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Molecules, Volume 18, Issue 12 (December 2013), Pages 14455-15803

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Open AccessArticle Three New Ursane-Type Triterpenoids from the Stems of Saprosma merrillii
Molecules 2013, 18(12), 14496-14504; doi:10.3390/molecules181214496
Received: 25 September 2013 / Revised: 13 November 2013 / Accepted: 14 November 2013 / Published: 25 November 2013
Cited by 4 | PDF Full-text (330 KB) | HTML Full-text | XML Full-text | Correction
Abstract
Three new ursane-type triterpenoids, 3α,6α,30-trihydroxy-ursan-28-oic acid (1), 3α,30-dihydroxy-6-oxo-ursan-28-oic acid (2) and 3α,6α,7α,30-tetrahydroxy-ursan-28-oic acid (3), together with one known triterpenoid, betulinic acid (4), one
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Three new ursane-type triterpenoids, 3α,6α,30-trihydroxy-ursan-28-oic acid (1), 3α,30-dihydroxy-6-oxo-ursan-28-oic acid (2) and 3α,6α,7α,30-tetrahydroxy-ursan-28-oic acid (3), together with one known triterpenoid, betulinic acid (4), one known anthraquinone, 1,7-dihydroxy-2-methylanthraquinone (5), four known phenols, 1,3,5-trimethoxybenzene (6), p-hydroxybenzoic acid (7), syringic acid (8), isovanillin (9), two steroids, sitosterol (10) and daucosterol (11), were isolated from the ethanol extract of the stems of S. merrillii. Their structures were elucidated on the basis of physical and spectral techniques, besides comparison with literature data. Compounds 13 showed inhibitory activities against the A549, HEPG2, and B16F10 cell lines. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Facile Creation of 3-Substituted-3-Hydroxy-2-Oxindoles by Arginine-Catalyzed Aldol Reactions of α,β-Unsaturated Ketones with Isatins
Molecules 2013, 18(12), 14505-14518; doi:10.3390/molecules181214505
Received: 14 October 2013 / Revised: 15 November 2013 / Accepted: 19 November 2013 / Published: 25 November 2013
Cited by 12 | PDF Full-text (444 KB) | HTML Full-text | XML Full-text
Abstract
An efficient approach for the synthesis of 3-substituted-3-hydroxy-2-oxindoles has been achieved via an aldol reaction of α,β-unsaturated ketones and isatins using arginine as an organocatalyst. A range of 3-substituted-3-hydroxy-2-oxindoles were obtained in moderate to high (up to 99%) yields. These 3-substituted-3-hydroxy-2-oxindoles with an
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An efficient approach for the synthesis of 3-substituted-3-hydroxy-2-oxindoles has been achieved via an aldol reaction of α,β-unsaturated ketones and isatins using arginine as an organocatalyst. A range of 3-substituted-3-hydroxy-2-oxindoles were obtained in moderate to high (up to 99%) yields. These 3-substituted-3-hydroxy-2-oxindoles with an additional enone moiety provide an opportunity for further elaboration of the products and for potentially interesting biological activities. In addition, the formation of 3-substituted-3-hydroxy-2-oxindole 3a was confirmed by X-ray crystallography. The possible reaction mechanism reveals that the reaction proceeds via a double action process. Full article
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Open AccessArticle Ultrasound-Promoted One-Pot, Four-Component Synthesis of Pyridin-2(1H)-One Derivatives
Molecules 2013, 18(12), 14519-14528; doi:10.3390/molecules181214519
Received: 30 September 2013 / Revised: 19 November 2013 / Accepted: 19 November 2013 / Published: 25 November 2013
Cited by 4 | PDF Full-text (365 KB) | HTML Full-text | XML Full-text
Abstract
An efficient one-pot synthesis of 1,6-diamino-2-oxo-1,2,3,4-tetrahydro- pyridine-3,5-dicarbonitrile derivatives by four-component piperidine-catalyzed reactions of a ketone, malononitrile, ethyl cyanoacetate and hydrazine hydrate under ultrasound irradiation is described. This method provides several advantages such as shorter reaction times, excellent yields, and a simple workup procedure.
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An efficient one-pot synthesis of 1,6-diamino-2-oxo-1,2,3,4-tetrahydro- pyridine-3,5-dicarbonitrile derivatives by four-component piperidine-catalyzed reactions of a ketone, malononitrile, ethyl cyanoacetate and hydrazine hydrate under ultrasound irradiation is described. This method provides several advantages such as shorter reaction times, excellent yields, and a simple workup procedure. Full article
(This article belongs to the Special Issue Combinatorial Synthesis)
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Open AccessArticle Perfluoroalkanesulfonamide Organocatalysts for Asymmetric Conjugate Additions of Branched Aldehydes to Vinyl Sulfones
Molecules 2013, 18(12), 14529-14542; doi:10.3390/molecules181214529
Received: 30 October 2013 / Revised: 20 November 2013 / Accepted: 21 November 2013 / Published: 25 November 2013
Cited by 2 | PDF Full-text (393 KB) | HTML Full-text | XML Full-text
Abstract Asymmetric conjugate additions of branched aldehydes to vinyl sulfones promoted by sulfonamide organocatalyst 6 or 7 have been developed, allowing facile synthesis of the corresponding adducts with all-carbon quaternary stereocenters in excellent yields with up to 95% ee. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Open AccessArticle Evaluation of Sulfated Polysaccharides from the Brown Seaweed Dictyopteris Justii as Antioxidant Agents and as Inhibitors of the Formation of Calcium Oxalate Crystals
Molecules 2013, 18(12), 14543-14563; doi:10.3390/molecules181214543
Received: 8 October 2013 / Revised: 8 November 2013 / Accepted: 12 November 2013 / Published: 25 November 2013
Cited by 7 | PDF Full-text (1001 KB) | HTML Full-text | XML Full-text
Abstract
Oxalate crystals and other types of crystals are the cause of urolithiasis, and these are related to oxidative stress. The search for new compounds with antioxidant qualities and inhibitors of these crystal formations is therefore necessary. In this study, we extracted four sulfated
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Oxalate crystals and other types of crystals are the cause of urolithiasis, and these are related to oxidative stress. The search for new compounds with antioxidant qualities and inhibitors of these crystal formations is therefore necessary. In this study, we extracted four sulfated polysaccharides, a fucoglucoxyloglucuronan (DJ-0.3v), a heterofucan (DJ-0.4v), and two glucans (DJ-0.5v and DJ-1.2v), from the marine alga Dictyopteris justii. The presence of sulfated polysaccharides was confirmed by chemical analysis and FT-IR. All the sulfated polysaccharides presented antioxidant activity under different conditions in some of the in vitro tests and inhibited the formation of calcium oxalate crystals. Fucan DJ-0.4v was the polysaccharide that showed the best antioxidant activity and was one of the best inhibitors of the crystallization of calcium oxalate. Glucan DJ-0.5v was the second most potent inhibitor of the formation of oxalate crystals, as it stabilized dehydrated oxalate crystals (less aggressive form), preventing them from transforming into monohydrate crystals (more aggressive form). The obtained data lead us to propose that these sulfated polysaccharides are promising agents for use in the treatment of urolithiasis. Full article
Open AccessArticle Insights into Structure-Activity Relationships of Somatostatin Analogs Containing Mesitylalanine
Molecules 2013, 18(12), 14564-14584; doi:10.3390/molecules181214564
Received: 30 October 2013 / Revised: 12 November 2013 / Accepted: 13 November 2013 / Published: 25 November 2013
Cited by 3 | PDF Full-text (2320 KB) | HTML Full-text | XML Full-text
Abstract
The non-natural amino acid mesitylalanine (2,4,6-trimethyl-L-phenylalanine; Msa) has an electron-richer and a more conformationally restricted side-chain than that of its natural phenylalanine counterpart. Taking these properties into account, we have synthesized ten somatostatin analogs containing Msa residues in different key positions to modify
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The non-natural amino acid mesitylalanine (2,4,6-trimethyl-L-phenylalanine; Msa) has an electron-richer and a more conformationally restricted side-chain than that of its natural phenylalanine counterpart. Taking these properties into account, we have synthesized ten somatostatin analogs containing Msa residues in different key positions to modify the intrinsic conformational flexibility of the natural hormone. We have measured the binding affinity of these analogs and correlated it with the main conformations they populate in solution. NMR and computational analysis revealed that analogs containing one Msa residue were conformationally more restricted than somatostatin under similar experimental conditions. Furthermore, we were able to characterize the presence of a hairpin at the pharmacophore region and a non-covalent interaction between aromatic residues 6 and 11. In all cases, the inclusion of a D-Trp in the eighth position further stabilized the main conformation. Some of these peptides bound selectively to one or two somatostatin receptors with similar or even higher affinity than the natural hormone. However, we also found that multiple incorporations of Msa residues increased the life span of the peptides in serum but with a loss of conformational rigidity and binding affinity. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Astataricusones A–D and Astataricusol A, Five New Anti-HBV Shionane-Type Triterpenes from Aster tataricus L. f.
Molecules 2013, 18(12), 14585-14596; doi:10.3390/molecules181214585
Received: 9 October 2013 / Revised: 13 November 2013 / Accepted: 15 November 2013 / Published: 25 November 2013
Cited by 3 | PDF Full-text (388 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Five new shionane-type triterpenes, astataricusones A–D (compounds 14) and astataricusol A (5), together with one known shionane-type triterpene 6 were obtained from the roots and rhizomes of Aster tataricus L. f. Their structures were elucidated on the basis
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Five new shionane-type triterpenes, astataricusones A–D (compounds 14) and astataricusol A (5), together with one known shionane-type triterpene 6 were obtained from the roots and rhizomes of Aster tataricus L. f. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configurations of 1 and 4 was determined by single crystal X-ray diffraction and CD analysis. Compound 2 showed inhibitory activity on HBsAg secretion with an IC50 value of 23.5 μM, while 2 and 6 showed inhibitory activities on HBeAg secretion with IC50 values of 18.6 and 40.5 μM, and cytotoxicity on HepG 2.2.15 cells with CC50 values of 172.4 and 137.7 μM, respectively. Compounds 2 and 6 also exhibited inhibitory activities on HBV DNA replication with IC50 values of 2.7 and 30.7 μM, respectively. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Nutraceutical Value of Black Cherry Prunus serotina Ehrh. Fruits: Antioxidant and Antihypertensive Properties
Molecules 2013, 18(12), 14597-14612; doi:10.3390/molecules181214597
Received: 8 October 2013 / Revised: 12 November 2013 / Accepted: 14 November 2013 / Published: 25 November 2013
Cited by 8 | PDF Full-text (1022 KB) | HTML Full-text | XML Full-text
Abstract
In Mexico black cherry (Prunus serotina Ehrh.) fruits are consumed fresh, dried or prepared in jam. Considering the evidence that has linked intake of fruits and vegetables rich in polyphenols to cardiovascular risk reduction, the aim of this study was to characterize
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In Mexico black cherry (Prunus serotina Ehrh.) fruits are consumed fresh, dried or prepared in jam. Considering the evidence that has linked intake of fruits and vegetables rich in polyphenols to cardiovascular risk reduction, the aim of this study was to characterize the phenolic profile of black cherry fruits and to determine their antioxidant, vasorelaxant and antihypertensive effects. The proximate composition and mineral contents of these fruits were also assessed. Black cherry fruits possess a high content of phenolic compounds and display a significant antioxidant capacity. High-performance liquid chromatography/mass spectrometric analysis indicated that hyperoside, anthocyanins and chlorogenic acid were the main phenolic compounds found in these fruits. The black cherry aqueous extract elicited a concentration-dependent relaxation of aortic rings and induced a significant reduction on systolic blood pressure in L-NAME induced hypertensive rats after four weeks of treatment. Proximate analysis showed that black cherry fruits have high sugar, protein, and potassium contents. The results derived from this study indicate that black cherry fruits contain phenolic compounds which elicit significant antioxidant and antihypertensive effects. These findings suggest that these fruits might be considered as functional foods useful for the prevention and treatment of cardiovascular diseases. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Liposomal Encapsulation Enhances In Vivo Near Infrared Imaging of Exposed Phosphatidylserine in a Mouse Glioma Model
Molecules 2013, 18(12), 14613-14628; doi:10.3390/molecules181214613
Received: 8 October 2013 / Revised: 18 November 2013 / Accepted: 21 November 2013 / Published: 26 November 2013
Cited by 6 | PDF Full-text (3549 KB) | HTML Full-text | XML Full-text
Abstract
We have previously demonstrated that exposed phosphatidylserine (PS) on tumor vascular endothelial cells is highly tumor specific, and development of the PS targeted near infrared (NIR) optical probe enables successful in vivo optical imaging of U87 gliomas in a mouse model. Liposomes have
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We have previously demonstrated that exposed phosphatidylserine (PS) on tumor vascular endothelial cells is highly tumor specific, and development of the PS targeted near infrared (NIR) optical probe enables successful in vivo optical imaging of U87 gliomas in a mouse model. Liposomes have been widely used as a nanovector for delivery of chemotherapeutics and imaging contrast agents due to their high payload and longer circulation time. In the current study, we have fabricated PS-targeted liposomal nanoprobes encapsulating a NIR dye, IRDye® 800CW, aiming to enhance PS-targeted tumor imaging. Hydrophilic 800CW dye was packed into the core of polyethylene glycol (PEG)-coated liposomes functionalized with F(ab’)2 fragments of PGN635, a fully human monoclonal antibody that binds PS. As expected, in vivo dynamic NIR imaging revealed significantly improved tumor/normal contrast (TNR = 20 ± 3; p < 0.01) of subcutaneous U87 gliomas in mice after injection of the liposomal nanoprobes. Markedly enhanced TNR was observed after the tumors were irradiated to increase PS exposure (TNR = 48 ± 6; p < 0.05). Intriguingly, the liposomal nanoprobes, PGN-L-800CW showed distinct biodistribution and pharmacokinetics compared to the 800CW-PGN probes used in our previous study. Our data further suggest the usefulness of PS-targeted imaging probes for sensitive tumor detection and the potential of utilizing liposomal platform for glioma theranostics. Full article
(This article belongs to the Special Issue Contrast Agents)
Open AccessArticle Bio-Activity and Dereplication-Based Discovery of Ophiobolins and Other Fungal Secondary Metabolites Targeting Leukemia Cells
Molecules 2013, 18(12), 14629-14650; doi:10.3390/molecules181214629
Received: 12 October 2013 / Revised: 15 November 2013 / Accepted: 21 November 2013 / Published: 26 November 2013
Cited by 8 | PDF Full-text (746 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The purpose of this study was to identify and characterize fungal natural products (NPs) with in vitro bioactivity towards leukemia cells. We based our screening on a combined analytical and bio-guided approach of LC-DAD-HRMS dereplication, explorative solid-phase extraction (E-SPE), and a co-culture platform
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The purpose of this study was to identify and characterize fungal natural products (NPs) with in vitro bioactivity towards leukemia cells. We based our screening on a combined analytical and bio-guided approach of LC-DAD-HRMS dereplication, explorative solid-phase extraction (E-SPE), and a co-culture platform of CLL and stromal cells. A total of 289 fungal extracts were screened and we tracked the activity to single compounds in seven of the most active extracts. The novel ophiobolin U was isolated together with the known ophiobolins C, H, K as well as 6-epiophiobolins G, K and N from three fungal strains in the Aspergillus section Usti. Ophiobolins A, B, C and K displayed bioactivity towards leukemia cells with induction of apoptosis at nanomolar concentrations. The remaining ophiobolins were mainly inactive or only slightly active at micromolar concentrations. Dereplication of those ophiobolin derivatives possessing different activity in combination with structural analysis allowed a correlation of the chemical structure and conformation with the extent of bioactivity, identifying the hydroxy group at C3 and an aldehyde at C21, as well as the A/B-cis ring structure, as indispensible for the strong activity of the ophiobolins. The known compounds penicillic acid, viridicatumtoxin, calbistrin A, brefeldin A, emestrin A, and neosolaniol monoacetate were identified from the extracts and also found generally cytotoxic. Full article
