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Molecules, Volume 21, Issue 6 (June 2016)

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Cover Story Natural products have always been exploited to promote health and have served as a valuable source [...] Read more.
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Editorial

Jump to: Research, Review, Other

Open AccessEditorial Special Issue: Coinage Metal (Copper, Silver, and Gold) Catalysis
Molecules 2016, 21(6), 746; doi:10.3390/molecules21060746
Received: 3 June 2016 / Accepted: 4 June 2016 / Published: 8 June 2016
Cited by 1 | PDF Full-text (145 KB) | HTML Full-text | XML Full-text
Abstract
The subject of catalysis by coinage metals (copper, silver, and gold) comes up increasingly day-by-day. This Special Issue aims to cover the numerous aspects of the use of these metals as catalysts for several reactions. It deals with synthesis and characterization of copper,
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The subject of catalysis by coinage metals (copper, silver, and gold) comes up increasingly day-by-day. This Special Issue aims to cover the numerous aspects of the use of these metals as catalysts for several reactions. It deals with synthesis and characterization of copper, silver and gold based catalysis, their characterization and use, both for heterogeneous and homogeneous catalysis, and some of their potential applications. Full article
(This article belongs to the Special Issue Coinage Metal (Copper, Silver, and Gold) Catalysis)

Research

Jump to: Editorial, Review, Other

Open AccessArticle Methyl Jasmonate: An Alternative for Improving the Quality and Health Properties of Fresh Fruits
Molecules 2016, 21(6), 567; doi:10.3390/molecules21060567
Received: 14 March 2016 / Revised: 19 April 2016 / Accepted: 21 April 2016 / Published: 31 May 2016
Cited by 3 | PDF Full-text (1177 KB) | HTML Full-text | XML Full-text
Abstract
Methyl jasmonate (MeJA) is a plant growth regulator belonging to the jasmonate family. It plays an important role as a possible airborne signaling molecule mediating intra- and inter-plant communications and modulating plant defense responses, including antioxidant systems. Most assessments of this compound have
[...] Read more.
Methyl jasmonate (MeJA) is a plant growth regulator belonging to the jasmonate family. It plays an important role as a possible airborne signaling molecule mediating intra- and inter-plant communications and modulating plant defense responses, including antioxidant systems. Most assessments of this compound have dealt with post-harvest fruit applications, demonstrating induced plant resistance against the detrimental impacts of storage (chilling injuries and pathogen attacks), enhancing secondary metabolites and antioxidant activity. On the other hand, the interactions between MeJA and other compounds or technological tools for enhancing antioxidant capacity and quality of fruits were also reviewed. The pleiotropic effects of MeJA have raisen numerous as-yet unanswered questions about its mode of action. The aim of this review was endeavored to clarify the role of MeJA on improving pre- and post-harvest fresh fruit quality and health properties. Interestingly, the influence of MeJA on human health will be also discussed. Full article
Open AccessArticle ESeroS-GS Protects Neuronal Cells from Oxidative Stress by Stabilizing Lysosomes
Molecules 2016, 21(6), 637; doi:10.3390/molecules21060637
Received: 24 March 2016 / Revised: 9 May 2016 / Accepted: 10 May 2016 / Published: 25 May 2016
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Abstract
γ-l-glutamyl-S-[2-[[[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl]oxy]carbonyl]-3-[[2-(1H-indol-3-yl)ethyl]amino]-3-oxopropyl]-l-cysteinylglycine sodium salt (ESeroS-GS) is a water-soluble derivative of α-tocopherol (vitamin E). We reported previously that ESeroS-GS can act as an anti-inflammatory agent and can induce cell death in breast cancer cells. However,
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γ-l-glutamyl-S-[2-[[[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl]oxy]carbonyl]-3-[[2-(1H-indol-3-yl)ethyl]amino]-3-oxopropyl]-l-cysteinylglycine sodium salt (ESeroS-GS) is a water-soluble derivative of α-tocopherol (vitamin E). We reported previously that ESeroS-GS can act as an anti-inflammatory agent and can induce cell death in breast cancer cells. However, the potential antioxidant capacities of ESeroS-GS remain elusive. Here, we measured its scavenging effects on free radicals and evaluated its protective effects on neuronal cells against oxidative stress. The results indicated that ESeroS-GS effectively scavenged both 2,2’-azinobis(3-ethylbenzothiazoline)-6-sulfonate free radicals (ABTS•+) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals, and attenuated H2O2-induced neuronal cell death. H2O2 treatment induced lysosomal membrane permeabilization rapidly, and caused the redistribution of lysosomal proteases, which were responsible for the neuronal cell death. ESeroS-GS abolished the interaction between tBid and the lysosomal membranes, blocked the translocation of tBid to the lysosomal membranes, decreased its oligomerization within the membrane circumstances, prevented the lysosomal membrane permeabilization, and thus attenuated the neuronal cell death. These data suggest that ESeroS-GS protected the neuronal cells from oxidative stress by stabilizing lysosomal membranes, and thus might act as a novel neuroprotector for neuronal diseases associated with oxidative stress. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Bioactive Constituents of Zanthoxylum rhetsa Bark and Its Cytotoxic Potential against B16-F10 Melanoma Cancer and Normal Human Dermal Fibroblast (HDF) Cell Lines
Molecules 2016, 21(6), 652; doi:10.3390/molecules21060652
Received: 1 April 2016 / Revised: 7 May 2016 / Accepted: 11 May 2016 / Published: 24 May 2016
Cited by 4 | PDF Full-text (1379 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Zanthoxylum rhetsa is an aromatic tree, known vernacularly as “Indian Prickly Ash”. It has been predominantly used by Indian tribes for the treatment of many infirmities like diabetes, inflammation, rheumatism, toothache and diarrhea. In this study, we identified major volatile constituents present in
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Zanthoxylum rhetsa is an aromatic tree, known vernacularly as “Indian Prickly Ash”. It has been predominantly used by Indian tribes for the treatment of many infirmities like diabetes, inflammation, rheumatism, toothache and diarrhea. In this study, we identified major volatile constituents present in different solvent fractions of Z. rhetsa bark using GC-MS analysis and isolated two tetrahydrofuran lignans (yangambin and kobusin), a berberine alkaloid (columbamine) and a triterpenoid (lupeol) from the bioactive chloroform fraction. The solvent fractions and purified compounds were tested for their cytotoxic potential against human dermal fibroblasts (HDF) and mouse melanoma (B16-F10) cells, using the MTT assay. All the solvent fractions and purified compounds were found to be non-cytotoxic to HDF cells. However, the chloroform fraction and kobusin exhibited cytotoxic effect against B16-F10 melanoma cells. The presence of bioactive lignans and alkaloids were suggested to be responsible for the cytotoxic property of Z. rhetsa bark against B16-F10 cells. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Catalysts with Cerium in a Membrane Reactor for the Removal of Formaldehyde Pollutant from Water Effluents
Molecules 2016, 21(6), 668; doi:10.3390/molecules21060668
Received: 18 March 2016 / Revised: 29 April 2016 / Accepted: 13 May 2016 / Published: 24 May 2016
Cited by 1 | PDF Full-text (5191 KB) | HTML Full-text | XML Full-text
Abstract
We report the synthesis of cerium oxide, cobalt oxide, mixed cerium, and cobalt oxides and a Ce–Co/Al2O3 membrane, which are employed as catalysts for the catalytic wet oxidation (CWO) reaction process and the removal of formaldehyde from industrial effluents. Formaldehyde
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We report the synthesis of cerium oxide, cobalt oxide, mixed cerium, and cobalt oxides and a Ce–Co/Al2O3 membrane, which are employed as catalysts for the catalytic wet oxidation (CWO) reaction process and the removal of formaldehyde from industrial effluents. Formaldehyde is present in numerous waste streams from the chemical industry in a concentration low enough to make its recovery not economically justified but high enough to create an environmental hazard. Common biological degradation methods do not work for formaldehyde, a highly toxic but refractory, low biodegradability substance. The CWO reaction is a recent, promising alternative that also permits much lower temperature and pressure conditions than other oxidation processes, resulting in economic benefits. The CWO reaction employing Ce- and Co-containing catalysts was carried out inside a slurry batch reactor and a membrane reactor. Experimental results are reported. Next, a mixed Ce–Co oxide film was supported on an γ-alumina membrane used in a catalytic membrane reactor to compare formaldehyde removal between both types of systems. Catalytic materials with cerium and with a relatively large amount of cerium favored the transformation of formaldehyde. Cerium was present as cerianite in the catalytic materials, as indicated by X-ray diffraction patterns. Full article
(This article belongs to the Special Issue Membrane Catalysis)
Open AccessArticle Synthesis and Anticancer Activities of Novel Guanylhydrazone and Aminoguanidine Tetrahydropyran Derivatives
Molecules 2016, 21(6), 671; doi:10.3390/molecules21060671
Received: 28 March 2016 / Revised: 5 May 2016 / Accepted: 11 May 2016 / Published: 21 June 2016
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Abstract
In this paper we present the convenient syntheses of six new guanylhydrazone and aminoguanidine tetrahydropyran derivatives 27. The guanylhydrazone 2, 3 and 4 were prepared in 100% yield, starting from corresponding aromatic ketones 8ac and aminoguanidine hydrochloride
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In this paper we present the convenient syntheses of six new guanylhydrazone and aminoguanidine tetrahydropyran derivatives 27. The guanylhydrazone 2, 3 and 4 were prepared in 100% yield, starting from corresponding aromatic ketones 8ac and aminoguanidine hydrochloride accessed by microwave irradiation. The aminoguanidine 5, 6 and 7 were prepared by reduction of guanylhydrazone 24 with sodium cyanoborohydride (94% yield of 5, and 100% yield of 6 and 7). The aromatic ketones 8ac were prepared from the Barbier reaction followed by the Prins cyclization reaction (two steps, 63%–65% and 95%–98%). Cytotoxicity studies have demonstrated the effects of compounds 27 in various cancer and normal cell lines. That way, we showed that these compounds decreased cell viabilities in a micromolar range, and from all the compounds tested we can state that, at least, compound 3 can be considered a promising molecule for target-directed drug design. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessArticle Liquid Crystal Formation from Sunflower Oil: Long Term Stability Studies
Molecules 2016, 21(6), 680; doi:10.3390/molecules21060680
Received: 12 March 2016 / Revised: 27 April 2016 / Accepted: 4 May 2016 / Published: 9 June 2016
Cited by 1 | PDF Full-text (15540 KB) | HTML Full-text | XML Full-text
Abstract
The Brazilian biodiversity offers a multiplicity of raw materials with great potential in cosmetics industry applications. Some vegetable oils and fatty esters increase skin hydration by occlusivity, keeping the skin hydrated and with a shiny appearance. Sunflower (Helianthus annus L.) oil is
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The Brazilian biodiversity offers a multiplicity of raw materials with great potential in cosmetics industry applications. Some vegetable oils and fatty esters increase skin hydration by occlusivity, keeping the skin hydrated and with a shiny appearance. Sunflower (Helianthus annus L.) oil is widely employed in cosmetic emulsions in the form of soaps, creams, moisturizers and skin cleansers due to the presence of polyphenols and its high vitamin E content. Liquid crystals are systems with many applications in both pharmaceutical and cosmetic formulations and are easily detected by microscopy under polarized light due to their birefringence properties. The aim of this research was to develop emulsions from natural sunflower oil for topical uses. Sunflower oil (75.0% w/w) was combined with liquid vaseline (25.0% w/w) employing a natural self-emulsifying base (SEB) derivative. The high temperature of the emulsification process did not influence the antioxidant properties of sunflower oil. Fatty esters were added to cosmetic formulations and extended stability tests were performed to characterize the emulsions. Fatty esters like cetyl palmitate and cetyl ester increase the formation of anisotropic structures. O/W emulsions showed acidic pH values and pseudoplastic behavior. The presence of a lamellar phase was observed after a period of 90 days under different storage conditions. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Ethanolic Extract of Acanthopanax koreanum Nakai Alleviates Alcoholic Liver Damage Combined with a High-Fat Diet in C57BL/6J Mice
Molecules 2016, 21(6), 681; doi:10.3390/molecules21060681
Received: 20 March 2016 / Revised: 15 May 2016 / Accepted: 18 May 2016 / Published: 24 May 2016
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Abstract
Alcoholic and nonalcoholic liver steatosis have an indistinguishable spectrum of histological features and liver enzyme elevations. In this study, we investigated the potential of the ethanolic extract of Acanthopanax koreanum Nakai (AK) to protect against experimental alcoholic liver disease in a mouse model
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Alcoholic and nonalcoholic liver steatosis have an indistinguishable spectrum of histological features and liver enzyme elevations. In this study, we investigated the potential of the ethanolic extract of Acanthopanax koreanum Nakai (AK) to protect against experimental alcoholic liver disease in a mouse model that couples diet and daily ethanol bolus gavage. Fifty-six C57BL/6J mice were randomly divided into seven groups: normal control (NC), alcohol control (AC), alcohol/HFD control (AH), low-dose (1%) AK in alcohol group (ACL), high-dose (3%) AK in alcohol group (ACH), low-dose AK in alcohol/HFD group (AHL), and high-dose AK in alcohol/HFD group (AHH). The AH group showed more severe damage than the AC group in terms of biochemical and molecular data that were observed in this study. The administration of AK exerted remarkable effects in: plasma ALT (p < 0.0001), total lipid (p = 0.014), TG (p = 0.0037) levels; CPT-1α (p = 0.0197), TLR4 (p < 0.0001), CD14 (p = 0.0002), IL-6 (p = 0.0264) and MCP-1 (p = 0.0045) gene expressions; and ALDH (p < 0.0001) and CAT (p = 0.0076) activities. The data suggested that at least the high dose AK might confer protection against alcoholic liver damage combined with an HFD by accelerating lipid oxidation and alcohol metabolism and by suppressing the inflammatory response, including the TLR pathway. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Bioprospecting the Curculigoside-Cinnamic Acid-Rich Fraction from Molineria latifolia Rhizome as a Potential Antioxidant Therapeutic Agent
Molecules 2016, 21(6), 682; doi:10.3390/molecules21060682
Received: 11 April 2016 / Revised: 9 May 2016 / Accepted: 19 May 2016 / Published: 17 June 2016
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Abstract
Increasing evidence from both experimental and clinical studies depicts the involvement of oxidative stress in the pathogenesis of various diseases. Specifically, disruption of homeostatic redox balance in accumulated body fat mass leads to obesity-associated metabolic syndrome. Strategies for the restoration of redox balance,
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Increasing evidence from both experimental and clinical studies depicts the involvement of oxidative stress in the pathogenesis of various diseases. Specifically, disruption of homeostatic redox balance in accumulated body fat mass leads to obesity-associated metabolic syndrome. Strategies for the restoration of redox balance, potentially by exploring potent plant bioactives, have thus become the focus of therapeutic intervention. The present study aimed to bioprospect the potential use of the curculigoside-cinnamic acid-rich fraction from Molineria latifolia rhizome as an antioxidant therapeutic agent. The ethyl acetate fraction (EAF) isolated from M. latifolia rhizome methanolic extract (RME) contained the highest amount of phenolic compounds, particularly curculigoside and cinnamic acid. EAF demonstrated glycation inhibitory activities in both glucose- and fructose-mediated glycation models. In addition, in vitro chemical-based and cellular-based antioxidant assays showed that EAF exhibited high antioxidant activities and a protective effect against oxidative damage in 3T3-L1 preadipocytes. Although the efficacies of individual phenolics differed depending on the structure and concentration, a correlational study revealed strong correlations between total phenolic contents and antioxidant capacities. The results concluded that enriched phenolic contents in EAF (curculigoside-cinnamic acid-rich fraction) contributed to the overall better reactivity. Our data suggest that this bioactive-rich fraction warrants therapeutic potential against oxidative stress-related disorders. Full article
Open AccessArticle Clematichinenoside (AR) Attenuates Hypoxia/Reoxygenation-Induced H9c2 Cardiomyocyte Apoptosis via a Mitochondria-Mediated Signaling Pathway
Molecules 2016, 21(6), 683; doi:10.3390/molecules21060683
Received: 11 April 2016 / Revised: 8 May 2016 / Accepted: 20 May 2016 / Published: 30 May 2016
Cited by 2 | PDF Full-text (3517 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mitochondria-mediated cardiomyocyte apoptosis is involved in myocardial ischemia/reperfusion (MI/R) injury. Clematichinenoside (AR) is a triterpenoid saponin isolated from the roots of Clematis chinensis with antioxidant and anti-inflammatory cardioprotection effects against MI/R injury, yet the anti-apoptotic effect and underlying mechanisms of AR in MI/R
[...] Read more.
Mitochondria-mediated cardiomyocyte apoptosis is involved in myocardial ischemia/reperfusion (MI/R) injury. Clematichinenoside (AR) is a triterpenoid saponin isolated from the roots of Clematis chinensis with antioxidant and anti-inflammatory cardioprotection effects against MI/R injury, yet the anti-apoptotic effect and underlying mechanisms of AR in MI/R injury remain unclear. We hypothesize that AR may improve mitochondrial function to inhibit MI/R-induced cardiomyocyte apoptosis. In this study, we replicated an in vitro H9c2 cardiomyocyte MI/R model by hypoxia/reoxygenation (H/R) treatment. The viability of H9c2 cardiomyocytes was determined by MTT assay; apoptosis was evaluated by flow cytometry and TUNEL experiments; mitochondrial permeability transition pore (mPTP) opening was analyzed by a calcein-cobalt quenching method; and mitochondrial membrane potential (ΔΨm) was detected by JC-1. Moreover, we used western blots to determine the mitochondrial cytochrome c translocation to cytosolic and the expression of caspase-3, Bcl-2, and Bax proteins. These results showed that the application of AR decreased the ratio of apoptosis and the extent of mPTP opening, but increased ΔΨm. AR also inhibited H/R-induced release of mitochondrial cytochrome c and decreased the expression of the caspase-3, Bax proteins. Conversely, it remarkably increased the expression of Bcl-2 protein. Taken together, these results revealed that AR protects H9c2 cardiomyocytes against H/R-induced apoptosis through mitochondrial-mediated apoptotic signaling pathway. Full article
(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)
Open AccessArticle Synthesis and Characterization of Glutamic-Chitosan Hydrogel for Copper and Nickel Removal from Wastewater
Molecules 2016, 21(6), 684; doi:10.3390/molecules21060684
Received: 24 March 2016 / Revised: 17 May 2016 / Accepted: 20 May 2016 / Published: 25 May 2016
Cited by 1 | PDF Full-text (5398 KB) | HTML Full-text | XML Full-text
Abstract
Chitosan was reacted with four concentrations (2.5, 5, 10 and 20 mmol) of glutamic acid resulting in four types of glutamic-chitosan hydrogels (GCs), the activity of the resulted compounds on the removal of copper(II) and nickel(II) from wastewater were tested. The results indicated
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Chitosan was reacted with four concentrations (2.5, 5, 10 and 20 mmol) of glutamic acid resulting in four types of glutamic-chitosan hydrogels (GCs), the activity of the resulted compounds on the removal of copper(II) and nickel(II) from wastewater were tested. The results indicated that by increasing glutamic acid concentration from GCs-1 to GCs-4, the efficiency of removing Cu(II) and Ni(II) were decreased, which may be due to a decrease in the pore size of the hydrogels as a result of the increased degree of crosslinking. Full article
(This article belongs to the Special Issue Chitin, Chitosan and Related Enzymes)
Open AccessArticle Characterization of New PEEK/HA Composites with 3D HA Network Fabricated by Extrusion Freeforming
Molecules 2016, 21(6), 687; doi:10.3390/molecules21060687
Received: 7 April 2016 / Revised: 20 May 2016 / Accepted: 20 May 2016 / Published: 26 May 2016
Cited by 4 | PDF Full-text (7903 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Addition of bioactive materials such as calcium phosphates or Bioglass, and incorporation of porosity into polyetheretherketone (PEEK) has been identified as an effective approach to improve bone-implant interfaces and osseointegration of PEEK-based devices. In this paper, a novel production technique based on the
[...] Read more.
Addition of bioactive materials such as calcium phosphates or Bioglass, and incorporation of porosity into polyetheretherketone (PEEK) has been identified as an effective approach to improve bone-implant interfaces and osseointegration of PEEK-based devices. In this paper, a novel production technique based on the extrusion freeforming method is proposed that yields a bioactive PEEK/hydroxyapatite (PEEK/HA) composite with a unique configuration in which the bioactive phase (i.e., HA) distribution is computer-controlled within a PEEK matrix. The 100% interconnectivity of the HA network in the biocomposite confers an advantage over alternative forms of other microstructural configurations. Moreover, the technique can be employed to produce porous PEEK structures with controlled pore size and distribution, facilitating greater cellular infiltration and biological integration of PEEK composites within patient tissue. The results of unconfined, uniaxial compressive tests on these new PEEK/HA biocomposites with 40% HA under both static and cyclic mode were promising, showing the composites possess yield and compressive strength within the range of human cortical bone suitable for load bearing applications. In addition, preliminary evidence supporting initial biological safety of the new technique developed is demonstrated in this paper. Sufficient cell attachment, sustained viability in contact with the sample over a seven-day period, evidence of cell bridging and matrix deposition all confirmed excellent biocompatibility. Full article
(This article belongs to the Special Issue Biomaterials and Bioprinting)
Open AccessArticle Phenolic Profile and Antioxidant Potential of Leaves from Selected Cotoneaster Medik. Species
Molecules 2016, 21(6), 688; doi:10.3390/molecules21060688
Received: 29 April 2016 / Revised: 19 May 2016 / Accepted: 20 May 2016 / Published: 26 May 2016
Cited by 3 | PDF Full-text (2397 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The antioxidant efficiency of 70% aqueous methanolic extracts from the leaves of twelve selected Cotoneaster Medik. species was evaluated using four complementary in vitro tests based on SET- (single electron transfer) and HAT-type (hydrogen atom transfer) mechanisms (DPPH, FRAP, O2•− and
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The antioxidant efficiency of 70% aqueous methanolic extracts from the leaves of twelve selected Cotoneaster Medik. species was evaluated using four complementary in vitro tests based on SET- (single electron transfer) and HAT-type (hydrogen atom transfer) mechanisms (DPPH, FRAP, O2•− and H2O2 scavenging assays). The samples exhibited the dose-dependent responses in all assays with activity parameters of EC50 = 18.5–34.5 µg/mL for DPPH; 0.9–3.8 mmol Fe2+/g for FRAP; SC50 = 27.7–74.8 µg/mL for O2•−; and SC50 = 29.0–91.3 µg/mL for H2O2. Significant linear correlations (|r| = 0.76–0.97, p < 0.01) between activity parameters and total contents of phenolics (5.2%–15.4% GAE) and proanthocyanidins (2.1%–15.0% CYE), with weak or no effects for chlorogenic acid isomers (0.69%–2.93%) and total flavonoids (0.28%–1.40%) suggested that among the listed polyphenols, proanthocyanidins are the most important determinants of the tested activity. UHPLC-PDA-ESI-QTOF-MS analyses led to detection of 34 polyphenols, of which 10 B-type procyanidins, 5 caffeoylquinic acids and 14 flavonoids were identified. After cluster analysis of the data matrix, the leaves of Cotoneaster zabelii, C. splendens, C. bullatus, C. divaricatus, C. hjelmqvistii and C. lucidus were selected as the most promising sources of natural antioxidants, exhibiting the highest phenolic levels and antioxidant capacities, and therefore the greatest potential for pharmaceutical applications. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Enantiopure Trisubstituted Tetrahydrofurans with Appendage Diversity: Vinyl Sulfone- and Vinyl Sulfoxide-Modified Furans Derived from Carbohydrates as Synthons for Diversity Oriented Synthesis
Molecules 2016, 21(6), 690; doi:10.3390/molecules21060690
Received: 19 March 2016 / Revised: 12 May 2016 / Accepted: 19 May 2016 / Published: 26 May 2016
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Abstract
Enantiomerically pure 2-substituted-2,5-dihydro-3-(aryl) sulfonyl/sulfinyl furans have been prepared from the easily accessible carbohydrate derivatives. The orientation of the substituents attached at the C-2 position of furans is sufficient to control the diastereoselectivity of the addition of various nucleophiles to the vinyl sulfone/sulfoxide-modified tetrahydrofurans,
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Enantiomerically pure 2-substituted-2,5-dihydro-3-(aryl) sulfonyl/sulfinyl furans have been prepared from the easily accessible carbohydrate derivatives. The orientation of the substituents attached at the C-2 position of furans is sufficient to control the diastereoselectivity of the addition of various nucleophiles to the vinyl sulfone/sulfoxide-modified tetrahydrofurans, irrespective of the size of the group. The orientation of the substituents at the C-2 center also suppresses the influence of sulfoxides on the diastereoselectivity of the addition of various nucleophiles. The strategy leads to the creation of appendage diversity, affording a plethora of enantiomerically pure trisubstituted furanics for the first time. Full article
(This article belongs to the Special Issue Diversity Oriented Synthesis 2016)
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Open AccessArticle Expression of Terpenoid Biosynthetic Genes and Accumulation of Chemical Constituents in Valeriana fauriei
Molecules 2016, 21(6), 691; doi:10.3390/molecules21060691
Received: 2 April 2016 / Revised: 20 May 2016 / Accepted: 20 May 2016 / Published: 27 May 2016
Cited by 1 | PDF Full-text (1552 KB) | HTML Full-text | XML Full-text
Abstract
Valeriana fauriei (V. fauriei), which emits a characteristic and unpleasant odor, is important in traditional medicine. In this study, the expression of terpenoid biosynthetic genes was investigated in different organs that were also screened for volatile compounds including valerenic acid and
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Valeriana fauriei (V. fauriei), which emits a characteristic and unpleasant odor, is important in traditional medicine. In this study, the expression of terpenoid biosynthetic genes was investigated in different organs that were also screened for volatile compounds including valerenic acid and its derivatives. Specific expression patterns from different parts of V. fauriei were observed using quantitative real-time PCR (qRT-PCR). The highest transcript levels of biosynthetic genes involved in mevalonic acid (MVA) and methylerythritol phosphate (MEP) production were found in the stem. Although the amounts of volatile compounds were varied by organ, most of the volatile terpenoids were accumulated in the root. Gas chromatography mass spectrometry (GC-MS) analysis identified 128 volatile compounds, which represented 65.33% to 95.66% of total volatiles. Certain compounds were only found in specific organs. For example, isovalerenic acid and valerenic acid and its derivatives were restricted to the root. Organs with high transcript levels did not necessarily have high levels of the corresponding chemical constituents. According to these results, we hypothesize that translocation may occur between different organs in V. fauriei. Full article
(This article belongs to the Special Issue Biosynthesis of Natural Products)
Open AccessArticle Effects of Rhodomyrtus tomentosa Extract on Killing Activity of Human Neutrophils and Membrane Integrity of Enterohaemorrhagic Escherichia coli O157:H7
Molecules 2016, 21(6), 692; doi:10.3390/molecules21060692
Received: 20 February 2016 / Revised: 21 May 2016 / Accepted: 23 May 2016 / Published: 27 May 2016
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Abstract
Enterohaemorrhagic Escherichia coli (E. coli) O157:H7 is one of the most virulent causative agents of foodborne disease. Use of antibiotics for the treatment against E. coli O157:H7 infection leads to hemolytic uremic syndrome. The present study evaluated the potential of ethanolic
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Enterohaemorrhagic Escherichia coli (E. coli) O157:H7 is one of the most virulent causative agents of foodborne disease. Use of antibiotics for the treatment against E. coli O157:H7 infection leads to hemolytic uremic syndrome. The present study evaluated the potential of ethanolic leaf extract of a medicinal plant, Rhodomyrtus tomentosa in enhancing the killing activity of human neutrophils against E. coli O157:H7. In addition, the effects of the extract on membrane permeability of the organisms were studied. In the killing assay, percentage survival of the bacterial cells after being exposed to human neutrophils in the presence of various concentrations of the extract were determined. At 45 min, percentage survival of E. coli O157:H7 and E. coli ATCC 25922 after treated with neutrophils in the presence of the extract at 125–250 µg/mL was 58.48%–50.28% and 69.13%–35.35%, respectively. Furthermore, upon treatment with R. tomentosa at 250 µg/mL uptake of crystal violet by E. coli O157:H7 and E. coli ATCC 25922 was increased to 40.07% and 36.16%, respectively. Therefore, it is suggested that the extract exhibited dual effects as immunostimulant and membrane permeabilizing agent perhaps resulted in enhancing the killing activity of neutrophils against the organisms. Full article
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Open AccessArticle Efficient Preparation of Streptochlorin from Marine Streptomyces sp. SYYLWHS-1-4 by Combination of Response Surface Methodology and High-Speed Counter-Current Chromatography
Molecules 2016, 21(6), 693; doi:10.3390/molecules21060693
Received: 28 March 2016 / Revised: 16 May 2016 / Accepted: 23 May 2016 / Published: 27 May 2016
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Abstract
Since first isolated from the lipophilic extract of Streptomyces sp. SF2583, streptochlorin, has attracted a lot of attention because of its various pharmacological properties, such as antibiotic, antiallergic, antitumor, and anti-inflammatory activities. For the efficient preparation of streptochlorin from a producing strain Streptomyces
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Since first isolated from the lipophilic extract of Streptomyces sp. SF2583, streptochlorin, has attracted a lot of attention because of its various pharmacological properties, such as antibiotic, antiallergic, antitumor, and anti-inflammatory activities. For the efficient preparation of streptochlorin from a producing strain Streptomyces sp. SYYLWHS-1-4, we developed a combinative method by using response surface methodology (RSM) and high-speed counter-current chromatography (HSCCC). In the fermentation process, we used RSM to optimize the condition for the efficient accumulation of streptochlorin, and the optimal parameters were: yeast extract 1.889 g/L, soluble starch 8.636 g/L, K2HPO4 0.359 g/L, CaCl2 2.5 g/L, MgSO4 0.625 g/L, marine salt 25 g/L, medium volume 50%, initial pH value 7.0, temperature 27.5 °C, which enhanced streptochlorin yield by 17.7-fold. During the purification process, the preparative HSCCC separation was performed using a petroleum ether–ethyl acetate–methanol–water (9:0.8:5:5, v/v/v/v) biphasic solvent system, where 300 mg of crude sample yielded 16.5 mg streptochlorin with over 95% purity as determined by UPLC. Consequently, the combination method provided a feasible strategy for highly effective preparation of streptochlorin, which ensured the supply of large amounts of streptochlorin for in vivo pharmacological assessments or other requirements. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle The Effect of New Thiophene-Derived Aminophosphonic Derivatives on Growth of Terrestrial Plants: A Seedling Emergence and Growth Test
