxic, biorenewable and cheap reaction media is a crucial goal in organic synthesis. Thus, this Special Issue on “Organic Reactions in Green Solvents” has been aimed to showcase a series of stimulating contributions from international experts within different sub-areas of organic synthesis in Green Solvents (ranging from metal- to organo-catalyzed organic reactions). Full article
(This article belongs to the Special Issue Organic Reaction in Green Solvents)

Research

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Open AccessArticle The Role of Concentration and Solvent Character in the Molecular Organization of Humic Acids
Molecules 2016, 21(11), 1410; doi:10.3390/molecules21111410
Received: 19 July 2016 / Revised: 14 October 2016 / Accepted: 19 October 2016 / Published: 27 October 2016
Cited by 1 | PDF Full-text (1251 KB) | HTML Full-text | XML Full-text
Abstract
The molecular organization of humic acids in different aqueous solutions was studied over a wide concentration range (0.01–10 g·dm−3). Solutions of humic acids were prepared in three different media: NaOH, NaCl, and NaOH neutralized by HCl after dissolution of the humic
[...] Read more.
The molecular organization of humic acids in different aqueous solutions was studied over a wide concentration range (0.01–10 g·dm−3). Solutions of humic acids were prepared in three different media: NaOH, NaCl, and NaOH neutralized by HCl after dissolution of the humic sample. Potentiometry, conductometry, densitometry, and high resolution ultrasound spectrometry were used in order to investigate conformational changes in the humic systems. The molecular organization of humic acids in the studied systems could be divided into three concentration ranges. The rearrangements were observed at concentrations of ~0.02 g·dm−3 and ~1 g·dm−3. The first “switch-over point” was connected with changes in the hydration shells of humic particles resulting in changes in their elasticity. The compressibility of water in the hydration shells is less than the compressibility of bulk water. The transfer of hydration water into bulk water increased the total compressibility of the solution, reducing the ultrasonic velocity. The aggregation of humic particles and the formation of rigid structures in systems with concentrations higher than 1 g·dm−3 was detected. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Antimalarial Activity of the Chemical Constituents of the Leaf Latex of Aloe pulcherrima Gilbert and Sebsebe
Molecules 2016, 21(11), 1415; doi:10.3390/molecules21111415
Received: 29 August 2016 / Revised: 11 October 2016 / Accepted: 17 October 2016 / Published: 28 October 2016
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Abstract
Malaria is one of the three major global public health threats due to a wide spread resistance of the parasites to the standard antimalarial drugs. Considering this growing problem, the ethnomedicinal approach in the search for new antimalarial drugs from plant sources has
[...] Read more.
Malaria is one of the three major global public health threats due to a wide spread resistance of the parasites to the standard antimalarial drugs. Considering this growing problem, the ethnomedicinal approach in the search for new antimalarial drugs from plant sources has proven to be more effective and inexpensive. The leaves of Aloe pulcherrima Gilbert and Sebsebe, an endemic Ethiopian plant, are locally used for the treatment of malaria and other infectious diseases. Application of the leaf latex of A. pulcherrima on preparative silica gel TLC led to the isolation of two C-glycosylated anthrones, identified as nataloin (1) and 7-hydroxyaloin (2) by spectroscopic techniques (UV, IR, 1H- and 13C-NMR, HR-ESIMS). Both the latex and isolated compounds displayed antimalarial activity in a dose-independent manner using a four-day suppressive test, with the highest percent suppression of 56.2% achieved at 200 mg/kg/day for 2. The results indicate that both the leaf latex of A. pulcherrima and its two major constituents are endowed with antiplasmodial activities, which support the traditional use of the leaves of the plant for the treatment of malaria. Full article
(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)
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Open AccessArticle Piceatannol Exerts Anti-Obesity Effects in C57BL/6 Mice through Modulating Adipogenic Proteins and Gut Microbiota
Molecules 2016, 21(11), 1419; doi:10.3390/molecules21111419
Received: 10 September 2016 / Revised: 20 October 2016 / Accepted: 21 October 2016 / Published: 25 October 2016
Cited by 7 | PDF Full-text (4020 KB) | HTML Full-text | XML Full-text
Abstract
Obesity is a global health concern. Piceatannol (Pic), an analog of resveratrol (Res), has many reported biological activities. In this study, we investigated the anti-obesity effect of Pic in a high-fat diet (HFD)-induced obese animal model. The results showed that Pic significantly reduced
[...] Read more.
Obesity is a global health concern. Piceatannol (Pic), an analog of resveratrol (Res), has many reported biological activities. In this study, we investigated the anti-obesity effect of Pic in a high-fat diet (HFD)-induced obese animal model. The results showed that Pic significantly reduced mouse body weight in a dose-dependent manner without affecting food intake. Serum total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) levels, and blood glucose (GLU) were significantly lowered in Pic-treated groups. Pic significantly decreased the weight of liver, spleen, perigonadal and retroperitoneal fat compared with the HFD group. Pic significantly reduced the adipocyte cell size of perigonadal fat and decreased the weight of liver. Pic-treated mice showed higher phosphorylated adenosine 5′-monophosphate-activated protein kinase (pAMPK) and phosphorylated acetyl-CoA carboxylase (pACC) protein levels and decreased protein levels of CCAAT/enhancer-binding protein C/EBPα, peroxisome proliferator-activated receptor PPARγ and fatty acid synthase (FAS), resulting in decreased lipid accumulation in adipocytes and the liver. Pic altered the composition of the gut microbiota by increasing Firmicutes and Lactobacillus and decreasing Bacteroidetes compared with the HFD group. Collectively, these results suggest that Pic may be a candidate for obesity treatment. Full article
(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)
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Open AccessArticle Synthesis and the Biological Activity of Phosphonylated 1,2,3-Triazolenaphthalimide Conjugates
Molecules 2016, 21(11), 1420; doi:10.3390/molecules21111420
Received: 3 October 2016 / Revised: 19 October 2016 / Accepted: 20 October 2016 / Published: 26 October 2016
Cited by 1 | PDF Full-text (803 KB) | HTML Full-text | XML Full-text
Abstract
A novel series of diethyl {4-[(5-substituted-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates designed as analogues of amonafide was synthesized. All phosphonates were assessed for antiviral activity against a broad range of DNA and RNA viruses and several of them showed potency
[...] Read more.
A novel series of diethyl {4-[(5-substituted-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates designed as analogues of amonafide was synthesized. All phosphonates were assessed for antiviral activity against a broad range of DNA and RNA viruses and several of them showed potency against varicella-zoster virus (VZV) [EC50 (50% effective concentration) = 27.6–91.5 μM]. Compound 16b exhibited the highest activity against a thymidine kinase-deficient (TK) VZV strain (EC50 = 27.59 μM), while 16d was the most potent towards TK+ VZV (EC50 = 29.91 μM). Cytostatic properties of the compounds 14ai17ai were studied on L1210, CEM, HeLa and HMEC-1 cell lines and most of them were slightly cytostatic for HeLa [IC50 (50% inhibitory concentration) = 29–130 µM] and L1210 cells [IC50 (50% inhibitory concentration) = 14–142 µM]. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessArticle Novel Halogenated Pyrazine-Based Chalcones as Potential Antimicrobial Drugs
Molecules 2016, 21(11), 1421; doi:10.3390/molecules21111421
Received: 23 September 2016 / Revised: 14 October 2016 / Accepted: 14 October 2016 / Published: 27 October 2016
Cited by 3 | PDF Full-text (889 KB) | HTML Full-text | XML Full-text
Abstract
Chalcones, i.e., compounds with the chemical pattern of 1,3-diphenylprop-2-en-1-ones, exert a wide range of bio-activities, e.g., antioxidant, anti-inflammatory, anticancer, anti-infective etc. Our research group has been focused on pyrazine analogues of chalcones; several series have been synthesized and tested in vitro on antifungal
[...] Read more.
Chalcones, i.e., compounds with the chemical pattern of 1,3-diphenylprop-2-en-1-ones, exert a wide range of bio-activities, e.g., antioxidant, anti-inflammatory, anticancer, anti-infective etc. Our research group has been focused on pyrazine analogues of chalcones; several series have been synthesized and tested in vitro on antifungal and antimycobacterial activity. The highest potency was exhibited by derivatives with electron withdrawing groups (EWG) in positions 2 and 4 of the ring B. As halogens also have electron withdrawing properties, novel halogenated derivatives were prepared by Claisen-Schmidt condensation. All compounds were submitted for evaluation of their antifungal and antibacterial activity, including their antimycobacterial effect. In the antifungal assay against eight strains of selected fungi, growth inhibition of Candida glabrata and Trichophyton interdigitale (formerly T. mentagrophytes) was shown by non-alkylated derivatives with 2-bromo or 2-chloro substitution. In the panel of selected bacteria, 2-chloro derivatives showed the highest inhibitory effect on Staphylococcus sp. In addition, all products were also screened for their antimycobacterial activity against Mycobacterium tuberculosis H37RV My 331/88, M. kansasii My 235/80, M. avium 152/80 and M. smegmatis CCM 4622. Some of the examined compounds, inhibited growth of M. kansasii and M. smegmatis with minimum inhibitory concentrations (MICs) comparable with those of isoniazid. Full article
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Open AccessArticle Substituent Inductive Effects on the Electrochemical Oxidation of Flavonoids Studied by Square Wave Voltammetry and Ab Initio Calculations
Molecules 2016, 21(11), 1422; doi:10.3390/molecules21111422
Received: 2 September 2016 / Revised: 11 October 2016 / Accepted: 18 October 2016 / Published: 27 October 2016
Cited by 1 | PDF Full-text (1620 KB) | HTML Full-text | XML Full-text
Abstract
Flavonoids are natural products commonly found in the human diet that show antioxidant, anti-inflammatory and anti-hepatotoxic activities. These nutraceutical properties may relate to the electrochemical activity of flavonoids. To increase the understanding of structure–electrochemical activity relations and the inductive effects that OH substituents
[...] Read more.
Flavonoids are natural products commonly found in the human diet that show antioxidant, anti-inflammatory and anti-hepatotoxic activities. These nutraceutical properties may relate to the electrochemical activity of flavonoids. To increase the understanding of structure–electrochemical activity relations and the inductive effects that OH substituents have on the redox potential of flavonoids, we carried out square-wave voltammetry experiments and ab initio calculations of eight flavonoids selected following a systematic variation in the number of hydroxyl substituents and their location on the flavan backbone: three flavonols, three anthocyanidins, one anthocyanin and the flavonoid backbone flavone. We compared the effect that the number of –OH groups in the ring B of flavan has on the oxidation potential of the flavonoids considered, finding linear correlations for both flavonols and anthocyanidins ( R 2 = 0.98 ). We analyzed the effects that position and number of –OH substituents have on electron density distributions via ab initio quantum chemical calculations. We present direct correlations between structural features and oxidation potentials that provide a deeper insight into the redox chemistry of these molecules. Full article
(This article belongs to the Special Issue Organic Electrochemistry)
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Open AccessArticle Discrimination and Nitric Oxide Inhibitory Activity Correlation of Ajwa Dates from Different Grades and Origin
Molecules 2016, 21(11), 1423; doi:10.3390/molecules21111423
Received: 12 August 2016 / Revised: 13 October 2016 / Accepted: 20 October 2016 / Published: 28 October 2016
Cited by 1 | PDF Full-text (1861 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This study was aimed at examining the variations in the metabolite constituents of the different Ajwa grades and farm origins. It is also targeted at establishing the correlations between the metabolite contents and the grades and further to the nitric oxide (NO) inhibitory
[...] Read more.
This study was aimed at examining the variations in the metabolite constituents of the different Ajwa grades and farm origins. It is also targeted at establishing the correlations between the metabolite contents and the grades and further to the nitric oxide (NO) inhibitory activity. Identification of the metabolites was generated using 1H-NMR spectroscopy metabolomics analyses utilizing multivariate methods. The NO inhibitory activity was determined using a Griess assay. Multivariate data analysis, for both supervised and unsupervised approaches, showed clusters among different grades of Ajwa dates obtained from different farms. The compounds that contribute towards the observed separation between Ajwa samples were suggested to be phenolic compounds, ascorbic acid and phenylalanine. Ajwa dates were shown to have different metabolite compositions and exhibited a wide range of NO inhibitory activity. It is also revealed that Ajwa Grade 1 from the al-Aliah farm exhibited more than 90% NO inhibitory activity compared to the other grades and origins. Phenolic compounds were among the compounds that played a role towards the greater capacity of NO inhibitory activity shown by Ajwa Grade 1 from the al-Aliah farm. Full article
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Open AccessArticle Herbal Formula HT048 Attenuates Diet-Induced Obesity by Improving Hepatic Lipid Metabolism and Insulin Resistance in Obese Rats
Molecules 2016, 21(11), 1424; doi:10.3390/molecules21111424
Received: 19 August 2016 / Revised: 7 October 2016 / Accepted: 21 October 2016 / Published: 25 October 2016
Cited by 2 | PDF Full-text (1703 KB) | HTML Full-text | XML Full-text
Abstract
It is well established that obesity causes a variety of chronic diseases such as cardiovascular diseases and diabetes. Despite the diligent scientific efforts to find effective ways to lower the level of obesity, the size of obese population grows continuously around the world.
[...] Read more.
It is well established that obesity causes a variety of chronic diseases such as cardiovascular diseases and diabetes. Despite the diligent scientific efforts to find effective ways to lower the level of obesity, the size of obese population grows continuously around the world. Here we present the results that show feeding diet containing HT048, a mixture of the extracts of Crataegus pinnatifida leaves and Citrus unshiu peel, two of the well-known traditional herbal medicines in Eastern Asia, decreases obesity in rats. We fed rats with five different diets for 10 weeks: chow diet (STD), high-fat diet (HFD), high-fat diet with 0.04% orlistat, a drug to treat obesity (HFD + Orlistat), high-fat diet with 0.2% HT048 (w/w; HFD + 0.2% HT048), and high-fat diet with 0.6% HT048 (w/w; HFD + 0.6% HT048). It was found that both body and total white adipose tissue weight of HT048 groups significantly decreased compared to those of the HFD group. Moreover, HT048 decreased serum insulin levels in HFD-fed obese rats. At the molecular level, HT048 supplementation downregulated genes involved in lipogenesis, gluconeogenesis, and adipogenesis, while the expression level of β-oxidation genes was increased. Supplementation-drug interactions are not likely as HFD and HT048-containing diet did not significantly induce genes encoding CYPs. Collectively, this study suggests that HT048 taken as dietary supplement helps to decrease obesity and insulin resistance in HFD-fed obese rats. Full article
(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)
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Open AccessArticle Effect of the Aged Garlic Extract on Cardiovascular Function in Metabolic Syndrome Rats
Molecules 2016, 21(11), 1425; doi:10.3390/molecules21111425
Received: 29 September 2016 / Revised: 16 October 2016 / Accepted: 21 October 2016 / Published: 26 October 2016
Cited by 2 | PDF Full-text (885 KB) | HTML Full-text | XML Full-text
Abstract
The antioxidant properties of aged garlic extract (AGE) on cardiovascular functioning (CF) in metabolic syndrome (MS) remains poorly studied. Here we study the AGE effects on CF in a rat model of MS. Control rats plus saline solution (C + SS), MS rats
[...] Read more.
The antioxidant properties of aged garlic extract (AGE) on cardiovascular functioning (CF) in metabolic syndrome (MS) remains poorly studied. Here we study the AGE effects on CF in a rat model of MS. Control rats plus saline solution (C + SS), MS rats (30% sucrose in drinking water from weaning) plus saline solution (MS + SS), control rats receiving AGE (C + AGE 125 mg/Kg/12 h) and MS rats with AGE (MS + AGE) were studied. MS + SS had increased triglycerides, systolic blood pressure, insulin, leptin, HOMA index, and advanced glycation end products. AGE returned their levels to control values (p < 0.01). Cholesterol was decreased by AGE (p = 0.05). Glutathion and GPx activity were reduced in MS + SS rats and increased with AGE (p = 0.05). Lipid peroxidation was increased in MS + SS and AGE reduced it (p = 0.001). Vascular functioning was deteriorated by MS (increased vasocontraction and reduced vasodilation) and AGE improved it (p = 0.001). Coronary vascular resistance was increased in MS rats and AGE decreased it (p = 0.001). Cardiac performance was not modified by MS but AGE increased it. NO measured in the perfusate liquid from the heart and serum citrulline, nitrites/nitrates were decreased in MS and AGE increased them (p < 0.01). In conclusion, AGE reduces MS-induced cardiovascular risk, through its anti-oxidant properties. Full article
(This article belongs to the Special Issue The Chemistry of Alliums)
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Open AccessArticle Assessment of the Presence and Strength of H-Bonds by Means of Corrected NMR
Molecules 2016, 21(11), 1426; doi:10.3390/molecules21111426
Received: 23 September 2016 / Revised: 19 October 2016 / Accepted: 21 October 2016 / Published: 27 October 2016
Cited by 6 | PDF Full-text (1605 KB) | HTML Full-text | XML Full-text
Abstract
The downfield shift of the NMR signal of the bridging proton in a H-bond (HB) is composed of two elements. The formation of the HB causes charge transfer and polarization that lead to a deshielding. A second factor is the mere presence of
[...] Read more.
The downfield shift of the NMR signal of the bridging proton in a H-bond (HB) is composed of two elements. The formation of the HB causes charge transfer and polarization that lead to a deshielding. A second factor is the mere presence of the proton-accepting group, whose electron density and response to an external magnetic field induce effects at the position of the bridging proton, exclusive of any H-bonding phenomenon. This second positional shielding must be subtracted from the full observed shift in order to assess the deshielding of the proton caused purely by HB formation. This concept is applied to a number of H-bonded systems, both intramolecular and intermolecular. When the positional shielding is removed, the remaining chemical shift is in much better coincidence with other measures of HB strength. Full article
(This article belongs to the Special Issue Intramolecular Hydrogen Bonding 2017)
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Open AccessArticle Properties of Manganese(III) Ferrocenyl-β-Diketonato Complexes Revealed by Charge Transfer and Multiplet Splitting in the Mn 2p and Fe 2p X-Ray Photoelectron Envelopes
Molecules 2016, 21(11), 1427; doi:10.3390/molecules21111427
Received: 9 September 2016 / Revised: 14 October 2016 / Accepted: 19 October 2016 / Published: 26 October 2016
Cited by 5 | PDF Full-text (2540 KB) | HTML Full-text | XML Full-text
Abstract
A series of ferrocenyl-functionalized β-diketonato manganese(III) complexes, [Mn(FcCOCHCOR)3] with R = CF3, CH3, Ph (phenyl) and Fc (ferrocenyl) was subjected to a systematic XPS study of the Mn 2p3/2 and Fe 2p3/2 core-level photoelectron lines
[...] Read more.