(This article belongs to the Special Issue Bioassay-Guided Isolation of Natural Products)
Open AccessArticle Anti- and Pro-Lipase Activity of Selected Medicinal, Herbal and Aquatic Plants, and Structure Elucidation of an Anti-Lipase Compound
Molecules 2013, 18(12), 14651-14669; doi:10.3390/molecules181214651
Received: 10 September 2013 / Revised: 4 November 2013 / Accepted: 11 November 2013 / Published: 26 November 2013
Cited by 6 | PDF Full-text (380 KB) | HTML Full-text | XML Full-text
Abstract
Plants that help in slowing down the digestion of triacylglycerols (TAGs) in the pancreas and small intestine of humans play an important role in the reduction of obesity. On the other hand, there may be plants or plant parts that stimulate intestinal lipolytic
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Plants that help in slowing down the digestion of triacylglycerols (TAGs) in the pancreas and small intestine of humans play an important role in the reduction of obesity. On the other hand, there may be plants or plant parts that stimulate intestinal lipolytic activity, thus contributing to greater TAG assimilation. The aim of this study was to evaluate the aqueous methanolic extracts of ninety eight (98) medicinal, herbal and aquatic plant materials from Malaysia for their effect on porcine pancreatic lipase (PPL) activity and to identify the structure of an anti-lipase compound from one of the sources. The degree of inhibition was also quantified as relative to orlistat activity against PPL (orlistat equivalents). Results revealed that while 19.4% of the extracts were found to have anti-lipase activity ≥80%, 12% were actually found to promote PPL activity. Twenty two percent (22.4%) exhibited moderate inhibition (41%–80%) and 2% were neutral toward PPL activity. The ripe fruit of Averrhoa carambola and the leaves of Archidendron jiringa (Jack) I.C Nielsen L. (jering), Cynometra cauliflora (nam-nam) and Aleurites moluccana (L.) Willd (candle nut/buah keras) had the highest (100%) anti-lipase activity and are equivalent to 0.11 µg orlistat/mL. Plants that stimulated lipase activity included Pimpinella anisum L. (aniseed/jintan manis), activating the enzyme by 186.5%. Kaempferol 3-O-rhamnoside was isolated from the ethyl acetate fraction of C. cauliflora leaves and found to be an active lipase inhibitor. The structure was elucidated using 1H-NMR, 13C-NMR and 2D-NMR analyses. Full article
Open AccessArticle Two-Year Variations of Phenolics, Flavonoids and Antioxidant Contents in Acacia Honey
Molecules 2013, 18(12), 14694-14710; doi:10.3390/molecules181214694
Received: 23 September 2013 / Revised: 5 November 2013 / Accepted: 6 November 2013 / Published: 27 November 2013
Cited by 3 | PDF Full-text (474 KB) | HTML Full-text | XML Full-text
Abstract
Honey is a good source of several important chemical compounds and antioxidants and is harvested throughout the year. However, no study has determined how their contents change over the years. The aim of the present research was to investigate the changes in the
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Honey is a good source of several important chemical compounds and antioxidants and is harvested throughout the year. However, no study has determined how their contents change over the years. The aim of the present research was to investigate the changes in the phenolics, flavonoids and antioxidant properties, as well as other physicochemical properties, of Malaysian acacia honey collected during different months during a two year period. The DPPH (1,1-diphenyl-2-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) methods were used to determine the total antioxidant activity of the honey samples. Generally, honey samples collected in the beginning and the middle of the year tended to have higher sugar content, which may be attributed to its high acidic nature and low moisture content. There was a gradual increase in the phenolic content of the acacia honey samples collected between September 2010 and December 2010. The honey sample collected at the beginning of the year (January) showed the highest color intensity and was dark amber in color. It also contained the highest concentration of phenolic compounds (341.67 ± 2.94 mggallic acid/kg), the highest flavonoid content (113.06 ± 6.18 mgcatechin/kg) andthe highest percentage of DPPH inhibition and the highest FRAP value, confirming its high antioxidant potential. There was a positive correlation between DPPH and total phenolic content, suggesting that phenolic compounds are the strongest contributing factor to the radical scavenging activity of Malaysian acacia honeys. Overall, our results indicated that there were significant seasonal variations in the antioxidant potentials of honey over the two year period and the time of honey collection affects its physicochemical properties. Therefore, acacia honey from Malaysia should ideally be collected during the dry season, particularly in the months of January, May and June. Full article
Open AccessArticle Design and Synthesis of Arylthiophene-2-Carbaldehydes via Suzuki-Miyaura Reactions and Their Biological Evaluation
Molecules 2013, 18(12), 14711-14725; doi:10.3390/molecules181214711
Received: 30 September 2013 / Revised: 13 November 2013 / Accepted: 14 November 2013 / Published: 27 November 2013
Cited by 7 | PDF Full-text (351 KB) | HTML Full-text | XML Full-text
Abstract
A series of various novel 4-arylthiophene-2-carbaldehyde compounds were synthesized in moderate to excellent yields via Suzuki-Miyaura cross-coupling with different arylboronic pinacol esters/acids. The synthesized products were screened for their antibacterial, haemolytic, antiurease, and nitric oxide (NO) scavenging capabilities and interestingly, almost all products
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A series of various novel 4-arylthiophene-2-carbaldehyde compounds were synthesized in moderate to excellent yields via Suzuki-Miyaura cross-coupling with different arylboronic pinacol esters/acids. The synthesized products were screened for their antibacterial, haemolytic, antiurease, and nitric oxide (NO) scavenging capabilities and interestingly, almost all products turned out to have good activities. 3-(5-Formyl-thiophene-3-yl)-5-(trifloromethyl)benzonitrile (2d) revealed excellent antibacterial activity, showing an IC50 value of 29.7 µg/mL against Pseudomonas aeruginosa, compared to the standard drug streptomycin with an IC50 value 35.2 µg/mL and was also found to be the best NO scavenger, with an IC50 value of 45.6 µg/mL. Moreover, 4-(3-chloro-4-fluoro-phenyl)thiophene-2-carbaldehyde (2i) exhibited a superior haemolytic action and an outstanding urease inhibition, showing an IC50 value of 27.1 µg/mL. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Baicalein Prevents 6-Hydroxydopamine-Induced Mitochondrial Dysfunction in SH-SY5Y Cells via Inhibition of Mitochondrial Oxidation and Up-Regulation of DJ-1 Protein Expression
Molecules 2013, 18(12), 14726-14738; doi:10.3390/molecules181214726
Received: 24 September 2013 / Revised: 18 November 2013 / Accepted: 19 November 2013 / Published: 27 November 2013
Cited by 18 | PDF Full-text (809 KB) | HTML Full-text | XML Full-text
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DA) neurons at the substantia nigra. Mitochondrial dysfunction is involved in the mechanism of cell damage in Parkinson’s disease (PD). 6-Hydroxydopamine (6-OHDA) is a dopamine analog which specifically damages dopaminergic
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Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DA) neurons at the substantia nigra. Mitochondrial dysfunction is involved in the mechanism of cell damage in Parkinson’s disease (PD). 6-Hydroxydopamine (6-OHDA) is a dopamine analog which specifically damages dopaminergic neurons. Baicalein has been previously reported to have potential in the treatment of PD. The purpose of the present study was to investigate the mechanism of action of baicalein against 6-OHDA injury in SH-SY5Y cells. The results showed that baicalein significantly alleviated alterations of mitochondrial redox activity and mitochondrial membrane potential induced by 6-OHDA in a dose-dependent manner in SH-SY5Y cells compared with vehicle group. Futhermore, baicalein decreased the production of ROS and upregulated the DJ-1 protein expression in SH-SY5Y cells. In addition, baicalein also inhibited ROS production and lipid peroxidation (IC50 = 6.32 ± 0.03 μM) in rat brain mitochondia. In summary, the underlying mechanisms of baicalein against 6-OHDA-induced mitochondrial dysfunction may involve inhibition of mitochondrial oxidation and upregulation of DJ-1 protein expression. Full article
Open AccessArticle Examination of the Potential for Adaptive Chirality of the Nitrogen Chiral Center in Aza-Aspartame
Molecules 2013, 18(12), 14739-14746; doi:10.3390/molecules181214739
Received: 3 October 2013 / Revised: 7 November 2013 / Accepted: 12 November 2013 / Published: 28 November 2013
Cited by 2 | PDF Full-text (465 KB) | HTML Full-text | XML Full-text
Abstract
The potential for dynamic chirality of an azapeptide nitrogen was examined by substitution of nitrogen for the α-carbon of the aspartate residue in the sweetener S,S-aspartame. Considering that S,S- and R,S-aspartame possess sweet and
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The potential for dynamic chirality of an azapeptide nitrogen was examined by substitution of nitrogen for the α-carbon of the aspartate residue in the sweetener S,S-aspartame. Considering that S,S- and R,S-aspartame possess sweet and bitter tastes, respectively, a bitter-sweet taste of aza-aspartame 9 could be indicative of a low isomerization barrier for nitrogen chirality inter-conversion. Aza-aspartame 9 was synthesized by a combination of hydrazine and peptide chemistry. Crystallization of 9 indicated a R,S-configuration in the solid state; however, the aza-residue chiral center was considerably flattened relative to its natural amino acid counterpart. On tasting, the authors considered aza-aspartame 9 to be slightly bitter or tasteless. The lack of bitter sweet taste of aza-aspartame 9 may be due to flattening from sp2 hybridization in the urea as well as a high barrier for sp3 nitrogen inter-conversion, both of which may interfere with recognition by taste receptors. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
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Open AccessArticle OxymaPure/DIC: An Efficient Reagent for the Synthesis of a Novel Series of 4-[2-(2-Acetylaminophenyl)-2-oxo-acetylamino] Benzoyl Amino Acid Ester Derivatives
Molecules 2013, 18(12), 14747-14759; doi:10.3390/molecules181214747
Received: 24 September 2013 / Revised: 15 November 2013 / Accepted: 20 November 2013 / Published: 28 November 2013
Cited by 1 | PDF Full-text (266 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
OxymaPure (ethyl 2-cyano-2-(hydroxyimino)acetate) was tested as an additive for use in the carbodiimide (DIC) approach for the synthesis of a novel series of α-ketoamide derivatives (4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino]benzoyl amino acid ester derivatives). OxymaPure showed clear superiority to HOBt/DIC or carbodiimide alone in terms of purity
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OxymaPure (ethyl 2-cyano-2-(hydroxyimino)acetate) was tested as an additive for use in the carbodiimide (DIC) approach for the synthesis of a novel series of α-ketoamide derivatives (4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino]benzoyl amino acid ester derivatives). OxymaPure showed clear superiority to HOBt/DIC or carbodiimide alone in terms of purity and yield. The title compounds were synthesized via the ring opening of N-acylisatin. First, N-acetylisatin was reacted with 4-aminobenzoic acid under conventional heating as well as microwave irradiation to afford 4-(2-(2-acetamidophenyl)-2-oxoacetamido)benzoic acid. This α-ketoamide was coupled to different amino acid esters using OxymaPure/DIC as a coupling reagent to afford 4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino]benzoyl amino acid ester derivatives in excellent yield and purity. The synthesized compounds were characterized using FT-IR, NMR, and elemental analysis. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Novel Method of Synthesis of 5''-Phosphate 2'-O-ribosyl-ribonucleosides and Their 3'-Phosphoramidites
Molecules 2013, 18(12), 14780-14796; doi:10.3390/molecules181214780
Received: 27 September 2013 / Revised: 23 November 2013 / Accepted: 25 November 2013 / Published: 29 November 2013
PDF Full-text (345 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Synthesis of 5''-phosphate 2'-O-ribosylribonucleosides [Nr(p)] of four common ribonucleosides, and 3'-phosphoramidites of 5''-phosphate 2'-O-ribosyladenosine and 2'-O-ribosylguanosine using the H-phosphonate chemistry is described. An additional ring protected by benzoyl groups was incorporated into the main
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Synthesis of 5''-phosphate 2'-O-ribosylribonucleosides [Nr(p)] of four common ribonucleosides, and 3'-phosphoramidites of 5''-phosphate 2'-O-ribosyladenosine and 2'-O-ribosylguanosine using the H-phosphonate chemistry is described. An additional ring protected by benzoyl groups was incorporated into the main ribosyl ring in the reaction with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d-ribofuranose in the presence of SnCl4. The obtained 2'-O-ribosylribonucleosides (Nr) were applied in the subsequent transformations with selective deprotection. Ethanolamine was applied as a very convenient reagent for selective removal of benzoyl groups. Additionally, the tetraisopropyldisiloxane-1,3-diyl (TIPDSi) group was found to be stable under these deprotection conditions. Thus, the selectively deprotected 5''-hydroxyl group of Nr was transformed into an H-phosphonate monoester which was found to be stable under the following conditions: the removal of the TIPDSi group with triethylammonium fluoride and the dimethoxytritylation of the 5''-hydroxyl function. The 5''-H-phosphonate of Nr precursors was easily transformed to the corresponding dicyanoethyl 5''-O-phosphotriesters before phosphitylation, which gave 3'-phosphoramidite units of Nr(p) in high yield. The derived phosphoramidite units were used in an automated oligonucleotide synthesizer to produce dimer Ar(p)T via the phosphoramidite approach. The obtained products were fully deprotected under standard deprotection conditions giving dimers with a 5''-phosphate monoester function. Application of an alkaline phosphatase to prove the presence of an additional phosphate group was described. Full article
(This article belongs to the Special Issue Synthesis of Nucleosides, Nucleotides and Their Derivatives)
Open AccessArticle New Short Strategy for the Synthesis of the Dibenz[b,f]oxepin Scaffold
Molecules 2013, 18(12), 14797-14806; doi:10.3390/molecules181214797
Received: 14 November 2013 / Revised: 26 November 2013 / Accepted: 26 November 2013 / Published: 29 November 2013
Cited by 4 | PDF Full-text (257 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this report a short and efficient synthesis of the dibenz[b,f]oxepin framework through intramolecular SNAr and McMurry reactions is described. The diaryl ethers required for the McMurry reaction have been obtained in good yields under microwave-assisted conditions
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In this report a short and efficient synthesis of the dibenz[b,f]oxepin framework through intramolecular SNAr and McMurry reactions is described. The diaryl ethers required for the McMurry reaction have been obtained in good yields under microwave-assisted conditions of the reaction of salicylaldehydes with fluorobenzaldehydes without catalysts. Application of an intramolecular McMurry reaction to the synthesized diarylethers using TiCl4/Zn in THF gave the target dibenzo[b,f]oxepin system in 53%–55% yields. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Synthesis, Antimycobacterial Activity and In Vitro Cytotoxicity of 5-Chloro-N-phenylpyrazine-2-carboxamides
Molecules 2013, 18(12), 14807-14825; doi:10.3390/molecules181214807
Received: 15 November 2013 / Revised: 26 November 2013 / Accepted: 26 November 2013 / Published: 2 December 2013
Cited by 8 | PDF Full-text (330 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
5-Chloropyrazinamide (5-Cl-PZA) is an inhibitor of mycobacterial fatty acid synthase I with a broad spectrum of antimycobacterial activity in vitro. Some N-phenylpyrazine-2-carboxamides with different substituents on both the pyrazine and phenyl core possess significant in vitro activity against Mycobacterium tuberculosis.
