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

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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; https://doi.org/10.3390/molecules181215788
Received: 5 November 2013 / Revised: 9 December 2013 / Accepted: 10 December 2013 / Published: 17 December 2013
Cited by 18 | 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)
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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 Chemistry)
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Open AccessArticle 4,6,8-Triarylquinoline-3-carbaldehyde Derivatives: Synthesis and Photophysical Properties
Molecules 2013, 18(12), 15769-15787; https://doi.org/10.3390/molecules181215769
Received: 1 November 2013 / Revised: 11 December 2013 / Accepted: 12 December 2013 / Published: 17 December 2013
Cited by 4 | 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
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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 Chemistry)
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Open AccessArticle Design, Synthesis and Evaluation of N13-Substituted Evodiamine Derivatives against Human Cancer Cell Lines
Molecules 2013, 18(12), 15750-15768; https://doi.org/10.3390/molecules181215750
Received: 23 October 2013 / Revised: 7 November 2013 / Accepted: 12 November 2013 / Published: 17 December 2013
Cited by 6 | 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
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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
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Open AccessArticle Crystal Structures and Antifungal Activities of Fluorine-Containing Thioureido Complexes with Nickel(II)
Molecules 2013, 18(12), 15737-15749; https://doi.org/10.3390/molecules181215737
Received: 13 November 2013 / Revised: 3 December 2013 / Accepted: 5 December 2013 / Published: 17 December 2013
Cited by 6 | 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)
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Open AccessArticle Madecassoside Inhibits Melanin Synthesis by Blocking Ultraviolet-Induced Inflammation
Molecules 2013, 18(12), 15724-15736; https://doi.org/10.3390/molecules181215724
Received: 29 October 2013 / Revised: 10 December 2013 / Accepted: 11 December 2013 / Published: 16 December 2013
Cited by 5 | 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
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Open AccessArticle Synthesis of Dimethyl Aryl Acylsulfonium Bromides from Aryl Methyl Ketones in a DMSO-HBr System
Molecules 2013, 18(12), 15717-15723; https://doi.org/10.3390/molecules181215717
Received: 26 November 2013 / Revised: 10 December 2013 / Accepted: 10 December 2013 / Published: 16 December 2013
Cited by 5 | 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 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; https://doi.org/10.3390/molecules181215704
Received: 8 August 2013 / Revised: 20 November 2013 / Accepted: 10 December 2013 / Published: 16 December 2013
Cited by 11 | 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 Chemistry)
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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; https://doi.org/10.3390/molecules181215689
Received: 18 November 2013 / Revised: 10 December 2013 / Accepted: 11 December 2013 / Published: 16 December 2013
Cited by 14 | 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 Chemistry)
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Open AccessReview Stimulation of Natural Killer T Cells by Glycolipids
Molecules 2013, 18(12), 15662-15688; https://doi.org/10.3390/molecules181215662
Received: 4 November 2013 / Revised: 11 December 2013 / Accepted: 11 December 2013 / Published: 16 December 2013
Cited by 29 | 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
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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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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; https://doi.org/10.3390/molecules181215648
Received: 17 October 2013 / Revised: 9 December 2013 / Accepted: 10 December 2013 / Published: 16 December 2013
Cited by 24 | 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 Chemistry)
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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; https://doi.org/10.3390/molecules181215636
Received: 13 September 2013 / Revised: 10 December 2013 / Accepted: 10 December 2013 / Published: 13 December 2013
Cited by 3 | 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
[...] Read more.
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)
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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; https://doi.org/10.3390/molecules181215624
Received: 4 November 2013 / Revised: 5 December 2013 / Accepted: 6 December 2013 / Published: 13 December 2013
Cited by 17 | 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
[...] Read more.
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
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Open AccessArticle Total Synthesis of Six 3,4-Unsubstituted Coumarins
Molecules 2013, 18(12), 15613-15623; https://doi.org/10.3390/molecules181215613
Received: 28 October 2013 / Revised: 8 December 2013 / Accepted: 10 December 2013 / Published: 13 December 2013
Cited by 15 | 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.
[...] Read more.
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 In Vitro Evaluation of Novel Inhibitors against the NS2B-NS3 Protease of Dengue Fever Virus Type 4
Molecules 2013, 18(12), 15600-15612; https://doi.org/10.3390/molecules181215600
Received: 28 October 2013 / Revised: 2 December 2013 / Accepted: 11 December 2013 / Published: 13 December 2013
Cited by 10 | 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)
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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; https://doi.org/10.3390/molecules181215587
Received: 8 October 2013 / Revised: 3 December 2013 / Accepted: 9 December 2013 / Published: 13 December 2013
Cited by 8 | 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
[...] Read more.
