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Molecules, Volume 17, Issue 10 (October 2012), Pages 11294-12468

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Open AccessArticle Synthesis and Cytotoxicity Evaluation of 13-n-Alkyl Berberine and Palmatine Analogues as Anticancer Agents
Molecules 2012, 17(10), 11294-11302; doi:10.3390/molecules171011294
Received: 30 August 2012 / Revised: 11 September 2012 / Accepted: 17 September 2012 / Published: 25 September 2012
Cited by 16 | PDF Full-text (225 KB)
Abstract
By introducing long carbon-chain alkyl groups at the C-13 position of berberine and palmatine, 13-n-hexyl/13-n-octyl berberine and palmatine chloride analogues 4ad were synthesized and examined by MTT assays for cytotoxic activity in seven human cancer cell [...] Read more.
By introducing long carbon-chain alkyl groups at the C-13 position of berberine and palmatine, 13-n-hexyl/13-n-octyl berberine and palmatine chloride analogues 4ad were synthesized and examined by MTT assays for cytotoxic activity in seven human cancer cell lines (7701QGY, SMMC7721, HepG2, CEM, CEM/VCR, KIII, Lewis), yielding IC50 values of 0.02 ± 0.01–13.58 ± 2.84 μM. 13-n-Octyl palmatine (compound 4d) gave the most potent inhibitor activity, with an IC50 of 0.02 ± 0.01 μM for SMMC7721. In all cases, the 13-n-alkyl berberine and palmatine analogues 4ad were more cytotoxic than berberine and palmatine. In addition, compounds 4ad also exhibited more potent cytotoxicity than berberine and palmatine in mice with S180 sarcoma xenografted in vivo. The primary screening results indicated that the 13-n-hexyl/13-n-octyl berberine and palmatine analogues might be valuable source for new potent anticancer drug candidates. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Benzopyranones from the Endophytic Fungus Hyalodendriella sp. Ponipodef12 and Their Bioactivities
Molecules 2012, 17(10), 11303-11314; doi:10.3390/molecules171011303
Received: 16 August 2012 / Revised: 4 September 2012 / Accepted: 19 September 2012 / Published: 25 September 2012
Cited by 18 | PDF Full-text (202 KB)
Abstract
The endophytic fungus Hyalodendriella sp. Ponipodef12 was isolated from the hybrid ‘Neva’ of Populus deltoides Marsh × P. nigra L. In this study, four benzopyranones were isolated from the ethyl acetate extract of Hyalodendriella sp. Ponipodef12, and identified as palmariol B ( [...] Read more.
The endophytic fungus Hyalodendriella sp. Ponipodef12 was isolated from the hybrid ‘Neva’ of Populus deltoides Marsh × P. nigra L. In this study, four benzopyranones were isolated from the ethyl acetate extract of Hyalodendriella sp. Ponipodef12, and identified as palmariol B (1), 4-hydroxymellein (2), alternariol 9-methyl ether (3), and botrallin (4) by means of physicochemical and spectroscopic analysis. All the compounds were evaluated for their antibacterial, antifungal, antinematodal and acetylcholinesterase inhibitory activities. 4-Hydroxymellein (2) exhibited stronger antibacterial activity than the other compounds. Palmariol B (1) showed stronger antimicrobial, antinematodal and acetylcholinesterase inhibitory activities than alternariol 9-methyl ether (3) which indicated that the chlorine substitution at position 2 may contribute to its bioactivity. The results indicate the potential of this endophytic fungus as a source of bioactive benzopyranones. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Chemical Composition and Biological Activity of Extracts from Salvia bicolor Desf. Growing in Egypt
Molecules 2012, 17(10), 11315-11334; doi:10.3390/molecules171011315
Received: 16 July 2012 / Revised: 20 August 2012 / Accepted: 14 September 2012 / Published: 25 September 2012
Cited by 9 | PDF Full-text (229 KB)
Abstract
A petroleum ether extract (PEE) and a methanolic extract (ME) of aerial parts of Salvia bicolor Desf were prepared, and their chemical compositions and antioxidant, anti-inflammatory, analgesic and antimicrobial activities were evaluated. GC/MS analysis of the PEE revealed the presence of 20 [...] Read more.
A petroleum ether extract (PEE) and a methanolic extract (ME) of aerial parts of Salvia bicolor Desf were prepared, and their chemical compositions and antioxidant, anti-inflammatory, analgesic and antimicrobial activities were evaluated. GC/MS analysis of the PEE revealed the presence of 20 compounds in the unsaponifiable matter, among which β-sitosterol and β-amyrin (constituting 24.75% and 15.62%, respectively) were the main constituents, and 21 fatty acids, with linolenic acid and erucic acid being the main fatty acid constituents (21.65% and 16.65%, respectively). HPLC/MS analysis of the methanol extract for individual phenolics revealed the presence of 14 phenolic acids; protocatchuic acid was predominant (75.22 mg/g dry sample), followed by p-coumaric, gallic and synergic acids (70.27, 68.26 and 54.38 mg/g dry weight, respectively). HPLC/MS analysis of flavonoid contents revealed the presence of five flavonoid compounds, among which luteolin 7-O-glucoside and apigenin were the major constituents (120.25 mg/100g dry sample and 88.48 mg/100g dry sample, respectively). The antioxidant activities of both extracts were evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and the total antioxidant capacity was determined in terms of GAE (gallic acid equivalents). Anti-inflammatory and analgesic activities were evaluated using the rat paw edema and hot plate testing methods, respectively. The antimicrobial activities of both the PEE and ME were examined by means of the disk-diffusion method. The Salvia bicolor PEE and ME exhibited significant antioxidant, anti-inflammatory, and analgesic properties, in addition to antimicrobial effects against the selected microorganisms. Full article
Open AccessArticle Effects of Yeast Polysaccharide on Growth and Flavonoid Accumulation in Fagopyrum tataricum Sprout Cultures
Molecules 2012, 17(10), 11335-11345; doi:10.3390/molecules171011335
Received: 27 August 2012 / Revised: 10 September 2012 / Accepted: 17 September 2012 / Published: 25 September 2012
Cited by 8 | PDF Full-text (238 KB) | HTML Full-text | XML Full-text
Abstract
The purpose of this study was to investigate the effects of yeast polysaccharide (YPS) on growth and flavonoid accumulation in sprout cultures of Fagopyrum tataricum (tartary buckwheat). Without obvious change in the appearance of the sprouts, the exogenous YPS notably stimulated the [...] Read more.
The purpose of this study was to investigate the effects of yeast polysaccharide (YPS) on growth and flavonoid accumulation in sprout cultures of Fagopyrum tataricum (tartary buckwheat). Without obvious change in the appearance of the sprouts, the exogenous YPS notably stimulated the production of functional metabolites in F. tataricum sprouts, and the stimulation effect was concentration-dependent. With 400 mg/L of YPS applied to the sprout cultures on day 6, the total rutin and quercentin content was effectively increased to 42.8 mg/gdw, or about 1.4-fold in comparison with the control of 31.2 mg/gdw. Feeding with 800 mg/L of YPS on day 9, the sprouts biomass was increased by about 8% compared to the control culture (0.99 gdw/100 sprouts versus 0.92 gdw/100 sprouts). Moreover, the present study revealed that the accumulation of these bioactive metabolites resulted from the stimulation of the phenylpropanoid pathway by YPS treatment. It could be an effective strategy for improving the functional quality of the F. tataricum sprouts provided with YPS. Full article
Open AccessArticle A Concise Synthesis of Glycolipids Based on Aspartic Acid Building Blocks
Molecules 2012, 17(10), 11346-11362; doi:10.3390/molecules171011346
Received: 31 July 2012 / Revised: 15 September 2012 / Accepted: 21 September 2012 / Published: 25 September 2012
Cited by 3 | PDF Full-text (288 KB) | HTML Full-text | XML Full-text
Abstract
L-Aspartic acid building blocks bearing galactosyl moieties were used to synthesise glycolipid mimetics of variable hydrocarbon chain length. The glycolipids were readily prepared through amide bond formation using the TBTU/HOBt coupling methodology. It was observed that, under these conditions, activation of the [...] Read more.
L-Aspartic acid building blocks bearing galactosyl moieties were used to synthesise glycolipid mimetics of variable hydrocarbon chain length. The glycolipids were readily prepared through amide bond formation using the TBTU/HOBt coupling methodology. It was observed that, under these conditions, activation of the α-carboxylic acid of the intermediates led to near complete racemisation of the chiral centre if the reaction was carried out in the presence of a base such as triethylamine. The enantiomerically pure glycolipids were obtained after careful consideration of the synthetic sequence and by performing the coupling reactions in the absence of base. Full article
(This article belongs to the Special Issue Advances in Carbohydrate Chemistry 2012)
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Open AccessArticle Weinreb Amidation as the Cornerstone of an Improved Synthetic Route to A-Ring-Modified Derivatives of Luotonin A
Molecules 2012, 17(10), 11363-11378; doi:10.3390/molecules171011363
Received: 21 August 2012 / Revised: 14 September 2012 / Accepted: 18 September 2012 / Published: 25 September 2012
Cited by 3 | PDF Full-text (258 KB) | HTML Full-text | XML Full-text
Abstract
Weinreb amidation of ethyl 4-oxo-3,4-dihydroquinazoline-2-carboxylate with aromatic amines provides a significantly improved route to anilide-type key intermediates for the synthesis of the anticancer alkaloid, luotonin A, and new A-ring-modified derivatives thereof. This method has advantages concerning overall yield, brevity, and [...] Read more.
Weinreb amidation of ethyl 4-oxo-3,4-dihydroquinazoline-2-carboxylate with aromatic amines provides a significantly improved route to anilide-type key intermediates for the synthesis of the anticancer alkaloid, luotonin A, and new A-ring-modified derivatives thereof. This method has advantages concerning overall yield, brevity, and versatility with regard to the aromatic amine component, even if the latter has less favourable nucleophilicity, solubility and/or stability properties. This is demonstrated by the concise synthesis of a small library of luotonin A analogues, including a novel thiophene isostere of the alkaloid. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Study of the in Vitro Antiplasmodial, Antileishmanial and Antitrypanosomal Activities of Medicinal Plants from Saudi Arabia
Molecules 2012, 17(10), 11379-11390; doi:10.3390/molecules171011379
Received: 8 August 2012 / Revised: 15 September 2012 / Accepted: 18 September 2012 / Published: 25 September 2012
Cited by 12 | PDF Full-text (187 KB)
Abstract
The present study investigated the in vitro antiprotozoal activity of sixteen selected medicinal plants. Plant materials were extracted with methanol and screened in vitro against erythrocytic schizonts of Plasmodium falciparum, intracellular amastigotes of Leishmania infantum and Trypanosoma cruzi and free trypomastigotes of T. brucei. Cytotoxic activity was determined against MRC-5 cells to assess selectivity. The criterion for activity was an IC50 < 10 µg/mL (4. Antiplasmodial activity was found in the extracts of Prosopis juliflora and Punica granatum. Antileishmanial activity against L. infantum was demonstrated in Caralluma sinaica and Periploca aphylla. Amastigotes of T. cruzi were affected by the methanol extract of Albizia lebbeck pericarp, Caralluma sinaica, Periploca aphylla and Prosopius juliflora. Activity against T. brucei was obtained in Prosopis juliflora. Cytotoxicity (MRC-5 IC50 < 10 µg/mL) and hence non-specific activities were observed for Conocarpus lancifolius. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Effects of Cultivar and Process Variables on Dynamic-Mechanical and Sensorial Behavior of Value-Added Grape-Based Smoothies
Molecules 2012, 17(10), 11421-11434; doi:10.3390/molecules171011421
Received: 7 August 2012 / Revised: 19 September 2012 / Accepted: 20 September 2012 / Published: 26 September 2012
Cited by 2 | PDF Full-text (301 KB) | HTML Full-text | XML Full-text
Abstract
The effects of either cooking temperature (45, 80, and 100 °C) or inclusion of seed particles on the dynamic-mechanical and sensorial properties of value-added Crimson seedless, Black Pearl, or Baresana grape-based smoothies were studied. The inclusion of seed particles resulted in significant [...] Read more.
The effects of either cooking temperature (45, 80, and 100 °C) or inclusion of seed particles on the dynamic-mechanical and sensorial properties of value-added Crimson seedless, Black Pearl, or Baresana grape-based smoothies were studied. The inclusion of seed particles resulted in significant increases of the phenolic content, both in Black Pearl and Baresana, but it did not affect in a negative way the sensorial characteristics of smoothies whereas it caused an increase of the viscoelastic behavior of Black Pearl and a slight decrease in Baresana grape-based smoothies. In particular, the investigated rheological parameters were the loss and storage modulus. Moreover, the loss tangent value (the ratio between loss and storage modulus) remained unchanged, indicating a pseudoplastic behavior of all samples, independent on the process conditions. The smoothies produced from Crimson grapes at the intermediate temperature (80 °C) showed sensorial and rheological characteristics similar to those manufactured at 45 °C and better than those manufactured at 100 °C. Full article
(This article belongs to the Special Issue Antioxidants 2012)
Open AccessArticle Recombinant VAA-I from Viscum album Induces Apoptotic Cell Death of Hepatocellular Carcinoma SMMC7721 Cells
Molecules 2012, 17(10), 11435-11446; doi:10.3390/molecules171011435
Received: 4 June 2012 / Revised: 30 August 2012 / Accepted: 3 September 2012 / Published: 26 September 2012
Cited by 4 | PDF Full-text (600 KB)
Abstract
Researchers have proposed that VAA-I, a specific plant lectin found in Viscum album, has therapeutic effects on cancer and autoimmune diseases. VAA-I has shown some promising treatment results in some types of tumor cell lines, especially SMMC-7721 cells (human hepatocellular carcinoma [...] Read more.
Researchers have proposed that VAA-I, a specific plant lectin found in Viscum album, has therapeutic effects on cancer and autoimmune diseases. VAA-I has shown some promising treatment results in some types of tumor cell lines, especially SMMC-7721 cells (human hepatocellular carcinoma cells). However, few details are known about the mechanism and process of cell death induced by VAA-I in tumor cells. In this study, the cell morphology results showed that SMMC-7721 cells treated with VAA-I exhibited several features typical of apoptotic cell death, which was confirmed by the Caspase inhibition assay. Fluo-3-acetoxymethyl ester (AM) fluorescence imaging techniques showed that rVAA-I significantly elevated the intracellular calcium level ([Ca2+]i) in SMMC-7721 cells. These findings suggest that apoptosis may play the most important role in SMMC-7721 cell death induced by rVAA-I. Finally, in the SMMC-7721 cells treated with rVAA-I, a series of genes in the p38 mitogen-activated protein kinase (MAPK) signaling pathway were expressed differentially, and further found that PI 3-kinase pathway is involved in rVAA-I signal transduction in SMMC-7721 cells. Full article
Open AccessArticle Chemical Characterization of Volatile Compounds of Lantana camara L. and L. radula Sw. and Their Antifungal Activity
Molecules 2012, 17(10), 11447-11455; doi:10.3390/molecules171011447
Received: 10 August 2012 / Revised: 20 September 2012 / Accepted: 20 September 2012 / Published: 27 September 2012
Cited by 6 | PDF Full-text (287 KB) | HTML Full-text | XML Full-text
Abstract
A comparative study of the chemical composition of essential oils of two very similar species of the Verbenaceae family (Lantana camara and L. radula) revealed that the main components of essential oil of L. camara were germacrene-D (19.8%) and E [...] Read more.
A comparative study of the chemical composition of essential oils of two very similar species of the Verbenaceae family (Lantana camara and L. radula) revealed that the main components of essential oil of L. camara were germacrene-D (19.8%) and E-caryophyllene (19.7%), while those of L. radula were E-caryophyllene (25.3%), phytol (29.2%) and E-nerolidol (19.0%). We have hypothesized that the observed differences could contribute to the differentiated reaction of the two species of Lantana to the attack of the phytopathogenic fungi Corynespora cassiicola. An experiment, involving C. cassiicola cultivation in culture media containing volatile oils of the two species demonstrated that the oils of L. radula were more fungistatic than the oils of L. camara, in accordance with the in vivo observations. It is likely that E-nerolidol and phytol, only found in the oil of L. radula, play a significant role in the effects of L. radula on C. cassiicola. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Anticancer Activity of Di(3-thienyl)methanol and Di(3-thienyl)methane
Molecules 2012, 17(10), 11456-11468; doi:10.3390/molecules171011456
Received: 2 August 2012 / Revised: 24 September 2012 / Accepted: 25 September 2012 / Published: 27 September 2012
Cited by 10 | PDF Full-text (517 KB) | HTML Full-text | XML Full-text
Abstract
Di(3-thienyl)methanol (2) and di(3-thienyl)methane (3) have been synthesized and screened against the T98G (brain cancer) cell line. Treatment induced cell death (MTT and macro-colony assay), growth inhibition, cytogenetic damage (micronuclei formation), were studied as cellular response parameters. Treatment [...] Read more.