A series of ferrocenyl-functionalized β-diketonato manganese(III) complexes, [Mn(FcCOCHCOR)3] with R = CF3, CH3, Ph (phenyl) and Fc (ferrocenyl) was subjected to a systematic XPS study of the Mn 2p3/2 and Fe 2p3/2 core-level photoelectron lines and their satellite structures. A charge-transfer process from the β-diketonato ligand to the Mn(III) metal center is responsible for the prominent shake-up satellite peaks of the Mn 2p photoelectron lines and the shake-down satellite peaks of the Fe 2p photoelectron lines. Multiplet splitting simulations of the photoelectron lines of the Mn(III) center of [Mn(FcCOCHCOR)3] resemble the calculated Mn 2p3/2 envelope of Mn3+ ions well, indicating the Mn(III) centers are in the high spin state. XPS spectra of complexes with unsymmetrical β-diketonato ligands (i.e., R not Fc) were described with two sets of multiplet splitting peaks representing fac and the more stable mer isomers respectively. Stronger electron-donating ligands stabilize fac more than mer isomers. The sum of group electronegativities, ΣχR, of the β-diketonato pendant side groups influences the binding energies of the multiplet splitting and charge transfer peaks in both Mn and Fe 2p3/2 photoelectron lines, the ratio of satellite to main peak intensities, and the degree of covalence of the Mn–O bond. Full article
(This article belongs to the Section Organometallic Chemistry)
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Open AccessArticle Molecular Mechanism of the Flavonoid Natural Product Dryocrassin ABBA against Staphylococcus aureus Sortase A
Molecules 2016, 21(11), 1428; doi:10.3390/molecules21111428
Received: 6 September 2016 / Revised: 14 October 2016 / Accepted: 23 October 2016 / Published: 26 October 2016
Cited by 1 | PDF Full-text (2534 KB) | HTML Full-text | XML Full-text
Abstract
The intractability of bacterial resistance presents a dilemma for therapies against Staphylococcus aureus (S. aureus) infection. Effective anti-virulence strategies are urgently needed, reflecting the proliferation of resistant strains. Inhibitors of sortase A (SrtA), enzymes that anchor virulence-related surface proteins, are regarded
[...] Read more.
The intractability of bacterial resistance presents a dilemma for therapies against Staphylococcus aureus (S. aureus) infection. Effective anti-virulence strategies are urgently needed, reflecting the proliferation of resistant strains. Inhibitors of sortase A (SrtA), enzymes that anchor virulence-related surface proteins, are regarded as promising candidates for countermeasures against bacterial infections. In the present study, the inhibitory effect of dryocrassin ABBA (ABBA) against SrtA and its molecular basis has been examined. Fluorescence resonance energy transfer (FRET) assays were used to determine the inhibitory activity of ABBA against SrtA. To identify the mechanism underlying this activity, molecular dynamics simulations and mutagenesis assays were applied, and the results revealed that the direct engagement of SrtA via ABBA through binding to V166 and V168 significantly attenuated the catalytic activity of SrtA. Taken together, these findings indicated that ABBA is a potential novel antimicrobial agent for S. aureus infection via targeting SrtA. Full article
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Open AccessArticle A Combined Molecular Cloning and Mass Spectrometric Method to Identify, Characterize, and Design Frenatin Peptides from the Skin Secretion of Litoria infrafrenata
Molecules 2016, 21(11), 1429; doi:10.3390/molecules21111429
Received: 10 September 2016 / Revised: 18 October 2016 / Accepted: 22 October 2016 / Published: 26 October 2016
Cited by 1 | PDF Full-text (3320 KB) | HTML Full-text | XML Full-text
Abstract
Amphibian skin secretions are unique sources of bioactive molecules, particularly bioactive peptides. In this study, the skin secretion of the white-lipped tree frog (Litoria infrafrenata) was obtained to identify peptides with putative therapeutic potential. By utilizing skin secretion-derived mRNA, a cDNA
[...] Read more.
Amphibian skin secretions are unique sources of bioactive molecules, particularly bioactive peptides. In this study, the skin secretion of the white-lipped tree frog (Litoria infrafrenata) was obtained to identify peptides with putative therapeutic potential. By utilizing skin secretion-derived mRNA, a cDNA library was constructed, a frenatin gene was cloned and its encoded peptides were deduced and confirmed using RP-HPLC, MALDI-TOF and MS/MS. The deduced peptides were identified as frenatin 4.1 (GFLEKLKTGAKDFASAFVNSIKGT) and a post-translationally modified peptide, frenatin 4.2 (GFLEKLKTGAKDFASAFVNSIK.NH2). Antimicrobial activity of the peptides was assessed by determining their minimal inhibitory concentrations (MICs) using standard model microorganisms. Through studying structure–activity relationships, analogues of the two peptides were designed, resulting in synthesis of frenatin 4.1a (GFLEKLKKGAKDFASALVNSIKGT) and frenatin 4.2a (GFLLKLKLGAKLFASAFVNSIK.NH2). Both analogues exhibited improved antimicrobial activities, especially frenatin 4.2a, which displayed significant enhancement of broad spectrum antimicrobial efficiency. The peptide modifications applied in this study, may provide new ideas for the generation of leads for the design of antimicrobial peptides with therapeutic applications. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Two New Stilbenoids from the Aerial Parts of Arundina graminifolia (Orchidaceae)
Molecules 2016, 21(11), 1430; doi:10.3390/molecules21111430
Received: 29 August 2016 / Revised: 21 October 2016 / Accepted: 23 October 2016 / Published: 27 October 2016
PDF Full-text (862 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new phenanthrene derivatives, a phenanthrenequinone named arundiquinone (1) and a 9,10-dihydrophenanthrene named arundigramin (2) together with a known lignin dimer (3) and seven known stilbenoids (410) were isolated from the aerial parts
[...] Read more.
Two new phenanthrene derivatives, a phenanthrenequinone named arundiquinone (1) and a 9,10-dihydrophenanthrene named arundigramin (2) together with a known lignin dimer (3) and seven known stilbenoids (410) were isolated from the aerial parts of the Asian orchid Arundina graminifolia. The structures of the isolated compounds were elucidated by spectroscopic methods, including extensive 1D, 2D NMR (heteronuclear single quantum coherence (HSQC), heteronuclear multiple-bond correlation spectroscopy (HMBC), and HR-ESI-MS techniques, as well as comparison with respective literature reports. The cytoprotective activity of the isolated compounds were evaluated for their ability to reduce beta amyloid induced toxicity on undifferentiated PC12 cells. Compound 8 showed moderate cytoprotective activity at 0.5 µmol/L (71% of cell viability) while the other compounds showed no significant activity at the highest concentration tested. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Comparative Transcriptomic Analysis of Grape Berry in Response to Root Restriction during Developmental Stages
Molecules 2016, 21(11), 1431; doi:10.3390/molecules21111431
Received: 13 September 2016 / Revised: 16 October 2016 / Accepted: 22 October 2016 / Published: 28 October 2016
Cited by 3 | PDF Full-text (1819 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Root restriction improved berry quality by being involved in diverse aspects of grapevine life. However, the molecular mechanism driving this process is not understood very well. In this study, the ‘Summer Black’ grape berry (Vitis vinifera × V. labrusca) under root
[...] Read more.
Root restriction improved berry quality by being involved in diverse aspects of grapevine life. However, the molecular mechanism driving this process is not understood very well. In this study, the ‘Summer Black’ grape berry (Vitis vinifera × V. labrusca) under root restriction was investigated, which showed an increase of total soluble solids (TSS), color index of red grapes (CIRG) value, anthocyanins accumulation, total phenolics and total procyanidins contents during berry development compared with those in control berries. The transcriptomic changes induced by root restriction in ‘Summer Black’ grape over the course of berry development were analyzed by RNA-Seq method. A total of 29,971 genes were generated in ‘Summer Black’ grape berry during development, among which, 1606 genes were significantly responded to root restriction. Furthermore, 1264, 313, 141, 246 and 19 sequences were significantly changed at S1, S2, S3, S4 and S5 sample points, respectively. The gene (VIT_04s0023g02290) predicted as a salicylate O-methyltransferase was differentially expressed in all developmental stages. Gene Ontology (GO) enrichment showed that response to organic nitrogen, response to endogenous stimulus, flavonoid metabolic process, phenylpropanoid biosynthetic process and cell wall macromolecule metabolic process were the main significant differential categories. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment revealed plant–pathogen interaction, plant hormone signal transduction, flavone and flavonol biosynthesis, flavonoid biosynthesis and glucosinolate biosynthesis were the main significant differential pathways. The results of the present study provided a genetic base for the understanding of grape berry fruit quality improvement under root restriction. Full article
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Open AccessArticle Alkaloids with Activity against the Zika Virus Vector Aedes aegypti (L.)—Crinsarnine and Sarniensinol, Two New Crinine and Mesembrine Type Alkaloids Isolated from the South African Plant Nerine sarniensis
Molecules 2016, 21(11), 1432; doi:10.3390/molecules21111432
Received: 19 September 2016 / Revised: 17 October 2016 / Accepted: 19 October 2016 / Published: 27 October 2016
Cited by 4 | PDF Full-text (798 KB) | HTML Full-text | XML Full-text
Abstract
Two new Amaryllidaceae alkaloids, belonging to the mesembrine- and crinine-types, named crinsarnine (1) and sarniensinol (2), were isolated from the dried bulbs of Nerine sarniensis together with bowdensine (3), sarniensine (4), hippadine (5)
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Two new Amaryllidaceae alkaloids, belonging to the mesembrine- and crinine-types, named crinsarnine (1) and sarniensinol (2), were isolated from the dried bulbs of Nerine sarniensis together with bowdensine (3), sarniensine (4), hippadine (5) and 1-O-acetyl-lycorine (6). Crinsarnine (1) and sarniensinol (2) were characterized using spectroscopic and chiroptical methods as (1S,2S,4aR,10bS)-2,7-dimethoxy-1,2,3,4,4a,6-hexahydro-5,11b-ethano[1,3]dioxolo-[4,5-j]phenanthridin-1-yl acetate and (6-(3aR,4Z,6S,7aS)-6-methoxy-1-methyl-2,3,3a,6,7,7a-hexa-hydro-1H-indol-3a-yl)benzo[d][1,3]dioxol-5-yl)methanol, respectively. Furthermore, the complete spectroscopic characterization of bowdensine (3) is reported for the first time. Compounds 16 were evaluated against the Orlando reference strain of Aedes aegypti. None of compounds showed mortality against 1st instar Ae. aegypti larvae at the concentrations tested. In adult topical bioassays, only 1 displayed adulticidal activity with an LD50 = 2.29 ± 0.049 μg/mosquito. As regards the structure-activity relationship, the pretazettine and crinine scaffold in 2 and 4 and in 1 and 3 respectively, proved to be important for their activity, while the pyrrole[de]phenanthridine scaffold present in 5 and 6 was important for their reactivity. Among the pretazettine group compounds, opening of the B ring or the presence of a B ring lactone as well as the trans-stereochemistry of the A/B ring junction, appears to be important for activity, while in crinine-type alkaloids, the substituent at C-2 seems to play a role in their activity. Full article
(This article belongs to the Special Issue Diversity of Alkaloids)
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Open AccessArticle Four New 2-(2-Phenylethyl)chromone Derivatives from Chinese Agarwood Produced via the Whole-Tree Agarwood-Inducing Technique
Molecules 2016, 21(11), 1433; doi:10.3390/molecules21111433
Received: 26 August 2016 / Revised: 2 October 2016 / Accepted: 22 October 2016 / Published: 27 October 2016
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Abstract
Four new 2-(2-phenylethyl)chromone derivatives (14) were isolated from the EtOH extract of Chinese agarwood produced via the whole-tree agarwood-inducing technique, coming from Aquilaria sinensis (Lour.) Spreng. (Thymelaeaceae). Their structures were elucidated by extensive spectroscopic methods, such as UV, IR,
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Four new 2-(2-phenylethyl)chromone derivatives (14) were isolated from the EtOH extract of Chinese agarwood produced via the whole-tree agarwood-inducing technique, coming from Aquilaria sinensis (Lour.) Spreng. (Thymelaeaceae). Their structures were elucidated by extensive spectroscopic methods, such as UV, IR, MS, 1D as well as 2D NMR. All of the isolates were then assessed for their anti-inflammatory activities on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7. Compound 1 exhibited significant inhibitory activity with an IC50 value of 4.6 μM. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle A Theoretical Study of the Relationship between the Electrophilicity ω Index and Hammett Constant σp in [3+2] Cycloaddition Reactions of Aryl Azide/Alkyne Derivatives
Molecules 2016, 21(11), 1434; doi:10.3390/molecules21111434
Received: 14 August 2016 / Revised: 14 October 2016 / Accepted: 21 October 2016 / Published: 27 October 2016
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Abstract
The relationship between the electrophilicity ω index and the Hammett constant σp has been studied for the [2+3] cycloaddition reactions of a series of para-substituted phenyl azides towards para-substituted phenyl alkynes. The electrophilicity ω index—a reactivity density functional theory (DFT)
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The relationship between the electrophilicity ω index and the Hammett constant σp has been studied for the [2+3] cycloaddition reactions of a series of para-substituted phenyl azides towards para-substituted phenyl alkynes. The electrophilicity ω index—a reactivity density functional theory (DFT) descriptor evaluated at the ground state of the molecules—shows a good linear relationship with the Hammett substituent constants σp. The theoretical scale of reactivity correctly explains the electrophilic activation/deactivation effects promoted by electron-withdrawing and electron-releasing substituents in both azide and alkyne components. Full article
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Open AccessArticle Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability
Molecules 2016, 21(11), 1435; doi:10.3390/molecules21111435
Received: 5 September 2016 / Revised: 25 October 2016 / Accepted: 25 October 2016 / Published: 28 October 2016
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Abstract
Metronidazole (MNZ) is an effective agent that has been employed to eradicate Helicobacter pylori (H. pylori). The emergence of broad MNZ resistance in H. pylori has affected the efficacy of this therapeutic agent. The concentration of MNZ, especially the mutant prevention
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Metronidazole (MNZ) is an effective agent that has been employed to eradicate Helicobacter pylori (H. pylori). The emergence of broad MNZ resistance in H. pylori has affected the efficacy of this therapeutic agent. The concentration of MNZ, especially the mutant prevention concentration (MPC), plays an important role in selecting or enriching resistant mutants and regulating therapeutic effects. A strategy to reduce the MPC that can not only effectively treat H. pylori but also prevent resistance mutations is needed. H. pylori is highly resistant to lysozyme. Lysozyme possesses a hydrolytic bacterial cell wall peptidoglycan and a cationic dependent mode. These effects can increase the permeability of bacterial cells and promote antibiotic absorption into bacterial cells. In this study, human lysozyme (hLYS) was used to probe its effects on the integrity of the H. pylori outer and inner membranes using as fluorescent probe hydrophobic 1-N-phenyl-naphthylamine (NPN) and the release of aspartate aminotransferase. Further studies using a propidium iodide staining method assessed whether hLYS could increase cell permeability and promote cell absorption. Finally, we determined the effects of hLYS on the bactericidal dynamics and MPC of MNZ in H. pylori. Our findings indicate that hLYS could dramatically increase cell permeability, reduce the MPC of MNZ for H. pylori, and enhance its bactericidal dynamic activity, demonstrating that hLYS could reduce the probability of MNZ inducing resistance mutations. Full article
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Open AccessArticle Penicitroamide, an Antimicrobial Metabolite with High Carbonylization from the Endophytic Fungus Penicillium sp. (NO. 24)
Molecules 2016, 21(11), 1438; doi:10.3390/molecules21111438
Received: 5 September 2016 / Revised: 21 October 2016 / Accepted: 25 October 2016 / Published: 28 October 2016
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Abstract
Penicitroamide (1), a new metabolite with a new framework, was isolated from the ethyl acetate extract of the PDB (Potato Dextrose Broth) medium of Penicillium sp. (NO. 24). The endophytic fungus Penicillium sp. (NO. 24) was obtained from the healthy leaves
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Penicitroamide (1), a new metabolite with a new framework, was isolated from the ethyl acetate extract of the PDB (Potato Dextrose Broth) medium of Penicillium sp. (NO. 24). The endophytic fungus Penicillium sp. (NO. 24) was obtained from the healthy leaves of Tapiscia sinensis Oliv. The structure of penicitroamide (1) features a bicyclo[3.2.1]octane core unit with a high degree of carbonylization (four carbonyl groups and one enol group). The chemical structure of penicitroamide (1) was elucidated by analysis of 1D-, 2D-NMR and MS data. In bioassays, penicitroamide (1) displayed antibacterial potency against two plant pathogens, Erwinia carotovora subsp. Carotovora (Jones) Bersey, et al. and Sclerotium rolfsii Sacc. with MIC50 at 45 and 50 μg/mL. Compound 1 also showed 60% lethality against brine shrimp at 10 μg/mL. Penicitroamide (1) exhibited no significant activity against A549, Caski, HepG2 and MCF-7 cells with IC50 > 50 μg/mL. Finally, the possible biosynthetic pathway of penicitroamide (1) was discussed. Full article
(This article belongs to the Special Issue Diversity of Alkaloids)
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Open AccessArticle Antioxidant Enzyme Activities and Lipid Oxidation in Rape (Brassica campestris L.) Bee Pollen Added to Salami during Processing
Molecules 2016, 21(11), 1439; doi:10.3390/molecules21111439
Received: 9 September 2016 / Revised: 21 October 2016 / Accepted: 25 October 2016 / Published: 28 October 2016
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Abstract
The present research investigated the antioxidant effect of rape (Brassica campestris L.) bee pollen (RBP) on salami during processing. Eight flavonoids in RBP ethanol extract were quantified by high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis, and quercetin, rutin, and kaempferol were the major
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The present research investigated the antioxidant effect of rape (Brassica campestris L.) bee pollen (RBP) on salami during processing. Eight flavonoids in RBP ethanol extract were quantified by high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis, and quercetin, rutin, and kaempferol were the major bioactive compounds. The RBP ethanol extract exhibited higher total antioxidant capacity than 6-hydroxy-2,5,7,8-tertramethylchromancarboxylic acid (trolox) at the same concentration. The salami with 0.05% RBP extract had higher catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities than that of the control throughout the processing time (p < 0.05). Significant decreases in peroxide value (POV) and thiobarbituric acid-reactive substances (TBARS) were obtained in the final salami product with 0.05% RBP ethanol extract or 1% RBP (p < 0.05). These results suggested that RBP could improve oxidative stability and had a good potential as a natural antioxidant for retarding lipid oxidation. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Screening Auxin Response, In Vitro Culture Aptitude and Susceptibility to Agrobacterium-Mediated Transformation of Italian Commercial Durum Wheat Varieties
Molecules 2016, 21(11), 1440; doi:10.3390/molecules21111440
Received: 4 August 2016 / Revised: 11 October 2016 / Accepted: 23 October 2016 / Published: 28 October 2016
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Abstract
The development of a robust Agrobacterium-mediated transformation protocol for a recalcitrant species like durum wheat requires the identification and optimization of factors affecting T-DNA delivery and plant regeneration. The purpose of this research was to compare the behavior of diverse durum wheat
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The development of a robust Agrobacterium-mediated transformation protocol for a recalcitrant species like durum wheat requires the identification and optimization of factors affecting T-DNA delivery and plant regeneration. The purpose of this research was to compare the behavior of diverse durum wheat genotypes during in vitro culture and Agrobacterium tumefaciens-mediated transformation, using immature embryos as explants. Apart from plant genotype, two of the main influencing factors for a successful genetic transformation have been examined here, i.e., auxin source (Dicamba and 2,4-D) and duration of the pre-culture period (one, seven and 21 days). The addition of Dicamba to the media in combination with seven days pre-cultivation resulted in a general enhancement of T-DNA delivery for most of the analyzed cultivars, as revealed by β-glucuronidase (GUS) histochemical assay. Although all genotypes were able to produce calli, significant differences were detected in regeneration and transformation efficiencies, since only two (Karalis and Neolatino) out of 14 cultivars produced fertile transgenic plants. The estimated transformation efficiencies were 6.25% and 1.66% for Karalis and Neolatino, respectively, and χ2 analysis revealed the stable integration and segregation of the gus transgene in T1 and T2 progenies. This research has demonstrated that, among the influencing factors, genotype and auxin type play the most important role in the success of durum wheat transformation. Full article