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5-Chloropyrazinamide (5-Cl-PZA) is an inhibitor of mycobacterial fatty acid synthase I with a broad spectrum of antimycobacterial activity in vitro. Some N-phenylpyrazine-2-carboxamides with different substituents on both the pyrazine and phenyl core possess significant in vitro activity against Mycobacterium tuberculosis. To test the activity of structures combining both the 5-Cl-PZA and anilide motifs a series of thirty 5-chloro-N-phenylpyrazine-2-carboxamides with various substituents R on the phenyl ring were synthesized and screened against M. tuberculosis H37Rv, M. kansasii and two strains of M. avium. Most of the compounds exerted activity against M. tuberculosis H37Rv in the range of MIC = 1.56–6.25 µg/mL and only three derivatives were inactive. The phenyl part of the molecule tolerated many different substituents while maintaining the activity. In vitro cytotoxicity was decreased in compounds with hydroxyl substituents, preferably combined with other hydrophilic substituents. 5-Chloro-N-(5-chloro-2-hydroxyphenyl)pyrazine-2-carboxamide (21) inhibited all of the tested strains (MIC = 1.56 µg/mL for M. tuberculosis; 12.5 µg/mL for other strains). 4-(5-Chloropyrazine-2-carboxamido)-2-hydroxybenzoic acid (30) preserved good activity (MIC = 3.13 µg/mL M. tuberculosis) and was rated as non-toxic in two in vitro models (Chinese hamster ovary and renal cell adenocarcinoma cell lines; SI = 47 and 35, respectively). Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synthesis, Structures and Properties of Two Metal-Organic Coordination Polymers Derived from Manganese(ΙΙ), Thiabendazole and Polydentate Carboxylic Acids
Molecules 2013, 18(12), 14826-14839; doi:10.3390/molecules181214826
Received: 14 October 2013 / Revised: 22 November 2013 / Accepted: 26 November 2013 / Published: 2 December 2013
Cited by 2 | PDF Full-text (2694 KB) | HTML Full-text | XML Full-text
Abstract
Two novel binuclear Mn(II) metal-organic coordination complexes [Mn2(TBZ)2(CDC)(C2O4)]n (1), {[Mn2(TBZ)2(BDC)0.5(BTC)(H2O)2]·ET}n (2), (where TBZ = thiabendazole, H2CDC =
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Two novel binuclear Mn(II) metal-organic coordination complexes [Mn2(TBZ)2(CDC)(C2O4)]n (1), {[Mn2(TBZ)2(BDC)0.5(BTC)(H2O)2]·ET}n (2), (where TBZ = thiabendazole, H2CDC = trans-1,4-cyclohexanedicarboxylic acid, H2C2O4 = oxalic acid, H3BTC = 1,3,5-benzenetricarboxylic acid, ET = ethanol, H2BDC = 1,4-benzenedicarboxylate) have been hydrothermally synthesized and characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, electrochemical analysis and single crystal X-ray diffraction. The X-ray structure analysis reveals that 1 is s two-dimensional layer and 2 is s one-dimensional chain. In complex 1, it reveals 2-D layers composed of multi-(bidentate) bridging ligands (CDC and C2O4), and in 2, the coordinated BTC ligands adopt a monodentate mode and with BDC ligands adopt alternately chelating Mn1 and Mn2 bridges into 1-D chains. The 3-D structures of the two complexes are stabilized by π-π stacking interactions and hydrogen bonds. Full article
Open AccessArticle Synthesis and Binding Ability of Molecular Probes Based on a Phenanthroline Derivative: Theory and Experiment
Molecules 2013, 18(12), 14840-14848; doi:10.3390/molecules181214840
Received: 22 October 2013 / Revised: 13 November 2013 / Accepted: 13 November 2013 / Published: 3 December 2013
Cited by 4 | PDF Full-text (705 KB) | HTML Full-text | XML Full-text
Abstract
A fluorescent and colorimetric molecular probe containing phenol groups has been designed and synthesized. The anion binding ability was evaluated for biolgically important anions (F, Cl, Br, I, AcO and H2PO4
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A fluorescent and colorimetric molecular probe containing phenol groups has been designed and synthesized. The anion binding ability was evaluated for biolgically important anions (F, Cl, Br, I, AcO and H2PO4) by theoretical investigation, UV-Vis and fluorescence spectroscopy and 1H-NMR titration experiments. Results indicated the probe showed strong binding ability for H2PO4 without the interference of other anions tested and the interaction process was accompanied by color changes. Theoretical investigation analysis revealed that intramolecular hydrogen bonds existed in the structure of the probe and the roles of molecular frontier orbitals in molecular interplay were determined. Full article
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Open AccessArticle Quality Evaluation of Panax ginseng Roots Using a Rapid Resolution LC-QTOF/MS-Based Metabolomics Approach
Molecules 2013, 18(12), 14849-14861; doi:10.3390/molecules181214849
Received: 26 August 2013 / Revised: 24 November 2013 / Accepted: 26 November 2013 / Published: 3 December 2013
Cited by 3 | PDF Full-text (778 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Korean ginseng (Panax ginseng C.A. Meyer) contains several types of ginsenosides, which are considered the major active medicinal components of ginseng. The types and quantities of ginsenosides found in ginseng may differ, depending on the location of cultivation, making it necessary to
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Korean ginseng (Panax ginseng C.A. Meyer) contains several types of ginsenosides, which are considered the major active medicinal components of ginseng. The types and quantities of ginsenosides found in ginseng may differ, depending on the location of cultivation, making it necessary to establish a reliable method for distinguishing cultivation locations of ginseng roots. P. ginseng roots produced in different regions of Korea, China, and Japan have been unintentionally confused in herbal markets owing to their complicated plant sources. PCA and PLS-DA using RRLC-QTOF/MS data was able to differentiate between ginsengs cultivated in Korea, China, and Japan. The chemical markers accountable for such variations were identified through a PCA loadings plot, tentatively identified by RRLC-QTOF/MS and partially verified by available reference standards. The classification result can be used to identify P. ginseng origin. Full article
Open AccessArticle Immunomodulatory Effects of Hedysarum polybotrys Extract in Mice Macrophages, Splenocytes and Leucopenia
Molecules 2013, 18(12), 14862-14875; doi:10.3390/molecules181214862
Received: 30 September 2013 / Revised: 27 November 2013 / Accepted: 28 November 2013 / Published: 3 December 2013
PDF Full-text (645 KB) | HTML Full-text | XML Full-text
Abstract
Astragali Radix (Huang-Qi) is a popular herbal medicine commonly used as a constituent in tonic herbal preparations. Hedysarum polybotrys Handel-Mazzetti is one species used of Astragali Radix. In this study, the immunomodulatory properties of H. polybotrys were explored by LPS-activated and SNP-treated RAW
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Astragali Radix (Huang-Qi) is a popular herbal medicine commonly used as a constituent in tonic herbal preparations. Hedysarum polybotrys Handel-Mazzetti is one species used of Astragali Radix. In this study, the immunomodulatory properties of H. polybotrys were explored by LPS-activated and SNP-treated RAW 264.7 cells and splenocytes and, daunoblastina-induced leucopenia BALB/c mice. Formononetin was used as the bioactive marker to monitor the quality of the H. polybotrys extracts. H. polybotrys was extracted with hot-water and methanol, and MeOH extract partitioned with H2O (M-H) and ethyl acetate (M-EA) to yield four different fractions. M-EA had the highest formononetin and total proanthocyanidin content and showed stronger inhibitory effects on the production and expression of NO, PGE2, iNOS and COX-2 in LPS-activated RAW 264.7 cells and splenocytes than the other fractions. In addition, M-EA significantly stimulated the proliferation of LPS-activated RAW 264.7 cells and splenocytes, enhanced NO radicals scavenging and attenuated NO-induced cytotoxicity.  Furthermore, M-EA also significantly increased the rate of recovery of white blood cells level in daunoblastina-induced leucopenia mice. These evidences suggest that this traditional Qi-tonifying herb has potential effects in clinical conditions when immune-enhancing and anti-inflammatory effect is desired. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Design, Synthesis, Biological Activities and 3D-QSAR of New N,N'-Diacylhydrazines Containing 2,4-Dichlorophenoxy Moieties
Molecules 2013, 18(12), 14876-14891; doi:10.3390/molecules181214876
Received: 21 October 2013 / Revised: 27 November 2013 / Accepted: 28 November 2013 / Published: 3 December 2013
Cited by 10 | PDF Full-text (430 KB) | HTML Full-text | XML Full-text
Abstract
A series of new N,N'-diacylhydrazine derivatives were designed and synthesized. Their structures were verified by 1H-NMR, MS and elemental analysis. The herbicidal activities and plant growth regulating activity of these N,N'-diacylhydrazines were evaluated. The herbicidal activity results showed
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A series of new N,N'-diacylhydrazine derivatives were designed and synthesized. Their structures were verified by 1H-NMR, MS and elemental analysis. The herbicidal activities and plant growth regulating activity of these N,N'-diacylhydrazines were evaluated. The herbicidal activity results showed that most of these N,N'-diacyl-hydrazines showed excellent in vivo activities against Echinochloa crus-galli, Digitaria sanguinalis, Brassica napus, Amaranthus retroflerus. Most of them exhibited higher herbicidal activities against dicotyledonous weeds than monocotyledonous weeds. To further investigate the structure-activity relationship, comparative molecular field analysis (CoMFA) was performed on the basis of herbicidal activity data. Both the steric and electronic field distributions of CoMFA are in good agreement in this work. Full article
Open AccessArticle Phenolic Esters of O-Desmethylvenlafaxine with Improved Oral Bioavailability and Brain Uptake
Molecules 2013, 18(12), 14920-14934; doi:10.3390/molecules181214920
Received: 30 October 2013 / Revised: 2 December 2013 / Accepted: 2 December 2013 / Published: 4 December 2013
PDF Full-text (357 KB) | HTML Full-text | XML Full-text
Abstract
O-Desmethylvenlafaxine (desvenlafaxine, ODV) is a recently approved antidepressant which in some clinical studies failed to meet a satisfactory end-point. The aim of this study was to prepare a series of phenolic esters of ODV and evaluate their potential as ODV prodrugs with
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O-Desmethylvenlafaxine (desvenlafaxine, ODV) is a recently approved antidepressant which in some clinical studies failed to meet a satisfactory end-point. The aim of this study was to prepare a series of phenolic esters of ODV and evaluate their potential as ODV prodrugs with improved brain uptake. Fifteen phenolic esters (compounds 1ao) were synthesized and their pharmacokinetic profiles evaluated in rat. The four compounds producing the highest relative bioavailability of ODV in rat (compounds 1c, 1e, 1n, 1o) were then studied to evaluate their brain uptake. Of these four compounds, compound 1n (the piperonylic acid ester of ODV) demonstrated the highest Cmax of ODV both in the rat hypothalamus and total brain. Finally the pharmacokinetics of 1n were evaluated in beagle dog where the increase in relative bioavailability of ODV was found to be as great as in rat. This high relative bioavailability of ODV coupled with its good brain penetration make 1n the most promising candidate for development as an ODV prodrug. Full article
Open AccessArticle Sodium Valproate Induces Cell Senescence in Human Hepatocarcinoma Cells
Molecules 2013, 18(12), 14935-14947; doi:10.3390/molecules181214935
Received: 4 November 2013 / Revised: 27 November 2013 / Accepted: 27 November 2013 / Published: 4 December 2013
Cited by 3 | PDF Full-text (1571 KB) | HTML Full-text | XML Full-text
Abstract
Hepatocarcinogenesis is associated with epigenetic changes, including histone deacetylases (HDACs). Epigenetic modulation by HDAC inhibition is a potentially valuable approach for hepatocellular carcinoma treatment. In present study, we evaluated the anticancer effects of sodium valproate (SVP), a known HDAC inhibitor, in human hepatocarcinoma
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Hepatocarcinogenesis is associated with epigenetic changes, including histone deacetylases (HDACs). Epigenetic modulation by HDAC inhibition is a potentially valuable approach for hepatocellular carcinoma treatment. In present study, we evaluated the anticancer effects of sodium valproate (SVP), a known HDAC inhibitor, in human hepatocarcinoma cells. The results showed SVP inhibited the proliferation of Bel-7402 cells in a dose-dependent manner. Low dose SVP treatment caused a large and flat morphology change, positive SA-β-gal staining, and G0/G1 phase cell cycle arrest in human hepatocarcinoma cells. Low dose SVP treatment also increased acetylation of histone H3 and H4 on p21 promoter, accompanied by up-regulation of p21 and down-regulation of RB phosphorylation. These observations suggested that a low dose of SVP could induce cell senescence in hepatocarcinoma cells, which might correlate with hyperacetylation of histone H3 and H4, up-regulation of p21, and inhibition of RB phosphorylation. Since the effective concentration inducing cell senescence in hepatocarcinoma cells is clinically available, whether a clinical dose of SVP could induce cell senescence in clinical hepatocarcinoma is worthy of further study. Full article
Open AccessArticle Chemical Composition and Biological Activity of Essential Oils of Origanum vulgare L. subsp. vulgare L. under Different Growth Conditions
Molecules 2013, 18(12), 14948-14960; doi:10.3390/molecules181214948
Received: 24 October 2013 / Revised: 25 November 2013 / Accepted: 27 November 2013 / Published: 4 December 2013
Cited by 19 | PDF Full-text (246 KB) | HTML Full-text | XML Full-text
Abstract
This research was aimed at investigating the essential oil production, chemical composition and biological activity of a crop of pink flowered oregano (Origanum vulgare L. subsp. vulgare L.) under different spatial distribution of the plants (single and binate rows). This plant factor
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This research was aimed at investigating the essential oil production, chemical composition and biological activity of a crop of pink flowered oregano (Origanum vulgare L. subsp. vulgare L.) under different spatial distribution of the plants (single and binate rows). This plant factor was shown to affect its growth, soil covering, fresh biomass, essential oil amount and composition. In particular, the essential oil percentage was higher for the binate row treatment at the full bloom. The chemical composition of the oils obtained by hydrodistillation was fully characterized by GC and GC-MS. The oil from plants grown in single rows was rich in sabinene, while plants grown in double rows were richer in ocimenes. The essential oils showed antimicrobial action, mainly against Gram-positive pathogens and particularly Bacillus cereus and B. subtilis. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis, Spectroscopic and Semiempirical Studies of New Quaternary Alkylammonium Conjugates of Sterols
Molecules 2013, 18(12), 14961-14976; doi:10.3390/molecules181214961
Received: 6 November 2013 / Revised: 27 November 2013 / Accepted: 28 November 2013 / Published: 5 December 2013
Cited by 6 | PDF Full-text (691 KB) | HTML Full-text | XML Full-text
Abstract
New quaternary alkylammonium conjugates of steroids were obtained by two step reaction of sterols (ergosterol, cholesterol, dihydrocholesterol) with bromoacetic acid bromide, followed by bimolecular nucleophilic substitution with a long chain tertiary alkylamine. The structures of products were confirmed by spectral (1H-NMR,
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New quaternary alkylammonium conjugates of steroids were obtained by two step reaction of sterols (ergosterol, cholesterol, dihydrocholesterol) with bromoacetic acid bromide, followed by bimolecular nucleophilic substitution with a long chain tertiary alkylamine. The structures of products were confirmed by spectral (1H-NMR, 13C-NMR, and FT-IR) analysis, mass spectrometry and PM5 semiempirical methods. The pharmacotherapeutic potential of synthesized compounds has been estimated on the basis of Prediction of Activity Spectra for Substances (PASS). Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Multiplexed Analysis of Cage and Cage Free Chicken Egg Fatty Acids Using Stable Isotope Labeling and Mass Spectrometry
Molecules 2013, 18(12), 14977-14988; doi:10.3390/molecules181214977
Received: 23 September 2013 / Revised: 29 November 2013 / Accepted: 2 December 2013 / Published: 5 December 2013
Cited by 3 | PDF Full-text (296 KB) | HTML Full-text | XML Full-text
Abstract
Binary stable isotope labeling couple with LC-ESI-MS has been used as a powerful non-targeted approach for the relative quantification of lipids, amino acids, and many other important metabolite classes. A multiplexed approach using three or more isotopic labeling reagents greatly reduces analytical run-time
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Binary stable isotope labeling couple with LC-ESI-MS has been used as a powerful non-targeted approach for the relative quantification of lipids, amino acids, and many other important metabolite classes. A multiplexed approach using three or more isotopic labeling reagents greatly reduces analytical run-time while maintaining excellent sensitivity and reproducibility. Three isotopic cholamine labeling reagents have been developed to take advantage of the pre-ionized character of cholamine, for ESI, and the ease by which stable isotopes can be incorporated into the cholamine structure. These three cholamine labeling reagents have been used to relatively quantify three fatty acid samples simultaneously. The quantification resulted in the observation of 12 fatty acids that had an average absolute error of 0.9% and an average coefficient of variation of 6.1%. Caged versus cage-free isotope labeling experiments showed that cage-free eggs have an increased level of omega-3 fatty acids as compared to caged eggs. This multiplexed fatty acid analysis provides an inexpensive and expedited tool for broad-based lipid profiling that will further aid discoveries in the mechanisms of fatty acid action in cells. Full article
(This article belongs to the Special Issue Fatty Acids)
Open AccessArticle Effects of Aronia melanocarpa Constituents on Biofilm Formation of Escherichia coli and Bacillus cereus
Molecules 2013, 18(12), 14989-14999; doi:10.3390/molecules181214989
Received: 8 October 2013 / Revised: 30 November 2013 / Accepted: 2 December 2013 / Published: 5 December 2013
Cited by 5 | PDF Full-text (447 KB) | HTML Full-text | XML Full-text
Abstract
Many bacteria growing on surfaces form biofilms. Adaptive and genetic changes of the microorganisms in this structure make them resistant to antimicrobial agents. Biofilm-forming organisms on medical devices can pose serious threats to human health. Thus, there is a need for novel prevention
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Many bacteria growing on surfaces form biofilms. Adaptive and genetic changes of the microorganisms in this structure make them resistant to antimicrobial agents. Biofilm-forming organisms on medical devices can pose serious threats to human health. Thus, there is a need for novel prevention and treatment strategies. This study aimed to evaluate the ability of Aronia melanocarpa extracts, subfractions and compounds to prevent biofilm formation and to inhibit bacterial growth of Escherichia coli and Bacillus cereus in vitro. It was found that several aronia substances possessed anti-biofilm activity, however, they were not toxic to the species screened. This non-toxic inhibition may confer a lower potential for resistance development compared to conventional antimicrobials. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Biological Activity of 3-[Phenyl(1,3-thiazol-2-yl)-amino]propanoic Acids and Their Derivatives
Molecules 2013, 18(12), 15000-15018; doi:10.3390/molecules181215000
Received: 24 October 2013 / Revised: 3 December 2013 / Accepted: 3 December 2013 / Published: 5 December 2013
Cited by 7 | PDF Full-text (313 KB) | HTML Full-text | XML Full-text
Abstract
New N,N-disubstituted β-amino acids and their derivatives with thiazole, aromatic, and heterocyclic substituents were synthesized from N-phenyl-N-thiocarbamoyl-β-alanine by the Hantzsch method; derivatives with hydrazone fragments were also obtained. Some of the synthesized compounds exhibited discrete antimicrobial activity,
[...] Read more.
New N,N-disubstituted β-amino acids and their derivatives with thiazole, aromatic, and heterocyclic substituents were synthesized from N-phenyl-N-thiocarbamoyl-β-alanine by the Hantzsch method; derivatives with hydrazone fragments were also obtained. Some of the synthesized compounds exhibited discrete antimicrobial activity, and 3-[(4-oxo-4,5-dihydro-1,3-thiazol-2-yl)(phenyl)amino]propanoic acid was found to promote rapeseed growth and to increase seed yield and oil content. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Helping Eve Overcome ADAM: G-Quadruplexes in the ADAM-15 Promoter as New Molecular Targets for Breast Cancer Therapeutics
Molecules 2013, 18(12), 15019-15034; doi:10.3390/molecules181215019
Received: 25 September 2013 / Revised: 25 November 2013 / Accepted: 26 November 2013 / Published: 5 December 2013
Cited by 1 | PDF Full-text (742 KB) | HTML Full-text | XML Full-text
Abstract
ADAM-15, with known zymogen, secretase, and disintegrin activities, is a catalytically active member of the ADAM family normally expressed in early embryonic development and aberrantly expressed in various cancers, including breast, prostate and lung. ADAM-15 promotes extracellular shedding of E-cadherin, a soluble ligand
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ADAM-15, with known zymogen, secretase, and disintegrin activities, is a catalytically active member of the ADAM family normally expressed in early embryonic development and aberrantly expressed in various cancers, including breast, prostate and lung. ADAM-15 promotes extracellular shedding of E-cadherin, a soluble ligand for the HER2/neu receptor, leading to activation, increased motility, and proliferation. Targeted downregulation of both ADAM-15 and HER2/neu function synergistically kills breast cancer cells, but to date there are no therapeutic options for decreasing ADAM-15 function or expression. In this vein, we have examined a unique string of guanine-rich DNA within the critical core promoter of ADAM-15. This region of DNA consists of seven contiguous runs of three or more consecutive guanines, which, under superhelical stress, can relax from duplex DNA to form an intrastrand secondary G-quadruplex (G4) structure. Using biophysical and biological techniques, we have examined the G4 formation within the entire and various truncated regions of the ADAM-15 promoter, and demonstrate strong intrastrand G4 formation serving to function as a biological silencer element. Characterization of the predominant G4 species formed within the ADAM-15 promoter will allow for specific drug targeting and stabilization, and the further development of novel, targeted therapeutics. Full article
(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)
Open AccessArticle Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives
Molecules 2013, 18(12), 15035-15050; doi:10.3390/molecules181215035
Received: 22 September 2013 / Revised: 27 November 2013 / Accepted: 2 December 2013 / Published: 6 December 2013
Cited by 9 | PDF Full-text (693 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Thiazacridine and imidazacridine derivatives have shown promising results as tumors suppressors in some cancer cell lines. For a better understanding of the mechanism of action of these compounds, binding studies of 5-acridin-9-ylmethylidene-3-amino-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-imidazolidin-4-one and 3-acridin-9-ylmethyl-thiazolidin-2,4-dione with calf thymus DNA (ctDNA) by electronic
[...] Read more.
