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Molecules, Volume 18, Issue 9 (September 2013), Pages 10095-11657

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Open AccessArticle Enhancement of Cunninghamella elegans UCP/WFCC 0542 Biomass and Chitosan with Amino Acid Supply
Molecules 2013, 18(9), 10095-10107; doi:10.3390/molecules180910095
Received: 29 May 2013 / Revised: 8 August 2013 / Accepted: 12 August 2013 / Published: 22 August 2013
Cited by 3 | PDF Full-text (379 KB) | HTML Full-text | XML Full-text
Abstract
Studies were carried out with Cunninghamella elegans UCP/WFCC 0542 to evaluate the effects of an abundant supply of amino acids, asparagine and corn steep liquor associated with sucrose on the production of biomass and chitosan by submerged fermentation. The concentrations of the [...] Read more.
Studies were carried out with Cunninghamella elegans UCP/WFCC 0542 to evaluate the effects of an abundant supply of amino acids, asparagine and corn steep liquor associated with sucrose on the production of biomass and chitosan by submerged fermentation. The concentrations of the components of the culture medium which were determined by a 23 full factorial design evaluated the interactions and effects of the independent variables of the sucrose, asparagine and corn steep liquor in relation to carbon and nitrogen sources, on the production of chitosan regarding biomass. The best results were observed at the central point [asparagine 0.025%, sucrose 0.15% and 0.45% of corn steep liquor, ratio C:N=2:6], and produced maximum yields of 16.95 g/L biomass and 2.14 g/L chitosan, after 96 h of submerged fermentation. However, the lowest level of sucrose, asparagine and corn steep liquor produced a low amount of biomass (10.83 g/L) and chitosan (0.60g/L). The infrared spectrum absorption of the chitosan produced by C. elegans showed bands regarding OH-axial stretching between 3406 and 3432 cm−1, superimposed on the NH stretching band with axial deformation of the amide C=O group at about 1639 cm−1, NH angular deformation at approximately 1560 cm−1; axial deformation of amide-CN at around 1421 cm−1, symmetrical angular deformation in CH3 at 1379 cm−1, -CN axial deformation of amino groups from 1125 to 1250 cm−1 and polysaccharide structure bands in the range of between 890–1150 cm−1. The crystallinity index of chitosan was 60.92%, and its degree of deacetylation was 75.25%. A low percentage of a supply of sucrose and asparagine with corn steep liquor offered higher yields of biomass and chitosan production at low cost. Full article
(This article belongs to the Special Issue Triterpenes and Triterpenoids)
Open AccessArticle Variation of Vitamin D in Cow’s Milk and Interaction with β-Lactoglobulin
Molecules 2013, 18(9), 10122-10131; doi:10.3390/molecules180910122
Received: 1 July 2013 / Revised: 14 August 2013 / Accepted: 15 August 2013 / Published: 22 August 2013
Cited by 1 | PDF Full-text (287 KB) | HTML Full-text | XML Full-text
Abstract
Vitamin D is the collective name for a group of closely related lipids, whose main biological function is to maintain serum calcium and phosphorus concentrations within the normal range by enhancing the efficiency of the small intestine to absorb these minerals from [...] Read more.
Vitamin D is the collective name for a group of closely related lipids, whose main biological function is to maintain serum calcium and phosphorus concentrations within the normal range by enhancing the efficiency of the small intestine to absorb these minerals from the diet. We used a commercially available ELISA method for the determination of vitamin D in bovine milk. Individual milk samples from two different Italian Friesian herds were analysed. The enzyme immunoassay method used was confirmed as a useful tool to measure the vitamin D in the milk as it greatly reduces the time required to perform the conventional HPLC analysis. An interesting variation was found among individual animals that may be associated with management factors and specific genetic effects. A relationship was highlighted between vitamin D and the genetic polymorphism of β-lactoglobulin, the main bovine whey protein which is involved in the transport of small hydrophobic molecules such as retinol and vitamin D. The relatively high content of vitamin D in most milk samples suggests an opportunity to improve the natural content of vitamin D in milk either by acting on the herd management or selecting individuals genetically predisposed to produce milk with a higher vitamin D content. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Cyclooxygenase-2 (COX-2) Inhibition Constrains Indoleamine 2,3-Dioxygenase 1 (IDO1) Activity in Acute Myeloid Leukaemia Cells
Molecules 2013, 18(9), 10132-10145; doi:10.3390/molecules180910132
Received: 4 July 2013 / Revised: 14 August 2013 / Accepted: 15 August 2013 / Published: 22 August 2013
Cited by 7 | PDF Full-text (897 KB) | HTML Full-text | XML Full-text
Abstract
Indoleamine 2,3-dioxygenase 1 (IDO1) metabolizes L-tryptophan to kynurenines (KYN), inducing T-cell suppression either directly or by altering antigen-presenting-cell function. Cyclooxygenase (COX)-2, the rate-limiting enzyme in the synthesis of prostaglandins, is over-expressed by several tumours. We aimed at determining whether COX-2 inhibitors down-regulate [...] Read more.
Indoleamine 2,3-dioxygenase 1 (IDO1) metabolizes L-tryptophan to kynurenines (KYN), inducing T-cell suppression either directly or by altering antigen-presenting-cell function. Cyclooxygenase (COX)-2, the rate-limiting enzyme in the synthesis of prostaglandins, is over-expressed by several tumours. We aimed at determining whether COX-2 inhibitors down-regulate the IFN-g-induced expression of IDO1 in acute myeloid leukaemia (AML) cells. IFN-γ at 100 ng/mL up-regulated COX-2 and IDO1 in HL-60 AML cells, both at mRNA and protein level. The increased COX-2 and IDO1 expression correlated with heightened production of prostaglandin (PG)E2 and kynurenines, respectively. Nimesulide, a preferential COX-2 inhibitor, down-regulated IDO1 mRNA/protein and attenuated kynurenine synthesis, suggesting that overall IDO inhibition resulted both from reduced IDO1 gene transcription and from inhibited IDO1 catalytic activity. From a functional standpoint, IFN-g-challenged HL-60 cells promoted the in vitro conversion of allogeneic CD4+CD25 T cells into bona fide CD4+CD25+FoxP3+ regulatory T cells, an effect that was significantly reduced by treatment of IFN-γ-activated HL-60 cells with nimesulide. Overall, these data point to COX-2 inhibition as a potential strategy to be pursued with the aim at circumventing leukaemia-induced, IDO-mediated immune dysfunction. Full article
(This article belongs to the Special Issue Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry)
Open AccessArticle Sinulariolide Induced Hepatocellular Carcinoma Apoptosis through Activation of Mitochondrial-Related Apoptotic and PERK/eIF2α/ATF4/CHOP Pathway
Molecules 2013, 18(9), 10146-10161; doi:10.3390/molecules180910146
Received: 22 July 2013 / Revised: 14 August 2013 / Accepted: 19 August 2013 / Published: 22 August 2013
Cited by 15 | PDF Full-text (1673 KB) | HTML Full-text | XML Full-text
Abstract
Sinulariolide, an active compound isolated from the cultured soft coral Sinularia flexibilis, has potent anti-microbial and anti-tumorigenesis effects towards melanoma and bladder cancer cells. In this study, we investigated the effects of sinulariolide on hepatocellular carcinoma (HCC) cell growth and protein [...] Read more.
Sinulariolide, an active compound isolated from the cultured soft coral Sinularia flexibilis, has potent anti-microbial and anti-tumorigenesis effects towards melanoma and bladder cancer cells. In this study, we investigated the effects of sinulariolide on hepatocellular carcinoma (HCC) cell growth and protein expression. Sinulariolide suppressed the proliferation and colony formation of HCC HA22T cells in a dose-dependent manner and induced both early and late apoptosis according to flow cytometry, Annexin V/PI stain and TUNEL/DAPI stain analyses. A mechanistic analysis demonstrated that sinulariolide-induced apoptosis was activated through a mitochondria-related pathway, showing up-regulation of Bax, Bad and AIF, and down- regulation of Bcl-2, Bcl-xL, MCl-1 and p-Bad. Sinulariolide treatment led to loss of the mitochondrial membrane potential, release of mitochondrial cytochrome c to the cytosol, and activation of both caspase-9 and caspase-3. Sinulariolide-induced apoptosis was significantly blocked by the caspase inhibitors Z-VAD-FMK and Z-DEVD-FMK. The increased expression of cleaved PARP also suggested that caspase-independent apoptotic pathway was involved. In the western blotting; the elevation of ER chaperones GRP78; GRP94; and CALR; as well as up-regulations of PERK/eIF2α/ATF4/CHOP; and diminished cell death with pre-treatment of eIF2α phosphatase inhibitor; salubrinal; implicated the involvement of ER stress-mediated PERK/eIF2α/ATF4/CHOP apoptotic pathway following sinulariolide treatment in hepatoma cells. The current study suggested sinulariolide-induced hepatoma cell cytotoxicity involved multiple apoptotic signal pathways. This may implicate that sinulariolide is a potential compound for the treatment of hepatocellular carcinoma. Full article
Open AccessArticle Protein Structure Validation and Identification from Unassigned Residual Dipolar Coupling Data Using 2D-PDPA
Molecules 2013, 18(9), 10162-10188; doi:10.3390/molecules180910162
Received: 23 May 2013 / Revised: 10 August 2013 / Accepted: 13 August 2013 / Published: 22 August 2013
Cited by 2 | PDF Full-text (1627 KB) | HTML Full-text | XML Full-text
Abstract
More than 90% of protein structures submitted to the PDB each year are homologous to some previously characterized protein structure. The extensive resources that are required for structural characterization of proteins can be justified for the 10% of the novel structures, but [...] Read more.
More than 90% of protein structures submitted to the PDB each year are homologous to some previously characterized protein structure. The extensive resources that are required for structural characterization of proteins can be justified for the 10% of the novel structures, but not for the remaining 90%. This report presents the 2D-PDPA method, which utilizes unassigned residual dipolar coupling in order to address the economics of structure determination of routine proteins by reducing the data acquisition and processing time. 2D-PDPA has been demonstrated to successfully identify the correct structure of an array of proteins that range from 46 to 445 residues in size from a library of 619 decoy structures by using unassigned simulated RDC data. When using experimental data, 2D-PDPA successfully identified the correct NMR structures from the same library of decoy structures. In addition, the most homologous X-ray structure was also identified as the second best structural candidate. Finally, success of 2D-PDPA in identifying and evaluating the most appropriate structure from a set of computationally predicted structures in the case of a previously uncharacterized protein Pf2048.1 has been demonstrated. This protein exhibits less than 20% sequence identity to any protein with known structure and therefore presents a compelling and practical application of our proposed work. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
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Open AccessArticle Synthesis and Anti-HBV Activity of Novel 3′-N-phenylsulfonyl Docetaxel Analogs
Molecules 2013, 18(9), 10189-10212; doi:10.3390/molecules180910189
Received: 13 June 2013 / Revised: 15 August 2013 / Accepted: 17 August 2013 / Published: 22 August 2013
PDF Full-text (301 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nine new 3′-N-phenylsulfonyl docetaxel analogs were synthesized in good yields from the key intermediate N-phenylsulfonyl oxazolidine via a six-step route. These analogs were tested for anti-hepatitis B virus (HBV) activity in vitro. Compounds 3e, 3g and 3j showed [...] Read more.
Nine new 3′-N-phenylsulfonyl docetaxel analogs were synthesized in good yields from the key intermediate N-phenylsulfonyl oxazolidine via a six-step route. These analogs were tested for anti-hepatitis B virus (HBV) activity in vitro. Compounds 3e, 3g and 3j showed more potent inhibitory activity against HBeAg secretion than the positive control lamivudine. Further extensive SAR and mechanistic studies will be reported in due course. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Comparison of Two Methods, UHPLC-UV and UHPLC-MS/MS, for the Quantification of Polyphenols in Cider Apple Juices
Molecules 2013, 18(9), 10213-10227; doi:10.3390/molecules180910213
Received: 11 July 2013 / Revised: 12 August 2013 / Accepted: 12 August 2013 / Published: 22 August 2013
Cited by 3 | PDF Full-text (408 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to develop faster and more efficient phenotyping methods for in-depth genetic studies on cider apple progeny. The UHPLC chromatographic system was chosen to separate polyphenolic compounds, and quantifications were then simultaneously performed with a UV-PDA detector [...] Read more.
The aim of this study was to develop faster and more efficient phenotyping methods for in-depth genetic studies on cider apple progeny. The UHPLC chromatographic system was chosen to separate polyphenolic compounds, and quantifications were then simultaneously performed with a UV-PDA detector and an ESI-triple quadrupole mass analyzer (SRM mode). Both quantification methods were validated for 15 major compounds using two apple juice samples, on the basis of linearity, limits of detection and quantification, recovery and precision tests. The comparison between UV and SRM quantifications in 120 different samples of a cider apple progeny showed an excellent correlation for major compounds quantified with both methods. However, an overestimation was revealed for five compounds with the UV detector and the mass analyzer. Co-elution and matrix effects are discussed to explain this phenomenon. SRM methods should therefore be considered with restrictions in some cases for quantification measurements when several phenolic compounds are simultaneously quantified in complex matrices such as apple juices. For both methods, analyses were carried out over short periods of time while maintaining a high quality for the simultaneous quantification of phenolic compounds in apple juice. Each method is relevant for more in-depth genetic studies of the polyphenol content of apple juice. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle A 3D QSAR Study of Betulinic Acid Derivatives as Anti-Tumor Agents Using Topomer CoMFA: Model Building Studies and Experimental Verification
Molecules 2013, 18(9), 10228-10241; doi:10.3390/molecules180910228
Received: 2 July 2013 / Revised: 13 August 2013 / Accepted: 13 August 2013 / Published: 22 August 2013
Cited by 14 | PDF Full-text (424 KB) | HTML Full-text | XML Full-text
Abstract
Betulinic acid (BA) is a natural product that exerts its cytotoxicity against various malignant carcinomas without side effects by triggering the mitochondrial pathway to apoptosis. Betulin (BE), the 28-hydroxyl analog of BA, is present in large amounts (up to 30% dry weight) [...] Read more.
Betulinic acid (BA) is a natural product that exerts its cytotoxicity against various malignant carcinomas without side effects by triggering the mitochondrial pathway to apoptosis. Betulin (BE), the 28-hydroxyl analog of BA, is present in large amounts (up to 30% dry weight) in the outer bark of birch trees, and shares the same pentacyclic triterpenoid core as BA, yet exhibits no significant cytotoxicity. Topomer CoMFA studies were performed on 37 BA and BE derivatives and their in vitro anti-cancer activity results (reported as IC50 values) against HT29 human colon cancer cells in the present study. All derivatives share a common pentacyclic triterpenoid core and the molecules were split into three pieces by cutting at the C-3 and C-28 sites with a consideration toward structural diversity. The analysis gave a leave-one-out cross-validation q2 value of 0.722 and a non-cross-validation r2 value of 0.974, which suggested that the model has good predictive ability (q2 > 0.2). The contour maps illustrated that bulky and electron-donating groups would be favorable for activity at the C-28 site, and a moderately bulky and electron-withdrawing group near the C-3 site would improve this activity. BE derivatives were designed and synthesized according to the modeling result, whereby bulky electronegative groups (maleyl, phthalyl, and hexahydrophthalyl groups) were directly introduced at the C-28 position of BE. The in vitro cytotoxicity values of the given analogs against HT29 cells were consistent with the predicted values, proving that the present topomer CoMFA model is successful and that it could potentially guide the synthesis of new betulinic acid derivatives with high anti-cancer activity. The IC50 values of these three new compounds were also assayed in five other tumor cell lines. 28-O-hexahydrophthalyl BE exhibited the greatest anti-cancer activities and its IC50 values were lower than those of BA in all cell lines, excluding DU145 cells. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Brefeldin A Effectively Inhibits Cancer Stem Cell-Like Properties and MMP-9 Activity in Human Colorectal Cancer Colo 205 Cells
Molecules 2013, 18(9), 10242-10253; doi:10.3390/molecules180910242
Received: 30 May 2013 / Revised: 14 August 2013 / Accepted: 19 August 2013 / Published: 22 August 2013
Cited by 8 | PDF Full-text (915 KB) | HTML Full-text | XML Full-text
Abstract
Cancer stem cells (CSCs) are a small subset of cancer cells with indefinite potential for self-renewal and the capacity to drive tumorigenesis. Brefeldin A (BFA) is an antibiotic that is known to block protein transport and induce endoplasmic reticulum (ER) stress in [...] Read more.
Cancer stem cells (CSCs) are a small subset of cancer cells with indefinite potential for self-renewal and the capacity to drive tumorigenesis. Brefeldin A (BFA) is an antibiotic that is known to block protein transport and induce endoplasmic reticulum (ER) stress in eukaryotic cells, but its effects on colorectal CSCs are unknown. We investigated the inhibitory effect of BFA on human colorectal cancer Colo 205 cells. We found that BFA effectively reduced the survival of suspension Colo 205 cells (IC50 = ~15 ng/mL) by inducing apoptosis, and inhibited the clonogenic activity of Colo 205 CSCs in tumorsphere formation assay and soft agar colony formation assay in the same nanogram per milliliter range. We also discovered that at such low concentrations, BFA effectively induced endoplasmic reticulum (ER) stress response as indicated by the increased mRNA expression of ER stress-related genes, such as glucose-regulated protein 78 (GRP78), X-box binding protein 1 (XBP1), and C/EBP homologous protein (CHOP). Finally, we found that BFA reduced the activity of matrix metallopeptidase 9 (MMP-9). These findings suggest that BFA can effectively suppress the progression of colorectal cancer during the tumorigenesis and metastasis stages. These results may lead to the development of novel therapies for the treatment of colorectal cancer. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Understanding the Nucleophilic Character and Stability of the Carbanions and Alkoxides of 1-(9-Anthryl)ethanol and Derivatives
Molecules 2013, 18(9), 10254-10265; doi:10.3390/molecules180910254
Received: 3 June 2013 / Revised: 13 August 2013 / Accepted: 16 August 2013 / Published: 22 August 2013
Cited by 1 | PDF Full-text (412 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The nucleophilic character and stability of the carbanions vs. alkoxides derived from 2,2,2-trifluoro-1-(9-anthryl)ethanol and 1-(9-anthryl)ethanol containing X electron-releasing and X electron-acceptor substituents attached to C-10, have been studied at the B3LYP/6-31+G(d,p) level of theory. Results analyzed in terms of the absolute [...] Read more.
The nucleophilic character and stability of the carbanions vs. alkoxides derived from 2,2,2-trifluoro-1-(9-anthryl)ethanol and 1-(9-anthryl)ethanol containing X electron-releasing and X electron-acceptor substituents attached to C-10, have been studied at the B3LYP/6-31+G(d,p) level of theory. Results analyzed in terms of the absolute gas-phase acidity, Fukui function, the local hard and soft acids and bases principle, and the molecular electrostatic potential, show that the central ring of the 9-anthryl group confers an ambident nucleophilic character and stabilizes the conjugated carbanion by electron-acceptor delocalization. Full article
(This article belongs to the Special Issue Electrophilic & Nucleophilic Substitution)
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Open AccessArticle GABAB-Agonistic Activity of Certain Baclofen Homologues
Molecules 2013, 18(9), 10266-10284; doi:10.3390/molecules180910266
Received: 12 July 2013 / Revised: 13 August 2013 / Accepted: 15 August 2013 / Published: 22 August 2013
Cited by 1 | PDF Full-text (271 KB) | HTML Full-text | XML Full-text
Abstract
Baclofen (1) is a potent and selective agonist for bicuculline-insensitive GABAB receptors and is used clinically as an antispastic and muscle relaxant agent. In the search for new bioactive chemical entities that bind specifically to GABAB receptors, we [...] Read more.
