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Molecules, Volume 19, Issue 9 (September 2014), Pages 12898-15360

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Research

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Open AccessArticle GA3 and Other Signal Regulators (MeJA and IAA) Improve Xanthumin Biosynthesis in Different Manners in Xanthium strumarium L.
Molecules 2014, 19(9), 12898-12908; doi:10.3390/molecules190912898
Received: 22 June 2014 / Revised: 9 August 2014 / Accepted: 11 August 2014 / Published: 25 August 2014
PDF Full-text (1558 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Xanthanolides from Xanthium strumarium L. exhibit various pharmacological activities and these compounds are mainly produced in the glandular trichomes of aerial plant parts. The regulation of xanthanolide biosynthesis has never been reported in the literature. In this study, the effects of phytohormonal stimulation
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Xanthanolides from Xanthium strumarium L. exhibit various pharmacological activities and these compounds are mainly produced in the glandular trichomes of aerial plant parts. The regulation of xanthanolide biosynthesis has never been reported in the literature. In this study, the effects of phytohormonal stimulation on xanthumin (a xanthanolide compound) biosynthesis, glandular trichomes and germacrene A synthase (GAS) gene expression in X. strumarium L. young leaves were investigated. The exogenous applications of methyl jasmonate (MeJA), indole-3-acetic acid (IAA), and gibberrellin A3 (GA3) at appropriate concentrations were all found to improve xanthumin biosynthesis, but in different ways. It was suggested that a higher gland density stimulated by MeJA (400 µM) or IAA (200 µM) treatment caused at least in part an improvement in xanthumin production, whereas GA3 (10 µM) led to an improvement by up-regulating xanthumin biosynthetic genes within gland cells, not by forming more glandular trichomes. Compared to the plants before the flowering stage, plants that had initiated flowering showed enhanced xanthumin biosynthesis, but no higher gland density, an effect was similar to that caused by exogenous GA3 treatment. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Effects of Egg Yolk-Derived Peptide on Osteogenic Gene Expression and MAPK Activation
Molecules 2014, 19(9), 12909-12924; doi:10.3390/molecules190912909
Received: 16 June 2014 / Revised: 7 August 2014 / Accepted: 12 August 2014 / Published: 25 August 2014
Cited by 6 | PDF Full-text (2578 KB) | HTML Full-text | XML Full-text
Abstract
The present study investigated the effects of egg yolk-derived peptide (YPEP) on osteogenic activities and MAPK-regulation of osteogenic gene expressions. The effects of YPEP on cell proliferation, alkaline phosphatase activity, collagen synthesis, and mineralization were measured in human osteoblastic MG-63 cells. Activation of
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The present study investigated the effects of egg yolk-derived peptide (YPEP) on osteogenic activities and MAPK-regulation of osteogenic gene expressions. The effects of YPEP on cell proliferation, alkaline phosphatase activity, collagen synthesis, and mineralization were measured in human osteoblastic MG-63 cells. Activation of MAPKs and downstream transcription factors such as extracellular-signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1/2 (JNK1/2), p38, ELK1, and cJUN were examined using western blot analysis. YPEP dose-dependently increased MG-63 cell proliferation, ALP activity, collagen synthesis, and calcium deposition. YPEP activated ERK1/2, p38, and ELK1 phosphorylation whereas JNK and cJUN were not affected by YPEP. The COL1A1 (collagen, type I, alpha 1), ALPL (alkaline phosphatase), and SPP1 (secreted phosphoprotein 1, osteopontin) gene expressions were increased while BGLAP (osteocalcin) was not affected by YPEP. The ERK1/2 inhibitor (PD98509) blocked the YPEP-induced COL1A1 and ALPL gene expressions as well as ELK1 phosphorylation. The p38 inhibitor (SB203580) blocked YPEP-induced COL1A1 and ALPL gene expressions. SPP1 gene expression was not affected by these MAPK inhibitors. In conclusion, YPEP treatment stimulates the osteogenic differentiation via the MAPK/ELK1 signaling pathway. These results could provide a mechanistic explanation for the bone-strengthening effects of YPEP. Full article
(This article belongs to the Special Issue Peptide Chemistry)
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Open AccessArticle Effect of Meadowsweet Flower Extract-Pullulan Coatings on Rhizopus Rot Development and Postharvest Quality of Cold-Stored Red Peppers
Molecules 2014, 19(9), 12925-12939; doi:10.3390/molecules190912925
Received: 16 July 2014 / Revised: 12 August 2014 / Accepted: 15 August 2014 / Published: 25 August 2014
Cited by 5 | PDF Full-text (1104 KB) | HTML Full-text | XML Full-text
Abstract
The study involved an examination of the antifungal activity on red peppers of pullulan coating (P) and pullulan coating containing either water-ethanol (P + eEMF) or ethanol extract of meadowsweet flowers (P + eEMF). Pullulan was obtained from a culture of Aureobasidium pullulans
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The study involved an examination of the antifungal activity on red peppers of pullulan coating (P) and pullulan coating containing either water-ethanol (P + eEMF) or ethanol extract of meadowsweet flowers (P + eEMF). Pullulan was obtained from a culture of Aureobasidium pullulans B-1 mutant. Both non-inoculated peppers and those artificially inoculated with Rhizopus arrhizus were coated and incubated at 24 °C for 5 days. The intensity of the decay caused by Rhizopus arrhizus in the peppers with P and P + eEMF coatings was nearly 3-fold lower, and in the case of P + weEMF 5-fold lower, than that observed in the control peppers. Additionally, the P + weEMF coating decreased, almost two-fold the severity of pepper decay compared to other samples. The influence of coating of pepper postharvest quality was examined after 30 days of storage at 6 °C and 70%–75% RH. All coatings formed a thin and well-attached additional layer of an intensified gloss. During storage, color, total soluble solid content and weight loss of coated peppers were subject to lower changes in comparison with uncoated ones. The results indicate the possibility of the application of pullulan coatings containing MFEs as an alternative to the chemical fungicides used to combat pepper postharvest diseases. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Effect of Chlorogenic Acid on Melanogenesis of B16 Melanoma Cells
Molecules 2014, 19(9), 12940-12948; doi:10.3390/molecules190912940
Received: 17 July 2014 / Revised: 11 August 2014 / Accepted: 18 August 2014 / Published: 25 August 2014
Cited by 7 | PDF Full-text (2539 KB) | HTML Full-text | XML Full-text
Abstract
Chlorogenic acid (CGA), the ester formed between caffeic acid and l-quinic acid, is a widespread phenolic compound. It is part of the human diet, found in foods such as coffee, apples, pears, etc. CGA is also was widely used in cosmetics, but
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Chlorogenic acid (CGA), the ester formed between caffeic acid and l-quinic acid, is a widespread phenolic compound. It is part of the human diet, found in foods such as coffee, apples, pears, etc. CGA is also was widely used in cosmetics, but the effects of CGA on melanogenesis are unknown. In this study, we analyzed the effects of CGA on cell proliferation, melanin content and tyrosinase of B16 murine melanoma cells. Additionally, the enzymatic reactions of CGA in B16 melanoma cells lytic solution were detected by UV spectrophotometry. Results showed CGA at 30 and 60 μM significantly suppresses cell proliferation. 8-MOP at 100 μM significantly promotes cell proliferation, but CGA can counter this. Incubated for 24 h, CGA (500 μM) improves melanogenesis while suppressing tyrosinase activity in B16 melanoma cells or 8-methoxypsoralen (8-MOP) co-incubated B16 melanoma cells. After 12 h, B16 melanoma cell treatment with CGA leads to an increase in melanin accumulation, however, after 48 h there is a decrease in melanin production which correlates broadly with a decrease in tyrosinase activity. CGA incubated with lytic solution 24 h turned brown at 37 °C. The formation of new products (with a maximum absorption at 295 nm) is associated with reduction of CGA (maximum absorption at 326 nm). Therefore, CGA has its two sidesroles in melanogenesis of B16 melanoma cells. CGA is a likely a substrate of melanin, but the metabolic product(s) of CGA may suppress melanogenesis in B16 melanoma cells by inhibiting tyrosinase activity. Full article
(This article belongs to the Special Issue Cinnamic Acids Hybrids with Biological Interest)
Open AccessArticle Nanoscale Lithography Mediated by Surface Self-Assembly of 16-[3,5-Bis(Mercaptomethyl)phenoxy]hexadecanoic Acid on Au(111) Investigated by Scanning Probe Microscopy
Molecules 2014, 19(9), 13010-13026; doi:10.3390/molecules190913010
Received: 7 May 2014 / Revised: 9 August 2014 / Accepted: 18 August 2014 / Published: 25 August 2014
Cited by 3 | PDF Full-text (4584 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The solution-phase self-assembly of bidentate 16-[3,5-bis(mercapto-methyl)phenoxy]hexadecanoic acid (BMPHA) on Au(111) was studied using nano-fabrication protocols with scanning probe nanolithography and immersion particle lithography. Molecularly thin films of BMPHA prepared by surface self-assembly have potential application as spatially selective layers in sensor designs. Either
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The solution-phase self-assembly of bidentate 16-[3,5-bis(mercapto-methyl)phenoxy]hexadecanoic acid (BMPHA) on Au(111) was studied using nano-fabrication protocols with scanning probe nanolithography and immersion particle lithography. Molecularly thin films of BMPHA prepared by surface self-assembly have potential application as spatially selective layers in sensor designs. Either monolayer or bilayer films of BMPHA can be formed under ambient conditions, depending on the parameters of concentration and immersion intervals. Experiments with scanning probe-based lithography (nanoshaving and nanografting) were applied to measure the thickness of BMPHA films. The thickness of a monolayer and bilayer film of BMPHA on Au(111) were measured in situ with atomic force microscopy using n-octadecanethiol as an internal reference. Scanning probe-based nanofabrication provides a way to insert nanopatterns of a reference molecule of known dimensions within a matrix film of unknown thickness to enable a direct comparison of heights and surface morphology. Immersion particle lithography was used to prepare a periodic arrangement of nanoholes within films of BMPHA. The nanoholes could be backfilled by immersion in a SAM solution to produce nanodots of n-octadecanethiol surrounded by a film of BMPHA. Test platforms prepared by immersion particle lithography enables control of the dimensions of surface sites to construct supramolecular assemblies. Full article
(This article belongs to the Special Issue Template Directed Synthesis and Self-Assembly in Organic Systems)
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Open AccessArticle Structures of New Phenolics Isolated from Licorice, and the Effectiveness of Licorice Phenolics on Vancomycin-Resistant Enterococci
Molecules 2014, 19(9), 13027-13041; doi:10.3390/molecules190913027
Received: 19 June 2014 / Revised: 19 August 2014 / Accepted: 20 August 2014 / Published: 25 August 2014
Cited by 5 | PDF Full-text (854 KB) | HTML Full-text | XML Full-text
Abstract
Licorice, which is the underground part of Glycyrrhiza species, has been used widely in Asian and Western countries as a traditional medicine and as a food additive. Our continuous investigation on the constituents of roots and stolons of Glycyrrhiza uralensis led to the
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Licorice, which is the underground part of Glycyrrhiza species, has been used widely in Asian and Western countries as a traditional medicine and as a food additive. Our continuous investigation on the constituents of roots and stolons of Glycyrrhiza uralensis led to the isolation of two new phenolics, in addition to 14 known compounds. Structural studies including spectroscopic and simple chemical derivatizations revealed that both of the new compounds had 2-aryl-3-methylbenzofuran structures. An examination of the effectiveness of licorice phenolics obtained in this study on vancomycin-resistant strains Enterococcus faecium FN-1 and Enterococcus faecalis NCTC12201 revealed that licoricidin showed the most potent antibacterial effects against both of E. faecalis and E. faecium with a minimum inhibitory concentration (MIC) of 1.9 × 10−5 M. 8-(γ,γ-Dimethylallyl)-wighteone, isoangustone A, 3'-(γ,γ-dimethylallyl)-kievitone, glyasperin C, and one of the new 3-methyl-2-phenylbenzofuran named neoglycybenzofuran also showed potent anti-vancomycin-resistant Enterococci effects (MIC 1.9 × 10−5–4.5 × 10−5 M for E. faecium and E. faecalis). The HPLC condition for simultaneous detection of the phenolics in the extract was investigated to assess the quality control of the natural antibacterial resource, and quantitative estimation of several major phenolics in the extract with the established HPLC condition was also performed. The results showed individual contents of 0.08%–0.57% w/w of EtOAc extract for the major phenolics in the materials examined. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Effects of P-Glycoprotein and Its Inhibitors on Apoptosis in K562 Cells
Molecules 2014, 19(9), 13061-13075; doi:10.3390/molecules190913061
Received: 5 June 2014 / Revised: 12 August 2014 / Accepted: 18 August 2014 / Published: 25 August 2014
Cited by 6 | PDF Full-text (915 KB) | HTML Full-text | XML Full-text
Abstract
P-glycoprotein (P-gp) is a major factor in multidrug resistance (MDR) which is a serious obstacle in chemotherapy. P-gp has also been implicated in causing apoptosis of tumor cells, which was shown to be another important mechanism of MDR recently. To study the influence
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P-glycoprotein (P-gp) is a major factor in multidrug resistance (MDR) which is a serious obstacle in chemotherapy. P-gp has also been implicated in causing apoptosis of tumor cells, which was shown to be another important mechanism of MDR recently. To study the influence of P-gp in tumor cell apoptosis, K562/A cells (P-gp+) and K562/S cells (P-gp−) were subjected to doxorubicin (Dox), serum withdrawal, or independent co-incubation with multiple P-gp inhibitors, including valspodar (PSC833), verapamil (Ver) and H108 to induce apoptosis. Apoptosis was simultaneously detected by apoptotic rate, cell cycle by flow cytometry and cysteine aspartic acid-specific protease 3 (caspase 3) activity by immunoassay. Cytotoxicity and apoptosis induced by PSC833 were evaluated through an MTT method and apoptosis rate, and cell cycle combined with caspase 3 activity, respectively. The results show that K562/A cells are more resistant to apoptosis and cell cycle arrest than K562/S cells after treatment with Dox or serum deprivation. The apoptosis of K562/A cells increased after co-incubation with each of the inhibitors of P-gp. P-gp inhibitors also enhanced cell cycle arrest in K562/A cell. PSC833 most strikingly decreased viability and led to apoptosis and S phase arrest of cell cycle in K562/A cells. Our study demonstrates that P-gp inhibits the apoptosis of tumor cells in addition to participating in the efflux of intracellular chemotherapy drugs. The results of the caspase 3 activity assay also suggest that the role of P-gp in apoptosis avoidance is caspase-related. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synthesis and Biological Evaluation of New Pyridone-Annelated Isoindigos as Anti-Proliferative Agents
Molecules 2014, 19(9), 13076-13092; doi:10.3390/molecules190913076
Received: 3 July 2014 / Revised: 12 August 2014 / Accepted: 18 August 2014 / Published: 25 August 2014
Cited by 4 | PDF Full-text (1088 KB) | HTML Full-text | XML Full-text
Abstract
A selected set of substituted pyridone-annelated isoindigos 3af has been synthesized via interaction of 5- and 6-substituted oxindoles 2af with 6-ethyl-1,2,9-trioxopyrrolo[3,2-f]quinoline-8-carboxylic acid (1) in acetic acid at reflux. Among these isoindigos, the 5'-chloro and 5'-bromo
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A selected set of substituted pyridone-annelated isoindigos 3af has been synthesized via interaction of 5- and 6-substituted oxindoles 2af with 6-ethyl-1,2,9-trioxopyrrolo[3,2-f]quinoline-8-carboxylic acid (1) in acetic acid at reflux. Among these isoindigos, the 5'-chloro and 5'-bromo derivatives 3b and 3d show strong and selective antiproliferative activities against a panel of human hematological and solid tumor cell-lines, but not against noncancerous cells, suggesting their potential use as anticancer agents. In all the tested cell lines, compound 3b was a 25%–50% more potent inhibitor of cell growth than 3d, suggesting the critical role of the substitution at 5'-position of the benzo-ring E. The IC50 values after 48 hours incubation with the 5'-chloro compound 3b were 6.60 µM in K562, 8.21 µM in THP-1, 8.97 µM in HepG2, 11.94 µM in MCF-7 and 14.59 µM in Caco-2 cancer cells, while the IC50 values in noncancerous HEK-293 and L-929 were 30.65 µM and 40.40 µM, respectively. In addition, compound 3b induced higher levels apoptosis in K562 cells than 3d, as determined by annexin V/7-AAD flowcytometry analysis. Therefore, further characterization of the antitproliferative mechanisms of compounds 3b and 3d may provide a novel chemotherapeutic agents. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Microwave Assisted Convenient One-Pot Synthesis of Coumarin Derivatives via Pechmann Condensation Catalyzed by FeF3 under Solvent-Free Conditions and Antimicrobial Activities of the Products
Molecules 2014, 19(9), 13093-13103; doi:10.3390/molecules190913093
Received: 30 June 2014 / Revised: 4 August 2014 / Accepted: 11 August 2014 / Published: 26 August 2014
Cited by 4 | PDF Full-text (472 KB) | HTML Full-text | XML Full-text
Abstract
A rapid and efficient solvent-free one-pot synthesis of coumarin derivatives by Pechmann condensation reactions of phenols with ethyl acetoacetate using FeF3 as a catalyst under microwave irradiation is described. This one-pot synthesis on a solid inorganic support provides the products in good
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A rapid and efficient solvent-free one-pot synthesis of coumarin derivatives by Pechmann condensation reactions of phenols with ethyl acetoacetate using FeF3 as a catalyst under microwave irradiation is described. This one-pot synthesis on a solid inorganic support provides the products in good yields. The newly synthesized compounds were systematically characterized by IR, 1H-NMR, 13C-NMR, MS and elemental CHN analyses. The proposed solvent-free microwave irradiation method using the environmentally friendly catalyst FeF3 offers the unique advantages of high yields, shorter reaction times, easy and quick isolation of the products, excellent chemoselectivity, and a one-pot, green synthesis. The products were screened for antimicrobial activity, and the results showed that the compounds reacted against all the tested bacteria. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Hyperspectral Imaging and Chemometric Modeling of Echinacea — A Novel Approach in the Quality Control of Herbal Medicines
Molecules 2014, 19(9), 13104-13121; doi:10.3390/molecules190913104
Received: 17 June 2014 / Revised: 7 August 2014 / Accepted: 17 August 2014 / Published: 26 August 2014
Cited by 5 | PDF Full-text (7078 KB) | HTML Full-text | XML Full-text
Abstract
Echinacea species are popularly included in various formulations to treat upper respiratory tract infections. These products are of commercial importance, with a collective sales figure of $132 million in 2009. Due to their close taxonomic alliance it is difficult to distinguish between the
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Echinacea species are popularly included in various formulations to treat upper respiratory tract infections. These products are of commercial importance, with a collective sales figure of $132 million in 2009. Due to their close taxonomic alliance it is difficult to distinguish between the three Echinacea species and incidences of incorrectly labeled commercial products have been reported. The potential of hyperspectral imaging as a rapid quality control method for raw material and products containing Echinacea species was investigated. Hyperspectral images of root and leaf material of authentic Echinacea species (E. angustifolia, E. pallida and E. purpurea) were acquired using a sisuChema shortwave infrared (SWIR) hyperspectral pushbroom imaging system with a spectral range of 920–2514 nm. Principal component analysis (PCA) plots showed a clear distinction between the root and leaf samples of the three Echinacea species and further differentiated the roots of different species. A classification model with a high coefficient of determination was constructed to predict the identity of the species included in commercial products. The majority of products (12 out of 20) were convincingly predicted as containing E. purpurea, E. angustifolia or both. The use of ultra performance liquid chromatography-mass spectrometry (UPLC-MS) in the differentiation of the species presented a challenge due to chemical similarities between the solvent extracts. The results show that hyperspectral imaging is an objective and non-destructive quality control method for authenticating raw material. Full article
(This article belongs to the Special Issue Advances of Vibrational Spectroscopic Technologies in Life Sciences)
Open AccessArticle In Vivo Antiplasmodial Potentials of the Combinations of Four Nigerian Antimalarial Plants
Molecules 2014, 19(9), 13136-13146; doi:10.3390/molecules190913136
Received: 18 June 2014 / Revised: 18 August 2014 / Accepted: 19 August 2014 / Published: 26 August 2014
Cited by 3 | PDF Full-text (681 KB) | HTML Full-text | XML Full-text
Abstract
Various combinations of Nauclea latifolia root, Artocarpus altilis stem bark, Murraya koenigii leaf and Enantia chlorantha stem bark used in African ethnomedicine as decoctions for malaria and fevers, and combinations with standard drugs, were investigated for antiplasmodial activities using Plasmodium berghei berghei-infected
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Various combinations of Nauclea latifolia root, Artocarpus altilis stem bark, Murraya koenigii leaf and Enantia chlorantha stem bark used in African ethnomedicine as decoctions for malaria and fevers, and combinations with standard drugs, were investigated for antiplasmodial activities using Plasmodium berghei berghei-infected mice. The respective prophylactic and curative ED50 values of 189.4 and 174.5 mg/kg for N. latifolia and chemosuppressive ED50 value of 227.2 mg/kg for A. altilis showed that they were the best antimalarial herbal drugs. A 1.6-fold increase of the survival time given by the negative control was elicited by M. koenigii, thereby confirming its curative activity. Pyrimethamine with an ED50 of 0.5 ± 0.1 mg/kg for the prophylactic, and chloroquine with ED50 = 2.2 ± 0.1 and 2.2 ± 0.0 mg/kg for the chemosuppressive and curative tests, respectively, were significantly (p < 0.05) more active. Co-administrations of N. latifolia with the standard drugs significantly reduced their prophylactic, chemosuppressive and curative actions, possibly increasing the parasites’ resistance. Binary combinations of N. latifolia or M. koenigii with any of the other plants significantly increased the prophylactic and suppressive activities of their individual plants, respectively. Also, E. chlorantha with A. altilis or N. latifolia enhanced their respective prophylactic or curative activities, making these combinations most beneficial against malaria infections. Combinations of three and four extracts gave varied activities. Hence, the results justified the combinations of ethnomedicinal plants in antimalarial herbal remedies and showed the importance of the three in vivo models in establishing antimalarial activity. Full article
Open AccessArticle Antioxidant and Nitrite-Scavenging Capacities of Phenolic Compounds from Sugarcane (Saccharum officinarum L.) Tops
Molecules 2014, 19(9), 13147-13160; doi:10.3390/molecules190913147
Received: 4 July 2014 / Revised: 15 August 2014 / Accepted: 15 August 2014 / Published: 26 August 2014
Cited by 2 | PDF Full-text (715 KB) | HTML Full-text | XML Full-text
Abstract
Sugarcane tops were extracted with 50% ethanol and fractionated by petroleum ether, ethyl acetate (EtOAc), and n-butyl alcohol successively. Eight phenolic compounds in EtOAc extracts were purified through silica gel and Sephadex LH-20 column chromatographies, and then identified by nuclear magnetic resonance
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Sugarcane tops were extracted with 50% ethanol and fractionated by petroleum ether, ethyl acetate (EtOAc), and n-butyl alcohol successively. Eight phenolic compounds in EtOAc extracts were purified through silica gel and Sephadex LH-20 column chromatographies, and then identified by nuclear magnetic resonance and electrospray ionization mass spectra. The results showed that eight phenolic compounds from EtOAc extracts were identified as caffeic acid, cis-p-hydroxycinnamic acid, quercetin, apigenin, albanin A, australone A, moracin M, and 5'-geranyl-5,7,2',4'-tetrahydroxyflavone. The antioxidant and nitrite-scavenging capacities of different solvent extracts correlated positively with their total phenolic (TP) contents. Amongst various extracts, EtOAc extracts possessed the highest TP content and presented the strongest oxygen radical absorbance capacity (ORAC), 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging capacity, 2,2'-azobis-3-ethylbenthiaazoline-6-sulfonic acid (ABTS) radical-scavenging capacity, ferric reducing antioxidant power (FRAP) and nitrite-scavenging capacity. Thus, sugarcane tops could be promoted as a source of natural antioxidant. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
Open AccessArticle Design and Synthesis of New Cholesterol-Conjugated 5-Fluorouracil: A Novel Potential Delivery System for Cancer Treatment
Molecules 2014, 19(9), 13177-13187; doi:10.3390/molecules190913177
Received: 12 May 2014 / Revised: 9 July 2014 / Accepted: 15 July 2014 / Published: 26 August 2014
Cited by 3 | PDF Full-text (1981 KB) | HTML Full-text | XML Full-text
Abstract
Cholesterol-conjugated 5-fluorouracil prodrugs were designed to be carried in vivo via low density lipoproteins (LDL) and subsequently undergo LDL-receptor-mediated internalisation into cancer cells. In vivo anti-cancer evaluation was performed using 5-fluorouracil-cholesterol conjugate in a mouse model. The obtained prodrugs were more potent than
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Cholesterol-conjugated 5-fluorouracil prodrugs were designed to be carried in vivo via low density lipoproteins (LDL) and subsequently undergo LDL-receptor-mediated internalisation into cancer cells. In vivo anti-cancer evaluation was performed using 5-fluorouracil-cholesterol conjugate in a mouse model. The obtained prodrugs were more potent than 5-fluorouracil control drug at the same 5-fluorouracil content (3 mg·kg−1). Full article
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Open AccessArticle Synthesis and Cytotoxic Evaluation of a Series of 2-Amino-Naphthoquinones against Human Cancer Cells
Molecules 2014, 19(9), 13188-13199; doi:10.3390/molecules190913188
Received: 9 June 2014 / Revised: 22 August 2014 / Accepted: 22 August 2014 / Published: 26 August 2014
Cited by 6 | PDF Full-text (765 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The cytotoxicity of a series of aminonaphthoquinones resulting from the reaction of suitable aminoacids with 1,4-naphthoquinone was assayed against SF-295 (glioblastoma), MDAMB-435 (breast), HCT-8 (colon), HCT-116 (colon), HL-60 (leukemia), OVCAR-8 (ovarian), NCI-H358M (bronchoalveolar lung carcinoma) and PC3-M (prostate) cancer cells and also against
[...] Read more.
