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Molecules, Volume 21, Issue 10 (October 2016)

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Open AccessArticle Bioactivity of a Novel Glycolipid Produced by a Halophilic Buttiauxella sp. and Improving Submerged Fermentation Using a Response Surface Method
Molecules 2016, 21(10), 1256; doi:10.3390/molecules21101256
Received: 29 August 2016 / Revised: 13 September 2016 / Accepted: 15 September 2016 / Published: 22 September 2016
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Abstract
An antimicrobial glycolipid biosurfactant (GBS), extracted and identified from a marine bacterium, was studied to inhibit pathogenic microorganisms. Production of the GBS was optimized using a statistical method, a response surface method (RSM) with a central composite design (CCD) for obtaining maximum yields
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An antimicrobial glycolipid biosurfactant (GBS), extracted and identified from a marine bacterium, was studied to inhibit pathogenic microorganisms. Production of the GBS was optimized using a statistical method, a response surface method (RSM) with a central composite design (CCD) for obtaining maximum yields on a cost-effective substrate, molasses. The GBS-producing bacterium was identified as Buttiauxella Species in terms of biochemical and molecular characteristics. This compound showed a desirable antimicrobial activity against some pathogens such as E. coli, Bacillus subtilis, Bacillus cereus, Candida albicans, Aspergilus niger, Salmonella enterica. The rheological studies described the stability of the GBS at high values in a range of pH (7–8), temperature (20–60) and salinity (0%–3%). The statistical optimization of GBS fermentation was found to be pH 7, temperature 33 °C, Peptone 1%, NaCl 1% and molasses 1%. The potency of the GBS as an effective antimicrobial agent provides evidence for its use against food and human pathogens. Moreover, favorable production of the GBS in the presence of molasses as a cheap substrate and the feasibility of pilot scale fermentation using an RSM method could expand its uses in food, pharmaceutical products and oil industries. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle Effects of Sanguis Draconis on Perforator Flap Survival in Rats
Molecules 2016, 21(10), 1262; doi:10.3390/molecules21101262
Received: 20 July 2016 / Revised: 14 September 2016 / Accepted: 19 September 2016 / Published: 26 September 2016
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Abstract
Sanguis draconis, a resin known to improve blood circulation, relieve pain, stimulate tissue regeneration, and heal wounds, is widely used in clinical practice. In this study, we prepared an ethanol extract of sanguis draconis (EESD) containing 75.08 mg/g of dracorhodin. The experiment was
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Sanguis draconis, a resin known to improve blood circulation, relieve pain, stimulate tissue regeneration, and heal wounds, is widely used in clinical practice. In this study, we prepared an ethanol extract of sanguis draconis (EESD) containing 75.08 mg/g of dracorhodin. The experiment was carried out on 20 rats that were divided into two groups, a control group (n = 10) and an EESD group (n = 10). All the rats underwent a perforator flap surgery, after which post-operative abdominal compressions of EESD were given to the EESD group for seven days, while the control group received saline. Flap survival percentages were determined after seven days, and were found to be significantly higher in the EESD group than in the control group. Results of laser Doppler flowmetry (LDF) showed that perforator flaps in the EESD group had higher perfusion values than those of the control group. The flap tissues were stained with hematoxylin and eosin, followed by immunohistochemical evaluation. Superoxide dismutase (SOD) expression and micro-vessel development markedly increased in the EESD group, while malondialdehyde (MDA) levels decreased. This is the first study to investigate the effect of sanguis draconis on perforator flap survival. Our results demonstrate that sanguis draconis can improve perforator flap survival in rats by promoting microvessel regeneration and blood perfusion. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessCommunication Identification of Metabolites of 6′-Hydroxy-3,4,5,2′,4′-pentamethoxychalcone in Rats by a Combination of Ultra-High-Performance Liquid Chromatography with Linear Ion Trap-Orbitrap Mass Spectrometry Based on Multiple Data Processing Techniques
Molecules 2016, 21(10), 1266; doi:10.3390/molecules21101266
Received: 20 July 2016 / Revised: 17 September 2016 / Accepted: 19 September 2016 / Published: 22 September 2016
Cited by 4 | PDF Full-text (1202 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, an efficient strategy was established using ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) to profile the in vivo metabolic fate of 6′-hydroxy-3,4,5,2′,4′-pentamethoxychalcone (PTC) in rat urine and feces. The UHPLC-LTQ-Orbitrap method combines the high trapping
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In this study, an efficient strategy was established using ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) to profile the in vivo metabolic fate of 6′-hydroxy-3,4,5,2′,4′-pentamethoxychalcone (PTC) in rat urine and feces. The UHPLC-LTQ-Orbitrap method combines the high trapping capacity and MSn scanning function of the linear ion trap along with accurate mass measurements within 5 ppm and a resolving power of up to 30,000 over a wider dynamic range compared to many other mass spectrometers. In order to reduce the potential interferences of endogenous substances, the post-acquisition processing method including high-resolution extracted ion chromatogram (HREIC) and multiple mass defect filters (MMDF) were developed for metabolite detection. As a result, a total of 60 and 35 metabolites were detected in the urine and feces, respectively. The corresponding in vivo reactions such as methylation, hydroxylation, hydrogenation, decarbonylation, demethylation, dehydration, methylation, demethoxylation, sulfate conjugation, glucuronide conjugation, and their composite reactions were all detected in this study. The result on PTC metabolites significantly expanded the understanding of its pharmacological effects, and could be targets for future studies on the important chemical constituents from herbal medicines. Full article
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Open AccessArticle Cordycepin Induces Apoptosis and Inhibits Proliferation of Human Lung Cancer Cell Line H1975 via Inhibiting the Phosphorylation of EGFR
Molecules 2016, 21(10), 1267; doi:10.3390/molecules21101267
Received: 10 July 2016 / Revised: 13 September 2016 / Accepted: 19 September 2016 / Published: 27 September 2016
Cited by 3 | PDF Full-text (2014 KB) | HTML Full-text | XML Full-text
Abstract