Baclofen (1) is a potent and selective agonist for bicuculline-insensitive GABAB receptors and is used clinically as an antispastic and muscle relaxant agent. In the search for new bioactive chemical entities that bind specifically to GABAB receptors, we report here the synthesis of certain baclofen homologues, namely (R,S)-5-amino-3-arylpentanoic acid hydrochlorides (R,S)-1ah as well as (R,S)-5-amino-3-methylpentanoic acid [(RS)-1i] to be evaluated as GABABR agonists. Compound 1a is an agonist to GABAB receptors with an EC50 value of 46 μM on tsA201 cells transfected with GABAB1b/GABAB2/Gqz5, being the most active congener among all the synthesized compounds. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Protective Effects of Alkaloid Compounds from Nelumbinis Plumula on tert-Butyl Hydroperoxide-Induced Oxidative Stress
Molecules 2013, 18(9), 10285-10300; doi:10.3390/molecules180910285
Received: 11 July 2013 / Revised: 12 August 2013 / Accepted: 16 August 2013 / Published: 26 August 2013
Cited by 8 | PDF Full-text (266 KB) | HTML Full-text | XML Full-text
Abstract
This study was conducted to investigate the effect of Nelumbinis Plumula total alkaloid (NPA) and its main alkaloid components on oxidative stress induced by tert-butyl hydroperoxide (t-BHP) in the human hepatocellular HepG2 cell line. According to HPLC analysis, several [...] Read more.
This study was conducted to investigate the effect of Nelumbinis Plumula total alkaloid (NPA) and its main alkaloid components on oxidative stress induced by tert-butyl hydroperoxide (t-BHP) in the human hepatocellular HepG2 cell line. According to HPLC analysis, several major alkaloid compounds such as liensinine, isoliensinine and neferine were present in NPA. The cytotoxic effects in 0.55 mM t-BHP-induced HepG2 cells were significantly inhibited by NPA and the major compound in NPA, neferine, showed the strongest activities. The protective effect of neferine against oxidative stress induced by t-BHP may be associated with decreased ROS formation, TBARS generation, LDH release and increased GSH levels, suggesting their involvement of the cytoprotective on oxidative stress. The effects were comparable with quercetin, which was used as positive control. Overall, total alkaloid and alkaloid compounds from Nelumbinis Plumula displayed a significant cytoprotective effect against oxidative stress. Further study is needed to elucidate the relationship between the chemical structures of the components in NPA and their protective effect on oxidative stress. Full article
Open AccessArticle Coverage Dependent Variation of the Adsorption Structure of 2-Thiophenecarboxaldehyde on the Ge(100)-2 × 1 Reconstructed Surface
Molecules 2013, 18(9), 10301-10311; doi:10.3390/molecules180910301
Received: 22 July 2013 / Revised: 16 August 2013 / Accepted: 19 August 2013 / Published: 26 August 2013
Cited by 1 | PDF Full-text (739 KB) | HTML Full-text | XML Full-text
Abstract
High-resolution photoemission spectroscopy (HRPES) measurements were collected and density functional theory (DFT) calculations were performed to track the exposure-dependent variation of the adsorption structure of 2-thiophenecarboxaldehyde (C4H3SCHO: TPCA) on the Ge(100) 2 × 1 reconstructed surface at room [...] Read more.
High-resolution photoemission spectroscopy (HRPES) measurements were collected and density functional theory (DFT) calculations were performed to track the exposure-dependent variation of the adsorption structure of 2-thiophenecarboxaldehyde (C4H3SCHO: TPCA) on the Ge(100) 2 × 1 reconstructed surface at room temperature. In an effort to identify the most probable adsorption structures on the Ge(100)-2 × 1 reconstructed surface, we deposited TPCA molecules at low exposure and at high exposure and compared the differences between the electronic features measured using HRPES. The HRPES data suggested three possible adsorption structures of TPCA on the Ge(100)-2 × 1 reconstructed surface, and DFT calculations were used to determine the plausibility of these structures. HRPES analysis corroborated by DFT calculations, indicated that an S-dative bonded structure is the most probable adsorption structure at relatively low exposure levels, the [4 + 2] cycloadduct structure is the second most probable structure, and the [2 + 2]-C=O cycloadduct structure is the least probable structure on the Ge(100)-2 × 1 reconstructed surface at relatively high exposure levels. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Bioactive Flavone-C-Glycosides of the African Medicinal Plant Biophytum umbraculum
Molecules 2013, 18(9), 10312-10319; doi:10.3390/molecules180910312
Received: 3 July 2013 / Revised: 8 August 2013 / Accepted: 14 August 2013 / Published: 26 August 2013
Cited by 3 | PDF Full-text (257 KB) | HTML Full-text | XML Full-text
Abstract
Three flavone-C-glycosides—cassiaoccidentalin A (1), isovitexin (2) and isoorientin (3)—were isolated from the ethyl acetate (EtOAc) soluble fraction of the methanol crude extract of the African medicinal plant Biophytum umbraculum, This is the first [...] Read more.
Three flavone-C-glycosides—cassiaoccidentalin A (1), isovitexin (2) and isoorientin (3)—were isolated from the ethyl acetate (EtOAc) soluble fraction of the methanol crude extract of the African medicinal plant Biophytum umbraculum, This is the first report of these compounds in this plant. All compounds were identified by spectroscopic analysis and comparison with published data. Isoorientin (3) and the EtOAc extract showed the greatest antioxidant activity in the DPPH assay as well as the strongest inhibition of xanthine oxidase (XO) and 15-lipoxygenase (15-LO). From these results, the extract of B. umbraculum might be a valuable source of flavone C-glycosides. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Volatile Organic Compounds Obtained by in Vitro Callus Cultivation of Plectranthus ornatus Codd. (Lamiaceae)
Molecules 2013, 18(9), 10320-10333; doi:10.3390/molecules180910320
Received: 22 July 2013 / Revised: 10 August 2013 / Accepted: 22 August 2013 / Published: 26 August 2013
Cited by 4 | PDF Full-text (950 KB) | HTML Full-text | XML Full-text
Abstract
Plectranthus spp (Lamiaceae) are plants of economic importance because they are sources of aromatic essential oils and are also cultivated and several species of this genus are used as folk medicines. This paper describes the effects of different concentrations of the 2,4-dichlorophenoxyacetic [...] Read more.
Plectranthus spp (Lamiaceae) are plants of economic importance because they are sources of aromatic essential oils and are also cultivated and several species of this genus are used as folk medicines. This paper describes the effects of different concentrations of the 2,4-dichlorophenoxyacetic acid (2,4-D) and 1-naphthaleneacetic acid (NAA) on the induction of callus from nodal segments of Plectranthus ornatus Codd and in the production of volatile organic compounds (monoterpenes and sesquiterpenes). The 20 and 40 day calli were subjected to solid phase micro extraction (HS-SPME) and submitted to GCMS analysis. Variations in VOCs between the samples were observed and, a direct relationship was observed between of the major constituent detected (α-terpinyl acetate) and the monoterpenes α-thujene, α-pinene, β-pinene, camphene, sabinene and α-limonene that were present in the volatile fractions. Besides α-terpinyl acetate, isobornyl acetate and α-limonene were also major constituents. Variations were observed in VOCs in the analyzed periods. The best cultivation media for the production of VOCs was found to be MS0 (control). Moderate success was achieved by treatment with 2.68 µM and 5:37 µM NAA (Group 2). With 2,4-D (9.0 µM), only the presence of α-terpinyl acetate and isocumene were detected and, with 2.26 µM of 2,4-D was produced mainly α-terpinyl acetate, α-thujene and β-caryophyllene (16.2%). The VOC profiles present in P. ornatus were interpreted using PCA and HCA. The results permitted us to determine the best cultivation media for VOC production and, the PCA and HCA analysis allowed us to recognize four groups among the different treatments from the compounds identified in this set of treatments. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Palladium-Catalyzed Synthesis of Natural and Unnatural 2-, 5-, and 7-Oxygenated Carbazole Alkaloids from N-Arylcyclohexane Enaminones
Molecules 2013, 18(9), 10334-10351; doi:10.3390/molecules180910334
Received: 5 July 2013 / Revised: 5 August 2013 / Accepted: 12 August 2013 / Published: 26 August 2013
Cited by 3 | PDF Full-text (330 KB) | HTML Full-text | XML Full-text
Abstract
A palladium-catalyzed synthesis of the carbazole framework is described, including the preparation of 2-, 5-, and 7-oxygenated natural and unnatural carbazole alkaloids. A series of N-arylcyclohexane enaminones, generated by condensation of cyclohexane-1,3-dione with diverse anilines, were aromatized by a Pd(0)-catalyzed thermal [...] Read more.
A palladium-catalyzed synthesis of the carbazole framework is described, including the preparation of 2-, 5-, and 7-oxygenated natural and unnatural carbazole alkaloids. A series of N-arylcyclohexane enaminones, generated by condensation of cyclohexane-1,3-dione with diverse anilines, were aromatized by a Pd(0)-catalyzed thermal treatment to afford the corresponding diarylamines. The latter were submitted to a Pd(II)-catalyzed cyclization and methylation processes to provide the desired carbazoles, including clausine V. Following an inverse strategy, a new and short total synthesis of glycoborine is also reported. Full article
(This article belongs to the Special Issue Palladium Catalysts)
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Open AccessArticle Bioactive Protopanaxatriol Type Saponins Isolated from the Roots of Panax Notoginseng (Burk.) F. H. Chen
Molecules 2013, 18(9), 10352-10366; doi:10.3390/molecules180910352
Received: 22 July 2013 / Revised: 12 August 2013 / Accepted: 20 August 2013 / Published: 26 August 2013
Cited by 9 | PDF Full-text (353 KB) | HTML Full-text | XML Full-text
Abstract
Seven new protopanaxatriol type saponins, 20S-sanchirhinosides A1 (1), A2 (2), A3 (3), A4 (4), A5 (5), and A6 (6), and sanchirhinoside B [...] Read more.
Seven new protopanaxatriol type saponins, 20S-sanchirhinosides A1 (1), A2 (2), A3 (3), A4 (4), A5 (5), and A6 (6), and sanchirhinoside B (7) were obtained as minor constituents from the root extract of Panax notoginseng (Burkill, F. H. Chen), which showed protection effects against antimycin A induced mitochondrial oxidative stress. Their structures were elucidated by chemical and spectroscopic methods (IR, HRESI-TOF-MS, 1D and 2D NMR). Among them, compounds 4, 6 and 7 showed significant protective effects against antimycin A-induced L6 cell injury. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication 3-Bromo-1-Hydroxy-9,10-Anthraquinone (BHAQ) Inhibits Growth and Migration of the Human Breast Cancer Cell Lines MCF-7 and MDA-MB231
Molecules 2013, 18(9), 10367-10377; doi:10.3390/molecules180910367
Received: 8 June 2013 / Revised: 12 August 2013 / Accepted: 15 August 2013 / Published: 27 August 2013
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Abstract
Breast cancer is becoming more prominent in women today. As of now, there are no effective treatments in treating metastatic breast cancer. We have tested the cytotoxic and anti-migration effects of BHAQ, a synthesized anthraquinone, on two breast cancer cell lines, MCF-7 [...] Read more.
Breast cancer is becoming more prominent in women today. As of now, there are no effective treatments in treating metastatic breast cancer. We have tested the cytotoxic and anti-migration effects of BHAQ, a synthesized anthraquinone, on two breast cancer cell lines, MCF-7 and MDA-MB231. Anthraquinones are an interesting class of molecules that display a wide spectrum of biological applications, including anticancer properties. Cellular inhibition was tested through a MTT assay, double acridine orange/propidium iodide staining and FACS cell cycle analysis. Inhibition of migration was tested by the wound healing method, and migration through a Boyden chamber. BHAQ was cytotoxic towards both cell lines in a dose dependent and possibly cell-dependent manner. Additionally, BHAQ also inhibited the migration of the highly metastatic MDA-MB231 cell line. Full article
Open AccessArticle Antitumor, Antioxidant and Antimicrobial Studies of Substituted Pyridylguanidines
Molecules 2013, 18(9), 10378-10396; doi:10.3390/molecules180910378
Received: 14 July 2013 / Revised: 23 July 2013 / Accepted: 26 July 2013 / Published: 27 August 2013
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Abstract
A series of N-pivaloyl-N-(alkyl/aryl)-N′′-pyridylguanidine of general formula C4H9CONHC(NR1R2)NPy have been synthesized and characterized using elemental analysis, FT-IR, multinuclear NMR spectroscopy, and in the case of compounds 7 [...] Read more.
A series of N-pivaloyl-N-(alkyl/aryl)-N′′-pyridylguanidine of general formula C4H9CONHC(NR1R2)NPy have been synthesized and characterized using elemental analysis, FT-IR, multinuclear NMR spectroscopy, and in the case of compounds 7 and 11, by single crystal X-ray diffraction (XRD). The synthesized guanidines were tested for antitumor activities against potato tumor, and showed excellent inhibition against Agrobacterium tumefaciens (AT10)-induced tumor. The antioxidant and antimicrobial activities of these new compounds against various bacterial and fungal strains were also investigated. Full article
Open AccessArticle Three New Phenolics and Other Constituents from the Seeds of Lithocarpus pachylepis
Molecules 2013, 18(9), 10397-10403; doi:10.3390/molecules180910397
Received: 1 July 2013 / Revised: 25 August 2013 / Accepted: 26 August 2013 / Published: 28 August 2013
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Abstract
Twelve phenolics, including the three new compounds balanophonin C (1), balanophonin D (2), balanophonin E (3), were isolated from the seeds of Lithocarpus pachylepis. Their structures were elucidated by various spectroscopic techniques (UV, IR, MS, [...] Read more.
Twelve phenolics, including the three new compounds balanophonin C (1), balanophonin D (2), balanophonin E (3), were isolated from the seeds of Lithocarpus pachylepis. Their structures were elucidated by various spectroscopic techniques (UV, IR, MS, 1D and 2D NMR). Compounds 19 were evaluated for their anti-inflammatory activities on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 and showed moderate inhibitory activities, with IC50 values ranging from 10.9 to 34.7 μM. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Anti-Inflammatory Effects of Total Isoflavones from Pueraria lobata on Cerebral Ischemia in Rats
Molecules 2013, 18(9), 10404-10412; doi:10.3390/molecules180910404
Received: 17 July 2013 / Revised: 21 August 2013 / Accepted: 23 August 2013 / Published: 28 August 2013
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Abstract
Puerariae radix, the dried root of Pueraria lobata Ohwi, is one of earliest and most important edible crude herbs used for various medical purposes in Oriental medicine. The aim of the present study was to determine the anti-inflammatory effects of Total Isoflavones [...] Read more.
Puerariae radix, the dried root of Pueraria lobata Ohwi, is one of earliest and most important edible crude herbs used for various medical purposes in Oriental medicine. The aim of the present study was to determine the anti-inflammatory effects of Total Isoflavones from P. lobata (TIPL), which contains the unique isoflavone puerarin, in ischemia in vivo models. Oral administration of TIPL (100 mg/kg) reduced the brain infarct volume and attenuated ischemia-induced cyclooxygenase-2 (COX-2) up-regulation at 2 days after middle cerebral artery occlusion (MCAo) in rats. Moreover, TIPL reduced activation of glial fibrillary acid protein (GFAP) and CD11b antibody (OX-42) at 7 days after MCAo in hippocampal CA1 region. These results show that TIPL can protect the brain from ischemic damage after MCAo. Regarding the immunohistochemical study, the effects of TIPL may be attributable to its anti-inflammatory properties by the inhibition of COX-2 expression, astrocyte expression, and microglia. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle 2-(Substituted phenyl)-3,4-dihydroisoquinolin-2-iums as Novel Antifungal Lead Compounds: Biological Evaluation and Structure-Activity Relationships
Molecules 2013, 18(9), 10413-10424; doi:10.3390/molecules180910413
Received: 5 July 2013 / Revised: 18 July 2013 / Accepted: 22 August 2013 / Published: 29 August 2013
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Abstract
The title compounds are a class of structurally simple analogues of quaternary benzo[c]phenanthridine alkaloids (QBAs). In order to develop novel QBA-like antifungal drugs, in this study, 24 of the title compounds with various substituents on the N-phenyl ring were [...] Read more.
The title compounds are a class of structurally simple analogues of quaternary benzo[c]phenanthridine alkaloids (QBAs). In order to develop novel QBA-like antifungal drugs, in this study, 24 of the title compounds with various substituents on the N-phenyl ring were evaluated for bioactivity against seven phytopathogenic fungi using the mycelial growth rate method and their SAR discussed. Almost all the compounds showed definite activities in vitro against each of the test fungi at 50 μg/mL and a broad antifungal spectrum. In most cases, the mono-halogenated compounds 212 exhibited excellent activities superior to the QBAs sanguinarine and chelerythrine. Compound 8 possessed the strongest activities on each of the fungi with EC50 values of 8.88–19.88 µg/mL and a significant concentration-dependent relationship. The SAR is as follows: the N-phenyl group is a high sensitive structural moiety for the activity and the characteristics and position of substituents intensively influence the activity. Generally, electron-withdrawing substituents remarkably enhance the activity while electron-donating substituents cause a decrease of the activity. In most cases, ortha- and para-halogenated isomers were more active than the corresponding m-halogenated isomers. Thus, the title compounds emerged as promising lead compounds for the development of novel biomimetic antifungal agrochemicals. Compounds 8 and 2 should have great potential as new broad spectrum antifungal agents for plant protection. Full article
Open AccessArticle Cosmos Caudatus as a Potential Source of Polyphenolic Compounds: Optimisation of Oven Drying Conditions and Characterisation of Its Functional Properties
Molecules 2013, 18(9), 10452-10464; doi:10.3390/molecules180910452
Received: 28 July 2013 / Revised: 7 August 2013 / Accepted: 12 August 2013 / Published: 29 August 2013
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Abstract
The aim of the study was to analyze the influence of oven thermal processing of Cosmos caudatus on the total polyphenolic content (TPC) and antioxidant capacity (DPPH) of two different solvent extracts (80% methanol, and 80% ethanol). Sonication was used to extract [...] Read more.
The aim of the study was to analyze the influence of oven thermal processing of Cosmos caudatus on the total polyphenolic content (TPC) and antioxidant capacity (DPPH) of two different solvent extracts (80% methanol, and 80% ethanol). Sonication was used to extract bioactive compounds from this herb. The results showed that the optimised conditions for the oven drying method for 80% methanol and 80% ethanol were 44.5 °C for 4 h with an IC50 of 0.045 mg/mL and 43.12 °C for 4.05 h with an IC50 of 0.055 mg/mL, respectively. The predicted values for TPC under the optimised conditions for 80% methanol and 80% ethanol were 16.5 and15.8 mg GAE/100 g DW, respectively. The results obtained from this study demonstrate that Cosmos caudatus can be used as a potential source of antioxidants for food and medicinal applications. Full article
Open AccessArticle Salicortin-Derivatives from Salix pseudo-lasiogyne Twigs Inhibit Adipogenesis in 3T3-L1 Cells via Modulation of C/EBPα and SREBP1c Dependent Pathway
Molecules 2013, 18(9), 10484-10496; doi:10.3390/molecules180910484
Received: 22 July 2013 / Revised: 26 August 2013 / Accepted: 27 August 2013 / Published: 30 August 2013
Cited by 6 | PDF Full-text (942 KB) | HTML Full-text | XML Full-text
Abstract
Obesity is reported to be associated with excessive growth of adipocyte mass tissue as a result of increases in the number and size of adipocytes differentiated from preadipocytes. To search for anti-adipogenic phytochemicals, we screened for inhibitory activities of various plant sources [...] Read more.
