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Molecules, Volume 20, Issue 8 (August 2015), Pages 13496-15448

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Editorial

Jump to: Research, Review

Open AccessEditorial Protein-Carbohydrate Interactions, and Beyond …
Molecules 2015, 20(8), 15202-15205; doi:10.3390/molecules200815202
Received: 17 August 2015 / Revised: 17 August 2015 / Accepted: 19 August 2015 / Published: 20 August 2015
Cited by 2 | PDF Full-text (630 KB) | HTML Full-text | XML Full-text
Abstract
Carbohydrates are ubiquitous and play an intriguing role inside the cell as well as on the cell surface.[...] Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)

Research

Jump to: Editorial, Review

Open AccessArticle Hepatocyte Growth Factor Mediates the Antifibrogenic Action of Ocimum bacilicum Essential Oil against CCl4-Induced Liver Fibrosis in Rats
Molecules 2015, 20(8), 13518-13535; doi:10.3390/molecules200813518
Received: 11 May 2015 / Revised: 2 July 2015 / Accepted: 7 July 2015 / Published: 23 July 2015
Cited by 10 | PDF Full-text (2511 KB) | HTML Full-text | XML Full-text
Abstract
The current investigation aimed to evaluate the antifibrogenic potential of Ocimum basilicum essential oil (OBE) and further to explore some of its underlying mechanisms. Three groups of rats were used: group I (control), group II (CCl4 model) and group III (OBE-treated) received
[...] Read more.
The current investigation aimed to evaluate the antifibrogenic potential of Ocimum basilicum essential oil (OBE) and further to explore some of its underlying mechanisms. Three groups of rats were used: group I (control), group II (CCl4 model) and group III (OBE-treated) received CCl4 and OBE 2 weeks after the start of CCl4 administration. Oxidative damage was assessed by the measurement of MDA, NO, SOD, CAT, GSH and total antioxidant capacity (TAC). Liver fibrosis was assessed histopathologically by Masson’s trichrome staining and α-smooth muscle actin (α-SMA) immunostaining. Expression of hepatocyte growth factor (HGF) and cytochrome P450 (CYP2EI isoform) was estimated using real-time PCR and immunohistochemistry. OBE successfully attenuated liver injury, as shown by histopathology, decreased serum transaminases and improved oxidative status of the liver. Reduced collagen deposition and α-SMA immuopositive cells indicated an abrogation of hepatic stellate cell activation by OBE. Furthermore, OBE was highly effective in stimulating HGF mRNA and protein expression and inhibiting CCl4-induced CYP2E1 down-regulation. The mechanism of antifibrogenic action of OBE is hypothesized to proceed via scavenging free radicals and activating liver regeneration by induction of HGF. These data suggest the use of OBE as a complementary treatment in liver fibrosis. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Antibacterial Activity of Protocatechuic Acid Ethyl Ester on Staphylococcus aureus Clinical Strains Alone and in Combination with Antistaphylococcal Drugs
Molecules 2015, 20(8), 13536-13549; doi:10.3390/molecules200813536
Received: 19 June 2015 / Revised: 13 July 2015 / Accepted: 20 July 2015 / Published: 23 July 2015
Cited by 2 | PDF Full-text (724 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the presented study was to examine in vitro the antibacterial activity of protocatechuic acid ethyl ester (ethyl 3,4-dihydroxybenzoate, EDHB) against Staphylococcus aureus clinical isolates alone and in the combination with four selected antibiotics. The EDHB antimicrobial activity was tested against
[...] Read more.
The aim of the presented study was to examine in vitro the antibacterial activity of protocatechuic acid ethyl ester (ethyl 3,4-dihydroxybenzoate, EDHB) against Staphylococcus aureus clinical isolates alone and in the combination with four selected antibiotics. The EDHB antimicrobial activity was tested against twenty S. aureus strains isolated from the clinical samples, and three reference strains. The phenotypes and genotypes of resistance to methicillin for the tested strains were defined as well as the phenotypic resistance to macrolides, lincosamides and streptogramin B (MLSB). EDHB displayed diverse activity against examined S. aureus strains with the minimal inhibitory concentration (MIC) within the range from 64 to 1024 µg/mL. Addition of ¼ MIC of EDHB into the Mueller-Hinton Agar (MHA) resulted in augmented antibacterial effect in the presence of clindamycin. In the case of cefoxitin no synergistic effect with EDHB was noted. For erythromycin and vancomycin the decrease of mean MICs in the presence of EDHB was observed but did not reach statistical significance. The results of the present study showed that in vitro EDHB possesses antibacterial activity against S. aureus clinical strains and triggers a synergistic antimicrobial effect with clindamycin and to the lesser extent with erythromycin and vancomycin. Full article
Open AccessArticle A Fungal α-Galactosidase from Tricholoma matsutake with Broad Substrate Specificity and Good Hydrolytic Activity on Raffinose Family Oligosaccharides
Molecules 2015, 20(8), 13550-13562; doi:10.3390/molecules200813550
Received: 23 June 2015 / Revised: 17 July 2015 / Accepted: 17 July 2015 / Published: 24 July 2015
Cited by 3 | PDF Full-text (815 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An acidic α-galactosidase designated as TMG was purified from the fruiting bodies The purification protocol entailed ion exchange chromatography on Q-Sepharose and of Tricholoma matsutake with 136-fold purification and a specific activity of 909 units/mg. Mono-Q and fast protein liquid chromatography on Superdex
[...] Read more.
An acidic α-galactosidase designated as TMG was purified from the fruiting bodies The purification protocol entailed ion exchange chromatography on Q-Sepharose and of Tricholoma matsutake with 136-fold purification and a specific activity of 909 units/mg. Mono-Q and fast protein liquid chromatography on Superdex 75. TMG is a monomeric protein exhibiting a molecular mass of 47 kDa in SDS-PAGE and gel filtration. The purified enzyme was identified by LC-MS/MS and three inner amino acid sequences were obtained. The optimum pH and temperature for TMG with pNPGal as substrate were pH 4.5 and 55 °C, respectively. The α-galactosidase activity was strongly inhibited by K+, Ca2+, Cd2+, Hg2+, Ag+ and Zn2+ ions. The enzyme activity was inhibited by the chemical modification agent N-bromosuccinimide (NBS), indicating the importance of tryptophan residue(s) at or near the active site. Besides hydrolyzing pNPGal, TMG also efficaciously catalyzed the degradation of natural substrates such as stachyose, raffinose, and melibiose. Thus TMG can be exploited commercially for improving the nutritional value of soy milk by degradation of indigestible oligosaccharides. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Isolation and Identification of Cytotoxic Compounds from Aeschynomene fascicularis, a Mayan Medicinal Plant
Molecules 2015, 20(8), 13563-13574; doi:10.3390/molecules200813563
Received: 28 May 2015 / Revised: 8 July 2015 / Accepted: 10 July 2015 / Published: 24 July 2015
Cited by 8 | PDF Full-text (737 KB) | HTML Full-text | XML Full-text
Abstract
The plant Aeschynomene fascicularis (Fabaceae) has been used in Mayan traditional medicine in the Yucatan peninsula. However, the compounds present in the plant responsible for its curative properties have not yet been investigated. Aeschynomene fascicularis root bark was extracted with 100% methanol to
[...] Read more.
The plant Aeschynomene fascicularis (Fabaceae) has been used in Mayan traditional medicine in the Yucatan peninsula. However, the compounds present in the plant responsible for its curative properties have not yet been investigated. Aeschynomene fascicularis root bark was extracted with 100% methanol to obtain a crude extract. The methanol extract was partitioned successively with solvents with increasing polarity to obtain the corresponding hexane (Hx), dichloromethane (DCM) and ethyl acetate fractions (EtOAc), as well as a residual water-alcoholic fraction. These fractions were tested for their cytotoxic activities using an MTT assay against Hep-2 cancer cell lines. The Hx fraction led to the isolation of spinochalcone C (1), spinochalcone A (2), isocordoin (3) and secundiflorol G (4). Their structures were identified based on spectroscopic evidence and chemical properties. All compounds were subjected to cytotoxicity and antiproliferative assays against a panel of seven cell lines, including one normal-type cell line. Spinochalcone A (2) exhibited cytotoxic activity against DU-145 cell line and antiproliferative activity against the KB cell line. Secundiflorol G (4) showed strong cytotoxic activity towards KB and Hep-2 cell lines. In addition, isocordoin (3) showed moderate activity on KB, Hep-2 and DU-145 cell lines. The active Compounds 2, 3 and 4 are potential therapeutic entities against cancer. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Photochemical and Photophysical Properties of Phthalocyanines Modified with Optically Active Alcohols
Molecules 2015, 20(8), 13575-13590; doi:10.3390/molecules200813575
Received: 26 May 2015 / Accepted: 2 July 2015 / Published: 24 July 2015
Cited by 4 | PDF Full-text (1892 KB) | HTML Full-text | XML Full-text
Abstract
Three phthalocyanine derivatives were synthesized and characterized: one modified with a racemic mixture of 1-(4-bromophenyl)ethanol and two other macrocycles modified with each one of the enantioenriched isomers (R)-1-(4-bromophenyl)ethanol and (S)-1-(4-bromophenyl)ethanol. The compounds were characterized by 1H-NMR spectroscopy, mass
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Three phthalocyanine derivatives were synthesized and characterized: one modified with a racemic mixture of 1-(4-bromophenyl)ethanol and two other macrocycles modified with each one of the enantioenriched isomers (R)-1-(4-bromophenyl)ethanol and (S)-1-(4-bromophenyl)ethanol. The compounds were characterized by 1H-NMR spectroscopy, mass spectrometry, UV-Vis absorption, and excitation and emission spectra. Additionally, partition coefficient values and the quantum yield of the generation of oxygen reactive species were determined. Interestingly, the phthalocyanine containing a (R)-1-(4-bromophenyl)ethoxy moiety showed higher quantum yield of reactive oxygen species generation than other compounds under the same conditions. In addition, the obtained fluorescence microscopy and cell viability results have shown that these phthalocyanines have different interactions with mammary MCF-7 cells. Therefore, our results indicate that the photochemical and biological properties of phthalocyanines with chiral ligands should be evaluated separately for each enantiomeric species. Full article
(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)
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Open AccessCommunication Synthesis and Enzymatic Incorporation of Modified Deoxyuridine Triphosphates
Molecules 2015, 20(8), 13591-13602; doi:10.3390/molecules200813591
Received: 2 June 2015 / Revised: 16 July 2015 / Accepted: 20 July 2015 / Published: 24 July 2015
Cited by 5 | PDF Full-text (1128 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
To expand the chemical functionality of DNAzymes and aptamers, several new modified deoxyuridine triphosphates have been synthesized. An important precursor that enables this aim is 5-aminomethyl dUTP, whereby the pendent amine serves as a handle for further synthetic functionalization. Five functional groups were
[...] Read more.
To expand the chemical functionality of DNAzymes and aptamers, several new modified deoxyuridine triphosphates have been synthesized. An important precursor that enables this aim is 5-aminomethyl dUTP, whereby the pendent amine serves as a handle for further synthetic functionalization. Five functional groups were conjugated to 5-aminomethyl dUTP. Incorporation assays were performed on several templates that demand 2–5 sequential incorporation events using several commercially available DNA polymerases. It was found that Vent (exo-) DNA polymerase efficiently incorporates all five modified dUTPs. In addition, all nucleoside triphosphates were capable of supporting a double-stranded exponential PCR amplification. Modified PCR amplicons were PCR amplified into unmodified DNA and sequenced to verify that genetic information was conserved through incorporation, amplification, and reamplification. Overall these modified dUTPs represent new candidate substrates for use in selections using modified nucleotide libraries. Full article
(This article belongs to the Special Issue Frontiers in Nucleic Acid Chemistry)
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Open AccessArticle A Near Infrared Spectroscopy (NIRS) and Chemometric Approach to Improve Apple Fruit Quality Management: A Case Study on the Cultivars “Cripps Pink” and “Braeburn”
Molecules 2015, 20(8), 13603-13619; doi:10.3390/molecules200813603
Received: 8 May 2015 / Revised: 10 July 2015 / Accepted: 14 July 2015 / Published: 24 July 2015
Cited by 7 | PDF Full-text (1581 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The potential of near infrared spectroscopy (NIRS) in the wavelength range of 1000–2500 nm for predicting quality parameters such as total soluble solids (TSS), acidity (TA), firmness, and individual sugars (glucose, fructose, sucrose, and xylose) for two cultivars of apples (“Braeburn” and “Cripps
[...] Read more.
The potential of near infrared spectroscopy (NIRS) in the wavelength range of 1000–2500 nm for predicting quality parameters such as total soluble solids (TSS), acidity (TA), firmness, and individual sugars (glucose, fructose, sucrose, and xylose) for two cultivars of apples (“Braeburn” and “Cripps Pink”) was studied during the pre- and post-storage periods. Simultaneously, a qualitative investigation on the capability of NIRS to discriminate varieties, harvest dates, storage periods and fruit inhomogeneity was carried out. In order to generate a sample set with high variability within the most relevant apple quality traits, three different harvest time points in combination with five different storage periods were chosen, and the evolution of important quality parameters was followed both with NIRS and wet chemical methods. By applying a principal component analysis (PCA) a differentiation between the two cultivars, freshly harvested vs. long-term stored apples and, notably, between the sun-exposed vs. shaded side of apples could be found. For the determination of quality parameters effective prediction models for titratable acid (TA) and individual sugars such as fructose, glucose and sucrose by using partial least square (PLS) regression have been developed. Our results complement earlier reports, highlighting the versatility of NIRS as a fast, non-invasive method for quantitative and qualitative studies on apples. Full article
(This article belongs to the Special Issue Advances of Vibrational Spectroscopic Technologies in Life Sciences)
Open AccessArticle Metabolic Analysis of Various Date Palm Fruit (Phoenix dactylifera L.) Cultivars from Saudi Arabia to Assess Their Nutritional Quality
Molecules 2015, 20(8), 13620-13641; doi:10.3390/molecules200813620
Received: 21 June 2015 / Revised: 9 July 2015 / Accepted: 16 July 2015 / Published: 27 July 2015
Cited by 14 | PDF Full-text (1721 KB) | HTML Full-text | XML Full-text
Abstract
Date palm is an important crop, especially in the hot-arid regions of the world. Date palm fruits have high nutritional and therapeutic value and possess significant antibacterial and antifungal properties. In this study, we performed bioactivity analyses and metabolic profiling of date fruits
[...] Read more.
Date palm is an important crop, especially in the hot-arid regions of the world. Date palm fruits have high nutritional and therapeutic value and possess significant antibacterial and antifungal properties. In this study, we performed bioactivity analyses and metabolic profiling of date fruits of 12 cultivars from Saudi Arabia to assess their nutritional value. Our results showed that the date extracts from different cultivars have different free radical scavenging and anti-lipid peroxidation activities. Moreover, the cultivars showed significant differences in their chemical composition, e.g., the phenolic content (10.4–22.1 mg/100 g DW), amino acids (37–108 μmol·g−1 FW) and minerals (237–969 mg/100 g DW). Principal component analysis (PCA) showed a clear separation of the cultivars into four different groups. The first group consisted of the Sokary, Nabtit Ali cultivars, the second group of Khlas Al Kharj, Khla Al Qassim, Mabroom, Khlas Al Ahsa, the third group of Khals Elshiokh, Nabot Saif, Khodry, and the fourth group consisted of Ajwa Al Madinah, Saffawy, Rashodia, cultivars. Hierarchical cluster analysis (HCA) revealed clustering of date cultivars into two groups. The first cluster consisted of the Sokary, Rashodia and Nabtit Ali cultivars, and the second cluster contained all the other tested cultivars. These results indicate that date fruits have high nutritive value, and different cultivars have different chemical composition. Full article
Open AccessArticle Diastereodivergent and Enantioselective [4+2] Annulations of γ-Butenolides with Cyclic 1-Azadienes
Molecules 2015, 20(8), 13642-13658; doi:10.3390/molecules200813642
Received: 9 June 2015 / Revised: 12 July 2015 / Accepted: 13 July 2015 / Published: 27 July 2015
Cited by 7 | PDF Full-text (1174 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An asymmetric annulation reaction of γ-butenolides and cyclic 1-azadienes containing a 1,2-benzoisothiazole-1,1-dioxide motif has been studied, proceeding in a tandem Michael addition-aza-Michael addition sequence. Endo-type cycloadducts bearing fused tetracyclic skeletons were isolated in fair yields and with high enantioselectivity (up to >99%
[...] Read more.
An asymmetric annulation reaction of γ-butenolides and cyclic 1-azadienes containing a 1,2-benzoisothiazole-1,1-dioxide motif has been studied, proceeding in a tandem Michael addition-aza-Michael addition sequence. Endo-type cycloadducts bearing fused tetracyclic skeletons were isolated in fair yields and with high enantioselectivity (up to >99% ee) under the catalysis of modified cinchona alkaloid (DHQD)2PHAL. Besides, exo-type diastereomers could be produced using β-isocupreidine (β-ICD) as the catalyst, though with moderate enantioselectivity. Full article
(This article belongs to the Special Issue Brønsted Base Catalysis in Organic Synthesis)
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Open AccessArticle Steroidal Saponins from the Roots and Rhizomes of Tupistra chinensis
Molecules 2015, 20(8), 13659-13669; doi:10.3390/molecules200813659
Received: 25 June 2015 / Revised: 22 July 2015 / Accepted: 23 July 2015 / Published: 28 July 2015
Cited by 3 | PDF Full-text (2016 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new furostanol saponins 12 and a new spirostanol saponin 3 were isolated together with two known furostanol saponins 45 from the roots and rhizomes of Tupistra chinensis. Their structures were characterized as 1β,2β,3β,4β,5β,26-hexahydroxyfurost-20(22), 25(27)-dien-5,26-O-β-d-glucopyranoside (
[...] Read more.
Two new furostanol saponins 12 and a new spirostanol saponin 3 were isolated together with two known furostanol saponins 45 from the roots and rhizomes of Tupistra chinensis. Their structures were characterized as 1β,2β,3β,4β,5β,26-hexahydroxyfurost-20(22), 25(27)-dien-5,26-O-β-d-glucopyranoside (1), 1β,2β,3β,4β,5β,6β,7α,23ξ,26-nona-hydroxyfurost- 20(22),25(27)-dien-26-O-β-d-glucopyranoside (2), (20S,22R)-spirost-25 (27)-en-1β,3β,5β- trihydroxy-1-O-β-d-xyloside (3), tupisteroide B (4) and 5β-furost-Δ25(27)-en-1β,2β,3β,4β,5β,7α, 22ξ,26-octahydroxy-6-one-26-O-β-d-glucopyranoside (5), respectively, by extensive use of spectroscopic techniques and chemical evidence. Additionally, the in vitro cytotoxic activity of 14 was evaluated on human A549 and H1299 tumor cell lines, and compound 3 exhibited cytotoxicity against A549 cells (IC50 86.63 ± 2.33 μmol·L−1) and H1299 cells (IC50 88.21 ± 1.34 μmol·L−1). Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Oleanolic Acid, a Compound Present in Grapes and Olives, Protects against Genotoxicity in Human Mammary Epithelial Cells
Molecules 2015, 20(8), 13670-13688; doi:10.3390/molecules200813670
Received: 26 June 2015 / Revised: 15 July 2015 / Accepted: 24 July 2015 / Published: 28 July 2015
Cited by 6 | PDF Full-text (2653 KB) | HTML Full-text | XML Full-text
Abstract
Oleanolic acid (AO) and maslinic acid (MA) are constituents of the skins of different fruits, including olives and white or red grapes. Although both compounds are known to have beneficial properties against different types of cancers, thus far, there are no studies about
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Oleanolic acid (AO) and maslinic acid (MA) are constituents of the skins of different fruits, including olives and white or red grapes. Although both compounds are known to have beneficial properties against different types of cancers, thus far, there are no studies about their chemopreventive effects in human breast cancer. Thus, we sought to elucidate whether both compounds possess chemopreventive activity. Two cell lines of human breast cancer cells and one noncancerous human mammary epithelial cells were used to determine the effects of OA and MA. The results showed that OA inhibited the proliferation and increased the oxidative stress of highly invasive cells. Additionally, OA decreased oxidative stress and oxidative damage to the DNA in human mammary epithelial cells. These results suggest that OA could act as a chemopreventive agent in human breast cancer and could inhibit the proliferation of highly invasive breast cancer cells. Full article
(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)
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Open AccessArticle Inhibition of Oral Streptococci Growth Induced by the Complementary Action of Berberine Chloride and Antibacterial Compounds
Molecules 2015, 20(8), 13705-13724; doi:10.3390/molecules200813705
Received: 24 May 2015 / Revised: 22 July 2015 / Accepted: 23 July 2015 / Published: 28 July 2015
Cited by 7 | PDF Full-text (846 KB) | HTML Full-text | XML Full-text
Abstract
Synergistic interactions between natural bioactive compounds from medicinal plants and antibiotics may exhibit therapeutic benefits, acting against oral cariogenic and opportunistic pathogens. The aim of the presented work was to assess the antibacterial activity of berberine chloride (BECl) in light of the effect
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Synergistic interactions between natural bioactive compounds from medicinal plants and antibiotics may exhibit therapeutic benefits, acting against oral cariogenic and opportunistic pathogens. The aim of the presented work was to assess the antibacterial activity of berberine chloride (BECl) in light of the effect exerted by common antibiotics on selected reference strains of oral streptococci (OST), and to evaluate the magnitude of interactions. Three representative oral microorganisms were investigated: Streptococcus mutans ATCC 25175 (SM), S. sanguinis ATCC 10556 (SS), S. oralis ATCC 9811 (SO) and microdilution tests, along with disc diffusion assays were applied. Here, we report that growth (viability) of all oral streptococci was reduced by exposure to BECl and was dependent primarily on exposure/ incubation time. A minimum inhibitory concentrations (MIC) of BECl against OST ranged from 512 µg/mL (SS) to 1024 µg/mL (SM, SO). The most noticeable antibacterial effects were observed for S. sanguinis (MIC 512 µg/mL) and the most significant synergistic action was found for the combinations BECl-penicillin, BECl-clindamycin and BECl-erythromycin. The S. oralis reflects the highest MBC value as assessed by the AlamarBlue assay (2058 µg/mL). The synergy between berberine and common antibiotics demonstrates its potential use as a novel antibacterial tool for opportunistic infections and also provides a rational basis for the use of berberine as an oral hygiene measure. Full article
Open AccessArticle Phenolic Compounds from the Roots of Rhodiola crenulata and Their Antioxidant and Inducing IFN-γ Production Activities
Molecules 2015, 20(8), 13725-13739; doi:10.3390/molecules200813725
Received: 30 June 2015 / Revised: 20 July 2015 / Accepted: 23 July 2015 / Published: 28 July 2015
Cited by 6 | PDF Full-text (1032 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the present study, two new phenolic compounds 1 and 11, a pair of lignan isomers 12 and 13 with their absolute configurations established for the first time, were isolated from the ethanol extract of the roots of Rhodiola crenulata, together
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In the present study, two new phenolic compounds 1 and 11, a pair of lignan isomers 12 and 13 with their absolute configurations established for the first time, were isolated from the ethanol extract of the roots of Rhodiola crenulata, together with 13 known phenolic compounds, and their structures were elucidated via NMR, HRESIMS, UV, IR and CD analyses. All the isolated compounds were evaluated for their in vitro antioxidant activities using the 2,2-diphenyl-1-picryhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays. Ten of them exhibited significant antioxidant activities compared to ascorbic acid. Furthermore, the inducibilities of the isolated compounds to IFN-γ production were also assessed. Compounds 1, 8, 9, 12, 13, 14 and 15 could moderately stimulate IFN-γ expression. Full article
(This article belongs to the Special Issue Recent Advances in Plant Phenolics)
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Open AccessArticle Discovery of 5-(5,5-Dimethylbutenolide-3-ethylidene)-2-amino-imidazolinone Derivatives as Fungicidal Agents
Molecules 2015, 20(8), 13740-13752; doi:10.3390/molecules200813740
Received: 3 July 2015 / Revised: 24 July 2015 / Accepted: 24 July 2015 / Published: 28 July 2015
Cited by 4 | PDF Full-text (1136 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The novel fungicidal agents 5-(5,5-dimethylbutenolide-3-ethylidene)-2-amino-imidazolinone derivatives, were designed and synthesized in moderate to excellent yields in four steps by αa-hydroxyketone and diketene as raw materials and characterized by HR-ESI-MS and 1H-NMR. The preliminary bioassay showed that some of these compounds, such as
[...] Read more.