The cytotoxicity of a series of aminonaphthoquinones resulting from the reaction of suitable aminoacids with 1,4-naphthoquinone was assayed against SF-295 (glioblastoma), MDAMB-435 (breast), HCT-8 (colon), HCT-116 (colon), HL-60 (leukemia), OVCAR-8 (ovarian), NCI-H358M (bronchoalveolar lung carcinoma) and PC3-M (prostate) cancer cells and also against PBMC (peripheral blood mononuclear cells). The results demonstrated that all the synthetic aminonaphthoquinones had relevant cytotoxic activity against all human cancer lines used in this experiment. Five of the compounds showed high cytotoxicity and selectivity against all cancer cell lines tested (IC50 = 0.49 to 3.89 µg·mL−1). The title compounds were less toxic to PBMC, since IC50 was 1.5 to eighteen times higher (IC50 = 5.51 to 17.61 µg·mL−1) than values shown by tumour cell lines. The mechanism of cell growth inhibition and structure–activity relationships remains as a target for future investigations. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Cytotoxic Activity of 3,6-Dihydroxyflavone in Human Cervical Cancer Cells and Its Therapeutic Effect on c-Jun N-Terminal Kinase Inhibition
Molecules 2014, 19(9), 13200-13211; doi:10.3390/molecules190913200
Received: 15 July 2014 / Revised: 18 August 2014 / Accepted: 22 August 2014 / Published: 27 August 2014
Cited by 6 | PDF Full-text (1330 KB) | HTML Full-text | XML Full-text
Abstract
Previously we have shown that 3,6-dihydroxyflavone (3,6-DHF) is a potent agonist of the human peroxisome proliferator-activated receptor (hPPAR) with cytotoxic effects on human cervical cancer cells. To date, the mechanisms by which 3,6-DHF exerts its antitumor effects on cervical cells have not been
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Previously we have shown that 3,6-dihydroxyflavone (3,6-DHF) is a potent agonist of the human peroxisome proliferator-activated receptor (hPPAR) with cytotoxic effects on human cervical cancer cells. To date, the mechanisms by which 3,6-DHF exerts its antitumor effects on cervical cells have not been clearly defined. Here, we demonstrated that 3,6-DHF exhibits a novel antitumor activity against HeLa cells with IC50 values of 25 μM and 9.8 μM after 24 h and 48 h, respectively. We also showed that the anticancer effects of 3,6-DHF are mediated via the toll-like receptor (TLR) 4/CD14, p38 mitogen-activated protein kinase (MAPK), Jun-N terminal kinase (JNK), extracellular-signaling regulated kinase (ERK), and cyclooxygenase (COX)-2 pathways in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. We found that 3,6-DHF showed a similar IC50 (113 nM) value to that of the JNK inhibitor, SP600125 (IC50 = 118 nM) in a JNK1 kinase assay. Binding studies revealed that 3,6-DHF had a strong binding affinity to JNK1 (1.996 × 105 M1) and that the 6-OH and the carbonyl oxygen of the C ring of 3,6-DHF participated in hydrogen bonding interactions with the carbonyl oxygen and the amide proton of Met111, respectively. Therefore, 3,6-DHF may be a candidate inhibitor of JNKs, with potent anticancer effects. Full article
(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)
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Open AccessArticle Inhibitory Effects of Colocasia esculenta (L.) Schott Constituents on Aldose Reductase
Molecules 2014, 19(9), 13212-13224; doi:10.3390/molecules190913212
Received: 21 July 2014 / Revised: 19 August 2014 / Accepted: 22 August 2014 / Published: 27 August 2014
Cited by 8 | PDF Full-text (721 KB) | HTML Full-text | XML Full-text
Abstract
The goal of this study was to determine the rat lens aldose reductase-inhibitory effects of 95% ethanol extracts from the leaves of C. esculenta and, its organic solvent soluble fractions, including the dichloromethane (CH2Cl2), ethyl acetate (EtOAc), n-butanol
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The goal of this study was to determine the rat lens aldose reductase-inhibitory effects of 95% ethanol extracts from the leaves of C. esculenta and, its organic solvent soluble fractions, including the dichloromethane (CH2Cl2), ethyl acetate (EtOAc), n-butanol (BuOH) and water (H2O) layers, using dl-glyceraldehyde as a substrate. Ten compounds, namely tryptophan (1), orientin (2), isoorientin (3), vitexin (4), isovitexin (5), luteolin-7-O-glucoside (6), luteolin-7-O-rutinoside (7), rosmarinic acid (8), 1-O-feruloyl-d-glucoside (9) and 1-O-caffeoyl-d-glucoside (10) were isolated from the EtOAc and BuOH fractions of C. esculenta. The structures of compounds 110 were elucidated by spectroscopic methods and comparison with previous reports. All the isolates were subjected to an in vitro bioassay to evaluate their inhibitory activity against rat lens aldose reductase. Among tested compounds, compounds 2 and 3 significantly inhibited rat lens aldose reductase, with IC50 values of 1.65 and 1.92 μM, respectively. Notably, the inhibitory activity of orientin was 3.9 times greater than that of the positive control, quercetin (4.12 μM). However, the isolated compounds showed only moderate ABTS+ [2,29-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)] activity. These results suggest that flavonoid derivatives from Colocasia esculenta (L.) Schott represent potential compounds for the prevention and/or treatment of diabetic complications. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Cytotoxic Compounds Isolated from Murraya tetramera Huang
Molecules 2014, 19(9), 13225-13234; doi:10.3390/molecules190913225
Received: 21 July 2014 / Revised: 21 August 2014 / Accepted: 21 August 2014 / Published: 27 August 2014
Cited by 4 | PDF Full-text (710 KB) | HTML Full-text | XML Full-text
Abstract
A new compound and seven known compounds were isolated from Murraya tetramera Huang for the first time, and they were identified with NMR and MS spectral analysis. It was confirmed that the new compound was 10-methoxy-7-methyl-2H-benzo[g]chromen-2-one (3) and the
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A new compound and seven known compounds were isolated from Murraya tetramera Huang for the first time, and they were identified with NMR and MS spectral analysis. It was confirmed that the new compound was 10-methoxy-7-methyl-2H-benzo[g]chromen-2-one (3) and the others were β-eudesmol (1), trans-3β-(1-hydroxy-1-methylethyl)-8-methyl-5-methylenedecalin-2-one (2), 5,7-dimethoxy-8-[(Z)-3'-methyl-butan-1',3'-dienyl]coumarin (4), 7-geranyloxy-6-methoxycoumarin (5), 5,7-dimethoxy-8-(3-methyl-2-oxo-butyl)coumarin (6), murrangatin acetate (7) and toddalenone (8). Furthermore, the cytotoxic activity against human lung adenocarcinoma (A549), human hepatocellular carcinoma cells (SMMC-7721), human bladder tumor cells (EJ), human cervical carcinoma cells (HeLa), and human B-lineage acute lymphoblastic leukemia 1 cells (BALL-1) was evaluated for all compounds. It was found that five of them displayed various degrees of cytotoxicity against different testing targets. Compound 1 showed significant cytotoxic activity against the five cell lines (A549, SMMC-7721, EJ, Hela and BALL-1). Compounds 2 and 5 showed significant cytotoxicity against three cell lines (A549, SMMC-7721 and BALL-1). Compound 4 showed significant cytotoxicity against three cell lines (A549, EJ and BALL-1). However, compound 3 only showed fair cytotoxicity against the BALL-1 cell line. The structure-active relationships were investigated as well. These active compounds might be potential lead compounds for the treatment of cancer. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Schisandrin B Induces Apoptosis and Cell Cycle Arrest of Gallbladder Cancer Cells
Molecules 2014, 19(9), 13235-13250; doi:10.3390/molecules190913235
Received: 29 July 2014 / Revised: 13 August 2014 / Accepted: 18 August 2014 / Published: 27 August 2014
Cited by 7 | PDF Full-text (4185 KB) | HTML Full-text | XML Full-text | Correction
Abstract
Gallbladder cancer, with high aggressivity and extremely poor prognosis, is the most common malignancy of the bile duct. The main objective of the paper was to investigate the effects of schisandrin B (Sch B) on gallbladder cancer cells and identify the mechanisms underlying
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Gallbladder cancer, with high aggressivity and extremely poor prognosis, is the most common malignancy of the bile duct. The main objective of the paper was to investigate the effects of schisandrin B (Sch B) on gallbladder cancer cells and identify the mechanisms underlying its potential anticancer effects. We showed that Sch B inhibited the viability and proliferation of human gallbladder cancer cells in a dose-, time -dependent manner through MTT and colony formation assays, and decrease mitochondrial membrane potential (ΔΨm) at a dose-dependent manner through flow cytometry. Flow cytometry assays also revealed G0/G1 phase arrest and apoptosis in GBC-SD and NOZ cells. Western blot analysis of Sch B-treated cells revealed the upregulation of Bax, cleaved caspase-9, cleaved caspase-3, cleaved PARP and downregulation of Bcl-2, NF-κB, cyclin D1 and CDK-4. Moreover, this drug also inhibited the tumor growth in nude mice carrying subcutaneous NOZ tumor xenografts. These data demonstrated that Sch B induced apoptosis in gallbladder cancer cells by regulating apoptosis-related protein expression, and suggests that Sch B may be a promising drug for the treatment of gallbladder cancer. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis, Leishmanicidal and Cytotoxic Activity of Triclosan-Chalcone, Triclosan-Chromone and Triclosan-Coumarin Hybrids
Molecules 2014, 19(9), 13251-13266; doi:10.3390/molecules190913251
Received: 19 May 2014 / Revised: 17 July 2014 / Accepted: 7 August 2014 / Published: 28 August 2014
Cited by 4 | PDF Full-text (826 KB) | HTML Full-text | XML Full-text
Abstract
Twelve hybrids derived from triclosan were obtained via Williamson etherification of O-triclosan alkyl bromide plus chalcone and O-coumarin or O-chromone alkyl bromide plus triclosan, respectively. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against
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Twelve hybrids derived from triclosan were obtained via Williamson etherification of O-triclosan alkyl bromide plus chalcone and O-coumarin or O-chromone alkyl bromide plus triclosan, respectively. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. (V) panamensis amastigotes. Cytotoxic activity was also evaluated against mammalian U-937 cells. Compounds 79 and 17, were active against Leishmania parasites (EC50 = 9.4; 10.2; 13.5 and 27.5 µg/mL, respectively) and showed no toxicity toward mammalian cells (>200 µg/mL). They are potential candidates for antileishmanial drug development. Compounds 2527, were active and cytotoxic. Further studies using other cell types are needed in order to discriminate whether the toxicity shown by these compounds is against tumor or non-tumor cells. The results indicate that compounds containing small alkyl chains show better selectivity indices. Moreover, Michael acceptor moieties may modify both the leishmanicidal activity and cytotoxicity. Further studies are required to evaluate if the in vitro activity against Leishmania panamensis demonstrated here is also observed in vivo. Full article
(This article belongs to the Special Issue Prodrugs)
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Open AccessArticle Neuronal Nitric Oxide Synthase Induction in the Antitumorigenic and Neurotoxic Effects of 2-Methoxyestradiol
Molecules 2014, 19(9), 13267-13281; doi:10.3390/molecules190913267
Received: 3 June 2014 / Revised: 8 August 2014 / Accepted: 18 August 2014 / Published: 28 August 2014
Cited by 6 | PDF Full-text (1439 KB) | HTML Full-text | XML Full-text
Abstract
Objective: 2-Methoxyestradiol, one of the natural 17β-estradiol derivatives, is a novel, potent anticancer agent currently being evaluated in advanced phases of clinical trials. The main goal of the study was to investigate the anticancer activity of 2-methoxy-estradiol towards osteosarcoma cells and its
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Objective: 2-Methoxyestradiol, one of the natural 17β-estradiol derivatives, is a novel, potent anticancer agent currently being evaluated in advanced phases of clinical trials. The main goal of the study was to investigate the anticancer activity of 2-methoxy-estradiol towards osteosarcoma cells and its possible neurodegenerative effects. We used an experimental model of neurotoxicity and anticancer activity of the physiological agent, 2-methoxyestradiol. Thus, we used highly metastatic osteosarcoma 143B and mouse immortalized hippocampal HT22 cell lines. The cells were treated with pharmacological (1 μM, 10 μM) concentrations of 2-methoxyestradiol. Experimental: Neuronal nitric oxide synthase and 3-nitrotyrosine protein levels were determined by western blotting. Cell viability and induction of cell death were measured by MTT and PI/Annexin V staining and a DNA fragmentation ELISA kit, respectively. Intracellular levels of nitric oxide were determined by flow cytometry. Results: Here we demonstrated that the signaling pathways of neurodegenerative diseases and cancer may overlap. We presented evidence that 2-methoxyestradiol, in contrast to 17β-estradiol, specifically affects neuronal nitric oxide synthase and augments 3-nitrotyrosine level leading to osteosarcoma and immortalized hippocampal cell death. Conclusions: We report the dual facets of 2-methoxyestradiol, that causes cancer cell death, but on the other hand may play a key role as a neurotoxin. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Elucidation of the Relationships between H-Bonding Patterns and Excited State Dynamics in Cyclovalone
Molecules 2014, 19(9), 13282-13304; doi:10.3390/molecules190913282
Received: 7 July 2014 / Revised: 8 August 2014 / Accepted: 20 August 2014 / Published: 28 August 2014
Cited by 5 | PDF Full-text (2177 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cyclovalone is a synthetic curcumin derivative in which the keto-enolic system is replaced by a cyclohexanone ring. This modification of the chemical structure might in principle result in an excited state that is more stable than that of curcumin, which in turn should
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Cyclovalone is a synthetic curcumin derivative in which the keto-enolic system is replaced by a cyclohexanone ring. This modification of the chemical structure might in principle result in an excited state that is more stable than that of curcumin, which in turn should produce an enhanced phototoxicity. Indeed, although curcumin exhibits photosensitized antibacterial activity, this compound is characterized by very fast excited-state dynamics which limit its efficacy as a photosensitizer. In previous works we showed that the main non-radiative decay pathway of keto-enolic curcuminoids is through excited-state transfer of the enolic proton to the keto-oxygen. Another effective deactivation pathway involves an intermolecular charge transfer mechanism occurring at the phenyl rings, made possible by intramolecular H-bonding between the methoxy and the hydroxyl substituent. In this paper we present UV-Vis and IR absorption spectra data with the aim of elucidating the intramolecular charge distribution of this compound and its solvation patterns in different environments, with particular focus on solute-solvent H-bonding features. Moreover, we discuss steady state and time-resolved fluorescence data that aim at characterizing the excited-state dynamics of cyclovalone, and we compare its decay photophysics to that of curcumin. Finally, because during the characterization procedures we found evidence of very fast photodegradation of cyclovalone, its photostability in four organic solvents was studied by HPLC and the corresponding relative degradation rates were calculated. Full article
(This article belongs to the Special Issue Intramolecular Hydrogen Bonding)
Open AccessArticle Self-Assembled Nanoparticles of Glycyrrhetic Acid-Modified Pullulan as a Novel Carrier of Curcumin
Molecules 2014, 19(9), 13305-13318; doi:10.3390/molecules190913305
Received: 18 June 2014 / Revised: 22 August 2014 / Accepted: 25 August 2014 / Published: 28 August 2014
Cited by 9 | PDF Full-text (2104 KB) | HTML Full-text | XML Full-text
Abstract
Glycyrrhetic acid (GA)-modified pullulan nanoparticles (GAP NPs) were synthesized as a novel carrier of curcumin (CUR) with a degree of substitution (DS) of GA moieties within the range of 1.2–6.2 groups per hundred glucose units. In the present study, we investigated the physicochemical
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Glycyrrhetic acid (GA)-modified pullulan nanoparticles (GAP NPs) were synthesized as a novel carrier of curcumin (CUR) with a degree of substitution (DS) of GA moieties within the range of 1.2–6.2 groups per hundred glucose units. In the present study, we investigated the physicochemical characteristics, release behavior, in vitro cytotoxicity and cellular uptake of the particles. Self-assembled GAP NPs with spherical shapes could readily improve the water solubility and stability of CUR. The CUR release was sustained and pH-dependent. The cellular uptake of CUR-GAP NPs was confirmed by green fluorescence in the cells. An MTT study showed CUR-GAP NPs with higher cytotoxicity in HepG2 cells than free CUR, but GAP NPs had no significant cytotoxicity. GAP is thus an excellent carrier for the solubilization, stabilization, and controlled delivery of CUR. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Cyclic Peptide-Capped Gold Nanoparticles for Enhanced siRNA Delivery
Molecules 2014, 19(9), 13319-13331; doi:10.3390/molecules190913319
Received: 9 June 2014 / Revised: 22 August 2014 / Accepted: 22 August 2014 / Published: 28 August 2014
Cited by 5 | PDF Full-text (1061 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Previously, we have reported the synthesis of a homochiral l-cyclic peptide [WR]5 and its use for delivery of anti-HIV drugs and biomolecules. A physical mixture of HAuCl4 and the peptide generated peptide-capped gold nanoparticles. Here, [WR]5 and [WR]5-AuNPs
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Previously, we have reported the synthesis of a homochiral l-cyclic peptide [WR]5 and its use for delivery of anti-HIV drugs and biomolecules. A physical mixture of HAuCl4 and the peptide generated peptide-capped gold nanoparticles. Here, [WR]5 and [WR]5-AuNPs were tested for their efficiency to deliver a small interfering RNA molecule (siRNA) in human cervix adenocarcinoma (HeLa) cells. Flow cytometry investigation revealed that the intracellular uptake of a fluorescence-labeled non-targeting siRNA (200 nM) was enhanced in the presence of [WR]5 and [WR]5-AuNPs by 2- and 3.8-fold when compared with that of siRNA alone after 24 h incubation. Comparative toxicity results showed that [WR]5 and [WR]5-AuNPs were less toxic in cells compared to other available carrier systems, such as Lipofectamine. Full article
(This article belongs to the Special Issue Delivery Systems of Anticancer Agents)
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Open AccessArticle Protoberberine Isoquinoline Alkaloids from Arcangelisia gusanlung
Molecules 2014, 19(9), 13332-13341; doi:10.3390/molecules190913332
Received: 25 July 2014 / Revised: 20 August 2014 / Accepted: 21 August 2014 / Published: 29 August 2014
Cited by 2 | PDF Full-text (730 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
HPLC-DAD-directed isolation and purification of the methanol extract of stems of Arcangelisia gusanlung H. S. Lo. led to the isolation of a new protoberberine alkaloid, gusanlung E (1), along with fourteen known derivatives 215, seven
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HPLC-DAD-directed isolation and purification of the methanol extract of stems of Arcangelisia gusanlung H. S. Lo. led to the isolation of a new protoberberine alkaloid, gusanlung E (1), along with fourteen known derivatives 215, seven of which were obtained from the genus Arcangelisia for the first time. The structures and absolute stereochemistry of these compounds were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR, mass spectrometry, and CD analyses. Gusanlung E (1) expressed weak cytotoxic activity against the SGC 7901 cell line with an IC50 value of 85.1 µM. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis of the New Ring System Bispyrido[4',3':4,5]pyrrolo [1,2-a:1',2'-d]pyrazine and Its Deaza Analogue
Molecules 2014, 19(9), 13342-13357; doi:10.3390/molecules190913342
Received: 24 July 2014 / Revised: 18 August 2014 / Accepted: 20 August 2014 / Published: 29 August 2014
Cited by 5 | PDF Full-text (2350 KB) | HTML Full-text | XML Full-text
Abstract
Derivatives of the new ring systems bispyrido[4',3':4,5]pyrrolo[1,2-a:1',2'-d] pyrazine-6,13-dione and its deaza analogue pyrido[4'',3'':4',5']pyrrolo-[1',2':4,5]pyrazino [1,2-a]indole-6,13-dione were conveniently synthesized through a four-step sequence. Symmetrical derivatives of the former ring system were obtained through self condensation. On the other hand, condensation of
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Derivatives of the new ring systems bispyrido[4',3':4,5]pyrrolo[1,2-a:1',2'-d] pyrazine-6,13-dione and its deaza analogue pyrido[4'',3'':4',5']pyrrolo-[1',2':4,5]pyrazino [1,2-a]indole-6,13-dione were conveniently synthesized through a four-step sequence. Symmetrical derivatives of the former ring system were obtained through self condensation. On the other hand, condensation of 6-azaindole carboxylic acid with indole 2-carboxylic acid afforded the deaza analogue ring system. Derivatives of the title ring system were tested by the National Cancer Institute (Bethesda, MD, USA) and four of them exhibited modest activity against MCF7 (a breast cancer cell line) and/or UO-31 (a renal cancer cell line). Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Theoretical Investigation on Nearsightedness of Finite Model and Molecular Systems Based on Linear Response Function Analysis
Molecules 2014, 19(9), 13358-13373; doi:10.3390/molecules190913358
Received: 16 June 2014 / Revised: 31 July 2014 / Accepted: 14 August 2014 / Published: 29 August 2014
Cited by 3 | PDF Full-text (3807 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We examined nearsightedness of electronic matter (NEM) of finite systems on the basis of linear response function (LRF). From the computational results of a square-well model system, the behavior of responses obviously depends on the number of electrons (N): as N increases, LRF,
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We examined nearsightedness of electronic matter (NEM) of finite systems on the basis of linear response function (LRF). From the computational results of a square-well model system, the behavior of responses obviously depends on the number of electrons (N): as N increases, LRF, δρ(r)/δv(r′), decays rapidly for the distance, |r−r′|. This exemplifies that the principle suggested by Kohn and Prodan holds even for finite systems: the cause of NEM is destructive interference among electron density amplitudes. In addition, we examined double-well model systems, which have low-lying degenerate levels. In this case, there are two types of LRF: the cases of the half-filled and of full-filled in low-lying degenerate levels. The response for the former is delocalized, while that of the later is localized. These behaviors of model systems are discussed in relation to the molecular systems’ counterparts, H2, He22+, and He2 systems. We also see that NEM holds for the dissociated limit of H2, of which the mechanism is similar to that of the insulating state of solids as suggested by Kohn. We also examined LRF of alanine tripeptide system as well as butane and butadiene molecules, showing that NEM of the polypeptide system is caused by sp3 junctions at Cα atoms that prevent propagation of amplitudes of LRF, which is critically different from that of NEM for finite and infinite homogeneous systems. Full article
(This article belongs to the Special Issue Quantum Information in Molecular Structures and Nanosystems)
Open AccessArticle Effect of Apitherapy Formulations against Carbon Tetrachloride-Induced Toxicity in Wistar Rats after Three Weeks of Treatment
Molecules 2014, 19(9), 13374-13391; doi:10.3390/molecules190913374
Received: 24 March 2014 / Revised: 19 August 2014 / Accepted: 21 August 2014 / Published: 29 August 2014
Cited by 3 | PDF Full-text (3304 KB) | HTML Full-text | XML Full-text
Abstract
The human body is exposed nowadays to increasing attacks by toxic compounds in polluted air, industrially processed foods, alcohol and drug consumption that increase liver toxicity, leading to more and more severe cases of hepatic disorders. The present paper aims to evaluate the
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The human body is exposed nowadays to increasing attacks by toxic compounds in polluted air, industrially processed foods, alcohol and drug consumption that increase liver toxicity, leading to more and more severe cases of hepatic disorders. The present paper aims to evaluate the influence of the apitherapy diet in Wistar rats with carbon tetrachloride-induced hepatotoxicity, by analyzing the biochemical determinations (enzymatic, lipid and protein profiles, coagulation parameters, minerals, blood count parameters, bilirubin levels) and histopathological changes at the level of liver, spleen and pancreas. The experiment was carried out on six groups of male Wistar rats. Hepatic lesions were induced by intraperitoneal injection of carbon tetrachloride (dissolved in paraffin oil, 10% solution). Two mL per 100 g were administered, every 2 days, for 2 weeks. Hepatoprotection was achieved with two apitherapy diet formulations containing honey, pollen, propolis, Apilarnil, with/without royal jelly. Biochemical results reveal that the two apitherapy diet formulations have a positive effect on improving the enzymatic, lipid, and protein profiles, coagulation, mineral and blood count parameters and bilirubin levels. The histopathological results demonstrate the benefits of the two apitherapy diet formulations on reducing toxicity at the level of liver, spleen and pancreas in laboratory animals. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Effects of Endogenous Signals and Fusarium oxysporum on the Mechanism Regulating Genistein Synthesis and Accumulation in Yellow Lupine and Their Impact on Plant Cell Cytoskeleton
Molecules 2014, 19(9), 13392-13421; doi:10.3390/molecules190913392
Received: 26 April 2014 / Revised: 7 August 2014 / Accepted: 18 August 2014 / Published: 29 August 2014
Cited by 5 | PDF Full-text (5565 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The aim of the study was to examine cross-talk interactions of soluble sugars (sucrose, glucose and fructose) and infection caused by Fusarium oxysporum f.sp. lupini on the synthesis of genistein in embryo axes of Lupinus luteus L.cv. Juno. Genistein is a free aglycone,
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The aim of the study was to examine cross-talk interactions of soluble sugars (sucrose, glucose and fructose) and infection caused by Fusarium oxysporum f.sp. lupini on the synthesis of genistein in embryo axes of Lupinus luteus L.cv. Juno. Genistein is a free aglycone, highly reactive and with the potential to inhibit fungal infection and development of plant diseases. As signal molecules, sugars strongly stimulated accumulation of isoflavones, including genistein, and the expression of the isoflavonoid biosynthetic genes. Infection significantly enhanced the synthesis of genistein and other isoflavone aglycones in cells of embryo axes of yellow lupine with high endogenous sugar levels. The activity of β-glucosidase, the enzyme that releases free aglycones from their glucoside bindings, was higher in the infected tissues than in the control ones. At the same time, a very strong generation of the superoxide anion radical was observed in tissues with high sugar contents already in the initial stage of infection. During later stages after inoculation, a strong generation of semiquinone radicals was observed, which level was relatively higher in tissues deficient in sugars than in those with high sugar levels. Observations of actin and tubulin cytoskeletons in cells of infected embryo axes cultured on the medium with sucrose, as well as the medium without sugar, showed significant differences in their organization. Full article
Open AccessCommunication A New Cycloartane-Type Triterpenoid Saponin Xanthine Oxidase Inhibitor from Homonoia riparia Lour
Molecules 2014, 19(9), 13422-13431; doi:10.3390/molecules190913422
Received: 30 June 2014 / Revised: 6 August 2014 / Accepted: 7 August 2014 / Published: 29 August 2014
Cited by 4 | PDF Full-text (733 KB) | HTML Full-text | XML Full-text
Abstract
A new cycloartane-type triterpenoid saponin named riparsaponin (1) was isolated from the stem of Homonoia riparia Lour together with six known compounds. The structure of riparsaponin was determined by using NMR and mass spectroscopy and X-ray crystallography techniques. Additionally, riparsaponin has
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A new cycloartane-type triterpenoid saponin named riparsaponin (1) was isolated from the stem of Homonoia riparia Lour together with six known compounds. The structure of riparsaponin was determined by using NMR and mass spectroscopy and X-ray crystallography techniques. Additionally, riparsaponin has a significant inhibitory effect on xanthine oxidase in vitro, and the IC50 was 11.16 nmol/mL. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Immunomodulatory Activity and Partial Characterisation of Polysaccharides from Momordica charantia
Molecules 2014, 19(9), 13432-13447; doi:10.3390/molecules190913432
Received: 23 July 2014 / Revised: 27 August 2014 / Accepted: 27 August 2014 / Published: 29 August 2014
Cited by 5 | PDF Full-text (730 KB) | HTML Full-text | XML Full-text
Abstract
Momordica charantia Linn. is used as an edible and medicinal vegetable in sub-tropical areas. Until now, studies on its composition and related activities have been confined to compounds of low molecular mass, and no data have been reported concerning the plant’s polysaccharides. In
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Momordica charantia Linn. is used as an edible and medicinal vegetable in sub-tropical areas. Until now, studies on its composition and related activities have been confined to compounds of low molecular mass, and no data have been reported concerning the plant’s polysaccharides. In this work, a crude polysaccharide of M. charantia (MCP) fruit was isolated by hot water extraction and then purified using DEAE-52 cellulose anion-exchange chromatography to produce two main fractions MCP1 and MCP2. The immunomodulatory effects and physicochemical characteristics of these fractions were investigated in vitro and in vivo. The results showed that intragastric administration of 150 or 300 mg·kg·d−1 of MCP significantly increased the carbolic particle clearance index, serum haemolysin production, spleen index, thymus index and NK cell cytotoxicity to normal control levels in cyclophosphamide (Cy)-induced immunosuppressed mice. Both MCP1 and MCP2 effectively stimulated normal and concanavalin A-induced splenic lymphocyte proliferation in vitro at various doses. The average molecular weights of MCP1 and MCP2, which were measured using high-performance gel permeation chromatography, were 8.55 × 104 Da and 4.41 × 105 Da, respectively. Both fractions exhibited characteristic polysaccharide bands in their Fourier transform infrared spectrum. MCP1 is mainly composed of glucose and galactose, and MCP2 is mainly composed of glucose, mannose and galactose. The results indicate that MCP and its fractions have good potential as immunotherapeutic adjuvants. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Copper/N,N-Dimethylglycine Catalyzed Goldberg Reactions Between Aryl Bromides and Amides, Aryl Iodides and Secondary Acyclic Amides
Molecules 2014, 19(9), 13448-13460; doi:10.3390/molecules190913448
Received: 26 June 2014 / Revised: 14 July 2014 / Accepted: 4 August 2014 / Published: 29 August 2014
Cited by 4 | PDF Full-text (735 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An efficient and general copper-catalyzed Goldberg reaction at 90–110 °C between aryl bromides and amides providing the desired products in good to excellent yields has been developed using N,N-dimethylglycine as the ligand. The reaction is tolerant toward a wide range of amides
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An efficient and general copper-catalyzed Goldberg reaction at 90–110 °C between aryl bromides and amides providing the desired products in good to excellent yields has been developed using N,N-dimethylglycine as the ligand. The reaction is tolerant toward a wide range of amides and a variety of functional group substituted aryl bromides. In addition, hindered, unreactive aromatic and aliphatic secondary acyclic amides, known to be poor nucleophiles, are efficiently coupled with aryl iodides through this simple and cheap copper/N,N-dimethylglycine catalytic system. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Bagging Treatment Influences Production of C6 Aldehydes and Biosynthesis-Related Gene Expression in Peach Fruit Skin
Molecules 2014, 19(9), 13461-13472; doi:10.3390/molecules190913461
Received: 27 June 2014 / Revised: 20 August 2014 / Accepted: 25 August 2014 / Published: 29 August 2014
Cited by 2 | PDF Full-text (733 KB) | HTML Full-text | XML Full-text
Abstract
Bagging is a useful method to improve fruit quality by altering its exposure to light, whereas its effect on fruit volatiles production is inconsistent, and the genes responsible for the observed changes remain unknown. In the present study, single-layer yellow paper bags were
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Bagging is a useful method to improve fruit quality by altering its exposure to light, whereas its effect on fruit volatiles production is inconsistent, and the genes responsible for the observed changes remain unknown. In the present study, single-layer yellow paper bags were used to study the effects of bagging treatment on the formation of C6 aldehydes in peach fruit (Prunus persica L. Batsch, cv. Yulu) over two succeeding seasons. Higher concentrations of n-hexanal and (E)-2-hexenal, which are characteristic aroma volatiles of peach fruit, were induced by bagging treatment. After bagging treatment, peach fruit had significantly higher LOX and HPL enzyme activities, accompanying increased contents of C6 aldehydes. The gene expression data obtained through real-time PCR showed that no consistent significant differences in transcript levels of LOX genes were observed over the two seasons, but significantly up-regulated expression was found for PpHPL1 after bagging treatment In addition, bagging-treated fruit produced more (E)-2-hexenal and had higher expression levels of PpHPL1 during postharvest ripening at room temperature. The regulatory role of the LOX-HPL pathway on the biosynthesis of n-hexanal and (E)-2-hexenal in response to bagging treatment during peach fruit development is discussed in the text. Full article