Di(3-thienyl)methanol (2) and di(3-thienyl)methane (3) have been synthesized and screened against the T98G (brain cancer) cell line. Treatment induced cell death (MTT and macro-colony assay), growth inhibition, cytogenetic damage (micronuclei formation), were studied as cellular response parameters. Treatment with the compounds enhanced growth inhibition and cell death in a concentration dependent manner in both T98G and HEK (normal) cell lines. At higher concentrations (>20 µg/mL) the cytotoxic effects of the compounds were highly significant. The effect on clonogenic capacity and micronuclei formation observed after treatment of cells. Amongst the compounds, compound 2 exhibited potent activity against T98G brain cancer cells. Despite potent in vitro activity, both compounds exhibited less cytotoxicity against normal human HEK cells at all effective concentrations. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Silica Gel-Mediated Organic Reactions under Organic Solvent-Free Conditions
Molecules 2012, 17(10), 11469-11483; doi:10.3390/molecules171011469
Received: 24 August 2012 / Revised: 18 September 2012 / Accepted: 20 September 2012 / Published: 27 September 2012
Cited by 3 | PDF Full-text (271 KB)
Abstract
Silica gel was found to be an excellent medium for some useful organic transformations under organic solvent-free conditions, such as (1) the Friedel-Crafts-type nitration of arenes using commercial aqueous 69% nitric acid alone at room temperature, (2) one-pot Wittig-type olefination of aldehydes [...] Read more.
Silica gel was found to be an excellent medium for some useful organic transformations under organic solvent-free conditions, such as (1) the Friedel-Crafts-type nitration of arenes using commercial aqueous 69% nitric acid alone at room temperature, (2) one-pot Wittig-type olefination of aldehydes with activated organic halides in the presence of tributyl- or triphenylphosphine and Hunig’s base, and (3) the Morita-Baylis-Hillman reaction of aldehydes with methyl acrylate. After the reactions, the desired products were easily obtained in good to excellent yields through simple manipulation. Full article
(This article belongs to the Special Issue Solvent-Free Synthesis)
Open AccessArticle The Antioxidant and Anti-inflammatory Effects of Phenolic Compounds Isolated from the Root of Rhodiola sachalinensis A. BOR
Molecules 2012, 17(10), 11484-11494; doi:10.3390/molecules171011484
Received: 4 July 2012 / Revised: 28 August 2012 / Accepted: 21 September 2012 / Published: 27 September 2012
Cited by 15 | PDF Full-text (283 KB)
Abstract
Isolation of compounds from the root of Rhodiola sachalinensis (RRS) yielded tyrosol (1), salidroside (2), multiflorin B (3), kaempferol-3,4′-di-O-β-D-glucopyranoside (4), afzelin (5), kaempferol (6), rhodionin (7), [...] Read more.
Isolation of compounds from the root of Rhodiola sachalinensis (RRS) yielded tyrosol (1), salidroside (2), multiflorin B (3), kaempferol-3,4′-di-O-β-D-glucopyranoside (4), afzelin (5), kaempferol (6), rhodionin (7), and rhodiosin (8). Quantification of these compounds was performed by high-performance liquid chromatography (HPLC). To investigate the antioxidant and anti-inflammatory effects of the compounds, DPPH radical scavenging, NBT superoxide scavenging and nitric oxide production inhibitory activities were examined in LPS-stimulated Raw 264.7 cells. We suggest that the major active components of RRS are herbacetin glycosides, exhibiting antioxidant activity, and kaempferol, exhibiting anti-inflammatory activity. Full article
(This article belongs to the Special Issue Antioxidants 2012)
Open AccessArticle A Facile Synthesis of Arylazonicotinates for Dyeing Polyester Fabrics under Microwave Irradiation and Their Biological Activity Profiles
Molecules 2012, 17(10), 11495-11506; doi:10.3390/molecules171011495
Received: 17 August 2012 / Revised: 12 September 2012 / Accepted: 24 September 2012 / Published: 27 September 2012
Cited by 4 | PDF Full-text (318 KB)
Abstract
A as textile dyes and the fastness properties of the dyed samples were measured. Most of the dyed fabrics tested displayed very good washing and perspiration fastness and series of 2-hydroxy- and 2-amino-6-substituted-5-arylazonicotinate monoazo compounds 7ae and 9ac [...] Read more.
A as textile dyes and the fastness properties of the dyed samples were measured. Most of the dyed fabrics tested displayed very good washing and perspiration fastness and series of 2-hydroxy- and 2-amino-6-substituted-5-arylazonicotinate monoazo compounds 7ae and 9ac were prepared via condensation of 3-oxo-3-substituted-2-arylhydrazonals 2ae with active methylene nitriles 3ad using microwave irradiation as an energy source. These substances were then tested moderate light fastness. Finally, the biological activity of the synthesized compounds against Gram positive bacteria, Gram negative bacteria and yeast were evaluated. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle 3-Amino-8-hydroxy-4-imino-6-methyl-5-phenyl-4,5-dihydro-3H-chromeno [2,3-d ]pyrimidine: An Effecient Key Precursor for Novel Synthesis of Some Interesting Triazines and Triazepines as Potential Anti-Tumor Agents
Molecules 2012, 17(10), 11538-11553; doi:10.3390/molecules171011538
Received: 6 August 2012 / Revised: 27 August 2012 / Accepted: 20 September 2012 / Published: 27 September 2012
Cited by 20 | PDF Full-text (236 KB) | HTML Full-text | XML Full-text
Abstract
A number of interesting heterocycles were prepared through interaction of the intermediate 3-amino-8-hydroxy-4-imino-6-methyl-5-phenyl-4,5-dihydro-3H-chromeno-[2,3-d]pyrimidine (1) and reagents such as hydrazonyl halides 2 to furnish triazine derivatives 4al. Reaction of 1 with phenacyl bromide afforded compound 5 [...] Read more.
A number of interesting heterocycles were prepared through interaction of the intermediate 3-amino-8-hydroxy-4-imino-6-methyl-5-phenyl-4,5-dihydro-3H-chromeno-[2,3-d]pyrimidine (1) and reagents such as hydrazonyl halides 2 to furnish triazine derivatives 4al. Reaction of 1 with phenacyl bromide afforded compound 5. Moreover, the title compound 1 was subjected to condensation with active methylene compounds (ethyl acetoacetate and ethyl benzoylacetate) to give triazipinones 8a,b. The condensation with aromatic aldehydes afforded either the triazole derivatives 10ad or Schiff base 11. In addition, the behaviour of compound 1 towards activated unsaturated compounds namely dimethyl acetylene dicarboxylate and ethoxymethylenemalonitrile was studied and it was found to furnish the triazine 13 and triazepine derivative 15, respectively. Combination of title compound 1 with chlorinated active methylene compounds delivered the triazine derivatives 18ac. Reaction of 1 with chloroacetonitrile furnished compound 20. The structures of the products were elucidated based on their microanalyses and spectroscopic data. Finally, the antitumor activity of the new compounds 4a and 8a against human breast cell MCF-7 line and liver carcinoma cell line HepG2 were recorded. Full article
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Open AccessArticle Design and Synthesis of an 18F-Labeled Version of Phenylethyl Orvinol ([18F]FE-PEO) for PET-Imaging of Opioid Receptors
Molecules 2012, 17(10), 11554-11569; doi:10.3390/molecules171011554
Received: 13 July 2012 / Revised: 10 September 2012 / Accepted: 11 September 2012 / Published: 28 September 2012
Cited by 4 | PDF Full-text (263 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The semisynthetic oripavine derivative phenethyl orvinol (PEO), a full agonist at opioid receptors (OR), is an attractive structural motif for developing 18F-labeled PET tracers with a high degree of sensitivity for competition between endogenous and exogenous OR-ligands. The target cold reference [...] Read more.
The semisynthetic oripavine derivative phenethyl orvinol (PEO), a full agonist at opioid receptors (OR), is an attractive structural motif for developing 18F-labeled PET tracers with a high degree of sensitivity for competition between endogenous and exogenous OR-ligands. The target cold reference compound 6-O-(2-fluoroethyl)-6-O-desmethylphenylethyl orvinol (FE-PEO) was obtained via two separate reaction routes. A three-step synthesis was developed for the preparation of a tosyloxyethyl precursor (TE-TDPEO), the key precursor for a direct, nucleophilic radiofluorination to yield [18F]FE-PEO. The developed radiosynthesis provides the target compound in relevantly high yield and purity, and is adaptable to routine production. Full article
Open AccessArticle An Expeditious Iodine-Catalyzed Synthesis of 3-Pyrrole-substituted 2-Azetidinones
Molecules 2012, 17(10), 11570-11584; doi:10.3390/molecules171011570
Received: 10 September 2012 / Revised: 25 September 2012 / Accepted: 26 September 2012 / Published: 28 September 2012
Cited by 8 | PDF Full-text (314 KB) | HTML Full-text | XML Full-text
Abstract
2-Azetidinones and pyrroles are two highly important classes of molecules in organic and medicinal chemistry. A green and practical method for the synthesis of 3-pyrrole-substituted 2-azetidinones using catalytic amounts of molecular iodine under microwave irradiation has been developed. Following this method, a [...] Read more.
2-Azetidinones and pyrroles are two highly important classes of molecules in organic and medicinal chemistry. A green and practical method for the synthesis of 3-pyrrole-substituted 2-azetidinones using catalytic amounts of molecular iodine under microwave irradiation has been developed. Following this method, a series of 3-pyrrole- substituted 2-azetidinones have been synthesized with a variety of substituents at N-1 and at C-4. The procedure is equally effective for mono- as well as polyaromatic groups at the N-1 position of the 2-azetidinone ring. The C-4 substituent has no influence either on the yield or the rate of the reaction. Optically pure 3-pyrrole-substituted 2-azetidinones have also been synthesized following this methodology. No deprotection/rearrangement has been identified in this process, even with highly acid sensitive group-containing substrates. A plausible mechanistic pathway has also been suggested based on the evidence obtained from 1H-NMR spectroscopy. The extreme rapidity with excellent reaction yields is believed to be the result of a synergistic effect of the Lewis acid catalyst (molecular iodine) and microwave irradiation. Full article
(This article belongs to the Special Issue Organic Iodine Chemistry)
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Open AccessArticle Protective Effect of Total Flavonoids of Seabuckthorn (Hippophae rhamnoides) in Simulated High-Altitude Polycythemia in Rats
Molecules 2012, 17(10), 11585-11597; doi:10.3390/molecules171011585
Received: 14 May 2012 / Revised: 4 September 2012 / Accepted: 4 September 2012 / Published: 28 September 2012
Cited by 4 | PDF Full-text (347 KB)
Abstract
Seabuckthorn (Hippophae rhamnoides L.) has been used to treat high altitude diseases. The effects of five-week treatment with total flavonoids of seabuckthorn (35, 70, 140 mg/kg, ig) on cobalt chloride (5.5 mg/kg, ip)- and hypobaric chamber (simulating 5,000 m)-induced high-altitude polycythemia [...] Read more.
Seabuckthorn (Hippophae rhamnoides L.) has been used to treat high altitude diseases. The effects of five-week treatment with total flavonoids of seabuckthorn (35, 70, 140 mg/kg, ig) on cobalt chloride (5.5 mg/kg, ip)- and hypobaric chamber (simulating 5,000 m)-induced high-altitude polycythemia in rats were measured. Total flavonoids decreased red blood cell number, hemoglobin, hematocrit, mean corpuscular hemoglobin levels, span of red blood cell electrophoretic mobility, aggregation index of red blood cell, plasma viscosity, whole blood viscosity, and increased deformation index of red blood cell, erythropoietin level in serum. Total flavonoids increased pH, pO2, SpO2, pCO2 levels in arterial blood, and increased Na+, HCO3, Cl, but decreased K+ concentrations. Total flavonoids increased mean arterial pressure, left ventricular systolic pressure, end-diastolic pressure, maximal rate of rise and decrease, decreased heart rate and protected right ventricle morphology. Changes in hemodynamic, hematologic parameters, and erythropoietin content suggest that administration of total flavonoids from seabuckthorn may be useful in the prevention of high altitude polycythaemia in rats. Full article
Open AccessArticle E- and Z-Isomers of New Phytoecdysteroid Conjugates from French Polynesian Microsorum membranifolium (Polypodiaceae) Fronds
Molecules 2012, 17(10), 11598-11606; doi:10.3390/molecules171011598
Received: 29 August 2012 / Revised: 21 September 2012 / Accepted: 24 September 2012 / Published: 28 September 2012
PDF Full-text (234 KB)
Abstract
Phytochemical investigation of the fronds of Microsorum membranifolium resulted in the isolation of a new phytoecdysteroid, E-2-deoxy-20-hydroxyecdysone 3-[4-(1-b-D-glucopyranosyl)]-caffeate (1), together with two known phytoecdysteroids, E-2-deoxy-20-hydroxyecdysone 3-[4-(1-b-D-glucopyranosyl)]-ferulate (2), E-2-deoxyecdysone 3-[4-(1-b-D-glucopyranosyl)]-ferulate (3). Their respective Z [...] Read more.
Phytochemical investigation of the fronds of Microsorum membranifolium resulted in the isolation of a new phytoecdysteroid, E-2-deoxy-20-hydroxyecdysone 3-[4-(1-b-D-glucopyranosyl)]-caffeate (1), together with two known phytoecdysteroids, E-2-deoxy-20-hydroxyecdysone 3-[4-(1-b-D-glucopyranosyl)]-ferulate (2), E-2-deoxyecdysone 3-[4-(1-b-D-glucopyranosyl)]-ferulate (3). Their respective Z-isomers 46 were also observed and identified for the first time. The new structures were elucidated on the basis of extensive spectroscopic data analysis (1D, 2D-NMR and HR-MS techniques). Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Microwave Assisted Synthesis of 2,2'-Arylene-substituted Bis(4H-3,1-Benzoxazin-4-one) Derivatives Using the Complex Cyanuric Chloride/N,N-Dimethylformamide
Molecules 2012, 17(10), 11607-11615; doi:10.3390/molecules171011607
Received: 13 June 2012 / Revised: 13 September 2012 / Accepted: 24 September 2012 / Published: 28 September 2012
PDF Full-text (202 KB)
Abstract A new and efficient method has been designed to prepare 2,2'-arylene-substituted bis(4H-3,1-benzoxazin-4-one) derivatives by using the mixture of cyanuric chloride and N,N-dimethylformamide in a microwave-assisted reaction. The method used and presented here has good rate enhancement and excellent yields. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Synthesis and Antitumor Evaluation of 6-Aryl-substituted benzo[j]phenanthridine- and Benzo[g]pyrimido[4,5-c]isoquinolinequinones
Molecules 2012, 17(10), 11616-11629; doi:10.3390/molecules171011616
Received: 10 September 2012 / Revised: 23 September 2012 / Accepted: 25 September 2012 / Published: 28 September 2012
Cited by 5 | PDF Full-text (353 KB)
Abstract
A variety of novel 6-arylsubstituted benzo[j]phenanthridine- and benzo[g]-pyrimido[4,5-c]isoquinolinequinones were synthesized from 1,4-naphthoquinone, aryl-aldehydes and enaminones via a two-step synthetic approach. The cytotoxic activity of the aminoquinone derivatives was evaluated in vitro against one normal cell line [...] Read more.
A variety of novel 6-arylsubstituted benzo[j]phenanthridine- and benzo[g]-pyrimido[4,5-c]isoquinolinequinones were synthesized from 1,4-naphthoquinone, aryl-aldehydes and enaminones via a two-step synthetic approach. The cytotoxic activity of the aminoquinone derivatives was evaluated in vitro against one normal cell line (MRC-5 lung fibroblasts) and three human cancer cell lines (AGS human gastric adenocarcinoma; SK-MES-1 human lung cancer cells, and J82 human bladder carcinoma) in 72-h drug exposure assays using the MTT colorimetric method. Structure–activity relationships within the series of angular quinones reveal that the insertion of pyrrol-2-yl and furan-2-yl groups at the 6-position is more significant for the increase of the potency and selectivity index of the pharmacophores. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Degradation Kinetics of Anthocyanins from European Cranberrybush (Viburnum opulus L.) Fruit Extracts. Effects of Temperature, pH and Storage Solvent
Molecules 2012, 17(10), 11655-11666; doi:10.3390/molecules171011655
Received: 20 August 2012 / Revised: 20 September 2012 / Accepted: 21 September 2012 / Published: 28 September 2012
Cited by 13 | PDF Full-text (256 KB)
Abstract
European cranberrybush (Viburnum opulus L.) fruits are well known for their biological properties, of which some are due to the presence of anthocyanins in the berries. Current literature provides little information concerning these fruits. The stability of anthocyanins from Viburnum opulus [...] Read more.