The novel fungicidal agents 5-(5,5-dimethylbutenolide-3-ethylidene)-2-amino-imidazolinone derivatives, were designed and synthesized in moderate to excellent yields in four steps by αa-hydroxyketone and diketene as raw materials and characterized by HR-ESI-MS and 1H-NMR. The preliminary bioassay showed that some of these compounds, such as 4a, 4e and 5g exhibit 94.9%, 92.8% and 81.4% inhibition rates against Sclerotinia scleotiorum at the concentration of 50 µg/mL, respectively. The EC50 values of compounds 4e and 4i were 4.14 and 3.27 µM against Alternaria Solani, and 5g had EC50 value of 3.23 µM against S. scleotiorum. Compounds 4d and 4g displayed 98.0% and 97.8% control of spore germination against Botrytis cinerea at the concentration of 100 µg/mL, respectively. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Identification of Eupatilin from Artemisia argyi as a Selective PPARα Agonist Using Affinity Selection Ultrafiltration LC-MS
Molecules 2015, 20(8), 13753-13763; doi:10.3390/molecules200813753
Received: 7 May 2015 / Revised: 20 July 2015 / Accepted: 23 July 2015 / Published: 28 July 2015
Cited by 7 | PDF Full-text (1217 KB) | HTML Full-text | XML Full-text
Abstract
Peroxisome proliferator-activated receptors (PPARs) are key nuclear receptors and therapeutic targets for the treatment of metabolic diseases through the regulation of insulin resistance, diabetes, and dyslipidemia. Although a few drugs that target PPARs have been approved, more diverse and novel PPAR ligands are
[...] Read more.
Peroxisome proliferator-activated receptors (PPARs) are key nuclear receptors and therapeutic targets for the treatment of metabolic diseases through the regulation of insulin resistance, diabetes, and dyslipidemia. Although a few drugs that target PPARs have been approved, more diverse and novel PPAR ligands are necessary to improve the safety and efficacy of available drugs. To expedite the search for new natural agonists of PPARs, we developed a screening assay based on ultrafiltration liquid chromatography-mass spectrometry (LC-MS) that is compatible with complex samples such as dietary foods or botanical extracts. The known PPARα and/or PPARγ ligands resveratrol and rosiglitazone were used as positive controls to validate the developed method. When applied to the screening of an Artemisia argyi extract, eupatilin was identified as a selective PPARα ligand. A PPAR competitive binding assay based on FRET detection also confirmed eupatilin as a selective PPARα agonist exhibiting a binding affinity of 1.18 μM (IC50). Furthermore, eupatilin activation of the transcriptional activity of PPARα was confirmed using a cell-based transactivation assay. Thus, ultrafiltration LC-MS is a suitable assay for the identification of PPAR ligands in complex matrixes such as extracts of dietary foods and botanicals. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Salix daphnoides: A Screening for Oligomeric and Polymeric Proanthocyanidins
Molecules 2015, 20(8), 13764-13779; doi:10.3390/molecules200813764
Received: 28 June 2015 / Revised: 8 July 2015 / Accepted: 16 July 2015 / Published: 29 July 2015
Cited by 5 | PDF Full-text (1575 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the present study, a qualitative analysis of proanthocyanidins (PAs) from an aqueous-methanolic extract of Salix daphnoides VILL. bark is described. Procyanidin B1 (1), B2 (2), B3 (3), B4 (4), C1 (5), epicatechin-(4
[...] Read more.
In the present study, a qualitative analysis of proanthocyanidins (PAs) from an aqueous-methanolic extract of Salix daphnoides VILL. bark is described. Procyanidin B1 (1), B2 (2), B3 (3), B4 (4), C1 (5), epicatechin-(4β→8)-epicatechin-(4β→8)-catechin (6) and epicatechin-(4β→8)-epicatechin-(4β→8)-epicatechin-(4β→8)-catechin (7) have been isolated by a combination of different chromatographic separations on Sephadex® LH-20-, MCI®-, Diol-and RP-18-phases. Mass spectrometry, 1D- and 2D-NMR, circular dichroism and polarimetry were used for their structure elucidation and verification by comparison with the literature. Additionally, two fractions of very polar flavan-3-ols were compared: “regular” polymeric PAs received at the very end of the Sephadex® LH-20 chromatography showing no mobility on silica TLC and “unusual” PAs with the same RF-value but already eluting together with flavonoids in the Sephadex® LH-20 system. These “unusual” PAs were subsequently enriched by centrifugal partition chromatography (CPC). 13C-NMR, polarimetry, thiolysis, acid hydrolysis and phloroglucinol degradation were used to characterize both fractions. Differences in the composition of different flavan-3-ol units and the middle chain length were observed. Full article
Open AccessArticle Mixed-Sequence Recognition of Double-Stranded DNA Using Enzymatically Stable Phosphorothioate Invader Probes
Molecules 2015, 20(8), 13780-13793; doi:10.3390/molecules200813780
Received: 1 July 2015 / Revised: 23 July 2015 / Accepted: 24 July 2015 / Published: 29 July 2015
Cited by 3 | PDF Full-text (2359 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Development of probes that allow for sequence-unrestricted recognition of double-stranded DNA (dsDNA) continues to attract much attention due to the prospect for molecular tools that enable detection, regulation, and manipulation of genes. We have recently introduced so-called Invader probes as alternatives to more
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Development of probes that allow for sequence-unrestricted recognition of double-stranded DNA (dsDNA) continues to attract much attention due to the prospect for molecular tools that enable detection, regulation, and manipulation of genes. We have recently introduced so-called Invader probes as alternatives to more established approaches such as triplex-forming oligonucleotides, peptide nucleic acids and polyamides. These short DNA duplexes are activated for dsDNA recognition by installment of +1 interstrand zippers of intercalator-functionalized nucleotides such as 2′-N-(pyren-1-yl)methyl-2′-N-methyl-2′-aminouridine and 2′-O-(pyren-1-yl)methyluridine, which results in violation of the nearest neighbor exclusion principle and duplex destabilization. The individual probes strands have high affinity toward complementary DNA strands, which generates the driving force for recognition of mixed-sequence dsDNA regions. In the present article, we characterize Invader probes that are based on phosphorothioate backbones (PS-DNA Invaders). The change from the regular phosphodiester backbone furnishes Invader probes that are much more stable to nucleolytic degradation, while displaying acceptable dsDNA-recognition efficiency. PS-DNA Invader probes therefore present themselves as interesting probes for dsDNA-targeting applications in cellular environments and living organisms. Full article
(This article belongs to the Special Issue Frontiers in Nucleic Acid Chemistry)
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Open AccessArticle Synthesis of Chiral 1,4,2-Oxazaphosphepines
Molecules 2015, 20(8), 13794-13813; doi:10.3390/molecules200813794
Received: 11 June 2015 / Revised: 17 July 2015 / Accepted: 22 July 2015 / Published: 29 July 2015
Cited by 2 | PDF Full-text (1309 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Synthesis and structural characterization of 1,4,2-oxazaphosphepines is described. The 1,4,2-oxazaphosphepines were obtained from reaction of chiral 1,3-benzoxazines with dichlorophenylphosphine or triethyl phosphite. The configuration of some of these compounds was stablished by X-ray analysis. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle New Polymorphic Forms of Pemetrexed Diacid and Their Use for the Preparation of Pharmaceutically Pure Amorphous and Hemipentahydrate Forms of Pemetrexed Disodium
Molecules 2015, 20(8), 13814-13829; doi:10.3390/molecules200813814
Received: 21 May 2015 / Revised: 22 July 2015 / Accepted: 24 July 2015 / Published: 30 July 2015
Cited by 1 | PDF Full-text (1246 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The preparation of stable amorphous pemetrexed disodium of pharmaceutical purity as well as the process optimization for the preparation of the hemipentahydrate form of pemetrexed disodium are described. Analytical methods for the polymorphic and chemical purity studies of pemetrexed disodium and pemetrexed diacid
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The preparation of stable amorphous pemetrexed disodium of pharmaceutical purity as well as the process optimization for the preparation of the hemipentahydrate form of pemetrexed disodium are described. Analytical methods for the polymorphic and chemical purity studies of pemetrexed disodium and pemetrexed diacid forms were developed. The physicochemical properties of the amorphous and hydrate forms of pemetrexed disodium, as well as new forms of pemetrexed diacid (a key synthetic intermediate) were studied by thermal analysis and powder X-ray diffraction. High-performance liquid chromatography and gas chromatography methods were used for the chemical purity and residual solvents determination. In order to study the polymorphic and chemical stability of the amorphous and hemipentahydrate forms, a hygroscopicity test (25 °C, 80% RH) was performed. Powder diffraction and high-performance liquid chromatography analyses revealed that the amorphous character and high chemical purity were preserved after the hygroscopicity test. The hemipentahydrate form transformed completely to the heptahydrate form of pemetrexed disodium. Both pemetrexed disodium forms were produced with high efficiency and pharmaceutical purity in a small commercial scale. Amorphous pemetrexed disodium was selected for further pharmaceutical development. Two new polymorphs (forms 1 and 2) of pemetrexed diacid were used for the preparation of high purity amorphous pemetrexed disodium. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Imaging the Ultrafast Photoelectron Transfer Process in Alizarin-TiO2
Molecules 2015, 20(8), 13830-13853; doi:10.3390/molecules200813830
Received: 15 May 2015 / Revised: 9 July 2015 / Accepted: 20 July 2015 / Published: 30 July 2015
Cited by 13 | PDF Full-text (14232 KB) | HTML Full-text | XML Full-text | Correction
Abstract
In this work, we adopt a quantum mechanical approach based on time-dependent density functional theory (TDDFT) to study the optical and electronic properties of alizarin supported on TiO2 nano-crystallites, as a prototypical dye-sensitized solar cell. To ensure proper alignment of the donor
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In this work, we adopt a quantum mechanical approach based on time-dependent density functional theory (TDDFT) to study the optical and electronic properties of alizarin supported on TiO2 nano-crystallites, as a prototypical dye-sensitized solar cell. To ensure proper alignment of the donor (alizarin) and acceptor (TiO2 nano-crystallite) levels, static optical excitation spectra are simulated using time-dependent density functional theory in response. The ultrafast photoelectron transfer from the dye to the cluster is simulated using an explicitly time-dependent, one-electron TDDFT ansatz. The model considers the δ-pulse excitation of a single active electron localized in the dye to the complete set of energetically accessible, delocalized molecular orbitals of the dye/nano-crystallite complex. A set of quantum mechanical tools derived from the transition electronic flux density is introduced to visualize and analyze the process in real time. The evolution of the created wave packet subject to absorbing boundary conditions at the borders of the cluster reveal that, while the electrons of the aromatic rings of alizarin are heavily involved in an ultrafast charge redistribution between the carbonyl groups of the dye molecule, they do not contribute positively to the electron injection and, overall, they delay the process. Full article
(This article belongs to the Special Issue Molecular Engineering for Electrochemical Power Sources)
Open AccessArticle Antiproliferative and Structure Activity Relationships of Amaryllidaceae Alkaloids
Molecules 2015, 20(8), 13854-13863; doi:10.3390/molecules200813854
Received: 19 June 2015 / Revised: 23 July 2015 / Accepted: 27 July 2015 / Published: 30 July 2015
Cited by 4 | PDF Full-text (797 KB) | HTML Full-text | XML Full-text
Abstract
The antiproliferative activity of a set of seven natural Amaryllidaceae alkaloids and 32 derivatives against four cancer cell lines (A2780, SW1573, T47-D and WiDr) was determined. The best antiproliferative activities were achieved with alkaloids derived from pancracine (2), haemanthamine (6
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The antiproliferative activity of a set of seven natural Amaryllidaceae alkaloids and 32 derivatives against four cancer cell lines (A2780, SW1573, T47-D and WiDr) was determined. The best antiproliferative activities were achieved with alkaloids derived from pancracine (2), haemanthamine (6) and haemantidine (7). For each skeleton, some structure-activity relationships were outlined. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis of a Spirocyclic Oxetane-Fused Benzimidazole
Molecules 2015, 20(8), 13864-13874; doi:10.3390/molecules200813864
Received: 24 June 2015 / Revised: 22 July 2015 / Accepted: 24 July 2015 / Published: 30 July 2015
Cited by 3 | PDF Full-text (1082 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new synthesis of 2-oxa-7-azaspiro[3.5]nonane is described. Spirocyclic oxetanes, including 2-oxa-6-azaspiro[3.3]heptane were converted into o-cycloalkylaminoacetanilides for oxidative cyclizations using Oxone® in formic acid. The expanded spirocyclic oxetane successfully gave the [1,2-a] ring-fused benzimidazole. X-ray crystal structure of the resultant
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A new synthesis of 2-oxa-7-azaspiro[3.5]nonane is described. Spirocyclic oxetanes, including 2-oxa-6-azaspiro[3.3]heptane were converted into o-cycloalkylaminoacetanilides for oxidative cyclizations using Oxone® in formic acid. The expanded spirocyclic oxetane successfully gave the [1,2-a] ring-fused benzimidazole. X-ray crystal structure of the resultant new tetracyclic system, 1ʹ,2ʹ-dihydro-4ʹH-spiro[oxetane-3,3ʹ-pyrido[1,2-a]benzimidazole] and the azetidine ring-opened adduct, N-(2-acetamido-4-bromophenyl)-N-{[3-(chloromethyl) oxetan-3-yl]methyl}acetamide are disclosed. Full article
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Open AccessArticle Aspects of a Distinct Cytotoxicity of Selenium Salts and Organic Selenides in Living Cells with Possible Implications for Drug Design
Molecules 2015, 20(8), 13894-13912; doi:10.3390/molecules200813894
Received: 30 April 2015 / Revised: 14 July 2015 / Accepted: 22 July 2015 / Published: 31 July 2015
Cited by 7 | PDF Full-text (1468 KB) | HTML Full-text | XML Full-text
Abstract
Selenium is traditionally considered as an antioxidant element and selenium compounds are often discussed in the context of chemoprevention and therapy. Recent studies, however, have revealed a rather more colorful and diverse biological action of selenium-based compounds, including the modulation of the intracellular
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Selenium is traditionally considered as an antioxidant element and selenium compounds are often discussed in the context of chemoprevention and therapy. Recent studies, however, have revealed a rather more colorful and diverse biological action of selenium-based compounds, including the modulation of the intracellular redox homeostasis and an often selective interference with regulatory cellular pathways. Our basic activity and mode of action studies with simple selenium and tellurium salts in different strains of Staphylococcus aureus (MRSA) and Saccharomyces cerevisiae indicate that such compounds are sometimes not particularly toxic on their own, yet enhance the antibacterial potential of known antibiotics, possibly via the bioreductive formation of insoluble elemental deposits. Whilst the selenium and tellurium compounds tested do not necessarily act via the generation of Reactive Oxygen Species (ROS), they seem to interfere with various cellular pathways, including a possible inhibition of the proteasome and hindrance of DNA repair. Here, organic selenides are considerably more active compared to simple salts. The interference of selenium (and tellurium) compounds with multiple targets could provide new avenues for the development of effective antibiotic and anticancer agents which may go well beyond the traditional notion of selenium as a simple antioxidant. Full article
(This article belongs to the Special Issue Selenium Catalysts and Antioxidants)
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Open AccessArticle Caesalpinia decapetala Extracts as Inhibitors of Lipid Oxidation in Beef Patties
Molecules 2015, 20(8), 13913-13926; doi:10.3390/molecules200813913
Received: 20 May 2015 / Revised: 13 July 2015 / Accepted: 24 July 2015 / Published: 31 July 2015
Cited by 3 | PDF Full-text (1107 KB) | HTML Full-text | XML Full-text
Abstract
In this study we investigated the effects of Caesalpinia decapetala (CD) extracts on lipid oxidation in ground beef patties. Plant extracts and butylated hydroxytoluene (BHT) were individually added to patties at both 0.1% and 0.5% (w/w) concentrations. We assessed
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In this study we investigated the effects of Caesalpinia decapetala (CD) extracts on lipid oxidation in ground beef patties. Plant extracts and butylated hydroxytoluene (BHT) were individually added to patties at both 0.1% and 0.5% (w/w) concentrations. We assessed the antioxidant efficacy of CD by the ferric reducing antioxidant power (FRAP) assay and evaluated their potential as natural antioxidants for meat preservation by thiobarbituric acid reactive substance (TBARS) values, hexanal content, fatty acid composition and color parameters. These were tested periodically during 11 days of refrigerated storage. TBARS levels were significantly lower (p ≤ 0.05) in the samples containing plant extracts or BHT than in the non-treated control. In addition, the beef patties formulated with the selected plant extracts showed significantly (p ≤ 0.05) better color stability than those without antioxidants. These results indicate that edible plant extracts are promising sources of natural antioxidants and can potentially be used as functional preservatives in meat products. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle Cordyceps militaris (L.) Link Fruiting Body Reduces the Growth of a Non-Small Cell Lung Cancer Cell Line by Increasing Cellular Levels of p53 and p21
Molecules 2015, 20(8), 13927-13940; doi:10.3390/molecules200813927
Received: 17 June 2015 / Revised: 16 July 2015 / Accepted: 27 July 2015 / Published: 31 July 2015
Cited by 3 | PDF Full-text (1270 KB) | HTML Full-text | XML Full-text
Abstract
Cordyceps militaris (L.) Link, an edible entomopathogenic fungus widely used in traditional Chinese medicine, has numerous potential medicinal properties including antitumor activity. The methanolic extract of C. militaris fruiting body was recently shown to have tumor cell growth inhibitory activity in several human
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Cordyceps militaris (L.) Link, an edible entomopathogenic fungus widely used in traditional Chinese medicine, has numerous potential medicinal properties including antitumor activity. The methanolic extract of C. militaris fruiting body was recently shown to have tumor cell growth inhibitory activity in several human tumor cell lines. Nonetheless, the mechanism of action involved is still not known. This work aimed at further studying the effect of the methanolic extract of C. militaris regarding its antitumor mechanism of action, using the non-small cell lung cancer cell line (NCI-H460) as a model. Results showed that treatment with the extract decreased cellular proliferation, induced cell cycle arrest at G0/G1 and increased apoptosis. In addition, the extract increased the levels of p53 and p21. Moreover, an increase in p-H2A.X and 53BP1 levels, together with an increase in the number of 53BP1 foci/cell (all indicative of DNA damage), were also observed after treatment with the extract. This work suggests that this extract affected NCI-H460 cellular viability through a mechanism involving DNA damage and p53 activation. This further supports the potential of this extract as a source of bioactive compounds, which may be used in anticancer strategies. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Synthesis and Fungicidal Activity of β-Carboline Alkaloids and Their Derivatives
Molecules 2015, 20(8), 13941-13957; doi:10.3390/molecules200813941
Received: 15 July 2015 / Revised: 28 July 2015 / Accepted: 29 July 2015 / Published: 31 July 2015
Cited by 4 | PDF Full-text (1022 KB) | HTML Full-text | XML Full-text
Abstract
A series of β-Carboline derivatives were designed, synthesized, and evaluated for their fungicidal activities in this study. Several derivatives electively exhibited fungicidal activities against some fungi. Especially, compound F5 exhibited higher fungicidal activity against Rhizoctonia solani (53.35%) than commercial antiviral agent validamycin (36.4%);
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A series of β-Carboline derivatives were designed, synthesized, and evaluated for their fungicidal activities in this study. Several derivatives electively exhibited fungicidal activities against some fungi. Especially, compound F5 exhibited higher fungicidal activity against Rhizoctonia solani (53.35%) than commercial antiviral agent validamycin (36.4%); compound F16 exhibited high fungicidal activity against Oospora citriaurantii ex Persoon (43.28%). Some of the alkaloids and their derivatives (compounds F4 and F25) exhibited broad-spectrum fungicidal activity. Specifically, compound F4 exhibited excellent high broad-spectrum fungicidal activity in vitro, and the curative and protection activities against P. litchi in vivo reached 92.59% and 59.26%, respectively. The new derivative, F4, with optimized physicochemical properties, obviously exhibited higher activities both in vitro and in vivo; therefore, F4 may be used as a new lead structure for the development of fungicidal drugs. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Qualitative and Quantitative Analysis of Major Triterpenoids in Alismatis Rhizoma by High Performance Liquid Chromatography/Diode-Array Detector/Quadrupole-Time-of-Flight Mass Spectrometry and Ultra-Performance Liquid Chromatography/Triple Quadrupole Mass Spectrometry
Molecules 2015, 20(8), 13958-13981; doi:10.3390/molecules200813958
Received: 30 June 2015 / Revised: 26 July 2015 / Accepted: 28 July 2015 / Published: 31 July 2015
Cited by 8 | PDF Full-text (2406 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Alismatis Rhizoma (AMR) is a well-known natural medicine with a long history in Chinese medicine and has been commonly used for treating a wide range of ailments related to dysuria, edema, nephropathy, hyperlipidaemia, diabetes, inflammation as well as tumors in clinical applications. Most
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Alismatis Rhizoma (AMR) is a well-known natural medicine with a long history in Chinese medicine and has been commonly used for treating a wide range of ailments related to dysuria, edema, nephropathy, hyperlipidaemia, diabetes, inflammation as well as tumors in clinical applications. Most beneficial effects of AMR are attributed to the presence of protostane terpenoids, the major active ingredients of Alismatis Rhizoma (AMR). In this study, a systematic high performance liquid chromatography/diode-array detector/quadrupole-time-of-flight mass spectrometry (HPLC-DAD-Q-TOF MS) and ultra-performance liquid chromatography/triple quadrupole mass spectrometry (UPLC-QqQ MS) method was developed for qualitative and quantitative analyses of the major AMR triterpenoids. First, a total of 25 triterpenoid components, including 24 known compounds and one new compound were identified by comparison with UV spectra, molecular ions and fragmentation behaviors of reference standards or the literature. Second, an efficient method was established for the rapid simultaneous determination of 14 representative triterpenoids by UPLC-QqQ MS. Forty-three batches of AMR were analyzed with linearity (r, 0.9980–0.9999), intra-day precision (RSD, 1.18%–3.79%), inter-day precision (RSD, 1.53%–3.96%), stability (RSD, 1.32%–3.97%), repeatability (RSD, 2.21%–4.25%), and recovery (98.11%–103.8%). These results indicated that new approaches combining HPLC-DAD-Q-TOF MS and UPLC-QqQ MS are applicable in the qualitative and quantitative analysis of AMR. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle New Rare Sinapoyl Acylated Flavonoid Glycosides Obtained from the Seeds of Lepidium apetalum Willd
Molecules 2015, 20(8), 13982-13996; doi:10.3390/molecules200813982
Received: 17 June 2015 / Accepted: 29 July 2015 / Published: 3 August 2015
Cited by 3 | PDF Full-text (260 KB) | HTML Full-text | XML Full-text
Abstract
Seven new rare sinapoyl acylated flavonoid glycosides, apetalumosides A1 (1), B8 (2), B9 (3), B10 (4), B11 (5), B12 (6), and C1 (7) were isolated from the seeds of Lepidium apetalum Willd. Their structures were elucidated by chemical and spectroscopic methods. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle A Database of Force-Field Parameters, Dynamics, and Properties of Antimicrobial Compounds
Molecules 2015, 20(8), 13997-14021; doi:10.3390/molecules200813997
Received: 11 June 2015 / Accepted: 28 July 2015 / Published: 3 August 2015
Cited by 11 | PDF Full-text (2521 KB) | HTML Full-text | XML Full-text
Abstract
We present an on-line database of all-atom force-field parameters and molecular properties of compounds with antimicrobial activity (mostly antibiotics and some beta-lactamase inhibitors). For each compound, we provide the General Amber Force Field parameters for the major species at physiological pH, together with
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We present an on-line database of all-atom force-field parameters and molecular properties of compounds with antimicrobial activity (mostly antibiotics and some beta-lactamase inhibitors). For each compound, we provide the General Amber Force Field parameters for the major species at physiological pH, together with an analysis of properties of interest as extracted from µs-long molecular dynamics simulations in explicit water solution. The properties include number and population of structural clusters, molecular flexibility, hydrophobic and hydrophilic molecular surfaces, the statistics of intraand inter-molecular H-bonds, as well as structural and dynamical properties of solvent molecules within first and second solvation shells. In addition, the database contains several key molecular parameters, such as energy of the frontier molecular orbitals, vibrational properties, rotational constants, atomic partial charges and electric dipole moment, computed by Density Functional Theory. The present database (to our knowledge the first extensive one including dynamical properties) is part of a wider project aiming to build-up a database containing structural, physico-chemical and dynamical properties of medicinal compounds using different force-field parameters with increasing level of complexity and reliability. The database is freely accessible at http://www.dsf.unica.it/translocation/db/. Full article