(This article belongs to the Special Issue Aromas and Volatiles of Fruits)
Open AccessArticle Hypotensive Effects and Angiotensin-Converting Enzyme Inhibitory Peptides of Reishi (Ganoderma lingzhi) Auto-Digested Extract
Molecules 2014, 19(9), 13473-13485; doi:10.3390/molecules190913473
Received: 19 June 2014 / Revised: 14 July 2014 / Accepted: 25 August 2014 / Published: 29 August 2014
Cited by 2 | PDF Full-text (767 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Reishi (Ganoderma lingzhi) has been used as a traditional medicine for millennia. However, relatively little is known about this mushroom’s proteins and their bioactivities. In this study, we used reishi’s own proteases to hydrolyze its protein and obtained auto-digested reishi (ADR)
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Reishi (Ganoderma lingzhi) has been used as a traditional medicine for millennia. However, relatively little is known about this mushroom’s proteins and their bioactivities. In this study, we used reishi’s own proteases to hydrolyze its protein and obtained auto-digested reishi (ADR) extract. The extract was subjected to in vitro assays and administered to spontaneous hypertensive rats (SHRs) to determine its potential for use as a hypotensive medication. Bioassay-guided fractionation and de novo sequencing were used for identifying the active compounds. After 4 h administration of ADR, the systolic pressure of SHRs significantly decreased to 34.3 mmHg (19.5% change) and the effect was maintained up to 8 h of administration, with the decrease reaching as low as 26.8 mmHg (15% reduction–compare to base line a decrease of 26.8 mmHg is less than a decrease of 34.3 mmHg so it should give a smaller % reduction). Eleven peptides were identified and four of them showed potent inhibition against ACE with IC50 values ranging from 73.1 μM to 162.7 μM. The results showed that ADR could be a good source of hypotensive peptides that could be used for antihypertensive medication or incorporation into functional foods. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Presolvated Electron Reactions with Methyl Acetoacetate: Electron Localization, Proton-Deuteron Exchange, and H-Atom Abstraction
Molecules 2014, 19(9), 13486-13497; doi:10.3390/molecules190913486
Received: 24 July 2014 / Revised: 22 August 2014 / Accepted: 25 August 2014 / Published: 1 September 2014
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Abstract
Radiation-produced electrons initiate various reaction processes that are important to radiation damage to biomolecules. In this work, the site of attachment of the prehydrated electrons with methyl acetoacetate (MAA, CH3-CO-CH2-COOCH3) at 77 K and subsequent reactions of
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Radiation-produced electrons initiate various reaction processes that are important to radiation damage to biomolecules. In this work, the site of attachment of the prehydrated electrons with methyl acetoacetate (MAA, CH3-CO-CH2-COOCH3) at 77 K and subsequent reactions of the anion radical (CH3-CO•-CH2-COOCH3) in the 77 to ca. 170 K temperature range have been investigated in homogeneous H2O and D2O aqueous glasses by electron spin resonance (ESR) spectroscopy. At 77 K, the prehydrated electron attaches to MAA forming the anion radical in which the electron is delocalized over the two carbonyl groups. This species readily protonates to produce the protonated electron adduct radical CH3-C(•)OH-CH2-COOCH3. The ESR spectrum of CH3-C(•)OH-CH2-COOCH3 in H2O shows line components due to proton hyperfine couplings of the methyl and methylene groups. Whereas, the ESR spectrum of CH3-C(•)OH-CH2-COOCH3 in D2O glass shows only the line components due to proton hyperfine couplings of CH3 group. This is expected since the methylene protons in MAA are readily exchangeable in D2O. On stepwise annealing to higher temperatures (ca. 150 to 170 K), CH3-C(•)OH-CH2-COOCH3 undergoes bimolecular H-atom abstraction from MAA to form the more stable radical, CH3-CO-CH•-COOCH3. Theoretical calculations using density functional theory (DFT) support the radical assignments. Full article
(This article belongs to the Special Issue Free Radicals and Radical Ions)
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Open AccessArticle Anti-Angiogenesis Effect of Biogenic Silver Nanoparticles Synthesized Using Saliva officinalis on Chick Chorioalantoic Membrane (CAM)
Molecules 2014, 19(9), 13498-13508; doi:10.3390/molecules190913498
Received: 1 June 2014 / Revised: 18 July 2014 / Accepted: 26 July 2014 / Published: 1 September 2014
Cited by 11 | PDF Full-text (2372 KB) | HTML Full-text | XML Full-text
Abstract
Angiogenesis, which is required for physiological events, plays a crucial role in several pathological conditions, such as tumor growth and metastasis. The use of plant extracts is a cost effective and eco-friendly way to synthesize nanoparticles. In the present study, we investigated the
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Angiogenesis, which is required for physiological events, plays a crucial role in several pathological conditions, such as tumor growth and metastasis. The use of plant extracts is a cost effective and eco-friendly way to synthesize nanoparticles. In the present study, we investigated the anti-angiogenesis properties of silver nanoparticles synthesized using Saliva officinalis extract on chick chorioalantoic membrane. The production of nanoparticles was confirmed by the color change from yellow to brown observed after approximately 3 h at 37 °C. Then, the nanoparticles were characterized by UV-visible spectroscopy, FTIR, and TEM. The UV-visible spectroscopy results showed that the surface plasmon resonance band for AgNPs was around 430 nm. The intensity of the AgNP-specific absorption peak improved with an increase of 0.5 mL of extract into 10 mL of AgNO3 (2.5 mM). The FTIR results showed good interaction between the plant extracts and AgNPs. The TEM images of the samples revealed that the NPs varied in morphology and size from 1 to 40 nm; the average was recorded at 16.5 ± 1.2 nm. Forty Ross fertilized eggs were divided into four groups; the control and three experimental groups. On the 8th day, gelatin sponges containing albumin were placed on the chorioalantoic membrane and soaked with different concentrations of NPs. On the 12th day, all the cases were photographed using a photostereomicroscope. The number and the lengths of the vessels were measured using Image J software. The crown rump (CR) and weight of the embryo were also recorded. Then the hemoglobin content was measured using Drabkin’s reagent kit for quantification of the blood vessel formation. According to the data analysis, the number and length of the blood vessels, as well as the CR and weight of the embryos reduced significantly compared to the control (p < 0.05), dose dependently. The total hemoglobin was quantified as an indicator of the blood vessel formation. The hemoglobin content in the treated samples with AgNPs decreased, which showed its inhibitory effect on angiogenesis. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Novel Schiff Bases Based on the Quinolinone Skeleton: Syntheses, X-ray Structures and Fluorescent Properties
Molecules 2014, 19(9), 13509-13525; doi:10.3390/molecules190913509
Received: 1 July 2014 / Revised: 12 August 2014 / Accepted: 25 August 2014 / Published: 1 September 2014
PDF Full-text (1579 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of a new type of Schiff bases 17, derived from 2-phenyl-3-amino-4(1H)-quinolinone and R-salicyladehyde derivatives wherein R = 3-hydroxy (1), 3,4-dihydroxy (2), 3-methoxy (3), 3-carboxy (4), 3-allyl (5
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A series of a new type of Schiff bases 17, derived from 2-phenyl-3-amino-4(1H)-quinolinone and R-salicyladehyde derivatives wherein R = 3-hydroxy (1), 3,4-dihydroxy (2), 3-methoxy (3), 3-carboxy (4), 3-allyl (5), 5-chloro (6), and 5-nitro (7), was synthesized and structurally characterized. Each of the molecules 1, 3 and 7 consists of three planar moieties (i.e., a quinolinone and two phenyl rings), which are mutually oriented differently depending on the appropriate substituent R and the extent of non-covalent contacts stabilizing the crystal structures. The compounds were studied for their fluorescence properties, where compound 6 yielded the strongest intensity both in the solid phase and in 100 μM ethanol solution with a quantum yield of φ = 3.6% as compared to quinine sulfate used as a standard. The in vitro cytotoxicity of these compounds was tested against the human osteosarcoma (HOS) and breast adenocarcinoma (MCF7) cell lines, revealing no activity up to the concentration of 50 µM. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Synthesis of [13C4]-labeled ∆9-Tetrahydrocannabinol and 11-nor-9-Carboxy-∆9-tetrahydrocannabinol as Internal Standards for Reducing Ion Suppressing/Alteration Effects in LC/MS-MS Quantification
Molecules 2014, 19(9), 13526-13540; doi:10.3390/molecules190913526
Received: 30 July 2014 / Revised: 22 August 2014 / Accepted: 26 August 2014 / Published: 1 September 2014
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Abstract
(−)-∆9-Tetrahydrocannabinol is the principal psychoactive component of the cannabis plant and also the active ingredient in some prescribed drugs. To detect and control misuse and monitor administration in clinical settings, reference samples of the native drugs and their metabolites are needed. The accuracy
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(−)-∆9-Tetrahydrocannabinol is the principal psychoactive component of the cannabis plant and also the active ingredient in some prescribed drugs. To detect and control misuse and monitor administration in clinical settings, reference samples of the native drugs and their metabolites are needed. The accuracy of liquid chromatography/mass spectrometric quantification of drugs in biological samples depends among others on ion suppressing/alteration effects. Especially, 13C-labeled drug analogues are useful for minimzing such interferences. Thus, to provide internal standards for more accurate quantification and for identification purpose, synthesis of [13C4]-∆9-tetrahydro-cannabinol and [13C4]-11-nor-9-carboxy-∆9-tetrahydrocannabinol was developed via [13C4]-olivetol. Starting from [13C4]-olivetol the synthesis of [13C4]-11-nor-9-carboxy-∆9-tetrahydrocannabinol was shortened from three to two steps by employing nitromethane as a co-solvent in condensation with (+)-apoverbenone. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Effects of Heat Acclimation on Photosynthesis, Antioxidant Enzyme Activities, and Gene Expression in Orchardgrass under Heat Stress
Molecules 2014, 19(9), 13564-13576; doi:10.3390/molecules190913564
Received: 12 July 2014 / Revised: 22 August 2014 / Accepted: 22 August 2014 / Published: 1 September 2014
Cited by 4 | PDF Full-text (3063 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The present study was designed to examine the effects of heat acclimation on enzymatic activity, transcription levels, the photosynthesis processes associated with thermostability in orchardgrass (Dactylis glomerata L.).The stomatal conductance (Gs), net photosynthetic rate (Pn), and transpiration rates (Tr) of both heat-acclimated
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The present study was designed to examine the effects of heat acclimation on enzymatic activity, transcription levels, the photosynthesis processes associated with thermostability in orchardgrass (Dactylis glomerata L.).The stomatal conductance (Gs), net photosynthetic rate (Pn), and transpiration rates (Tr) of both heat-acclimated (HA) and non-acclimated (NA) plants were drastically reduced during heat treatment [using a 5-day heat stress treatment (38/30 °C ‒ day/night) followed by a 3-day recovery under control conditions (25/20 °C ‒ day/night), in order to consolidate the second cycle was permitted]. Water use efficiency increased more steeply in the HA (4.9 times) versus the NA (1.8 times) plants, and the intercellular CO2 concentration decreased gently in NA (10.9%) and HA (25.3%) plants after 20 d of treatments compared to 0 days’. Furthermore, heat-acclimated plants were able to maintain significant activity levels of superoxide disumutase (SOD), catalase (CAT), guaiacol peroxidase (POD), and transcription levels of genes encoding these enzymes; in addition, HA plants displayed lower malondialdehyde content and lower electrolyte leakage than NA plants. These results suggest that maintenance of activity and transcription levels of antioxidant enzymes as well as photosynthesis are associated with variable thermostability in HA and NA plants. This likely occurs through cellular membrane stabilization and improvements in water use efficiency in the photosynthetic process during heat stress. The association between antioxidant enzyme activity and gene expression, both of which may vary with genetic variation in heat tolerance, is important to further understand the molecular mechanisms that contribute to heat tolerance. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Synthesis and Antibacterial Activity of Analogs of 5-Arylidene-3-(4-methylcoumarin-7-yloxyacetylamino)-2-thioxo-1,3-thiazoli-din-4-one
Molecules 2014, 19(9), 13577-13586; doi:10.3390/molecules190913577
Received: 30 June 2014 / Revised: 26 August 2014 / Accepted: 27 August 2014 / Published: 1 September 2014
Cited by 2 | PDF Full-text (708 KB) | HTML Full-text | XML Full-text
Abstract
In an effort to develop new antimicrobial agents, 3-(4-methylcoumarin-7-yloxyacetylamino)-2-thioxo-1,3-thiazolidin-4-one (4) was synthesized by reaction of thiocarbonylbisthioglycolic acid with ethyl (4-methyl-2-oxo-2H-chromen-7-yloxy)aceto- hydrazide (3), which was prepared in turn from 7-hydroxy-4-methylcoumarin (1). The condensation of compound 4
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In an effort to develop new antimicrobial agents, 3-(4-methylcoumarin-7-yloxyacetylamino)-2-thioxo-1,3-thiazolidin-4-one (4) was synthesized by reaction of thiocarbonylbisthioglycolic acid with ethyl (4-methyl-2-oxo-2H-chromen-7-yloxy)aceto- hydrazide (3), which was prepared in turn from 7-hydroxy-4-methylcoumarin (1). The condensation of compound 4 with different aromatic aldehydes afforded a series of 5-(arylidene)-3-(4-methylcoumarin-7-yloxyacetyl-amino)-2-thioxo-1,3-thiozolidin-4-one analogs 5ah. The structures of these synthetic compounds were elucidated on the basis of IR, 1H-NMR and 13C-NMR spectral data and ESI-MS spectrometric analysis. Compounds 5ah were examined for their antibacterial activity against several strains of Gram-positive and Gram-negative bacteria. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Peptides Derived from Rhopilema esculentum Hydrolysate Exhibit Angiotensin Converting Enzyme (ACE) Inhibitory and Antioxidant Abilities
Molecules 2014, 19(9), 13587-13602; doi:10.3390/molecules190913587
Received: 8 July 2014 / Revised: 22 August 2014 / Accepted: 26 August 2014 / Published: 2 September 2014
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Abstract
Jellyfish (Rhopilema esculentum) was hydrolyzed using alcalase, and two peptides with angiotensin-I-converting enzyme (ACE) inhibitory and antioxidant activities were purified by ultrafiltration and consecutive chromatographic methods. The amino acid sequences of the two peptides were identified as VKP (342 Da) and
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Jellyfish (Rhopilema esculentum) was hydrolyzed using alcalase, and two peptides with angiotensin-I-converting enzyme (ACE) inhibitory and antioxidant activities were purified by ultrafiltration and consecutive chromatographic methods. The amino acid sequences of the two peptides were identified as VKP (342 Da) and VKCFR (651 Da) by electrospray ionization tandem mass spectrometry. The IC50 values of ACE inhibitory activities of the two peptides were 1.3 μM and 34.5 μM, respectively. Molecular docking results suggested that VKP and VKCFR bind to ACE through coordinating with the active site Zn(II) atom. Free radical scavenging activity and protection against hydrogen peroxide (H2O2)-induced rat cerebral microvascular endothelial cell (RCMEC) injury were used to evaluate the antioxidant activities of the two peptides. As the results clearly showed that the peptides increased the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-px) activities in RCMEC cells), it is proposed that the R. esculentum peptides exert significant antioxidant effects. Full article
(This article belongs to the Special Issue Peptide Chemistry)
Open AccessArticle Synthesis and Reactivity of New Aminophenolate Complexes of Nickel
Molecules 2014, 19(9), 13603-13613; doi:10.3390/molecules190913603
Received: 8 July 2014 / Revised: 27 August 2014 / Accepted: 28 August 2014 / Published: 2 September 2014
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Abstract
New well-defined, paramagnetic nickel complexes have been prepared and characterized by X-ray crystallography. The complexes were found to be active for the cross-coupling of alkyl electrophiles (especially ethyl 2-bromobutyrate) with alkyl Grignard reagents. The ligand architecture in these new complexes could potentially be
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New well-defined, paramagnetic nickel complexes have been prepared and characterized by X-ray crystallography. The complexes were found to be active for the cross-coupling of alkyl electrophiles (especially ethyl 2-bromobutyrate) with alkyl Grignard reagents. The ligand architecture in these new complexes could potentially be rendered chiral, opening up future possibilities for performing asymmetric cross-coupling reactions. Full article
(This article belongs to the Special Issue Practical Applications of Metal Complexes)
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Open AccessArticle A One-Pot Approach to Pyridyl Isothiocyanates from Amines
Molecules 2014, 19(9), 13631-13642; doi:10.3390/molecules190913631
Received: 9 August 2014 / Revised: 27 August 2014 / Accepted: 28 August 2014 / Published: 2 September 2014
Cited by 2 | PDF Full-text (742 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A one-pot preparation of pyridyl isothiocyanates (ITCs) from their corresponding amines has been developed. This method involves aqueous iron(III) chloride-mediated desulfurization of a dithiocarbamate salt that is generated in situ by treatment of an amine with carbon disulfide in the present of DABCO
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A one-pot preparation of pyridyl isothiocyanates (ITCs) from their corresponding amines has been developed. This method involves aqueous iron(III) chloride-mediated desulfurization of a dithiocarbamate salt that is generated in situ by treatment of an amine with carbon disulfide in the present of DABCO or sodium hydride. The choice of base is of decisive importance for the formation of the dithiocarbamate salts. This one-pot process works well for a wide range of pyridyl ITCs. Utilizing this protocol, some highly electron-deficient pyridyl and aryl ITCs are obtained in moderate to good yields. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Effects of Climatic Conditions and Soil Properties on Cabernet Sauvignon Berry Growth and Anthocyanin Profiles
Molecules 2014, 19(9), 13683-13703; doi:10.3390/molecules190913683
Received: 26 June 2014 / Revised: 28 August 2014 / Accepted: 29 August 2014 / Published: 2 September 2014
Cited by 8 | PDF Full-text (2048 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Climatic conditions and soil type have significant influence on grape ripening and wine quality. The reported study was conducted in two “Cabernet Sauvignon (Vitis vinifera L.V)” vineyards located in Xinjiang, a semiarid wine-producing region of China during two vintages (2011 and 2012).
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Climatic conditions and soil type have significant influence on grape ripening and wine quality. The reported study was conducted in two “Cabernet Sauvignon (Vitis vinifera L.V)” vineyards located in Xinjiang, a semiarid wine-producing region of China during two vintages (2011 and 2012). The results indicate that soil and climate affected berry growth and anthocyanin profiles. These two localities were within a distance of 5 km from each other and had soils of different physical and chemical composition. For each vineyard, the differences of anthocyanin concentrations, and parameters concerning berry growth and composition between the two years could be explained by different climatic conditions. Soil effect was studied by investigation of differences in berry composition and anthocyanin profiles between the two vineyards in the same year, which could be explained mainly by the different soil properties, vine water and nitrogen status. Specifically, the soils with less water and organic matter produced looser clusters, heavier berry skins and higher TSS, which contributed to the excellent performance of grapes. Compared with 2011, the increases in anthocyanin concentrations for each vineyard in 2012 could be attributed to smaller number of extreme temperature (>35 °C) days and rainfall, lower vine water status and N level. The explanation for higher anthocyanin concentrations in grape skins from the soils with less water and organic matter could be the vine status differences, lighter berry weight and heavier skin weight at harvest. In particular, grapes from the soils with less water and organic matter had higher levels of 3′5′-substituded, O-methylated and acylated anthocyanins, which represented a positive characteristic conferring more stable pigmentation to the corresponding wine in the future. The present work clarifies the effects of climate and soil on berry growth and anthocyanin profiles, thus providing guidance for production of high-quality wine grapes in different regions. Full article
(This article belongs to the Special Issue Anthocyanins) Print Edition available
Open AccessArticle Synthesis and Anti-Yeast Evaluation of Novel 2-Alkylthio-4-chloro-5-methyl-N-[imino-(1-oxo-(1H)-phthalazin-2-yl)methyl]benzenesulfonamide Derivatives
Molecules 2014, 19(9), 13704-13723; doi:10.3390/molecules190913704
Received: 11 July 2014 / Revised: 13 August 2014 / Accepted: 25 August 2014 / Published: 2 September 2014
Cited by 2 | PDF Full-text (487 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Pathogenic fungi are one of the main causes of hospital-related infections. Since conventional antifungals have become less effective because of the increasing fungal resistance to the standard drugs, the need for new agents is becoming urgent. Herein we report a synthesis of a
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Pathogenic fungi are one of the main causes of hospital-related infections. Since conventional antifungals have become less effective because of the increasing fungal resistance to the standard drugs, the need for new agents is becoming urgent. Herein we report a synthesis of a series of novel N-[imino-(1-oxo-(1H)-phthalazin-2-yl)methyl]-benzenesulfonamide derivatives with in vitro activity against yeast-like fungi isolated from the oral cavity and respiratory tract of patients with candidiasis. These compounds were synthesized by the one-step or two-step reactions of 1-(2-alkylthiobenzensulfonyl)-2-aminoguanidines with the appropriate ortho-carbonyl benzoic acids. The biological study revealed that new derivatives have shown significant growth-inhibitory activity, superior or comparable, than those of the reference drug fluconazole. The most promising activities were observed against Candida albicans, with inhibition at least 1–3 (12.5%–37.5%) of the eight tested strains at the low MIC level of ≤6.2–25 µg/mL. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Anti-Stress Action of an Orally-Given Combination of Resveratrol, β-Glucan, and Vitamin C
Molecules 2014, 19(9), 13724-13734; doi:10.3390/molecules190913724
Received: 17 July 2014 / Revised: 30 August 2014 / Accepted: 1 September 2014 / Published: 3 September 2014
PDF Full-text (858 KB) | HTML Full-text | XML Full-text
Abstract
Stress has repeatedly been found to reduce the abilities of the immune system to fight against individual attacks. The current dissatisfaction with classical medications has led to more attention being focused on natural molecules. As recent studies have suggested that some bioactive molecules
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Stress has repeatedly been found to reduce the abilities of the immune system to fight against individual attacks. The current dissatisfaction with classical medications has led to more attention being focused on natural molecules. As recent studies have suggested that some bioactive molecules can have synergistic effects in stimulation of immune system and reduction of stress, we have evaluated the stress-reducing effects of the resveratrol-β-glucan-vitamin C combination. We found that compared to its individual components, this combination was the strongest reducer of stress-related symptoms, including corticosterone levels and IL-6, IL-12 and IFN-γ production. Full article
(This article belongs to the Special Issue Resveratrol)
Open AccessArticle Different Fluorophore Labeling Strategies and Designs Affect Millisecond Kinetics of DNA Hairpins
Molecules 2014, 19(9), 13735-13754; doi:10.3390/molecules190913735
Received: 18 July 2014 / Revised: 21 August 2014 / Accepted: 26 August 2014 / Published: 3 September 2014
Cited by 4 | PDF Full-text (1621 KB) | HTML Full-text | XML Full-text
Abstract
Changes in molecular conformations are one of the major driving forces of complex biological processes. Many studies based on single-molecule techniques have shed light on conformational dynamics and contributed to a better understanding of living matter. In particular, single-molecule FRET experiments have revealed
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Changes in molecular conformations are one of the major driving forces of complex biological processes. Many studies based on single-molecule techniques have shed light on conformational dynamics and contributed to a better understanding of living matter. In particular, single-molecule FRET experiments have revealed unprecedented information at various time scales varying from milliseconds to seconds. The choice and the attachment of fluorophores is a pivotal requirement for single-molecule FRET experiments. One particularly well-studied millisecond conformational change is the opening and closing of DNA hairpin structures. In this study, we addressed the influence of base- and terminal-labeled fluorophores as well as the fluorophore DNA interactions on the extracted kinetic information of the DNA hairpin. Gibbs free energies varied from ∆G0 = −3.6 kJ/mol to ∆G0 = −0.2 kJ/mol for the identical DNA hairpin modifying only the labeling scheme and design of the DNA sample. In general, the base-labeled DNA hairpin is significantly destabilized compared to the terminal-labeled DNA hairpin and fluorophore DNA interactions additionally stabilize the closed state of the DNA hairpin. Careful controls and variations of fluorophore attachment chemistry are essential for a mostly undisturbed measurement of the underlying energy landscape of biomolecules. Full article
(This article belongs to the Special Issue Single Molecule Techniques)
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Open AccessArticle Structure and Absolute Configuration of 20β-Hydroxyprednisolone, a Biotransformed Product of Predinisolone by the Marine Endophytic Fungus Penicilium lapidosum
Molecules 2014, 19(9), 13775-13787; doi:10.3390/molecules190913775
Received: 4 April 2014 / Revised: 22 July 2014 / Accepted: 11 August 2014 / Published: 3 September 2014
Cited by 5 | PDF Full-text (801 KB) | HTML Full-text | XML Full-text
Abstract
The anti-inflammatory drug predinisolone (1) was reduced to 20β-hydroxyprednisolone (2) by the marine endophytic fungus Penicilium lapidosum isolated from an alga. The structural elucidation of 2 was achieved by 1D- and 2D-NMR, MS, IR data. Although, 2 is a
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The anti-inflammatory drug predinisolone (1) was reduced to 20β-hydroxyprednisolone (2) by the marine endophytic fungus Penicilium lapidosum isolated from an alga. The structural elucidation of 2 was achieved by 1D- and 2D-NMR, MS, IR data. Although, 2 is a known compound previously obtained through microbial transformation, the data provided failed to prove the C20 stereochemistry. To solve this issue, DFT and TD-DFT calculations have been carried out at the B3LYP/6–31+G (d,p) level of theory in gas and solvent phase. The absolute configuration of C20 was eventually assigned by combining experimental and calculated electronic circular dichroism spectra and 3JHH chemical coupling constants. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Design, Synthesis and the Biological Evaluation of New 1,3-Thiazolidine-4-ones Based on the 4-Amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one Scaffold
Molecules 2014, 19(9), 13824-13847; doi:10.3390/molecules190913824
Received: 5 August 2014 / Revised: 28 August 2014 / Accepted: 29 August 2014 / Published: 4 September 2014
Cited by 5 | PDF Full-text (1012 KB) | HTML Full-text | XML Full-text
Abstract
New thiazolidine-4-one derivatives based on the 4-aminophenazone (4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one) scaffold have been synthesized as potential anti-inflammatory drugs. The pyrazoline derivatives are known especially for their antipyretic, analgesic and anti-inflammatory effects, but recently there were synthesized new compounds with important antioxidant, antiproliferative, anticancer and antidiabetic
[...] Read more.
New thiazolidine-4-one derivatives based on the 4-aminophenazone (4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one) scaffold have been synthesized as potential anti-inflammatory drugs. The pyrazoline derivatives are known especially for their antipyretic, analgesic and anti-inflammatory effects, but recently there were synthesized new compounds with important antioxidant, antiproliferative, anticancer and antidiabetic activities. The beneficial effects of these compounds are explained by nonselective inhibition of cyclooxygenase izoenzymes, but also by their potential scavenging ability for reactive oxygen and nitrogen species. The structure of the new compounds was proved using spectroscopic methods (FR-IR, 1H-NMR, 13C-NMR, MS). The in vitro antioxidant potential of the synthesized compounds was evaluated according to the ferric reducing antioxidant power, phosphomolydenum reducing antioxidant power, DPPH and ABTS radical scavenging assays. The chemical modulation of 4-aminophenazone (6) through linkage to thiazolidine-propanoic acid derivatives 5al led to improved antioxidant potential, all derivatives 7al being more active than phenazone. The most active compounds are the derivatives 7e, and 7k, which showed the higher antioxidant effect depending on the antioxidant assay considered. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synthesis and Structure of Sulfur Derivatives from 2-Aminobenzimidazole
Molecules 2014, 19(9), 13878-13893; doi:10.3390/molecules190913878
Received: 11 June 2014 / Revised: 14 August 2014 / Accepted: 14 August 2014 / Published: 4 September 2014
Cited by 1 | PDF Full-text (1273 KB) | HTML Full-text | XML Full-text
Abstract
The reactions of the benzimidazole nitrogen atoms and the exocyclic amino group of 2-aminobenzimidazole with CS2 in NaOH basic medium followed by methylation with methyl iodide was explored. With careful control of the stoichiometric quantities and addition sequences, this set of reactions
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The reactions of the benzimidazole nitrogen atoms and the exocyclic amino group of 2-aminobenzimidazole with CS2 in NaOH basic medium followed by methylation with methyl iodide was explored. With careful control of the stoichiometric quantities and addition sequences, this set of reactions allows the selective functionalization of the benzimidazole ring with N-dithiocarbamate, S-methyldithiocarbamate or dimethyl- dithiocarboimidate groups. The products were characterized by 1H-, 13C-NMR spectroscopy and three of them by X-ray diffraction analysis. The preferred isomers, tautomers and conformers were established. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Second Order Kinetic Modeling of Headspace Solid Phase Microextraction of Flavors Released from Selected Food Model Systems
Molecules 2014, 19(9), 13894-13908; doi:10.3390/molecules190913894
Received: 16 April 2014 / Revised: 29 July 2014 / Accepted: 11 August 2014 / Published: 4 September 2014
Cited by 1 | PDF Full-text (1214 KB) | HTML Full-text | XML Full-text
Abstract
The application of headspace-solid phase microextraction (HS-SPME) has been widely used in various fields as a simple and versatile method, yet challenging in quantification. In order to improve the reproducibility in quantification, a mathematical model with its root in psychological modeling and chemical
[...] Read more.
The application of headspace-solid phase microextraction (HS-SPME) has been widely used in various fields as a simple and versatile method, yet challenging in quantification. In order to improve the reproducibility in quantification, a mathematical model with its root in psychological modeling and chemical reactor modeling was developed, describing the kinetic behavior of aroma active compounds extracted by SPME from two different food model systems, i.e., a semi-solid food and a liquid food. The model accounted for both adsorption and release of the analytes from SPME fiber, which occurred simultaneously but were counter-directed. The model had four parameters and their estimated values were found to be more reproducible than the direct measurement of the compounds themselves by instrumental analysis. With the relative standard deviations (RSD) of each parameter less than 5% and root mean square error (RMSE) less than 0.15, the model was proved to be a robust one in estimating the release of a wide range of low molecular weight acetates at three environmental temperatures i.e., 30, 40 and 60 °C. More insights of SPME behavior regarding the small molecule analytes were also obtained through the kinetic parameters and the model itself. Full article
(This article belongs to the Special Issue Microextraction)
Open AccessArticle Hydrogel Polysaccharides of Tamarind and Xanthan to Formulate Hydrodynamically Balanced Matrix Tablets of Famotidine
Molecules 2014, 19(9), 13909-13931; doi:10.3390/molecules190913909
Received: 13 July 2014 / Revised: 25 August 2014 / Accepted: 28 August 2014 / Published: 5 September 2014
Cited by 3 | PDF Full-text (5288 KB) | HTML Full-text | XML Full-text
Abstract
The gastroretentive dosage form of famotidine was modified using tamarind seed powders to prolong the gastric retention time. Tamarind seeds were used in two different forms having different swelling and gelling properties: with husk (TSP) or without husk (TKP). TKP (TKP1 to TKP
[...] Read more.