Thiazacridine and imidazacridine derivatives have shown promising results as tumors suppressors in some cancer cell lines. For a better understanding of the mechanism of action of these compounds, binding studies of 5-acridin-9-ylmethylidene-3-amino-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-imidazolidin-4-one and 3-acridin-9-ylmethyl-thiazolidin-2,4-dione with calf thymus DNA (ctDNA) by electronic absorption and fluorescence spectroscopy and circular dichroism spectroscopy were performed. The binding constants ranged from 1.46 × 104 to 6.01 × 104 M−1. UV-Vis, fluorescence and circular dichroism measurements indicated that the compounds interact effectively with ctDNA, both by intercalation or external binding. They demonstrated inhibitory activities to human topoisomerase I, except for 5-acridin-9-ylmethylidene-2-thioxo-1,3-thiazolidin-4-one. These results provide insight into the DNA binding mechanism of imidazacridines and thiazacridines. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis and Pharmacological Activities of Some New Triazolo- and Tetrazolopyrimidine Derivatives
Molecules 2013, 18(12), 15051-15063; doi:10.3390/molecules181215051
Received: 27 September 2013 / Revised: 21 November 2013 / Accepted: 29 November 2013 / Published: 6 December 2013
Cited by 7 | PDF Full-text (231 KB) | HTML Full-text | XML Full-text
Abstract
A new series of fused triazolo- and tetrazolopyrimidine derivatives 214 were synthesized and their anti-inflammatory and ulcerogenic activities were evaluated. The pharmacological screening showed that many of these obtained compounds have good anti-inflammatory activities, comparable to the reference drug. The toxicity
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A new series of fused triazolo- and tetrazolopyrimidine derivatives 214 were synthesized and their anti-inflammatory and ulcerogenic activities were evaluated. The pharmacological screening showed that many of these obtained compounds have good anti-inflammatory activities, comparable to the reference drug. The toxicity of the compounds was also assayed via the determination of their LD50 values. The structures of newly synthesized compounds were confirmed by IR, 1H-NMR, MS spectral data and elemental analysis. Full article
Open AccessArticle Multicomponent Click Synthesis of New 1,2,3-Triazole Derivatives of Pyrimidine Nucleobases: Promising Acidic Corrosion Inhibitors for Steel
Molecules 2013, 18(12), 15064-15079; doi:10.3390/molecules181215064
Received: 6 November 2013 / Revised: 30 November 2013 / Accepted: 2 December 2013 / Published: 6 December 2013
Cited by 10 | PDF Full-text (388 KB) | HTML Full-text | XML Full-text
Abstract
A series of new mono-1,2,3-triazole derivatives of pyrimidine nucleobases were synthesized by one-pot copper(I)-catalyzed 1,3-dipolar cycloaddition reactions between N-1-propargyluracil and thymine, sodium azide and several benzyl halides. The desired heterocyclic compounds were obtained in good yields and characterized by NMR, IR, and
[...] Read more.
A series of new mono-1,2,3-triazole derivatives of pyrimidine nucleobases were synthesized by one-pot copper(I)-catalyzed 1,3-dipolar cycloaddition reactions between N-1-propargyluracil and thymine, sodium azide and several benzyl halides. The desired heterocyclic compounds were obtained in good yields and characterized by NMR, IR, and high resolution mass spectrometry. These compounds were investigated as corrosion inhibitors for steel in 1 M HCl solution, using electrochemical impedance spectroscopy (EIS) technique. The results indicate that these heterocyclic compounds are promising acidic corrosion inhibitors for steel. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Syntheses of Four Enantiomers of 2,3-Diendo- and 3-Endo-aminobicyclo[2.2.2]oct-5-ene-2-exo-carboxylic Acid and Their Saturated Analogues
Molecules 2013, 18(12), 15080-15093; doi:10.3390/molecules181215080
Received: 11 November 2013 / Revised: 2 December 2013 / Accepted: 3 December 2013 / Published: 6 December 2013
Cited by 3 | PDF Full-text (359 KB) | HTML Full-text | XML Full-text
Abstract
Ethyl 2,3-diendo-3-aminobicyclo[2.2.2]oct-5-ene-2-carboxylate ((±)-1) was resolved with O,O'-dibenzoyltartaric acid via diastereomeric salt formation. The efficient synthesis of the enantiomers of 2,3-diendo-3-aminobicyclo[2.2.2]oct-5-ene-2-carboxylic acid ((+)-7 and (–)-7), 3-endo-aminobicyclo[2.2.2]oct-5-ene-2-exo-carboxylic acid ((+)-
[...] Read more.
Ethyl 2,3-diendo-3-aminobicyclo[2.2.2]oct-5-ene-2-carboxylate ((±)-1) was resolved with O,O'-dibenzoyltartaric acid via diastereomeric salt formation. The efficient synthesis of the enantiomers of 2,3-diendo-3-aminobicyclo[2.2.2]oct-5-ene-2-carboxylic acid ((+)-7 and (–)-7), 3-endo-aminobicyclo[2.2.2]oct-5-ene-2-exo-carboxylic acid ((+)-5 and (–)-5), cis- and trans-3-aminobicyclo[2.2.2]octane-2-carboxylic acid ((+)-6, (–)-6, (+)-8 and (–)-8) was achieved via isomerization, hydrogenation and hydrolysis of the corresponding esters (–)-1 and (+)-1. The stereochemistry and relative configurations of the synthesized compounds were determined by NMR spectroscopy (based on the 3J(H,H) coupling constants) and X-ray crystallography. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Maternal High Fat Feeding Does Not Have Long-Lasting Effects on Body Composition and Bone Health in Female and Male Wistar Rat Offspring at Young Adulthood
Molecules 2013, 18(12), 15094-15109; doi:10.3390/molecules181215094
Received: 30 October 2013 / Revised: 27 November 2013 / Accepted: 3 December 2013 / Published: 6 December 2013
Cited by 9 | PDF Full-text (320 KB) | HTML Full-text | XML Full-text
Abstract
High fat diets adversely affect body composition, bone mineral and strength, and alter bone fatty acid composition. It is unclear if maternal high fat (HF) feeding permanently alters offspring body composition and bone health. Female rats were fed control (CON) or HF diet
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High fat diets adversely affect body composition, bone mineral and strength, and alter bone fatty acid composition. It is unclear if maternal high fat (HF) feeding permanently alters offspring body composition and bone health. Female rats were fed control (CON) or HF diet for 10 weeks, bred, and continued their diets throughout pregnancy and lactation. Male and female offspring were studied at weaning and 3 months, following consumption of CON diet. At weaning, but not 3 months of age, male and female offspring from dams fed HF diet had lower lean mass and higher fat and bone mass, and higher femur bone mineral density (females only) than offspring of dams fed CON diet. Male and female offspring femurs from dams fed HF diet had higher monounsaturates and lower n6 polyunsaturates at weaning than offspring from dams fed CON diet, where females from dams fed HF diet had higher saturates and lower n6 polyunsaturates at 3 months of age. There were no differences in strength of femurs or lumbar vertebrae at 3 months of age in either male or female offspring. In conclusion, maternal HF feeding did not permanently affect body composition and bone health at young adulthood in offspring. Full article
(This article belongs to the Special Issue Fatty Acids)
Open AccessArticle Implications of Partial Conjugation of Whey Protein Isolate to Durian Seed Gum through Maillard Reactions: Foaming Properties, Water Holding Capacity and Interfacial Activity
Molecules 2013, 18(12), 15110-15125; doi:10.3390/molecules181215110
Received: 24 September 2013 / Revised: 28 November 2013 / Accepted: 29 November 2013 / Published: 6 December 2013
Cited by 4 | PDF Full-text (405 KB) | HTML Full-text | XML Full-text
Abstract
This paper deals with the conjugation of durian seed gum (DSG) with whey protein isolate (WPI) through Maillard reactions. Subsequently, the functional properties of durian seed gum in the non-conjugated (control sample) and conjugated forms were compared with several commercial gums (i.e.
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This paper deals with the conjugation of durian seed gum (DSG) with whey protein isolate (WPI) through Maillard reactions. Subsequently, the functional properties of durian seed gum in the non-conjugated (control sample) and conjugated forms were compared with several commercial gums (i.e., Arabic gum, sodium alginate, kappa carrageenan, guar gum, and pectin). The current study revealed that the conjugation of durian seed gum with whey protein isolate significantly (p < 0.05) improved its foaming properties. In this study, the conjugated durian seed gum produced the most stable foam among all samples. On the other hand, the emulsion stabilized with the conjugated durian seed gum also showed more uniform particles with a larger specific surface area than the emulsion containing the non-conjugated durian seed gum. The conjugated durian seed gum showed significant different foaming properties, specific surface area, particle uniformity and water holding capacity (WHC) as compared to the target polysaccharide gums. The conjugated durian seed gum showed more similar functional properties to Arabic gum rather than other studied gums. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Polyketides from the Halotolerant Fungus Myrothecium sp. GS-17
Molecules 2013, 18(12), 15126-15133; doi:10.3390/molecules181215126
Received: 12 November 2013 / Revised: 29 November 2013 / Accepted: 4 December 2013 / Published: 6 December 2013
Cited by 2 | PDF Full-text (436 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new polyketides, myrothecol (1) and 5-hydroxy-3-methyl-4-(1- hydroxylethyl)-furan-2(5H)-one (2), were isolated from the fermentation broth of the halotolerant fungus Myrothecium sp. GS-17 along with three known compounds, 5-hydroxyl-3-[(1S)-1-hydroxyethyl]-4-methylfuran-2(5H)-one (3), 3,5-dimethyl-4- hydroxylmethyl-5-methoxyfuran-2(5
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Two new polyketides, myrothecol (1) and 5-hydroxy-3-methyl-4-(1- hydroxylethyl)-furan-2(5H)-one (2), were isolated from the fermentation broth of the halotolerant fungus Myrothecium sp. GS-17 along with three known compounds, 5-hydroxyl-3-[(1S)-1-hydroxyethyl]-4-methylfuran-2(5H)-one (3), 3,5-dimethyl-4- hydroxylmethyl-5-methoxyfuran-2(5H)-one (4), and 3,5-dimethyl-4-hydroxymethyl-5- hydroxyfuran-2(5H)-one (5). Compound 1 is the first natural occurring polyketide with a unique furylisobenzofuran skeleton. The structures of these compounds were established via extensive spectroscopic analyses including 1D-, 2D-NMR, HRESI-MS, and crystal X-ray diffraction analysis. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Characterization of Flavonoids in the Ethomedicine Fordiae Cauliflorae Radix and Its Adulterant Millettiae Pulchrae Radix by HPLC-DAD-ESI-IT-TOF-MSn
Molecules 2013, 18(12), 15134-15152; doi:10.3390/molecules181215134
Received: 14 October 2013 / Revised: 26 November 2013 / Accepted: 4 December 2013 / Published: 9 December 2013
Cited by 5 | PDF Full-text (1399 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fordiae Cauliflorae Radix (FC, the root of Fordia cauliflora Hemsl) and Millettiae Pulchrae Radix [MP, the root of Millettia pulchra (Benth.) Kurz var. laxior (Dunn) Z. Wei], which go under the same local name of “Daluosan”, have long been used in Southern China
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Fordiae Cauliflorae Radix (FC, the root of Fordia cauliflora Hemsl) and Millettiae Pulchrae Radix [MP, the root of Millettia pulchra (Benth.) Kurz var. laxior (Dunn) Z. Wei], which go under the same local name of “Daluosan”, have long been used in Southern China for the treatment of stroke, paralysis, dementia in children, Alzheimer’s disease and other diseases. The same local name and similar functions always confuse users. To further utilize these two ethnodrugs and identify them unambiguously, an HPLC-DAD-ESI-IT-TOF-MSn method was developed to separate and characterize the flavonoids in FC and MP. A total of 41 flavonoids were detected, of which six compounds were identified by comparing their retention time and MS data with those of the reference standards, and the others were tentatively identified based on their tandem mass spectrometry data obtained in the positive ion detection mode. Nineteen of these characterized compounds are reported from these two plants for the first time. Full article
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Open AccessArticle Extending the Glucosyl Ceramide Cassette Approach: Application in the Total Synthesis of Ganglioside GalNAc-GM1b
Molecules 2013, 18(12), 15153-15181; doi:10.3390/molecules181215153
Received: 7 November 2013 / Revised: 1 December 2013 / Accepted: 2 December 2013 / Published: 10 December 2013
Cited by 4 | PDF Full-text (610 KB) | HTML Full-text | XML Full-text
Abstract
The development of a novel cyclic glucosyl ceramide cassette acceptor for efficient glycolipid syntheses was investigated. p-Methoxybenzyl (PMB) groups were selected as protecting groups at C2 and C3 of the glucose residue with the aim of improving the functionality of the cassette
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The development of a novel cyclic glucosyl ceramide cassette acceptor for efficient glycolipid syntheses was investigated. p-Methoxybenzyl (PMB) groups were selected as protecting groups at C2 and C3 of the glucose residue with the aim of improving the functionality of the cassette acceptor. The choice of the PMB group resulted in a loss of β-selectivity, which was corrected by using an appropriate tether to control the spatial arrangement and the nitrile solvent effect. To investigate the effect of linker structure on the β-selectivity of intramolecular glycosylation, several linkers for tethering the glucose and ceramide moiety were designed and prepared, namely, succinyl, glutaryl, dimethylmalonyl, and phthaloyl esters. The succinyl ester linker was the best for accessing the cassette form. The newly designed glucosyl ceramide cassette acceptor was then applied in the total synthesis of ganglioside GalNAc-GM1b. Full article
(This article belongs to the Special Issue Synthesis, Structure, Analysis and Properties of Glycolipids)
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Open AccessCommunication Efficient PPA-SiO2-catalyzed Synthesis of β-enaminones Under Solvent-Free Conditions
Molecules 2013, 18(12), 15182-15192; doi:10.3390/molecules181215182
Received: 30 September 2013 / Revised: 14 November 2013 / Accepted: 14 November 2013 / Published: 10 December 2013
Cited by 3 | PDF Full-text (350 KB) | HTML Full-text | XML Full-text
Abstract
An efficient method has been developed for the synthesis of β-enaminones under solvent-free reaction conditions using PPA-SiO2 as catalyst. The reaction yields were good to excellent (up to 90%). This methodology affords high selectivity and good tolerance of a variety of different
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An efficient method has been developed for the synthesis of β-enaminones under solvent-free reaction conditions using PPA-SiO2 as catalyst. The reaction yields were good to excellent (up to 90%). This methodology affords high selectivity and good tolerance of a variety of different functional groups present on both aromatic and aliphatic amines. In addition, the methodology is environmentally benign and cost-effective due to absence of solvent and easy work-up. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Facile Synthesis of the Naturally Cytotoxic Triterpenoid Saponin Patrinia-Glycoside B-II and Its Conformer
Molecules 2013, 18(12), 15193-15206; doi:10.3390/molecules181215193
Received: 30 October 2013 / Revised: 2 December 2013 / Accepted: 3 December 2013 / Published: 10 December 2013
Cited by 3 | PDF Full-text (522 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The first chemical synthesis of the natural triterpenoid saponin Patrinia-glycoside B-II, namely oleanolic acid 3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-gluco-pyranosyl-(1→3)]-α-L-arabinopyranoside, has been accomplished in a linear 11-step sequence 11 with 9.4% overall yield. The abnormal 1C4 conformation of the arabinose residue was found to
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The first chemical synthesis of the natural triterpenoid saponin Patrinia-glycoside B-II, namely oleanolic acid 3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-gluco-pyranosyl-(1→3)]-α-L-arabinopyranoside, has been accomplished in a linear 11-step sequence 11 with 9.4% overall yield. The abnormal 1C4 conformation of the arabinose residue was found to occur via conformational fluctuation during preparation of the intermediates. Molecular mechanism and quantum chemistry calculations showed that Patrinia-glycoside B-II and its conformer 1 cannot interconvert under normal conditions. Preliminary structure-activity relationships studies indicated that the 4C1 chair conformation of the arabinose residue in the unique α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl disaccharide moiety is one of the chief positive factors responsible for its cytotoxic activity against tumors. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Repetitive Two-Step Method for o,o,p- and o,p-Oligophenylene Synthesis through Pd-Catalyzed Cross-Coupling of Hydroxyterphenylboronic Acid
Molecules 2013, 18(12), 15207-15219; doi:10.3390/molecules181215207
Received: 16 October 2013 / Revised: 22 November 2013 / Accepted: 27 November 2013 / Published: 10 December 2013
Cited by 1 | PDF Full-text (447 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A repetitive two-step method involving the Pd-catalyzed Suzuki-Miyaura coupling of hydroxyterphenylboronic acid and the subsequent nonaflation of the hydroxy group has been developed for the synthesis of oligophenylenes. This method readily afforded o,o,p- and o,p-oligophenylenes
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A repetitive two-step method involving the Pd-catalyzed Suzuki-Miyaura coupling of hydroxyterphenylboronic acid and the subsequent nonaflation of the hydroxy group has been developed for the synthesis of oligophenylenes. This method readily afforded o,o,p- and o,p-oligophenylenes with defined chain lengths. X-ray crystallography was employed to obtain the structure of the o,p-oligophenylene 9-mer. Full article