Molecules 2016, 21(6), 694; doi:10.3390/molecules21060694
Received: 22 April 2016 / Revised: 22 May 2016 / Accepted: 23 May 2016 / Published: 30 May 2016
Cited by 6 | PDF Full-text (1796 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The aim of this work was to synthesize selected thiophene-derived aminophosphonic systems and evaluate the phytotoxicity of newly obtained products according to the OECD 208 Guideline. Seven new thiophene-derived N-substituted dimethyl aminomethylphosphonic acid esters 2ah were synthesized by the addition
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The aim of this work was to synthesize selected thiophene-derived aminophosphonic systems and evaluate the phytotoxicity of newly obtained products according to the OECD 208 Guideline. Seven new thiophene-derived N-substituted dimethyl aminomethylphosphonic acid esters 2ah were synthesized by the addition of an appropriate phosphite to azomethine bond of starting Schiff bases 1ah, and NMR spectroscopic properties of aminophosphonates were investigated. These eight compounds were analyzed in regard to their phytotoxicity towards two plants, radish (Raphanus sativus) and oat (Avena sativa). On the basis of the obtained results, it was found that tested aminophosphonates 2ah showed an ecotoxicological impact against selected plants, albeit to various degrees. Full article
(This article belongs to the Special Issue Recent Advances in Organophosphorus Chemistry)
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Open AccessArticle Characterization of Active Packaging Films Made from Poly(Lactic Acid)/Poly(Trimethylene Carbonate) Incorporated with Oregano Essential Oil
Molecules 2016, 21(6), 695; doi:10.3390/molecules21060695
Received: 17 March 2016 / Revised: 6 May 2016 / Accepted: 11 May 2016 / Published: 27 May 2016
Cited by 4 | PDF Full-text (6008 KB) | HTML Full-text | XML Full-text
Abstract
Antimicromial and antioxidant bioactive films based on poly(lactic acid)/poly(trimenthylene carbonate) films incorporated with different concentrations of oregano essential oil (OEO) were prepared by solvent casting. The antimicrobial, antioxidant, physical, thermal, microstructural, and mechanical properties of the resulting films were examined. Scanning electron microscopy
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Antimicromial and antioxidant bioactive films based on poly(lactic acid)/poly(trimenthylene carbonate) films incorporated with different concentrations of oregano essential oil (OEO) were prepared by solvent casting. The antimicrobial, antioxidant, physical, thermal, microstructural, and mechanical properties of the resulting films were examined. Scanning electron microscopy analysis revealed that the cross-section of films became rougher when OEO was incorporated into PLA/PTMC blends. Differential scanning calorimetry analysis indicated that crystallinity of PLA phase decreased by the addition of OEO, but this did not affect the thermal stability of the films. Water vapor permeability of films slightly increased with increasing concentration of OEO. However, active PLA/PTMC/OEO composite films showed adequate barrier properties for food packaging application. The antimicrobial and antioxidant capacities were significantly improved with the incorporation of OEO (p < 0.05). The results demonstrated that an optimal balance between the mechanical, barrier, thermal, antioxidant, and antimicrobial properties of the films was achieved by the incorporation of 9 wt % OEO into PLA/PTMC blends. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Pharmacokinetic Evaluation of Clozapine in Concomitant Use of Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, or Fructus Gardeniae in Rats
Molecules 2016, 21(6), 696; doi:10.3390/molecules21060696
Received: 9 March 2016 / Revised: 9 May 2016 / Accepted: 24 May 2016 / Published: 27 May 2016
Cited by 2 | PDF Full-text (848 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, and Fructus Gardeniae are often used alongside with clozapine (CLZ) for schizophrenia patients in order to reduce side effects and enhance therapeutic efficacy. However, worse outcomes were observed raising concern about a critical issue,
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Radix Rehmanniae, Fructus Schisandrae, Radix Bupleuri, and Fructus Gardeniae are often used alongside with clozapine (CLZ) for schizophrenia patients in order to reduce side effects and enhance therapeutic efficacy. However, worse outcomes were observed raising concern about a critical issue, herb-drug interactions, which were rarely reported when antipsychotics were included. This study aims to determine whether the concomitant use of these herbal medicines affects the pharmacokinetic characteristics of CLZ in rat models. Rats were given a single or multiple intraperitoneal injections of 10 mg/kg CLZ, either alone or with individual herbal water extracts administered orally. CLZ and its two inactive metabolites, norclozapine and clozapine N-oxide, were determined by high-performance liquid chromatography/tandem mass spectrometry. In the acute treatment, the formation of both metabolites was reduced, while no significant change was observed in the CLZ pharmacokinetics for any of the herbal extracts. In the chronic treatment, none of the four herbal extracts significantly influenced the pharmacokinetic parameters of CLZ and its metabolites. Renal and liver functions stayed normal after the 11-day combined use of herbal medicines. Overall, the four herbs had limited interaction effect on CLZ pharmacokinetics in the acute and chronic treatment. Herb-drug interaction includes both pharmacokinetic and pharmacodynamic mechanisms. This result gives us a hint that pharmacodynamic herb-drug interaction, instead of pharmacokinetic types, may exist and need further confirmation. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Anticoagulant Activity and Structural Characterization of Polysaccharide from Abalone (Haliotis discus hannai Ino) Gonad
Molecules 2016, 21(6), 697; doi:10.3390/molecules21060697
Received: 4 April 2016 / Revised: 20 May 2016 / Accepted: 23 May 2016 / Published: 8 June 2016
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Abstract
In this study, we aimed at characterizing the structure and the anticoagulant activity of a polysaccharide fraction (AGP33) isolated from the gonads of Haliotis discus hannai Ino. AGP33 was extracted by enzymatic hydrolysis and purified by ion-exchange and gel-filtration chromatography. The backbone fraction
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In this study, we aimed at characterizing the structure and the anticoagulant activity of a polysaccharide fraction (AGP33) isolated from the gonads of Haliotis discus hannai Ino. AGP33 was extracted by enzymatic hydrolysis and purified by ion-exchange and gel-filtration chromatography. The backbone fraction of AGP33 (BAGP33), which appeared to contain of mannose, glucose and galactose, was prepared by partial acid hydrolysis. According to methylation and nuclear magnetic resonance (NMR) spectroscopy, the backbone of AGP33 was identified as mainly consisting of 1→3-linked, 1→4-linked, and 1→6-linked monosaccharides. AGP33 is a sulfated polysaccharide with sulfates occur at 3-O- and 4-O-positions. It prolonged thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) compared to a saline control solution in a dosage-dependent manner. AGP33 exhibited an extension (p < 0.01) of APTT compared to the saline group at concentrations higher than 5 μg/mL. AGP33 exhibited higher anticoagulant activity than its desulfated product (AGP33-des) and BAGP33. The results showed that polysaccharide with higher molecular weight and sulfate content demonstrated greater anticoagulant activity. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Metabolic Profile Changes of CCl4-Liver Fibrosis and Inhibitory Effects of Jiaqi Ganxian Granule
Molecules 2016, 21(6), 698; doi:10.3390/molecules21060698
Received: 17 February 2016 / Revised: 18 May 2016 / Accepted: 20 May 2016 / Published: 30 May 2016
Cited by 1 | PDF Full-text (3985 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Jiaqi Ganxian Granule (JGG) is a famous traditional Chinese medicine, which has been long used in clinical practice for treating liver fibrosis. However, the mechanism underlying its anti-hepatic fibrosis is still not clear. In this study, an Ultra-Performance Liquid Chromatography-Time-Of-Flight Mass
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Jiaqi Ganxian Granule (JGG) is a famous traditional Chinese medicine, which has been long used in clinical practice for treating liver fibrosis. However, the mechanism underlying its anti-hepatic fibrosis is still not clear. In this study, an Ultra-Performance Liquid Chromatography-Time-Of-Flight Mass Spectrometry (UPLC-TOF-MS)-based metabolomics strategy was used to profile the metabolic characteristic of serum obtained from a carbon tetrachloride (CCl4)-induced hepatic fibrosis model in Sprague-Dawley (SD) rats with JGG treatment. Through Principal Component Analysis (PCA) and Partial Least Square Discriminant Analysis (PLS-DA), it was shown that metabolic perturbations induced by CCl4 were inhibited after treatment of JGG, for 17 different metabolites related to CCl4. Among these compounds, the change tendency of eight potential drug targets was restored after the intervention with JGG. The current study indicates that JGG has a significant anti-fibrosis effect on CCl4-induced liver fibrosis in rats, which might be by regulating the dysfunction of sphingolipid metabolism, glycerophospholipid metabolism, N-acylethanolamine biosynthesis, fat digestion and absorption, while glycerophospholipid metabolism played vital roles in the inhibitory effects of JGG on hepatic fibrosis according to Metabolic Pathway Analysis (MetPA). Our findings indicated that the metabolomics approach may provide a useful tool for exploring potential biomarkers involved in hepatic fibrosis and elucidate the mechanisms underlying the action of therapies used in traditional Chinese medicine. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Preparative Purification of Anti-Proliferative Diarylheptanoids from Betula platyphylla by High-Speed Counter-Current Chromatography
Molecules 2016, 21(6), 700; doi:10.3390/molecules21060700
Received: 1 April 2016 / Revised: 20 May 2016 / Accepted: 24 May 2016 / Published: 28 May 2016
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Abstract
A simple and rapid method using high-speed counter-current chromatography (HSCCC), along with bioassay-guided fractionation based on the anti-proliferative activity against renal and colon cancer cells, has been developed for the preparative separation of aceroside VIII (1) and platyphylloside (2)
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A simple and rapid method using high-speed counter-current chromatography (HSCCC), along with bioassay-guided fractionation based on the anti-proliferative activity against renal and colon cancer cells, has been developed for the preparative separation of aceroside VIII (1) and platyphylloside (2) from Betula platyphylla. A solvent system composed of ethyl acetate/acetonitrile/water (1:0.1:1, v/v/v) was optimized for the separation. The upper phase was used as the stationary phase, and the lower phase was used as the mobile phase. Among these isolated diarylheptanoids, platyphylloside (2) showed anti-proliferative activity in the COLO205 and KM12 colon cells and renal cancer cell lines A498, U031, as well as in MG63 and MG 63.3 osteosarcoma cells. In addition, it showed dose dependent inhibitory effects in the NCI 60 cell line assay. These results suggest that the diarylheptanoids isolated from B. platyphylla with an efficient HSCCC method could be potential multi-targeted therapeutic agents for cancer. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Purification, Characterization and Biological Activity of Polysaccharides from Dendrobium officinale
Molecules 2016, 21(6), 701; doi:10.3390/molecules21060701
Received: 22 March 2016 / Revised: 24 May 2016 / Accepted: 25 May 2016 / Published: 30 May 2016
Cited by 6 | PDF Full-text (4910 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Polysaccharide (DOPA) from the stem of D. officinale, as well as two fractions (DOPA-1 and DOPA-2) of it, were isolated and purified by DEAE cellulose-52 and Sephacryl S-300 chromatography, and their structural characteristics and bioactivities were investigated. The average molecular weights of
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Polysaccharide (DOPA) from the stem of D. officinale, as well as two fractions (DOPA-1 and DOPA-2) of it, were isolated and purified by DEAE cellulose-52 and Sephacryl S-300 chromatography, and their structural characteristics and bioactivities were investigated. The average molecular weights of DOPA-1 and DOPA-2 were 394 kDa and 362 kDa, respectively. They were mainly composed of d-mannose, d-glucose, and had a backbone consisting of 1,4-linked β-d-Manp and 1,4-linked β-d-Glcp with O-acetyl groups. Bioactivity studies indicated that both DOPA and its purified fractions (DOPA-1 and DOPA-2) could activate splenocytes and macrophages. The D. officinale polysaccharides had stimulatory effects on splenocytes, T-lymphocytes and B-lymphocytes, promoting the cell viability and NO production of RAW 264.7 macrophages. Furthermore, DOPA, DOPA-1 and DOPA-2 were found to protect RAW 264.7 macrophages against hydrogen peroxide (H2O2)-induced oxidative injury by promoting cell viability, suppressing apoptosis and ameliorating oxidative lesions. These results suggested that D. officinale polysaccharides possessed antioxidant activity and mild immunostimulatory activity. Full article
(This article belongs to the collection Herbal Medicine Research)
Open AccessArticle Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles
Molecules 2016, 21(6), 702; doi:10.3390/molecules21060702
Received: 13 February 2016 / Revised: 14 May 2016 / Accepted: 19 May 2016 / Published: 28 May 2016
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Abstract
Tuberculosis remains a major global health problem and alternative therapeutic approaches are needed. Considering the high prevalence of lung tuberculosis (80% of cases), the pulmonary delivery of antitubercular drugs in a carrier system capable of reaching the alveoli, being recognised and phagocytosed by
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Tuberculosis remains a major global health problem and alternative therapeutic approaches are needed. Considering the high prevalence of lung tuberculosis (80% of cases), the pulmonary delivery of antitubercular drugs in a carrier system capable of reaching the alveoli, being recognised and phagocytosed by alveolar macrophages (mycobacterium hosts), would be a significant improvement to current oral drug regimens. Locust bean gum (LBG) is a polysaccharide composed of galactose and mannose residues, which may favour specific recognition by macrophages and potentiate phagocytosis. LBG microparticles produced by spray-drying are reported herein for the first time, incorporating either isoniazid or rifabutin, first-line antitubercular drugs (association efficiencies >82%). Microparticles have adequate theoretical properties for deep lung delivery (aerodynamic diameters between 1.15 and 1.67 μm). The cytotoxic evaluation in lung epithelial cells (A549 cells) and macrophages (THP-1 cells) revealed a toxic effect from rifabutin-loaded microparticles at the highest concentrations, but we may consider that these were very high comparing with in vivo conditions. LBG microparticles further evidenced strong ability to be captured by macrophages (percentage of phagocytosis >94%). Overall, the obtained data indicated the potential of the proposed system for tuberculosis therapy. Full article
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Open AccessArticle Characterization and Enhanced Antioxidant Activity of the Cysteinyl β-Cyclodextrin-Baicalein Inclusion Complex
Molecules 2016, 21(6), 703; doi:10.3390/molecules21060703
Received: 4 May 2016 / Revised: 20 May 2016 / Accepted: 25 May 2016 / Published: 27 May 2016
Cited by 1 | PDF Full-text (2482 KB) | HTML Full-text | XML Full-text
Abstract
Baicalein is a type of flavonoid isolated from the roots of a medicinal plant, Scutellaria baicalensis. Although it has attracted considerable attention due to its antiviral, anti-tumor, and anti-inflammatory activities, its limited aqueous solubility inhibits the clinical application of this flavonoid. The
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Baicalein is a type of flavonoid isolated from the roots of a medicinal plant, Scutellaria baicalensis. Although it has attracted considerable attention due to its antiviral, anti-tumor, and anti-inflammatory activities, its limited aqueous solubility inhibits the clinical application of this flavonoid. The present study aimed to prepare and characterize a host-guest complex in an effort to improve the solubility and antioxidant activity of baicalein. The host molecule is a macrocyclic β-cyclodextrin (β-CD) functionalized with cysteine for a synergetic effect. The structure of the synthesized cysteinyl β-CD was analyzed using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. The inclusion complex with baicalein was studied by UV-vis, NMR spectroscopy, scanning electron microscopy, and X-ray powder diffractometry. The formed cysteinyl β-CD/baicalein inclusion complex efficiently improved the solubility and antioxidant ability of baicalein. Therefore, we suggest that the present cysteinyl β-CD is a potential host molecule for inclusion complexation and for bioavailability augmentation. Full article
(This article belongs to the Special Issue Cyclodextrin Chemistry)
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Open AccessArticle Significant Improvement of Metabolic Characteristics and Bioactivities of Clopidogrel and Analogs by Selective Deuteration
Molecules 2016, 21(6), 704; doi:10.3390/molecules21060704
Received: 28 March 2016 / Revised: 19 May 2016 / Accepted: 25 May 2016 / Published: 30 May 2016
Cited by 2 | PDF Full-text (1184 KB) | HTML Full-text | XML Full-text
Abstract
In the search for prodrug analogs of clopidogrel with improved metabolic characteristics and antiplatelet bioactivity, a group of clopidogrel and vicagrel analogs selectively deuterated at the benzylic methyl ester group were synthesized, characterized, and evaluated. The compounds included clopidogrel-d3 (8
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In the search for prodrug analogs of clopidogrel with improved metabolic characteristics and antiplatelet bioactivity, a group of clopidogrel and vicagrel analogs selectively deuterated at the benzylic methyl ester group were synthesized, characterized, and evaluated. The compounds included clopidogrel-d3 (8), 2-oxoclopidogrel-d3 (9), vicagrel-d3 (10a), and 12 vicagrel-d3 analogs (10b10m) with different alkyl groups in the thiophene ester moiety. The D3C-O bond length in 10a was shown by X-ray single crystal diffraction to be shorter than the H3C-O bond length in clopidogrel, consistent with the slower rate of hydrolysis of 8 than of clopidogrel in rat whole blood in vitro. A study of the ability of the compounds to inhibit ADP-induced platelet aggregation in fresh rat whole blood collected 2 h after oral dosing of rats with the compounds (7.8 μmol/kg) showed that deuteration increased the activity of clopidogrel and that increasing the size of the alkyl group in the thiophene ester moiety reduced activity. A preliminary pharmacokinetic study comparing 10a with vicagrel administered simultaneously as single oral doses (72 μmol/kg of each drug) to male Wistar rats showed 10a generated more of its active metabolite than vicagrel. These results suggest that 10a is a potentially superior antiplatelet agent with improved metabolic characteristics and bioactivity, and less dose-related toxicity. Full article
(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)
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Open AccessArticle Trans-Fatty Acids Aggravate Obesity, Insulin Resistance and Hepatic Steatosis in C57BL/6 Mice, Possibly by Suppressing the IRS1 Dependent Pathway
Molecules 2016, 21(6), 705; doi:10.3390/molecules21060705
Received: 23 March 2016 / Revised: 12 May 2016 / Accepted: 19 May 2016 / Published: 30 May 2016
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Abstract
Trans-fatty acid consumption has been reported as a risk factor for metabolic disorders and targeted organ damages. Nonetheless, little is known about the roles and mechanisms of trans-fatty acids in obesity, insulin resistance (IR) and hepatic steatosis. Adult C57BL/6 male mice
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Trans-fatty acid consumption has been reported as a risk factor for metabolic disorders and targeted organ damages. Nonetheless, little is known about the roles and mechanisms of trans-fatty acids in obesity, insulin resistance (IR) and hepatic steatosis. Adult C57BL/6 male mice were fed with four different diets for 20 weeks: normal diet (ND), high fat diet (HFD), low trans-fatty acids diet (LTD) and high trans-fatty acid diet (HTD). The diet-induced metabolic disorders were assessed by evaluating body weight, glucose tolerance test, hepatic steatosis and plasma lipid profiles post 20-week diet. Histological (H&E, Oil-Red-O) staining and western blot analysis were employed to assess liver steatosis and potential signaling pathways. After 20-weeks of diet, the body weights of the four groups were 29.61 ± 1.89 g (ND), 39.04 ± 4.27 g (HFD), 34.09 ± 2.62 g (LTD) and 43.78 ± 4.27 g (HTD) (p < 0.05), respectively. HFD intake significantly impaired glucose tolerance, which was impaired further in the mice consuming the HTD diet. The effect was further exacerbated by HTD diet. Moreover, the HTD group exhibited significantly more severe liver steatosis compared with HFD group possibly through regulating adipose triglyceride lipase. The group consuming the HTD also exhibited significantly reduced levels of IRS1, phosphor-PKC and phosphor-AKT. These results support our hypothesis that consumption of a diet high in trans-fatty acids induces higher rates of obesity, IR and hepatic steatosis in male C57BL/6 mice, possibly by suppressing the IRS1dependent pathway. Full article
(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)
Open AccessArticle An Approach to Characterizing the Complicated Sequential Metabolism of Salidroside in Rats
Molecules 2016, 21(6), 706; doi:10.3390/molecules21060706
Received: 11 April 2016 / Revised: 25 May 2016 / Accepted: 25 May 2016 / Published: 30 May 2016
Cited by 2 | PDF Full-text (825 KB) | HTML Full-text | XML Full-text
Abstract
Metabolic study of bioactive compounds that undergo a dynamic and sequential process of metabolism is still a great challenge. Salidroside, one of the most active ingredients of Rhodiola crenulata, can be metabolized in different sites before being absorbed into the systemic blood
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Metabolic study of bioactive compounds that undergo a dynamic and sequential process of metabolism is still a great challenge. Salidroside, one of the most active ingredients of Rhodiola crenulata, can be metabolized in different sites before being absorbed into the systemic blood stream. This study proposed an approach for describing the sequential biotransformation process of salidroside based on comparative analysis. In vitro incubation, in situ closed-loop and in vivo blood sampling were used to determine the relative contribution of each site to the total metabolism of salidroside. The results showed that salidroside was stable in digestive juice, and it was metabolized primarily by the liver and the intestinal flora and to a lesser extent by the gut wall. The sequential metabolism method described in this study could be a general approach to characterizing the metabolic routes in the digestive system for natural products. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Characterization of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4-Propoxybenzoates and Their Hydrochloride Salts
Molecules 2016, 21(6), 707; doi:10.3390/molecules21060707
Received: 12 April 2016 / Revised: 16 May 2016 / Accepted: 23 May 2016 / Published: 1 June 2016
Cited by 2 | PDF Full-text (3406 KB) | HTML Full-text | XML Full-text
Abstract
Five new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates were designed and synthesized as potential dual antihypertensive agents. The compounds were prepared as free bases and subsequently transformed to hydrochloride salts. The position of protonation of nitrogen atoms in the piperazine ring of hydrochloride salts was determined by
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Five new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates were designed and synthesized as potential dual antihypertensive agents. The compounds were prepared as free bases and subsequently transformed to hydrochloride salts. The position of protonation of nitrogen atoms in the piperazine ring of hydrochloride salts was determined by means of 13C-CP/MAS and 15N-CP/MAS NMR and IR spectroscopy. Using these solid-state analytical techniques, it was found that both nitrogen atoms were protonated when excess hydrogen chloride was used for preparation of salts. On the other hand, when the equimolar amount of hydrogen chloride was used, piperazine nitrogen substituted by aryl was protonated. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle A Deoxyuridine-Based Far-Red Emitting Viscosity Sensor
Molecules 2016, 21(6), 709; doi:10.3390/molecules21060709
Received: 13 April 2016 / Revised: 20 May 2016 / Accepted: 24 May 2016 / Published: 30 May 2016
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Abstract
A novel deoxyuridine (dU) benzothiazolium (BZ) derivative, referred to as dU-BZ, is reported that was synthesized via Sonogashira coupling reaction methodology. The deoxyuridine building block was introduced to enhance hydrophilicity, while an alkynylated benzothiazolium dye was incorporated for long wavelength absorption to reduce
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A novel deoxyuridine (dU) benzothiazolium (BZ) derivative, referred to as dU-BZ, is reported that was synthesized via Sonogashira coupling reaction methodology. The deoxyuridine building block was introduced to enhance hydrophilicity, while an alkynylated benzothiazolium dye was incorporated for long wavelength absorption to reduce potential phototoxicity that is characteristic of using UV light to excite common fluorphores, better discriminate from native autofluorescence, and potentially facilitate deep tissue imaging. An impressive 30-fold enhancement of fluorescence intensity of dU-BZ was achieved upon increasing viscosity. Fluorescence quantum yields in 99% glycerol/1% methanol (v/v) solution as a function of temperature (293–343 K), together with viscosity-dependent fluorescence lifetimes and radiative and non-radiative rate constants in glycerol/methanol solutions (ranging from 4.8 to 950 cP) were determined. Both fluorescence quantum yields and lifetimes increased with increased viscosity, consistent with results predicted by theory. This suggests that the newly-designed compound, dU-BZ, is capable of functioning as a probe of local microviscosity, an aspect examined by in vitro bioimaging experiments. Full article
(This article belongs to the Special Issue Molecular Imaging Probes)
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Open AccessArticle Molecular Genetic Characterization of an Anthrabenzoxocinones Gene Cluster in Streptomyces Sp. FJS31-2 for the Biosynthesis of BE-24566B and Zunyimycin Ale
Molecules 2016, 21(6), 711; doi:10.3390/molecules21060711
Received: 11 April 2016 / Revised: 8 May 2016 / Accepted: 18 May 2016 / Published: 30 May 2016
Cited by 2 | PDF Full-text (1952 KB) | HTML Full-text | XML Full-text
Abstract
Genome mining is an effective tool used to discover novel natural products from actinomycetes. Genome sequence analysis of Streptomyces sp. FJS31-2 revealed the presence of one putative type II polyketide gene cluster (ABX), which may correspond to type II polyketide products including BE-24566B
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Genome mining is an effective tool used to discover novel natural products from actinomycetes. Genome sequence analysis of Streptomyces sp. FJS31-2 revealed the presence of one putative type II polyketide gene cluster (ABX), which may correspond to type II polyketide products including BE-24566B and its chloro-derivatives. The addition of natural humus acid successfully activated the biosynthsis of the abx gene cluster. BE-24566B and its chloro-derivatives, named zunyimycin A, were also detected. The targeted deletion of the polyketide skeleton synthesis genes such as abxp, abxk, and abxs was performed in the wild strain to identify the gene cluster for BE-24566B biosynthesis. Full article
(This article belongs to the Special Issue Polyketides)
Open AccessArticle A Hydrogel-Based Epirubicin Delivery System for Intravesical Chemotherapy
Molecules 2016, 21(6), 712; doi:10.3390/molecules21060712
Received: 20 March 2016 / Revised: 15 May 2016 / Accepted: 26 May 2016 / Published: 1 June 2016
PDF Full-text (8593 KB) | HTML Full-text | XML Full-text
Abstract
This study aimed to examine the efficacy of epirubicin-loaded gelatin hydrogel (EPI-H) in the treatment of superficial urothelium carcinoma. Hydrogel was prepared by Schiff base-crosslinking of gelatin with glutaraldehyde. EPI-H exhibited high entrapment efficiency (59.87% ± 0.51%). EPI-H also increased epirubicin accumulation in
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This study aimed to examine the efficacy of epirubicin-loaded gelatin hydrogel (EPI-H) in the treatment of superficial urothelium carcinoma. Hydrogel was prepared by Schiff base-crosslinking of gelatin with glutaraldehyde. EPI-H exhibited high entrapment efficiency (59.87% ± 0.51%). EPI-H also increased epirubicin accumulation in AY-27 cells when compared with the effect of aqueous solutions of epirubicin (EPI-AQ); respective epirubicin-positive cell counts were 69.0% ± 7.6% and 38.3% ± 5.8%. EPI-H also exhibited greater cytotoxicity against AY-27 cells than that of EPI-AQ; IC50 values were 13.1 ± 1.1 and 7.5 ± 0.3 μg/mL, respectively. Cystometrograms showed that EPI-H reduced peak micturition, threshold pressures, and micturition duration, and that it increased bladder compliance more so than EPI-AQ. EPI-H enhanced epirubicin penetration into basal cells of urothelium in vivo, whereas EPI-AQ did so only to the umbrella cells. EPI-H inhibited tumor growth upon intravesical instillation to tumor-bearing bladder of F344 rats, inducing higher levels of caspase-3 expression than that observed with EPI-AQ treatment; the number of caspase-3 positive cells in treated urothelium carcinoma was 13.9% ± 4.0% (EPI-AQ) and 34.1% ± 1.0%, (EPI-H). EPI-H has value as an improved means to administer epirubicin in intravesical instillation treatments for bladder cancer. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessCommunication Organocatalyzed Intramolecular Carbonyl-Ene Reactions
Molecules 2016, 21(6), 713; doi:10.3390/molecules21060713
Received: 2 May 2016 / Revised: 24 May 2016 / Accepted: 27 May 2016 / Published: 31 May 2016
PDF Full-text (1748 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An organocatalyzed intramolecular carbonyl-ene reaction was developed to produce carbocyclic and heterocyclic 5- and 6-membered rings from a citronellal-derived trifluoroketone and a variety of aldehydes. A phosphoramide derivative was found to promote the cyclization of the trifluoroketone, whereas a less acidic phosphoric acid
[...] Read more.
An organocatalyzed intramolecular carbonyl-ene reaction was developed to produce carbocyclic and heterocyclic 5- and 6-membered rings from a citronellal-derived trifluoroketone and a variety of aldehydes. A phosphoramide derivative was found to promote the cyclization of the trifluoroketone, whereas a less acidic phosphoric acid proved to be a superior catalyst for the aldehyde substrates. Full article
(This article belongs to the collection Recent Advances in Organocatalysis)
Open AccessArticle Hydrazino-methoxy-1,3,5-triazine Derivatives’ Excellent Corrosion Organic Inhibitors of Steel in Acidic Chloride Solution
Molecules 2016, 21(6), 714; doi:10.3390/molecules21060714
Received: 29 April 2016 / Revised: 27 May 2016 / Accepted: 27 May 2016 / Published: 1 June 2016
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Abstract
The corrosion inhibition performance of 2-hydrazino-4,6-dimethoxy-1,3,5-tirazine (DMeHT), 2,4-dihydrazino-6-methoxy-1,3,5-triaizine (DHMeT), and 2,4,6-tridydrazino-1,3,5-triaizne (TH3) on steel corrosion in acidic media was examined using electrochemical techniques. The results showed 2,4-Ddihydrazino-6-methoxy-1,3,5-triaizine (DHMeT) gave the best corrosion protection performance among the other hydrazino derivatives even at
[...] Read more.