(This article belongs to the Special Issue Chemoinformatics)
Open AccessArticle Palladium-Catalyzed One-Pot Approach to 3-(Diarylmethylene)oxindoles from Propiolamidoaryl Triflate
Molecules 2015, 20(8), 14022-14032; doi:10.3390/molecules200814022
Received: 7 July 2015 / Revised: 29 July 2015 / Accepted: 31 July 2015 / Published: 3 August 2015
Cited by 1 | PDF Full-text (761 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
3-(Diarylmethylene)oxindoles have been synthesized from propiolamidoaryl triflate utilizing a palladium-catalyzed one-pot reaction consisting of three successive reactions: Sonogashira, Heck, and Suzuki-Miyaura. This method allows for the production of a complex skeleton of 3-(diarylmethylene)oxindole from propiolamidoaryl triflate using a commercially available aryl iodide and
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3-(Diarylmethylene)oxindoles have been synthesized from propiolamidoaryl triflate utilizing a palladium-catalyzed one-pot reaction consisting of three successive reactions: Sonogashira, Heck, and Suzuki-Miyaura. This method allows for the production of a complex skeleton of 3-(diarylmethylene)oxindole from propiolamidoaryl triflate using a commercially available aryl iodide and arylboronic acid in a simple and efficient way with moderate yield and stereoselectivity. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Comparative Immunogenicity of a Cytotoxic T Cell Epitope Delivered by Penetratin and TAT Cell Penetrating Peptides
Molecules 2015, 20(8), 14033-14050; doi:10.3390/molecules200814033
Received: 1 May 2015 / Revised: 16 July 2015 / Accepted: 29 July 2015 / Published: 3 August 2015
Cited by 5 | PDF Full-text (1355 KB) | HTML Full-text | XML Full-text
Abstract
Cell penetrating peptides (CPP), including the TAT peptide from the human immunodeficiency virus transactivator of transcription (HIV-TAT) protein and penetratin from Drosophila Antennapedia homeodomain protein, translocate various cargos including peptides and proteins across cellular barriers. This mode of delivery has been harnessed by
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Cell penetrating peptides (CPP), including the TAT peptide from the human immunodeficiency virus transactivator of transcription (HIV-TAT) protein and penetratin from Drosophila Antennapedia homeodomain protein, translocate various cargos including peptides and proteins across cellular barriers. This mode of delivery has been harnessed by our group and others to deliver antigenic proteins or peptides into the cytoplasm of antigen processing cells (APC) such as monocyte-derived dendritic cells (MoDC). Antigens or T cell epitopes delivered by CPP into APC in vivo generate antigen-specific cytotoxic T cell and helper T cell responses in mice. Furthermore, mice immunised with these peptides or proteins are protected from a tumour challenge. The functional properties of CPP are dependent on the various cargos being delivered and the target cell type. Despite several studies demonstrating superior immunogenicity of TAT and Antp-based immunogens, none has compared the immunogenicity of antigens delivered by TAT and Antp CPP. In the current study we demonstrate that a cytotoxic T cell epitope from the mucin 1 (MUC1) tumour associated antigen, when delivered by TAT or Antp, generates identical immune responses in mice resulting in specific MUC1 T cell responses as measured by in vivo CTL assays, IFNγ ELISpot assays and prophylactic tumour protection. Full article
(This article belongs to the Special Issue Cell Penetrating Peptides (CPPs))
Open AccessArticle Mosquitocidal and Oviposition Repellent Activities of the Extracts of Seaweed Bryopsis pennata on Aedes aegypti and Aedes albopictus
Molecules 2015, 20(8), 14082-14102; doi:10.3390/molecules200814082
Received: 16 June 2015 / Revised: 28 July 2015 / Accepted: 29 July 2015 / Published: 4 August 2015
Cited by 4 | PDF Full-text (2167 KB) | HTML Full-text | XML Full-text
Abstract
The ever-increasing threat from infectious diseases and the development of insecticide resistance in mosquito populations drive the global search for new natural insecticides. The aims of this study were to evaluate the mosquitocidal activity of the extracts of seaweed Bryopsis pennata against dengue
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The ever-increasing threat from infectious diseases and the development of insecticide resistance in mosquito populations drive the global search for new natural insecticides. The aims of this study were to evaluate the mosquitocidal activity of the extracts of seaweed Bryopsis pennata against dengue vectors Aedes aegypti and Aedes albopictus, and determine the seaweed’s toxic effect on brine shrimp nauplii (as a non-target organism). In addition, the chemical compositions of the active larvicidal extract and fraction were analyzed by using liquid chromatography-mass spectrometry (LC-MS). Chloroform extract exhibited strong ovicidal activity (with LC50 values of 229.3 and 250.5 µg/mL) and larvicidal activity against Ae. aegypti and Ae. albopictus. The larvicidal potential of chloroform extract was further ascertained when its A7 fraction exhibited strong toxic effect against Ae. aegypti (LC50 = 4.7 µg/mL) and Ae. albopictus (LC50 = 5.3 µg/mL). LC-MS analysis of the chloroform extract gave a tentative identification of 13 compounds; Bis-(3-oxoundecyl) tetrasulfide was identified as the major compound in A7 fraction. Methanol extract showed strong repellent effect against female oviposition, along with weak adulticidal activity against mosquito and weak toxicity against brine shrimp nauplii. The mosquitocidal results of B. pennata suggest further investigation for the development of effective insecticide. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle The Efficacy and Underlying Mechanism of Sulfone Derivatives Containing 1,3,4-oxadiazole on Citrus Canker
Molecules 2015, 20(8), 14103-14117; doi:10.3390/molecules200814103
Received: 4 June 2015 / Revised: 14 July 2015 / Accepted: 29 July 2015 / Published: 4 August 2015
Cited by 2 | PDF Full-text (1192 KB) | HTML Full-text | XML Full-text
Abstract
The objectives of the current study were to isolate and identify the pathogen responsible for citrus canker and investigate the efficacy of sulfone derivatives containing 1,3,4-oxadiazole moiety on controlling citrus canker caused by Xanthomonas citri subsp. citri (Xcc) under in
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The objectives of the current study were to isolate and identify the pathogen responsible for citrus canker and investigate the efficacy of sulfone derivatives containing 1,3,4-oxadiazole moiety on controlling citrus canker caused by Xanthomonas citri subsp. citri (Xcc) under in vitro and field conditions. In an in vitro study, we tested eight sulfone derivatives against Xcc and the results demonstrated that compound 3 exhibited the best antibacterial activity against Xcc, with a half-maximal effective concentration (EC50) value of 1.23 μg/mL, which was even better than those of commercial bactericides Kocide 3000 (58.21 μg/mL) and Thiodiazole copper (77.04 μg/mL), respectively. Meanwhile, under field experiments, compound 3 treatments demonstrated the highest ability to reduce the disease of citrus canker in leaves and fruits in two different places relative to an untreated control as well as the commercial bactericides Kocide 3000 and Thiodiazole copper. Meanwhile, compound 3 could stimulate the increase in peroxidase (POD), polyphenol oxidase (PPO), and phenylalanine ammonia lyase (PAL) activities in the navel orange leaves, causing marked enhancement of plant resistance against citrus canker. Moreover, compound 3 could damage the cell membranes, destruct the biofilm formation, inhibit the production of extracellular polysaccharide (EPS), and affect the cell membrane permeability to restrain the growth of the bacteria. Full article
Open AccessArticle Search for Antiprotozoal Activity in Herbal Medicinal Preparations; New Natural Leads against Neglected Tropical Diseases
Molecules 2015, 20(8), 14118-14138; doi:10.3390/molecules200814118
Received: 27 June 2015 / Revised: 21 July 2015 / Accepted: 28 July 2015 / Published: 4 August 2015
Cited by 3 | PDF Full-text (525 KB) | HTML Full-text | XML Full-text
Abstract
Sleeping sickness, Chagas disease, Leishmaniasis, and Malaria are infectious diseases caused by unicellular eukaryotic parasites (“protozoans”). The three first mentioned are classified as Neglected Tropical Diseases (NTDs) by the World Health Organization and together threaten more than one billion lives worldwide. Due to
[...] Read more.
Sleeping sickness, Chagas disease, Leishmaniasis, and Malaria are infectious diseases caused by unicellular eukaryotic parasites (“protozoans”). The three first mentioned are classified as Neglected Tropical Diseases (NTDs) by the World Health Organization and together threaten more than one billion lives worldwide. Due to the lack of research interest and the high increase of resistance against the existing treatments, the search for effective and safe new therapies is urgently required. In view of the large tradition of natural products as sources against infectious diseases [1,2], the aim of the present study is to investigate the potential of legally approved and marketed herbal medicinal products (HMPs) as antiprotozoal agents. Fifty-eight extracts from 53 HMPs on the German market were tested by a Multiple-Target-Screening (MTS) against parasites of the genera Leishmania, Trypanosoma, and Plasmodium. Sixteen HMPs showed in vitro activity against at least one of the pathogens (IC50 < 10 µg/mL). Six extracts from preparations of Salvia, Valeriana, Hypericum, Silybum, Arnica, and Curcuma exhibited high activity (IC50 < 2.5 µg/mL). They were analytically characterized by UHPLC/ESI-QqTOF-MSMS and the activity-guided fractionation of the extracts with the aim to isolate and identify the active compounds is in progress. Full article
Open AccessCommunication Synthesis and Herbicidal Activity of New Hydrazide and Hydrazonoyl Derivatives
Molecules 2015, 20(8), 14139-14154; doi:10.3390/molecules200814139
Received: 18 June 2015 / Revised: 30 July 2015 / Accepted: 31 July 2015 / Published: 4 August 2015
Cited by 2 | PDF Full-text (1044 KB) | HTML Full-text | XML Full-text
Abstract
Three new hydrazide and five new hydrazonoyl derivatives were synthesized. The chemical structures of these compounds were confirmed by 1H-NMR, IR spectroscopy and elemental analysis. The prepared compounds were tested for their activity to inhibit photosynthetic electron transport in spinach chloroplasts and
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Three new hydrazide and five new hydrazonoyl derivatives were synthesized. The chemical structures of these compounds were confirmed by 1H-NMR, IR spectroscopy and elemental analysis. The prepared compounds were tested for their activity to inhibit photosynthetic electron transport in spinach chloroplasts and growth of the green algae Chlorella vulgaris. IC50 values of these compounds varied in wide range, from a strong to no inhibitory effect. EPR spectroscopy showed that the active compounds interfered with intermediates Z/D, which are localized on the donor side of photosystem II. Fluorescence spectroscopy suggested that the mechanism of inhibitory action of the prepared compounds possibly involves interactions with aromatic amino acids present in photosynthetic proteins. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synthesis of Radiation Curable Palm Oil–Based Epoxy Acrylate: NMR and FTIR Spectroscopic Investigations
Molecules 2015, 20(8), 14191-14211; doi:10.3390/molecules200814191
Received: 3 September 2014 / Revised: 12 January 2015 / Accepted: 29 January 2015 / Published: 4 August 2015
Cited by 9 | PDF Full-text (1521 KB) | HTML Full-text | XML Full-text
Abstract
Over the past few decades, there has been an increasing demand for bio-based polymers and resins in industrial applications, due to their potential lower cost and environmental impact compared with petroleum-based counterparts. The present research concerns the synthesis of epoxidized palm oil acrylate
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Over the past few decades, there has been an increasing demand for bio-based polymers and resins in industrial applications, due to their potential lower cost and environmental impact compared with petroleum-based counterparts. The present research concerns the synthesis of epoxidized palm oil acrylate (EPOLA) from an epoxidized palm oil product (EPOP) as environmentally friendly material. EPOP was acrylated by acrylic acid via a ring opening reaction. The kinetics of the acrylation reaction were monitored throughout the reaction course and the acid value of the reaction mixture reached 10 mg KOH/g after 16 h, indicating the consumption of the acrylic acid. The obtained epoxy acrylate was investigated intensively by means of FTIR and NMR spectroscopy, and the results revealed that the ring opening reaction was completed successfully with an acrylation yield about 82%. The UV free radical polymerization of EPOLA was carried out using two types of photoinitiators. The radiation curing behavior was determined by following the conversion of the acrylate groups. The cross-linking density and the hardness of the cured EPOLA films were measured to evaluate the effect of the photoinitiator on the solid film characteristics, besides, the thermal and mechanical properties were also evaluated. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Isolation, Characterization, Crystal Structure Elucidation of Two Flavanones and Simultaneous RP-HPLC Determination of Five Major Compounds from Syzygium campanulatum Korth
Molecules 2015, 20(8), 14212-14233; doi:10.3390/molecules200814212
Received: 24 May 2015 / Accepted: 6 July 2015 / Published: 4 August 2015
Cited by 3 | PDF Full-text (4980 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two flavanones named (2S)-7-Hydroxy-5-methoxy-6,8-dimethyl flavanone (1), (S)-5,7-dihydroxy-6,8-dimethyl-flavanone (2), along with known chalcone, namely, (E)-2ʹ,4ʹ- dihydroxy-6ʹ-methoxy-3ʹ,5ʹ-dimethylchalcone (3) and two triterpenoids, namely, betulinic and ursolic acids (4 and 5), were isolated from the leaves of Syzygium campanulatum Korth (Myrtaceae). The structures of compounds (1 and
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Two flavanones named (2S)-7-Hydroxy-5-methoxy-6,8-dimethyl flavanone (1), (S)-5,7-dihydroxy-6,8-dimethyl-flavanone (2), along with known chalcone, namely, (E)-2ʹ,4ʹ- dihydroxy-6ʹ-methoxy-3ʹ,5ʹ-dimethylchalcone (3) and two triterpenoids, namely, betulinic and ursolic acids (4 and 5), were isolated from the leaves of Syzygium campanulatum Korth (Myrtaceae). The structures of compounds (1 and 2) were determined on the basis of UV-visible, FTIR, NMR spectroscopies and LC-EIMS analytical techniques. Furthermore, new, simple, precise, selective, accurate, highly sensitive, efficient and reproducible RP-HPLC method was developed and validated for the quantitative analysis of the compounds (1–5) from S. campanulatum plants of five different age. RP-HPLC method was validated in terms of specificity, linearity (r2 ≤ 0.999), precision (2.0% RSD), and recoveries (94.4%–105%). The LOD and LOQ of these compounds ranged from 0.13–0.38 and 0.10–2.23 μg·mL−1, OPEN ACCESS respectively. Anti-proliferative activity of isolated flavanones (1 and 2) and standardized extract of S. campanulatum was evaluated on human colon cancer (HCT 116) cell line. Compounds (1 and 2) and extract revealed potent and dose-dependent activity with IC50 67.6, 132.9 and 93.4 μg·mL−1, respectively. To the best of our knowledge, this is the first study on isolation, characterization, X-ray crystallographic analysis of compounds (1 and 2) and simultaneous RP-HPLC determination of five major compounds (1–5) from different age of S. campanulatum plants. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle An Unusual Carbohydrate Conformation is Evident in Moraxella catarrhalis Oligosaccharides
Molecules 2015, 20(8), 14234-14253; doi:10.3390/molecules200814234
Received: 23 May 2015 / Revised: 24 July 2015 / Accepted: 27 July 2015 / Published: 5 August 2015
Cited by 3 | PDF Full-text (3093 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Oligosaccharide structures derived from the lipooligosaccharide of M. catarrhalis show that the highly branched glucose-rich inner core of the oligosaccharide has an altered conformation compared to the most truncated tetra-glucose-Kdo lgt1/4Δ oligosaccharide structure. Addition of one residue each to the (1-4) and (1-6)
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Oligosaccharide structures derived from the lipooligosaccharide of M. catarrhalis show that the highly branched glucose-rich inner core of the oligosaccharide has an altered conformation compared to the most truncated tetra-glucose-Kdo lgt1/4Δ oligosaccharide structure. Addition of one residue each to the (1-4) and (1-6) chains to give the lgt2Δ oligosaccharide is the minimum requirement for this conformational change to occur. Extensive molecular modeling and NMR investigations have shown that the (1-3), (1-4), and (1-6) glycosidic linkages from the central α-D-Glcp have significantly altered conformational preferences between the two structures. For the lgt1/4Δ oligosaccharide the (1-3) and (1-4) linkage populates predominantly the syn minimum on the conformational free energy map and for the (1-6) linkage conformational flexibility is observed, which is supported by 1H-NMR T1 measurements. For the lgt2Δ oligosaccharide the unusual “(1-4)anti-ψ(1-6)gg” conformation, which could be confirmed by long-range NOE signals, is a dominant conformation in which the oligosaccharide is very compact with the terminal α-D-GlcNAc residue folding back towards the center of the molecule leading to an extensive intra-molecular hydrophobic interaction between the terminal residues. Comparing effective H-H distances, which were calculated for conformational sub-ensembles, with the NOE distances revealed that typically multiple conformations could be present without significantly violating the measured NOE restraints. For lgt2Δ the presence of more than one conformation is supported by the NOE data. Full article
(This article belongs to the collection Advances in Carbohydrate Chemistry)
Open AccessArticle Protective Effect of 2,4′,5′-Trihydroxyl-5,2′-dibromo diphenylmethanone, a New Halophenol, against Hydrogen Peroxide-Induced EA.hy926 Cells Injury
Molecules 2015, 20(8), 14254-14264; doi:10.3390/molecules200814254
Received: 6 June 2015 / Revised: 24 July 2015 / Accepted: 29 July 2015 / Published: 5 August 2015
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Abstract
Vascular endothelial cells produce reactive oxygen species (ROS) during the process of energy metabolism in aerobic respiration. A growing body of evidence indicates that excessive ROS is implicated in the pathogenesis of cardiovascular diseases including atherosclerosis. The newly synthesized halophenol, 2,4′,5′-trihydroxyl-5,2′-dibromo diphenylmethanone (TDD),
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Vascular endothelial cells produce reactive oxygen species (ROS) during the process of energy metabolism in aerobic respiration. A growing body of evidence indicates that excessive ROS is implicated in the pathogenesis of cardiovascular diseases including atherosclerosis. The newly synthesized halophenol, 2,4′,5′-trihydroxyl-5,2′-dibromo diphenylmethanone (TDD), exhibits antioxidative and cytoprotective activities in vitro. In this study, the protective effect of TDD against hydrogen peroxide (H2O2)-induced oxidative injury of EA.hy926 cells was investigated. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyltetrazolium bromide (MTT) assay, while the effect of TDD on the transcription profile of EA.hy926 cells subjected to H2O2-induced oxidative injury was evaluated by microarray analysis. Several signaling pathways, including apoptosis, were significantly associated with TDD. Flow cytometric analysis was used to evaluate anti-apoptotic effect of TDD. Subsequently, RT-PCR and Western blot were used to detect the expressions of the apoptosis-associated protein, Bcl-2 and Bax. Meanwhile the expression of cleaved caspase-3, an executioner of apoptosis, was also detected by Western blot. The results showed that pretreatment of EA.hy926 cells with TDD prevented the decrease of cell viability induced by H2O2, and attenuated H2O2-induced elevation of Bax and cleaved caspase-3 while increased Bcl-2 expressions. In summary, TDD inhibited H2O2-induced oxidative injury of EA.hy926 cells through negative regulation of apoptosis. These findings suggest that TDD is a potential candidate for therapeutic intervention in oxidative stress-associated cardiovascular diseases. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle The Stability, Sustained Release and Cellular Antioxidant Activity of Curcumin Nanoliposomes
Molecules 2015, 20(8), 14293-14311; doi:10.3390/molecules200814293
Received: 9 June 2015 / Revised: 18 July 2015 / Accepted: 22 July 2015 / Published: 5 August 2015
Cited by 19 | PDF Full-text (3214 KB) | HTML Full-text | XML Full-text
Abstract
Curcumin is a multifunctional and natural agent considered to be pharmacologically safe. However, its application in the food and medical industry is greatly limited by its poor water solubility, physicochemical instability and inadequate bioavailability. Nanoliposome encapsulation could significantly enhance the solubility and stability
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Curcumin is a multifunctional and natural agent considered to be pharmacologically safe. However, its application in the food and medical industry is greatly limited by its poor water solubility, physicochemical instability and inadequate bioavailability. Nanoliposome encapsulation could significantly enhance the solubility and stability of curcumin. Curcumin nanoliposomes exhibited good physicochemical properties (entrapment efficiency = 57.1, particle size = 68.1 nm, polydispersity index = 0.246, and zeta potential = −3.16 mV). Compared with free curcumin, curcumin nanoliposomes exhibited good stability against alkaline pH and metal ions as well as good storage stability at 4 °C. Curcumin nanoliposomes also showed good sustained release properties. Compared with free curcumin, curcumin nanoliposomes presented an equal cellular antioxidant activity, which is mainly attributed to its lower cellular uptake as detected by fluorescence microscopy and flow cytometry. This study provide theoretical and practical guides for the further application of curcumin nanoliposomes. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Removal of 4-Ethylphenol and 4-Ethylguaiacol with Polyaniline-Based Compounds in Wine-Like Model Solutions and Red Wine
Molecules 2015, 20(8), 14312-14325; doi:10.3390/molecules200814312
Received: 9 April 2015 / Revised: 17 July 2015 / Accepted: 27 July 2015 / Published: 5 August 2015
Cited by 1 | PDF Full-text (1715 KB) | HTML Full-text | XML Full-text
Abstract
Volatile phenols, such as 4-ethyphenol (4-EP) and 4-ethylguaiacol (4-EG), are responsible for the “Brett character” found in wines contaminated with Brettanomyces yeast (i.e., barnyard, animal, spicy and smoky aromas). In these trials, we explore the effectiveness of polyaniline-based compounds (polyaniline emeraldin
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Volatile phenols, such as 4-ethyphenol (4-EP) and 4-ethylguaiacol (4-EG), are responsible for the “Brett character” found in wines contaminated with Brettanomyces yeast (i.e., barnyard, animal, spicy and smoky aromas). In these trials, we explore the effectiveness of polyaniline-based compounds (polyaniline emeraldin salt (PANI-ES) and polyanaline emeraldin base (PANI-EB)), for the removal of 4-EP and 4-EG from acidic model solutions and red wine. First, a screening study, performed in an acidified 12% ethanol solution, was used to optimize parameters such as contact time and the amount of polymers required to remove 4-EP and 4-EG. Then, the trapping ability of PANI agents towards 4-EP and 4-EG was evaluated in a model solution containing other wine phenolics that could potentially be trapped by PANI (i.e., gallic acid and 4-methylcatechol). The results of this trial showed that both PANI compounds were capable of removing 4-EP, 4-EG, regardless of the presence of other phenolic compounds present at a much higher concentration. Finally, the capturing ability of PANI was evaluated in a red wine sample containing 5 mg·L−1 of 4-EP, 5 mg·L−1 of 4-EG and 2.03 ± 0.02 g·L−1 of total phenolics. The results showed that PANI-EB removed significantly more 4-EP and 4-EG than PANI-ES. For instance, a treatment with 10 mg·mL−1 of PANI-EB produced a 67.8% reduction of 4-EP, 50% reduction of 4-EG and 41.38% decrease in total phenols. Full article
(This article belongs to the collection Wine Chemistry)
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Open AccessArticle New Polyprenylated Phloroglucinol and Other Compounds Isolated from the Fruits of Clusia nemorosa (Clusiaceae)
Molecules 2015, 20(8), 14326-14333; doi:10.3390/molecules200814326
Received: 21 May 2015 / Revised: 27 June 2015 / Accepted: 22 July 2015 / Published: 6 August 2015
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Abstract
Clusia nemorosa has been widely used in folk medicine to treat various ailments, including headaches and inflammation. Investigation of the fruits of Clusia nemorosa (Clusiaceae) led to the isolation and characterization of a new phloroglucinol derivative, named 6S,8S,28S
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Clusia nemorosa has been widely used in folk medicine to treat various ailments, including headaches and inflammation. Investigation of the fruits of Clusia nemorosa (Clusiaceae) led to the isolation and characterization of a new phloroglucinol derivative, named 6S,8S,28S-nemorosic acid (1), together with seven known compounds: friedelin (2), β-sitosterol (3), stigmasterol (4), β-sitosterol glycoside (5), kaempferol (6), quercetin (7) and dimethyl citrate (8). The structures were determined by extensive 1D- and 2D-NMR, CD and MS spectroscopic analyses. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Mimosine Dipeptide Enantiomsers: Improved Inhibitors against Melanogenesis and Cyclooxygenase
Molecules 2015, 20(8), 14334-14347; doi:10.3390/molecules200814334
Received: 9 July 2015 / Revised: 31 July 2015 / Accepted: 3 August 2015 / Published: 6 August 2015
Cited by 4 | PDF Full-text (770 KB) | HTML Full-text | XML Full-text
Abstract
Melanogenesis plays an important role in the protection of skin against UV through production of melanin pigments, but abnormal accumulation of this pigment causes unaesthetic hyperpigmentation. Much effort is being made to develop effective depigmenting agents. Here, we show for the first time