(This article belongs to the Section Natural Products)
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Open AccessCommunication In Vitro Antimicrobial Activity of Embothrium coccineum Used as Traditional Medicine in Patagonia against Multiresistant Bacteria
Molecules 2016, 21(11), 1441; doi:10.3390/molecules21111441
Received: 29 August 2016 / Revised: 24 October 2016 / Accepted: 25 October 2016 / Published: 31 October 2016
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Abstract
Embothrium coccineum J.R. Forst. & G. Forst is an evergreen tree that has been used as a folk remedy for the treatment of neuralgia, tooth pains, wound healing, and glandular conditions, as well as an antiseptic agent against bacterial infection. The antibacterial activities
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Embothrium coccineum J.R. Forst. & G. Forst is an evergreen tree that has been used as a folk remedy for the treatment of neuralgia, tooth pains, wound healing, and glandular conditions, as well as an antiseptic agent against bacterial infection. The antibacterial activities of sequential extracts (hexane, dichloromethane, ethyl acetate, and ethanol) from the leaves of E. coccineum were evaluated by means of the micro-dilution assay against six (Escherichia coli; Klebsiella pneumoniae; Proteus mirabilis; Pseudomonas aeruginosa; Staphylococcus aureus and Streptococcus pyogenes) multiresistant bacteria strains. Ethyl acetate extract showed the best spectra of antibacterial activity against all tested bacteria, and was analyzed by gas chromatography–mass spectrometry (GC-MS) for its composition. The results of the present work provide useful baseline information for the potential development and use of nanoparticles and/or nanofibers doped with extracts of E. coccineum in the fight against multiresistant bacteria, which would allow the validation of the traditional use of E. coccineum by native peoples of Patagonia as an antimicrobial agent in the biomedical Field. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Characterisation of the Broadly-Specific O-Methyl-transferase JerF from the Late Stages of Jerangolid Biosynthesis
Molecules 2016, 21(11), 1443; doi:10.3390/molecules21111443
Received: 4 October 2016 / Revised: 20 October 2016 / Accepted: 21 October 2016 / Published: 29 October 2016
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Abstract
We describe the characterisation of the O-methyltransferase JerF from the late stages of jerangolid biosynthesis. JerF is the first known example of an enzyme that catalyses the formation of a non-aromatic, cyclic methylenolether. The enzyme was overexpressed in E. coli and the
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We describe the characterisation of the O-methyltransferase JerF from the late stages of jerangolid biosynthesis. JerF is the first known example of an enzyme that catalyses the formation of a non-aromatic, cyclic methylenolether. The enzyme was overexpressed in E. coli and the cell-free extracts were used in bioconversion experiments. Chemical synthesis gave access to a series of substrate surrogates that covered a broad structural space. Enzymatic assays revealed a broad substrate tolerance and high regioselectivity of JerF, which makes it an attractive candidate for an application in chemoenzymatic synthesis with particular usefulness for late stage application on 4-methoxy-5,6-dihydro-2H-pyran-2-one-containing natural products. Full article
(This article belongs to the Special Issue Biosynthesis of Natural Products)
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Open AccessArticle Evidence of the Disassembly of α-Cyclodextrin-octylamine Inclusion Compounds Conjugated to Gold Nanoparticles via Thermal and Photothermal Effects
Molecules 2016, 21(11), 1444; doi:10.3390/molecules21111444
Received: 14 September 2016 / Revised: 14 October 2016 / Accepted: 19 October 2016 / Published: 29 October 2016
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Abstract
Cyclodextrin (CD) molecules form inclusion compounds (ICs), generating dimers that are capable of encapsulating molecules derived from long-chain hydrocarbons. The aim of this study is to evaluate the structural changes experienced by ICs in solution with increasing temperatures. For this, a nuclear magnetic
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Cyclodextrin (CD) molecules form inclusion compounds (ICs), generating dimers that are capable of encapsulating molecules derived from long-chain hydrocarbons. The aim of this study is to evaluate the structural changes experienced by ICs in solution with increasing temperatures. For this, a nuclear magnetic resonance (1H-NMR) titration was performed to determinate the stoichiometric α-cyclodextrin (α-CD):octylamine (OA) 2:1 and binding constant (k = 2.16 M−2) of ICs. Solution samples of α-CD-OA ICs conjugated with gold nanoparticles (AuNPs) were prepared, and 1H-NMR spectra at different temperatures were recorded. Comparatively, 1H-NMR spectra of the sample irradiated with a laser with tunable wavelengths, with plasmons of conjugated AuNPs, were recorded. In this work, we present evidence of the disassembly of ICs conjugated with AuNPs. Thermal studies demonstrated that, at 114 °C, there are reversible rearrangements of the host and guests in the ICs in a solid state. Migration movements of the guest molecules from the CD cavity were monitored via temperature-dependent 1H-NMR, and were verified comparing the chemical shifts of octylamine dissolved in deuterated dimethylsulfoxide (DMSO-d6) with the OA molecule included in α-CD dissolved in the same solvent. It was observed that, at 117 °C, OA exited the α-CD cavity. CD IC dimer disassembly was also observed when the sample was irradiated with green laser light. Full article
(This article belongs to the Special Issue Cyclodextrin Chemistry)
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Open AccessArticle The Effects of Pre-Fermentative Addition of Oenological Tannins on Wine Components and Sensorial Qualities of Red Wine
Molecules 2016, 21(11), 1445; doi:10.3390/molecules21111445
Received: 29 July 2016 / Revised: 21 October 2016 / Accepted: 22 October 2016 / Published: 31 October 2016
Cited by 2 | PDF Full-text (2051 KB) | HTML Full-text | XML Full-text
Abstract
Today in the wine industry, oenological tannins are widely used to improve wine quality and prevent oxidation in wine aging. With the development of tannin products, new oenological tannins are developed with many specific functions, such as modifying antioxidant effect, colour stabilization and
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Today in the wine industry, oenological tannins are widely used to improve wine quality and prevent oxidation in wine aging. With the development of tannin products, new oenological tannins are developed with many specific functions, such as modifying antioxidant effect, colour stabilization and aroma modifications. The aim of this work is to investigate effects of pre-fermentative addition of oenological tannins on wine colour, anthocyanins, volatile compounds and sensorial properties. In this case, Syrah juice was extracted with classic flash thermovinification from fresh must in order to release more colour and tannins. Three types of oenological tannins, which are, respectively, derived from grape skin, seed (Vitis vinifera) and French oak (Quercus robur and Querrus petraea), were selected to carry out the experiments with seven treatments. Results indicated that tannin treatments significantly improved wine aroma complexity and sensorial properties. However, the concentration of some stable pigments such as Vitisin A, Vitisin A-Ac and Vitisin B was negatively affected by tannin additions. Nevertheless, by means of cluster analysis and principal component analysis, it was observed that higher alcohols were significantly promoted by grape seed tannin while most anthocyanins can be improved by addition of grape tannins. In conclusion, low amount of oenological tannin derived from grape seed is a promising method to be applied especially for young red wine making. Full article
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Open AccessArticle Urinary Metabolomic Profiling in Zucker Diabetic Fatty Rats with Type 2 Diabetes Mellitus Treated with Glimepiride, Metformin, and Their Combination
Molecules 2016, 21(11), 1446; doi:10.3390/molecules21111446
Received: 13 September 2016 / Revised: 22 October 2016 / Accepted: 26 October 2016 / Published: 31 October 2016
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Abstract
Type 2 diabetes mellitus (T2DM) is a high incidence metabolic disease. Glimepiride, metformin, and their combination are the most commonly used therapeutics for T2DM in the clinic, but little is known about the metabolic responses of these therapies. In this study, ultrahigh-pressure liquid
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Type 2 diabetes mellitus (T2DM) is a high incidence metabolic disease. Glimepiride, metformin, and their combination are the most commonly used therapeutics for T2DM in the clinic, but little is known about the metabolic responses of these therapies. In this study, ultrahigh-pressure liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC/ESI-QTOF-MS)-based metabolomics was applied to detect changes in the urinary metabolomic profile of Zucker diabetic fatty (ZDF) rats in response to these treatments. Additionally, standard biochemical parameters (e.g., fasting plasma glucose, glycosylated hemoglobin, oral glucose tolerance, urinary glucose, triglyceride, total cholesterol, and insulin) and liver histopathology were monitored and observed. Six metabolites, including 3-galactosyl lactose, citric acid, sphingosine, phytosphingosine, ribothymidine, and succinoadenosine, were found significantly reverted to the normal level after these therapies. The present study is the first to present citric acid and sphinganine as the potential markers of T2DM, which could be used as indicators to observe the anti-diabetic effects of glimepiride, metformin, and their combination treatments. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle Synthesis and Biological Evaluation of Novel 4-Morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine Derivatives Bearing Phenylpyridine/ Phenylpyrimidine-Carboxamides
Molecules 2016, 21(11), 1447; doi:10.3390/molecules21111447
Received: 27 September 2016 / Revised: 24 October 2016 / Accepted: 26 October 2016 / Published: 31 October 2016
Cited by 1 | PDF Full-text (2255 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four series of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives 11aj, 12aj, 13ag and 14ag bearing phenylpyridine/phenylpyrimidine- carboxamide scaffolds were designed, synthesized and their IC50 values against three cancer cell lines (A549,
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Four series of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives 11aj, 12aj, 13ag and 14ag bearing phenylpyridine/phenylpyrimidine- carboxamide scaffolds were designed, synthesized and their IC50 values against three cancer cell lines (A549, PC-3 and MCF-7) were evaluated. Eleven of the compounds showed moderate cytotoxicity activity against the cancer cell lines. Structure-activity relationships (SARs) and pharmacological results indicated that the introduction of phenylpyridine-carboxamide scaffold was beneficial for the activity. What’s more, the oxidation of the sulfur atom in thiopyran and various types of substituents on the aryl group have different impacts on different series of compounds. Furthermore, the positions of aryl group substituents have a slight impact on the activity of the phenylpyridine-carboxamide series compounds. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Structural Characterization and Antimicrobial Activities of 7H-Benzo[h]chromeno[2,3-d]pyrimidine and 14H-Benzo[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c] pyrimidine Derivatives
Molecules 2016, 21(11), 1450; doi:10.3390/molecules21111450
Received: 30 September 2016 / Revised: 22 October 2016 / Accepted: 28 October 2016 / Published: 1 November 2016
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Abstract
Three new series of chromene molecules have been synthesized in order to explore their antimicrobial activity. The series encompass 2-substituted 14-(4-halophenyl)-12-methoxy-14H-benzo[h]chromeno[3,2-e][1,2,4]-triazolo[1,5-c]pyrimidines 7ao, 9-benzylideneamino-7-(4-halo-phenyl)-5-methoxy-8-imino-7H-benzo-[h]chromeno[2,3-d]pyrimidines 8ab
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Three new series of chromene molecules have been synthesized in order to explore their antimicrobial activity. The series encompass 2-substituted 14-(4-halophenyl)-12-methoxy-14H-benzo[h]chromeno[3,2-e][1,2,4]-triazolo[1,5-c]pyrimidines 7ao, 9-benzylideneamino-7-(4-halo-phenyl)-5-methoxy-8-imino-7H-benzo-[h]chromeno[2,3-d]pyrimidines 8ab and 3-ethoxycarbonyl-14-(4-halophenyl)-12-methoxy-14H-benzo-[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-one derivatives 12ab. The structure of these novel compounds were confirmed using IR, 1H- and 13C-NMR as well as MS spectroscopy. The new compounds were evaluated in vitro for their antimicrobial activity and it was demonstrated that 7H-benzochromenopyrimidine and derivatives of 14H-benzochromenotriazolopyrimidine exhibited the most promising antibacterial activities compared to the reference antimicrobial agents. The structure activity relationship (SAR) studies of the target compounds agreed with the in vitro essays and confirmed higher potent antimicrobial activity against some of the tested microorganisms. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessFeature PaperArticle Accumulation of Stable Full-Length Circular Group I Intron RNAs during Heat-Shock
Molecules 2016, 21(11), 1451; doi:10.3390/molecules21111451
Received: 20 September 2016 / Revised: 25 October 2016 / Accepted: 27 October 2016 / Published: 31 October 2016
Cited by 3 | PDF Full-text (3553 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Group I introns in nuclear ribosomal RNA of eukaryotic microorganisms are processed by splicing or circularization. The latter results in formation of full-length circular introns without ligation of the exons and has been proposed to be active in intron mobility. We applied qRT-PCR
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Group I introns in nuclear ribosomal RNA of eukaryotic microorganisms are processed by splicing or circularization. The latter results in formation of full-length circular introns without ligation of the exons and has been proposed to be active in intron mobility. We applied qRT-PCR to estimate the copy number of circular intron RNA from the myxomycete Didymium iridis. In exponentially growing amoebae, the circular introns are nuclear and found in 70 copies per cell. During heat-shock, the circular form is up-regulated to more than 500 copies per cell. The intron harbours two ribozymes that have the potential to linearize the circle. To understand the structural features that maintain circle integrity, we performed chemical and enzymatic probing of the splicing ribozyme combined with molecular modeling to arrive at models of the inactive circular form and its active linear counterpart. We show that the two forms have the same overall structure but differ in key parts, including the catalytic core element P7 and the junctions at which reactions take place. These differences explain the relative stability of the circular species, demonstrate how it is prone to react with a target molecule for circle integration and thus supports the notion that the circular form is a biologically significant molecule possibly with a role in intron mobility. Full article
(This article belongs to the Special Issue Ribozymes and RNA Catalysis)
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Open AccessArticle Anti-Inflammatory Potential of Ethyl Acetate Fraction of Moringa oleifera in Downregulating the NF-κB Signaling Pathway in Lipopolysaccharide-Stimulated Macrophages
Molecules 2016, 21(11), 1452; doi:10.3390/molecules21111452
Received: 29 August 2016 / Revised: 22 October 2016 / Accepted: 24 October 2016 / Published: 31 October 2016
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Abstract
In the present investigation, we prepared four different solvent fractions (chloroform, hexane, butanol, and ethyl acetate) of Moringa oleifera extract to evaluate its anti-inflammatory potential and cellular mechanism of action in lipopolysaccharide (LPS)-induced RAW264.7 cells. Cell cytotoxicity assay suggested that the solvent fractions
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In the present investigation, we prepared four different solvent fractions (chloroform, hexane, butanol, and ethyl acetate) of Moringa oleifera extract to evaluate its anti-inflammatory potential and cellular mechanism of action in lipopolysaccharide (LPS)-induced RAW264.7 cells. Cell cytotoxicity assay suggested that the solvent fractions were not cytotoxic to macrophages at concentrations up to 200 µg/mL. The ethyl acetate fraction suppressed LPS-induced production of nitric oxide and proinflammatory cytokines in macrophages in a concentration-dependent manner and was more effective than the other fractions. Immunoblot observations revealed that the ethyl acetate fraction effectively inhibited the expression of inflammatory mediators including cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor (NF)-κB p65 through suppression of the NF-κB signaling pathway. Furthermore, it upregulated the expression of the inhibitor of κB (IκBα) and blocked the nuclear translocation of NF-κB. These findings indicated that the ethyl acetate fraction of M. oleifera exhibited potent anti-inflammatory activity in LPS-stimulated macrophages via suppression of the NF-κB signaling pathway. Full article
(This article belongs to the Special Issue Natural Products and Chronic Diseases)
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Open AccessArticle Biotransformation of Bicyclic Halolactones with a Methyl Group in the Cyclohexane Ring into Hydroxylactones and Their Biological Activity
Molecules 2016, 21(11), 1453; doi:10.3390/molecules21111453
Received: 15 September 2016 / Revised: 23 October 2016 / Accepted: 28 October 2016 / Published: 31 October 2016
Cited by 1 | PDF Full-text (3299 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The aim of this study was the chemical synthesis of a series of halo- and unsaturated lactones, as well as their microbial transformation products. Finally some of their biological activities were assessed. Three bicyclic halolactones with a methyl group in the cyclohexane ring
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The aim of this study was the chemical synthesis of a series of halo- and unsaturated lactones, as well as their microbial transformation products. Finally some of their biological activities were assessed. Three bicyclic halolactones with a methyl group in the cyclohexane ring were obtained from the corresponding γ,δ-unsaturated ester during a two-step synthesis. These lactones were subjected to screening biotransformation using twenty two fungal strains. These strains were tested on their ability to transform halolactones into new hydroxylactones. Among the six strains able to catalyze hydrolytic dehalogenation, only two (Fusarium equiseti, AM22 and Yarrowia lipolytica, AM71) gave a product in a high yield. Moreover, one strain (Penicillium wermiculatum, AM30) introduced the hydroxy group on the cyclohexane ring without removing the halogen atom. The biological activity of five of the obtained lactones was tested. Some of these compounds exhibited growth inhibition against bacteria, yeasts and fungi and deterrent activity against peach-potato aphid. Full article
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Open AccessArticle Synthesis and In Vitro Antiproliferative Activity of Novel Phenyl Ring-Substituted 5-Alkyl-12(H)-quino[3,4-b][1,4]benzothiazine Derivatives
Molecules 2016, 21(11), 1455; doi:10.3390/molecules21111455
Received: 5 October 2016 / Revised: 20 October 2016 / Accepted: 24 October 2016 / Published: 4 November 2016
Cited by 1 | PDF Full-text (2344 KB) | HTML Full-text | XML Full-text
Abstract
A novel series of tetracyclic quinobenzothiazine derivatives was synthetized. Compounds containing a substituent (hydroxyl, methyl, phenyl, piperidyl, or piperazinyl) in positions 9 and 11 were obtained by cyclization of suitable 4-aminoquinolinium-3-thiolates. Quinobenzothiazine 10-O-substituted derivatives were obtained by alkylating the hydroxyl group
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A novel series of tetracyclic quinobenzothiazine derivatives was synthetized. Compounds containing a substituent (hydroxyl, methyl, phenyl, piperidyl, or piperazinyl) in positions 9 and 11 were obtained by cyclization of suitable 4-aminoquinolinium-3-thiolates. Quinobenzothiazine 10-O-substituted derivatives were obtained by alkylating the hydroxyl group in position 10 of the parent (quinobenzothiazine) system. Antiproliferative activity of the synthesized compounds was studied using cultured neoplastic cells (MDA-MB-231, SNB-19, and C-32 cell lines). Four selected compounds were investigated in more detail for cytotoxicity and antiproliferative effect. Transcriptional activity of genes regulating cell cycle (TP53), apoptosis (BAX, BCL-2), as well as proliferation (H3) were assessed. Finally, the ability of the selected compounds to bind DNA was checked in the presence of ethidium bromide. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Heat-Killed Lactobacillus salivarius and Lactobacillus johnsonii Reduce Liver Injury Induced by Alcohol In Vitro and In Vivo
Molecules 2016, 21(11), 1456; doi:10.3390/molecules21111456
Received: 20 September 2016 / Revised: 26 October 2016 / Accepted: 27 October 2016 / Published: 31 October 2016
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Abstract
The aim of the present study was to determine whether Lactobacillus salivarius (LS) and Lactobacillus johnsonii (LJ) prevent alcoholic liver damage in HepG2 cells and rat models of acute alcohol exposure. In this study, heat-killed LS and LJ were screened from 50 Lactobacillus