The corrosion inhibition performance of 2-hydrazino-4,6-dimethoxy-1,3,5-tirazine (DMeHT), 2,4-dihydrazino-6-methoxy-1,3,5-triaizine (DHMeT), and 2,4,6-tridydrazino-1,3,5-triaizne (TH3) on steel corrosion in acidic media was examined using electrochemical techniques. The results showed 2,4-Ddihydrazino-6-methoxy-1,3,5-triaizine (DHMeT) gave the best corrosion protection performance among the other hydrazino derivatives even at a low concentration of 25 ppm (95%). The number of hydrazino groups play an important role in the corrosion inhibition, where the two hydrazine groups increased the electrostatic interactions between the protonated tested compounds, the negatively charged steel surface resulted from the adsorption of the chloride anions, and the presence of the methoxy group made the compound more reliable for formation of film protection on the surface of steel through the lone pair of oxygen atoms. Electrochemical Impedance Spectroscopy (EIS) measurements suggested that the corrosion process of steel in presence of the hydrazino-s-triazine derivatives (TH3, DMeHT and DHMeT) were being controlled by the charge transfer reaction. Polarization curves indicated that the examined TH3, DMeHT and DHMeT behaved as mixed type inhibitors. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Extraction, Purification and Primary Characterization of Polysaccharides from Defatted Peanut (Arachis hypogaea) Cakes
Molecules 2016, 21(6), 716; doi:10.3390/molecules21060716
Received: 20 April 2016 / Revised: 21 May 2016 / Accepted: 24 May 2016 / Published: 1 June 2016
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Abstract
The hot-water extraction, purification and characterization of polysaccharides from defatted peanut cake (PPC) were investigated in this study. A Box-Behnken factorial design (BBD) was used to investigate the effects of three independent variables, namely extraction temperature (X1), extraction time (X2
[...] Read more.
The hot-water extraction, purification and characterization of polysaccharides from defatted peanut cake (PPC) were investigated in this study. A Box-Behnken factorial design (BBD) was used to investigate the effects of three independent variables, namely extraction temperature (X1), extraction time (X2) and ratio of water to raw material (X3). The optimum conditions were 85 °C, 3 h and 20:1 (mL/g) respectively. Regression analysis was done to reveal the experimental results which include 34.97% extraction rate while the value verified under these conditions was 34.49%. The crude PPC was sequentially further purified by Sephadex G-100 chromatography, and one purified fraction was obtained. The PPC purified fraction was characterized by FT-IR, HPAEC; SEC-MALLS. The average molecular weight of the PPC purified fraction was 2.383 × 105 Da. The polysaccharide was mainly composed of glucose, galactose, arabinose and xylose. The PPC have the typical absorption of polysaccharide. Full article
(This article belongs to the Special Issue Natural Polysaccharides)
Open AccessArticle Simultaneous Determination of Purpurin, Munjistin and Mollugin in Rat Plasma by Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study after Oral Administration of Rubia cordifolia L. Extract
Molecules 2016, 21(6), 717; doi:10.3390/molecules21060717
Received: 29 April 2016 / Revised: 25 May 2016 / Accepted: 28 May 2016 / Published: 1 June 2016
Cited by 2 | PDF Full-text (1628 KB) | HTML Full-text | XML Full-text
Abstract
A specific, simple, sensitive Ultra High Performance Liquid Chromatography-tandem Mass Spectrometry (UHPLC-MS/MS) method has been developed and validated for the simultaneous determination and pharmacokinetic study of purpurin, munjistin, and mollugin in rat plasma. Chromatographic separation was carried out using a C18 column
[...] Read more.
A specific, simple, sensitive Ultra High Performance Liquid Chromatography-tandem Mass Spectrometry (UHPLC-MS/MS) method has been developed and validated for the simultaneous determination and pharmacokinetic study of purpurin, munjistin, and mollugin in rat plasma. Chromatographic separation was carried out using a C18 column (ACQUITY UPLC® HSS T3, 1.8 μm, 2.1 × 100 mm) with gradient elution. The compounds were detected on a 6430 triple-quadrupole tandem MS with an electrospray ionization (ESI) interface using multiple reaction monitoring (MRM) in positive ionization mode. The samples were prepared by a liquid-liquid extraction (LLE) method with ethyl acetate after being spiked with an internal standard (bifendate). The current UHPLC-MS/MS assay was validated for its linearity, intra-day and inter-day precisions, accuracy, extraction recovery, matrix effect and stability in different conditions. The method was linear for all analytes over the investigated range with all determined correlation coefficients exceeding 0.9900. The intra-day and inter-day precisions were in the range of 4.21% to 14.84%, and the relative errors of accuracies were in the range of −14.05% to 14.75%. The mean recoveries and matrix effects of purpurin, munjistin, and mollugin were higher than 78.87% and 92.56%, repectively. After oral administration of 0.82 g/kg of Rubia cordifolia extract, the maximum plasma concentrations (Cmax) were 70.10 ± 11.78 ng/mL for purpurin, 26.09 ± 6.6 ng/mL for munjistin, and 52.10 ± 6.71 ng/mL for mollugin. The time for maximal concentration (Tmax) was 1.61 ± 0.24 h for purpurin, 2.58 ± 0.19 h for munjistin, and 1.99 ± 0.21 h for mollugin. The established method was further applied to a pharmacokinetic study of purpurin, munjistin, and mollugin in rat plasma. It was concluded from the pharmacokinetic parameters that the three analytes showed a process of slow absorption and metabolism after oral administration of R. cordifolia extract to rats. Full article
Open AccessArticle Synthesis of Novel UV Absorbers Bisindolylmethanes and Investigation of Their Applications on Cotton-Based Textile Materials
Molecules 2016, 21(6), 718; doi:10.3390/molecules21060718
Received: 14 April 2016 / Revised: 25 May 2016 / Accepted: 27 May 2016 / Published: 3 June 2016
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Abstract
Nowadays modified textiles, especially UV-protective, antibacterial and antimicrobial ones, have become the focus of great interest. In this study, several new UV absorbers, bis(indolyl)methane derivatives, were synthesized and grafted onto polyvinyl alcohol polymer (PVA). Their application properties on cotton-based textile materials were determined;
[...] Read more.
Nowadays modified textiles, especially UV-protective, antibacterial and antimicrobial ones, have become the focus of great interest. In this study, several new UV absorbers, bis(indolyl)methane derivatives, were synthesized and grafted onto polyvinyl alcohol polymer (PVA). Their application properties on cotton-based textile materials were determined; the UV protection factor values of the modified fabrics were measured (UPF); and the antibacterial features of the fabrics were tested. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Hydrogen Bonding: Between Strengthening the Crystal Packing and Improving Solubility of Three Haloperidol Derivatives
Molecules 2016, 21(6), 719; doi:10.3390/molecules21060719
Received: 16 January 2016 / Revised: 9 May 2016 / Accepted: 21 May 2016 / Published: 1 June 2016
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Abstract
The purpose of this study is to confirm the impact of polar functional groups on inter and intra-molecular hydrogen bonding in haloperidol (HP) and droperidol (DP) and, hence, their effects on dissolution using a new approach. To confirm our theory, a new molecule:
[...] Read more.
The purpose of this study is to confirm the impact of polar functional groups on inter and intra-molecular hydrogen bonding in haloperidol (HP) and droperidol (DP) and, hence, their effects on dissolution using a new approach. To confirm our theory, a new molecule: deshydroxy-haloperidol (DHP) was designed and its synthesis was requested from a contract laboratory. The molecule was then studied and compared to DP and HP. Unlike DHP, both the HP and DP molecules have hydrogen donor groups, therefore, DHP was used to confirm the relative effects of the hydrogen donor group on solubility and crystal packing. The solid dispersions of the three structurally related molecules: HP, DP, and DHP were prepared using PVPK30, and characterized using XRPD and IR. A comparative dissolution study was carried out in aqueous medium. The absence of a hydrogen bonding donor group in DHP resulted in an unexpected increase in its aqueous solubility and dissolution rate from solid dispersion, which is attributed to weaker crystal pack. The increased dissolution rate of HP and DP from solid dispersions is attributed to drug-polymer hydrogen bonding that interferes with the drug-drug intermolecular hydrogen bonding and provides thermodynamic stability of the dispersed drug molecules. The drug-drug intermolecular hydrogen bond is the driving force for precipitation and crystal packing. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Poly (l-γ-glutamylglutamine) Polymer Enhances Doxorubicin Accumulation in Multidrug Resistant Breast Cancer Cells
Molecules 2016, 21(6), 720; doi:10.3390/molecules21060720
Received: 28 February 2016 / Revised: 22 May 2016 / Accepted: 27 May 2016 / Published: 2 June 2016
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Abstract
Background: Drug resistance is one of the bottlenecks of cancer chemotherapy in the clinic. Polymeric nanomedicine is one of the most promising strategies for overcoming poor chemotherapy responses due to the multidrug resistance (MDR). Methods: In this study, a new polymer-based
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Background: Drug resistance is one of the bottlenecks of cancer chemotherapy in the clinic. Polymeric nanomedicine is one of the most promising strategies for overcoming poor chemotherapy responses due to the multidrug resistance (MDR). Methods: In this study, a new polymer-based drug delivery system, poly (l-γ-glutamylglutamine)-doxorubicin (PGG-Dox) conjugate, was studied in both drug-induced resistant human breast cancer MDA-MB-231/MDR cells and their parent human breast cancer MDA-MB-231 cells. The effect of PGG on facilitating the growth inhibition of Dox against multidrug resistant cells were investigated by evaluating the cytotoxicity of PGG-Dox conjugate, PGG/Dox unconjugated complex and free Dox on both cells. The underlying mechanisms in resistant cells were further studied via the intracellular traffic studies. Results: Both conjugated and unconjugated PGG significantly increased Dox uptake, prolonged Dox retention and reduced Dox efflux in the MDA-MB-231/MDR cells. The PGG-Dox conjugate is taken up by tumor cells mainly by pinocytosis pathway, in which PGG-Dox conjugate-containing vesicles are formed and enter the cells. Conclusions: This study indicated that both polymer-drug conjugate and unconjugated complex are promising strategies of overcoming resistance of anti-tumor drugs. Full article
(This article belongs to the collection Nanomedicine)
Open AccessArticle Coffee Silverskin Extract Protects against Accelerated Aging Caused by Oxidative Agents
Molecules 2016, 21(6), 721; doi:10.3390/molecules21060721
Received: 14 April 2016 / Revised: 20 May 2016 / Accepted: 20 May 2016 / Published: 1 June 2016
Cited by 6 | PDF Full-text (2356 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nowadays, coffee beans are almost exclusively used for the preparation of the beverage. The sustainability of coffee production can be achieved introducing new applications for the valorization of coffee by-products. Coffee silverskin is the by-product generated during roasting, and because of its powerful
[...] Read more.
Nowadays, coffee beans are almost exclusively used for the preparation of the beverage. The sustainability of coffee production can be achieved introducing new applications for the valorization of coffee by-products. Coffee silverskin is the by-product generated during roasting, and because of its powerful antioxidant capacity, coffee silverskin aqueous extract (CSE) may be used for other applications, such as antiaging cosmetics and dermaceutics. This study aims to contribute to the coffee sector’s sustainability through the application of CSE to preserve skin health. Preclinical data regarding the antiaging properties of CSE employing human keratinocytes and Caenorhabditis elegans are collected during the present study. Accelerated aging was induced by tert-butyl hydroperoxide (t-BOOH) in HaCaT cells and by ultraviolet radiation C (UVC) in C. elegans. Results suggest that the tested concentrations of coffee extracts were not cytotoxic, and CSE 1 mg/mL gave resistance to skin cells when oxidative damage was induced by t-BOOH. On the other hand, nematodes treated with CSE (1 mg/mL) showed a significant increased longevity compared to those cultured on a standard diet. In conclusion, our results support the antiaging properties of the CSE and its great potential for improving skin health due to its antioxidant character associated with phenols among other bioactive compounds present in the botanical material. Full article
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Open AccessArticle Eriobotrya japonica Water Extract Characterization: An Inducer of Interferon-Gamma Production Mainly by the JAK-STAT Pathway
Molecules 2016, 21(6), 722; doi:10.3390/molecules21060722
Received: 17 April 2016 / Revised: 26 May 2016 / Accepted: 27 May 2016 / Published: 2 June 2016
Cited by 3 | PDF Full-text (926 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Eriobotrya japonica (Thunb.) Lindl. (Loquat) (EJ) has been used as a medicinal plant to treat chronic bronchitis, coughs, phlegm, high fever and gastro-enteric disorders. Since the traditional use of EJ is related to modulating inflammation processes, our earlier studies on EJ leaves were
[...] Read more.
Eriobotrya japonica (Thunb.) Lindl. (Loquat) (EJ) has been used as a medicinal plant to treat chronic bronchitis, coughs, phlegm, high fever and gastro-enteric disorders. Since the traditional use of EJ is related to modulating inflammation processes, our earlier studies on EJ leaves were performed on the water extract to investigate specific cytokines’ modulation. These earlier studies, however, have shown that EJ leaf water extract (WE) and the water phase (WP) induce cytokines’ production in in vitro and in vivo models. Therefore, the aim of this study was to specify the group(s) of compounds in EJ leaves that have this immunomodulatory activity and their mechanism of action. WE was obtained from boiling the leaves followed by butanol extraction, yielding a butanol-water phase (WP). WP was then subjected to methanol:acetone fractionation, yielding upper (MAU) and lower (MAL) phases. For further fractionation, MAU was subjected to column chromatography followed by elution with ethanol:water (EW), methanol:ethanol (ME) and, lastly, acetone:water (AW), respectively, to reveal three sub-fractions; MAU-EW, MAU-ME and MAU-AW. MAU-AW significantly increased IFN-γ production from unstimulated and stimulated mouse spleen cells, as well as CD3+ T cells and natural killer cells. Furthermore, the fold increase of IFN-γ production by MAU-AW was concentration dependent, higher than the parent extract or any of the other sub-fractions, and such an IFN-γ increase was reversed by two JAK-STAT inhibitors. In addition, MALDI-TOF-MS analysis of the extracts and sub-fractions showed compounds with molecular weights of >500 Daltons. The MAU-AW sub-fraction contained more polar compounds, such as flavonol and caffeic glycosides. In conclusion, these polar compounds in the EJ extract are responsible for inducing IFN-γ production. Further chemical elucidation is warranted to lead to a specific IFN-γ inducer and an immunomodulator in polarizing immune cells and balancing immune responses in certain diseases. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Aza-Henry Reactions on C-Alkyl Substituted Aldimines
Molecules 2016, 21(6), 723; doi:10.3390/molecules21060723
Received: 3 May 2016 / Revised: 26 May 2016 / Accepted: 26 May 2016 / Published: 2 June 2016
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Abstract
The reactivity of C-CH3 substituted N-protected aldimines in aza-Henry addition reactions was compared with that of the analogous trifluoromethylated compounds. C-Alkyl aldimines easily reacted with nitro alkanes under solvent-free conditions and in the absence of catalyst, despite being worse
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The reactivity of C-CH3 substituted N-protected aldimines in aza-Henry addition reactions was compared with that of the analogous trifluoromethylated compounds. C-Alkyl aldimines easily reacted with nitro alkanes under solvent-free conditions and in the absence of catalyst, despite being worse electrophiles than C-CF3 aldimines, they gave the aza-Henry addition only when ZrCl4 was added. The presence of a bulky group on the imine carbon deeply influenced the reactivity. Full article
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Open AccessArticle Synthesis, Spectroscopic, X-ray Diffraction and DFT Studies of Novel Benzimidazole Fused-1,4-Oxazepines
Molecules 2016, 21(6), 724; doi:10.3390/molecules21060724
Received: 16 April 2016 / Revised: 22 May 2016 / Accepted: 27 May 2016 / Published: 3 June 2016
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Abstract
A series of benzimidazole-tethered oxazepine heterocyclic hybrids has been synthesized in good to excellent yields from an N-alkylated benzimidazole 2-carboxaldehyde, which in turn was accomplished from o-phenylenediamine in three good yielding steps. The calculated molecular structure of compounds 2-methyl-4-(2-((phenylimino)methyl)-1H-benzo-[
[...] Read more.
A series of benzimidazole-tethered oxazepine heterocyclic hybrids has been synthesized in good to excellent yields from an N-alkylated benzimidazole 2-carboxaldehyde, which in turn was accomplished from o-phenylenediamine in three good yielding steps. The calculated molecular structure of compounds 2-methyl-4-(2-((phenylimino)methyl)-1H-benzo-[d]imidazol-1-yl)-butan-2-ol 9 and 10 3,3-dimethyl-N-phenyl-1,2,3,5-tetrahydrobenzo-[4,5]imidazo[2,1-c][1,4]oxazepin-5-amine using the B3LYP/6–31 G(d, p) method were found to agree well with their X-ray structures. The charge distributions at the different atomic sites were computed using the natural bond orbital (NBO) method. The regions of electrophilic and nucleophilic reactivity were shown using a molecular electrostatic potential (MEP) map. In addition, the frontier molecular orbitals of these compounds were discussed at the same level of theory. Nonlinear optical (NLO) properties have also been investigated by computational hyperpolarizability studies, and it was found that Compound 9 is the best candidate for NLO applications. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Polyphenols from Erythrina crista-galli: Structures, Molecular Docking and Phytoestrogenic Activity
Molecules 2016, 21(6), 726; doi:10.3390/molecules21060726
Received: 30 March 2016 / Revised: 21 May 2016 / Accepted: 27 May 2016 / Published: 3 June 2016
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Abstract
Objectives: The current study aimed at exploring the secondary metabolites content of Erythrina crista-galli aqueous methanol extract and assessing its phytoestrogenic and cytoprotective activities. Methods: Isolation of the compounds was carried out using conventional chromatographic techniques. The structures of the isolated compounds were
[...] Read more.
Objectives: The current study aimed at exploring the secondary metabolites content of Erythrina crista-galli aqueous methanol extract and assessing its phytoestrogenic and cytoprotective activities. Methods: Isolation of the compounds was carried out using conventional chromatographic techniques. The structures of the isolated compounds were elucidated based on the UV, NMR spectral data along with their mass-spectrometric analyses. The phytoestrogenic activity was evaluated in-silico and in vitro using the Arabidopsis thaliana pER8: GUS reporter assay and the proliferation-enhancing activity of MCF-7 cells. Key findings: Phytochemical investigation of E. crista-galli aqueous methanol extract resulted in the isolation and identification of five flavonoids. The plant extract and its fractions showed significant estrogenic activities compared to controls. Conclusion: Five flavonoids were identified from E. crista-galli aqueous methanol extract. To the best of our knowledge, among these flavonoids, apigenin-7-O-rhamnosyl-6-C-glucoside was isolated for the first time from nature. Moreover, luteolin-6-C-glucoside was isolated for the first time from this plant. The plant revealed promising phytoestrogenic activities. This gives rationale to some of its pharmacological properties and suggests additional phytoestrogenic effects, which have not been reported yet. Full article
Open AccessArticle Aqueous Extract of Paris polyphylla (AEPP) Inhibits Ovarian Cancer via Suppression of Peroxisome Proliferator-Activated Receptor-Gamma Coactivator (PGC)-1alpha
Molecules 2016, 21(6), 727; doi:10.3390/molecules21060727
Received: 13 May 2016 / Revised: 27 May 2016 / Accepted: 30 May 2016 / Published: 3 June 2016
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Abstract
Chemotherapy, a major approach was used in carcinoma treatment, always involves the development of drug resistance as well as side-effects that affect the quality of patients’ lives. An association between epithelial-mesenchymal transition (EMT) and chemotherapy resistance was established recently. We demonstrate in this
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Chemotherapy, a major approach was used in carcinoma treatment, always involves the development of drug resistance as well as side-effects that affect the quality of patients’ lives. An association between epithelial-mesenchymal transition (EMT) and chemotherapy resistance was established recently. We demonstrate in this paper that the aqueous extract of Paris polyphylla (AEPP)—a traditional Chinese medicine—can be used in various cancer types for suppression of carcinogenesis. We evaluated the suppressions of EMT and mitochondrial activity by AEPP treatment in a high-glucose (HG) induced-human ovarian carcinoma cell line (OVCAR-3 cells). The mitochondrial morphology was investigated using MitoTracker Deep Red FM staining. Our results indicated that AEPP reduced the viability of OVCAR-3 cells considerably through induction of apoptosis. However, this inhibitory potential of AEPP was attenuated by HG induction in OVCAR-3 cells. The levels of estrogen-related receptor (ERR)-alpha activator and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha were elevated by HG induction, but were suppressed by AEPP treatment. Down-regulations of cell survival and EMT were oberved in OVCAR-3 cells through suppression of PGC-1alpha by AEPP treatment. These results were confirmed through PGC-1alpha knockdown and overexpression in OVCAR-3 cells. Thus, AEPP can be beneficial for treating ovarian cancer and has potential for development of an integrative cancer therapy against ovarian cancer proliferation, metastasis, and migration. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Four New Monoterpenoid Glycosides from the Flower Buds of Magnolia biondii
Molecules 2016, 21(6), 728; doi:10.3390/molecules21060728
Received: 19 April 2016 / Accepted: 30 April 2016 / Published: 3 June 2016
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Abstract
Four new monoterpenoid glycosides 14, named magnoliaterpenoid A–D, were isolated from a 50% aqueous acetone extract of flower buds of Magnolia biondii, along with one known compound, (1′R,3′S,5′R,8′S,2Z,4E
[...] Read more.
Four new monoterpenoid glycosides 14, named magnoliaterpenoid A–D, were isolated from a 50% aqueous acetone extract of flower buds of Magnolia biondii, along with one known compound, (1′R,3′S,5′R,8′S,2Z,4E)-dihydrophaseic acid 3-O-β-d-glucopyranoside (5). Their structures and relative configuration were identified by extensive spectroscopic analysis (IR, UV, MS, 1D and 2D NMR). The aglycones of these four new compounds possess seven-membered rings systems, which are very rare. A plausible biosynthetic route for the four new compounds was proposed via the biogenetic isoprene rule. Compounds 1, 2, 3, and 4 showed no antimicrobial activity at the concentration range of 1.95–250 µg/mL. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Effect of Steam Blanching and Drying on Phenolic Compounds of Litchi Pericarp
Molecules 2016, 21(6), 729; doi:10.3390/molecules21060729
Received: 18 April 2016 / Revised: 13 May 2016 / Accepted: 30 May 2016 / Published: 3 June 2016
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Abstract
The effects of different treatment methods on the stability and antioxidant capacity of the bioactive phenolic compounds of litchi pericarps were investigated. Fresh litchi pericarps were open air–dried, steam-blanched for 3 min in combination with hot air oven drying at 60 and 80
[...] Read more.
The effects of different treatment methods on the stability and antioxidant capacity of the bioactive phenolic compounds of litchi pericarps were investigated. Fresh litchi pericarps were open air–dried, steam-blanched for 3 min in combination with hot air oven drying at 60 and 80 °C, and unblanched pericarps were dried in a hot air oven at 40, 60, 70 and 80 °C until equilibrium weight was reached. The total phenolic compounds, flavonoids, anthocyanins, proanthocyanidins and individual procyanidins, and antioxidant activity were analyzed. The combination of blanching and drying at 60 °C significantly (p < 0.05) improved the release of phenolic compounds, individual procyanidins, and the extracts′ antioxidant capacity compared with the unblanched hot air oven-dried and open air–dried pericarps. Drying of fresh unblanched litchi pericarps in either open air or a hot air oven caused significant losses (p < 0.05) in phenolic compounds and individual procyanidins, leading to a reduction in the antioxidant activity. A similar increase, retention or reduction was reflected in flavonoids, proanthocyanidins and anthocyanins because they are sub-groups of phenolic compounds. Ferric reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picryldydrazyl (DPPH) radical-scavenging capacity of the treated pericarps were significantly correlated (r ≥ 0.927, p < 0.01) with the total phenolic compounds. Thus, the combination of steam blanching and drying treatments of fresh litchi pericarps could produce a stable and dry litchi pericarp that maintains phenolic compounds and antioxidant capacity as a raw material for further recovery of the phytochemicals. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Dioscin Induces Apoptosis in Human Cervical Carcinoma HeLa and SiHa Cells through ROS-Mediated DNA Damage and the Mitochondrial Signaling Pathway
Molecules 2016, 21(6), 730; doi:10.3390/molecules21060730
Received: 30 April 2016 / Revised: 24 May 2016 / Accepted: 31 May 2016 / Published: 4 June 2016
Cited by 3 | PDF Full-text (9793 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Dioscin, a natural product, has activity against glioblastoma multiforme, lung cancer and colon cancer. In this study, the effects of dioscin against human cervical carcinoma HeLa and SiHa cells were further confirmed, and the possible mechanism(s) were investigated. A transmission electron microscopy (TEM)
[...] Read more.
Dioscin, a natural product, has activity against glioblastoma multiforme, lung cancer and colon cancer. In this study, the effects of dioscin against human cervical carcinoma HeLa and SiHa cells were further confirmed, and the possible mechanism(s) were investigated. A transmission electron microscopy (TEM) assay and DAPI staining were used to detect the cellular morphology. Flow cytometry was used to assay cell apoptosis, ROS and Ca2+ levels. Single cell gel electrophoresis and immunofluorescence assays were used to test DNA damage and cytochrome C release. The results showed that dioscin significantly inhibited cell proliferation and caused DNA damage in HeLa and SiHa cells. The mechanistic investigation showed that dioscin caused the release of cytochrome C from mitochondria into the cytosol. In addition, dioscin significantly up-regulated the protein levels of Bak, Bax, Bid, p53, caspase-3, caspase-9, and down-regulated the protein levels of Bcl-2 and Bcl-xl. Our work thus demonstrated that dioscin notably induces apoptosis in HeLa and SiHa cells through adjusting ROS-mediated DNA damage and the mitochondrial signaling pathway. Full article
Open AccessArticle Biologically Synthesized Gold Nanoparticles Ameliorate Cold and Heat Stress-Induced Oxidative Stress in Escherichia coli
Molecules 2016, 21(6), 731; doi:10.3390/molecules21060731
Received: 28 April 2016 / Revised: 19 May 2016 / Accepted: 30 May 2016 / Published: 4 June 2016
Cited by 7 | PDF Full-text (1755 KB) | HTML Full-text | XML Full-text
Abstract
Due to their unique physical, chemical, and optical properties, gold nanoparticles (AuNPs) have recently attracted much interest in the field of nanomedicine, especially in the areas of cancer diagnosis and photothermal therapy. Because of the enormous potential of these nanoparticles, various physical, chemical,
[...] Read more.
Due to their unique physical, chemical, and optical properties, gold nanoparticles (AuNPs) have recently attracted much interest in the field of nanomedicine, especially in the areas of cancer diagnosis and photothermal therapy. Because of the enormous potential of these nanoparticles, various physical, chemical, and biological methods have been adopted for their synthesis. Synthetic antioxidants are dangerous to human health. Thus, the search for effective, nontoxic natural compounds with effective antioxidative properties is essential. Although AuNPs have been studied for use in various biological applications, exploration of AuNPs as antioxidants capable of inhibiting oxidative stress induced by heat and cold stress is still warranted. Therefore, one goal of our study was to produce biocompatible AuNPs using biological methods that are simple, nontoxic, biocompatible, and environmentally friendly. Next, we aimed to assess the antioxidative effect of AuNPs against oxidative stress induced by cold and heat in Escherichia coli, which is a suitable model for stress responses involving AuNPs. The response of aerobically grown E. coli cells to cold and heat stress was found to be similar to the oxidative stress response. Upon exposure to cold and heat stress, the viability and metabolic activity of E. coli was significantly reduced compared to the control. In addition, levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and leakage of proteins and sugars were significantly elevated, and the levels of lactate dehydrogenase activity (LDH) and adenosine triphosphate (ATP) significantly lowered compared to in the control. Concomitantly, AuNPs ameliorated cold and heat-induced oxidative stress responses by increasing the expression of antioxidants, including glutathione (GSH), glutathione S-transferase (GST), super oxide dismutase (SOD), and catalase (CAT). These consistent physiology and biochemical data suggest that AuNPs can ameliorate cold and heat stress-induced oxidative damage in E. coli. Our results indicate that AuNPs may be effective antioxidants. However, further studies are needed to confirm the role of AuNPs as antioxidative agents, as well as their mechanism of action. Full article
Open AccessArticle Design, Synthesis and Antifungal Activity of Novel Benzofuran-Triazole Hybrids
Molecules 2016, 21(6), 732; doi:10.3390/molecules21060732
Received: 20 April 2016 / Revised: 27 May 2016 / Accepted: 1 June 2016 / Published: 7 June 2016
Cited by 2 | PDF Full-text (1315 KB) | HTML Full-text | XML Full-text
Abstract
A series of novel benzofuran-triazole hybrids was designed and synthesized by click chemistry, and their structures were characterized by HRMS, FTIR and NMR. The in vitro antifungal activity of target compounds was evaluated using the microdilution broth method against five strains of pathogenic
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A series of novel benzofuran-triazole hybrids was designed and synthesized by click chemistry, and their structures were characterized by HRMS, FTIR and NMR. The in vitro antifungal activity of target compounds was evaluated using the microdilution broth method against five strains of pathogenic fungi. The result indicated that the target compounds exhibited moderate to satisfactory activity. Furthermore, molecular docking was performed to investigate the binding affinities and interaction modes between the target compound and N-myristoyltransferase. Based on the results, preliminary structure activity relationships (SARs) were summarized to serve as a foundation for further investigation. Full article
(This article belongs to the collection Heterocyclic Compounds)
Open AccessArticle Capsaicin Inhibited Aggressive Phenotypes through Downregulation of Tumor-Associated NADH Oxidase (tNOX) by POU Domain Transcription Factor POU3F2
Molecules 2016, 21(6), 733; doi:10.3390/molecules21060733
Received: 29 April 2016 / Revised: 26 May 2016 / Accepted: 31 May 2016 / Published: 4 June 2016
Cited by 2 | PDF Full-text (5026 KB) | HTML Full-text | XML Full-text
Abstract
Capsaicin has been reported to preferentially inhibit the activity of tumor-associated NADH oxidase (tNOX), which belongs to a family of growth-related plasma membrane hydroquinone oxidases in cancer/transformed cells. The inhibitory effect of capsaicin on tNOX is associated with cell growth attenuation and apoptosis.