Cordycepin is an active component of the traditional Chinese medicine Cordyceps sinensis and Cordyceps militaris with notable anticancer activity. Though the prominent inhibitory activity was reported in different kinds of cancer cell lines, the concrete mechanisms remain elusive. It was reported that cordycepin
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Cordycepin is an active component of the traditional Chinese medicine Cordyceps sinensis and Cordyceps militaris with notable anticancer activity. Though the prominent inhibitory activity was reported in different kinds of cancer cell lines, the concrete mechanisms remain elusive. It was reported that cordycepin could be converted into tri-phosphates in vivo to confuse a number of enzymes and interfere the normal cell function. For the inhibitory mechanism of EGFR inhibitors and the structure similarity of ATP and tri-phosphated cordycepin, human lung cancer cell line H1975 was employed to investigate the inhibitory effect of cordycepin. The results showed that cordycepin could inhibit cell proliferation and induce apoptosis in a dose-dependent manner. Cell cycle analysis revealed that H1975 cells could be arrested at the G0/G1 phase after cordycepin treatment. The expression levels of apoptosis-related protein Caspase-3 and Bcl-2 and phosphorylated expression levels of EGFR, AKT and ERK1/2 were all decreased compared with the control group stimulated with EGF. However, the protein expression levels of proapoptotic protein Bax and cleaved caspase-3 were increased. These results implied that cordycepin could inhibit cell proliferation and induce apoptosis via the EGFR signaling pathway. Our results indicated that there was potential to seek a novel EGFR inhibitor from cordycepin and its chemical derivatives. Full article
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Open AccessCommunication Palladium-Catalyzed C–H Arylation of 1,2,3-Triazoles
Molecules 2016, 21(10), 1268; doi:10.3390/molecules21101268
Received: 5 August 2016 / Revised: 15 September 2016 / Accepted: 16 September 2016 / Published: 22 September 2016
Cited by 1 | PDF Full-text (457 KB) | HTML Full-text | XML Full-text
Abstract
Palladium(II) acetate, in combination with triphenylphosphine, catalyzes direct arylation of 1,4-disubstituted 1,2,3-triazoles effectively. This C–H arylation reaction provides facile access to fully substituted triazoles with well-defined regiochemistry. Full article
(This article belongs to the Special Issue Reactions of Hydrocarbons and other C‒H Compounds)
Open AccessArticle Efficacy of Pre- and Post-Treatment by Topical Formulations Containing Dissolved and Suspended Silybum marianum against UVB-Induced Oxidative Stress in Guinea Pig and on HaCaT Keratinocytes
Molecules 2016, 21(10), 1269; doi:10.3390/molecules21101269
Received: 18 May 2016 / Revised: 14 September 2016 / Accepted: 17 September 2016 / Published: 22 September 2016
Cited by 1 | PDF Full-text (2790 KB) | HTML Full-text | XML Full-text
Abstract
Plants with high amounts of antioxidants may be a promising therapy for preventing and curing UV-induced oxidative skin damage. The objective of this study was to verify the efficacy of topical formulations containing dissolved and suspended Silybum marianum extract against UVB-induced oxidative stress
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Plants with high amounts of antioxidants may be a promising therapy for preventing and curing UV-induced oxidative skin damage. The objective of this study was to verify the efficacy of topical formulations containing dissolved and suspended Silybum marianum extract against UVB-induced oxidative stress in guinea pig and HaCaT keratinocytes. Herbal extract was dissolved in Transcutol HP (TC) and sucrose-esters were incorporated as penetration enhancers in creams. Biocompatibility of compositions was tested on HeLa cells and HaCaT keratinocytes as in vitro models. Transepidermal water loss (TEWL) tests were performed to prove the safety of formulations in vivo. Drug release of different compositions was assessed by Franz diffusion methods. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and lipid peroxidation (MDA) activities were evaluated before and after UVB irradiation in a guinea pig model and HaCaT cells. Heme oxygenase-1 (HO-1) enzyme activity was measured in the epidermis of guinea pigs treated by different creams before and after UVB irradiation. Treatment with compositions containing silymarin powder (SM) dissolved in TC and sucrose stearate SP 50 or SP 70 resulted in increased activities of all reactive oxygen species (ROS) eliminating enzymes in the case of pre- and post-treatment as well. Reduction in the levels of lipid peroxidation end products was also detected after treatment with these two compositions. Post-treatment was more effective as the increase of the activity of antioxidants was higher. Lower HO-1 enzyme levels were measured in the case of pre- and post-treatment groups compared to control groups. Therefore, this study demonstrates the effectiveness of topical formulations containing silymarin in inhibiting UVB irradiation induced oxidative stress of the skin. Full article
(This article belongs to the Special Issue Silymarin)
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Open AccessArticle Structural Characterization of the Avidin Interactions with Fluorescent Pyrene-Conjugates: 1-Biotinylpyrene and 1-Desthiobiotinylpyrene
Molecules 2016, 21(10), 1270; doi:10.3390/molecules21101270
Received: 24 June 2016 / Revised: 7 September 2016 / Accepted: 17 September 2016 / Published: 27 September 2016
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Abstract
Avidin is a tetrameric protein that belongs to the calycin superfamily. It has been studied mainly because of its extraordinary affinity to biotin, which led to a wide range of applications based on the avidin-biotin system. In the present study, we report the
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Avidin is a tetrameric protein that belongs to the calycin superfamily. It has been studied mainly because of its extraordinary affinity to biotin, which led to a wide range of applications based on the avidin-biotin system. In the present study, we report the first crystal structures of avidin in a complex with two novel fluorescent pyrene derivatives: 1-biotinylpyrene (B9P) and 1-desthiobiotinylpyrene (D9P). The crystal structures were solved by molecular replacement using the coordinates of avidin molecule as a starting model and the final models of avidin/B9P and avidin/D9P were refined to resolutions of 2.0 Å and 2.1 Å, respectively. Our data reveal changes in loop conformation as well as in overall fold and quaternary arrangement of the avidin upon the binding of these fluorescent probes. Moreover, the crystal structures allowed analysis of the details of the interactions between the protein and the pyrene derivatives. Structural description of the complexes will contribute to the design of conjugates for expanding the capabilities of avidin–biotin technology. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessArticle Nanoemulsion Formulations of Fungicide Tebuconazole for Agricultural Applications