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The aim of the present study was to determine whether Lactobacillus salivarius (LS) and Lactobacillus johnsonii (LJ) prevent alcoholic liver damage in HepG2 cells and rat models of acute alcohol exposure. In this study, heat-killed LS and LJ were screened from 50 Lactobacillus strains induced by 100 mM alcohol in HepG2 cells. The severity of alcoholic liver injury was determined by measuring the levels of aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (γ-GT), lipid peroxidation, triglyceride (TG) and total cholesterol. Our results indicated that heat-killed LS and LJ reduced AST, ALT, γ-GT and malondialdehyde (MDA) levels and outperformed other bacterial strains in cell line studies. We further evaluated these findings by administering these strains to rats. Only LS was able to reduce serum AST levels, which it did by 26.2%. In addition LS significantly inhibited serum TG levels by 39.2%. However, both strains were unable to inhibit ALT levels. In summary, we demonstrated that heat-killed LS and LJ possess hepatoprotective properties induced by alcohol both in vitro and in vivo. Full article
(This article belongs to the Special Issue Natural Products and Chronic Diseases)
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Open AccessArticle Mono-PEGylation of Alpha-MMC and MAP30 from Momordica charantia L.: Production, Identification and Anti-Tumor Activity
Molecules 2016, 21(11), 1457; doi:10.3390/molecules21111457
Received: 20 September 2016 / Revised: 29 October 2016 / Accepted: 29 October 2016 / Published: 31 October 2016
Cited by 2 | PDF Full-text (2638 KB) | HTML Full-text | XML Full-text
Abstract
PEGylation is a well-established and effective strategy to decrease immunogenicity, which can increase the stability and in vivo half-life time. However, the generation of multi-site modified products is inevitable due to the lysine chemistry, which will bring difficulties in subsequent research, such as
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PEGylation is a well-established and effective strategy to decrease immunogenicity, which can increase the stability and in vivo half-life time. However, the generation of multi-site modified products is inevitable due to the lysine chemistry, which will bring difficulties in subsequent research, such as purification and quantification. Site-specific modification by mPEG-succinimidyl carbonate (mPEG-SC) is a widely used method for N-terminal conjugation. In this study, we used it for site-directed modification on two ribosome-inactivating proteins (RIPs), alpha-momorcharin (α-MMC) and momordica anti-HIV protein (MAP30), from Momordica charantia L. According to the optimization of previous modification conditions, we compared Macro-Cap SP with SP-Sepharose FF chromatography for separating the final mPEGylated RIPs. Two kinds of methods both can obtain homogenous mPEGylated RIPs which were identified by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing electrophoresis (IEF), and matrix-assisted laser desorption ionization-time of flight/time of flight (MALDI-TOF/TOF) analysis. We also used iodine staining method to detect the amount of unmodified PEG. Furthermore, the inhibition activity of both mPEGylated and non-PEGylated RIPs against human lung adenocarcinoma epithelial A549 cells was detected. All of the results suggested that the mPEGylated α-MMC/MAP30 might be potentially developed as new anti-tumor drugs. Full article
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Open AccessArticle Developing HIV-1 Protease Inhibitors through Stereospecific Reactions in Protein Crystals
Molecules 2016, 21(11), 1458; doi:10.3390/molecules21111458
Received: 26 September 2016 / Revised: 26 October 2016 / Accepted: 26 October 2016 / Published: 31 October 2016
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Abstract
Protease inhibitors are key components in the chemotherapy of HIV infection. However, the appearance of viral mutants routinely compromises their clinical efficacy, creating a constant need for new and more potent inhibitors. Recently, a new class of epoxide-based inhibitors of HIV-1 protease was
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Protease inhibitors are key components in the chemotherapy of HIV infection. However, the appearance of viral mutants routinely compromises their clinical efficacy, creating a constant need for new and more potent inhibitors. Recently, a new class of epoxide-based inhibitors of HIV-1 protease was investigated and the configuration of the epoxide carbons was demonstrated to play a crucial role in determining the binding affinity. Here we report the comparison between three crystal structures at near-atomic resolution of HIV-1 protease in complex with the epoxide-based inhibitor, revealing an in-situ epoxide ring opening triggered by a pH change in the mother solution of the crystal. Increased pH in the crystal allows a stereospecific nucleophile attack of an ammonia molecule onto an epoxide carbon, with formation of a new inhibitor containing amino-alcohol functions. The described experiments open a pathway for the development of new stereospecific protease inhibitors from a reactive lead compound. Full article
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Open AccessArticle Phylogenetic and Diversity Analysis of Dactylis glomerata Subspecies Using SSR and IT-ISJ Markers
Molecules 2016, 21(11), 1459; doi:10.3390/molecules21111459
Received: 31 August 2016 / Revised: 13 October 2016 / Accepted: 26 October 2016 / Published: 31 October 2016
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Abstract
The genus Dactylis, an important forage crop, has a wide geographical distribution in temperate regions. While this genus is thought to include a single species, Dactylis glomerata, this species encompasses many subspecies whose relationships have not been fully characterized. In this
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The genus Dactylis, an important forage crop, has a wide geographical distribution in temperate regions. While this genus is thought to include a single species, Dactylis glomerata, this species encompasses many subspecies whose relationships have not been fully characterized. In this study, the genetic diversity and phylogenetic relationships of nine representative Dactylis subspecies were examined using SSR and IT-ISJ markers. In total, 21 pairs of SSR primers and 15 pairs of IT-ISJ primers were used to amplify 295 polymorphic bands with polymorphic rates of 100%. The average polymorphic information contents (PICs) of SSR and IT-ISJ markers were 0.909 and 0.780, respectively. The combined data of the two markers indicated a high level of genetic diversity among the nine D. glomerata subspecies, with a Nei’s gene diversity index value of 0.283 and Shannon’s diversity of 0.448. Preliminarily phylogenetic analysis results revealed that the 20 accessions could be divided into three groups (A, B, C). Furthermore, they could be divided into five clusters, which is similar to the structure analysis with K = 5. Phylogenetic placement in these three groups may be related to the distribution ranges and the climate types of the subspecies in each group. Group A contained eight accessions of four subspecies, originating from the west Mediterranean, while Group B contained seven accessions of three subspecies, originating from the east Mediterranean. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Red Light Activation of Ru(II) Polypyridyl Prodrugs via Triplet-Triplet Annihilation Upconversion: Feasibility in Air and through Meat
Molecules 2016, 21(11), 1460; doi:10.3390/molecules21111460
Received: 5 October 2016 / Revised: 24 October 2016 / Accepted: 26 October 2016 / Published: 1 November 2016
Cited by 2 | PDF Full-text (3669 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Triplet-triplet annihilation upconversion (TTA-UC) is a promising photophysical tool to shift the activation wavelength of photopharmacological compounds to the red or near-infrared wavelength domain, in which light penetrates human tissue optimally. However, TTA-UC is sensitive to dioxygen, which quenches the triplet states needed
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Triplet-triplet annihilation upconversion (TTA-UC) is a promising photophysical tool to shift the activation wavelength of photopharmacological compounds to the red or near-infrared wavelength domain, in which light penetrates human tissue optimally. However, TTA-UC is sensitive to dioxygen, which quenches the triplet states needed for upconversion. Here, we demonstrate not only that the sensitivity of TTA-UC liposomes to dioxygen can be circumvented by adding antioxidants, but also that this strategy is compatible with the activation of ruthenium-based chemotherapeutic compounds. First, red-to-blue upconverting liposomes were functionalized with a blue-light sensitive, membrane-anchored ruthenium polypyridyl complex, and put in solution in presence of a cocktail of antioxidants composed of ascorbic acid and glutathione. Upon red light irradiation with a medical grade 630 nm PDT laser, enough blue light was produced by TTA-UC liposomes under air to efficiently trigger full activation of the Ru-based prodrug. Then, the blue light generated by TTA-UC liposomes under red light irradiation (630 nm, 0.57 W/cm2) through different thicknesses of pork or chicken meat was measured, showing that TTA-UC still occurred even beyond 10 mm of biological tissue. Overall, the rate of activation of the ruthenium compound in TTA-UC liposomes using either blue or red light (1.6 W/cm2) through 7 mm of pork fillet were found comparable, but the blue light caused significant tissue damage, whereas red light did not. Finally, full activation of the ruthenium prodrug in TTA-UC liposomes was obtained under red light irradiation through 7 mm of pork fillet, thereby underlining the in vivo applicability of the activation-by-upconversion strategy. Full article
(This article belongs to the Special Issue Photoresponsive Drugs)
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Open AccessArticle Chemical Constituents of Muehlenbeckia tamnifolia (Kunth) Meisn (Polygonaceae) and Its In Vitro α-Amilase and α-Glucosidase Inhibitory Activities
Molecules 2016, 21(11), 1461; doi:10.3390/molecules21111461
Received: 13 September 2016 / Revised: 26 October 2016 / Accepted: 28 October 2016 / Published: 2 November 2016
Cited by 2 | PDF Full-text (380 KB) | HTML Full-text | XML Full-text
Abstract
The phytochemical investigation of Muehlenbeckia tamnifolia, collected in Loja-Ecuador, led to the isolation of nine known compounds identified as: lupeol acetate (1); cis-p-coumaric acid (2); lupeol (3); β-sitosterol (4) trans-
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The phytochemical investigation of Muehlenbeckia tamnifolia, collected in Loja-Ecuador, led to the isolation of nine known compounds identified as: lupeol acetate (1); cis-p-coumaric acid (2); lupeol (3); β-sitosterol (4) trans-p-coumaric acid (5); linoleic acid (6) (+)-catechin (7); afzelin (8) and quercitrin (9). The structures of the isolated compounds were determined based on analysis of NMR and MS data, as well as comparison with the literature. The hypoglycemic activity of crude extracts and isolated compounds was assessed by the ability to inhibit α-amylase and α-glucosidase enzymes. The hexane extract showed weak inhibitory activity on α-amylase, with an IC50 value of 625 µg·mL−1, while the other extracts and isolated compounds were inactive at the maximum dose tested. The results on α-glucosidase showed more favorable effects; the hexanic and methanolic extracts exhibited a strong inhibitory activity with IC50 values of 48.22 µg·mL−1 and 19.22 µg·mL−1, respectively. Four of the nine isolated compounds exhibited strong inhibitory activity with IC50 values below 8 µM, much higher than acarbose (377 uM). Linoleic acid was the most potent compound (IC50 = 0.42 µM) followed by afzelin, (+)-catechin and quercitrin. Full article
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Open AccessArticle Novel Selective and Potent EGFR Inhibitor that Overcomes T790M-Mediated Resistance in Non-Small Cell Lung Cancer
Molecules 2016, 21(11), 1462; doi:10.3390/molecules21111462
Received: 30 September 2016 / Revised: 26 October 2016 / Accepted: 29 October 2016 / Published: 2 November 2016
Cited by 2 | PDF Full-text (5564 KB) | HTML Full-text | XML Full-text
Abstract
Treating patients suffering from EGFR mutant non-small cell lung cancer (NSCLC) with first-generation EGFR tyrosine kinase inhibitors (EGFR TKI) provides excellent response rates. However, approximately 60% of all patients ultimately develop drug resistance due to a second T790M EGFR TKI mutation. In this
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Treating patients suffering from EGFR mutant non-small cell lung cancer (NSCLC) with first-generation EGFR tyrosine kinase inhibitors (EGFR TKI) provides excellent response rates. However, approximately 60% of all patients ultimately develop drug resistance due to a second T790M EGFR TKI mutation. In this study, we report the novel molecule N-(3-((5-chloro-2-(4-((1-morpholino)methyl)phenylamino)-4-pyrimidinyl)amino)phenyl)acrylamide (DY3002) to preferentially inhibit the EGFR T790M mutant (EGFRT790M) (IC50 = 0.71 nM) over wild-type EGFR (IC50 = 448.7 nM) in kinase assays. Compared to rociletinib (SI = 21.4) and osimertinib (SI = 40.9), it significantly increased selectivity (SI = 632.0) against EGFRT790M over wild-type EGFR. Furthermore, in cell-based tests, DY3002, with an IC50 value of 0.037 μM, exhibited enhanced inhibitory potency against H1975 cells. Moreover, AO/EB and DAPI staining assays as well as flow cytometer analyses indicated that DY3002 possesses superior biological properties compared to alternatives. In addition, a rat oral glucose tolerance test revealed that treatment with high drug doses (50 mg/kg) of DY3002 did not result in hyperglycemia, suggesting a reduction of side effects in NSCLC patients will be achievable relative to established EGFR inhibitors. In summary, our findings indicate DY3002 as a promising preclinical candidate for effective treatment of patients with EGFRT790M-mutated NSCLC. Full article
(This article belongs to the Special Issue Kinase Inhibitor Chemistry)
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Open AccessArticle LC-MS/MS Validation Analysis of Trastuzumab Using dSIL Approach for Evaluating Pharmacokinetics
Molecules 2016, 21(11), 1464; doi:10.3390/molecules21111464
Received: 29 August 2016 / Revised: 25 October 2016 / Accepted: 26 October 2016 / Published: 2 November 2016
Cited by 1 | PDF Full-text (205 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Quantitative targeted proteomics based approaches deploy state-of-the-art Liquid chromatography tandem mass spectrometry LC-MS technologies and are evolving as a complementary technique to standard ligand-binding based assays. Advancements in MS technology, which have augmented the specificity, selectivity and sensitivity limits of detection and freedom
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Quantitative targeted proteomics based approaches deploy state-of-the-art Liquid chromatography tandem mass spectrometry LC-MS technologies and are evolving as a complementary technique to standard ligand-binding based assays. Advancements in MS technology, which have augmented the specificity, selectivity and sensitivity limits of detection and freedom from antibody generation, have made it amicable towards various clinical applications. In our current work, a surrogate peptide based quantitative proteomics assessment is performed by selecting specific signature peptides from the complementary determining region CDR region of trastuzumab (Herclon®, Roche products in India). We developed a double Stable Isotope Label (dSIL) approach by using two different surrogate peptides to evaluate the proteolytic digestion efficiency and accurate quantification of the target analyte peptide of Herclon® in human serum. Method validation experiments were meticulously performed as per bioanalytical method validation guidelines. The dSIL approach, using an LC-MS/MS based quantification assay demonstrated good linearity over a range of 5–500 µg/mL of Herclon®, and validation experimental data is in compliance with bioanalytical regulatory guidelines. Full article
Open AccessArticle Cytotoxic, Antitumor and Immunomodulatory Effects of the Water-Soluble Polysaccharides from Lotus (Nelumbo nucifera Gaertn.) Seeds
Molecules 2016, 21(11), 1465; doi:10.3390/molecules21111465
Received: 10 October 2016 / Revised: 25 October 2016 / Accepted: 28 October 2016 / Published: 2 November 2016
Cited by 3 | PDF Full-text (4601 KB) | HTML Full-text | XML Full-text
Abstract
Lotus is an edible and medicinal plant, and the extracts from its different parts exhibit various bioactivities. In the present study, the hot water–soluble polysaccharides from lotus seeds (LSPS) were evaluated for their cancer cell cytotoxicity, immunomodulatory and antitumor activities. LSPS showed significant
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Lotus is an edible and medicinal plant, and the extracts from its different parts exhibit various bioactivities. In the present study, the hot water–soluble polysaccharides from lotus seeds (LSPS) were evaluated for their cancer cell cytotoxicity, immunomodulatory and antitumor activities. LSPS showed significant inhibitory effects on the mouse gastric cancer MFC cells, human liver cancer HuH-7 cells and mouse hepatocarcinoma H22 cells. The animal studies showed that LSPS inhibited tumor growth in H22 tumor-bearing mice with the highest inhibition rate of 45.36%, which is comparable to that induced by cyclophosphamide (30 mg/kg) treatment (50.79%). The concentrations of white blood cells were significantly reduced in cyclophosphamide-treated groups (p < 0.01), while LSPS showed much fewer side effects according to the hematology analysis. LSPS improved the immune response in H22 tumor-bearing mice by enhancing the spleen and thymus indexes, and increasing the levels of serum cytokines including tumor necrosis factor-α and interleukin-2. Moreover, LSPS also showed in vivo antioxidant activity by increasing superoxide dismutase activity, thus reducing the malondialdehyde level in the liver tissue. These results suggested that LSPS can be used as an antitumor and immunomodulatory agent. Full article
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Open AccessArticle Application of Homochiral Alkylated Organic Cages as Chiral Stationary Phases for Molecular Separations by Capillary Gas Chromatography
Molecules 2016, 21(11), 1466; doi:10.3390/molecules21111466
Received: 16 September 2016 / Revised: 22 October 2016 / Accepted: 28 October 2016 / Published: 8 November 2016
Cited by 2 | PDF Full-text (2578 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Molecular organic cage compounds have attracted considerable attention due to their potential applications in gas storage, catalysis, chemical sensing, molecular separations, etc. In this study, a homochiral pentyl cage compound was synthesized from a condensation reaction of (S,S)-1,2-pentyl-1,2-diaminoethane and
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Molecular organic cage compounds have attracted considerable attention due to their potential applications in gas storage, catalysis, chemical sensing, molecular separations, etc. In this study, a homochiral pentyl cage compound was synthesized from a condensation reaction of (S,S)-1,2-pentyl-1,2-diaminoethane and 1,3,5-triformylbenzene. The imine-linked pentyl cage diluted with a polysiloxane (OV-1701) was explored as a novel stationary phase for high-resolution gas chromatographic separation of organic compounds. Some positional isomers were baseline separated on the pentyl cage-coated capillary column. In particular, various types of enantiomers including chiral alcohols, esters, ethers and epoxides can be resolved without derivatization on the pentyl cage-coated capillary column. The reproducibility of the pentyl cage-coated capillary column for separation was investigated using nitrochlorobenzene and styrene oxide as analytes. The results indicate that the column has good stability and separation reproducibility after being repeatedly used. This work demonstrates that molecular organic cage compounds could become a novel class of chiral separation media in the near future. Full article
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Open AccessCommunication Preparation of Cu@Cu2O Nanocatalysts by Reduction of HKUST-1 for Oxidation Reaction of Catechol
Molecules 2016, 21(11), 1467; doi:10.3390/molecules21111467
Received: 30 August 2016 / Revised: 25 October 2016 / Accepted: 26 October 2016 / Published: 2 November 2016
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Abstract
HKUST-1, a copper-based metal organic framework (MOF), has been investigated as a catalyst in various reactions. However, the HKUST-1 shows low catalytic activity in the oxidation of catechol. Therefore, we synthesized Fe3O4@HKUST-1 by layer-by layer assembly strategy and Cu@Cu
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HKUST-1, a copper-based metal organic framework (MOF), has been investigated as a catalyst in various reactions. However, the HKUST-1 shows low catalytic activity in the oxidation of catechol. Therefore, we synthesized Fe3O4@HKUST-1 by layer-by layer assembly strategy and Cu@Cu2O by reduction of HKUST-1 for enhancement of catalytic activity. Cu@Cu2O nanoparticles exhibited highly effective catalytic activity in oxidation of 3,5-di-tert-butylcatechol. Through this method, MOF can maintain the original core-shell structure and be used in various other reactions with enhanced catalytic activity. Full article
(This article belongs to the Special Issue Metal Nanocatalysts in Green Synthesis and Energy Applications)
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Open AccessArticle Bauhinia championii Flavone Attenuates Hypoxia-Reoxygenation Induced Apoptosis in H9c2 Cardiomyocytes by Improving Mitochondrial Dysfunction
Molecules 2016, 21(11), 1469; doi:10.3390/molecules21111469
Received: 7 September 2016 / Revised: 22 October 2016 / Accepted: 31 October 2016 / Published: 4 November 2016
Cited by 2 | PDF Full-text (7376 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This study aimed to determine the effects of Bauhinia championii flavone (BCF) on hypoxia-reoxygenation (H/R) induced apoptosis in H9c2 cardiomyocytes and to explore potential mechanisms. The H/R model in H9c2 cardiomyocytes was established by 6 h of hypoxia and 12 h of reoxygenation.