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Capsaicin has been reported to preferentially inhibit the activity of tumor-associated NADH oxidase (tNOX), which belongs to a family of growth-related plasma membrane hydroquinone oxidases in cancer/transformed cells. The inhibitory effect of capsaicin on tNOX is associated with cell growth attenuation and apoptosis. However, no previous study has examined the transcriptional regulation of tNOX protein expression. Bioinformatic analysis has indicated that the tNOX promoter sequence harbors a binding motif for POU3F2, which is thought to play important roles in neuronal differentiation, melanocytes growth/differentiation and tumorigenesis. In this study, we found that capsaicin-mediated tNOX downregulation and cell migration inhibition were through POU3F2. The protein expression levels of POU3F2 and tNOX are positively correlated, and that overexpression of POU3F2 (and the corresponding upregulation of tNOX) enhanced the proliferation, migration and invasion in AGS (human gastric carcinoma) cells. In contrast, knockdown of POU3F2 downregulates tNOX, and the cancer phenotypes are affected. These findings not only shed light on the molecular mechanism of the anticancer properties of capsaicin, but also the transcription regulation of tNOX expression that may potentially explain how POU3F2 is associated with tumorigenesis. Full article
(This article belongs to the Special Issue Capsaicin)
Open AccessArticle New 30-Noroleanane Triterpenoid Saponins from Holboellia coriacea Diels
Molecules 2016, 21(6), 734; doi:10.3390/molecules21060734
Received: 10 May 2016 / Revised: 31 May 2016 / Accepted: 2 June 2016 / Published: 4 June 2016
PDF Full-text (455 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three new 30-noroleanane triterpenoid saponins, akebonoic acid 28-O-β-d-glucopyranosyl-(1′′→6′)-β-d-glucopyranosyl ester (1), akebonoic acid 28-O-(6′′-O-caffeoyl)-β-d-glucopyranosyl-(1′′→6′)-β-d-glucopyranosyl ester (Holboelliside A, 2) and
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Three new 30-noroleanane triterpenoid saponins, akebonoic acid 28-O-β-d-glucopyranosyl-(1′′→6′)-β-d-glucopyranosyl ester (1), akebonoic acid 28-O-(6′′-O-caffeoyl)-β-d-glucopyranosyl-(1′′→6′)-β-d-glucopyranosyl ester (Holboelliside A, 2) and 3β,20α,24-trihydroxy-29-norolean-12-en-28-oic acid 3-O-(6′-O-caffeoyl)-β-d-glucopyranoside (Holboelliside B, 3) were isolated from the stems of Holboellia coriacea Diels, together with five known compounds, eupteleasaponin VIII (4), 3α-akebonoic acid (5), quinatic acid (6), 3β-hydroxy-30-norhederagenin (7) and quinatoside A (8). The structures of these compounds were determined on the basis of spectral and chemical evidence. Compounds 15 were evaluated for their inhibitory activity against three human tumors HepG2, HCT116 and SGC-7901 cell lines in vitro. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Photocatalytic Activities of Copper Doped Cadmium Sulfide Microspheres Prepared by a Facile Ultrasonic Spray-Pyrolysis Method
Molecules 2016, 21(6), 735; doi:10.3390/molecules21060735
Received: 9 May 2016 / Revised: 1 June 2016 / Accepted: 2 June 2016 / Published: 15 June 2016
Cited by 3 | PDF Full-text (3710 KB) | HTML Full-text | XML Full-text
Abstract
Ultrasonic spray pyrolysis is a superior method for preparing and synthesizing spherical particles of metal oxide or sulfide semiconductors. Cadmium sulfide (CdS) photocatalysts with different sizes and doped-CdS with different dopants and doping levels have been synthesized to study their properties of photocatalytic
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Ultrasonic spray pyrolysis is a superior method for preparing and synthesizing spherical particles of metal oxide or sulfide semiconductors. Cadmium sulfide (CdS) photocatalysts with different sizes and doped-CdS with different dopants and doping levels have been synthesized to study their properties of photocatalytic hydrogen production from water. The CdS photocatalysts were characterized with scanning electron microscopy (SEM), X-ray fluorescence-spectrometry (XRF), UV-Vis absorption spectra and X-ray diffraction (XRD) to study their morphological and optical properties. The sizes of the prepared CdS particles were found to be proportional to the concentration of the metal nitrates in the solution. The CdS photocatalyst with smaller size showed a better photocatalytic activity. In addition, Cu doped CdS were also deposited and their photocatalytic activities were also investigated. Decreased bandgaps of CdS synthesized with this method were found and could be due to high density surface defects originated from Cd vacancies. Incorporating the Cu elements increased the bandgap by taking the position of Cd vacancies and reducing the surface defect states. The optimal Cu-doped level was found to be 0.5 mol % toward hydrogen evolution from aqueous media in the presence of sacrificial electron donors (Na2S and Na2SO3) at a pH of 13.2. This study demonstrated that ultrasonic spray pyrolysis is a feasible approach for large-scale photocatalyst synthesis and corresponding doping modification. Full article
(This article belongs to the Special Issue Photocatalytic Water Splitting—the Untamed Dream)
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Open AccessArticle Solid Phase Formylation of N-Terminus Peptides
Molecules 2016, 21(6), 736; doi:10.3390/molecules21060736
Received: 26 April 2016 / Revised: 27 May 2016 / Accepted: 1 June 2016 / Published: 4 June 2016
Cited by 5 | PDF Full-text (1030 KB) | HTML Full-text | XML Full-text
Abstract
Formylation of amino groups is a critical reaction involved in several biological processes including post-translational modification of histones. The addition of a formyl group (CHO) to the N-terminal end of a peptide chain generates biologically active molecules. N-formyl-peptides can be produced by different
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Formylation of amino groups is a critical reaction involved in several biological processes including post-translational modification of histones. The addition of a formyl group (CHO) to the N-terminal end of a peptide chain generates biologically active molecules. N-formyl-peptides can be produced by different methods. We performed the N-formylation of two chemotactic hexapetides, Met1-Leu2-Lys3-Leu4-Ile5-Val6 and Met1-Met2-Tyr3-Ala4-Leu5-Phe6, carrying out the reaction directly on peptidyl-resin following pre-activation of formic acid with N,N-dicyclohexylcarbodiimmide (DCC) in liquid phase. The overnight incubation at 4 °C resulted in a significant increase in production yields of formylated peptides compared to the reaction performed at room temperature. The method is consistently effective, rapid, and inexpensive. Moreover, the synthetic strategy can be applied for the formylation of all primary amines at N-terminus of peptide chains or amino groups of lysine side-chains in solid phase. Full article
Open AccessArticle Synthesis, Anti-HCV, Antioxidant and Reduction of Intracellular Reactive Oxygen Species Generation of a Chlorogenic Acid Analogue with an Amide Bond Replacing the Ester Bond
Molecules 2016, 21(6), 737; doi:10.3390/molecules21060737
Received: 16 May 2016 / Revised: 28 May 2016 / Accepted: 31 May 2016 / Published: 8 June 2016
Cited by 2 | PDF Full-text (746 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chlorogenic acid is a well known natural product with important bioactivities. It contains an ester bond formed between the COOH of caffeic acid and the 3-OH of quinic acid. We synthesized a chlorogenic acid analogue, 3α-caffeoylquinic acid amide, using caffeic and quinic acids
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Chlorogenic acid is a well known natural product with important bioactivities. It contains an ester bond formed between the COOH of caffeic acid and the 3-OH of quinic acid. We synthesized a chlorogenic acid analogue, 3α-caffeoylquinic acid amide, using caffeic and quinic acids as starting materials. The caffeoylquinc acid amide was found to be much more stable than chlorogenic acid and showed anti-Hepatitis C virus (anti-HCV) activity with a potency similar to chlorogenic acid. The caffeoylquinc acid amide potently protected HepG2 cells against oxidative stress induced by tert-butyl hydroperoxide. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Effects of Flavonoids in Lysimachia clethroides Duby on the Activities of Cytochrome P450 CYP2E1 and CYP3A4 in Rat Liver Microsomes
Molecules 2016, 21(6), 738; doi:10.3390/molecules21060738
Received: 3 May 2016 / Revised: 27 May 2016 / Accepted: 1 June 2016 / Published: 14 June 2016
Cited by 1 | PDF Full-text (2167 KB) | HTML Full-text | XML Full-text
Abstract
Incubation systems were established to investigate the effects of quercetin, kaempferol, isoquercitrin and astragalin in Lysimachia clethroides Duby on the activities of CYP2E1 and CYP3A4 in rat liver microsomes in vitro. Probe substrates of 4-nitrophenol and testosterone as well as flavonoids at
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Incubation systems were established to investigate the effects of quercetin, kaempferol, isoquercitrin and astragalin in Lysimachia clethroides Duby on the activities of CYP2E1 and CYP3A4 in rat liver microsomes in vitro. Probe substrates of 4-nitrophenol and testosterone as well as flavonoids at different concentrations were added to the incubation systems. After incubation, a validated high performance liquid chromatography (HPLC) method was applied to separate and determine the relevant metabolites. The results suggested that kaempferol exhibited a weak inhibition of CYP2E1 activity with an IC50 of 60.26 ± 2.54 μM, while quercetin and kaempferol caused a moderate inhibition of CYP3A4 activity with IC50 values of 18.77 ± 1.69 μM and 32.65 ± 1.32 μM, respectively. Isoquercitrin and astragalin had no effects on the activities of either CYP2E1 or CYP3A4. It could be speculated from these results that the inhibitory effects of quercetin and kaempferol on the activities of CYP2E1 and CYP3A4 could be the mechanisms underlying the hepatoprotective effects of L. clethroides. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Inhibition of Advanced Glycation End-Product Formation and Antioxidant Activity by Extracts and Polyphenols from Scutellaria alpina L. and S. altissima L.
Molecules 2016, 21(6), 739; doi:10.3390/molecules21060739
Received: 24 April 2016 / Revised: 24 May 2016 / Accepted: 1 June 2016 / Published: 14 June 2016
Cited by 2 | PDF Full-text (599 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Methanolic extracts from the aerial parts and roots of two Scutellaria species, S. alpina and S. altissima, and five polyphenols from these plants demonstrated a significant ability to inhibit the formation of advanced glycation end-products (AGE) in vitro. S. alpina,
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Methanolic extracts from the aerial parts and roots of two Scutellaria species, S. alpina and S. altissima, and five polyphenols from these plants demonstrated a significant ability to inhibit the formation of advanced glycation end-products (AGE) in vitro. S. alpina, which is richer in polyphenolic compounds, had strong antiglycation properties. These extracts demonstrated also high activity in the FRAP (ferric-reducing antioxidant power), antiradical (DPPH) and lipid peroxidation inhibition assays. Among the pure compounds, baicalin was the strongest glycation inhibitor (90.4% inhibition at 100 μg/mL), followed by luteolin (85.4%). Two other flavone glycosides had about half of this activity. Verbascoside was similar to the reference drug aminoguanidine (71.2% and 75.9%, respectively). The strong correlation observed between AGE inhibition and total flavonoid content indicated that flavonoids contribute significantly to antiglycation properties. A positive correlation was also observed between antiglycative and antioxidant activities. The studied skullcap species can be considered as a potential source of therapeutic agents for hyperglycemia-related disorders. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Functionalized Antimicrobial Composite Thin Films Printing for Stainless Steel Implant Coatings
Molecules 2016, 21(6), 740; doi:10.3390/molecules21060740
Received: 12 April 2016 / Revised: 1 June 2016 / Accepted: 2 June 2016 / Published: 9 June 2016
Cited by 3 | PDF Full-text (5203 KB) | HTML Full-text | XML Full-text
Abstract
In this work we try to address the large interest existing nowadays in the better understanding of the interaction between microbial biofilms and metallic implants. Our aimed was to identify a new preventive strategy to control drug release, biofilm formation and contamination of
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In this work we try to address the large interest existing nowadays in the better understanding of the interaction between microbial biofilms and metallic implants. Our aimed was to identify a new preventive strategy to control drug release, biofilm formation and contamination of medical devices with microbes. The transfer and printing of novel bioactive glass-polymer-antibiotic composites by Matrix-Assisted Pulsed Laser Evaporation into uniform thin films onto 316 L stainless steel substrates of the type used in implants are reported. The targets were prepared by freezing in liquid nitrogen mixtures containing polymer and antibiotic reinforced with bioglass powder. The cryogenic targets were submitted to multipulse evaporation by irradiation with an UV KrF* (λ = 248 nm, τFWHM ≤ 25 ns) excimer laser source. The prepared structures were analyzed by infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy and profilometry, before and after immersion in physiological fluids. The bioactivity and the release of the antibiotic have been evaluated. We showed that the incorporated antibiotic underwent a gradually dissolution in physiological fluids thus supporting a high local treatment efficiency. Electrochemical measurements including linear sweep voltammetry and impedance spectroscopy studies were carried out to investigate the corrosion resistance of the coatings in physiological environments. The in vitro biocompatibility assay using the MG63 mammalian cell line revealed that the obtained nanostructured composite films are non-cytotoxic. The antimicrobial effect of the coatings was tested against Staphylococcus aureus and Escherichia coli strains, usually present in implant-associated infections. An anti-biofilm activity was evidenced, stronger against E. coli than the S. aureus strain. The results proved that the applied method allows for the fabrication of implantable biomaterials which shield metal ion release and possess increased biocompatibility and resistance to microbial colonization and biofilm growth. Full article
(This article belongs to the Special Issue Biomaterials and Bioprinting)
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Open AccessArticle Optimization of Preparation Conditions for Lysozyme Nanoliposomes Using Response Surface Methodology and Evaluation of Their Stability
Molecules 2016, 21(6), 741; doi:10.3390/molecules21060741
Received: 31 March 2016 / Revised: 25 May 2016 / Accepted: 31 May 2016 / Published: 8 June 2016
Cited by 1 | PDF Full-text (3658 KB) | HTML Full-text | XML Full-text
Abstract
The main purpose of this study was to optimize the preparation of lysozyme nanoliposomes using response surface methodology and measure their stability. The stabilities of lysozyme nanoliposomes in simulated gastrointestinal fluid (SGF), simulated intestinal fluid (SIF), as well as pH, temperature and sonication
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The main purpose of this study was to optimize the preparation of lysozyme nanoliposomes using response surface methodology and measure their stability. The stabilities of lysozyme nanoliposomes in simulated gastrointestinal fluid (SGF), simulated intestinal fluid (SIF), as well as pH, temperature and sonication treatment time were evaluated. Reverse-phase evaporation method is an easy, speedy, and beneficial approach for nanoliposomes’ preparation and optimization. The optimal preparative conditions were as follows: phosphatidylcholine-to-cholesterol ratio of 3.86, lysozyme concentration of 1.96 mg/mL, magnetic stirring time of 40.61 min, and ultrasound time of 14.15 min. At the optimal point, encapsulation efficiency and particle size were found to be 75.36% ± 3.20% and 245.6 nm ± 5.2 nm, respectively. The lysozyme nanoliposomes demonstrated certain stability in SGF and SIF at a temperature of 37 °C for 4 h, and short sonication handling times were required to attain nano-scaled liposomes. Under conditions of high temperature, acidity and alkalinity, lysozyme nanoliposomes are unstable. Full article
(This article belongs to the collection Nanomedicine)
Open AccessCommunication Synthesis of C2-Symmetric Benzimidazolium Salts and Their Application in Palladium-Catalyzed Enantioselective Intramolecular α-Arylation of Amides
Molecules 2016, 21(6), 742; doi:10.3390/molecules21060742
Received: 14 April 2016 / Revised: 26 May 2016 / Accepted: 1 June 2016 / Published: 8 June 2016
Cited by 2 | PDF Full-text (886 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of C2-symmetric chiral benzimidazolium salts, the precursor of N-heterocyclic carbene ligands, were designed and synthesized from 1,2-dibromobenzene. In situ prepared corresponding carbenes were tested in the asymmetric palladium-catalyzed intramolecular α-arylation of amides, affording chiral diarylmethanols with high yields
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A series of C2-symmetric chiral benzimidazolium salts, the precursor of N-heterocyclic carbene ligands, were designed and synthesized from 1,2-dibromobenzene. In situ prepared corresponding carbenes were tested in the asymmetric palladium-catalyzed intramolecular α-arylation of amides, affording chiral diarylmethanols with high yields and moderate enantioselectivities. Full article
(This article belongs to the Special Issue Palladium Catalysts 2016)
Open AccessArticle Antimicrobial Activity and Modulatory Effect of Essential Oil from the Leaf of Rhaphiodon echinus (Nees & Mart) Schauer on Some Antimicrobial Drugs
Molecules 2016, 21(6), 743; doi:10.3390/molecules21060743
Received: 3 April 2016 / Revised: 30 May 2016 / Accepted: 31 May 2016 / Published: 8 June 2016
Cited by 6 | PDF Full-text (1373 KB) | HTML Full-text | XML Full-text
Abstract
Background: Rhaphiodon echinus is a weed plant used in the Brazilian folk medicinal for the treatment of infectious diseases. In this study, the essential oil of R. echinus leaf was investigated for its antimicrobial properties. Methods: The chemical constituents of the
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Background: Rhaphiodon echinus is a weed plant used in the Brazilian folk medicinal for the treatment of infectious diseases. In this study, the essential oil of R. echinus leaf was investigated for its antimicrobial properties. Methods: The chemical constituents of the essential oil were characterized by GC-MS. The antimicrobial properties were determined by studying by the microdilution method the effect of the oil alone, and in combination with antifungal or antibiotic drugs against the fungi Candida albicans, Candida krusei and Candida tropicalis and the microbes Escherichia coli, Staphylococcus aureus and Pseudomonas. In addition, the iron (II) chelation potential of the oil was determined. Results: The results showed the presence of β-caryophyllene and bicyclogermacrene in major compounds, and revealed a low antifungal and antibacterial activity of the essential oil, but a strong modulatory effect on antimicrobial drugs when associated with the oil. The essential oil showed iron (II) chelation activity. Conclusions: The GC-MS characterization revealed the presence of monoterpenes and sesquiterpenes in the essential oil and metal chelation potential, which may be responsible in part for the modulatory effect of the oil. These findings suggest that essential oil of R. echinus is a natural product capable of enhancing the antibacterial and antifungal activity of antimicrobial drugs. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
Open AccessArticle Tandem Catalysis of an Aldol-‘Click’ Reaction System within a Molecular Hydrogel
Molecules 2016, 21(6), 744; doi:10.3390/molecules21060744
Received: 26 April 2016 / Revised: 2 June 2016 / Accepted: 3 June 2016 / Published: 8 June 2016
Cited by 1 | PDF Full-text (2418 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A heterogeneous supramolecular catalytic system for multicomponent aldol-‘click’ reactions is reported. The copper(I) metallohydrogel functionalized with a phenyltriazole fragment was able to catalyze the multicomponent reaction between phenylacetylene, p-nitrobenzaldehyde, and an azide containing a ketone moiety, obtaining the corresponding aldol products in
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A heterogeneous supramolecular catalytic system for multicomponent aldol-‘click’ reactions is reported. The copper(I) metallohydrogel functionalized with a phenyltriazole fragment was able to catalyze the multicomponent reaction between phenylacetylene, p-nitrobenzaldehyde, and an azide containing a ketone moiety, obtaining the corresponding aldol products in good yields. A possible mechanistic pathway responsible for this unexpected catalytic behavior has been proposed. Full article
(This article belongs to the Special Issue New Molecular Materials)
Open AccessArticle Characterization of Secondary Metabolites from Purple Ipomoea batatas Leaves and Their Effects on Glucose Uptake
Molecules 2016, 21(6), 745; doi:10.3390/molecules21060745
Received: 5 May 2016 / Revised: 28 May 2016 / Accepted: 3 June 2016 / Published: 8 June 2016
Cited by 2 | PDF Full-text (3255 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ipomoea batatas has long been used in folk medicine for the treatment of hyperglycemia or as a food additive for the prevention of type 2 diabetes. However, neither the plant extract nor its active components have been evaluated systematically. In this work four
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Ipomoea batatas has long been used in folk medicine for the treatment of hyperglycemia or as a food additive for the prevention of type 2 diabetes. However, neither the plant extract nor its active components have been evaluated systematically. In this work four crude extracts, including n-hexane- (IBH), 95% MeOH- (IBM), n-BuOH- (IBB), and H2O-soluble (IBW) fractions, were prepared by fractionation of a methanolic extract of purple I. batatas leaves. Twenty-four pure compounds 124 were then isolated by various chromatographic techniques and their structures identified from NMR and MS data. Glucose uptake assays in differentiated 3T3-L1 adipocytes and rat primary hepatocytes, as well as western blot analysis, were carried out to evaluate the antidiabetic activity of this species. The IBH crude fraction, with methyl decanoate (22) as a major and active compound, showed the greatest effect on glucose uptake, most likely via activation of Glut4 and regulation of the PI3K/AKT pathway. Quercetin 3-O-β-d-sophoroside (1), quercetin (3), benzyl β-d-glucoside (10), 4-hydroxy-3-methoxybenzaldehyde (12), and methyl decanoate (22) could be important components contributing to the antidiabetic effects. We conclude that purple I. batatas leaves have potential as an antidiabetic plant source and the active constituents 1, 3, 10, 12, and 22 are promising lead candidates for future investigation. Full article
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Open AccessArticle Development and Validation of an Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Determination of Four Type B Trichothecenes and Masked Deoxynivalenol in Various Feed Products
Molecules 2016, 21(6), 747; doi:10.3390/molecules21060747
Received: 9 March 2016 / Revised: 21 May 2016 / Accepted: 30 May 2016 / Published: 8 June 2016
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Abstract
A reliable and sensitive analytical method was developed for simultaneous determination of deoxynivalenol(DON), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FUS-X), and masked deoxynivalenol (deoxynivalenol-3-glucoside, D3G) in formula feed, concentrated feed, and premixed feed products. The method was based on an improved sample pretreatment
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A reliable and sensitive analytical method was developed for simultaneous determination of deoxynivalenol(DON), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FUS-X), and masked deoxynivalenol (deoxynivalenol-3-glucoside, D3G) in formula feed, concentrated feed, and premixed feed products. The method was based on an improved sample pretreatment with the commercially available HLB cartridges used for sample purification and enrichment followed by analysis using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Several key parameters including the extraction solvents, the positions of sample loading solvents, washing and elution solvents for HLB cartridges were carefully optimized to achieve optimal extraction and purification efficiencies. The established method was extensively validated by determining the linearity (R2 ≥ 0.99), sensitivity (limit of quantification in the range of 0.08–4.85 μg/kg), recovery (79.3%–108.1%), precision (Intra-day RSDs ≤ 13.5% and Inter-day RSDs ≤ 14.9%), and then was successfully applied to determine the four type B trichothecenes and D3G in a total of 31 feed samples. Among them, 26 were contaminated with various mycotoxins at the levels of 2.1–864.5 μg/kg, and D3G has also been detected in 17 samples with the concentrations in the range of 2.1–34.8 μg/kg, proving the established method to be a valuable tool for type B trichothecenes and masked DON monitoring in complex feed matrices. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Cytotoxic Labdane Diterpenes from Hedychium ellipticum Buch.-Ham. ex Sm.
Molecules 2016, 21(6), 749; doi:10.3390/molecules21060749
Received: 11 May 2016 / Revised: 27 May 2016 / Accepted: 3 June 2016 / Published: 9 June 2016
Cited by 4 | PDF Full-text (363 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In order to reveal the constituents and their biological activities, we carried out a phytochemical study on Hedychium ellipticum Buch.-Ham. ex Sm. (Zingiberaceae). Ten labdane diterpenoids (110) were isolated from the rhizomes of H. ellipticum for the first time.
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In order to reveal the constituents and their biological activities, we carried out a phytochemical study on Hedychium ellipticum Buch.-Ham. ex Sm. (Zingiberaceae). Ten labdane diterpenoids (110) were isolated from the rhizomes of H. ellipticum for the first time. Their structures were identified on the basis of spectroscopic analyses including two-dimensional NMR and comparison with literature data. All of these compounds were evaluated for their antimycobacterial activity against Mycobacterium tuberculosis and cytotoxicity against KB, MCF7, NCI-H187 and Vero cells. The result showed that compounds 1 and 7 exhibited moderate activity against Mycobacterium tuberculosis and compounds 4, 6 and 7 displayed remarkable cytotoxic activity. This is the first report on the presence of all compounds in H. ellipticum and the first time that their structure activity relationship has been discussed. Full article
(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)
Open AccessArticle High Affinity Immobilization of Proteins Using the CrAsH/TC Tag
Molecules 2016, 21(6), 750; doi:10.3390/molecules21060750
Received: 5 May 2016 / Revised: 2 June 2016 / Accepted: 3 June 2016 / Published: 8 June 2016
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Abstract
Protein microarrays represent important tools for biomedical analysis. We have recently described the use of the biarsenical-tetracysteine (TC) tag for the preparation of protein microarrays. The unique feature of this tag enables the site-specific immobilization of TC-containing proteins on biarsenical-modified surfaces, resulting in
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Protein microarrays represent important tools for biomedical analysis. We have recently described the use of the biarsenical-tetracysteine (TC) tag for the preparation of protein microarrays. The unique feature of this tag enables the site-specific immobilization of TC-containing proteins on biarsenical-modified surfaces, resulting in a fluorescence enhancement that allows the direct quantification of the immobilized proteins. Moreover, the reversibility of the binding upon incubation with large quantities of thiols permits the detachment of the proteins from the surface, thereby enabling recovery of the substrate to extend the life time of the slide. Herein, we describe our recent results that further extend the applicability of the CrAsH/TC tag to the fabrication of biochips. With this aim, the immobilization of proteins on surfaces has been investigated using two different spacers and two TC tags, the minimal TC sequence (CCPGCC) and an optimized motif (FLNCCPGCCMEP). While the minimal peptide motif enables a rapid recycling of the slide, the optimized TC sequence reveals an increased affinity due to its greater resistance to displacement by thiols. Moreover, the developed methodology was applied to the immobilization of proteins via on-chip ligation of recombinant protein thioesters. Full article
(This article belongs to the Special Issue Biomolecules Modification)
Open AccessArticle Stabilization of Candida antarctica Lipase B (CALB) Immobilized on Octyl Agarose by Treatment with Polyethyleneimine (PEI)
Molecules 2016, 21(6), 751; doi:10.3390/molecules21060751
Received: 13 May 2016 / Revised: 1 June 2016 / Accepted: 6 June 2016 / Published: 8 June 2016
Cited by 15 | PDF Full-text (2855 KB) | HTML Full-text | XML Full-text
Abstract
Lipase B from Candida antarctica (CALB) was immobilized on octyl agarose (OC) and physically modified with polyethyleneimine (PEI) in order to confer a strong ion exchange character to the enzyme and thus enable the immobilization of other enzymes on its surface. The enzyme
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Lipase B from Candida antarctica (CALB) was immobilized on octyl agarose (OC) and physically modified with polyethyleneimine (PEI) in order to confer a strong ion exchange character to the enzyme and thus enable the immobilization of other enzymes on its surface. The enzyme activity was fully maintained during the coating and the thermal stability was marginally improved. The enzyme release from the support by incubation in the non-ionic detergent Triton X-100 was more difficult after the PEI-coating, suggesting that some intermolecular physical crosslinking had occurred, making this desorption more difficult. Thermal stability was marginally improved, but the stability of the OCCALB-PEI was significantly better than that of OCCALB during inactivation in mixtures of aqueous buffer and organic cosolvents. SDS-PAGE analysis of the inactivated biocatalyst showed the OCCALB released some enzyme to the medium during inactivation, and this was partially prevented by coating with PEI. This effect was obtained without preventing the possibility of reuse of the support by incubation in 2% ionic detergents. That way, this modified CALB not only has a strong anion exchange nature, while maintaining the activity, but it also shows improved stability under diverse reaction conditions without affecting the reversibility of the immobilization. Full article
(This article belongs to the Special Issue Enzyme Immobilization 2016)
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Open AccessArticle Hyper IgE in Childhood Eczema and Risk of Asthma in Chinese Children
Molecules 2016, 21(6), 753; doi:10.3390/molecules21060753
Received: 23 February 2016 / Revised: 25 May 2016 / Accepted: 3 June 2016 / Published: 10 June 2016
Cited by 1 | PDF Full-text (201 KB) | HTML Full-text | XML Full-text
Abstract
Background: Atopic eczema is a common childhood disease associated with high IgE and eosinophilia. We characterized the clinical features associated with hyper-IgE (defined as IgE > 2000 IU/L) in eczema. Methods: Nottingham Eczema Severity Score (NESS), family and personal history of atopy,
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Background: Atopic eczema is a common childhood disease associated with high IgE and eosinophilia. We characterized the clinical features associated with hyper-IgE (defined as IgE > 2000 IU/L) in eczema. Methods: Nottingham Eczema Severity Score (NESS), family and personal history of atopy, skin prick test (SPT) for common food and aeroallergens, highest serum IgE ever and eosinophil counts were evaluated in 330 children eczema patients. Childhood-NESS (NESS performed at <10 years of age) and adolescent-NESS (NESS performed at >10 years of age) were further analyzed. Results: IgE correlated with NESS (spearman coefficient 0.35, p < 0.001) and eosinophil percentage (spearman coefficient 0.56, p = 0.001). Compared with IgE ≤ 2000IU/L (n = 167), patients with hyper-IgE (n = 163) were associated with male gender (p = 0.002); paternal atopy (p = 0.026); personal history of atopic rhinitis (p = 0.016); asthma (p < 0.001); dietary avoidance (p < 0.001); use of wet wrap (p < 0.001); traditional Chinese medicine use (TCM, p < 0.001); immunomodulant use (azathioprine or cyclosporine, p < 0.001); skin prick sensitization by dust mites (p < 0.001), cats (p = 0.012), dogs (p = 0.018), food (p = 0.002); eosinophilia (p < 0.001); more severe disease during childhood (p < 0.0001) and during adolescence (p < 0.0001), but not onset age of eczema or maternal atopy. Logistic regression showed that hyper-IgE was associated with personal history of asthma (exp(B) = 5.12, p = 0.002) and eczema severity during childhood and adolescence (p < 0.001). For patients <10 years of age, dust mite sensitization (p = 0.008) was associated with hyper-IgE. For patients >10years of age, food allergen sensitization was associated with hyper-IgE (p = 0.008). Conclusions: Hyper-IgE is independently associated with asthma, more severe atopy and more severe eczema during childhood and adolescence. IgE > 2000 IU/L may be a tool to aid prognostication of this chronic relapsing dermatologic disease and its progression to asthma. Full article
Open AccessArticle Evaluation of the Antibacterial Effects and Mechanism of Action of Protocatechualdehyde against Ralstonia solanacearum
Molecules 2016, 21(6), 754; doi:10.3390/molecules21060754
Received: 1 May 2016 / Revised: 5 June 2016 / Accepted: 7 June 2016 / Published: 9 June 2016
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Abstract
Protocatechualdehyde (PCA) is an important plant-derived natural product that has been associated with a wide variety of biological activities and has been widely used in medicine as an antioxidant, anti-aging and an anti-inflammatory agent. However, fewer reports concerning its antibacterial effects on plant-pathogenic
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Protocatechualdehyde (PCA) is an important plant-derived natural product that has been associated with a wide variety of biological activities and has been widely used in medicine as an antioxidant, anti-aging and an anti-inflammatory agent. However, fewer reports concerning its antibacterial effects on plant-pathogenic bacteria exist. Therefore, in this study, protocatechualdehyde was evaluated for its antibacterial activity against plant pathogens along with the mechanism of its antibacterial action. PCA at 40 μg/mL was highly active against R. solanacearum and significantly inhibited its growth. The minimum bactericidal concentration and minimum inhibitory concentration values for PCA were 40 μg/mL and 20 μg/mL, respectively. Further investigation of the mechanism of action of PCA via transmission electron microscopy and biological assays indicated that the destruction of the cell structure, the shapes and the inhibition of biofilm formation were important. In addition, the application of PCA effectively reduced the incidence of bacterial wilt on tobacco under greenhouse conditions, and the control efficiency was as high as 92.01% at nine days after inoculation. Taken together, these findings suggest that PCA exhibits strong antibacterial activity against R. solanacearum and has the potential to be applied as an effective antibacterial agent for controlling bacterial wilt caused by R. solanacearum. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Antifungal Activity and Biochemical Response of Cuminic Acid against Phytophthora capsici Leonian
Molecules 2016, 21(6), 756; doi:10.3390/molecules21060756
Received: 21 April 2016 / Revised: 3 June 2016 / Accepted: 6 June 2016 / Published: 11 June 2016
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Abstract
Phytophthora blight of pepper caused by Phytophthora capsici Leonian is a destructive disease throughout the world. Cuminic acid, extracted from the seed of Cuminum cyminum L., belongs to the benzoic acid chemical class. In this study, the sensitivity and biochemical response of P.