European cranberrybush (Viburnum opulus L.) fruits are well known for their biological properties, of which some are due to the presence of anthocyanins in the berries. Current literature provides little information concerning these fruits. The stability of anthocyanins from Viburnum opulus fruits, in aqueous and ethanolic extracts, stored under darkness for 7 days at different temperatures (2 °C, 37 °C and 75 °C) and pH values (pH = 3 and 7), was studied here. The lowest stability was showed by the anthocyanins from the water extract stored at 75 °C and pH = 7, with half-life and constant rate values of 1.98 h and 0.3488 h−1, respectively. The results showed a good correlation between the total anthocyanin content (determined using the pH differential method) and the time of storage, with determination coefficients varying from R2 = 0.9298 to R2 = 0.9971. Results indicate that the storage degradation of anthocyanins followed first-order reaction kinetics under all investigated conditions. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Study of Active Ingredients in Black Soybean Sprouts and Their Safety in Cosmetic Use
Molecules 2012, 17(10), 11669-11679; doi:10.3390/molecules171011669
Received: 10 July 2012 / Revised: 13 September 2012 / Accepted: 19 September 2012 / Published: 1 October 2012
Cited by 3 | PDF Full-text (335 KB)
Abstract
Active ingredients in different lengths of black soybean sprouts were extracted with water. Concentrations of the main proteins and polysaccharides were determined by the Forint phenol assay and phenol-sulfuric acid assay, respectively. Anti-oxidizing capacities of the extracts were measured in vitro using [...] Read more.
Active ingredients in different lengths of black soybean sprouts were extracted with water. Concentrations of the main proteins and polysaccharides were determined by the Forint phenol assay and phenol-sulfuric acid assay, respectively. Anti-oxidizing capacities of the extracts were measured in vitro using the DPPH scavenging test and whitening capacity was measured in vitro using the tyrosinase inhibition test. The effects of the bean sprout extracts on human skin fibroblasts damnified by H2O2 were studied using an MTT colorimetric assay. The safety of the extracts was determined using the red blood cell (RBC) test, chick chorioallantoic membrane (CAM) assay and human patch test. Results show that DPPH radical scavenging rates at different shoot lengths were all greater than 95%, while the tyrosinase inhibition capacity of the extracts reached 98%. Hemolysis rate in all extracts were lower than 10%, below the 20% regulatory limit for the RBC test. No signs of allergic reactions were observed in the human patch tests. The optimum extract was obtained from bean sprouts grown to 0.5 cm. Extracts of black bean sprouts are safe and can be used as additives in anti-aging and whitening cosmetic products. Full article
Open AccessArticle Cytoprotective Effects of β-Melanocortin in the Rat Gastrointestinal Tract
Molecules 2012, 17(10), 11680-11692; doi:10.3390/molecules171011680
Received: 1 August 2012 / Revised: 19 September 2012 / Accepted: 26 September 2012 / Published: 1 October 2012
PDF Full-text (1447 KB)
Abstract
Recently discovered anti-inflammatory and immunomodulatory properties of melanocortin peptides led to the conclusion that they might serve as new anti-inflammatory therapeutics. The purpose of this work was to examine the effectiveness of β-melanocortin (β-MSH) in two experimental models: ethanol-induced gastric lesions and [...] Read more.
Recently discovered anti-inflammatory and immunomodulatory properties of melanocortin peptides led to the conclusion that they might serve as new anti-inflammatory therapeutics. The purpose of this work was to examine the effectiveness of β-melanocortin (β-MSH) in two experimental models: ethanol-induced gastric lesions and TNBS (2,4,6-trinitrobenzenesulfonic acid)-induced colitis in male Wistar rats. Three progressive doses of β-MSH were used: 0.125, 0.250 and 0.500 mg/kg. Our results suggest that β-MSH acts as a protective substance in the gastric lesions model, which can be seen as a statistically significant reduction of hemorrhagic lesions at all three doses, compared to the control group. The most efficient dose was 0.250 mg/kg. Statistically significant reduction in mucosal surface affected by necrosis and the reduction of overall degree of inflammation in the colitis model indicates an anti-inflammatory effect of β-MSH at a dose of 0.250 mg/kg. The results justify further research on β-MSH peptide and its derivates in the inflammatory gastrointestinal diseases, and point out the possibility of using β-MSH in studies of digestive system pharmacology. Full article
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Open AccessArticle Synthetic Flavanones Augment the Anticancer Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)
Molecules 2012, 17(10), 11693-11711; doi:10.3390/molecules171011693
Received: 31 July 2012 / Revised: 3 September 2012 / Accepted: 24 September 2012 / Published: 1 October 2012
Cited by 8 | PDF Full-text (525 KB) | HTML Full-text | XML Full-text
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered as the most promising anticancer agent in the TNF superfamily because of its selective cytotoxicity against tumor cells versus normal primary cells. However, as more tumor cells are reported to be resistant to TRAIL-mediated [...] Read more.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered as the most promising anticancer agent in the TNF superfamily because of its selective cytotoxicity against tumor cells versus normal primary cells. However, as more tumor cells are reported to be resistant to TRAIL-mediated death, it is important to develop new therapeutic strategies to overcome this resistance. Flavonoids have been shown to sensitize cancer cells to TRAIL-induced apoptosis. The aim of this study was to examine the cytotoxic and apoptotic activities of TRAIL on HeLa cancer cells in combination with two synthetic compounds: 6-hydroxyflavanone (6-HF) and its derivative 6-propionoxy-flavanone (6-PF) and to determine the mechanism by which the flavanones overcome the TRAIL-resistance. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected by annexin V-FITC fluorescence staining in flow cytometry and microscopy. Death receptor (TRAIL-R1/DR4 and TRAIL-R2/DR5) expression were analysed using flow cytometry. Mitochondrial membrane potential was evaluated using DePsipher staining by fluorescence microscopy. The synthetic flavanones enhanced TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2 death receptor and reduction of mitochondrial membrane potential. Our study indicates that the 6-HF and 6-PF augmented the anticancer effects of TRAIL and confirm a potential use of flavanones in TRAIL-based anticancer therapy and prevention. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Identification of Three New N-Demethylated and O-Demethyled Bisbenzylisoquinoline Alkaloid Metabolites of Isoliensinine from Dog Hepatic Microsomes
Molecules 2012, 17(10), 11712-11720; doi:10.3390/molecules171011712
Received: 20 August 2012 / Revised: 24 September 2012 / Accepted: 26 September 2012 / Published: 1 October 2012
Cited by 2 | PDF Full-text (215 KB) | HTML Full-text | XML Full-text
Abstract
Isoliensinine, a natural phenolic bisbenzyltetrahydroisoquinoline alkaloid, has received considerable attention for its potential biological effects such as antioxidant and anti-HIV activities. From the dog hepatic microsomes of isoliensinine, three new N-demethylated and O-demethylated metabolites, 2-N-desmethyl-isoliensinine (M1), [...] Read more.
Isoliensinine, a natural phenolic bisbenzyltetrahydroisoquinoline alkaloid, has received considerable attention for its potential biological effects such as antioxidant and anti-HIV activities. From the dog hepatic microsomes of isoliensinine, three new N-demethylated and O-demethylated metabolites, 2-N-desmethyl-isoliensinine (M1), 2'-N-desmethylisoliensinine (M2), and 2'-N-6-O-didesmethylisoliensinine (M3), were identified by high-performance liquid chromatography and data-dependent electrospray ionization tandem mass spectrometry. Possible metabolic pathways for isoliensinine have been proposed. The result should prove very helpful for evaluation of the drug-like properties of isoliensinine and other bisbenzylisoquinoline alkaloids. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle A New Saponin from Tea Seed Pomace (Camellia oleifera Abel) and Its Protective Effect on PC12 Cells
Molecules 2012, 17(10), 11721-11728; doi:10.3390/molecules171011721
Received: 31 August 2012 / Revised: 24 September 2012 / Accepted: 24 September 2012 / Published: 1 October 2012
Cited by 15 | PDF Full-text (217 KB)
Abstract
A new triterpenoid saponin, oleiferasaponin A1, was isolated from tea seed pomace (Camellia oleifera Abel). The structure of oleiferasaponin A1 was elucidated on the basis of chemical and physicochemical evidence and was found to be 22-O- [...] Read more.
A new triterpenoid saponin, oleiferasaponin A1, was isolated from tea seed pomace (Camellia oleifera Abel). The structure of oleiferasaponin A1 was elucidated on the basis of chemical and physicochemical evidence and was found to be 22-O-cis-2-hexenoyl-A1-barrigenol 3-O-[β-D-galactopyranosyl(1→2)] [β-D-glucopyranosyl(1→2)-α-L-arabinopyranosyl(1→3)]-β-D-glucopyranosiduronic acid. PC12 cells injured with H2O2 were used as the model to test the protective effects of oleiferasaponin A1. The results indicated that oleiferasaponin A1 can potentially prevent the H2O2-induced cell death of PC12 cells. Full article
(This article belongs to the Special Issue Triterpenes and Triterpenoids)
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Open AccessArticle Mechanical, Thermal and Morphological Properties of Poly(lactic acid)/Epoxidized Palm Olein Blend
Molecules 2012, 17(10), 11729-11747; doi:10.3390/molecules171011729
Received: 10 June 2012 / Revised: 1 October 2012 / Accepted: 5 October 2012 / Published: 8 October 2012
Cited by 22 | PDF Full-text (919 KB)
Abstract
Poly(lactic acid) (PLA) is known to be a useful material in substituting the conventional petroleum-based polymer used in packaging, due to its biodegradability and high mechanical strength. Despite the excellent properties of PLA, low flexibility has limited the application of this material. [...] Read more.
Poly(lactic acid) (PLA) is known to be a useful material in substituting the conventional petroleum-based polymer used in packaging, due to its biodegradability and high mechanical strength. Despite the excellent properties of PLA, low flexibility has limited the application of this material. Thus, epoxidized palm olein (EPO) was incorporated into PLA at different loadings (1, 2, 3, 4 and 5 wt%) through the melt blending technique and the product was characterized. The addition of EPO resulted in a decrease in glass transition temperature and an increase of elongation-at-break, which indicates an increase in the PLA chain mobility. PLA/EPO blends also exhibited higher thermal stability than neat PLA. Further, the PLA/1 wt% EPO blend showed enhancement in the tensile, flexural and impact properties. This is due to improved interaction in the blend producing good compatible morphologies, which can be revealed by Scanning Electron Microscopy (SEM) analysis. Therefore, PLA can be efficiently plasticized by EPO and the feasibility of its use as flexible film for food packaging should be considered. Full article
Open AccessArticle Optimization of Ultrasound-Assisted Extraction of Crude Oil from Winter Melon (Benincasa hispida) Seed Using Response Surface Methodology and Evaluation of Its Antioxidant Activity, Total Phenolic Content and Fatty Acid Composition
Molecules 2012, 17(10), 11748-11762; doi:10.3390/molecules171011748
Received: 27 August 2012 / Revised: 4 September 2012 / Accepted: 11 September 2012 / Published: 8 October 2012
Cited by 18 | PDF Full-text (2045 KB)
Abstract
In the present study, ultrasound-assisted extraction of crude oil from winter melon seeds was investigated through response surface methodology (RSM). Process variables were power level (25–75%), temperature (45–55 °C) and sonication time (20–40 min). It was found that all process variables have significant (p < 0.05) effects on the response variable. A central composite design (CCD) was used to determine the optimum process conditions. Optimal conditions were identified as 65% power level, 52 °C temperature and 36 min sonication time for maximum crude yield (108.62 mg-extract/g-dried matter). The antioxidant activity, total phenolic content and fatty acid composition of extract obtained under optimized conditions were determined and compared with those of oil obtained by the Soxhlet method. It was found that crude extract yield (CEY) of ultrasound-assisted extraction was lower than that of the Soxhlet method, whereas antioxidant activity and total phenolic content of the extract obtained by ultrasound-assisted extraction were clearly higher than those of the Soxhlet extract. Furthermore, both extracts were rich in unsaturated fatty acids. The major fatty acids of the both extracts were linoleic acid and oleic acid. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Structural Diversity of Streptococcal Mutans Synthesized under Different Culture and Environmental Conditions and Its Effect on Mutanase Synthesis
Molecules 2012, 17(10), 11800-11815; doi:10.3390/molecules171011800
Received: 14 August 2012 / Revised: 27 September 2012 / Accepted: 28 September 2012 / Published: 9 October 2012
Cited by 3 | PDF Full-text (271 KB) | HTML Full-text | XML Full-text
Abstract
Streptococcal mutans synthesized under different conditions by growing cultures or by their glucosyltransferases were shown to exhibit a great structural and property diversity. Culturing and environmental factors causing structural differences in mutans were specified. All of the obtained biopolymers (76 samples) were [...] Read more.
Streptococcal mutans synthesized under different conditions by growing cultures or by their glucosyltransferases were shown to exhibit a great structural and property diversity. Culturing and environmental factors causing structural differences in mutans were specified. All of the obtained biopolymers (76 samples) were water-insoluble and most of them (72) had a structure with a predominance of α-(1→3)-linked glucose (i.e., the content of α-(1→3)-linkages in the glucan was always higher than 50%, but did not exceed 76%). An exception were four glucans containing more than 50% of α-(1→6)-sequences. In these structurally unique mutans, the ratio of α-(1→3)- to α-(1→6)-bonds ranged from 0.75 to 0.97. Aside from one polymer, all others had a heavily branched structures and differed in the number of α-(1→3), α-(1→6), and α-(1→3,6) linkages and their mutual proportion. The induction of mutanase production in shaken flask cultures of Trichoderma harzianum by the structurally diverse mutans resulted in enzyme activities ranging from 0.144 to 1.051 U/mL. No statistical correlation was found between the total percentage content of α-(1→3)-linkages in the α-glucan and mutanase activity. Thus, despite biosynthetic differences causing structural variation in the mutans, it did not matter which mutan structures were used to induce mutanase production. Full article
Open AccessArticle Inhibitory Effects of Resveratrol Analogs on Mushroom Tyrosinase Activity
Molecules 2012, 17(10), 11816-11825; doi:10.3390/molecules171011816
Received: 26 July 2012 / Revised: 28 September 2012 / Accepted: 30 September 2012 / Published: 9 October 2012
Cited by 16 | PDF Full-text (240 KB) | HTML Full-text | XML Full-text
Abstract
Skin pigmentation disorders typically involve an overproduction or uneven distribution of melanin, which results in skin spots. Resveratrol can inhibit tyrosinase, the active enzyme in the synthesis of melanin, but it does not inhibit the synthesis of melanin to an extent that [...] Read more.
Skin pigmentation disorders typically involve an overproduction or uneven distribution of melanin, which results in skin spots. Resveratrol can inhibit tyrosinase, the active enzyme in the synthesis of melanin, but it does not inhibit the synthesis of melanin to an extent that enables its use alone as a skin whitening agent in pharmaceutical formulations, so its use as a coadjuvant in treatment of hyperpigmentation is suggested. Six resveratrol analogs were tested for tyrosinase inhibitory activity in vitro. Among the analogs tested, compound D was the most powerful tyrosinase inhibitor (IC50 = 28.66 µg/mL), two times more active than resveratrol (IC50 = 57.05 µg/mL), followed by the analogs A, E, B, F and C, respectively. This demonstrated that the hydroxylation at C4' on the phenolic ring was the molecular modification with most importance for the observed activity. Full article
(This article belongs to the Special Issue Antioxidants 2012)
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Open AccessArticle Inhibition of 11b-HSD1 by Tetracyclic Triterpenoids from Euphorbia kansui
Molecules 2012, 17(10), 11826-11838; doi:10.3390/molecules171011826
Received: 6 August 2012 / Revised: 13 September 2012 / Accepted: 18 September 2012 / Published: 9 October 2012
Cited by 4 | PDF Full-text (1631 KB) | HTML Full-text | XML Full-text
Abstract
The roots of Euphorbia kansui are considered an important traditional folk medicine. In this study the ethanol extracts of E. kansui were investigated. A new tetracyclic triterpenoid, euphane-3b,20-dihydroxy-24-ene, in addition to five known triterpenoids with euphane skeletons were isolated. Their structures were [...] Read more.