Molecules 2016, 21(10), 1271; doi:10.3390/molecules21101271
Received: 26 July 2016 / Revised: 14 September 2016 / Accepted: 17 September 2016 / Published: 26 September 2016
Cited by 2 | PDF Full-text (2770 KB) | HTML Full-text | XML Full-text
Abstract
Tebuconazole (TBZ) nanoemulsions (NEs) were formulated using a low energy method. TBZ composition directly affected the drop size and surface tension of the NE. Water fraction and the organic-to-surfactant-ratio (RO/S) were evaluated in the range of 1–90 and 1–10 wt %,
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Tebuconazole (TBZ) nanoemulsions (NEs) were formulated using a low energy method. TBZ composition directly affected the drop size and surface tension of the NE. Water fraction and the organic-to-surfactant-ratio (RO/S) were evaluated in the range of 1–90 and 1–10 wt %, respectively. The study was carried out with an organic phase (OP) consisting of an acetone/glycerol mixture containing TBZ at a concentration of 5.4 wt % and Tween 80 (TW80) as a nonionic and Agnique BL1754 (AG54) as a mixture of nonionic and anionic surfactants. The process involved a large dilution of a bicontinuous microemulsion (ME) into an aqueous phase (AP). Pseudo-ternary phase diagrams of the OP//TW80//AP and OP//AG54//AP systems at T = 25 °C were determined to map ME regions; these were in the range of 0.49–0.90, 0.01–0.23, and 0.07–0.49 of OP, AP, and surfactant, respectively. Optical microscope images helped confirm ME formation and system viscosity was measured in the range of 25–147 cP. NEs with drop sizes about 9 nm and 250 nm were achieved with TW80 and AG54, respectively. An innovative low-energy method was used to develop nanopesticide TBZ formulations based on nanoemulsion (NE) technology. The surface tension of the studied systems can be lowered 50% more than that of pure water. This study’s proposed low-energy NE formulations may prove useful in sustainable agriculture. Full article
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Open AccessArticle Enhanced Cellular Uptake and Pharmacokinetic Characteristics of Doxorubicin-Valine Amide Prodrug
Molecules 2016, 21(10), 1272; doi:10.3390/molecules21101272
Received: 1 August 2016 / Revised: 9 September 2016 / Accepted: 17 September 2016 / Published: 22 September 2016
Cited by 1 | PDF Full-text (1933 KB) | HTML Full-text | XML Full-text
Abstract
In this study, we synthesized the valine (Val)-conjugated amide prodrug of doxorubicin (DOX) by the formation of amide bonds between DOX and Val. The synthesis of the DOX-Val prodrug was identified by a proton nuclear magnetic resonance (1H-NMR) assay. In the
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In this study, we synthesized the valine (Val)-conjugated amide prodrug of doxorubicin (DOX) by the formation of amide bonds between DOX and Val. The synthesis of the DOX-Val prodrug was identified by a proton nuclear magnetic resonance (1H-NMR) assay. In the MCF-7 cells (human breast adenocarcinoma cell; amino acid transporter–positive cell), the cellular accumulation efficiency of DOX-Val was higher than that of DOX according to the flow cytometry analysis data. Using confocal laser scanning microscopy (CLSM) imaging, it was confirmed that DOX-Val as well as DOX was mainly distributed in the nucleus of cancer cells. DOX-Val was intravenously administered to rats at a dose of 4 mg/kg, and the plasma concentrations of DOX-Val (prodrug) and DOX (formed metabolite) were quantitatively determined. Based on the systemic exposure (represented as area under the curve (AUC) values) of DOX-Val (prodrug) and DOX (formed metabolite), approximately half of DOX-Val seemed to be metabolized into DOX. However, it is expected that the remaining DOX-Val may exert improved cellular uptake efficiency in cancer cells after its delivery to the cancer region. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle The Structure–Antimicrobial Activity Relationships of a Promising Class of the Compounds Containing the N-Arylpiperazine Scaffold
Molecules 2016, 21(10), 1274; doi:10.3390/molecules21101274
Received: 10 August 2016 / Revised: 18 September 2016 / Accepted: 19 September 2016 / Published: 26 September 2016
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Abstract
This research was focused on in silico characterization and in vitro biological testing of the series of the compounds carrying a N-arylpiperazine moiety. The in silico investigation was based on the prediction of electronic, steric and lipohydrophilic features. The molecules were screened
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This research was focused on in silico characterization and in vitro biological testing of the series of the compounds carrying a N-arylpiperazine moiety. The in silico investigation was based on the prediction of electronic, steric and lipohydrophilic features. The molecules were screened against Mycobacterium avium subsp. paratuberculosis CIT03, M. smegmatis ATCC 700084, M. kansasii DSM 44162, M. marinum CAMP 5644, Staphylococcus aureus ATCC 29213, methicillin-resistant S. aureus 63718, Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29212, Candida albicans CCM 8261, C. parapsilosis CCM 8260 and C. krusei CCM 8271, respectively, by standardized microdilution methods. The eventual antiproliferative (cytotoxic) impact of those compounds was examined on a human monocytic leukemia THP-1 cell line, as a part of the biological study. Promising potential against M. kansasii was found for 1-[3-(3-ethoxyphenylcarbamoyl)oxy-2-hydroxypropyl]-4-(3-trifluoromethylphenyl)piperazin-1-ium chloride (MIC = 31.75 μM), which was comparable to the activity of isoniazid (INH; MIC = 29.17 μM). Moreover, 1-{2-hydroxy-3-(3-methoxyphenylcarbamoyl)oxy)propyl}-4-(4-fluorophenyl)piperazin-1-ium chloride was even more effective (MIC = 17.62 μM) against given mycobacterium. Among the tested N-arylpiperazines, 1-{2-hydroxy-3-(4-methoxyphenylcarbamoyl)oxy)propyl}-4-(3-trifluorometh-ylphenyl)piperazin-1-ium chloride was the most efficient against M. marinum (MIC = 65.32 μM). One of the common features of all investigated substances was their insignificant antiproliferative (i.e., non-cytotoxic) effect. The study discussed structure–antimicrobial activity relationships considering electronic, steric and lipophilic properties. Full article
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Open AccessArticle Analysis of Flavonoids in Rhamnus davurica and Its Antiproliferative Activities
Molecules 2016, 21(10), 1275; doi:10.3390/molecules21101275
Received: 28 July 2016 / Revised: 18 September 2016 / Accepted: 21 September 2016 / Published: 23 September 2016
Cited by 5 | PDF Full-text (1748 KB) | HTML Full-text | XML Full-text
Abstract
Rhamnus davurica Pall. (R. davurica) has been used as a traditional medicinal herb for many years in China and abroad. It has been well documented as a rich source of flavonoids with diversified structures, which in turn results in far-ranging biological
[...] Read more.