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Phytophthora blight of pepper caused by Phytophthora capsici Leonian is a destructive disease throughout the world. Cuminic acid, extracted from the seed of Cuminum cyminum L., belongs to the benzoic acid chemical class. In this study, the sensitivity and biochemical response of P. capsici to cuminic acid was determined. The mean EC50 (50% effective concentration) values for cuminic acid in inhibiting mycelial growth and zoospore germination of the 54 studied P. capsici isolates were 14.54 ± 5.23 μg/mL and 6.97 ± 2.82 μg/mL, respectively. After treatment with cuminic acid, mycelial morphology, sporangium formation and mycelial respiration were significantly influenced; cell membrane permeability and DNA content increased markedly, but pyruvic acid content, adenosine triphosphate (ATP) content, and ATPase activity decreased compared with the untreated control. In pot experiments, cuminic acid exhibited both protective and curative activity. Importantly, POD and PAL activity of the pepper leaves increased after being treated with cuminic acid. These indicated that cuminic acid not only showed antifungal activity, but also could improve the defense capacity of the plants. All the results suggested that cuminic acid exhibits the potential to be developed as a new phytochemical fungicide, and this information increases our understanding of the mechanism of action of cuminic acid against Phytophthora capsici. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Metabolism of 20(S)-Ginsenoside Rg2 by Rat Liver Microsomes: Bioactivation to SIRT1-Activating Metabolites
Molecules 2016, 21(6), 757; doi:10.3390/molecules21060757
Received: 12 April 2016 / Revised: 22 May 2016 / Accepted: 7 June 2016 / Published: 10 June 2016
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Abstract
20(S)-Ginsenoside Rg2 (1) has recently become a hot research topic due to its potent bioactivities and abundance in natural sources such as the roots, rhizomes and stems-leaves of Panax ginseng. However, due to the lack of studies
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20(S)-Ginsenoside Rg2 (1) has recently become a hot research topic due to its potent bioactivities and abundance in natural sources such as the roots, rhizomes and stems-leaves of Panax ginseng. However, due to the lack of studies on systematic metabolic profiles, the prospects for new drug development of 1 are still difficult to predict, which has become a huge obstacle for its safe clinical use. To solve this problem, investigation of the metabolic profiles of 1 in rat liver microsomes was first carried out. To identify metabolites, a strategy of combined analyses based on prepared metabolites by column chromatography and ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was performed. As a result, four metabolites M1M4, including a rare new compound named ginsenotransmetin A (M1), were isolated and the structures were confirmed by spectroscopic analyses. A series of metabolites of 1, MAMG, were also tentatively identified by UPLC-Q-TOF/MS in rat liver microsomal incubate of 1. Partial metabolic pathways were proposed. Among them, 1 and its metabolites M1, M3 and M4 were discovered for the first time to be activators of SIRT1. The SIRT1 activating effects of the metabolite M1 was comparable to those of 1, while the most interesting SIRT1 activatory effects of M3 and M4 were higher than that of 1 and comparable with that of resveratrol, a positive SIRT1 activator. These results indicate that microsome-dependent metabolism may represent a bioactivation pathway for 1. This study is the first to report the metabolic profiles of 1 in vitro, and the results provide an experimental foundation to better understand the in vivo metabolic fate of 1. Full article
(This article belongs to the Special Issue Triterpenes and Triterpenoids 2016)
Open AccessArticle Design, Synthesis and Cytotoxicity of Novel Dihydroartemisinin-Coumarin Hybrids via Click Chemistry
Molecules 2016, 21(6), 758; doi:10.3390/molecules21060758
Received: 16 May 2016 / Revised: 5 June 2016 / Accepted: 7 June 2016 / Published: 10 June 2016
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Abstract
In order to develop novel chemotherapeutic agents with potent anticancer activities, we designed four series of novel compounds employing hybridization strategy. Twenty novel dihydroartemisinin-coumarin hybrids, 10ae, 11ae, 12ae, 13ae, were synthesized
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In order to develop novel chemotherapeutic agents with potent anticancer activities, we designed four series of novel compounds employing hybridization strategy. Twenty novel dihydroartemisinin-coumarin hybrids, 10ae, 11ae, 12ae, 13ae, were synthesized via click chemistry in this study and their structures were characterized by HRMS and NMR. The cytotoxic activities were measured by MTT assay against three cancer cell lines (HCT-116, MDA-MB-231, and HT-29) under normoxic or anoxic conditions, respectively. The target compounds exhibited moderate activity with IC50 values in the 0.05–125.40 μM range, and these compounds exhibited better activity against HT-29 cell line under anoxic condition. The cytotoxic activities of most compounds under anoxic condition displayed one- to 10-fold greater activity than under normoxic condition. Compounds 10ae showed better selectivity against the HT-29 cell line than the other two cell lines. These results indicated that our design of CA IX inhibitors does correspond with its action mode to some degree and deserves further investigation. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Probing Steroidal Substrate Specificity of Cytochrome P450 BM3 Variants
Molecules 2016, 21(6), 760; doi:10.3390/molecules21060760
Received: 27 April 2016 / Revised: 4 June 2016 / Accepted: 6 June 2016 / Published: 11 June 2016
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Abstract
M01A82W, M11A82W and M01A82WS72I are three cytochrome P450 BM3 (CYP102A1) variants. They can catalyze the hydroxylation of testosterone (TES) and norethisterone at different positions, thereby making them promising biocatalysts for steroid hydroxylation. With the aim of obtaining more hydroxylated steroid precursors it is
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M01A82W, M11A82W and M01A82WS72I are three cytochrome P450 BM3 (CYP102A1) variants. They can catalyze the hydroxylation of testosterone (TES) and norethisterone at different positions, thereby making them promising biocatalysts for steroid hydroxylation. With the aim of obtaining more hydroxylated steroid precursors it is necessary to probe the steroidal substrate diversity of these BM3 variants. Here, three purified BM3 variants were first incubated with eight steroids, including testosterone (TES), methyltestosterone (MT), cholesterol, β-sitosterol, dehydroepiandrosterone (DHEA), diosgenin, pregnenolone and ergosterol. The results indicated that the two 3-keto-Δ4-steroids TES and MT can be hydroxylated at various positions by the three BM3 mutants, respectively. On the contrary, the three enzymes displayed no any activity toward the remaining six 3-hydroxy-Δ5-steroids. This result indicates that the BM3 mutants prefer 3-keto-Δ4-steroids as hydroxylation substrates. To further verify this notion, five other substrates, including two 3-hydroxy-Δ5-steroids and three 3-keto-Δ4-steroids, were carefully selected to incubate with the three BM3 variants. The results indicated the three 3-keto-Δ4-steroids can be metabolized to form hydroxysteroids by the three BM3 variants. On the other hand, the two 3-hydroxy-Δ5-steroids cannot be hydroxylated at any position by the BM3 mutants. These results further support the above conclusion, therefore demonstrating the 3-keto-Δ4–steroid substrate preference of BM3 mutants, and laying a foundation for microbial production of more hydroxylated steroid intermediates using BM3 variants. Full article
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Open AccessArticle Fabrication, Characterization, and Evaluation of Bionanocomposites Based on Natural Polymers and Antibiotics for Wound Healing Applications
Molecules 2016, 21(6), 761; doi:10.3390/molecules21060761
Received: 7 March 2016 / Revised: 3 June 2016 / Accepted: 6 June 2016 / Published: 10 June 2016
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Abstract
The aim of our research activity was to obtain a biocompatible nanostructured composite based on naturally derived biopolymers (chitin and sodium alginate) loaded with commercial antibiotics (either Cefuroxime or Cefepime) with dual functions, namely promoting wound healing and assuring the local delivery of
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The aim of our research activity was to obtain a biocompatible nanostructured composite based on naturally derived biopolymers (chitin and sodium alginate) loaded with commercial antibiotics (either Cefuroxime or Cefepime) with dual functions, namely promoting wound healing and assuring the local delivery of the loaded antibiotic. Compositional, structural, and morphological evaluations were performed by using the thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and fourier transform infrared spectroscopy (FTIR) analytical techniques. In order to quantitatively and qualitatively evaluate the biocompatibility of the obtained composites, we performed the tetrazolium-salt (MTT) and agar diffusion in vitro assays on the L929 cell line. The evaluation of antimicrobial potential was evaluated by the viable cell count assay on strains belonging to two clinically relevant bacterial species (i.e., Escherichia coli and Staphylococcus aureus). Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)
Open AccessArticle Synthesis and Cytotoxic Activity of Biphenylurea Derivatives Containing Indolin-2-one Moieties
Molecules 2016, 21(6), 762; doi:10.3390/molecules21060762
Received: 12 April 2016 / Revised: 26 May 2016 / Accepted: 3 June 2016 / Published: 10 June 2016
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Abstract
In our endeavor towards the development of potent anticancer agents, two different sets of biphenylurea-indolinone conjugates, 5as and 8a,b were synthesized. The in vitro cytotoxicity of the synthesized compounds was examined in two human cancer cell lines, namely MCF-7
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In our endeavor towards the development of potent anticancer agents, two different sets of biphenylurea-indolinone conjugates, 5as and 8a,b were synthesized. The in vitro cytotoxicity of the synthesized compounds was examined in two human cancer cell lines, namely MCF-7 breast cancer and PC-3 prostate cancer cells using the sulforhodamine B (SRB) colorimetric assay. In particular, the MCF-7 cancer cell line was more susceptible to the synthesized compounds. Compound 5o (IC50 = 1.04 ± 0.10 μM) emerged as the most active member in this study against MCF-7, with 7-fold increased activity compared to the reference drug, doxorubicin (IC50 = 7.30 ± 0.84 μM). Compounds 5l, 5q and 8b also exhibited superior cytotoxic activity against MCF-7 with IC50 values of 1.93 ± 0.17, 3.87 ± 0.31 and 4.66 ± 0.42 μM, respectively. All of the tested compounds were filtered according to the Lipinski and Veber rules and all of them passed the filters. Additionally, several ADME descriptors for the synthesized compounds 5as and 8a,b were predicted via a theoretical kinetic study performed using the Discovery Studio 2.5 software. Full article
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Open AccessArticle Bioaccumulation and Subchronic Toxicity of 14 nm Gold Nanoparticles in Rats
Molecules 2016, 21(6), 763; doi:10.3390/molecules21060763
Received: 12 May 2016 / Revised: 2 June 2016 / Accepted: 6 June 2016 / Published: 10 June 2016
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Abstract
Colloidal suspensions of 14 nm gold nanoparticles (AuNPs) were repeatedly administered intravenously at three dose levels (0.9, 9 and 90 µg) to male Sprague Dawley rats weekly for 7 weeks, followed by a 14-day washout period. After sacrificing, the amount of gold was
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Colloidal suspensions of 14 nm gold nanoparticles (AuNPs) were repeatedly administered intravenously at three dose levels (0.9, 9 and 90 µg) to male Sprague Dawley rats weekly for 7 weeks, followed by a 14-day washout period. After sacrificing, the amount of gold was quantified in the liver, lungs, spleen, skeleton and carcass using neutron activation analysis (NAA). During the study, pre- and post (24 h) administration blood samples were collected from both the test and control groups, the latter which received an equal injection volume of normal saline. General health indicators were monitored together with markers of kidney and liver damage for acute and subchronic toxicity assessment. Histopathological assessments were done on the heart, kidneys, liver, lungs and spleen to assess any morphological changes as a result of the exposure to AuNPs. The mass measurements of all the groups showed a steady increase with no signs of overt toxicity. The liver had the highest amount of gold (µg) per gram of tissue after 56 days followed by the spleen, lungs, skeleton and carcass. Markers of kidney and liver damage showed similar trends between the pre and post samples within each group and across groups. The histopathological examination also showed no hepatotoxicity and nephrotoxicity. There was accumulation of Au in tissues after repeated dosing, albeit with no observable overt toxicity, kidney or liver damage. Full article
(This article belongs to the Special Issue Gold Nanoparticles for Biomedical Applications)
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Open AccessArticle A New Xanthone Glycoside from the Endolichenic Fungus Sporormiella irregularis
Molecules 2016, 21(6), 764; doi:10.3390/molecules21060764
Received: 14 April 2016 / Revised: 3 June 2016 / Accepted: 4 June 2016 / Published: 11 June 2016
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Abstract
A new xanthone glycoside, sporormielloside (1), was isolated from an EtOAc extract of an endolichenic fungal strain Sporormiella irregularis (No. 71-11-4-1), along with two known xanthones (2, 3). Their structures were determined by detailed spectroscopic analysis (IR, MS,
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A new xanthone glycoside, sporormielloside (1), was isolated from an EtOAc extract of an endolichenic fungal strain Sporormiella irregularis (No. 71-11-4-1), along with two known xanthones (2, 3). Their structures were determined by detailed spectroscopic analysis (IR, MS, and 1D- and 2D-NMR), a chemical method, and a comparison of NMR data with closely related compounds previously reported. According to the structures of isolated compounds, their plausible biosynthetic pathway was deduced. Full article
(This article belongs to the Section Natural Products)
Open AccessFeature PaperArticle A New Alkamide with an Endoperoxide Structure from Acmella ciliata (Asteraceae) and Its in Vitro Antiplasmodial Activity
Molecules 2016, 21(6), 765; doi:10.3390/molecules21060765
Received: 12 May 2016 / Revised: 1 June 2016 / Accepted: 2 June 2016 / Published: 11 June 2016
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Abstract
From the aerial parts of Acmella ciliata (H.B.K.) Cassini (basionym Spilanthes ciliata Kunth; Asteraceae), three alkamides were isolated and identified by mass- and NMR spectroscopic methods as (2E,6E,8E)-N-isobutyl-2,6,8-decatrienamide (spilanthol, (1)), N-(2-phenethyl)-2E
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From the aerial parts of Acmella ciliata (H.B.K.) Cassini (basionym Spilanthes ciliata Kunth; Asteraceae), three alkamides were isolated and identified by mass- and NMR spectroscopic methods as (2E,6E,8E)-N-isobutyl-2,6,8-decatrienamide (spilanthol, (1)), N-(2-phenethyl)-2E-en-6,8-nonadiynamide (2) and (2E,7Z)-6,9-endoperoxy-N-isobutyl-2,7-decadienamide (3). While 1 and 2 are known alkamides, compound 3 has not been described until now. It was found that the unusual cyclic peroxide 3 exists as a racemate of both enantiomers of each alkamide; the 6,9-cis- as well as the 6,9-trans-configured diastereomers, the former represents the major, the latter the minor constituent of the mixture. In vitro tests for activity against the human pathogenic parasites Trypanosoma brucei rhodesiense and Plasmodium falciparum revealed that 1 and 3 possess activity against the NF54 strain of the latter (IC50 values of 4.5 and 5.1 µM, respectively) while 2 was almost inactive. Compound 3 was also tested against multiresistant P. falciparum K1 and was found to be even more active against this parasite strain (IC50 = 2.1 µM) with considerable selectivity (IC50 against L6 rat skeletal myoblasts = 168 µM). Full article
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Open AccessArticle Chemical Incorporation of Chain-Terminating Nucleoside Analogs as 3′-Blocking DNA Damage and Their Removal by Human ERCC1-XPF Endonuclease
Molecules 2016, 21(6), 766; doi:10.3390/molecules21060766
Received: 13 May 2016 / Accepted: 3 June 2016 / Published: 11 June 2016
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Abstract
Nucleoside/nucleotide analogs that lack the 3′-hydroxy group are widely utilized for HIV therapy. These chain-terminating nucleoside analogs (CTNAs) block DNA synthesis after their incorporation into growing DNA, leading to the antiviral effects. However, they are also considered to be DNA damaging agents, and
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Nucleoside/nucleotide analogs that lack the 3′-hydroxy group are widely utilized for HIV therapy. These chain-terminating nucleoside analogs (CTNAs) block DNA synthesis after their incorporation into growing DNA, leading to the antiviral effects. However, they are also considered to be DNA damaging agents, and tyrosyl-DNA phosphodiesterase 1, a DNA repair enzyme, is reportedly able to remove such CTNA-modifications of DNA. Here, we have synthesized phosphoramidite building blocks of representative CTNAs, such as acyclovir, abacavir, carbovir, and lamivudine, and oligonucleotides with the 3′-CTNAs were successfully synthesized on solid supports. Using the chemically synthesized oligonucleotides, we investigated the excision of the 3′-CTNAs in DNA by the human excision repair cross complementing protein 1-xeroderma pigmentosum group F (ERCC1-XPF) endonuclease, which is one of the main components of the nucleotide excision repair pathway. A biochemical analysis demonstrated that the ERCC1-XPF endonuclease cleaved 2–7 nt upstream from the 3′-blocking CTNAs, and that DNA synthesis by the Klenow fragment was resumed after the removal of the CTNAs, suggesting that ERCC1-XPF participates in the repair of the CTNA-induced DNA damage. Full article
(This article belongs to the collection New Frontiers in Nucleic Acid Chemistry)
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Open AccessArticle Tailoring the Spacer Arm for Covalent Immobilization of Candida antarctica Lipase B—Thermal Stabilization by Bisepoxide-Activated Aminoalkyl Resins in Continuous-Flow Reactors
Molecules 2016, 21(6), 767; doi:10.3390/molecules21060767
Received: 10 May 2016 / Revised: 7 June 2016 / Accepted: 8 June 2016 / Published: 13 June 2016
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Abstract
An efficient and easy-to-perform method was developed for immobilization of CaLB on mesoporous aminoalkyl polymer supports by bisepoxide activation. Polyacrylate resins (100–300 µm; ~50 nm pores) with different aminoalkyl functional groups (ethylamine: EA and hexylamine: HA) were modified with bisepoxides differing in
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An efficient and easy-to-perform method was developed for immobilization of CaLB on mesoporous aminoalkyl polymer supports by bisepoxide activation. Polyacrylate resins (100–300 µm; ~50 nm pores) with different aminoalkyl functional groups (ethylamine: EA and hexylamine: HA) were modified with bisepoxides differing in the length, rigidity and hydrophobicity of the units linking the two epoxy functions. After immobilization, the different CaLB preparations were evaluated using the lipase-catalyzed kinetic resolution (KR) of racemic 1-phenylethanol (rac-1) in batch mode and in a continuous-flow reactor as well. Catalytic activity, enantiomer selectivity, recyclability, and the mechanical and long-term stability of CaLB immobilized on the various supports were tested. The most active CaLB preparation (on HA-resin activated with 1,6-hexanediol diglycidyl ether—HDGE) retained 90% of its initial activity after 13 consecutive reaction cycles or after 12 month of storage at 4 °C. The specific rate (rflow), enantiomer selectivity (E) and enantiomeric excess (ee) achievable with the best immobilized CaLB preparations were studied as a function of temperature in kinetic resolution of rac-1 performed in continuous-flow packed-bed bioreactors. The optimum temperature of the most active HA-HDGE CaLB in continuous-flow mode was 60 °C. Although CaLB immobilized on the glycerol diglycidyl ether (GDGE)-activated EA-resin was less active and less selective, a much higher optimum temperature (80 °C) was observed with this form in continuous-flow mode KR of rac-1. Full article
(This article belongs to the Special Issue Enzyme Immobilization 2016)
Open AccessArticle Preparative Separation and Purification of the Total Flavonoids in Scorzonera austriaca with Macroporous Resins
Molecules 2016, 21(6), 768; doi:10.3390/molecules21060768
Received: 7 May 2016 / Revised: 5 June 2016 / Accepted: 8 June 2016 / Published: 13 June 2016
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Abstract
The use of macroporous resins for the separation and purification of total flavonoids to obtain high-purity total flavonoids from Scorzonera austriaca was studied. The optimal conditions for separation and purification of total flavonoids in S. austriaca with macroporous resins were as follows: D4020
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The use of macroporous resins for the separation and purification of total flavonoids to obtain high-purity total flavonoids from Scorzonera austriaca was studied. The optimal conditions for separation and purification of total flavonoids in S. austriaca with macroporous resins were as follows: D4020 resin columns were loaded with crude flavonoid extract solution, and after reaching adsorptive saturation, the columns were eluted successively with 5 bed volumes (BV) of water, 5 BV of 5% (v/v) aqueous ethanol and 5 BV of 30% (v/v) aqueous ethanol at an elute flow rate of 2 BV·h−1. Total flavonoids were obtained from the 30% aqueous ethanol eluate by vacuum distillation recovery. The content of flavonoid compounds in the total flavonoids was 93.5%, which represents an improvement by about 150%. In addition, five flavonoid compounds in the product were identified as 2″-O-β-d-xylopyranosyl isoorientin, 6-C-α-l-arabipyranosyl orientin, orientin, isoorientin and vitexin by LC-ESI-MS analysis and internal standard methods. The results in this study could represent a method for the large-scale production of total flavonoids from S. austriaca. Full article
Open AccessArticle Rosmarinic Acid Attenuates Airway Inflammation and Hyperresponsiveness in a Murine Model of Asthma
Molecules 2016, 21(6), 769; doi:10.3390/molecules21060769
Received: 28 March 2016 / Revised: 2 June 2016 / Accepted: 8 June 2016 / Published: 13 June 2016
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Abstract
Rosmarinic acid (RA) has numerous pharmacologic effects, including anti-oxidant, anti-inflammatory, and analgesic effects. This study aimed to evaluate the preventive activity of RA in a murine model of asthma and to investigate its possible molecular mechanisms. Female BALB/c mice sensitized and challenged with
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Rosmarinic acid (RA) has numerous pharmacologic effects, including anti-oxidant, anti-inflammatory, and analgesic effects. This study aimed to evaluate the preventive activity of RA in a murine model of asthma and to investigate its possible molecular mechanisms. Female BALB/c mice sensitized and challenged with ovalbumin (Ova) were pretreated with RA (5, 10 or 20 mg/kg) at 1 h before Ova challenge. The results demonstrated that RA markedly inhibited increases in inflammatory cells and Th2 cytokines in the bronchoalveolar lavage fluid (BALF), significantly reduced the total IgE and Ova-specific IgE concentrations, and greatly ameliorated airway hyperresponsiveness (AHR) compared with the control Ova-induced mice. Histological analyses showed that RA substantially decreased the number of inflammatory cells and mucus hypersecretion in the airway. In addition, our results suggested that the protective effects of RA might be mediated by the suppression of ERK, JNK and p38 phosphorylation and activation of nuclear factor-κB (NF-κB). Furthermore, RA pretreatment resulted in a noticeable reduction in AMCase, CCL11, CCR3, Ym2 and E-selectin mRNA expression in lung tissues. These findings suggest that RA may effectively delay the progression of airway inflammation. Full article
(This article belongs to the Special Issue Natural Products and Inflammation)
Open AccessArticle The Fungicidal Activity of Thymol against Fusarium graminearum via Inducing Lipid Peroxidation and Disrupting Ergosterol Biosynthesis
Molecules 2016, 21(6), 770; doi:10.3390/molecules21060770
Received: 27 April 2016 / Revised: 6 June 2016 / Accepted: 7 June 2016 / Published: 18 June 2016
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Abstract
Thymol is a natural plant-derived compound that has been widely used in pharmaceutical and food preservation applications. However, the antifungal mechanism for thymol against phytopathogens remains unclear. In this study, we identified the antifungal action of thymol against Fusarium graminearum, an economically
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Thymol is a natural plant-derived compound that has been widely used in pharmaceutical and food preservation applications. However, the antifungal mechanism for thymol against phytopathogens remains unclear. In this study, we identified the antifungal action of thymol against Fusarium graminearum, an economically important phytopathogen showing severe resistance to traditional chemical fungicides. The sensitivity of thymol on different F. graminearum isolates was screened. The hyphal growth, as well as conidial production and germination, were quantified under thymol treatment. Histochemical, microscopic, and biochemical approaches were applied to investigate thymol-induced cell membrane damage. The average EC50 value of thymol for 59 F. graminearum isolates was 26.3 μg·mL−1. Thymol strongly inhibited conidial production and hyphal growth. Thymol-induced cell membrane damage was indicated by propidium iodide (PI) staining, morphological observation, relative conductivity, and glycerol measurement. Thymol induced a significant increase in malondialdehyde (MDA) concentration and a remarkable decrease in ergosterol content. Taken together, thymol showed potential antifungal activity against F. graminearum due to the cell membrane damage originating from lipid peroxidation and the disturbance of ergosterol biosynthesis. These results not only shed new light on the antifungal mechanism of thymol, but also imply a promising alternative for the control of Fusarium head blight (FHB) disease caused by F. graminearum. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Discovery of Novel Allopurinol Derivatives with Anticancer Activity and Attenuated Xanthine Oxidase Inhibition
Molecules 2016, 21(6), 771; doi:10.3390/molecules21060771
Received: 31 March 2016 / Revised: 24 May 2016 / Accepted: 8 June 2016 / Published: 20 June 2016
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Abstract
A series of pyrazolo[3,4-d]pyrimidine derivatives related to allopurinol has been synthesized and evaluated for its cytotoxicity against a panel of three cancer cell lines as well as its xanthine oxidase (XOD) inhibitory activities. Among them, compound 4 showed potent cytotoxicity with IC50
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A series of pyrazolo[3,4-d]pyrimidine derivatives related to allopurinol has been synthesized and evaluated for its cytotoxicity against a panel of three cancer cell lines as well as its xanthine oxidase (XOD) inhibitory activities. Among them, compound 4 showed potent cytotoxicity with IC50 values of 25.5 and 35.2 μM against human hepatoma carcinoma cell lines, BEL-7402 and SMMC-7221, respectively. The anticancer activity of 4 was comparable to that of Tanespimycin (17-N-allylamino-17-demethoxy geldanamycin, 17-AAG) that inhibited the growth of BEL-7402 and SMMC-7221 cells at IC50 values of 12.4 and 9.85 μM, respectively. However, unlike allopurinol, which is also a strong inhibitor of XOD, compound 4 is a much weaker XOD inhibitor, suggesting that the anticancer activities of the allopurinol derivatives may not be associated with XOD inhibition. Moreover, the cytotoxicity of 4 toward normal cells is significantly lower than that of 17-AAG, making 4 a promising lead compound for further optimization of structure-activity relationships that may lead to anticancer agents of clinical utility. Full article
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Open AccessArticle Design, Synthesis, and Biological Evaluation of Novel PARP-1 Inhibitors Based on a 1H-Thieno[3,4-d] Imidazole-4-Carboxamide Scaffold
Molecules 2016, 21(6), 772; doi:10.3390/molecules21060772
Received: 20 April 2016 / Revised: 4 June 2016 / Accepted: 6 June 2016 / Published: 13 June 2016
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Abstract
A series of poly(ADP-ribose)polymerase (PARP)-1 inhibitors containing a novel scaffold, the 1H-thieno[3,4-d]imidazole-4-carboxamide moiety, was designed and synthesized. These efforts provided some compounds with relatively good PARP-1 inhibitory activity, and among them, 16l was the most potent one. Cellular evaluations
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A series of poly(ADP-ribose)polymerase (PARP)-1 inhibitors containing a novel scaffold, the 1H-thieno[3,4-d]imidazole-4-carboxamide moiety, was designed and synthesized. These efforts provided some compounds with relatively good PARP-1 inhibitory activity, and among them, 16l was the most potent one. Cellular evaluations indicated that the anti-proliferative activities of 16g, 16i, 16j and 16l against BRCA-deficient cell lines were similar to that of olaparib, while the cytotoxicities of 16j and 16l toward human normal cells were lower. In addition, ADMET prediction results indicated that these compounds might possess more favorable toxicity and pharmacokinetic properties. This study provides a basis for our further investigation. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Metabolomic Profiles of Aspergillus oryzae and Bacillus amyloliquefaciens During Rice Koji Fermentation
Molecules 2016, 21(6), 773; doi:10.3390/molecules21060773
Received: 26 May 2016 / Revised: 8 June 2016 / Accepted: 8 June 2016 / Published: 14 June 2016
Cited by 4 | PDF Full-text (5210 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Rice koji, used early in the manufacturing process for many fermented foods, produces diverse metabolites and enzymes during fermentation. Using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS), ultrahigh-performance liquid chromatography linear trap quadrupole ion trap tandem mass spectrometry (UHPLC-LTQ-IT-MS/MS), and multivariate analysis we
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Rice koji, used early in the manufacturing process for many fermented foods, produces diverse metabolites and enzymes during fermentation. Using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS), ultrahigh-performance liquid chromatography linear trap quadrupole ion trap tandem mass spectrometry (UHPLC-LTQ-IT-MS/MS), and multivariate analysis we generated the metabolite profiles of rice koji produced by fermentation with Aspergillus oryzae (RK_AO) or Bacillus amyloliquefaciens (RK_BA) for different durations. Two principal components of the metabolomic data distinguished the rice koji samples according to their fermenter species and fermentation time. Several enzymes secreted by the fermenter species, including α-amylase, protease, and β-glucosidase, were assayed to identify differences in expression levels. This approach revealed that carbohydrate metabolism, serine-derived amino acids, and fatty acids were associated with rice koji fermentation by A. oryzae, whereas aromatic and branched chain amino acids, flavonoids, and lysophospholipids were more typical in rice koji fermentation by B. amyloliquefaciens. Antioxidant activity was significantly higher for RK_BA than for RK_AO, as were the abundances of flavonoids, including tricin, tricin glycosides, apigenin glycosides, and chrysoeriol glycosides. In summary, we have used MS-based metabolomics and enzyme activity assays to evaluate the effects of using different microbial species and fermentation times on the nutritional profile of rice koji. Full article
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Open AccessArticle Synthesis of Silver Nanoparticles Using Buchu Plant Extracts and Their Analgesic Properties
Molecules 2016, 21(6), 774; doi:10.3390/molecules21060774
Received: 20 March 2016 / Revised: 4 June 2016 / Accepted: 7 June 2016 / Published: 14 June 2016
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Abstract
We herein report for the first time the synthesis and analgesic properties of silver nanoparticles (Ag-NPs) using buchu plant extract. The as-synthesised Ag-NPs at different temperatures were characterised by UV-Vis spectroscopy, Fourier transform infra-red spectroscopy (FTIR) and transmission transform microscopy (TEM) to confirm
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We herein report for the first time the synthesis and analgesic properties of silver nanoparticles (Ag-NPs) using buchu plant extract. The as-synthesised Ag-NPs at different temperatures were characterised by UV-Vis spectroscopy, Fourier transform infra-red spectroscopy (FTIR) and transmission transform microscopy (TEM) to confirm the formation of silver nanoparticles. Phytochemical screening of the ethanolic extract revealed the presence of glycosides, proteins, tannins, alkaloids, flavonoids and saponins. The absorption spectra showed that the synthesis is temperature and time dependent. The TEM analysis showed that the as-synthesised Ag-NPs are polydispersed and spherical in shape with average particle diameter of 19.95 ± 7.76 nm while the FTIR results confirmed the reduction and capping of the as-synthesised Ag-NPs by the phytochemicals present in the ethanolic extract. The analgesic study indicated that the combined effect of the plant extract and Ag-NPs is more effective in pain management than both the aspirin drug and the extract alone. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Extraction and Characterization of Tamarind (Tamarind indica L.) Seed Polysaccharides (TSP) from Three Difference Sources
Molecules 2016, 21(6), 775; doi:10.3390/molecules21060775
Received: 18 February 2016 / Revised: 17 May 2016 / Accepted: 25 May 2016 / Published: 15 June 2016
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Abstract
Tamarind seed polysaccharide (TSP), a natural polysaccharide extracted from tamarind seeds is used in the pharmaceutical, textile and food industries as a mucoadhesive polymer. This work aimed to extract TSP from tamarind seeds from three sources with two methods and characterized its physical
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Tamarind seed polysaccharide (TSP), a natural polysaccharide extracted from tamarind seeds is used in the pharmaceutical, textile and food industries as a mucoadhesive polymer. This work aimed to extract TSP from tamarind seeds from three sources with two methods and characterized its physical and chemical properties. Kernel powder of tamarind seeds was slurried into a clear solution, set aside overnight and then centrifuged at 6000 rpm for 20 min to separate all foreign matter. The supernatant was separated and poured into excess 95% ethanol with continuous stirring. The precipitate obtained was collected and dried in the oven and then the dried TSP polymer was stored in a desiccator. The dried TSP was analyzed by 1H-NMR, FT-IR and XRD. The results showed TSP from tamarind seeds taken from paddy farmland (A), a waste from the export tamarind juice industry (B) and the export tamarind powder industry(C) gave yields of 31.55%, 26.95% and 17.30%, respectively, using method 1 and 11.15%, 53.65% and 54.65%, with method 2, respectively, but method 2 gave purer TSP than method 1. The FT-IR spectra displayed peaks at 3351.95 cm−1, 2920.76 cm−1, 1018.85 cm−1 and 555.16 cm−1. The 1H-NMR showed polysaccharide peaks between δ 3.50–4.20 ppm and XRD diagrams indicated their amorphous nature. Future works will focus on the quantitative analysis, biological activity and possible use of TSP as a drug delivery system. Full article
Open AccessCommunication A New One-Pot Synthesis of Quinoline-2-carboxylates under Heterogeneous Conditions
Molecules 2016, 21(6), 776; doi:10.3390/molecules21060776
Received: 24 May 2016 / Revised: 7 June 2016 / Accepted: 8 June 2016 / Published: 15 June 2016
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Abstract
Quinoline-2-carboxylates are an important subclass of quinoline derivatives largely present in a variety of biologically active molecules, as well as useful ligands in metal-catalyzed reactions. Herein, we present a new one-pot protocol for synthesizing this class of derivatives starting from β-nitroacrylates and 2-aminobenzaldehydes.