The roots of Euphorbia kansui are considered an important traditional folk medicine. In this study the ethanol extracts of E. kansui were investigated. A new tetracyclic triterpenoid, euphane-3b,20-dihydroxy-24-ene, in addition to five known triterpenoids with euphane skeletons were isolated. Their structures were elucidated on the basis of physical and spectral techniques (1D-, 2D-NMR and MS, respectively). Furthermore, these compounds 16 exhibited strong inhibitory activity against human 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1), with IC50 values of 34.86 nM, 1.115 mM, 16.08 nM, 2.815 nM, 26.47 nM, 15.99 nM, and 41.86 nM, respectively. The docking results show that the ring part of compounds can insert into the hydrophobic core of h11b-HSD1 and the alkane chain orientates toward the outside. The results presented herein provide a scientific explanation for the usage of the E. kansui in clinical treatment of diabetes. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle 10-Acetylirciformonin B, A Sponge Furanoterpenoid, Induces DNA Damage and Apoptosis in Leukemia Cells
Molecules 2012, 17(10), 11839-11848; doi:10.3390/molecules171011839
Received: 1 August 2012 / Revised: 16 August 2012 / Accepted: 14 September 2012 / Published: 9 October 2012
Cited by 7 | PDF Full-text (513 KB)
Abstract
10-Acetylirciformonin B, a furanoterpenoid derived from irciformonin B found in a marine sponge, has been reported to possess potent cytotoxic activity against several cancer cell lines. However, the mechanism of its apoptotic activity against human leukemia cells has never been reported. The [...] Read more.
10-Acetylirciformonin B, a furanoterpenoid derived from irciformonin B found in a marine sponge, has been reported to possess potent cytotoxic activity against several cancer cell lines. However, the mechanism of its apoptotic activity against human leukemia cells has never been reported. The purpose of this study was to investigate the cytotoxic effects of 10-acetylirciformonin B and its possible mechanism of action against leukemia HL 60 cells. We found that 10-acetylirciformonin B decreased cell viability through the inhibition of cell growth as well as the induction of DNA damage and apoptosis in a dose-dependent manner. The induction of DNA damage was mediated by the increase of p-CHK2 and γ-H2A.X, which was suggested from the increase of tail movement in the neutral Comet assay. Induction of apoptosis was mediated with the increase in caspases 8, 9 and 3 activation as well as PARP cleavage. In summary, our resultsindicate that 10-acetylirciformonin B treatment causes apoptosis in leukaemia cells; probably through a caspase-dependent regulatory pathway. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle A Practical Synthesis of Betulonic Acid Using Selective Oxidation of Betulin on Aluminium Solid Support
Molecules 2012, 17(10), 11849-11863; doi:10.3390/molecules171011849
Received: 10 August 2012 / Revised: 23 September 2012 / Accepted: 24 September 2012 / Published: 9 October 2012
Cited by 9 | PDF Full-text (311 KB)
Abstract
The room temperature oxidation of betulin by Cr(VI) compounds in aqueous acetone on solid supports such as alumina, zeolites and silica gel has been studied. The oxidation on alumina support leaded to a single product—betulonic acid—in quantitative yield. One hundred percent selective [...] Read more.
The room temperature oxidation of betulin by Cr(VI) compounds in aqueous acetone on solid supports such as alumina, zeolites and silica gel has been studied. The oxidation on alumina support leaded to a single product—betulonic acid—in quantitative yield. One hundred percent selective oxidation during 30 min of betulin up to betulonic aldehyde was determined when silica gel support was used. The oxidation of betulin using zeolites as a support gives a mixture of betulonic acid and aldehyde in a 2:1 ratio. It is proposed the selective oxidation up to betulonic acid is due to the influence of Al3+-ions. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Pumpkin (Cucurbita moschata) Fruit Extract Improves Physical Fatigue and Exercise Performance in Mice
Molecules 2012, 17(10), 11864-11876; doi:10.3390/molecules171011864
Received: 6 August 2012 / Revised: 8 September 2012 / Accepted: 8 October 2012 / Published: 9 October 2012
Cited by 20 | PDF Full-text (2445 KB)
Abstract
Pumpkin (Cucurbita moschata) is a popular and nutritious vegetable consumed worldwide. The overall purpose of this study was to evaluate the effects of C. moschata fruit extract (CME) on anti-fatigue and ergogenic functions following physiological challenges. Male ICR mice from [...] Read more.
Pumpkin (Cucurbita moschata) is a popular and nutritious vegetable consumed worldwide. The overall purpose of this study was to evaluate the effects of C. moschata fruit extract (CME) on anti-fatigue and ergogenic functions following physiological challenges. Male ICR mice from four groups designated vehicle, CME-50, CME-100 and CME-250, respectively (n = 8 per group in each test) were orally administered CME for 14 days at 0, 50, 100 and 250 mg/kg/day. The anti-fatigue activity and exercise performance were evaluated using exhaustive swimming time, forelimb grip strength, as well as levels of plasma lactate, ammonia, glucose, and creatine kinase after an acute swimming exercise. The resting muscular and hepatic glycogen was also analyzed after 14-day supplementation with CME. Trend analysis revealed that CME treatments increased grip strength. CME dose-dependently increased 5% body weight loaded swimming time, blood glucose, and muscular and hepatic glycogen levels. CME dose-dependently decreased plasma lactate and ammonia levels and creatine kinase activity after a 15-min swimming test. The mechanism was relevant to the increase in energy storage (as glycogen) and release (as blood glucose), and the decrease of plasma levels of lactate, ammonia, and creatine kinase. Therefore, CME may be potential for the pharmacological effect of anti-fatigue. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Syntheses of Sulfo-Glycodendrimers Using Click Chemistry and Their Biological Evaluation
Molecules 2012, 17(10), 11877-11896; doi:10.3390/molecules171011877
Received: 23 July 2012 / Revised: 5 September 2012 / Accepted: 18 September 2012 / Published: 9 October 2012
Cited by 5 | PDF Full-text (839 KB) | HTML Full-text | XML Full-text
Abstract
A series of novel glycol-clusters containing sulfonated N-acetyl-D-glucosamine (GlcNAc) have been synthesized using click chemistry. Three dendrimers with aromatic dendrons were synthesized using chlorination, azidation and click chemistries. The resulting dendrimers were modified with azide-terminated sulfonated GlcNAc using click chemistry. The [...] Read more.
A series of novel glycol-clusters containing sulfonated N-acetyl-D-glucosamine (GlcNAc) have been synthesized using click chemistry. Three dendrimers with aromatic dendrons were synthesized using chlorination, azidation and click chemistries. The resulting dendrimers were modified with azide-terminated sulfonated GlcNAc using click chemistry. The sulfonated dendrimers showed affinity for proteins, including the lectin wheat germ agglutinin and amyloid beta peptide (1-42). The dendrimers of G1 and G2 in particular showed the largest affinity for the proteins. The addition of the sulfonated GlcNAc dendrimers of G1 and G2 exhibited an inhibition effect on the aggregation of the amyloid beta peptide, reduced the b-sheet conformation, and led to a reduction in the level of nanofiber formation. Full article
(This article belongs to the Special Issue Advances in Carbohydrate Chemistry 2012)
Open AccessArticle Evaluation of the Antioxidant and Anti-glication Effects of the Hexane Extract from Piper auritum Leaves in Vitro and Beneficial Activity on Oxidative Stress and Advanced Glycation End-Product-Mediated Renal Injury in Streptozotocin-Treated Diabetic Rats
Molecules 2012, 17(10), 11897-11919; doi:10.3390/molecules171011897
Received: 15 September 2012 / Revised: 21 September 2012 / Accepted: 7 October 2012 / Published: 9 October 2012
Cited by 11 | PDF Full-text (377 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to investigate the antioxidant activity of hexane extracts from leaves of Piper auritum (HS). Eight complementary in vitro test methods were used, including inhibition of DPPH· radicals, nitric oxide, superoxide anion, ion-chelating, ABTS, oxygen radical absorbance [...] Read more.
The aim of this study was to investigate the antioxidant activity of hexane extracts from leaves of Piper auritum (HS). Eight complementary in vitro test methods were used, including inhibition of DPPH· radicals, nitric oxide, superoxide anion, ion-chelating, ABTS, oxygen radical absorbance capacity, β-carotene bleaching and peroxy radical scavenging. The results indicated that HS possesses high antioxidant activity. To add to these finding we tested the effect against oxidative stress in liver, pancreas and kidney in diabetic rats. Low levels of SOD, CAT, GPx and GSH in diabetic rats were reverted to near normal values after treatment with HS. These results suggest that P. auritum prevents oxidative stress, acting as a suppressor of liver cell damage. Given the link between glycation and oxidation, we proposed that HS might possess significant in vitro antiglycation activity. Our data confirmed the inhibitory effect of HS on bovine serum albumin, serum glycosylated protein, glycation of LDL, and glycation hemoglobin. The effect of HS on diabetic renal damage was investigated using streptozotocin-induced diabetic rats. The oral administration of HS at a dose of 200 and 400 mg/kg body weight/day for 28 days significantly reduced advanced glycation endproduct (AGE) formation, elevated renal glucose and thiobarbituric acid-reactive substance levels in the kidneys of diabetic rats. This implies that HS would alleviate the oxidative stress under diabetes through the inhibition of lipid peroxidation. These findings indicate that oxidative stress is increased in the diabetic rat kidney and that HS can prevent renal damage associated with diabetes by attenuating the oxidative stress. Full article
(This article belongs to the Special Issue Antioxidants 2012)
Open AccessArticle trans-Caryophyllene, a Natural Sesquiterpene, Causes Tracheal Smooth Muscle Relaxation through Blockade of Voltage-Dependent Ca2+ Channels
Molecules 2012, 17(10), 11965-11977; doi:10.3390/molecules171011965
Received: 10 July 2012 / Revised: 19 September 2012 / Accepted: 5 October 2012 / Published: 11 October 2012
Cited by 2 | PDF Full-text (690 KB)
Abstract
trans-Caryophyllene is a major component in the essential oils of various species of medicinal plants used in popular medicine in Brazil. It belongs to the chemical class of the sesquiterpenes and has been the subject of a number of studies. Here, [...] Read more.
trans-Caryophyllene is a major component in the essential oils of various species of medicinal plants used in popular medicine in Brazil. It belongs to the chemical class of the sesquiterpenes and has been the subject of a number of studies. Here, we evaluated the effects of this compound in airway smooth muscle. The biological activities of trans-caryophyllene were examined in isolated bath organs to investigate the effect in basal tonus. Electromechanical and pharmacomechanical couplings were evaluated through the responses to K+ depolarization and exposure to acetylcholine (ACh), respectively. Isolated cells of rat tracheal smooth muscle were used to investigate trans-caryophyllene effects on voltage-dependent Ca2+ channels by using the whole-cell voltage-clamp configuration of the patch-clamp technique. trans-Caryophyllene showed more efficiency in the blockade of electromechanical excitation-contraction coupling while it has only minor inhibitory effect on pharmacomechanical coupling. Epithelium removal does not modify tracheal smooth muscle response elicited by trans-caryophyllene in the pharmacomechanical coupling. Under Ca2+-free conditions, pre-exposure to trans-caryophyllene did not reduce the contraction induced by ACh in isolated rat tracheal smooth muscle, regardless of the presence of intact epithelium. In the whole-cell configuration, trans-caryophyllene (3 mM), inhibited the inward Ba2+ current (IBa) to approximately 50% of control levels. Altogether, our results demonstrate that trans-caryophyllene has anti-spasmodic activity on rat tracheal smooth muscle which could be explained, at least in part, by the voltage-dependent Ca2+ channels blockade. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle The Binding Affinity and Molecular Basis of the Structure-Binding Relationship between Urinary Tamm-Horsfall Glycoprotein and Tumor Necrosis Factor-α
Molecules 2012, 17(10), 11978-11989; doi:10.3390/molecules171011978
Received: 13 July 2012 / Revised: 26 September 2012 / Accepted: 8 October 2012 / Published: 11 October 2012
Cited by 3 | PDF Full-text (936 KB) | HTML Full-text | XML Full-text
Abstract
In a previous study we noted significant THP binding to TNF-α, but did not explore the molecular basis of the structure-binding relationship. In this study, we used lectin-binding ELISA to assess the carbohydrate compositions of THP, BSA, IgG, TNF-α, and IFN-g. We [...] Read more.
In a previous study we noted significant THP binding to TNF-α, but did not explore the molecular basis of the structure-binding relationship. In this study, we used lectin-binding ELISA to assess the carbohydrate compositions of THP, BSA, IgG, TNF-α, and IFN-g. We identified β(1,4)-N-acetylglucosamine oligomers (GlcNAc) and GlcNAc/branched mannose in BSA, IgG, TNF-α, and THP, but not in IFN-g. These carbohydrate moieties mediated binding with THP. Small amounts of Siaα(2,3)Gal/ GalNAc, Sia(2,6)Gal/GalNAc, and mannose residues were also present in THP and TNF-α. Binding affinity (Kd) between THP and TNF-α by Scatchard plot analysis was 1.4–1.7 × 10−6 M, lower than antigen-antibody or ligand-receptor binding affinities. To elucidate the structure-binding relationship of THP-TNF-α, THP was digested with neuraminidase, β-galactosidase, O-sialoglycoprotein endopeptidase, carboxypeptidase Y, or proteinase K. β-galactosidase increased binding capacity of THP for TNF-α. Monosaccharide inhibition suggested that α-methyl-D-mannoside, GlcNAc, and GalNAc, but not sialic acid, suppress THP-TNF-α binding as detected by ELISA. We conclude that sugar-lectin and sugar-protein interactions between cognate sites in THP and TNF-α mediate their binding. Full article
(This article belongs to the Special Issue Advances in Carbohydrate Chemistry 2012)
Open AccessArticle In Vitro and in Vivo Metabolism of Verproside in Rats
Molecules 2012, 17(10), 11990-12002; doi:10.3390/molecules171011990
Received: 3 September 2012 / Revised: 28 September 2012 / Accepted: 8 October 2012 / Published: 12 October 2012
Cited by 4 | PDF Full-text (634 KB) | HTML Full-text | XML Full-text
Abstract
Verproside, a catalpol derivative iridoid glycoside isolated from Pseudolysimachion rotundum var. subintegrum, is a biologically active compound with anti-inflammatory, antinociceptic, antioxidant, and anti-asthmatic properties. Twenty-one metabolites were identified in bile and urine samples obtained after intravenous administration of verproside in rats using liquid chromatography-quadrupole Orbitrap mass spectrometry. Verproside was metabolized by O-methylation, glucuronidation, sulfation, and hydrolysis to verproside glucuronides (M1 and M2), verproside sulfates (M3 and M4), picroside II (M5), M5 glucuronide (M7), M5 sulfate (M9), isovanilloylcatalpol (M6), M6 glucuronide (M8), M6 sulfate (M10), 3,4-dihydroxybenzoic acid (M11), M11 glucuronide (M12), M11 sulfates (M13 and M14), 3-methyoxy-4-hydroxybenzoic acid (M15), M15 glucuronides (M17 and M18), M15 sulfate (M20), 3-hydroxy-4-methoxybenzoic acid (M16), M16 glucuronide (M19), and M16 sulfate (M21). Incubation of verproside with rat hepatocytes resulted in thirteen metabolites (M1–M11, M13, and M14). Verproside sulfate, M4 was a major metabolite in rat hepatocytes. After intravenous administration of verproside, the drug was recovered in bile (0.77% of dose) and urine (4.48% of dose), and O-methylation of verproside to picroside II (M5) and isovanilloylcatalpol (M6) followed by glucuronidation and sulfation was identified as major metabolic pathways compared to glucuronidation and sulfation of verproside in rats. Full article
(This article belongs to the Special Issue Active Pharmaceutical Ingredients)
Open AccessArticle Synthesis and Antiplasmodial Activity of Betulinic Acid and Ursolic Acid Analogues
Molecules 2012, 17(10), 12003-12014; doi:10.3390/molecules171012003
Received: 17 September 2012 / Revised: 24 September 2012 / Accepted: 7 October 2012 / Published: 12 October 2012
Cited by 19 | PDF Full-text (295 KB) | HTML Full-text | XML Full-text
Abstract
More than 40% of the World population is at risk of contracting malaria, which affects primarily poor populations in tropical and subtropical areas. Antimalarial pharmacotherapy has utilised plant-derived products such as quinine and artemisinin as well as their derivatives. However, worldwide use of these antimalarials has caused the spread of resistant parasites, resulting in increased malaria morbidity and mortality. Considering that the literature has demonstrated the antimalarial potential of triterpenes, specially betulinic acid (1) and ursolic acid (2), this study investigated the antimalarial activity against P. falciparum chloroquine-sensitive 3D7 strain of some new derivatives of 1 and 2 with modifications at C-3 and C-28. The antiplasmodial study employed flow cytometry and spectrofluorimetric analyses using YOYO-1, dihydroethidium and Fluo4/AM for staining. Among the six analogues obtained, compounds 1c and 2c showed excellent activity (IC50 = 220 and 175 nM, respectively) while 1a and b demonstrated good activity (IC50 = 4 and 5 μM, respectively). After cytotoxicity evaluation against HEK293T cells, 1a was not toxic, while 1c and 2c showed IC50 of 4 μM and a selectivity index (SI) value of 18 and 23, respectively. Moreover, compound 2c, which presents the best antiplasmodial activity, is involved in the calcium-regulated pathway(s). Full article
Open AccessArticle Nukuhivensiums, Indolo[2,3-a]quinoliziniums from the Marquesan Plant Rauvolfia nukuhivensis
Molecules 2012, 17(10), 12015-12022; doi:10.3390/molecules171012015
Received: 13 September 2012 / Revised: 7 October 2012 / Accepted: 9 October 2012 / Published: 12 October 2012
Cited by 7 | PDF Full-text (364 KB) | HTML Full-text | XML Full-text
Abstract
The first phytochemical inspection of the Marquesan endemic plant Rauvolfia nukuhivensis led to the isolation and structure characterization of two new indolo[2,3‑a]quinolizinium derivatives named nukuhivensium (1) and N12-methyl-nukuhivensium (2). They feature an aromatic indolo[2,3- [...] Read more.