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 Chemistry)
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Open AccessArticle Beads-Based Electrochemical Assay for the Detection of Influenza Hemagglutinin Labeled with CdTe Quantum Dots
Molecules 2013, 18(12), 15573-15586; https://doi.org/10.3390/molecules181215573
Received: 10 October 2013 / Revised: 25 November 2013 / Accepted: 5 December 2013 / Published: 13 December 2013
Cited by 7 | 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
[...] Read more.
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)
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Open AccessReview Stereocontrolled Synthesis and Functionalization of Cyclobutanes and Cyclobutanones
Molecules 2013, 18(12), 15541-15572; https://doi.org/10.3390/molecules181215541
Received: 7 November 2013 / Revised: 9 December 2013 / Accepted: 11 December 2013 / Published: 13 December 2013
Cited by 38 | 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)
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Open AccessArticle Synthesis of δ-Oxo-1,1-bis(triflyl)alkanes and Their Acidities
Molecules 2013, 18(12), 15531-15540; https://doi.org/10.3390/molecules181215531
Received: 4 November 2013 / Revised: 3 December 2013 / Accepted: 11 December 2013 / Published: 13 December 2013
Cited by 5 | 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)
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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; https://doi.org/10.3390/molecules181215519
Received: 8 October 2013 / Revised: 7 December 2013 / Accepted: 9 December 2013 / Published: 13 December 2013
Cited by 4 | 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 Chemistry)
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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; https://doi.org/10.3390/molecules181215501
Received: 6 November 2013 / Revised: 3 December 2013 / Accepted: 6 December 2013 / Published: 12 December 2013
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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 AccessArticle Preparative Separation of Six Rhynchophylla Alkaloids from Uncaria macrophylla Wall by pH-Zone Refining Counter-Current Chromatography
Molecules 2013, 18(12), 15490-15500; https://doi.org/10.3390/molecules181215490
Received: 12 November 2013 / Revised: 5 December 2013 / Accepted: 6 December 2013 / Published: 12 December 2013
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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 Chemistry)
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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; https://doi.org/10.3390/molecules181215474
Received: 25 October 2013 / Revised: 3 December 2013 / Accepted: 10 December 2013 / Published: 12 December 2013
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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
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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; https://doi.org/10.3390/molecules181215464
Received: 6 November 2013 / Revised: 9 December 2013 / Accepted: 10 December 2013 / Published: 12 December 2013
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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
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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; https://doi.org/10.3390/molecules181215448
Received: 28 October 2013 / Revised: 17 November 2013 / Accepted: 18 November 2013 / Published: 12 December 2013
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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.
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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 Chemistry)
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Open AccessArticle G-Quadruplex Guanosine Gels and Single Walled Carbon Nanotubes
Molecules 2013, 18(12), 15434-15447; https://doi.org/10.3390/molecules181215434
Received: 7 November 2013 / Revised: 25 November 2013 / Accepted: 3 December 2013 / Published: 11 December 2013
Cited by 6 | 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 Highly Enantioselective Addition of Phenylethynylzinc to Aldehydes Catalyzed by Chiral Cyclopropane-Based Amino Alcohols
Molecules 2013, 18(12), 15422-15433; https://doi.org/10.3390/molecules181215422
Received: 18 November 2013 / Revised: 28 November 2013 / Accepted: 29 November 2013 / Published: 11 December 2013
Cited by 3 | 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
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Open AccessCommunication A Triple Staining Method for Accurate Cell Cycle Analysis Using Multiparameter Flow Cytometry
Molecules 2013, 18(12), 15412-15421; https://doi.org/10.3390/molecules181215412
Received: 29 October 2013 / Revised: 5 November 2013 / Accepted: 6 December 2013 / Published: 11 December 2013
Cited by 6 | 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
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Open AccessArticle Bortezomib Congeners Induce Apoptosis of Hepatocellular Carcinoma via CIP2A Inhibition
Molecules 2013, 18(12), 15398-15411; https://doi.org/10.3390/molecules181215398
Received: 25 August 2013 / Revised: 20 November 2013 / Accepted: 28 November 2013 / Published: 11 December 2013
Cited by 6 | 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
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Open AccessReview Fluorescent Probes for Nucleic Acid Visualization in Fixed and Live Cells
Molecules 2013, 18(12), 15357-15397; https://doi.org/10.3390/molecules181215357
Received: 23 September 2013 / Revised: 20 November 2013 / Accepted: 5 December 2013 / Published: 11 December 2013
Cited by 45 | 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 AccessArticle Identification and Physicochemical Characteristics of Temozolomide Process-Related Impurities
Molecules 2013, 18(12), 15344-15356; https://doi.org/10.3390/molecules181215344
Received: 24 October 2013 / Revised: 27 November 2013 / Accepted: 3 December 2013 / Published: 11 December 2013
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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)
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