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Quinoline-2-carboxylates are an important subclass of quinoline derivatives largely present in a variety of biologically active molecules, as well as useful ligands in metal-catalyzed reactions. Herein, we present a new one-pot protocol for synthesizing this class of derivatives starting from β-nitroacrylates and 2-aminobenzaldehydes. In order to optimize the protocol, we investigated several reaction conditions, obtaining the best results using the 2-tert-Butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (BEMP) as solid base, in acetonitrile. Finally, we demonstrated the generality of our approach over several substrates which led to synthesize a plethora of functionalized quinolines-2-carboxylate derivatives in good overall yields. Full article
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Open AccessArticle Shikonin Inhibits the Proliferation of Human Breast Cancer Cells by Reducing Tumor-Derived Exosomes
Molecules 2016, 21(6), 777; doi:10.3390/molecules21060777
Received: 11 April 2016 / Revised: 2 June 2016 / Accepted: 7 June 2016 / Published: 16 June 2016
Cited by 9 | PDF Full-text (2312 KB) | HTML Full-text | XML Full-text
Abstract
Shikonin is a naphthoquinone isolated from the traditional Chinese medicine Lithospermum. It has been used in the treatment of various tumors. However, the effects of shikonin on such diseases have not been fully elucidated. In the present study, we detected the exosome
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Shikonin is a naphthoquinone isolated from the traditional Chinese medicine Lithospermum. It has been used in the treatment of various tumors. However, the effects of shikonin on such diseases have not been fully elucidated. In the present study, we detected the exosome release of a breast cancer cell line (MCF-7) with shikonin treatment and found a positive relationship between the level of secreted exosomes and cell proliferation. We next analyzed miRNA profiles in MCF-7 cells and exosomes and found that some miRNAs are specifically sorted and abundant in exosomes. Knockdown of the most abundant miRNAs in exosomes and the MCF-7 proliferation assay showed that miR-128 in exosomes negatively regulates the level of Bax in MCF-7 recipient cells and inhibits cell proliferation. These results show that shikonin inhibits the proliferation of MCF-7 cells through reducing tumor-derived exosomal miR-128. The current study suggests that shikonin suppresses MCF-7 growth by the inhibition of exosome release. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Comparison of Chip Inlet Geometry in Microfluidic Devices for Cell Studies
Molecules 2016, 21(6), 778; doi:10.3390/molecules21060778
Received: 11 May 2016 / Revised: 8 June 2016 / Accepted: 12 June 2016 / Published: 15 June 2016
Cited by 2 | PDF Full-text (2042 KB) | HTML Full-text | XML Full-text
Abstract
Micro-fabricated devices integrated with fluidic components provide an in vitro platform for cell studies best mimicking the in vivo micro-environment. These devices are capable of creating precise and controllable surroundings of pH value, temperature, salt concentration, and other physical or chemical stimuli. Various
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Micro-fabricated devices integrated with fluidic components provide an in vitro platform for cell studies best mimicking the in vivo micro-environment. These devices are capable of creating precise and controllable surroundings of pH value, temperature, salt concentration, and other physical or chemical stimuli. Various cell studies such as chemotaxis and electrotaxis can be performed by using such devices. Moreover, microfluidic chips are designed and fabricated for applications in cell separations such as circulating tumor cell (CTC) chips. Usually, there are two most commonly used inlets in connecting the microfluidic chip to sample/reagent loading tubes: the vertical (top-loading) inlet and the parallel (in-line) inlet. Designing this macro-to-micro interface is believed to play an important role in device performance. In this study, by using the commercial COMSOL Multiphysics software, we compared the cell capture behavior in microfluidic devices with different inlet types and sample flow velocities. Three different inlets were constructed: the vertical inlet, the parallel inlet, and the vertically parallel inlet. We investigated the velocity field, the flow streamline, the cell capture rate, and the laminar shear stress in these inlets. It was concluded that the inlet should be designed depending on the experimental purpose, i.e., one wants to maximize or minimize cell capture. Also, although increasing the flow velocity could reduce cell sedimentation, too high shear stresses are thought harmful to cells. Our findings indicate that the inlet design and flow velocity are crucial and should be well considered in fabricating microfluidic devices for cell studies. Full article
(This article belongs to the Special Issue Micro/Nano Fluidics and Bio-MEMS)
Open AccessArticle Chemical Structure and Immunomodulating Activities of an α-Glucan Purified from Lobelia chinensis Lour
Molecules 2016, 21(6), 779; doi:10.3390/molecules21060779
Received: 3 May 2016 / Revised: 3 June 2016 / Accepted: 7 June 2016 / Published: 15 June 2016
Cited by 3 | PDF Full-text (3349 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A neutral α-glucan, named BP1, with a molecular mass of approximately 9.45 kDa, was isolated from Lobelia chinensis by hot-water extraction, a Q-Sepharose Fast Flow column and Superdex-75 column chromatography. Its chemical structure was characterized by monosaccharide analysis, methylation analysis and analysis of
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A neutral α-glucan, named BP1, with a molecular mass of approximately 9.45 kDa, was isolated from Lobelia chinensis by hot-water extraction, a Q-Sepharose Fast Flow column and Superdex-75 column chromatography. Its chemical structure was characterized by monosaccharide analysis, methylation analysis and analysis of its FT-IR, high performance gel permeation chromatography (HPGPC) and 1D/2D-NMR spectra data. The backbone of BP1 consists of →6α-d-Glcp16,3α-d-Glcp1→(6α-d-Glcp1)x-6,3α-d-Glcp1-(6α-d-Glcp1)y→. The side chains were terminal α-d-Glcp1→ and α-d-Glcp1→ (6α-d-Glcp1)z→4α-d-Glcp13α-d-Glcp14α-d-Glcp1→ (x + y + z = 5), which are attached to the backbone at O-3 of 3,6α-d-Glcp1. The results of the effect of BP1 on mouse macrophage cell line RAW 264.7 indicate that BP1 enhances the cell proliferation, phagocytosis, nitric oxide production and cytokine secretion in a dose-dependent manner. Because the inhibitor of Toll-like receptor 4 blocks the BP1-induced secretion of TNF-α and IL-6, we hypothesize that α-glucan BP1 activates TLR4, which mediates the above-mentioned immunomodulating effects. Full article
(This article belongs to the Special Issue Natural Polysaccharides)
Open AccessArticle Variation of the Phytochemical Constituents and Antioxidant Activities of Zingiber officinale var. rubrum Theilade Associated with Different Drying Methods and Polyphenol Oxidase Activity
Molecules 2016, 21(6), 780; doi:10.3390/molecules21060780
Received: 3 May 2016 / Revised: 27 May 2016 / Accepted: 1 June 2016 / Published: 17 June 2016
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Abstract
The effects of different drying methods (freeze drying, vacuum oven drying, and shade drying) on the phytochemical constituents associated with the antioxidant activities of Z. officinale var. rubrum Theilade were evaluated to determine the optimal drying process for these rhizomes. Total flavonoid content
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The effects of different drying methods (freeze drying, vacuum oven drying, and shade drying) on the phytochemical constituents associated with the antioxidant activities of Z. officinale var. rubrum Theilade were evaluated to determine the optimal drying process for these rhizomes. Total flavonoid content (TFC), total phenolic content (TPC), and polyphenol oxidase (PPO) activity were measured using the spectrophotometric method. Individual phenolic acids and flavonoids, 6- and 8-gingerol and shogaol were identified by ultra-high performance liquid chromatography method. Ferric reducing antioxidant potential (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays were used for the evaluation of antioxidant activities. The highest reduction in moisture content was observed after freeze drying (82.97%), followed by vacuum oven drying (80.43%) and shade drying (72.65%). The highest TPC, TFC, and 6- and 8-shogaol contents were observed in samples dried by the vacuum oven drying method compared to other drying methods. The highest content of 6- and 8-gingerol was observed after freeze drying, followed by vacuum oven drying and shade drying methods. Fresh samples had the highest PPO activity and lowest content of flavonoid and phenolic acid compounds compared to dried samples. Rhizomes dried by the vacuum oven drying method represent the highest DPPH (52.9%) and FRAP activities (566.5 μM of Fe (II)/g DM), followed by freeze drying (48.3% and 527.1 μM of Fe (II)/g DM, respectively) and shade drying methods (37.64% and 471.8 μM of Fe (II)/g DM, respectively) with IC50 values of 27.2, 29.1, and 34.8 μg/mL, respectively. Negative and significant correlations were observed between PPO and antioxidant activity of rhizomes. Vacuum oven dried rhizomes can be utilized as an ingredient for the development of value-added food products as they contain high contents of phytochemicals with valuable antioxidant potential. Full article
(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)
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Open AccessArticle Two Trichothecene Mycotoxins from Myrothecium roridum Induce Apoptosis of HepG-2 Cells via Caspase Activation and Disruption of Mitochondrial Membrane Potential
Molecules 2016, 21(6), 781; doi:10.3390/molecules21060781
Received: 26 April 2016 / Revised: 7 June 2016 / Accepted: 13 June 2016 / Published: 17 June 2016
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Abstract
Trichothecene mycotoxins are a type of sesquiterpenoid produced by various kinds of plantpathogenic fungi. In this study, two trichothecene toxins, namely, a novel cytotoxic epiroridin acid and a known trichothecene, mytoxin B, were isolated from the endophytic fungus Myrothecium roridum derived from the
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Trichothecene mycotoxins are a type of sesquiterpenoid produced by various kinds of plantpathogenic fungi. In this study, two trichothecene toxins, namely, a novel cytotoxic epiroridin acid and a known trichothecene, mytoxin B, were isolated from the endophytic fungus Myrothecium roridum derived from the medicinal plant Pogostemon cablin. The two trichothecene mytoxins were confirmed to induce the apoptosis of HepG-2 cells by cytomorphology inspection, DNA fragmentation detection, and flow cytometry assay. The cytotoxic mechanisms of the two mycotoxins were investigated by quantitative real time polymerase chain reaction, western blot, and detection of mitochondrial membrane potential. The results showed that the two trichothecene mycotoxins induced the apoptosis of cancer cell HepG-2 via activation of caspase-9 and caspase-3, up-regulation of bax gene expression, down-regulation of bcl-2 gene expression, and disruption of the mitochondrial membrane potential of the HepG-2 cell. This study is the first to report on the cytotoxic mechanism of trichothecene mycotoxins from M. roridum. This study provides new clues for the development of attenuated trichothecene toxins in future treatment of liver cancer. Full article
(This article belongs to the Special Issue Natural Toxins)
Open AccessArticle High-Resolution α-Glucosidase Inhibition Profiling Combined with HPLC-HRMS-SPE-NMR for Identification of Antidiabetic Compounds in Eremanthus crotonoides (Asteraceae)
Molecules 2016, 21(6), 782; doi:10.3390/molecules21060782
Received: 9 May 2016 / Revised: 6 June 2016 / Accepted: 8 June 2016 / Published: 16 June 2016
Cited by 4 | PDF Full-text (1403 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
α-Glucosidase inhibitors decrease the cleavage- and absorption rate of monosaccharides from complex dietary carbohydrates, and represent therefore an important class of drugs for management of type 2 diabetes. In this study, a defatted ethyl acetate extract of Eremanthus crotonoides leaves with an inhibitory
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α-Glucosidase inhibitors decrease the cleavage- and absorption rate of monosaccharides from complex dietary carbohydrates, and represent therefore an important class of drugs for management of type 2 diabetes. In this study, a defatted ethyl acetate extract of Eremanthus crotonoides leaves with an inhibitory concentration (IC50) of 34.5 μg/mL towards α-glucosidase was investigated by high-resolution α-glucosidase inhibition profiling combined with HPLC-HRMS-SPE-NMR. This led to identification of six α-glucosidase inhibitors, namely quercetin (16), trans-tiliroside (17), luteolin (19), quercetin-3-methyl ether (20), 3,5-di-O-caffeoylquinic acid n-butyl ester (26) and 4,5-di-O-caffeoylquinic acid n-butyl ester (29). In addition, nineteen other metabolites were identified. The most active compounds were the two regioisomeric di-O-caffeoylquinic acid derivatives 26 and 29, with IC50 values of 5.93 and 5.20 μM, respectively. This is the first report of the α-glucosidase inhibitory activity of compounds 20, 26, and 29, and the findings support the important role of Eremanthus species as novel sources of new drugs and/or herbal remedies for treatment of type 2 diabetes. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Antispasmodic Effects and Action Mechanism of Essential Oil of Chrysactinia mexicana A. Gray on Rabbit Ileum
Molecules 2016, 21(6), 783; doi:10.3390/molecules21060783
Received: 22 March 2016 / Revised: 8 June 2016 / Accepted: 12 June 2016 / Published: 16 June 2016
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Abstract
The Chrysactinia mexicana A. Gray (C. mexicana) plant is used in folk medicine to treat fever and rheumatism; it is used as a diuretic, antispasmodic; and it is used for its aphrodisiac properties. This study investigates the effects of the essential oil of
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The Chrysactinia mexicana A. Gray (C. mexicana) plant is used in folk medicine to treat fever and rheumatism; it is used as a diuretic, antispasmodic; and it is used for its aphrodisiac properties. This study investigates the effects of the essential oil of C. mexicana (EOCM) on the contractility of rabbit ileum and the mechanisms of action involved. Muscle contractility studies in vitro in an organ bath to evaluate the response to EOCM were performed in the rabbit ileum. EOCM (1–100 µg·mL−1) reduced the amplitude and area under the curve of spontaneous contractions of the ileum. The contractions induced by carbachol 1 µM, potassium chloride (KCl) 60 mM or Bay K8644 1 µM were reduced by EOCM (30 µg·mL−1). Apamin 1 µM and charybdotoxin 0.01 µM decreased the inhibition induced by EOCM. The d-cAMP 1 µM decreased the inhibition induced by EOCM. l-NNA 10 µM, Rp-8-Br-PET-cGMPS 1 µM, d,l-propargylglycine 2 mM, or aminooxyacetic acid hemihydrochloride 2 mM did not modify the EOCM effect. In conclusion, EOCM induces an antispasmodic effect and could be used in the treatment of intestinal spasms or diarrhea processes. This effect would be mediated by Ca2+, Ca2+-activated K+ channels and cAMP. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
Open AccessArticle Ultrasound-Assisted Extraction of Stilbenes from Grape Canes
Molecules 2016, 21(6), 784; doi:10.3390/molecules21060784
Received: 26 May 2016 / Revised: 8 June 2016 / Accepted: 12 June 2016 / Published: 16 June 2016
Cited by 5 | PDF Full-text (1287 KB) | HTML Full-text | XML Full-text
Abstract
An analytical ultrasound-assisted extraction (UAE) method has been optimized and validated for the rapid extraction of stilbenes from grape canes. The influence of sample pre-treatment (oven or freeze-drying) and several extraction variables (solvent, sample-solvent ratio and extraction time between others) on the extraction
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An analytical ultrasound-assisted extraction (UAE) method has been optimized and validated for the rapid extraction of stilbenes from grape canes. The influence of sample pre-treatment (oven or freeze-drying) and several extraction variables (solvent, sample-solvent ratio and extraction time between others) on the extraction process were analyzed. The new method allowed the main stilbenes in grape canes to be extracted in just 10 min, with an extraction temperature of 75 °C and 60% ethanol in water as the extraction solvent. Validation of the extraction method was based on analytical properties. The resulting RSDs (n = 5) for interday/intraday precision were less than 10%. Furthermore, the method was successfully applied in the analysis of 20 different grape cane samples. The result showed that grape cane byproducts are potentially sources of bioactive compounds of interest for pharmaceutical and food industries. Full article
(This article belongs to the Special Issue Sonochemistry and Green Chemistry Applications)
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Open AccessArticle Flow and Thixotropic Parameters for Rheological Characterization of Hydrogels
Molecules 2016, 21(6), 786; doi:10.3390/molecules21060786
Received: 21 April 2016 / Revised: 6 June 2016 / Accepted: 13 June 2016 / Published: 16 June 2016
Cited by 1 | PDF Full-text (1565 KB) | HTML Full-text | XML Full-text
Abstract
The goal of this paper was to design several sodium carboxymethylcellulose hydrogels containing a BCS class II model drug and to evaluate their flow and thixotropic properties. The rheological measurements were performed at two temperatures (23 °C and 37 °C), using a rotational
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The goal of this paper was to design several sodium carboxymethylcellulose hydrogels containing a BCS class II model drug and to evaluate their flow and thixotropic properties. The rheological measurements were performed at two temperatures (23 °C and 37 °C), using a rotational viscometer. The hydrogels were stirred at different time intervals (10 s, 2, 5, 10 and 20 min at 23 °C, and 10 s, 2 and 5 min at 37 °C), with a maximum rotational speed of 60 rpm, and the corresponding forward and backward rheograms were recorded as shear stress vs. shear rate. For all hydrogels, the rheological data obtained at both temperatures showed a decrease of viscosity with the increase of the shear rate, highlighting a pseudoplastic behaviour. The flow profiles viscosity vs. shear rate were quantified through power law model, meanwhile the flow curves shear stress vs. shear rate were assessed by applying the Herschel-Bulkley model. The thixotropic character was evaluated through different descriptors: thixotropic area, thixotropic index, thixotropic constant and destructuration thixotropic coefficient. The gel-forming polymer concentration and the rheological experiments temperature significantly influence the flow and thixotropic parameters values of the designed hydrogels. The rheological characteristics described have an impact on the drug release microenvironment and determine the stasis time at the application site. Full article
(This article belongs to the Special Issue Transdermal Delivery Systems: Current Landscape and Trends)
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Open AccessArticle Expression Profiling of Glucosinolate Biosynthetic Genes in Brassica oleracea L. var. capitata Inbred Lines Reveals Their Association with Glucosinolate Content
Molecules 2016, 21(6), 787; doi:10.3390/molecules21060787
Received: 28 April 2016 / Revised: 13 June 2016 / Accepted: 14 June 2016 / Published: 17 June 2016
Cited by 8 | PDF Full-text (5292 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Glucosinolates are the biochemical compounds that provide defense to plants against pathogens and herbivores. In this study, the relative expression level of 48 glucosinolate biosynthesis genes was explored in four morphologically-different cabbage inbred lines by qPCR analysis. The content of aliphatic and indolic
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Glucosinolates are the biochemical compounds that provide defense to plants against pathogens and herbivores. In this study, the relative expression level of 48 glucosinolate biosynthesis genes was explored in four morphologically-different cabbage inbred lines by qPCR analysis. The content of aliphatic and indolic glucosinolate molecules present in those cabbage lines was also estimated by HPLC analysis. The possible association between glucosinolate accumulation and related gene expression level was explored by principal component analysis (PCA). The genotype-dependent variation in the relative expression level of different aliphatic and indolic glucosinolate biosynthesis genes is the novel result of this study. A total of eight different types of glucosinolates, including five aliphatic and three indolic glucosinolates, was detected in four cabbage lines. Three inbred lines BN3383, BN4059 and BN4072 had no glucoraphanin, sinigrin and gluconapin detected, but the inbred line BN3273 had these three aliphatic glucosinolate compounds. PCA revealed that a higher expression level of ST5b genes and lower expression of GSL-OH was associated with the accumulation of these three aliphatic glucosinolate compounds. PCA further revealed that comparatively higher accumulation of neoglucobrassicin in the inbred line, BN4072, was associated with a high level of expression of MYB34 (Bol017062) and CYP81F1 genes. The Dof1 and IQD1 genes probably trans-activated the genes related to biosynthesis of glucoerucin and methoxyglucobrassicin for their comparatively higher accumulation in the BN4059 and BN4072 lines compared to the other two lines, BN3273 and BN3383. A comparatively higher progoitrin level in BN3273 was probably associated with the higher expression level of the GSL-OH gene. The cabbage inbred line BN3383 accounted for the significantly higher relative expression level for the 12 genes out of 48, but this line had comparatively lower total glucosinolates detected compared to the other three cabbage lines. The reason for the genotypic variation in gene expression and glucosinolate accumulation is a subject of further investigation. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Aldol Reactions of Axially Chiral 5-Methyl-2-(o-aryl)imino-3-(o-aryl)-thiazolidine-4-ones
Molecules 2016, 21(6), 788; doi:10.3390/molecules21060788
Received: 21 April 2016 / Revised: 6 June 2016 / Accepted: 8 June 2016 / Published: 18 June 2016
PDF Full-text (1425 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Axially chiral 5-methyl-2-(o-aryl)imino-3-(o-aryl)-thiazolidine-4-ones have been subjected to aldol reactions with benzaldehyde to produce secondary carbinols which have been found to be separable by HPLC on a chiral stationary phase. Based on the reaction done on a single enantiomer resolved
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Axially chiral 5-methyl-2-(o-aryl)imino-3-(o-aryl)-thiazolidine-4-ones have been subjected to aldol reactions with benzaldehyde to produce secondary carbinols which have been found to be separable by HPLC on a chiral stationary phase. Based on the reaction done on a single enantiomer resolved via a chromatographic separation from a racemic mixture of 5-methyl-2-(α-naphthyl)imino-3-(α-naphthyl)-thiazolidine-4-one by HPLC on a chiral stationary phase, the aldol reaction was shown to proceed via an enolate intermediate. The axially chiral enolate of the thiazolidine-4-one was found to shield one face of the heterocyclic ring rendering face selectivity with respect to the enolate. The selectivities observed at C-5 of the ring varied from none to 11.5:1 depending on the size of the ortho substituent. Although the aldol reaction proceeded with a lack of face selectivity with respect to benzaldehyde, recrystallization returned highly diastereomerically enriched products. Full article
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Open AccessArticle Synthesis of a Conjugated D-A Polymer with Bi(disilanobithiophene) as a New Donor Component
Molecules 2016, 21(6), 789; doi:10.3390/molecules21060789
Received: 30 April 2016 / Revised: 7 June 2016 / Accepted: 13 June 2016 / Published: 17 June 2016
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Abstract
A new conjugated donor-acceptor (D-A) polymer pDSBT2-BT containing bi(disilano-bisthiophene) and benzothiadiazole as donor and acceptor units, respectively, was prepared. The polymer showed a broad UV-vis absorption band at λmax = 599 nm in chlorobenzene. The absorption band was shifted to λmax
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A new conjugated donor-acceptor (D-A) polymer pDSBT2-BT containing bi(disilano-bisthiophene) and benzothiadiazole as donor and acceptor units, respectively, was prepared. The polymer showed a broad UV-vis absorption band at λmax = 599 nm in chlorobenzene. The absorption band was shifted to λmax = 629 nm when the polymer was measured as a film, indicating enhanced interchain interactions of the polymer. Bulk hetero-junction polymer solar cells (BHJ-PSCs) were fabricated using pDSBT2-BT and PC71BM as host and guest materials, respectively. Optimization of cell fabrication conditions provided a maximal power conversion efficiency of 3.3% and the following cell parameters: Voc = 0.86 V, Jsc = 7.56 mA/cm2, and FF = 0.51. Although the efficiency still leaves much to be desired, these data underscore the potential of pDSBT2-BT as a high-voltage polymer solar cell material. Full article
(This article belongs to the Special Issue Advances in Silicon Chemistry)
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Open AccessArticle Cytotoxic and Pro-Apoptotic Effects of Cassane Diterpenoids from the Seeds of Caesalpinia sappan in Cancer Cells
Molecules 2016, 21(6), 791; doi:10.3390/molecules21060791
Received: 1 May 2016 / Revised: 12 June 2016 / Accepted: 15 June 2016 / Published: 18 June 2016
Cited by 4 | PDF Full-text (3997 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The chemical study on the seeds of Caesalpinia sappan led to the isolation of five new cassane diterpenoids, phanginins R‒T (13) and caesalsappanins M and N (4 and 5), together with seven known compounds 612
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The chemical study on the seeds of Caesalpinia sappan led to the isolation of five new cassane diterpenoids, phanginins R‒T (13) and caesalsappanins M and N (4 and 5), together with seven known compounds 612. Their structures were elucidated on the basis of NMR and HRESIMS analyses. The absolute configurations of compounds 1 and 4 were determined by the corresponding CD spectra. All the isolated compounds were tested for their cytotoxicity against ovarian cancer A2780 and HEY, gastric cancer AGS, and non-small cell lung cancer A549 cells. Compound 1 displayed significant toxicity against the four cell lines with the IC50 values of 9.9 ± 1.6 µM, 12.2 ± 6.5 µM, 5.3 ± 1.9 µM, and 12.3 ± 3.1 µM, respectively. Compound 1 induced G1 phase cell cycle arrest in A2780 cells. Furthermore, compound 1 dose-dependently induced A2780 cells apoptosis as evidenced by Hoechst 33342 staining, Annexin V positive cells, the up-regulated cleaved-PARP and the enhanced Bax/Bcl-2 ratio. What’s more, compound 1 also promoted the expression of the tumor suppressor p53 protein. These findings indicate that cassane diterpenoids might have potential as anti-cancer agents, and further in vivo animal studies and structural modification investigation are needed. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Anti-Inflammatory Effects of Agrimoniin-Enriched Fractions of Potentilla erecta
Molecules 2016, 21(6), 792; doi:10.3390/molecules21060792
Received: 6 April 2016 / Revised: 3 June 2016 / Accepted: 10 June 2016 / Published: 18 June 2016
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Abstract
Potentilla erecta (PE) is a small herbaceous plant with four yellow petals belonging to the Rosaceae family. The rhizome of PE has traditionally been used as an antidiarrheal, hemostatic and antihemorrhoidal remedy. PE contains up to 20% tannins and 5% ellagitannins, mainly agrimoniin.