The gastroretentive dosage form of famotidine was modified using tamarind seed powders to prolong the gastric retention time. Tamarind seeds were used in two different forms having different swelling and gelling properties: with husk (TSP) or without husk (TKP). TKP (TKP1 to TKP 6) and TSP (TSP1 to TSP 6) series were prepared using tamarind powder:xanthan in the ratios of 5:0, 4:1, 3:2, 2:3, 1:4, 0:5, respectively. The matrix tablets were prepared by the wet granulation method and evaluated for pharmacopoeial requirements. TKP2 was the optimum formulation as it had a short floating lag time (FLT < 30 s) and more than 98.5% drug release in 12 h. The dissolution data were fitted to popular mathematical models to assess the mechanism of drug release, and the optimum formulation showed a predominant first order release and diffusion mechanism. It was concluded that the TKP2 prepared using tamarind kernel powder:xanthan (4:1) was the optimum formulation with shortest floating lag time and more than 90% release in the determined period of time. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Development of a Calcium Phosphate Nanocomposite for Fast Fluorogenic Detection of Bacteria
Molecules 2014, 19(9), 13948-13964; doi:10.3390/molecules190913948
Received: 30 April 2014 / Revised: 30 June 2014 / Accepted: 2 July 2014 / Published: 5 September 2014
Cited by 1 | PDF Full-text (1026 KB) | HTML Full-text | XML Full-text
Abstract
Current procedures for the detection and identification of bacterial infections are laborious, time-consuming, and require a high workload and well-equipped laboratories. Therefore the work presented herein developed a simple, fast, and low cost method for bacterial detection based on hydroxyapatite nanoparticles with a
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Current procedures for the detection and identification of bacterial infections are laborious, time-consuming, and require a high workload and well-equipped laboratories. Therefore the work presented herein developed a simple, fast, and low cost method for bacterial detection based on hydroxyapatite nanoparticles with a nutritive mixture and the fluorogenic substrate. Calcium phosphate ceramic nanoparticles were characterized and integrated with a nutritive mixture for the early detection of bacteria by visual as well as fluorescence spectroscopy techniques. The composite was obtained by combining calcium phosphate nanoparticles (Ca:P ratio, 1.33:1) with a nutritive mixture of protein hydrolysates and carbon sources, which promote fast bacterial multiplication, and the fluorogenic substrate 4-methylumbellipheryl-β-d-glucuronide (MUG). The composite had an average particle size of 173.2 nm and did not show antibacterial activity against Gram-negative or Gram-positive bacteria. After an Escherichia coli suspension was in contact with the composite for 60–90 min, fluorescence detected under UV light or by fluorescence spectrophotometer indicated the presence of bacteria. Intense fluorescence was observed after incubation for a maximum of 90 min. Thus, this calcium phosphate nanocomposite system may be useful as a model for the development of other nanoparticle composites for detection of early bacterial adhesion. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Total Aglycones from Marsdenia tenacissima Increases Antitumor Efficacy of Paclitaxel in Nude Mice
Molecules 2014, 19(9), 13965-13975; doi:10.3390/molecules190913965
Received: 6 August 2014 / Revised: 23 August 2014 / Accepted: 1 September 2014 / Published: 5 September 2014
Cited by 4 | PDF Full-text (1195 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Marsdeniae tenacissimae Caulis (MTC) is a Chinese herbal medicine used mainly for treatment of cancer, whose pharmacologically active constituents responsible for its in vivo activity and clinical efficacy have not been clearly elucidated. In this study, total aglycones of MTC (ETA) showed the
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Marsdeniae tenacissimae Caulis (MTC) is a Chinese herbal medicine used mainly for treatment of cancer, whose pharmacologically active constituents responsible for its in vivo activity and clinical efficacy have not been clearly elucidated. In this study, total aglycones of MTC (ETA) showed the ability to sensitize KB-3-1, HeLa, HepG2 and K562 cells to paclitaxel treatment. More inspiringly, ETA markedly enhanced the antitumor activity of paclitaxel in nude mice bearing HeLa or KB-3-1 xenografts. Compared to treatment with paclitaxel alone, treatment with combination of paclitaxel and ETA achieved significant reduction in volume and weight of HeLa tumors (p < 0.05), and remarkable inhibition to the growth of KB-3-1 tumors (p < 10−6). ETA was characterized by the presence of a group of tenacigenin B ester derivatives, among which four reference compounds, 11α-O-tigloyl-12β-O-acetyltenacigenin B, 11α,12β-di-O-tigloyltenacigenin B, 11α-O-2-methylbutanoyl-12β-O-tigloyltenacigenin B, and 11α-O-(2-methylbutanoyl)-12β-O-benzoyltenacigenin B, accounted for 42.14% of the total peak area of 19 detectable components assayed by HPLC. Our study has identified ETA as a promising sensitizer for cancer chemotherapy. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle A Galactose-Binding Lectin Isolated from Aplysia kurodai (Sea Hare) Eggs Inhibits Streptolysin-Induced Hemolysis
Molecules 2014, 19(9), 13990-14003; doi:10.3390/molecules190913990
Received: 13 July 2014 / Revised: 21 August 2014 / Accepted: 2 September 2014 / Published: 5 September 2014
Cited by 4 | PDF Full-text (1082 KB) | HTML Full-text | XML Full-text | Correction
Abstract
A specific galactose-binding lectin was shown to inhibit the hemolytic effect of streptolysin O (SLO), an exotoxin produced by Streptococcus pyogenes. Commercially available lectins that recognize N-acetyllactosamine (ECA), T-antigen (PNA), and Tn-antigen (ABA) agglutinated rabbit erythrocytes, but had no effect on
[...] Read more.
A specific galactose-binding lectin was shown to inhibit the hemolytic effect of streptolysin O (SLO), an exotoxin produced by Streptococcus pyogenes. Commercially available lectins that recognize N-acetyllactosamine (ECA), T-antigen (PNA), and Tn-antigen (ABA) agglutinated rabbit erythrocytes, but had no effect on SLO-induced hemolysis. In contrast, SLO-induced hemolysis was inhibited by AKL, a lectin purified from sea hare (Aplysia kurodai) eggs that recognizes α-galactoside oligosaccharides. This inhibitory effect was blocked by the co-presence of d-galactose, which binds to AKL. A possible explanation for these findings is that cholesterol-enriched microdomains containing glycosphingolipids in the erythrocyte membrane become occupied by tightly stacked lectin molecules, blocking the interaction between cholesterol and SLO that would otherwise result in penetration of the membrane. Growth of S. pyogenes was inhibited by lectins from a marine invertebrate (AKL) and a mushroom (ABA), but was promoted by a plant lectin (ECA). Both these inhibitory and promoting effects were blocked by co-presence of galactose in the culture medium. Our findings demonstrate the importance of glycans and lectins in regulating mechanisms of toxicity, creation of pores in the target cell membrane, and bacterial growth. Full article
(This article belongs to the Special Issue Lectins)
Open AccessArticle Study of Leaf Metabolome Modifications Induced by UV-C Radiations in Representative Vitis, Cissus and Cannabis Species by LC-MS Based Metabolomics and Antioxidant Assays
Molecules 2014, 19(9), 14004-14021; doi:10.3390/molecules190914004
Received: 10 June 2014 / Revised: 14 August 2014 / Accepted: 27 August 2014 / Published: 5 September 2014
Cited by 9 | PDF Full-text (1304 KB) | HTML Full-text | XML Full-text
Abstract
UV-C radiation is known to induce metabolic modifications in plants, particularly to secondary metabolite biosynthesis. To assess these modifications from a global and untargeted perspective, the effects of the UV-C radiation of the leaves of three different model plant species, Cissus antarctica Vent
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UV-C radiation is known to induce metabolic modifications in plants, particularly to secondary metabolite biosynthesis. To assess these modifications from a global and untargeted perspective, the effects of the UV-C radiation of the leaves of three different model plant species, Cissus antarctica Vent. (Vitaceae), Vitis vinifera L. (Vitaceae) and Cannabis sativa L. (Cannabaceae), were evaluated by an LC-HRMS-based metabolomic approach. The approach enabled the detection of significant metabolite modifications in the three species studied. For all species, clear modifications of phenylpropanoid metabolism were detected that led to an increased level of stilbene derivatives. Interestingly, resveratrol and piceid levels were strongly induced by the UV-C treatment of C. antarctica leaves. In contrast, both flavonoids and stilbene polymers were upregulated in UV-C-treated Vitis leaves. In Cannabis, important changes in cinnamic acid amides and stilbene-related compounds were also detected. Overall, our results highlighted phytoalexin induction upon UV-C radiation. To evaluate whether UV-C stress radiation could enhance the biosynthesis of bioactive compounds, the antioxidant activity of extracts from control and UV-C-treated leaves was measured. The results showed increased antioxidant activity in UV-C-treated V. vinifera extracts. Full article
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Open AccessArticle Synthesis with Perfect Atom Economy: Generation of Furan Derivatives by 1,3-Dipolar Cycloaddition of Acetylenedicarboxylates at Cyclooctynes
Molecules 2014, 19(9), 14022-14035; doi:10.3390/molecules190914022
Received: 1 August 2014 / Revised: 28 August 2014 / Accepted: 1 September 2014 / Published: 5 September 2014
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Abstract
Cyclooctyne and cycloocten-5-yne undergo, at room temperature, a 1,3-dipolar cycloaddition with dialkyl acetylenedicarboxylates 1a,b to generate furan-derived short-lived intermediates 2, which can be trapped by two additional equivalents of 1a,b or alternatively by methanol, phenol, water or aldehydes
[...] Read more.
Cyclooctyne and cycloocten-5-yne undergo, at room temperature, a 1,3-dipolar cycloaddition with dialkyl acetylenedicarboxylates 1a,b to generate furan-derived short-lived intermediates 2, which can be trapped by two additional equivalents of 1a,b or alternatively by methanol, phenol, water or aldehydes to yield polycyclic products 3bd, orthoesters 4ac, ketones 5 or epoxides 6a,b, respectively. Treatment of bis(trimethylsilyl) acetylenedicarboxylate (1c) with cyclooctyne leads to the ketone 7 via retro-Brook rearrangement of the dipolar intermediate 2c. In all cases, the products are formed with perfect atom economy. Full article
(This article belongs to the Special Issue Cycloaddition Chemistry)
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Open AccessArticle Design, Synthesis and Fungicidal Activities of Some Novel Pyrazole Derivatives
Molecules 2014, 19(9), 14036-14051; doi:10.3390/molecules190914036
Received: 7 August 2014 / Revised: 1 September 2014 / Accepted: 2 September 2014 / Published: 8 September 2014
Cited by 4 | PDF Full-text (736 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In order to discover new compounds with good fungicidal activities, 32 pyrazole derivatives were designed and synthesized. The structures of the target compounds were confirmed by 1H-NMR, 13C-NMR, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and their fungicidal activities against Botrytis
[...] Read more.
In order to discover new compounds with good fungicidal activities, 32 pyrazole derivatives were designed and synthesized. The structures of the target compounds were confirmed by 1H-NMR, 13C-NMR, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and their fungicidal activities against Botrytis cinerea, Rhizoctonia solani Kuhn, Valsa mali Miyabe et Yamada, Thanatephorus cucumeris (Frank) Donk, Fusarium oxysporum (S-chl) f.sp. cucumerinum Owen, and Fusarium graminearum Schw were tested. The bioassay results indicated that most of the derivatives exhibited considerable antifungal activities, especially compound 26 containing a p-trifluoromethyl- phenyl moiety showed the highest activity, with EC50 values of 2.432, 2.182, 1.787, 1.638, 6.986, and 6.043 μg/mL against B. cinerea, R. solani, V. mali, T. cucumeris, F. oxysporum, and F. graminearum, respectively. Moreover, the activities of compounds such as compounds 2732 were enhanced by introducing isothiocyanate and carboxamide moieties to the 5-position of the pyrazole ring. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle The in Vitro Biological Activity of the Brazilian Brown Seaweed Dictyota mertensii against Leishmania amazonensis
Molecules 2014, 19(9), 14052-14065; doi:10.3390/molecules190914052
Received: 11 July 2014 / Revised: 30 August 2014 / Accepted: 30 August 2014 / Published: 9 September 2014
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Abstract
Seaweeds present a wide variety of interesting bioactive molecules. In the present work we evaluated the biological activity of the dichloromethane/methanol (2:1) extract (DME) from the brown seaweed Dictyota mertensii against Leishmania amazonensis and its cytotoxic potential on mammalian cells. The extract showed
[...] Read more.
Seaweeds present a wide variety of interesting bioactive molecules. In the present work we evaluated the biological activity of the dichloromethane/methanol (2:1) extract (DME) from the brown seaweed Dictyota mertensii against Leishmania amazonensis and its cytotoxic potential on mammalian cells. The extract showed significant inhibitory effect on the growth of promastigote forms (IC50 = 71.60 μg/mL) and low toxicity against mammalian cells (CC50 = 233.10 μg/mL). The DME was also efficient in inhibiting the infection in macrophages, with CC50 of 81.4 μg/mL and significantly decreased the survival of amastigote forms within these cells. The selectivity index showed that DME was more toxic to both promastigote (SI = 3.25) and amastigote (SI = 2.86) forms than to macrophages. Increased NO production was observed in treated macrophages suggesting that besides acting directly on the parasites, the DME also shows an immunomodulatory effect on macrophages. Drastic ultrastructural alterations consistent with loss of viability and cell death were observed in treated parasites. Confocal microscopy and cytometry analyzes showed no significant impairment of plasma membrane integrity, whereas an intense depolarization of mitochondrial membrane could be observed by using propidium iodide and rhodamine 123 staining, respectively. The low toxicity to mammalian cells and the effective activity against promastigotes and amastigotes, point to the use of DME as a promising agent for the treatment of cutaneous leishmaniasis. Full article
Open AccessArticle Headspace Solid-Phase Microextraction Analysis of Volatile Components in Phalaenopsis Nobby’s Pacific Sunset
Molecules 2014, 19(9), 14080-14093; doi:10.3390/molecules190914080
Received: 30 May 2014 / Revised: 13 August 2014 / Accepted: 30 August 2014 / Published: 9 September 2014
Cited by 4 | PDF Full-text (699 KB) | HTML Full-text | XML Full-text
Abstract
Phalaenopsis is the most important economic crop in the Orchidaceae family. There are currently numerous beautiful and colorful Phalaenopsis flowers, but only a few species of Phalaenopsis have an aroma. This study reports the analysis volatile components present in P. Nobby’s Pacific Sunset
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Phalaenopsis is the most important economic crop in the Orchidaceae family. There are currently numerous beautiful and colorful Phalaenopsis flowers, but only a few species of Phalaenopsis have an aroma. This study reports the analysis volatile components present in P. Nobby’s Pacific Sunset by solid-phase microextraction (SPME) coupled with gas chromatography (GC) and gas chromatography/mass spectrometry (GC-MS). The results show that the optimal extraction conditions were obtained by using a DVB/CAR/PDMS fiber. A total of 31 compounds were identified, with the major compounds being geraniol, linalool and α-farnesene. P. Nobby’s Pacific Sunset had the highest odor concentration from 09:00 to 13:00 on the eighth day of storage. It was also found that in P. Nobby’s Pacific Sunset orchids the dorsal sepals and petals had the highest odor concentrations, whereas the column had the lowest. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle RP-HPLC Characterization of Lupenone and β-Sitosterol in Rhizoma Musae and Evaluation of the Anti-Diabetic Activity of Lupenone in Diabetic Sprague-Dawley Rats
Molecules 2014, 19(9), 14114-14127; doi:10.3390/molecules190914114
Received: 23 June 2014 / Revised: 17 August 2014 / Accepted: 1 September 2014 / Published: 9 September 2014
Cited by 4 | PDF Full-text (1025 KB) | HTML Full-text | XML Full-text
Abstract
With the aim of characterizing the active ingredients lupenone and β-sitosterol in Rhizoma Musae samples a reversed-phase HPLC method for the separation of these two compounds in Rhizoma Musae samples was developed (regression coefficient > 0.9996). The method was further applied to quantify
[...] Read more.
With the aim of characterizing the active ingredients lupenone and β-sitosterol in Rhizoma Musae samples a reversed-phase HPLC method for the separation of these two compounds in Rhizoma Musae samples was developed (regression coefficient > 0.9996). The method was further applied to quantify lupenone and β-sitosterol content in Rhizoma Musae samples cultured in different growth environments. Different variables such as geographical location, growth stage, and harvest time, demonstrated differential effects on lupenone and β-sitosterol levels. Moreover, we determined the optimum conditions for cultivation and harvesting of Rhizoma Musae herbs. Lupenone administration caused a significant reduction in fasting blood glucose (FBG) levels in diabetic rats at doses of 1.78, 5.33, and 16.00 mg·kg−1·day−1 for 14 days, the glycated hemoglobin (HbA1c) levels of diabetic rats also significantly reduced at doses of 5.33, and 16.00 mg·kg−1·day−1, indicating a robust antidiabetic activity. To our knowledge, this is the first report of an optimized HPLC method successfully applied to quantify lupenone and β-sitosterol, and its applicability in optimizing Rhizoma Musae growth. Animal experiments also showed for the first time that lupenone from Rhizoma Musae has anti-diabetic activity. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Simultaneous Quantification of Three Polymorphic Forms of Carbamazepine in the Presence of Excipients Using Raman Spectroscopy
Molecules 2014, 19(9), 14128-14138; doi:10.3390/molecules190914128
Received: 9 July 2014 / Revised: 29 August 2014 / Accepted: 1 September 2014 / Published: 9 September 2014
Cited by 3 | PDF Full-text (725 KB) | HTML Full-text | XML Full-text
Abstract
The occurrence of polymorphic transitions is a serious problem for pharmaceutical companies, because it can affect the bioavailability of the final product. With several known polymorphic forms carbamazepine is one of the most problematic drugs in this respect. Raman spectroscopy is a vibrational
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The occurrence of polymorphic transitions is a serious problem for pharmaceutical companies, because it can affect the bioavailability of the final product. With several known polymorphic forms carbamazepine is one of the most problematic drugs in this respect. Raman spectroscopy is a vibrational technique that is becoming very important in the pharmaceutical field, mainly due to its highly specific molecular fingerprint capabilities and easy use as a process analytical tool. However, multivariate methods are necessary both for identification and quantification. In this work an analytical methodology using Raman spectroscopy and interval Partial Least Squares Regression (iPLS), was developed in order to quantify mixtures of carbamazepine polymorphs in the presence of the most common excipients. The three polymorphs CBZ I, CBZ III and CBZ DH (which is a dihydrate) were synthesized and characterized by PXRD and DSC. Subsequently, tablets were manufactured using excipients and 15 different mixtures of carbamazepine polymorphs. The iPLS model presented average prediction validation errors of 1.58%, 1.04% and 0.22% wt/wt, for CBZ I, CBZ III and CBZ DH, respectively, considering the whole mass of the tablet. The model presents a good prediction capacity and the proposed methodology could be used to perform quality control in final products. Full article
(This article belongs to the Special Issue Advances of Vibrational Spectroscopic Technologies in Life Sciences)
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Open AccessArticle Cytotoxic Illudalane Sesquiterpenes from the Wood-Decay Fungus Granulobasidium vellereum (Ellis & Cragin) Jülich
Molecules 2014, 19(9), 14195-14203; doi:10.3390/molecules190914195
Received: 6 August 2014 / Revised: 28 August 2014 / Accepted: 4 September 2014 / Published: 9 September 2014
Cited by 4 | PDF Full-text (908 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Seven illudalane sesquiterpenes were obtained from the wood decomposing fungus Granulobasidium vellereum: granuloinden A, granuloinden B and dihydrogranuloinden, along with the previously known compounds radulactone, pterosin M, echinolactone A and D. Granuloinden B showed potent cytotoxic activity against the Huh7 and MT4
[...] Read more.
Seven illudalane sesquiterpenes were obtained from the wood decomposing fungus Granulobasidium vellereum: granuloinden A, granuloinden B and dihydrogranuloinden, along with the previously known compounds radulactone, pterosin M, echinolactone A and D. Granuloinden B showed potent cytotoxic activity against the Huh7 and MT4 tumor cell lines (CC50 values of 6.7 and 0.15 µM, respectively), whereas granuloinden A and dihydrogranuloinden had no or moderate activity. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle 1,2-Substituted 4-(1H)-Quinolones: Synthesis, Antimalarial and Antitrypanosomal Activities in Vitro
Molecules 2014, 19(9), 14204-14220; doi:10.3390/molecules190914204
Received: 7 July 2014 / Revised: 28 August 2014 / Accepted: 1 September 2014 / Published: 10 September 2014
Cited by 4 | PDF Full-text (802 KB) | HTML Full-text | XML Full-text
Abstract
A diverse array of 4-(1H)-quinolone derivatives bearing substituents at positions 1 and 2 were synthesized and evaluated for antiprotozoal activities against Plasmodium falciparum and Trypanosoma brucei rhodesiense, and cytotoxicity against L-6 cells in vitro. Furthermore, selectivity indices were also
[...] Read more.
A diverse array of 4-(1H)-quinolone derivatives bearing substituents at positions 1 and 2 were synthesized and evaluated for antiprotozoal activities against Plasmodium falciparum and Trypanosoma brucei rhodesiense, and cytotoxicity against L-6 cells in vitro. Furthermore, selectivity indices were also determined for both parasites. All compounds tested showed antimalarial activity at low micromolar concentrations, with varied degrees of selectivity against L-6 cells. Compound 5a was found to be the most active against P. falciparum, with an IC50 value of 90 nM and good selectivity for the malarial parasite compared to the L-6 cells. Compound 10a, on the other hand, showed a strong antitrypanosomal effect with an IC50 value of 1.25 µM. In this study side chain diversity was explored by varying the side chain length and substitution pattern on the aliphatic group at position-2 and a structure-antiprotozoal activity study revealed that the aromatic ring introduced at C-2 contributed significantly to the antiprotozoal activities. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Enhanced Production of Botrallin and TMC-264 with in Situ Macroporous Resin Adsorption in Mycelial Liquid Culture of the Endophytic Fungus Hyalodendriella sp. Ponipodef12
Molecules 2014, 19(9), 14221-14234; doi:10.3390/molecules190914221
Received: 22 July 2014 / Accepted: 3 September 2014 / Published: 10 September 2014
Cited by 4 | PDF Full-text (702 KB) | HTML Full-text | XML Full-text
Abstract
Hyalodendriella sp. Ponipodef12, an endophytic fungus from the hybrid “Neva” of Populus deltoides × P. nigra, is a high producer of the bioactive dibenzo-α-pyrones botrallin and TMC-264. However, both the botrallin and TMC-264 produced by Hyalodendriella sp. Ponipodef12 were retained as both
[...] Read more.
Hyalodendriella sp. Ponipodef12, an endophytic fungus from the hybrid “Neva” of Populus deltoides × P. nigra, is a high producer of the bioactive dibenzo-α-pyrones botrallin and TMC-264. However, both the botrallin and TMC-264 produced by Hyalodendriella sp. Ponipodef12 were retained as both intracellular and extracellular products. The aim of this study was to evaluate an in situ macroporous resin adsorption for enhancement of botrallin and TMC-264 production in mycelial liquid culture of Hyalodendriella sp. Ponipodef12. Production of botrallin and TMC-264 was most effectively enhanced by macroporous resin DM-301 among the thirteen nonionic macroporous resins tested. The highest botrallin yield (51.47 mg/L, which was 2.29-fold higher than the control at 22.49 mg/L) was obtained by adding resin DM-301 at 4.38% (g/mL) to the culture broth on day 24 and allowing a period of 4 days for adsorption. The highest TMC-264 yield reached 47.74 mg/L, which was 11.76-fold higher than that of the control (4.06 mg/L), and was achieved by adding DM-301 resin at 4.38% (w/v) in the culture broth on day 24 and allowing a period of 6 days for adsorption. The results show that in situ resin adsorption is an effective strategy for enhancing production of botrallin and TMC-264, and also for facilitating their recovery from mycelial liquid culture of Hyalodendriella sp. Ponipodef12. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Constituents of the Roots and Leaves of Ekebergia capensis and Their Potential Antiplasmodial and Cytotoxic Activities
Molecules 2014, 19(9), 14235-14246; doi:10.3390/molecules190914235
Received: 18 July 2014 / Revised: 24 August 2014 / Accepted: 2 September 2014 / Published: 10 September 2014
Cited by 6 | PDF Full-text (1487 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new triterpenoid, 3-oxo-12β-hydroxy-oleanan-28,13β-olide (1), and six known triterpenoids 27 were isolated from the root bark of Ekebergia capensis, an African medicinal plant. A limonoid 8 and two glycoflavonoids 910 were found in its leaves. The
[...] Read more.