Obesity is reported to be associated with excessive growth of adipocyte mass tissue as a result of increases in the number and size of adipocytes differentiated from preadipocytes. To search for anti-adipogenic phytochemicals, we screened for inhibitory activities of various plant sources on adipocyte differentiation in 3T3-L1 preadipocytes. Among the sources, a methanolic extract of Salix pseudo-lasiogyne twigs (Salicaceae) reduced lipid accumulation in a concentration-dependent manner. During our search for anti-adipogenic constituents from S. pseudo-lasiogyne, five salicortin derivatives isolated from an EtOAc fraction of this plant and bearing 1-hydroxy-6-oxo-2-cyclohexene-carboxylate moieties, namely 2′,6′-O-acetylsalicortin (1), 2′-O-acetylsalicortin (2), 3′-O-acetylsalicortin (3), 6′-O-acetylsalicortin (4), and salicortin (5), were found to significantly inhibit adipocyte differentiation in 3T3-L1 cells. In particular, 2′,6′-O-acetylsalicortin (1) had the most potent inhibitory activity on adipocyte differentiation, with an IC50 value of 11.6 μM, and it significantly down-regulated the expressions of CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element binding protein 1 (SREBP1c). Furthermore, 2′,6′-O-acetylsalicortin (1) suppressed mRNA expression levels of C/EBPβ during the early stage of adipocyte differentiation and stearoyl coenzyme A desaturase 1 (SCD-1), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) expression, target genes of SREBP1c. In the present study, we demonstrate that the anti-adipogenesis mechanism of 2′,6′-O-acetylsalicortin (1) may be mediated via down-regulation of C/EBPα and SREBP1c dependent pathways. Through their anti-adipogenic activity, salicortin derivatives may be potential novel therapeutic agents against obesity. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Quantitative Structure-Property Relationships of Side Chain-Modified Hyodeoxycholic Acid Derivatives
Molecules 2013, 18(9), 10497-10513; doi:10.3390/molecules180910497
Received: 9 July 2013 / Revised: 21 August 2013 / Accepted: 27 August 2013 / Published: 30 August 2013
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Abstract
Bile acids have emerged as versatile signalling compounds of a complex network of nuclear and membrane receptors regulating various endocrine and paracrine functions. The elucidation of the interconnection between the biological pathways under the bile acid control and manifestations of hepatic and [...] Read more.
Bile acids have emerged as versatile signalling compounds of a complex network of nuclear and membrane receptors regulating various endocrine and paracrine functions. The elucidation of the interconnection between the biological pathways under the bile acid control and manifestations of hepatic and metabolic diseases have extended the scope of this class of steroids for in vivo investigations. In this framework, the design and synthesis of novel biliary derivatives able to modulate a specific receptor requires a deep understanding of both structure-activity and structure-property relationships of bile acids. In this paper, we report the preparation and the critical micellization concentration evaluation of a series of hyodeoxycholic acid derivatives characterized by a diverse side chain length and by the presence of a methyl group at the alpha position with respect to the terminal carboxylic acid moiety. The data collected are instrumental to extend on a quantitative basis, the knowledge of the current structure-property relationships of bile acids and will be fruitful, in combination with models of receptor activity, to design and prioritize the synthesis of novel pharmacokinetically suitable ligands useful in the validation of bile acid-responsive receptors as therapeutic targets. Full article
(This article belongs to the Special Issue Steroids)
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Open AccessArticle A Macrocyclic Peptide that Serves as a Cocrystallization Ligand and Inhibits the Function of a MATE Family Transporter
Molecules 2013, 18(9), 10514-10530; doi:10.3390/molecules180910514
Received: 18 June 2013 / Revised: 24 August 2013 / Accepted: 27 August 2013 / Published: 30 August 2013
Cited by 14 | PDF Full-text (991 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The random non-standard peptide integrated discovery (RaPID) system has proven to be a powerful approach to discover de novo natural product-like macrocyclic peptides that inhibit protein functions. We have recently reported three macrocyclic peptides that bind to Pyrococcus furiosus multidrug and toxic [...] Read more.
The random non-standard peptide integrated discovery (RaPID) system has proven to be a powerful approach to discover de novo natural product-like macrocyclic peptides that inhibit protein functions. We have recently reported three macrocyclic peptides that bind to Pyrococcus furiosus multidrug and toxic compound extrusion (PfMATE) transporter and inhibit the transport function. Moreover, these macrocyclic peptides were successfully employed as cocrystallization ligands of selenomethionine-labeled PfMATE. In this report, we disclose the details of the RaPID selection strategy that led to the identification of these three macrocyclic peptides as well as a fourth macrocyclic peptide, MaD8, which is exclusively discussed in this article. MaD8 was found to bind within the cleft of PfMATE’s extracellular side and blocked the path of organic small molecules being extruded. The results of an ethidium bromide efflux assay confirmed the efflux inhibitory activity of MaD8, whose behavior was similar to that of previously reported MaD5. Full article
(This article belongs to the Special Issue Macrocyclic Chemistry)
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Open AccessArticle Automated Solid-Phase Radiofluorination Using Polymer-Supported Phosphazenes
Molecules 2013, 18(9), 10531-10547; doi:10.3390/molecules180910531
Received: 24 July 2013 / Revised: 26 August 2013 / Accepted: 27 August 2013 / Published: 30 August 2013
Cited by 3 | PDF Full-text (1621 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The polymer supported phosphazene bases PS-P2tBu and the novel PS-P2PEG allowed for efficient extraction of [18F]F from proton irradiated [18O]H2O and subsequent radiofluorination of a broad range of substrates [...] Read more.
The polymer supported phosphazene bases PS-P2tBu and the novel PS-P2PEG allowed for efficient extraction of [18F]F from proton irradiated [18O]H2O and subsequent radiofluorination of a broad range of substrates directly on the resin. The highest radiochemical yields were obtained with aliphatic sulfonates (69%) and bromides (42%); the total radiosynthesis time was 35–45 min. The multivariate analysis showed that the radiochemical yields and purities were controlled by the resin load, reaction temperature, and column packing effects. The resins could be reused several times with the same or different substrates. The fully automated on-column radiofluorination methodology was applied to the radiosynthesis of the important PET radiotracers [18F]FLT and [18F]FDG. The latter was produced with 40% yield on a 120 GBq scale and passed GMP-regulated quality control required for commercial production of [18F]FDG. The combination of compact form factor, simplicity of [18F]F recovery and processing, and column reusability can make solid phase radiofluorination an attractive radiochemistry platform for the emerging dose-on-demand instruments for bedside production of PET radiotracers. Full article
(This article belongs to the Special Issue Fluorine Chemistry 2016)
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Open AccessArticle Synthesis and NMR-Study of 1-Trimethylsilyl Substituted Silole Anion [Ph4C4Si(SiMe3)]•[Li]+ and 3-Silolenide 2,5-carbodianions {[Ph4C4Si(n-Bu)2]2•2[Li]+, [Ph4C4Si(t-Bu)2]2•2[Li]+} via Silole Dianion [Ph4C4Si]2•2[Li]+
Molecules 2013, 18(9), 10568-10579; doi:10.3390/molecules180910568
Received: 24 July 2013 / Revised: 21 August 2013 / Accepted: 22 August 2013 / Published: 30 August 2013
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Abstract
1-Trimethylsilyl, 1-R (R = Me, Et, i-Bu)-2,3,4,5-tetraphenyl-1-silacyclopentadiene [Ph4C4Si(SiMe3)R] are synthesized from the reaction of 1-trimethylsilyl,1-lithio-2,3,4,5-tetraphenyl-1-silacyclopentadienide anion [Ph4C4SiMe3]•[Li]+ (3) with methyl iodide, ethyl iodide, and [...] Read more.
1-Trimethylsilyl, 1-R (R = Me, Et, i-Bu)-2,3,4,5-tetraphenyl-1-silacyclopentadiene [Ph4C4Si(SiMe3)R] are synthesized from the reaction of 1-trimethylsilyl,1-lithio-2,3,4,5-tetraphenyl-1-silacyclopentadienide anion [Ph4C4SiMe3]•[Li]+ (3) with methyl iodide, ethyl iodide, and i-butyl bromide. The versatile intermediate 3 is prepared by hemisilylation of the silole dianion [Ph4C4Si]−2•2[Li]+ (2) with trimethylsilyl chloride and characterized by 1H-, 13C-, and 29Si-NMR spectroscopy. 1,1-bis(R)-2,3,4,5-tetraphenyl-1-silacyclopentadiene [Ph4C4SiR2] {R = n-Bu (7); t-Bu (8)} are synthesized from the reaction of 2 with n-butyl bromide and t-butyl bromide. Reduction of 7 and 8 with lithium under sonication gives the respective 3-silolenide 2,5-carbodianions {[Ph4C4Si(n-Bu)2]−2•2[Li]+ (10) and [Ph4C4Si(t-Bu)2]−2•2[Li]+ (11)}, which are characterized by 1H-, 13C-, and 29Si-NMR spectroscopy. Polarization of phenyl groups in 3 is compared with those of silole anion/dianion, germole anion/dianion, and 3-silolenide 2,5-carbodianions 10 and 11. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle In Vitro Delivery and Controlled Release of Doxorubicin for Targeting Osteosarcoma Bone Cancer
Molecules 2013, 18(9), 10580-10598; doi:10.3390/molecules180910580
Received: 14 July 2013 / Revised: 30 July 2013 / Accepted: 1 August 2013 / Published: 30 August 2013
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Abstract
Drug delivery systems are designed to achieve drug therapeutic index and enhance the efficacy of controlled drug release targeting with specificity and selectivity by successful delivery of therapeutic agents at the desired sites without affecting the non-diseased neighbouring cells or tissues. In [...] Read more.
Drug delivery systems are designed to achieve drug therapeutic index and enhance the efficacy of controlled drug release targeting with specificity and selectivity by successful delivery of therapeutic agents at the desired sites without affecting the non-diseased neighbouring cells or tissues. In this research, we developed and demonstrated a bio-based calcium carbonate nanocrystals carrier that can be loaded with anticancer drug and selectively deliver it to cancer cells with high specificity by achieving the effective osteosarcoma cancer cell death without inducing specific toxicity. The results showed pH sensitivity of the controlled release characteristics of the drug at normal physiological pH 7.4 with approximately 80% released within 1,200 min but when exposed pH 4.8 the corresponding 80% was released in 50 min. This study showed that the DOX-loaded CaCO3 nanocrystals have promising applications in delivery of anticancer drugs. Full article
Open AccessArticle Phytochemical, Antimicrobial and Antiprotozoal Evaluation of Garcinia Mangostana Pericarp and α-Mangostin, Its Major Xanthone Derivative
Molecules 2013, 18(9), 10599-10608; doi:10.3390/molecules180910599
Received: 6 August 2013 / Revised: 21 August 2013 / Accepted: 28 August 2013 / Published: 2 September 2013
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Abstract
Five xanthone derivatives and one flavanol were isolated from the dichloromethane extract of Garcinia mangostana. Dichloromethane, ethyl acetate extract and the major xanthone (α-mangostin) were evaluated in vitro against erythrocytic schizonts of Plasmodium falciparum, intracellular amastigotes of Leishmania infantum and Trypanosoma [...] Read more.
Five xanthone derivatives and one flavanol were isolated from the dichloromethane extract of Garcinia mangostana. Dichloromethane, ethyl acetate extract and the major xanthone (α-mangostin) were evaluated in vitro against erythrocytic schizonts of Plasmodium falciparum, intracellular amastigotes of Leishmania infantum and Trypanosoma cruzi and free trypomastigotes of T. brucei. The major constituent α-mangostin was also checked for antimicrobial potential against Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Bacillius subtilis, Staphylococcus aureus, Mycobacterium smegmatis, M. cheleneoi, M. xenopi and M. intracellulare. Activity against P. falciparum (IC50 2.7 μg/mL) and T. brucei (IC50 0.5 μg/mL) were observed for the dichloromethane extract, however, with only moderate selectivity was seen based on a parallel cytotoxicity evaluation on MRC-5 cells (IC50 9.4 μg/mL). The ethyl acetate extract was inactive (IC50 > 30 µg/mL). The major constituent α-mangostin showed rather high cytotoxicity (IC50 7.5 µM) and a broad but non-selective antiprotozoal and antimicrobial activity profile. This in vitro study endorses that the antiprotozoal and antimicrobial potential of prenylated xanthones is non-conclusive in view of the low level of selectivity. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Effect of Salicylic Acid and Structurally Related Compounds in the Accumulation of Phytoalexins in Cotyledons of Common Bean (Phaseolus vulgaris L.) Cultivars
Molecules 2013, 18(9), 10609-10628; doi:10.3390/molecules180910609
Received: 26 July 2013 / Revised: 29 August 2013 / Accepted: 29 August 2013 / Published: 2 September 2013
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Abstract
In the present work, isoflavonoid phytoalexin production in response to the application of salicylic acid in cotyledons of four common bean (Phaseolus vulgaris) cultivars (SA) was evaluated. The time-course and dose-response profiles of the induction process were established by quantifying [...] Read more.
In the present work, isoflavonoid phytoalexin production in response to the application of salicylic acid in cotyledons of four common bean (Phaseolus vulgaris) cultivars (SA) was evaluated. The time-course and dose-response profiles of the induction process were established by quantifying the isoflavonoids by HPLC. Cotyledons of anthracnose-resistant cultivars induced by SA produced substantially higher phytoalexin contents as compared to the susceptible ones. In addition, maximum levels of phytoalexins (50–100 fold increases) were reached between 96 and 144 h, and when a concentration of SA from 3.62 to 14.50 mM was used. The observations also indicate that there was a relatively good correlation between the phytoalexin contents and the inhibitory effect against C. lindemuthianum; the higher antifungal activity was observed during the first 48 hours for extracts from cotyledons treated with SA at 1.45 and 3.62 mM, and between 96 and 144 h after induction. Finally, compounds structurally related to SA (dihydro-quinazolinones and some imines) showed a strong elicitor effect. Moreover, induced extracts from cotyledons treated with these potential elicitors, besides the properly elicitors, displayed a weak to moderated antifungal activity. These compounds may be considered good candidates for developing of new phytoprotectants. Furthermore, phytoalexin-eliciting substances may contribute for selecting disease resistant cultivars. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Pancreatic Lipase Inhibitory Gallotannins from Galla Rhois with Inhibitory Effects on Adipocyte Differentiation in 3T3-L1 Cells
Molecules 2013, 18(9), 10629-10638; doi:10.3390/molecules180910629
Received: 21 June 2013 / Revised: 26 August 2013 / Accepted: 26 August 2013 / Published: 2 September 2013
Cited by 6 | PDF Full-text (302 KB) | HTML Full-text | XML Full-text
Abstract
Activity-guided isolation of a methanolic extract of Galla Rhois using pancreatic lipase and 3T3-L1 adipocytes led to the isolation of seven phenolic compounds: protoaphin-fb (1), 2-O-digalloyl-1,3,4,6-tetra-O-galloyl-b-D-glucose (2), 1,2,3,4,6-penta-O-galloyl-b-D-glucose (3), [...] Read more.
Activity-guided isolation of a methanolic extract of Galla Rhois using pancreatic lipase and 3T3-L1 adipocytes led to the isolation of seven phenolic compounds: protoaphin-fb (1), 2-O-digalloyl-1,3,4,6-tetra-O-galloyl-b-D-glucose (2), 1,2,3,4,6-penta-O-galloyl-b-D-glucose (3), 1,2,4,6-tetra-O-galloyl-b-D-glucose (4), 3-hydroxy-5-methoxy-phenol 1-O-b-D-glucoside (5), methylgallate (6), and gallic acid (7). Their structures were established on the basis of NMR and MS spectroscopic data interpretation. All isolates were evaluated for their inhibitory effects on pancreatic lipase, and compounds 1-5 exhibited potent inhibitory effects on this enzyme, with IC50 values ranging from 30.6 ± 2.4 to 3.5 ± 0.5 mM. In addition, the highly galloylated compound 2 was also found to induce potent inhibition of adipocyte differentiation in 3T3-L1 cells. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Volatile Constituents and Antioxidant Activity of Peel, Flowers and Leaf Oils of Citrus aurantium L. Growing in Greece
Molecules 2013, 18(9), 10639-10647; doi:10.3390/molecules180910639
Received: 24 June 2013 / Revised: 23 August 2013 / Accepted: 28 August 2013 / Published: 2 September 2013
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Abstract
The volatile constituents of the essential oils of the peel, flower (neroli) and leaves (petitgrain) of bitter orange (Citrus aurantium L.) growing in Greece were studied by GC-MS. The analytical procedures enabled the quantitative determination of 31 components. More specifically, the [...] Read more.
The volatile constituents of the essential oils of the peel, flower (neroli) and leaves (petitgrain) of bitter orange (Citrus aurantium L.) growing in Greece were studied by GC-MS. The analytical procedures enabled the quantitative determination of 31 components. More specifically, the components of the essential oils identified were: twelve in the peel, twenty-six in the flowers, and twenty and sixteen in old and young leaves, respectively. The major constituents of the different parts of Citrus aurantium L. essential oils were: β-pinene (0.62%–19.08%), limonene (0.53%–94.67%), trans-β-ocimene (3.11%–6.06%), linalool (0.76%–58.21%), and α-terpineol (0.13%–12.89%). The DPPH test demonstrated that the essential oils in the old leaves had the maximum antioxidant activity, followed by the flowers, young leaves and the peel in that order. This study updates the data in the literature on the essential oils of bitter orange, and provides information on the composition of the oils for a further evaluation of this product. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Antimycobacterial and Photosynthetic Electron Transport Inhibiting Activity of Ring-Substituted 4-Arylamino-7-Chloroquinolinium Chlorides
Molecules 2013, 18(9), 10648-10670; doi:10.3390/molecules180910648
Received: 17 July 2013 / Revised: 19 August 2013 / Accepted: 26 August 2013 / Published: 2 September 2013
Cited by 5 | PDF Full-text (325 KB) | HTML Full-text | XML Full-text
Abstract
In this study, a series of twenty-five ring-substituted 4-arylamino-7-chloroquinolinium chlorides were prepared and characterized. The compounds were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts and also primary in vitro screening [...] Read more.
In this study, a series of twenty-five ring-substituted 4-arylamino-7-chloroquinolinium chlorides were prepared and characterized. The compounds were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts and also primary in vitro screening of the synthesized compounds was performed against mycobacterial species. 4-[(2-Bromophenyl)amino]-7-chloroquinolinium chloride showed high biological activity against M. marinum, M. kansasii, M. smegmatis and 7-chloro-4-[(2-methylphenyl)amino]quinolinium chloride demonstrated noteworthy biological activity against M. smegmatis and M. avium subsp. paratuberculosis. The most effective compounds demonstrated quite low toxicity (LD50 > 20 μmol/L) against the human monocytic leukemia THP-1 cell line within preliminary in vitro cytotoxicity screening. The tested compounds were found to inhibit PET in photosystem II. The PET-inhibiting activity expressed by IC50 value of the most active compound 7-chloro-4-[(3-trifluoromethylphenyl)amino]quinolinium chloride was 27 μmol/L and PET-inhibiting activity of ortho-substituted compounds was significantly lower than this of meta- and para-substituted ones. The structure-activity relationships are discussed for all compounds. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Effect of Non-Pharmacologic Vitamin D Status Correction on Circulating Bone Markers in Healthy Overweight and Obese Saudis
Molecules 2013, 18(9), 10671-10680; doi:10.3390/molecules180910671
Received: 1 June 2013 / Revised: 22 August 2013 / Accepted: 28 August 2013 / Published: 2 September 2013
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Abstract
While moderate to severe vitamin D deficiency is prevalent in Saudi Arabia, skeletal effects associated with this deficiency are not common in this population. In this interventional study we measured the effects of improving vitamin D status on bone biochemical markers in [...] Read more.