Rhamnus davurica Pall. (R. davurica) has been used as a traditional medicinal herb for many years in China and abroad. It has been well documented as a rich source of flavonoids with diversified structures, which in turn results in far-ranging biological activities, such as anti-inflammation, anticancer, antibacterial and antioxidant activities. In order to further correlate their anticancer potentials with the phytochemical components, the fingerprint profile of R. davurica herb from Dongbei was firstly investigated using HPLC-ESI-MS/MS. Thirty two peaks were detected and identified, 14 of which were found in R. davurica for the first time in this work. Furthermore, a total of 23 peaks were resolved as flavonoids, which are the major components found in R. davurica. Meanwhile, the antiproliferative activities against human cancer cells of HT-29 and SGC-7901 in vitro exhibited distinct inhibitory effects with IC50 values at 24.96 ± 0.74 and 89.53 ± 4.11 μg/mL, respectively. Finally, the general toxicity against L-O2 cells displayed a much higher IC50 at 229.19 ± 8.52 μg/mL, which suggested very low or no toxicity on hepatic cell viability. The current study revealed for the first time the correlations between the flavonoids of R. davurica with their antiproliferative activities, which indicated that the fingerprint profile of flavonoids and their anticancer activities could provide valuable information on the quality control for herbal medicines and their derived natural remedies from this valuable medicinal plant. Full article
(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)
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Open AccessArticle Identification of Nematicidal Constituents of Notopterygium incisum Rhizomes against Bursaphelenchus xylophilus and Meloidogyne incognita
Molecules 2016, 21(10), 1276; doi:10.3390/molecules21101276
Received: 28 July 2016 / Revised: 12 September 2016 / Accepted: 20 September 2016 / Published: 23 September 2016
Cited by 1 | PDF Full-text (389 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
During a screening program for new agrochemicals from Chinese medicinal herbs, the ethanol extract of Notopterygium incisum rhizomes was found to possess strong nematicidal activity against the two species of nematodes, Bursaphelenchus xylophilus and Meloidogyne incognita. Based on bioactivity-guided fractionation, the four
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During a screening program for new agrochemicals from Chinese medicinal herbs, the ethanol extract of Notopterygium incisum rhizomes was found to possess strong nematicidal activity against the two species of nematodes, Bursaphelenchus xylophilus and Meloidogyne incognita. Based on bioactivity-guided fractionation, the four constituents were isolated from the ethanol extract and identified as columbianetin, falcarindiol, falcarinol, and isoimperatorin. Among the four isolated constituents, two acetylenic compounds, falcarindiol and falcarinol (2.20–12.60 μg/mL and 1.06–4.96 μg/mL, respectively) exhibited stronger nematicidal activity than two furanocoumarins, columbianetin, and isoimperatorin (21.83–103.44 μg/mL and 17.21–30.91 μg/mL, respectively) against the two species of nematodes, B. xylophilus and M. incognita. The four isolated constituents also displayed phototoxic activity against the nematodes. The results indicate that the ethanol extract of N. incisum and its four isolated constituents have potential for development into natural nematicides for control of plant-parasitic nematodes. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Theoretical Study on Regioselectivity of the Diels-Alder Reaction between 1,8-Dichloroanthracene and Acrolein
Molecules 2016, 21(10), 1277; doi:10.3390/molecules21101277
Received: 21 August 2016 / Revised: 15 September 2016 / Accepted: 17 September 2016 / Published: 23 September 2016
PDF Full-text (2097 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A theoretical study of the regioselectivity of the Diels-Alder reaction between 1,8-dichloroanthracene and acrolein is performed using DFT at the B3LYP/6-31G(d,p) level of theory. The FMO analysis, global and local reactivity indices confirmed the reported experimental results. Potential energy surface analysis showed that
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A theoretical study of the regioselectivity of the Diels-Alder reaction between 1,8-dichloroanthracene and acrolein is performed using DFT at the B3LYP/6-31G(d,p) level of theory. The FMO analysis, global and local reactivity indices confirmed the reported experimental results. Potential energy surface analysis showed that the cycloadditions (CAs) favor the formation of the anti product. These results are in good agreement with the reported results obtained experimentally where the anti is the major product. Full article
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Open AccessArticle Development of an Innovative Intradermal siRNA Delivery System Using a Combination of a Functional Stearylated Cytoplasm-Responsive Peptide and a Tight Junction-Opening Peptide
Molecules 2016, 21(10), 1279; doi:10.3390/molecules21101279
Received: 29 July 2016 / Revised: 30 August 2016 / Accepted: 17 September 2016 / Published: 24 September 2016
Cited by 1 | PDF Full-text (1767 KB) | HTML Full-text | XML Full-text
Abstract
As a new category of therapeutics for skin diseases including atopic dermatitis (AD), nucleic acids are gaining importance in the clinical setting. Intradermal administration is noninvasive and improves patients′ quality of life. However, intradermal small interfering RNA (siRNA) delivery is difficult because of
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As a new category of therapeutics for skin diseases including atopic dermatitis (AD), nucleic acids are gaining importance in the clinical setting. Intradermal administration is noninvasive and improves patients′ quality of life. However, intradermal small interfering RNA (siRNA) delivery is difficult because of two barriers encountered in the skin: intercellular lipids in the stratum corneum and tight junctions in the stratum granulosum. Tight junctions are the major barrier in AD; therefore, we focused on functional peptides to devise an intradermal siRNA delivery system for topical skin application. In this study, we examined intradermal siRNA permeability in the tape-stripped (20 times) back skin of mice or AD-like skin of auricles treated with 6-carboxyfluorescein-aminohexyl phosphoramidite (FAM)-labeled siRNA, the tight junction modulator AT1002, and the functional cytoplasm-responsive stearylated peptide STR-CH2R4H2C by using confocal laser microscopy. We found that strong fluorescence was observed deep and wide in the epidermis and dermis of back skin and AD-like ears after siRNA with STR-CH2R4H2C and AT1002 treatment. After 10 h from administration, brightness of FAM-siRNA was significantly higher for STR-CH2R4H2C + AT1002, compared to other groups. In addition, we confirmed the nontoxicity of STR-CH2R4H2C as a siRNA carrier using PAM212 cells. Thus, our results demonstrate the applicability of the combination of STR-CH2R4H2C and AT1002 for effective intradermal siRNA delivery. Full article
(This article belongs to the Special Issue Nucleic Acid-based Drug)
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Open AccessArticle Cytoproliferative and Cytoprotective Effects of Striatisporolide A Isolated from Rhizomes of Athyrium multidentatum (Doell.) Ching on Human Umbilical Vein Endothelial Cells
Molecules 2016, 21(10), 1280; doi:10.3390/molecules21101280