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Potentilla erecta (PE) is a small herbaceous plant with four yellow petals belonging to the Rosaceae family. The rhizome of PE has traditionally been used as an antidiarrheal, hemostatic and antihemorrhoidal remedy. PE contains up to 20% tannins and 5% ellagitannins, mainly agrimoniin. Agrimoniin is a hydrolyzable tannin that is a potent radical scavenger. In this study we tested the anti-inflammatory effect of four PE fractions with increasing amounts of agrimoniin obtained by Sephadex column separation. First, we analyzed in HaCaT keratinocytes the expression of cyclooxygenase-2 (COX-2) induced by ultraviolet-B (UVB) irradiation. As COX-2 catalyzes the metabolism of arachidonic acid to prostanoids such as PGE2, we also measured the PGE2 concentration in cell culture supernatants. PE inhibited UVB-induced COX-2 expression in HaCaT cells and dose-dependently reduced PGE2. The PE fraction with the highest agrimoniin amount (PE4) was the most effective in this experiment, whereas fraction PE1 containing mainly sugars had no effect. PE4 also dose dependently inhibited the phosphorylation of the epidermal growth factor receptor (EGFR) which plays a crucial role in UVB-mediated COX-2 upregulation. A placebo-controlled UV-erythema study with increasing concentrations of PE4 demonstrated a dose dependent inhibition of UVB-induced inflammation in vivo. Similarly, PE4 significantly reduced UVB-induced PGE2 production in suction blister fluid in vivo. In summary, PE fractions with a high agrimoniin content display anti-inflammatory effects in vitro and in vivo in models of UVB-induced inflammation. Full article
(This article belongs to the Special Issue Natural Products and Inflammation)
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Open AccessArticle Synthesis of Bioactive 2-(Arylamino)thiazolo[5,4-f]-quinazolin-9-ones via the Hügershoff Reaction or Cu- Catalyzed Intramolecular C-S Bond Formation
Molecules 2016, 21(6), 794; doi:10.3390/molecules21060794
Received: 22 April 2016 / Revised: 12 June 2016 / Accepted: 13 June 2016 / Published: 18 June 2016
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Abstract
A library of thirty eight novel thiazolo[5,4-f]quinazolin-9(8H)-one derivatives (series 8, 10, 14 and 17) was prepared via the Hügershoff reaction and a Cu catalyzed intramolecular C-S bond formation, helped by microwave-assisted technology when required. The efficient
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A library of thirty eight novel thiazolo[5,4-f]quinazolin-9(8H)-one derivatives (series 8, 10, 14 and 17) was prepared via the Hügershoff reaction and a Cu catalyzed intramolecular C-S bond formation, helped by microwave-assisted technology when required. The efficient multistep synthesis of the key 6-amino-3-cyclopropylquinazolin-4(3H)-one (3) has been reinvestigated and performed on a multigram scale from the starting 5-nitroanthranilic acid. The inhibitory potency of the final products was evaluated against five kinases involved in Alzheimer’s disease and showed that some molecules of the 17 series described in this paper are particularly promising for the development of novel multi-target inhibitors of kinases. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Antioxidative, Antibacterial, and Food Functional Properties of the Half-Fin Anchovy Hydrolysates-Glucose Conjugates Formed via Maillard Reaction
Molecules 2016, 21(6), 795; doi:10.3390/molecules21060795
Received: 14 April 2016 / Revised: 13 June 2016 / Accepted: 13 June 2016 / Published: 20 June 2016
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Abstract
The antioxidative, antibacterial, and food functional properties of the half-fin anchovy hydrolysates (HAHp)-glucose conjugates formed by Maillard reaction (MR) were investigated, respectively. Results of sugar and amino acid contents loss rates, browning index, and molecular weight distribution indicated that the initial pH of
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The antioxidative, antibacterial, and food functional properties of the half-fin anchovy hydrolysates (HAHp)-glucose conjugates formed by Maillard reaction (MR) were investigated, respectively. Results of sugar and amino acid contents loss rates, browning index, and molecular weight distribution indicated that the initial pH of HAHp played an important role in the process of MR between HAHp and glucose. HAHp-glucose Maillard reaction products (HAHp-G MRPs) demonstrated enhanced antioxidative activities of reducing power and scavenging DPPH radicals compared to control groups. HAHp-G MRPs produced from the condition of pH 9.6 displayed the strongest reducing power. The excellent scavenging activity on DPPH radicals was found for HAHp(5.6)-G MRPs which was produced at pH 5.6. Additionally, HAHp(5.6)-G MRPs showed variable antibacterial activities against Escherichia coli, Pseudomonas fluorescens, Proteus vulgaris, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Bacillus megaterium, and Sarcina lutea, with the MIC values ranging from 8.3 to 16.7 μg/mL. Result of scanning electron microscopy (SEM) on E. coli suggested that HAHp(5.6)-G MRPs exhibited antibacterial activity by destroying the cell integrity through membrane permeabilization. Moreover, HAHp(5.6)-G MRPs had excellent foaming ability and stability at alkaline conditions of pH 8.0, and showed emulsion properties at acidic pH 4.0. These results suggested that specific HAHp-G MRPs should be promising functional ingredients used in foods. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Construction of an Immobilized Thermophilic Esterase on Epoxy Support for Poly(ε-caprolactone) Synthesis
Molecules 2016, 21(6), 796; doi:10.3390/molecules21060796
Received: 4 May 2016 / Revised: 14 June 2016 / Accepted: 16 June 2016 / Published: 18 June 2016
Cited by 1 | PDF Full-text (1809 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Developing an efficient immobilized enzyme is of great significance for improving the operational stability of enzymes in poly(ε-caprolactone) synthesis. In this paper, a thermophilic esterase AFEST from the archaeon Archaeoglobus fulgidus was successfully immobilized on the epoxy support Sepabeads EC-EP via covalent attachment,
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Developing an efficient immobilized enzyme is of great significance for improving the operational stability of enzymes in poly(ε-caprolactone) synthesis. In this paper, a thermophilic esterase AFEST from the archaeon Archaeoglobus fulgidus was successfully immobilized on the epoxy support Sepabeads EC-EP via covalent attachment, and the immobilized enzyme was then employed as a biocatalyst for poly(ε-caprolactone) synthesis. The enzyme loading and recovered activity of immobilized enzyme was measured to be 72 mg/g and 10.4 U/mg using p-nitrophenyl caprylate as the substrate at 80 °C, respectively. Through the optimization of reaction conditions (enzyme concentration, temperature, reaction time and medium), poly(ε-caprolactone) was obtained with 100% monomer conversion and low number-average molecular weight (Mn < 1300 g/mol). Further, the immobilized enzyme exhibited excellent reusability, with monomer conversion values exceeding 75% during 15 batch reactions. Finally, poly(ε-caprolactone) was enzymatically synthesized with an isolated yield of 75% and Mn value of 3005 g/mol in a gram-scale reaction. Full article
(This article belongs to the Special Issue Enzyme Immobilization 2016)
Open AccessArticle The Deformation of Polydimethylsiloxane (PDMS) Microfluidic Channels Filled with Embedded Circular Obstacles under Certain Circumstances
Molecules 2016, 21(6), 798; doi:10.3390/molecules21060798
Received: 20 May 2016 / Revised: 9 June 2016 / Accepted: 16 June 2016 / Published: 18 June 2016
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Abstract
Experimental investigations were conducted to determine the influence of polydimethylsiloxane (PDMS) microfluidic channels containing aligned circular obstacles (with diameters of 172 µm and 132 µm) on the flow velocity and pressure drop under steady-state flow conditions. A significant PDMS bulging was observed when
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Experimental investigations were conducted to determine the influence of polydimethylsiloxane (PDMS) microfluidic channels containing aligned circular obstacles (with diameters of 172 µm and 132 µm) on the flow velocity and pressure drop under steady-state flow conditions. A significant PDMS bulging was observed when the fluid flow initially contacted the obstacles, but this phenomenon decreased in the 1 mm length of the microfluidic channels when the flow reached a steady-state. This implies that a microfluidic device operating with steady-state flows does not provide fully reliable information, even though less PDMS bulging is observed compared to quasi steady-state flow. Numerical analysis of PDMS bulging using ANSYS Workbench showed a relatively good agreement with the measured data. To verify the influence of PDMS bulging on the pressure drop and flow velocity, theoretical analyses were performed and the results were compared with the experimental results. The measured flow velocity and pressure drop data relatively matched well with the classical prediction under certain circumstances. However, discrepancies were generated and became worse as the microfluidic devices were operated under the following conditions: (1) restricted geometry of the microfluidic channels (i.e., shallow channel height, large diameter of obstacles and a short microchannel length); (2) operation in quasi-steady state flow; (3) increasing flow rates; and (4) decreasing amount of curing agent in the PDMS mixture. Therefore, in order to obtain reliable data a microfluidic device must be operated under appropriate conditions. Full article
(This article belongs to the Special Issue Micro/Nano Fluidics and Bio-MEMS)
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Open AccessArticle Capsaicin Synthesis Requires in Situ Phenylalanine and Valine Formation in in Vitro Maintained Placentas from Capsicum chinense
Molecules 2016, 21(6), 799; doi:10.3390/molecules21060799
Received: 26 April 2016 / Revised: 9 June 2016 / Accepted: 15 June 2016 / Published: 21 June 2016
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Abstract
Capsaicinoids (CAP) are nitrogenous metabolites formed from valine (Val) and phenylalanine (Phe) in the placentas of hot Capsicum genotypes. Placentas of Habanero peppers can incorporate inorganic nitrogen into amino acids and have the ability to secure the availability of the required amino acids
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Capsaicinoids (CAP) are nitrogenous metabolites formed from valine (Val) and phenylalanine (Phe) in the placentas of hot Capsicum genotypes. Placentas of Habanero peppers can incorporate inorganic nitrogen into amino acids and have the ability to secure the availability of the required amino acids for CAP biosynthesis. In order to determine the participation of the placental tissue as a supplier of these amino acids, the effects of blocking the synthesis of Val and Phe by using specific enzyme inhibitors were analyzed. Isolated placentas maintained in vitro were used to rule out external sources′ participation. Blocking Phe synthesis, through the inhibition of arogenate dehydratase, significantly decreased CAP accumulation suggesting that at least part of Phe required in this process has to be produced in situ. Chlorsulfuron inhibition of acetolactate synthase, involved in Val synthesis, decreased not only Val accumulation but also that of CAP, pointing out that the requirement for this amino acid can also be fulfilled by this tissue. The presented data demonstrates that CAP accumulation in in vitro maintained placentas can be accomplished through the in situ availability of Val and Phe and suggests that the synthesis of the fatty acid chain moiety may be a limiting factor in the biosynthesis of these alkaloids. Full article
(This article belongs to the Special Issue Capsaicin)
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Open AccessArticle In Vitro Assessment of CYP-Mediated Drug Interactions for Kinsenoside, an Antihyperlipidemic Candidate
Molecules 2016, 21(6), 800; doi:10.3390/molecules21060800
Received: 7 April 2016 / Revised: 7 June 2016 / Accepted: 15 June 2016 / Published: 18 June 2016
Cited by 1 | PDF Full-text (1477 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Kinsenoside, the herb-derived medicine isolated from the plant Anoect chilus, has diverse pharmacological actions, and it is considered to be a promising antihyperlipidemic drug candidate. This study evaluates the effects of kinsenoside on CYP enzyme-mediated drug metabolism in order to predict the
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Kinsenoside, the herb-derived medicine isolated from the plant Anoect chilus, has diverse pharmacological actions, and it is considered to be a promising antihyperlipidemic drug candidate. This study evaluates the effects of kinsenoside on CYP enzyme-mediated drug metabolism in order to predict the potential for kinsenoside-drug interactions. Kinsenoside was tested at different concentrations of 0.1, 0.3, 1, 3, 10, 30, and 100 µM in human liver microsomes. The c Cktail probe assay based on liquid chromatography-tandem mass spectrometry was conducted to measure the CYP inhibitory effect of kinsenoside. Subsequently, the metabolism profiles of amlodipine and lovastatin in human liver microsomes were analyzed following co-incubation with kinsenoside. The concentration levels of the parent drug and the major metabolites were compared with the kinsenoside-cotreated samples. The effect of kinsenoside was negligible on the enzyme activity of all the CYP isozymes tested even though CYP2A6 was slightly inhibited at higher concentrations. The drug-drug interaction assay also showed that the concomitant use of kinsenoside has a non-significant effect on the concentration of lovastatin or amlodipine, and their major metabolites. So, it was concluded that there is almost no risk of drug interaction between kinsenoside and CYP drug substrates via CYP inhibition. Full article
Open AccessArticle Synthesis and Characterization of a Novel Borazine-Type UV Photo-Induced Polymerization of Ceramic Precursors
Molecules 2016, 21(6), 801; doi:10.3390/molecules21060801
Received: 20 March 2016 / Revised: 25 May 2016 / Accepted: 7 June 2016 / Published: 21 June 2016
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Abstract
A preceramic polymer of B,B′,B′′-(dimethyl)ethyl-acrylate-silyloxyethyl-borazine was synthesized by three steps from a molecular single-source precursor and characterized by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectrometry. Six-member borazine rings and acrylate groups were effectively introduced into the preceramic polymer to activate
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A preceramic polymer of B,B′,B′′-(dimethyl)ethyl-acrylate-silyloxyethyl-borazine was synthesized by three steps from a molecular single-source precursor and characterized by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectrometry. Six-member borazine rings and acrylate groups were effectively introduced into the preceramic polymer to activate UV photo-induced polymerization. Photo-Differential Scanning Calorimetry (Photo-DSC) and real-time FTIR techniques were adapted to investigate the photo-polymerization process. The results revealed that the borazine derivative exhibited dramatic activity by UV polymerization, the double-bond conversion of which reached a maximum in 40 s. Furthermore, the properties of the pyrogenetic products were studied by scanning electron microscopy (SEM) and X-ray diffraction (XRD), which proved the ceramic annealed at 1100 °C retained the amorphous phase. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Antileishmanial Activity and Structure-Activity Relationship of Triazolic Compounds Derived from the Neolignans Grandisin, Veraguensin, and Machilin G
Molecules 2016, 21(6), 802; doi:10.3390/molecules21060802
Received: 26 May 2016 / Revised: 15 June 2016 / Accepted: 16 June 2016 / Published: 20 June 2016
Cited by 4 | PDF Full-text (1954 KB) | HTML Full-text | XML Full-text
Abstract
Sixteen 1,4-diaryl-1,2,3-triazole compounds 419 derived from the tetrahydrofuran neolignans veraguensin 1, grandisin 2, and machilin G 3 were tested against Leishmania (Leishmania) amazonensis intracellular amastigotes. Triazole compounds 419 were synthetized via Click Chemistry strategy by
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Sixteen 1,4-diaryl-1,2,3-triazole compounds 419 derived from the tetrahydrofuran neolignans veraguensin 1, grandisin 2, and machilin G 3 were tested against Leishmania (Leishmania) amazonensis intracellular amastigotes. Triazole compounds 419 were synthetized via Click Chemistry strategy by 1,3-dipolar cycloaddition between terminal acetylenes and aryl azides containing methoxy and methylenedioxy groups as substituents. Our results suggest that most derivatives were active against intracellular amastigotes, with IC50 values ranging from 4.4 to 32.7 µM. The index of molecular hydrophobicity (ClogP) ranged from 2.8 to 3.4, reflecting a lipophilicity/hydrosolubility rate suitable for transport across membranes, which may have resulted in the potent antileishmanial activity observed. Regarding structure-activity relationship (SAR), compounds 14 and 19, containing a trimethoxy group, were the most active (IC50 values of 5.6 and 4.4 µM, respectively), with low cytotoxicity on mammalian cells (SI = 14.1 and 10.6). These compounds induced nitric oxide production by the host macrophage cells, which could be suggested as the mechanism involved in the intracellular killing of parasites. These results would be useful for the planning of new derivatives with higher antileishmanial activities. Full article
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Open AccessArticle Flavonoid Glycosides and Their Derivatives from the Herbs of Scorzonera austriaca Wild
Molecules 2016, 21(6), 803; doi:10.3390/molecules21060803
Received: 22 May 2016 / Revised: 15 June 2016 / Accepted: 17 June 2016 / Published: 21 June 2016
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Abstract
Five flavonoid glycosides and two derivatives were isolated from the herbs of Scorzonera austriaca Wild by silica gel column chromatography and preparative HPLC. Their structures were identified, using chemical and spectroscopic methods, as 5,7,4′-trihydroxyflavone 6-C-(2''-O-β-d-glucopyranosyl β-d
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Five flavonoid glycosides and two derivatives were isolated from the herbs of Scorzonera austriaca Wild by silica gel column chromatography and preparative HPLC. Their structures were identified, using chemical and spectroscopic methods, as 5,7,4′-trihydroxyflavone 6-C-(2''-O-β-d-glucopyranosyl β-d-glucopyranoside) (1), 5,7,3′,4′-tetrahydroxyflavone 6-C-(2''-O-β-d-glucopyranosyl β-d-glucopyranoside) (2), quercetin 3-O-rutinoside (3), 5,7,4′-trihydroxyflavone 6-C-β-d-glucopyranoside (4), 3′-methoxy-5,7,4′-trihydroxyflavone 6-C-β-d-glucopyranoside (5), 5,7,4′-trihydroxyflavone 8-C-(6''-O-trans-caffeoyl β-d-glucopyranoside) (6), and 5,7,3′,4′-tetrahydroxyflavone 8-C-(6''-O-trans-caffeoyl β-d-glucopyranoside) (7). Compounds 6 and 7 are new flavonoid glycoside derivatives, and compounds 15 were isolated from the herbs of Scorzonera austriaca for the first time. Compounds 6 and 7 were also assayed for their hepatoprotective activities with rat hepatocytes in vitro. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis of Chiral, Enantiopure Allylic Amines by the Julia Olefination of α-Amino Esters
Molecules 2016, 21(6), 805; doi:10.3390/molecules21060805
Received: 24 May 2016 / Revised: 14 June 2016 / Accepted: 14 June 2016 / Published: 21 June 2016
PDF Full-text (4150 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The four-step conversion of a series of N-Boc-protected l-amino acid methyl esters into enantiopure N-Boc allylamines by a modified Julia olefination is described. Key steps include the reaction of a lithiated phenylalkylsulfone with amino esters, giving chiral β-ketosulfones, and the
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The four-step conversion of a series of N-Boc-protected l-amino acid methyl esters into enantiopure N-Boc allylamines by a modified Julia olefination is described. Key steps include the reaction of a lithiated phenylalkylsulfone with amino esters, giving chiral β-ketosulfones, and the reductive elimination of related α-acetoxysulfones. The overall transformation takes place under mild conditions, with good yields, and without loss of stereochemical integrity, being in this respect superior to the conventional Julia reaction of α-amino aldehydes. Full article
(This article belongs to the Special Issue Synthesis of Bioactive Compounds from the Chiral Pool)
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Open AccessArticle Novel 5-Substituted 2-(Aylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl)benzenesulfonamides: Synthesis, Molecular Structure, Anticancer Activity, Apoptosis-Inducing Activity and Metabolic Stability
Molecules 2016, 21(6), 808; doi:10.3390/molecules21060808
Received: 13 May 2016 / Revised: 8 June 2016 / Accepted: 17 June 2016 / Published: 22 June 2016
Cited by 6 | PDF Full-text (5550 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of novel 5-substituted 2-(arylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl) benzenesulfonamide derivatives 2760 have been synthesized by the reaction of aminoguanidines with an appropriate phenylglyoxal hydrate in glacial acetic acid. A majority of the compounds showed cytotoxic activity toward the human cancer cell
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A series of novel 5-substituted 2-(arylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl) benzenesulfonamide derivatives 2760 have been synthesized by the reaction of aminoguanidines with an appropriate phenylglyoxal hydrate in glacial acetic acid. A majority of the compounds showed cytotoxic activity toward the human cancer cell lines HCT-116, HeLa and MCF-7, with IC50 values below 100 μM. It was found that for the analogues 3638 the naphthyl moiety contributed significantly to the anticancer activity. Cytometric analysis of translocation of phosphatidylserine as well as mitochondrial membrane potential and cell cycle revealed that the most active compounds 37 (HCT-116 and HeLa) and 46 (MCF-7) inhibited the proliferation of cells by increasing the number of apoptotic cells. Apoptotic-like, dose dependent changes in morphology of cell lines were also noticed after treatment with 37 and 46. Moreover, triazines 37 and 46 induced caspase activity in the HCT-116, HeLa and MCF-7 cell lines. Selected compounds were tested for metabolic stability in the presence of pooled human liver microsomes and NADPH, both R2 and Ar = 4-CF3-C6H4 moiety in 2-(R2-methylthio)-N-(5-aryl-1,2,4-triazin-3-yl)benzenesulfonamides simultaneously increased metabolic stability. The results pointed to 37 as a hit compound with a good cytotoxicity against HCT-116 (IC50 = 36 μM), HeLa (IC50 = 34 μM) cell lines, apoptosis-inducing activity and moderate metabolic stability. Full article
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Open AccessArticle Syk and IRAK1 Contribute to Immunopharmacological Activities of Anthraquinone-2-carboxlic Acid
Molecules 2016, 21(6), 809; doi:10.3390/molecules21060809
Received: 21 May 2016 / Revised: 16 June 2016 / Accepted: 18 June 2016 / Published: 22 June 2016
Cited by 4 | PDF Full-text (4164 KB) | HTML Full-text | XML Full-text
Abstract
Anthraquinone-2-carboxlic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA) was identified as one of the major anthraquinones in Brazilian taheebo. Since there was no report explaining its immunopharmacological actions, in this study, we aimed to investigate the molecular mechanism of AQCA-mediated anti-inflammatory activity using reporter gene assays,
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Anthraquinone-2-carboxlic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA) was identified as one of the major anthraquinones in Brazilian taheebo. Since there was no report explaining its immunopharmacological actions, in this study, we aimed to investigate the molecular mechanism of AQCA-mediated anti-inflammatory activity using reporter gene assays, kinase assays, immunoblot analyses, and overexpression strategies with lipopolysaccharide (LPS)-treated macrophages. AQCA was found to suppress the release of nitric oxide (NO) and prostaglandin (PG) E2 from LPS-treated peritoneal macrophages without displaying any toxic side effects. Molecular analysis revealed that AQCA was able to inhibit the activation of the nuclear factor (NF)-κB and activator protein (AP)-1 pathways by direct suppression of upstream signaling enzymes including interleukin-1 receptor-associated kinase 1 (IRAK1) and spleen tyrosine kinase (Syk). Therefore, our data strongly suggest that AQCA-mediated suppression of inflammatory responses could be managed by a direct interference of signaling cascades including IRAK and Syk, linked to the activation of NF-κB and AP-1. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle The Changes in Color, Soluble Sugars, Organic Acids, Anthocyanins and Aroma Components in “Starkrimson” during the Ripening Period in China
Molecules 2016, 21(6), 812; doi:10.3390/molecules21060812
Received: 23 May 2016 / Revised: 17 June 2016 / Accepted: 17 June 2016 / Published: 22 June 2016
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Abstract
“Starkrimson” is a traditional apple cultivar that was developed a long time ago and was widely cultivated in the arid region of the northern Wei River of China. However, little information regarding the quality characteristics of “Starkrimson” fruit has been reported in this
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“Starkrimson” is a traditional apple cultivar that was developed a long time ago and was widely cultivated in the arid region of the northern Wei River of China. However, little information regarding the quality characteristics of “Starkrimson” fruit has been reported in this area. To elucidate these characteristics, the color, soluble sugars, organic acids, anthocyanins and aroma components were measured during the ripening period through the use of high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). The results indicated that the changes in anthocyanin contents took place later than the changes in the Commission International Eclairage (CIE) parameters. Meanwhile, cyanidin 3-galactoside (cy3-gal), fructose, sucrose, glucose and malic acid were the primary organic compounds, and 1-butanol-2-methyl-acetate, 2-hexenal and 1-hexanol were the most abundant aroma components in the skin. Furthermore, rapidly changing soluble sugars and organic acid synchronization took place in the early ripening period, while rapidly changing aroma components occurred later, on the basis of fresh weight. This result suggested that the production of aroma components might be a useful index of apple maturity. Full article
(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products)
Open AccessArticle An Ingenol Derived from Euphorbia kansui Induces Hepatocyte Cytotoxicity by Triggering G0/G1 Cell Cycle Arrest and Regulating the Mitochondrial Apoptosis Pathway in Vitro
Molecules 2016, 21(6), 813; doi:10.3390/molecules21060813
Received: 5 May 2016 / Revised: 16 June 2016 / Accepted: 17 June 2016 / Published: 22 June 2016
Cited by 3 | PDF Full-text (8974 KB) | HTML Full-text | XML Full-text
Abstract
Natural product lingenol, a purified diterpenoid compound derived from the root of Euphorbia kansui, exerts serious hepatotoxicity; however, the molecular mechanisms remain to be defined. In the present study, cell counting Kit-8 (CCK-8), inverted phase contrast microscope and flow cytometry were used
[...] Read more.
Natural product lingenol, a purified diterpenoid compound derived from the root of Euphorbia kansui, exerts serious hepatotoxicity; however, the molecular mechanisms remain to be defined. In the present study, cell counting Kit-8 (CCK-8), inverted phase contrast microscope and flow cytometry were used to demonstrate that lingenol significantly inhibited L-O2 cells proliferation, and induced cell cycle arrest and apoptosis. Moreover, the results investigated that lingenol markedly disrupted mitochondrial functions by high content screening (HCS). In addition, the up-regulation of cytochrome c, AIF and Apaf-1 and activation of caspases were found in L-O2 cells detected by Western blotting and ELISA assay, which was required for lingenol activation of cytochrome c-mediated caspase cascades and AIF-mediated DNA damage. Mechanistic investigations revealed that lingenol significantly down-regulated the Bcl-2/Bax ratio and enhanced the reactive oxygen species (ROS) in L-O2 cells. These data collectively indicated that lingenol modulation of ROS and Bcl-2/Bax ratio led to cell cycle arrest and mitochondrial-mediated apoptosis in L-O2 cells in vitro. All of these results will be helpful to reveal the hepatotoxicity mechanism of Euphorbia kansui and to effectively guide safer and better clinical application of this herb. Full article
(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)
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Open AccessArticle Essential Oil Variation from Twenty Two Genotypes of Citrus in Brazil—Chemometric Approach and Repellency Against Diaphorina citri Kuwayama
Molecules 2016, 21(6), 814; doi:10.3390/molecules21060814
Received: 21 May 2016 / Revised: 15 June 2016 / Accepted: 17 June 2016 / Published: 22 June 2016
Cited by 3 | PDF Full-text (1210 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The chemical composition of volatile oils from 22 genotypes of Citrus and related genera was poorly differentiated, but chemometric techniques have clarified the relationships between the 22 genotypes, and allowed us to understand their resistance to D. citri. The most convincing similarities
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The chemical composition of volatile oils from 22 genotypes of Citrus and related genera was poorly differentiated, but chemometric techniques have clarified the relationships between the 22 genotypes, and allowed us to understand their resistance to D. citri. The most convincing similarities include the synthesis of (Z)-β-ocimene and (E)-caryophyllene for all 11 genotypes of group A. Genotypes of group B are not uniformly characterized by essential oil compounds. When stimulated with odor sources of 22 genotypes in a Y-tube olfactometer D. citri preferentially entered the arm containing the volatile oils of Murraya paniculata, confirming orange jasmine as its best host. C. reticulata × C. sinensis was the least preferred genotype, and is characterized by the presence of phytol, (Z)-β-ocimene, and β-elemene, which were not found in the most preferred genotype. We speculate that these three compounds may act as a repellent, making these oils less attractive to D. citri. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Aza-Michael Mono-addition Using Acidic Alumina under Solventless Conditions
Molecules 2016, 21(6), 815; doi:10.3390/molecules21060815
Received: 20 May 2016 / Revised: 10 June 2016 / Accepted: 16 June 2016 / Published: 22 June 2016
Cited by 4 | PDF Full-text (1284 KB) | HTML Full-text | XML Full-text
Abstract
Aza-Michael reactions between primary aliphatic and aromatic amines and various Michael acceptors have been performed under environmentally-friendly solventless conditions using acidic alumina as a heterogeneous catalyst to selectively obtain the corresponding mono-adducts in high yields. Ethyl acrylate was the main acceptor used, although
[...] Read more.