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This study aimed to determine the effects of Bauhinia championii flavone (BCF) on hypoxia-reoxygenation (H/R) induced apoptosis in H9c2 cardiomyocytes and to explore potential mechanisms. The H/R model in H9c2 cardiomyocytes was established by 6 h of hypoxia and 12 h of reoxygenation. Cell viability was detected by CCK-8 assay. Apoptotic rate was measured by Annexin V/PI staining. Levels of mitochondria-associated ROS, mitochondrial transmembrane potential (∆Ψm) and mitochondrial permeability transition pores (MPTP) opening were assessed by fluorescent probes. ATP production was measured by ATP assay kit. The release of cytochrome c, translocation of Bax, and related proteins were measured by western blotting. Our results showed that pretreatment with BCF significantly improved cell viability and attenuated the cardiomyocyte apoptosis caused by H/R. Furthermore, BCF increased ATP production and inhibited ROS-generating mitochondria, depolarization of ΔΨm, and MPTP opening. Moreover, BCF pretreatment decreased Bax mitochondrial translocation, cytochrome c release, and activation of caspase-3, as well as increased the expression of p-PI3K, p-Akt, and the ratio of Bcl-2 to Bax. Interestingly, a specific inhibitor of phosphatidylinositol 3-kinase, LY294002, partly reversed the anti-apoptotic effect of BCF. These observations indicated that BCF pretreatment attenuates H/R-induced myocardial apoptosis strength by improving mitochondrial dysfunction via PI3K/Akt signaling pathway. Full article
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Open AccessArticle In Vitro Photodynamic Effect of Phycocyanin against Breast Cancer Cells
Molecules 2016, 21(11), 1470; doi:10.3390/molecules21111470
Received: 29 September 2016 / Accepted: 1 October 2016 / Published: 3 November 2016
Cited by 2 | PDF Full-text (5416 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
C-phycocyanin, a natural blue-colored pigment-protein complex was explored as a novel photosensitizer for use in low-level laser therapy under 625-nm laser illumination. C-phycocyanin produced singlet oxygen radicals and the level of reactive oxygen species (ROS) were raised in extended time of treatment. It
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C-phycocyanin, a natural blue-colored pigment-protein complex was explored as a novel photosensitizer for use in low-level laser therapy under 625-nm laser illumination. C-phycocyanin produced singlet oxygen radicals and the level of reactive oxygen species (ROS) were raised in extended time of treatment. It did not exhibit any visible toxic effect in the absence of light. Under 625-nm laser irradiation, c-phycocyanin generated cytotoxic stress through ROS induction, which killed MDA-MB-231 breast cancer cells depending on concentrations. Different fluorescent staining of laser-treated cells explored apoptotic cell death characteristics like the shrinking of cells, cytoplasmic condensation, nuclei cleavage, and the formation of apoptotic bodies. In conclusion, phycocyanin is a non-toxic fluorescent pigment that can be used in low-level light therapy. Full article
(This article belongs to the Special Issue Photodynamic Therapy)
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Open AccessArticle Rapid Screening and Identification of BSA Bound Ligands from Radix astragali Using BSA Immobilized Magnetic Nanoparticles Coupled with HPLC-MS
Molecules 2016, 21(11), 1471; doi:10.3390/molecules21111471
Received: 27 September 2016 / Revised: 31 October 2016 / Accepted: 1 November 2016 / Published: 5 November 2016
Cited by 3 | PDF Full-text (9323 KB) | HTML Full-text | XML Full-text
Abstract
Radix astragali is widely used either as a single herb or as a collection of herbs in a complex prescription in China. In this study, bovine serum albumin functionalized magnetic nanoparticles (BSA-MN) coupled with high performance liquid chromatography-mass spectrometry (HPLC-MS) were used to
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Radix astragali is widely used either as a single herb or as a collection of herbs in a complex prescription in China. In this study, bovine serum albumin functionalized magnetic nanoparticles (BSA-MN) coupled with high performance liquid chromatography-mass spectrometry (HPLC-MS) were used to screen and identify bound ligands from the n-butanol part of a Radix astragali extract. The prepared BSA-MN showed sufficient magnetic response for the separation with an ordinary magnet and satisfied reusability. Fundamental parameters affecting the preparation of BSA-MN and the screening efficiency were studied and optimized. Under the optimum conditions, four bound ligands were screened out from the n-butanol part of a Radix astragali extract and identified as genistin (1), calycosin-7-O-β-d-glucoside (2), ononin (3) and formononetin (4). This effective method could be widely applied for rapid screening and identification of active compounds from complex mixtures without the need for preparative isolation. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Practical and Metal-Free Synthesis of Novel Enantiopure Amides Containing the Potentially Bioactive 5-Nitroimidazole Moiety
Molecules 2016, 21(11), 1472; doi:10.3390/molecules21111472
Received: 30 September 2016 / Revised: 26 October 2016 / Accepted: 28 October 2016 / Published: 4 November 2016
Cited by 1 | PDF Full-text (1077 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We report here a practical and metal-free synthesis of novel enantiopure amides containing the drug-like 5-nitroimidazole scaffold. The first step was a metal-free diastereoselective addition of 4-(4-(chloromethyl)phenyl)-1,2-dimethyl-5-nitro-1H-imidazole to enantiomerically pure N-tert-butanesulfinimine. Then, the N-tert-butanesulfinyl–protected amine
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We report here a practical and metal-free synthesis of novel enantiopure amides containing the drug-like 5-nitroimidazole scaffold. The first step was a metal-free diastereoselective addition of 4-(4-(chloromethyl)phenyl)-1,2-dimethyl-5-nitro-1H-imidazole to enantiomerically pure N-tert-butanesulfinimine. Then, the N-tert-butanesulfinyl–protected amine was easily deprotected under acidic conditions. Finally, the primary amine was coupled with different acid chlorides or acids to give the corresponding amides. The mild reaction conditions and high tolerance for various substitutions make this approach attractive for constructing pharmacologically interesting 5-nitroimidazoles. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Synthesis and Formulation of Thermosensitive Drug Carrier for Temperature Triggered Delivery of Naproxen Sodium
Molecules 2016, 21(11), 1473; doi:10.3390/molecules21111473
Received: 1 October 2016 / Revised: 26 October 2016 / Accepted: 28 October 2016 / Published: 4 November 2016
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Abstract
Nanospheres and microspheres are known as a multipurpose compounds and are used in various branches of science. Recent controlled delivery systems for drugs are also based on poly-micro and nanospheres. In our study we describe an investigation of the influence of thermosensitive polymer
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Nanospheres and microspheres are known as a multipurpose compounds and are used in various branches of science. Recent controlled delivery systems for drugs are also based on poly-micro and nanospheres. In our study we describe an investigation of the influence of thermosensitive polymer N-isopropylacrylamide (NIPA) on the release of the drug naproxen sodium (NS) with a hydrogel hydroxypropyl methylcellulose (HPMC) base. The hydrodynamic diameter (DH) of the obtained polymer was measured by using dynamic light scattering (DLS) at a wavelength of 678 nm. Hydrogel formulations of NS were prepared in a specific way ex tempore. NS was sprinkled on the surface of a distilled water, then polymer soluted in water was added. Afterward, HPMC was affixed to the solution. Prepared samples were stored at room temperature for 24 h. Release tests showed that modification of thevcross-linker type influenced the properties of synthesized polymeric particles. The NIPA derivatives obtained via surfactant free precipitation polymerization (SFPP) may be formulated as hydrogel preparations using HPMC. The obtained formulations presented varied half-release times, depending on the type of applied NIPA derivatives in hydrogel formulations. At 18 °C, the release rates were lower comparing to the reference HPMC hydrogel, whereas at 42 °C, the release rates were significantly higher. The synthesized thermosensitive polymers enabled temperature-triggered release of NS. Full article
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Open AccessArticle Effects of Light Intensity on the Growth, Photosynthetic Characteristics, and Flavonoid Content of Epimedium pseudowushanense B.L.Guo
Molecules 2016, 21(11), 1475; doi:10.3390/molecules21111475
Received: 7 October 2016 / Revised: 29 October 2016 / Accepted: 2 November 2016 / Published: 4 November 2016
Cited by 1 | PDF Full-text (2295 KB) | HTML Full-text | XML Full-text
Abstract
Epimedium pseudowushanense B.L.Guo is used in traditional medicine as an aphrodisiac and to strengthen muscles and bones. Several recent reports have shown that flavonoids from Epimedium also significantly affect the treatment of breast cancer, liver cancer, and leukemia. However, few studies have examined
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Epimedium pseudowushanense B.L.Guo is used in traditional medicine as an aphrodisiac and to strengthen muscles and bones. Several recent reports have shown that flavonoids from Epimedium also significantly affect the treatment of breast cancer, liver cancer, and leukemia. However, few studies have examined the medicinal-ingredient yield of Epimedium, a light-demanding shade herb, under different light intensities. To investigate the effects of light intensity on medicinal-ingredient yields, Epimedium was exposed to five levels of light intensity until harvest time. Leaf dry biomass under L4 was the highest among different light treatments. L4 was also associated with the highest net photosynthetic rate. Quantification of epimedin A, epimedin B, epimedin C, and icariin showed that L3 produced the highest amount of epimedin C, and that flavonoid content responded to light levels differently. Results indicated that L3 and L4 were the optimal light levels for medicinal-ingredient yield. Full article
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Open AccessArticle Assessment of Chemical Impact of Invasive Bryozoan Pectinatella magnifica on the Environment: Cytotoxicity and Antimicrobial Activity of P. magnifica Extracts
Molecules 2016, 21(11), 1476; doi:10.3390/molecules21111476
Received: 28 September 2016 / Revised: 23 October 2016 / Accepted: 31 October 2016 / Published: 4 November 2016
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Abstract
Pectinatella magnifica, an invasive bryozoan, might significantly affect ecosystem balance due to its massive occurrence in many areas in Europe and other parts of the world. Biological and chemical analyses are needed to get complete information about the impact of the animal
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Pectinatella magnifica, an invasive bryozoan, might significantly affect ecosystem balance due to its massive occurrence in many areas in Europe and other parts of the world. Biological and chemical analyses are needed to get complete information about the impact of the animal on the environment. In this paper, we aimed to evaluate in vitro cytotoxic effects of five extracts prepared from P. magnifica using LDH assay on THP-1 cell line. Antimicrobial activities of extracts against 22 different bacterial strains were tested by microdilution method. Our study showed that all extracts tested, except aqueous portion, demonstrated LD50 values below 100 μg/mL, which indicates potential toxicity. The water extract of P. magnifica with LD50 value of 250 μg/mL also shows potentially harmful effects. Also, an environmental risk resulting from the presence and increasing biomass of potentially toxic benthic cyanobacteria in old colonies should not be underestimated. Toxicity of Pectinatella extracts could be partially caused by presence of Aeromonas species in material, since we found members of these genera as most abundant bacteria associated with P. magnifica. Furthermore, P. magnifica seems to be a promising source of certain antimicrobial agents. Its methanolic extract, hexane, and chloroform fractions possessed selective inhibitory effect on some potential pathogens and food spoiling bacteria in the range of MIC 0.5–10 mg/mL. Future effort should be made to isolate and characterize the content compounds derived from P. magnifica, which could help to identify the substance(s) responsible for the toxic effects of P. magnifica extracts. Full article
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Open AccessArticle Statistical Significance of the Maximum Hardness Principle Applied to Some Selected Chemical Reactions
Molecules 2016, 21(11), 1477; doi:10.3390/molecules21111477
Received: 16 September 2016 / Revised: 24 October 2016 / Accepted: 1 November 2016 / Published: 5 November 2016
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Abstract
The validity of the maximum hardness principle (MHP) is tested in the cases of 50 chemical reactions, most of which are organic in nature and exhibit anomeric effect. To explore the effect of the level of theory on the validity of MHP in
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The validity of the maximum hardness principle (MHP) is tested in the cases of 50 chemical reactions, most of which are organic in nature and exhibit anomeric effect. To explore the effect of the level of theory on the validity of MHP in an exothermic reaction, B3LYP/6-311++G(2df,3pd) and LC-BLYP/6-311++G(2df,3pd) (def2-QZVP for iodine and mercury) levels are employed. Different approximations like the geometric mean of hardness and combined hardness are considered in case there are multiple reactants and/or products. It is observed that, based on the geometric mean of hardness, while 82% of the studied reactions obey the MHP at the B3LYP level, 84% of the reactions follow this rule at the LC-BLYP level. Most of the reactions possess the hardest species on the product side. A 50% null hypothesis is rejected at a 1% level of significance. Full article
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Open AccessArticle “Miswak” Based Green Synthesis of Silver Nanoparticles: Evaluation and Comparison of Their Microbicidal Activities with the Chemical Synthesis
Molecules 2016, 21(11), 1478; doi:10.3390/molecules21111478
Received: 25 August 2016 / Revised: 24 October 2016 / Accepted: 31 October 2016 / Published: 6 November 2016
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Abstract
Microbicidal potential of silver nanoparticles (Ag-NPs) can be drastically improved by improving their solubility or wettability in the aqueous medium. In the present study, we report the synthesis of both green and chemical synthesis of Ag-NPs, and evaluate the effect of the dispersion
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Microbicidal potential of silver nanoparticles (Ag-NPs) can be drastically improved by improving their solubility or wettability in the aqueous medium. In the present study, we report the synthesis of both green and chemical synthesis of Ag-NPs, and evaluate the effect of the dispersion qualities of as-prepared Ag-NPs from both methods on their antimicrobial activities. The green synthesis of Ag-NPs is carried out by using an aqueous solution of readily available Salvadora persica L. root extract (RE) as a bioreductant. The formation of highly crystalline Ag-NPs was established by various analytical and microscopic techniques. The rich phenolic contents of S. persica L. RE (Miswak) not only promoted the reduction and formation of NPs but they also facilitated the stabilization of the Ag-NPs, which was established by Fourier transform infrared spectroscopy (FT-IR) analysis. Furthermore, the influence of the volume of the RE on the size and the dispersion qualities of the NPs was also evaluated. It was revealed that with increasing the volume of RE the size of the NPs was deteriorated, whereas at lower concentrations of RE smaller size and less aggregated NPs were obtained. During this study, the antimicrobial activities of both chemically and green synthesized Ag-NPs, along with the aqueous RE of S. persica L., were evaluated against various microorganisms. It was observed that the green synthesized Ag-NPs exhibit comparable or slightly higher antibacterial activities than the chemically obtained Ag-NPs. Full article
(This article belongs to the Section Green Chemistry)
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Open AccessArticle Medium Optimization and Fermentation Kinetics for κ-Carrageenase Production by Thalassospira sp. Fjfst-332
Molecules 2016, 21(11), 1479; doi:10.3390/molecules21111479
Received: 11 August 2016 / Revised: 17 October 2016 / Accepted: 31 October 2016 / Published: 5 November 2016
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Abstract
Effective degradation of κ-carrageenan by isolated Thalassospira sp. fjfst-332 is reported for the first time in this paper. It was identified by 16S rDNA sequencing and morphological observation using Transmission Electron Microscopy (TEM). Based on a Plackett–Burman design for significant variables, Box–Behnken experimental
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Effective degradation of κ-carrageenan by isolated Thalassospira sp. fjfst-332 is reported for the first time in this paper. It was identified by 16S rDNA sequencing and morphological observation using Transmission Electron Microscopy (TEM). Based on a Plackett–Burman design for significant variables, Box–Behnken experimental design and response surface methodology were used to optimize the culture conditions. Through statistical optimization, the optimum medium components were determined as follows: 2.0 g/L κ-carrageenan, 1.0 g/L yeast extract, 1.0 g/L FOS, 20.0 g/L NaCl, 2.0 g/L NaNO3, 0.5 g/L MgSO4·7H2O, 0.1 g/L K2HPO4, and 0.1 g/L CaCl2. The highest activity exhibited by Thalassospira sp. fjfst-332 was 267 U/mL, which makes it the most vigorous wild bacterium for κ-carrageenan production. In order to guide scaled-up production, two empirical models—the logistic equation and Luedeking–Piretequation—were proposed to predict the strain growth and enzyme production, respectively. Furthermore, we report the fermentation kinetics and every empirical equation of the coefficients (α, β, X0, Xm and μm) for the two models, which could be used to design and optimize industrial processes. Full article
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Open AccessArticle Comparative Analysis of the Effects of Hydroxysafflor Yellow A and Anhydrosafflor Yellow B in Safflower Series of Herb Pairs Using Prep-HPLC and a Selective Knock-Out Approach
Molecules 2016, 21(11), 1480; doi:10.3390/molecules21111480
Received: 2 October 2016 / Revised: 29 October 2016 / Accepted: 1 November 2016 / Published: 6 November 2016
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Abstract
The flower of Carthamus tinctorius L. (Carthami Flos, safflower), important in traditional Chinese medicine (TCM), is known for treating blood stasis, coronary heart disease, hypertension, and cerebrovascular disease in clinical and experimental studies. It is widely accepted that hydroxysafflor yellow A (HSYA) and
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The flower of Carthamus tinctorius L. (Carthami Flos, safflower), important in traditional Chinese medicine (TCM), is known for treating blood stasis, coronary heart disease, hypertension, and cerebrovascular disease in clinical and experimental studies. It is widely accepted that hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (ASYB) are the major bioactive components of many formulae comprised of safflower. In this study, selective knock-out of target components such as HSYA and ASYB by using preparative high performance liquid chromatography (prep-HPLC) followed by antiplatelet and anticoagulation activities evaluation was used to investigate the roles of bioactive ingredients in safflower series of herb pairs. The results showed that both HSYA and ASYB not only played a direct role in activating blood circulation, but also indirectly made a contribution to the total bioactivity of safflower series of herb pairs. The degree of contribution of HSYA in the safflower and its series herb pairs was as follows: Carthami Flos-Ginseng Radix et Rhizoma Rubra (CF-GR) > Carthami Flos-Sappan Lignum (CF-SL) > Carthami Flos-Angelicae Sinensis Radix (CF-AS) > Carthami Flos-Astragali Radix (CF-AR) > Carthami Flos-Angelicae Sinensis Radix (CF-AS) > Carthami Flos-Glycyrrhizae Radix et Rhizoma (CF-GL) > Carthami Flos-Salviae Miltiorrhizae Radix et Rhizoma (CF-SM) > Carthami Flos (CF), and the contribution degree of ASYB in the safflower and its series herb pairs: CF-GL > CF-PS > CF-AS > CF-SL > CF-SM > CF-AR > CF-GR > CF. So, this study provided a significant and effective approach to elucidate the contribution of different herbal components to the bioactivity of the herb pair, and clarification of the variation of herb-pair compatibilities. In addition, this study provides guidance for investigating the relationship between herbal compounds and the bioactivities of herb pairs. It also provides a scientific basis for reasonable clinical applications and new drug development on the basis of the safflower series of herb pairs. Full article