(This article belongs to the Special Issue Palladium Catalysts)
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Open AccessArticle Synthesis and Structure-Activity Relationships of Novel Ecdysteroid Dioxolanes as MDR Modulators in Cancer
Molecules 2013, 18(12), 15255-15275; doi:10.3390/molecules181215255
Received: 31 October 2013 / Revised: 30 November 2013 / Accepted: 2 December 2013 / Published: 10 December 2013
Cited by 7 | PDF Full-text (357 KB) | HTML Full-text | XML Full-text
Abstract
Ecdysteroids, molting hormones of insects, can exert several mild, non-hormonal bioactivities in mammals, including humans. In a previous study, we have found a significant effect of certain derivatives on the ABCB1 transporter mediated multi-drug resistance of a transfected murine leukemia cell line. In
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Ecdysteroids, molting hormones of insects, can exert several mild, non-hormonal bioactivities in mammals, including humans. In a previous study, we have found a significant effect of certain derivatives on the ABCB1 transporter mediated multi-drug resistance of a transfected murine leukemia cell line. In this paper, we present a structure-activity relationship study focused on the apolar dioxolane derivatives of 20-hydroxyecdysone. Semi-synthesis and bioactivity of a total of 32 ecdysteroids, including 20 new compounds, is presented, supplemented with their complete 1H- and 13C-NMR signal assignment. Full article
(This article belongs to the Special Issue Bioactivity-focused Semi-synthesis in Drug Discovery)
Open AccessArticle Antimalarial Activity of 4-Metoxychalcones: Docking Studies as Falcipain/Plasmepsin Inhibitors, ADMET and Lipophilic Efficiency Analysis to Identify a Putative Oral Lead Candidate
Molecules 2013, 18(12), 15276-15287; doi:10.3390/molecules181215276
Received: 20 September 2013 / Revised: 23 November 2013 / Accepted: 30 November 2013 / Published: 10 December 2013
Cited by 4 | PDF Full-text (603 KB) | HTML Full-text | XML Full-text
Abstract
Herein, we report the antimalarial activity of nine 4-methoxychalcone derivatives 1ai and an initial analysis of their ADMET properties. All compounds showed potent activity against the P. falciparum chloroquine-resistant clone W2, with IC50 values ranging from 1.96 µM to 10.99
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Herein, we report the antimalarial activity of nine 4-methoxychalcone derivatives 1ai and an initial analysis of their ADMET properties. All compounds showed potent activity against the P. falciparum chloroquine-resistant clone W2, with IC50 values ranging from 1.96 µM to 10.99 µM, with moderate or low cytotoxicity against the HeLa cell line. The compound 1a (IC50 = 2.06 µM) had the best selectivity index (9.0). All the sulfonamide 4-metychalcone derivatives synthesized had cLogP values between 2 and 5 (mean value 3.79) and molecular weights (MWs) below 500. The substitution of the pyrrolidine group in 1i by a morpholine group in 1a reduced the cLogP value from 3.05 in compound 1i to 2.34 in compound 1a. Indeed, compound 1a had the highest LipE value. The binding free energy of compound 1a showed it to be the most optimal chalcone derivative for plasmepsin-2 (−7.3 Kcal/mol). The physicochemical properties and LipE analysis of the dataset allowed us to establish that compound 1a is the highest quality compound of the series and a potential oral lead candidate. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessCommunication Structure Activity Relationships of N-linked and Diglycosylated Glucosamine-Based Antitumor Glycerolipids
Molecules 2013, 18(12), 15288-15304; doi:10.3390/molecules181215288
Received: 15 November 2013 / Revised: 3 December 2013 / Accepted: 4 December 2013 / Published: 10 December 2013
Cited by 3 | PDF Full-text (494 KB) | HTML Full-text | XML Full-text
Abstract
1-O-Hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol (1) was previously reported to show potent in vitro antitumor activity on a range of cancer cell lines derived from breast, pancreas and prostate cancer. This compound was not toxic to mice
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1-O-Hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol (1) was previously reported to show potent in vitro antitumor activity on a range of cancer cell lines derived from breast, pancreas and prostate cancer. This compound was not toxic to mice and was inactive against breast tumor xenografts in mice. This inactivity was attributed to hydrolysis of the glycosidic linkage by glycosidases. Here three N-linked (glycosylamide) analogs 24, one triazole-linked analog 5 of 1 as well as two diglycosylated analogs 6 and 7 with different stereochemistry at the C2-position of the glycerol moiety were synthesized and their antitumor activity against breast (JIMT-1, BT-474, MDA-MB-231), pancreas (MiaPaCa2) and prostrate (DU145, PC3) cancer cell lines was determined. The diglycosylated analogs 1-O-hexadecyl-2(R)-, 3-O-di-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol (7) and the 1:1 diastereomeric mixture of 1-O-hexadecyl-2(R/S), 3-O-di-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol (6) showed the most potent cytotoxic activity at CC50 values of 17.5 µM against PC3 cell lines. The replacement of the O-glycosidic linkage by a glycosylamide or a glycosyltriazole linkage showed little or no activity at highest concentration tested (30 µM), whereas the replacement of the glycerol moiety by triazole resulted in CC50 values in the range of 20 to 30 µM. In conclusion, the replacement of the O-glycosidic linkage by an N-glycosidic linkage or triazole-linkage resulted in about a two to three fold loss in activity, whereas the replacement of the methoxy group on the glycerol backbone by a second glucosamine moiety did not improve the activity. The stereochemistry at the C2-position of the glycero backbone has minimal effect on the anticancer activities of these diglycosylated analogs. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle In Vitro and In Vivo Antiangiogenic Activity of Caged Polyprenylated Xanthones Isolated from Garcinia hanburyi Hook. f.
Molecules 2013, 18(12), 15305-15313; doi:10.3390/molecules181215305
Received: 16 September 2013 / Revised: 3 December 2013 / Accepted: 4 December 2013 / Published: 11 December 2013
Cited by 3 | PDF Full-text (572 KB) | HTML Full-text | XML Full-text
Abstract
Eleven known caged polyprenylated xanthones 111 were isolated from the resin of Garcinia hanburyi Hook. f., and their structures were identified by their MS, NMR and UV spectra. These xanthones showed significant cytotoxicities against four human cancer cell lines (HeLa, A549,
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Eleven known caged polyprenylated xanthones 111 were isolated from the resin of Garcinia hanburyi Hook. f., and their structures were identified by their MS, NMR and UV spectra. These xanthones showed significant cytotoxicities against four human cancer cell lines (HeLa, A549, HCT-116, and HepG-2) and strong inhibition against the proliferation of the HUVEC cell line in vitro by the MTT method. Furthermore, in an in vivo zebrafish model, xanthones 3 (morellic acid), 7 (gambogenin) and 9 (isogambogenic acid) showed comparable antiangiogenic activities with less toxicities than xanthone 1 (gambogic acid), as evaluated by death and heart rates of treated zebrafish. Xanthone 7 exhibited antiangiogenic activity with no toxicity at concentrations ranging from 8 µM to 16 µM. Meanwhile, xanthones 1, 3, 7 and 9 strongly inhibited the migration of HUVEC at a low concentration of 0.5 µM in HUVEC cell migration assay in vitro. Taken together, these findings strongly suggest that xanthone 7 might be a novel angiogenesis inhibitor. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Discrimination of Multi-Origin Chinese Herbal Medicines Using Gas Chromatography-Mass Spectrometry-Based Fatty Acid Profiling
Molecules 2013, 18(12), 15329-15343; doi:10.3390/molecules181215329
Received: 5 November 2013 / Revised: 3 December 2013 / Accepted: 5 December 2013 / Published: 11 December 2013
Cited by 6 | PDF Full-text (1914 KB) | HTML Full-text | XML Full-text
Abstract
Multi-origin Chinese herbal medicines, with herbs originating from more than one species of plants, is a common phenomenon but an important issue in Traditional Chinese Medicines (TCMs). In the present study, a gas chromatography-mass spectrometry (GC-MS)—based fatty acid profiling approach to rapidly discriminate
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Multi-origin Chinese herbal medicines, with herbs originating from more than one species of plants, is a common phenomenon but an important issue in Traditional Chinese Medicines (TCMs). In the present study, a gas chromatography-mass spectrometry (GC-MS)—based fatty acid profiling approach to rapidly discriminate multi-origin Chinese medicines in terms of species and medicinal parts was proposed and validated using tuberous roots (Curcumae Radix) and rhizomes (Curcumae Rhizoma and Curcumae Longae Rhizoma) derived from four Curcuma species (e.g., C. wenyujin, C. kwangsiensis, C. phaeocaulis and C. longa) as models. Both type and content of fatty acids varied among different species of either tuberous roots or rhizomes, indicating each species has its own fatty acid pattern. Orthogonal partial least squares discriminant analysis (OPLS-DA) and hierarchical clustering analysis (HCA) based on dataset of global fatty acid profiling showed that either tuberous roots or rhizomes samples could be clearly classified into four clusters according to their species. Furthermore, those tested samples could also be discriminated in terms of their medicinal parts (e.g., tuberous root and rhizome). Our findings suggest that the proposed GC-MS-based fatty acid profiling followed by multivariate statistical analysis provides a reliable platform to discriminate multi-origin Chinese herbal medicines according to species and medicinal parts, which will be helpful for ensuring their quality, safety and efficacy. Full article
(This article belongs to the Special Issue Fatty Acids)
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Open AccessArticle Identification and Physicochemical Characteristics of Temozolomide Process-Related Impurities
Molecules 2013, 18(12), 15344-15356; doi:10.3390/molecules181215344
Received: 24 October 2013 / Revised: 27 November 2013 / Accepted: 3 December 2013 / Published: 11 December 2013
Cited by 3 | PDF Full-text (1251 KB) | HTML Full-text | XML Full-text
Abstract
In this article the crystal structures of the starting material TZ-5 and the key intermediate TZ-6 of temozolomide (TZ-7), an anticancer therapeutic agent, are presented, together with their spectroscopic and thermal characteristics. Both compounds crystallize in the triclinic P-1 space group.
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In this article the crystal structures of the starting material TZ-5 and the key intermediate TZ-6 of temozolomide (TZ-7), an anticancer therapeutic agent, are presented, together with their spectroscopic and thermal characteristics. Both compounds crystallize in the triclinic P-1 space group. X-ray crystallography studies proved that the compound TZ-6 exists as a monohydrate. A complete structural assignment was obtained for the signals in the 1H-, 13C- and 15N-nuclear magnetic resonance spectra and the structures were confirmed by Fourier-Transform infrared and Raman spectroscopy. The article describes the importance of the high purity of TZ-6 during the small-scale plant production of TZ-7 in a desired polymorphic form III with the purity higher than 99.50%, according to an HPLC method. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Bortezomib Congeners Induce Apoptosis of Hepatocellular Carcinoma via CIP2A Inhibition
Molecules 2013, 18(12), 15398-15411; doi:10.3390/molecules181215398
Received: 25 August 2013 / Revised: 20 November 2013 / Accepted: 28 November 2013 / Published: 11 December 2013
Cited by 3 | PDF Full-text (1074 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
CIP2A is an oncoprotein that upregulates p-Akt and promotes cancer cell proliferation and survival. The proteasome inhibitor bortezomib has been shown to reduce CIP2A and lead to cell apoptosis. Here; we modified the functional group of bortezomib to generate a series of novel
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CIP2A is an oncoprotein that upregulates p-Akt and promotes cancer cell proliferation and survival. The proteasome inhibitor bortezomib has been shown to reduce CIP2A and lead to cell apoptosis. Here; we modified the functional group of bortezomib to generate a series of novel compounds and conducted a structure–activity relationship (SAR) study. The results showed that compound 1 was able to repress CIP2A expression and cell apoptosis in the same manner as bortezomib, but with less potency in inhibition of proteasome activity. This finding provides a new direction for the design of CIP2A inhibitors. Full article
Open AccessCommunication A Triple Staining Method for Accurate Cell Cycle Analysis Using Multiparameter Flow Cytometry
Molecules 2013, 18(12), 15412-15421; doi:10.3390/molecules181215412
Received: 29 October 2013 / Revised: 5 November 2013 / Accepted: 6 December 2013 / Published: 11 December 2013
Cited by 3 | PDF Full-text (1327 KB) | HTML Full-text | XML Full-text
Abstract
Cell cycle analysis is important for cancer research. We present herein a novel method for accurate cell cycle analysis. This method analyzes the cell cycle by multiparameter flow cytometry based on simultaneously labeling the cell nuclear DNA, RNA, and phosphorylated mitotic nuclei protein,
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Cell cycle analysis is important for cancer research. We present herein a novel method for accurate cell cycle analysis. This method analyzes the cell cycle by multiparameter flow cytometry based on simultaneously labeling the cell nuclear DNA, RNA, and phosphorylated mitotic nuclei protein, using Hoechst 33342, pyronin Y, and MPM-2-Cy5, respectively, and our results demonstrated that this method could effectively divide the cell cycle into G0, G1, S, G2, and M phases. We further tested this method using the clinical anticancer agents crizotinib and taxol, and the results clearly illustrated that crizotinib and taxol arrested Jurkat cells in G0 and M phase, respectively. These results indicate that this method could be a very useful tool for cytokinetic and pharmacological research. Full article
Open AccessArticle Highly Enantioselective Addition of Phenylethynylzinc to Aldehydes Catalyzed by Chiral Cyclopropane-Based Amino Alcohols
Molecules 2013, 18(12), 15422-15433; doi:10.3390/molecules181215422
Received: 18 November 2013 / Revised: 28 November 2013 / Accepted: 29 November 2013 / Published: 11 December 2013
Cited by 2 | PDF Full-text (337 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The enantioselective addition of phenylethynylzinc to aldehydes catalyzed by a series of cyclopropane-based amino alcohol ligands 7 was investigated. The reactions afforded chiral propargylic alcohols in high yields (up to 96%) and with excellent enantioselectivities (up to 98% ee) under mild conditions.
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The enantioselective addition of phenylethynylzinc to aldehydes catalyzed by a series of cyclopropane-based amino alcohol ligands 7 was investigated. The reactions afforded chiral propargylic alcohols in high yields (up to 96%) and with excellent enantioselectivities (up to 98% ee) under mild conditions. Furthermore, studies on the structural relationship show that the matching of the chiral center configuration is crucial to obtain the high enantioselectivity. Full article
Open AccessArticle G-Quadruplex Guanosine Gels and Single Walled Carbon Nanotubes
Molecules 2013, 18(12), 15434-15447; doi:10.3390/molecules181215434
Received: 7 November 2013 / Revised: 25 November 2013 / Accepted: 3 December 2013 / Published: 11 December 2013
Cited by 4 | PDF Full-text (1752 KB) | HTML Full-text | XML Full-text
Abstract
Solubilization of single walled carbon nanotubes (SWNTs) in aqueous gel phases formed by reversible, G-quadruplex self-assembly of guanosine monophosphate (GMP) alone or with guanosine (Guo) is described. Unlike other media and methods for aqueous solubilization of SWNTs, the guanosine gels (“G-gels”) are found
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Solubilization of single walled carbon nanotubes (SWNTs) in aqueous gel phases formed by reversible, G-quadruplex self-assembly of guanosine monophosphate (GMP) alone or with guanosine (Guo) is described. Unlike other media and methods for aqueous solubilization of SWNTs, the guanosine gels (“G-gels”) are found to readily disperse high (>mg/mL) concentrations of individual rather than bundled SWNTs. SWNT dispersions in GMP alone precipitate in several hours and re-form upon shaking; however, dispersions in the binary GMP/Guo gels are indefinitely stable. Increasing GMP or KCl concentration in the binary gels increased the relative abundance of large diameter and semi-conducting SWNTs. Different gel compositions also displayed different selectivities toward SWNTs of different chiralities. These results indicate a strong connection between the self-assembled G-gels and the dimensions and structures of the SWNTs that they solubilize. Full article
(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)
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Open AccessArticle In Vitro Action of Flavonoids in the Canine Malignant Histiocytic Cell Line DH82
Molecules 2013, 18(12), 15448-15463; doi:10.3390/molecules181215448
Received: 28 October 2013 / Revised: 17 November 2013 / Accepted: 18 November 2013 / Published: 12 December 2013
Cited by 4 | PDF Full-text (2842 KB) | HTML Full-text | XML Full-text
Abstract
Cancer is commonly diagnosed in dogs over the age of 10 and is a leading cause of death due to the lack of effective drugs. Flavonoids possess antioxidant, anti-inflammatory and anticarcinogenic properties and have been studied as chemopreventive agents in human cancer therapy.
[...] Read more.