Aza-Michael reactions between primary aliphatic and aromatic amines and various Michael acceptors have been performed under environmentally-friendly solventless conditions using acidic alumina as a heterogeneous catalyst to selectively obtain the corresponding mono-adducts in high yields. Ethyl acrylate was the main acceptor used, although others such as acrylonitrile, methyl acrylate and acrylamide were also utilized successfully. Bi-functional amines also gave the mono-adducts in good to excellent yields. Such compounds can serve as intermediates for the synthesis of anti-cancer and antibiotic drugs. Full article
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Open AccessArticle Ultrahigh Pressure Processing Produces Alterations in the Metabolite Profiles of Panax ginseng
Molecules 2016, 21(6), 816; doi:10.3390/molecules21060816
Received: 25 May 2016 / Revised: 20 June 2016 / Accepted: 20 June 2016 / Published: 22 June 2016
PDF Full-text (2630 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ultrahigh pressure (UHP) treatments are non-thermal processing methods that have customarily been employed to enhance the quality and productivity of plant consumables. We aimed to evaluate the effects of UHP treatments on ginseng samples (white ginseng: WG; UHP-treated WG: UWG; red ginseng: RG;
[...] Read more.
Ultrahigh pressure (UHP) treatments are non-thermal processing methods that have customarily been employed to enhance the quality and productivity of plant consumables. We aimed to evaluate the effects of UHP treatments on ginseng samples (white ginseng: WG; UHP-treated WG: UWG; red ginseng: RG; UHP-treated RG: URG; ginseng berries: GB; and UHP-treated GB: UGB) using metabolite profiling based on ultrahigh performance liquid chromatography-linear trap quadrupole-ion trap-tandem mass spectrometry (UHPLC-LTQ-IT-MS/MS) and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). Multivariate data analyses revealed a clear demarcation among the GB and UGB samples, and the phenotypic evaluations correlated the highest antioxidant activities and the total phenolic and flavonoid compositions with the UGB samples. Overall, eight amino acids, seven organic acids, seven sugars and sugar derivatives, two fatty acids, three notoginsenosides, three malonylginsenosides, and three ginsenosides, were identified as significantly discriminant metabolites between the GB and UGB samples, with relatively higher proportions in the latter. Ideally, these metabolites can be used as quality biomarkers for the assessment of ginseng products and our results indicate that UHP treatment likely led to an elevation in the proportions of total extractable metabolites in ginseng samples. Full article
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Open AccessArticle Synthesis and Evaluation of 99mTc-Labeled Dimeric Folic Acid for FR-Targeting
Molecules 2016, 21(6), 817; doi:10.3390/molecules21060817
Received: 30 May 2016 / Revised: 17 June 2016 / Accepted: 20 June 2016 / Published: 22 June 2016
Cited by 4 | PDF Full-text (1663 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The folate receptor (FR) is overexpressed in a wide variety of human tumors. In our study, the multimeric concept was used to synthesize a dimeric folate derivative via a click reaction. The novel folate derivative (HYNIC-D1-FA2) was radiolabeled with
[...] Read more.
The folate receptor (FR) is overexpressed in a wide variety of human tumors. In our study, the multimeric concept was used to synthesize a dimeric folate derivative via a click reaction. The novel folate derivative (HYNIC-D1-FA2) was radiolabeled with 99mTc using tricine and trisodium triphenylphosphine-3,3′,3″-trisulfonate (TPPTS) as coligands (99mTc-HYNIC-D1-FA2) and its in vitro physicochemical properties, ex vivo biodistribution and in vivo micro-SPECT/CT imaging as a potential FR targeted agent were evaluated. It is a hydrophilic compound (log P = −2.52 ± 0.13) with high binding affinity (IC50 = 19.06 nM). Biodistribution in KB tumor-bearing mice showed that 99mTc-HYNIC-D1-FA2 had high uptake in FR overexpressed tumor and kidney at all time-points, and both of them could obviously be inhibited when blocking with free FA in the blocking studies. From the in vivo micro-SPECT/CT imaging results, good tumor uptake of 99mTc-HYNIC-D1-FA2 was observed in KB tumor-bearing mice and it could be blocked obviously. Based on the results, this new radiolabeled dimeric FA tracer might be a promising candidate for FR-targeting imaging with high affinity and selectivity. Full article
(This article belongs to the Special Issue Molecular Imaging Probes)
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Open AccessArticle Anti-Inflammatory Effects of Melandrii Herba Ethanol Extract via Inhibition of NF-κB and MAPK Signaling Pathways and Induction of HO-1 in RAW 264.7 Cells and Mouse Primary Macrophages
Molecules 2016, 21(6), 818; doi:10.3390/molecules21060818
Received: 20 April 2016 / Revised: 15 June 2016 / Accepted: 20 June 2016 / Published: 22 June 2016
Cited by 3 | PDF Full-text (2067 KB) | HTML Full-text | XML Full-text
Abstract
Melandrii Herba (MH) is a traditional Asian medicinal herb used to treat breast cancer, anuria, and diseases of lactation. However, its biological properties and molecular mechanisms have not been fully elucidated. The purpose of this study was to investigate the anti-inflammatory activity and
[...] Read more.
Melandrii Herba (MH) is a traditional Asian medicinal herb used to treat breast cancer, anuria, and diseases of lactation. However, its biological properties and molecular mechanisms have not been fully elucidated. The purpose of this study was to investigate the anti-inflammatory activity and underlying molecular mechanism of MH ethanol extract (MHE) on the lipopolysaccharide (LPS)-mediated inflammatory response in macrophages. MHE cytotoxicity was determined using a cell counting kit (CCK) assay. The effects of MHE on the production of NO, inflammatory cytokines, and related proteins and mRNAs were determined using the Griess test, ELISA, Western blotting, and real-time RT-PCR, respectively. In addition, intracellular signaling pathways, such as NF-κB, MAPK, and HO-1, were analyzed using Western blotting. Our results revealed that MHE treatment significantly inhibited the secretion of NO and inflammatory cytokines, including TNF-α, IL-6, and IL-1β in macrophages, at sub-cytotoxic concentrations. Furthermore, MHE treatment inhibited iNOS expression and induced HO-1 expression. Finally, the transcriptional activities of NF-κB and MAPK activation were significantly suppressed by MHE in LPS-stimulated macrophages. The results indicate that MHE exerts anti-inflammatory effects by suppressing inflammatory mediator production via NF-κB and MAPK signaling pathways inhibition and induction of HO-1 expression in macrophages. Therefore, our results suggest the potential value of MHE as an inflammatory therapeutic agent developed from a natural substance. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Uprolides N, O and P from the Panamanian Octocoral Eunicea succinea
Molecules 2016, 21(6), 819; doi:10.3390/molecules21060819
Received: 11 May 2016 / Revised: 17 June 2016 / Accepted: 18 June 2016 / Published: 22 June 2016
PDF Full-text (1507 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three new diterpenes, uprolide N (1), uprolide O (2), uprolide P (3) and a known one, dolabellane (4), were isolated from the CH2Cl2-MeOH extract of the gorgonian octocoral Eunicea succinea,
[...] Read more.
Three new diterpenes, uprolide N (1), uprolide O (2), uprolide P (3) and a known one, dolabellane (4), were isolated from the CH2Cl2-MeOH extract of the gorgonian octocoral Eunicea succinea, collected from Bocas del Toro, on the Caribbean coast of Panama. Their structures were determined using spectroscopic analyses, including 1D and 2D NMR and high-resolution mass spectrometry (HRMS) together with molecular modeling studies. Compounds 13 displayed anti-inflammatory properties by inhibiting production of Tumor Necrosis Factor (TNF) and Interleukin (IL)-6 induced by lipopolysaccharide (LPS) in murine macrophages. Full article
(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)
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Open AccessReview Current Status of Bioinks for Micro-Extrusion-Based 3D Bioprinting
Molecules 2016, 21(6), 685; doi:10.3390/molecules21060685
Received: 19 April 2016 / Revised: 16 May 2016 / Accepted: 19 May 2016 / Published: 25 May 2016
Cited by 22 | PDF Full-text (2985 KB) | HTML Full-text | XML Full-text
Abstract
Recent developments in 3D printing technologies and design have been nothing short of spectacular. Parallel to this, development of bioinks has also emerged as an active research area with almost unlimited possibilities. Many bioinks have been developed for various cells types, but bioinks
[...] Read more.
Recent developments in 3D printing technologies and design have been nothing short of spectacular. Parallel to this, development of bioinks has also emerged as an active research area with almost unlimited possibilities. Many bioinks have been developed for various cells types, but bioinks currently used for 3D printing still have challenges and limitations. Bioink development is significant due to two major objectives. The first objective is to provide growth- and function-supportive bioinks to the cells for their proper organization and eventual function and the second objective is to minimize the effect of printing on cell viability, without compromising the resolution shape and stability of the construct. Here, we will address the current status and challenges of bioinks for 3D printing of tissue constructs for in vitro and in vivo applications. Full article
(This article belongs to the Special Issue Biomaterials and Bioprinting)
Open AccessReview Dendrimer Prodrugs
Molecules 2016, 21(6), 686; doi:10.3390/molecules21060686
Received: 7 April 2016 / Revised: 10 May 2016 / Accepted: 17 May 2016 / Published: 31 May 2016
Cited by 5 | PDF Full-text (4027 KB) | HTML Full-text | XML Full-text
Abstract
The main objective of this review is to describe the importance of dendrimer prodrugs in the design of new drugs, presenting numerous applications of these nanocomposites in the pharmaceutical field. Therefore, the use of dendrimer prodrugs as carrier for drug delivery, to improve
[...] Read more.
The main objective of this review is to describe the importance of dendrimer prodrugs in the design of new drugs, presenting numerous applications of these nanocomposites in the pharmaceutical field. Therefore, the use of dendrimer prodrugs as carrier for drug delivery, to improve pharmacokinetic properties of prototype, to promote drug sustained-release, to increase selectivity and, consequently, to decrease toxicity, are just some examples of topics that have been extensively reported in the literature, especially in the last decade. The examples discussed here give a panel of the growing interest dendrimer prodrugs have been evoking in the scientific community. Full article
(This article belongs to the Special Issue Functional Dendrimers)
Open AccessReview The Rationale for Insulin Therapy in Alzheimer’s Disease
Molecules 2016, 21(6), 689; doi:10.3390/molecules21060689
Received: 14 March 2016 / Revised: 14 May 2016 / Accepted: 19 May 2016 / Published: 26 May 2016
Cited by 4 | PDF Full-text (708 KB) | HTML Full-text | XML Full-text
Abstract
Alzheimer’s disease (AD) is the most common form of dementia, with a prevalence that increases with age. By 2050, the worldwide number of patients with AD is projected to reach more than 140 million. The prominent signs of AD are progressive memory loss,
[...] Read more.
Alzheimer’s disease (AD) is the most common form of dementia, with a prevalence that increases with age. By 2050, the worldwide number of patients with AD is projected to reach more than 140 million. The prominent signs of AD are progressive memory loss, accompanied by a gradual decline in cognitive function and premature death. AD is the clinical manifestation of altered proteostasis. The initiating step of altered proteostasis in most AD patients is not known. The progression of AD is accelerated by several chronic disorders, among which the contribution of diabetes to AD is well understood at the cell biology level. The pathological mechanisms of AD and diabetes interact and tend to reinforce each other, thus accelerating cognitive impairment. At present, only symptomatic interventions are available for treating AD. To optimise symptomatic treatment, a personalised therapy approach has been suggested. Intranasal insulin administration seems to open the possibility for a safe, and at least in the short term, effective symptomatic intervention that delays loss of cognition in AD patients. This review summarizes the interactions of AD and diabetes from the cell biology to the patient level and the clinical results of intranasal insulin treatment of cognitive decline in AD. Full article
(This article belongs to the Special Issue Molecules against Alzheimer)
Open AccessReview The Chiral Pool in the Pictet–Spengler Reaction for the Synthesis of β-Carbolines
Molecules 2016, 21(6), 699; doi:10.3390/molecules21060699
Received: 27 April 2016 / Revised: 18 May 2016 / Accepted: 24 May 2016 / Published: 27 May 2016
Cited by 4 | PDF Full-text (4732 KB) | HTML Full-text | XML Full-text
Abstract
The Pictet–Spengler reaction (PSR) is the reaction of a β-arylethylamine with an aldehyde or ketone, followed by ring closure to give an aza-heterocycle. When the β-arylethylamine is tryptamine, the product is a β-carboline, a widespread skeleton in natural alkaloids. In the natural occurrence,
[...] Read more.
The Pictet–Spengler reaction (PSR) is the reaction of a β-arylethylamine with an aldehyde or ketone, followed by ring closure to give an aza-heterocycle. When the β-arylethylamine is tryptamine, the product is a β-carboline, a widespread skeleton in natural alkaloids. In the natural occurrence, these compounds are generally enantiopure, thus the asymmetric synthesis of these compounds have been attracting the interest of organic chemists. This review aims to give an overview of the asymmetric PSR, in which the chirality arises from optically pure amines or carbonyl compounds both from natural sources and from asymmetric syntheses to assemble the reaction partners. Full article
(This article belongs to the Special Issue Synthesis of Bioactive Compounds from the Chiral Pool)
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Open AccessReview Antioxidative and Antidiabetic Effects of Natural Polyphenols and Isoflavones
Molecules 2016, 21(6), 708; doi:10.3390/molecules21060708
Received: 2 May 2016 / Revised: 23 May 2016 / Accepted: 25 May 2016 / Published: 30 May 2016
Cited by 25 | PDF Full-text (1021 KB) | HTML Full-text | XML Full-text
Abstract
Many polyphenols that contain more than two phenolic hydroxyl groups are natural antioxidants and can provide health benefits to humans. These polyphenols include, for example, oleuropein, hydroxytyrosol, catechin, chlorogenic acids, hesperidin, nobiletin, and isoflavones. These have been studied widely because of their strong
[...] Read more.
Many polyphenols that contain more than two phenolic hydroxyl groups are natural antioxidants and can provide health benefits to humans. These polyphenols include, for example, oleuropein, hydroxytyrosol, catechin, chlorogenic acids, hesperidin, nobiletin, and isoflavones. These have been studied widely because of their strong radical-scavenging and antioxidative effects. These effects may contribute to the prevention of diseases, such as diabetes. Insulin secretion, insulin resistance, and homeostasis are important factors in the onset of diabetes, a disease that is associated with dysfunction of pancreatic β-cells. Oxidative stress is thought to contribute to this dysfunction and the effects of antioxidants on the pathogenesis of diabetes have, therefore, been investigated. Here, we summarize the antioxidative effects of polyphenols from the perspective of their radical-scavenging activities as well as their effects on signal transduction pathways. We also describe the preventative effects of polyphenols on diabetes by referring to recent studies including those reported by us. Appropriate analytical approaches for evaluating antioxidants in studies on the prevention of diabetes are comprehensively reviewed. Full article
(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)
Open AccessReview The Hedyotis diffusa Willd. (Rubiaceae): A Review on Phytochemistry, Pharmacology, Quality Control and Pharmacokinetics
Molecules 2016, 21(6), 710; doi:10.3390/molecules21060710
Received: 26 April 2016 / Revised: 22 May 2016 / Accepted: 24 May 2016 / Published: 30 May 2016
Cited by 2 | PDF Full-text (1675 KB) | HTML Full-text | XML Full-text
Abstract
Hedyotis diffusa Willd (H. diffusa) is a well-known Chinese medicine with a variety of activities, especially its anti-cancer effect in the clinic. Up to now, 171 compounds have been reported from H. diffusa, including 32 iridoids, 26 flavonoids, 24 anthraquinones,
[...] Read more.
Hedyotis diffusa Willd (H. diffusa) is a well-known Chinese medicine with a variety of activities, especially its anti-cancer effect in the clinic. Up to now, 171 compounds have been reported from H. diffusa, including 32 iridoids, 26 flavonoids, 24 anthraquinones, 26 phenolics and their derivatives, 50 volatile oils and 13 miscellaneous compounds. In vitro and in vivo studies show these phytochemicals and plant extracts to exhibit a range of pharmacological activities of anti-cancer, antioxidant, anti-inflammatory, anti-fibroblast, immunomodulatory and neuroprotective effects. Although a series of methods have been established for the quality control of H. diffusa, a feasible and reliable approach is still needed in consideration of its botanical origin, collecting time and bioactive effects. Meanwhile, more pharmacokinetics researches are needed to illustrate the characteristics of H. diffusa in vivo. The present review aims to provide up-to-date and comprehensive information on the phytochemistry, pharmacology, quality control and pharmacokinetic characteristics of H. diffusa for its clinical use and further development. Full article
(This article belongs to the collection Herbal Medicine Research)
Open AccessReview Sorbicillinoids from Fungi and Their Bioactivities
Molecules 2016, 21(6), 715; doi:10.3390/molecules21060715
Received: 6 April 2016 / Revised: 26 May 2016 / Accepted: 27 May 2016 / Published: 1 June 2016
Cited by 5 | PDF Full-text (1496 KB) | HTML Full-text | XML Full-text
Abstract
Sorbicillinoids are important hexaketide metabolites derived from fungi. They have a variety of biological activities including cytotoxic, antioxidant, antiviral and antimicrobial activity. The unique structural features of the sorbicillinoids make them attractive candidates for developing new pharmaceutical and agrochemical agents. About 90 sorbicillinoids
[...] Read more.
Sorbicillinoids are important hexaketide metabolites derived from fungi. They have a variety of biological activities including cytotoxic, antioxidant, antiviral and antimicrobial activity. The unique structural features of the sorbicillinoids make them attractive candidates for developing new pharmaceutical and agrochemical agents. About 90 sorbicillinoids have been reported in the past few decades. This mini-review aims to briefly summarize their occurrence, structures, and biological activities. Full article
(This article belongs to the Special Issue Polyketides)
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Open AccessReview Applications of the Conceptual Density Functional Theory Indices to Organic Chemistry Reactivity
Molecules 2016, 21(6), 748; doi:10.3390/molecules21060748
Received: 12 May 2016 / Revised: 1 June 2016 / Accepted: 2 June 2016 / Published: 9 June 2016
Cited by 46 | PDF Full-text (3597 KB) | HTML Full-text | XML Full-text
Abstract
Theoretical reactivity indices based on the conceptual Density Functional Theory (DFT) have become a powerful tool for the semiquantitative study of organic reactivity. A large number of reactivity indices have been proposed in the literature. Herein, global quantities like the electronic chemical potential
[...] Read more.
Theoretical reactivity indices based on the conceptual Density Functional Theory (DFT) have become a powerful tool for the semiquantitative study of organic reactivity. A large number of reactivity indices have been proposed in the literature. Herein, global quantities like the electronic chemical potential μ, the electrophilicity ω and the nucleophilicity N indices, and local condensed indices like the electrophilic P k + and nucleophilic P k Parr functions, as the most relevant indices for the study of organic reactivity, are discussed. Full article
Open AccessFeature PaperReview Antimicrobial Activity of Lactoferrin-Related Peptides and Applications in Human and Veterinary Medicine
Molecules 2016, 21(6), 752; doi:10.3390/molecules21060752
Received: 18 May 2016 / Revised: 3 June 2016 / Accepted: 6 June 2016 / Published: 11 June 2016
Cited by 10 | PDF Full-text (1188 KB) | HTML Full-text | XML Full-text
Abstract
Antimicrobial peptides (AMPs) represent a vast array of molecules produced by virtually all living organisms as natural barriers against infection. Among AMP sources, an interesting class regards the food-derived bioactive agents. The whey protein lactoferrin (Lf) is an iron-binding glycoprotein that plays a
[...] Read more.
Antimicrobial peptides (AMPs) represent a vast array of molecules produced by virtually all living organisms as natural barriers against infection. Among AMP sources, an interesting class regards the food-derived bioactive agents. The whey protein lactoferrin (Lf) is an iron-binding glycoprotein that plays a significant role in the innate immune system, and is considered as an important host defense molecule. In search for novel antimicrobial agents, Lf offers a new source with potential pharmaceutical applications. The Lf-derived peptides Lf(1–11), lactoferricin (Lfcin) and lactoferrampin exhibit interesting and more potent antimicrobial actions than intact protein. Particularly, Lfcin has demonstrated strong antibacterial, anti-fungal and antiparasitic activity with promising applications both in human and veterinary diseases (from ocular infections to osteo-articular, gastrointestinal and dermatological diseases). Full article
Open AccessReview Applications and Developments on the Use of Vibrational Spectroscopy Imaging for the Analysis, Monitoring and Characterisation of Crops and Plants
Molecules 2016, 21(6), 755; doi:10.3390/molecules21060755
Received: 10 April 2016 / Revised: 30 May 2016 / Accepted: 7 June 2016 / Published: 10 June 2016
Cited by 3 | PDF Full-text (200 KB) | HTML Full-text | XML Full-text
Abstract
The adaptation and use of advanced technologies is an effective and encouraging way to efficiently and reliably characterise crops and plants. Additionally advances in these technologies will improve the information available for agronomists, breeders and plant physiologists in order to develop best management
[...] Read more.
The adaptation and use of advanced technologies is an effective and encouraging way to efficiently and reliably characterise crops and plants. Additionally advances in these technologies will improve the information available for agronomists, breeders and plant physiologists in order to develop best management practices in the process and commercialization of agricultural products and commodities. Methods based on vibrational spectroscopy such as near infrared (NIR) spectroscopy using either single spot or hyperspectral measurements are now more available and ready to use than ever before. The main characteristics of these methodologies (high-throughput, non-destructive) have determined a growth in basic and applied research using NIR spectroscopy in many disciplines related with crop and plant sciences. A wide range of studies have demonstrated the ability of NIR spectroscopy to analyse different parameters in crops. Recently the use of hyperspectral imaging techniques have expanded the range of applications in crop and plant sciences. This article provides an overview of applications and developments of NIR hyperspectral image for the analysis, monitoring and characterisation of crops and plants. Full article
(This article belongs to the Special Issue Vibrational Spectroscopic Imaging and Mapping)
Open AccessReview Synthesis of Linearly Fused Benzodipyrrole Based Organic Materials
Molecules 2016, 21(6), 785; doi:10.3390/molecules21060785
Received: 20 May 2016 / Revised: 10 June 2016 / Accepted: 13 June 2016 / Published: 17 June 2016
Cited by 4 | PDF Full-text (11078 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this review is to give an overview of the synthetic methods to prepare different indolo[3,2-b]carbazoles and similar systems with a potential use in electro-optical devices such as OLEDs (organic light emitting diode), OPVs (organic photovoltaic) and OFETs (organic
[...] Read more.
The objective of this review is to give an overview of the synthetic methods to prepare different indolo[3,2-b]carbazoles and similar systems with a potential use in electro-optical devices such as OLEDs (organic light emitting diode), OPVs (organic photovoltaic) and OFETs (organic field effect transistor). Some further modifications to the core units and their implications for specific applications are also discussed. Full article
(This article belongs to the collection Heterocyclic Compounds)
Open AccessReview Emerging Roles of Toxin-Antitoxin Modules in Bacterial Pathogenesis
Molecules 2016, 21(6), 790; doi:10.3390/molecules21060790
Received: 3 May 2016 / Revised: 6 June 2016 / Accepted: 13 June 2016 / Published: 17 June 2016
Cited by 9 | PDF Full-text (1547 KB) | HTML Full-text | XML Full-text
Abstract
Toxin-antitoxin (TA) cassettes are encoded widely by bacteria. The modules typically comprise a protein toxin and protein or RNA antitoxin that sequesters the toxin factor. Toxin activation in response to environmental cues or other stresses promotes a dampening of metabolism, most notably protein
[...] Read more.
Toxin-antitoxin (TA) cassettes are encoded widely by bacteria. The modules typically comprise a protein toxin and protein or RNA antitoxin that sequesters the toxin factor. Toxin activation in response to environmental cues or other stresses promotes a dampening of metabolism, most notably protein translation, which permits survival until conditions improve. Emerging evidence also implicates TAs in bacterial pathogenicity. Bacterial persistence involves entry into a transient semi-dormant state in which cells survive unfavorable conditions including killing by antibiotics, which is a significant clinical problem. TA complexes play a fundamental role in inducing persistence by downregulating cellular metabolism. Bacterial biofilms are important in numerous chronic inflammatory and infectious diseases and cause serious therapeutic problems due to their multidrug tolerance and resistance to host immune system actions. Multiple TAs influence biofilm formation through a network of interactions with other factors that mediate biofilm production and maintenance. Moreover, in view of their emerging contributions to bacterial virulence, TAs are potential targets for novel prophylactic and therapeutic approaches that are required urgently in an era of expanding antibiotic resistance. This review summarizes the emerging evidence that implicates TAs in the virulence profiles of a diverse range of key bacterial pathogens that trigger serious human disease. Full article
(This article belongs to the Special Issue Natural Toxins)
Open AccessReview Capsaicin, Nociception and Pain
Molecules 2016, 21(6), 797; doi:10.3390/molecules21060797
Received: 29 April 2016 / Revised: 6 June 2016 / Accepted: 14 June 2016 / Published: 18 June 2016
Cited by 9 | PDF Full-text (3258 KB) | HTML Full-text | XML Full-text
Abstract
Capsaicin, the pungent ingredient of the hot chili pepper, is known to act on the transient receptor potential cation channel vanilloid subfamily member 1 (TRPV1). TRPV1 is involved in somatic and visceral peripheral inflammation, in the modulation of nociceptive inputs to spinal cord
[...] Read more.
Capsaicin, the pungent ingredient of the hot chili pepper, is known to act on the transient receptor potential cation channel vanilloid subfamily member 1 (TRPV1). TRPV1 is involved in somatic and visceral peripheral inflammation, in the modulation of nociceptive inputs to spinal cord and brain stem centers, as well as the integration of diverse painful stimuli. In this review, we first describe the chemical and pharmacological properties of capsaicin and its derivatives in relation to their analgesic properties. We then consider the biochemical and functional characteristics of TRPV1, focusing on its distribution and biological effects within the somatosensory and viscerosensory nociceptive systems. Finally, we discuss the use of capsaicin as an agonist of TRPV1 to model acute inflammation in slices and other ex vivo preparations. Full article
(This article belongs to the Special Issue Capsaicin)
Open AccessReview Exploiting the Biosynthetic Potential of Type III Polyketide Synthases
Molecules 2016, 21(6), 806; doi:10.3390/molecules21060806
Received: 20 May 2016 / Revised: 15 June 2016 / Accepted: 17 June 2016 / Published: 22 June 2016
Cited by 3 | PDF Full-text (9927 KB) | HTML Full-text | XML Full-text
Abstract
Polyketides are structurally and functionally diverse secondary metabolites that are biosynthesized by polyketide synthases (PKSs) using acyl-CoA precursors. Recent studies in the engineering and structural characterization of PKSs have facilitated the use of target enzymes as biocatalysts to produce novel functionally optimized polyketides.
[...] Read more.
Polyketides are structurally and functionally diverse secondary metabolites that are biosynthesized by polyketide synthases (PKSs) using acyl-CoA precursors. Recent studies in the engineering and structural characterization of PKSs have facilitated the use of target enzymes as biocatalysts to produce novel functionally optimized polyketides. These compounds may serve as potential drug leads. This review summarizes the insights gained from research on type III PKSs, from the discovery of chalcone synthase in plants to novel PKSs in bacteria and fungi. To date, at least 15 families of type III PKSs have been characterized, highlighting the utility of PKSs in the development of natural product libraries for therapeutic development. Full article
(This article belongs to the Special Issue Polyketides)
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Open AccessReview Natural Products to Counteract the Epidemic of Cardiovascular and Metabolic Disorders
Molecules 2016, 21(6), 807; doi:10.3390/molecules21060807
Received: 1 April 2016 / Revised: 9 June 2016 / Accepted: 13 June 2016 / Published: 22 June 2016
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Abstract
Natural products have always been exploited to promote health and served as a valuable source for the discovery of new drugs. In this review, the great potential of natural compounds and medicinal plants for the treatment or prevention of cardiovascular and metabolic disorders,
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Natural products have always been exploited to promote health and served as a valuable source for the discovery of new drugs. In this review, the great potential of natural compounds and medicinal plants for the treatment or prevention of cardiovascular and metabolic disorders, global health problems with rising prevalence, is addressed. Special emphasis is laid on natural products for which efficacy and safety have already been proven and which are in clinical trials, as well as on plants used in traditional medicine. Potential benefits from certain dietary habits and dietary constituents, as well as common molecular targets of natural products, are also briefly discussed. A glimpse at the history of statins and biguanides, two prominent representatives of natural products (or their derivatives) in the fight against metabolic disease, is also included. The present review aims to serve as an “opening” of this special issue of Molecules, presenting key historical developments, recent advances, and future perspectives outlining the potential of natural products for prevention or therapy of cardiovascular and metabolic disease. Full article
(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)
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Open AccessExpression of Concern Expression of Concern: Segneanu et al. Helleborus purpurascens—Amino Acid and Peptide Analysis Linked to the Chemical and Antiproliferative Properties of the Extracted Compounds. Molecules 2015, 20, 22170–22187
Molecules 2016, 21(6), 725; doi:10.3390/molecules21060725
Received: 30 May 2016 / Accepted: 1 June 2016 / Published: 2 June 2016
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Abstract
As Editor in Chief of Molecules and Academic Editor of the article [1], respectively, we wish to advise readers that Molecules has been informed that its authorship is currently in dispute and the subject of a formal lawsuit.[...] Full article
Open AccessCorrection Correction: Zhao, J., et al. Pharmacokinetics of Ginkgolide B after Oral Administration of Three Different Ginkgolide B Formulations in Beagle Dogs. Molecules 2015, 20, 20031–20041
Molecules 2016, 21(6), 759; doi:10.3390/molecules21060759
Received: 3 June 2016 / Accepted: 3 June 2016 / Published: 9 June 2016
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Abstract
The authors wish to correct the funding projects number of “Natural Science Foundation of Jiangsu Province” in the Acknowledgments section of this paper [1]: The correct funding projects number should be “No. BK20130403”, not “No. BK2013403”.[...] Full article
(This article belongs to the Section Medicinal Chemistry)
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