The first phytochemical inspection of the Marquesan endemic plant Rauvolfia nukuhivensis led to the isolation and structure characterization of two new indolo[2,3‑a]quinolizinium derivatives named nukuhivensium (1) and N12-methyl-nukuhivensium (2). They feature an aromatic indolo[2,3-a]quinolizinium core, substituted at C-2 by a n-propyl group, which is unusual in this family of alkaloid derivatives. The structure elucidation was performed on the basis of NMR spectroscopy and especially by interpretation of 2D HMBC correlations. A biosynthetic pathway is proposed on the basis of known enzymatic transformations for this family of natural products. These compounds exhibited low antimicrobial activities. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synergistic Antibacterial Activity of the Essential Oil of Aguaribay (Schinus molle L.)
Molecules 2012, 17(10), 12023-12036; doi:10.3390/molecules171012023
Received: 10 August 2012 / Revised: 17 August 2012 / Accepted: 21 September 2012 / Published: 12 October 2012
Cited by 6 | PDF Full-text (234 KB) | HTML Full-text | XML Full-text
Abstract
Schinus molle L. (aguaribay, aroeira-falsa, “molle”, family Anacardiaceae), a native of South America, produces an active antibacterial essential oil extracted from the leaves and fruits. This work reports a complete study of its chemical composition and determines the antibacterial activity of Schinus molle L. essential oil and its main components. The results showed that the crude extract essential oil has a potent antibacterial effect on Staphylococcus aureus ATCC 25923, a strong/moderate effect on Escherichia coli ATCC 25922 and moderate/weak one on Pseudomonas aeruginosa ATCC 27853. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle MiR-15a Decreases Bovine Mammary Epithelial Cell Viability and Lactation and Regulates Growth Hormone Receptor Expression
Molecules 2012, 17(10), 12037-12048; doi:10.3390/molecules171012037
Received: 17 July 2012 / Revised: 24 August 2012 / Accepted: 25 September 2012 / Published: 12 October 2012
Cited by 20 | PDF Full-text (295 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate the expression of target genes at the post-transcriptional level by transcript degradation or translational inhibition. The role of bta-miR-15a in bovine mammary gland hasn’t been reported. Using miRNAs prediction software, GHR [...] Read more.
MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate the expression of target genes at the post-transcriptional level by transcript degradation or translational inhibition. The role of bta-miR-15a in bovine mammary gland hasn’t been reported. Using miRNAs prediction software, GHR gene was predicted to be a potential target of bta-miR-15a. In this study, bovine mammary epithelial cell line was used as an in vitro cell model to address the function of bta-miR-15a on bovine mammary epithelial cells. The expression changes of bta-miR-15a and Ghr after bta-miR-15a transfection were detected by qRT-PCR; the expression of GHR protein and casein was detected by western blotting. To determine whether bta-miR-15a can affect cell viability, cells were examined using an electronic Coulter counter (CASY-TT). In conclusion, bta-miR-15a inhibited the expression of casein of bovine mammary epithelial cells, and cell number and viability were reduced by bta-miR-15a expression. Bta-miR-15a inhibited the viability of mammary epithelial cells as well as the expression of GHR mRNA and protein level, therefore suggesting that bta-miR-15a may play an important role in mammary gland physiology. Full article
Open AccessArticle Identification of Insecticidal Constituents of the Essential Oil of Curcuma wenyujin Rhizomes Active against Liposcelis bostrychophila Badonnel
Molecules 2012, 17(10), 12049-12060; doi:10.3390/molecules171012049
Received: 7 August 2012 / Revised: 8 October 2012 / Accepted: 9 October 2012 / Published: 15 October 2012
Cited by 33 | PDF Full-text (208 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this research was to determine the chemical composition and insecticidal activity of the essential oil of Curcuma wenyujin Y.H. Chen et C. Ling rhizomes against the booklouse Liposcelis bostrychophila Badonnel and to isolate any insecticidal constituents from the essential oil. The essential oil of C. wenyujin rhizomes was obtained by hydrodistillation and analyzed by GC-MS. A total of 43 components of the essential oil were identified and the principal compounds in the essential oil were 1,8-cineole (15.26%), camphor (10.12%), germacrone (6.86%), β-elemene (6.33%), curzerene (6.70%), and β-elemenone (5.23%). followed by curzerenone (4.52%), curdione (4.45%) and linalool (4.43%). Based on bioactivity-guided fractionation, the two main active constituents were isolated from the essential oil and identified as 1,8-cineole and camphor. The essential oil of C. wenyujin rhizomes exhibited contact toxicity against L. bostrychophila with an LD50 value of 208.85 µg/cm2. Camphor (LD50 = 207.26 µg/cm2) exhibited stronger contact toxicity than 1,8-cineole (LD50 = 1048.75 µg/cm2) against booklouse. The essential oil of C. wenyujin (LC50 = 2.76 mg/L air) also possessed fumigant toxicity against L. bostrychophila, while the two constituents, camphor and 1,8-cineole had LC50 values of 1.03 mg/L air and 1.13 mg/L air, respectively. The results indicate that the essential oil of C. wenyujin rhizomes and its constituent compounds have potential for development as natural insecticides or fumigants for control of insects in stored grains. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Photophysical Study of 2′-Deoxyuridines Labeled with Fluorene Derivatives
Molecules 2012, 17(10), 12061-12071; doi:10.3390/molecules171012061
Received: 14 September 2012 / Revised: 3 October 2012 / Accepted: 10 October 2012 / Published: 15 October 2012
Cited by 7 | PDF Full-text (561 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We examined microenvironment-sensitive fluorescent 2′-deoxyuridines labeled with fluorene derivatives that exhibited solvent-dependent photophysical properties. The high sensitivity of the fluorescence shift and the nucleoside intensity dependence on solvent polarity provided information useful for estimating the polarity of the environment surrounding the fluorescent [...] Read more.
We examined microenvironment-sensitive fluorescent 2′-deoxyuridines labeled with fluorene derivatives that exhibited solvent-dependent photophysical properties. The high sensitivity of the fluorescence shift and the nucleoside intensity dependence on solvent polarity provided information useful for estimating the polarity of the environment surrounding the fluorescent nucleoside. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
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Open AccessArticle A Novel Class of Selective Acetylcholinesterase Inhibitors: Synthesis and Evaluation of (E)-2-(Benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles
Molecules 2012, 17(10), 12072-12085; doi:10.3390/molecules171012072
Received: 23 July 2012 / Revised: 30 August 2012 / Accepted: 17 September 2012 / Published: 15 October 2012
Cited by 11 | PDF Full-text (328 KB) | HTML Full-text | XML Full-text
Abstract
(E)-2-(benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles are described as a new class of selective inhibitors of acetylcholinesterase (AChE). The most potent compound in the series exhibited good AChE inhibitory activity (IC50 = 64 µM). Compound 7f was found to be more selective than galanthamine in inhibiting AChE and it showed a moderate selectivity index. Kinetic studies on AChE indicated that a competitive type of inhibition pattern exist for these acrylonitrile derivates. Molecular docking models of the ligand-AChE complexes suggest that compound 7g is located on the periphery of the AChE active site. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle c-IAP1 Binds and Processes PCSK9 Protein: Linking the c-IAP1 in a TNF-α Pathway to PCSK9-Mediated LDLR Degradation Pathway
Molecules 2012, 17(10), 12086-12101; doi:10.3390/molecules171012086
Received: 17 August 2012 / Revised: 8 October 2012 / Accepted: 9 October 2012 / Published: 15 October 2012
Cited by 7 | PDF Full-text (528 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Recent genetic studies have shown that PCSK9, one of the key genes in cholesterol metabolism, plays a critical role by controlling the level of low-density lipoprotein receptor. However, how PCSK9 mediates LDLR degradation is still unknown. By combining a shotgun proteomic method [...] Read more.
Recent genetic studies have shown that PCSK9, one of the key genes in cholesterol metabolism, plays a critical role by controlling the level of low-density lipoprotein receptor. However, how PCSK9 mediates LDLR degradation is still unknown. By combining a shotgun proteomic method and differential analysis of natural occurring mutations of the PCSK9 gene, we found that an E3 ubiquitin ligase c-IAP1 binds and processes PCSK9 protein. One of the ‘gain-of-function’ mutations, S127R, is defective with respect to binding to c-IAP1, and thus has defective autocatalytic activity. Knockdown of c-IAP1 impairs PCSK9 processing and autocatalytic cleavage. In c-IAP1 null mouse embryonic fibroblasts (MEFs), there is a dramatic decrease in secreted mature PCSK9 protein accompanied by a significant increase in LDLR protein levels compared with matched wild-type MEF cells. c-IAP1 also acts as an E3 ligase for ubiquitination of PCSK9. Ubiquitin containing only lysine-27 mediated PCSK9 ubiquitination by c-IAP1. Given K27-linked polyubiquitination promotes lysosomal localization, the finding indicates the c-IAP1 acts on both secretion of PCSK9 and its lysosomal localization. The novel pathway described here will open new avenues for exploring novel disease treatments. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Acetylated and Methylated β-Cyclodextrins as Viable Soluble Supports for the Synthesis of Short 2′-Oligodeoxyribo-nucleotides in Solution
Molecules 2012, 17(10), 12102-12120; doi:10.3390/molecules171012102
Received: 12 September 2012 / Revised: 12 October 2012 / Accepted: 12 October 2012 / Published: 16 October 2012
Cited by 6 | PDF Full-text (479 KB) | HTML Full-text | XML Full-text
Abstract
Novel soluble supports for oligonucleotide synthesis 11ac have been prepared by immobilizing a 5′-O-protected 3′-O-(hex-5-ynoyl)thymidine (6 or 7) to peracetylated or permethylated 6-deoxy-6-azido-β-cyclodextrins 10a or 10b by Cu(I)-promoted 1,3-dipolar cycloaddition. The applicability of the supports to oligonucleotide synthesis by the phosphoramidite strategy has been demonstrated by assembling a 3′-TTT-5′ trimer from commercially available 5′-O-(4,4′-dimethoxytrityl)thymidine 3′-phosphoramidite. To simplify the coupling cycle, the 5′-O-(4,4′-dimethoxytrityl) protecting group has been replaced with an acetal that upon acidolytic removal yields volatile products. For this purpose, 5′-O-(1-methoxy-1-methylethyl)-protected 3′-(2-cyanoethyl-N,N-diisopropyl-phosphoramidite)s of thymidine (5a), N4-benzoyl-2′-deoxycytidine (5b) and N6-benzoyl-2′-deoxyadenosine (5c) have been synthesized and utilized in synthesis of a pentameric oligonucleotide 3′-TTCAT-5′ on the permethylated cyclodextrin support 11c. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
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Open AccessArticle Suzuki-Miyaura Reactions Catalyzed by C2-Symmetric Pd-Multi-Dentate N-Heterocyclic Carbene Complexes
Molecules 2012, 17(10), 12121-12139; doi:10.3390/molecules171012121
Received: 20 September 2012 / Revised: 6 October 2012 / Accepted: 9 October 2012 / Published: 16 October 2012
Cited by 4 | PDF Full-text (390 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Suzuki-Miyaura coupling reactions are promoted by Pd complexes ligated with C2-symmetric multi-dentate N-heterocyclic carbenes derived in situ from Pd(OAc)2 and imidazolium salts. Good to excellent yields were obtained for aryl bromides as substrates. Turnover numbers of up to 105 could be achieved with 5 × 10−4 mol% of Pd(OAc)2/1 × 10−3 mol% NHC precatalyst in 24 h. Full article
Open AccessArticle Synthesis and Field Evaluation of the Sex Pheromone Analogues to Soybean Pod Borer Leguminivora glycinivorella
Molecules 2012, 17(10), 12140-12150; doi:10.3390/molecules171012140
Received: 4 September 2012 / Revised: 17 September 2012 / Accepted: 21 September 2012 / Published: 16 October 2012
Cited by 2 | PDF Full-text (246 KB) | HTML Full-text | XML Full-text
Abstract
In order to develop efficient lures for soybean pod borer Leguminivora glycinivorella (Matsumura) in China, (E,E)-8,10-dodecadienyl acetate (EE-8,10-12:Ac), the main component of the pheromone of L. glycinivorella, and 12 structurally-related compounds were synthesised in good overall yields, [...] Read more.
In order to develop efficient lures for soybean pod borer Leguminivora glycinivorella (Matsumura) in China, (E,E)-8,10-dodecadienyl acetate (EE-8,10-12:Ac), the main component of the pheromone of L. glycinivorella, and 12 structurally-related compounds were synthesised in good overall yields, regiospecificities, and stereo-selectivities via coupling reactions catalysed by Li2CuCl4. The effect of different synthetic compounds, alone or in combination with EE-8,10-12:Ac, on numbers of captured L. glycinivorella males was evaluated. EE-8,10-12:Ac, (E)-10-dodecenyl acetate (E-10-12:Ac), (E)-8-dodecenol (E-8-12:OH), tetradecyl acetate (14:Ac), and (Z)-9-tetradecenyl acetate (Z-9-14:Ac) alone displayed different attractiveness to L. glycinivorella males. 14:Ac, E-8-12:OH, E-10-12:Ac, (E,E)-8,10-dodecadienal (EE-8,10-12:Ald), (E)-8-dodecenal (E-8-12:Ald), (E)-10-dodecenal (E-10-12:Ald) and Z-9-14:Ac all showed a synergistic effect to EE-8,10-12:Ac at certain dosages. The binary mixtures of EE-8,10-12:Ac and E-10-12:Ald, Z-9-14:Ac,14:Ac, E-8-12:Ald, EE-8,10-12:Ald, E-8-12:OH, or E-10-12:Ac in suitable ratios give 17.00-, 10.98-, 10.67-, 6.73-, 5.54-, 4.30- and 4.50-fold increases in trap catch, respectively, over the standard pheromone lure, and as novel pheromone blends, demonstrated potential use in pheromone traps to monitor or control L. glycinivorella populations in China. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Side-chain Modifications of Highly Functionalized 3(2H)-Furanones
Molecules 2012, 17(10), 12151-12162; doi:10.3390/molecules171012151
Received: 29 August 2012 / Revised: 14 September 2012 / Accepted: 7 October 2012 / Published: 16 October 2012
Cited by 1 | PDF Full-text (234 KB) | Supplementary Files
Abstract
A series of 3(2H)-furanones, based on side-chain modifications of a parent 3(2H)-furanone, was synthesized in good yield. The parent compound was prepared by hydrogenolysis, and subsequent acid hydrolysis, of isoxazole derivatives. The isoxazole was prepared by a [3+2] [...] Read more.
A series of 3(2H)-furanones, based on side-chain modifications of a parent 3(2H)-furanone, was synthesized in good yield. The parent compound was prepared by hydrogenolysis, and subsequent acid hydrolysis, of isoxazole derivatives. The isoxazole was prepared by a [3+2] 1,3-dipolar cycloaddition reaction between 3-butyn-2-ol and nitrile oxide. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Synthesis and Characterization of New Thieno[3,2-b]thiophene Derivatives
Molecules 2012, 17(10), 12163-12171; doi:10.3390/molecules171012163
Received: 12 September 2012 / Revised: 5 October 2012 / Accepted: 12 October 2012 / Published: 16 October 2012
Cited by 6 | PDF Full-text (309 KB) | Supplementary Files
Abstract
Three derivatives of thieno[3,2-b]thiophene end-capped with phenyl units have been synthesized and characterized by MALDI TOF mass spectroscopy, elemental analysis, UV-vis absorption spectroscopy and thermogravimetric analysis (TGA). All compounds were prepared using Pd-catalyzed Stille or Suzuki coupling reactions. Optical measurements [...] Read more.