Cancer is commonly diagnosed in dogs over the age of 10 and is a leading cause of death due to the lack of effective drugs. Flavonoids possess antioxidant, anti-inflammatory and anticarcinogenic properties and have been studied as chemopreventive agents in human cancer therapy. However, the literature on dogs is sparse. In this study, we analyzed the effect of nine flavonoids on cell viability, DNA damage and topoisomerase IIa/IIb gene expression in a canine tumor cell line (DH82). Apigenin, luteolin, trans-chalcone and 4-methoxychalcone showed the highest degree of cytotoxicity in the absence of considerable DNA damage, whereas genistein exhibited low cytotoxicity but induced a high level of DNA damage. These five flavonoids inhibited topoisomerase IIa and IIb gene expression to variable extents and with variable specificity. Genistein exerted a lower inhibitory effect on the two topoisomerases than luteolin and apigenin. trans-Chalcone and 4-methoxychalcone exerted greater inhibition of topoisomerase IIa expression than topoisomerase IIb. The differences in the effects between genistein and luteolin and apigenin might be explained by the position of ring B, whereas the more specific effect of chalcones on topoisomerase IIa might be due to their open chain structure. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Effect of Delayed Icing on Biogenic Amines Formation and Bacterial Contribution of Iced Common Carp (Cyprinus carpio)
Molecules 2013, 18(12), 15464-15473; doi:10.3390/molecules181215464
Received: 6 November 2013 / Revised: 9 December 2013 / Accepted: 10 December 2013 / Published: 12 December 2013
Cited by 4 | PDF Full-text (208 KB) | HTML Full-text | XML Full-text
Abstract
The variation of six biogenic amines (BAs) and total viable count (TVC) in common carp (Cyprinus carpio) stored in ice with 0, 4 and 8 h delay before icing was evaluated in a period of 4 days. Delayed icing led to
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The variation of six biogenic amines (BAs) and total viable count (TVC) in common carp (Cyprinus carpio) stored in ice with 0, 4 and 8 h delay before icing was evaluated in a period of 4 days. Delayed icing led to significant (p < 0.05) increases in TVC throughout the period of storage and showed a good correlation with BAs content. The obtained data showed that putrescine and cadaverine were predominant in all samples and it was indicated that they could be proper indicators to determine the carp quality. Spermidine and spermine increased slightly toward the end of storage and the levels of dangerous BAs (histamine and tyramine) were under the limit over the period. As a result, it is indicated that delaying time affects on formation of BAs and the effect in samples with 8 h delay was significantly (p < 0.05) more than those with 0 and 4 h delay. Full article
Open AccessArticle Osteogenic Activity of Collagen Peptide via ERK/MAPK Pathway Mediated Boosting of Collagen Synthesis and Its Therapeutic Efficacy in Osteoporotic Bone by Back-Scattered Electron Imaging and Microarchitecture Analysis
Molecules 2013, 18(12), 15474-15489; doi:10.3390/molecules181215474
Received: 25 October 2013 / Revised: 3 December 2013 / Accepted: 10 December 2013 / Published: 12 December 2013
Cited by 15 | PDF Full-text (2057 KB) | HTML Full-text | XML Full-text
Abstract
Collagen hydrolysate (CH) has been reported to exhibit a positive effect on bone. In the present study, the in vitro effects of CH (<3 kDa) were examined and the in vivo experiments confirmed the positive effects of CH in ovariectomized (OVX) rats. Bone
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Collagen hydrolysate (CH) has been reported to exhibit a positive effect on bone. In the present study, the in vitro effects of CH (<3 kDa) were examined and the in vivo experiments confirmed the positive effects of CH in ovariectomized (OVX) rats. Bone mineral density (BMD) was examined by DXA analysis. Scanning electron microscopic analysis and quantitative 3D-color backscattered electrons imaging analysis were performed on the lumbar vertebrae. CH increased osteoblastic cell proliferation and alkaline phosphatase activity in a dose-dependent manner. Collagen synthesis and collagen, type1, alpha1 (COL1A1) gene expression were also increased by CH treatment. Furthermore, CH-induced COL1A1 gene expression was completely abolished by extracellular signal-regulated kinase (ERK) inhibitor, suggesting the involvement of ERK/MAPK signaling for transcriptional effects on COL1A1 expression. OVX rats supplemented with CH showed osteoprotective effects as the BMD levels were increased compared with control. Moreover, CH prevented the trabecular bone loss induced by OVX and improved the microarchitecture of lumbar vertebrae. CH administration dose-dependently reduced the serum procollagen type I N-terminal propeptide level, which was elevated by OVX. The present study suggests that CH isolated in this study is a promising alternative to current therapeutic agents for the management of osteoporosis. Full article
Open AccessArticle Preparative Separation of Six Rhynchophylla Alkaloids from Uncaria macrophylla Wall by pH-Zone Refining Counter-Current Chromatography
Molecules 2013, 18(12), 15490-15500; doi:10.3390/molecules181215490
Received: 12 November 2013 / Revised: 5 December 2013 / Accepted: 6 December 2013 / Published: 12 December 2013
Cited by 1 | PDF Full-text (656 KB) | HTML Full-text | XML Full-text
Abstract
pH-Zone refining counter-current chromatography was successfully applied to the preparative isolation and purification of six alkaloids from the ethanol extracts of Uncaria macrophylla Wall. Because of the low content of alkaloids (about 0.2%, w/w) in U. macrophylla Wall, the target compounds were
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pH-Zone refining counter-current chromatography was successfully applied to the preparative isolation and purification of six alkaloids from the ethanol extracts of Uncaria macrophylla Wall. Because of the low content of alkaloids (about 0.2%, w/w) in U. macrophylla Wall, the target compounds were enriched by pH-zone refining counter-current chromatography using a two-phase solvent system composed of petroleum ether–ethyl acetate–isopropanol–water (2:6:3:9, v/v), adding 10 mM triethylamine in organic stationary phase and 5 mM hydrochloric acid in aqueous mobile phase. Then pH-zone refining counter-current chromatography using the other two-phase solvent system was used for final purification. Six target compounds were finally isolated and purified by following two-phase solvent system composed of methyl tert-butyl ether (MTBE)–acetonitrile–water (4:0.5:5, v/v), adding triethylamine (TEA) (10 mM) to the organic phase and HCl (5 mM) to aqueous mobile phase. The separation of 2.8 g enriched total alkaloids yielded 36 mg hirsutine, 48 mg hirsuteine, 82 mg uncarine C, 73 mg uncarine E, 163 mg rhynchophylline, and 149 mg corynoxeine, all with purities above 96% as verified by HPLC Their structures were identified by electrospray ionization-mass spectrometry (ESI-MS) and 1H-NMR spectroscopy. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle The Effect of Conformational Variability of Phosphotriesterase upon N-acyl-L-homoserine Lactone and Paraoxon Binding: Insights from Molecular Dynamics Studies
Molecules 2013, 18(12), 15501-15518; doi:10.3390/molecules181215501
Received: 6 November 2013 / Revised: 3 December 2013 / Accepted: 6 December 2013 / Published: 12 December 2013
Cited by 3 | PDF Full-text (3026 KB) | HTML Full-text | XML Full-text
Abstract
The organophosphorous hydrolase (PTE) from Brevundimonas diminuta is capable of degrading extremely toxic organophosphorous compounds with a high catalytic turnover and broad substrate specificity. Although the natural substrate for PTE is unknown, its loop remodeling (loop 7-2/H254R) led to the emergence of a
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The organophosphorous hydrolase (PTE) from Brevundimonas diminuta is capable of degrading extremely toxic organophosphorous compounds with a high catalytic turnover and broad substrate specificity. Although the natural substrate for PTE is unknown, its loop remodeling (loop 7-2/H254R) led to the emergence of a homoserine lactonase (HSL) activity that is undetectable in PTE (kcat/km values of up to 2 × 104), with only a minor decrease in PTE paraoxonase activity. In this study, homology modeling and molecular dynamics simulations have been undertaken seeking to explain the reason for the substrate specificity for the wild-type and the loop 7-2/H254R variant. The cavity volume estimated results showed that the active pocket of the variant was almost two fold larger than that of the wild-type (WT) enzyme. pKa calculations for the enzyme (the WT and the variant) showed a significant pKa shift from WT standard values (ΔpKa = 3.5 units) for the His254residue (in the Arg254 variant). Molecular dynamics simulations indicated that the displacement of loops 6 and 7 over the active site in loop 7-2/H254R variant is useful for N-acyl-L-homoserine lactone (C4-HSL) with a large aliphatic chain to site in the channels easily. Thence the expanding of the active pocket is beneficial to C4-HSL binding and has a little effect on paraoxon binding. Our results provide a new theoretical contribution of loop remodeling to the rapid divergence of new enzyme functions. Full article
(This article belongs to the Special Issue In-Silico Drug Design and In-Silico Screening)
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Open AccessCommunication Seed Germination-Influencing Bioactive Secondary Metabolites Secreted by the Endophyte Cladosporium cladosporioides LWL5
Molecules 2013, 18(12), 15519-15530; doi:10.3390/molecules181215519
Received: 8 October 2013 / Revised: 7 December 2013 / Accepted: 9 December 2013 / Published: 13 December 2013
Cited by 3 | PDF Full-text (1208 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The present study was aimed to isolate bioactive metabolites produced by a fungal endophyte from Helianthus annuus, Capsicum annuum, and Cucumis sativus and to assess their role in seed germination. Culture filtrate of the endophyte HA-3B from H. annuus was significantly
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The present study was aimed to isolate bioactive metabolites produced by a fungal endophyte from Helianthus annuus, Capsicum annuum, and Cucumis sativus and to assess their role in seed germination. Culture filtrate of the endophyte HA-3B from H. annuus was significantly inhibitory towards the germination and growth of lettuce seeds. HA-3B was identified as Cladosporium cladosporioides LWL5 through molecular techniques. Different concentrations (100, 500 and 1000 ppm) of the ethyl acetate extract obtained from the culture inhibited the lettuce seed germination. The extract was subjected to column chromatography and a bioassay-guided isolation method, which yielded compounds 1, 2 and an oily fraction. The oily fraction, subjected to fractionation and spectroscopic techniques, resulted in the identification of 31 different constituents. Compounds 1 and 2 were identified and characterized through MS and NMR spectroscopic techniques as benzoic acid. The bioassay results showed that this compound significantly inhibited the growth and germination of lettuce seeds. In conclusion, assessing the role of endophytes harboring essential crop plants can help us to develop potentially eco-friendly herbicides. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of δ-Oxo-1,1-bis(triflyl)alkanes and Their Acidities
Molecules 2013, 18(12), 15531-15540; doi:10.3390/molecules181215531
Received: 4 November 2013 / Revised: 3 December 2013 / Accepted: 11 December 2013 / Published: 13 December 2013
Cited by 4 | PDF Full-text (300 KB) | HTML Full-text | XML Full-text
Abstract The reaction of 1,1-bis(triflyl)ethylene generated in situ with enolizable carbonyls yielded δ-oxo-1,1-bis(triflyl)alkane derivatives. Their acidities in both the gas and solution phases were determined. Full article
(This article belongs to the Special Issue Fluorine Chemistry 2016)
Open AccessArticle Beads-Based Electrochemical Assay for the Detection of Influenza Hemagglutinin Labeled with CdTe Quantum Dots
Molecules 2013, 18(12), 15573-15586; doi:10.3390/molecules181215573
Received: 10 October 2013 / Revised: 25 November 2013 / Accepted: 5 December 2013 / Published: 13 December 2013
Cited by 4 | PDF Full-text (674 KB) | HTML Full-text | XML Full-text
Abstract
In this study we describe a beads-based assay for rapid, sensitive and specific isolation and detection of influenza vaccine hemagglutinin (HA). Amplification of the hemagglutinin signal resulted from binding of an electrochemical label as quantum dots (QDs). For detection of the metal and
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In this study we describe a beads-based assay for rapid, sensitive and specific isolation and detection of influenza vaccine hemagglutinin (HA). Amplification of the hemagglutinin signal resulted from binding of an electrochemical label as quantum dots (QDs). For detection of the metal and protein part of the resulting HA-CdTe complex, two differential pulse voltammetric methods were used. The procedure includes automated robotic isolation and electrochemical analysis of the isolated product. The isolation procedure was based on the binding of paramagnetic particles (MPs) with glycan (Gly), where glycan was used as the specific receptor for linkage of the QD-labeled hemagglutinin. Full article
(This article belongs to the Special Issue Bio and Nanomaterials Based on Fe3O4)
Open AccessArticle Antimicrobial and Antioxidant Activities and Effect of 1-Hexadecene Addition on Palmarumycin C2 and C3 Yields in Liquid Culture of Endophytic Fungus Berkleasmium sp. Dzf12
Molecules 2013, 18(12), 15587-15599; doi:10.3390/molecules181215587
Received: 8 October 2013 / Revised: 3 December 2013 / Accepted: 9 December 2013 / Published: 13 December 2013
Cited by 6 | PDF Full-text (289 KB) | HTML Full-text | XML Full-text
Abstract
Two spirobisnaphthalenes, namely palmarumycins C2 and C3, were isolated from cultures of the endophytic fungus Berkleasmium sp. Dzf12 after treatment with 1-hexadecene. After addition of 1-hexadecene at 10% to the medium on day 6 of culture, the maximal yields of
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Two spirobisnaphthalenes, namely palmarumycins C2 and C3, were isolated from cultures of the endophytic fungus Berkleasmium sp. Dzf12 after treatment with 1-hexadecene. After addition of 1-hexadecene at 10% to the medium on day 6 of culture, the maximal yields of palmarumycins C2 and C3 were obtained as 0.40 g/L and 1.19 g/L, which were 40.00 fold and 59.50 fold higher, respectively, in comparison with those of the control (0.01 g/L and 0.02 g/L). The results indicated that addition of 1-hexadecene can be an effective strategy for enhancing the production of palmarumycins C2 and C3 in liquid culture of endophytic fungus Berkleasmium sp. Dzf12. Palmarumycin C3 exhibited stronger antimicrobial and antioxidant activities than palmarumycin C2. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle In Vitro Evaluation of Novel Inhibitors against the NS2B-NS3 Protease of Dengue Fever Virus Type 4
Molecules 2013, 18(12), 15600-15612; doi:10.3390/molecules181215600
Received: 28 October 2013 / Revised: 2 December 2013 / Accepted: 11 December 2013 / Published: 13 December 2013
Cited by 8 | PDF Full-text (897 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The discovery of potent therapeutic compounds against dengue virus is urgently needed. The NS2B-NS3 protease (NS2B-NS3pro) of dengue fever virus carries out all enzymatic activities needed for polyprotein processing and is considered to be amenable to antiviral inhibition by analogy. Virtual
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The discovery of potent therapeutic compounds against dengue virus is urgently needed. The NS2B-NS3 protease (NS2B-NS3pro) of dengue fever virus carries out all enzymatic activities needed for polyprotein processing and is considered to be amenable to antiviral inhibition by analogy. Virtual screening of 300,000 compounds using Autodock 3 on the GVSS platform was conducted to identify novel inhibitors against the NS2B-NS3pro. Thirty-six compounds were selected for in vitro assay against NS2B-NS3pro expressed in Pichia pastoris. Seven novel compounds were identified as inhibitors with IC50 values of 3.9 ± 0.6–86.7 ± 3.6 μM. Three strong NS2B-NS3pro inhibitors were further confirmed as competitive inhibitors with Ki values of 4.0 ± 0.4, 4.9 ± 0.3, and 3.4 ± 0.1 μM, respectively. Hydrophobic and hydrogen bond interactions between amino acid residues in the NS3pro active site with inhibition compounds were also identified. Full article
(This article belongs to the Special Issue In-Silico Drug Design and In-Silico Screening)
Open AccessArticle Total Synthesis of Six 3,4-Unsubstituted Coumarins
Molecules 2013, 18(12), 15613-15623; doi:10.3390/molecules181215613
Received: 28 October 2013 / Revised: 8 December 2013 / Accepted: 10 December 2013 / Published: 13 December 2013
Cited by 10 | PDF Full-text (235 KB) | HTML Full-text | XML Full-text
Abstract
In this article we describe a new methodology for the total synthesis of 3,4-unsubstituted coumarins from commercially available starting materials. Six examples were prepared, including five naturally occurring coumarins—7-hydroxy-6,8-dimethoxy-coumarin (isofraxidin), 7-hydroxy-6-methoxycoumarin (scopoletin), 6,7,8-trimethoxy-coumarin, 6,7-dimethoxycoumarin (scoparone), and 7,8-dihydroxycoumarin (daphnetin) and one synthetic coumarin, 7-hydroxy-6-ethoxycoumarin.