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Melanogenesis plays an important role in the protection of skin against UV through production of melanin pigments, but abnormal accumulation of this pigment causes unaesthetic hyperpigmentation. Much effort is being made to develop effective depigmenting agents. Here, we show for the first time that a small library of mimosine dipeptide enantiomers (Mi-L/D-amino acid) inhibit the melanogenesis in B16F10 melanoma cells by down-regulating the cellular tyrosinase with little effect on their growth or viability. Two of them, Mi-D-Trp and Mi-D-Val, turned out to be the most potent inhibitors on melanin content and cellular tyrosinase in B16F10 melanoma cells. In addition, most of the mimosine dipeptides were more potent than mimosine for inhibiting cyclooxygenase 1 (COX-1) with IC50 of 18–26 μM. Among them, Mi-L-Val and Mi-L-Trp inhibited cyclooxygenase 2 (COX-2) more potently than indomethacin, with IC50 values of 22 and 19 μM, respectively. Taken together, our results suggest the possibility that mimosine dipeptides could be better candidates (than mimosine) for anti-melanogenic (skin hyperpigmentation treatment) and cyclooxygenase (COX) inhibition. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Macrophage Activation by Ursolic and Oleanolic Acids during Mycobacterial Infection
Molecules 2015, 20(8), 14348-14364; doi:10.3390/molecules200814348
Received: 25 April 2015 / Revised: 30 July 2015 / Accepted: 31 July 2015 / Published: 6 August 2015
Cited by 8 | PDF Full-text (1424 KB) | HTML Full-text | XML Full-text
Abstract
Oleanolic (OA) and ursolic acids (UA) are triterpenes that are abundant in vegetables, fruits and medicinal plants. They have been described as active moieties in medicinal plants used for the treatment of tuberculosis. In this study, we analyzed the effects of these triterpenes
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Oleanolic (OA) and ursolic acids (UA) are triterpenes that are abundant in vegetables, fruits and medicinal plants. They have been described as active moieties in medicinal plants used for the treatment of tuberculosis. In this study, we analyzed the effects of these triterpenes on macrophages infected in vitro with Mycobacterium tuberculosis (MTB). We evaluated production of nitric oxide (NO), reactive oxygen species (ROS), and cytokines (TNF-α and TGF-β) as well as expression of cell membrane receptors (TGR5 and CD36) in MTB-infected macrophages following treatment with OA and UA. Triterpenes caused reduced MTB growth in macrophages, stimulated production of NO and ROS in the early phase, stimulated TNF-α, suppressed TGF-β and caused over-expression of CD36and TGR5 receptors. Thus, our data suggest immunomodulatory properties of OA and UA on MTB infected macrophages. In conclusion, antimycobacterial effects induced by these triterpenes may be attributable to the conversion of macrophages from stage M2 (alternatively activated) to M1 (classically activated). Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Stable Hemiaminals: 2-Aminopyrimidine Derivatives
Molecules 2015, 20(8), 14365-14376; doi:10.3390/molecules200814365
Received: 9 July 2015 / Revised: 20 July 2015 / Accepted: 21 July 2015 / Published: 6 August 2015
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Abstract
Stable hemiaminals can be obtained in the one-pot reaction between 2-aminopyrimidine and nitrobenzaldehyde derivatives. Ten new hemiaminals have been obtained, six of them in crystal state. The molecular stability of these intermediates results from the presence of both electron-withdrawing nitro groups as substituents
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Stable hemiaminals can be obtained in the one-pot reaction between 2-aminopyrimidine and nitrobenzaldehyde derivatives. Ten new hemiaminals have been obtained, six of them in crystal state. The molecular stability of these intermediates results from the presence of both electron-withdrawing nitro groups as substituents on the phenyl ring and pyrimidine ring, so no further stabilisation by intramolecular interaction is required. Hemiaminal molecules possess a tetrahedral carbon atom constituting a stereogenic centre. As the result of crystallisation in centrosymmetric space groups both enantiomers are present in the crystal structure. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Pheonolic Compounds from the Fruits of Viburnum sargentii Koehne
Molecules 2015, 20(8), 14377-14385; doi:10.3390/molecules200814377
Received: 10 June 2015 / Accepted: 3 August 2015 / Published: 6 August 2015
Cited by 4 | PDF Full-text (714 KB) | HTML Full-text | XML Full-text
Abstract
Seven phenolic compounds were isolated from the fruits of Viburnum sargentii Koehne by silica gel column chromatography and preparative HPLC. On the grounds of chemical and spectroscopic methods, their structures were identified as (−)-Epicatechin (1), 5,7,4′-trihydroxy-flavonoid-8-C-β-D-glucopyranoside (2),
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Seven phenolic compounds were isolated from the fruits of Viburnum sargentii Koehne by silica gel column chromatography and preparative HPLC. On the grounds of chemical and spectroscopic methods, their structures were identified as (−)-Epicatechin (1), 5,7,4′-trihydroxy-flavonoid-8-C-β-D-glucopyranoside (2), 1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-α-L-rhamnopyranoxypropyl)-2-methoxyphenoxy]-1,3-propane-diol (erythro) (3), 1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-α-L-rhamnopyranoxypropyl)-2-methoxyphenoxy]-1,3-propanediol (threo) (4), (R)-4-hydroxylphenol O-(6-O-oleuropeoyl)-β-D-glucopyranoside (5), (R)-3-methoxy-4-hydroxylphenol O-(6-O-oleuropeoyl)-β-D-glucopyranoside (6), quercetin-3-O-rutinoside (7). Compounds 5 and 6 are new monoterpene phenolic glycosides, compounds 1, 3 and 4 were isolated from the Viburnum genus for the first time, and compounds 2 and 7 from the Viburnum sargentii Koehne for the first time. Compounds 17 were also assayed for their antioxidant activities with DPPH free radicals. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synergy of Cobalt and Silver Microparticles Electrodeposited on Glassy Carbon for the Electrocatalysis of the Oxygen Reduction Reaction: An Electrochemical Investigation
Molecules 2015, 20(8), 14386-14401; doi:10.3390/molecules200814386
Received: 8 May 2015 / Revised: 23 July 2015 / Accepted: 4 August 2015 / Published: 7 August 2015
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Abstract
The combination of two different metals, each of them acting on different steps of the oxygen reduction reaction (ORR), yields synergic catalytic effects. In this respect, the electrocatalytic effect of silver is enhanced by the addition of cobalt, which is able to break
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The combination of two different metals, each of them acting on different steps of the oxygen reduction reaction (ORR), yields synergic catalytic effects. In this respect, the electrocatalytic effect of silver is enhanced by the addition of cobalt, which is able to break the O–O bond of molecular oxygen, thus accelerating the first step of the reduction mechanism. At the same time, research is to further reduce the catalyst’s cost, reducing the amount of Ag, which, even though being much less expensive than Pt, is still a noble metal. From this point of view, using a small amount of Ag together with an inexpensive material, such as graphite, represents a good compromise. The aim of this work was to verify if the synergic effects are still operating when very small amounts of cobalt (2–10 μg·cm−2) are added to the microparticles of silver electrodeposited on glassy carbon, described in a preceding paper from us. To better stress the different behaviour observed when cobalt and silver are contemporarily present in the deposit, the catalytic properties of cobalt alone were investigated. The analysis was completed by the Levich plots to evaluate the number of electrons involved and by Tafel plots to show the effects on the reaction mechanism. Full article
(This article belongs to the Special Issue Metal Nanocatalysts in Green Synthesis and Energy Applications)
Open AccessArticle Mentha spicata Essential Oil: Chemical Composition, Antioxidant and Antibacterial Activities against Planktonic and Biofilm Cultures of Vibrio spp. Strains
Molecules 2015, 20(8), 14402-14424; doi:10.3390/molecules200814402
Received: 12 May 2015 / Revised: 12 May 2015 / Accepted: 3 August 2015 / Published: 7 August 2015
Cited by 15 | PDF Full-text (1711 KB) | HTML Full-text | XML Full-text
Abstract
Chemical composition, antioxidant and anti-Vibrio spp. activities of the essential oil isolated from the aerial parts of Mentha spicata L. (spearmint) are investigated in the present study. The effect of the essential oil on Vibrio spp. biofilm inhibition and eradication was tested
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Chemical composition, antioxidant and anti-Vibrio spp. activities of the essential oil isolated from the aerial parts of Mentha spicata L. (spearmint) are investigated in the present study. The effect of the essential oil on Vibrio spp. biofilm inhibition and eradication was tested using the XTT assay. A total of 63 chemical constituents were identified in spearmint oil using GC/MS, constituting 99.9% of the total identified compounds. The main components were carvone (40.8% ± 1.23%) and limonene (20.8% ± 1.12%). The antimicrobial activity against 30 Vibrio spp. strains (16 species) was evaluated by disc diffusion and microdilution assays. All microorganisms were strongly affected, indicating an appreciable antimicrobial potential of the oil. Moreover, the investigated oil exhibited high antioxidant potency, as assessed by four different tests in comparison with BHT. The ability of the oil, belonging to the carvone chemotype, to inhibit or reduce Vibrio spp. biofilm warrants further investigation to explore the use of natural products in antibiofilm adhesion and reinforce the possibility of its use in the pharmaceutical or food industry as a natural antibiotic and seafood preservative against Vibrio contamination. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Management of Hyperglycaemia by Ethyl Acetate Extract of Balanites aegyptiaca (Desert Date)
Molecules 2015, 20(8), 14425-14434; doi:10.3390/molecules200814425
Received: 29 June 2015 / Revised: 4 August 2015 / Accepted: 5 August 2015 / Published: 7 August 2015
Cited by 3 | PDF Full-text (726 KB) | HTML Full-text | XML Full-text
Abstract
Reactive oxygen species play a significant role in the pathogenesis of retinopathy in diabetes patients. The current study aimed to assess the effect of ethyl acetate extract (EAE) from Balanites aegyptiaca (10, 25 or 50 mg/kg b.w.) in experimental diabetic rats. To achieve
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Reactive oxygen species play a significant role in the pathogenesis of retinopathy in diabetes patients. The current study aimed to assess the effect of ethyl acetate extract (EAE) from Balanites aegyptiaca (10, 25 or 50 mg/kg b.w.) in experimental diabetic rats. To achieve this aim, five groups of male rats were included: control, diabetic, and diabetic rats treated with 10, 25, and 50 µg/kg b.w. of EAE for eight weeks. Our results suggests a protective role of EAE against oxidative stress induced by streptozocine. EAE treatment produced a reduction in blood glucose levels, HbA1c, malondialdehyde and vascular endothelial growth factor (VEGF) in diabetic retina (p < 0.001), as well as an enhancement in antioxidant capacity against streptozocine-induced oxidative stress. Tumor necrosis factor alpha (TNF-α), interleukin (IL-1β) and vascular endothelial growth factor (VEGF) were significantly reduced in diabetic rats treated with EAE, compared with untreated diabetic rats. Analysis of EAE by GC-MS indicated the presence of β-sistosterol. Overall, EAE modulates oxidative stress induced by streptozocine and enhances antioxidant activity, which may provide additional endothelial protection in retina of diabetic rats. These results hold great promise in the management of diabetic complications. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Molecular Structures of the Products of a Diphosphonate Ester Building Block with Lewis Bases
Molecules 2015, 20(8), 14435-14450; doi:10.3390/molecules200814435
Received: 29 December 2014 / Revised: 18 June 2015 / Accepted: 23 June 2015 / Published: 7 August 2015
Cited by 1 | PDF Full-text (2410 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
By treating a suitable Wittig reagent under acid conditions, the phosphonate ester 1,4-bimethylenebenzene phosphonate ethyl ester (H2[BBPE], 1) was obtained. As a building block, compound 1 has been reacted with the Lewis-base N,N-dimethylpiperazine, ammonia and NaOH yielded compounds 2
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By treating a suitable Wittig reagent under acid conditions, the phosphonate ester 1,4-bimethylenebenzene phosphonate ethyl ester (H2[BBPE], 1) was obtained. As a building block, compound 1 has been reacted with the Lewis-base N,N-dimethylpiperazine, ammonia and NaOH yielded compounds 24. The crystal structures show that a 1D chain forming a tubular channel is constructed through hydrogen bonds in 1; hydrogen bonds form two 1D chains with left-hand and right-hand helixes and form 3D networks in compound 2; 1D hydrogen-bond chains are further connected together to afford a 3D network architecture in compound 3; the phosphonate is coordinated by two Na atoms which present different coordination environments in compound 4. Additionally, the relationships between the structure and fluorescence of the four compounds in the solid state and in different solvents have also been studied at room temperature. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Anti-Inflammatory Activity of Heterocarpin from the Salt Marsh Plant Corydalis heterocarpa in LPS-Induced RAW 264.7 Macrophage Cells
Molecules 2015, 20(8), 14474-14486; doi:10.3390/molecules200814474
Received: 11 June 2015 / Revised: 14 July 2015 / Accepted: 30 July 2015 / Published: 10 August 2015
Cited by 3 | PDF Full-text (1198 KB) | HTML Full-text | XML Full-text
Abstract
The inhibitory effect of three chromones 13 and two coumarins 45 on the production of nitric oxide (NO) was evaluated in LPS-induced RAW 264.7 macrophage cells. Among the compounds tested heterocarpin (1), a furochromone, significantly inhibited its
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The inhibitory effect of three chromones 13 and two coumarins 45 on the production of nitric oxide (NO) was evaluated in LPS-induced RAW 264.7 macrophage cells. Among the compounds tested heterocarpin (1), a furochromone, significantly inhibited its production in a dose-dependent manner. In addition, heterocarpin suppressed prostaglandin E2 (PGE2) production and expression of cytokines such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Neuroprotective Effects of Mitochondria-Targeted Plastoquinone and Thymoquinone in a Rat Model of Brain Ischemia/Reperfusion Injury
Molecules 2015, 20(8), 14487-14503; doi:10.3390/molecules200814487
Received: 1 July 2015 / Revised: 3 August 2015 / Accepted: 5 August 2015 / Published: 11 August 2015
Cited by 18 | PDF Full-text (5503 KB) | HTML Full-text | XML Full-text
Abstract
We explored the neuroprotective properties of natural plant-derived antioxidants plastoquinone and thymoquinone (2-demethylplastoquinone derivative) modified to be specifically accumulated in mitochondria. The modification was performed through chemical conjugation of the quinones with penetrating cations: Rhodamine 19 or tetraphenylphosphonium. Neuroprotective properties were evaluated in
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We explored the neuroprotective properties of natural plant-derived antioxidants plastoquinone and thymoquinone (2-demethylplastoquinone derivative) modified to be specifically accumulated in mitochondria. The modification was performed through chemical conjugation of the quinones with penetrating cations: Rhodamine 19 or tetraphenylphosphonium. Neuroprotective properties were evaluated in a model of middle cerebral artery occlusion. We demonstrate that the mitochondria-targeted compounds, introduced immediately after reperfusion, possess various neuroprotective potencies as judged by the lower brain damage and higher neurological status. Plastoquinone derivatives conjugated with rhodamine were the most efficient, and the least efficiency was shown by antioxidants conjugated with tetraphenylphosphonium. Antioxidants were administered intraperitoneally or intranasally with the latter demonstrating a high level of penetration into the brain tissue. The therapeutic effects of both ways of administration were similar. Long-term administration of antioxidants in low doses reduced the neurological deficit, but had no effect on the volume of brain damage. At present, cationic decylrhodamine derivatives of plastoquinone appear to be the most promising anti-ischemic mitochondria-targeted drugs of the quinone family. We suggest these antioxidants could be potentially used for a stroke treatment. Full article
Open AccessArticle Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca2+ Influx
Molecules 2015, 20(8), 14504-14521; doi:10.3390/molecules200814504
Received: 18 June 2015 / Revised: 31 July 2015 / Accepted: 4 August 2015 / Published: 11 August 2015
Cited by 3 | PDF Full-text (2109 KB) | HTML Full-text | XML Full-text
Abstract
Up to 40% of patients with gastroesophageal reflux disease (GERD) suffer from proton pump inhibitor refractory GERD but clinically the medications to strengthen the lower esophageal sphincter (LES) to avoid irritating reflux are few in number. This study aimed to examine whether Salvia
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Up to 40% of patients with gastroesophageal reflux disease (GERD) suffer from proton pump inhibitor refractory GERD but clinically the medications to strengthen the lower esophageal sphincter (LES) to avoid irritating reflux are few in number. This study aimed to examine whether Salvia miltiorrhiza (SM) extracts induce tonic contraction of rat LES ex vivo and elucidate the underlying mechanisms. To investigate the mechanism underlying the SM extract-induced contractile effects, rats were pretreated with atropine (a muscarinic receptor antagonist), tetrodotoxin (a sodium channel blocker), nifedipine (a calcium channel blocker), and Ca2+-free Krebs-Henseleit solution with ethylene glycol tetraacetic acid (EGTA), followed by administration of cumulative dosages of SM extracts. SM extracts induced dose-related tonic contraction of the LES, which was unaffected by tetrodotoxin, atropine, or nifedipine. However, the SM extract-induced LES contraction was significantly inhibited by Ca2+-free Krebs-Henseleit solution with EGTA. Next, SM extracts significantly induce extracellular Ca2+ entry into primary LES cells in addition to intracellular Ca2+ release and in a dose-response manner. Confocal fluorescence microscopy showed that the SM extracts consistently induced significant extracellular Ca2+ influx into primary LES cells in a time-dependent manner. In conclusion, SM extracts could induce tonic contraction of LES mainly through the extracellular Ca2+ influx pathway. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Direct Exchange of Oxygen and Selenium Atoms in the 1,2,5-Oxadiazoles and 1,2,5-Selenadiazoles by Action of Sulfur Monochloride
Molecules 2015, 20(8), 14522-14532; doi:10.3390/molecules200814522
Received: 14 July 2015 / Revised: 31 July 2015 / Accepted: 3 August 2015 / Published: 12 August 2015
Cited by 6 | PDF Full-text (764 KB) | HTML Full-text | XML Full-text
Abstract
A short synthetic approach to fused 1,2,5-thiadiazoles from the corresponding 1,2,5-oxadiazoles and 1,2,5-selenadiazoles has been developed. Mono- and bis(1,2,5-thiadiazoles) were selectively obtained in high yields. The pathways for these novel reactions were discussed. Full article
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Open AccessArticle Prazosin-Conjugated Matrices Based on Biodegradable Polymers and α-Amino Acids—Synthesis, Characterization, and in Vitro Release Study
Molecules 2015, 20(8), 14533-14551; doi:10.3390/molecules200814533
Received: 22 May 2015 / Revised: 24 July 2015 / Accepted: 5 August 2015 / Published: 12 August 2015
Cited by 1 | PDF Full-text (1450 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Novel and promising macromolecular conjugates of the α1-adrenergic blocker prazosin were directly synthesized by covalent incorporation of the drug to matrices composed of biodegradable polymers and α-amino acids for the development of a polymeric implantable drug delivery carrier. The cyto- and genotoxicity of
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Novel and promising macromolecular conjugates of the α1-adrenergic blocker prazosin were directly synthesized by covalent incorporation of the drug to matrices composed of biodegradable polymers and α-amino acids for the development of a polymeric implantable drug delivery carrier. The cyto- and genotoxicity of the synthesized matrices were evaluated using a bacterial luminescence test, protozoan assay, and Salmonella typhimurium TA1535. A new urethane bond was formed between the hydroxyl end-groups of the synthesized polymer matrices and an amine group of prazosin, using 1,1′-carbonyldiimidazole (CDI) as a coupling agent. The structure of the polymeric conjugates was characterized by various spectroscopy techniques. A study of hydrogen nuclear magnetic resonance (1H-NMR) and differential scanning calorimetry (DSC) thermodiagrams indicated that the presence of prazosin pendant groups in the macromolecule structures increased the polymer’s rigidity alongside increasing glass transition temperature. It has been found that the kinetic release of prazosin from the obtained macromolecular conjugates, tested in vitro under different conditions, is strongly dependent on the physicochemical properties of polymeric matrices. Furthermore, the presence of a urethane bond in the macromolecular conjugates allowed for obtaining a relatively controlled release profile of the drug. The obtained results confirm that the pharmacokinetics of prazosin might be improved through the synthesis of polymeric conjugates containing biomedical polymers and α-amino acids in the macromolecule. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Optical Properties of Titania Coatings Prepared by Inkjet Direct Patterning of a Reverse Micelles Sol-Gel Composition
Molecules 2015, 20(8), 14552-14564; doi:10.3390/molecules200814552
Received: 17 June 2015 / Revised: 20 July 2015 / Accepted: 21 July 2015 / Published: 12 August 2015
Cited by 3 | PDF Full-text (3285 KB) | HTML Full-text | XML Full-text
Abstract
Thin layers of titanium dioxide were fabricated by direct inkjet patterning of a reverse micelles sol-gel composition onto soda-lime glass plates. Several series of variable thickness samples were produced by repeated overprinting and these were further calcined at different temperatures. The resulting layers
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Thin layers of titanium dioxide were fabricated by direct inkjet patterning of a reverse micelles sol-gel composition onto soda-lime glass plates. Several series of variable thickness samples were produced by repeated overprinting and these were further calcined at different temperatures. The resulting layers were inspected by optical and scanning electronic microscopy and their optical properties were investigated by spectroscopic ellipsometry in the range of 200–1000 nm. Thus the influence of the calcination temperature on material as well as optical properties of the patterned micellar titania was studied. The additive nature of the deposition process was demonstrated by a linear dependence of total thickness on the number of printed layers without being significantly affected by the calcination temperature. The micellar imprints structure of the titania layer resulted into significant deviation of measured optical constants from the values reported for bulk titania. The introduction of a void layer into the ellipsometric model was found necessary for this particular type of titania and enabled correct ellipsometric determination of layer thickness, well matching the thickness values from mechanical profilometry. Full article
Open AccessArticle Four New Cyclohexylideneacetonitrile Derivatives from the Hypocotyl of Mangrove (Bruguiera gymnorrhiza)
Molecules 2015, 20(8), 14565-14575; doi:10.3390/molecules200814565
Received: 3 July 2015 / Revised: 28 July 2015 / Accepted: 31 July 2015 / Published: 12 August 2015
Cited by 4 | PDF Full-text (746 KB) | HTML Full-text | XML Full-text
Abstract
Four new cyclohexylideneacetonitrile derivatives 14, named menisdaurins B–E, as well as three known cyclohexylideneacetonitrile derivatives—menisdaurin (5), coclauril (6), and menisdaurilide (7)—were isolated from the hypocotyl of a mangrove (Bruguiera gymnorrhiza). The structures
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Four new cyclohexylideneacetonitrile derivatives 14, named menisdaurins B–E, as well as three known cyclohexylideneacetonitrile derivatives—menisdaurin (5), coclauril (6), and menisdaurilide (7)—were isolated from the hypocotyl of a mangrove (Bruguiera gymnorrhiza). The structures of the isolates were elucidated on the basis of extensive spectroscopic analysis. Compounds 17 showed anti-Hepatitis B virus (HBV) activities, with EC50 values ranging from 5.1 ± 0.2 μg/mL to 87.7 ± 5.8 μg/mL. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle A Qualitative Comparison of the Reactivities of 3,4,4,5-Tetrachloro-4H-1,2,6-thiadiazine and 4,5-Dichloro-1,2,3-dithiazolium Chloride
Molecules 2015, 20(8), 14576-14594; doi:10.3390/molecules200814576
Received: 9 July 2015 / Revised: 5 August 2015 / Accepted: 6 August 2015 / Published: 12 August 2015
Cited by 4 | PDF Full-text (780 KB) | HTML Full-text | XML Full-text
Abstract
The high yielding transformations of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine into 3,5-dichloro-4H-1,2,6-thiadiazin-4-one (up to 85%) and 2-(3,5-dichloro-4H-1,2,6-thiadiazin-4-ylidene)malononitrile (up to 83%) have been investigated and compared to the analogous transformations of the closely-related 4,5-dichloro-1,2,3-dithiazolium chloride (Appel’s salt) into 4-chloro-5H-1,2,3-dithiazol-5-one and
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The high yielding transformations of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine into 3,5-dichloro-4H-1,2,6-thiadiazin-4-one (up to 85%) and 2-(3,5-dichloro-4H-1,2,6-thiadiazin-4-ylidene)malononitrile (up to 83%) have been investigated and compared to the analogous transformations of the closely-related 4,5-dichloro-1,2,3-dithiazolium chloride (Appel’s salt) into 4-chloro-5H-1,2,3-dithiazol-5-one and 2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)malononitrile. Furthermore, cyclocondensation of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine with 2-aminophenol and 1,2-benzenediamines gave fused 4H-1,2,6-thiadiazines in 68%–85% yields. Full article
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Open AccessArticle 3-H-[1,2]Dithiole as a New Anti-Trypanosoma cruzi Chemotype: Biological and Mechanism of Action Studies
Molecules 2015, 20(8), 14595-14610; doi:10.3390/molecules200814595
Received: 29 May 2015 / Accepted: 7 August 2015 / Published: 12 August 2015
Cited by 8 | PDF Full-text (1011 KB) | HTML Full-text | XML Full-text
Abstract
The current pharmacological Chagas disease treatments, using Nifurtimox or Benznidazole, show limited therapeutic results and are associated with potential side effects, like mutagenicity. Using random screening we have identified new chemotypes that were able to inhibit relevant targets of the Trypanosoma cruzi.