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Open AccessArticle Triterpenoids from Ainsliaea yunnanensis Franch. and Their Biological Activities
Molecules 2016, 21(11), 1481; doi:10.3390/molecules21111481
Received: 17 September 2016 / Revised: 2 November 2016 / Accepted: 4 November 2016 / Published: 7 November 2016
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Abstract
One new pentacyclic triterpenoid, 3β-carboxylicfilic-4(23)-ene (1), and three known pentacyclic triterpenoids, adian-5-en-3α-ol (2), fernenol (3), and fern-7-en-3β-ol (4) were isolated from the petroleum ether phase of the ethanolic extract of Ainsliaea yunnanensis Franch. Their structures
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One new pentacyclic triterpenoid, 3β-carboxylicfilic-4(23)-ene (1), and three known pentacyclic triterpenoids, adian-5-en-3α-ol (2), fernenol (3), and fern-7-en-3β-ol (4) were isolated from the petroleum ether phase of the ethanolic extract of Ainsliaea yunnanensis Franch. Their structures were established by spectroscopic methods including 1-D and 2-D NMR, and MS experiments. Compounds 1, 2, 3, and 4 showed significant selective cytotoxicity against human acute monocytic leukemia cell line (THP-1) with IC50 values of 5.12 μM, 1.78 μM, 1.74 μM, and 1.75 μΜ, respectively. Compound 1 also showed an anti-inflammatory effect through the inhibition of the activity of NF-κB by blocking the nuclear translocation of p65. Full article
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Open AccessArticle Synthesis and In Vitro Anti Leishmania amazonensis Biological Screening of Morita-Baylis-Hillman Adducts Prepared from Eugenol, Thymol and Carvacrol
Molecules 2016, 21(11), 1483; doi:10.3390/molecules21111483
Received: 11 October 2016 / Revised: 1 November 2016 / Accepted: 1 November 2016 / Published: 8 November 2016
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Abstract
Leishmaniasis represents a series of severe neglected tropical diseases caused by protozoa of the genus Leishmania and is widely distributed around the world. Here, we present the syntheses of Morita-Baylis-Hillman adducts (MBHAs) prepared from eugenol, thymol and carvacrol, and their bioevaluation against promastigotes
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Leishmaniasis represents a series of severe neglected tropical diseases caused by protozoa of the genus Leishmania and is widely distributed around the world. Here, we present the syntheses of Morita-Baylis-Hillman adducts (MBHAs) prepared from eugenol, thymol and carvacrol, and their bioevaluation against promastigotes of Leishmania amazonensis. The new MBHAs are prepared in two steps from essential oils in moderate to good yields and present IC50 values in the range of 22.30–4.71 μM. Moreover, the selectivity index to the most potent compound is very high (SIrb > 84.92), far better than that of Glucantime® (SIrb 1.39) and amphotericin B (SIrb = 22.34). Conformational analysis were carried out at the M062X//6-31+G(d,p) level of theory to corroborate a hypothesis about the nitroaromatic bioreduction mechanism. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Enantioseparation Using Cellulose Tris(3,5-dimethylphenylcarbamate) as Chiral Stationary Phase for HPLC: Influence of Molecular Weight of Cellulose
Molecules 2016, 21(11), 1484; doi:10.3390/molecules21111484
Received: 6 October 2016 / Revised: 1 November 2016 / Accepted: 2 November 2016 / Published: 8 November 2016
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Abstract
The cellulose oligomers with different degrees of polymerization (DP), 7, 11, 18, 24, 26, 40 and 52, were prepared by hydrolysis of microcrystalline cellulose with phosphoric acid. These oligomers including the starting microcrystalline cellulose (DP 124) were converted to tris(3,5-dimethylphenylcarbamate) (CDMPC) derivatives by
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The cellulose oligomers with different degrees of polymerization (DP), 7, 11, 18, 24, 26, 40 and 52, were prepared by hydrolysis of microcrystalline cellulose with phosphoric acid. These oligomers including the starting microcrystalline cellulose (DP 124) were converted to tris(3,5-dimethylphenylcarbamate) (CDMPC) derivatives by the reaction with an excess of 3,5-dimethylphenyl isocyanate to be used as the chiral stationary phase (CSP) in high-performance liquid chromatography (HPLC). The structures of the CDMPC derivatives were investigated by infrared spectroscopy (IR), 1H-NMR, circular dichroism (CD) and size exclusion chromatography (SEC), and the DPs of the derivatives estimated by SEC agreed with those estimated by 1H-NMR. After coating the derivatives on silica gel, their chiral recognition abilities were evaluated using eight racemates under a normal phase condition with a hexane-2-propanol (99/1) mixture as an eluent. The chiral recognition abilities of 7- and 11-mers, particularly the former, were lower than those of the higher oligomers from DP 18 to 52, which had rather similar abilities to that of 124-mer, although the abilities depended on the racemates. DP 18 seems to be sufficient for CDMPC to exhibit chiral recognition similar to that of the CDMPC with larger DPs. Full article
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Open AccessArticle Aroma Release in Wine Using Co-Immobilized Enzyme Aggregates
Molecules 2016, 21(11), 1485; doi:10.3390/molecules21111485
Received: 31 August 2016 / Revised: 18 October 2016 / Accepted: 19 October 2016 / Published: 8 November 2016
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Abstract
Aroma is a remarkable factor of quality and consumer preference in wine, representing a distinctive feature of the product. Most aromatic compounds in varietals are in the form of glycosidic precursors, which are constituted by a volatile aglycone moiety linked to a glucose
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Aroma is a remarkable factor of quality and consumer preference in wine, representing a distinctive feature of the product. Most aromatic compounds in varietals are in the form of glycosidic precursors, which are constituted by a volatile aglycone moiety linked to a glucose residue by an O-glycosidic bond; glucose is often linked to another sugar (arabinose, rhamnose or apiose). The use of soluble β-glycosidases for aroma liberation implies the addition of a precipitating agent to remove it from the product and precludes its reuse after one batch. An attractive option from a technological perspective that will aid in removing such constraints is the use of immobilized glycosidases. Immobilization by aggregation and crosslinking is a simple strategy producing enzyme catalysts of very high specific activity, being an attractive option to conventional immobilization to solid inert supports. The purpose of this work was the evaluation of co-immobilized β-glycosidases crosslinked aggregates produced from the commercial preparation AR2000, which contains the enzymes involved in the release of aromatic terpenes in Muscat wine (α-l-arabinofuranosidase and β-d-glucopyranosidase). To do so, experiments were conducted with co-immobilized crosslinked enzyme aggregates (combi-CLEAs), and with the soluble enzymes, using an experiment without enzyme addition as control. Stability of the enzymes at the conditions of winemaking was assessed and the volatiles composition of wine was determined by SPE-GC-MS. Stability of enzymes in combi-CLEAs was much higher than in soluble form, 80% of the initial activity remaining after 60 days in contact with the wine; at the same conditions, the soluble enzymes had lost 80% of their initial activities after 20 days. Such higher stabilities will allow prolonged use of the enzyme catalyst reducing its impact in the cost of winemaking. Wine treated with combi-CLEAs was the one exhibiting the highest concentration of total terpenes (18% higher than the control) and the highest concentrations of linalool (20% higher), nerol (20% higher) and geraniol (100% higher), which are the most important terpenes in determining Muscat typicity. Co-immobilized enzymes were highly stable at winemaking conditions, so their reutilization is possible and technologically attractive by reducing the impact of enzyme cost on winemaking cost. Full article
(This article belongs to the Special Issue Enzyme Immobilization 2016)
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Open AccessArticle Proteomic Analysis of Tung Tree (Vernicia fordii) Oilseeds during the Developmental Stages
Molecules 2016, 21(11), 1486; doi:10.3390/molecules21111486
Received: 17 August 2016 / Revised: 28 October 2016 / Accepted: 1 November 2016 / Published: 8 November 2016
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Abstract
The tung tree (Vernicia fordii), a non-model woody plant belonging to the Euphorbiaceae family, is a promising economic plant due to the high content of a novel high-value oil in its seeds. Many metabolic pathways are active during seed development. Oil
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The tung tree (Vernicia fordii), a non-model woody plant belonging to the Euphorbiaceae family, is a promising economic plant due to the high content of a novel high-value oil in its seeds. Many metabolic pathways are active during seed development. Oil (triacylglycerols (TAGs)) accumulates in oil bodies distributed in the endosperm cells of tung tree seeds. The relationship between oil bodies and oil content during tung tree seed development was analyzed using ultrastructural observations, which confirmed that oil accumulation was correlated with the volumes and numbers of oil bodies in the endosperm cells during three different developmental stages. For a deeper understanding of seed development, we carried out proteomic analyses. At least 144 proteins were differentially expressed during three different developmental stages. A total of 76 proteins were successfully identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry/mass spectrometry (MALDI-TOF/MS/MS). These proteins were grouped into 11 classes according to their functions. The major groups of differentially expressed proteins were associated with energy metabolism (25%), fatty acid metabolism (15.79%) and defense (14.47%). These results strongly suggested that a very high percentage of gene expression in seed development is dedicated to the synthesis and accumulation of TAGs. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessArticle Synthesis of Optically Active Poly(diphenylacetylene)s Using Polymer Reactions and an Evaluation of Their Chiral Recognition Abilities as Chiral Stationary Phases for HPLC
Molecules 2016, 21(11), 1487; doi:10.3390/molecules21111487
Received: 14 October 2016 / Revised: 3 November 2016 / Accepted: 4 November 2016 / Published: 7 November 2016
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Abstract
A series of optically active poly(diphenylacetylene) derivatives bearing a chiral substituent (poly-2S) or chiral and achiral substituents (poly-(2Sx-co-31−x)) on all of their pendant phenyl rings were synthesized by the reaction of
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A series of optically active poly(diphenylacetylene) derivatives bearing a chiral substituent (poly-2S) or chiral and achiral substituents (poly-(2Sx-co-31−x)) on all of their pendant phenyl rings were synthesized by the reaction of poly(bis(4-carboxyphenyl)acetylene) with (S)-1-phenylethylamine ((S)-2) or benzylamine (3) in the presence of a condensing reagent. Their chiroptical properties and chiral recognition abilities as chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC) were investigated. Poly-2S and poly-(2Sx-co-31−x) (0.06 < x < 0.71) formed a preferred-handed helical conformation with opposite helical senses after thermal annealing despite possessing the same chiral pendant (h-poly-2S and h-poly-(2Sx-co-31−x)). Furthermore, h-poly-2S and h-poly-(2S0.36-co-30.64) emitted circularly polarized luminescence with opposite signs. h-Poly-2S showed higher chiral recognition abilities toward a larger number of racemates than poly-2S without a preferred-handed helicity and the previously reported preferred-handed poly(diphenylacetylene) derivative bearing the same chiral substituent on half of its pendant phenyl rings. h-Poly-(2S0.36-co-30.64) also exhibited good chiral recognition abilities toward several racemates, though the elution order of some enantiomers was reversed compared with h-poly-2S. Full article
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Open AccessArticle Synthesis and Pharmacological Evaluation of Novel Pleuromutilin Derivatives with Substituted Benzimidazole Moieties
Molecules 2016, 21(11), 1488; doi:10.3390/molecules21111488
Received: 13 October 2016 / Revised: 2 November 2016 / Accepted: 2 November 2016 / Published: 8 November 2016
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Abstract
A series of novel pleuromutilin derivatives with substituted benzimidazole moieties were designed and synthesized from pleuromutilin and 5-amino-2-mercaptobenzimidazole through sequential reactions. All the newly synthesized compounds were characterized by IR, NMR, and HRMS. Each of the derivatives was evaluated in vitro for their
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A series of novel pleuromutilin derivatives with substituted benzimidazole moieties were designed and synthesized from pleuromutilin and 5-amino-2-mercaptobenzimidazole through sequential reactions. All the newly synthesized compounds were characterized by IR, NMR, and HRMS. Each of the derivatives was evaluated in vitro for their antibacterial activity against Escherichia coli (E. coli) and five Gram (+) inoculums. 14-O-((5-amino-benzimidazole-2-yl) thioacetyl) mutilin (3) was the most active compound and showed highest antibacterial activities. Furthermore, we evaluated the inhibition activities of compound 3 on short-term S. aureus and MRSA growth and cytochrome P450 (CYP). The bioassay results indicate that compound 3 could be considered potential antibacterial agents but with intermediate inhibition of CYP3A4. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle The Cooperative Effect of Genistein and Protein Hydrolysates on the Proliferation and Survival of Osteoblastic Cells (hFOB 1.19)
Molecules 2016, 21(11), 1489; doi:10.3390/molecules21111489
Received: 24 September 2016 / Revised: 3 November 2016 / Accepted: 4 November 2016 / Published: 8 November 2016
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Abstract
Chum salmon skin gelatin, de-isoflavoned soy protein, and casein were hydrolyzed at two degrees of hydrolysis. Genistein, the prepared hydrolysates, and genistein-hydrolysate combinations were assessed for their proliferative and anti-apoptotic effects on human osteoblasts (hFOB 1.19) to clarify potential cooperative effects between genistein
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Chum salmon skin gelatin, de-isoflavoned soy protein, and casein were hydrolyzed at two degrees of hydrolysis. Genistein, the prepared hydrolysates, and genistein-hydrolysate combinations were assessed for their proliferative and anti-apoptotic effects on human osteoblasts (hFOB 1.19) to clarify potential cooperative effects between genistein and these hydrolysates in these two activities. Genistein at 2.5 μg/L demonstrated the highest proliferative activity, while the higher dose of genistein inhibited cell growth. All hydrolysates promoted osteoblast proliferation by increasing cell viability to 102.9%–131.1%. Regarding etoposide- or NaF-induced osteoblast apoptosis, these hydrolysates at 0.05 g/L showed both preventive and therapeutic effects against apoptosis. In the mode of apoptotic prevention, the hydrolysates decreased apoptotic cells from 32.9% to 15.2%–23.7% (etoposide treatment) or from 23.6% to 14.3%–19.6% (NaF treatment). In the mode of apoptotic rescue, the hydrolysates lessened the extent of apoptotic cells from 15.9% to 13.0%–15.3% (etoposide treatment) or from 13.3% to 10.9%–12.7% (NaF treatment). Gelatin hydrolysates showed the highest activities among all hydrolysates in all cases. All investigated combinations (especially the genistein-gelatin hydrolysate combination) had stronger proliferation, apoptotic prevention, and rescue than genistein itself or their counterpart hydrolysates alone, suggesting that genistein cooperated with these hydrolysates, rendering greater activities in osteoblast proliferation and anti-apoptosis. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Salidroside Regulates Inflammatory Response in Raw 264.7 Macrophages via TLR4/TAK1 and Ameliorates Inflammation in Alcohol Binge Drinking-Induced Liver Injury
Molecules 2016, 21(11), 1490; doi:10.3390/molecules21111490
Received: 27 September 2016 / Revised: 3 November 2016 / Accepted: 4 November 2016 / Published: 9 November 2016
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Abstract
The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking-induced liver injury in vivo. SDS downregulated protein expression of toll-like
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The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking-induced liver injury in vivo. SDS downregulated protein expression of toll-like receptor 4 (TLR4) and CD14. SDS inhibited LPS-triggered phosphorylation of LPS-activated kinase 1 (TAK1), p38, c-Jun terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Degradation of IκB-α and nuclear translocation of nuclear factor (NF)-κB were effectively blocked by SDS. SDS concentration-dependently suppressed LPS mediated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels, as well as their downstream products, NO. SDS significantly inhibited protein secretion and mRNA expression of of interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Additionally C57BL/6 mice were orally administrated SDS for continuous 5 days, followed by three gavages of ethanol every 30 min. Alcohol binge drinking caused the increasing of hepatic lipid accumulation and serum transaminases levels. SDS pretreatment significantly alleviated liver inflammatory changes and serum transaminases levels. Further investigation indicated that SDS markedly decreased protein level of IL-1β in serum. Taken together, these data implied that SDS inhibits liver inflammation both in vitro and in vivo, and may be a promising candidate for the treatment of inflammatory liver injury. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Catalytic Oxidation of NO over MnOx–CeO2 and MnOx–TiO2 Catalysts
Molecules 2016, 21(11), 1491; doi:10.3390/molecules21111491
Received: 4 October 2016 / Revised: 27 October 2016 / Accepted: 5 November 2016 / Published: 14 November 2016
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Abstract
A series of MnOx–CeO2 and MnOx–TiO2 catalysts were prepared by a homogeneous precipitation method and their catalytic activities for the NO oxidation in the absence or presence of SO2 were evaluated. Results show that the optimal
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A series of MnOx–CeO2 and MnOx–TiO2 catalysts were prepared by a homogeneous precipitation method and their catalytic activities for the NO oxidation in the absence or presence of SO2 were evaluated. Results show that the optimal molar ratio of Mn/Ce and Mn/Ti are 0.7 and 0.5, respectively. The MnOx–CeO2 catalyst exhibits higher catalytic activity and better resistance to SO2 poisoning than the MnOx–TiO2 catalyst. On the basis of Brunauer–Emmett–Teller (BET), X-ray diffraction (XRD), and scanning transmission electron microscope with mapping (STEM-mapping) analyses, it is seen that the MnOx–CeO2 catalyst possesses higher BET surface area and better dispersion of MnOx over the catalyst than MnOx–TiO2 catalyst. X-ray photoelectron spectroscopy (XPS) measurements reveal that MnOx–CeO2 catalyst provides the abundance of Mn3+ and more surface adsorbed oxygen, and SO2 might be preferentially adsorbed to the surface of CeO2 to form sulfate species, which provides a protection of MnOx active sites from being poisoned. In contrast, MnOx active sites over the MnOx–TiO2 catalyst are easily and quickly sulfated, leading to rapid deactivation of the catalyst for NO oxidation. Furthermore, temperature programmed desorption with NO and O2 (NO + O2-TPD) and in situ diffuse reflectance infrared transform spectroscopy (in situ DRIFTS) characterizations results show that the MnOx–CeO2 catalyst displays much stronger ability to adsorb NOx than the MnOx–TiO2 catalyst, especially after SO2 poisoning. Full article
(This article belongs to the Special Issue Transition Metal Catalysis 2016)
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Open AccessArticle A Stereocontrolled Protocol to Highly Functionalized Fluorinated Scaffolds through a Fluoride Opening of Oxiranes
Molecules 2016, 21(11), 1493; doi:10.3390/molecules21111493
Received: 31 August 2016 / Revised: 19 September 2016 / Accepted: 4 November 2016 / Published: 17 November 2016
Cited by 3 | PDF Full-text (1093 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A novel selective and substrate-dependent synthetic protocol has been developed towards the synthesis of various fluorine-containing, highly functionalized cycloalkane derivatives. The method involves the stereoselective epoxidation of some unsaturated cyclic β-amino acid derivatives as model compounds, followed by a regioselective fluoride opening of
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A novel selective and substrate-dependent synthetic protocol has been developed towards the synthesis of various fluorine-containing, highly functionalized cycloalkane derivatives. The method involves the stereoselective epoxidation of some unsaturated cyclic β-amino acid derivatives as model compounds, followed by a regioselective fluoride opening of oxiranes under various conditions with Deoxofluor and XtalFluor-E reagents, thereby offering an insight into this new epoxide opening methodology with fluoride. Full article