Three derivatives of thieno[3,2-b]thiophene end-capped with phenyl units have been synthesized and characterized by MALDI TOF mass spectroscopy, elemental analysis, UV-vis absorption spectroscopy and thermogravimetric analysis (TGA). All compounds were prepared using Pd-catalyzed Stille or Suzuki coupling reactions. Optical measurements and thermal analysis revealed that these compounds are promising candidates for p-type organic semiconductor applications. Full article
(This article belongs to the Special Issue Macromolecules: Chemistry, Medicinal and Functional Materials)
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Open AccessArticle Synthesis and Herbicidal Activity of Substituted Pyrazole Isothiocyanates
Molecules 2012, 17(10), 12187-12196; doi:10.3390/molecules171012187
Received: 29 August 2012 / Revised: 8 October 2012 / Accepted: 9 October 2012 / Published: 17 October 2012
Cited by 10 | PDF Full-text (182 KB) | HTML Full-text | XML Full-text
Abstract
Isothiocyanates and substituted pyrazoles were combined to form a series of novel isothiocyanates with highly effective herbicidal activity. The target compounds were analyzed by elemental analysis, 1H-NMR, EI-MS and IR spectroscopy. The synthesized compounds, particularly compounds 3-1 and 3 [...] Read more.
Isothiocyanates and substituted pyrazoles were combined to form a series of novel isothiocyanates with highly effective herbicidal activity. The target compounds were analyzed by elemental analysis, 1H-NMR, EI-MS and IR spectroscopy. The synthesized compounds, particularly compounds 3-1 and 3-7, exhibited good herbicidal activities against four weeds. The EC50 values of compound 3-1 against Echinochloa crusgalli L., Cyperus iria L., Dactylis glomerata L., and Trifolium repens L. were 64.32, 65.83, 62.42, and 67.72 µg/mL, respectively. The EC50 values of compound 3-7 against E. crusgalli L., C. iria L., D. glomerata L., T. repens L. were 65.33, 64.90, 59.41 and 67.41 µg/mL, respectively. Compounds 3-1 and 3-7 may be further optimized as lead compounds for new herbicides. Full article
Open AccessCommunication Bioactive Oleanane, Lupane and Ursane Triterpene Acid Derivatives
Molecules 2012, 17(10), 12197-12205; doi:10.3390/molecules171012197
Received: 14 September 2012 / Revised: 9 October 2012 / Accepted: 10 October 2012 / Published: 17 October 2012
Cited by 12 | PDF Full-text (194 KB) | HTML Full-text | XML Full-text
Abstract
Betulinic, ursolic and oleanolic acids isolated from the aerial parts of Eriope blanchetii (Lamiaceae) were subjected to different esterification reactions, yielding 12 C-3 position ester derivatives. All compounds were identified using spectroscopic techniques, such as IR, 1H-NMR and MS. The derivatives [...] Read more.
Betulinic, ursolic and oleanolic acids isolated from the aerial parts of Eriope blanchetii (Lamiaceae) were subjected to different esterification reactions, yielding 12 C-3 position ester derivatives. All compounds were identified using spectroscopic techniques, such as IR, 1H-NMR and MS. The derivatives were further investigated for their antioxidant level, Artemia salina lethality and antimicrobial activity. Full article
(This article belongs to the Special Issue Triterpenes and Triterpenoids)
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Open AccessArticle Discovery and Validation of SIRT2 Inhibitors Based on Tenovin-6: Use of a 1H-NMR Method to Assess Deacetylase Activity
Molecules 2012, 17(10), 12206-12224; doi:10.3390/molecules171012206
Received: 14 September 2012 / Revised: 21 September 2012 / Accepted: 15 October 2012 / Published: 18 October 2012
Cited by 3 | PDF Full-text (497 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The search for potent and selective sirtuin inhibitors continues as chemical tools of this type are of use in helping to assign the function of this interesting class of deacetylases. Here we describe SAR studies starting from the unselective sirtuin inhibitor tenovin-6. [...] Read more.
The search for potent and selective sirtuin inhibitors continues as chemical tools of this type are of use in helping to assign the function of this interesting class of deacetylases. Here we describe SAR studies starting from the unselective sirtuin inhibitor tenovin-6. These studies identify a sub-micromolar inhibitor that has increased selectivity for SIRT2 over SIRT1 compared to tenovin-6. In addition, a 1H-NMR-based method is developed and used to validate further this class of sirtuin inhibitors. A thermal shift analysis of SIRT2 in the presence of tenovin-6, -43, a control tenovin and the known SIRT2 inhibitor AGK2 is also presented. Full article
(This article belongs to the Special Issue Chemical Genetics)
Open AccessArticle Studies on 2-Arylhydrazononitriles: Synthesis of 3-Aryl-2-arylhydrazopropanenitriles and Their Utility as Precursors to 2-Substituted Indoles, 2-Substituted-1,2,3-Triazoles, and 1-Substituted Pyrazolo[4,3-d]pyrimidines
Molecules 2012, 17(10), 12225-12233; doi:10.3390/molecules171012225
Received: 27 August 2012 / Revised: 23 September 2012 / Accepted: 26 September 2012 / Published: 18 October 2012
Cited by 1 | PDF Full-text (190 KB) | HTML Full-text | XML Full-text
Abstract
Coupling of 2-benzylmalononitrile with aromatic diazonium salts afforded 3-phenyl-2-arylhydrazonopropanenitriles 4a,b, which were rearranged into 2-cyanoindoles 5a,b upon heating with ZnCl2 in the presence of glacial acetic acid. The produced indole derivatives 5a,b can be [...] Read more.
Coupling of 2-benzylmalononitrile with aromatic diazonium salts afforded 3-phenyl-2-arylhydrazonopropanenitriles 4a,b, which were rearranged into 2-cyanoindoles 5a,b upon heating with ZnCl2 in the presence of glacial acetic acid. The produced indole derivatives 5a,b can be successfully used as valuable precursors to synthesize 1,2,4-oxadiazolylindoles 8a,b. The reaction of arylhydrazononitriles 4a,b with hydroxylamine afforded an amidoximes 9a,b that could be cyclized into 1,2,3-triazole-4-amines 10a,b. In addition, 4a,b could be converted into 4-aminopyrazoles 12a,b via condensation with chloroacetonitrile in the presence of triethylamine as a basic catalyst. Finally, compounds 12a,b were refluxed with dimethylformamide dimethylacetal (DMFDMA) to afford amidines 13a,b that were readily cyclized to the corresponding pyrazolo[4,3-d]pyrimidines 14a,b when refluxed with ammonium acetate. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessCommunication Solvent-Free Synthesis of Modified Pectin Compounds Promoted by Microwave Irradiation
Molecules 2012, 17(10), 12234-12242; doi:10.3390/molecules171012234
Received: 14 September 2012 / Revised: 1 October 2012 / Accepted: 16 October 2012 / Published: 18 October 2012
Cited by 9 | PDF Full-text (268 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Microwave-assisted solvent-free modification of pectin was successfully accomplished, consisting in the esterification of several fatty acids by pectin alcoholic functions. The reaction was performed by simply mixing the reagents with a catalytic amount of the inorganic base (potassium carbonate) and irradiating the [...] Read more.
Microwave-assisted solvent-free modification of pectin was successfully accomplished, consisting in the esterification of several fatty acids by pectin alcoholic functions. The reaction was performed by simply mixing the reagents with a catalytic amount of the inorganic base (potassium carbonate) and irradiating the obtained mixture with microwaves for a short time (3–6 min). The replacement of the traditional heating with a microwave source allowed the development of a new synthetic protocol which provided increased yield of the final products, since it eliminates the small amount of degraded polysaccharide produced during traditional oil bath heating. The desired esters were fully characterized by FT-IR spectroscopy and thermogravimetric analysis. Full article
(This article belongs to the Special Issue Solvent-Free Synthesis)
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Open AccessArticle Identification of Fungicidal 2,6-Disubstituted Quinolines with Activity against Candida Biofilms
Molecules 2012, 17(10), 12243-12251; doi:10.3390/molecules171012243
Received: 13 September 2012 / Revised: 27 September 2012 / Accepted: 15 October 2012 / Published: 18 October 2012
Cited by 3 | PDF Full-text (192 KB) | HTML Full-text | XML Full-text
Abstract
We have identified two subseries of 2,6-disubstituted quinolines, consisting of 6-amide and 6-urea derivatives, which are characterized by fungicidal activity against Candida albicans with minimal fungicidal concentration (MFC) values < 15 µM. The 6-amide derivatives displayed the highest fungicidal activity against C. albicans, in particular compounds 1, 5 and 6 characterized by MFC values of 6.25–12.5 µM. Compounds 1 and 5 of this series displayed fungicidal activity against the emerging pathogen Candida glabrata (MFC < 50 µM). The 6-amide derivatives 1, 2, 5, and 6 and the 6-urea derivatives 10, 12, 13 and 15 could also eradicate C. albicans biofilms. We found that the 6-urea derivatives 10, 13, and 15 induced accumulation of endogenous reactive oxygen species in Candida albicans biofilms. Full article
(This article belongs to the Special Issue Advances in Medicinal Chemistry of Antibiotics)
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Open AccessCommunication First Example of a Lipophilic Porphyrin-Cardanol Hybrid Embedded in a Cardanol-Based Micellar Nanodispersion
Molecules 2012, 17(10), 12252-12261; doi:10.3390/molecules171012252
Received: 27 August 2012 / Revised: 15 October 2012 / Accepted: 16 October 2012 / Published: 18 October 2012
Cited by 3 | PDF Full-text (361 KB) | HTML Full-text | XML Full-text
Abstract
Cardanol is a natural and renewable organic raw material obtained as the major chemical component by vacuum distillation of cashew nut shell liquid. In this work a new sustainable procedure for producing cardanol-based micellar nanodispersions having an embedded lipophilic porphyrin itself peripherally [...] Read more.
Cardanol is a natural and renewable organic raw material obtained as the major chemical component by vacuum distillation of cashew nut shell liquid. In this work a new sustainable procedure for producing cardanol-based micellar nanodispersions having an embedded lipophilic porphyrin itself peripherally functionalized with cardanol substituents (porphyrin-cardanol hybrid) has been described for the first time. In particular, cardanol acts as the solvent of the cardanol hybrid porphyrin and cholesterol as well as being the main component of the nanodispersions. In this way a “green” micellar nanodispersion, in which a high percentage of the micellar system is derived from renewable “functional” molecules, has been produced. Full article
(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)
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Open AccessArticle Design, Synthesis and in Vivo Anti-inflammatory Activities of 2,4-Diaryl-5-4H-imidazolone Derivatives
Molecules 2012, 17(10), 12262-12275; doi:10.3390/molecules171012262
Received: 22 August 2012 / Revised: 12 September 2012 / Accepted: 11 October 2012 / Published: 18 October 2012
Cited by 9 | PDF Full-text (318 KB) | HTML Full-text | XML Full-text
Abstract
A series of 2,4-diaryl-5(4H)-imidazolones were prepared and evaluated for their anti-inflammatory activities. Some selected 2,4-diaryl-5(4H)-imidazolones exhibited excellent anti-inflammatory activity in the carrageenan-induced rat paw edema model. Structure Activity Relationships within the series were studied. The substitution at the [...] Read more.
A series of 2,4-diaryl-5(4H)-imidazolones were prepared and evaluated for their anti-inflammatory activities. Some selected 2,4-diaryl-5(4H)-imidazolones exhibited excellent anti-inflammatory activity in the carrageenan-induced rat paw edema model. Structure Activity Relationships within the series were studied. The substitution at the N-sulfonamide moiety by a small hydrophilic acetyl group resulted in compounds with superior in vivo anti-inflammatory properties. As expected from their COX-2 selectivity, most of the active compounds lacked gastrointestinal toxicity in vivo in rats after a 3-day treatment of 25 mg/kg/day. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Interaction Profile of Diphenyl Diselenide with Pharmacologically Significant Thiols
Molecules 2012, 17(10), 12287-12296; doi:10.3390/molecules171012287
Received: 24 August 2012 / Revised: 27 September 2012 / Accepted: 29 September 2012 / Published: 19 October 2012
Cited by 6 | PDF Full-text (269 KB) | HTML Full-text | XML Full-text
Abstract
Diphenyl diselenide has shown interesting biological activities in various free-radical-induced damage models and can be considered as a potential candidate drug against oxidative stress. Apart from its anti-oxidant activity, this compound can oxidize various thiols. However there are no detailed studies in [...] Read more.
Diphenyl diselenide has shown interesting biological activities in various free-radical-induced damage models and can be considered as a potential candidate drug against oxidative stress. Apart from its anti-oxidant activity, this compound can oxidize various thiols. However there are no detailed studies in the literature about the thiol oxidase-like activity of this compound against biologically significant mono and di-thiols with respect to various pH conditions. Keeping in mind the scarcity of data in this area of organochalcogen chemistry, we report for the first time the kinetics of thiol oxidation by diphenyl diselenide, which was carried out in a commonly used phosphate buffer, not only at physiological pH, but also at a number of acidic values. The relative reactivities of the different thiols with diphenyl diselenide were independent of the pKa of the thiol group, such that at pH 7.4, cysteine and dithiothreitol were the most reactive, while 2,3-dimercapto-1-propanesulfonic acid and glutathione were weakly reactive and extremely low reactivity was observed with dimercaptosuccinic acid. Rate of oxidation was dependent on the pH of the incubation medium. The results obtained will help us in the design of rational strategies for the safe pharmacological use of diphenyl diselenide. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle TLC Screening for Antioxidant Activity of Extracts from Fifteen Bamboo Species and Identification of Antioxidant Flavone Glycosides from Leaves of Bambusa. textilis McClure
Molecules 2012, 17(10), 12297-12311; doi:10.3390/molecules171012297
Received: 10 September 2012 / Revised: 19 September 2012 / Accepted: 12 October 2012 / Published: 19 October 2012
Cited by 10 | PDF Full-text (317 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Interest in the antioxidant activity of bamboo leaves is growing. To discover new sources of natural antioxidants, a TLC bioautography method combined with a new image processing method was developed to evaluate the antioxidant activity of leaf extracts from 15 different species [...] Read more.
Interest in the antioxidant activity of bamboo leaves is growing. To discover new sources of natural antioxidants, a TLC bioautography method combined with a new image processing method was developed to evaluate the antioxidant activity of leaf extracts from 15 different species of bamboo. The results showed that the methanolic extract of Bambusa. textilis McClure possessed the highest antioxidant activity among the selected bamboo species. To rapidly identify the antioxidant compounds, the crude extract of B. textilis McClure was analysed by HPLC-UV, and HPLC-micro-fractionation of the extract was carried out. Based on TLC bioautography-guided fractionation, three antioxidant fractions were isolated from B. textilis McClure by preparative chromatography. These three antioxidant compounds were identified as isoorientin 4''-O β-D-xylopyranoside (1), isoorientin 2''-O-α-L-rhamnoside (2) and isoorientin (3) according to their UV, MS, and NMR data. The proposed TLC screening method could therefore be an easy way to evaluate the antioxidant activity of bamboo leaves, and the results achieved should prove very helpful for promoting their utilization, as B. textilis McClure can be considered a promising plant source of natural antioxidants. Full article
(This article belongs to the Special Issue Antioxidants 2012)
Open AccessArticle Bioassays Against Pinewood Nematode: Assessment of a Suitable Dilution Agent and Screening for Bioactive Essential Oils
Molecules 2012, 17(10), 12312-12329; doi:10.3390/molecules171012312
Received: 21 September 2012 / Revised: 10 October 2012 / Accepted: 10 October 2012 / Published: 19 October 2012
Cited by 11 | PDF Full-text (231 KB) | HTML Full-text | XML Full-text
Abstract
Acetone was investigated and found to be an appropriate alternative to Triton X-100 as a solvent of essential oils in bioassays aimed to investigate their effects on pinewood nematode (Bursaphelenchus xylophilus) mortality. Therefore it was used as dilution agent to [...] Read more.
Acetone was investigated and found to be an appropriate alternative to Triton X-100 as a solvent of essential oils in bioassays aimed to investigate their effects on pinewood nematode (Bursaphelenchus xylophilus) mortality. Therefore it was used as dilution agent to screen the effectiveness of fifty two essential oils against this pest. Thirteen essential oils were highly effective, resulting in more than 90% pinewood nematode mortality at 2 mg/mL, with six of them resulting in 100% mortality. LC100 values ranged between 0.50 mg/mL and 0.83 mg/mL for the essential oils of Origanum vulgare and Satureja montana, respectively. Essential oils were submitted to gas chromatography and gas chromatography-mass spectrometry analysis and their chemical composition established. Data from essential oils with 100% mortality at 2 mg/mL and other essential oils previously found to have LC100 ≤ 2 mg/mL was combined, their chemical profiles investigated by correspondences analysis plus automatic classification. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Phenolic and Lignan Glycosides from the Butanol Extract of Averrhoa carambola L. Root
Molecules 2012, 17(10), 12330-12340; doi:10.3390/molecules171012330
Received: 26 September 2012 / Revised: 11 October 2012 / Accepted: 12 October 2012 / Published: 19 October 2012
Cited by 9 | PDF Full-text (213 KB) | XML Full-text | Supplementary Files
Abstract
Fifteen compounds, which included six chiral lignans and nine phenolic glycosides, were separated from the butanol fraction of Averrhoa carambola L. root and identified. All of the compounds, namely 3,4,5-trimethoxyphenol-1-O-β-D-glucopyranoside (1), benzyl-1-O-β [...] Read more.