While moderate to severe vitamin D deficiency is prevalent in Saudi Arabia, skeletal effects associated with this deficiency are not common in this population. In this interventional study we measured the effects of improving vitamin D status on bone biochemical markers in overweight and obese adult Saudis. A total of 47 volunteers (21 males, 26 females) out of the initial 95 subjects were given verbal advice to expose themselves to sunlight for 5–30 min twice weekly and were encouraged to increase their intake of vitamin D–rich foods. Serum 25(OH)D, osteocalcin, and type 1 collagen cross-linked C-telopeptide (CTx), were measured at baseline and after one year. A significant decrease in the prevalence of vitamin D deficiency was observed (44% to 27%) after one year follow-up (p = 0.025). Also, a parallel significant increase in osteocalcin and a decrease in CTX and osteoprotegerin were observed. The results suggest that a modest increase in vitamin D levels among overweight and obese subjects through the promotion of lifestyle changes for one year have marginal effects in bone turnover markers as well as obesity itself. Full article
Open AccessArticle Effect of Honokiol on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes
Molecules 2013, 18(9), 10681-10693; doi:10.3390/molecules180910681
Received: 15 August 2013 / Revised: 28 August 2013 / Accepted: 28 August 2013 / Published: 3 September 2013
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Abstract
Honokiol is a bioactive component isolated from the medicinal herbs Magnolia officinalis and Magnolia grandiflora that has antioxidative, anti-inflammatory, antithrombotic, and antitumor activities. The inhibitory potentials of honokiol on eight major human cytochrome P450 (CYP) enzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, [...] Read more.
Honokiol is a bioactive component isolated from the medicinal herbs Magnolia officinalis and Magnolia grandiflora that has antioxidative, anti-inflammatory, antithrombotic, and antitumor activities. The inhibitory potentials of honokiol on eight major human cytochrome P450 (CYP) enzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4, and four UDP-glucuronosyltransferases (UGTs) 1A1, 1A4, 1A9, and 2B7 in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. Honokiol strongly inhibited CYP1A2-mediated phenacetin O-deethylation, CYP2C8-mediated amodiaquine N-deethylation, CYP2C9-mediated diclofenac 4-hydroxylation, CYP2C19-mediated [S]-mephenytoin 4-hydroxylation, and UGT1A9-mediated propofol glucuronidation with Ki values of 1.2, 4.9, 0.54, 0.57, and 0.3 μM, respectively. Honokiol also moderately inhibited CYP2B6-mediated bupropion hydroxylation and CYP2D6-mediated bufuralol 1'-hydroxylation with Ki values of 17.5 and 12.0 μM, respectively. These in vitro results indicate that honokiol has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP1A2, CYP2C8, CYP2C9, CYP2C19, and UGT1A9. Full article
Open AccessArticle Pyrrolizidine Alkaloids and Fatty Acids from the Endemic Plant Species Rindera umbellata and the Effect of Lindelofine-N-oxide on Tubulin Polymerization
Molecules 2013, 18(9), 10694-10706; doi:10.3390/molecules180910694
Received: 20 July 2013 / Revised: 10 August 2013 / Accepted: 27 August 2013 / Published: 3 September 2013
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Abstract
The examination of the aerial parts, roots, and seeds of the endemic plant Rindera umbellata is reported in this paper for the first time. Phytochemical investigation of R. umbellata led to the isolation and characterization of ten pyrrolizidine alkaloids and eleven fatty [...] Read more.
The examination of the aerial parts, roots, and seeds of the endemic plant Rindera umbellata is reported in this paper for the first time. Phytochemical investigation of R. umbellata led to the isolation and characterization of ten pyrrolizidine alkaloids and eleven fatty acids in the form of triglycerides. Pyrrolizidine alkaloids 19 were found in the aerial parts, 7 and 8 in the roots, and 610, together with eleven fatty acids, in the seeds of this plant species. The structures of compounds 110 were established based on spectroscopic studies (1H- and 13C-NMR, 2D NMR, IR and CI-MS). After trans-esterification, methyl esters of the fatty acids were analyzed using GC-MS. The effect of lindelofine-N-oxide (7) on tubulin polymerization was determined. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle DNA Condensation by Partially Acetylated Poly(amido amine) Dendrimers: Effects of Dendrimer Charge Density on Complex Formation
Molecules 2013, 18(9), 10707-10720; doi:10.3390/molecules180910707
Received: 1 August 2013 / Revised: 29 August 2013 / Accepted: 30 August 2013 / Published: 3 September 2013
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Abstract
The ability of poly(amido amine) (or PAMAM) dendrimers to condense semiflexible dsDNA and penetrate cell membranes gives them great potential in gene therapy and drug delivery but their high positive surface charge makes them cytotoxic. Here, we describe the effects of partial [...] Read more.
The ability of poly(amido amine) (or PAMAM) dendrimers to condense semiflexible dsDNA and penetrate cell membranes gives them great potential in gene therapy and drug delivery but their high positive surface charge makes them cytotoxic. Here, we describe the effects of partial neutralization by acetylation on DNA condensation using light scattering, circular dichroism, and single molecule imaging of dendrimer-DNA complexes combed onto surfaces and tethered to those surfaces under flow. We find that DNA can be condensed by generation-five (G5) dendrimers even when the surface charges are more than 65% neutralized, but that such dendrimers bind negligibly when an end-tethered DNA is stretched in flow. We also find that when fully charged dendrimers are introduced by flow to end-tethered DNA, all DNA molecules become equally highly coated with dendrimers at a rate that becomes very fast at high dendrimer concentration, and that dendrimers remain bound during subsequent flow of dendrimer-free buffer. These results suggest that the presence of dendrimer-free DNA coexisting with dendrimer-bound DNA after bulk mixing of the two in solution may result from diffusion-limited irreversible dendrimer-DNA binding, rather than, or in addition to, the previously proposed cooperative binding mechanism of dendrimers to DNA. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
Open AccessArticle Hepatoprotective Effects of Ixora parviflora Extract against Exhaustive Exercise-Induced Oxidative Stress in Mice
Molecules 2013, 18(9), 10721-10732; doi:10.3390/molecules180910721
Received: 13 August 2013 / Revised: 29 August 2013 / Accepted: 30 August 2013 / Published: 3 September 2013
Cited by 7 | PDF Full-text (448 KB) | HTML Full-text | XML Full-text
Abstract
Ixora parviflora, a species of the Rubiaceae, is rich in polyphenols and flavonoids, and has been traditionally used as a folk medicine. An I. parviflora extract (IPE) has great antioxidant activity in vitro, including a scavenging effect on superoxide radicals, [...] Read more.
Ixora parviflora, a species of the Rubiaceae, is rich in polyphenols and flavonoids, and has been traditionally used as a folk medicine. An I. parviflora extract (IPE) has great antioxidant activity in vitro, including a scavenging effect on superoxide radicals, reducing power, and ferrous ion-chelating ability. However, whether IPE is efficacious against oxidative damage in vivo is not known. The purpose of this study was to determine the protective effects of IPE treatment on hepatic oxidative stress and antioxidant defenses after exhaustive exercise in mice. Fifty male C57BL/6 mice (6 week old) were randomly divided into five groups and designated a sedentary control with vehicle (C), and exhaustive exercise with vehicle (IPE0), low dosage (IPE10), medium dosage (IPE50) and high dosage (IPE100) of IPE at 0, 10, 50, and 100 mg/kg, respectively. After a single bout of exhaustive swimming exercise challenge, levels of blood ammonia and creatine kinase (CK), and hepatic superoxide dismutase (SOD) protein expression, thiobarbituric acid-reactive substance (TBARS), and gp91phox, p22phox, and p47phox subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expressions in the IPE0 group were significantly affected compared to those of the C group, but they were all significantly inhibited by the IPE treatments. Results of the present in vivo study in mice indicate that I. parviflora extract possesses antioxidative and hepatoprotective potential following exhaustive exercise. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Identification of Repellent and Insecticidal Constituents of the Essential Oil of Artemisia rupestris L. Aerial Parts against Liposcelis bostrychophila Badonnel
Molecules 2013, 18(9), 10733-10746; doi:10.3390/molecules180910733
Received: 22 July 2013 / Revised: 29 August 2013 / Accepted: 30 August 2013 / Published: 3 September 2013
Cited by 15 | PDF Full-text (236 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this research was to determine the chemical composition and insecticidal and repellent activity of the essential oil of Artemisia rupestris L. aerial parts against the booklice Liposcelis bostrychophila Badonnel and isolation of insecticidal and repellent constituents from the essential [...] Read more.
The aim of this research was to determine the chemical composition and insecticidal and repellent activity of the essential oil of Artemisia rupestris L. aerial parts against the booklice Liposcelis bostrychophila Badonnel and isolation of insecticidal and repellent constituents from the essential oil. The essential oil of A. rupestris was obtained by hydrodistillation and analyzed by GC-MS. A total of 30 components of the essential oil of A. rupestris was identified and the principal compounds in the essential oil were α-terpinyl acetate (37.18%), spathulenol (10.65%), α-terpineol (10.09%), and linalool (7.56%), followed by 4-terpineol (3.92%) and patchoulol (3.05%). Based on bioactivity-guided fractionation, the four active constituents were isolated from the essential oil and identified as α-terpineol, α-terpinyl acetate, 4-terpineol and linalool. The essential oil of A. rupestris exhibited contact toxicity against L. bostrychophila with LD50 value of 414.48 µg/cm2. α-Terpinyl acetate (LD50 = 92.59 µg/cm2) exhibited stronger contact toxicity against booklice than α-terpineol (LD50 = 140.30 µg/cm2), 4-terpineol (LD50 = 211.35 µg/cm2), and linalool (LD50 = 393.16 µg/cm2). The essential oil of A. rupestris (LC50 = 6.67 mg/L air) also possessed fumigant toxicity against L. bostrychophila while the four constituents, 4-terpineol, α-terpineol, α-terpinyl acetate and linalool had LC50 values of 0.34, 1.12, 1.26 and 1.96 mg/L air, respectively. α-Terpinol and α-terpinyl acetate showed strong repellency against L. bostrychophila, while linalool and 4-terpinol exhibited weak repellency. The results indicate that the essential oil of A. rupestris aerial parts and its constituent compounds have potential for development into natural insecticides or fumigants as well as repellents for control of insects in stored grains. Full article
Open AccessArticle New Flurbiprofen Derivatives: Synthesis, Membrane Affinity and Evaluation of in Vitro Effect on β-Amyloid Levels
Molecules 2013, 18(9), 10747-10767; doi:10.3390/molecules180910747
Received: 28 June 2013 / Revised: 14 August 2013 / Accepted: 27 August 2013 / Published: 3 September 2013
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Abstract
Alzheimer’s disease (AD) is characterized by irreversible and progressive loss of memory and cognition and profound neuronal loss. Current therapeutic strategies for the treatment of AD have been directed to a variety of targets with the aim of reversing or preventing the [...] Read more.
Alzheimer’s disease (AD) is characterized by irreversible and progressive loss of memory and cognition and profound neuronal loss. Current therapeutic strategies for the treatment of AD have been directed to a variety of targets with the aim of reversing or preventing the disease but, unfortunately, the available treatments often produce no significant clinical benefits. During the last decades compounds that inhibit or modulate γ-secretase, reducing β amyloid (Aβ) levels, have been considered as potential therapeutics for AD. Among these the (R)-enantiomer of flurbiprofen (FLU) seems to be very promising, but it shows low brain penetration. In this study, in order to improve the properties of FLU against Alzheimer’s pathogenesis we synthesized some novel FLU lipophilic analogues. Lipophilicity of the new molecules has been characterized in terms of clogP, log KC18/W and log K IAM/W values. Permeability has been determined in both gastrointestinal PAMPA (PAMPA-GI) at different pH values and in brain blood barrier PAMPA (PAMPA-BBB) models. They were also tested for their ability to inhibit in vitro γ-secretase activity using rat CTXTNA2 astrocytes. Interestingly, the investigated molecules demonstrated to reduce Aβ 42 levels without affecting the amyloid precursor protein APP level in a clear concentrations-dependent manner. Full article
Open AccessArticle Cytotoxic Constituents from the Stems of Clausena lansium (Lour.) Skeels
Molecules 2013, 18(9), 10768-10775; doi:10.3390/molecules180910768
Received: 27 June 2013 / Revised: 22 July 2013 / Accepted: 21 August 2013 / Published: 3 September 2013
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Abstract
Six compounds were isolated from the stems of Clausena lansium (Lour.) Skeels by repeated sillica gel column chromatography. Their chemical structures were elucidated on the basic of physicochemical and spectroscopic data. Among them, 8-geranyloxypsolaren (3) and 2-methoxy-1-(3-methyl-buten-1-yl)-9H-carbazole-3-carbaldehyde ( [...] Read more.
Six compounds were isolated from the stems of Clausena lansium (Lour.) Skeels by repeated sillica gel column chromatography. Their chemical structures were elucidated on the basic of physicochemical and spectroscopic data. Among them, 8-geranyloxypsolaren (3) and 2-methoxy-1-(3-methyl-buten-1-yl)-9H-carbazole-3-carbaldehyde (6) were isolated for the first time from this plant. These compounds were screened for cytotoxicity in human cervical cancer (Hela), leukemia (K562), lung cancer (A549), non-small lung carcinoma (H1299) and liver cancer (SMMC-7721). Within the series of cytotoxic tests, compounds 46 displayed potent cytotoxic activity against H1299 and SMMC-7721, with the IC50 values of 6.19 to 26.84 μg/mL. Full article
Open AccessArticle A Highly Efficient Regioselective Addition of Acetylides to Enediones Based on Steric Effects
Molecules 2013, 18(9), 10776-10788; doi:10.3390/molecules180910776
Received: 19 July 2013 / Revised: 20 August 2013 / Accepted: 20 August 2013 / Published: 3 September 2013
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Abstract
A simple and efficient strategy for the synthesis of 1-ethynylcyclohex-2-enol derivatives was developed utilizing regioselective addition of acetylides to enediones based on steric effects. Further investigation of the substrate scope of enediones indicated that all the addition reactions ocurred in good yield. [...] Read more.
A simple and efficient strategy for the synthesis of 1-ethynylcyclohex-2-enol derivatives was developed utilizing regioselective addition of acetylides to enediones based on steric effects. Further investigation of the substrate scope of enediones indicated that all the addition reactions ocurred in good yield. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Enhanced QSAR Model Performance by Integrating Structural and Gene Expression Information
Molecules 2013, 18(9), 10789-10801; doi:10.3390/molecules180910789
Received: 14 June 2013 / Revised: 20 July 2013 / Accepted: 26 July 2013 / Published: 4 September 2013
PDF Full-text (931 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Despite decades of intensive research and a number of demonstrable successes, quantitative structure-activity relationship (QSAR) models still fail to yield predictions with reasonable accuracy in some circumstances, especially when the QSAR paradox occurs. In this study, to avoid the QSAR paradox, we [...] Read more.
Despite decades of intensive research and a number of demonstrable successes, quantitative structure-activity relationship (QSAR) models still fail to yield predictions with reasonable accuracy in some circumstances, especially when the QSAR paradox occurs. In this study, to avoid the QSAR paradox, we proposed a novel integrated approach to improve the model performance through using both structural and biological information from compounds. As a proof-of-concept, the integrated models were built on a toxicological dataset to predict non-genotoxic carcinogenicity of compounds, using not only the conventional molecular descriptors but also expression profiles of significant genes selected from microarray data. For test set data, our results demonstrated that the prediction accuracy of QSAR model was dramatically increased from 0.57 to 0.67 with incorporation of expression data of just one selected signature gene. Our successful integration of biological information into classic QSAR model provided a new insight and methodology for building predictive models especially when QSAR paradox occurred. Full article
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Open AccessArticle An Insight into the Anticancer Activities of Ru(II)-Based Metallocompounds Using Docking Methods
Molecules 2013, 18(9), 10829-10856; doi:10.3390/molecules180910829
Received: 21 June 2013 / Revised: 19 August 2013 / Accepted: 22 August 2013 / Published: 4 September 2013
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Abstract
Unlike organic molecules, reports on docking of metal complexes are very few; mainly due to the inadequacy of force fields in docking packages to appropriately characterize the metal atoms that consequentially hinder the rational design of metal-based drug complexes. In this study [...] Read more.
Unlike organic molecules, reports on docking of metal complexes are very few; mainly due to the inadequacy of force fields in docking packages to appropriately characterize the metal atoms that consequentially hinder the rational design of metal-based drug complexes. In this study we have made used Molegro and Autodock to predict the anticancer activities of selected Ru(II) complexes against twelve anticancer targets. We observed that introducing the quantum calculated atomic charges of the optimized geometries significantly improved the docking predictions of these anticancer metallocompounds. Despite several limitations in the docking of metal-based complexes, we obtained results that are highly correlated with the available experimental results. Most of our newly proposed metallocompounds are found theoretically to be better anticancer metallocompounds than all the experimentally proposed RAPTA complexes. An interesting features of a strong interactions of new modeled of metallocompounds against the two base edges of DNA strands suggest similar mechanisms of anticancer activities similar to that of cisplatin. There is possibility of covalent bonding between the metal center of the metallocompounds and the residues of the receptors DNA-1, DNA-2, HDAC7, HIS and RNR. However, the general results suggest the possibility of metals positioning the coordinated ligands in the right position for optimal receptor interactions and synergistic effects, rather than forming covalent bonds. Full article
Open AccessArticle Purification, Partial Characterization and Immobilization of a Mannose-Specific Lectin from Seeds of Dioclea lasiophylla Mart.
Molecules 2013, 18(9), 10857-10869; doi:10.3390/molecules180910857
Received: 31 July 2013 / Revised: 29 August 2013 / Accepted: 30 August 2013 / Published: 4 September 2013
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Abstract
Lectin from the seeds of Dioclea lasiophylla (DlyL) was purified in a single step by affinity chromatography on a Sephadex® G-50 column. DlyL strongly agglutinated rabbit erythrocytes and was inhibited by monosaccharides (D-mannose and α-methyl-D-mannoside) and glycoproteins (ovalbumin and [...] Read more.
Lectin from the seeds of Dioclea lasiophylla (DlyL) was purified in a single step by affinity chromatography on a Sephadex® G-50 column. DlyL strongly agglutinated rabbit erythrocytes and was inhibited by monosaccharides (D-mannose and α-methyl-D-mannoside) and glycoproteins (ovalbumin and fetuin). Similar to other Diocleinae lectins, DlyL has three chains, α, β and γ, with mass of 25,569 ± 2, 12,998 ± 1 and 12,588 ± 1 Da, respectively, and has no disulfide bonds. The hemagglutinating activity of DlyL was optimal in pH 8.0, stable at a temperature of 70 °C and decreased in EDTA solution, indicating that lectin activity is dependent on divalent metals. DlyL exhibited low toxicity on Artemia sp. nauplii, but this effect was dependent on the concentration of lectin in solution. DlyL immobilized on cyanogen bromide-activated Sepharose® 4B bound 0.917 mg of ovalbumin per cycle, showing the ability to become a tool for glycoproteomics studies. Full article
Open AccessArticle A Recyclable Palladium-Catalyzed Synthesis of 2-Methylene-2,3-Dihydrobenzofuran-3-ols by Cycloisomerization of 2-(1-Hydroxyprop-2-ynyl)phenols in Ionic Liquids
Molecules 2013, 18(9), 10901-10911; doi:10.3390/molecules180910901
Received: 29 July 2013 / Revised: 21 August 2013 / Accepted: 2 September 2013 / Published: 4 September 2013
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Abstract
A recyclable palladium-catalyzed synthesis of 2-methylene-2,3-dihydrobenzofuran-3-ols 2 by heterocyclization of 2-(1-hydroxyprop-2-ynyl)phenols 1 in an ionic liquid medium (BmimBF4) is presented. The process takes place under relatively mild conditions (100 °C, 5 h) in the presence of catalytic amounts (2 mol [...] Read more.