Received: 21 August 2016 / Revised: 18 September 2016 / Accepted: 20 September 2016 / Published: 24 September 2016
Cited by 1 | PDF Full-text (915 KB) | HTML Full-text | XML Full-text
Abstract
Objectives: The aim of this study was to investigate the proliferative and protective effects of striatisporolide A (SA) obtained from the rhizomes of Athyrium multidentatum (Doell.) Ching on human umbilical vein endothelial cells (HUVECs). Methods: Cell viability was measured by the
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Objectives: The aim of this study was to investigate the proliferative and protective effects of striatisporolide A (SA) obtained from the rhizomes of Athyrium multidentatum (Doell.) Ching on human umbilical vein endothelial cells (HUVECs). Methods: Cell viability was measured by the MTT method. Cell apoptosis was determined by flow cytometry. Intracellular ROS was measured by the 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe. Results: The viability rate in cells treated with 100 µM SA alone was increased to 128.72% ± 0.19% and showed a significant difference compared with the control group (p < 0.05). Meanwhile, SA augmented the cell viabilities in H2O2-treated HUVECs, and the cell viability was enhanced to 56.94% ± 0.13% (p < 0.01) when pre-incubated with 50 µM SA. The cell apoptosis rates were reduced to 2.17% ± 0.20% (p < 0.05) and 3.1% ± 0.34% (p < 0.01), respectively, after treatment with SA alone or SA/H2O2. SA inhibited the overproduction of reactive oxygen species (ROS) in HUVECs induced by H2O2 and the fluorescent intensity was abated to 9.47 ± 0.61 after pre-incubated with 100 μM SA. Conclusions: The biological activities of SA were explored for the first time. Our results stated that SA exhibited significant cytoproliferative and minor cytoprotective effects on HUVECs. We presume that the mechanisms of the proliferation and protection actions of SA involve interference with the generation of ROS and the cell apoptosis. These findings provide a new perspective on the biological potential of butenolides. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Nanostructured Samarium Doped Fluorapatites and Their Catalytic Activity towards Synthesis of 1,2,4-Triazoles
Molecules 2016, 21(10), 1281; doi:10.3390/molecules21101281
Received: 29 July 2016 / Revised: 16 September 2016 / Accepted: 20 September 2016 / Published: 24 September 2016
Cited by 5 | PDF Full-text (3448 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An investigation was conducted into the influence of the amino acids as organic modifiers in the facile synthesis of metal incorporated fluorapatites (FAp) and their properties. The nanostructured Sm doped fluorapatites (Sm-FAp) were prepared by a co-precipitation method using four different amino acids,
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An investigation was conducted into the influence of the amino acids as organic modifiers in the facile synthesis of metal incorporated fluorapatites (FAp) and their properties. The nanostructured Sm doped fluorapatites (Sm-FAp) were prepared by a co-precipitation method using four different amino acids, namely glutamic acid, aspartic acid, glycine and histidine. The materials were characterized by various techniques including X-ray diffraction (XRD), Fourier transform infra-red spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), high resolution transmission electron microscopy (HR-TEM), N2-adsorption/desorption isotherm, temperature programmed desorption (TPD) and fluorescence spectrophotometry. Under similar conditions, Sm-FAp prepared using different amino acids exhibited distinctly different morphological structures, surface area and pore properties. Their activity as catalysts was assessed and Sm-FAp/Glycine displayed excellent efficiency in the synthesis of 1,2,4-triazole catalyzing the reaction between 2-nitrobenzaldehyde and thiosemicarbazide with exceptional selectivity and 98% yield in a short time interval (10 min). The study provides an insight into the role of organic modifiers as controllers of nucleation, growth and aggregation which significantly influence the nature and activity of the catalytic sites on Sm-FAp. Sm-FAp could also have potential as photoactive material. Full article
(This article belongs to the Section Organometallic Chemistry)
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Open AccessArticle Novel Diterpenoids from the Twigs of Podocarpus nagi
Molecules 2016, 21(10), 1282; doi:10.3390/molecules21101282
Received: 25 August 2016 / Revised: 25 August 2016 / Accepted: 22 September 2016 / Published: 25 September 2016
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Abstract
Phytochemical investigation of the twigs of Podocarpus nagi (Podocarpaceae) led to the isolation of two new abietane-type diterpenoids, named 1β,16-dihydroxylambertic acid (1) and 3β,16-dihydroxylambertic acid (2), along with two new ent-pimarane-type diterpenoids, named ent-2β,15,16,18-tetrahydroxypimar-8(14)-ene (3)
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Phytochemical investigation of the twigs of Podocarpus nagi (Podocarpaceae) led to the isolation of two new abietane-type diterpenoids, named 1β,16-dihydroxylambertic acid (1) and 3β,16-dihydroxylambertic acid (2), along with two new ent-pimarane-type diterpenoids, named ent-2β,15,16,18-tetrahydroxypimar-8(14)-ene (3) and ent-15-oxo-2β,16,18-trihydroxypimar-8(14)-ene (4). Their respective structures were elucidated on the basis of spectroscopic analyses, including 1D- and 2D-NMR, IR, CD, and HR-ESI-MS. This is the first time ent-pimarane-type diterpenoids from the genus Podocarpus has been reported. All four new compounds were tested for cytotoxic activity. The MTT assay results showed that compounds 3 and 4 significantly inhibited the proliferation of human cervical cancer Hela cells, human lung cancer A549 cells, and human breast cancer MCF-7 cells at a concentration of 10 μM. Furthermore, using the lipopolysaccharide (LPS)-stimulated RAW264.7 cells, compounds 2 and 4 were found to significantly inhibit nitrogen oxide (NO) production with IC50 values of 26.5 ± 6.1 and 17.1 ± 1.5 μM, respectively. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Terminamines K–S, Antimetastatic Pregnane Alkaloids from the Whole Herb of Pachysandra terminalis
Molecules 2016, 21(10), 1283; doi:10.3390/molecules21101283
Received: 11 August 2016 / Revised: 12 September 2016 / Accepted: 13 September 2016 / Published: 26 September 2016
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Abstract
Nine new pregnane alkaloids (19), together with eight known alkaloids (1017), were isolated from the whole herb of Pachysandra terminalis. Their structures were elucidated on the basis of spectroscopic analyses. In addition, the isolates
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Nine new pregnane alkaloids (19), together with eight known alkaloids (1017), were isolated from the whole herb of Pachysandra terminalis. Their structures were elucidated on the basis of spectroscopic analyses. In addition, the isolates were examined for their ability to inhibit the migration of MDA-MB-231 cells induced by the chemokine epidermal growth factor (EGF). Alkaloids 1, 5, 7, 9, 12, and 17 presented significant anti-metastasis activities compared with the positive reagent, LY294002. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Improvement of Peptide-Based Tumor Immunotherapy Using pH-Sensitive Fusogenic Polymer-Modified Liposomes
Molecules 2016, 21(10), 1284; doi:10.3390/molecules21101284
Received: 15 July 2016 / Revised: 21 September 2016 / Accepted: 21 September 2016 / Published: 26 September 2016
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Abstract
