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Molecules, Volume 18, Issue 6 (June 2013), Pages 6128-7335

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Open AccessArticle Superoxide Scavenging Effects of Some Novel Bis-Ligands and Their Solvated Metal Complexes Prepared by the Reaction of Ligands with Aluminum, Copper and Lanthanum Ions
Molecules 2013, 18(6), 6128-6141; doi:10.3390/molecules18066128
Received: 4 March 2013 / Revised: 20 May 2013 / Accepted: 20 May 2013 / Published: 23 May 2013
Cited by 3 | PDF Full-text (705 KB) | HTML Full-text | XML Full-text
Abstract
Novel antioxidants have been synthesized and characterized by their chemical properties as antioxidants with high superoxide scavenging activity. (2R,3R)-diphenylethylenediamine is a spacer in antioxidants, and we synthesized targets 11a and 11b by conjugation with o-hydroquinone and p-hydroquinone
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Novel antioxidants have been synthesized and characterized by their chemical properties as antioxidants with high superoxide scavenging activity. (2R,3R)-diphenylethylenediamine is a spacer in antioxidants, and we synthesized targets 11a and 11b by conjugation with o-hydroquinone and p-hydroquinone at the two N-termini, respectively. Superoxide scavenging activities of the plant flavonoid-like 11a and 11b were compared with those of known antioxidants, and shown to increase in the following order: curcumin << ascorbic acid < Trolox < ()-epicatechin < 11a < quercetin ≤ 11b . Compound 11a also formed a solvated 11a–metal complex with metal ions. The 11a–Cu2+ complex was shown to have higher superoxide scavenging activity than that of 11a, 11b, Cu2+, and the 11a–Al3+ and 11a–La3+ complexes, whereas the 11a–Al3+ complex increased rather than decreased superoxide levels. The 11a–Al3+ complex did not abstract one electron from the SOMO of O2−. since the HOMO and LUMO phases of Al3+ do not exist in the center of the 11a–Al3+ complex. However, the SOMO of the 11a–Cu2+ complex distributed in the center of Cu2+ may abstract one electron from the SOMO of O2−.. These results suggest that 11a and 11b are powerful antioxidants. Full article
(This article belongs to the Special Issue Antioxidants 2012)
Open AccessArticle One-Pot Synthesis of Novel Chiral β-Amino Acid Derivatives by Enantioselective Mannich Reactions Catalyzed by Squaramide Cinchona Alkaloids
Molecules 2013, 18(6), 6142-6152; doi:10.3390/molecules18066142
Received: 1 April 2013 / Revised: 13 May 2013 / Accepted: 16 May 2013 / Published: 23 May 2013
Cited by 7 | PDF Full-text (320 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An efficient one-pot synthesis of novel β-amino acid derivatives containing a thiadiazole moiety was developed using a chiral squaramide cinchona alkaloid as organocatalyst. The reactions afforded chiral β-amino acid derivatives in moderate yields and with moderate to excellent enantioselectivities. The present
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An efficient one-pot synthesis of novel β-amino acid derivatives containing a thiadiazole moiety was developed using a chiral squaramide cinchona alkaloid as organocatalyst. The reactions afforded chiral β-amino acid derivatives in moderate yields and with moderate to excellent enantioselectivities. The present study demonstrated for the first time the use of a Mannich reaction catalyzed by a chiral bifunctional organocatalyst for the one-pot synthesis of novel β-amino acid derivatives bearing a 1,3,4-thiadiazole moiety on nitrogen. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Phenolic Glucosides from Dendrobium aurantiacum var. denneanum and Their Bioactivities
Molecules 2013, 18(6), 6153-6160; doi:10.3390/molecules18066153
Received: 15 April 2013 / Revised: 16 May 2013 / Accepted: 20 May 2013 / Published: 23 May 2013
Cited by 7 | PDF Full-text (268 KB) | HTML Full-text | XML Full-text
Abstract
A new 8,4¢-oxyneolignane glucoside 1 has been isolated from the stems of Dendrobium aurantiacum var. denneanum together with six known phenolic glucosides 2-7. The structure of the new compound, including its absolute configuration, was determined by spectroscopic and chemical methods
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A new 8,4¢-oxyneolignane glucoside 1 has been isolated from the stems of Dendrobium aurantiacum var. denneanum together with six known phenolic glucosides 2-7. The structure of the new compound, including its absolute configuration, was determined by spectroscopic and chemical methods as (–)-(7S,8R,7¢E)-4-hydroxy-3,3¢,5,5¢-tetramethoxy-8,4¢-oxyneolign-7¢-ene-7,9,9¢-triol 7,9¢-bis-O-β-D-glucopyranoside (1). In the in vitro assays, compound 1 and (-)-syringaresinol-4,4¢-bis-O-β-D-glucopyranoside (2) showed evident activity against glutamate-induced neurotoxicity in PC12 cells. Shashenoside I (4) showed a selective cytotoxic activity with the IC50 value of 4.17 μM against the acute myeloid leukemia cell line MV4-11, while it was inactive against 10 other human tumor cell lines. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Carvacrol: From Ancient Flavoring to Neuromodulatory Agent
Molecules 2013, 18(6), 6161-6172; doi:10.3390/molecules18066161
Received: 10 April 2013 / Revised: 8 May 2013 / Accepted: 20 May 2013 / Published: 24 May 2013
Cited by 17 | PDF Full-text (114 KB) | HTML Full-text | XML Full-text
Abstract
Oregano and thyme essential oils are used for therapeutic, aromatic and gastronomic purposes due to their richness in active substances, like carvacrol; however, the effects of the latter on the central nervous system have been poorly investigated. The aim of our study was
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Oregano and thyme essential oils are used for therapeutic, aromatic and gastronomic purposes due to their richness in active substances, like carvacrol; however, the effects of the latter on the central nervous system have been poorly investigated. The aim of our study was to define the effects of carvacrol on brain neurochemistry and behavioural outcome in rats. Biogenic amine content in the prefrontal cortex and hippocampus after chronic or acute oral carvacrol administration was measured. Animals were assessed by a forced swimming test. Carvacrol, administered for seven consecutive days (12.5 mg/kg p.o.), was able to increase dopamine and serotonin levels in the prefrontal cortex and hippocampus. When single doses were used (150 and 450 mg/kg p.o.), dopamine content was increased in the prefrontal cortex at both dose levels. On the contrary, a significant dopamine reduction in hippocampus of animals treated with 450 mg/kg of carvacrol was found. Acute carvacrol administration only significantly reduced serotonin content in either the prefrontal cortex or in the hippocampus at the highest dose. Moreover, acute carvacrol was ineffective in producing changes in the forced swimming test. Our data suggest that carvacrol is a brain-active molecule that clearly influences neuronal activity through modulation of neurotransmitters. If regularly ingested in low concentrations, it might determine feelings of well-being and could possibly have positive reinforcer effects. Full article
(This article belongs to the Special Issue Flavors and Fragrances)
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Open AccessArticle Mercury(II) Removal with Modified Magnetic Chitosan Adsorbents
Molecules 2013, 18(6), 6193-6214; doi:10.3390/molecules18066193
Received: 6 April 2013 / Revised: 15 May 2013 / Accepted: 20 May 2013 / Published: 24 May 2013
Cited by 32 | PDF Full-text (681 KB) | HTML Full-text | XML Full-text
Abstract
Two modified chitosan derivatives were prepared in order to compare their adsorption properties for Hg(II) removal from aqueous solutions. The one chitosan adsorbent (CS) is only cross–linked with glutaraldehyde, while the other (CSm), which is magnetic, is cross-linked with glutaraldehyde and functionalized with
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Two modified chitosan derivatives were prepared in order to compare their adsorption properties for Hg(II) removal from aqueous solutions. The one chitosan adsorbent (CS) is only cross–linked with glutaraldehyde, while the other (CSm), which is magnetic, is cross-linked with glutaraldehyde and functionalized with magnetic nanoparticles (Fe3O4). Many possible interactions between materials and Hg(II) were observed after adsorption and explained via characterization with various techniques (SEM/EDAX, FTIR, XRD, DTG, DTA, VSM, swelling tests). The adsorption evaluation was done studying various parameters as the effect of pH (optimum value 5 for adsorption and 2 for desorption), contact time (fitting to pseudo–first, –second order and Elovich equations), temperature (isotherms at 25, 45, 65 °C), in line with a brief thermodynamic analysis (ΔG0 < 0, ΔH0 > 0, ΔS0 > 0). The maximum adsorption capacity (fitting with Langmuir and Freundlich model) of CS and CSm at 25 °C was 145 and 152 mg/g, respectively. The reuse ability of the adsorbents prepared was confirmed with sequential cycles of adsorption-desorption. Full article
(This article belongs to the Special Issue Chitins and Chitosans)
Open AccessArticle Comparing Conventional and Supercritical Extraction of (−)-Mammea A/BB and the Antioxidant Activity of Calophyllum brasiliense Extracts
Molecules 2013, 18(6), 6215-6229; doi:10.3390/molecules18066215
Received: 5 March 2013 / Revised: 18 May 2013 / Accepted: 20 May 2013 / Published: 24 May 2013
Cited by 9 | PDF Full-text (389 KB) | HTML Full-text | XML Full-text
Abstract
Calophyllum brasiliense is a rich source of bioactive coumarins, xanthones and biflavonoids. The aim of the study was to compare the phenol contents and the antioxidant activity of C. brasiliense extracts obtained by conventional and supercritical fluid extraction (SFE) methods, as well as
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Calophyllum brasiliense is a rich source of bioactive coumarins, xanthones and biflavonoids. The aim of the study was to compare the phenol contents and the antioxidant activity of C. brasiliense extracts obtained by conventional and supercritical fluid extraction (SFE) methods, as well as the quantification of crude extracts and (−)-mammea A/BB yields. Dichloromethane and hexane were used as solvents for the conventional extractions and SFE was developed using supercritical CO2; the kinetic curves were modeled using a second-order empirical model. The dichloromethane extract presented the best total yield, although it showed the lowest content of (−)-mammea A/BB. The concentration of the coumarin was considerably higher in extracts obtained by the supercritical fluid method and a higher antioxidant activity was assigned to extracts obtained by this technique. Concerning the total phenolic contents, both the dichloro-methane and the supercritical extractions produced satisfactory amounts. The SFE method proved to be more promising than conventional methods. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis, Antibacterial and Thermal Studies of Cellulose Nanocrystal Stabilized ZnO-Ag Heterostructure Nanoparticles
Molecules 2013, 18(6), 6269-6280; doi:10.3390/molecules18066269
Received: 6 May 2013 / Revised: 22 May 2013 / Accepted: 22 May 2013 / Published: 28 May 2013
Cited by 16 | PDF Full-text (2769 KB) | HTML Full-text | XML Full-text
Abstract
Synthesis of ZnO-Ag heterostructure nanoparticles was carried out by a precipitation method with cellulose nanocrystals (CNCs) as a stabilizer for antimicrobial and thermal studies. ZnO-Ag nanoparticles were obtained from various weight percentages of added AgNO3 relative to Zn precursors for evaluating the
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Synthesis of ZnO-Ag heterostructure nanoparticles was carried out by a precipitation method with cellulose nanocrystals (CNCs) as a stabilizer for antimicrobial and thermal studies. ZnO-Ag nanoparticles were obtained from various weight percentages of added AgNO3 relative to Zn precursors for evaluating the best composition with enhanced functional properties. The ZnO-Ag/CNCs samples were characterized systematically by TEM, XRD, UV, TGA and DTG. From the TEM studies we observed that ZnO-Ag heterostructure nanoparticles have spherical shapes with size diameters in a 9–35 nm range. The antibacterial activities of samples were assessed against the bacterial species Salmonella choleraesuis and Staphylococcus aureus. The CNC-stabilized ZnO-Ag exhibited greater bactericidal activity compared to cellulose-free ZnO-Ag heterostructure nanoparticles of the same particle size. The incorporation of ZnO-Ag hetreostructure nanoparticles significantly increased the thermal stability of cellulose nanocrystals. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Chemical Composition of Aspidosperma ulei Markgr. and Antiplasmodial Activity of Selected Indole Alkaloids
Molecules 2013, 18(6), 6281-6297; doi:10.3390/molecules18066281
Received: 1 April 2013 / Revised: 15 May 2013 / Accepted: 16 May 2013 / Published: 29 May 2013
Cited by 14 | PDF Full-text (218 KB) | HTML Full-text | XML Full-text
Abstract
A new indole alkaloid, 12-hydroxy-N-acetyl-21(N)-dehydroplumeran-18-oic acid (13), and 11 known indole alkaloids: 3,4,5,6-tetradehydro-β-yohimbine (3), 19(E)-hunteracine (4), b-yohimbine (5), yohimbine (6), 19,20-dehydro-17-a-yohimbine (7), uleine (10
[...] Read more.