A recyclable palladium-catalyzed synthesis of 2-methylene-2,3-dihydrobenzofuran-3-ols 2 by heterocyclization of 2-(1-hydroxyprop-2-ynyl)phenols 1 in an ionic liquid medium (BmimBF4) is presented. The process takes place under relatively mild conditions (100 °C, 5 h) in the presence of catalytic amounts (2 mol %) of PdI2 in conjunction with KI (5 equiv with respect to PdI2) and an organic base, such as morpholine (1 equiv with respect to 1), to give 2 in high yields (70%–86%). The PdI2-KI catalytic system could be recycled up to six times without appreciable loss of activity. Moreover, products 2 could be easily converted in a one-pot fashion into 2-hydroxymethylbenzofurans 3 (52%–71%, based on 1) and 2-methoxymethylbenzofurans 4 (52%–80%, based on 1) by acid-catalyzed allylic isomerization or allylic nucleophilic substitution. Full article
(This article belongs to the Special Issue Palladium Catalysts)
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Open AccessArticle Synthesis, Evaluation of Antioxidant Activity and Crystal Structure of 2,4-Dimethylbenzoylhydrazones
Molecules 2013, 18(9), 10912-10929; doi:10.3390/molecules180910912
Received: 14 August 2013 / Revised: 2 September 2013 / Accepted: 4 September 2013 / Published: 5 September 2013
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Abstract
2,4-Dimethylbenzoylhydrazones 130 were synthesized by condensation reactions of 2,4-dimethylbenzoylhydrazide with various aromatic aldehydes and characterized. The assigned structures of compounds 10, 15 and 22 were further supported by single-crystal X-ray diffraction data. The synthesized compounds were evaluated for their [...] Read more.
2,4-Dimethylbenzoylhydrazones 130 were synthesized by condensation reactions of 2,4-dimethylbenzoylhydrazide with various aromatic aldehydes and characterized. The assigned structures of compounds 10, 15 and 22 were further supported by single-crystal X-ray diffraction data. The synthesized compounds were evaluated for their in vitro DPPH radical scavenging activity. They exerted varying degree of scavenging activity toward DPPH radical with IC50 values between 25.6–190 µM. Compounds 1, 4, 2, 3, 7, and 6 have IC50 values of 25.6, 28.1, 29.3, 29.8, 30.0 and 30.1 µM respectively, showing better activity than an n-propyl gallate standard (IC50 value = 30.30 µM). For super oxide anion scavenging activity compounds 1, 2 and 3 with IC50 values of 98.3, 102.6, and 105.6, respectively, also showed better activity than the n-propyl gallate standard (IC50 value = 106.34 µM). Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Identification of Compounds from the Water Soluble Extract of Cinnamomum cassia Barks and Their Inhibitory Effects against High-Glucose-Induced Mesangial Cells
Molecules 2013, 18(9), 10930-10943; doi:10.3390/molecules180910930
Received: 16 July 2013 / Revised: 21 August 2013 / Accepted: 27 August 2013 / Published: 5 September 2013
Cited by 7 | PDF Full-text (354 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The difficulty of diabetic nephropathy (DN) treatment makes prevention the best choice. Cinnamomum cassia barks, known as Chinese cinnamon or Chinese cassia, is one of the most popular natural spices and flavoring agents in many parts of the World. Since previous reports [...] Read more.
The difficulty of diabetic nephropathy (DN) treatment makes prevention the best choice. Cinnamomum cassia barks, known as Chinese cinnamon or Chinese cassia, is one of the most popular natural spices and flavoring agents in many parts of the World. Since previous reports indicated that Chinese cinnamon extract could be used for the treatment of diabetes, we proposed that this spice may be beneficial for the prevention of DN. However, the responsible compounds need to be further identified. In this study, we isolated three new phenolic glycosides, cinnacassosides A–C (1-3), together with fifteen known compounds from the water soluble extract of Chinese cinnamon. The structures of the new compounds were identified by comprehensive spectroscopic evidence. Eleven compounds (6-9, 11, 13-18) were isolated from this spice for the first time, despite extensive research on this species in the past, which added new facets for the chemical profiling of this spice. These isolates were purposely evaluated for their inhibitory effects on IL-6 and extracellular matrix production in mesangial cells which are definitely implicated in DN. The results showed that compounds 4-8 could inhibit over secretion of IL-6, collagen IV and fibronectin against high-glucose-induced mesangial cells at 10 mM, suggesting that Chinese cinnamon could be used as a functional food against DN. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Chaetochromones A and B, Two New Polyketides from the Fungus Chaetomium indicum (CBS.860.68)
Molecules 2013, 18(9), 10944-10952; doi:10.3390/molecules180910944
Received: 22 July 2013 / Revised: 28 August 2013 / Accepted: 2 September 2013 / Published: 5 September 2013
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Abstract
Chaetochromones A (1) and B (2), two novel polyketides, were isolated from the crude extract of fungus Chaetomium indicum (CBS.860.68) together with three known analogues PI-3(3), PI-4 (4) and SB236050 (5). The [...] Read more.
Chaetochromones A (1) and B (2), two novel polyketides, were isolated from the crude extract of fungus Chaetomium indicum (CBS.860.68) together with three known analogues PI-3(3), PI-4 (4) and SB236050 (5). The structures of these compounds were determined by HRESI-MS and NMR experiments. Chaetochromones A (1) and B (2) are a member of the polyketides family, which might originate from a similar biogenetic pathway as the known compounds PI-3 (3), PI-4 (4) and SB236050 (5). The biological activities of these secondary metabolites were evaluated against eight plant pathogens, including Alternaria alternata, Ilyonectria radicicola, Trichoderma viride pers, Aspergillus niger, Fusarium verticillioide, Irpex lacteus (Fr.), Poria placenta (Fr.) Cooke and Coriolus versicolor (L.) Quél. Compound 1 displayed moderate inhibitory rate (>60%) against the brown rot fungus Poria placenta (Fr.) Cooke, which causes significant wood decay. In addition, the cytotoxic activities against three cancer cell lines A549, MDA-MB-231, PANC-1 were also tested, without any inhibitory activities being detected. Full article
Open AccessArticle Impact of Organic and Inorganic Fertilizers Application on the Phytochemical and Antioxidant Activity of Kacip Fatimah (Labisia pumila Benth)
Molecules 2013, 18(9), 10973-10988; doi:10.3390/molecules180910973
Received: 8 July 2013 / Revised: 29 August 2013 / Accepted: 2 September 2013 / Published: 5 September 2013
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Abstract
A study was conducted to compare secondary metabolites and antioxidant activity of Labisia pumila Benth (Kacip Fatimah) in response to two sources of fertilizer [i.e., organic (chicken dung; 10% N:10% P2O5:10% K2O) and inorganic [...] Read more.
A study was conducted to compare secondary metabolites and antioxidant activity of Labisia pumila Benth (Kacip Fatimah) in response to two sources of fertilizer [i.e., organic (chicken dung; 10% N:10% P2O5:10% K2O) and inorganic fertilizer (NPK green; 15% N, 15% P2O5, 15% K2O)] under different N rates of 0, 90, 180 and 270 kg N/ha. The experiment was arranged in a randomized complete block design replicated three times. At the end of 15 weeks, it was observed that the application of organic fertilizer enhanced the production of total phenolics, flavonoids, ascorbic acid, saponin and gluthathione content in L. pumila, compared to the use of inorganic fertilizer. The nitrate content was also reduced under organic fertilization. The application of nitrogen at 90 kg N/ha improved the production of secondary metabolites in Labisia pumila. Higher rates in excess of 90 kg N/ha reduced the level of secondary metabolites and antioxidant activity of this herb. The DPPH and FRAP activity was also highest at 90 kg N/ha. The results indicated that the use of chicken dung can enhance the production of secondary metabolites and improve antioxidant activity of this herb. Full article
Open AccessArticle Chemical Composition and Biological Activity of the Essential Oil from Leaves of Moringa oleifera Lam. Cultivated in Mozambique
Molecules 2013, 18(9), 10989-11000; doi:10.3390/molecules180910989
Received: 19 July 2013 / Revised: 2 September 2013 / Accepted: 3 September 2013 / Published: 9 September 2013
Cited by 7 | PDF Full-text (207 KB) | HTML Full-text | XML Full-text
Abstract
The antioxidant capacity and antimicrobial activity of the essential oil of Moringa oleifera (Moringaceae) grown in Mozambique was investigated. The chemical composition was studied by means of GC and GC-MS analysis. Hexacosane (13.9%), pentacosane (13.3%) and heptacosane (11.4%) were the [...] Read more.
The antioxidant capacity and antimicrobial activity of the essential oil of Moringa oleifera (Moringaceae) grown in Mozambique was investigated. The chemical composition was studied by means of GC and GC-MS analysis. Hexacosane (13.9%), pentacosane (13.3%) and heptacosane (11.4%) were the main components. Ultra High Performance Chromatography-DAD analysis detected the flavonoids quercetin (126 μg/g) and luteolin (6.2 μg/g). The essential oil exhibited a relatively low free radical scavenging capacity. The antimicrobial activity of the essential oil was assayed against two Gram-positive strains (Bacillus cereus, Staphylococcus aureus), two Gram-negative strains (Escherichia coli, Pseudomonas aeruginosa), and five fungal strains of agro-food interest (Penicillium aurantiogriseum, Penicillium expansum, Penicillium citrinum, Penicillium digitatum, and Aspergillus niger spp.). B. cereus and P. aeruginosa, as well as the fungal strains were sensitive to the essential oil. Full article
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Open AccessArticle Antioxidant and Anti-Fatigue Activities of Phenolic Extract from the Seed Coat of Euryale ferox Salisb. and Identification of Three Phenolic Compounds by LC-ESI-MS/MS
Molecules 2013, 18(9), 11003-11021; doi:10.3390/molecules180911003
Received: 5 August 2013 / Revised: 1 September 2013 / Accepted: 2 September 2013 / Published: 9 September 2013
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Abstract
This study investigated the antioxidant potential and anti-fatigue effects of phenolics extracted from the seed coat of Euryale ferox Salisb. The in vitro antioxidant potentials, including scavenging DPPH, hydroxyl radical activities and reducing power were evaluated. Antioxidant status in vivo was analyzed [...] Read more.
This study investigated the antioxidant potential and anti-fatigue effects of phenolics extracted from the seed coat of Euryale ferox Salisb. The in vitro antioxidant potentials, including scavenging DPPH, hydroxyl radical activities and reducing power were evaluated. Antioxidant status in vivo was analyzed by SOD, CAT, GSH-Px activities and the MDA content in liver and kidneys of D-galactose-induced aging mice. The anti-fatigue effect was evaluated using an exhaustive swimming test, along with the determination of LDH, BUN and HG content. The phenolic extract possessed notable antioxidant effects on DPPH, hydroxyl radical scavenging and reducing power. The mice which received the phenolic extract showed significant increases of SOD, CAT (except for in the kidney), GSH-Px activities, and a decrease of MDA content. The average exhaustive swimming time was obviously prolonged. Meanwhile, increase of LDH content and decrease of BUN content were observed after mice had been swimming for 15 min. The HG storage of mice was improved in the high and middle dose extract groups compared with the normal group. The contents of total phenols and gallic acid of the extract were determined. Three compounds in the extract were identified as 5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-chroman-4-one, 5,7,4-trihydroxyflavanone and buddlenol E. These results suggest that the extract of E. ferox is a promising source of natural antioxidants and anti-fatigue material for use in functional foods and medicines. Full article
Open AccessArticle The Inhibitory Effects of Phenolic and Terpenoid Compounds from Baccharis trimera in Siha Cells: Differences in Their Activity and Mechanism of Action
Molecules 2013, 18(9), 11022-11032; doi:10.3390/molecules180911022
Received: 25 July 2013 / Revised: 3 September 2013 / Accepted: 3 September 2013 / Published: 9 September 2013
Cited by 5 | PDF Full-text (466 KB) | HTML Full-text | XML Full-text
Abstract
Baccharis trimera is used in folk medicine as a tea for digestive and liver diseases. It possesses anti-inflammatory and antioxidant properties that are related to the presence of phenolic compounds. The aim of this work was to investigate the anti-proliferative properties of [...] Read more.
Baccharis trimera is used in folk medicine as a tea for digestive and liver diseases. It possesses anti-inflammatory and antioxidant properties that are related to the presence of phenolic compounds. The aim of this work was to investigate the anti-proliferative properties of phenolic (PHE) and terpenoid (SAP) compounds from B. trimera on human cervical cancer. The treatment of SiHa cells with PHE for 24 h suppressed colony formation in a dose-dependent manner, inhibited proliferation and inhibited cell motility. Although SAP inhibited the proliferation of SiHa cells in a dose-dependent manner, it increased colony formation and did not inhibit cell motility. PHE and SAP also promoted a significant increase in lactate dehydrogenase levels in the culture medium in a dose-dependent manner, indicating a loss of cell membrane integrity. Moreover, PHE promoted necrotic cell death, whereas SAP induced apoptosis. These compounds are new anticancer prototypes due their significant anticancer activity demonstrated herein. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Microwave Assisted Dyeing of Polyester Fabrics with Disperse Dyes
Molecules 2013, 18(9), 11033-11043; doi:10.3390/molecules180911033
Received: 8 July 2013 / Revised: 29 August 2013 / Accepted: 29 August 2013 / Published: 9 September 2013
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Abstract
Dyeing of polyester fabrics with thienobenzochromene disperse dyes under conventional and microwave heating conditions was studied in order to determine whether microwave heating could be used to enhance the dyeability of polyester fabrics. Fastness properties of the dyed samples were measured. All [...] Read more.
Dyeing of polyester fabrics with thienobenzochromene disperse dyes under conventional and microwave heating conditions was studied in order to determine whether microwave heating could be used to enhance the dyeability of polyester fabrics. Fastness properties of the dyed samples were measured. All samples dyed with or without microwave heating displayed excellent washing and perspiration fastness. The biological activities of the synthesized dyes against Gram positive bacteria, Gram negative bacteria, yeast and fungus were also evaluated. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Diterpenylquinone Hybrids: Synthesis and Assessment of Gastroprotective Mechanisms of Action in Human Cells
Molecules 2013, 18(9), 11044-11066; doi:10.3390/molecules180911044
Received: 6 August 2013 / Revised: 23 August 2013 / Accepted: 3 September 2013 / Published: 10 September 2013
Cited by 3 | PDF Full-text (277 KB) | HTML Full-text | XML Full-text
Abstract
A modern approach in the search for new bioactive molecules is the synthesis of novel chemical entities combining molecules of different biosynthetic origin presenting biological effects as single compounds. Gastroprotective compounds from South American medicinal plants, namely quinones and diterpenes, were used [...] Read more.
A modern approach in the search for new bioactive molecules is the synthesis of novel chemical entities combining molecules of different biosynthetic origin presenting biological effects as single compounds. Gastroprotective compounds from South American medicinal plants, namely quinones and diterpenes, were used as building blocks to obtain hybrid diterpenylquinones. Starting from the labdane diterpene junicedric acid and two isomers, as well as from three quinones, including lapachol, 18 hybrid molecules were synthesized. Six of them are described for the first time. The potential gastroprotective mechanisms of action of the compounds were assessed in dose-response experiments using human gastric epithelial cells (AGS) and human lung fibroblasts (MRC-5). The following studies were carried out: stimulation of cell proliferation, cytoprotection against sodium taurocholate (NaT)-induced damage, synthesis of PGE2 and total reduced sulfhydryl (GSH) content. The antioxidant capacity of the compounds was determined on the inhibition of the lipoperoxidation in human erythrocyte membranes. Hybrid compounds presented activities different from those shown by the starting compounds, supporting the potential of this approach in the search for new bioactive molecules. The effects might be modulated by selective modification in the terpene or quinone moieties of the new molecules. Structure-activity relationships are discussed. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Sex Differences in the Hepatic Cholesterol Sensing Mechanisms in Mice
Molecules 2013, 18(9), 11067-11085; doi:10.3390/molecules180911067
Received: 25 July 2013 / Revised: 2 September 2013 / Accepted: 5 September 2013 / Published: 10 September 2013
Cited by 6 | PDF Full-text (1171 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cholesterol is linked to many multifactorial disorders, including different forms of liver disease where development and severity depend on the sex. We performed a detailed analysis of cholesterol and bile acid synthesis pathways at the level of genes and metabolites combined with [...] Read more.
Cholesterol is linked to many multifactorial disorders, including different forms of liver disease where development and severity depend on the sex. We performed a detailed analysis of cholesterol and bile acid synthesis pathways at the level of genes and metabolites combined with the expression studies of hepatic cholesterol uptake and transport in female and male mice fed with a high-fat diet with or without cholesterol. Lack of dietary cholesterol led to a stronger response of the sterol sensing mechanism in females, resulting in higher expression of cholesterogenic genes compared to males. With cholesterol in the diet, the genes were down-regulated in both sexes; however, males maintained a more efficient hepatic metabolic flux through the pathway. Females had higher content of hepatic cholesterol but this was likely not due to diminished excretion but rather due to increased synthesis and absorption. Dietary cholesterol and sex were not important for gallbladder bile acids composition. Neither sex up-regulated Cyp7a1 upon cholesterol loading and there was no compensatory up-regulation of Abcg5 or Abcg8 transporters. On the other hand, females had higher expression of the Ldlr and Cd36 genes. These findings explain sexual dimorphism of cholesterol metabolism in response to dietary cholesterol in a high-fat diet in mice, which contributes to understanding the sex-basis of cholesterol-associated liver diseases. Full article
(This article belongs to the Special Issue Steroids)
Open AccessArticle First Chemical Constituents from Cordia exaltata Lam and Antimicrobial Activity of Two Neolignans
Molecules 2013, 18(9), 11086-11099; doi:10.3390/molecules180911086
Received: 21 June 2013 / Revised: 29 August 2013 / Accepted: 29 August 2013 / Published: 10 September 2013
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Abstract
The phytochemical study of Cordia exaltata Lam. (Boraginaceae) led to the isolation, through chromatographic techniques, of nineteen secondary metabolites: 8,8'dimethyl-3,4,3',4'-dimethylenedioxy-7-oxo-2,7'cyclolignan (1), 8,8'-dimethyl-4,5-dimethoxy-3',4'-methylenodioxy-7-oxo-2,7'cyclolignan (2), sitosterol (3a), stigmasterol (3b), sitosterol-3-O-β-d-glucopyranoside (4a), stigmasterol-3-O-β-d-glucopyranoside (4b [...] Read more.
The phytochemical study of Cordia exaltata Lam. (Boraginaceae) led to the isolation, through chromatographic techniques, of nineteen secondary metabolites: 8,8'dimethyl-3,4,3',4'-dimethylenedioxy-7-oxo-2,7'cyclolignan (1), 8,8'-dimethyl-4,5-dimethoxy-3',4'-methylenodioxy-7-oxo-2,7'cyclolignan (2), sitosterol (3a), stigmasterol (3b), sitosterol-3-O-β-d-glucopyranoside (4a), stigmasterol-3-O-β-d-glucopyranoside (4b), phaeophytin A (5), 132-hydroxyphaeophytin A (6), 173-ethoxypheophorbide A (7), 132-hydroxy-173-ethoxypheophorbide A (8), m-methoxy-p-hydroxybenzaldehyde (9), (E)-7-(3,4-dihydroxyphenyl)-7-propenoic acid (10), 1-benzopyran-2-one (11), 7-hydroxy-1-benzopyran-2-one (12), 2,5-bis-(3',4'-methylenedioxiphenyl)-3,4-dimethyltetrahydrofuran (13), 3,4,5,3',5'-pentamethoxy-1'-allyl-8.O.4'-neolignan (14), 3,5,7,3',4'-pentahydroxyflavonol (15), 5,7-dihydroxy-4'-methoxyflavone (16), 5,8-dihydroxy-7,4’-dimethoxyflavone (17), kaempherol 3-O-β-d-glucosyl-6''-α-L-ramnopyranoside (18) and kaempherol 3,7-di-O-α-l-ramnopyranoside (19). Their structures were identified by 1H and 13C-NMR using one and two-dimensional techniques. In addition, the antimicrobial activity of compounds 1, 2, 13 and 14 against bacteria and fungi are reported here for the first time. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Iodine-Catalyzed Prins Cyclization of Homoallylic Alcohols and Aldehydes
Molecules 2013, 18(9), 11100-11130; doi:10.3390/molecules180911100
Received: 24 July 2013 / Revised: 6 August 2013 / Accepted: 23 August 2013 / Published: 10 September 2013
Cited by 3 | PDF Full-text (1554 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The iodine-catalyzed Prins cyclization of homoallylic alcohols and aldehydes was investigated under metal-free conditions and without additives. Anhydrous conditions and inert atmosphere are not required. The reaction of 2-(3,4-dihydronaphthalen-1-yl)propan-1-ol and 21 aldehydes (aliphatic and aromatic) in CH2Cl2 in the [...] Read more.