To establish peptide vaccine-based cancer immunotherapy, we investigated the improvement of antigenic peptides by encapsulation with pH-sensitive fusogenic polymer-modified liposomes for induction of antigen-specific immunity. The liposomes were prepared by modification of egg yolk phosphatidylcholine and l-dioleoyl phosphatidylethanolamine with 3-methyl-glutarylated hyperbranched poly(glycidol)
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To establish peptide vaccine-based cancer immunotherapy, we investigated the improvement of antigenic peptides by encapsulation with pH-sensitive fusogenic polymer-modified liposomes for induction of antigen-specific immunity. The liposomes were prepared by modification of egg yolk phosphatidylcholine and l-dioleoyl phosphatidylethanolamine with 3-methyl-glutarylated hyperbranched poly(glycidol) (MGlu-HPG) and were loaded with antigenic peptides derived from ovalbumin (OVA) OVA-I (SIINFEKL), and OVA-II (PSISQAVHAAHAEINEAPβA), which bind, respectively, to major histocompatibility complex (MHC) class I and class II molecules on dendritic cell (DCs). The peptide-loaded liposomes were taken up efficiently by DCs. The peptides were delivered into their cytosol. Administration of OVA-I-loaded MGlu-HPG-modified liposomes to mice bearing OVA-expressing E.G7-OVA tumors induced the activation of OVA-specific CTLs much more efficiently than the administration of free OVA-I peptide did. Mice strongly rejected E.G7-OVA cells after immunization with OVA-I peptide-loaded MGlu-HPG liposomes, although mice treated with free OVA-I peptide only slightly rejected the cells. Furthermore, efficient suppression of tumor volume was observed when tumor-bearing mice were immunized with OVA-I-peptide-loaded liposomes. Immunization with OVA-II-loaded MGlu-HPG-modified liposomes exhibited much lower tumor-suppressive effects. Results indicate that MGlu-HPG liposomes might be useful for improvement of CTL-inducing peptides for efficient cancer immunotherapy. Full article
(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)
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Open AccessArticle Acacetin Protects Mice from Staphylococcus aureus Bloodstream Infection by Inhibiting the Activity of Sortase A
Molecules 2016, 21(10), 1285; doi:10.3390/molecules21101285
Received: 16 August 2016 / Revised: 20 September 2016 / Accepted: 22 September 2016 / Published: 26 September 2016
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Abstract
Staphylococcus aureus (S. aureus) is a major cause of infection in hospitals and communities. Widespread dissemination of multi-drug resistant S. aureus is a serious threat to the health of humans and animals. An anti-virulence strategy has been widely considered as an
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Staphylococcus aureus (S. aureus) is a major cause of infection in hospitals and communities. Widespread dissemination of multi-drug resistant S. aureus is a serious threat to the health of humans and animals. An anti-virulence strategy has been widely considered as an alternative therapeutic approach. Inhibitors of virulence factors are able to treat S. aureus infections without influencing the growth or viability of bacteria and rarely lead to bacterial resistance. Sortase A (SrtA) is a membrane-associated cysteine transpeptidase that catalyzes up to 25 surface proteins that covalently bind to cell wall peptidoglycans. In S. aureus, most of these surface proteins have been identified as important virulence factors that are vital in bacterial pathogenesis. In the present study, we show that acacetin, a natural flavonoid compound, inhibits the activity of SrtA in S. aureus (IC50 = 36.46 ± 4.69 μg/mL, 128 μM) which affects the assembly of protein A (SpA) to cell walls and reduces the binding of S. aureus to fibrinogen (Fg). The mechanism of the interaction between acacetin and SrtA were preliminarily discussed using molecular dynamics simulations. The results suggested that acacetin adopted a compact conformation binding at the pocket of the SrtA via residues Arg-139 and Lys-140. By performing an animal infection model, we demonstrated that acacetin was able to protect mice from renal abscess formation induced by S. aureus and significantly increased survival rates. Taken together, these findings suggest that acacetin may be a promising candidate for the development of anti-S. aureus drugs. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Anti-Cancer Effect of Quercetin in Xenograft Models with EBV-Associated Human Gastric Carcinoma
Molecules 2016, 21(10), 1286; doi:10.3390/molecules21101286
Received: 13 July 2016 / Revised: 8 September 2016 / Accepted: 13 September 2016 / Published: 26 September 2016
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Abstract
Licorice extracts have been widely used in herbal and folk medications. Glycyrrhiza contains diverse range of biological compounds including triterpenes (glycyrrhizin, glycyrrhizic acid) and flavonoids (quercetin, liquiritin, liquiritigenin, glabridin, licoricidin, isoliquiritigenin). The flavonoids in licorice are known to have strong anti-cancer activities. Quercetin,
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Licorice extracts have been widely used in herbal and folk medications. Glycyrrhiza contains diverse range of biological compounds including triterpenes (glycyrrhizin, glycyrrhizic acid) and flavonoids (quercetin, liquiritin, liquiritigenin, glabridin, licoricidin, isoliquiritigenin). The flavonoids in licorice are known to have strong anti-cancer activities. Quercetin, the most abundant flavonoid, has been shown to have anti-ulcer, anti-cancer, antioxidant, and anti-inflammatory properties. Latent Epstein-Barr virus (EBV) infection can lead to serious malignancies, such as, Burkitt’s lymphoma, Hodgkin’s disease and gastric carcinoma(GC), and (Epstein-Barr virus associated gastric carcinoma) EBVaGC is one of the most common EBV-associated cancers. In this study, the authors first examined the anti-cancer effects of quercetin and isoliquiritigenin in vivo xenograft animal models implanted with EBV(+) human gastric carcinoma (SNU719) or EBV(−) human gastric carcinoma (MKN74), and then explored the molecular mechanisms responsible for their anti-cancer activities. The results obtained showed that anti-cancer effect of quercetin was greater than isoliquiritigenin in mice injected with EBV(+) human gastric carcinoma (SNU719) cells. On the other hand, quercetin and isoliquiritigenin had similar anti-cancer effects in mice injected with EBV(−) human gastric carcinoma (MKN74) cells. Interestingly, quercetin inhibited EBV viral protein expressions, including EBNA-1 and LMP-2 proteins in tumor tissues from mice injected with EBV(+) human gastric carcinoma. Quercetin more effectively induced p53-dependent apoptosis than isoliquiritigenin in EBV(+) human gastric carcinoma, and this induction was correlated with increased expressions of the cleaved forms of caspase-3, -9, and Parp. In EBV(−)human gastric carcinoma (MKN74), both quercetin and isoliquiritigenin induced the expressions of p53, Bax, and Puma and the cleaved forms of caspase-3 and -9 and Parp at similar levels. Full article
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Open AccessArticle Antiprotozoal and Antiglycation Activities of Sesquiterpene Coumarins from Ferula narthex Exudate
Molecules 2016, 21(10), 1287; doi:10.3390/molecules21101287
Received: 23 August 2016 / Revised: 19 September 2016 / Accepted: 22 September 2016 / Published: 26 September 2016
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Abstract