A new indole alkaloid, 12-hydroxy-N-acetyl-21(N)-dehydroplumeran-18-oic acid (13), and 11 known indole alkaloids: 3,4,5,6-tetradehydro-β-yohimbine (3), 19(E)-hunteracine (4), b-yohimbine (5), yohimbine (6), 19,20-dehydro-17-a-yohimbine (7), uleine (10), 20-epi-dasycarpidone (11), olivacine (8), 20-epi-N-nor-dasycarpidone (14), N-demethyluleine (15) and 20(E)-nor-subincanadine E (12) and a boonein d-lactone 9, ursolic acid (1) and 1D,1O-methyl-chiro-inositol (2) were isolated from the EtOH extracts of different parts of Aspidosperma ulei Markgr. (Apocynaceae). Identification and structural elucidation were based on IR, MS, 1H- and 13C-NMR spectral data and comparison to literature data. The antiplasmodial and antimalarial activity of 1, 5, 6, 8, 10 and 15 has been previously evaluated and 1 and 10 have important in vitro and in vivo antimalarial properties according to patent and/or scientific literature. With the aim of discovering new antiplasmodial indole alkaloids, 3, 4, 11, 12 and 13 were evaluated for in vitro inhibition against the multi-drug resistant K1 strain of the human malaria parasite Plasmodium falciparum. IC50 values of 14.0 (39.9), 4.5 (16.7) and 14.5 (54.3) mg/mL (mM) were determined for 3, 11 and 12, respectively. Inhibitory activity of 3, 4, 11, 12 and 13 was evaluated against NIH3T3 murine fibroblasts. None of these compounds exhibited toxicity to fibroblasts (IC50 > 50 mg/mL). Of the five compounds screened for in vitro antiplasmodial activity, only 11 was active. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Fucoxanthin from Undaria pinnatifida: Photostability and Coextractive Effects
Molecules 2013, 18(6), 6298-6310; doi:10.3390/molecules18066298
Received: 11 April 2013 / Revised: 17 May 2013 / Accepted: 24 May 2013 / Published: 29 May 2013
Cited by 6 | PDF Full-text (301 KB) | HTML Full-text | XML Full-text
Abstract
Fucoxanthin is one of the most abundant carotenoids and possesses a number of beneficial medicinal qualities which include its anti-oxidant, anti-obesity and anti-cancer properties. In this study, the photostability of fucoxanthin in extracts with different chemical profiles was studied. The extracts were obtained
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Fucoxanthin is one of the most abundant carotenoids and possesses a number of beneficial medicinal qualities which include its anti-oxidant, anti-obesity and anti-cancer properties. In this study, the photostability of fucoxanthin in extracts with different chemical profiles was studied. The extracts were obtained from Undaria pinnatifida, a seaweed rich in this carotenoid, using conventional liquid solvent extraction procedures and the QuEChERS method. All the extracts contained all-trans-fucoxanthin as the major compound. Conventional procedures produced a fucoxanthin purity of lower than 50%, whereas after liquid-liquid partition, PSA cleanup, and PSA and GCB cleanup (QuEChERS method) fucoxanthin purity increased to 70%, 86%, and 94%, respectively. Although in the acetone extract the initial content of fucoxanthin was the highest, results demonstrate that coextractives play an important role in enhancing the rate of photodegradation. After light exposure, the conventional extracts lost around 90% of the initial fucoxanthin content. On the other hand, the extracts obtained by the QuEChERS method showed significantly higher light stability than the conventional extracts. These results suggest that the QuEChERS method could be used and further improved to obtain more purified and stable extracts for fucoxanthin from U. pinnatifida. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Antioxidant and Antimicrobial Activities of Ethanol Extract from the Stem and Leaf of Impatiens balsamina L. (Balsaminaceae) at Different Harvest Times
Molecules 2013, 18(6), 6356-6365; doi:10.3390/molecules18066356
Received: 6 May 2013 / Revised: 16 May 2013 / Accepted: 27 May 2013 / Published: 29 May 2013
Cited by 5 | PDF Full-text (202 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to investigate the total phenolic content, total flavonoid contents, antioxidant activity and antimicrobial activity of ethanolic extract from stems (S) and leaves (L) of Impatiens balsamina L. (Balsaminaceae), which were harvested in Korea on March 10, 2011
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The aim of this study was to investigate the total phenolic content, total flavonoid contents, antioxidant activity and antimicrobial activity of ethanolic extract from stems (S) and leaves (L) of Impatiens balsamina L. (Balsaminaceae), which were harvested in Korea on March 10, 2011 (S1 and L1), May 14, 2011 (S2 and L2), and July 5, 2011 (S3 and L3), respectively. Our results revealed that the total phenolic (79.55–103.94 mg CE/g extract) and flavonoid (57.43–104.28 mg QE/g extract) contents of leaf extract were higher (p < 0.01) than those of stem extract. Leaf extracts (L1, L2, and L3) exhibited stronger (p < 0.01) free radical scavenging activity (66.06, 63.71, and 72.19%, respectively) than that of the positive control. In terms of antimicrobial activity, leaf extracts showed higher inhibitory effects against microorganisms than those of stem extracts (S1, S2, and S3). Among the leaf extracts at different harvest times, L3 showed the greatest antimicrobial activity against both Gram negative and Gram positive strains. From these results, the leaf extract from I. balsamina L. might be a valuable bioactive resource, and would seem to be applicable as a natural antioxidant in food preservation. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Design, Synthesis and Trypanocidal Evaluation of Novel 1,2,4-Triazoles-3-thiones Derived from Natural Piperine
Molecules 2013, 18(6), 6366-6382; doi:10.3390/molecules18066366
Received: 29 March 2013 / Revised: 16 May 2013 / Accepted: 21 May 2013 / Published: 29 May 2013
Cited by 14 | PDF Full-text (233 KB) | HTML Full-text | XML Full-text
Abstract
The work reported herein describes the synthesis and the assessment of the trypanocidal activity of thirteen new 1,2,4-triazole-3-thiones obtained from natural piperine, the main constituent of the dry fruits of Piper nigrum. It is part of a research program aiming to use
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The work reported herein describes the synthesis and the assessment of the trypanocidal activity of thirteen new 1,2,4-triazole-3-thiones obtained from natural piperine, the main constituent of the dry fruits of Piper nigrum. It is part of a research program aiming to use abundant and easily available natural products as starting materials for the design and synthesis of new molecules potentially useful as antiparasitic drugs. The variously substituted triazole derivatives were synthesized from the natural amide in four steps with the use of microwave irradiation on overall yields ranging from 32% to 51%. The cyclohexyl substituted derivative showed the best trypanocidal profile on proliferative forms of Trypanosoma cruzi (Y strain), with IC50s = 18.3 and 8.87 mM against epimastigotes and amastigotes, respectively. Full article
(This article belongs to the Special Issue Plant Natural Products against Human Parasites)
Open AccessArticle [Fe2L3]4+ Cylinders Derived from Bis(bidentate) 2-Pyridyl-1,2,3-triazole “Click” Ligands: Synthesis, Structures and Exploration of Biological Activity
Molecules 2013, 18(6), 6383-6407; doi:10.3390/molecules18066383
Received: 12 April 2013 / Revised: 16 May 2013 / Accepted: 17 May 2013 / Published: 29 May 2013
Cited by 25 | PDF Full-text (1476 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of metallosupramolecular [Fe2L3](BF4)4 “click” cylinders have been synthesized in excellent yields (90%–95%) from [Fe(H2O)6](BF4)2 and bis(bidentate) pyridyl-1,2,3-triazole ligands. All complexes were characterized by elemental analysis, IR, UV-vis,
[...] Read more.
A series of metallosupramolecular [Fe2L3](BF4)4 “click” cylinders have been synthesized in excellent yields (90%–95%) from [Fe(H2O)6](BF4)2 and bis(bidentate) pyridyl-1,2,3-triazole ligands. All complexes were characterized by elemental analysis, IR, UV-vis, 1H-, 13C- and DOSY-NMR spectroscopies and, in four cases, the structures confirmed by X-ray crystallography. Molecular modeling indicated that some of these “click” complexes were of similar size and shape to related biologically active pyridylimine-based iron(II) helicates and suggested that the “click” complexes may bind both duplex and triplex DNA. Cell-based agarose diffusion assays showed that the metallosupramolecular [Fe2L3](BF4)4 “click” cylinders display no antifungal activity against S. cerevisiae. This observed lack of antifungal activity appears to be due to the poor stability of the “click” complexes in DMSO and biological media. Full article
(This article belongs to the Special Issue Advances in Click Chemistry)
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Open AccessArticle The Mathematics of a Successful Deconvolution: A Quantitative Assessment of Mixture-Based Combinatorial Libraries Screened Against Two Formylpeptide Receptors
Molecules 2013, 18(6), 6408-6424; doi:10.3390/molecules18066408
Received: 10 April 2013 / Revised: 20 May 2013 / Accepted: 24 May 2013 / Published: 30 May 2013
Cited by 7 | PDF Full-text (1810 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the past 20 years, synthetic combinatorial methods have fundamentally advanced the ability to synthesize and screen large numbers of compounds for drug discovery and basic research. Mixture-based libraries and positional scanning deconvolution combine two approaches for the rapid identification of specific scaffolds
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In the past 20 years, synthetic combinatorial methods have fundamentally advanced the ability to synthesize and screen large numbers of compounds for drug discovery and basic research. Mixture-based libraries and positional scanning deconvolution combine two approaches for the rapid identification of specific scaffolds and active ligands. Here we present a quantitative assessment of the screening of 32 positional scanning libraries in the identification of highly specific and selective ligands for two formylpeptide receptors. We also compare and contrast two mixture-based library approaches using a mathematical model to facilitate the selection of active scaffolds and libraries to be pursued for further evaluation. The flexibility demonstrated in the differently formatted mixture-based libraries allows for their screening in a wide range of assays. Full article
(This article belongs to the Special Issue Computational Chemistry)
Open AccessArticle Design, Synthesis and Evaluation of Dual-Modality Glyco-Nanoparticles for Tumor Imaging
Molecules 2013, 18(6), 6425-6438; doi:10.3390/molecules18066425
Received: 26 March 2013 / Revised: 22 May 2013 / Accepted: 27 May 2013 / Published: 30 May 2013
Cited by 8 | PDF Full-text (960 KB) | HTML Full-text | XML Full-text
Abstract
d-Glucosamine (DG) was conjugated to a core-cross linked polymeric micelle (CCPM) system equipped with both a near-infrared fluorophore (NIRF) and a gamma emitter (111In). The resultant nano-scale tumor-targeting imaging tracer, 111In-DG-NIRF-CCPM, selectively accumulated in a human epithelial carcinoma A-431 xenograft
[...] Read more.
d-Glucosamine (DG) was conjugated to a core-cross linked polymeric micelle (CCPM) system equipped with both a near-infrared fluorophore (NIRF) and a gamma emitter (111In). The resultant nano-scale tumor-targeting imaging tracer, 111In-DG-NIRF-CCPM, selectively accumulated in a human epithelial carcinoma A-431 xenograft model in mice. At 24 hrs post injection, the tumor uptake was 2.62 ± 0.80 % of the injected dose per gram of tissue (%ID/g). Tumors were clearly delineated in both single-photon emission computed tomography (SPECT) and optical imaging. The results suggest that the prepared imaging tracer is a promising agent for tumor diagnosis. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Isoferulic Acid, a New Anti-Glycation Agent, Inhibits Fructose- and Glucose-Mediated Protein Glycation in Vitro
Molecules 2013, 18(6), 6439-6454; doi:10.3390/molecules18066439
Received: 25 February 2013 / Revised: 2 May 2013 / Accepted: 28 May 2013 / Published: 30 May 2013
Cited by 20 | PDF Full-text (809 KB) | HTML Full-text | XML Full-text
Abstract
The inhibitory activity of isoferulic acid (IFA) on fructose- and glucose-mediated protein glycation and oxidation of bovine serum albumin (BSA) was investigated. Our data showed that IFA (1.25–5 mM) inhibited the formation of fluorescent advanced glycation end products (AGEs) and non-fluorescent AGE [N
[...] Read more.
The inhibitory activity of isoferulic acid (IFA) on fructose- and glucose-mediated protein glycation and oxidation of bovine serum albumin (BSA) was investigated. Our data showed that IFA (1.25–5 mM) inhibited the formation of fluorescent advanced glycation end products (AGEs) and non-fluorescent AGE [Nε-(carboxymethyl) lysine: CML], as well as the level of fructosamine. IFA also prevented protein oxidation of BSA indicated by decreasing protein carbonyl formation and protein thiol modification. Furthermore, IFA suppressed the formation of β-cross amyloid structures of BSA. Therefore, IFA might be a new promising anti-glycation agent for the prevention of diabetic complications via inhibition of AGEs formation and oxidation-dependent protein damage. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Bioactive Secondary Metabolites of a Marine Bacillus sp. Inhibit Superoxide Generation and Elastase Release in Human Neutrophils by Blocking Formyl Peptide Receptor 1
Molecules 2013, 18(6), 6455-6468; doi:10.3390/molecules18066455
Received: 25 April 2013 / Revised: 28 May 2013 / Accepted: 30 May 2013 / Published: 3 June 2013
Cited by 5 | PDF Full-text (1551 KB) | HTML Full-text | XML Full-text
Abstract
It is well known that overwhelming neutrophil activation is closely related to acute and chronic inflammatory injuries. Formyl peptide receptor 1 (FPR1) plays an important role in activation of neutrophils and may represent a potent therapeutic target in inflammatory diseases. In the present
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It is well known that overwhelming neutrophil activation is closely related to acute and chronic inflammatory injuries. Formyl peptide receptor 1 (FPR1) plays an important role in activation of neutrophils and may represent a potent therapeutic target in inflammatory diseases. In the present study, we demonstrated that IA-LBI07-1 (IA), an extract of bioactive secondary metabolites from a marine Bacillus sp., has anti-inflammatory effects in human neutrophils. IA significantly inhibited superoxide generation and elastase release in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-activated neutrophils, but failed to suppress the cell responses activated by non-FPR1 agonists. IA did not alter superoxide production and elastase activity in cell-free systems. IA also attenuated the downstream signaling from FPR1, such as the Ca2+, MAP kinases and AKT pathways. In addition, IA inhibited the binding of N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein, a fluorescent analogue of FMLP, to FPR1 in human neutrophils and FPR1-transfected HEK293 cells. Taken together, these results show that the anti-inflammatory effects of IA in human neutrophils are through the inhibition of FPR1. Also, our data suggest that IA may have therapeutic potential to decrease tissue damage induced by human neutrophils. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted Inhibitors
Molecules 2013, 18(6), 6491-6503; doi:10.3390/molecules18066491
Received: 13 May 2013 / Revised: 21 May 2013 / Accepted: 24 May 2013 / Published: 3 June 2013
Cited by 17 | PDF Full-text (258 KB) | HTML Full-text | XML Full-text
Abstract
Over the years, the development of targeted medicines has made significant achievements. As a typical example, receptor tyrosine kinases (RTK) inhibitors have become important chemotherapy drugs for a variety of cancers. However, the effectiveness of these agents is always hindered by poor response
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Over the years, the development of targeted medicines has made significant achievements. As a typical example, receptor tyrosine kinases (RTK) inhibitors have become important chemotherapy drugs for a variety of cancers. However, the effectiveness of these agents is always hindered by poor response rates and acquired drug resistance. In order to overcome these limitations, several dual-targeted inhibitors with quinazoline core were designed and synthesized. Though these compounds can simultaneously inhibit histone deacetylases (HDAC) as well as RTK, the structure-activity relationship (SAR) is still not clear enough. To further explore this type of dual-targeted inhibitors, a new class of quinazoline derivatives were designed and synthesized. Their activity evaluations include in vitro inhibitory activity of HDAC, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). The SAR study indicated that the introduction of polar group such as hydroxamate on the 4-position of the quinazoline core is more likely to provide a potent HDACi/HER2i hybrid rather than HDACi/EGFRi molecule. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle The Development, Physicochemical Characterisation and in Vitro Drug Release Studies of Pectinate Gel Beads Containing Thai Mango Seed Kernel Extract
Molecules 2013, 18(6), 6504-6520; doi:10.3390/molecules18066504
Received: 2 May 2013 / Revised: 27 May 2013 / Accepted: 28 May 2013 / Published: 3 June 2013
Cited by 3 | PDF Full-text (2814 KB) | HTML Full-text | XML Full-text
Abstract
Pectinate gel beads containing Thai mango seed kernel extract (MSKE, cultivar ‘Fahlun’) were developed and characterised for the purpose of colon-targeted delivery. The MSKE-loaded pectinate beads were prepared using ionotropic gelation with varying pectin-to-MSKE ratios, MSKE concentrations, and concentrations of two cross-linkers (calcium
[...] Read more.