Fifteen compounds, which included six chiral lignans and nine phenolic glycosides, were separated from the butanol fraction of Averrhoa carambola L. root and identified. All of the compounds, namely 3,4,5-trimethoxyphenol-1-O-β-D-glucopyranoside (1), benzyl-1-O-β-D-glucopyranoside (2), (+)-5'-methoxyisolariciresinol 3α-O-β-D-gluco-pyranoside (3), (+)-isolariciresinol 3α-O-β-D-glucopyranoside (4), koaburaside (5), (+)-lyoniresinol 3α-O-β-D-glucopyranoside (6), (−)-lyoniresinol 3α-O-β-D-glucopyranoside (7), (−)-5'-methoxyisolariciresinol 3α-O-β-D-glucopyranoside (8), (−)-isolariciresinol 3α-O-β-D-glucopyranoside (9), 3,5-dimethoxy-4-hydroxyphenyl 1-O-β-apiofuranosyl (1''→6')-O-β-D-glucopyranoside (10), 3,4,5-trimethoxyphenyl 1-O-β-apiofuranosyl (1''→6')-β-gluco-pyranoside (11), methoxyhydroquinone-4-β-D-glucopyranoside (12), (2S)-2-O-β-D-gluco-pyranosyl-2-hydroxyphenylacetic acid (13), 3-hydroxy-4-methoxyphenol 1-O-D-apio-furanosyl-(1''→6')-O-β-D-glucopyranoside (14) and 4-hydroxy-3-methoxyphenol 1-O-D-apiofuranosyl-(1''→6')-O-β-D-glucopyranoside (15) were isolated from this plant for the first time. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Comparison of the Phenolic Compounds, Carotenoids and Tocochromanols Content in Wheat Grain under Organic and Mineral Fertilization Regimes
Molecules 2012, 17(10), 12341-12356; doi:10.3390/molecules171012341
Received: 21 July 2012 / Revised: 26 September 2012 / Accepted: 9 October 2012 / Published: 19 October 2012
Cited by 10 | PDF Full-text (364 KB) | HTML Full-text | XML Full-text
Abstract
A field study was performed to evaluate the effect of mineral (NPK) and organic-based fertilizers such as compost (C), manure (FYM) and meat and bone meal (MBM) on the appearance (dimensions and color) of spring wheat kernels and on the total content [...] Read more.
A field study was performed to evaluate the effect of mineral (NPK) and organic-based fertilizers such as compost (C), manure (FYM) and meat and bone meal (MBM) on the appearance (dimensions and color) of spring wheat kernels and on the total content in grain of main its phytochemicals (polyphenols, carotenoids and tocochromanols) and phenolic acids composition. Total phenolic compounds were determined using the Folin-Ciocalteu assay after alkaline hydrolysis of grain and carotenoids were analyzed spectrophotometrically. Composition of tocochromanols and phenolic acids was determined using RP-HPLC techniques. Only insignificant differences in the appearance of kernels and small changes in the content and composition of grain phytochemicals were noted between the studied fertilization systems. Among the analyzed phytochemicals the greatest variation was observed in the group of polyphenol compounds, with a stated increase of their total content of 6.7 and 11.2% in grain fertilized with MBM and compost, respectively. Simultaneously the grain from organic fertilization contained significantly less phenolic acids, and the decrease in their content ranged from 10.0% for FYM to 24.8% for MBM+EM-1. Organically and conventionally fertilized grain had similar amounts of tocochromanols and carotenoids. Comparison of MBM and MBM+EM-1 variants showed that application of effective microorganisms decreased carotenoids and tocochromanols content by 8.5 and 9.7%, respectively. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Two New Cholic Acid Derivatives from the Marine Ascidian-Associated Bacterium Hasllibacter halocynthiae
Molecules 2012, 17(10), 12357-12364; doi:10.3390/molecules171012357
Received: 13 August 2012 / Revised: 8 October 2012 / Accepted: 17 October 2012 / Published: 22 October 2012
Cited by 2 | PDF Full-text (251 KB) | HTML Full-text | XML Full-text
Abstract
The investigation of secondary metabolites in liquid cultures of a recently discovered marine bacterium, Hasllibacter halocynthiae strain KME 002T, led to the isolation of two new cholic acid derivatives. The structures of these compounds were determined to be 3,3,12-trihydroxy-7-ketocholanic acid [...] Read more.
The investigation of secondary metabolites in liquid cultures of a recently discovered marine bacterium, Hasllibacter halocynthiae strain KME 002T, led to the isolation of two new cholic acid derivatives. The structures of these compounds were determined to be 3,3,12-trihydroxy-7-ketocholanic acid (1) and 3,3,12-trihydroxy-7-deoxycholanic acid (2) through HRFABMS and NMR data analyses. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Phenylmethimazole Blocks dsRNA-Induced IRF3 Nuclear Translocation and Homodimerization
Molecules 2012, 17(10), 12365-12377; doi:10.3390/molecules171012365
Received: 5 October 2012 / Revised: 16 October 2012 / Accepted: 19 October 2012 / Published: 22 October 2012
Cited by 4 | PDF Full-text (856 KB) | HTML Full-text | XML Full-text
Abstract
Previous studies revealed that phenylmethimazole (C10) inhibits IRF3 signaling, preventing dsRNA-induction of type 1 interferon gene expression, production, and downstream signaling. In the present study, we investigated the molecular basis for C10 inhibition of dsRNA-stimulated IRF3 signaling. IRF-3 Trans-AM assays were used [...] Read more.
Previous studies revealed that phenylmethimazole (C10) inhibits IRF3 signaling, preventing dsRNA-induction of type 1 interferon gene expression, production, and downstream signaling. In the present study, we investigated the molecular basis for C10 inhibition of dsRNA-stimulated IRF3 signaling. IRF-3 Trans-AM assays were used to measure C10 effects on dsRNA induction of IRF3 DNA binding. Green fluorescent protein-labeled IRF3 was used to measure C10 effects on dsRNA-induced IRF3 nuclear translocation. Native PAGE, SDS PAGE, and western blotting were used to identify effects of C10 on IRF3 homodimer formation and phosphorylation, respectively. There was a significant impairment of dsRNA-induced IRF3 DNA binding activity in human embryonic kidney and pancreatic cancer cells with C10 treatment. C10 also blocked dsRNA-induced IRF3 nuclear translocation and homodimer formation without blocking serine 396 phosphorylation of IRF3. Together, these results indicate that C10 interferes with IRF3 signaling by blocking dsRNA-induced IRF3 homodimer formation, a prerequisite for nuclear translocation and DNA binding activities. Full article
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Open AccessArticle Synthesis of a Cholesteryl-HEG Phosphoramidite Derivative and Its Application to Lipid-conjugates of the Anti-HIV 5'TGGGAG3' Hotoda’s Sequence
Molecules 2012, 17(10), 12378-12392; doi:10.3390/molecules171012378
Received: 19 September 2012 / Revised: 16 October 2012 / Accepted: 17 October 2012 / Published: 22 October 2012
Cited by 4 | PDF Full-text (316 KB) | HTML Full-text | XML Full-text
Abstract
A novel phosphoramidite derivative of cholesterol, with an ether-linked hexaethylene glycol (HEG) spacer arm, has been obtained through simple and reproducible solid phase modified oligonucleotide synthesis manipulations. This building block and the known phosphoramidite derivative of 3b-(2-hydroxyethoxy)cholesterol have been exploited in standard [...] Read more.
A novel phosphoramidite derivative of cholesterol, with an ether-linked hexaethylene glycol (HEG) spacer arm, has been obtained through simple and reproducible solid phase modified oligonucleotide synthesis manipulations. This building block and the known phosphoramidite derivative of 3b-(2-hydroxyethoxy)cholesterol have been exploited in standard oligonucleotide synthesis protocols for the preparation of 5'- conjugates of the G-quadruplex-forming 5'TGGGAG3' oligomer, known as the Hotoda’s sequence, to produce new potential anti-HIV agents. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
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Open AccessArticle trans-Resveratrol in Nutraceuticals: Issues in Retail Quality and Effectiveness
Molecules 2012, 17(10), 12393-12405; doi:10.3390/molecules171012393
Received: 31 August 2012 / Revised: 13 September 2012 / Accepted: 15 October 2012 / Published: 22 October 2012
Cited by 19 | PDF Full-text (398 KB) | HTML Full-text | XML Full-text
Abstract
Fourteen brands of resveratrol-containing nutraceuticals were evaluated in order to verify their actual resveratrol content and to control if their health-promoting properties are related to manufacturing quality. Products included pure resveratrol capsules or multi-ingredient formulations with standardized amounts of resveratrol and other [...] Read more.
Fourteen brands of resveratrol-containing nutraceuticals were evaluated in order to verify their actual resveratrol content and to control if their health-promoting properties are related to manufacturing quality. Products included pure resveratrol capsules or multi-ingredient formulations with standardized amounts of resveratrol and other phytochemicals. Samples were analyzed for total trans-resveratrol, flavonoids, procyanidin, polyphenol content and the results were compared with the content declared on-label. Only five out of 14 brands had near label values, compliant with Good Manufacturing Practices (GMP) requirements (95–105% content of active constituent), four products were slightly out of this range (83–111%) and three were in the 8–64% range. Two samples were below the limit of detection. The greater the difference between actual and labeled resveratrol content, the lower was the antioxidant and antiproliferative activity strength. Dietary supplements containing pure trans-resveratrol exhibited a greater induction of differentiation towards human leukemic K562 cells when compared to multicomponent products. Great differences currently exist among resveratrol food supplements commercially available and GMP-grade quality should not be taken for granted. On the other side, dosages suggested by most “pure”, “high-dosage” supplements may allow a supplementation level adequate to obtain some of the purported health benefits. Full article
(This article belongs to the Special Issue Methods in Polyphenol Analysis)
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Open AccessArticle The Effect of Curcumin on Human Bronchial Epithelial Cells Exposed to Fine Particulate Matter: A Predictive Analysis
Molecules 2012, 17(10), 12406-12426; doi:10.3390/molecules171012406
Received: 12 July 2012 / Revised: 15 October 2012 / Accepted: 16 October 2012 / Published: 22 October 2012
Cited by 4 | PDF Full-text (2059 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fine particulate matter (PM2.5) has been associated in humans with inflammation, oxidative stress and cancer. Studies had shown that curcumin could potentially inhibit these effects; however, there had been no in vivo or in vitro reports about the effects of [...] Read more.
Fine particulate matter (PM2.5) has been associated in humans with inflammation, oxidative stress and cancer. Studies had shown that curcumin could potentially inhibit these effects; however, there had been no in vivo or in vitro reports about the effects of curcumin on organisms exposed to PM2.5. This predictive study explored the possible biological functions and pathways involved in the mechanism of curcumin inhibition of the hazardous effects of PM2.5. For predictive analysis, microarray data were used to investigate the effect of PM2.5 on human bronchial epithelial cells (HBEC), and human target proteins of curcumin were retrieved from PubChem. Two protein-protein interaction (PPI) networks were established based upon differential genes and target proteins, respectively, and the common network of these two networks was found. Functional and pathway analysis of the common network was performed using the Ingenuity Pathways Analysis (IPA) software. The results suggested that the predictive effects of curcumin on HBEC exposed to PM2.5 were involved in bio-functions, including inflammatory response of airway, cancerogenesis, and apoptosis, and in pathways such as cancer, glucocorticoid receptor signaling, and NF-kappaB signaling. This study predicted for the first time that curcumin could be a potential therapeutic agent for protecting the human airway from the hazardous effects of PM2.5. Full article
Open AccessArticle Synthesis, FTIR, 13C-NMR and Temperature-Dependent 1H‑NMR Characteristics of Bis-naphthalimide Derivatives
Molecules 2012, 17(10), 12427-12448; doi:10.3390/molecules171012427
Received: 5 September 2012 / Revised: 17 October 2012 / Accepted: 18 October 2012 / Published: 22 October 2012
Cited by 1 | PDF Full-text (1010 KB) | HTML Full-text | XML Full-text
Abstract
Chemotherapy is still the most important method of cancer treatment. To make this method more effective and safe, new drugs to destroy cancer cells are needed. Some bis-naphthalimide derivatives show potential anticancer activity via an intercalation mechanism. A higher degree of DNA [...] Read more.
Chemotherapy is still the most important method of cancer treatment. To make this method more effective and safe, new drugs to destroy cancer cells are needed. Some bis-naphthalimide derivatives show potential anticancer activity via an intercalation mechanism. A higher degree of DNA intercalation corresponds to better therapeutic effects. The degree of intercalation of naphthalimides depends on their structure, molecular dynamics and intermolecular interactions with DNA. In order to apply any active substance as a drug, its molecular dynamics as well as possible interactions with target molecules have to be examined in exhaustive details. This paper describes a practical preparation of some novel bis-naphthalimide derivatives with different functional groups and their FTIR and 1H- and 13C-NMR spectral characteristics. To determine the molecular dynamics of the obtained compounds the temperature, their 1H-NMR spectra were measured. It has been clearly proven in this paper that the unusual temperature-dependent 1H-NMR behavior of the aromatic protons of phthalimide derivatives, previously described in the literature as “hypersensitivity” and explained by n-π interactions and molecular motions of aromatic amide rings, is a result of temperature driven changes of the geometry of carbonyl groups. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Acute Toxicity and Gastroprotective Effect of the Schiff Base Ligand 1H-Indole-3-ethylene-5-nitrosalicylaldimine and Its Nickel (II) Complex on Ethanol Induced Gastric Lesions in Rats
Molecules 2012, 17(10), 12449-12459; doi:10.3390/molecules171012449
Received: 12 September 2012 / Revised: 4 October 2012 / Accepted: 5 October 2012 / Published: 22 October 2012
Cited by 3 | PDF Full-text (355 KB) | HTML Full-text | XML Full-text
Abstract
The present study was performed to evaluate the gastroprotective activity of Schiff base ligand derived from the condensation reaction of tryptamine (an indole derivative) and 5-nitrosalicylaldehyde (TNS) and its nickel (II) complex against ethanol-induced gastric ulcer in rats. The compounds were orally [...] Read more.
The present study was performed to evaluate the gastroprotective activity of Schiff base ligand derived from the condensation reaction of tryptamine (an indole derivative) and 5-nitrosalicylaldehyde (TNS) and its nickel (II) complex against ethanol-induced gastric ulcer in rats. The compounds were orally administered with low (30 mg/kg) and high (60 mg/kg) doses to ulcer-induced Sprague-Dawley rats. Macroscopically, the ulcer control group exhibited severe mucosal injury, whereas pre-treatment with either cimetidine or TNS and its nickel (II) complex each resulted in significant protection against gastric mucosal injury. Flattening of gastric mucosal folds was also observed in rats pretreated with TNS and its nickel complex. Histological studies of the gastric wall of ulcer control group revealed severe damage of gastric mucosa, along with edema and leucocytes infiltration of the submucosal layer compared to rats pre-treated with either cimetidine or TNS and its nickel (II) compound, where there was marked gastric protection along with reduction of edema and leucocytes infiltration of the submucosal layer. Acute toxicity study done on mice with a higher dose of 5 g/kg of TNS and its nickel (II) complex did not manifest any toxicological signs. Research finding suggest that TNS and its nickel (II) complex could be considered as effective gastroprotective compounds. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle A Sub-Pathway Based Method to Identify Candidate Agents for Ankylosing Spondylitis
Molecules 2012, 17(10), 12460-12468; doi:10.3390/molecules171012460
Received: 26 June 2012 / Revised: 25 September 2012 / Accepted: 26 September 2012 / Published: 22 October 2012
PDF Full-text (219 KB) | HTML Full-text | XML Full-text
Abstract
The need for new therapeutics for Ankylosing Spondylitis (AS) is highlighted by the general lack of efficacy for most agents currently available for this disease. Many recent studies have detailed molecular pathways in AS, and several molecule-targeting agents are undergoing evaluation. We aimed to explore the mechanism of AS and identify biologically active small molecules capable of targeting the sub-pathways which were disregulated in the development of AS. By using the GSE25101 microarray data accessible from the Gene Expression Omnibus database, we first identified the differentially expressed genes (DEGs) between AS samples and healthy controls, followed by the sub-pathway enrichment analysis of the DEGs. In addition, we propose the use of an approach based on targeting sub-pathways to identify potential agents for AS. A total of 3,280 genes were identified as being significantly different between patients and controls with p-values < 0.1. Our study showed that neurotrophic signaling pathway and some immune-associated pathways may be involved in the development of AS. Besides, our bioinformatics analysis revealed a total of 15 small molecules which may play a role in perturbing the development of AS. Our study proposes the use of an approach based on targeting sub-pathways to identify potential agents for AS. Candidate agents identified by our approach may provide the groundwork for a combination therapy approach for AS. Full article

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Open AccessReview Recent Updates in Redox Regulation and Free Radical Scavenging Effects by Herbal Products in Experimental Models of Parkinson’s Disease
Molecules 2012, 17(10), 11391-11420; doi:10.3390/molecules171011391
Received: 30 August 2012 / Revised: 12 September 2012 / Accepted: 21 September 2012 / Published: 26 September 2012
Cited by 11 | PDF Full-text (353 KB) | HTML Full-text | XML Full-text
Abstract
Parkinson’s disease (PD) is a complex multifactorial disease marked by extensive neuropathology in the brain with selective yet prominent and progressive loss of mid-brain dopaminergic neurons. The etiological factors involved in the development of PD are still elusive, but oxidative stress arising [...] Read more.