The exudate of Ferula narthex Boiss. (Apiaceae) is widely used in the Indian subcontinent as a spice and because of its health effects. Six sesquiterpene coumarins have been isolated from this exudate: feselol, ligupersin A, asacoumarin A, 8′-O-acetyl-asacoumarin A, 10′R
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The exudate of Ferula narthex Boiss. (Apiaceae) is widely used in the Indian subcontinent as a spice and because of its health effects. Six sesquiterpene coumarins have been isolated from this exudate: feselol, ligupersin A, asacoumarin A, 8′-O-acetyl-asacoumarin A, 10′R-karatavacinol and 10′R-acetyl-karatavacinol. Based on its use in infectious and diabetic conditions, the isolated constituents were evaluated for antimicrobial and antiglycation activities. Some compounds showed activity against protozoal parasites, asacoumarin A being the most active one against Plasmodium falciparum K1 (IC50 1.3 μM). With regard to antiglycation activity, in the BSA-glucose test, ligupersin A displayed the highest activity (IC50 0.41 mM), being more active than the positive control aminiguanidine (IC50 1.75 mM). In the BSA-MGO assay, the highest activity was shown by 8′-O-acetyl-asacoumarin A (IC50 1.03 mM), being less active than aminoguanidine (IC50 0.15 mM). Hence, the antiglycation activity of the isolated constituents was due to both oxidative and non-oxidative modes of inhibition. Full article
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Open AccessArticle CO Oxidation over Pd/ZrO2 Catalysts: Role of Support′s Donor Sites
Molecules 2016, 21(10), 1289; doi:10.3390/molecules21101289
Received: 26 July 2016 / Revised: 21 September 2016 / Accepted: 22 September 2016 / Published: 27 September 2016
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Abstract
A series of supported Pd/ZrO2 catalysts with Pd loading from 0.2 to 2 wt % was synthesized. The ZrO2 material prepared by a similar technique was used as a reference sample. The samples have been characterized by means of transmission electron
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A series of supported Pd/ZrO2 catalysts with Pd loading from 0.2 to 2 wt % was synthesized. The ZrO2 material prepared by a similar technique was used as a reference sample. The samples have been characterized by means of transmission electron microscopy (TEM), X-ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS), temperature-programmed reduction (TPR), testing reaction of ethane hydrogenolysis (HGE), N2 adsorption, and electron paramagnetic resonance (EPR) spectroscopy. 1,3,5-trinitrobenzene was used as a probe molecule for the EPR spin probe method. The catalytic performance of samples was tested in the model reaction of CO oxidation. It was shown that the concentration of donor sites of support measured by EPR spin probe correlates with catalytic behavior during light-off tests. Low concentration of donor sites on a support’s surface was found to be caused by the presence of the specific surface defects that are related to existence of coordinately unsaturated structures. Full article
(This article belongs to the Special Issue Palladium Catalysts 2016)
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Open AccessArticle Design, Synthesis, and Cytotoxicity of 5-Fluoro-2-methyl-6-(4-aryl-piperazin-1-yl) Benzoxazoles
Molecules 2016, 21(10), 1290; doi:10.3390/molecules21101290
Received: 5 August 2016 / Revised: 21 September 2016 / Accepted: 22 September 2016 / Published: 27 September 2016
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Abstract
To design new compounds suitable as starting points for anticancer drug development, we have synthesized a novel series of benzoxazoles with pharmaceutically advantageous piperazine and fluorine moieties attached to them. The newly synthesized benzoxazoles and their corresponding precursors were evaluated for cytotoxicity on
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To design new compounds suitable as starting points for anticancer drug development, we have synthesized a novel series of benzoxazoles with pharmaceutically advantageous piperazine and fluorine moieties attached to them. The newly synthesized benzoxazoles and their corresponding precursors were evaluated for cytotoxicity on human A-549 lung carcinoma cells and non-cancer HepaRG hepatocyes. Some of these new benzoxazoles show potential anticancer activity, while two of the intermediates show lung cancer selective properties at low concentrations where healthy cells are unaffected, indicating a selectivity window for anticancer compounds. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Glycyrrhizic Acid Reduces Heart Rate and Blood Pressure by a Dual Mechanism
Molecules 2016, 21(10), 1291; doi:10.3390/molecules21101291
Received: 7 July 2016 / Revised: 14 September 2016 / Accepted: 22 September 2016 / Published: 27 September 2016
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Abstract
Beta adrenergic receptors are crucial for their role in rhythmic contraction of heart along with their role in the pathological conditions such as tachycardia and high risk of heart failure. Studies report that the levels of beta-1 adrenergic receptor tend to decrease by
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Beta adrenergic receptors are crucial for their role in rhythmic contraction of heart along with their role in the pathological conditions such as tachycardia and high risk of heart failure. Studies report that the levels of beta-1 adrenergic receptor tend to decrease by 50%, whereas, the levels of beta-2 adrenergic receptor remains constant during the risk of heart failure. Beta blockers—the antagonistic molecules for beta-adrenergic receptors, function by slowing the heart rate, which thereby allows the left ventricle to fill completely during tachycardia incidents and hence helps in blood pumping capacity of heart and reducing the risk of heart failure. In the present study, we investigate the potential of glycyrrhizic acid (GA) as a possible principal drug molecule for cardiac arrhythmias owing to its ability to induce reduction in the heart rate and blood pressure. We use in vitro and in silico approach to study GA′s effect on beta adrenergic receptor along with an in vivo study to examine its effect on heart rate and blood pressure. Additionally, we explore GA′s proficiency in eliciting an increase in the plasma levels of vasoactive intestinal peptide, which by dilating the blood vessel consequently, can be a crucial aid during the occurrence of a potential heart attack. Therefore, we propose GA as a potential principal drug molecule via its potential in modulating heart rate and blood pressure. Full article
(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products)
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Open AccessArticle Phytochemical Compositions of Immature Wheat Bran, and Its Antioxidant Capacity, Cell Growth Inhibition, and Apoptosis Induction through Tumor Suppressor Gene
Molecules 2016, 21(10), 1292; doi:10.3390/molecules21101292
Received: 31 August 2016 / Revised: 22 September 2016 / Accepted: 23 September 2016 / Published: 27 September 2016
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Abstract
The purpose of this study was to investigate the phytochemical compositions and antioxidant capacity, cell growth inhibition, and apoptosis induction in extracts of immature wheat bran. Immature wheat bran (IWB) was obtained from immature wheat harvested 10 days earlier than mature wheat. The