Pectinate gel beads containing Thai mango seed kernel extract (MSKE, cultivar ‘Fahlun’) were developed and characterised for the purpose of colon-targeted delivery. The MSKE-loaded pectinate beads were prepared using ionotropic gelation with varying pectin-to-MSKE ratios, MSKE concentrations, and concentrations of two cross-linkers (calcium chloride and zinc acetate). The formulated beads were spherical in shape and ranged in size between 1.13 mm and 1.88 mm. Zinc-pectinate (ZPG) beads containing high amounts of MSKE showed complete entrapment efficiency (EE) of MSKE (100%), while calcium-pectinate (CPG) beads demonstrated 70% EE. The in vitro release tests indicated that MSKE-loaded CPG beads were unstable in both simulated gastric medium (SGM) and simulated intestinal medium (SIM), while MSKE-loaded ZPG beads were stable in SIM but unable to prevent the release of MSKE in SGM. The protection of ZPG beads with gastro-resistant capsules (Eudragit® L 100-55) resulted in stability in both SGM and SIM; they disintegrated immediately in simulated colonic medium containing pectinolytic enzymes. MSKE-loaded ZPG beads were stable at 4, 25 and 45 °C during the study period of four months. The present study revealed that ZPG beads in enteric-coated capsules might be a promising carrier for delivering MSKE to the colon. Full article
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Open AccessArticle A Microfluidic Chip Using Phenol Formaldehyde Resin for Uniform-Sized Polycaprolactone and Chitosan Microparticle Generation
Molecules 2013, 18(6), 6521-6531; doi:10.3390/molecules18066521
Received: 17 April 2013 / Revised: 25 May 2013 / Accepted: 29 May 2013 / Published: 3 June 2013
Cited by 6 | PDF Full-text (1997 KB) | HTML Full-text | XML Full-text
Abstract
This study develops a new solvent-compatible microfluidic chip based on phenol formaldehyde resin (PFR). In addition to its solvent-resistant characteristics, this microfluidic platform also features easy fabrication, organization, decomposition for cleaning, and reusability compared with conventional chips. Both solvent-dependent (e.g., polycaprolactone) and nonsolvent-dependent
[...] Read more.
This study develops a new solvent-compatible microfluidic chip based on phenol formaldehyde resin (PFR). In addition to its solvent-resistant characteristics, this microfluidic platform also features easy fabrication, organization, decomposition for cleaning, and reusability compared with conventional chips. Both solvent-dependent (e.g., polycaprolactone) and nonsolvent-dependent (e.g., chitosan) microparticles were successfully prepared. The size of emulsion droplets could be easily adjusted by tuning the flow rates of the dispersed/continuous phases. After evaporation, polycaprolactone microparticles ranging from 29.3 to 62.7 μm and chitosan microparticles ranging from 215.5 to 566.3 μm were obtained with a 10% relative standard deviation in size. The proposed PFR microfluidic platform has the advantages of active control of the particle size with a narrow size distribution as well as a simple and low cost process with a high throughput. Full article
(This article belongs to the Special Issue Chitins and Chitosans)
Open AccessArticle Isocyanate-Functionalized Chitin and Chitosan as Gelling Agents of Castor Oil
Molecules 2013, 18(6), 6532-6549; doi:10.3390/molecules18066532
Received: 19 March 2013 / Revised: 29 May 2013 / Accepted: 31 May 2013 / Published: 3 June 2013
Cited by 9 | PDF Full-text (440 KB) | HTML Full-text | XML Full-text
Abstract
The main objective of this work was the incorporation of reactive isocyanate groups into chitin and chitosan in order to effectively use the products as reactive thickening agents in castor oil. The resulting gel-like dispersions could be potentially used as biodegradable lubricating greases.
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The main objective of this work was the incorporation of reactive isocyanate groups into chitin and chitosan in order to effectively use the products as reactive thickening agents in castor oil. The resulting gel-like dispersions could be potentially used as biodegradable lubricating greases. Three different NCO–functionalized polymers were obtained: two of them by promoting the reaction of chitosan with 1,6-hexamethylene diisocyanate (HMDI), and the other by using chitin instead of chitosan. These polymers were characterized through 1H-NMR, FTIR and thermogravimetric analysis (TGA). Thermal and rheological behaviours of the oleogels prepared by dispersing these polymers in castor oil were studied by means of TGA and small-amplitude oscillatory shear (SAOS) measurements. The evolution and values of the linear viscoelasticity functions with frequency for –NCO–functionalized chitosan- and chitin-based oleogels are quite similar to those found for standard lubricating greases. In relation to long-term stability of these oleogels, no phase separation was observed and the values of viscoelastic functions increase significantly during the first seven days of ageing, and then remain almost constant. TGA analysis showed that the degradation temperature of the resulting oleogels is higher than that found for traditional lubricating greases. Full article
(This article belongs to the Special Issue Chitins and Chitosans)
Open AccessArticle One-Step Biofunctionalization of Quantum Dots with Chitosan and N-palmitoyl Chitosan for Potential Biomedical Applications
Molecules 2013, 18(6), 6550-6572; doi:10.3390/molecules18066550
Received: 23 April 2013 / Revised: 27 May 2013 / Accepted: 29 May 2013 / Published: 4 June 2013
Cited by 17 | PDF Full-text (1847 KB) | HTML Full-text | XML Full-text
Abstract
Carbohydrates and derivatives (such as glycolipids, glycoproteins) are of critical importance for cell structure, metabolism and functions. The effects of carbohydrate and lipid metabolic imbalances most often cause health disorders and diseases. In this study, new carbohydrate-based nanobioconjugates were designed and synthesized at
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Carbohydrates and derivatives (such as glycolipids, glycoproteins) are of critical importance for cell structure, metabolism and functions. The effects of carbohydrate and lipid metabolic imbalances most often cause health disorders and diseases. In this study, new carbohydrate-based nanobioconjugates were designed and synthesized at room temperature using a single-step aqueous route combining chitosan and acyl-modified chitosan with fluorescent inorganic nanoparticles. N-palmitoyl chitosan (C-Pal) was prepared aiming at altering the lipophilic behavior of chitosan (CHI), but also retaining its reasonable water solubility for potential biomedical applications. CHI and C-Pal were used for producing biofunctionalized CdS quantum dots (QDs) as colloidal water dispersions. Fourier transform infrared spectroscopy (FTIR), thermal analysis (TG/DSC), surface contact angle (SCA), and degree of swelling (DS) in phosphate buffer were used to characterize the carbohydrates. Additionally, UV-Visible spectroscopy (UV-Vis), photoluminescence spectroscopy (PL), dynamic light scattering (DLS), scanning and transmission electron microscopy (SEM/TEM) were used to evaluate the precursors and nanobioconjugates produced. The FTIR spectra associated with the thermal analysis results have undoubtedly indicated the presence of N-palmitoyl groups “grafted” to the chitosan chain (C-Pal) which significantly altered its behavior towards water swelling and surface contact angle as compared to the unmodified chitosan. Furthermore, the results have evidenced that both CHI and C-Pal performed as capping ligands on nucleating and stabilizing colloidal CdS QDs with estimated average size below 3.5 nm and fluorescent activity in the visible range of the spectra. Therefore, an innovative “one-step” process was developed via room temperature aqueous colloidal chemistry for producing biofunctionalized quantum dots using water soluble carbohydrates tailored with amphiphilic behavior offering potential applications as fluorescent biomarkers in the investigation of glycoconjugates for the nutrition, biology, pharmaceutical, and medicine fields. Full article
(This article belongs to the Special Issue Chitins and Chitosans)
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Open AccessArticle New Lignans from the Leaves and Stems of Kadsura philippinensis
Molecules 2013, 18(6), 6573-6583; doi:10.3390/molecules18066573
Received: 13 May 2013 / Revised: 29 May 2013 / Accepted: 30 May 2013 / Published: 4 June 2013
Cited by 4 | PDF Full-text (429 KB) | HTML Full-text | XML Full-text
Abstract
Three novel C19 homolignans, taiwankadsurins D (1), E (2) and F (4), and two new C18 lignans kadsuphilins N (3) and O (5) were isolated from the aerial parts of Taiwanese medicinal plant
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Three novel C19 homolignans, taiwankadsurins D (1), E (2) and F (4), and two new C18 lignans kadsuphilins N (3) and O (5) were isolated from the aerial parts of Taiwanese medicinal plant Kadsura philippinensis. The structures of compounds 15 were determined by spectroscopic analyses, especially 2D NMR techniques. The structure of compound 5 was further confirmed by X-ray crystallographic analysis. Compounds 1 and 2 have a 3,4-{1'-[(Z)-2''-methoxy-2''-oxoethylidene]}-pentano(2,3-dihydrobenzo[b]furano)-3-(2'''-methoxycarbonyl-2'''-hydroxy-2''',3'-epoxide) skeleton. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Indomethacin Inhibits Cancer Cell Migration via Attenuation of Cellular Calcium Mobilization
Molecules 2013, 18(6), 6584-6596; doi:10.3390/molecules18066584
Received: 18 March 2013 / Revised: 27 May 2013 / Accepted: 31 May 2013 / Published: 4 June 2013
Cited by 11 | PDF Full-text (2293 KB) | HTML Full-text | XML Full-text
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) were shown to reduce the risk of colorectal cancer recurrence and are widely used to modulate inflammatory responses. Indomethacin is an NSAID. Herein, we reported that indomethacin can suppress cancer cell migration through its influence on the focal complexes
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Non-steroidal anti-inflammatory drugs (NSAIDs) were shown to reduce the risk of colorectal cancer recurrence and are widely used to modulate inflammatory responses. Indomethacin is an NSAID. Herein, we reported that indomethacin can suppress cancer cell migration through its influence on the focal complexes formation. Furthermore, endothelial growth factor (EGF)-mediated Ca2+ influx was attenuated by indomethacin in a dose dependent manner. Our results identified a new mechanism of action for indomethacin: inhibition of calcium influx that is a key determinant of cancer cell migration. Full article
(This article belongs to the Special Issue Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry)
Open AccessArticle Synthesis and Characterization of Rice Straw/Fe3O4 Nanocomposites by a Quick Precipitation Method
Molecules 2013, 18(6), 6597-6607; doi:10.3390/molecules18066597
Received: 27 April 2013 / Revised: 27 May 2013 / Accepted: 30 May 2013 / Published: 5 June 2013
Cited by 13 | PDF Full-text (1101 KB) | HTML Full-text | XML Full-text
Abstract
Small sized magnetite iron oxide nanoparticles (Fe3O4-NPs) with were successfully synthesized on the surface of rice straw using the quick precipitation method in the absence of any heat treatment. Ferric chloride (FeCl3·6H2O), ferrous chloride (FeCl
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Small sized magnetite iron oxide nanoparticles (Fe3O4-NPs) with were successfully synthesized on the surface of rice straw using the quick precipitation method in the absence of any heat treatment. Ferric chloride (FeCl3·6H2O), ferrous chloride (FeCl2·4H2O), sodium hydroxide (NaOH) and urea (CH4N2O) were used as Fe3O4-NPs precursors, reducing agent and stabilizer, respectively. The rice straw fibers were dispersed in deionized water, and then urea was added to the suspension, after that ferric and ferrous chloride were added to this mixture and stirred. After the absorption of iron ions on the surface layer of the fibers, the ions were reduced with NaOH by a quick precipitation method. The reaction was carried out under N2 gas. The mean diameter and standard deviation of metal oxide NPs synthesized in rice straw/Fe3O4 nanocomposites (NCs) were 9.93 ± 2.42 nm. The prepared rice straw/Fe3O4-NCS were characterized using powder X-ray diffraction (PXRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive X-ray fluorescence (EDXF) and Fourier transforms infrared spectroscopy (FT‒IR). The rice straw/Fe3O4-NCs prepared by this method have magnetic properties. Full article
Open AccessArticle Self-Assembly of a 1D Hydrogen-Bonded Polymer from a Hexamethyltetraaza Macrocyclic Nickel(II) Complex and Isophthalic Acid
Molecules 2013, 18(6), 6608-6619; doi:10.3390/molecules18066608
Received: 3 May 2013 / Revised: 31 May 2013 / Accepted: 3 June 2013 / Published: 6 June 2013
PDF Full-text (346 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The compound [Ni(L)(isoph)2][Ni(L)]·8H2O (1; L = C-meso-5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane; H2-isoph = isophthalic acid) has been synthesized and structurally characterized. Complex 1 exhibits a geometrically symmetric core with a {4/6} coordination number set. The coordination environment
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The compound [Ni(L)(isoph)2][Ni(L)]·8H2O (1; L = C-meso-5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane; H2-isoph = isophthalic acid) has been synthesized and structurally characterized. Complex 1 exhibits a geometrically symmetric core with a {4/6} coordination number set. The coordination environment around the Ni(1) ion is a distorted octahedron, while the geometry around the four-coordinate Ni(2) is depicted as square planar in 1D hydrogen-bonded infinite chain. The compound crystallizes in the triclinic system P-1 with a = 8.602(2), b = 10.684(7), c = 16.550(3) Å, a = 91.04(4), b = 94.09(2), g = 111.09(4)°, V = 1413.9(10) Å3, Z = 1. The cyclic voltammogram of 1 undergoes one-electron wave corresponding to NiII/NiI process. The electronic spectra, electrochemical and TGA behavior of the complex are significantly affected by the nature of the hexamethyltetraaza macrocycle and the axial isoph2− ligand. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Acetylcholinesterase Inhibition and in Vitro and in Vivo Antioxidant Activities of Ganoderma lucidum Grown on Germinated Brown Rice
Molecules 2013, 18(6), 6663-6678; doi:10.3390/molecules18066663
Received: 16 May 2013 / Revised: 31 May 2013 / Accepted: 3 June 2013 / Published: 7 June 2013
Cited by 18 | PDF Full-text (251 KB) | HTML Full-text | XML Full-text
Abstract
In this study, the acetylcholinesterase inhibition and in vitro and in vivo antioxidant activities of Ganoderma lucidum grown on germinated brown rice (GLBR) were evaluated. In antioxidant assays in vitro, GLBR was found to have strong metal chelating activity, DPPH, ABTS, hydroxyl
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In this study, the acetylcholinesterase inhibition and in vitro and in vivo antioxidant activities of Ganoderma lucidum grown on germinated brown rice (GLBR) were evaluated. In antioxidant assays in vitro, GLBR was found to have strong metal chelating activity, DPPH, ABTS, hydroxyl and superoxide radical scavenging activity. Cell-based antioxidant methods were used, including lipid peroxidation on brain homogenate and AAPH-induced erythrocyte haemolysis. In antioxidant assays in vivo, mice were administered with GLBR and this significantly enhanced the activities of antioxidant enzymes in the mice sera, livers and brains. The amount of total phenolic and flavonoid compounds were 43.14 mg GAE/g and 13.36 mg CE/g dry mass, respectively. GLBR also exhibited acetylcholinesterase inhibitory activity. In addition, HPLC analyses of GLBR extract revealed the presence of different phenolic compounds. These findings demonstrate the remarkable potential of GLBR extract as valuable source of antioxidants which exhibit interesting acetylcholinesterase inhibitory activity. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle General Intermediates for the Synthesis of 6-C-Alkylated DMDP-Related Natural Products
Molecules 2013, 18(6), 6723-6733; doi:10.3390/molecules18066723
Received: 8 May 2013 / Revised: 24 May 2013 / Accepted: 27 May 2013 / Published: 7 June 2013
Cited by 1 | PDF Full-text (348 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Protected L-homoDMDP en-8 and its C-6 epimer en-7 were prepared through two different pathways starting from the vinylpyrrolidine en-9. Based on the NMR and X-ray analysis, the stereochemistry of homoDMDP at C-6 was confirmed to be consistent
[...] Read more.