(This article belongs to the Special Issue Fluorine Chemistry 2016)
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Open AccessArticle Feasibility of Fraction Collection in HPLC Systems with Evaporative Light Scattering Detector: Analysis of Pectinatella magnifica
Molecules 2016, 21(11), 1495; doi:10.3390/molecules21111495
Received: 5 September 2016 / Revised: 28 October 2016 / Accepted: 30 October 2016 / Published: 8 November 2016
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Abstract
The use of a liquid chromatography (LC) splitter inserted between an HPLC column and an evaporative light scattering detector (ELSD) is described. This paper aims to show the feasibility of using the splitter in an HPLC-ELSD system to fractionate a model mixture of
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The use of a liquid chromatography (LC) splitter inserted between an HPLC column and an evaporative light scattering detector (ELSD) is described. This paper aims to show the feasibility of using the splitter in an HPLC-ELSD system to fractionate a model mixture of analytes, namely salicin (2-(hydroxymethyl)-phenyl-β-d-glucopyranoside) and glucose. The retention factors and efficiency of the separation were studied under various temperatures and water contents in the mobile phase in order to clarify the mechanism of polyols separation on a diol column under the conditions of hydrophilic liquid chromatography (HILIC). Finally, the system was applied to a biological sample (a lyophilized colony gel of Pectinatella magnifica), where the presence of fructose and glucose was confirmed. Full article
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Open AccessArticle Sugar Composition Analysis of Fuzi Polysaccharides by HPLC-MSn and Their Protective Effects on Schwann Cells Exposed to High Glucose
Molecules 2016, 21(11), 1496; doi:10.3390/molecules21111496
Received: 26 September 2016 / Revised: 2 November 2016 / Accepted: 2 November 2016 / Published: 9 November 2016
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Abstract
Fuzi has been used to treat diabetic complications for many years in china. In a previous study, we have shown that Fuzi aqueous extract can attenuate Diabetic peripheral neuropathy (DPN) in rats and protect Schwann cells from injury. Thus, the protective effect of
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Fuzi has been used to treat diabetic complications for many years in china. In a previous study, we have shown that Fuzi aqueous extract can attenuate Diabetic peripheral neuropathy (DPN) in rats and protect Schwann cells from injury. Thus, the protective effect of Fuzi polysaccharides (FPS) on high glucose-induced SCs and the preliminary mechanism were investigated. Firstly, the FPS were obtained and their monose composition was analyzed by the combination of pre-column derivatization and high performance liquid chromatography coupled with electrospray ionization multi-tandem mass spectrometry (HPLC/ESI-MSn). The results witnessed the efficiency of this method and seven monosaccharides were tentatively identified, among which fucose was first reported. Simultaneously, m/z 215 can be considered as diagnostic ions to confirm the number of monosaccharides. Next, high glucose-induced SC model was applied and divided into model group, treated group of FPS, normal and osmotic control group. After treatment for 48 h, the data showed FPS could significantly decrease the intracellular ROS and apoptosis, which were determined by the corresponding fluorescent probes. Then, the expression of oxidative stress-related proteins in SCs were measured by Western blot. Furthermore, the protein tests found that FPS markedly up-regulated superoxide dismutase (SOD), catalase (CAT) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) protein level, but down-regulated NADPH oxidase-1 (Nox1) protein level. Moreover, FPS could also increase AMP-activated protein kinase (AMPK) activation significantly. Hence, we preliminary deduced that AMPK-PGC-1α pathway may play an important role in the protective effect of FPS against high glucose-induced cell damage. Full article
(This article belongs to the Special Issue Natural Polysaccharides)
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Open AccessArticle A Modular Synthetic Approach to Isosteric Sulfonic Acid Analogues of the Anticoagulant Pentasaccharide Idraparinux
Molecules 2016, 21(11), 1497; doi:10.3390/molecules21111497
Received: 7 September 2016 / Revised: 1 November 2016 / Accepted: 3 November 2016 / Published: 11 November 2016
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Abstract
Heparin-based anticoagulants are drugs of choice in the therapy and prophylaxis of thromboembolic diseases. Idraparinux is a synthetic anticoagulant pentasaccharide based on the heparin antithrombin-binding domain. In the frame of our ongoing research aimed at the synthesis of sulfonic acid-containing heparinoid anticoagulants, we
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Heparin-based anticoagulants are drugs of choice in the therapy and prophylaxis of thromboembolic diseases. Idraparinux is a synthetic anticoagulant pentasaccharide based on the heparin antithrombin-binding domain. In the frame of our ongoing research aimed at the synthesis of sulfonic acid-containing heparinoid anticoagulants, we elaborated a modular pathway to obtain a series of idraparinux-analogue pentasaccharides bearing one or two primary sulfonic acid moieties. Five protected pentasaccharides with different C-sulfonation patterns were prepared by two subsequent glycosylation reactions, respectively, using two monosaccharide and four disaccharide building blocks. Transformation of the protected derivatives into the fully O-sulfated, O-methylated sulfonic acid end-products was also studied. Full article
(This article belongs to the collection Advances in Carbohydrate Chemistry)
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Open AccessArticle Large Scale Screening of Southern African Plant Extracts for the Green Synthesis of Gold Nanoparticles Using Microtitre-Plate Method
Molecules 2016, 21(11), 1498; doi:10.3390/molecules21111498
Received: 10 August 2016 / Revised: 28 October 2016 / Accepted: 1 November 2016 / Published: 8 November 2016
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Abstract
The preparation of gold nanoparticles (AuNPs) involves a variety of chemical and physical methods. These methods use toxic and environmentally harmful chemicals. Consequently, the synthesis of AuNPs using green chemistry has been under investigation to develop eco-friendly nanoparticles. One approach to achieve this
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The preparation of gold nanoparticles (AuNPs) involves a variety of chemical and physical methods. These methods use toxic and environmentally harmful chemicals. Consequently, the synthesis of AuNPs using green chemistry has been under investigation to develop eco-friendly nanoparticles. One approach to achieve this is the use of plant-derived phytochemicals that are capable of reducing gold ions to produce AuNPs. The aim of this study was to implement a facile microtitre-plate method to screen a large number of aqueous plant extracts to determine the optimum concentration (OC) for the bio-synthesis of the AuNPs. Several AuNPs of different sizes and shapes were successfully synthesized and characterized from 17 South African plants. The characterization was done using Ultra Violet-Visible Spectroscopy, Dynamic Light Scattering, High Resolution Transmission Electron Microscopy and Energy-Dispersive X-ray Spectroscopy. We also studied the effects of temperature on the synthesis of the AuNPs and showed that changes in temperatures affect the size and dispersity of the generated AuNPs. We also evaluated the stability of the synthesized AuNPs and showed that some of them are stable in biological buffer solutions. Full article
(This article belongs to the Section Green Chemistry)
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Open AccessArticle Biocatalytic Synthesis of Novel Partial Esters of a Bioactive Dihydroxy 4-Methylcoumarin by Rhizopus oryzae Lipase (ROL)
Molecules 2016, 21(11), 1499; doi:10.3390/molecules21111499
Received: 31 July 2016 / Revised: 24 October 2016 / Accepted: 2 November 2016 / Published: 9 November 2016
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Abstract
Highly regioselective acylation has been observed in 7,8-dihydroxy-4-methylcoumarin (DHMC) by the lipase from Rhizopus oryzae suspended in tetrahydrofuran (THF) at 45 °C using six different acid anhydrides as acylating agents. The acylation occurred regioselectively at one of the two hydroxy groups of the
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Highly regioselective acylation has been observed in 7,8-dihydroxy-4-methylcoumarin (DHMC) by the lipase from Rhizopus oryzae suspended in tetrahydrofuran (THF) at 45 °C using six different acid anhydrides as acylating agents. The acylation occurred regioselectively at one of the two hydroxy groups of the coumarin moiety resulting in the formation of 8-acyloxy-7-hydroxy-4-methylcoumarins, which are important bioactive molecules for studying biotansformations in animals, and are otherwise very difficult to obtain by only chemical steps. Six monoacylated, monohydroxy 4-methylcoumarins have been biocatalytically synthesised and identified on the basis of their spectral data and X-ray crystal analysis. Full article
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Open AccessArticle Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study
Molecules 2016, 21(11), 1500; doi:10.3390/molecules21111500
Received: 22 August 2016 / Revised: 26 October 2016 / Accepted: 28 October 2016 / Published: 9 November 2016
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Abstract
This study aims to evaluate the in vitro angiotensin-converting enzyme (ACE) inhibition activity of different extracts of Orthosiphon stamineus (OS) leaves and their main flavonoids, namely rosmarinic acid (RA), sinensetin (SIN), eupatorin (EUP) and 3′-hydroxy-5,6,7,4′-tetramethoxyflavone (TMF). Furthermore, to identify possible mechanisms of action
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This study aims to evaluate the in vitro angiotensin-converting enzyme (ACE) inhibition activity of different extracts of Orthosiphon stamineus (OS) leaves and their main flavonoids, namely rosmarinic acid (RA), sinensetin (SIN), eupatorin (EUP) and 3′-hydroxy-5,6,7,4′-tetramethoxyflavone (TMF). Furthermore, to identify possible mechanisms of action based on structure–activity relationships and molecular docking. The in vitro ACE inhibition activity relied on determining hippuric acid (HA) formation from ACE-specific substrate (hippuryl-histidyl-leucine (HHL)) by the action of ACE enzyme. A High Performance Liquid Chromatography method combined with UV detection was developed and validated for measurement the concentration of produced HA. The chelation ability of OS extract and its reference compounds was evaluated by tetramethylmurexide reagent. Furthermore, molecular docking study was performed by LeadIT-FlexX: BioSolveIT’s LeadIT program. OS ethanolic extract (OS-E) exhibited highest inhibition and lowest IC50 value (45.77 ± 1.17 µg/mL) against ACE compared to the other extracts. Among the tested reference compounds, EUP with IC50 15.35 ± 4.49 µg/mL had highest inhibition against ACE and binding ability with Zn (II) (56.03% ± 1.26%) compared to RA, TMF and SIN. Molecular docking studies also confirmed that flavonoids inhibit ACE via interaction with the zinc ion and this interaction is stabilized by other interactions with amino acids in the active site. In this study, we have demonstrated that changes in flavonoids active core affect their capacity to inhibit ACE. Moreover, we showed that ACE inhibition activity of flavonoids compounds is directly related to their ability to bind with zinc ion in the active site of ACE enzyme. It was also revealed that OS extract contained high amount of flavonoids other than RA, TMF, SIN and EUP. As such, application of OS extract is useful as inhibitors of ACE. Full article
(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)
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Open AccessArticle Resveratrol and Coumarin: Novel Agricultural Antibacterial Agent against Ralstonia solanacearum In Vitro and In Vivo
Molecules 2016, 21(11), 1501; doi:10.3390/molecules21111501
Received: 13 October 2016 / Revised: 28 October 2016 / Accepted: 4 November 2016 / Published: 9 November 2016
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Abstract
Bacterial wilt is a destructive disease caused by the phytopathogen Ralstonia solanacearum (R. solanacearum), which is widely found in various tobacco-growing areas all over the world. Botanical bactericidal substances have gradually emerged as a hot topic in modern pesticide research. In
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Bacterial wilt is a destructive disease caused by the phytopathogen Ralstonia solanacearum (R. solanacearum), which is widely found in various tobacco-growing areas all over the world. Botanical bactericidal substances have gradually emerged as a hot topic in modern pesticide research. In this study, the antibacterial activities of two phytochemicals (resveratrol and coumarin) against R. solanacearum and their in vivo and in vitro efficacy for controlling tobacco bacterial wilt were evaluated. We rule out significant biological effects of both phytochemicals using transmission electron microscope (TEM) and fluorescence microscope, which suppressed the growth of R. solanacearum. Furthermore, we demonstrated that the toxicity mechanisms mainly involved damaging bacterial cell membrane and preventing swarming motility and biofilm formation. A further pot experiment demonstrated that coumarin and resveratrol significantly inhibited early adhesion and colonization of R. solanacearum in tobacco plants and the corresponding control efficacies were 68% and 85% after incubation for 13 days, respectively. The findings of this study suggest that both resveratrol and coumarin have potential as non-toxic antimicrobial strategies for controlling tobacco bacterial wilt disease. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Chemistry and Photochemistry of Anthocyanins and Related Compounds: A Thermodynamic and Kinetic Approach
Molecules 2016, 21(11), 1502; doi:10.3390/molecules21111502
Received: 28 September 2016 / Revised: 2 November 2016 / Accepted: 3 November 2016 / Published: 10 November 2016
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Abstract
Anthocyanins are identified by the respective flavylium cation, which is only one species of a multistate of different molecules reversibly interconverted by external inputs such as pH, light and temperature. The flavylium cation (acidic form) is involved in an apparent acid-base reaction, where
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Anthocyanins are identified by the respective flavylium cation, which is only one species of a multistate of different molecules reversibly interconverted by external inputs such as pH, light and temperature. The flavylium cation (acidic form) is involved in an apparent acid-base reaction, where the basic species is the sum of quinoidal base, hemiketal and cis- and trans-chalcones, their relative fraction depending on the substitution pattern of the flavylium cation. The full comprehension of this complex system requires a thermodynamic and kinetic approach. The first consists in drawing an energy level diagram where the relative positions of the different species are represented as a function of pH. On the other hand, the kinetic approach allows measuring the rates of the reactions that interconnect reversibly the multistate species. The kinetics is greatly dependent on the existence or not of a high cis-trans isomerization barrier. In this work, the procedure to obtain the energy level diagram and the rates of inter-conversion in the multistate in both cases (low or high isomerization barrier) are described. Practical examples of this approach are presented to illustrate the theory, and recently reported applications based on host–guest complexes are reviewed. Full article
(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)
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Open AccessArticle Double Intramolecular Transacetalization of Polyhydroxy Acetals: Synthesis of Conformationally-Restricted 1,3-Dioxanes with Axially-Oriented Phenyl Moiety
Molecules 2016, 21(11), 1503; doi:10.3390/molecules21111503
Received: 14 October 2016 / Revised: 31 October 2016 / Accepted: 3 November 2016 / Published: 9 November 2016
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Abstract
The synthesis of conformationally-restricted 1,3-dioxanes with a phenyl moiety fixed in an axial orientation at the acetalic center is described. Starting with diethyl 3-hydroxyglutarate (15), benzaldehyde acetal 12a and acetophenone ketal 12b bearing a protected 1,3,5-trihydroxypentyl side chain in the o
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The synthesis of conformationally-restricted 1,3-dioxanes with a phenyl moiety fixed in an axial orientation at the acetalic center is described. Starting with diethyl 3-hydroxyglutarate (15), benzaldehyde acetal 12a and acetophenone ketal 12b bearing a protected 1,3,5-trihydroxypentyl side chain in the o-position were prepared. The first acid-catalyzed intramolecular transacetalization gave a mixture of diastereomeric 2-benzofurans 18 (ratio of diastereomers 2:2:1:1). After OH group deprotection, the second intramolecular transacetalization afforded tricyclic alcohol 14a (2-(1,5-epoxy-1,3,4,5-tetrahydro-2-benzoxepin-3-yl]ethan-1-ol). Analogous cyclizations led to the corresponding silyl ether 22a (19%) and azide 23a (13%). Whereas tricyclic alcohol 14a was obtained as a 1:1 mixture of diastereomers, the silyl ether 22a and the azide 23a afforded only one diastereomer. This observation indicates a faster cyclization of the minor diastereomers providing the thermodynamically-favored compounds with equatorially-oriented substituents in the 3-position of the tricyclic 1,5-epoxy-2-benzoxepine system. In general, acetophenone-derived ketalic compounds (b-series) required very mild reaction conditions and gave lower yields than the corresponding acetalic compounds (a-series). Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Unraveling the Roots of Selectivity of Peptide Affinity Reagents for Structurally Similar Ribosomal Inactivating Protein Derivatives
Molecules 2016, 21(11), 1504; doi:10.3390/molecules21111504
Received: 26 September 2016 / Revised: 2 November 2016 / Accepted: 4 November 2016 / Published: 9 November 2016
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Abstract
Peptide capture agents have become increasingly useful tools for a variety of sensing applications due to their ease of discovery, stability, and robustness. Despite the ability to rapidly discover candidates through biopanning bacterial display libraries and easily mature them to Protein Catalyzed Capture
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Peptide capture agents have become increasingly useful tools for a variety of sensing applications due to their ease of discovery, stability, and robustness. Despite the ability to rapidly discover candidates through biopanning bacterial display libraries and easily mature them to Protein Catalyzed Capture (PCC) agents with even higher affinity and selectivity, an ongoing challenge and critical selection criteria is that the peptide candidates and final reagent be selective enough to replace antibodies, the gold-standard across immunoassay platforms. Here, we have discovered peptide affinity reagents against abrax, a derivative of abrin with reduced toxicity. Using on-cell Fluorescence Activated Cell Sorting (FACS) assays, we show that the peptides are highly selective for abrax over RiVax, a similar derivative of ricin originally designed as a vaccine, with significant structural homology to abrax. We rank the newly discovered peptides for strongest affinity and analyze three observed consensus sequences with varying affinity and specificity. The strongest (Tier 1) consensus was FWDTWF, which is highly aromatic and hydrophobic. To better understand the observed selectivity, we use the XPairIt peptide–protein docking protocol to analyze binding location predictions of the individual Tier 1 peptides and consensus on abrax and RiVax. The binding location profiles on the two proteins are quite distinct, which we determine is due to differences in pocket size, pocket environment (including hydrophobicity and electronegativity), and steric hindrance. This study provides a model system to show that peptide capture candidates can be quite selective for a structurally similar protein system, even without further maturation, and offers an in silico method of analysis for understanding binding and down-selecting candidates. Full article
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Open AccessArticle cDNA Isolation and Functional Characterization of UDP-d-glucuronic Acid 4-Epimerase Family from Ornithogalum caudatum
Molecules 2016, 21(11), 1505; doi:10.3390/molecules21111505
Received: 12 October 2016 / Revised: 1 November 2016 / Accepted: 6 November 2016 / Published: 9 November 2016
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Abstract
d-Galacturonic acid (GalA) is an important component of GalA-containing polysaccharides in Ornithogalum caudatum. The incorporation of GalA into these polysaccharides from UDP-d-galacturonic acid (UDP-GalA) was reasonably known. However, the cDNAs involved in the biosynthesis of UDP-GalA were still unknown.