A new triterpenoid, 3-oxo-12β-hydroxy-oleanan-28,13β-olide (1), and six known triterpenoids 27 were isolated from the root bark of Ekebergia capensis, an African medicinal plant. A limonoid 8 and two glycoflavonoids 910 were found in its leaves. The metabolites were identified by NMR and MS analyses, and their cytotoxicity was evaluated against the mammalian African monkey kidney (vero), mouse breast cancer (4T1), human larynx carcinoma (HEp2) and human breast cancer (MDA-MB-231) cell lines. Out of the isolates, oleanonic acid (2) showed the highest cytotoxicity, i.e., IC50’s of 1.4 and 13.3 µM against the HEp2 and 4T1 cells, respectively. Motivated by the higher cytotoxicity of the crude bark extract as compared to the isolates, the interactions of oleanonic acid (2) with five triterpenoids 37 were evaluated on vero cells. In an antiplasmodial assay, seven of the metabolites were observed to possess moderate activity against the D6 and W2 strains of P. falciparum (IC50 27.1–97.1 µM), however with a low selectivity index (IC50(vero)/IC50(P. falciparum-D6) < 10). The observed moderate antiplasmodial activity may be due to general cytotoxicity of the isolated triterpenoids. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Novel Hole Transporting Materials Based on 4-(9H-Carbazol-9-yl)triphenylamine Derivatives for OLEDs
Molecules 2014, 19(9), 14247-14256; doi:10.3390/molecules190914247
Received: 3 July 2014 / Revised: 2 September 2014 / Accepted: 4 September 2014 / Published: 10 September 2014
Cited by 1 | PDF Full-text (1182 KB) | HTML Full-text | XML Full-text
Abstract
During the past few years, organic light emitting diodes (OLEDs) have been increasingly studied due to their emerging applicability. However, some of the properties of existing OLEDs could be improved, such as their overall efficiency and durability; these aspects have been addressed in
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During the past few years, organic light emitting diodes (OLEDs) have been increasingly studied due to their emerging applicability. However, some of the properties of existing OLEDs could be improved, such as their overall efficiency and durability; these aspects have been addressed in the current study. A series of novel hole-transporting materials (HTMs) 3ac based on 4-(9H-carbazol-9-yl)triphenylamine conjugated with different carbazole or triphenylamine derivatives have been readily synthesized by Suzuki coupling reactions. The resulting compounds showed good thermal stabilities with high glass transition temperatures between 148 and 165 °C. The introduction of HTMs 3b and 3c into the standard devices ITO/HATCN/NPB/HTMs 3 (indium tin oxide/dipyrazino(2,3-f:2ꞌ,3ꞌ-h)quinoxaline 2,3,6,7,10,11-hexacarbonitrile/N,Nꞌ-bis(naphthalen-1-yl)-N,Nꞌ-bis(phenyl)-benzidine/HTMs)/CBP (4,4ꞌ-Bis(N-carbazolyl)-1,1ꞌ-biphenyl): 5% Ir(ppy)3/Bphen/LiF/Al (tris[2-phenylpyridinato-C2,N]iridium(III)/4,7-diphenyl-1,10-phenanthroline/LiF/Al) resulted in significantly enhanced current, power, and external quantum efficiencies (EQE) as compared to the reference device without any layers of HTMs 3. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Preparation of Astaxanthin Nanodispersions Using Gelatin-Based Stabilizer Systems
Molecules 2014, 19(9), 14257-14265; doi:10.3390/molecules190914257
Received: 6 July 2014 / Revised: 19 August 2014 / Accepted: 3 September 2014 / Published: 10 September 2014
Cited by 2 | PDF Full-text (857 KB) | HTML Full-text | XML Full-text
Abstract
The incorporation of lipophilic nutrients, such as astaxanthin (a fat soluble carotenoid) in nanodispersion systems can either increase the water solubility, stability and bioavailability or widen their applications in aqueous food and pharmaceutical formulations. In this research, gelatin and its combinations with sucrose
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The incorporation of lipophilic nutrients, such as astaxanthin (a fat soluble carotenoid) in nanodispersion systems can either increase the water solubility, stability and bioavailability or widen their applications in aqueous food and pharmaceutical formulations. In this research, gelatin and its combinations with sucrose oleate as a small molecular emulsifier, sodium caseinate (SC) as a protein and gum Arabic as a polysaccharide were used as stabilizer systems in the formation of astaxanthin nanodispersions via an emulsification-evaporation process. The results indicated that the addition of SC to gelatin in the stabilizer system could increase the chemical stability of astaxanthin nanodispersions significantly, while using a mixture of gelatin and sucrose oleate as a stabilizer led to production of nanodispersions with the smallest particle size (121.4 ± 8.6 nm). It was also shown that a combination of gelatin and gum Arabic could produce optimal astaxanthin nanodispersions in terms of physical stability (minimum polydispersity index (PDI) and maximum zeta-potential). This study demonstrated that the mixture of surface active compounds showed higher emulsifying and stabilizing functionality compared to using them individually in the preparation of astaxanthin nanodispersions. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Two New Guaiane Sesquiterpenoids from Daphne holosericea (Diels) Hamaya
Molecules 2014, 19(9), 14266-14272; doi:10.3390/molecules190914266
Received: 12 August 2014 / Revised: 2 September 2014 / Accepted: 3 September 2014 / Published: 11 September 2014
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Abstract
Two new sesquiterpenoids with guaiane skeletons—holosericin A (1) and holosericin B (2)—were isolated from the medicinal plant Daphne holosericea (Diels) Hamawa (Thymelaeceae). Their structures were elucidated by 1D and 2D-NMR spectroscopy, as well as HR-ESI-MS data. Compounds 1 and
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Two new sesquiterpenoids with guaiane skeletons—holosericin A (1) and holosericin B (2)—were isolated from the medicinal plant Daphne holosericea (Diels) Hamawa (Thymelaeceae). Their structures were elucidated by 1D and 2D-NMR spectroscopy, as well as HR-ESI-MS data. Compounds 1 and 2 were evaluated for inhibitory activities against acetylcholinesterase and compound 2 showed a moderate activity with 31% inhibition. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Access to Optically Pure β-Hydroxy Esters via Non-Enzymatic Kinetic Resolution by a Planar-Chiral DMAP Catalyst
Molecules 2014, 19(9), 14273-14291; doi:10.3390/molecules190914273
Received: 15 July 2014 / Revised: 26 August 2014 / Accepted: 27 August 2014 / Published: 11 September 2014
Cited by 2 | PDF Full-text (952 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The development of new approaches to obtain optically pure β-hydroxy esters is an important area in synthetic organic chemistry since they are precursors of other high value compounds. Herein, the kinetic resolution of racemic β-hydroxy esters using a planar-chiral DMAP derivative catalyst is
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The development of new approaches to obtain optically pure β-hydroxy esters is an important area in synthetic organic chemistry since they are precursors of other high value compounds. Herein, the kinetic resolution of racemic β-hydroxy esters using a planar-chiral DMAP derivative catalyst is presented. Following this procedure, a range of aromatic β-hydroxy esters was obtained in excellent selectivities (up to s = 107) and high enantiomeric excess (up to 99% ee). Furthermore, the utility of the present method was demonstrated in the synthesis of (S)-3-hydroxy-N-methyl-3-phenylpropanamide, a key intermediate for bioactive molecules such as fluoxetine, tomoxetine or nisoxetine, in its enantiomerically pure form. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle On the Nature of the Transition State Characterizing Gated Molecular Encapsulations
Molecules 2014, 19(9), 14292-14303; doi:10.3390/molecules190914292
Received: 17 July 2014 / Revised: 21 August 2014 / Accepted: 28 August 2014 / Published: 11 September 2014
Cited by 1 | PDF Full-text (1369 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Gated molecular encapsulations, with baskets of type 1, are postulated to occur by the mechanism in which solvent molecule penetrates the inner space of 1, through one of its apertures, while the residing guest simultaneously departs the cavity. In the transition
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Gated molecular encapsulations, with baskets of type 1, are postulated to occur by the mechanism in which solvent molecule penetrates the inner space of 1, through one of its apertures, while the residing guest simultaneously departs the cavity. In the transition state of the exchange, three pyridine-based gates are proposed to assume an open position with both incoming solvent and departing guest molecules interacting with the concave surface of the host. The More O’Ferrall-Jencks diagram and linear free energy relationships (LFERs) suggest a more advanced departure of the guest when bigger solvents partake in the displacement. Full article
(This article belongs to the Special Issue Intramolecular Hydrogen Bonding)
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Open AccessArticle Understanding the Interaction Determinants of CAPN1 Inhibition by CAST4 from Bovines Using Molecular Modeling Techniques
Molecules 2014, 19(9), 14316-14351; doi:10.3390/molecules190914316
Received: 18 June 2014 / Revised: 21 August 2014 / Accepted: 1 September 2014 / Published: 11 September 2014
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Abstract
HCV-induced CAPN activation and its effects on virus-infected cells in a host-immune system have been studied recently. It has been shown that the HCV-nonstructural 5A protein acts as both an inducer and a substrate for host CAPN protease; it participates in suppressing the
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HCV-induced CAPN activation and its effects on virus-infected cells in a host-immune system have been studied recently. It has been shown that the HCV-nonstructural 5A protein acts as both an inducer and a substrate for host CAPN protease; it participates in suppressing the TNF-α-induced apoptosis response and downstream IFN-induced antiviral processes. However, little is known regarding the disturbance of antiviral responses generated by bovine CAPN activation by BVDV, which is a surrogate model of HCV and is one of the most destructive diseases leading to great economic losses in cattle herds worldwide. This is also thought to be associated with the effects of either small CAPN inhibitors or the natural inhibitor CAST. They mainly bind to the binding site of CAPN substrate proteins and competitively inhibit the binding of the enzyme substrates to possibly defend against the two viruses (HCV and BVDV) for anti-viral immunity. To devise a new stratagem to discover lead candidates for an anti-BVDV drug, we first attempted to understand the bovine CAPN-CAST interaction sites and the interaction constraints of local binding architectures, were well reflected in the geometry between the pharmacophore features and its shape constraints identified using our modeled bovine CAPN1/CAST4 complex structures. We propose a computer-aided molecular design of an anti-BVDV drug as a mimetic CAST inhibitor to develop a rule-based screening function for adjusting the puzzle of relationship between bovine CAPN1 and the BVDV nonstructural proteins from all of the data obtained in the study. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Three Novel Lanthanide Metal-Organic Frameworks (Ln-MOFs) Constructed by Unsymmetrical Aromatic Dicarboxylatic Tectonics: Synthesis, Crystal Structures and Luminescent Properties
Molecules 2014, 19(9), 14352-14365; doi:10.3390/molecules190914352
Received: 30 June 2014 / Revised: 4 August 2014 / Accepted: 12 August 2014 / Published: 11 September 2014
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Abstract
Three novel Ln(III)-based coordination polymers, {[Ln2 (2,4-bpda)3 (H2O)xyH2O}n (Ln = La (III) (1), x = 2, y = 0, Ce (III) (2), Pr (III) (3), x
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Three novel Ln(III)-based coordination polymers, {[Ln2 (2,4-bpda)3 (H2O)xyH2O}n (Ln = La (III) (1), x = 2, y = 0, Ce (III) (2), Pr (III) (3), x = 4, y = 1) (2,4-H2bpda = benzophenone-2,4-dicarboxylic acid) have been prepared via a solvothermal method and characterized by elemental analysis, IR, and single-crystal X-ray diffraction techniques. Complex 1 exhibits a 3D complicated framework with a new 2-nodal (3,7)-connected (42·5) (44·51·66·8) topology. Complexes 2 and 3 are isomorphous, and feature a 3D 4-connected (65·8)-CdSO4 network. Moreover, solid-state properties such as thermal stabilities and luminescent properties of 1 and 2 were also investigated. Complex 1 crystallized in a monoclinic space group P21/c with a = 14.800 (3), b = 14.500 (3), c = 18.800 (4) Å, β = 91.00 (3), V = 4033.9 (14) Å3 and Z = 4. Complex 2 crystallized in a monoclinic space group Cc with a = 13.5432 (4), b = 12.9981 (4), c = 25.7567 (11) Å, β = 104.028 (4), V = 1374.16 (7) Å3 and Z = 4. Full article
(This article belongs to the Special Issue Practical Applications of Metal Complexes)
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Open AccessArticle CARI III Inhibits Tumor Growth in a Melanoma-Bearing Mouse Model through Induction of G0/G1 Cell Cycle Arrest
Molecules 2014, 19(9), 14383-14395; doi:10.3390/molecules190914383
Received: 23 June 2014 / Revised: 23 July 2014 / Accepted: 25 July 2014 / Published: 12 September 2014
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Abstract
Mushroom-derived natural products have been used to prevent or treat cancer for millennia. In this study, we evaluated the anticancer effects of CARI (Cell Activation Research Institute) III, which consists of a blend of mushroom mycelia from Phellinus linteus grown on germinated brown
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Mushroom-derived natural products have been used to prevent or treat cancer for millennia. In this study, we evaluated the anticancer effects of CARI (Cell Activation Research Institute) III, which consists of a blend of mushroom mycelia from Phellinus linteus grown on germinated brown rice, Inonotus obliquus grown on germinated brown rice, Antrodia camphorata grown on germinated brown rice and Ganoderma lucidum. Here, we showed that CARI III exerted anti-cancer activity, which is comparable to Dox against melanoma in vivo. B16F10 cells were intraperitoneally injected into C57BL6 mice to develop solid intra-abdominal tumors. Three hundred milligrams of the CARI III/kg/day p.o. regimen reduced tumor weight, comparable to the doxorubicin (Dox)-treated group. An increase in life span (ILS% = 50.88%) was observed in the CARI III-administered group, compared to the tumor control group. CARI III demonstrates anti-proliferative activity against B16F10 melanoma cells through inducing G0/G1 cell cycle arrest. CARI III inhibits the expression of cyclin D1, CDK4 and CDK2 and induces p21. Therefore, CARI III could be a potential chemopreventive supplement to melanoma patients. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessCommunication Identification, Characterization, and Immobilization of an Organic Solvent-Stable Alkaline Hydrolase (PA27) from Pseudomonas aeruginosa MH38
Molecules 2014, 19(9), 14396-14405; doi:10.3390/molecules190914396
Received: 19 May 2014 / Revised: 29 July 2014 / Accepted: 14 August 2014 / Published: 12 September 2014
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Abstract
An organic solvent-stable alkaline hydrolase (PA27) from Pseudomonas aeruginosa MH38 was expressed, characterized, and immobilized for biotechnological applications. Recombinant PA27 was expressed in Escherichia coli as a 27 kDa soluble protein and was purified by standard procedures. PA27 was found to be stable
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An organic solvent-stable alkaline hydrolase (PA27) from Pseudomonas aeruginosa MH38 was expressed, characterized, and immobilized for biotechnological applications. Recombinant PA27 was expressed in Escherichia coli as a 27 kDa soluble protein and was purified by standard procedures. PA27 was found to be stable at pH 8–11 and below 50 °C. It maintained more than 80% of its activity under alkaline conditions (pH 8.0–11.0). Furthermore, PA27 exhibited remarkable stability in benzene and n-hexane at concentrations of 30% and 50%. Based on these properties, immobilization of PA27 for biotechnological applications was explored. Scanning electron microscopy revealed a very smooth spherical structure with numerous large pores. Interestingly, immobilized PA27 displayed improved thermal/chemical stabilities and high reusability. Specifically, immobilized PA27 has improved thermal stability, maintaining over 90% of initial activity after 1 h of incubation at 80 °C, whereas free PA27 had only 35% residual activity. Furthermore, immobilized PA27 showed higher residual activity than the free enzyme biocatalysts against detergents, urea, and phenol. Immobilized PA27 could be recycled 20 times with retention of ~60% of its initial activity. Furthermore, macroscopic hydrogel formation of PA27 was also investigated. These characteristics make PA27 a great candidate for an industrial biocatalyst with potential applications. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Enantiomerically Pure Phosphonated Carbocyclic 2'-Oxa-3'-Azanucleosides: Synthesis and Biological Evaluation
Molecules 2014, 19(9), 14406-14416; doi:10.3390/molecules190914406
Received: 30 July 2014 / Revised: 26 August 2014 / Accepted: 29 August 2014 / Published: 12 September 2014
Cited by 8 | PDF Full-text (781 KB) | HTML Full-text | XML Full-text
Abstract
Starting from enantiomeric pure 1-[(3S,5R)- and 1-[(3R,5S)-3-(hydroxymethyl)-2-methylisoxazolidin-5-yl]-5-methylpyrimidine-2,4(1H,3H)-diones (−)7a and (+)7b, obtained by lipase-catalyzed resolution, pure diethyl{[(3S,5R)-2-methyl-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)isoxazolidin-3-yl]methyl}phosphonate (−)12a and diethyl{[(3R,5
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Starting from enantiomeric pure 1-[(3S,5R)- and 1-[(3R,5S)-3-(hydroxymethyl)-2-methylisoxazolidin-5-yl]-5-methylpyrimidine-2,4(1H,3H)-diones (−)7a and (+)7b, obtained by lipase-catalyzed resolution, pure diethyl{[(3S,5R)-2-methyl-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)isoxazolidin-3-yl]methyl}phosphonate (−)12a and diethyl{[(3R,5S)-2-methyl-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)isoxazolidin-3-yl]methyl}phosphonate (+)12b have been synthesized. The obtained compounds showed no cytotoxic activity versus the U937 cell line in comparison with AZT, and were poorly able to inhibit HIV infection in vitro. Full article
(This article belongs to the Special Issue Cycloaddition Chemistry)
Open AccessArticle Solid State Structure and Solution Thermodynamics of Three-Centered Hydrogen Bonds (O∙∙∙H∙∙∙O) Using N-(2-Benzoyl-phenyl) Oxalyl Derivatives as Model Compounds
Molecules 2014, 19(9), 14446-14460; doi:10.3390/molecules190914446
Received: 27 August 2014 / Accepted: 9 September 2014 / Published: 12 September 2014
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Abstract
Intramolecular hydrogen bond (HB) formation was analyzed in the model compounds N-(2-benzoylphenyl)acetamide, N-(2-benzoylphenyl)oxalamate and N1,N2-bis(2-benzoylphenyl)oxalamide. The formation of three-center hydrogen bonds in oxalyl derivatives was demonstrated in the solid state by the X-ray diffraction analysis of
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Intramolecular hydrogen bond (HB) formation was analyzed in the model compounds N-(2-benzoylphenyl)acetamide, N-(2-benzoylphenyl)oxalamate and N1,N2-bis(2-benzoylphenyl)oxalamide. The formation of three-center hydrogen bonds in oxalyl derivatives was demonstrated in the solid state by the X-ray diffraction analysis of the geometric parameters associated with the molecular structures. The solvent effect on the chemical shift of H6 [δH6(DMSO-d6)–δH6(CDCl3)] and Δδ(ΝΗ)/ΔT measurements, in DMSO-d6 as solvent, have been used to establish the energetics associated with intramolecular hydrogen bonding. Two center intramolecular HB is not allowed in N-(2-benzoylphenyl)acetamide either in the solid state or in DMSO-d6 solution because of the unfavorable steric effects of the o-benzoyl group. The estimated Δ and Δ values for the hydrogen bonding disruption by DMSO-d6 of 28.3(0.1) kJ·mol−1 and 69.1(0.4) J·mol−1·K−1 for oxalamide, are in agreement with intramolecular three-center hydrogen bonding in solution. In the solid, the benzoyl group contributes to develop 1-D and 2-D crystal networks, through C–H∙∙∙A (A = O, π) and dipolar C=O∙∙∙A (A = CO, π) interactions, in oxalyl derivatives. To the best of our knowledge, this is the first example where three-center hydrogen bond is claimed to overcome steric constraints. Full article
(This article belongs to the Special Issue Intramolecular Hydrogen Bonding)
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Open AccessCommunication MALDI-TOF MS Analysis of Proanthocyanidins in Two Lowland Tropical Forest Species of Cecropia: A First Look at Their Chemical Structures
Molecules 2014, 19(9), 14484-14495; doi:10.3390/molecules190914484
Received: 23 June 2014 / Revised: 5 August 2014 / Accepted: 1 September 2014 / Published: 12 September 2014
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Abstract
The structural chemistry of proanthocyanidin molecules has been investigated in temperate zone plants, but few studies have been done with plants of the Amazonian lowland tropical wet forests where herbivore pressure is more extensive and diverse. Using MALDI-TOF mass spectrometry, we report unique
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The structural chemistry of proanthocyanidin molecules has been investigated in temperate zone plants, but few studies have been done with plants of the Amazonian lowland tropical wet forests where herbivore pressure is more extensive and diverse. Using MALDI-TOF mass spectrometry, we report unique properties of the proanthocyanidin structural chemistry in two neotropical Cecropia species, C. polystachya, a myrmecophyte with mutualistic ants, and C. sciadophylla, a non-myrmecophyte lacking mutualistic ants. Our preliminary data suggests the presence of reportedly uncommon propelargonidin subunits in a majority of proanthocyanidin oligomers. The presence of 3-O-gallate proanthocyanidin monomers was also detected in the mass spectra of both species. Unlike other studies that have examined species growing at higher latitudes, oligomers composed of procyanidin, propelargonidin, and their 3-O-gallates were present in both Cecropia species while the presence of oligomers containing prodelphinidin units were absent or at lower levels. These distinctive features may suggest that proanthocyanidins in some tropical plant species may be an untapped source of proanthocyanidin structural complexity that warrants further investigation. Several differences between spectra of the two Cecropia species could also point to the presence of anti-herbivore defense tradeoffs between chemical defense quality and biotic defense between the two species. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Tocotrienol-Rich Fraction, [6]-Gingerol and Epigallocatechin Gallate Inhibit Proliferation and Induce Apoptosis of Glioma Cancer Cells
Molecules 2014, 19(9), 14528-14541; doi:10.3390/molecules190914528
Received: 24 July 2014 / Revised: 26 August 2014 / Accepted: 1 September 2014 / Published: 12 September 2014
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Abstract
Plant bioactives [6]-gingerol (GING), epigallocatechin gallate (EGCG) and asiaticoside (AS) and vitamin E, such as tocotrienol-rich fraction (TRF), have been reported to possess anticancer activity. In this study, we investigated the apoptotic properties of these bioactive compounds alone or in combination on glioma
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Plant bioactives [6]-gingerol (GING), epigallocatechin gallate (EGCG) and asiaticoside (AS) and vitamin E, such as tocotrienol-rich fraction (TRF), have been reported to possess anticancer activity. In this study, we investigated the apoptotic properties of these bioactive compounds alone or in combination on glioma cancer cells. TRF, GING, EGCG and AS were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) in culture by the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. With the exception of AS, combinations of two compounds were tested, and the interactions of each combination were evaluated by the combination index (CI) using an isobologram. Different grades of glioma cancer cells showed different cytotoxic responses to the compounds, where in 1321N1 and LN18 cells, the combination of EGCG + GING exhibited a synergistic effect with CI = 0.77 and CI = 0.55, respectively. In contrast, all combinations tested (TRF + GING, TRF + EGCG and EGCG + GING) were found to be antagonistic on SW1783 with CI values of 1.29, 1.39 and 1.39, respectively. Combined EGCG + GING induced apoptosis in both 1321N1 and LN18 cells, as evidenced by Annexin-V FITC/PI staining and increased active caspase-3. Our current data suggests that the combination of EGCG + GING synergistically induced apoptosis and inhibits the proliferation 1321N1 and LN18 cells, but not SW1783 cells, which may be due to their different genetic profiles. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated Excitotoxicity
Molecules 2014, 19(9), 14542-14555; doi:10.3390/molecules190914542
Received: 7 July 2014 / Revised: 4 August 2014 / Accepted: 6 August 2014 / Published: 15 September 2014
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Abstract
The accumulation of glutamate can excessively activate the N-methyl-d-aspartate (NMDA) receptors and cause excitotoxicity. Daphnetin (Dap), a coumarin derivative, is a protein kinase inhibitor that exhibits antioxidant and neuroprotective properties. However, little is known about the neuroprotective effects of Dap on glutamate-induced
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The accumulation of glutamate can excessively activate the N-methyl-d-aspartate (NMDA) receptors and cause excitotoxicity. Daphnetin (Dap), a coumarin derivative, is a protein kinase inhibitor that exhibits antioxidant and neuroprotective properties. However, little is known about the neuroprotective effects of Dap on glutamate-induced excitotoxicity. We evaluated the neuroprotective activities in the primary cultured cortical neurons against NMDA-induced excitotoxicity. Pretreatment with Dap significantly prevented NMDA-induced neuronal cell loss. Dap significantly inhibited the neuronal apoptosis by regulating balance of Bcl-2 and Bax expression. Furthermore, pretreatment of Dap reversed the up-regulation of NR2B-containing NMDA receptors and inhibited the intracellular Ca2+ overload induced by NMDA exposure. In addition, Dap prevented cerebral ischemic injury in mice induced via a 2 h middle cerebral artery occlusion and a 24 h reperfusion in vivo. The findings suggest that Dap prevents the excitotoxicity through inhibiting the NR2B-containing NMDA receptors and the subsequent calcium overload in cultured cortical neurons. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Preparation of Calcium- and Magnesium-Fortified Potato Starches with Altered Pasting Properties
Molecules 2014, 19(9), 14556-14566; doi:10.3390/molecules190914556
Received: 14 August 2014 / Revised: 9 September 2014 / Accepted: 10 September 2014 / Published: 15 September 2014
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Abstract
Calcium- and magnesium-fortified potato starches were prepared by immersion in various concentrations of CaCl2 and MgCl2 aqueous solutions, respectively. The pasting properties, i.e., peak viscosity and breakdown, of all the starches obtained above were analyzed using a Rapid Visco Analyzer.
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Calcium- and magnesium-fortified potato starches were prepared by immersion in various concentrations of CaCl2 and MgCl2 aqueous solutions, respectively. The pasting properties, i.e., peak viscosity and breakdown, of all the starches obtained above were analyzed using a Rapid Visco Analyzer. Furthermore, the gelatinization properties and in vitro digestibility of the representative calcium- and magnesium-fortified starches were tested. The maximum calcium content of the fortified potato starches was as high as 686 ppm with the addition of a high-concentration CaCl2 solution, while the calcium content of the control potato starch was 99 ppm. The magnesium content increased from 89 to 421 ppm by treatment of the potato starch with an MgCl2 solution. Markedly lower values of peak viscosity and breakdown were observed in calcium- and magnesium-fortified potato starches than in the control potato starch. However, the gelatinization temperature and enthalpy as well as resistant starch content of calcium- and magnesium-fortified potato starches were similar to those of the control potato starch. It is concluded that potato starches with altered pasting properties can be easily manufactured by the use of solutions containing high levels of calcium and magnesium. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Evaluation of the Antioxidant, Anti-Inflammatory, and Anticancer Activities of Euphorbia hirta Ethanolic Extract
Molecules 2014, 19(9), 14567-14581; doi:10.3390/molecules190914567
Received: 9 August 2014 / Accepted: 4 September 2014 / Published: 15 September 2014
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Abstract
This study evaluated the chemical composition, antioxidant, anti-inflammatory and anticancer activities of a Euphorbia hirta L. extract. The antioxidant activities of whole E. hirta ethanol extract were determined by electron spin resonance spectrophotometric analysis of 1,1-diphenyl-2-picryl-hydrazyl (DPPH), hydroxyl, and alkyl radical levels and
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This study evaluated the chemical composition, antioxidant, anti-inflammatory and anticancer activities of a Euphorbia hirta L. extract. The antioxidant activities of whole E. hirta ethanol extract were determined by electron spin resonance spectrophotometric analysis of 1,1-diphenyl-2-picryl-hydrazyl (DPPH), hydroxyl, and alkyl radical levels and by using an online high-performance liquid chromatography (HPLC)-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assay. The E. hirta ethanol extract (0.5 mg/mL) exhibited DPPH-scavenging activity of 61.19% ± 0.22%, while the positive control (0.5 mg/mL ascorbic acid) had 100% ± 0.22% activity. The concentration of the extract required to trap 50% of DPPH (IC50) was 0.205 mg/mL. Online HPLC analysis of the extract also showed strong antioxidant activity. The anti-inflammatory activity of the E. hirta extract was assessed in lipopolysaccharide-induced RAW 264.7 macrophages. The anti-inflammatory activity was highest in the presence of 200 µg/mL E. hirta extract, and nitric oxide production was decreased significantly (p < 0.05). The extract also showed selective anticancer activity at a concentration of 100 µg/mL (p < 0.05). These results indicated that E. hirta may warrant further investigation for the development of antioxidant, anti-inflammatory, and anticancer herbal medications. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Carbon Nanotubes as Supports for Inulinase Immobilization
Molecules 2014, 19(9), 14615-14624; doi:10.3390/molecules190914615
Received: 16 May 2014 / Revised: 16 August 2014 / Accepted: 22 August 2014 / Published: 15 September 2014
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Abstract
The commercial inulinase obtained from Aspergillus niger was non-covalently immobilized on multiwalled carbon nanotubes (MWNT-COOH). The immobilization conditions for the carbon nanotubes were defined by the central composite rotational design (CCRD). The effects of enzyme concentration (0.8%–1.7% v/v) and adsorbent:adsorbate ratio (1:460–1:175) on
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The commercial inulinase obtained from Aspergillus niger was non-covalently immobilized on multiwalled carbon nanotubes (MWNT-COOH). The immobilization conditions for the carbon nanotubes were defined by the central composite rotational design (CCRD). The effects of enzyme concentration (0.8%–1.7% v/v) and adsorbent:adsorbate ratio (1:460–1:175) on the enzyme immobilization were studied. The adsorbent:adsorbate ratio variable has positive effect and the enzyme concentration has a negative effect on the inulinase immobilization (U/g) response at the 90% significance level. These results show that the lower the enzyme concentration and the higher the adsorbent:adsorbate ratio, better is the immobilization. According to the results, it is possible to observe that the carbon nanotubes present an effective inulinase adsorption. Fast adsorption in about six minutes and a loading capacity of 51,047 U/g support using a 1.3% (v/v) inulinase concentration and a 1:460 adsorbent:adsorbate ratio was observed. The effects of temperature on the immobilized enzyme activity were evaluated, showing better activity at 50 °C. The immobilized enzyme maintained 100% of its activity during five weeks at room temperature. The immobilization strategy with MWNT-COOH was defined by the experimental design, showing that inulinase immobilization is a promising biotechnological application of carbon nanotubes. Full article
(This article belongs to the Special Issue Enzyme Immobilization)
Open AccessArticle The Content of Phenolic Compounds in Leaf Tissues of White (Aesculus hippocastanum L.) and Red Horse Chestnut (Aesculus carea H.) Colonized by the Horse Chestnut Leaf Miner (Cameraria ohridella Deschka & Dimić)
Molecules 2014, 19(9), 14625-14636; doi:10.3390/molecules190914625
Received: 5 July 2014 / Revised: 9 August 2014 / Accepted: 1 September 2014 / Published: 15 September 2014
Cited by 6 | PDF Full-text (828 KB) | HTML Full-text | XML Full-text
Abstract
Normally, plant phenolics are secondary metabolites involved in the defense mechanisms of plants against fungal pathogens. Therefore, in this study we attempted to quantify and characterize phenolic compounds in leaves of white and red horse chestnut with leaf miner larvae before and after
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Normally, plant phenolics are secondary metabolites involved in the defense mechanisms of plants against fungal pathogens. Therefore, in this study we attempted to quantify and characterize phenolic compounds in leaves of white and red horse chestnut with leaf miner larvae before and after Cameraria ohridella attack. A total of 17 phenolic compounds belonging to the hydroxycinnamic acid, flavan-3-ols and flavonol groups were identified and quantified in white and red horse chestnut leaf extracts. Significantly decreased concentrations of some phenolic compounds, especially of flavan-3-ols, were observed in infected leaves compared to the non-infected ones. Additionally, a higher content of polyphenolic compounds especially (−)-epicatechin and procyanidins in leaves of red-flowering than in white-flowering horse chestnut may explain their greater resistance to C. ohridella insects. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle A Novel 3,9-(1,2,3-Trioxocine)-Type Steroid of Rauia nodosa (Rutaceae)
Molecules 2014, 19(9), 14637-14648; doi:10.3390/molecules190914637
Received: 23 June 2014 / Revised: 25 August 2014 / Accepted: 1 September 2014 / Published: 16 September 2014
Cited by 2 | PDF Full-text (1026 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new natural product, a 3,9-(1,2,3-trioxocine)-type steroid, named rauianodoxy (6), was isolated from Rauia nodosa, together with five steroids: sistostenone (1), stigmastenone (2), sitosterol (3), stigmasterol (4) and ergosterol peroxide (5
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A new natural product, a 3,9-(1,2,3-trioxocine)-type steroid, named rauianodoxy (6), was isolated from Rauia nodosa, together with five steroids: sistostenone (1), stigmastenone (2), sitosterol (3), stigmasterol (4) and ergosterol peroxide (5), one coumarin, O-geranylosthenol (7), and three alkaloids, N-methylflindersine (8), zantobungeanine (9) and veprissine (10). Compounds 58 were isolated for the first time in the genus Rauia. These compounds were characterized on the basis of their spectral data, mainly one and two-dimensional NMR, and mass spectra, also involving comparison with the literature data. Theoretical studies at the DFT level reveal structural parameters for the 1,2,3-trioxole bridge compatible with known structures containing a similar group. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Eurycomanone and Eurycomanol from Eurycoma longifolia Jack as Regulators of Signaling Pathways Involved in Proliferation, Cell Death and Inflammation
Molecules 2014, 19(9), 14649-14666; doi:10.3390/molecules190914649
Received: 15 July 2014 / Revised: 1 September 2014 / Accepted: 3 September 2014 / Published: 16 September 2014
Cited by 4 | PDF Full-text (5054 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Eurycomanone and eurycomanol are two quassinoids from the roots of Eurycoma longifolia Jack. The aim of this study was to assess the bioactivity of these compounds in Jurkat and K562 human leukemia cell models compared to peripheral blood mononuclear cells from healthy donors.