Protected L-homoDMDP en-8 and its C-6 epimer en-7 were prepared through two different pathways starting from the vinylpyrrolidine en-9. Based on the NMR and X-ray analysis, the stereochemistry of homoDMDP at C-6 was confirmed to be consistent with reported data. Compounds en-7 and en-8 are general intermediates for the synthesis of a series of 6-C-alkylated DMDP-related natural products, such as broussonetine G, homoDMDP-7-O-apioside, homoDMDP-7-O-b-D-xyloside and so on. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Eudragit® L100/N-Trimethylchitosan Chloride Microspheres for Oral Insulin Delivery
Molecules 2013, 18(6), 6734-6747; doi:10.3390/molecules18066734
Received: 3 April 2013 / Revised: 29 May 2013 / Accepted: 31 May 2013 / Published: 7 June 2013
Cited by 11 | PDF Full-text (641 KB) | HTML Full-text | XML Full-text
Abstract
Effective oral delivery of protein and peptide drugs remains an active topic in scientific research. In this study, matrix type microspheres were prepared with Eudragit® L100 containing N-trimethylchitosan chloride to improve the permeation of insulin across the intestinal epithelium via the
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Effective oral delivery of protein and peptide drugs remains an active topic in scientific research. In this study, matrix type microspheres were prepared with Eudragit® L100 containing N-trimethylchitosan chloride to improve the permeation of insulin across the intestinal epithelium via the paracellular pathway. Insulin loaded microspheres were initially formulated in accordance with a factorial design (23) and manufactured by means of a single water-in-oil emulsification/evaporation method. Based on external and internal morphology two microsphere formulations were selected from the initial formulations for further investigation in terms of particle size, dissolution behaviour and in vitro insulin transport across excised rat intestinal tissue. The initial eight microsphere formulations exhibited drug loading capacities ranging from 27.9–52.4% with different shapes and internal structures. The two selected microsphere formulations had average particle sizes of 157.3 ± 31.74 µm and 135.7 ± 41.05 µm, respectively, and mean dissolution time values for insulin release of 34.47 and 42.63 min, respectively. In vitro transport of insulin across excised rat intestinal tissue from the two selected microsphere formulations was 10.67–fold and 9.68–fold higher than the control group (insulin alone). The microsphere delivery system prepared from Eudragit® L100 containing N-trimethylchitosan chloride is therefore a promising candidate for effective oral insulin delivery. Full article
(This article belongs to the Special Issue Chitins and Chitosans)
Open AccessArticle Water Complexes of Cytochrome P450: Insights from Energy Decomposition Analysis
Molecules 2013, 18(6), 6782-6791; doi:10.3390/molecules18066782
Received: 28 May 2013 / Revised: 4 June 2013 / Accepted: 5 June 2013 / Published: 10 June 2013
Cited by 10 | PDF Full-text (316 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Water is a small molecule that nevertheless perturbs, sometimes significantly, the electronic properties of an enzyme’s active site. In this study, interactions of a water molecule with the ferric heme and the compound I (Cpd I) intermediate of cytochrome P450 are studied. Energy
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Water is a small molecule that nevertheless perturbs, sometimes significantly, the electronic properties of an enzyme’s active site. In this study, interactions of a water molecule with the ferric heme and the compound I (Cpd I) intermediate of cytochrome P450 are studied. Energy decomposition analysis (EDA) schemes are used to investigate the physical origins of these interactions. Localized molecular orbital EDA (LMOEDA) implemented in the quantum chemistry software GAMESS and the EDA method implemented in the ADF quantum chemistry program are used. EDA reveals that the electrostatic and polarization effects act as the major driving force in both of these interactions. The hydrogen bonding in the Cpd I•••H2O complex is similar to that in the water dimer; however, the relative importance of the electrostatic effect is somewhat larger in the water dimer. Full article
(This article belongs to the Special Issue Computational Chemistry)
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Open AccessArticle Reduction of Saltiness and Acrylamide Levels in Palm Sugar-Like Flavouring through Buffer Modification and the Addition of Calcium Chloride
Molecules 2013, 18(6), 6792-6803; doi:10.3390/molecules18066792
Received: 18 March 2013 / Revised: 9 May 2013 / Accepted: 23 May 2013 / Published: 10 June 2013
Cited by 1 | PDF Full-text (242 KB) | HTML Full-text | XML Full-text
Abstract
Palm sugar-like flavouring (PSLF) is a type of flavour product that is formed by heating amino acids and sugar under specific heating conditions. Unfortunately, PSLF has a salty taste and contains high amounts of acrylamide. Hence, the objective of this research was to
[...] Read more.
Palm sugar-like flavouring (PSLF) is a type of flavour product that is formed by heating amino acids and sugar under specific heating conditions. Unfortunately, PSLF has a salty taste and contains high amounts of acrylamide. Hence, the objective of this research was to reduce saltiness and acrylamide without negatively affecting the aroma properties of PSLF. A decrease in the sodium phosphate (NaHPO4) buffer concentration from 0.20 to 0.02 M was found to reduce sodium to approximately 15% of the level found in original PSLF. A further decrease (~25%) in the sodium content was achieved by removing monobasic sodium phosphate (NaH2PO4) from the buffer system. Meanwhile, the addition of CaCl2 at 20–40 mg/L reduced the acrylamide content in PSLF by as much as 58%. A CaCl2 concentration of 20 mg/mL was most favourable as it most efficiently suppressed acrylamide formation while providing an acceptably high flavour yield in PSLF. In view of the high acrylamide content in PSLF, additional work is necessary to further reduce the amount of acrylamide by controlling the asparagine concentration in the precursor mixture. Full article
Open AccessArticle Exploring the C-X…π Halogen Bonding Motif: An Infrared and Raman Study of the Complexes of CF3X (X = Cl, Br and I) with the Aromatic Model Compounds Benzene and Toluene
Molecules 2013, 18(6), 6829-6851; doi:10.3390/molecules18066829
Received: 23 April 2013 / Revised: 29 May 2013 / Accepted: 31 May 2013 / Published: 10 June 2013
Cited by 25 | PDF Full-text (450 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The formation of halogen bonded complexes formed between the trifluorohalomethanes CF3Cl, CF3Br and CF3I and the Lewis bases benzene and toluene at temperatures below 150K was investigated using FTIR and Raman spectroscopy. Experiments using liquid krypton as
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The formation of halogen bonded complexes formed between the trifluorohalomethanes CF3Cl, CF3Br and CF3I and the Lewis bases benzene and toluene at temperatures below 150K was investigated using FTIR and Raman spectroscopy. Experiments using liquid krypton as solvent show that for both CF3Br and CF3I substantial fractions of the monomers can be involved in 1:1 complexes. In addition, weak absorptions illustrating the formation of 2:1 complexes between CF3I and benzene are observed. Using spectra recorded at temperatures between 120 and 140 K, observed information on the relative stability was obtained for all complexes by determining the complexation enthalpies in solution. The resulting values for CF3Br.benzene, CF3I.benzene and (CF3I)2.benzene are −6.5(3), −7.6(2) and −14.5(9) kJ mol−1. The values for CF3Br.toluene and CF3I.toluene are −6.2(5) and −7.4(5) kJ mol−1. The experimental complexation enthalpies are compared with theoretical data obtained by combining results from MP2/aug-cc-pVDZ(-PP) and MP2/aug-cc-pVTZ(-PP) ab initio calculations, from statistical thermodynamical calculations and from Monte Carlo Free Energy Perturbation simulations. The data are also compared with results derived for other C-X···π halogen bonded complexes involving unsaturated Lewis bases such as ethene and ethyne. Full article
(This article belongs to the Special Issue Halogen Bond: Application and Prospect)
Open AccessArticle Application and Analysis of the Folin Ciocalteu Method for the Determination of the Total Phenolic Content from Limonium Brasiliense L.
Molecules 2013, 18(6), 6852-6865; doi:10.3390/molecules18066852
Received: 1 April 2013 / Revised: 1 June 2013 / Accepted: 6 June 2013 / Published: 10 June 2013
Cited by 64 | PDF Full-text (313 KB) | HTML Full-text | XML Full-text
Abstract
Limonium brasiliense is a common plant on the southern coast of Brazil. The roots are traditionally used for treatment of premenstrual syndrome, menstrual disturbances and genito-urinary infections. Pharmaceutical preparations obtained from its roots and used for these purposes were marketed in Brazil in
[...] Read more.
Limonium brasiliense is a common plant on the southern coast of Brazil. The roots are traditionally used for treatment of premenstrual syndrome, menstrual disturbances and genito-urinary infections. Pharmaceutical preparations obtained from its roots and used for these purposes were marketed in Brazil in the 1980s and 1990s. Currently, the Brazilian Drug Agency (National Health Surveillance Agency, ANVISA) has canceled the registration of these products, and their use was discontinued because of a lack of studies to characterize the plant raw material and ensure the effectiveness and safety of its use. The aim of the present study was to develop and validate an analytical method to determine the content of total polyphenols (TP) in an extract from L. brasiliense roots, by the UV/Vis spectrophotometric method. L. brasiliense roots were extracted in acetone:water (7:3, v/v-10% w/v). The crude extract was used to develop a method for TP assay. The method was validated according to national and international guidelines. The optimum conditions for analysis time, wavelength, and standard substance were 30 min, 760 nm, and pyrogallol, respectively. Under these conditions, validation by UV/Vis spectrophotometry proved the method to be linear, specific, precise, accurate, reproducible, robust, and easy to perform. This methodology complies with the requirements for analytical application and to ensure the reliability of the results. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Design, Synthesis and Evaluation of the Antibacterial Enhancement Activities of Amino Dihydroartemisinin Derivatives
Molecules 2013, 18(6), 6866-6882; doi:10.3390/molecules18066866
Received: 14 May 2013 / Revised: 29 May 2013 / Accepted: 30 May 2013 / Published: 10 June 2013
Cited by 6 | PDF Full-text (736 KB) | XML Full-text
Abstract
Artemisinin (ART) and its derivatives artesunate (AS), dihydroartemisinin (DHA) are a group of drugs containing a sesquiterpene lactone used to treat malaria. Previously, AS was shown to not have antibacterial activity but to significantly increase the antibacterial activities of β-lactam antibiotics against E.
[...] Read more.