The iodine-catalyzed Prins cyclization of homoallylic alcohols and aldehydes was investigated under metal-free conditions and without additives. Anhydrous conditions and inert atmosphere are not required. The reaction of 2-(3,4-dihydronaphthalen-1-yl)propan-1-ol and 21 aldehydes (aliphatic and aromatic) in CH2Cl2 in the presence of 5 mol % of iodine gave 1,4,5,6-tetrahydro-2H-benzo[f]isochromenes in 54%–86% yield. Under similar conditions, the Prins cyclization of six alcohols containing an endocyclic double bond (primary, secondary, or tertiary) led to dihydropyrans in 52%–91% yield. The acyclic homoallylic alcohols gave 4-iodo-tetrahydropyran in 29%–41% yield in the presence of 50 mol % of iodine. This type of substrate is the main limitation of the methodology. The relative configuration of the products was assigned by NMR and X-ray analysis. The mechanism and the ratio of the products are discussed, based on DFT calculations. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle In Vivo and in Vitro Effects of Secondary Metabolites against Xanthomonas campestris pv. campestris
Molecules 2013, 18(9), 11131-11143; doi:10.3390/molecules180911131
Received: 13 August 2013 / Revised: 6 September 2013 / Accepted: 9 September 2013 / Published: 11 September 2013
Cited by 2 | PDF Full-text (491 KB) | HTML Full-text | XML Full-text
Abstract
Brassica rapa is a crucifer that is grown worldwide, mainly as a vegetable. The quality of B. rapa crops is highly affected by the disease caused by the bacteria Xanthomonas campestris pv. campestris (Xcc). Glucosinolates and phenolic compounds can confer resistance [...] Read more.
Brassica rapa is a crucifer that is grown worldwide, mainly as a vegetable. The quality of B. rapa crops is highly affected by the disease caused by the bacteria Xanthomonas campestris pv. campestris (Xcc). Glucosinolates and phenolic compounds can confer resistance to Brassica crops against pests and diseases, but few works have been done to evaluate their role in Xcc resistance. The objectives of this work were: (1) to evaluate the in vivo and in vitro antibacterial effect of gluconapin, its isothiocyanate and the methanolic extracts of B. rapa against the type 4 of Xcc, and (2) to test if there is induced resistance mediated by glucosinolates or phenolic compounds in two varieties of B. rapa. Gluconapin and its ITC varieties had an antibacterial effect on the development of Xanthomonas and this effect was strongly dependent on the concentration applied. Methanolic extracts from B. rapa, containing glucosinolates and phenolic compounds, inhibited the growth of these bacteria. Concentration of gluconapin is higher in resistant plants than in the susceptible ones and there is an induction of gluconapin, some flavonoids and sinapic acid 48 to 72 h after inoculation. Gluconapin plays a role in the constitutive resistance to Xcc, while gluconapin, some flavonoids and hydroxycinnamic acids are induced by a Xcc infection but it is not clear if this induction confers resistance to this disease. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle An Efficient Synthesis of Enantiopure (R)-heteroarylpyrimidine Analogs
Molecules 2013, 18(9), 11144-11152; doi:10.3390/molecules180911144
Received: 23 August 2013 / Revised: 3 September 2013 / Accepted: 4 September 2013 / Published: 11 September 2013
Cited by 1 | PDF Full-text (333 KB) | HTML Full-text | XML Full-text
Abstract
An efficient synthesis of enantiopure (R)-heteroarylpyrimidine analogs is described here, which involves introduction of a chiral group, formation and separation of diasteroisomers and final transformation of an amide to an ester. The absolute configuration of the enantiopure HAPs is confirmed [...] Read more.
An efficient synthesis of enantiopure (R)-heteroarylpyrimidine analogs is described here, which involves introduction of a chiral group, formation and separation of diasteroisomers and final transformation of an amide to an ester. The absolute configuration of the enantiopure HAPs is confirmed by X-ray analysis of their intermediates. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis of a-O- and a-S-Glycosphingolipids Related to Sphingomonous cell Wall Antigens Using Anomerisation
Molecules 2013, 18(9), 11198-11218; doi:10.3390/molecules180911198
Received: 31 July 2013 / Revised: 4 September 2013 / Accepted: 5 September 2013 / Published: 12 September 2013
Cited by 3 | PDF Full-text (560 KB) | HTML Full-text | XML Full-text
Abstract
Analogues of glycolipids from Spingomonadacaece with O- and S- and SO2-linkages have been prepared using chelation induced anomerisation promoted by TiCl4. Included are examples of the anomerisation of intermediates with O- and S-glycosidic linkages [...] Read more.
Analogues of glycolipids from Spingomonadacaece with O- and S- and SO2-linkages have been prepared using chelation induced anomerisation promoted by TiCl4. Included are examples of the anomerisation of intermediates with O- and S-glycosidic linkages as well as isomerisation of β-thioglycuronic acids (β-glycosyl thiols). The β-O-glucuronide and β-O-galacturonide precursors were efficiently prepared using benzoylated trichloroacetimidates. β-Glycosyl thiols were precursors to β-S-derivatives. Triazole containing mimics of the natural glycolipids were prepared using CuI promoted azide-alkyne cycloaddition reactions in THF. The glycolipid antigens are being evaluated currently for their effects on iNKT cells. Full article
(This article belongs to the Special Issue Synthesis, Structure, Analysis and Properties of Glycolipids)
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Open AccessArticle Thymoquinone Induces Mitochondria-Mediated Apoptosis in Acute Lymphoblastic Leukaemia in Vitro
Molecules 2013, 18(9), 11219-11240; doi:10.3390/molecules180911219
Received: 18 July 2013 / Revised: 25 August 2013 / Accepted: 30 August 2013 / Published: 12 September 2013
Cited by 11 | PDF Full-text (1807 KB) | HTML Full-text | XML Full-text
Abstract
There has been a growing interest in naturally occurring compounds from traditional medicine with anti-cancer potential. Nigella sativa (black seed) is one of the most widely studied plants. This annual herb grows in countries bordering the Mediterranean Sea and India. Thymoquinone (TQ) [...] Read more.
There has been a growing interest in naturally occurring compounds from traditional medicine with anti-cancer potential. Nigella sativa (black seed) is one of the most widely studied plants. This annual herb grows in countries bordering the Mediterranean Sea and India. Thymoquinone (TQ) is an active ingredient isolated from Nigella sativa. The anti-cancer effect of TQ, via the induction of apoptosis resulting from mitochondrial dysfunction, was assessed in an acute lymphocyte leukemic cell line (CEMss) with an IC50 of 1.5 µg/mL. A significant increase in chromatin condensation in the cell nucleus was observed using fluorescence analysis. The apoptosis was then confirmed by Annexin V and an increased number of cellular DNA breaks in treated cells were observed as a DNA ladder. Treatment of CEMss cells with TQ encouraged apoptosis with cell death-transducing signals by a down-regulation of Bcl-2 and up-regulation of Bax. Moreover, the significant generation of cellular ROS, HSP70 and activation of caspases 3 and 8 were also observed in the treated cells. The mitochondrial apoptosis was clearly associated with the S phase cell cycle arrest. In conclusion, the results from the current study indicated that TQ could be a promising agent for the treatment of leukemia. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Two New Sphingolipids from the Leaves of Piper betle L.
Molecules 2013, 18(9), 11241-11249; doi:10.3390/molecules180911241
Received: 14 July 2013 / Revised: 4 September 2013 / Accepted: 5 September 2013 / Published: 12 September 2013
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Abstract
Two new sphingolipids, pipercerebrosides A (1) and B (2), were isolated from the leaves of Piper betle L. Their structures, including absolute configurations, were determined by spectroscopic analysis and chemical degradation. These two compounds did not show significant [...] Read more.
Two new sphingolipids, pipercerebrosides A (1) and B (2), were isolated from the leaves of Piper betle L. Their structures, including absolute configurations, were determined by spectroscopic analysis and chemical degradation. These two compounds did not show significant cytotoxic activity against the cancer cell lines K562 and HL-60 in a MTT assay. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Design and Synthesis of N1,N5-bis[4-(5-Alkyl-1,2,4-oxadiazol-3-yl)phenyl]glutaramides as Potential Antifungal Prodrugs
Molecules 2013, 18(9), 11250-11263; doi:10.3390/molecules180911250
Received: 29 July 2013 / Revised: 4 September 2013 / Accepted: 10 September 2013 / Published: 12 September 2013
Cited by 3 | PDF Full-text (494 KB) | HTML Full-text | XML Full-text
Abstract A facile three step synthesis of a group of N1,N5-bis[4-(5-alkyl-1,2,4-oxadiazol-3-yl)phenyl]glutaramides, N1,N5-bis[4-(1,2,4-oxadiazol-3-yl)phenyl]glutaramide and N1,N5-bis[4-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)phenyl]glutaramide is described. These products are designed to function as masked bis-amidine prodrugs of a promising N1,N5-bis[4-(N'-(carbamimidoyl)phenyl]glutaramide antifungal lead. Full article
(This article belongs to the Special Issue Advances in Medicinal Chemistry of Antifungals)
Open AccessArticle Anti-Peroxyl Radical Quality and Antibacterial Properties of Rooibos Infusions and Their Pure Glycosylated Polyphenolic Constituents
Molecules 2013, 18(9), 11264-11280; doi:10.3390/molecules180911264
Received: 26 July 2013 / Revised: 3 September 2013 / Accepted: 9 September 2013 / Published: 12 September 2013
Cited by 6 | PDF Full-text (1002 KB) | HTML Full-text | XML Full-text
Abstract
The anti-peroxyl radical quality of two aqueous rooibos infusions and solutions of their most abundant glycosylated polyphenols was evaluated using pyrogallol red and fluorescein-based oxygen radical absorbance ratios. It was observed that the artificial infusions, prepared using only the most abundant polyphenols [...] Read more.
The anti-peroxyl radical quality of two aqueous rooibos infusions and solutions of their most abundant glycosylated polyphenols was evaluated using pyrogallol red and fluorescein-based oxygen radical absorbance ratios. It was observed that the artificial infusions, prepared using only the most abundant polyphenols present in rooibos and at concentrations similar to those found in the natural infusions, showed greater antioxidant quality than the latter infusions, reaching values close to those reported for tea infusions. Additionally, the antimicrobial activity of the natural and artificial infusions was assessed against three species of bacteria: Gram (+) Staphylococus epidermidis and Staphylococcus aureus and Gram (−) Escherichia coli. When compared to the natural infusions the artificial beverages did not demonstrate any bacterostatic/cidal activity, suggesting that the antibacterial activity of rooibos is related to compounds other than the glycosylated polyphenols employed in our study. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Identification of Multiple Ingredients for a Traditional Chinese Medicine Preparation (Bu-yang-huan-wu-tang) by Liquid Chromatography Coupled with Tandem Mass Spectrometry
Molecules 2013, 18(9), 11281-11298; doi:10.3390/molecules180911281
Received: 19 July 2013 / Revised: 5 September 2013 / Accepted: 10 September 2013 / Published: 12 September 2013
Cited by 9 | PDF Full-text (1076 KB) | HTML Full-text | XML Full-text
Abstract
Bu-yang-huan-wu-tang (BYHWT) is a popular Traditional Chinese Medicine formula consisting of seven herbal medicines (Astragalus membranaceus, Angelica sinensis, Paeonia lactiflora, Ligusticum chuanxiong, Carthamus tinctorius, Amygdalus persica and Pheretima aspergillum), that has been used in China for centuries to overcome stroke-induced disability. To [...] Read more.
Bu-yang-huan-wu-tang (BYHWT) is a popular Traditional Chinese Medicine formula consisting of seven herbal medicines (Astragalus membranaceus, Angelica sinensis, Paeonia lactiflora, Ligusticum chuanxiong, Carthamus tinctorius, Amygdalus persica and Pheretima aspergillum), that has been used in China for centuries to overcome stroke-induced disability. To ensure the consistency of quality, a reliable analytical method is required, therefore, we developed a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for quantitative analysis of the major constituents in BYHWT. The herbal ingredients consisting of the cycloartane-type triterpene glycosides of astragaloside I, astragaloside II and astragaloside IV; isoflavones of formononetin, ononin calycosin, calycosin-7-O-β-d-glucoside; ligustilide and paeoniflorin were separated on a C18 column with gradient elution of methanol/10 mM ammonium acetate buffer–formic acid (100:0.1, v/v). This study was performed by a mass spectrometer using electrospray ionization (ESI) with positive ionization ions monitored in the multiple reaction-monitoring (MRM) mode. The linearity, accuracy, precision, limit of detection (LOD) and lower limit of quantification (LLOQ) were validated for this quantification method, and the sensitivity, reliability and reproducibility were all confirmed. The experiments provided a good method for analyzing BYHWT extracts. This study also quantitated the active components in various brands of commercially available products. The results indicated that the pharmaceutical industrial products of BYHWT exhibited considerable variation in their contents of the herbal compounds. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Isolation and Identification of Two Novel Attractant Compounds from Chinese Cockroach (Eupolyphaga sinensis Walker) by Combination of HSCCC, NMR and CD Techniques
Molecules 2013, 18(9), 11299-11310; doi:10.3390/molecules180911299
Received: 5 August 2013 / Revised: 6 September 2013 / Accepted: 6 September 2013 / Published: 13 September 2013
Cited by 2 | PDF Full-text (234 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
High-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of n-hextane-ethyl acetate-methanol-water (1.5:1:1.5:1, v/v/v/v) was applied to the isolation and purification of attractants from Chinese cockroach, Eupolyphaga sinensis Walker. Two new attractants with attractant activity towards the male insects [...] Read more.
High-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of n-hextane-ethyl acetate-methanol-water (1.5:1:1.5:1, v/v/v/v) was applied to the isolation and purification of attractants from Chinese cockroach, Eupolyphaga sinensis Walker. Two new attractants with attractant activity towards the male insects were obtained from the extract sample in a one-step separation. Their purities were determined by HPLC. Subsequent MS, NMR and CD analyses have led to the characterization of (R)-3-ethyl-6,8-dihydroxy-7-methyl-3,4-dihydroisochromen-1-one (1) and (R)-6,8-dihydroxy-3,7-dimethyl-3,4-dihydroisochromen-1-one (2), two novel isocumarin type attractants. Based on these results, it is concluded that HSCCC is a viable separation method option for purifying insect attractants, while effectively maintaining the attracting activity of the isolates. This is the first attempt to apply counter-current chromatography technique to separate attractants from Chinese cockroach. Full article
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Open AccessArticle Dillapiole, Isolated from Peperomia pellucida, Shows Gastroprotector Activity against Ethanol-Induced Gastric Lesions in Wistar Rats
Molecules 2013, 18(9), 11327-11337; doi:10.3390/molecules180911327
Received: 15 July 2013 / Revised: 4 September 2013 / Accepted: 10 September 2013 / Published: 13 September 2013
Cited by 4 | PDF Full-text (221 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Peperomia pellucida is a plant used in traditional medicine to treat gastric ulcers. Although this gastroprotective activity was reported, the active compounds have not been identified. Therefore, the aim herein was to identify the most active compound in the gastroprotective activity of [...] Read more.
Peperomia pellucida is a plant used in traditional medicine to treat gastric ulcers. Although this gastroprotective activity was reported, the active compounds have not been identified. Therefore, the aim herein was to identify the most active compound in the gastroprotective activity of P. pellucida using an ethanol-induced gastric ulcer experimental rat model. A gastroprotective effect was observed when the hexane and dichloromethane extracts were tested, with the higher effect being obtained with the dichloromethane extract (82.3 ± 5.6%) at 100 mg/kg. Dillapiole was identified as the most active compound in this extract. Although there have been previous reports on dillapiole, this is the first on its gastroprotective activity. Rats treated with this compound at 3, 10, 30 and 100 mg/kg showed 23.1, 56.1, 73.2 and 85.5% gastroprotection, respectively. The effect elicited by dillapiole at 100 mg/kg was not attenuated by pretreatment with indomethacin (10 mg/kg, s.c.), a prostaglandin synthesis blocker, NG-nitro-l-arginine methyl ester (70 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, or N-ethylmaleimide (10 mg/kg, s.c.), a blocker of sulfhydryl groups. This suggests that the gastroprotective mechanism of action of dillapiole does not involve prostaglandins, NO or sulfhydryl groups. Full article
Open AccessArticle Harvestman Phenols and Benzoquinones: Characterisation and Biosynthetic Pathway
Molecules 2013, 18(9), 11429-11451; doi:10.3390/molecules180911429
Received: 19 July 2013 / Revised: 5 September 2013 / Accepted: 6 September 2013 / Published: 16 September 2013
Cited by 8 | PDF Full-text (1006 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Benzoquinones are usually present in arthropod defence exudates. Here, we describe the chemical profiles of 12 harvestman species belonging to the neotropical family Gonyleptidae. Nine of the studied species produced benzoquinones, while three produced alkyl phenols. Two benzoquinones and one phenol exhibited [...] Read more.
Benzoquinones are usually present in arthropod defence exudates. Here, we describe the chemical profiles of 12 harvestman species belonging to the neotropical family Gonyleptidae. Nine of the studied species produced benzoquinones, while three produced alkyl phenols. Two benzoquinones and one phenol exhibited biological activity against bacteria and fungi. We also studied the biosynthesis of 2-ethyl-1,4-benzoquinone by feeding Magnispina neptunus individuals with 13C-labelled precursors; the benzoquinones were biosynthesised through a polyketide pathway using acetate and propionate building blocks. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Determination and Pharmacokinetics of Di-(2-ethylhexyl) Phthalate in Rats by Ultra Performance Liquid Chromatography with Tandem Mass Spectrometry
Molecules 2013, 18(9), 11452-11466; doi:10.3390/molecules180911452
Received: 22 July 2013 / Revised: 1 September 2013 / Accepted: 13 September 2013 / Published: 16 September 2013
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Abstract
Di-(2-ethylhexyl) phthalate (DEHP) is used to increase the flexibility of plastics for industrial products. However, the illegal use of the plasticizer DEHP in food and drinks has been reported in Taiwan in 2011. In order to assess the exact extent of the [...] Read more.