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Eurycomanone and eurycomanol are two quassinoids from the roots of Eurycoma longifolia Jack. The aim of this study was to assess the bioactivity of these compounds in Jurkat and K562 human leukemia cell models compared to peripheral blood mononuclear cells from healthy donors. Both eurycomanone and eurycomanol inhibited Jurkat and K562 cell viability and proliferation without affecting healthy cells. Interestingly, eurycomanone inhibited NF-κB signaling through inhibition of IκBα phosphorylation and upstream mitogen activated protein kinase (MAPK) signaling, but not eurycomanol. In conclusion, both quassinoids present differential toxicity towards leukemia cells, and the presence of the α,β-unsaturated ketone in eurycomanone could be prerequisite for the NF-κB inhibition. Full article
Open AccessArticle Anti-Inflammatory and Analgesic Effects of the Marine-Derived Compound Comaparvin Isolated from the Crinoid Comanthus bennetti
Molecules 2014, 19(9), 14667-14686; doi:10.3390/molecules190914667
Received: 29 July 2014 / Revised: 9 September 2014 / Accepted: 10 September 2014 / Published: 16 September 2014
Cited by 6 | PDF Full-text (2139 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
To date, no study has been conducted to explore the bioactivity of the crinoid Comanthus bennetti. Here we report the anti-inflammatory properties of comaparvin (5,8-dihydroxy-10-methoxy-2-propylbenzo[h]chromen-4-one) based on in vivo experiments. Our preliminary screening for anti-inflammatory activity revealed that the crude extract of
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To date, no study has been conducted to explore the bioactivity of the crinoid Comanthus bennetti. Here we report the anti-inflammatory properties of comaparvin (5,8-dihydroxy-10-methoxy-2-propylbenzo[h]chromen-4-one) based on in vivo experiments. Our preliminary screening for anti-inflammatory activity revealed that the crude extract of Comanthus bennetti significantly inhibited the expression of pro-inflammatory proteins in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophage cells. Comaparvin isolated from crinoids significantly decreased the expression of inducible nitric oxide synthase (iNOS) protein and mRNA in LPS-stimulated macrophage cells. Moreover, our results showed that post-treatment with comaparvin significantly inhibited mechanical allodynia, thermal hyperalgesia and weight-bearing deficits in rats with carrageenan-induced inflammation. Comaparvin also attenuated leukocyte infiltration and iNOS protein expression in carrageenan-induced inflamed paws. These results suggest that comaparvin is a potential anti-inflammatory therapeutic agent against inflammatory pain. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Pharmacological Effects of the Water Fraction of Key Components in the Traditional Chinese Prescription Mai Tong Fang on 3T3-L1 Adipocytes and ob/ob Diabetic Mice
Molecules 2014, 19(9), 14687-14698; doi:10.3390/molecules190914687
Received: 20 June 2014 / Revised: 1 September 2014 / Accepted: 2 September 2014 / Published: 16 September 2014
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Abstract
Mai Tong Fang (MTF), a Chinese herbal combination, has been used for the treatment of diabetic nephropathy in traditional medical clinics in China. However, the anti-adipogenic and anti-hyperglycemic effects of MTF have not been fully elucidated, so this study explored these pharmacological activities
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Mai Tong Fang (MTF), a Chinese herbal combination, has been used for the treatment of diabetic nephropathy in traditional medical clinics in China. However, the anti-adipogenic and anti-hyperglycemic effects of MTF have not been fully elucidated, so this study explored these pharmacological activities in 3T3-L1 adipocytes and ob/ob mice, respectively, of the water fraction of milkvetch root, salviae miltiorrhizae and mulberry as key components of MTF. MTF was found to inhibit adipogenesis and triglyceride accumulation in 3T3-L1 adipocytes. Oral administration of MTF in ob/ob mice for 8 weeks, exhibited positive controls on blood glucose and body weight, and further improved glucose tolerance according to an oral glucose tolerance test. Importantly, MTF extract alleviated fat deposition and ballooning degeneration in liver tissue and blocked the increase of adipocyte size in adipose tissue from treated ob/ob mice. These results indicated that the extract of key components in the traditional Chinese prescription MTF continue a potent anti-adipogenic and glucose-lowering agent. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Assessment of Mechanisms Involved in Antinociception Produced by the Alkaloid Caulerpine
Molecules 2014, 19(9), 14699-14709; doi:10.3390/molecules190914699
Received: 15 August 2014 / Revised: 7 September 2014 / Accepted: 9 September 2014 / Published: 16 September 2014
Cited by 4 | PDF Full-text (852 KB) | HTML Full-text | XML Full-text
Abstract
In previous works we showed that oral administration of caulerpine, a bisindole alkaloid isolated from algae of the genus Caulerpa, produced antinociception when assessed in chemical and thermal models of nociception. In this study, we evaluated the possible mechanism of action of
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In previous works we showed that oral administration of caulerpine, a bisindole alkaloid isolated from algae of the genus Caulerpa, produced antinociception when assessed in chemical and thermal models of nociception. In this study, we evaluated the possible mechanism of action of this alkaloid in mice, using the writhing test. The antinociceptive effect of caulerpine was not affected by intraperitoneal (i.p.) pretreatment of mice with naloxone, flumazenil, l-arginine or atropine, thus discounting the involvement of the opioid, GABAergic, l-arginine-nitric oxide and (muscarinic) cholinergic pathways, respectively. In contrast, i.p. pretreatment with yohimbine, an α2-adrenoceptor antagonist, or tropisetron, a 5-HT3 antagonist, significantly blocked caulerpine-induced antinociception. These results suggest that caulerpine exerts its antinociceptive effect in the writhing test via pathways involving α2-adrenoceptors and 5-HT3 receptors. In summary, this alkaloid could be of interest in the development of new dual-action analgesic drugs. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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Open AccessArticle Chitosan Combined with Molecular Beacon for Mir-155 Detection and Imaging in Lung Cancer
Molecules 2014, 19(9), 14710-14722; doi:10.3390/molecules190914710
Received: 7 July 2014 / Revised: 30 August 2014 / Accepted: 3 September 2014 / Published: 16 September 2014
Cited by 3 | PDF Full-text (3410 KB) | HTML Full-text | XML Full-text
Abstract
Lung cancer is the major cause of cancer-related deaths worldwide, thus developing effective methods for its early diagnosis is urgently needed. In recent years, microRNAs (miRNAs, miR) have been reported to play important roles in carcinogenesis and have become potential biomarkers for cancer
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Lung cancer is the major cause of cancer-related deaths worldwide, thus developing effective methods for its early diagnosis is urgently needed. In recent years, microRNAs (miRNAs, miR) have been reported to play important roles in carcinogenesis and have become potential biomarkers for cancer diagnosis and treatment. Molecular beacon (MB) technology is a universal technology to detect DNA/RNA expression in living cells. As a natural polymers, chitosan (CS) nanoparticles could be used as a carrier for safe delivery of nucleic acid. In this study, we developed a probe using nanoparticles of miR-155 MB self assembled with CS (CS-miR-155 MB) to image the expression of miR-155 in cancer cells. Hybridization assay showed that the locked nucleic acid (LAN) modified miR-155 MB could target miR-155 effectively and sensitively. The miR-155 MB self-assembly with CS nanoparticles formed stable complexes at the proper weight ratio. The CS nanoparticles showed higher fluorescence intensity and transfection efficiency than the lipid-based formulation transfection agent by confocal microscopy and flow cytometry analysis. The CS-MB complexes were found to be easily synthesized and exhibited strong enzymatic stability, efficient cellular uptake, high target selectivity and biocompatibility. The CS-MB complexes can also be applied in other cancers just by simply changing for a targeted miRNA highly expressed in those cancer cells. Therefore, it is a promising vehicle used for detecting miRNA expression in living cells. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Emodin Protects against Diabetic Cardiomyopathy by Regulating the AKT/GSK-3β Signaling Pathway in the Rat Model
Molecules 2014, 19(9), 14782-14793; doi:10.3390/molecules190914782
Received: 17 July 2014 / Revised: 18 August 2014 / Accepted: 1 September 2014 / Published: 17 September 2014
Cited by 7 | PDF Full-text (743 KB) | HTML Full-text | XML Full-text
Abstract
Diabetes mellitus (DM) has been recognized as a major health problem. Emodin (Emo) has been reported to exhibit protective effects against diabetic nephropathy. However, little has been known about the effect of Emo on diabetic cardiomyopathy (DCM). A type 2 DM model was
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Diabetes mellitus (DM) has been recognized as a major health problem. Emodin (Emo) has been reported to exhibit protective effects against diabetic nephropathy. However, little has been known about the effect of Emo on diabetic cardiomyopathy (DCM). A type 2 DM model was induced in rats by low dose streptozotocin (STZ) combined with high energy intake. We found that Emo-treated groups displayed significantly higher body weight (BW) and lower heart weight (HW)/BW. Furthermore, Emo could significantly decrease blood glucose, total cholesterol (TG) levels, and triglyceride (TC) levels in diabetic rats. Moreover, the Emo-treated group showed a marked increase in heart rate (HR) and showed lower left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular posterior wall thickness (LWPWT), and interventricular septal diastolic wall thickness (IVSD). Emo induced a significant increase in phosphorylation of Akt and GSK-3β in myocardium. These results suggest that Emo may have great therapeutic potential in the treatment of DCM by Akt/GSK-3β signaling pathway. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Enhanced Antioxidant Capacity and Anti-Ageing Biomarkers after Diet Micronutrient Supplementation
Molecules 2014, 19(9), 14794-14808; doi:10.3390/molecules190914794
Received: 17 July 2014 / Revised: 3 September 2014 / Accepted: 9 September 2014 / Published: 17 September 2014
Cited by 4 | PDF Full-text (748 KB) | HTML Full-text | XML Full-text
Abstract
A growing number of studies confirm an important effect of diet, lifestyle and physical activity on health status, the ageing process and many metabolic disorders. This study focuses on the influence of a diet supplement, NucleVital®Q10 Complex, on parameters related to
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A growing number of studies confirm an important effect of diet, lifestyle and physical activity on health status, the ageing process and many metabolic disorders. This study focuses on the influence of a diet supplement, NucleVital®Q10 Complex, on parameters related to redox homeostasis and ageing. An experimental group of 66 healthy volunteer women aged 35–55 supplemented their diet for 12 weeks with the complex, which contained omega-3 acids (1350 mg/day), ubiquinone (300 mg/day), astaxanthin (15 mg/day), lycopene (45 mg/day), lutein palmitate (30 mg/day), zeaxanthine palmitate (6 mg/day), L-selenomethionine (330 mg/day), cholecalciferol (30 µg/day) and α-tocopherol (45 mg/day). We found that NucleVital®Q10 Complex supplementation significantly increased total antioxidant capacity of plasma and activity of erythrocyte superoxide dismutase, with slight effects on oxidative stress biomarkers in erythrocytes; MDA and 4-hydroxyalkene levels. Apart from the observed antioxidative effects, the tested supplement also showed anti-ageing activity. Analysis of expression of SIRT1 and 2 in PBMCs showed significant changes for both genes on a mRNA level. The level of telomerase was also increased by more than 25%, although the length of lymphocyte telomeres, determined by RT-PCR, remained unchanged. Our results demonstrate beneficial effects concerning the antioxidant potential of plasma as well as biomarkers related to ageing even after short term supplementation of diet with NucleVital®Q10 Complex. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
Open AccessArticle Synthesis and in Vitro Evaluation of New Nitro-Substituted Thiazolyl Hydrazone Derivatives as Anticandidal and Anticancer Agents
Molecules 2014, 19(9), 14809-14820; doi:10.3390/molecules190914809
Received: 7 August 2014 / Revised: 25 August 2014 / Accepted: 2 September 2014 / Published: 17 September 2014
Cited by 7 | PDF Full-text (717 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fourteen new thiazolyl hydrazone derivatives were synthesized and evaluated for their anticandidal activity using a broth microdilution assay. Among the synthesized compounds, 2-[2-((5-(4-chloro-2-nitrophenyl)furan-2-yl)methylene)hydrazinyl]-4-(4-fluorophenyl)thiazole and 2-[2-((5-(4-chloro-2-nitrophenyl)furan-2-yl)methylene) hydrazinyl]-4-(4-methoxyphenyl)thiazole were found to be the most effective antifungal compounds against Candida utilis, with a MIC value
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Fourteen new thiazolyl hydrazone derivatives were synthesized and evaluated for their anticandidal activity using a broth microdilution assay. Among the synthesized compounds, 2-[2-((5-(4-chloro-2-nitrophenyl)furan-2-yl)methylene)hydrazinyl]-4-(4-fluorophenyl)thiazole and 2-[2-((5-(4-chloro-2-nitrophenyl)furan-2-yl)methylene) hydrazinyl]-4-(4-methoxyphenyl)thiazole were found to be the most effective antifungal compounds against Candida utilis, with a MIC value of 250 µg/mL, when compared with fluconazole (MIC = 2 µg/mL). Additionally, the synthesized compounds were evaluated for their in vitro cytotoxic effects on the MCF-7 and NIH/3T3 cell lines. As a result, 2-[2-((5-(4-chloro-2-nitrophenyl)furan-2-yl)methylene)hydrazinyl]-4-(4-chlorophenyl)thiazole was identified as the most promising anticancer compound against MCF-7 cancer cells due to its inhibitory effects (IC50 = 125 µg/mL) and relatively low toxicity towards the NIH/3T3 cell line (IC50 > 500 µg/mL). Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Simple Rain-Shelter Cultivation Prolongs Accumulation Period of Anthocyanins in Wine Grape Berries
Molecules 2014, 19(9), 14843-14861; doi:10.3390/molecules190914843
Received: 11 August 2014 / Revised: 30 August 2014 / Accepted: 9 September 2014 / Published: 17 September 2014
Cited by 1 | PDF Full-text (4566 KB) | HTML Full-text | XML Full-text
Abstract
Simple rain-shelter cultivation is normally applied during the grape growth season in continental monsoon climates aiming to reduce the occurrence of diseases caused by excessive rainfall. However, whether or not this cultivation practice affects the composition and concentration of phenolic compounds in wine
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Simple rain-shelter cultivation is normally applied during the grape growth season in continental monsoon climates aiming to reduce the occurrence of diseases caused by excessive rainfall. However, whether or not this cultivation practice affects the composition and concentration of phenolic compounds in wine grapes remains unclear. The objective of this study was to investigate the effect of rain-shelter cultivation on the accumulation of anthocyanins in wine grapes (Vitis vinifera L. Cabernet Sauvignon) grown in eastern China. The results showed that rain-shelter cultivation, compared with the open-field, extended the period of rapid accumulation of sugar, increased the soluble solid content in the grape berries, and delayed the senescence of the green leaves at harvest. The concentrations of most anthocyanins were significantly enhanced in the rain-shelter cultivated grapes, and their content increases were closely correlated with the accumulation of sugar. However, the compositions of anthocyanins in the berries were not altered. Correspondingly, the expressions of VvF3'H, VvF3'5'H, and VvUFGT were greatly up-regulated and this rising trend appeared to continue until berry maturation. These results suggested that rain-shelter cultivation might help to improve the quality of wine grape berries by prolonging the life of functional leaves and hence increasing the assimilation products. Full article
(This article belongs to the Special Issue Anthocyanins) Print Edition available
Open AccessArticle Effect of Standardized Cranberry Extract on the Activity and Expression of Selected Biotransformation Enzymes in Rat Liver and Intestine
Molecules 2014, 19(9), 14948-14960; doi:10.3390/molecules190914948
Received: 8 August 2014 / Revised: 28 August 2014 / Accepted: 4 September 2014 / Published: 18 September 2014
Cited by 4 | PDF Full-text (997 KB) | HTML Full-text | XML Full-text
Abstract
The use of dietary supplements containing cranberry extract is a common way to prevent urinary tract infections. As consumption of these supplements containing a mixture of concentrated anthocyanins and proanthocyanidins has increased, interest in their possible interactions with drug-metabolizing enzymes has grown. In
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The use of dietary supplements containing cranberry extract is a common way to prevent urinary tract infections. As consumption of these supplements containing a mixture of concentrated anthocyanins and proanthocyanidins has increased, interest in their possible interactions with drug-metabolizing enzymes has grown. In this in vivo study, rats were treated with a standardized cranberry extract (CystiCran®) obtained from Vaccinium macrocarpon in two dosage schemes (14 days, 0.5 mg of proanthocyanidins/kg/day; 1 day, 1.5 mg of proanthocyanidins/kg/day). The aim of this study was to evaluate the effect of anthocyanins and proanthocyanidins contained in this extract on the activity and expression of intestinal and hepatic biotransformation enzymes: cytochrome P450 (CYP1A1, CYP1A2, CYP2B and CYP3A), carbonyl reductase 1 (CBR1), glutathione-S-transferase (GST) and UDP-glucuronosyl transferase (UGT). Administration of cranberry extract led to moderate increases in the activities of hepatic CYP3A (by 34%), CYP1A1 (by 38%), UGT (by 40%), CBR1 (by 17%) and GST (by 13%), while activities of these enzymes in the small intestine were unchanged. No changes in the relative amounts of these proteins were found. Taken together, the interactions of cranberry extract with simultaneously administered drugs seem not to be serious. Full article
(This article belongs to the Special Issue Anthocyanins) Print Edition available
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Open AccessArticle A Multi-Scale–Multi-Stable Model for the Rhodopsin Photocycle
Molecules 2014, 19(9), 14961-14978; doi:10.3390/molecules190914961
Received: 21 July 2014 / Revised: 28 August 2014 / Accepted: 8 September 2014 / Published: 18 September 2014
Cited by 4 | PDF Full-text (4310 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We report a multi-scale simulation study of the photocycle of the rhodopsins. The quasi-atomistic representation (“united atoms” UA) of retinal is combined with a minimalist coarse grained (CG, one-bead-per amino acid) representation of the protein, in a hybrid UA/CG approach, which is the
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We report a multi-scale simulation study of the photocycle of the rhodopsins. The quasi-atomistic representation (“united atoms” UA) of retinal is combined with a minimalist coarse grained (CG, one-bead-per amino acid) representation of the protein, in a hybrid UA/CG approach, which is the homolog of QM/MM, but at lower resolution. An accurate multi-stable parameterization of the model allows simulating each state and transition among them, and the combination of different scale representation allows addressing the entire photocycle. We test the model on bacterial rhodopsin, for which more experimental data are available, and then also report results for mammalian rhodopsins. In particular, the analysis of simulations reveals the spontaneous appearance of meta-stable states in quantitative agreement with experimental data. Full article
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Open AccessArticle Pharmacological Effects of “Jutsu” (Atractylodis rhizome and Atractylodis lanceae rhizome) on 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-Induced Head Twitch Response in Mice (I)
Molecules 2014, 19(9), 14979-14986; doi:10.3390/molecules190914979
Received: 17 July 2014 / Revised: 10 September 2014 / Accepted: 12 September 2014 / Published: 18 September 2014
PDF Full-text (705 KB) | HTML Full-text | XML Full-text
Abstract
Hallucinations are a common non-motor symptom of Parkinson’s disease and various forms of dementias. Yokukansan and Yokukansankachimpihange have attracted attention due to their effectiveness in the treatment of hallucinations of dementia. To clarify which component in these formulas contribute to the effects, at
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Hallucinations are a common non-motor symptom of Parkinson’s disease and various forms of dementias. Yokukansan and Yokukansankachimpihange have attracted attention due to their effectiveness in the treatment of hallucinations of dementia. To clarify which component in these formulas contribute to the effects, at first, we focused on their differences in compositions to examine the pharmacological effects on the selective 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head-twitch response (HTR) in mice that has been used as animal hallucination model. Results indicated that water extract of Byaku-jutsu (Atractylodes japonica) showed a stronger inhibitory effect on DOI-induced HTR than that of So-jutsu (A. lancea) corresponding to their major constituents of atractylenolide III and β-eudesmol, and suggested that the major constituents should be active constituents contributing to the antihallucination effects of Byaku- and So-jutsu. Besides, the part B–C ring (butenolide) in atractylenolide III was found to be similar to the structure of serotonin and suggested that the B–C ring may partially play role in antagonistic activity against serotonin receptors. Thus, a novel, rational design of butenolide-related compounds may as potential lead compounds for new drug development. Analysis of the chemical components of Byaku- and So-jutsu and further study on their structure-activity relationships are currently in progress. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of New Quinoxalines Containing an Oxirane Ring by the TDAE Strategy and in Vitro Evaluation in Neuroblastoma Cell Lines
Molecules 2014, 19(9), 14987-14998; doi:10.3390/molecules190914987
Received: 25 July 2014 / Revised: 9 September 2014 / Accepted: 11 September 2014 / Published: 18 September 2014
Cited by 6 | PDF Full-text (815 KB) | HTML Full-text | XML Full-text
Abstract
Neuroblastoma is an aggressive pediatric malignancy with significant chemotherapeutic resistance. In order to obtain new compounds active on neuroblastoma cell lines, we investigated the reactivity of carbanion formed via TDAE in quinoxaline series. The new synthesized compounds were tested for their anti-proliferative activity
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Neuroblastoma is an aggressive pediatric malignancy with significant chemotherapeutic resistance. In order to obtain new compounds active on neuroblastoma cell lines, we investigated the reactivity of carbanion formed via TDAE in quinoxaline series. The new synthesized compounds were tested for their anti-proliferative activity on two neuroblastoma cell lines, and seven oxirane derivatives obtained interesting activities. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessCommunication A Novel Synthesis of the Oxazolidinone Antithrombotic Agent Rivaroxaban
Molecules 2014, 19(9), 14999-15004; doi:10.3390/molecules190914999
Received: 26 June 2014 / Revised: 9 September 2014 / Accepted: 9 September 2014 / Published: 18 September 2014
Cited by 3 | PDF Full-text (672 KB) | HTML Full-text | XML Full-text
Abstract
A facile synthetic route of rivaroxaban has been developed. Using commercially available (R)-epichlorohydrin and bromobenzene as the starting materials, rivaroxaban was obtained in 39% overall yield using a Goldberg coupling as the key step. The synthetic route represents a convenient procedure
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A facile synthetic route of rivaroxaban has been developed. Using commercially available (R)-epichlorohydrin and bromobenzene as the starting materials, rivaroxaban was obtained in 39% overall yield using a Goldberg coupling as the key step. The synthetic route represents a convenient procedure for the production of rivaroxaban. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Synthesis and Biological Evaluation of New 1,3-Thiazolidine-4-one Derivatives of 2-(4-Isobutylphenyl)propionic Acid
Molecules 2014, 19(9), 15005-15025; doi:10.3390/molecules190915005
Received: 3 July 2014 / Revised: 21 August 2014 / Accepted: 10 September 2014 / Published: 18 September 2014
Cited by 3 | PDF Full-text (785 KB) | HTML Full-text | XML Full-text
Abstract
New thiazolidine-4-one derivatives of 2-(4-isobutylphenyl)propionic acid (ibuprofen) have been synthesized as potential anti-inflammatory drugs. The structure of the new compounds was proved using spectral methods (FR-IR, 1H-NMR, 13C-NMR, MS). The in vitro antioxidant potential of the synthesized compounds was evaluated according
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New thiazolidine-4-one derivatives of 2-(4-isobutylphenyl)propionic acid (ibuprofen) have been synthesized as potential anti-inflammatory drugs. The structure of the new compounds was proved using spectral methods (FR-IR, 1H-NMR, 13C-NMR, MS). The in vitro antioxidant potential of the synthesized compounds was evaluated according to the total antioxidant activity, the DPPH and ABTS radical scavenging assays. Reactive oxygen species (ROS) and free radicals are considered to be involved in many pathological events like diabetes mellitus, neurodegenerative diseases, cancer, infections and more recently, in inflammation. It is known that overproduction of free radicals may initiate and amplify the inflammatory process via upregulation of genes involved in the production of proinflammatory cytokines and adhesion molecules. The chemical modulation of acyl hydrazones of ibuprofen 3al through cyclization to the corresponding thiazolidine-4-ones 4an led to increased antioxidant potential, as all thiazolidine-4-ones were more active than their parent acyl hydrazones and also ibuprofen. The most active compounds are the thiazolidine-4-ones 4e, m, which showed the highest DPPH radical scavenging ability, their activity being comparable with vitamin E. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Photochemistry and Radical Chemistry under Low Intensity Visible Light Sources: Application to Photopolymerization Reactions
Molecules 2014, 19(9), 15026-15041; doi:10.3390/molecules190915026
Received: 28 July 2014 / Revised: 9 September 2014 / Accepted: 12 September 2014 / Published: 18 September 2014
Cited by 3 | PDF Full-text (1382 KB) | HTML Full-text | XML Full-text
Abstract
The search for radical initiators able to work under soft conditions is a great challenge, driven by the fact that the use of safe and cheap light sources is very attractive. In the present paper, a review of some recently reported photoinitiating systems
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The search for radical initiators able to work under soft conditions is a great challenge, driven by the fact that the use of safe and cheap light sources is very attractive. In the present paper, a review of some recently reported photoinitiating systems for polymerization under soft conditions is provided. Different approaches based on multi-component systems (e.g., photoredox catalysis) or light harvesting photoinitiators are described and discussed. The chemical mechanisms associated with the production of free radicals usable as initiating species or mediators of cations are reported. Full article
(This article belongs to the Special Issue Free Radicals and Radical Ions)
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Open AccessArticle Rapid Identification of Coumarins from Micromelum falcatum by UPLC-HRMS/MS and Targeted Isolation of Three New Derivatives
Molecules 2014, 19(9), 15042-15057; doi:10.3390/molecules190915042
Received: 13 July 2014 / Revised: 8 September 2014 / Accepted: 9 September 2014 / Published: 19 September 2014
Cited by 1 | PDF Full-text (1578 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Micromelum falcatum, a medicinal plant of the Rutaceae family, has been used in the Traditional Chinese Medicine (TCM) mainly against colds and rheumatoid arthritis. Despite its traditional use the association of its constituents with possible anti-inflammatory activity has not been explored. During
[...] Read more.
Micromelum falcatum, a medicinal plant of the Rutaceae family, has been used in the Traditional Chinese Medicine (TCM) mainly against colds and rheumatoid arthritis. Despite its traditional use the association of its constituents with possible anti-inflammatory activity has not been explored. During this study, a rapid UPLC-ESI(+)-HRMS method was developed for the profiling of M. falcatum leave extracts and the targeted isolation of coumarin constituents. Based on chromatographic, spectroscopic and spectrometric features several 7-oxygenated coumarin derivatives were detected. After targeted isolation, eight coumarins, among them three new natural products, namely microfalcrin, microcoumaririn and micromelosidester, were purified using semi-preparative HPLC and unambiguously identified by 1 and 2D NMR. Furthermore, important spectrometric characteristics were revealed based on the HRMS and HRMS/MS spectra of the isolated 7-oxygenated coumarins facilitating their identification in complex mixtures. Finally, the anti-inflammatory properties of the extracts and representative compounds were evaluated by measuring the inhibition of the pro-inflammatory mediator NF-κB induction and nitric oxide (NO) production. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle The Plant Decapeptide OSIP108 Can Alleviate Mitochondrial Dysfunction Induced by Cisplatin in Human Cells
Molecules 2014, 19(9), 15088-15102; doi:10.3390/molecules190915088
Received: 11 July 2014 / Revised: 10 September 2014 / Accepted: 11 September 2014 / Published: 19 September 2014
Cited by 2 | PDF Full-text (1182 KB) | HTML Full-text | XML Full-text
Abstract
We investigated the effect of the Arabidopsis thaliana-derived decapeptide OSIP108 on human cell tolerance to the chemotherapeutic agent cisplatin (Cp), which induces apoptosis and mitochondrial dysfunction. We found that OSIP108 increases the tolerance of HepG2 cells to Cp and prevents Cp-induced changes in
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We investigated the effect of the Arabidopsis thaliana-derived decapeptide OSIP108 on human cell tolerance to the chemotherapeutic agent cisplatin (Cp), which induces apoptosis and mitochondrial dysfunction. We found that OSIP108 increases the tolerance of HepG2 cells to Cp and prevents Cp-induced changes in basic cellular metabolism. More specifically, we demonstrate that OSIP108 reduces Cp-induced inhibition of respiration, decreases glycolysis and prevents Cp-uptake in HepG2 cells. Apart from its protective action against Cp in human cells, OSIP108 also increases the yeast Saccharomyces cerevisiae tolerance to Cp. A limited yeast-based study of OSIP108 analogs showed that cyclization does not severely affect its activity, which was further confirmed in HepG2 cells. Furthermore, the similarity in the activity of the D-stereoisomer (mirror image) form of OSIP108 with the L-stereoisomer suggests that its mode of action does not involve binding to a stereospecific receptor. In addition, as OSIP108 decreases Cp uptake in HepG2 cells and the anti-Cp activity of OSIP108 analogs without free cysteine is reduced, OSIP108 seems to protect against Cp-induced toxicity only partly via complexation. Taken together, our data indicate that OSIP108 and its cyclic derivatives can protect against Cp-induced toxicity and, thus, show potential as treatment options for mitochondrial dysfunction- and apoptosis-related conditions. Full article
(This article belongs to the Special Issue Peptide Chemistry)
Open AccessArticle LC-ESI-MS/MS Analysis and Pharmacokinetics of Plantainoside D Isolated from Chirita longgangensis var. hongyao, a Potential Anti-Hypertensive Active Component in Rats
Molecules 2014, 19(9), 15103-15115; doi:10.3390/molecules190915103
Received: 17 July 2014 / Revised: 4 September 2014 / Accepted: 4 September 2014 / Published: 22 September 2014
PDF Full-text (1231 KB) | HTML Full-text | XML Full-text
Abstract
Plantainoside D (PD) is a potential anti-hypertensive active ingredient newly isolated from the dried plants of Chirita longgangensis var. hongyao. A sensitive and specific LC-ESI-MS/MS method was first developed and validated for the analysis of PD in rat plasma using genistein as
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Plantainoside D (PD) is a potential anti-hypertensive active ingredient newly isolated from the dried plants of Chirita longgangensis var. hongyao. A sensitive and specific LC-ESI-MS/MS method was first developed and validated for the analysis of PD in rat plasma using genistein as the internal standard (IS). The plasma samples were pretreated with methanol-acetonitrile (50:50, v/v) to precipitate protein, and then chromatographed on a reverse-phase Agilent Zorbax XDB C18 column (50 mm × 2.1 mm, 3.5 μm). Gradient elution was utilized, with a mobile phase consisting of water and acetonitrile both containing 0.1% formic acid, and the flow rate was set at 0.50 mL/min. The analytes were monitored by tandem-mass spectrometry with negative electrospray ionization. The precursor/product transitions (m/z) in the negative ion mode were 639.2 → 160.9 Thomson (Th) and 268.9 → 158.9 Thomson (Th) for PD and IS, respectively. Linearity was achieved in the 0.10–200 ng/mL range, with a lower limit of quantification of 0.10 ng/mL. The precision and accuracy for both intra- and inter-day determination of the analyte were all within ±15%. The present method has been applied for pharmacokinetic study of PD after oral and intravenous administration in rats. The oral absolute bioavailability (F) of PD in rats was estimated to be 1.12% ± 0.46% with an elimination half-life (t1/2) value of 1.63 ± 0.19 h, suggesting its poor absorption and/or strong metabolism in vivo. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Comparative Studies on Polyphenolic Composition, Antioxidant and Antimicrobial Activities of Schisandra chinensis Leaves and Fruits
Molecules 2014, 19(9), 15162-15179; doi:10.3390/molecules190915162
Received: 30 July 2014 / Revised: 12 September 2014 / Accepted: 12 September 2014 / Published: 22 September 2014
Cited by 20 | PDF Full-text (808 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this paper was to evaluate the antioxidant and antimicrobial activities and the polyphenolic content of Schisandra chinensis (Turcz.) Baill. leaves and fruits. The leaves are an important source of flavonoids (35.10 ± 1.23 mg RE/g plant material). Qualitative and quantitative
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The aim of this paper was to evaluate the antioxidant and antimicrobial activities and the polyphenolic content of Schisandra chinensis (Turcz.) Baill. leaves and fruits. The leaves are an important source of flavonoids (35.10 ± 1.23 mg RE/g plant material). Qualitative and quantitative analyses of the polyphenolic compounds were achieved using a HPLC-UV-MS method. The main flavonoid from the leaves was isoquercitrin (2486.18 ± 5.72 μg/g plant material), followed by quercitrin (1645.14 ± 2.12 μg/g plant material). Regarding the fruit composition, the dominant compound there was rutin (13.02 ± 0.21 μg/g plant material), but comparing with the leaves, fruits can be considered a poor source of phenolic compounds. The antioxidant activity was evaluated by DPPH, TEAC, hemoglobin ascorbate peroxidase activity inhibition (HAPX), inhibition of lipid peroxidation catalyzed by cytochrome c and EPR spectroscopic assays, revealing a better antioxidant activity for the S. chinensis leaves extract. In the antimicrobial assay, S. chinensis leaves extract showed efficient activities against the targeted bacteria, being more active than the fruits extract. The results suggest the leaves of S. chinensis as a valuable source of antioxidant compounds with significant antioxidant activity. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis, Leishmanicidal Activity and Theoretical Evaluations of a Series of Substituted bis-2-Hydroxy-1,4-Naphthoquinones
Molecules 2014, 19(9), 15180-15195; doi:10.3390/molecules190915180
Received: 8 August 2014 / Revised: 29 August 2014 / Accepted: 9 September 2014 / Published: 22 September 2014
Cited by 4 | PDF Full-text (963 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of eight substituted bis-2-hydroxy-1,4-naphthoquinone derivatives was synthesized through lawsone condensation with various aromatic and aliphatic aldehydes under mild acidic conditions. The title compounds were evaluated for antileishmanial activity in vitro against Leishmania amazonensis and Leishmania braziliensis promastigotes; six compounds showed good
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A series of eight substituted bis-2-hydroxy-1,4-naphthoquinone derivatives was synthesized through lawsone condensation with various aromatic and aliphatic aldehydes under mild acidic conditions. The title compounds were evaluated for antileishmanial activity in vitro against Leishmania amazonensis and Leishmania braziliensis promastigotes; six compounds showed good activity without significant toxic effects. The compound with the highest activity was used for an in vivo assay with Leishmania amazonensis. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Antioxidant Effects of Grape Vine Cane Extracts from Different Chinese Grape Varieties on Edible Oils
Molecules 2014, 19(9), 15213-15223; doi:10.3390/molecules190915213
Received: 23 July 2014 / Revised: 11 September 2014 / Accepted: 17 September 2014 / Published: 23 September 2014
Cited by 2 | PDF Full-text (712 KB) | HTML Full-text | XML Full-text
Abstract
This study involved the determination of the peroxide value (POV) as a measure of the resistance of the oxidation of edible oil with grape vine cane additives to assess their antioxidation potential. The study demonstrated that grape extracts of canes could effectively inhibit
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This study involved the determination of the peroxide value (POV) as a measure of the resistance of the oxidation of edible oil with grape vine cane additives to assess their antioxidation potential. The study demonstrated that grape extracts of canes could effectively inhibit the lipid oxidation of edible oils and that this ability varied significantly due to the different extraction solvents employed, as well as to the different varieties of canes used. Lipid oxidation of edible oils was significantly reduced under an accelerated storage condition of 70 ± 1 °C in the presence of Vitamin C (VC), which was chosen as a synergist of grape vine cane extract. A 4:1 ratio of Victoria Blanc-ethyl acetate fraction (EAF) and VC led to a significant lowering of the peroxide value and indicated a better antioxidant effect. Thus, these results indicated that some varieties of grape vine cane extracts could be applied as natural antioxidants for elevation of the quality of edible oils in the food industry. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Regulatory Effect of Astragalus Polysaccharides on Intestinal Intraepithelial γδT Cells of Tumor Bearing Mice
Molecules 2014, 19(9), 15224-15236; doi:10.3390/molecules190915224
Received: 11 August 2014 / Revised: 11 September 2014 / Accepted: 18 September 2014 / Published: 23 September 2014
Cited by 7 | PDF Full-text (851 KB) | HTML Full-text | XML Full-text
Abstract
Astragalus polysaccharides (APS) possess multiple immunomodulatory activities. Due to its high molecular weight, orally administration of APS is not easily absorbed into the blood stream, and how APS exerts its capacity in vivo is still not well elucidated. We assume that enteric mucosal
[...] Read more.