Artemisinin (ART) and its derivatives artesunate (AS), dihydroartemisinin (DHA) are a group of drugs containing a sesquiterpene lactone used to treat malaria. Previously, AS was shown to not have antibacterial activity but to significantly increase the antibacterial activities of β-lactam antibiotics against E. coli. Herein, molecular docking experiments showed that ART, AS and DHA could dock into AcrB very well, especially DHA and AS; both DHA and AS had the same docking pose. The affinity between AS and AcrB seemed weaker than that of DHA, while the succinate tail of AS, which was like a “bug”, could extend in the binding pocket very well. Imitating the parent nucleus of DHA and the succinate tail of AS, twenty-one DHA derivatives 4au were designed and synthesized. Among them, seventeen were new compounds. The synergistic effects against E. coli AG100A/pET28a-AcrB showed among the new structures 4k, 4l, 4m, 4n, and 4r exhibited significant synergism with β-lactam antibiotics although they had no direct antibacterial activities themelves. The bacterial growth assay showed that only 4k in combination with ampicillin or cefuroxime could totally inhibit bacterial growth from 0 to 12 h, demonstrating that 4k had the best antibacterial enhancement effect. In conclusion, our results provided a new idea and several candidate compounds for antibacterial activity enhancers against multidrug resistant E. coli. Full article
Open AccessArticle Arylsulfonylamino-Benzanilides as Inhibitors of the Apical Sodium-Dependent Bile Salt Transporter (SLC10A2)
Molecules 2013, 18(6), 6883-6897; doi:10.3390/molecules18066883
Received: 2 May 2013 / Revised: 4 June 2013 / Accepted: 5 June 2013 / Published: 10 June 2013
Cited by 2 | PDF Full-text (300 KB) | HTML Full-text | XML Full-text
Abstract
The apical sodium-dependent bile salt transporter (ASBT) plays a pivotal role in maintaining bile acid homeostasis. Inhibition of ASBT would reduce bile acid pool size and lower cholesterol levels. In this report, a series of novel arylsulfonylaminobenzanilides were designed and synthesized as potential
[...] Read more.
The apical sodium-dependent bile salt transporter (ASBT) plays a pivotal role in maintaining bile acid homeostasis. Inhibition of ASBT would reduce bile acid pool size and lower cholesterol levels. In this report, a series of novel arylsulfonylaminobenzanilides were designed and synthesized as potential inhibitors of ASBT. Most of them demonstrated great potency against ASBT’s bile acid transport activity. In particular, compound 5g2 inhibited ASBT activity with an IC50 value of 0.11 μM. These compounds represent potential cholesterol-lowering drugs. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Dihydrochalcones with Antiinflammatory Activity from Leaves and Twigs of Cyathostemma argenteum
Molecules 2013, 18(6), 6898-6907; doi:10.3390/molecules18066898
Received: 8 May 2013 / Revised: 30 May 2013 / Accepted: 7 June 2013 / Published: 10 June 2013
Cited by 2 | PDF Full-text (412 KB) | HTML Full-text | XML Full-text
Abstract
A new dihydrochalcone derivative, 4',6'-dihydroxy-2',4-dimethoxy-5'-(2''-hydroxybenzyl)dihydrochalcone (1) and one known dihydrochalcone, 4',6'-dihydroxy-2',4- dimethoxydihydrochalcone (2) were isolated from leaves and twigs of Cyathostemma argenteum. Their structures were established by spectral methods, mainly 2D NMR spectroscopic techniques, which involved combined applications
[...] Read more.
A new dihydrochalcone derivative, 4',6'-dihydroxy-2',4-dimethoxy-5'-(2''-hydroxybenzyl)dihydrochalcone (1) and one known dihydrochalcone, 4',6'-dihydroxy-2',4- dimethoxydihydrochalcone (2) were isolated from leaves and twigs of Cyathostemma argenteum. Their structures were established by spectral methods, mainly 2D NMR spectroscopic techniques, which involved combined applications of DEPT, COSY, HMQC and HMBC. The molecular structure of 1 was also confirmed by single crystal X-ray diffraction. The test compounds 1 and 2 displayed significant inhibitory activity at a dose of 1 mg/ear on edema formation at all determination times, with similar intensity as phenylbutazone. Full article
Open AccessArticle Preliminary Biological Evaluation of Novel 99mTc-Cys-Annexin A5 as a Apoptosis Imaging Agent
Molecules 2013, 18(6), 6908-6918; doi:10.3390/molecules18066908
Received: 15 May 2013 / Revised: 24 May 2013 / Accepted: 5 June 2013 / Published: 10 June 2013
Cited by 5 | PDF Full-text (327 KB) | XML Full-text
Abstract
A novel annexin A5 derivative (cys-annexin A5) with a single cysteine residue at its C-terminal has been developed and successfully labeled in high labeling yield with 99mTc by a ligand exchange reaction. Like the 1st generation 99mTc-HYNIC-annexin A5, the novel 99m
[...] Read more.
A novel annexin A5 derivative (cys-annexin A5) with a single cysteine residue at its C-terminal has been developed and successfully labeled in high labeling yield with 99mTc by a ligand exchange reaction. Like the 1st generation 99mTc-HYNIC-annexin A5, the novel 99mTc-cys-annexin A5 derivative shows in normal mice mainly renal and, to a lesser extent, hepatobiliary excretion. In rat models of hepatic apoptosis there was 283% increase in hepatic uptake of 99mTc-cys-annexin A5 as compared to normal mice. The results indicate that the novel 99mTc-cys-annexin A5 is a potential apoptosis imaging agent. Full article
Open AccessArticle Application of a Rapid and Efficient Quantitative Analysis Method for Traditional Chinese Medicines: The Case Study of Quality Assessment of Salvia miltiorrhiza Bunge
Molecules 2013, 18(6), 6919-6935; doi:10.3390/molecules18066919
Received: 2 May 2013 / Revised: 30 May 2013 / Accepted: 7 June 2013 / Published: 13 June 2013
Cited by 3 | PDF Full-text (396 KB) | HTML Full-text | XML Full-text
Abstract
A reference extractive, containing multiple active known compounds, has been considered to be an alternative to individual reference standards. However, in the Chinese Pharmacopoeia (ChP) the great majority of reference extractives have been primarily used for qualitative identification by thin-layer chromatography (TLC) and
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A reference extractive, containing multiple active known compounds, has been considered to be an alternative to individual reference standards. However, in the Chinese Pharmacopoeia (ChP) the great majority of reference extractives have been primarily used for qualitative identification by thin-layer chromatography (TLC) and few studies on the applicability of reference extractives for quantitative analysis have been presented. Using Salvia miltiorrhiza Bunge as an example in this paper, we first present a preliminary discussion on the feasibility and applicability of reference extractives for the quantitative analysis of TCMs. The reference extractive of S. miltiorrhiza Bunge, comprised of three pharmacological marker compounds, namely cryptotanshinone, tanshinone I and tanshinone IIA, was prepared from purchased Salvia miltiorrhiza Bunge by extraction with acetone under reflux, followed by silica gel column chromatography with stepwise elution with petroleum ether-ethyl acetate (25:1, v/v, 4.5 BV) to remove the non-target components and chloroform-methanol (10:1, v/v; 3 BV) to yield a crude reference extractive solution. After concentration, the solution was further purified by preparative reversed-phase HPLC on a C18 column with isocratic elution with 77% methanol aqueous solution to yield the total reference extractive of S. miltiorrhiza Bunge. Thereafter, the reference extractive was applied to the quality assessment of S. miltiorrhiza Bunge using high-performance liquid chromatography (HPLC) coupled with diode array detection (DAD). The validation of the method, including linearity, sensitivity, repeatability, stability and recovery testing, indicated that this method was valid, reliable and sensitive, with good reproducibility. The developed method was successfully applied to quantify seven batches of samples collected from different regions in China and the results were also similar to those obtained using reference standards, with relative standard deviation (RSD) <3%. Preparation of a reference extractive of S. miltiorrhiza Bunge was significantly less expensive and time consuming than preparation of a corresponding reference standard. Quantitative analysis using a reference extractive was shown to be simple, low-cost, time-saving and practical, with high sensitivity and good stability; and is, therefore, a strong alternative to the use of reference standards. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle N6-Benzyladenosine Derivatives as Novel N-Donor Ligands of Platinum(II) Dichlorido Complexes
Molecules 2013, 18(6), 6990-7003; doi:10.3390/molecules18066990
Received: 3 May 2013 / Revised: 7 June 2013 / Accepted: 8 June 2013 / Published: 14 June 2013
Cited by 6 | PDF Full-text (946 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The platinum(II) complexes trans-[PtCl2(Ln)2]∙xSolv 113 (Solv = H2O or CH3OH), involving N6-benzyladenosine-based N-donor ligands, were synthesized; Ln stands for N6-(2-methoxybenzyl)adenosine (L1, involved in complex
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The platinum(II) complexes trans-[PtCl2(Ln)2]∙xSolv 113 (Solv = H2O or CH3OH), involving N6-benzyladenosine-based N-donor ligands, were synthesized; Ln stands for N6-(2-methoxybenzyl)adenosine (L1, involved in complex 1), N6-(4-methoxy-benzyl)adenosine (L2, 2), N6-(2-chlorobenzyl)adenosine (L3, 3), N6-(4-chlorobenzyl)-adenosine (L4, 4), N6-(2-hydroxybenzyl)adenosine (L5, 5), N6-(3-hydroxybenzyl)-adenosine (L6, 6), N6-(2-hydroxy-3-methoxybenzyl)adenosine (L7, 7), N6-(4-fluoro-benzyl)adenosine (L8, 8), N6-(4-methylbenzyl)adenosine (L9, 9), 2-chloro-N6-(3-hydroxy-benzyl)adenosine (L10, 10), 2-chloro-N6-(4-hydroxybenzyl)adenosine (L11, 11), 2-chloro-N6-(2-hydroxy-3-methoxybenzyl)adenosine (L12, 12) and 2-chloro-N6-(2-hydroxy-5-methylbenzyl)adenosine (L13, 13). The compounds were characterized by elemental analysis, mass spectrometry, IR and multinuclear (1H-, 13C-, 195Pt- and 15N-) and two-dimensional NMR spectroscopy, which proved the N7-coordination mode of the appropriate N6-benzyladenosine derivative and trans-geometry of the title complexes. The complexes 113 were found to be non-toxic in vitro against two selected human cancer cell lines (HOS and MCF7; with IC50 > 50.0 µM). However, they were found (by ESI-MS study) to be able to interact with the physiological levels of the sulfur-containing biogenic biomolecule L-methionine by a relatively simple 1:1 exchange mechanism (one Ln molecule was replaced by one L-methionine molecule), thus forming a mixed-nitrogen/sulfur-ligand dichlorido-platinum(II) coordination species. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Optimal Binary Solvent Extraction System for Phenolic Antioxidants from Mengkudu (Morinda citrifolia) Fruit
Molecules 2013, 18(6), 7004-7022; doi:10.3390/molecules18067004
Received: 24 April 2013 / Revised: 26 May 2013 / Accepted: 9 June 2013 / Published: 14 June 2013
Cited by 4 | PDF Full-text (334 KB) | HTML Full-text | XML Full-text
Abstract
Antioxidants have been widely used in the food industry to enhance product quality by preventing oxidation of susceptible substances. This work was carried out to maximise the recovery of total phenolic content (TPC), total flavonoid content (TFC), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical-scavenging capacity and
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Antioxidants have been widely used in the food industry to enhance product quality by preventing oxidation of susceptible substances. This work was carried out to maximise the recovery of total phenolic content (TPC), total flavonoid content (TFC), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical-scavenging capacity and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging capacity from Morinda citrifolia fruit via modification of the ethanol concentration, extraction time and extraction temperature at minimal processing cost. The optimised conditions yielded values of 881.57 ± 17.74 mg GAE/100 g DW for TPC, 552.53 ± 34.16 mg CE/100 g DW for TFC, 799.20 ± 2.97 µmol TEAC/100 g DW for ABTS and 2,317.01 ± 18.13 µmol TEAC/100 g DW for DPPH were 75% ethanol, 40 min of time and 57 °C. The four responses did not differ significantly (p > 0.05) from predicted values, indicating that models obtained are suitable to the optimisation of extraction conditions for phenolics from M. citrifolia. The relative amounts of flavonoids were 0.784 ± 0.01 mg quercetin/g of extract and 1.021 ± 0.04 mg rutin/g of extract. On the basis of the results obtained, M. citrifolia extract can be used as a valuable bioactive source of natural antioxidants. Full article
Open AccessArticle A Soft Coral Natural Product, 11-Episinulariolide Acetate, Inhibits Gene Expression of Cyclooxygenase-2 and Interleukin-8 through Attenuation of Calcium Signaling
Molecules 2013, 18(6), 7023-7034; doi:10.3390/molecules18067023
Received: 22 April 2013 / Revised: 30 May 2013 / Accepted: 13 June 2013 / Published: 17 June 2013
Cited by 4 | PDF Full-text (765 KB) | HTML Full-text | XML Full-text
Abstract
Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancer cells. EGFR-mediated signaling involves inflammatory gene expression including cyclooxygenase (COX)-2 and interleukin (IL)-8, and is associated with cancer pathogenesis. In a search of phytochemicals with anti-inflammatory activity, the COX-2 and IL-8
[...] Read more.
Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancer cells. EGFR-mediated signaling involves inflammatory gene expression including cyclooxygenase (COX)-2 and interleukin (IL)-8, and is associated with cancer pathogenesis. In a search of phytochemicals with anti-inflammatory activity, the COX-2 and IL-8 inhibitory activities of some marine compounds were examined. After screening these compounds 11-episinulariolide acetate (1) from soft coral exhibited the most potent activity. Reverse-transcription PCR; western blotting; ELISA and luciferase assays were used to test the effect of compound 1 on EGF-stimulated expressions of COX-2 and IL-8 in A431 human epidermoid carcinoma cells. After exposure to 10 μM of compound 1, expression levels of COX-2 and IL-8 were reduced. In addition; intracellular Ca2+ increase and Ca2+-dependent transcription factor activation were blocked by compound 1. Thus, compound 1 can potentially serve as a lead compound for targeting Ca2+ signaling-dependent inflammatory diseases. Full article
(This article belongs to the Special Issue Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry)
Open AccessArticle Mirror-Symmetry-Breaking in Poly[(9,9-di-n-octylfluorenyl-2,7-diyl)-alt-biphenyl] (PF8P2) is Susceptible to Terpene Chirality, Achiral Solvents, and Mechanical Stirring
Molecules 2013, 18(6), 7035-7057; doi:10.3390/molecules18067035
Received: 13 May 2013 / Revised: 3 June 2013 / Accepted: 3 June 2013 / Published: 17 June 2013
Cited by 8 | PDF Full-text (2464 KB) | HTML Full-text | XML Full-text
Abstract
Solvent chirality transfer of (S)-/(R)-limonenes allows the instant generation of optically active PF8P2 aggregates with distinct circular dichroism (CD)/circularly polarized luminescence (CPL) amplitudes with a high quantum yield of 16–20%. The present paper also reports subtle mirror-symmetry-breaking effects in
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Solvent chirality transfer of (S)-/(R)-limonenes allows the instant generation of optically active PF8P2 aggregates with distinct circular dichroism (CD)/circularly polarized luminescence (CPL) amplitudes with a high quantum yield of 16–20%. The present paper also reports subtle mirror-symmetry-breaking effects in CD-/CPL-amplitude and sign, CD/UV-vis spectral wavelengths, and photodynamics of the aggregates, though the reasons for the anomaly are unsolved. However, these photophysical properties depend on (i) the chemical natures of chiral and achiral molecules when used in solvent quantity, (ii) clockwise and counterclockwise stirring operations, and (iii) the order of addition of limonene and methanol to the chloroform solution. Full article
(This article belongs to the Special Issue Asymmetric Catalysis)
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Open AccessArticle The Skin Secretion of the Amphibian Phyllomedusa nordestina: A Source of Antimicrobial and Antiprotozoal Peptides
Molecules 2013, 18(6), 7058-7070; doi:10.3390/molecules18067058
Received: 6 May 2013 / Revised: 6 June 2013 / Accepted: 7 June 2013 / Published: 17 June 2013
Cited by 5 | PDF Full-text (694 KB) | HTML Full-text | XML Full-text
Abstract
Antimicrobial peptides (AMPs) from the dermaseptin and phylloseptin families were isolated from the skin secretion of Phyllomedusa nordestina, a recently described amphibian species from Northeastern Brazil. One dermaseptin and three phylloseptins were chosen for solid phase peptide synthesis. The antiprotozoal and antimicrobial
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Antimicrobial peptides (AMPs) from the dermaseptin and phylloseptin families were isolated from the skin secretion of Phyllomedusa nordestina, a recently described amphibian species from Northeastern Brazil. One dermaseptin and three phylloseptins were chosen for solid phase peptide synthesis. The antiprotozoal and antimicrobial activities of the synthetic peptides were determined, as well as their cytotoxicity in mouse peritoneal cells. AMPs are being considered as frameworks for the development of novel drugs inspired by their mechanism of action. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Vortex-Induced Alignment of a Water Soluble Supramolecular Nanofiber Composed of an Amphiphilic Dendrimer
Molecules 2013, 18(6), 7071-7080; doi:10.3390/molecules18067071
Received: 14 May 2013 / Revised: 7 June 2013 / Accepted: 8 June 2013 / Published: 17 June 2013
Cited by 3 | PDF Full-text (511 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We have synthesized a novel amphiphilic naphthalene imide bearing a cationic dendrimer wedge (NID). NID molecules in water self-assemble to form a two-dimensional ribbon, which further coils to give a linear supramolecular nanofiber. The sample solution showed linear dichroism (LD) upon stirring of
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We have synthesized a novel amphiphilic naphthalene imide bearing a cationic dendrimer wedge (NID). NID molecules in water self-assemble to form a two-dimensional ribbon, which further coils to give a linear supramolecular nanofiber. The sample solution showed linear dichroism (LD) upon stirring of the solution, where NID nanofibers dominantly align at the center of vortex by hydrodynamic interaction with the downward torsional flows. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
Open AccessArticle Disperse Dyes Based on Aminothiophenes: Their Dyeing Applications on Polyester Fabrics and Their Antimicrobial Activity
Molecules 2013, 18(6), 7081-7092; doi:10.3390/molecules18067081
Received: 31 May 2013 / Revised: 13 June 2013 / Accepted: 14 June 2013 / Published: 18 June 2013
Cited by 5 | PDF Full-text (1115 KB) | HTML Full-text | XML Full-text
Abstract
A series of monoazo disperse dyes derived from arylazothienopyridazines were synthesized. Fastness properties of dyed polyester samples were measured. Most of the dyed fabrics tested displayed excellent washing and perspiration fastness and moderate light fastness. Finally, the biological activity of the synthesized dyes
[...] Read more.
A series of monoazo disperse dyes derived from arylazothienopyridazines were synthesized. Fastness properties of dyed polyester samples were measured. Most of the dyed fabrics tested displayed excellent washing and perspiration fastness and moderate light fastness. Finally, the biological activity of the synthesized dyes against Gram positive bacteria, Gram negative bacteria and yeast were evaluated. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle New Resveratrol Oligomer Derivatives from the Roots of Rheum lhasaense
Molecules 2013, 18(6), 7093-7102; doi:10.3390/molecules18067093
Received: 27 May 2013 / Revised: 10 June 2013 / Accepted: 13 June 2013 / Published: 18 June 2013
Cited by 6 | PDF Full-text (270 KB) | HTML Full-text | XML Full-text
Abstract
Two new resveratrol trimer derivatives, named rheumlhasol A (1) and rheumlhasol B (2) were isolated from the methanolic extract of roots of Rheum lhasaense A. J. Li et P. K. Hsiao together with four known resveratrol dimer derivatives, including
[...] Read more.
Two new resveratrol trimer derivatives, named rheumlhasol A (1) and rheumlhasol B (2) were isolated from the methanolic extract of roots of Rheum lhasaense A. J. Li et P. K. Hsiao together with four known resveratrol dimer derivatives, including maximol A (3), gnetin C (4), e-viniferin (5), and pallidol (6). The structures were determined by combined spectroscopic methods and by comparison of their spectral data with those reported in the literature. All the compounds isolated from R. lhasaense were tested for their ability to scavenge1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. Full article
Open AccessArticle Application of Reductive 13C-Methylation of Lysines to Enhance the Sensitivity of Conventional NMR Methods
Molecules 2013, 18(6), 7103-7119; doi:10.3390/molecules18067103
Received: 20 May 2013 / Revised: 13 June 2013 / Accepted: 14 June 2013 / Published: 18 June 2013
Cited by 8 | PDF Full-text (1489 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
NMR is commonly used to investigate macromolecular interactions. However, sensitivity problems hamper its use for studying such interactions at low physiologically relevant concentrations. At high concentrations, proteins or peptides tend to aggregate. In order to overcome this problem, we make use of reductive
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NMR is commonly used to investigate macromolecular interactions. However, sensitivity problems hamper its use for studying such interactions at low physiologically relevant concentrations. At high concentrations, proteins or peptides tend to aggregate. In order to overcome this problem, we make use of reductive 13C-methylation to study protein interactions at low micromolar concentrations. Methyl groups in dimethyl lysines are degenerate with one 13CH3 signal arising from two carbons and six protons, as compared to one carbon and three protons in aliphatic amino acids. The improved sensitivity allows us to study protein-protein or protein-peptide interactions at very low micromolar concentrations. We demonstrate the utility of this method by studying the interaction between the post-translationally lipidated hypervariable region of a human proto-oncogenic GTPase K-Ras and a calcium sensor protein calmodulin. Calmodulin specifically binds K-Ras and modulates its downstream signaling. This binding specificity is attributed to the unique lipidated hypervariable region of K-Ras. At low micromolar concentrations, the post-translationally modified hypervariable region of K-Ras aggregates and binds calmodulin in a non-specific manner, hence conventional NMR techniques cannot be used for studying this interaction, however, upon reductively methylating the lysines of calmodulin, we detected signals of the lipidated hypervariable region of K-Ras at physiologically relevant nanomolar concentrations. Thus, we utilize 13C-reductive methylation of lysines to enhance the sensitivity of conventional NMR methods for studying protein interactions at low concentrations. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
Open AccessArticle Novel Antimicrobial Peptide Dendrimers with Amphiphilic Surface and Their Interactions with Phospholipids — Insights from Mass Spectrometry
Molecules 2013, 18(6), 7120-7144; doi:10.3390/molecules18067120
Received: 9 April 2013 / Revised: 4 June 2013 / Accepted: 6 June 2013 / Published: 18 June 2013
Cited by 8 | PDF Full-text (977 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of new peptide dendrimers with amphiphilic surface, designed around a dendronized ornithine (Orn) core were synthesized and characterized by ESI-MS, 1H-, 13C- NMR, and CD spectrometry. An improved antimicrobial potency against S. aureus and E. coli was detected as
[...] Read more.
A series of new peptide dendrimers with amphiphilic surface, designed around a dendronized ornithine (Orn) core were synthesized and characterized by ESI-MS, 1H-, 13C- NMR, and CD spectrometry. An improved antimicrobial potency against S. aureus and E. coli was detected as a result of an increased charge, higher branching and variable lipophilicity of the residues located at the C-terminus. Minimal inhibitory concentration (MIC) values indicated that the selected dendrimers were not sensitive to the physiological concentration of Na+ and K+ ions (100 mM), but expressed reduced potency at 10 mM concentration of Mg2+ and Ca2+ ions. Circular dichroism (CD) curves measured under various conditions revealed structure and solvent-dependent curve evolution. ESI-MS studies of gas-phase interactions between selected dendrimers and both anionic (DMPG) and neutral (DMPC) phospholipids revealed the presence of variously charged dendrimer/phospholipid aggregates with 1:1 to 1:5 stoichiometry. The collision-induced fragmentation (CID) of the most abundant [dendrimer/phospholipid]2+ ions of the 1:1 stoichiometry demonstrated that the studied dendrimers formed stronger complexes with anionic DMPG. Both phospholipids have higher affinity towards dendrimers with a more compact structure. Higher differences in CID energy necessary for dissociation of 50% of the complex formed by dendrimers with DMPG vs. DMPC (DCID50) correlate with a lower hemotoxicity. Mass spectrometry results suggest that for a particular group of compounds the DCID50 might be one of the important factors explaining selectivity of antimicrobial peptides and their branched analogs targeting the bacterial membrane. Both circular dichroism and mass spectrometry studies demonstrated that dendrimers of Nα- and Nε-series possess a different conformation in solution and different affinity to model phospholipids, what might influence their specific microbicidal mechanism. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
Open AccessArticle Synthesis and Radiolabelling of DOTA-Linked Glutamine Analogues with 67,68Ga as Markers for Increased Glutamine Metabolism in Tumour Cells
Molecules 2013, 18(6), 7160-7178; doi:10.3390/molecules18067160
Received: 1 April 2013 / Revised: 10 May 2013 / Accepted: 8 June 2013 / Published: 19 June 2013
Cited by 5 | PDF Full-text (511 KB) | HTML Full-text | XML Full-text
Abstract
DOTA-linked glutamine analogues with a C6- alkyl and polyethyleneglycol (PEG) chain between the chelating group and the L-glutamine moiety were synthesised and labelled with 67,68Ga using established methods. High yields were achieved for the radiolabelling of the molecules with both
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DOTA-linked glutamine analogues with a C6- alkyl and polyethyleneglycol (PEG) chain between the chelating group and the L-glutamine moiety were synthesised and labelled with 67,68Ga using established methods. High yields were achieved for the radiolabelling of the molecules with both radionuclides (>90%), although conversion of the commercially available 67Ga-citrate to the chloride species was a requirement for consistent high radiochemical yields. The generator produced 68Ga was in the [68Ga(OH)4] form. The 67Ga complexes and the 67Ga complexes were demonstrated to be stable in PBS buffer for a week. Uptake studies were performed with longer lived 67Ga analogues against four tumour cell lines, as well as uptake inhibition studies against L-glutamine, and two known amino acid transporter inhibitors. Marginal uptake was exhibited in the PEG variant radio-complex, and inhibition studies indicate this uptake is via a non-targeted amino acid pathway. Full article
(This article belongs to the Special Issue PET Chemistry in Molecular Imaging)
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Open AccessArticle Immunomodulatory Effect of Stichopus japonicus Acid Mucopolysaccharide on Experimental Hepatocellular Carcinoma in Rats
Molecules 2013, 18(6), 7179-7193; doi:10.3390/molecules18067179
Received: 3 May 2013 / Revised: 17 May 2013 / Accepted: 9 June 2013 / Published: 19 June 2013
Cited by 13 | PDF Full-text (4360 KB) | HTML Full-text | XML Full-text
Abstract
Stichopus japonicus acid mucopolysaccharide (SJAMP) is an important biologically active compound that can be extracted from the body wall of the sea cucumber. The present study investigated the anti-tumor and immunomodulatory effects of SJAMP in an experimental hepatocellular carcinoma (HCC) model in rats.
[...] Read more.
Stichopus japonicus acid mucopolysaccharide (SJAMP) is an important biologically active compound that can be extracted from the body wall of the sea cucumber. The present study investigated the anti-tumor and immunomodulatory effects of SJAMP in an experimental hepatocellular carcinoma (HCC) model in rats. Three doses of SJAMP (17.5 mg/kg, 35 mg/kg, and 70 mg/kg administered 5 days/week via oral gavage) were given to rats with diethylnitrosamine (DEN)-induced HCC. SJAMP treatment significantly inhibited DEN-induced HCC by reducing both the number and mean volume of nodules, decreasing serum a-fetoprotein (AFP) levels and proliferating cell nuclear antigen (PCNA) expression in liver, and increasing p21 expression. Furthermore, SJAMP decreased the serum levels of ALT, AST, GGT and TNF-α and increased serum IL-2. SJAMP administration also improved indices of spleen and thymus function and improved both macrophage phagocytosis and NK cell-mediated tumoricidal activity. Moreover, CD3+ and CD4+ T lymphocyte levels recovered significantly and the CD4+/CD8+ T cell ratio normalized in a dose-dependent manner. In conclusion, SJAMP effectively inhibited the growth of HCC through the stimulation of immune organs and tissue proliferation, leading to the enhancement of cellular immunity pathways in rats. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Enhancement of the Controlled-Release Properties of Chitosan Membranes by Crosslinking with Suberoyl Chloride
Molecules 2013, 18(6), 7239-7252; doi:10.3390/molecules18067239
Received: 6 May 2013 / Revised: 7 June 2013 / Accepted: 17 June 2013 / Published: 19 June 2013
Cited by 10 | PDF Full-text (1125 KB) | HTML Full-text | XML Full-text
Abstract
A novel crosslinking agent, suberoyl chloride, was used to crosslink N-phthaloyl acylated chitosan and improves the properties of chitosan membranes. Membranes with different crosslinking degrees were synthesized. The derivatives were characterized by Fourier transform infrared spectroscopy and 13C solid state nuclear
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A novel crosslinking agent, suberoyl chloride, was used to crosslink N-phthaloyl acylated chitosan and improves the properties of chitosan membranes. Membranes with different crosslinking degrees were synthesized. The derivatives were characterized by Fourier transform infrared spectroscopy and 13C solid state nuclear magnetic resonance spectroscopy, which indicated that the crosslinking degrees ranged from 0 to 7.4%. The permeabilities of various plant nutrients, including macroelements (N, P, K), microelements (Zn2+ and Cu2+), and a plant growth regulator (naphthylacetic acid), were varied by moderate changes in crosslinking degree, indicating that the controlled-release properties can be regulated in this way. The film-forming ability of native chitosan was maintained, whilst mechanical properties, hydrophobicity and controlled permeability were improved. These dramatic improvements occurred with a small amount of added suberoyl chloride; excessive crosslinking led to membranes with unwanted poor permeability. Thus, both the mechanical properties and permeability of the crosslinked membrane can be optimized. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle A Fully Automated Radiosynthesis of [18F]Fluoroethyl-Diprenorphine on a Single Module by Use of SPE Cartridges for Preparation of High Quality 2-[18F]Fluoroethyl Tosylate
Molecules 2013, 18(6), 7271-7278; doi:10.3390/molecules18067271
Received: 1 May 2013 / Revised: 16 May 2013 / Accepted: 4 June 2013 / Published: 20 June 2013
Cited by 4 | PDF Full-text (300 KB) | HTML Full-text | XML Full-text
Abstract
We have developed a new method for automated production of 2-[18F]fluoroethyl tosylate ([18F]FETos) that enables 18F-alkylation to provide PET tracers with high chemical purity. The method is based on the removal of excess ethylene glycol bistosylate precursor by
[...] Read more.