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In this article we describe a new methodology for the total synthesis of 3,4-unsubstituted coumarins from commercially available starting materials. Six examples were prepared, including five naturally occurring coumarins—7-hydroxy-6,8-dimethoxy-coumarin (isofraxidin), 7-hydroxy-6-methoxycoumarin (scopoletin), 6,7,8-trimethoxy-coumarin, 6,7-dimethoxycoumarin (scoparone), and 7,8-dihydroxycoumarin (daphnetin) and one synthetic coumarin, 7-hydroxy-6-ethoxycoumarin. Moreover, five important o-hydroxybenzaldehyde intermediates were also obtained, namely 2,4-dihydroxy-3,5-dimethoxybenzaldehyde, 2,4-dihydroxy-5-methoxybenzaldehyde, 5-ethoxy-2,4-dihydroxy-benzaldehyde, 2-hydroxy-3,4,5-trimethoxybenzaldehyde, and 2-hydroxy-4,5-dimethoxy-benzaldehyde. The method developed herein involves just three or four steps and allows for the rapid synthesis of these important molecules in excellent yields. This is the first synthesis of 6,7,8-trimethoxycoumarin and 7-hydroxy-6-ethoxycoumarin. Full article
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Open AccessArticle Modulation of Lipogenesis and Glucose Consumption in HepG2 Cells and C2C12 Myotubes by Sophoricoside
Molecules 2013, 18(12), 15624-15635; doi:10.3390/molecules181215624
Received: 4 November 2013 / Revised: 5 December 2013 / Accepted: 6 December 2013 / Published: 13 December 2013
Cited by 9 | PDF Full-text (550 KB) | HTML Full-text | XML Full-text
Abstract
Sophoricoside, an isoflavone glycoside isolated from Sophora japonica (Leguminosae), has been widely reported as an immunomodulator. In this study, the effects of sophoricoside on lipogenesis and glucose consumption in HepG2 cells and C2C12 myotubes were investigated. Treatment with sophoricoside at concentrations of 1–10
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Sophoricoside, an isoflavone glycoside isolated from Sophora japonica (Leguminosae), has been widely reported as an immunomodulator. In this study, the effects of sophoricoside on lipogenesis and glucose consumption in HepG2 cells and C2C12 myotubes were investigated. Treatment with sophoricoside at concentrations of 1–10 μM inhibited lipid accumulation in HepG2 cells in a dose-dependent manner. At the same concentration range, no effect on cell viability was observed in the MTT assay. Inhibition of lipogenesis was associated with the downregulation of SREBP-1a, SREBP-1c, SREBP-2 and their downstream target genes (FAS, ACC, HMGR) as revealed by realtime quantitative PCR. The lipid-lowering effect was mediated via the phosphorylation of AMPK. Further investigation of the activities of this isoflavone showed that sophoricoside has the capability to increase glucose uptake by C2C12 myotubes. It also effectively inhibited the activities of α-glucosidase and α-amylase in vitro and remarkably lowered postprandial hyperglycaemia in starch-loaded C57BL6/J mice. These results suggest that sophoricoside is an effective regulator of lipogenesis and glucose consumption and may find utility in the treatment of obesity and type 2 diabetes. Full article
Open AccessArticle Vascular Aldosterone Production at the Pre-Diabetic Stage of Young Otsuka Long-Evans Tokushima Fatty (OLETF) Rats, Compared with Long-Evans Tokushima Otsuka (LETO) Rats
Molecules 2013, 18(12), 15636-15647; doi:10.3390/molecules181215636
Received: 13 September 2013 / Revised: 10 December 2013 / Accepted: 10 December 2013 / Published: 13 December 2013
Cited by 1 | PDF Full-text (1039 KB) | HTML Full-text | XML Full-text
Abstract
We examined the ability of aortic smooth muscle cells (AoSMC) prepared from spontaneously diabetic rats to produce aldosterone (Aldo) and the regulatory mechanism that controls their Aldo production. AoSMC of 6 week-old Long-Evans Tokushima Otsuka (LETO: the control group) and 6 week-old Otsuka
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We examined the ability of aortic smooth muscle cells (AoSMC) prepared from spontaneously diabetic rats to produce aldosterone (Aldo) and the regulatory mechanism that controls their Aldo production. AoSMC of 6 week-old Long-Evans Tokushima Otsuka (LETO: the control group) and 6 week-old Otsuka Long-Evans Tokushima Fatty (OLETF: the type 2 diabetes group) rats were used in the present experiments. CYP11B2 (Aldo synthetase) mRNA expression was detected in both the LETO and OLETF AoSMC. Basal Aldo production was significantly greater (4–5 fold higher) in the OLETF AoSMC culture medium than in the LETO AoSMC culture medium. When AoSMC were co-incubated with high-density lipoproteins (HDL), supplying cholesterol as a substrate for steroidogenesis in rats, angiotensin II (AII) significantly increased greater Aldo production in the OLETF AoSMC than in the LETO AoSMC. The present data suggested that future onset of diabetic vascular dysfunction is partly caused by excess Aldo production by AoSMC in young OLETF rats. Concomitant stimulation by HDL and AII resulted in elevated Aldo production in the OLETF and the LETO AoSMC, and also demonstrated that AII-induced Aldo production is greatly enhanced by HDL in OLETF, rather than in LETO. In conclusion, our data clearly demonstrated that Aldo production in the OLETF AoSMC was significantly higher than in the LETO AoSMC, suggesting possible future onset of vascular dysfunction in diabetes, induced by local Aldo production in the AoSMC. Full article
(This article belongs to the Special Issue Steroids)
Open AccessArticle Preparative Isolation and Purification of Five Flavonoid Glycosides and One Benzophenone Galloyl Glycoside from Psidium guajava by High-Speed Counter-Current Chromatography (HSCCC)
Molecules 2013, 18(12), 15648-15661; doi:10.3390/molecules181215648
Received: 17 October 2013 / Revised: 9 December 2013 / Accepted: 10 December 2013 / Published: 16 December 2013
Cited by 10 | PDF Full-text (1449 KB) | HTML Full-text | XML Full-text
Abstract
Psidium guajava leaves have a diverse phytochemical composition including flavonoids, phenolics, meroterpenoids and triterpenes, responsible for the biological activities of the medicinal parts. In particular, flavonol glycosides show beneficial effects on type II diabetes mellitus. A simple and efficient HSCCC method has been
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Psidium guajava leaves have a diverse phytochemical composition including flavonoids, phenolics, meroterpenoids and triterpenes, responsible for the biological activities of the medicinal parts. In particular, flavonol glycosides show beneficial effects on type II diabetes mellitus. A simple and efficient HSCCC method has been developed for the preparative separation of five flavonoid glycosides and one diphenylmethane glycoside from P. guajava. A solvent system composed of n-hexane–ethyl acetate–methanol–water (0.7:4:0.8:4, v/v/v/v) was optimized for the separation. The upper phase was used as the stationary phase, and the lower phase was used as the mobile phase. Under the optimized conditions, hyperoside (15.3 mg), isoquercitrin (21.1 mg), reynoutrin (65.2 mg), quercetin-3-O-β-D-arabinopyranoside (71.7 mg), quercetin-3-O-α-L-arabinofuranoside (105.6 mg) and 2,4,6-trihydroxy-3,5-dimethylbenzophenone 4-O-(6''-O-galloyl)-β-D-glucopyranoside (98.4 mg) were separated from crude sample (19.8 g). The structures of all the isolates were identified by ESI-MS, 1H- and 13C-NMR analyses and their purities (>95%) were determined using HPLC. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Characterization of the Nutraceutical Quality and Antioxidant Activity in Bell Pepper in Response to Grafting
Molecules 2013, 18(12), 15689-15703; doi:10.3390/molecules181215689
Received: 18 November 2013 / Revised: 10 December 2013 / Accepted: 11 December 2013 / Published: 16 December 2013
Cited by 3 | PDF Full-text (312 KB) | HTML Full-text | XML Full-text
Abstract
The grafting of fruits and vegetables influences fruit quality. The aim of the present work was to assess the effect of the rootstock and the scion on the antioxidant activity and the content in vitamin C, total phenols, lycopene and β-carotene of bell
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The grafting of fruits and vegetables influences fruit quality. The aim of the present work was to assess the effect of the rootstock and the scion on the antioxidant activity and the content in vitamin C, total phenols, lycopene and β-carotene of bell pepper. The cultivars Fascinato and Jeanette were used as scion and Terrano was used as rootstock. Four harvests in the production cycle of the vegetable were analyzed in a cultivation system under shading nets. The results indicate statistical differences in the content of these bioactive compounds between the varieties, between grafting and not grafting and between sampling dates (p ≤ 0.05). The vitamin C content, β-carotene, and antioxidant capacity proved significantly higher in Fascinato than in Janette. On average, grafting increased β-carotene and vitamin C concentrations and improved the antioxidant capacity, but had no influence on the total phenol or lycopene contents. It is concluded that grafting to the rootstock Terrano improves the nutritional quality of the fruit produced in both varieties of bell pepper studied. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle An Efficient Approach to the Synthesis of Highly Congested 9,10-Dihydrophenanthrene-2,4-dicarbonitriles and Their Biological Evaluation as Antimicrobial Agents
Molecules 2013, 18(12), 15704-15716; doi:10.3390/molecules181215704
Received: 8 August 2013 / Revised: 20 November 2013 / Accepted: 10 December 2013 / Published: 16 December 2013
Cited by 1 | PDF Full-text (496 KB) | HTML Full-text | XML Full-text
Abstract
An efficient and novel method for the synthesis in moderate to good yield (72%–84%) of a series of 3-amino-1-substituted-9,10-dihydrophenanthrene-2,4-dicarbonitriles 15 via one-pot multi-component reactions of aldehydes, malononitrile, 1-tetralone and ammonium acetate has been delineated. Cyclocondensation attempts of aminocyanophenanthrene derivatives 1,
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An efficient and novel method for the synthesis in moderate to good yield (72%–84%) of a series of 3-amino-1-substituted-9,10-dihydrophenanthrene-2,4-dicarbonitriles 15 via one-pot multi-component reactions of aldehydes, malononitrile, 1-tetralone and ammonium acetate has been delineated. Cyclocondensation attempts of aminocyanophenanthrene derivatives 1, 2, 4 and 5 with acetic anhydride in the presence of conc. H2SO4 failed and instead the diacetylamino derivatives 1013 were obtained. All prepared compounds were structurally elucidated by various spectroscopic methods and X-ray crystallography. N,N-diacetylamino-derivatives of phenanthrene have shown good antimicrobial activity. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Synthesis of Dimethyl Aryl Acylsulfonium Bromides from Aryl Methyl Ketones in a DMSO-HBr System
Molecules 2013, 18(12), 15717-15723; doi:10.3390/molecules181215717
Received: 26 November 2013 / Revised: 10 December 2013 / Accepted: 10 December 2013 / Published: 16 December 2013
Cited by 3 | PDF Full-text (257 KB) | HTML Full-text | XML Full-text
Abstract
A new, simplified method for the synthesis of dimethyl aryl acylsulfonium salts has been developed. A series of dimethyl aryl acylsulfonium bromides were prepared by the reaction of aryl methyl ketones with hydrobromic acid and dimethylsulfoxide (DMSO). This sulfonium salt confirms that bromine
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A new, simplified method for the synthesis of dimethyl aryl acylsulfonium salts has been developed. A series of dimethyl aryl acylsulfonium bromides were prepared by the reaction of aryl methyl ketones with hydrobromic acid and dimethylsulfoxide (DMSO). This sulfonium salt confirms that bromine production and the bromination reaction take place in the DMSO-HBr oxidation system. What’s more, it is also a key intermediate for the synthesis of arylglyoxals. Full article
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Open AccessArticle Madecassoside Inhibits Melanin Synthesis by Blocking Ultraviolet-Induced Inflammation
Molecules 2013, 18(12), 15724-15736; doi:10.3390/molecules181215724
Received: 29 October 2013 / Revised: 10 December 2013 / Accepted: 11 December 2013 / Published: 16 December 2013
Cited by 4 | PDF Full-text (777 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Madecassoside (MA), a pentacyclic triterpene isolated from Centella asitica (L.), is used as a therapeutic agent in wound healing and also as an anti-inflammatory and anti-aging agent. However, the involvement of MA in skin-pigmentation has not been reported. This study was conducted to
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Madecassoside (MA), a pentacyclic triterpene isolated from Centella asitica (L.), is used as a therapeutic agent in wound healing and also as an anti-inflammatory and anti-aging agent. However, the involvement of MA in skin-pigmentation has not been reported. This study was conducted to investigate the effects of MA on ultraviolet (UV)-induced melanogenesis and mechanisms in a co-culture system of keratinocytes and melanocytes. MA significantly inhibited UVR-induced melanin synthesis and melanosome transfer in the co-culture system. These effects were further demonstrated by the MA-induced inhibition of protease-activated receptor-2 expression and its signaling pathway, cyclooxygenase-2, prostaglandin E2 and prostaglandin F2 alpha in keratinocytes. The clinical efficacy of MA was confirmed on artificially tanned human skin. MA significantly reduced UV-induced melanin index at 8 weeks after topical application. Overall, the study demonstrated significant benefits of MA use in the inhibition of hyperpigmentation caused by UV irradiation. Full article
Open AccessArticle Crystal Structures and Antifungal Activities of Fluorine-Containing Thioureido Complexes with Nickel(II)
Molecules 2013, 18(12), 15737-15749; doi:10.3390/molecules181215737
Received: 13 November 2013 / Revised: 3 December 2013 / Accepted: 5 December 2013 / Published: 17 December 2013
Cited by 5 | PDF Full-text (776 KB) | HTML Full-text | XML Full-text
Abstract
Ni(II) complexes with N-2-fluorobenzoylpiperidine-1-carbothioimidate (L2), N-4-fluorobenzoylpiperidine-1-carbothioimidate (L3), N-2-fluorobenzoylmorpholine- 1-carbothioimidate (L5) and N-4-fluorobenzoylmorpholine-1-carbothioimidate (L6)  have been synthesized and characterized by elemental analysis, FTIR and 1H-NMR. The crystal structures of three ligands (HL2, HL3
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Ni(II) complexes with N-2-fluorobenzoylpiperidine-1-carbothioimidate (L2), N-4-fluorobenzoylpiperidine-1-carbothioimidate (L3), N-2-fluorobenzoylmorpholine- 1-carbothioimidate (L5) and N-4-fluorobenzoylmorpholine-1-carbothioimidate (L6)  have been synthesized and characterized by elemental analysis, FTIR and 1H-NMR. The crystal structures of three ligands (HL2, HL3 and HL6) and the corresponding Ni(II) complexes ([Ni(L2)2], [Ni(L3)2] and [Ni(L6)2]) have been determined by X-ray diffraction. The antifungal activities of the Ni(II) complexes together and the corresponding ligands against the fungi Botrytis cinerea, Trichoderma spp., Myrothecium and Verticillium spp. have been investigated. The experimental results showed that the ligands and their complexes have antifungal abilities. When the fluorine was substituted on the para-benzoyl moiety, the antifungal activity of the ligands was obviously increased. Moreover, the ligands were stronger than their complexes in inhibiting fungal activities. The antifungal ability of HL6 is especially strong, and similar to that of the commercial fungicide fluconazole. Full article
(This article belongs to the Special Issue Fluorine Chemistry 2016)
Open AccessArticle Design, Synthesis and Evaluation of N13-Substituted Evodiamine Derivatives against Human Cancer Cell Lines
Molecules 2013, 18(12), 15750-15768; doi:10.3390/molecules181215750
Received: 23 October 2013 / Revised: 7 November 2013 / Accepted: 12 November 2013 / Published: 17 December 2013
Cited by 3 | PDF Full-text (402 KB) | HTML Full-text | XML Full-text
Abstract
Attempting to improve the anticancer activity and solubility of evodiamine in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) solutions, thirty-eight N13-substituted evodiamine derivatives were designed, synthesized and tested for antitumor activities against six kinds of human cancer cell lines, namely prostate
[...] Read more.
Attempting to improve the anticancer activity and solubility of evodiamine in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) solutions, thirty-eight N13-substituted evodiamine derivatives were designed, synthesized and tested for antitumor activities against six kinds of human cancer cell lines, namely prostate cancer (DU-145 and PC-3), lung cancer (H460), breast cancer (MCF-7), colon cancer (HCT-5) and glioblastoma (SF-268). The solubility of these compounds in SGF and SIF solutions was evaluated, and apoptosis induced by 2-2, 2-3, 2-16 and 3-2 was determined. The results showed: (1) among all compounds examined, 2-16 showed the highest antitumor activity and a broader spectrum of activity, with IC50 values ranging from 1–2 µM; (2) their solubility was obviously improved; (3) 2-3, 2-16 and 3-2 had a significant impact inducing apoptosis in some cancer cell lines. The preliminary structure-activity relationships of these derivatives were discussed. Full article
Open AccessArticle 4,6,8-Triarylquinoline-3-carbaldehyde Derivatives: Synthesis and Photophysical Properties
Molecules 2013, 18(12), 15769-15787; doi:10.3390/molecules181215769
Received: 1 November 2013 / Revised: 11 December 2013 / Accepted: 12 December 2013 / Published: 17 December 2013
Cited by 1 | PDF Full-text (515 KB) | HTML Full-text | XML Full-text
Abstract
Palladium catalyzed Suzuki-Miyaura cross-coupling of 6,8-dibromo-4-chloroquinoline-3-carbaldehyde with arylboronic and arylvinylboronic acid derivatives in the presence of potassium carbonate in aqueous dioxane afforded the corresponding 4,6,8-triarylquinoline-3-carbaldehydes, exclusively. These products were transformed into 4,6,8-triaryl-3-(4-fluorophenyl)amino)-N-(quinolin-3-yl)methylenes and their 4,6,8-triaryl-quinoline-3-methanol derivatives. The absorption and emission spectra
[...] Read more.
Palladium catalyzed Suzuki-Miyaura cross-coupling of 6,8-dibromo-4-chloroquinoline-3-carbaldehyde with arylboronic and arylvinylboronic acid derivatives in the presence of potassium carbonate in aqueous dioxane afforded the corresponding 4,6,8-triarylquinoline-3-carbaldehydes, exclusively. These products were transformed into 4,6,8-triaryl-3-(4-fluorophenyl)amino)-N-(quinolin-3-yl)methylenes and their 4,6,8-triaryl-quinoline-3-methanol derivatives. The absorption and emission spectra were measured for the 4,6,8-triarylquinoline-3-carbaldehydes and their derivatives in selected solvents of different polarity. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Glycyrrhizin Alleviates Neuroinflammation and Memory Deficit Induced by Systemic Lipopolysaccharide Treatment in Mice
Molecules 2013, 18(12), 15788-15803; doi:10.3390/molecules181215788
Received: 5 November 2013 / Revised: 9 December 2013 / Accepted: 10 December 2013 / Published: 17 December 2013
Cited by 9 | PDF Full-text (1175 KB) | HTML Full-text | XML Full-text
Abstract
The present study investigated the effects of glycyrrhizin (GRZ) on neuroinflammation and memory deficit in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Varying doses of GRZ was orally administered (10, 30, or 50 mg/kg) once a day for 3 days before the LPS (3 mg/kg)
[...] Read more.