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The current pharmacological Chagas disease treatments, using Nifurtimox or Benznidazole, show limited therapeutic results and are associated with potential side effects, like mutagenicity. Using random screening we have identified new chemotypes that were able to inhibit relevant targets of the Trypanosoma cruzi. We found 3H-[1,2]dithioles with the ability to inhibit Trypanosoma cruzi triosephosphate isomerase (TcTIM). Herein, we studied the structural modifications of this chemotype to analyze the influence of volume, lipophilicity and electronic properties in the anti-T. cruzi activity. Their selectivity to parasites vs. mammalian cells was also examined. To get insights into a possible mechanism of action, the inhibition of the enzymatic activity of TcTIM and cruzipain, using the isolated enzymes, and the inhibition of membrane sterol biosynthesis and excreted metabolites, using the whole parasite, were achieved. We found that this structural framework is interesting for the generation of innovative drugs for the treatment of Chagas disease. Full article
(This article belongs to the Special Issue Antiparasitic Agents)
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Open AccessArticle New Bergamotane Sesquiterpenoids from the Plant Endophytic Fungus Paraconiothyrium brasiliense
Molecules 2015, 20(8), 14611-14620; doi:10.3390/molecules200814611
Received: 7 July 2015 / Revised: 29 July 2015 / Accepted: 30 July 2015 / Published: 12 August 2015
Cited by 8 | PDF Full-text (750 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Brasilamides K-N (14), four new bergamotane sesquiterpenoids; with 4-oxatricyclo (3.3.1.0 2,7)nonane (1)and 9-oxatricyclo(4.3.0.0 4,7)nonane (24) skeletons; were isolated from the scale-up fermentation cultures of the plant endophytic fungus Paraconiothynium brasiliense Verkley.
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Brasilamides K-N (14), four new bergamotane sesquiterpenoids; with 4-oxatricyclo (3.3.1.0 2,7)nonane (1)and 9-oxatricyclo(4.3.0.0 4,7)nonane (24) skeletons; were isolated from the scale-up fermentation cultures of the plant endophytic fungus Paraconiothynium brasiliense Verkley. The previously identified sesquiterpenoids brasilamides A and C (5 and 6) were also reisolated in the current work. The structures of 14 were elucidated primarily by interpretation of NMR spectroscopic data. The absolute configurations of 13 were deduced by analogy to the co-isolated metabolites 5 and 6; whereas that of C-12 in 4 was assigned using the modified Mosher method. The cytotoxicity of all compounds against a panel of eight human tumor cell lines were assayed. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Regulation of the scp Genes in the Cyanobacterium Synechocystis sp. PCC 6803—What is New?
Molecules 2015, 20(8), 14621-14637; doi:10.3390/molecules200814621
Received: 30 April 2015 / Revised: 5 August 2015 / Accepted: 7 August 2015 / Published: 12 August 2015
Cited by 1 | PDF Full-text (2401 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the cyanobacterium Synechocystis sp. PCC 6803 there are five genes encoding small CAB-like (SCP) proteins, which have been shown to be up-regulated under stress. Analyses of the promoter sequences of the scp genes revealed the existence of an NtcA binding motif
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In the cyanobacterium Synechocystis sp. PCC 6803 there are five genes encoding small CAB-like (SCP) proteins, which have been shown to be up-regulated under stress. Analyses of the promoter sequences of the scp genes revealed the existence of an NtcA binding motif in two scp genes, scpB and scpE. Binding of NtcA, the key transcriptional regulator during nitrogen stress, to the promoter regions was shown by electrophoretic mobility shift assay. The metabolite 2-oxoglutarate did not increase the affinity of NtcA for binding to the promoters of scpB and scpE. A second motif, the HIP1 palindrome 5ʹ GGCGATCGCC 3ʹ, was detected in the upstream regions of scpB and scpC. The transcription factor encoded by sll1130 has been suggested to recognize this motif to regulate heat-responsive genes. Our data suggest that HIP1 is not a regulatory element within the scp genes. Further, the presence of the high light regulatory (HLR1) motif was confirmed in scpB-E, in accordance to their induced transcriptions in cells exposed to high light. The HLR1 motif was newly discovered in eight additional genes. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis, Characterization, and Anti-Cancer Activity of Some New N′-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives
Molecules 2015, 20(8), 14638-14655; doi:10.3390/molecules200814638
Received: 5 July 2015 / Revised: 30 July 2015 / Accepted: 6 August 2015 / Published: 13 August 2015
Cited by 6 | PDF Full-text (1826 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Eight novel N′-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4ah were synthesized and fully characterized by IR, NMR (1H-NMR and 13C-NMR), elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against
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Eight novel N′-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4ah were synthesized and fully characterized by IR, NMR (1H-NMR and 13C-NMR), elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC50 values between 3 and 7 μM) as compared to the known anti-cancer drug 5-Fluorouracil (IC50 32–50 μM). Among the tested compounds, 4a showed specificity against leukaemia (Jurkat) cells, with an IC50 value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Synthesis and Photophysical Properties of Polycarbo-Substituted Quinazolines Derived from the 2-Aryl-4-chloro-6-iodoquinazolines
Molecules 2015, 20(8), 14656-14683; doi:10.3390/molecules200814656
Received: 3 July 2015 / Revised: 3 August 2015 / Accepted: 7 August 2015 / Published: 13 August 2015
Cited by 2 | PDF Full-text (2341 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The reactivity of the 2-aryl-4-chloro-6-iodoquinazolines towards palladium catalyzed sequential (Sonogashira/Suzuki-Miyaura) and one-pot two-step cross-coupling (bis-Sonogashira, and successive Sonogashira/Stille) reactions to afford novel unsymmetrical polycarbo-substituted quinazolines has been evaluated. In contrast to the chloro-bromo substituted quinazolines in which selectivity has been previously found to
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The reactivity of the 2-aryl-4-chloro-6-iodoquinazolines towards palladium catalyzed sequential (Sonogashira/Suzuki-Miyaura) and one-pot two-step cross-coupling (bis-Sonogashira, and successive Sonogashira/Stille) reactions to afford novel unsymmetrical polycarbo-substituted quinazolines has been evaluated. In contrast to the chloro-bromo substituted quinazolines in which selectivity has been previously found to generally favor substitution at the more activated C(4)-Cl bond over the weaker Csp2-Br bond, substitution in the case of the chloro-iodo derivatives favors cross-coupling through the intrinsically more reactive Csp2-I bond. The electronic absorption and emission properties of the prepared 2,3-diaryl-6-(phenylethynyl)quinazolines were studied in solvents of different polarity (dichloromethane, toluene, DMF, methanol) and CH2Cl2-TFA mixture using UV-Vis and emission spectroscopic techniques complemented with density functional theory method to establish the effect of substituents on intramolecular charge transfer properties. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability
Molecules 2015, 20(8), 14684-14698; doi:10.3390/molecules200814684
Received: 9 June 2015 / Revised: 26 July 2015 / Accepted: 5 August 2015 / Published: 13 August 2015
Cited by 9 | PDF Full-text (1309 KB) | HTML Full-text | XML Full-text
Abstract
The majority of drugs have a low dissolution rate, which is a limiting step for their absorption. In this manuscript, solid dispersions (SD), solid self-microemulsifying drug delivery systems (S-SMEDDS) and solid self-nanoemulsifying drug delivery systems (S-SNEDDS) were evaluated as potential formulation strategies to
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The majority of drugs have a low dissolution rate, which is a limiting step for their absorption. In this manuscript, solid dispersions (SD), solid self-microemulsifying drug delivery systems (S-SMEDDS) and solid self-nanoemulsifying drug delivery systems (S-SNEDDS) were evaluated as potential formulation strategies to increase the dissolution rate of carbamazepine. Influence of increased dissolution rate on permeability of carbamazepine was evaluated using PAMPA test. In S-SMEDDS and S-SNEDDS formulations, the ratio of liquid SMEDDS/SNEDDS and solid carrier (Neusilin® UFL2) was varied, and carbamazepine content was constant. In SD formulations, the ratio of carbamazepine and Neusilin® UFL2, was varied. Formulations that showed the best dissolution rate of carbamazepine (SD_1:6, SMEDDS_1:1, SNEDDS_1:6) were mutually compared, characterization of these formulations was performed by DSC, PXRD and FT-IR analyses, and a PAMPA test was done. All formulations have shown a significant increase in dissolution rate compared to pure carbamazepine and immediate-release carbamazepine tablets. Formulation S-SMEDDS_1:1 showed the fastest release rate and permeability of carbamazepine. DSC, PXRD and FT-IR analyses confirmed that in S-SMEDDS and S-SNEDDS carbamazepine remained in polymorph form III, and that it was converted to an amorphous state in SD formulations. All formulations showed increased permeability of carbamazepine, compared to pure carbamazepine. Full article
(This article belongs to the collection Poorly Soluble Drugs)
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Open AccessArticle Synthesis of Photoswitchable Magnetic Au–Fullerosome Hybrid Nanomaterials for Permittivity Enhancement Applications
Molecules 2015, 20(8), 14746-14760; doi:10.3390/molecules200814746
Received: 9 July 2015 / Revised: 3 August 2015 / Accepted: 7 August 2015 / Published: 13 August 2015
Cited by 2 | PDF Full-text (1841 KB) | HTML Full-text | XML Full-text
Abstract
We designed and synthesized several nanomaterials 3 of three-layered core-shell (γ-FeOx@AuNP)@[C60(>DPAF-C9)1or2]n nanoparticles (NPs). These NPs having e-polarizable fullerosome structures located at the outer layer were fabricated from highly magnetic core-shell γ-FeOx
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We designed and synthesized several nanomaterials 3 of three-layered core-shell (γ-FeOx@AuNP)@[C60(>DPAF-C9)1or2]n nanoparticles (NPs). These NPs having e-polarizable fullerosome structures located at the outer layer were fabricated from highly magnetic core-shell γ-FeOx@AuNPs. Fullerosomic polarization of 3 was found to be capable of causing a large amplification of material permittivity that is also associated with the photoswitching effect in the frequency range of 0.5‒4.0 GHz. Multilayered synthetic construction allows Förster resonance energy transfer (FRET) of photoinduced accumulative surface plasmon resonance (SPR) energy in the gold layer to the partially bilayered C60(>DPAF-C9)1or2-derived fullerosome membrane shell layer in a near-field of direct contact without producing radiation heat, which is commonly associated with SPR. Full article
(This article belongs to the Special Issue Fullerene and the Related Curved-pi Materials Chemistry)
Open AccessArticle Synthesis, Structural Studies and Molecular Modelling of a Novel Imidazoline Derivative with Antifungal Activity
Molecules 2015, 20(8), 14761-14776; doi:10.3390/molecules200814761
Received: 14 July 2015 / Revised: 14 July 2015 / Accepted: 10 August 2015 / Published: 13 August 2015
Cited by 4 | PDF Full-text (1304 KB) | HTML Full-text | XML Full-text
Abstract
Six novel imidazoline derivatives were synthesized and tested in antifungal assays. One of the compounds, N-cyclohexyl-2-imino-3-(4-nitrophenyl)imidazolidine-1-carboxamide showed moderate activity against several clinical strains of Candida albicans. Its structure was solved by X-ray crystallography and its mode of action was deduced using
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Six novel imidazoline derivatives were synthesized and tested in antifungal assays. One of the compounds, N-cyclohexyl-2-imino-3-(4-nitrophenyl)imidazolidine-1-carboxamide showed moderate activity against several clinical strains of Candida albicans. Its structure was solved by X-ray crystallography and its mode of action was deduced using molecular modelling. It was found to be similar to that of fluconazole. The potential for further optimization including SAR of the compound is briefly discussed. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Rapid Estimation of Tocopherol Content in Linseed and Sunflower Oils-Reactivity and Assay
Molecules 2015, 20(8), 14777-14790; doi:10.3390/molecules200814777
Received: 16 June 2015 / Revised: 15 July 2015 / Accepted: 23 July 2015 / Published: 13 August 2015
Cited by 1 | PDF Full-text (758 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The reactivity of tocopherols with 2,2-diphenyl-1-picrylhydrazyl (DPPH) was studied in model systems in order to establish a method for quantifying vitamin E in plant oils. The method was optimized with respect to solvent composition of the assay medium, which has a large influence
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The reactivity of tocopherols with 2,2-diphenyl-1-picrylhydrazyl (DPPH) was studied in model systems in order to establish a method for quantifying vitamin E in plant oils. The method was optimized with respect to solvent composition of the assay medium, which has a large influence on the course of reaction of tocopherols with DPPH. The rate of reaction of α-tocopherol with DPPH is higher than that of γ-tocopherol in both protic and aprotic solvents. In ethyl acetate, routinely applied for the analysis of antioxidant potential (AOP) of plant oils, reactions of tocopherols with DPPH are slower and concentration of tocopherols in the assay has a large influence on their molar reactivity. In 2-propanol, however, two electrons are exchanged for both α- and γ-tocopherols, independent of their concentration. 2-propanol is not toxic and is fully compatible with polypropylene labware. The chromatographically determined content of tocopherols and their molar reactivity in the DPPH assay reveal that only tocopherols contribute to the AOP of sunflower oil, whereas the contribution of tocopherols to the AOP of linseed oil is 75%. The DPPH assay in 2-propanol can be applied for rapid and cheap estimation of vitamin E content in plant oils where tocopherols are major antioxidants. Full article
(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)
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Open AccessArticle Novel Coumarin-Containing Aminophosphonatesas Antitumor Agent: Synthesis, Cytotoxicity, DNA-Binding and Apoptosis Evaluation
Molecules 2015, 20(8), 14791-14809; doi:10.3390/molecules200814791
Received: 29 June 2015 / Revised: 6 August 2015 / Accepted: 10 August 2015 / Published: 13 August 2015
Cited by 9 | PDF Full-text (1417 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of novel coumarin-containing α-aminophosphonates were synthesized and evaluated for their antitumor activities against Human colorectal (HCT-116), human nasopharyngeal carcinoma (human KB) and human lung adenocarcinoma (MGC-803) cell lines in vitro. Compared with 7-hydroxy-4-methylcoumarin (4-MU), most of the derivatives
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A series of novel coumarin-containing α-aminophosphonates were synthesized and evaluated for their antitumor activities against Human colorectal (HCT-116), human nasopharyngeal carcinoma (human KB) and human lung adenocarcinoma (MGC-803) cell lines in vitro. Compared with 7-hydroxy-4-methylcoumarin (4-MU), most of the derivatives showed an improved antitumor activity. Compound 8j (diethyl 1-(3-(4-methyl-2-oxo-2H-chromen-7-yloxy) propanamido)-1-phenylethyl-Phosphonate), with IC50 value of 8.68 μM against HCT-116 cell lines, was about 12 fold than that of unsubstituted parent compound. The mechanism investigation proved that 8c, 8d, 8f and 8j were achieved through the induction of cell apoptosis by G1 cell-cycle arrest. In addition, the further mechanisms of compound 8j-induced apoptosis in HCT-116 cells demonstrated that compound 8j induced the activations of caspase-9 and caspase-3 for causing cell apoptosis, and altered anti- and pro-apoptotic proteins. DNA-binding experiments suggested that some derivatives bind to DNA through intercalation. The results seem to imply the presence of an important synergistic effect between coumarin and aminophosphonate, which could contribute to the strong chelating properties of aminophosphonate moiety. Full article
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Open AccessArticle Bioassay-Guided Fractionation of a Leaf Extract from Combretum mucronatum with Anthelmintic Activity: Oligomeric Procyanidins as the Active Principle
Molecules 2015, 20(8), 14810-14832; doi:10.3390/molecules200814810
Received: 7 July 2015 / Revised: 5 August 2015 / Accepted: 11 August 2015 / Published: 14 August 2015
Cited by 9 | PDF Full-text (1530 KB) | HTML Full-text | XML Full-text
Abstract
Combretum mucronatum Schumach. & Thonn. is a medicinal plant widely used in West African traditional medicine for wound healing and the treatment of helminth infections. The present study aimed at a phytochemical characterization of a hydroalcoholic leaf extract of this plant and the
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Combretum mucronatum Schumach. & Thonn. is a medicinal plant widely used in West African traditional medicine for wound healing and the treatment of helminth infections. The present study aimed at a phytochemical characterization of a hydroalcoholic leaf extract of this plant and the identification of the anthelmintic compounds by bioassay-guided fractionation. An EtOH-H2O (1:1) extract from defatted leaves was partitioned between EtOAc and H2O. Further fractionation was performed by fast centrifugal partition chromatography, RP18-MPLC and HPLC. Epicatechin (1), oligomeric proanthocyanidins (OPC) 2 to 10 (mainly procyanidins) and flavonoids 11 to 13 were identified as main components of the extract. The hydroalcoholic extract, fractions and purified compounds were tested in vitro for their anthelmintic activity using the model nematode Caenorhabditis elegans. The bioassay-guided fractionation led to the identification of OPCs as the active compounds with a dose-dependent anthelmintic activity ranging from 1 to 1000 μM. Using OPC-clusters with a defined degree of polymerization (DP) revealed that a DP ≥ 3 is necessary for an anthelmintic activity, whereas a DP > 4 does not lead to a further increased inhibitory effect against the helminths. In summary, the findings rationalize the traditional use of C. mucronatum and provide further insight into the anthelmintic activity of condensed tannins. Full article
Open AccessArticle Structural Stabilities and Transformation Mechanism of Rhynchophylline and Isorhynchophylline by Ultra Performance Liquid Chromatography/Time-of-Flight Mass Spectrometry (UPLC/Q-TOF-MS)
Molecules 2015, 20(8), 14849-14859; doi:10.3390/molecules200814849
Received: 16 June 2015 / Accepted: 10 August 2015 / Published: 14 August 2015
Cited by 4 | PDF Full-text (804 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
To reveal the structural stabilities and transformation mechanism of rhynchophylline (RIN) and isorhynchophylline (IRN), HPLC and UPLC-Q-TOF-MS method were developed for the qualitative and quantitative analysis of the conversion rate. The method was validated for linearity, inter- and intra-day precisions, repeatability and stability.