We have developed a new method for automated production of 2-[18F]fluoroethyl tosylate ([18F]FETos) that enables 18F-alkylation to provide PET tracers with high chemical purity. The method is based on the removal of excess ethylene glycol bistosylate precursor by precipitation and subsequent filtration and purification of the filtrate by means of solid phase extraction cartridges (SPE). The method is integrated to a single synthesis module and thereby provides the advantage over previous methods of not requiring HPLC purification, as demonstrated by the full radiosynthesis of the potent opioid receptor PET tracer [18F]fluoroethyldiprenorphine. Full article
(This article belongs to the Special Issue PET Chemistry in Molecular Imaging)
Open AccessArticle Monoterpenoid Indole Alkaloids from Alstonia rupestris with Cytotoxic, Anti-Inflammatory and Antifungal Activities
Molecules 2013, 18(6), 7309-7322; doi:10.3390/molecules18067309
Received: 22 April 2013 / Revised: 3 June 2013 / Accepted: 9 June 2013 / Published: 21 June 2013
Cited by 6 | PDF Full-text (371 KB) | HTML Full-text | XML Full-text
Abstract
Phytochemical investigation of the 70% EtOH extract of the leaves of Alstonia scholaris afforded seven new monoterpenoid indole alkaloids: scholarisins I-VII (1-7), and three known compounds: (3R,5S,7R,15R,16R,19E)-scholarisine F (
[...] Read more.
Phytochemical investigation of the 70% EtOH extract of the leaves of Alstonia scholaris afforded seven new monoterpenoid indole alkaloids: scholarisins I-VII (1-7), and three known compounds: (3R,5S,7R,15R,16R,19E)-scholarisine F (8), 3-epi-dihydro- corymine (9), and (E)-16-formyl-5α-methoxystrictamine (10). Structural elucidation of all the compounds was accomplished by spectral methods such as 1D- and 2D-NMR, IR, UV, and HRESIMS. The isolated compounds were tested in vitro for cytotoxicity against seven tumor cell lines, anti-inflammatory activities against Cox-1 and Cox-2, and antifungal potential against five species of fungi. Compounds 1, 6, and 10 exhibited significant cytotoxicities against all the tested tumor cell lines with IC50 values of less than 30 μM and selective inhibition of Cox-2 comparable with the standard drug NS-398 (>90%). Additionally, 1, 2, 3 and 8 showed antifungal activity against two fungal strains (G. pulicaris and C. nicotianae). Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Herb-Drug Interaction of Epimedium sagittatum (Sieb. et Zucc.) Maxim Extract on the Pharmacokinetics of Sildenafil in Rats
Molecules 2013, 18(6), 7323-7335; doi:10.3390/molecules18067323
Received: 9 April 2013 / Revised: 16 May 2013 / Accepted: 19 June 2013 / Published: 21 June 2013
Cited by 8 | PDF Full-text (323 KB) | HTML Full-text | XML Full-text
Abstract
Epimedium sagittatum (Sieb. et Zucc.) Maxim is one of the herbs used to treat erectile dysfunction in Traditional Chinese Medicine. Sildenafil is a phosphodiesterase 5 inhibitor used to treat erectile dysfunction in Western Medicine. This study evaluates the herbal-drug interaction of Epimedium sagittatum
[...] Read more.
Epimedium sagittatum (Sieb. et Zucc.) Maxim is one of the herbs used to treat erectile dysfunction in Traditional Chinese Medicine. Sildenafil is a phosphodiesterase 5 inhibitor used to treat erectile dysfunction in Western Medicine. This study evaluates the herbal-drug interaction of Epimedium sagittatum extract on the pharmacokinetics of sildenafil in rats by ultra-performance liquid chromatography. The rat plasma was sampled from each anesthetized rat after pretreatment with 3-days Epimedium sagittatum extract (1/2 g/kg/day) and intravenous injection with sildenafil (10/30 mg/kg). The pharmacokinetic data demonstrate that the area under the concentration-time curve (AUC) of sildenafil (10 mg/kg) was significantly decreased in groups that received a high dose of Epimedium sagittatum extract. In conclusion, the study demonstrates that there was significant herb-drug interaction of Epimedium sagittatum extract on the pharmacokinetics of sildenafil at low and high daily doses, suggesting co-administration use of Epimedium sagittatum extract and sildenafil in clinical practice should be prevented due to possible herb-drug interactions. Full article
(This article belongs to the Section Natural Products)
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Open AccessReview Asymmetric Palladium-Catalysed Intramolecular Wacker-Type Cyclisations of Unsaturated Alcohols and Amino Alcohols
Molecules 2013, 18(6), 6173-6192; doi:10.3390/molecules18066173
Received: 28 April 2013 / Revised: 20 May 2013 / Accepted: 20 May 2013 / Published: 24 May 2013
Cited by 10 | PDF Full-text (320 KB) | HTML Full-text | XML Full-text
Abstract
The palladium (II)-catalysed reactions of alkenols and aminoalkenols such as oxycarbonylations or bicyclisations are powerful methods for the construction of oxygen and nitrogen-containing heterocyclic compounds. This review highlights recent progress in the development of the asymmetric palladium(II)-catalysed Wacker-type cyclisations of unsaturated polyols and
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The palladium (II)-catalysed reactions of alkenols and aminoalkenols such as oxycarbonylations or bicyclisations are powerful methods for the construction of oxygen and nitrogen-containing heterocyclic compounds. This review highlights recent progress in the development of the asymmetric palladium(II)-catalysed Wacker-type cyclisations of unsaturated polyols and aminoalcohols. The scope, limitations, and applications of these reactions are presented. Full article
(This article belongs to the Special Issue Asymmetric Catalysis)
Open AccessReview Macrocyclic Drugs and Synthetic Methodologies toward Macrocycles
Molecules 2013, 18(6), 6230-6268; doi:10.3390/molecules18066230
Received: 3 April 2013 / Revised: 15 May 2013 / Accepted: 20 May 2013 / Published: 24 May 2013
Cited by 44 | PDF Full-text (1200 KB) | HTML Full-text | XML Full-text
Abstract
Macrocyclic scaffolds are commonly found in bioactive natural products and pharmaceutical molecules. So far, a large number of macrocyclic natural products have been isolated and synthesized. The construction of macrocycles is generally considered as a crucial and challenging step in the synthesis of
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Macrocyclic scaffolds are commonly found in bioactive natural products and pharmaceutical molecules. So far, a large number of macrocyclic natural products have been isolated and synthesized. The construction of macrocycles is generally considered as a crucial and challenging step in the synthesis of macrocyclic natural products. Over the last several decades, numerous efforts have been undertaken toward the synthesis of complex naturally occurring macrocycles and great progresses have been made to advance the field of total synthesis. The commonly used synthetic methodologies toward macrocyclization include macrolactonization, macrolactamization, transition metal-catalyzed cross coupling, ring-closing metathesis, and click reaction, among others. Selected recent examples of macrocyclic synthesis of natural products and druglike macrocycles with significant biological relevance are highlighted in each class. The primary goal of this review is to summarize currently used macrocyclic drugs, highlight the therapeutic potential of this underexplored drug class and outline the general synthetic methodologies for the synthesis of macrocycles. Full article
(This article belongs to the Special Issue Macrocyclic Chemistry)
Open AccessReview Radiolabeled COX-2 Inhibitors for Non-Invasive Visualization of COX-2 Expression and Activity — A Critical Update
Molecules 2013, 18(6), 6311-6355; doi:10.3390/molecules18066311
Received: 29 March 2013 / Revised: 16 May 2013 / Accepted: 24 May 2013 / Published: 29 May 2013
Cited by 21 | PDF Full-text (654 KB) | HTML Full-text | XML Full-text
Abstract
Cyclooxygenase-2 (COX-2) is a key player in inflammation. Its overexpression is directly associated with various inflammatory diseases and, additionally, with several processes of carcinogenesis. The development of new selective COX-2 inhibitors (COXIBs) for use in cancer treatment is in the focus of the
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Cyclooxygenase-2 (COX-2) is a key player in inflammation. Its overexpression is directly associated with various inflammatory diseases and, additionally, with several processes of carcinogenesis. The development of new selective COX-2 inhibitors (COXIBs) for use in cancer treatment is in the focus of the medicinal chemistry research field. For this purpose, a set of methods is available to determine COX-2 expression and activity in vitro and ex vivo but it is still a problem to functionally characterize COX-2 in vivo. This review focusses on imaging agents targeting COX-2 which have been developed for positron emission tomography (PET) and single photon emission computed tomography (SPECT) since 2005. The literature reveals that different radiochemical methods are available to synthesize COXIBs radiolabeled with fluorine-18, carbon-11, and isotopes of radioiodine. Unfortunately, most of the compounds tested did not show sufficient stability in vivo due to de[18F]fluorination or de[11C]methylation or they failed to bind specifically in the target region. So, suitable stability in vivo, matching lipophilicity for the target compartment and both high affinity and selectivity for COX-2 were identified as prominent criteria for radiotracer development. Up to now, it is not clear what approach and which model is the most suited to evaluate COX-2 targeting imaging agents in vivo. However, for proof of principle it has been shown that some radiolabeled compounds can bind specifically in COX-2 overexpressing tissue which gives hope for future work in this field. Full article
(This article belongs to the Special Issue PET Chemistry in Molecular Imaging)
Open AccessReview 89Zr, a Radiometal Nuclide with High Potential for Molecular Imaging with PET: Chemistry, Applications and Remaining Challenges
Molecules 2013, 18(6), 6469-6490; doi:10.3390/molecules18066469
Received: 26 March 2013 / Revised: 24 May 2013 / Accepted: 29 May 2013 / Published: 3 June 2013
Cited by 24 | PDF Full-text (406 KB) | HTML Full-text | XML Full-text
Abstract
Molecular imaging—and especially Positron Emission Tomography (PET)—is of increasing importance for the diagnosis of various diseases and thus is experiencing increasing dissemination. Consequently, there is a growing demand for appropriate PET tracers which allow for a specific accumulation in the target structure as
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Molecular imaging—and especially Positron Emission Tomography (PET)—is of increasing importance for the diagnosis of various diseases and thus is experiencing increasing dissemination. Consequently, there is a growing demand for appropriate PET tracers which allow for a specific accumulation in the target structure as well as its visualization and exhibit decay characteristics matching their in vivo pharmacokinetics. To meet this demand, the development of new targeting vectors as well as the use of uncommon radionuclides becomes increasingly important. Uncommon nuclides in this regard enable the utilization of various selectively accumulating bioactive molecules such as peptides, antibodies, their fragments, other proteins and artificial structures for PET imaging in personalized medicine. Among these radionuclides, 89Zr (t1/2 = 3.27 days and mean Eβ+ = 0.389 MeV) has attracted increasing attention within the last years due to its favorably long half-life, which enables imaging at late time-points, being especially favorable in case of slowly-accumulating targeting vectors. This review outlines the recent developments in the field of 89Zr-labeled bioactive molecules, their potential and application in PET imaging and beyond, as well as remaining challenges. Full article
(This article belongs to the Special Issue PET Chemistry in Molecular Imaging)
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Open AccessReview Biomedical Importance of Indoles
Molecules 2013, 18(6), 6620-6662; doi:10.3390/molecules18066620
Received: 17 April 2013 / Revised: 27 May 2013 / Accepted: 28 May 2013 / Published: 6 June 2013
Cited by 160 | PDF Full-text (724 KB) | HTML Full-text | XML Full-text
Abstract
The indole nucleus is an important element of many natural and synthetic molecules with significant biological activity. This review covers some of the relevant and recent achievements in the biological, chemical and pharmacological activity of important indole derivatives in the areas of drug
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The indole nucleus is an important element of many natural and synthetic molecules with significant biological activity. This review covers some of the relevant and recent achievements in the biological, chemical and pharmacological activity of important indole derivatives in the areas of drug discovery and analysis. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessReview Isotope Effects in ESR Spectroscopy
Molecules 2013, 18(6), 6679-6722; doi:10.3390/molecules18066679
Received: 26 March 2013 / Revised: 14 May 2013 / Accepted: 29 May 2013 / Published: 7 June 2013
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Abstract
In order to present the relationship between ESR spectroscopy and isotope effects three levels are considered: (i) ESR spectroscopy is described on a general level up to the models for interpretation of the experimental spectra, which go beyond the usually used time and
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In order to present the relationship between ESR spectroscopy and isotope effects three levels are considered: (i) ESR spectroscopy is described on a general level up to the models for interpretation of the experimental spectra, which go beyond the usually used time and mass independent spin-Hamilton operator, (ii) the main characteristics of the generalized isotope effects are worked out, and finally (iii) the basic, mainly quantum mechanical effects are used to describe the coupling of electron spins with the degrees of freedom, which are accessible under the selected conditions, of the respective paramagnetic object under investigation. The ESR parameters and the respective models are formalized so far, that they include the time and mass depending influences and reflect the specific isotope effects. Relations will be established between the effects in ESR spectra to spin relaxation, to spin exchange, to the magnetic isotope effect, to the Jahn-Teller effects, as well as to the influence of zero-point vibrations. Examples will be presented which demonstrate the influence of isotopes as well as the kind of accessible information. It will be differentiated with respect to isotope effects in paramagnetic centres itself and in the respective matrices up to the technique of ESR imaging. It is shown that the use of isotope effects is indispensable in ESR spectroscopy. Full article
(This article belongs to the Special Issue Isotope Effects)
Open AccessReview The Development of Aromas in Ruminant Meat
Molecules 2013, 18(6), 6748-6781; doi:10.3390/molecules18066748
Received: 28 March 2013 / Revised: 26 May 2013 / Accepted: 4 June 2013 / Published: 7 June 2013
Cited by 20 | PDF Full-text (323 KB) | HTML Full-text | XML Full-text
Abstract
This review provides an update on our understanding of the chemical reactions (lipid oxidation, Strecker and Maillard reactions, thiamine degradation) and a discussion of the principal aroma compounds derived from those reaction or other sources in cooked meat, mainly focused on ruminant species.