Astragalus polysaccharides (APS) possess multiple immunomodulatory activities. Due to its high molecular weight, orally administration of APS is not easily absorbed into the blood stream, and how APS exerts its capacity in vivo is still not well elucidated. We assume that enteric mucosal immune response might trigger the immune regulation of APS, and our previous studies demonstrated that APS had regulatory activity on intraepithelial lymphocytes (IELs). Therefore, this study aimed to investigate the functions of APS on intestinal intraepithelial γδT cells, a major subset in IELs and an essential component of maintaining homeostasis and immune regulation in enteric mucosa. Results showed that APS could promote proliferation and function of intestinal intraepithelial γδT cells in vitro, the IFN-γ, FasL and GrB mRNA levels in γδT cells were all significantly increased. Moreover, APS also improved the activity of intestinal intraepithelial γδT cells in vivo, as cytokines production and cytotoxicity of γδT cells were all remarkably improved in tumor-bearing mice treated with APS. In addition, the levels of TNF-α and IFN-γ were significantly increased, whereas the levels of IL-10 and TGF-β were significantly decreased in tumor-bearing mice treated with APS. In conclusion, this study demonstrated that APS could improve proliferation and function of intestinal intraepithelial γδT cells, which might an important pathway for immunomodulation of APS in cancer therapy. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Several Human Cyclin-Dependent Kinase Inhibitors, Structurally Related to Roscovitine, As New Anti-Malarial Agents
Molecules 2014, 19(9), 15237-15257; doi:10.3390/molecules190915237
Received: 31 July 2014 / Revised: 8 September 2014 / Accepted: 11 September 2014 / Published: 23 September 2014
Cited by 7 | PDF Full-text (877 KB) | HTML Full-text | XML Full-text
Abstract
In Africa, malaria kills one child each minute. It is also responsible for about one million deaths worldwide each year. Plasmodium falciparum, is the protozoan responsible for the most lethal form of the disease, with resistance developing against the available anti-malarial drugs.
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In Africa, malaria kills one child each minute. It is also responsible for about one million deaths worldwide each year. Plasmodium falciparum, is the protozoan responsible for the most lethal form of the disease, with resistance developing against the available anti-malarial drugs. Among newly proposed anti-malaria targets, are the P. falciparum cyclin-dependent kinases (PfCDKs). There are involved in different stages of the protozoan growth and development but share high sequence homology with human cyclin-dependent kinases (CDKs). We previously reported the synthesis of CDKs inhibitors that are structurally-related to (R)-roscovitine, a 2,6,9-trisubstituted purine, and they showed activity against neuronal diseases and cancers. In this report, we describe the synthesis and the characterization of new CDK inhibitors, active in reducing the in vitro growth of P. falciparum (3D7 and 7G8 strains). Six compounds are more potent inhibitors than roscovitine, and three exhibited IC50 values close to 1 µM for both 3D7 and 7G8 strains. Although, such molecules do inhibit P. falciparum growth, they require further studies to improve their selectivity for PfCDKs. Full article
(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)
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Open AccessArticle Electrochemistry of the Self-Assembled Monolayers of Dyads Consisting of Tripod-Shaped Trithiol and Bithiophene on Gold
Molecules 2014, 19(9), 15298-15313; doi:10.3390/molecules190915298
Received: 11 August 2014 / Revised: 2 September 2014 / Accepted: 17 September 2014 / Published: 24 September 2014
Cited by 2 | PDF Full-text (1165 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Self-assembled monolayers (SAMs) of tripod-shaped trithiols, consisting of an adamantane core with three CH2SH legs and a bithiophene group, were prepared on a Au(111) surface. Adsorption in a tripod-like fashion was supported by polarization modulation-infrared reflection absorption spectroscopy (PM-IRRAS) of the
[...] Read more.
Self-assembled monolayers (SAMs) of tripod-shaped trithiols, consisting of an adamantane core with three CH2SH legs and a bithiophene group, were prepared on a Au(111) surface. Adsorption in a tripod-like fashion was supported by polarization modulation-infrared reflection absorption spectroscopy (PM-IRRAS) of the SAMs, which indicated the absence of free SH groups. Cyclic voltammetry showed an irreversible cathodic wave due to reductive desorption. The SAM also showed an anodic wave due to the single-electron oxidation of the bithiophene moiety without concomitant desorption of the molecules. Although oxidation was irreversible in the absence of a protecting group, it became reversible with the introduction of a terminal phenyl group. The charge of the oxidation was one-third that of the reductive desorption, confirming a three-point adsorption. The surface coverage was ca. 50% of that expected for the anti bithiophene conformation, which suggested that an increase in the surface area per molecule had been caused by the presence of an energetically high-lying syn conformer. In accordance with this, the line shape of the oxidation wave suggested an electrostatic repulsive interaction between neighboring molecules. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Hydrogenations without Hydrogen: Titania Photocatalyzed Reductions of Maleimides and Aldehydes
Molecules 2014, 19(9), 15324-15338; doi:10.3390/molecules190915324
Received: 20 August 2014 / Revised: 16 September 2014 / Accepted: 17 September 2014 / Published: 24 September 2014
Cited by 4 | PDF Full-text (825 KB) | HTML Full-text | XML Full-text
Abstract
A mild procedure for the reduction of electron-deficient alkenes and carbonyl compounds is described. UVA irradiations of substituted maleimides with dispersions of titania (Aeroxide P25) in methanol/acetonitrile (1:9) solvent under dry anoxic conditions led to hydrogenation and production of the corresponding succinimides. Aromatic
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A mild procedure for the reduction of electron-deficient alkenes and carbonyl compounds is described. UVA irradiations of substituted maleimides with dispersions of titania (Aeroxide P25) in methanol/acetonitrile (1:9) solvent under dry anoxic conditions led to hydrogenation and production of the corresponding succinimides. Aromatic and heteroaromatic aldehydes were reduced to primary alcohols in similar titania photocatalyzed reactions. A mechanism is proposed which involves two proton-coupled electron transfers to the substrates at the titania surface. Full article
(This article belongs to the Special Issue Free Radicals and Radical Ions)
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Open AccessArticle Surface Properties and Photocatalytic Activity of KTaO3, CdS, MoS2 Semiconductors and Their Binary and Ternary Semiconductor Composites
Molecules 2014, 19(9), 15339-15360; doi:10.3390/molecules190915339
Received: 30 July 2014 / Revised: 27 August 2014 / Accepted: 15 September 2014 / Published: 24 September 2014
Cited by 9 | PDF Full-text (4683 KB) | HTML Full-text | XML Full-text
Abstract
Single semiconductors such as KTaO3, CdS MoS2 or their precursor solutions were combined to form novel binary and ternary semiconductor nanocomposites by the calcination or by the hydro/solvothermal mixed solutions methods, respectively. The aim of this work was to study
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Single semiconductors such as KTaO3, CdS MoS2 or their precursor solutions were combined to form novel binary and ternary semiconductor nanocomposites by the calcination or by the hydro/solvothermal mixed solutions methods, respectively. The aim of this work was to study the influence of preparation method as well as type and amount of the composite components on the surface properties and photocatalytic activity of the new semiconducting photoactive materials. We presented different binary and ternary combinations of the above semiconductors for phenol and toluene photocatalytic degradation and characterized by X-ray powder diffraction (XRD), UV-Vis diffuse reflectance spectroscopy (DRS), scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET) specific surface area and porosity. The results showed that loading MoS2 onto CdS as well as loading CdS onto KTaO3 significantly enhanced absorption properties as compared with single semiconductors. The highest photocatalytic activity in phenol degradation reaction under both UV-Vis and visible light irradiation and very good stability in toluene removal was observed for ternary hybrid obtained by calcination of KTaO3, CdS, MoS2 powders at the 10:5:1 molar ratio. Enhanced photoactivity could be related to the two-photon excitation in KTaO3-CdS-MoS2 composite under UV-Vis and/or to additional presence of CdMoO4 working as co-catalyst. Full article
(This article belongs to the Special Issue Photocatalysis) Print Edition available
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Jump to: Research

Open AccessReview Chemistry of Phosphorylated Formaldehyde Derivatives. Part I
Molecules 2014, 19(9), 12949-13009; doi:10.3390/molecules190912949
Received: 8 July 2014 / Revised: 8 August 2014 / Accepted: 15 August 2014 / Published: 25 August 2014
Cited by 3 | PDF Full-text (981 KB) | HTML Full-text | XML Full-text
Abstract
The underinvestigated derivatives of unstable phosphorylated formaldehyde acetals and some of the structurally related compounds, such as thioacetals, aminonitriles, aminomethylphosphinoyl compounds, are considered. Separately considered are halogen aminals of phosphorylated formaldehyde, acetals of phosphorylated formaldehyde of H-phosphinate-type and a phosphorylated gem-diol of formaldehyde.
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The underinvestigated derivatives of unstable phosphorylated formaldehyde acetals and some of the structurally related compounds, such as thioacetals, aminonitriles, aminomethylphosphinoyl compounds, are considered. Separately considered are halogen aminals of phosphorylated formaldehyde, acetals of phosphorylated formaldehyde of H-phosphinate-type and a phosphorylated gem-diol of formaldehyde. Synthetic methods, chemical properties and examples of practical applications are given. Full article
(This article belongs to the Special Issue Organophosphorus Chemistry)
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Open AccessReview Alkaloids from the Tribe Bocconieae (Papaveraceae): A Chemical and Biological Review
Molecules 2014, 19(9), 13042-13060; doi:10.3390/molecules190913042
Received: 14 May 2014 / Accepted: 20 August 2014 / Published: 25 August 2014
Cited by 7 | PDF Full-text (836 KB) | HTML Full-text | XML Full-text
Abstract
The Bocconieae tribe, consisting of only the genera Macleaya and Bocconia, possesses significant economic and medicinal value and plays an important role in health management for people in developing countries. During the past decades, research on metabolites and relative pharmacology, including the
[...] Read more.
The Bocconieae tribe, consisting of only the genera Macleaya and Bocconia, possesses significant economic and medicinal value and plays an important role in health management for people in developing countries. During the past decades, research on metabolites and relative pharmacology, including the isolation and identification of a variety of molecules, has shed light on the tribe. Among those molecules, isoquinoline alkaloids, and their antimicrobial, antifungal, and anti-inflammatory activities are especially noteworthy. This paper presents a comprehensive compilation of current research progress, with emphasis on the alkaloids and their distribution, phytochemical and pharmacological investigation, toxicity and side effects, related chemotaxonomy and future use prospects, and hopefully provides a valuable reference as an effort to promote further exploration and application of this tribe. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessReview Fermented Broth in Tyrosinase- and Melanogenesis Inhibition
Molecules 2014, 19(9), 13122-13135; doi:10.3390/molecules190913122
Received: 7 July 2014 / Revised: 21 August 2014 / Accepted: 21 August 2014 / Published: 26 August 2014
Cited by 4 | PDF Full-text (772 KB) | HTML Full-text | XML Full-text
Abstract
Fermented broth has a long history of applications in the food, pharmaceutical and cosmetic industries. Recently, the use of fermented broth in skin care products is in ascendance. This review investigates the efficacy of fermented broth in inhibiting tyrosinase and melanogenesis. Possible active
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Fermented broth has a long history of applications in the food, pharmaceutical and cosmetic industries. Recently, the use of fermented broth in skin care products is in ascendance. This review investigates the efficacy of fermented broth in inhibiting tyrosinase and melanogenesis. Possible active ingredients and hypopigmentation mechanisms of fermented broth are discussed, and potential applications of fermented broth in the cosmetic industry are also addressed. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessReview Inhibition of Glutamine Synthetase: A Potential Drug Target in Mycobacterium tuberculosis
Molecules 2014, 19(9), 13161-13176; doi:10.3390/molecules190913161
Received: 4 July 2014 / Revised: 12 August 2014 / Accepted: 18 August 2014 / Published: 26 August 2014
Cited by 6 | PDF Full-text (1660 KB) | HTML Full-text | XML Full-text
Abstract
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. Globally, tuberculosis is second only to AIDS in mortality and the disease is responsible for over 1.3 million deaths each year. The impractically long treatment schedules (generally 6–9 months) and unpleasant side effects
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Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. Globally, tuberculosis is second only to AIDS in mortality and the disease is responsible for over 1.3 million deaths each year. The impractically long treatment schedules (generally 6–9 months) and unpleasant side effects of the current drugs often lead to poor patient compliance, which in turn has resulted in the emergence of multi-, extensively- and totally-drug resistant strains. The development of new classes of anti-tuberculosis drugs and new drug targets is of global importance, since attacking the bacterium using multiple strategies provides the best means to prevent resistance. This review presents an overview of the various strategies and compounds utilized to inhibit glutamine synthetase, a promising target for the development of drugs for TB therapy. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessReview Elicitation: A Tool for Enriching the Bioactive Composition of Foods
Molecules 2014, 19(9), 13541-13563; doi:10.3390/molecules190913541
Received: 26 June 2014 / Revised: 25 August 2014 / Accepted: 26 August 2014 / Published: 1 September 2014
Cited by 23 | PDF Full-text (964 KB) | HTML Full-text | XML Full-text
Abstract
Elicitation is a good strategy to induce physiological changes and stimulate defense or stress-induced responses in plants. The elicitor treatments trigger the synthesis of phytochemical compounds in fruits, vegetables and herbs. These metabolites have been widely investigated as bioactive compounds responsible of plant
[...] Read more.
Elicitation is a good strategy to induce physiological changes and stimulate defense or stress-induced responses in plants. The elicitor treatments trigger the synthesis of phytochemical compounds in fruits, vegetables and herbs. These metabolites have been widely investigated as bioactive compounds responsible of plant cell adaptation to the environment, specific organoleptic properties of foods, and protective effects in human cells against oxidative processes in the development of neurodegenerative and cardiovascular diseases and certain types of cancer. Biotic (biological origin), abiotic (chemical or physical origin) elicitors and phytohormones have been applied alone or in combinations, in hydroponic solutions or sprays, and in different selected time points of the plant growth or during post-harvest. Understanding how plant tissues and their specific secondary metabolic pathways respond to specific treatments with elicitors would be the basis for designing protocols to enhance the production of secondary metabolites, in order to produce quality and healthy fresh foods. Full article
(This article belongs to the Section Natural Products)
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Open AccessReview Natural Insect and Plant Micro-/Nanostructsured Surfaces: An Excellent Selection of Valuable Templates with Superhydrophobic and Self-Cleaning Properties
Molecules 2014, 19(9), 13614-13630; doi:10.3390/molecules190913614
Received: 15 July 2014 / Revised: 15 August 2014 / Accepted: 18 August 2014 / Published: 2 September 2014
Cited by 6 | PDF Full-text (6115 KB) | HTML Full-text | XML Full-text
Abstract
Insects and plants are two types of organisms that are widely separated on the evolutionary tree; for example, plants are mostly phototrophic organisms whilst insects are heterotrophic organisms. In order to cope with environmental stresses, their surfaces have developed cuticular layers that consist
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Insects and plants are two types of organisms that are widely separated on the evolutionary tree; for example, plants are mostly phototrophic organisms whilst insects are heterotrophic organisms. In order to cope with environmental stresses, their surfaces have developed cuticular layers that consist of highly sophisticated structures. These structures serve a number of purposes, and impart useful properties to these surfaces. These two groups of organisms are the only ones identified thus far that possess truly superhydrophobic and self-cleaning properties. These properties result from their micro- and nano-scale structures, comprised of three-dimensional wax formations. This review analyzes the surface topologies and surface chemistry of insects and plants in order to identify the features common to both organisms, with particular reference to their superhydrophobic and self-cleaning properties. This information will be valuable when determining the potential application of these surfaces in the design and manufacture of superhydrophobic and self-cleaning devices, including those that can be used in the manufacture of biomedical implants. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessReview 1H-NMR as a Structural and Analytical Tool of Intra- and Intermolecular Hydrogen Bonds of Phenol-Containing Natural Products and Model Compounds
Molecules 2014, 19(9), 13643-13682; doi:10.3390/molecules190913643
Received: 30 June 2014 / Revised: 20 August 2014 / Accepted: 21 August 2014 / Published: 2 September 2014
Cited by 16 | PDF Full-text (7867 KB) | XML Full-text
Abstract
Experimental parameters that influence the resolution of 1H-NMR phenol OH signals are critically evaluated with emphasis on the effects of pH, temperature and nature of the solvents. Extremely sharp peaks (Δν1/2 ≤ 2 Hz) can be obtained under optimized experimental conditions
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Experimental parameters that influence the resolution of 1H-NMR phenol OH signals are critically evaluated with emphasis on the effects of pH, temperature and nature of the solvents. Extremely sharp peaks (Δν1/2 ≤ 2 Hz) can be obtained under optimized experimental conditions which allow the application of 1H-13C HMBC-NMR experiments to reveal long range coupling constants of hydroxyl protons and, thus, to provide unequivocal assignment of the OH signals even in cases of complex polyphenol natural products. Intramolecular and intermolecular hydrogen bonds have a very significant effect on 1H OH chemical shifts which cover a region from 4.5 up to 19 ppm. Solvent effects on –OH proton chemical shifts, temperature coefficients (Δδ/ΔT), OH diffusion coefficients, and nJ(13C, O1H) coupling constants are evaluated as indicators of hydrogen bonding and solvation state of phenol –OH groups. Accurate 1H chemical shifts of the OH groups can be calculated using a combination of DFT and discrete solute-solvent hydrogen bond interaction at relatively inexpensive levels of theory, namely, DFT/B3LYP/6-311++G (2d,p). Excellent correlations between experimental 1H chemical shifts and those calculated at the ab initio level can provide a method of primary interest in order to obtain structural and conformational description of solute-solvent interactions at a molecular level. The use of the high resolution phenol hydroxyl group 1H-NMR spectral region provides a general method for the analysis of complex plant extracts without the need for the isolation of the individual components. Full article
(This article belongs to the Special Issue Intramolecular Hydrogen Bonding)
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Open AccessReview Recent Advances in Chemoenzymatic Peptide Syntheses
Molecules 2014, 19(9), 13755-13774; doi:10.3390/molecules190913755
Received: 31 July 2014 / Revised: 24 August 2014 / Accepted: 26 August 2014 / Published: 3 September 2014
Cited by 13 | PDF Full-text (1667 KB) | HTML Full-text | XML Full-text
Abstract
Chemoenzymatic peptide synthesis is the hydrolase-catalyzed stereoselective formation of peptide bonds. It is a clean and mild procedure, unlike conventional chemical synthesis, which involves complicated and laborious protection-deprotection procedures and harsh reaction conditions. The chemoenzymatic approach has been utilized for several decades because
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Chemoenzymatic peptide synthesis is the hydrolase-catalyzed stereoselective formation of peptide bonds. It is a clean and mild procedure, unlike conventional chemical synthesis, which involves complicated and laborious protection-deprotection procedures and harsh reaction conditions. The chemoenzymatic approach has been utilized for several decades because determining the optimal conditions for conventional synthesis is often time-consuming. The synthesis of poly- and oligopeptides comprising various amino acids longer than a dipeptide continues to pose a challenge owing to the lack of knowledge about enzymatic mechanisms and owing to difficulty in optimizing the pH, temperature, and other reaction conditions. These drawbacks limit the applications of the chemoenzymatic approach. Recently, a variety of enzymes and substrates produced using recombinant techniques, substrate mimetics, and optimal reaction conditions (e.g., frozen aqueous media and ionic liquids) have broadened the scope of chemoenzymatic peptide syntheses. In this review, we highlight the recent advances in the chemoenzymatic syntheses of various peptides and their use in developing new materials and biomedical applications. Full article
(This article belongs to the Special Issue Peptide Chemistry)
Open AccessReview Cycloaddition of 1,3-Butadiynes: Efficient Synthesis of Carbo- and Heterocycles
Molecules 2014, 19(9), 13788-13802; doi:10.3390/molecules190913788
Received: 31 July 2014 / Revised: 26 August 2014 / Accepted: 29 August 2014 / Published: 3 September 2014
Cited by 4 | PDF Full-text (760 KB) | HTML Full-text | XML Full-text
Abstract
Cycloaddition reactions of alkynes are elegant, atom-efficient transformations for the synthesis of carbo- and heterocycles, mostly aromatic, involving the construction of challenging skeletons of complex molecules. Therefore significant efforts have recently been devoted to the development of novel methodologies, efficient strategies and different
[...] Read more.
Cycloaddition reactions of alkynes are elegant, atom-efficient transformations for the synthesis of carbo- and heterocycles, mostly aromatic, involving the construction of challenging skeletons of complex molecules. Therefore significant efforts have recently been devoted to the development of novel methodologies, efficient strategies and different catalytic systems to broaden the scope of these reactions. We summarize in this review the recent advances in the cycloaddition reactions of 1,3-butadiynes to provide facile and reliable approaches to various functionalized carbo- and heterocycles. Full article
(This article belongs to the Special Issue Cycloaddition Chemistry)
Open AccessReview Molecular Processes Studied at a Single-Molecule Level Using DNA Origami Nanostructures and Atomic Force Microscopy
Molecules 2014, 19(9), 13803-13823; doi:10.3390/molecules190913803
Received: 23 July 2014 / Revised: 21 August 2014 / Accepted: 29 August 2014 / Published: 3 September 2014
Cited by 10 | PDF Full-text (14040 KB) | HTML Full-text | XML Full-text
Abstract
DNA origami nanostructures allow for the arrangement of different functionalities such as proteins, specific DNA structures, nanoparticles, and various chemical modifications with unprecedented precision. The arranged functional entities can be visualized by atomic force microscopy (AFM) which enables the study of molecular processes
[...] Read more.