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To reveal the structural stabilities and transformation mechanism of rhynchophylline (RIN) and isorhynchophylline (IRN), HPLC and UPLC-Q-TOF-MS method were developed for the qualitative and quantitative analysis of the conversion rate. The method was validated for linearity, inter- and intra-day precisions, repeatability and stability. All the quantitative determination method validation results were satisfactory. Under the optimized chromatographic conditions, the effect of various heat temperatures, retention time, and solvent polarities on conversion rate and equilibrium were systematically investigated for the first time. Besides, a model relating the retention yield value and time-temperature was built to predict the t0.5 and Ea of the conversion rate by the Arrhenius equation. The experimental results proved to be in good accordance with the predicted values. Furthermore, UPLC-Q-TOF-MS analysis was performed to verify the transformation mechanism and provide valuable information for stability analysis of the conversion products. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Development of a Single Vial Kit Solution for Radiolabeling of 68Ga-DKFZ-PSMA-11 and Its Performance in Prostate Cancer Patients
Molecules 2015, 20(8), 14860-14878; doi:10.3390/molecules200814860
Received: 31 May 2015 / Revised: 31 July 2015 / Accepted: 3 August 2015 / Published: 14 August 2015
Cited by 16 | PDF Full-text (1391 KB) | HTML Full-text | XML Full-text
Abstract
Prostate-specific membrane antigen (PSMA), a type II glycoprotein, is highly expressed in almost all prostate cancers. By playing such a universal role in the disease, PSMA provides a target for diagnostic imaging of prostate cancer using positron emission tomography/computed tomography (PET/CT). The PSMA-targeting
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Prostate-specific membrane antigen (PSMA), a type II glycoprotein, is highly expressed in almost all prostate cancers. By playing such a universal role in the disease, PSMA provides a target for diagnostic imaging of prostate cancer using positron emission tomography/computed tomography (PET/CT). The PSMA-targeting ligand Glu-NH-CO-NH-Lys-(Ahx)-HBED-CC (DKFZ-PSMA-11) has superior imaging properties and allows for highly-specific complexation of the generator-based radioisotope Gallium-68 (68Ga). However, only module-based radiolabeling procedures are currently available. This study intended to develop a single vial kit solution to radiolabel buffered DKFZ-PSMA-11 with 68Ga. A 68Ge/68Ga-generator was utilized to yield 68GaCl3 and major aspects of the kit development were assessed, such as radiolabeling performance, quality assurance, and stability. The final product was injected into patients with prostate cancer for PET/CT imaging and the kit performance was evaluated on the basis of the expected biodistribution, lesion detection, and dose optimization. Kits containing 5 nmol DKFZ-PSMA-11 showed rapid, quantitative 68Ga-complexation and all quality measurements met the release criteria for human application. The increased precursor content did not compromise the ability of 68Ga-DKFZ-PSMA-11 PET/CT to detect primary prostate cancer and its advanced lymphatic- and metastatic lesions. The 68Ga-DKFZ-PSMA-11 kit is a robust, ready-to-use diagnostic agent in prostate cancer with high diagnostic performance. Full article
(This article belongs to the Special Issue Preparation of Radiopharmaceuticals and Their Use in Drug Development)
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Open AccessArticle Diterpenoids from Saliva plebeia R. Br. and Their Antioxidant and Anti-Inflammatory Activities
Molecules 2015, 20(8), 14879-14888; doi:10.3390/molecules200814879
Received: 24 May 2015 / Revised: 13 July 2015 / Accepted: 22 July 2015 / Published: 14 August 2015
Cited by 8 | PDF Full-text (834 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new skeleton of diterpenoid, 1,2,3,4,4α,9,10,10α-octahydro-(4α-hydroxyymethyl) -1,1-dimethyl-9-(1-methylethyl)-(2S,3S,4αR,9R,10αS)-2,3,5,7-phenanthrenetertrol, named plebeianiol A (1), along with four known diterpenoids (25), were isolated from Salvia plebeia R. Br. Their structures were
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A new skeleton of diterpenoid, 1,2,3,4,4α,9,10,10α-octahydro-(4α-hydroxyymethyl) -1,1-dimethyl-9-(1-methylethyl)-(2S,3S,4αR,9R,10αS)-2,3,5,7-phenanthrenetertrol, named plebeianiol A (1), along with four known diterpenoids (25), were isolated from Salvia plebeia R. Br. Their structures were determined on the basis of spectral analysis. In the bioactivity tests, compounds 1, 2 and 5 showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities with IC50 values of 20.0–29.6 µM. In addition, these three compounds had significant inhibitory effects on reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-induced macrophages. Compounds 13 inhibited nitric oxide (NO) production in LPS-induced macrophages with IC50 values of 18.0–23.6 µM. These results showed that compounds 1, 2 had significant antioxidant and anti-inflammatory activities and might provide basis for the treatment of diseases associated with oxidative lesions and inflammation. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Recombinant Production of Snakin-2 (an Antimicrobial Peptide from Tomato) in E. coli and Analysis of Its Bioactivity
Molecules 2015, 20(8), 14889-14901; doi:10.3390/molecules200814889
Received: 17 June 2015 / Revised: 11 August 2015 / Accepted: 12 August 2015 / Published: 14 August 2015
Cited by 10 | PDF Full-text (2695 KB) | HTML Full-text | XML Full-text
Abstract
Antimicrobial peptides (AMPs) represent a diverse group of biologically active molecules that are part of the innate immune systems of a variety of organisms. Their primary function consists of protecting the host organism against invading microorganisms, including pathogens. AMPs show a broad spectrum
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Antimicrobial peptides (AMPs) represent a diverse group of biologically active molecules that are part of the innate immune systems of a variety of organisms. Their primary function consists of protecting the host organism against invading microorganisms, including pathogens. AMPs show a broad spectrum of secondary structures, which are essential for antimicrobial activity. In this study, we produced snakin-2 (SN2), a 66-amino-acid-(aa)-long AMP from Solanum lycopersicum as a recombinant protein in E. coli. This AMP belongs to the GASA/GAST protein family and possesses a highly conserved 60-aa-long domain with six disulfide bonds in the C-terminus of the peptide. Because of the toxicity of SN2 against its producing E. coli strain, the AMP was attached to an N-terminal fusion protein (thioredoxin A), which was removed after affinity chromatography purification. The total yield of recombinant SN2 was approximately 1 mg/L. The membrane-active SN2 showed a bactericidal and fungicidal bioactivity, which can be explained by perforation of biomembranes of bacteria and fungi. Full article
Open AccessArticle Synthesis of C3/C1-Substituted Tetrahydroisoquinolines
Molecules 2015, 20(8), 14902-14914; doi:10.3390/molecules200814902
Received: 22 July 2015 / Revised: 5 August 2015 / Accepted: 10 August 2015 / Published: 14 August 2015
PDF Full-text (814 KB) | HTML Full-text | XML Full-text
Abstract
A broad biological screening of the natural alkaloid N-methylisosalsoline (2) extracted from Hammada scoparia leaves against a panel of human and parasitic proteases revealed an interesting activity profile of 2 towards human 20S proteasome. This outcome suggests that the 1,2,3,4-tetrahydroisoquinoline
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A broad biological screening of the natural alkaloid N-methylisosalsoline (2) extracted from Hammada scoparia leaves against a panel of human and parasitic proteases revealed an interesting activity profile of 2 towards human 20S proteasome. This outcome suggests that the 1,2,3,4-tetrahydroisoquinoline skeleton may be exploited as a template for the development of novel anticancer agents. In this article, we report the synthesis and chemical characterization of a new series of isosalsoline-type alkaloids (1011) with variations at N2 and C3 positions with respect to the natural Compound 2, obtained by a synthetic strategy that involves the Bischler-Napieralski cyclization. The substrate for the condensation to the tetrahydroisoquinoline system, i.e., a functionalized β-arylethyl amine, was obtained through an original double reduction of nitroalkene. The synthetic strategy can be directed to the construction of highly substituted and functionalized 1,2,3,4-tetrahydroisoquinolines. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle A Combined Molecular Docking/Dynamics Approach to Probe the Binding Mode of Cancer Drugs with Cytochrome P450 3A4
Molecules 2015, 20(8), 14915-14935; doi:10.3390/molecules200814915
Received: 8 July 2015 / Revised: 11 August 2015 / Accepted: 12 August 2015 / Published: 14 August 2015
Cited by 4 | PDF Full-text (3898 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cytarabine, daunorubicin, doxorubicin and vincristine are clinically used for combinatorial therapies of cancers in different combinations. However, the knowledge about the interaction of these drugs with the metabolizing enzyme cytochrome P450 is limited. Therefore, we utilized computational methods to predict and assess the
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Cytarabine, daunorubicin, doxorubicin and vincristine are clinically used for combinatorial therapies of cancers in different combinations. However, the knowledge about the interaction of these drugs with the metabolizing enzyme cytochrome P450 is limited. Therefore, we utilized computational methods to predict and assess the drug-binding modes. In this study, we performed docking, MD simulations and free energy landscape analysis to understand the drug-enzyme interactions, protein domain motions and the most populated free energy minimum conformations of the docked protein-drug complexes, respectively. The outcome of docking and MD simulations predicted the productive, as well as the non-productive binding modes of the selected drugs. Based on these interaction studies, we observed that S119, R212 and R372 are the major drug-binding residues in CYP3A4. The molecular mechanics Poisson–Boltzmann surface area analysis revealed the dominance of hydrophobic forces in the CYP3A4-drug association. Further analyses predicted the residues that may contain favorable drug-specific interactions. The probable binding modes of the cancer drugs from this study may extend the knowledge of the protein-drug interaction and pave the way to design analogs with reduced toxicity. In addition, they also provide valuable insights into the metabolism of the cancer drugs. Full article
(This article belongs to the collection Nanomedicine)
Open AccessArticle Eco-Friendly Synthesis of a New Class of Pyridinium-Based Ionic Liquids with Attractive Antimicrobial Activity
Molecules 2015, 20(8), 14936-14949; doi:10.3390/molecules200814936
Received: 16 June 2015 / Revised: 30 July 2015 / Accepted: 5 August 2015 / Published: 14 August 2015
Cited by 8 | PDF Full-text (713 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The present study reports a green synthesis of a new family of ionic liquids (ILs) based on functionalized 4-dimethylaminopyridinium derivatives. The structures of 23 newly synthesized ILs (224) were confirmed by FT-IR, 1H-, 13C-, 11B-, 19
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The present study reports a green synthesis of a new family of ionic liquids (ILs) based on functionalized 4-dimethylaminopyridinium derivatives. The structures of 23 newly synthesized ILs (224) were confirmed by FT-IR, 1H-, 13C-, 11B-, 19F-, and 31P-NMR spectroscopy and mass spectrometry. The antimicrobial activity of all novel ILs was tested against a panel of bacteria and fungi. The results prove that all tested ILs are effective antibacterial and antifungal agents, especially 4-(dimethylamino)-1-(4-phenoxybutyl) pyridinium derivatives 5 and 19. Full article
(This article belongs to the Special Issue Ionic Liquids in Organic Synthesis)
Open AccessArticle Oral Intake of Carboxymethyl-Glucan (CM-G) from Yeast (Saccharomyces uvarum) Reduces Malondialdehyde Levels in Healthy Men
Molecules 2015, 20(8), 14950-14958; doi:10.3390/molecules200814950
Received: 20 June 2015 / Revised: 10 August 2015 / Accepted: 12 August 2015 / Published: 14 August 2015
Cited by 2 | PDF Full-text (1652 KB) | HTML Full-text | XML Full-text
Abstract
Carboxymethyl-glucan (CM-G) is a water-soluble derivative of β(1→3)(1→6) glucan, a well-known immunostimulant and antioxidant compound. In this experimental, randomized and placebo-controlled study, the effects of oral CM-G intake over a 60-day period on the peripheral blood, cholesterol, glycemic index and malondialdehyde (MDA) levels
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Carboxymethyl-glucan (CM-G) is a water-soluble derivative of β(1→3)(1→6) glucan, a well-known immunostimulant and antioxidant compound. In this experimental, randomized and placebo-controlled study, the effects of oral CM-G intake over a 60-day period on the peripheral blood, cholesterol, glycemic index and malondialdehyde (MDA) levels of healthy men was assessed. The CM-G was obtained from spent brewer’s yeast (S. uvarum) with DS 0.8 and molecular weight of 2.2 × 105 Da. Following CM-G administration, no changes were observed in red and white blood cell, hematocrit, hemoglobin and platelet counts, or in cholesterol and glycemic indices. After 30 days of CM-G administration, the MDA levels decreased significantly (p ≤ 0.05) in men receiving CM-G. The results showed for the first time that CM-G may act as an adjuvant in preventing oxidative damage in healthy humans. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons
Molecules 2015, 20(8), 14959-14969; doi:10.3390/molecules200814959
Received: 15 June 2015 / Revised: 6 August 2015 / Accepted: 12 August 2015 / Published: 14 August 2015
Cited by 1 | PDF Full-text (3031 KB) | HTML Full-text | XML Full-text
Abstract
Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine) is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical
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Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine) is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH), a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly. In an attempt to clarify its pharmacological actions, in this study, we focused on the inhibitory activity of YKH against neurite growth induced with nerve growth factor (NGF) in cultured rat dorsal root ganglion (DRG) neurons because epidermal hyperinnervation is deeply related to itch sensitization. YKH showed approximately 200-fold inhibitory activity against NGF-induced neurite growth than that of neurotropin (positive control), a drug used clinically for treatment of chronic pruritus. Moreover, it also found that Uncaria hook, Bupleurum root and their chemical constituents rhynchophylline, hirsutine, and saikosaponin a, d showed inhibitory activities against NGF-induced neurite growth, suggesting they should mainly contribute to the inhibitory activity of YKH. Further study on the effects of YKH against epidermal nerve density in “itch-scratch” animal models is under investigation. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Fast Identification of Radical Scavengers from Securigera varia by Combining 13C-NMR-Based Dereplication to Bioactivity-Guided Fractionation
Molecules 2015, 20(8), 14970-14984; doi:10.3390/molecules200814970
Received: 1 July 2015 / Revised: 23 July 2015 / Accepted: 31 July 2015 / Published: 14 August 2015
Cited by 4 | PDF Full-text (1224 KB) | HTML Full-text | XML Full-text
Abstract
Securigera varia (Fabaceae) is a common herbaceous perennial plant widely growing in Europe and Asia and purposely established for erosion control, roadside planting, and soil rehabilitation. The aim of this study was to determine the radical scavenging activity of a crude methanol extract
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Securigera varia (Fabaceae) is a common herbaceous perennial plant widely growing in Europe and Asia and purposely established for erosion control, roadside planting, and soil rehabilitation. The aim of this study was to determine the radical scavenging activity of a crude methanol extract of S. varia aerial parts by using the free radical DPPH (1,1-diphenyl-2-picrylhydrazyl) and to rapidly identify the compounds involved in this activity. The crude extract was initially separated in five fractions on Diaion HP20 resin and the most active part was fractionated by Centrifugal Partition Extraction (CPE). Known compounds were directly identified by a 13C-NMR-based dereplication method. Semi-preparative high performance liquid chromatography purification experiments were further performed to identify unknown or minor active compounds. As a result, one new (13) and twelve known flavonoid glycosides together with three nitropropanoylglucopyranoses were isolated, including astragalin (1), kaempferol-3-O-(6-O-acetyl)-β-D-glucopyranoside (2), kaempferol-3,4′-di-O-β-D-glucopyranoside (3), trifolin (4), isoquercitrin (5), hyperoside (6), isovitexin (7), isoorientin (8), isovitexin 4′-O-β-D-glucopyranoside (9), apigenin 7-O-β-D-glucuronopyranoside (10), luteolin 7-O-β-D-glucuronopyranoside (11), apigenin 7-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucuronopyranoside (12), apigenin 7-O-β-D-glucopyranosyl-(1→2)-β-D-glucuronopyranoside (13), 6-O-(3-nitropropanoyl)-β-D-glucopyranoside (14), coronillin (16) and coronarian (15). 120 mg of the most active compound isoorientin against the free radical DPPH was recovered by CPE with an HPLC purity of 99%. Full article
(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)
Open AccessArticle Effect of Brewing Duration on the Antioxidant and Hepatoprotective Abilities of Tea Phenolic and Alkaloid Compounds in a t-BHP Oxidative Stress-Induced Rat Hepatocyte Model
Molecules 2015, 20(8), 14985-15002; doi:10.3390/molecules200814985
Received: 7 July 2015 / Revised: 7 August 2015 / Accepted: 11 August 2015 / Published: 17 August 2015
Cited by 5 | PDF Full-text (4022 KB) | HTML Full-text | XML Full-text
Abstract
Tea is an interesting source of antioxidants capable of counteracting the oxidative stress implicated in liver diseases. We investigated the impact of antioxidant molecules provided by a mixture of teas’ leaves (green, oolong, pu-erh) after different infusion durations in the prevention of oxidative
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Tea is an interesting source of antioxidants capable of counteracting the oxidative stress implicated in liver diseases. We investigated the impact of antioxidant molecules provided by a mixture of teas’ leaves (green, oolong, pu-erh) after different infusion durations in the prevention of oxidative stress in isolated rat hepatocytes, by comparison with pure epigallocatechin-3-gallate (EGCG), the main representative of tea catechins. Dried aqueous tea extracts (ATE) obtained after 5, 15 and 30 min infusion time were characterized for total polyphenols (gallic acid equivalent), catechins, gallic acid and caffeine (HPLC-DAD/ESI-MS) contents, and for scavenging ability against 2,2-diphenyl-1-picrylhydrazyl free radical. Hepatoprotection was evaluated through hepatocyte viability tests using tert-butyl hydroperoxide as a stress inducer, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, neutral red uptake, real-time cellular impedance) and mitochondrial function tests. We showed that a 5-min incubation time is sufficient for an optimal bioaccessibility of tea compounds with the highest antioxidative ability, which decreases for longer durations. A 4-h pretreatment of cells with ATE significantly prevented cell death by regulating reactive oxygen species production and maintaining mitochondrial integrity. Pure EGCG, at doses similar in ATE (5–12 µM), was inefficient, suggesting a plausible synergy of several water-soluble tea compounds to explain the ATE beneficial effects. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Copper-Catalyzed Dimerization/Cyclization of Itaconates
Molecules 2015, 20(8), 15023-15032; doi:10.3390/molecules200815023
Received: 7 June 2015 / Revised: 3 August 2015 / Accepted: 5 August 2015 / Published: 17 August 2015
Cited by 2 | PDF Full-text (717 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A copper-catalyzed domino reaction between itaconate esters and diethyl zinc (or silane) is developed, affording itaconate dimerization products, multi-ester-substituted cyclopentanones, in moderate to high yields. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Inhibition of Cytosolic Phospholipase A2α (cPLA2α) by Medicinal Plants in Relation to Their Phenolic Content
Molecules 2015, 20(8), 15033-15048; doi:10.3390/molecules200815033
Received: 7 July 2015 / Revised: 5 August 2015 / Accepted: 11 August 2015 / Published: 17 August 2015
Cited by 2 | PDF Full-text (476 KB) | HTML Full-text | XML Full-text
Abstract
The cytosolic phospholipase A2α(cPLA2α) is one of the potential targets for anti-inflammatory drugs, since this enzyme plays a key role in the inflammation processes seen in health disorders, like asthma, allergic reactions, arthritis and neuronal diseases. In this study,
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The cytosolic phospholipase A2α(cPLA2α) is one of the potential targets for anti-inflammatory drugs, since this enzyme plays a key role in the inflammation processes seen in health disorders, like asthma, allergic reactions, arthritis and neuronal diseases. In this study, cPLA2α inhibition by 43 methanol extracts from medicinal plants rich in polyphenols was determined. The eight most active extracts were derived from Ribes nigrum (IC50 of 27.7 μg/mL), Ononis spinosa (IC50 of 39.4 μg/mL), Urtica dioica (IC50 of 44.32 μg/mL), Betula sp. (IC50 of 58.02 μg/mL), Sanguisorba officinalis (IC50 of 76.25 μg/mL), Orthosiphon stamineus (IC50 of 78.83 μg/mL), Petasites hybridus (IC50 of 81.02 μg/mL) and Tussilago farfara (IC50 of 123.28 μg/mL). Additionally, the antioxidant activities of these extracts were determined with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and their phenolic content with the Folin–Ciocalteu reagent. Antioxidant activity showed a non-linear, positive correlation to the phenolic content, but no correlation of PLA2 inhibition with phenolic content could be established. This study provides evidence that cPLA2α may be a relevant target for anti-inflammatory agents. Full article
Open AccessArticle One-Pot Synthesis of Organic-Sulfur-Zinc Hybrid Materials via Polycondensation of a Zinc Salt and Thiols Generated in Situ from Cyclic Dithiocarbonates
Molecules 2015, 20(8), 15049-15059; doi:10.3390/molecules200815049
Received: 12 May 2015 / Revised: 12 May 2015 / Accepted: 10 August 2015 / Published: 17 August 2015
Cited by 2 | PDF Full-text (1137 KB) | HTML Full-text | XML Full-text
Abstract
Soluble organic-sulfur-zinc hybrid polymers were prepared via a one-pot reaction consisting of ring-opening addition and subsequent polycondensation. The first reaction is the nucleophilic ring-opening addition of 2-ethylhexylamine to multifunctional cyclic dithiocarbonates giving multiple thiols in situ. The sequential polycondensation of the in
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Soluble organic-sulfur-zinc hybrid polymers were prepared via a one-pot reaction consisting of ring-opening addition and subsequent polycondensation. The first reaction is the nucleophilic ring-opening addition of 2-ethylhexylamine to multifunctional cyclic dithiocarbonates giving multiple thiols in situ. The sequential polycondensation of the in situ generated thiols with Zn(OAc)2 gave the target hybrid polymers. This one-pot method enabled the use of a shorter amine than the previous polycondensation of Zn(OAc)2 and purified thiols, which required octadecylamine to obtain a soluble product. The obtained hybrid polymers may be cast as composite films with polystyrene and poly(methyl methacrylate). Owing to the shorter alkyl chain, the calculated nD values of the products (1.60 or 1.61) are higher than that of the previous product bearing octadecyl chains (1.53). Full article
(This article belongs to the Special Issue Ring-Opening Polymerization)
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Open AccessArticle Antioxidant, Antimicrobial Effects and Phenolic Profile of Lycium barbarum L. Flowers
Molecules 2015, 20(8), 15060-15071; doi:10.3390/molecules200815060
Received: 28 June 2015 / Revised: 28 June 2015 / Accepted: 10 August 2015 / Published: 17 August 2015
Cited by 8 | PDF Full-text (1176 KB) | HTML Full-text | XML Full-text
Abstract
L. barbarum L. is a widely-accepted nutraceutical presenting highly advantageous nutritive and antioxidant properties. Its flowers have been previously described as a source of diosgenin, β-sitosterol and lanosterol that can be further pharmaceutically developed, but no other data regarding their composition is available.
[...] Read more.