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This review provides an update on our understanding of the chemical reactions (lipid oxidation, Strecker and Maillard reactions, thiamine degradation) and a discussion of the principal aroma compounds derived from those reaction or other sources in cooked meat, mainly focused on ruminant species. This knowledge is essential in order to understand, control, and improve the quality of food products. More studies are necessary to fully understand the role of each compound in the overall cooked meat flavour and their possible effect in consumer acceptability. Full article
(This article belongs to the Special Issue Flavors and Fragrances)
Open AccessReview Practical Aspects and Mechanism of Asymmetric Hydrogenation with Chiral Half-Sandwich Complexes
Molecules 2013, 18(6), 6804-6828; doi:10.3390/molecules18066804
Received: 1 May 2013 / Revised: 27 May 2013 / Accepted: 4 June 2013 / Published: 10 June 2013
Cited by 19 | PDF Full-text (495 KB) | HTML Full-text | XML Full-text
Abstract
This review is oriented toward the asymmetric transfer hydrogenation (ATH) of imines regarding mostly fundamental, yet important topics from the practical point of view. Development of analytical methods for the monitoring of ATH (i.e., kinetics and stereoselectivity) belongs to those topics,
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This review is oriented toward the asymmetric transfer hydrogenation (ATH) of imines regarding mostly fundamental, yet important topics from the practical point of view. Development of analytical methods for the monitoring of ATH (i.e., kinetics and stereoselectivity) belongs to those topics, as well as studies on the influence of reaction conditions and structural variations on the reaction performance. The second part is devoted to the reaction mechanism with the emphasis on imine ATH and catalyst behaviour under acidic conditions. The review also addresses the asymmetric hydrogenation (AH) of ketones and imines using molecular hydrogen and the application of ATH in pharmaceutical projects. The contributions of our group to each area are included. Full article
(This article belongs to the Special Issue Asymmetric Catalysis)
Open AccessReview Natural 4-Hydroxy-2,5-dimethyl-3(2H)-furanone (Furaneol®)
Molecules 2013, 18(6), 6936-6951; doi:10.3390/molecules18066936
Received: 25 April 2013 / Revised: 6 June 2013 / Accepted: 7 June 2013 / Published: 13 June 2013
Cited by 12 | PDF Full-text (294 KB) | HTML Full-text | XML Full-text
Abstract
4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF, furaneol®) and its methyl ether 2,5-dimethyl-4-methoxy-3(2H)-furanone (DMMF) are import aroma chemicals and are considered key flavor compounds in many fruit. Due to their attractive sensory properties they are highly appreciated by the food industry. In
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4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF, furaneol®) and its methyl ether 2,5-dimethyl-4-methoxy-3(2H)-furanone (DMMF) are import aroma chemicals and are considered key flavor compounds in many fruit. Due to their attractive sensory properties they are highly appreciated by the food industry. In fruits 2,5-dimethyl-3(2H)-furanones are synthesized by a series of enzymatic steps whereas HDMF is also a product of the Maillard reaction. Numerous methods for the synthetic preparation of these compounds have been published and are applied by industry, but for the development of a biotechnological process the knowledge and availability of biosynthetic enzymes are required. During the last years substantial progress has been made in the elucidation of the biological pathway leading to HDMF and DMMF. This review summarizes the latest advances in this field. Full article
(This article belongs to the Special Issue Flavors and Fragrances)
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Open AccessReview Novel Biological Activities of Allosamidins
Molecules 2013, 18(6), 6952-6968; doi:10.3390/molecules18066952
Received: 26 April 2013 / Revised: 27 May 2013 / Accepted: 7 June 2013 / Published: 13 June 2013
Cited by 3 | PDF Full-text (309 KB) | HTML Full-text | XML Full-text
Abstract
Allosamidins, which are secondary metabolites of the Streptomyces species, have chitin-mimic pseudotrisaccharide structures. They bind to catalytic centers of all family 18 chitinases and inhibit their enzymatic activity. Allosamidins have been used as chitinase inhibitors to investigate the physiological roles of chitinases in
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Allosamidins, which are secondary metabolites of the Streptomyces species, have chitin-mimic pseudotrisaccharide structures. They bind to catalytic centers of all family 18 chitinases and inhibit their enzymatic activity. Allosamidins have been used as chitinase inhibitors to investigate the physiological roles of chitinases in a variety of organisms. Two prominent biological activities of allosamidins were discovered, where one has anti-asthmatic activity in mammals, while the other has the chitinase-production- promoting activity in allosamidin-producing Streptomyces. In this article, recent studies on the novel biological activities of allosamidins are reviewed. Full article
(This article belongs to the Special Issue Chitins and Chitosans)
Open AccessReview Diels-Alder Reactions of 12-Hydroxy-9(10®20)-5aH-abeo-abieta-1(10),8(9),12(13)-triene-11,14-dione
Molecules 2013, 18(6), 6969-6989; doi:10.3390/molecules18066969
Received: 1 March 2013 / Revised: 14 May 2013 / Accepted: 30 May 2013 / Published: 14 June 2013
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Abstract
12-Hydroxy-9(10®20)-5aH-abeo-abieta-1(10),8(9),12(13)-triene-11,14-dione (quinone 2) served as the dienophile in numerous intermolecular Diels-Alder reactions. These cycloadditions were conducted either thermally (including microwave heating) or with Lewis acid activation. While most dienes reacted with quinone 2 in good chemical yield, others were incompatible under the
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12-Hydroxy-9(10®20)-5aH-abeo-abieta-1(10),8(9),12(13)-triene-11,14-dione (quinone 2) served as the dienophile in numerous intermolecular Diels-Alder reactions. These cycloadditions were conducted either thermally (including microwave heating) or with Lewis acid activation. While most dienes reacted with quinone 2 in good chemical yield, others were incompatible under the experimental conditions used. Full article
(This article belongs to the Special Issue Diels-Alder Reaction)
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Open AccessReview Applications of Azide-Based Bioorthogonal Click Chemistry in Glycobiology
Molecules 2013, 18(6), 7145-7159; doi:10.3390/molecules18067145
Received: 20 May 2013 / Revised: 12 June 2013 / Accepted: 14 June 2013 / Published: 19 June 2013
Cited by 23 | PDF Full-text (679 KB) | HTML Full-text | XML Full-text
Abstract
Click chemistry is a powerful chemical reaction with excellent bioorthogonality features: biocompatible, rapid and highly specific in biological environments. For glycobiology, bioorthogonal click chemistry has created a new method for glycan non-invasive imaging in living systems, selective metabolic engineering, and offered an elite
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Click chemistry is a powerful chemical reaction with excellent bioorthogonality features: biocompatible, rapid and highly specific in biological environments. For glycobiology, bioorthogonal click chemistry has created a new method for glycan non-invasive imaging in living systems, selective metabolic engineering, and offered an elite chemical handle for biological manipulation and glycomics studies. Especially the [3 + 2] dipolar cycloadditions of azides with strained alkynes and the Staudinger ligation of azides and triarylphosphines have been widely used among the extant click reactions. This review focuses on the azide-based bioorthogonal click chemistry, describing the characteristics and development of these reactions, introducing some recent applications in glycobiology research, especially in glycan metabolic engineering, including glycan non-invasive imaging, glycomics studies and viral surface manipulation for drug discovery as well as other applications like activity-based protein profiling and carbohydrate microarrays. Full article
(This article belongs to the Special Issue Advances in Click Chemistry)
Open AccessReview Supercritical Fluid Extraction of Plant Flavors and Fragrances
Molecules 2013, 18(6), 7194-7238; doi:10.3390/molecules18067194
Received: 15 May 2013 / Revised: 13 June 2013 / Accepted: 14 June 2013 / Published: 19 June 2013
Cited by 36 | PDF Full-text (843 KB) | HTML Full-text | XML Full-text
Abstract
Supercritical fluid extraction (SFE) of plant material with solvents like CO2, propane, butane, or ethylene is a topic of growing interest. SFE allows the processing of plant material at low temperatures, hence limiting thermal degradation, and avoids the use of toxic
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Supercritical fluid extraction (SFE) of plant material with solvents like CO2, propane, butane, or ethylene is a topic of growing interest. SFE allows the processing of plant material at low temperatures, hence limiting thermal degradation, and avoids the use of toxic solvents. Although today SFE is mainly used for decaffeination of coffee and tea as well as production of hop extracts on a large scale, there is also a growing interest in this extraction method for other industrial applications operating at different scales. In this review we update the literature data on SFE technology, with particular reference to flavors and fragrance, by comparing traditional extraction techniques of some industrial medicinal and aromatic crops with SFE. Moreover, we describe the biological activity of SFE extracts by describing their insecticidal, acaricidal, antimycotic, antimicrobial, cytotoxic and antioxidant properties. Finally, we discuss the process modelling, mass-transfer mechanisms, kinetics parameters and thermodynamic by giving an overview of SFE potential in the flavors and fragrances arena. Full article
(This article belongs to the Special Issue Flavors and Fragrances)
Open AccessReview Natural Products as a Source of Anti-Inflammatory Agents Associated with Inflammatory Bowel Disease
Molecules 2013, 18(6), 7253-7270; doi:10.3390/molecules18067253
Received: 27 April 2013 / Revised: 5 June 2013 / Accepted: 14 June 2013 / Published: 19 June 2013
Cited by 26 | PDF Full-text (348 KB) | HTML Full-text | XML Full-text
Abstract
Accumulating epidemiological and clinical study indicates that inflammation is a significant risk factor to develop various human diseases such as inflammatory bowel disease (IBD), chronic asthma, rheumatoid arthritis, multiple sclerosis, and psoriasis. Suppressing inflammation is therefore important to control or prevent various diseases.
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Accumulating epidemiological and clinical study indicates that inflammation is a significant risk factor to develop various human diseases such as inflammatory bowel disease (IBD), chronic asthma, rheumatoid arthritis, multiple sclerosis, and psoriasis. Suppressing inflammation is therefore important to control or prevent various diseases. Among them, IBD is one of the major problems affecting people worldwide. IBD affects at least one in a thousand persons in many Western countries. Various natural products have been shown to safely suppress pro-inflammatory pathway and control IBD. In vivo and/or in vitro studies indicate that anti-IBD effects of natural products occur by inhibition of the expression of pro-inflammatory cytokines (for example, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule expression and pro-inflammatory mediators (such as inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2), master transcription factors (such as nuclear factor-κB (NF-κB)), reactive oxygen species (ROS) and by improving the antioxidant activity. In this review, we summarize recent research focused on IBD and the effects that natural products have on IBD factors. Full article
(This article belongs to the Special Issue Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry)
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Open AccessReview Chemical Reactions Catalyzed by Metalloporphyrin-Based Metal-Organic Frameworks
Molecules 2013, 18(6), 7279-7308; doi:10.3390/molecules18067279
Received: 7 May 2013 / Revised: 3 June 2013 / Accepted: 13 June 2013 / Published: 21 June 2013
Cited by 32 | PDF Full-text (716 KB) | HTML Full-text | XML Full-text
Abstract
The synthetic versatility and the potential application of metalloporphyrins (MP) in different fields have aroused researchers’ interest in studying these complexes, in an attempt to mimic biological systems such as cytochrome P-450. Over the last 40 years, synthetic MPs have been mainly used
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The synthetic versatility and the potential application of metalloporphyrins (MP) in different fields have aroused researchers’ interest in studying these complexes, in an attempt to mimic biological systems such as cytochrome P-450. Over the last 40 years, synthetic MPs have been mainly used as catalysts for homogeneous or heterogeneous chemical reactions. To employ them in heterogeneous catalysis, chemists have prepared new MP-based solids by immobilizing MP onto rigid inorganic supports, a strategy that affords hybrid inorganic-organic materials. More recently, materials obtained by supramolecular assembly processes and containing MPs as building blocks have been applied in a variety of areas, like gas storage, photonic devices, separation, molecular sensing, magnets, and heterogeneous catalysis, among others. These coordination polymers, known as metal-organic frameworks (MOFs), contain organic ligands or complexes connected by metal ions or clusters, which give rise to a 1-, 2- or 3-D network. These kinds of materials presents large surface areas, Brønsted or redox sites, and high porosity, all of which are desirable features in catalysts with potential use in heterogeneous phases. Building MOFs based on MP is a good way to obtain solid catalysts that offer the advantages of bioinspired systems and zeolitic materials. In this mini review, we will adopt a historical approach to present the most relevant MP-based MOFs applicable to catalytic reactions such as oxidation, reduction, insertion of functional groups, and exchange of organic functions. Full article
(This article belongs to the Special Issue Heterogeneous Catalysis)
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