Di-(2-ethylhexyl) phthalate (DEHP) is used to increase the flexibility of plastics for industrial products. However, the illegal use of the plasticizer DEHP in food and drinks has been reported in Taiwan in 2011. In order to assess the exact extent of the absorption of DEHP via the oral route, the aim of this study is to develop a reliable and validated ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method to evaluate the oral bioavailability of DEHP in rats. The optimal chromatographic separation of DEHP and butyl benzyl phthalate (BBP; used as internal standard) were achieved on a C18 column. The mobile phase was consisted of 5 mM ammonium acetate-methanol (11:89, v/v) with a flow rate of 0.25 mL/min. The monitoring ion transitions were m/z 391.4 → 149.0 for DEHP and m/z 313.3 → 149.0 for BBP. The mean matrix effects of DEHP at low, medium and high concentrations were 94.5 ± 5.7% and 100.1 ± 2.3% in plasma and feces homogenate samples, respectively. In conclusion, the validated UPLC-MS/MS method is suitable for analyzing the rat plasma sample of DEHP and the oral bioavailability of DEHP was about 7% in rats. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Probing the Residual Structure in Avian Prion Hexarepeats by CD, NMR and MD Techniques
Molecules 2013, 18(9), 11467-11484; doi:10.3390/molecules180911467
Received: 5 August 2013 / Revised: 3 September 2013 / Accepted: 9 September 2013 / Published: 16 September 2013
Cited by 1 | PDF Full-text (907 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Many proteins perform essential biological functions by means of regions that lacking specific organized structure exist as an ensemble of interconverting transient conformers. The characterization of such regions, including the description of their structural propensities, number of conformations and relative populations can [...] Read more.
Many proteins perform essential biological functions by means of regions that lacking specific organized structure exist as an ensemble of interconverting transient conformers. The characterization of such regions, including the description of their structural propensities, number of conformations and relative populations can provide useful insights. Prion diseases result from the conversion of a normal glycoprotein into a misfolded pathogenic isoform. The structures of mammal and chicken prion proteins show a similar fold with a globular domain and a flexible N-terminal portion that contains different repeated regions: octarepeats (PHGGGWGQ) in mammals and hexarepeats (PHNPGY) in chickens. The higher number of prolines in the hexarepeat region suggests that this region may retain a significant amount of residual secondary structure. Here, we report the CD, NMR and MD characterization of a peptide (2-HexaPY) composed of two hexarepeats. We combine experimental NMR data and MD to investigate at atomic level its ensemble-averaged structural properties, demonstrating how each residue of both repeats has a different quantified PPII propensity that shows a periodicity along the sequence. This feature explains the absence of cooperativity to stabilize a PPII conformation. Nonetheless, such residual structure can play a role in nucleating local structural transitions as well as modulating intra-molecular or inter-molecular interactions. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
Open AccessArticle Fremy’s Salt-Mediated Oxidative Addition. A New Approach in the Total Synthesis of Naturally Dipetalolactone and Its Immunomodulatory Activity
Molecules 2013, 18(9), 11485-11495; doi:10.3390/molecules180911485
Received: 2 July 2013 / Revised: 30 July 2013 / Accepted: 26 August 2013 / Published: 16 September 2013
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Abstract
The structure of the natural dipyranocoumarin dipetalolactone has been confirmed by an unambiguous synthetic route from resorcinol. This sequence was initiated by a pyran ring formation step which introduced the 3-chloro-3-methylbut-1-yne moiety. Then, the expected product undergoes a Fremy’s salt-meditated oxidative addition [...] Read more.
The structure of the natural dipyranocoumarin dipetalolactone has been confirmed by an unambiguous synthetic route from resorcinol. This sequence was initiated by a pyran ring formation step which introduced the 3-chloro-3-methylbut-1-yne moiety. Then, the expected product undergoes a Fremy’s salt-meditated oxidative addition followed by ring closure to yield dipetalolactone. Dipetalolactone was also found to have immunological activity in a mouse carcinoma S180-bearing mice cell line. Full article
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Open AccessArticle Synthesis and Biological Evaluation of Apigenin Derivatives as Antibacterial and Antiproliferative Agents
Molecules 2013, 18(9), 11496-11511; doi:10.3390/molecules180911496
Received: 8 July 2013 / Revised: 2 September 2013 / Accepted: 12 September 2013 / Published: 17 September 2013
Cited by 8 | PDF Full-text (266 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two series of apigenin [5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one] derivatives, 3a3j and 4a4j, were synthesized. The apigenin and alkyl amines moieties of these compounds were separated by C2 or C3 spacers, respectively. The chemical structures of the apigenin derivatives [...] Read more.
Two series of apigenin [5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one] derivatives, 3a3j and 4a4j, were synthesized. The apigenin and alkyl amines moieties of these compounds were separated by C2 or C3 spacers, respectively. The chemical structures of the apigenin derivatives were confirmed using 1H-NMR, 13C-NMR, and electrospray ionization mass spectroscopy. The in vitro antibacterial and antiproliferative activities of all synthesized compounds were determined. Among the tested compounds, 4a4j displayed significant antibacterial activity against the tested strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa). Additionally, 4i showed the best inhibitory activity with minimum inhibitory concentrations of 1.95, 3.91, 3.91, and 3.91 μg/mL against S. aureus, B. subtilis, E. coli, and P. aeruginosa, respectively. The antiproliferative activity of the apigenin derivatives was evaluated by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. We determined that 4a4j displayed better growth inhibition activity against four human cancer cell lines, namely, human lung (A549), human cervical (HeLa), human hepatocellular liver (HepG2), and human breast (MCF-7) cancer cells, than the parent apigenin. Compound 4j was found to be the most active antiproliferative compound against the selected cancer cells. Structure-activity relationships were also discussed based on the obtained experimental data. Full article
Open AccessArticle Click Reactions as a Key Step for an Efficient and Selective Synthesis of D-Xylose-Based ILs
Molecules 2013, 18(9), 11512-11525; doi:10.3390/molecules180911512
Received: 27 June 2013 / Revised: 7 August 2013 / Accepted: 10 September 2013 / Published: 17 September 2013
Cited by 4 | PDF Full-text (456 KB) | HTML Full-text | XML Full-text
Abstract
D-Xylose-based ionic liquids have been prepared from D-xylose following a five steps reaction sequence, the key step being a click cycloaddition. These ionic liquids (ILs) have been characterized through classical analytical methods (IR, NMR, mass spectroscopy, elemental analysis) and their stability constants, [...] Read more.
D-Xylose-based ionic liquids have been prepared from D-xylose following a five steps reaction sequence, the key step being a click cycloaddition. These ionic liquids (ILs) have been characterized through classical analytical methods (IR, NMR, mass spectroscopy, elemental analysis) and their stability constants, Tg and Tdec, were also determined. Considering their properties and their hydrophilicity, these compounds could be alternative solvents for chemical applications under mild conditions. Full article
(This article belongs to the Special Issue Advances in Click Chemistry)
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Open AccessArticle Effect of Tomato Industrial Processing on Phenolic Profile and Antiplatelet Activity
Molecules 2013, 18(9), 11526-11536; doi:10.3390/molecules180911526
Received: 8 August 2013 / Revised: 12 September 2013 / Accepted: 12 September 2013 / Published: 17 September 2013
Cited by 11 | PDF Full-text (915 KB) | HTML Full-text | XML Full-text
Abstract
Background: Regular consumption of fruits and vegetables (e.g., tomatoes) has been shown to be beneficial in terms of reducing the incidence of cardiovascular diseases. The industrial processing of tomatoes into tomato-based products includes several thermal treatments. Very little is known on [...] Read more.
Background: Regular consumption of fruits and vegetables (e.g., tomatoes) has been shown to be beneficial in terms of reducing the incidence of cardiovascular diseases. The industrial processing of tomatoes into tomato-based products includes several thermal treatments. Very little is known on the effect of tomato industrial processing on antiaggregatory activity and phenolic profile. Methods: It was assessed the effect of tomato and by-products extracts on platelet aggregation induced by ADP, collagen, TRAP-6 and arachidonic acid. These in vitro antithrombotic properties were further supported in an in vivo model of thrombosis. A set of antiplatelet compounds has been selected for HPLC analysis in the different extracts. Results: Some natural compounds such as chlorogenic, caffeic, ferulic and p-coumaric acids were identified by HPLC in tomatoes and its products may inhibit platelet activation. Red tomatoes, tomato products (sauce, ketchup and juice) and by-products extracts inhibited platelet aggregation induced adenosine 5'-diphosphate, collagen, thrombin receptor activator peptide-6 and arachidonic acid, but to a different extent. Also, pomace extract presents antithrombotic activity. Conclusions: Processed tomatoes may have a higher content of health-benefiting compounds than fresh ones. Pomace even presents the best antiplatelet activity. Finally, tomato products may be used as a functional ingredient adding antiplatelet activities to processed foods. Full article
Open AccessArticle Analysis of Biotinylated Generation 4 Poly(amidoamine) (PAMAM) Dendrimer Distribution in the Rat Brain and Toxicity in a Cellular Model of the Blood-Brain Barrier
Molecules 2013, 18(9), 11537-11552; doi:10.3390/molecules180911537
Received: 23 July 2013 / Revised: 3 September 2013 / Accepted: 10 September 2013 / Published: 17 September 2013
Cited by 6 | PDF Full-text (3257 KB) | HTML Full-text | XML Full-text
Abstract
Dendrimers are highly customizable nanopolymers with qualities that make them ideal for drug delivery. The high binding affinity of biotin/avidin provides a useful approach to fluorescently label synthesized dendrimer-conjugates in cells and tissues. In addition, biotin may facilitate delivery of dendrimers through [...] Read more.
Dendrimers are highly customizable nanopolymers with qualities that make them ideal for drug delivery. The high binding affinity of biotin/avidin provides a useful approach to fluorescently label synthesized dendrimer-conjugates in cells and tissues. In addition, biotin may facilitate delivery of dendrimers through the blood-brain barrier (BBB) via carrier-mediated endocytosis. The purpose of this research was to: (1) measure toxicity using lactate dehydrogenase (LDH) assays of generation (G)4 biotinylated and non-biotinylated poly(amidoamine) (PAMAM) dendrimers in a co-culture model of the BBB, (2) determine distribution of dendrimers in the rat brain, kidney, and liver following systemic administration of dendrimers, and (3) conduct atomic force microscopy (AFM) on rat brain sections following systemic administration of dendrimers. LDH measurements showed that biotinylated dendrimers were toxic to cell co-culture after 48 h of treatment. Distribution studies showed evidence of biotinylated and non-biotinylated PAMAM dendrimers in brain. AFM studies showed evidence of dendrimers only in brain tissue of treated rats. These results indicate that biotinylation does not decrease toxicity associated with PAMAM dendrimers and that biotinylated PAMAM dendrimers distribute in the brain. Furthermore, this article provides evidence of nanoparticles in brain tissue following systemic administration of nanoparticles supported by both fluorescence microscopy and AFM. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
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Open AccessArticle A pH-Sensitive Peptide-Containing Lasso Molecular Switch
Molecules 2013, 18(9), 11553-11575; doi:10.3390/molecules180911553
Received: 24 July 2013 / Revised: 9 September 2013 / Accepted: 11 September 2013 / Published: 17 September 2013
Cited by 9 | PDF Full-text (2753 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The synthesis of a peptide-containing lasso molecular switch by a self-entanglement strategy is described. The interlocked [1] rotaxane molecular machine consists of a benzometaphenylene[25]crown-8 (BMP25C8) macrocycle surrounding a molecular axle. This molecular axle contains a tripeptidic sequence and two molecular stations: a [...] Read more.
The synthesis of a peptide-containing lasso molecular switch by a self-entanglement strategy is described. The interlocked [1] rotaxane molecular machine consists of a benzometaphenylene[25]crown-8 (BMP25C8) macrocycle surrounding a molecular axle. This molecular axle contains a tripeptidic sequence and two molecular stations: a N-benzyltriazolium and a pH-sensitive anilinium station. The tripeptide is located between the macrocycle and the triazolium station, so that its conformation can be tailored depending on the shuttling of the macrocycle from one station to the other. At acidic pH, the macrocycle resides around the anilinium moiety, whereas it shuttles around the triazolium station after deprotonation. This molecular machinery thus forces the lasso to adopt a tightened or a loosened conformation. Full article
(This article belongs to the Special Issue Rotaxanes)
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Open AccessArticle Synthesis of a Novel Carbocyclic Analog of Bredinin
Molecules 2013, 18(9), 11576-11585; doi:10.3390/molecules180911576
Received: 23 August 2013 / Revised: 5 September 2013 / Accepted: 10 September 2013 / Published: 17 September 2013
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Abstract
The natural nucleoside antibiotic, bredinin, exhibits antiviral and other biological activities. While various nucleosides related to bredinin have been synthesized, its carbocyclic analog has remained unknown. Synthesis of this heretofore unknown analog of bredinin is described. The key precursor, (3aS,4 [...] Read more.
The natural nucleoside antibiotic, bredinin, exhibits antiviral and other biological activities. While various nucleosides related to bredinin have been synthesized, its carbocyclic analog has remained unknown. Synthesis of this heretofore unknown analog of bredinin is described. The key precursor, (3aS,4R,6R,6aR)-6-((methoxy-methoxy)methyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-amine (5), was prepared from the commercially available compound, (1R,4S)-2-azabicyclo[2.2.1] hept-5-en-3-one (4). Our initial approach used intermediate 6, derived in three transformations from 5, for the key photolytic step to produce the desired ring-opened precursor to the target compound. This photochemical transformation was unsuccessful. However, an appropriately protected and related precursor was synthesized from 5 through the following side-chain functional group transformations: elaboration of the amino group through malonyl ester formation, oximation at the central carbon, conversion of ester to amide and catalytic reduction of the oxime group. This precursor, on treatment with triethylorthoformate and catalytic acetic acid in ethanol, underwent cyclization to produce the desired 4-carbamoyl-imidazolium-5-olate ring. Deprotection of the latter product proceeded smoothly to give the carbocyclic analog of bredinin. This target molecule exhibits antiviral activity, albeit low, against a number of RNA viruses. Further biological evaluations are in progress. Full article
(This article belongs to the Special Issue Synthesis of Nucleosides, Nucleotides and Their Derivatives)
Open AccessArticle Solution Properties and in Vitro Anti-Tumor Activities of Polysaccharides from Longan Pulp
Molecules 2013, 18(9), 11601-11613; doi:10.3390/molecules180911601
Received: 13 June 2013 / Revised: 28 August 2013 / Accepted: 11 September 2013 / Published: 18 September 2013
Cited by 9 | PDF Full-text (586 KB) | HTML Full-text | XML Full-text
Abstract
The solution properties of four fractions (LPI–IV) from crude longan pulp polysaccharides (LP3) were analyzed by size-exclusion chromatography combined with laser light scattering, viscometry, complex formation with Congo red, and atomic force microscopy. Their radii of gyration (<S2>z1/2 [...] Read more.
The solution properties of four fractions (LPI–IV) from crude longan pulp polysaccharides (LP3) were analyzed by size-exclusion chromatography combined with laser light scattering, viscometry, complex formation with Congo red, and atomic force microscopy. Their radii of gyration (<S2>z1/2) were 43.3, 62.6, 43.2 and 77.3 nm, exponents of <S2>z1/2 = k Mwv were 0.04, 0.50, 0.52 and 0.02, and intrinsic viscosities ([η]) were 9.945, 25.38, 308.2 and 452.1 mL/g, respectively. Moreover, the dependence of [η] on Mw was established to be [η] = 5.3 × 10−2Mw0.61 (mL/g). LPI had both a sphere-like conformation and a triple-helix structure, and LPII–IV existed as flexible chains. LP3, LPI, LPII and LPIII all exhibited direct inhibitory effects on A549, HeLa and HepG2 cells in a positive dose-dependent manner in the range of 50–400 µg/mL. The activities of LPIII, especially the inhibition of HepG2 cell proliferation, were stronger than those of others, which may be partly related to its flexible conformation. The present results support the cancer therapeutic potential of longan polysaccharides. Full article
Open AccessArticle Combined Effects of Green Tea Extracts, Green Tea Polyphenols or Epigallocatechin Gallate with Acarbose on Inhibition against α-Amylase and α-Glucosidase in Vitro
Molecules 2013, 18(9), 11614-11623; doi:10.3390/molecules180911614
Received: 7 August 2013 / Revised: 13 September 2013 / Accepted: 16 September 2013 / Published: 18 September 2013
Cited by 15 | PDF Full-text (526 KB) | HTML Full-text | XML Full-text
Abstract
Green tea, green tea polyphenols and epigallocatechin gallate (EGCG) are confirmed to have beneficial effects in the treatment of diabetes mellitus, and a possible mechanism can be ascribed to their inhibitory effect against α-amylase and α-glucosidase in the digestive tract. In this [...] Read more.
Green tea, green tea polyphenols and epigallocatechin gallate (EGCG) are confirmed to have beneficial effects in the treatment of diabetes mellitus, and a possible mechanism can be ascribed to their inhibitory effect against α-amylase and α-glucosidase in the digestive tract. In this paper, we first investigated the combined inhibitory effect of green tea extracts, green tea polyphenols or EGCG with acarbose on α-amylase and α-glucosidase in vitro. Our results indicated that the interaction between green tea extracts (green tea polyphenols or EGCG) and acarbose was complicated. The combination of green tea extracts, green tea polyphenols or EGCG with acarbose had a synergistic effect on α-amylase and α-glucosidase at low concentrations and the combined effect turned out to be antagonistic at high concentrations according to the Combination Index (CI) values. These findings not only provided some significant quantitative values, but also provide some valuable implications for the combined use of acarbose and GTE (GTP or EGCG) in the treatment of diabetes mellitus. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Bioactivity-Guided Fractionation of Physical Fatigue-Attenuating Components from Rubus parvifolius L.
Molecules 2013, 18(9), 11624-11638; doi:10.3390/molecules180911624
Received: 19 July 2013 / Revised: 25 August 2013 / Accepted: 6 September 2013 / Published: 23 September 2013
Cited by 2 | PDF Full-text (278 KB) | HTML Full-text | XML Full-text
Abstract
Alleviation of fatigue has been emerging as a serious issue that requires urgent attention. Health professionals and sports physiologists have been looking for active natural products and synthetic compounds to overcome fatigue in humans. This study was designed to define the anti-fatigue [...] Read more.
Alleviation of fatigue has been emerging as a serious issue that requires urgent attention. Health professionals and sports physiologists have been looking for active natural products and synthetic compounds to overcome fatigue in humans. This study was designed to define the anti-fatigue property of Rubus parvifolius L. (RPL) by characterization of active constituents using a mouse forced swimming test model. Four RPL fractions with different polarities containing anti-fatigue activity were sequentially isolated from the n-butanol RPL extract, followed by elution of 50% ethanol-water fraction from D101 macroporous resin chromatography to obtain nigaichigoside F1, suavissimoside R1 and coreanoside F1. Active constituents of the 50% ethanol-water eluate of RPL were total saponins. The fractions were examined based on the effect on weight-loaded swimming capacity of mice. Serum levels of urea nitrogen (SUN), triglyceride fatty acids (TG), lactate dehydrogenase (LDH), lactic acid (LA), ammonia and hepatic glycogen (HG) were also examined for potential mechanisms underlying the anti-fatigue effect of RPL extracts. During the experiment, two inflammatory markers, interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) in serum, were measured. We found that total saponins from RPL possess potent capabilities to alleviate mouse fatigue induced by forced swimming and that nigaichigoside F1 was responsible for the pharmacological effect. The underlying mechanisms include delays of SUN and LA accumulation, a decrease in TG level by increasing fat consumption, increases in HG and LDH so that lactic acid accumulation and ammonia in the muscle were reduced, and suppression of increased immune activation and inflammatory cytokine production. Our findings will be helpful for functional identification of novel anti-fatigue components from natural medicinal herbs. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle A Modular Approach to Triazole-Containing Chemical Inducers of Dimerisation for Yeast Three-Hybrid Screening
Molecules 2013, 18(9), 11639-11657; doi:10.3390/molecules180911639
Received: 1 August 2013 / Revised: 5 September 2013 / Accepted: 6 September 2013 / Published: 23 September 2013
Cited by 4 | PDF Full-text (1196 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The yeast three-hybrid (Y3H) approach shows considerable promise for the unbiased identification of novel small molecule-protein interactions. In recent years, it has been successfully used to link a number of bioactive molecules to novel protein binding partners. However despite its potential importance [...] Read more.