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d-Galacturonic acid (GalA) is an important component of GalA-containing polysaccharides in Ornithogalum caudatum. The incorporation of GalA into these polysaccharides from UDP-d-galacturonic acid (UDP-GalA) was reasonably known. However, the cDNAs involved in the biosynthesis of UDP-GalA were still unknown. In the present investigation, one candidate UDP-d-glucuronic acid 4-epimerase (UGlcAE) family with three members was isolated from O. caudatum based on RNA-Seq data. Bioinformatics analyses indicated all of the three isoforms, designated as OcUGlcAE1~3, were members of short-chain dehydrogenases/reductases (SDRs) and shared two conserved motifs. The three full-length cDNAs were then transformed to Pichia pastoris GS115 for heterologous expression. Data revealed both the supernatant and microsomal fractions from the recombinant P. pastoris expressing OcUGlcAE3 can interconvert UDP-GalA and UDP-d-glucuronic acid (UDP-GlcA), while the other two OcUGlcAEs had no activity on UDP-GlcA and UDP-GalA. Furthermore, expression analyses of the three epimerases in varied tissues of O. caudatum were performed by real-time quantitative PCR (RT-qPCR). Results indicated OcUGlcAE3, together with the other two OcUGlcAE-like genes, was root-specific, displaying highest expression in roots. OcUGlcAE3 was UDP-d-glucuronic acid 4-epimerase and thus deemed to be involved in the biosynthesis of root polysaccharides. Moreover, OcUGlcAE3 was proposed to be environmentally induced. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Anti-Complementary Components of Helicteres angustifolia
Molecules 2016, 21(11), 1506; doi:10.3390/molecules21111506
Received: 11 October 2016 / Revised: 5 November 2016 / Accepted: 6 November 2016 / Published: 10 November 2016
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Abstract
A first phenalenon derivative with an acetyl side chain at C-8, 8-acetyl-9-hydroxy-3-methoxy-7-methyl-1-phenalenon (compound 1), and a pair of new sesquilignan epimers at C-7″ of hedyotol C and hedyotol D analogs, hedyotol C 7″-O-β-d-glucopyranoside (compound 2) and hedyotol
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A first phenalenon derivative with an acetyl side chain at C-8, 8-acetyl-9-hydroxy-3-methoxy-7-methyl-1-phenalenon (compound 1), and a pair of new sesquilignan epimers at C-7″ of hedyotol C and hedyotol D analogs, hedyotol C 7″-O-β-d-glucopyranoside (compound 2) and hedyotol D 7″-O-β-d-glucopyranoside (compound 3) were isolated from the aerial parts of Helicteres angustifolia together with nine known compounds (412). Their structures were elucidated on the basis of spectroscopic methods, including mass spectroscopy, and 1D and 2D nuclear magnetic resonance. Eleven isolates exhibited anti-complementary activity. In particular, compounds 4 and 5 exhibited potent anti-complementary activities against the classical and alternative pathways with CH50 values of 0.040 ± 0.009 and 0.009 ± 0.002 mM, and AP50 values of 0.105 ± 0.015 and 0.021 ± 0.003 mM, respectively. The targets of compounds 4 and 5 in the complement activation cascade were also identified. In conclusion, the anti-complementary components of H. angustifolia possessed chemical diversity and consisted mostly of flavonoids and lignans in this study. Full article
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Open AccessArticle TTF1, in the Form of Nanoparticles, Inhibits Angiogenesis, Cell Migration and Cell Invasion In Vitro and In Vivo in Human Hepatoma through STAT3 Regulation
Molecules 2016, 21(11), 1507; doi:10.3390/molecules21111507
Received: 12 October 2016 / Revised: 3 November 2016 / Accepted: 5 November 2016 / Published: 10 November 2016
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Abstract
TTF1-NP (5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone nanoparticles), derived from the traditional Changbai Mountain medicinal plant Sorbaria sorbifolia (SS), has been showed its anti-cancer effect in various liver cancer cell types and tissues. The present study was designed to evaluate the antitumor mechanism of the TTF1-NP against HepG2
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TTF1-NP (5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone nanoparticles), derived from the traditional Changbai Mountain medicinal plant Sorbaria sorbifolia (SS), has been showed its anti-cancer effect in various liver cancer cell types and tissues. The present study was designed to evaluate the antitumor mechanism of the TTF1-NP against HepG2 hepatoma cells and HepG2 cells-induced hepatocarcinoma (HCC) in nude mouse model. Here we demonstrated that TTF1-NP inhibits tube formation of HUVECs and HepG2 cell migration and invasion, and inhibits tumor growth in nude mice implanted with HepG2 cells through the downregulation of STAT3 protein and activation, along with VEGF, KDR, bFGF, MMP2 and MMP9 levels. We further revealed that TTF1-NP decreased the DNA-binding capacity of STAT3. Together our results provide a mechanism by which TTF1-NP suppresses cancer cell migration, invasion and angiogenesis through the action of STAT3 and suggests TTF1-NP as a potential therapy for hepatocellular cancer treatment. Full article
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Open AccessArticle Bee Venom Inhibits Porphyromonas gingivalis Lipopolysaccharides-Induced Pro-Inflammatory Cytokines through Suppression of NF-κB and AP-1 Signaling Pathways
Molecules 2016, 21(11), 1508; doi:10.3390/molecules21111508
Received: 26 September 2016 / Revised: 28 October 2016 / Accepted: 4 November 2016 / Published: 10 November 2016
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Abstract
Periodontitis is a chronic inflammatory disease that leads to destruction of tooth supporting tissues. Porphyromonas gingivalis (P. gingivalis), especially its lipopolysaccharides (LPS), is one of major pathogens that cause periodontitis. Bee venom (BV) has been widely used as a traditional medicine
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Periodontitis is a chronic inflammatory disease that leads to destruction of tooth supporting tissues. Porphyromonas gingivalis (P. gingivalis), especially its lipopolysaccharides (LPS), is one of major pathogens that cause periodontitis. Bee venom (BV) has been widely used as a traditional medicine for various diseases. Previous studies have demonstrated the anti-inflammatory, anti-bacterial effects of BV. However, a direct role and cellular mechanism of BV on periodontitis-like human keratinocytes have not been explored. Therefore, we investigated the anti-inflammatory mechanism of BV against P. gingivalis LPS (PgLPS)-induced HaCaT human keratinocyte cell line. The anti-inflammatory effect of BV was demonstrated by various molecular biological methods. The results showed that PgLPS increased the expression of Toll-like receptor (TLR)-4 and pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, and interferon (IFN)-γ. In addition, PgLPS induced activation of the signaling pathways of inflammatory cytokines-related transcription factors, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1). BV effectively inhibited those pro-inflammatory cytokines through suppression of NF-κB and AP-1 signaling pathways. These results suggest that administration of BV attenuates PgLPS-induced inflammatory responses. Furthermore, BV may be a useful treatment to anti-inflammatory therapy for periodontitis. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Enantioselective Analytical- and Preparative-Scale Separation of Hexabromocyclododecane Stereoisomers Using Packed Column Supercritical Fluid Chromatography
Molecules 2016, 21(11), 1509; doi:10.3390/molecules21111509
Received: 14 October 2016 / Revised: 4 November 2016 / Accepted: 7 November 2016 / Published: 10 November 2016
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Abstract
Hexabromocyclododecane (HBCDD) is an additive brominated flame retardant which has been listed in Annex A of the Stockholm Convention for elimination of production and use. It has been reported to persist in the environment and has the potential for enantiomer-specific degradation, accumulation, or
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Hexabromocyclododecane (HBCDD) is an additive brominated flame retardant which has been listed in Annex A of the Stockholm Convention for elimination of production and use. It has been reported to persist in the environment and has the potential for enantiomer-specific degradation, accumulation, or both, making enantioselective analyses increasingly important. The six main stereoisomers of technical HBCDD (i.e., the (+) and (−) enantiomers of α-, β-, and γ-HBCDD) were separated and isolated for the first time using enantioselective packed column supercritical fluid chromatography (pSFC) separation methods on a preparative scale. Characterization was completed using published chiral liquid chromatography (LC) methods and elution profiles, as well as X-ray crystallography, and the isolated fractions were definitively identified. Additionally, the resolution of the enantiomers, along with two minor components of the technical product (δ- and ε-HBCDD), was investigated on an analytical scale using both LC and pSFC separation techniques, and changes in elution order were highlighted. Baseline separation of all HBCDD enantiomers was achieved by pSFC on an analytical scale using a cellulose-based column. The described method emphasizes the potential associated with pSFC as a green method of isolating and analyzing environmental contaminants of concern. Full article
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Open AccessArticle Simultaneous Determination of Coumarin and Its Derivatives in Tobacco Products by Liquid Chromatography-Tandem Mass Spectrometry
Molecules 2016, 21(11), 1511; doi:10.3390/molecules21111511
Received: 21 July 2016 / Revised: 30 October 2016 / Accepted: 1 November 2016 / Published: 10 November 2016
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Abstract
In this paper an analytical method based on high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for the determination of coumarin and its derivatives in tobacco products was developed. The MS/MS fragmentation pathways of the eight coumarins were elucidated. The new
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In this paper an analytical method based on high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for the determination of coumarin and its derivatives in tobacco products was developed. The MS/MS fragmentation pathways of the eight coumarins were elucidated. The new analytical method was defined based on two main axes, an extraction procedure with acetonitrile and analyte detection performed by HPLC-MS/MS in electron impact mode. The excellent selectivity and sensitivity achieved in multiple reaction monitoring (MRM) mode allowed satisfactory confirmation and quantitation for the coumarin flavor additives. Under the optimized gradient elution conditions, it took only 4.5 min to separate all eight coumarins. Good linearity for all the analytes were confirmed by the correlation coefficient r2, ranging from 0.9987 to 0.9996. The limits of detection (LODs) and limits of quantitation (LOQs) of these compounds were in the range of 0.5–1.7 μg/kg and 1.7–5.2 μg/kg, respectively. The average recoveries at three spiked levels (LOQ, 1.5LOQ, 2LOQ) were all in the range of 69.6%–95.1% with RSDs (n = 6) lower than 5.3%. The method of HPLC-MS/MS developed in this study was initially applied to the research of coumarin flavor additives in tobacco products collected from the located market in Beijing from China and proved to be accurate, sensitive, convenient and practical. Full article
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Open AccessArticle Kinetic Spectrophotometric Method for the 1,4-Diionic Organophosphorus Formation in the Presence of Meldrum′s Acid: Stopped-Flow Approach
Molecules 2016, 21(11), 1514; doi:10.3390/molecules21111514
Received: 6 August 2016 / Revised: 1 November 2016 / Accepted: 2 November 2016 / Published: 11 November 2016
Cited by 2 | PDF Full-text (2920 KB) | HTML Full-text | XML Full-text
Abstract
The kinetics of the reaction between triphenylphosphine (TPP) and dimethyl acetylenedicarboxylate (DMAD) in the presence of Meldrum’s acid (MA) for the generation of the 1,4-diionic organophosphorus compound has been investigated using the stopped-flow and UV-VIS spectrophotometry techniques. The first step of the reaction
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The kinetics of the reaction between triphenylphosphine (TPP) and dimethyl acetylenedicarboxylate (DMAD) in the presence of Meldrum’s acid (MA) for the generation of the 1,4-diionic organophosphorus compound has been investigated using the stopped-flow and UV-VIS spectrophotometry techniques. The first step of the reaction between TPP and DMAD for the generation of (I1) in ethanol was followed by the stopped-flow apparatus. This step was recognized as a fast step. The reaction between the intermediate (I1) and MA showed first-order kinetics, and it was followed by the UV-VIS spectrophotometry technique. The activation parameters for the slow step of the proposed mechanism were determined using two linearized forms of the Eyring equation. From the temperature, concentration and solvent studies, the activation energy (Ea = 20.16 kJ·mol−1) and the related activation parameters (ΔG = 71.17 ± 0.015 kJ·mol−1, ΔS = −185.49 ± 0.026 J·mol−1 and ΔH =17.72 ± 0.007 kJ·mol−1) were calculated. The experimental data indicated that the reaction was zero-order in MA and second-order overall. The proposed mechanism was confirmed with the observed kinetic data obtained from the UV-VIS and stopped-flow techniques. Full article
(This article belongs to the Special Issue Recent Advances in Flow Chemistry)
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Open AccessArticle Inhibitory Interactions of Aspalathus linearis (Rooibos) Extracts and Compounds, Aspalathin and Z-2-(β-d-Glucopyranosyloxy)-3-phenylpropenoic Acid, on Cytochromes Metabolizing Hypoglycemic and Hypolipidemic Drugs
Molecules 2016, 21(11), 1515; doi:10.3390/molecules21111515
Received: 5 October 2016 / Revised: 21 October 2016 / Accepted: 29 October 2016 / Published: 12 November 2016
Cited by 2 | PDF Full-text (1777 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Rooibos extract, due to its glucose and lipid lowering effects, has potential as a nutraceutical for improvement of metabolic dysfunction. Potential herb-drug interactions as a result of the use of natural products are of increasing concern. Cytochrome P450 enzymes, CYP2C8, CYP2C9, and CYP3A4,
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Rooibos extract, due to its glucose and lipid lowering effects, has potential as a nutraceutical for improvement of metabolic dysfunction. Potential herb-drug interactions as a result of the use of natural products are of increasing concern. Cytochrome P450 enzymes, CYP2C8, CYP2C9, and CYP3A4, are important in the metabolism of hypoglycemic drugs, such as thiazolidinediones (TZDs) and sulfonylureas, and hypocholesterolemic drugs, such as atorvastatin. This study investigated the effects of rooibos extracts, prepared from “unfermented” and “fermented” rooibos plant material and two of the major bioactive compounds, Z-2-(β-d-glucopyranosyloxy)-3-phenylpropenoic acid (PPAG) and aspalathin (ASP), on Vivid® recombinant CYP450 enzymes. Unfermented (GRT) and fermented (FRE) rooibos extracts inhibited the activity of CYP2C8 (7.69 ± 8.85 µg/mL and 8.93 ± 8.88 µg/mL, respectively) and CYP3A4 (31.33 ± 4.69 µg/mL and 51.44 ± 4.31 µg/mL, respectively) based on their respective IC50 concentrations. Both extracts dose- and time-dependently inhibited CYP2C8 activity, but only time-dependently inhibited CYP2C9. CYP3A4 showed concentration-dependent inhibition by ASP, GRT, and FRE at 25, 50, and 100 µg/mL concentrations. ASP, GRT, and FRE time-dependently inhibited CYP3A4 activity with GRT and FRE showing a more potent time-dependent inhibition, comparable to erythromycin. These findings suggest that herb-drug interactions may occur when nutraceuticals containing rooibos extracts are co-administered with hypoglycemic drugs such as TZDs, sulfonylureas, and dyslipidemic drug, atorvastatin. Full article
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Open AccessArticle Selenium Nanoparticles Attenuate Oxidative Stress and Testicular Damage in Streptozotocin-Induced Diabetic Rats
Molecules 2016, 21(11), 1517; doi:10.3390/molecules21111517
Received: 26 September 2016 / Revised: 4 November 2016 / Accepted: 8 November 2016 / Published: 19 November 2016
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Abstract
We investigated the protective and antioxidative effects of selenium nanoparticles (SeNPs) in streptozotocin STZ-induced diabetic rats. STZ-diabetic rats were exposed daily to treatments with SeNPs and/or insulin and then the effect of these treatments on the parameters correlated to oxidative damage of the
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We investigated the protective and antioxidative effects of selenium nanoparticles (SeNPs) in streptozotocin STZ-induced diabetic rats. STZ-diabetic rats were exposed daily to treatments with SeNPs and/or insulin and then the effect of these treatments on the parameters correlated to oxidative damage of the rat testes were assessed. Biochemical analysis revealed that SeNPs are able to ameliorate the reduction in the serum testosterone caused by STZ-induced diabetes. Furthermore, SeNPs could significantly decrease testicular tissue oxidative stress markers, namely lipid peroxidation and nitric oxide. In contrast, treatment of the STZ-diabetic rats with SeNPs increased the glutathione content and antioxidant enzyme activities in testicular tissues. Moreover, microscopic analysis proved that SeNPs are able to prevent histological damage in the testes of STZ-diabetic rats. Molecular analysis revealed that the mRNA level of Bcl-2 (B-cell lymphoma 2) is significantly upregulated. On the contrary, the mRNA level of Bax (Bcl-2 Associated X Protein) was significantly downregulated. Furthermore, treatment of STZ-diabetic rats with SeNPs led to an elevation in the expression of PCNA (Proliferating Cell Nuclear Antigen Gene). Interestingly, the insulin treatment also exhibited a significant improvement in the testicular function in STZ-diabetic rats. Collectively, our results demonstrated the possible effects of SeNPs in attenuating diabetes-induced oxidative damage, in particular in testicular tissue. Full article
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Open AccessArticle Development of Amylose- and β-Cyclodextrin-Based Chiral Fluorescent Sensors Bearing Terthienyl Pendants
Molecules 2016, 21(11), 1518; doi:10.3390/molecules21111518
Received: 13 October 2016 / Revised: 1 November 2016 / Accepted: 8 November 2016 / Published: 11 November 2016
Cited by 4 | PDF Full-text (1768 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phenylcarbamate derivatives of amylose and β-cyclodextrin show excellent chiral recognition when used as chiral stationary phases (CSPs) for high-performance liquid chromatography. To open up new possibilities of carbohydrate-based materials, we developed chiral fluorescent sensors based on amylose and β-cyclodextrin (Am-1b and CyD-
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Phenylcarbamate derivatives of amylose and β-cyclodextrin show excellent chiral recognition when used as chiral stationary phases (CSPs) for high-performance liquid chromatography. To open up new possibilities of carbohydrate-based materials, we developed chiral fluorescent sensors based on amylose and β-cyclodextrin (Am-1b and CyD-1b, respectively) by attaching fluorescent π-conjugated units on their side chains. Their recognition abilities toward chiral analytes containing a nitrophenyl unit were evaluated by measuring the enantioselective fluorescence quenching behavior. Both sensors showed the same degree of enantioselective fluorescence response for various aromatic nitro compounds. However, in some cases, their enantioselectivities were different depending on the analytes. The difference in the chiral recognition abilities between Am-1b and CyD-1b seems to be based on the structural difference of their inherent backbones, that is, the one-handed helical structure and cyclic structure, respectively. The study on the resolution ability of the Am-1b-based CSP revealed that the terthienyl-based pendant of Am-1b provides not only a fluorescent functionality but also a different chiral recognition site from that of amylose tris(phenylcarbamate). Full article
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