Parkinson’s disease (PD) is a complex multifactorial disease marked by extensive neuropathology in the brain with selective yet prominent and progressive loss of mid-brain dopaminergic neurons. The etiological factors involved in the development of PD are still elusive, but oxidative stress arising when reactive oxygen species (ROS) exceed amounts required for normal redox signaling is considered one of the major factors. ROS cause oxidative damage to proteins, lipids, and DNA and are one of the most prominent factors related to neurodegeneration. Pre-clinical and clinical studies clearly demonstrate the effectiveness of oxidative stress in the pathogenesis of PD. Therefore, regulation of redox signaling and inhibiting excess ROS would contribute greatly not only to extend longevity but also to ameliorate the progression of dopaminergic cell death seen in patients with PD. Several herbal products are beneficial for maintaining nerve cell function and for treating various neurodegenerative disorders by reducing oxidative stress. Here, we summarize the recent knowledge concerning promising herbs that have shown significant beneficial effects based on regulation of redox status and ROS inhibition in toxin-induced PD models. Full article
(This article belongs to the Special Issue Antioxidants 2012)
Open AccessReview The Expanding Role of Electrospray Ionization Mass Spectrometry for Probing Reactive Intermediates in Solution
Molecules 2012, 17(10), 11507-11537; doi:10.3390/molecules171011507
Received: 25 July 2012 / Revised: 29 August 2012 / Accepted: 5 September 2012 / Published: 27 September 2012
Cited by 13 | PDF Full-text (518 KB)
Abstract
Within the past decade, electrospray ionization mass spectrometry (ESI-MS) has rapidly occupied a prominent position for liquid-phase mechanistic studies due to its intrinsic advantages allowing for efficient “fishing” (rapid, sensitive, specific and simultaneous detection/identification) of multiple intermediates and products directly from a [...] Read more.
Within the past decade, electrospray ionization mass spectrometry (ESI-MS) has rapidly occupied a prominent position for liquid-phase mechanistic studies due to its intrinsic advantages allowing for efficient “fishing” (rapid, sensitive, specific and simultaneous detection/identification) of multiple intermediates and products directly from a “real-world” solution. In this review we attempt to offer a comprehensive overview of the ESI-MS-based methodologies and strategies developed up to date to study reactive species in reaction solutions. A full description of general issues involved with probing reacting species from complex (bio)chemical reaction systems is briefly covered, including the potential sources of reactive intermediate (metabolite) generation, analytical aspects and challenges, basic rudiments of ESI-MS and the state-of-the-art technology. The main purpose of the present review is to highlight the utility of ESI-MS and its expanding role in probing reactive intermediates from various reactions in solution, with special focus on current progress in ESI-MS-based approaches for improving throughput, testing reality and real-time detection by using newly developed MS instruments and emerging ionization sources (such as ambient ESI techniques). In addition, the limitations of modern ESI-MS in detecting intermediates in organic reactions is also discussed. Full article
(This article belongs to the Special Issue Reactive Intermediates)
Open AccessReview Recent Advances in Cyclonucleosides: C-Cyclonucleosides and Spore Photoproducts in Damaged DNA
Molecules 2012, 17(10), 11630-11654; doi:10.3390/molecules171011630
Received: 30 August 2012 / Revised: 25 September 2012 / Accepted: 26 September 2012 / Published: 28 September 2012
Cited by 4 | PDF Full-text (718 KB)
Abstract
Cyclonucleosides which are fixed in a specific conformation around the glycosyl bond by a carbon and heteroatom chain constitute a unique category of nucleoside derivatives. Because they are structural analogs, cyclonucleosides and oligodeoxynucleotides containing them would be useful tools for investigating the [...] Read more.
Cyclonucleosides which are fixed in a specific conformation around the glycosyl bond by a carbon and heteroatom chain constitute a unique category of nucleoside derivatives. Because they are structural analogs, cyclonucleosides and oligodeoxynucleotides containing them would be useful tools for investigating the biological functions and conformations of DNA, RNA as well as their steric interactions with proteins. C-Cyclonucleosides bridged by a carbon chain between the base and sugar moieties are the most attractive from the synthetic points of view as well as for use as biological tools. In this review, recent progress of the synthesis of C-cyclonucleosides is surveyed. Among the C-cyclonucleosides, 5′,8-C-cyclodeoxyadenosine is one of the well-known derivatives of which the first practical synthesis was reported over 30 years ago. Recently, 5′,8-C-cyclodeoxyadenosine has attracted considerable interest as a biomarker, since its formation in oxidatively-damaged DNA is considered to be related to various diseases and aging. Another important analogue of cyclonucleosides is a unique thymidine phosphate dimer, a so-called spore photoproduct, which has been found in photo-damaged DNA. Recent advances in the synthesis, mechanism-studies, and stereochemical preference of repairing enzymes related to 5′,8-C-cyclodeoxyadenosine and spore photoproducts are also reviewed. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
Open AccessReview Molecular Assemblies of Porphyrins and Macrocyclic Receptors: Recent Developments in Their Synthesis and Applications
Molecules 2012, 17(10), 11763-11799; doi:10.3390/molecules171011763
Received: 1 August 2012 / Revised: 8 September 2012 / Accepted: 11 September 2012 / Published: 9 October 2012
Cited by 20 | PDF Full-text (1027 KB) | HTML Full-text | XML Full-text
Abstract
Metalloporphyrins which form the core of many bioenzymes and natural light harvesting or electron transport systems, exhibit a variety of selective functional properties depending on the state and surroundings with which they exist in biological systems. The specificity and ease with which [...] Read more.
Metalloporphyrins which form the core of many bioenzymes and natural light harvesting or electron transport systems, exhibit a variety of selective functional properties depending on the state and surroundings with which they exist in biological systems. The specificity and ease with which they function in each of their bio-functions appear to be largely governed by the nature and disposition of the protein globule around the porphyrin reaction center. Synthetic porphyrin frameworks confined within or around a pre-organized molecular entity like the protein network in natural systems have attracted considerable attraction, especially in the field of biomimetic reactions. At the same time a large number of macrocyclic oligomers such as calixarenes, resorcinarenes, spherands, cyclodextrins and crown ethers have been investigated in detail as efficient molecular receptors. These molecular receptors are synthetic host molecules with enclosed interiors, which are designed three dimensionally to ensure strong and precise molecular encapsulation/recognition. Due to their complex structures, enclosed guest molecules reside in an environment isolated from the outside and as a consequence, physical properties and chemical reactions specific to that environment in these guest species can be identified. The facile incorporation of such molecular receptors into the highly photoactive and catalytically efficient porphyrin framework allows for convenient design of useful molecular systems with unique structural and functional properties. Such systems have provided over the years attractive model systems for the study of various biological and chemical processes, and the design of new materials and molecular devices. This review focuses on the recent developments in the synthesis of porphyrin assemblies associated with cyclodextrins, calixarenes and resorcinarenes and their potential applications in the fields of molecular encapsulation/recognition, and chemical catalysis. Full article
(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)
Open AccessReview Chemical Genetics — A Versatile Method to Combine Science and Higher Level Teaching in Molecular Genetics
Molecules 2012, 17(10), 11920-11930; doi:10.3390/molecules171011920
Received: 27 August 2012 / Revised: 26 September 2012 / Accepted: 28 September 2012 / Published: 9 October 2012
Cited by 1 | PDF Full-text (576 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phosphorylation is a key event in many cellular processes like cell cycle, transformation of environmental signals to transcriptional activation or polar growth. The chemical genetics approach can be used to analyse the effect of highly specific inhibition in vivo and is a [...] Read more.
Phosphorylation is a key event in many cellular processes like cell cycle, transformation of environmental signals to transcriptional activation or polar growth. The chemical genetics approach can be used to analyse the effect of highly specific inhibition in vivo and is a promising method to screen for kinase targets. We have used this approach to study the role of the germinal centre kinase Don3 during the cell division in the phytopathogenic fungus Ustilago maydis. Due to the easy determination of the don3 phenotype we have chosen this approach for a genetic course for M.Sc. students and for IMPRS (International Max-Planck research school) students. According to the principle of “problem-based learning” the aim of this two-week course is to transfer knowledge about the broad spectrum of kinases to the students and that the students acquire the ability to design their own analog-sensitive kinase of interest. In addition to these training goals, we benefit from these annual courses the synthesis of basic constructs for genetic modification of several kinases in our model system U. maydis. Full article
(This article belongs to the Special Issue Chemical Genetics)
Open AccessReview Fruit Pod Extracts as a Source of Nutraceuticals and Pharmaceuticals
Molecules 2012, 17(10), 11931-11946; doi:10.3390/molecules171011931
Received: 21 June 2012 / Revised: 27 September 2012 / Accepted: 29 September 2012 / Published: 10 October 2012
Cited by 7 | PDF Full-text (199 KB) | HTML Full-text | XML Full-text
Abstract
Fruit pods contain various beneficial compounds that have biological activities and can be used as a source of pharmaceutical and nutraceutical products. Although pods or pericarps are usually discarded when consuming the edible parts of fruits, they contain some compounds that exhibit [...] Read more.
Fruit pods contain various beneficial compounds that have biological activities and can be used as a source of pharmaceutical and nutraceutical products. Although pods or pericarps are usually discarded when consuming the edible parts of fruits, they contain some compounds that exhibit biological activities after extraction. Most fruit pods included in this review contain polyphenolic components that can promote antioxidant effects on human health. Additionally, anti-inflammatory, antibacterial, antifungal and chemopreventive effects are associated with these fruit pod extracts. Besides polyphenolics, other compounds such as xanthones, carotenoids and saponins also exhibit health effects and can be potential sources of nutraceutical and pharmaceutical components. In this review, information on fruit pods or pericarp of Garcinia mangostana, Ceratonia siliqua, Moringa oleifera, Acacia nilotica, Sapindus rarak and Prosopis cineraria is presented and discussed with regard to their biological activity of the major compounds existing in them. The fruit pods of other ethno- botanical plants have also been reviewed. It can be concluded that although fruit pods are considered as being of no practical use and are often being thrown away, they nevertheless contain compounds that might be useful sources of nutraceutical and other pharmaceutical components. Full article
(This article belongs to the Section Natural Products)
Open AccessReview DNA-Directed Base Pair Opening
Molecules 2012, 17(10), 11947-11964; doi:10.3390/molecules171011947
Received: 16 August 2012 / Revised: 28 September 2012 / Accepted: 9 October 2012 / Published: 11 October 2012
Cited by 3 | PDF Full-text (3200 KB) | HTML Full-text | XML Full-text
Abstract
Strand separation is a fundamental molecular process essential for the reading of the genetic information during DNA replication, transcription and recombination. However, DNA melting in physiological conditions in which the double helix is expected to be stable represents a challenging problem. Current [...] Read more.
Strand separation is a fundamental molecular process essential for the reading of the genetic information during DNA replication, transcription and recombination. However, DNA melting in physiological conditions in which the double helix is expected to be stable represents a challenging problem. Current models propose that negative supercoiling destabilizes the double helix and promotes the spontaneous, sequence-dependent DNA melting. The present review examines an alternative view and reveals how DNA compaction may trigger the sequence dependent opening of the base pairs. This analysis shows that in DNA crystals, tight DNA-DNA interactions destabilize the double helices at various degrees, from the alteration of the base-stacking to the opening of the base-pairs. The electrostatic repulsion generated by the DNA close approach of the negatively charged sugar phosphate backbones may therefore provide a potential source of the energy required for DNA melting. These observations suggest a new molecular mechanism for the initial steps of strand separation in which the coupling of the DNA tertiary and secondary interactions both actively triggers the base pair opening and stabilizes the intermediate states during the melting pathway. Full article
(This article belongs to the Special Issue DNA-Directed Chemistry)
Open AccessReview The Final Link: Tapping the Power of Chemical Genetics to Connect the Molecular and Biologic Functions of Mitotic Protein Kinases
Molecules 2012, 17(10), 12172-12186; doi:10.3390/molecules171012172
Received: 17 September 2012 / Revised: 26 September 2012 / Accepted: 12 October 2012 / Published: 17 October 2012
PDF Full-text (443 KB) | HTML Full-text | XML Full-text
Abstract
During mitosis, protein kinases coordinate cellular reorganization and chromosome segregation to ensure accurate distribution of genetic information into daughter cells. Multiple protein kinases contribute to mitotic regulation, modulating molecular signaling more rapidly than possible with gene expression. However, a comprehensive understanding of [...] Read more.
During mitosis, protein kinases coordinate cellular reorganization and chromosome segregation to ensure accurate distribution of genetic information into daughter cells. Multiple protein kinases contribute to mitotic regulation, modulating molecular signaling more rapidly than possible with gene expression. However, a comprehensive understanding of how kinases regulate mitotic progression remains elusive. The challenge arises from multiple functions and substrates, a large number of “bystander” phosphorylation events, and the brief window in which all mitotic events transpire. Analog-sensitive alleles of protein kinases are powerful chemical genetic tools for rapid and specific interrogation of kinase function. Moreover, combining these tools with advanced proteomics and substrate labeling has identified phosphorylation sites on numerous protein targets. Here, we review the chemical genetic tools available to study kinase function and identify substrates. We describe how chemical genetics can also be used to link kinase function with cognate phosphorylation events to provide mechanistic detail. This can be accomplished by dissecting subsets of kinase functions and chemical genetic complementation. We believe a complete “chemical genetic toolbox” will ultimately allow a comprehensive understanding of how protein kinases regulate mitosis. Full article
(This article belongs to the Special Issue Chemical Genetics)
Open AccessReview Antimicrobial Peptides for Therapeutic Applications: A Review
Molecules 2012, 17(10), 12276-12286; doi:10.3390/molecules171012276
Received: 12 September 2012 / Revised: 8 October 2012 / Accepted: 17 October 2012 / Published: 18 October 2012
Cited by 66 | PDF Full-text (179 KB) | HTML Full-text | XML Full-text
Abstract
Antimicrobial peptides (AMPs) have been considered as potential therapeutic sources of future antibiotics because of their broad-spectrum activities and different mechanisms of action compared to conventional antibiotics. Although AMPs possess considerable benefits as new generation antibiotics, their clinical and commercial development still [...] Read more.
Antimicrobial peptides (AMPs) have been considered as potential therapeutic sources of future antibiotics because of their broad-spectrum activities and different mechanisms of action compared to conventional antibiotics. Although AMPs possess considerable benefits as new generation antibiotics, their clinical and commercial development still have some limitations, such as potential toxicity, susceptibility to proteases, and high cost of peptide production. In order to overcome those obstacles, extensive efforts have been carried out. For instance, unusual amino acids or peptido-mimetics are introduced to avoid the proteolytic degradation and the design of short peptides retaining antimicrobial activities is proposed as a solution for the cost issue. In this review, we focus on small peptides, especially those with less than twelve amino acids, and provide an overview of the relationships between their three-dimensional structures and antimicrobial activities. The efforts to develop highly active AMPs with shorter sequences are also described. Full article
(This article belongs to the Special Issue Advances in Medicinal Chemistry of Antibiotics)

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Open AccessCorrection Matsuno, A., et al., Molecular Morphology of Pituitary Cells, from Conventional Immunohistochemistry to Fluorescence Imaging. Molecules 2011, 16, 3618-3635
Molecules 2012, 17(10), 11667-11668; doi:10.3390/molecules171011667
Received: 11 September 2012 / Revised: 18 September 2012 / Accepted: 19 September 2012 / Published: 28 September 2012
PDF Full-text (110 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the original manuscript, the word “fluorescein” was erroneously used indistinctly for “fluorescence” and “fluorescent”. Furthermore, “cyan fluorescent protein” was misspelled. These errors have been amended in an amended version of the manuscript, which is available from the Molecules website. The authors [...] Read more.
In the original manuscript, the word “fluorescein” was erroneously used indistinctly for “fluorescence” and “fluorescent”. Furthermore, “cyan fluorescent protein” was misspelled. These errors have been amended in an amended version of the manuscript, which is available from the Molecules website. The authors and publisher apologize for the inconvenience. [...] Full article

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