The yeast three-hybrid (Y3H) approach shows considerable promise for the unbiased identification of novel small molecule-protein interactions. In recent years, it has been successfully used to link a number of bioactive molecules to novel protein binding partners. However despite its potential importance as a protein target identification method, the Y3H technique has not yet been widely adopted, in part due to the challenges associated with the synthesis of the complex chemical inducers of dimerisation (CIDs). The development of a modular approach using potentially “off the shelf” synthetic components was achieved and allowed the synthesis of a family of four triazole-containing CIDs, MTX-Cmpd2.2-2.5. These CIDs were then compared using the Y3H approach with three of them giving a strong positive interaction with a known target of compound 2, TgCDPK1. These results showed that the modular nature of our synthetic strategy may help to overcome the challenges currently encountered with CID synthesis and should contribute to the Y3H approach reaching its full potential as an unbiased target identification strategy. Full article
(This article belongs to the Special Issue Reagents and Methods for Protein Target Identification)
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Open AccessReview Palladium and Organocatalysis: An Excellent Recipe for Asymmetric Synthesis
Molecules 2013, 18(9), 10108-10121; doi:10.3390/molecules180910108
Received: 16 July 2013 / Revised: 9 August 2013 / Accepted: 15 August 2013 / Published: 22 August 2013
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Abstract
The dual activation of simple substrates by the combination of organocatalysis and palladium catalysis has been successfully applied in a variety of different asymmetric transformations. Thus, the asymmetric a-allylation of carbonyl compounds, a-fluorination of acyl derivatives, decarboxylative protonation of β-dicarbonyl compounds, cyclization [...] Read more.
The dual activation of simple substrates by the combination of organocatalysis and palladium catalysis has been successfully applied in a variety of different asymmetric transformations. Thus, the asymmetric a-allylation of carbonyl compounds, a-fluorination of acyl derivatives, decarboxylative protonation of β-dicarbonyl compounds, cyclization reactions of alkynyl carbonyl compounds and β-functionalization of aldehydes have been efficiently achieved employing this double-catalytic methodology. Full article
(This article belongs to the Special Issue Palladium Catalysts)
Open AccessReview Recent Advances in Target Characterization and Identification by Photoaffinity Probes
Molecules 2013, 18(9), 10425-10451; doi:10.3390/molecules180910425
Received: 30 July 2013 / Revised: 23 August 2013 / Accepted: 23 August 2013 / Published: 29 August 2013
Cited by 18 | PDF Full-text (1586 KB) | HTML Full-text | XML Full-text
Abstract
Target identification of biologically active molecules such as natural products, synthetic small molecules, peptides, and oligonucleotides mainly relies on affinity chromatography, activity-based probes, or photoaffinity labeling (PAL). Amongst them, activity-based probes and PAL have offered great advantages in target identification technology due [...] Read more.
Target identification of biologically active molecules such as natural products, synthetic small molecules, peptides, and oligonucleotides mainly relies on affinity chromatography, activity-based probes, or photoaffinity labeling (PAL). Amongst them, activity-based probes and PAL have offered great advantages in target identification technology due to their ability to form covalent bonds with the corresponding targets. Activity-based probe technology mainly relies on the chemical reactivity of the target proteins, thereby limiting the majority of the biological targets to enzymes or proteins which display reactive residues at the probe-binding site. In general, the probes should bear a reactive moiety such as an epoxide, a Michael acceptor, or a reactive alkyl halide in their structures. On the other hand, photoaffinity probes (PAPs) are composed of a target-specific ligand and a photoactivatable functional group. When bound to the corresponding target proteins and activated with wavelength-specific light, PAPs generate highly reactive chemical species that covalently cross-link proximal amino acid residues. This process is better known as PAL and is widely employed to identify cellular targets of biologically active molecules. This review highlights recent advances in target identification by PAL, with a focus on the structure and chemistry of the photoaffinity probes developed in the recent decade, coupled to the target proteins identified using these probes. Full article
(This article belongs to the Special Issue Reagents and Methods for Protein Target Identification)
Open AccessReview Biological Activities and Phytochemicals of Swietenia macrophylla King
Molecules 2013, 18(9), 10465-10483; doi:10.3390/molecules180910465
Received: 24 June 2013 / Revised: 16 August 2013 / Accepted: 24 August 2013 / Published: 30 August 2013
Cited by 15 | PDF Full-text (401 KB) | HTML Full-text | XML Full-text
Abstract
Swietenia macrophylla King (Meliaceae) is an endangered and medicinally important plant indigenous to tropical and subtropical regions of the World. S. macrophylla has been widely used in folk medicine to treat various diseases. The review reveals that limonoids and its derivatives are [...] Read more.
Swietenia macrophylla King (Meliaceae) is an endangered and medicinally important plant indigenous to tropical and subtropical regions of the World. S. macrophylla has been widely used in folk medicine to treat various diseases. The review reveals that limonoids and its derivatives are the major constituents of S. macrophylla. There are several data in the literature indicating a great variety of pharmacological activities of S. macrophylla, which exhibits antimicrobial, anti-inflammatory, antioxidant effects, antimutagenic, anticancer, antitumor and antidiabetic activities. Various other activities like anti-nociceptive, hypolipidemic, antidiarrhoeal, anti-infective, antiviral, antimalarial, acaricidal, antifeedant and heavy metal phytoremediation activity have also been reported. In view of the immense medicinal importance of S. macrophylla, this review aimed at compiling all currently available information on its ethnomedicinal uses, phytochemistry and biological activities of S. macrophylla, showing its importance. Full article
(This article belongs to the Section Natural Products)
Open AccessReview Ensemble-Based Interpretations of NMR Structural Data to Describe Protein Internal Dynamics
Molecules 2013, 18(9), 10548-10567; doi:10.3390/molecules180910548
Received: 4 July 2013 / Revised: 9 August 2013 / Accepted: 22 August 2013 / Published: 30 August 2013
Cited by 7 | PDF Full-text (1317 KB) | HTML Full-text | XML Full-text
Abstract
NMR spectroscopy is the leading technique to characterize protein internal dynamics at the atomic level and on multiple time scales. However, the structural interpretation of the observables obtained by various measurements is not always straightforward and in many cases dynamics-related parameters are [...] Read more.
NMR spectroscopy is the leading technique to characterize protein internal dynamics at the atomic level and on multiple time scales. However, the structural interpretation of the observables obtained by various measurements is not always straightforward and in many cases dynamics-related parameters are only used to “decorate” static structural models without offering explicit description of conformational heterogeneity. To overcome such limitations, several computational techniques have been developed to generate ensemble-based representations of protein structure and dynamics with the use of NMR-derived data. An important common aspect of the methods is that NMR observables and derived parameters are interpreted as properties of the ensemble instead of individual conformers. The resulting ensembles reflect the experimentally determined internal mobility of proteins at a given time scale and can be used to understand the role of internal motions in biological processes at atomic detail. In this review we provide an overview of the calculation methods currently available and examples of biological insights obtained by the ensemble-based models of the proteins investigated. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
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Open AccessReview Structural Characterization of Intrinsically Disordered Proteins by NMR Spectroscopy
Molecules 2013, 18(9), 10802-10828; doi:10.3390/molecules180910802
Received: 1 July 2013 / Revised: 19 August 2013 / Accepted: 30 August 2013 / Published: 4 September 2013
Cited by 39 | PDF Full-text (1013 KB) | HTML Full-text | XML Full-text
Abstract
Recent advances in NMR methodology and techniques allow the structural investigation of biomolecules of increasing size with atomic resolution. NMR spectroscopy is especially well-suited for the study of intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) which are in general highly [...] Read more.
Recent advances in NMR methodology and techniques allow the structural investigation of biomolecules of increasing size with atomic resolution. NMR spectroscopy is especially well-suited for the study of intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) which are in general highly flexible and do not have a well-defined secondary or tertiary structure under functional conditions. In the last decade, the important role of IDPs in many essential cellular processes has become more evident as the lack of a stable tertiary structure of many protagonists in signal transduction, transcription regulation and cell-cycle regulation has been discovered. The growing demand for structural data of IDPs required the development and adaption of methods such as 13C-direct detected experiments, paramagnetic relaxation enhancements (PREs) or residual dipolar couplings (RDCs) for the study of ‘unstructured’ molecules in vitro and in-cell. The information obtained by NMR can be processed with novel computational tools to generate conformational ensembles that visualize the conformations IDPs sample under functional conditions. Here, we address NMR experiments and strategies that enable the generation of detailed structural models of IDPs. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
Open AccessReview Italian Chemists’ Contributions to Named Reactions in Organic Synthesis: An Historical Perspective
Molecules 2013, 18(9), 10870-10900; doi:10.3390/molecules180910870
Received: 6 August 2013 / Revised: 29 August 2013 / Accepted: 30 August 2013 / Published: 4 September 2013
Cited by 3 | PDF Full-text (879 KB) | HTML Full-text | XML Full-text
Abstract
From the second half of the 19th century up to modern times, the tremendous contribution of Italian chemists to the development of science resulted in the discovery of a number of innovative chemical transformations. These reactions were subsequently christened according to their [...] Read more.
From the second half of the 19th century up to modern times, the tremendous contribution of Italian chemists to the development of science resulted in the discovery of a number of innovative chemical transformations. These reactions were subsequently christened according to their inventors’ name and so entered into the organic chemistry portfolio of “named organic reactions”. As these discoveries were being conceived, massive social, political and geographical changes in these chemists’ homeland were also occurring. In this review, a brief survey of known (and some lesser known) named organic reactions discovered by Italian chemists, along with their historical contextualization, is presented. Full article
(This article belongs to the Special Issue Named Organic Reactions based on Italian Chemists)
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Open AccessReview Physiological Roles and Potential Therapeutic Applications of the P2X7 Receptor in Inflammation and Pain
Molecules 2013, 18(9), 10953-10972; doi:10.3390/molecules180910953
Received: 17 June 2013 / Revised: 26 August 2013 / Accepted: 27 August 2013 / Published: 5 September 2013
Cited by 33 | PDF Full-text (218 KB) | HTML Full-text | XML Full-text
Abstract
The P2X7 receptor (P2X7R) is a nonselective cation channel that is activated by extracellular ATP and triggers the secretion of several proinflammatory substances, such as IL-1β, IL-18, TNF-α, and nitric oxide. Recently, several preclinical studies have demonstrated that this receptor participates in [...] Read more.
The P2X7 receptor (P2X7R) is a nonselective cation channel that is activated by extracellular ATP and triggers the secretion of several proinflammatory substances, such as IL-1β, IL-18, TNF-α, and nitric oxide. Recently, several preclinical studies have demonstrated that this receptor participates in inflammation and pain mechanisms. Taken together, these results indicate that P2X7R is a promising pharmacological target, and compounds that modulate the function of this receptor show potential as new anti-inflammatory medicines. In this review, we discuss aspects of P2X7R pharmacology and the participation of this protein in inflammation and pain and provide an overview of some promising compounds that have been tested as antagonists of P2X7R, with clinical applicability. Full article
(This article belongs to the Special Issue Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry)
Open AccessReview Metal Complexes of Quinolone Antibiotics and Their Applications: An Update
Molecules 2013, 18(9), 11153-11197; doi:10.3390/molecules180911153
Received: 8 August 2013 / Revised: 2 September 2013 / Accepted: 2 September 2013 / Published: 11 September 2013
Cited by 36 | PDF Full-text (447 KB) | HTML Full-text | XML Full-text
Abstract
Quinolones are synthetic broad-spectrum antibiotics with good oral absorption and excellent bioavailability. Due to the chemical functions found on their nucleus (a carboxylic acid function at the 3-position, and in most cases a basic piperazinyl ring (or another N-heterocycle) at the 7-position, [...] Read more.
Quinolones are synthetic broad-spectrum antibiotics with good oral absorption and excellent bioavailability. Due to the chemical functions found on their nucleus (a carboxylic acid function at the 3-position, and in most cases a basic piperazinyl ring (or another N-heterocycle) at the 7-position, and a carbonyl oxygen atom at the 4-position) quinolones bind metal ions forming complexes in which they can act as bidentate, as unidentate and as bridging ligand, respectively. In the polymeric complexes in solid state, multiple modes of coordination are simultaneously possible. In strongly acidic conditions, quinolone molecules possessing a basic side nucleus are protonated and appear as cations in the ionic complexes. Interaction with metal ions has some important consequences for the solubility, pharmacokinetics and bioavailability of quinolones, and is also involved in the mechanism of action of these bactericidal agents. Many metal complexes with equal or enhanced antimicrobial activity compared to the parent quinolones were obtained. New strategies in the design of metal complexes of quinolones have led to compounds with anticancer activity. Analytical applications of complexation with metal ions were oriented toward two main directions: determination of quinolones based on complexation with metal ions or, reversely, determination of metal ions based on complexation with quinolones. Full article
Open AccessReview Revealing the Properties of Plant Defensins through Dynamics
Molecules 2013, 18(9), 11311-11326; doi:10.3390/molecules180911311
Received: 17 July 2013 / Revised: 7 September 2013 / Accepted: 10 September 2013 / Published: 13 September 2013
Cited by 4 | PDF Full-text (2050 KB) | HTML Full-text | XML Full-text
Abstract
Defensins are potent, ancient natural antibiotics that are present in organisms ranging from lower organisms to humans. Although the structures of several defensins have been well characterized, the dynamics of only a few have been studied. This review discusses the diverse dynamics [...] Read more.
Defensins are potent, ancient natural antibiotics that are present in organisms ranging from lower organisms to humans. Although the structures of several defensins have been well characterized, the dynamics of only a few have been studied. This review discusses the diverse dynamics of two plant defensins for which the structure and dynamics have been characterized, both in the free state and in the presence of target membranes. Multiple motions are observed in loops and in secondary structure elements and may be related to twisting or breathing of the α-helix and β-sheet. This complex behavior is altered in the presence of an interface and is responsive to the presence of the putative target. The stages of membrane recognition and disruption can be mapped over a large time scale range, demonstrating that defensins in solution exist as an ensemble of different conformations, a subset of which is selected upon membrane binding. Therefore, studies on the dynamics have revealed that defensins interact with membranes through a mechanism of conformational selection. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
Open AccessReview Anticancer and Antifungal Compounds from Aspergillus, Penicillium and Other Filamentous Fungi
Molecules 2013, 18(9), 11338-11376; doi:10.3390/molecules180911338
Received: 3 July 2013 / Revised: 23 August 2013 / Accepted: 3 September 2013 / Published: 13 September 2013
Cited by 12 | PDF Full-text (490 KB) | HTML Full-text | XML Full-text
Abstract
This review covers important anticancer and antifungal compounds reported from filamentous fungi and in particular from Aspergillus, Penicillium and Talaromyces. The taxonomy of these fungi is not trivial, so a focus of this review has been to report the correct [...] Read more.
This review covers important anticancer and antifungal compounds reported from filamentous fungi and in particular from Aspergillus, Penicillium and Talaromyces. The taxonomy of these fungi is not trivial, so a focus of this review has been to report the correct identity of the producing organisms based on substantial previous in-house chemotaxonomic studies. Full article
Open AccessReview Oxetane Synthesis through the Paternò-Büchi Reaction
Molecules 2013, 18(9), 11384-11428; doi:10.3390/molecules180911384
Received: 29 July 2013 / Revised: 5 September 2013 / Accepted: 10 September 2013 / Published: 16 September 2013
Cited by 16 | PDF Full-text (412 KB) | HTML Full-text | XML Full-text
Abstract
The Paternò-Büchi reaction is a photochemical reaction between a carbonyl compound and an alkene to give the corresponding oxetane. In this review the mechanism of the reaction is discussed. On this basis the described use in the reaction with electron rich alkenes [...] Read more.
The Paternò-Büchi reaction is a photochemical reaction between a carbonyl compound and an alkene to give the corresponding oxetane. In this review the mechanism of the reaction is discussed. On this basis the described use in the reaction with electron rich alkenes (enolethers, enol esters, enol silyl ethers, enanines, heterocyclic compounds has been reported. The stereochemical behavior of the reaction is particularly stressed. We pointed out the reported applications of this reaction to the synthesis of naturally occuring compounds. Full article
(This article belongs to the Special Issue Named Organic Reactions based on Italian Chemists)
Open AccessReview Plasticity of the Human Olfactory System: The Olfactory Bulb
Molecules 2013, 18(9), 11586-11600; doi:10.3390/molecules180911586
Received: 15 August 2013 / Revised: 3 September 2013 / Accepted: 11 September 2013 / Published: 17 September 2013
Cited by 15 | PDF Full-text (1392 KB) | HTML Full-text | XML Full-text
Abstract
In the last years, an increasing interest has been paid to the olfactory system, particularly to its abilities of plasticity and its potential continuous neurogenesis throughout adult life. Although mechanisms underlying adult neurogenesis have been largely investigated in animals, to some degree [...] Read more.
In the last years, an increasing interest has been paid to the olfactory system, particularly to its abilities of plasticity and its potential continuous neurogenesis throughout adult life. Although mechanisms underlying adult neurogenesis have been largely investigated in animals, to some degree they remain unclear in humans. Based on human research findings, the present review will focus on the olfactory bulb as an evidence of the astonishing plasticity of the human olfactory system. Full article
(This article belongs to the Special Issue Flavors and Fragrances)

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Open AccessRetraction Retraction: Al-Salahi, R.A. et al. Cytotoxicity and Anti-Inflammatory Activity of ethylsulfanyltriazoloquinazolines. Molecules 2013, 18, 1434-1446
Molecules 2013, 18(9), 11001-11002; doi:10.3390/molecules180911001
Received: 26 June 2013 / Accepted: 6 September 2013 / Published: 9 September 2013
PDF Full-text (88 KB) | HTML Full-text | XML Full-text
Abstract
We have been made aware of the fact that a large proportion of the Introduction section and corresponding references of the title paper [1] had been copied verbatim from an earlier paper by Hamdy and Gamal-Eldeen [2], and further, during our investigation [...] Read more.
We have been made aware of the fact that a large proportion of the Introduction section and corresponding references of the title paper [1] had been copied verbatim from an earlier paper by Hamdy and Gamal-Eldeen [2], and further, during our investigation it has also come to light that most of the text in question had been lifted unchanged from an even earlier review paper by a different group [3]. The authors have been contacted, these facts confirmed, and Dr. Amira M. Gamal-Eldeen has been identified as the person responsible for contributing that part of the paper. [...] Full article
Open AccessLetter A New Lignan Glucoside from the Whole Plants of Salvia Scapiformis
Molecules 2013, 18(9), 11377-11383; doi:10.3390/molecules180911377
Received: 30 August 2013 / Revised: 6 September 2013 / Accepted: 9 September 2013 / Published: 13 September 2013
Cited by 2 | PDF Full-text (467 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phytochemical investigation of the whole plants of Salvia scapiformis Hance afforded eight compounds, including one new lignan, (+)-8α-hydroxypinoresinol-8-O-[6′′-O-(4′′′-hydroxybenzoyl)]-β-d-glucopyranoside (1), four known lignans, (+)-8α-hydroxy-pinoresinol-8-O-β-d-glucopyranoside (2), [...] Read more.
Phytochemical investigation of the whole plants of Salvia scapiformis Hance afforded eight compounds, including one new lignan, (+)-8α-hydroxypinoresinol-8-O-[6′′-O-(4′′′-hydroxybenzoyl)]-β-d-glucopyranoside (1), four known lignans, (+)-8α-hydroxy-pinoresinol-8-O-β-d-glucopyranoside (2), (+)-8α-hydroxypinoresinol (3), (+)-pinoresinol (4), and (+)-medioresinol (5), and three known triterpenoids, ursolic acid (6), 4-epi-niga-ichigoside F1 (7), and niga-ichigoside F1 (8). Their structures were determined on the basis of extensive spectroscopic analyses and comparison with spectroscopic data in the literature. The absolute configuration of the new compound 1 was determined by chemical transformation and GC analysis. Full article

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