L. barbarum L. is a widely-accepted nutraceutical presenting highly advantageous nutritive and antioxidant properties. Its flowers have been previously described as a source of diosgenin, β-sitosterol and lanosterol that can be further pharmaceutically developed, but no other data regarding their composition is available. The purpose of this work was to investigate the chemical constituents, antioxidant and antimicrobial activities of L. barbarum flowers, as an alternative resource of naturally-occurring antioxidant compounds. The free radical scavenging activity of the ethanolic extract was tested by TEAC, two enzymatic assays with more physiological relevance and EPR spectroscopy. The presence of several phenolic compounds, such as chlorogenic, p-coumaric and ferulic acids, but also isoquercitrin, rutin and quercitrin, was assessed by an HPLC/MS method. The antioxidant assays revealed that the extract exhibited a moderate antioxidant potential. The antimicrobial activity was mild against Gram-positive bacteria and lacking against Escherichia coli. These findings complete the scarce existing data and offer new perspectives for further pharmaceutical valorization of L. barbarum flowers. Full article
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Open AccessArticle Preformulation Studies of Bee Venom for the Preparation of Bee Venom-Loaded PLGA Particles
Molecules 2015, 20(8), 15072-15083; doi:10.3390/molecules200815072
Received: 21 June 2015 / Revised: 4 August 2015 / Accepted: 5 August 2015 / Published: 18 August 2015
Cited by 3 | PDF Full-text (1647 KB) | HTML Full-text | XML Full-text
Abstract
It is known that allergic people was potentially vulnerable to bee venom (BV), which can induce an anaphylactic shock, eventually leading to death. Up until recently, this kind of allergy was treated only by venom immunotherapy (VIT) and its efficacy has been recognized
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It is known that allergic people was potentially vulnerable to bee venom (BV), which can induce an anaphylactic shock, eventually leading to death. Up until recently, this kind of allergy was treated only by venom immunotherapy (VIT) and its efficacy has been recognized worldwide. This treatment is practiced by subcutaneous injections that gradually increase the doses of the allergen. This is inconvenient for patients due to frequent injections. Poly (D,L-lactide-co-glycolide) (PLGA) has been broadly studied as a carrier for drug delivery systems (DDS) of proteins and peptides. PLGA particles usually induce a sustained release. In this study, the physicochemical properties of BV were examined prior to the preparation of BV-loaded PLGA nanoparticles NPs). The content of melittin, the main component of BV, was 53.3%. When protected from the light BV was stable at 4 °C in distilled water, during 8 weeks. BV-loaded PLGA particles were prepared using dichloromethane as the most suitable organic solvent and two min of ultrasonic emulsification time. This study has characterized the physicochemical properties of BV for the preparation BV-loaded PLGA NPs in order to design and optimize a suitable sustained release system in the future. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Phytophthora austrocedri Elicitates Changes in Diterpene Profile of Austrocedrus chilensis
Molecules 2015, 20(8), 15084-15097; doi:10.3390/molecules200815084
Received: 24 June 2015 / Revised: 24 June 2015 / Accepted: 8 August 2015 / Published: 18 August 2015
PDF Full-text (2605 KB) | HTML Full-text | XML Full-text
Abstract
The populations of the Andean Cupressaceae Austrocedrus chilensis have been severely affected by a disease caused by the phytopathogenic fungus Phytophthora austrocedri. A study was undertaken to disclose changes in the resin composition of P. austrocedri-infected individuals, including naturally infected and
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The populations of the Andean Cupressaceae Austrocedrus chilensis have been severely affected by a disease caused by the phytopathogenic fungus Phytophthora austrocedri. A study was undertaken to disclose changes in the resin composition of P. austrocedri-infected individuals, including naturally infected and artificially inoculated trees, compared with healthy A. chilensis trees. GC-MS and 1H-NMR studies showed a clear differentiation among healthy and infected resins, with the diterpene isopimara-8(9),15-dien-19-ol as a relevant constituent in resins from infected trees. The effect of resin fractions from P. austrocedri infected trees on the pathogen was assessed by measuring the mycelial growth in agar plates. The most active fractions from resin obtained from infected trees inhibited fungal growth by nearly 50% at 1 mg/dish (35.37 µg/cm2). The main constituent in the active fractions were 18-hydroxymanool and the aldehyde torulosal. Both compounds are oxidation products of manool and can be a chemical response of the tree to the pathogen or be formed from the pathogen as a biotransformation product of manool by microbial oxidation. While the diterpene profiles from A. chilensis tree resins can easily differentiate healthy and P. austrocedri infected individuals, the possible conversion of manool to the antifungal derivatives 4 and 6 by the microorganism remains to be established. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Addition of CFCl3 to Aromatic Aldehydes via in Situ Grignard Reaction
Molecules 2015, 20(8), 15098-15107; doi:10.3390/molecules200815098
Received: 16 June 2015 / Revised: 29 July 2015 / Accepted: 6 August 2015 / Published: 18 August 2015
Cited by 1 | PDF Full-text (798 KB) | HTML Full-text | XML Full-text
Abstract
Synthetic modification of trichlorofluoromethane (CFCl3) to non-volatile and useful fluorinated precursors is a cost-effective and an environmentally benign strategy for the safe consumption/destruction of the ozone depleting potential of the reagent. In this report, we present a novel method for in
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Synthetic modification of trichlorofluoromethane (CFCl3) to non-volatile and useful fluorinated precursors is a cost-effective and an environmentally benign strategy for the safe consumption/destruction of the ozone depleting potential of the reagent. In this report, we present a novel method for in situ Grignard reaction using magnesium powder and CFCl3 for synthesis of dichlorofluoromethyl aromatic alcohols. Full article
(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)
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Open AccessArticle Unconventional Bifunctional Lewis-Brønsted Acid Activation Mode in Bicyclic Guanidine-Catalyzed Conjugate Addition Reactions
Molecules 2015, 20(8), 15108-15121; doi:10.3390/molecules200815108
Received: 3 June 2015 / Revised: 3 June 2015 / Accepted: 10 August 2015 / Published: 18 August 2015
Cited by 5 | PDF Full-text (1476 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
DFT calculations have demonstrated that the unconventional bifunctional Brønsted-Lewis acid activation mode is generally applicable to a range of nucleophilic conjugate additions catalyzed by bicyclic guanidine catalysts. It competes readily with the conventional bifunctional Brønsted acid mode of activation. The optimal pro-nucleophiles for
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DFT calculations have demonstrated that the unconventional bifunctional Brønsted-Lewis acid activation mode is generally applicable to a range of nucleophilic conjugate additions catalyzed by bicyclic guanidine catalysts. It competes readily with the conventional bifunctional Brønsted acid mode of activation. The optimal pro-nucleophiles for this unconventional bifunctional activation are acidic substrates with low pKa, while the best electrophiles are flexible 1,4-diamide and 1,4-diester conjugated systems. Full article
(This article belongs to the Special Issue Brønsted Base Catalysis in Organic Synthesis)
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Open AccessArticle Porphyrins as Corrosion Inhibitors for N80 Steel in 3.5% NaCl Solution: Electrochemical, Quantum Chemical, QSAR and Monte Carlo Simulations Studies
Molecules 2015, 20(8), 15122-15146; doi:10.3390/molecules200815122
Received: 28 June 2015 / Revised: 28 July 2015 / Accepted: 30 July 2015 / Published: 18 August 2015
Cited by 15 | PDF Full-text (11175 KB) | HTML Full-text | XML Full-text
Abstract
The inhibition of the corrosion of N80 steel in 3.5 wt. % NaCl solution saturated with CO2 by four porphyrins, namely 5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphyrin (HPTB), 5,10,15,20-tetra(4-pyridyl)-21H,23H-porphyrin (T4PP), 4,4′,4″,4‴-(porphyrin-5,10,15,20-tetrayl)tetrakis(benzoic acid) (THP) and 5,10,15,20-tetraphenyl-21H,23H-porphyrin
[...] Read more.
The inhibition of the corrosion of N80 steel in 3.5 wt. % NaCl solution saturated with CO2 by four porphyrins, namely 5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphyrin (HPTB), 5,10,15,20-tetra(4-pyridyl)-21H,23H-porphyrin (T4PP), 4,4′,4″,4‴-(porphyrin-5,10,15,20-tetrayl)tetrakis(benzoic acid) (THP) and 5,10,15,20-tetraphenyl-21H,23H-porphyrin (TPP) was studied using electrochemical impedance spectroscopy (EIS), potentiodynamic polarization, scanning electrochemical microscopy (SECM) and scanning electron microscopy (SEM) techniques. The results showed that the inhibition efficiency, η% increases with increasing concentration of the inhibitors. The EIS results revealed that the N80 steel surface with adsorbed porphyrins exhibited non-ideal capacitive behaviour with reduced charge transfer activity. Potentiodynamic polarization measurements indicated that the studied porphyrins acted as mixed type inhibitors. The SECM results confirmed the adsorption of the porphyrins on N80 steel thereby forming a relatively insulated surface. The SEM also confirmed the formation of protective films of the porphyrins on N80 steel surface thereby protecting the surface from direct acid attack. Quantum chemical calculations, quantitative structure activity relationship (QSAR) were also carried out on the studied porphyrins and the results showed that the corrosion inhibition performances of the porphyrins could be related to their EHOMO, ELUMO, ω, and μ values. Monte Carlo simulation studies showed that THP has the highest adsorption energy, while T4PP has the least adsorption energy in agreement with the values of σ from quantum chemical calculations. Full article
(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)
Open AccessArticle Laccase Gene Expression and Vinasse Biodegradation by Trametes hirsuta Strain Bm-2
Molecules 2015, 20(8), 15147-15157; doi:10.3390/molecules200815147
Received: 17 June 2015 / Revised: 11 August 2015 / Accepted: 13 August 2015 / Published: 19 August 2015
Cited by 1 | PDF Full-text (1116 KB) | HTML Full-text | XML Full-text
Abstract
Vinasse is the dark-colored wastewater that is generated by bioethanol distilleries from feedstock molasses. The vinasse that is generated from molasses contains high amounts of pollutants, including phenolic compounds and melanoindin. The goal of this work was to study the expression of laccase
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Vinasse is the dark-colored wastewater that is generated by bioethanol distilleries from feedstock molasses. The vinasse that is generated from molasses contains high amounts of pollutants, including phenolic compounds and melanoindin. The goal of this work was to study the expression of laccase genes in the Trametes hirsuta strain Bm-2, isolated in Yucatan, Mexico, in the presence of phenolic compounds, as well as its effectiveness in removing colorants from vinasse. In the presence of all phenolic compounds tested (guaiacol, ferulic acid, and vanillic acid), increased levels of laccase-encoding mRNA were observed. Transcript levels in the presence of guaiacol were 40 times higher than those in the control. The lcc1 and lcc2 genes of T. hirsuta were differentially expressed; guaiacol and vanillin induced the expression of both genes, whereas ferulic acid only induced the expression of lcc2. The discoloration of vinasse was concomitant with the increase in laccase activity. The highest value of enzyme activity (2543.7 U/mL) was obtained in 10% (v/v) vinasse, which corresponded to a 69.2% increase in discoloration. This study demonstrates the potential of the Bm-2 strain of T. hirsuta for the biodegradation of vinasse. Full article
(This article belongs to the Special Issue Biocatalytic Lignin Modification)
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Open AccessArticle Mitochondrial DNA Variation Reveals a Sharp Genetic Break within the Distribution of the Blue Land Crab Cardisoma guanhumi in the Western Central Atlantic
Molecules 2015, 20(8), 15158-15174; doi:10.3390/molecules200815158
Received: 17 June 2015 / Revised: 11 July 2015 / Accepted: 13 July 2015 / Published: 19 August 2015
Cited by 1 | PDF Full-text (1115 KB) | HTML Full-text | XML Full-text
Abstract
The blue land crab Cardisoma guanhumi is widely distributed throughout tropical and subtropical estuarine regions in the Western Central Atlantic (WCA). Patterns of population genetic structure and historical demographics of the species were assessed by mtDNA control region sequence analysis to examine
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The blue land crab Cardisoma guanhumi is widely distributed throughout tropical and subtropical estuarine regions in the Western Central Atlantic (WCA). Patterns of population genetic structure and historical demographics of the species were assessed by mtDNA control region sequence analysis to examine the connectivity among five populations (n = 97) within the region for future conservation strategies and decision-making of fishery management. A total of 234 polymorphic nucleotides were revealed within the sequence region, which have defined 93 distinct haplotypes. No dominant mtDNA haplotypes were found but instead a distribution of a few low-frequency recurrent haplotypes with a large number of singletons. A NJ-tree and a median-joining haplotype network revealed two distinct clusters, corresponding to individuals from estuaries located along the Caribbean Sea and Brazilian waters, respectively. AMOVA and FST statistics supported the hypothesis that two main geographic regions exists. Phylogeographical discontinuity was further demonstrated by the Bayesian assignment analysis and a significant pattern of isolation-by-distance. Additionally, tests of neutral evolution and analysis of mismatch distribution indicate a complex demographic history in the WCA, which corresponds to bottleneck and subsequent population growth. Overall, a sharp genetic break between Caribbean and Brazilian populations raised concerns over the conservation status of the blue land crab. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Characterization of the Sublimation and Vapor Pressure of 2-(2-Nitrovinyl) Furan (G-0) Using Thermogravimetric Analysis: Effects of Complexation with Cyclodextrins
Molecules 2015, 20(8), 15175-15191; doi:10.3390/molecules200815175
Received: 3 July 2015 / Revised: 15 August 2015 / Accepted: 17 August 2015 / Published: 19 August 2015
Cited by 2 | PDF Full-text (2312 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the present work, the sublimation of crystalline solid 2-(2-nitrovinyl) furan (G-0) in the temperature range of 35 to 60 °C (below the melting point of the drug) was studied using thermogravimetric analysis (TGA). The sublimated product was characterized using Fourier-transformed-infrared spectroscopy (FT-IR)
[...] Read more.
In the present work, the sublimation of crystalline solid 2-(2-nitrovinyl) furan (G-0) in the temperature range of 35 to 60 °C (below the melting point of the drug) was studied using thermogravimetric analysis (TGA). The sublimated product was characterized using Fourier-transformed-infrared spectroscopy (FT-IR) and thin layer chromatography (TLC). The sublimation rate at each temperature was obtained using the slope of the linear regression model and followed apparent zero-order kinetics. The sublimation enthalpy from 35 to 60 °C was obtained from the Eyring equation. The Gückel method was used to estimate the sublimation rate and vapor pressure at 25 °C. Physical mixtures, kneaded and freeze-dried complexes were prepared with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutyl ether-β-cyclodextrin (SBE-β-CD) and analyzed using isothermal TGA at 50 °C. The complexation contributed to reducing the sublimation process. The best results were achieved using freeze-dried complexes with both cyclodextrins. Full article
(This article belongs to the collection Poorly Soluble Drugs)
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Open AccessArticle A New Ionone Glycoside and Three New Rhemaneolignans from the Roots of Rehmannia glutinosa
Molecules 2015, 20(8), 15192-15201; doi:10.3390/molecules200815192
Received: 25 June 2015 / Revised: 13 August 2015 / Accepted: 14 August 2015 / Published: 20 August 2015
Cited by 4 | PDF Full-text (1199 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new ionone glycoside, frehmaglutoside I (1), and three new rhemaneolignans AC (24) were isolated from the 95% EtOH extract of the roots of Rehmannia glutinosa. Their structures were determined by extensive spectroscopic (UV, IR,
[...] Read more.
A new ionone glycoside, frehmaglutoside I (1), and three new rhemaneolignans AC (24) were isolated from the 95% EtOH extract of the roots of Rehmannia glutinosa. Their structures were determined by extensive spectroscopic (UV, IR, HR-ESI-MS, 1D and 2D NMR) analyses. In addition, these compounds were evaluated for their protective effects on cardiocytes impaired by doxorubicin in H9c2 cells. Among them, compounds 13 exhibited protective effects against DOX-induced cardiotoxicity. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis and Evaluation of Selected Benzimidazole Derivatives as Potential Antimicrobial Agents
Molecules 2015, 20(8), 15206-15223; doi:10.3390/molecules200815206
Received: 28 June 2015 / Revised: 9 August 2015 / Accepted: 10 August 2015 / Published: 20 August 2015
Cited by 12 | PDF Full-text (782 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A library of 53 benzimidazole derivatives, with substituents at positions 1, 2 and 5, were synthesized and screened against a series of reference strains of bacteria and fungi of medical relevance. The SAR analyses of the most promising results showed that the antimicrobial
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A library of 53 benzimidazole derivatives, with substituents at positions 1, 2 and 5, were synthesized and screened against a series of reference strains of bacteria and fungi of medical relevance. The SAR analyses of the most promising results showed that the antimicrobial activity of the compounds depended on the substituents attached to the bicyclic heterocycle. In particular, some compounds displayed antibacterial activity against two methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentrations (MICs) comparable to the widely-used drug ciprofloxacin. The compounds have some common features; three possess 5-halo substituents; two are derivatives of (S)-2-ethanaminebenzimidazole; and the others are derivatives of one 2-(chloromethyl)-1H-benzo[d]imidazole and (1H-benzo[d]imidazol-2-yl)methanethiol. The results from the antifungal screening were also very interesting: 23 compounds exhibited potent fungicidal activity against the selected fungal strains. They displayed equivalent or greater potency in their MIC values than amphotericin B. The 5-halobenzimidazole derivatives could be considered promising broad-spectrum antimicrobial candidates that deserve further study for potential therapeutic applications. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Ultrasound-Assisted Aqueous Two-Phase System for Extraction and Enrichment of Zanthoxylum armatum Lignans
Molecules 2015, 20(8), 15273-15286; doi:10.3390/molecules200815273
Received: 16 June 2015 / Revised: 2 August 2015 / Accepted: 17 August 2015 / Published: 20 August 2015
Cited by 8 | PDF Full-text (1116 KB) | HTML Full-text | XML Full-text
Abstract
In the study, an aqueous two phase system (ATPS) coupled with ultrasound was employed to extract lignans from Zanthoxylum armatum. Three standard lignans, namely (−)-fargesin, sesamin and L-asarinin, were used as marker compounds, and extraction was optimized and projected by response surface
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In the study, an aqueous two phase system (ATPS) coupled with ultrasound was employed to extract lignans from Zanthoxylum armatum. Three standard lignans, namely (−)-fargesin, sesamin and L-asarinin, were used as marker compounds, and extraction was optimized and projected by response surface methodology (RSM) and artificial neural network (ANN). The optimal condition for ATPS with 20% n-propanol and 24% (NH4)2SO4 coupled with ultrasonic-assisted extraction including a solvent to solid ratio of 15:1, a temperature of 40 °C, and a treatment time of 55 min was obtained. Under the condition, the yield of (−)-fargesin increased 15.12%, and the purities of (−)-fargesin, sesamin and L-asarinin reached 2.222%, 1.066%, and 1.583%, with an increase of 44.38%, 25.70%, and 26.34% compared to those extracted with 95% ethanol, respectively. Coefficient of the determined (0.9855) and mean squared error (0.0018) of ANN model suggested good fitness and generalization of the ANN. Taken together, the results showed that ultrasonic-assisted ATPS can be a suitable method for extraction and enrichment of lignans from Z. armatum. Full article
(This article belongs to the Special Issue New Technologies for the Recovery of Natural Products)
Open AccessArticle Design and Synthesis of Imidazopyrazolopyridines as Novel Selective COX-2 Inhibitors
Molecules 2015, 20(8), 15287-15303; doi:10.3390/molecules200815287
Received: 22 July 2015 / Revised: 2 August 2015 / Accepted: 6 August 2015 / Published: 21 August 2015
Cited by 3 | PDF Full-text (1444 KB) | HTML Full-text | XML Full-text
Abstract
The usefulness of non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by their gastrointestinal side effects. Non-selective cyclooxygenases inhibitors interfere with both COX-1 and COX-2 isozymes. Since COX-1 mediates cytoprotection of gastric mucosa, its inhibition leads to the undesirable side effects. On the other hand,
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The usefulness of non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by their gastrointestinal side effects. Non-selective cyclooxygenases inhibitors interfere with both COX-1 and COX-2 isozymes. Since COX-1 mediates cytoprotection of gastric mucosa, its inhibition leads to the undesirable side effects. On the other hand, COX-2 is undetectable in normal tissues and selectively induced by inflammatory stimuli. Therefore, it is strongly believed that the therapeutic benefits derive from inhibition of COX-2 only. The presence of a strong connection between reported COX-2 inhibitors and cardiac toxicity encourages medicinal chemists to explore new scaffolds. In the present study, we introduced imidazopyrazolopyridines as new potent and selective COX-2 inhibitors that lack the standard pharmacophoric binding features to hERG. Starting from our lead compound 5a, structure-based drug-design was conducted and more potent analogues were obtained with high COX-2 selectivity and almost full edema protection, in carrageenan-induced edema assay, in case of compound 5e. Increased bulkiness around imidazopyrazolopyridines by adding a substituted phenyl ring(s) afforded less active compounds. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Optimization of Micellar Electrokinetic Chromatography Method for the Simultaneous Determination of Seven Hydrophilic and Four Lipophilic Bioactive Components in Three Salvia Species
Molecules 2015, 20(8), 15304-15318; doi:10.3390/molecules200815304
Received: 4 August 2015 / Revised: 15 August 2015 / Accepted: 18 August 2015 / Published: 21 August 2015
Cited by 4 | PDF Full-text (1062 KB) | HTML Full-text | XML Full-text
Abstract
A micellar electrokinetic chromatography (MEKC) method was developed for the simultaneous determination of seven hydrophilic phenolic acids and four lipophilic tanshinones in three Salvia species. In normal MEKC mode using SDS as surfactant, the investigated 11 compounds could not be well separated. Therefore,
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A micellar electrokinetic chromatography (MEKC) method was developed for the simultaneous determination of seven hydrophilic phenolic acids and four lipophilic tanshinones in three Salvia species. In normal MEKC mode using SDS as surfactant, the investigated 11 compounds could not be well separated. Therefore, several buffer modifiers including β-cyclodextrins (β-CD), ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4) and organic solvents have been added to the buffer solution to improve the separation selectivity. Under the optimized conditions (BGE, 15 mM sodium tetraborate with 10 mM SDS, 5 mM β-CD, 10 mM [bmim]BF4 and 15% ACN (v/v) as additives; buffer pH, 9.8; voltage, 20 kV; temperature, 25 °C), the 11 investigated analytes could achieve baseline separation in 34 min. The proposed MEKC was additionally validated by evaluating the linearity (R2 ≥ 0.9965), LODs (0.27–1.39 μg·mL–1), and recovery (94.26%–105.17%), demonstrating this method was reproducible, accurate and reliable. Moreover, the contents of the 11 compounds in three Salvia species, including S. miltiorrhiza, S. przewalskii and S. castanea were analyzed. The result showed that the established MEKC method was simple and practical for the simultaneous determination of the hydrophilic and lipophilic bioactive components in Salvia species, which could be used to effectively evaluate the quality of these valued medicinal plants. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Aqueous Extract of Tomato (Solanum lycopersicum L.) and Ferulic Acid Reduce the Expression of TNF-α and IL-1β in LPS-Activated Macrophages
Molecules 2015, 20(8), 15319-15329; doi:10.3390/molecules200815319
Received: 8 June 2015 / Revised: 14 August 2015 / Accepted: 17 August 2015 / Published: 21 August 2015
Cited by 14 | PDF Full-text (1028 KB) | HTML Full-text | XML Full-text
Abstract
Acute inflammation is essential for defending the body against pathogens; however, when inflammation becomes chronic, it is harmful to the body and is part of the pathophysiology of various diseases such as Diabetes Mellitus type 2 (DM2) and Cardiovascular Disease (CVD) among others.
[...] Read more.
Acute inflammation is essential for defending the body against pathogens; however, when inflammation becomes chronic, it is harmful to the body and is part of the pathophysiology of various diseases such as Diabetes Mellitus type 2 (DM2) and Cardiovascular Disease (CVD) among others. In chronic inflammation macrophages play an important role, mainly through the secretion of proinflammatory cytokines such as Tumor necrosis factor (TNF)-α and Interleukin (IL)-1β, explained in part by activation of the Toll-like receptor 4 (TLR4), a signaling pathway which culminates in the activation of Nuclear factor (NF)-κB, an important transcription factor in the expression of these proinflammatory genes. On the other hand, the benefits on health of a diet rich in fruit and vegetables are well described. In this work, the effects of aqueous extract of tomato and ferulic acid on the expression of proinflammatory cytokines in LPS activated monocyte-derived THP-1 macrophages were investigated. In addition, using Western blot, we investigated whether the inhibition was due to the interference on activation of NF-κB. We found that both the tomato extract and ferulic acid presented inhibitory activity on the expression of TNF-α and IL-1β cytokine by inhibiting the activation of NF-κB. The current results suggest that tomatoes and ferulic acid may contribute to prevention of chronic inflammatory diseases. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle α-Glucosidase Inhibitors from Vauquelinia corymbosa
Molecules 2015, 20(8), 15330-15342; doi:10.3390/molecules200815330
Received: 4 July 2015 / Revised: 15 August 2015 / Accepted: 18 August 2015 / Published: 21 August 2015
Cited by 6 | PDF Full-text (4048 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The α-glucosidase inhibitory activity of an aqueous extract and compounds from the aerial parts of V. corymbosa was demonstrated with yeast and rat small intestinal α-glucosidases. The aqueous extract inhibited yeast α-glucosidase with a half maximal inhibitory concentration (IC50) of 28.6
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The α-glucosidase inhibitory activity of an aqueous extract and compounds from the aerial parts of V. corymbosa was demonstrated with yeast and rat small intestinal α-glucosidases. The aqueous extract inhibited yeast α-glucosidase with a half maximal inhibitory concentration (IC50) of 28.6 μg/mL. Bioassay-guided fractionation of the extract led to the isolation of several compounds, including one cyanogenic glycoside [prunasin (1)], five flavonoids [(−)-epi-catechin (2), hyperoside (3), isoquercetin (4), quercitrin (5) and quercetin-3-O-(6′′-benzoyl)-β-galactoside (6)] and two simple aromatic compounds [picein (7) and methylarbutin (8)]. The most active compound was 6 with IC50 values of 30 μM in the case of yeast α-glucosidase, and 437 μM in the case of the mammalian enzyme. According to the kinetic analyses performed with rat and yeast enzymes, this compound behaved as mixed-type inhibitor; the calculated inhibition constants (Ki) were 212 and 50 μM, respectively. Molecular docking analyses with yeast and mammalian α-glucosidases revealed that compound 6 bind differently to these enzymes. Altogether, the results of this work suggest that preparations of V. corymbosa might delay glucose absorption in vivo. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle The Influence of Sesquiterpenes from Myrica rubra on the Antiproliferative and Pro-Oxidative Effects of Doxorubicin and Its Accumulation in Cancer Cells
Molecules 2015, 20(8), 15343-15358; doi:10.3390/molecules200815343
Received: 9 July 2015 / Revised: 6 August 2015 / Accepted: 13 August 2015 / Published: 21 August 2015
Cited by 11 | PDF Full-text (1161 KB) | HTML Full-text | XML Full-text
Abstract
The sesquiterpenes β-caryophyllene, β-caryophyllene oxide (CAO), α-humulene (HUM), trans-nerolidol (NER), and valencene (VAL) are substantial components of the essential oil from Myrica rubra leaves which has exhibited significant antiproliferative effects in several intestinal cancer cell lines, with CaCo-2 cells being the most
[...] Read more.