The present study investigated the effects of glycyrrhizin (GRZ) on neuroinflammation and memory deficit in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Varying doses of GRZ was orally administered (10, 30, or 50 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection. At 24 h after the LPS injection, GRZ significantly reduced TNF-α and IL-1β mRNA at doses of 30 and 50 mg/kg. COX-2 and iNOS protein expressions were significantly reduced by GRZ at doses of 30 and 50 mg/kg. In the Morris water maze test, GRZ (30 mg/kg) significantly prolonged the swimming time spent in the target and peri-target zones. GRZ also significantly increased the target heading and memory score numbers. In the hippocampal tissue, GRZ significantly reduced the up-regulated Iba1 protein expression and the average cell size of Iba1-expressing microglia induced by LPS. The results indicate that GRZ ameliorated the memory deficit induced by systemic LPS treatment and the effect of GRZ was found to be mediated through the inhibition of pro-inflammatory mediators and microglial activation in the brain tissue. This study supports that GRZ may be a putative therapeutic drug on neurodegenerative diseases associated with cognitive deficits and neuroinflammation such as Alzheimer’s disease. Full article
(This article belongs to the Section Natural Products)
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Review

Jump to: Research

Open AccessReview General Approach for Introduction of Various Chemical Labels in Specific RNA Locations Based on Insertion of Amino Linkers
Molecules 2013, 18(12), 14455-14469; doi:10.3390/molecules181214455
Received: 8 October 2013 / Revised: 12 November 2013 / Accepted: 18 November 2013 / Published: 25 November 2013
Cited by 5 | PDF Full-text (1331 KB) | HTML Full-text | XML Full-text
Abstract
Introduction of reporter groups at designed RNA sites is a widely accepted approach to gain information about the molecular environment of RNAs in their complexes with other biopolymers formed during various cellular processes. A general approach to obtain RNAs bearing diverse reporter groups
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Introduction of reporter groups at designed RNA sites is a widely accepted approach to gain information about the molecular environment of RNAs in their complexes with other biopolymers formed during various cellular processes. A general approach to obtain RNAs bearing diverse reporter groups at designed locations is based on site-specific insertion of groups containing primary aliphatic amine functions (amino linkers) with their subsequent selective derivatization by appropriate chemicals. This article is a brief review on methods for site-specific introduction of amino linkers in different RNAs. These methods comprise: (i) incorporation of a nucleoside carrying an amino-linker or a function that can be substituted with it into oligoribonucleotides in the course of their chemical synthesis; (ii) assembly of amino linker-containing RNAs from short synthetic fragments via their ligation; (iii) synthesis of amino linker-modified RNAs using T7 RNA polymerase; (iv) insertion of amino linkers into unmodified RNAs at functional groups of a certain type such as the 5'-phosphates and N7 of guanosine residues and (v) introduction of an amino linker into long highly structured RNAs exploiting an approach based on sequence-specific modification of nucleic acids. Particular reporter groups used for derivatization of amino linker-containing RNAs together with types of RNA derivatives obtained and fields of their application are presented. Full article
(This article belongs to the Special Issue Synthesis of Nucleosides, Nucleotides and Their Derivatives)
Open AccessReview Cytochrome P450 Family 1 Inhibitors and Structure-Activity Relationships
Molecules 2013, 18(12), 14470-14495; doi:10.3390/molecules181214470
Received: 22 September 2013 / Revised: 15 November 2013 / Accepted: 19 November 2013 / Published: 25 November 2013
Cited by 14 | PDF Full-text (983 KB) | HTML Full-text | XML Full-text
Abstract
With the widespread use of O-alkoxyresorufin dealkylation assays since the 1990s, thousands of inhibitors of cytochrome P450 family 1 enzymes (P450s 1A1, 1A2, and 1B1) have been identified and studied. Generally, planar polycyclic molecules such as polycyclic aromatic hydrocarbons, stilbenoids, and flavonoids
[...] Read more.
With the widespread use of O-alkoxyresorufin dealkylation assays since the 1990s, thousands of inhibitors of cytochrome P450 family 1 enzymes (P450s 1A1, 1A2, and 1B1) have been identified and studied. Generally, planar polycyclic molecules such as polycyclic aromatic hydrocarbons, stilbenoids, and flavonoids are considered to potentially be effective inhibitors of these enzymes, however, the details of the structure-activity relationships and selectivity of these inhibitors are still ambiguous. In this review, we thoroughly discuss the selectivity of many representative P450 family 1 inhibitors reported in the past 20 years through a meta-analysis. Full article
(This article belongs to the Special Issue Enzyme Chemistry)
Open AccessReview Traditional Korean East Asian Medicines and Herbal Formulations for Cognitive Impairment
Molecules 2013, 18(12), 14670-14693; doi:10.3390/molecules181214670
Received: 9 September 2013 / Revised: 8 November 2013 / Accepted: 18 November 2013 / Published: 26 November 2013
Cited by 7 | PDF Full-text (327 KB) | HTML Full-text | XML Full-text
Abstract
Hanbang, the Traditional Korean Medicine (TKM), is an inseparable component of Korean culture both within the country, and further afield. Korean traditional herbs have been used medicinally to treat sickness and injury for thousands of years. Oriental medicine reflects our ancestor’s wisdom
[...] Read more.
Hanbang, the Traditional Korean Medicine (TKM), is an inseparable component of Korean culture both within the country, and further afield. Korean traditional herbs have been used medicinally to treat sickness and injury for thousands of years. Oriental medicine reflects our ancestor’s wisdom and experience, and as the elderly population in Korea is rapidly increasing, so is the importance of their health problems. The proportion of the population who are over 65 years of age is expected to increase to 24.3% by 2031. Cognitive impairment is common with increasing age, and efforts are made to retain and restore the cognition ability of the elderly. Herbal materials have been considered for this purpose because of their low adverse effects and their cognitive-enhancing or anti-dementia activities. Herbal materials are reported to contain several active compounds that have effects on cognitive function. Here, we enumerate evidence linking TKMs which have shown benefits in memory improvements. Moreover, we have also listed Korean herbal formulations which have been the subject of scientific reports relating to memory improvement. Full article
(This article belongs to the Section Natural Products)
Open AccessReview G-Quadruplexes as Sensing Probes
Molecules 2013, 18(12), 14760-14779; doi:10.3390/molecules181214760
Received: 9 September 2013 / Revised: 13 November 2013 / Accepted: 13 November 2013 / Published: 28 November 2013
Cited by 16 | PDF Full-text (684 KB) | HTML Full-text | XML Full-text
Abstract
Guanine-rich sequences of DNA are able to create tetrastranded structures known as G-quadruplexes; they are formed by the stacking of planar G-quartets composed of four guanines paired by Hoogsteen hydrogen bonding. G-quadruplexes act as ligands for metal ions and aptamers for various molecules.
[...] Read more.
Guanine-rich sequences of DNA are able to create tetrastranded structures known as G-quadruplexes; they are formed by the stacking of planar G-quartets composed of four guanines paired by Hoogsteen hydrogen bonding. G-quadruplexes act as ligands for metal ions and aptamers for various molecules. Interestingly, the G-quadruplexes form a complex with anionic porphyrin hemin and exhibit peroxidase-like activity. This review focuses on overview of sensing techniques based on G-quadruplex complexes with anionic porphyrins for detection of various analytes, including metal ions such as K+, Ca2+, Ag+, Hg2+, Cu2+, Pb2+, Sr2+, organic molecules, nucleic acids, and proteins. Principles of G-quadruplex-based detection methods involve DNA conformational change caused by the presence of analyte which leads to a decrease or an increase in peroxidase activity, fluorescence, or electrochemical signal of the used probe. The advantages of various detection techniques are also discussed. Full article
(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)
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Open AccessReview C-4 Gem-Dimethylated Oleanes of Gymnema sylvestre and Their Pharmacological Activities
Molecules 2013, 18(12), 14892-14919; doi:10.3390/molecules181214892
Received: 27 September 2013 / Revised: 21 November 2013 / Accepted: 22 November 2013 / Published: 4 December 2013
PDF Full-text (344 KB) | HTML Full-text | XML Full-text
Abstract
Gymnema sylvestre R. Br., one of the most important medicinal plants of the Asclepiadaceae family, is a herb distributed throughout the World, predominantly in tropical countries. The plant, widely used for the treatment of diabetes and as a diuretic in Indian proprietary medicines,
[...] Read more.
Gymnema sylvestre R. Br., one of the most important medicinal plants of the Asclepiadaceae family, is a herb distributed throughout the World, predominantly in tropical countries. The plant, widely used for the treatment of diabetes and as a diuretic in Indian proprietary medicines, possesses beneficial digestive, anti-inflammatory, hypoglycemic and anti-helmentic effects. Furthermore, it is believed to be useful in the treatment of dyspepsia, constipation, jaundice, hemorrhoids, cardiopathy, asthma, bronchitis and leucoderma. A literature survey revealed that some other notable pharmacological activities of the plant such as anti-obesity, hypolipidemic, antimicrobial, free radical scavenging and anti-inflammatory properties have been proven too. This paper aims to summarize the chemical and pharmacological reports on a large group of C-4 gem-dimethylated pentacyclic triterpenoids from Gymnema sylvestre. Full article
(This article belongs to the Section Natural Products)
Open AccessReview Chemical and Biological Properties of Quinochalcone C-Glycosides from the Florets of Carthamus tinctorius
Molecules 2013, 18(12), 15220-15254; doi:10.3390/molecules181215220
Received: 2 September 2013 / Revised: 1 December 2013 / Accepted: 2 December 2013 / Published: 10 December 2013
Cited by 14 | PDF Full-text (576 KB) | HTML Full-text | XML Full-text
Abstract
Quinochalcone C-glycosides are regarded as characteristic components that have only been isolated from the florets of Carthamus tinctorius. Recently, quinochalcone C-glycosides were found to have multiple pharmacological activities, which has attracted the attention of many researchers to explore these compounds.
[...] Read more.
Quinochalcone C-glycosides are regarded as characteristic components that have only been isolated from the florets of Carthamus tinctorius. Recently, quinochalcone C-glycosides were found to have multiple pharmacological activities, which has attracted the attention of many researchers to explore these compounds. This review aims to summarize quinochalcone C-glycosides’ physicochemical properties, chromatographic behavior, spectroscopic characteristics, as well as their biological activities, which will be helpful for further study and development of quinochalcone C-glycosides. Full article
Open AccessReview A Novel Cardiac Bio-Marker: ST2: A Review
Molecules 2013, 18(12), 15314-15328; doi:10.3390/molecules181215314
Received: 15 October 2013 / Revised: 5 December 2013 / Accepted: 5 December 2013 / Published: 11 December 2013
Cited by 30 | PDF Full-text (225 KB) | HTML Full-text | XML Full-text
Abstract
Cardiovascular diseases (CVD) are the major cause of death worldwide. The identification of markers able to detect the early stages of such diseases and/or their progression is fundamental in order to adopt the best actions in order to reduce the worsening of clinical
[...] Read more.
Cardiovascular diseases (CVD) are the major cause of death worldwide. The identification of markers able to detect the early stages of such diseases and/or their progression is fundamental in order to adopt the best actions in order to reduce the worsening of clinical condition. Brain natriuretic peptide (BNP) and NT-proBNP are the best known markers of heart failure (HF), while troponins ameliorated the diagnosis of acute and chronic coronary artery diseases. Nevertheless, many limitations reduce their accuracy. Physicians have tried to develop further detectable molecules in order to improve the detection of the early moments of CVD and prevent their development. Soluble ST2 (suppression of tumorigenicity 2) is a blood protein confirmed to act as a decoy receptor for interleukin-33. It seems to be markedly induced in mechanically overloaded cardiac myocytes. Thus, HF onset or worsening of a previous chronic HF status, myocardial infarct able to induce scars that make the myocardium unable to stretch well, etc, are all conditions that could be detected by measuring blood levels of soluble ST2. The aim of this review is to explore the possible role of ST2 derived-protein as an early marker of cardiovascular diseases, above all in heart failure and ischemic heart diseases. Full article
(This article belongs to the Section Metabolites)
Open AccessReview Fluorescent Probes for Nucleic Acid Visualization in Fixed and Live Cells
Molecules 2013, 18(12), 15357-15397; doi:10.3390/molecules181215357
Received: 23 September 2013 / Revised: 20 November 2013 / Accepted: 5 December 2013 / Published: 11 December 2013
Cited by 30 | PDF Full-text (1305 KB) | HTML Full-text | XML Full-text
Abstract
This review analyses the literature concerning non-fluorescent and fluorescent probes for nucleic acid imaging in fixed and living cells from the point of view of their suitability for imaging intracellular native RNA and DNA. Attention is mainly paid to fluorescent probes for fluorescence
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This review analyses the literature concerning non-fluorescent and fluorescent probes for nucleic acid imaging in fixed and living cells from the point of view of their suitability for imaging intracellular native RNA and DNA. Attention is mainly paid to fluorescent probes for fluorescence microscopy imaging. Requirements for the target-binding part and the fluorophore making up the probe are formulated. In the case of native double-stranded DNA, structure-specific and sequence-specific probes are discussed. Among the latest, three classes of dsDNA-targeting molecules are described: (i) sequence-specific peptides and proteins; (ii) triplex-forming oligonucleotides and (iii) polyamide oligo(N-methylpyrrole/N-methylimidazole) minor groove binders. Polyamides seem to be the most promising targeting agents for fluorescent probe design, however, some technical problems remain to be solved, such as the relatively low sequence specificity and the high background fluorescence inside the cells. Several examples of fluorescent probe applications for DNA imaging in fixed and living cells are cited. In the case of intracellular RNA, only modified oligonucleotides can provide such sequence-specific imaging. Several approaches for designing fluorescent probes are considered: linear fluorescent probes based on modified oligonucleotide analogs, molecular beacons, binary fluorescent probes and template-directed reactions with fluorescence probe formation, FRET donor-acceptor pairs, pyrene excimers, aptamers and others. The suitability of all these methods for living cell applications is discussed. Full article
(This article belongs to the Special Issue Synthesis of Nucleosides, Nucleotides and Their Derivatives)
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Open AccessReview Stereocontrolled Synthesis and Functionalization of Cyclobutanes and Cyclobutanones
Molecules 2013, 18(12), 15541-15572; doi:10.3390/molecules181215541
Received: 7 November 2013 / Revised: 9 December 2013 / Accepted: 11 December 2013 / Published: 13 December 2013
Cited by 25 | PDF Full-text (423 KB) | HTML Full-text | XML Full-text
Abstract
In the last decade a certain number of new cyclobutane and cyclobutanone synthesis and functionalization protocols have been published. Organo- and biocatalyzed eco-friendly approaches to cyclobutane-containing molecules have been developed with interesting results. Also, successful new total synthesis of bioactive compounds and drugs
[...] Read more.
In the last decade a certain number of new cyclobutane and cyclobutanone synthesis and functionalization protocols have been published. Organo- and biocatalyzed eco-friendly approaches to cyclobutane-containing molecules have been developed with interesting results. Also, successful new total synthesis of bioactive compounds and drugs have been recently reported where a four membered ring represented the key intermediate. Therefore, the rising interest in this field represents a great point of discussion for the scientific community, disclosing the synthetic potential of strained four membered ring carbocyclic compounds. Herein we report a critical survey on the literature concerning the enantiocontrolled synthesis and functionalization of cyclobutane derivatives, with particular attention to metal-free, low impact methodologies, published during the period 2000–2013. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Open AccessReview Stimulation of Natural Killer T Cells by Glycolipids
Molecules 2013, 18(12), 15662-15688; doi:10.3390/molecules181215662
Received: 4 November 2013 / Revised: 11 December 2013 / Accepted: 11 December 2013 / Published: 16 December 2013
Cited by 16 | PDF Full-text (764 KB) | HTML Full-text | XML Full-text
Abstract
Natural killer T (NKT) cells are a subset of T cells that recognize glycolipid antigens presented by the CD1d protein. The initial discovery of immunostimulatory glycolipids from a marine sponge and the T cells that respond to the compounds has led to extensive
[...] Read more.
Natural killer T (NKT) cells are a subset of T cells that recognize glycolipid antigens presented by the CD1d protein. The initial discovery of immunostimulatory glycolipids from a marine sponge and the T cells that respond to the compounds has led to extensive research by chemists and immunologists to understand how glycolipids are recognized, possible responses by NKT cells, and the structural features of glycolipids necessary for stimulatory activity. The presence of this cell type in humans and most mammals suggests that it plays critical roles in antigen recognition and the interface between innate and adaptive immunity. Both endogenous and exogenous natural antigens for NKT cells have been identified, and it is likely that glycolipid antigens remain to be discovered. Multiple series of structurally varied glycolipids have been synthesized and tested for stimulatory activity. The structural features of glycolipids necessary for NKT cell stimulation are moderately well understood, and designed compounds have proven to be much more potent antigens than their natural counterparts. Nevertheless, control over NKT cell responses by designed glycolipids has not been optimized, and further research will be required to fully reveal the therapeutic potential of this cell type. Full article
(This article belongs to the Special Issue Synthesis, Structure, Analysis and Properties of Glycolipids)
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