DNA origami nanostructures allow for the arrangement of different functionalities such as proteins, specific DNA structures, nanoparticles, and various chemical modifications with unprecedented precision. The arranged functional entities can be visualized by atomic force microscopy (AFM) which enables the study of molecular processes at a single-molecular level. Examples comprise the investigation of chemical reactions, electron-induced bond breaking, enzymatic binding and cleavage events, and conformational transitions in DNA. In this paper, we provide an overview of the advances achieved in the field of single-molecule investigations by applying atomic force microscopy to functionalized DNA origami substrates. Full article
(This article belongs to the Special Issue Single Molecule Techniques)
Open AccessReview Tyrosine Kinase Inhibitors as Reversal Agents for ABC Transporter Mediated Drug Resistance
Molecules 2014, 19(9), 13848-13877; doi:10.3390/molecules190913848
Received: 31 July 2014 / Revised: 25 August 2014 / Accepted: 29 August 2014 / Published: 4 September 2014
Cited by 23 | PDF Full-text (1141 KB) | HTML Full-text | XML Full-text
Abstract
Tyrosine kinases (TKs) play an important role in pathways that regulate cancer cell proliferation, apoptosis, angiogenesis and metastasis. Aberrant activity of TKs has been implicated in several types of cancers. In recent years, tyrosine kinase inhibitors (TKIs) have been developed to interfere with
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Tyrosine kinases (TKs) play an important role in pathways that regulate cancer cell proliferation, apoptosis, angiogenesis and metastasis. Aberrant activity of TKs has been implicated in several types of cancers. In recent years, tyrosine kinase inhibitors (TKIs) have been developed to interfere with the activity of deregulated kinases. These TKIs are remarkably effective in the treatment of various human cancers including head and neck, gastric, prostate and breast cancer and several types of leukemia. However, these TKIs are transported out of the cell by ATP-binding cassette (ABC) transporters, resulting in development of a characteristic drug resistance phenotype in cancer patients. Interestingly, some of these TKIs also inhibit the ABC transporter mediated multi drug resistance (MDR) thereby; enhancing the efficacy of conventional chemotherapeutic drugs. This review discusses the clinically relevant TKIs and their interaction with ABC drug transporters in modulating MDR. Full article
(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)
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Open AccessReview Protein Expression Analyses at the Single Cell Level
Molecules 2014, 19(9), 13932-13947; doi:10.3390/molecules190913932
Received: 30 June 2014 / Revised: 13 August 2014 / Accepted: 29 August 2014 / Published: 5 September 2014
Cited by 3 | PDF Full-text (2164 KB) | HTML Full-text | XML Full-text
Abstract
The central dogma of molecular biology explains how genetic information is converted into its end product, proteins, which are responsible for the phenotypic state of the cell. Along with the protein type, the phenotypic state depends on the protein copy number. Therefore, quantification
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The central dogma of molecular biology explains how genetic information is converted into its end product, proteins, which are responsible for the phenotypic state of the cell. Along with the protein type, the phenotypic state depends on the protein copy number. Therefore, quantification of the protein expression in a single cell is critical for quantitative characterization of the phenotypic states. Protein expression is typically a dynamic and stochastic phenomenon that cannot be well described by standard experimental methods. As an alternative, fluorescence imaging is being explored for the study of protein expression, because of its high sensitivity and high throughput. Here we review key recent progresses in fluorescence imaging-based methods and discuss their application to proteome analysis at the single cell level. Full article
(This article belongs to the Special Issue Single Molecule Techniques)
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Open AccessReview Sorcin, a Calcium Binding Protein Involved in the Multidrug Resistance Mechanisms in Cancer Cells
Molecules 2014, 19(9), 13976-13989; doi:10.3390/molecules190913976
Received: 19 August 2014 / Revised: 27 August 2014 / Accepted: 28 August 2014 / Published: 5 September 2014
Cited by 8 | PDF Full-text (2616 KB) | HTML Full-text | XML Full-text
Abstract
Sorcin is a penta-EF hand calcium binding protein, which participates in the regulation of calcium homeostasis in cells. Sorcin regulates calcium channels and exchangers located at the plasma membrane and at the endo/sarcoplasmic reticulum (ER/SR), and allows high levels of calcium in the
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Sorcin is a penta-EF hand calcium binding protein, which participates in the regulation of calcium homeostasis in cells. Sorcin regulates calcium channels and exchangers located at the plasma membrane and at the endo/sarcoplasmic reticulum (ER/SR), and allows high levels of calcium in the ER to be maintained, preventing ER stress and possibly, the unfolded protein response. Sorcin is highly expressed in the heart and in the brain, and overexpressed in many cancer cells. Sorcin gene is in the same amplicon as other genes involved in the resistance to chemotherapeutics in cancer cells (multi-drug resistance, MDR) such as ABCB4 and ABCB1; its overexpression results in increased drug resistance to a number of chemotherapeutic agents, and inhibition of sorcin expression by sorcin-targeting RNA interference leads to reversal of drug resistance. Sorcin is increasingly considered a useful marker of MDR and may represent a therapeutic target for reversing tumor multidrug resistance. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessReview Inclusion and Functionalization of Polymers with Cyclodextrins: Current Applications and Future Prospects
Molecules 2014, 19(9), 14066-14079; doi:10.3390/molecules190914066
Received: 18 July 2014 / Revised: 27 August 2014 / Accepted: 2 September 2014 / Published: 9 September 2014
Cited by 13 | PDF Full-text (1802 KB) | HTML Full-text | XML Full-text
Abstract
The numerous hydroxyl groups available in cyclodextrins are active sites that can form different types of linkages. They can be crosslinked with one another, or they can be derivatized to produce monomers that can form linear or branched networks. Moreover, they can form
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The numerous hydroxyl groups available in cyclodextrins are active sites that can form different types of linkages. They can be crosslinked with one another, or they can be derivatized to produce monomers that can form linear or branched networks. Moreover, they can form inclusion complexes with polymers and different substrates, modifying their physicochemical properties. This review shows the different applications using polymers with cyclodextrins, either by forming inclusion complexes, ternary complexes, networks, or molecularly imprinted polymers (MIPs). On one hand, the use of cyclodextrins enhances the properties of each polymer, and on the other the use of polymers decreases the amount of cyclodextrins required in different formulations. Both cyclodextrins and polymers contribute synergistically in several applications such as pharmacological, nutritional, environmental, and other industrial fields. The use of polymers based on cyclodextrins is a low cost easy to use potential tool with great future prospects. Full article
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Open AccessReview 20 Years of Fatty Acid Analysis by Capillary Electrophoresis
Molecules 2014, 19(9), 14094-14113; doi:10.3390/molecules190914094
Received: 5 February 2014 / Revised: 7 August 2014 / Accepted: 25 August 2014 / Published: 9 September 2014
Cited by 9 | PDF Full-text (830 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A review taking into account the literature reports covering 20 years of fatty acid analysis by capillary electrophoresis is presented. This paper describes the evolution of fatty acid analysis using different CE modes such as capillary zone electrophoresis, non-aqueous capillary electrophoresis, micellar electrokinetic
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A review taking into account the literature reports covering 20 years of fatty acid analysis by capillary electrophoresis is presented. This paper describes the evolution of fatty acid analysis using different CE modes such as capillary zone electrophoresis, non-aqueous capillary electrophoresis, micellar electrokinetic capillary chromatography and microemulsion electrokinetic chromatography employing different detection systems, such as ultraviolet-visible, capacitively coupled contactless conductivity, laser-induced fluorescence and mass spectrometry. In summary, the present review signals that CE seems to be an interesting analytical separation technique that is very useful for screening analysis or quantification of the usual fatty acids present in different matrices, offering short analysis times and a simple sample preparation step as inherent advantages in comparison with the classical methodology, making it a separation technique that is very attractive for quality control in industry and government agencies. Full article
(This article belongs to the Special Issue Fatty Acids)
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Open AccessReview Inorganic Materials as Supports for Covalent Enzyme Immobilization: Methods and Mechanisms
Molecules 2014, 19(9), 14139-14194; doi:10.3390/molecules190914139
Received: 5 July 2014 / Revised: 9 August 2014 / Accepted: 22 August 2014 / Published: 9 September 2014
Cited by 45 | PDF Full-text (1733 KB) | HTML Full-text | XML Full-text
Abstract
Several inorganic materials are potentially suitable for enzymatic covalent immobilization, by means of several different techniques. Such materials must meet stringent criteria to be suitable as solid matrices: complete insolubility in water, reasonable mechanical strength and chemical resistance under the operational conditions, the
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Several inorganic materials are potentially suitable for enzymatic covalent immobilization, by means of several different techniques. Such materials must meet stringent criteria to be suitable as solid matrices: complete insolubility in water, reasonable mechanical strength and chemical resistance under the operational conditions, the capability to form manageable particles with high surface area, reactivity towards derivatizing/functionalizing agents. Non-specific protein adsorption should be always considered when planning covalent immobilization on inorganic solids. A huge mass of experimental work has shown that silica, silicates, borosilicates and aluminosilicates, alumina, titania, and other oxides, are the materials of choice when attempting enzyme immobilizations on inorganic supports. More recently, some forms of elemental carbon, silicon, and certain metals have been also proposed for certain applications. With regard to the derivatization/functionalization techniques, the use of organosilanes through silanization is undoubtedly the most studied and the most applied, although inorganic bridge formation and acylation with selected acyl halides have been deeply studied. In the present article, the most common inorganic supports for covalent immobilization of the enzymes are reviewed, with particular focus on their advantages and disadvantages in terms of enzyme loadings, operational stability, undesired adsorption, and costs. Mechanisms and methods for covalent immobilization are also discussed, focusing on the most widespread activating approaches (such as glutaraldehyde, cyanogen bromide, divinylsulfone, carbodiimides, carbonyldiimidazole, sulfonyl chlorides, chlorocarbonates, N-hydroxysuccinimides). Full article
(This article belongs to the Special Issue Enzyme Immobilization)
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Open AccessReview Inhibition of the PI3K/Akt/mTOR Signaling Pathway in Diffuse Large B-Cell Lymphoma: Current Knowledge and Clinical Significance
Molecules 2014, 19(9), 14304-14315; doi:10.3390/molecules190914304
Received: 22 July 2014 / Revised: 3 September 2014 / Accepted: 9 September 2014 / Published: 11 September 2014
Cited by 13 | PDF Full-text (1133 KB) | HTML Full-text | XML Full-text
Abstract
Diffuse large B-cell lymphoma (DLBCL) is one of the most common non-Hodgkin lymphomas in adults. The disease is very heterogeneous in its presentation, that is DLBCL patients may differ from each other not only in regard to histology of tissue infiltration, clinical course
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Diffuse large B-cell lymphoma (DLBCL) is one of the most common non-Hodgkin lymphomas in adults. The disease is very heterogeneous in its presentation, that is DLBCL patients may differ from each other not only in regard to histology of tissue infiltration, clinical course or response to treatment, but also in respect to diversity in gene expression profiling. A growing body of knowledge on the biology of DLBCL, including abnormalities in intracellular signaling, has allowed the development of new treatment strategies, specifically directed against lymphoma cells. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway plays an important role in controlling proliferation and survival of tumor cells in various types of malignancies, including DLBCL, and therefore it may be a promising target for therapeutic intervention. Currently, novel anticancer drugs are undergoing assessment in different phases of clinical trials in aggressive lymphomas, with promising outcomes. In this review we present a state of art review on various classes of small molecule inhibitors selectively involving PI3K/Akt/mTOR pathway and their clinical potential in this disease. Full article
(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)
Open AccessReview Cyclin-Dependent Kinase Inhibitors as Marketed Anticancer Drugs: Where Are We Now? A Short Survey
Molecules 2014, 19(9), 14366-14382; doi:10.3390/molecules190914366
Received: 25 July 2014 / Revised: 26 August 2014 / Accepted: 28 August 2014 / Published: 11 September 2014
Cited by 20 | PDF Full-text (938 KB) | HTML Full-text | XML Full-text
Abstract
In the early 2000s, the anticancer drug imatinib (Glivec®) appeared on the market, exhibiting a new mode of action by selective kinase inhibition. Consequently, kinases became a validated therapeutic target, paving the way for further developments. Although these kinases have been
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In the early 2000s, the anticancer drug imatinib (Glivec®) appeared on the market, exhibiting a new mode of action by selective kinase inhibition. Consequently, kinases became a validated therapeutic target, paving the way for further developments. Although these kinases have been thoroughly studied, none of the compounds commercialized since then target cyclin-dependent kinases (CDKs). Following a recent and detailed review on the subject by Galons et al., we concentrate our attention on an updated list of compounds under clinical evaluation (phase I/II/III) and discuss their mode of action as ATP-competitive inhibitors. CDK inhibition profiles and clinical development stages are reported for the 14 compounds under clinical evaluation. Also, tentative progress for forthcoming potential ATP non-competitive inhibitors and allosteric inhibitors are briefly described, along with their limitations. Full article
(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)
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Open AccessReview Enzyme Molecules in Solitary Confinement
Molecules 2014, 19(9), 14417-14445; doi:10.3390/molecules190914417
Received: 4 August 2014 / Revised: 3 September 2014 / Accepted: 3 September 2014 / Published: 12 September 2014
Cited by 7 | PDF Full-text (3050 KB) | HTML Full-text | XML Full-text
Abstract
Large arrays of homogeneous microwells each defining a femtoliter volume are a versatile platform for monitoring the substrate turnover of many individual enzyme molecules in parallel. The high degree of parallelization enables the analysis of a statistically representative enzyme population. Enclosing individual enzyme
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Large arrays of homogeneous microwells each defining a femtoliter volume are a versatile platform for monitoring the substrate turnover of many individual enzyme molecules in parallel. The high degree of parallelization enables the analysis of a statistically representative enzyme population. Enclosing individual enzyme molecules in microwells does not require any surface immobilization step and enables the kinetic investigation of enzymes free in solution. This review describes various microwell array formats and explores their applications for the detection and investigation of single enzyme molecules. The development of new fabrication techniques and sensitive detection methods drives the field of single molecule enzymology. Here, we introduce recent progress in single enzyme molecule analysis in microwell arrays and discuss the challenges and opportunities. Full article
(This article belongs to the Special Issue Single Molecule Techniques)
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Open AccessReview Native Chemical Ligation: A Boon to Peptide Chemistry
Molecules 2014, 19(9), 14461-14483; doi:10.3390/molecules190914461
Received: 31 July 2014 / Revised: 2 September 2014 / Accepted: 2 September 2014 / Published: 12 September 2014
Cited by 16 | PDF Full-text (839 KB) | HTML Full-text | XML Full-text
Abstract
The use of chemical ligation within the realm of peptide chemistry has opened various opportunities to expand the applications of peptides/proteins in biological sciences. Expansion and refinement of ligation chemistry has made it possible for the entry of peptides into the world of
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The use of chemical ligation within the realm of peptide chemistry has opened various opportunities to expand the applications of peptides/proteins in biological sciences. Expansion and refinement of ligation chemistry has made it possible for the entry of peptides into the world of viable oral therapeutic drugs through peptide backbone cyclization. This progression has been a journey of chemical exploration and transition, leading to the dominance of native chemical ligation in the present advances of peptide/protein applications. Here we illustrate and explore the historical and current nature of peptide ligation, providing a clear indication to the possibilities and use of these novel methods to take peptides outside their typically defined boundaries. Full article
(This article belongs to the Special Issue Peptide Chemistry)
Open AccessReview Antioxidant Activity and Mechanisms of Action of Natural Compounds Isolated from Lichens: A Systematic Review
Molecules 2014, 19(9), 14496-14527; doi:10.3390/molecules190914496
Received: 28 May 2014 / Revised: 2 September 2014 / Accepted: 3 September 2014 / Published: 12 September 2014
Cited by 14 | PDF Full-text (838 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chronic diseases such as cancer, diabetes, neurodegenerative and cardiovascular diseases are characterized by an enhanced state of oxidative stress, which may result from the overproduction of reactive species and/or a decrease in antioxidant defenses. The search for new chemical entities with antioxidant profile
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Chronic diseases such as cancer, diabetes, neurodegenerative and cardiovascular diseases are characterized by an enhanced state of oxidative stress, which may result from the overproduction of reactive species and/or a decrease in antioxidant defenses. The search for new chemical entities with antioxidant profile is still thus an emerging field on ongoing interest. Due to the lack of reviews concerning the antioxidant activity of lichen-derived natural compounds, we performed a review of the antioxidant potential and mechanisms of action of natural compounds isolated from lichens. The search terms “lichens”, “antioxidants” and “antioxidant response elements” were used to retrieve articles in LILACS, PubMed and Web of Science published until February 2014. From a total of 319 articles surveyed, 32 met the established inclusion and exclusion criteria. It was observed that the most common isolated compound studied was usnic acid, cited in 14 out of the 32 articles. The most often described antioxidant assays for the study of in vitro antioxidant activity were mainly DPPH, LPO and SOD. The most suggested mechanisms of action were scavenging of reactive species, enzymatic activation and inhibition of iNOS. Thus, compounds isolated from lichens are possible candidates for the management of oxidative stress, and may be useful in the treatment of chronic diseases. Full article
Open AccessReview Graphene-Based Nanomaterials as Heterogeneous Acid Catalysts: A Comprehensive Perspective
Molecules 2014, 19(9), 14582-14614; doi:10.3390/molecules190914582
Received: 28 May 2014 / Revised: 14 August 2014 / Accepted: 6 September 2014 / Published: 15 September 2014
Cited by 21 | PDF Full-text (1944 KB) | HTML Full-text | XML Full-text
Abstract
Acid catalysis is quite prevalent and probably one of the most routine operations in both industrial processes and research laboratories worldwide. Recently, “graphene”, a two dimensional single-layer carbon sheet with hexagonal packed lattice structure, imitative of nanomaterials, has shown great potential as alternative
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Acid catalysis is quite prevalent and probably one of the most routine operations in both industrial processes and research laboratories worldwide. Recently, “graphene”, a two dimensional single-layer carbon sheet with hexagonal packed lattice structure, imitative of nanomaterials, has shown great potential as alternative and eco-friendly solid carbocatalyst for a variety of acid-catalyzed reactions. Owing to their exceptional physical, chemical, and mechanical properties, graphene-based nanomaterials (G-NMs) offer highly stable Brønsted acidic sites, high mass transfer, relatively large surface areas, water tolerant character, and convenient recoverability as well as recyclability, whilst retaining high activity in acid-catalyzed chemical reactions. This comprehensive review focuses on the chemistry of G-NMs, including their synthesis, characterization, properties, functionalization, and up-to-date applications in heterogeneous acid catalysis. In line with this, in certain instances readers may find herein some criticisms that should be taken as constructive and would be of value in understanding the scope and limitations of current approaches utilizing graphene and its derivatives for the same. Full article
(This article belongs to the Special Issue Heterogeneous Acid Catalysts)
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Open AccessReview Challenges and Opportunities of MicroRNAs in Lymphomas
Molecules 2014, 19(9), 14723-14781; doi:10.3390/molecules190914723
Received: 29 April 2014 / Revised: 22 August 2014 / Accepted: 22 August 2014 / Published: 17 September 2014
Cited by 10 | PDF Full-text (2193 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that control the expression of many target messenger RNAs (mRNAs) involved in normal cell functions (differentiation, proliferation and apoptosis). Consequently their aberrant expression and/or functions are related to pathogenesis of many human diseases including cancers. Haematopoiesis is
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MicroRNAs (miRNAs) are small non-coding RNAs that control the expression of many target messenger RNAs (mRNAs) involved in normal cell functions (differentiation, proliferation and apoptosis). Consequently their aberrant expression and/or functions are related to pathogenesis of many human diseases including cancers. Haematopoiesis is a highly regulated process controlled by a complex network of molecular mechanisms that simultaneously regulate commitment, differentiation, proliferation, and apoptosis of hematopoietic stem cells (HSC). Alterations on this network could affect the normal haematopoiesis, leading to the development of haematological malignancies such as lymphomas. The incidence of lymphomas is rising and a significant proportion of patients are refractory to standard therapies. Accurate diagnosis, prognosis and therapy still require additional markers to be used for diagnostic and prognostic purpose and evaluation of clinical outcome. The dysregulated expression or function of miRNAs in various types of lymphomas has been associated with lymphoma pathogenesis. Indeed, many recent findings suggest that almost all lymphomas seem to have a distinct and specific miRNA profile and some miRNAs are related to therapy resistance or have a distinct kinetics during therapy. MiRNAs are easily detectable in fresh or paraffin-embedded diagnostic tissue and serum where they are highly stable and quantifiable within the diagnostic laboratory at each consultation. Accordingly they could be specific biomarkers for lymphoma diagnosis, as well as useful for evaluating prognosis or disease response to the therapy, especially for evaluation of early relapse detection and for greatly assisting clinical decisions making. Here we summarize the current knowledge on the role of miRNAs in normal and aberrant lymphopoiesis in order to highlight their clinical value as specific diagnosis and prognosis markers of lymphoid malignancies or for prediction of therapy response. Finally, we discuss their controversial therapeutic role and future applications in therapy by modulating miRNA. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessReview Recovery of Biomolecules from Food Wastes — A Review
Molecules 2014, 19(9), 14821-14842; doi:10.3390/molecules190914821
Received: 13 June 2014 / Revised: 23 August 2014 / Accepted: 4 September 2014 / Published: 17 September 2014
Cited by 18 | PDF Full-text (734 KB) | HTML Full-text | XML Full-text
Abstract
Food wastes are produced by a variety of sources, ranging from agricultural operations to household consumption. About 38% occurs during food processing. At present, the European Union legislation encourages the exploitation of co-products. This valorisation can be achieved through the extraction of high-value
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Food wastes are produced by a variety of sources, ranging from agricultural operations to household consumption. About 38% occurs during food processing. At present, the European Union legislation encourages the exploitation of co-products. This valorisation can be achieved through the extraction of high-value components such as proteins, polysaccharides, fibres, flavour compounds, and phytochemicals, which can be re-used as nutritionally and pharmacologically functional ingredients. Extraction can proceed according to solid-liquid extraction, Soxhlet extraction, pressurized fluid extraction, supercritical fluid extraction, ultrasound-assisted extraction, microwave-assisted extraction, pulsed electric field extraction, and enzyme-assisted extraction. Nevertheless, these techniques cannot be used indiscriminately and their choice depends on the type of biomolecules and matrix, the scale processing (laboratory or industrial), the ratio between production costs and economic values of the compounds to be extracted. The vegetable wastes include trimmings, peelings, stems, seeds, shells, bran, residues remaining after extraction of oil, starch, sugar, and juice. The animal-derived wastes include wastes from bred animals, wastes from seafood, wastes from dairy processing. The recovered biomolecules and by-products can be used to produce functional foods or as adjuvants in food processing or in medicinal and pharmaceutical preparations. This work is an overview of the type and amounts of food wastes; food waste legislation; conventional and novel techniques suitable for extracting biomolecules; food, medicinal and pharmaceutical uses of the recovered biomolecules and by-products, and future trends in these areas. Full article
(This article belongs to the Section Natural Products)
Open AccessReview Hinokinin, an Emerging Bioactive Lignan
Molecules 2014, 19(9), 14862-14878; doi:10.3390/molecules190914862
Received: 24 June 2014 / Revised: 10 September 2014 / Accepted: 10 September 2014 / Published: 17 September 2014
Cited by 6 | PDF Full-text (753 KB) | HTML Full-text | XML Full-text
Abstract Hinokinin is a lignan isolated from several plant species that has been recently investigated in order to establish its biological activities. So far, its cytotoxicity, its anti-inflammatory and antimicrobial activities have been studied. Particularly interesting is its notable anti-trypanosomal activity. Full article
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Open AccessReview Nopal Cactus (Opuntia ficus-indica) as a Source of Bioactive Compounds for Nutrition, Health and Disease
Molecules 2014, 19(9), 14879-14901; doi:10.3390/molecules190914879
Received: 10 July 2014 / Revised: 4 September 2014 / Accepted: 8 September 2014 / Published: 17 September 2014
Cited by 22 | PDF Full-text (832 KB) | HTML Full-text | XML Full-text
Abstract
Opuntia ficus-indica, commonly referred to as prickly pear or nopal cactus, is a dicotyledonous angiosperm plant. It belongs to the Cactaceae family and is characterized by its remarkable adaptation to arid and semi-arid climates in tropical and subtropical regions of the globe.
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Opuntia ficus-indica, commonly referred to as prickly pear or nopal cactus, is a dicotyledonous angiosperm plant. It belongs to the Cactaceae family and is characterized by its remarkable adaptation to arid and semi-arid climates in tropical and subtropical regions of the globe. In the last decade, compelling evidence for the nutritional and health benefit potential of this cactus has been provided by academic scientists and private companies. Notably, its rich composition in polyphenols, vitamins, polyunsaturated fatty acids and amino acids has been highlighted through the use of a large panel of extraction methods. The identified natural cactus compounds and derivatives were shown to be endowed with biologically relevant activities including anti-inflammatory, antioxidant, hypoglycemic, antimicrobial and neuroprotective properties. The present review is aimed at stressing the major classes of cactus components and their medical interest through emphasis on some of their biological effects, particularly those having the most promising expected health benefit and therapeutic impacts. Full article
Open AccessReview 1,4-Naphthoquinones: From Oxidative Damage to Cellular and Inter-Cellular Signaling
Molecules 2014, 19(9), 14902-14918; doi:10.3390/molecules190914902
Received: 29 July 2014 / Revised: 2 September 2014 / Accepted: 11 September 2014 / Published: 17 September 2014
Cited by 20 | PDF Full-text (2377 KB) | HTML Full-text | XML Full-text
Abstract
Naphthoquinones may cause oxidative stress in exposed cells and, therefore, affect redox signaling. Here, contributions of redox cycling and alkylating properties of quinones (both natural and synthetic, such as plumbagin, juglone, lawsone, menadione, methoxy-naphthoquinones, and others) to cellular and inter-cellular signaling processes are
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Naphthoquinones may cause oxidative stress in exposed cells and, therefore, affect redox signaling. Here, contributions of redox cycling and alkylating properties of quinones (both natural and synthetic, such as plumbagin, juglone, lawsone, menadione, methoxy-naphthoquinones, and others) to cellular and inter-cellular signaling processes are discussed: (i) naphthoquinone-induced Nrf2-dependent modulation of gene expression and its potentially beneficial outcome; (ii) the modulation of receptor tyrosine kinases, such as the epidermal growth factor receptor by naphthoquinones, resulting in altered gap junctional intercellular communication. Generation of reactive oxygen species and modulation of redox signaling are properties of naphthoquinones that render them interesting leads for the development of novel compounds of potential use in various therapeutic settings. Full article
Open AccessReview Experimental Studies of the Molecular Pathways Regulated by Exercise and Resveratrol in Heart, Skeletal Muscle and the Vasculature
Molecules 2014, 19(9), 14919-14947; doi:10.3390/molecules190914919
Received: 20 August 2014 / Revised: 10 September 2014 / Accepted: 10 September 2014 / Published: 18 September 2014
Cited by 9 | PDF Full-text (1014 KB) | HTML Full-text | XML Full-text
Abstract
Regular exercise contributes to healthy aging and the prevention of chronic disease. Recent research has focused on the development of molecules, such as resveratrol, that activate similar metabolic and stress response pathways as exercise training. In this review, we describe the effects of
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Regular exercise contributes to healthy aging and the prevention of chronic disease. Recent research has focused on the development of molecules, such as resveratrol, that activate similar metabolic and stress response pathways as exercise training. In this review, we describe the effects of exercise training and resveratrol on some of the organs and tissues that act in concert to transport oxygen throughout the body. In particular, we focus on animal studies that investigate the molecular signaling pathways induced by these interventions. We also compare and contrast the effects of exercise and resveratrol in diseased states. Full article
(This article belongs to the Special Issue Resveratrol)
Open AccessReview New Uses for Old Drugs: The Tale of Artemisinin Derivatives in the Elimination of Schistosomiasis Japonica in China
Molecules 2014, 19(9), 15058-15074; doi:10.3390/molecules190915058
Received: 29 July 2014 / Revised: 9 September 2014 / Accepted: 10 September 2014 / Published: 19 September 2014
Cited by 15 | PDF Full-text (679 KB) | HTML Full-text | XML Full-text
Abstract
Artemisinin (qinghaosu), extracted from the Chinese herb Artemisia annua L. in 1972, and its three major derivatives—artemether, artesunate and dihydroartemisinin—were firstly identified as antimalarials and found active against all species of the malaria parasite. Since the early 1980s, artemisinin and its derivatives have
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Artemisinin (qinghaosu), extracted from the Chinese herb Artemisia annua L. in 1972, and its three major derivatives—artemether, artesunate and dihydroartemisinin—were firstly identified as antimalarials and found active against all species of the malaria parasite. Since the early 1980s, artemisinin and its derivatives have been found efficacious against Schistosoma spp., notably larval parasites, and artemisinin derivatives have played a critical role in the prevention and treatment of human schistosomiasis in China. Currently, China is moving towards the progress of schistosomiasis elimination. However, the potential development of praziquantel resistance may pose a great threat to the progress of elimination of schistosomiasis japonica in China. Fortunately, these three major artemisinin derivatives also exhibit actions against adult parasites, and reduced sensitivity to artemether, artesunate and dihydroartemisinin has been detected in praziquantel-resistant S. japonicum. In this review, we describe the application of artemisinin derivatives in the prevention and treatment of schistosomiasis japonica in China, so as to provide tools for the global agenda of schistosomiasis elimination. In addition to antimalarial and antischistosomal actions, they also show activities against other parasites and multiple cancers. Artemisinin derivatives, as old drugs identified firstly as antimalarials, continue to create new stories. Full article
Open AccessReview Are TiO2 Nanotubes Worth Using in Photocatalytic Purification of Air and Water?
Molecules 2014, 19(9), 15075-15087; doi:10.3390/molecules190915075
Received: 24 July 2014 / Revised: 29 August 2014 / Accepted: 9 September 2014 / Published: 19 September 2014
Cited by 4 | PDF Full-text (2242 KB) | HTML Full-text | XML Full-text
Abstract
Titanium dioxide nanotubes (TNT) have mainly been used in dye sensitized solar cells, essentially because of a higher transport rate of electrons from the adsorbed photo-excited dye to the Ti electrode onto which TNT instead of TiO2 nanoparticles (TNP) are attached. The
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Titanium dioxide nanotubes (TNT) have mainly been used in dye sensitized solar cells, essentially because of a higher transport rate of electrons from the adsorbed photo-excited dye to the Ti electrode onto which TNT instead of TiO2 nanoparticles (TNP) are attached. The dimension ranges and the two main synthesis methods of TNT are briefly indicated here. Not surprisingly, the particular and regular texture of TNT was also expected to improve the photocatalytic efficacy for pollutant removal in air and water with respect to TNP. In this short review, the validity of this expectation is checked using the regrettably small number of literature comparisons between TNT and commercialized TNP referring to films of similar thickness and layers or slurries containing an equal TiO2 mass. Although the irradiated geometrical area differed for each study, it was identical for each comparison considered here. For the removal of toluene (methylbenzene) or acetaldehyde (ethanal) in air, the average ratio of the efficacy of TNT over that of TiO2 P25 was about 1.5, and for the removal of dyes in water, it was around 1. This lack of major improvement with TNT compared to TNP could partially be due to TNT texture disorders as seems to be suggested by the better average performance of anodic oxidation-prepared TNT. It could also come from the fact that the properties influencing the efficacy are more numerous, their interrelations more complex and their effects more important for pollutant removal than for dye sensitized solar cells and photoelectrocatalysis where the electron transport rate is the crucial parameter. Full article
(This article belongs to the Special Issue Photocatalysis) Print Edition available
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Open AccessReview Carbonylation of Ethene Catalysed by Pd(II)-Phosphine Complexes
Molecules 2014, 19(9), 15116-15161; doi:10.3390/molecules190915116
Received: 2 July 2014 / Revised: 2 September 2014 / Accepted: 11 September 2014 / Published: 22 September 2014
Cited by 5 | PDF Full-text (1465 KB) | XML Full-text
Abstract
This review deals with olefin carbonylation catalysed by Pd(II)-phosphine complexes in protic solvents. In particular, the results obtained in the carbonylation with ethene are reviewed. After a short description of the basic concepts relevant to this catalysis, the review treats in greater details
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This review deals with olefin carbonylation catalysed by Pd(II)-phosphine complexes in protic solvents. In particular, the results obtained in the carbonylation with ethene are reviewed. After a short description of the basic concepts relevant to this catalysis, the review treats in greater details the influence of the bite angle, skeletal rigidity, electronic and steric bulk properties of the ligand on the formation of the products, which range from high molecular weight perfectly alternating polyketones to methyl propanoate. It is shown that the steric bulk plays a major role in directing the selectivity. Particular emphasis is given to the factors governing the very active and selective catalysis to methyl propanoate, including the mechanism of the catalytic cycles with diphosphine- and monophosphine-catalysts. A brief note on the synthesis of methyl propanoate using a “Lucite” type catalyst in ionic liquids is also illustrated. A chapter is dedicated to the carbonylation of olefins in aqueous reaction media. The nonalternating CO-ethene copolymerization is also treated. Full article
(This article belongs to the Special Issue Carbonylation Chemistry)
Open AccessReview Small Molecule Tyrosine Kinase Inhibitors of ErbB2/HER2/Neu in the Treatment of Aggressive Breast Cancer
Molecules 2014, 19(9), 15196-15212; doi:10.3390/molecules190915196
Received: 6 August 2014 / Revised: 8 September 2014 / Accepted: 10 September 2014 / Published: 23 September 2014
Cited by 11 | PDF Full-text (756 KB) | HTML Full-text | XML Full-text
Abstract
The human epidermal growth factor receptor 2 (HER2) is a member of the erbB class of tyrosine kinase receptors. These proteins are normally expressed at the surface of healthy cells and play critical roles in the signal transduction cascade in a myriad of
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The human epidermal growth factor receptor 2 (HER2) is a member of the erbB class of tyrosine kinase receptors. These proteins are normally expressed at the surface of healthy cells and play critical roles in the signal transduction cascade in a myriad of biochemical pathways responsible for cell growth and differentiation. However, it is widely known that amplification and subsequent overexpression of the HER2 encoding oncogene results in unregulated cell proliferation in an aggressive form of breast cancer known as HER2-positive breast cancer. Existing therapies such as trastuzumab (Herceptin®) and lapatinib (Tyverb/Tykerb®), a monoclonal antibody inhibitor and a dual EGFR/HER2 kinase inhibitor, respectively, are currently used in the treatment of HER2-positive cancers, although issues with high recurrence and acquired resistance still remain. Small molecule tyrosine kinase inhibitors provide attractive therapeutic targets, as they are able to block cell signaling associated with many of the proposed mechanisms for HER2 resistance. In this regard we aim to present a review on the available HER2 tyrosine kinase inhibitors, as well as those currently in development. The use of tyrosine kinase inhibitors as sequential or combinatorial therapeutic strategies with other HER family inhibitors is also discussed. Full article
(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)
Open AccessReview Current and Potential Applications of Bismuth-Based Drugs
Molecules 2014, 19(9), 15258-15297; doi:10.3390/molecules190915258
Received: 25 July 2014 / Revised: 4 September 2014 / Accepted: 4 September 2014 / Published: 23 September 2014
Cited by 11 | PDF Full-text (3209 KB) | HTML Full-text | XML Full-text
Abstract
: Bismuth compounds have been used extensively as medicines and in particular for the treatment of gastrointestinal ailments. In addition to bismuth’s well known gastroprotective effects and efficacy in treating H. pylori infection it also has broad anti-microbial, anti-leishmanial and anti-cancer properties. Aspects
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: Bismuth compounds have been used extensively as medicines and in particular for the treatment of gastrointestinal ailments. In addition to bismuth’s well known gastroprotective effects and efficacy in treating H. pylori infection it also has broad anti-microbial, anti-leishmanial and anti-cancer properties. Aspects of the biological chemistry of bismuth are discussed and biomolecular targets associated with bismuth treatment are highlighted. This review strives to provide the reader with an up to date account of bismuth-based drugs currently used to treat patients and discuss potential medicinal applications of bismuth drugs with reference to recent developments in the literature. Ultimately this review aims to encourage original contributions to this exciting and important field. Full article
(This article belongs to the Special Issue Practical Applications of Metal Complexes)
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Open AccessReview Organic Nitrates: Past, Present and Future
Molecules 2014, 19(9), 15314-15323; doi:10.3390/molecules190915314
Received: 7 July 2014 / Revised: 31 August 2014 / Accepted: 12 September 2014 / Published: 24 September 2014
Cited by 1 | PDF Full-text (923 KB) | HTML Full-text | XML Full-text
Abstract
Nitric oxide (NO) is one of the most important vasodilator molecules produced by the endothelium. It has already been established that NO/cGMP signaling pathway deficiencies are involved in the pathophysiological mechanisms of many cardiovascular diseases. In this context, the development of NO-releasing drugs
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Nitric oxide (NO) is one of the most important vasodilator molecules produced by the endothelium. It has already been established that NO/cGMP signaling pathway deficiencies are involved in the pathophysiological mechanisms of many cardiovascular diseases. In this context, the development of NO-releasing drugs for therapeutic use appears to be an effective alternative to replace the deficient endogenous NO and mimic the role of this molecule in the body. Organic nitrates represent the oldest class of NO donors that have been clinically used. Considering that tolerance can occur when these drugs are applied chronically, the search for new compounds of this class with lower tolerance potential is increasing. Here, we briefly discuss the mechanisms involved in nitrate tolerance and highlight some achievements from our group in the development of new organic nitrates and their preclinical application in cardiovascular disorders. Full article
(This article belongs to the Section Organic Synthesis)

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