The sesquiterpenes β-caryophyllene, β-caryophyllene oxide (CAO), α-humulene (HUM), trans-nerolidol (NER), and valencene (VAL) are substantial components of the essential oil from Myrica rubra leaves which has exhibited significant antiproliferative effects in several intestinal cancer cell lines, with CaCo-2 cells being the most sensitive. The present study was designed to evaluate the effects of these sesquiterpenes on the efficacy and toxicity of the anticancer drug doxorubicin (DOX) in CaCo-2 cancer cells and in primary culture of rat hepatocytes. Our results showed that HUM, NER, VAL and CAO inhibited proliferation of CaCo-2 cancer cells but they did not affect the viability of hepatocytes. CAO, NER and VAL synergistically potentiated the efficacy of DOX in cancer cells killing. All sesquiterpenes exhibited the ability to selectively increase DOX accumulation in cancer cells and did not affect DOX concentration in hepatocytes. Additionally, CAO and VAL were able to increase the pro-oxidative effect of DOX in CaCo-2 cells. Moreover, CAO mildly ameliorated DOX toxicity in hepatocytes. Based on all results, CAO seems to be the most promising compound for further testing. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle Phenyllactic Acid from Lactobacillus plantarum PromotesAdipogenic Activity in 3T3-L1 Adipocyte via Up-Regulationof PPAR-γ2
Molecules 2015, 20(8), 15359-15373; doi:10.3390/molecules200815359
Received: 21 July 2015 / Revised: 17 August 2015 / Accepted: 19 August 2015 / Published: 24 August 2015
Cited by 1 | PDF Full-text (3108 KB) | HTML Full-text | XML Full-text
Abstract
Synthetic drugs are commonly used to cure various human ailments at present. However, the uses of synthetic drugs are strictly regulated because of their adverse effects. Thus, naturally occurring molecules may be more suitable for curing disease without unfavorable effects. Therefore, we investigated
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Synthetic drugs are commonly used to cure various human ailments at present. However, the uses of synthetic drugs are strictly regulated because of their adverse effects. Thus, naturally occurring molecules may be more suitable for curing disease without unfavorable effects. Therefore, we investigated phenyllactic acid (PLA) from Lactobacillus plantarum with respect to its effects on adipogenic genes and their protein expression in 3T3-L1 pre-adipocytes by qPCR and western blot techniques. PLA enhanced differentiation and lipid accumulation in 3T3-L1 cells at the concentrations of 25, 50, and 100 μM. Maximum differentiation and lipid accumulation were observed at a concentration of 100 μM of PLA, as compared with control adipocytes (p < 0.05). The mRNA and protein expression of PPAR-γ2, C/EBP‑α, adiponectin, fatty acid synthase (FAS), and SREBP-1 were increased by PLA treatment as compared with control adipocytes (p < 0.05). PLA stimulates PPAR-γ mRNA expression in a concentration dependent manner, but this expression was lesser than agonist (2.83 ± 0.014 fold) of PPAR-γ2. Moreover, PLA supplementation enhances glucose uptake in 3T3-L1 pre-adipocytes (11.81 ± 0.17 mM) compared to control adipocytes, but this glucose uptake was lesser than that induced by troglitazone (13.75 ± 0.95 mM) and insulin treatment (15.49 ± 0.20 mM). Hence, we conclude that PLA treatment enhances adipocyte differentiation and glucose uptake via activation of PPAR-γ2, and PLA may thus be the potential candidate for preventing Type 2 Diabetes Mellitus (T2DM). Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Structure-Activity Relationships of the Antitumor C5-Curcuminoid GO-Y030
Molecules 2015, 20(8), 15374-15391; doi:10.3390/molecules200815374
Received: 24 July 2015 / Revised: 19 August 2015 / Accepted: 19 August 2015 / Published: 24 August 2015
Cited by 4 | PDF Full-text (936 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
1,5-Bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (2) was isolated from Curcuma domestica as a curcumin (1)-related compound, which we named C5-curcumin. Intrigued by the potent antitumor activity of C5-curcumin (2)-related 1,5-bisaryl-1,4-pentadiene-3-ones [bis(arylmethylidene)acetones, termed C5-curcuminoids], we previously conducted a structure–activity relationship study of C5-curcuminoids and showed that highly active
[...] Read more.
1,5-Bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (2) was isolated from Curcuma domestica as a curcumin (1)-related compound, which we named C5-curcumin. Intrigued by the potent antitumor activity of C5-curcumin (2)-related 1,5-bisaryl-1,4-pentadiene-3-ones [bis(arylmethylidene)acetones, termed C5-curcuminoids], we previously conducted a structure–activity relationship study of C5-curcuminoids and showed that highly active GO-Y030 [1,5-bis(3,5-bis(methoxymethoxy)phenyl)-1,4-pentadiene-3-one (4)] is the most promising antitumor compound. In this study, a panel of C5-curcuminoids based on GO-Y030, consisting of 30 new and 10 known compounds, was synthesized to elucidate in detail which moiety of GO-Y030 is significant for antitumor activity. The results confirmed that both the cross-conjugated dienone moiety and the 3,5-bis(methoxymethoxy) substituent are important for the antitumor activity. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Fatty Acid Profile of Milk and Cheese from Dairy Cows Supplemented a Diet with Palm Kernel Cake
Molecules 2015, 20(8), 15434-15448; doi:10.3390/molecules200815434
Received: 8 July 2015 / Revised: 11 August 2015 / Accepted: 17 August 2015 / Published: 24 August 2015
Cited by 10 | PDF Full-text (697 KB) | HTML Full-text | XML Full-text
Abstract
Lipid supplements (oilseeds vegetables) are included in ruminant diet to increase its energy density and improve fatty acid composition of milk and consequently of fresh cheese. Milk and cheeses were evaluated from crossbred Holstein × Zebu, fed diets enriched with 0%, 25%, 50%,
[...] Read more.
Lipid supplements (oilseeds vegetables) are included in ruminant diet to increase its energy density and improve fatty acid composition of milk and consequently of fresh cheese. Milk and cheeses were evaluated from crossbred Holstein × Zebu, fed diets enriched with 0%, 25%, 50%, and 75% inclusion levels of palm kernel cake in concentrated supplement, which were supplied daily (3.0 kg). Milk and fresh cheese (p = 0.001) fatty acids C12:0 exhibited quadratic negative values. Milk fatty acids C13:0, C20:0, C18:2t10c12, and C20:2n-6 presented positive quadratic values. The milk C18:2n-6 decreased linearly and in fresh cheese exhibited an increasing linear effect (p = 0.016). However, the fatty acids grouped in milk fat were not affected. The medium-chain fatty acids varied negatively and quadratically (p = 0.045). There was no effect on milk and fresh cheese chemical composition (p > 0.05). The milk fat was increased (p = 0.0065) quadratically (minimum point of 24.7%). Thus, the addition of palm kernel cake to cow diets negatively altered the fatty acid profile, it raises the percentage of lauric (C12) and tridecanoic (C13) acids fat which is not beneficial to human health from a nutraceutical perspective, although it did not influence the atherogenicity index. Full article
(This article belongs to the Section Metabolites)

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Open AccessReview Recent Developments and Biological Activities of N-Substituted Carbazole Derivatives: A Review
Molecules 2015, 20(8), 13496-13517; doi:10.3390/molecules200813496
Received: 22 March 2015 / Revised: 9 June 2015 / Accepted: 24 June 2015 / Published: 23 July 2015
Cited by 17 | PDF Full-text (757 KB) | HTML Full-text | XML Full-text
Abstract
Carbazoles represent an important class of heterocycles. These have been reported to exhibit diverse biological activities such as antimicrobial, antitumor, antiepileptic, antihistaminic, antioxidative, anti-inflammatory, antidiarrhoeal, analgesic, neuroprotective and pancreatic lipase inhibition properties. A series of carbazole derivatives such as N-substituted carbazoles, benzocarbazoles,
[...] Read more.
Carbazoles represent an important class of heterocycles. These have been reported to exhibit diverse biological activities such as antimicrobial, antitumor, antiepileptic, antihistaminic, antioxidative, anti-inflammatory, antidiarrhoeal, analgesic, neuroprotective and pancreatic lipase inhibition properties. A series of carbazole derivatives such as N-substituted carbazoles, benzocarbazoles, furocarbazoles, pyrrolocarbazoles, indolocarbazoles, imidazocarbazoles, etc. have been synthesized. The N-substituted derivatives have gained the attention of researchers due to their therapeutic potential against neurological disorders and cell proliferation. Herein an attempt is made to review the medicinal importance of recently synthesized N-substituted carbazoles. Full article
(This article belongs to the collection Heterocyclic Compounds)
Open AccessReview Glycoprotein Quality Control and Endoplasmic Reticulum Stress
Molecules 2015, 20(8), 13689-13704; doi:10.3390/molecules200813689
Received: 27 April 2015 / Revised: 22 July 2015 / Accepted: 24 July 2015 / Published: 28 July 2015
Cited by 13 | PDF Full-text (1101 KB) | HTML Full-text | XML Full-text
Abstract
The endoplasmic reticulum (ER) supports many cellular processes and performs diverse functions, including protein synthesis, translocation across the membrane, integration into the membrane, folding, and posttranslational modifications including N-linked glycosylation; and regulation of Ca2+ homeostasis. In mammalian systems, the majority of
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The endoplasmic reticulum (ER) supports many cellular processes and performs diverse functions, including protein synthesis, translocation across the membrane, integration into the membrane, folding, and posttranslational modifications including N-linked glycosylation; and regulation of Ca2+ homeostasis. In mammalian systems, the majority of proteins synthesized by the rough ER have N-linked glycans critical for protein maturation. The N-linked glycan is used as a quality control signal in the secretory protein pathway. A series of chaperones, folding enzymes, glucosidases, and carbohydrate transferases support glycoprotein synthesis and processing. Perturbation of ER-associated functions such as disturbed ER glycoprotein quality control, protein glycosylation and protein folding results in activation of an ER stress coping response. Collectively this ER stress coping response is termed the unfolded protein response (UPR), and occurs through the activation of complex cytoplasmic and nuclear signaling pathways. Cellular and ER homeostasis depends on balanced activity of the ER protein folding, quality control, and degradation pathways; as well as management of the ER stress coping response. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessReview Natural Compounds from Saffron and Bear Bile Prevent Vision Loss and Retinal Degeneration
Molecules 2015, 20(8), 13875-13893; doi:10.3390/molecules200813875
Received: 19 June 2015 / Revised: 23 July 2015 / Accepted: 28 July 2015 / Published: 31 July 2015
Cited by 5 | PDF Full-text (2620 KB) | HTML Full-text | XML Full-text
Abstract
All retinal disorders, regardless of their aetiology, involve the activation of oxidative stress and apoptosis pathways. The administration of neuroprotective factors is crucial in all phases of the pathology, even when vision has been completely lost. The retina is one of the most
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All retinal disorders, regardless of their aetiology, involve the activation of oxidative stress and apoptosis pathways. The administration of neuroprotective factors is crucial in all phases of the pathology, even when vision has been completely lost. The retina is one of the most susceptible tissues to reactive oxygen species damage. On the other hand, proper development and functioning of the retina requires a precise balance between the processes of proliferation, differentiation and programmed cell death. The life-or-death decision seems to be the result of a complex balance between pro- and anti-apoptotic signals. It has been recently shown the efficacy of natural products to slow retinal degenerative process through different pathways. In this review, we assess the neuroprotective effect of two compounds used in the ancient pharmacopoeia. On one hand, it has been demonstrated that administration of the saffron constituent safranal to P23H rats, an animal model of retinitis pigmentosa, preserves photoreceptor morphology and number, the capillary network and the visual response. On the other hand, it has been shown that systemic administration of tauroursodeoxycholic acid (TUDCA), the major component of bear bile, to P23H rats preserves cone and rod structure and function, together with their contact with postsynaptic neurons. The neuroprotective effects of safranal and TUDCA make these compounds potentially useful for therapeutic applications in retinal degenerative diseases. Full article
Open AccessReview Nanostructures for the Inhibition of Viral Infections
Molecules 2015, 20(8), 14051-14081; doi:10.3390/molecules200814051
Received: 5 July 2015 / Revised: 21 July 2015 / Accepted: 28 July 2015 / Published: 3 August 2015
Cited by 11 | PDF Full-text (6604 KB) | HTML Full-text | XML Full-text
Abstract
Multivalent interactions are omnipresent in biology and confer biological systems with dramatically enhanced affinities towards different receptors. Such multivalent binding interactions have lately been considered for the development of new therapeutic strategies against bacterial and viral infections. Multivalent polymers, dendrimers, and liposomes have
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Multivalent interactions are omnipresent in biology and confer biological systems with dramatically enhanced affinities towards different receptors. Such multivalent binding interactions have lately been considered for the development of new therapeutic strategies against bacterial and viral infections. Multivalent polymers, dendrimers, and liposomes have successfully targeted pathogenic interactions. While a high synthetic effort was often needed for the development of such therapeutics, the integration of multiple ligands onto nanostructures turned to be a viable alternative. Particles modified with multiple ligands have the additional advantage of creating a high local concentration of binding molecules. This review article will summarize the different nanoparticle-based approaches currently available for the treatment of viral infections. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessReview Graphene-Based Nanomaterials as Efficient Peroxidase Mimetic Catalysts for Biosensing Applications: An Overview
Molecules 2015, 20(8), 14155-14190; doi:10.3390/molecules200814155
Received: 23 June 2015 / Accepted: 27 July 2015 / Published: 4 August 2015
Cited by 25 | PDF Full-text (4063 KB) | HTML Full-text | XML Full-text
Abstract
“Artificial enzymes”, a term coined by Breslow for enzyme mimics is an exciting and promising branch of biomimetic chemistry aiming to imitate the general and essential principles of natural enzymes using a variety of alternative materials including heterogeneous catalysts. Peroxidase enzymes represent a
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“Artificial enzymes”, a term coined by Breslow for enzyme mimics is an exciting and promising branch of biomimetic chemistry aiming to imitate the general and essential principles of natural enzymes using a variety of alternative materials including heterogeneous catalysts. Peroxidase enzymes represent a large family of oxidoreductases that typically catalyze biological reactions with high substrate affinity and specificity under relatively mild conditions and thus offer a wide range of practical applications in many areas of science. The increasing understanding of general principles as well as intrinsic drawbacks such as low operational stability, high cost, difficulty in purification and storage, and sensitivity of catalytic activity towards atmospheric conditions of peroxidases has triggered a dynamic field in nanotechnology, biochemical, and material science that aims at joining the better of three worlds by combining the concept adapted from nature with the processability of catalytically active graphene-based nanomaterials (G-NMs) as excellent peroxidase mimetic catalysts. This comprehensive review discusses an up-to-date synthesis, kinetics, mechanisms, and biosensing applications of a variety of G-NMs that have been explored as promising catalysts to mimic natural peroxidases. Full article
(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)
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Open AccessReview Evolution of Macromolecular Docking Techniques: The Case Study of Nickel and Iron Metabolism in Pathogenic Bacteria
Molecules 2015, 20(8), 14265-14292; doi:10.3390/molecules200814265
Received: 28 April 2015 / Revised: 23 July 2015 / Accepted: 28 July 2015 / Published: 5 August 2015
Cited by 2 | PDF Full-text (10313 KB) | HTML Full-text | XML Full-text
Abstract
The interaction between macromolecules is a fundamental aspect of most biological processes. The computational techniques used to study protein-protein and protein-nucleic acid interactions have evolved in the last few years because of the development of new algorithms that allow the a priori incorporation,
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The interaction between macromolecules is a fundamental aspect of most biological processes. The computational techniques used to study protein-protein and protein-nucleic acid interactions have evolved in the last few years because of the development of new algorithms that allow the a priori incorporation, in the docking process, of experimentally derived information, together with the possibility of accounting for the flexibility of the interacting molecules. Here we review the results and the evolution of the techniques used to study the interaction between metallo-proteins and DNA operators, all involved in the nickel and iron metabolism of pathogenic bacteria, focusing in particular on Helicobacter pylori (Hp). In the first part of the article we discuss the methods used to calculate the structure of complexes of proteins involved in the activation of the nickel-dependent enzyme urease. In the second part of the article, we concentrate on two applications of protein-DNA docking conducted on the transcription factors HpFur (ferric uptake regulator) and HpNikR (nickel regulator). In both cases we discuss the technical expedients used to take into account the conformational variability of the multi-domain proteins involved in the calculations. Full article
(This article belongs to the Special Issue Molecular Docking in Drug Design)
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Open AccessReview Absorption-Enhancing Effects of Bile Salts
Molecules 2015, 20(8), 14451-14473; doi:10.3390/molecules200814451
Received: 19 June 2015 / Revised: 28 July 2015 / Accepted: 31 July 2015 / Published: 10 August 2015
Cited by 19 | PDF Full-text (2307 KB) | HTML Full-text | XML Full-text
Abstract
Bile salts are ionic amphiphilic compounds with a steroid skeleton. Among the most important physiological properties of bile salts are lipid transport by solubilization and transport of some drugs through hydrophobic barriers. Bile salts have been extensively studied to enhance transepithelial permeability for
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Bile salts are ionic amphiphilic compounds with a steroid skeleton. Among the most important physiological properties of bile salts are lipid transport by solubilization and transport of some drugs through hydrophobic barriers. Bile salts have been extensively studied to enhance transepithelial permeability for different marker molecules and drugs. They readily agglomerate at concentrations above their critical micelle concentration (CMC). The mechanism of absorption enhancement by bile salts appears to be complex. The aim of the present article was to review bile salt structure and their application as absorption enhancers and the probable mechanism for increasing permeation based on previous studies. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessReview Synthesis and Consecutive Reactions of α-Azido Ketones: A Review
Molecules 2015, 20(8), 14699-14745; doi:10.3390/molecules200814699
Received: 20 April 2015 / Revised: 29 May 2015 / Accepted: 3 June 2015 / Published: 13 August 2015
Cited by 3 | PDF Full-text (1930 KB) | HTML Full-text | XML Full-text
Abstract
This review paper covers the major synthetic approaches attempted towards the synthesis of α-azido ketones, as well as the synthetic applications/consecutive reactions of α-azido ketones. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessReview Non-Covalent Derivatives: Cocrystals and Eutectics
Molecules 2015, 20(8), 14833-14848; doi:10.3390/molecules200814833
Received: 9 June 2015 / Accepted: 5 August 2015 / Published: 14 August 2015
Cited by 15 | PDF Full-text (695 KB) | HTML Full-text | XML Full-text
Abstract
Non-covalent derivatives (NCDs) are formed by incorporating one (or more) coformer molecule(s) into the matrix of a parent molecule via non-covalent forces. These forces can include ionic forces, Van der Waals forces, hydrogen bonding, lipophilic-lipophilic interactions and pi-pi interactions. NCDs, in both cocrystal
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Non-covalent derivatives (NCDs) are formed by incorporating one (or more) coformer molecule(s) into the matrix of a parent molecule via non-covalent forces. These forces can include ionic forces, Van der Waals forces, hydrogen bonding, lipophilic-lipophilic interactions and pi-pi interactions. NCDs, in both cocrystal and eutectic forms, possess properties that are unique to their supramolecular matrix. These properties include critical product performance factors such as solubility, stability and bioavailability. NCDs have been used to tailor materials for a variety of applications and have the potential to be used in an even broader range of materials and processes. NCDs can be prepared using little or no solvent and none of the reagents typical to synthetic modifications. Thus, NCDs represent a powerfully versatile, environmentally-friendly and cost-effective opportunity. Full article
(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)
Open AccessReview Ethnomedicinal, Phytochemical and Pharmacological Profile of Anthriscus sylvestris as an Alternative Source for Anticancer Lignans
Molecules 2015, 20(8), 15003-15022; doi:10.3390/molecules200815003
Received: 9 July 2015 / Revised: 6 August 2015 / Accepted: 11 August 2015 / Published: 17 August 2015
Cited by 3 | PDF Full-text (755 KB) | HTML Full-text | XML Full-text
Abstract
Anthriscus sylvestris (L.) Hoffm. is a wild herbaceous plant common in most temperate regions. It has been used traditionally to treat headaches, as a tonic, as antitussive, antipyretic, analgesic and diuretic. The plant contains deoxypodophyllotoxin, which is proven to have antitumor and anti-proliferative
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Anthriscus sylvestris (L.) Hoffm. is a wild herbaceous plant common in most temperate regions. It has been used traditionally to treat headaches, as a tonic, as antitussive, antipyretic, analgesic and diuretic. The plant contains deoxypodophyllotoxin, which is proven to have antitumor and anti-proliferative effects, anti-platelet aggregation, antiviral, anti-inflammatory and insecticidal activity. Deoxypodophyllotoxin is considered to be the plant’s most important constituent, because of its pharmacological properties and because it can be converted into epipodophyllotoxin, the main raw material for the semisynthesis of the cytostatic agents etoposide and teniposide. This work summarizes for the first time the results related to the botanical description, distribution and habitat, phytochemical and pharmacological properties and emphasizes the aspects for future biotechnological research to establish its utility in the therapeutic arsenal. Full article
(This article belongs to the Section Natural Products)
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Open AccessReview Optimal Energy Transfer in Light-Harvesting Systems
Molecules 2015, 20(8), 15224-15272; doi:10.3390/molecules200815224
Received: 22 June 2015 / Revised: 3 August 2015 / Accepted: 14 August 2015 / Published: 20 August 2015
Cited by 7 | PDF Full-text (4102 KB) | HTML Full-text | XML Full-text
Abstract
Photosynthesis is one of the most essential biological processes in which specialized pigment-protein complexes absorb solar photons, and with a remarkably high efficiency, guide the photo-induced excitation energy toward the reaction center to subsequently trigger its conversion to chemical energy. In this work,
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Photosynthesis is one of the most essential biological processes in which specialized pigment-protein complexes absorb solar photons, and with a remarkably high efficiency, guide the photo-induced excitation energy toward the reaction center to subsequently trigger its conversion to chemical energy. In this work, we review the principles of optimal energy transfer in various natural and artificial light harvesting systems. We begin by presenting the guiding principles for optimizing the energy transfer efficiency in systems connected to dissipative environments, with particular attention paid to the potential role of quantum coherence in light harvesting systems. We will comment briefly on photo-protective mechanisms in natural systems that ensure optimal functionality under varying ambient conditions. For completeness, we will also present an overview of the charge separation and electron transfer pathways in reaction centers. Finally, recent theoretical and experimental progress on excitation energy transfer, charge separation, and charge transport in artificial light harvesting systems is delineated, with organic solar cells taken as prime examples. Full article
(This article belongs to the Special Issue Light-Harvesting Complexes)
Open AccessReview The Potential Use of Natural and Structural Analogues of Antimicrobial Peptides in the Fight against Neglected Tropical Diseases
Molecules 2015, 20(8), 15392-15433; doi:10.3390/molecules200815392
Received: 13 July 2015 / Revised: 2 August 2015 / Accepted: 10 August 2015 / Published: 24 August 2015
Cited by 10 | PDF Full-text (1661 KB) | HTML Full-text | XML Full-text | Correction
Abstract
Recently, research into the development of new antimicrobial agents has been driven by the increase in resistance to traditional antibiotics and Emerging Infectious Diseases. Antimicrobial peptides (AMPs) are promising candidates as alternatives to current antibiotics in the treatment and prevention of microbial infections.
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Recently, research into the development of new antimicrobial agents has been driven by the increase in resistance to traditional antibiotics and Emerging Infectious Diseases. Antimicrobial peptides (AMPs) are promising candidates as alternatives to current antibiotics in the treatment and prevention of microbial infections. AMPs are produced by all known living species, displaying direct antimicrobial killing activity and playing an important role in innate immunity. To date, more than 2000 AMPs have been discovered and many of these exhibit broad-spectrum antibacterial, antiviral and anti-parasitic activity. Neglected tropical diseases (NTDs) are caused by a variety of pathogens and are particularly wide-spread in low-income and developing regions of the world. Alternative, cost effective treatments are desperately needed to effectively battle these medically diverse diseases. AMPs have been shown to be effective against a variety of NTDs, including African trypanosomes, leishmaniosis and Chagas disease, trachoma and leprosy. In this review, the potential of selected AMPs to successfully treat a variety of NTD infections will be critically evaluated. Full article
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