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The purpose of this study was to investigate the phytochemical compositions and antioxidant capacity, cell growth inhibition, and apoptosis induction in extracts of immature wheat bran. Immature wheat bran (IWB) was obtained from immature wheat harvested 10 days earlier than mature wheat. The phytochemical compositions of bran extract samples were analyzed by ultra-high performance liquid chromatography. The total ferulic acid (3.09 mg/g) and p-coumaric acid (75 µg/g) in IWB were significantly higher than in mature wheat bran (MWB, ferulic acid: 1.79 mg/g; p-coumaric acid: 55 µg/g). The oxygen radical absorbance capacity (ORAC: 327 µM Trolox equivalents (TE)/g) and cellular antioxidant activity (CAA: 4.59 µM Quercetin equivalents (QE)/g) of the IWB were higher than those of the MWB (ORAC: 281 µM TE/g; CAA: 0.63 µM QE/g). When assessing cell proliferation, the IWB extracts resulted in the lowest EC50 values against HT-29 (18.9 mg/mL), Caco-2 (7.74 mg/mL), and HeLa cells (8.17 mg/mL) among bran extract samples. Additionally, the IWB extracts increased the gene expression of p53 and PTEN (tumor suppressor genes) in HT-29 cells, indicating inhibited cell growth and induced apoptosis through tumor suppressor genes. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Group I Intron Internal Guide Sequence Binding Strength as a Component of Ribozyme Network Formation
Molecules 2016, 21(10), 1293; doi:10.3390/molecules21101293
Received: 17 August 2016 / Revised: 22 September 2016 / Accepted: 23 September 2016 / Published: 27 September 2016
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Abstract
Origins-of-life research requires searching for a plausible transition from simple chemicals to larger macromolecules that can both hold information and catalyze their own production. We have previously shown that some group I intron ribozymes possess the ability to help synthesize other ribozyme genotypes
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Origins-of-life research requires searching for a plausible transition from simple chemicals to larger macromolecules that can both hold information and catalyze their own production. We have previously shown that some group I intron ribozymes possess the ability to help synthesize other ribozyme genotypes by recombination reactions in small networks in an autocatalytic fashion. By simplifying these recombination reactions, using fluorescent anisotropy, we quantified the thermodynamic binding strength between two nucleotides of two group I intron RNA fragments for all 16 possible genotype combinations. We provide evidence that the binding strength (KD) between the 3-nucleotide internal guide sequence (IGS) of one ribozyme and its complement in another is correlated to the catalytic ability of the ribozyme. This work demonstrates that one can begin to deconstruct the thermodynamic basis of information in prebiotic RNA systems. Full article
(This article belongs to the Special Issue Ribozymes and RNA Catalysis)
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Open AccessArticle Enzymatic Synthesis of Glucose-Based Fatty Acid Esters in Bisolvent Systems Containing Ionic Liquids or Deep Eutectic Solvents
Molecules 2016, 21(10), 1294; doi:10.3390/molecules21101294
Received: 26 August 2016 / Revised: 20 September 2016 / Accepted: 20 September 2016 / Published: 27 September 2016
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Abstract
Sugar fatty acid esters (SFAEs) are biocompatible nonionic surfactants with broad applications in food, cosmetic, and pharmaceutical industries. They can be synthesized enzymatically with many advantages over their chemical synthesis. In this study, SFAE synthesis was investigated by using two reactions: (1) transesterification
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Sugar fatty acid esters (SFAEs) are biocompatible nonionic surfactants with broad applications in food, cosmetic, and pharmaceutical industries. They can be synthesized enzymatically with many advantages over their chemical synthesis. In this study, SFAE synthesis was investigated by using two reactions: (1) transesterification of glucose with fatty acid vinyl esters and (2) esterification of methyl glucoside with fatty acids, catalyzed by Lipozyme TLIM and Novozym 435 respectively. Fourteen ionic liquids (ILs) and 14 deep eutectic solvents (DESs) were screened as solvents, and the bisolvent system composed of 1-hexyl-3-methylimidazolium trifluoromethylsulfonate ([HMIm][TfO]) and 2-methyl-2-butanol (2M2B) was the best for both reactions, yielding optimal productivities (769.6 and 397.5 µmol/h/g, respectively) which are superior to those reported in the literature. Impacts of different reaction conditions were studied for both reactions. Response surface methodology (RSM) was employed to optimize the transesterification reaction. Results also demonstrated that as co-substrate, methyl glucoside yielded higher conversions than glucose, and that conversions increased with an increase in the chain length of the fatty acid moieties. DESs were poor solvents for the above reactions presumably due to their high viscosity and high polarity. Full article
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Open AccessArticle Palladium-Catalyzed Allylation/Benzylation of H-Phosphinate Esters with Alcohols
Molecules 2016, 21(10), 1295; doi:10.3390/molecules21101295
Received: 10 September 2016 / Revised: 18 September 2016 / Accepted: 19 September 2016 / Published: 28 September 2016
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Abstract
The Pd-catalyzed direct alkylation of H-phosphinic acids and hypophosphorous acid with allylic/benzylic alcohols has been described previously. Here, the extension of this methodology to H-phosphinate esters is presented. The new reaction appears general, although its scope is narrower than with the
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The Pd-catalyzed direct alkylation of H-phosphinic acids and hypophosphorous acid with allylic/benzylic alcohols has been described previously. Here, the extension of this methodology to H-phosphinate esters is presented. The new reaction appears general, although its scope is narrower than with the acids, and its mechanism is likely different. Various alcohols are examined in their reaction with phosphinylidene compounds R1R2P(O)H. Full article
(This article belongs to the Special Issue Recent Advances in Organophosphorus Chemistry)
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Open AccessArticle Constituents of Cryptotaenia japonica Inhibit Melanogenesis via CREB- and MAPK-Associated Signaling Pathways in Murine B16 Melanoma Cells
Molecules 2016, 21(10), 1296; doi:10.3390/molecules21101296
Received: 16 August 2016 / Revised: 20 September 2016 / Accepted: 23 September 2016 / Published: 28 September 2016
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Abstract
Melanin plays an important role in protecting the skin against ultraviolet light and is responsible for skin color. However, overproduction of melanin is related to several skin disorders, such as age spots, freckles, café au lait spots, Becker’s nevus and other hyperpigmentation syndromes.
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Melanin plays an important role in protecting the skin against ultraviolet light and is responsible for skin color. However, overproduction of melanin is related to several skin disorders, such as age spots, freckles, café au lait spots, Becker’s nevus and other hyperpigmentation syndromes. The aim of this study was to identify the effects of kaempferol-7-O-β-d-glucuronide (K7G) and tilianin, isolated from Cryptotaenia japonica, on melanogenesis and their mechanisms of action in murine B16 melanoma cells. The α-melanocyte-stimulating hormone (α-MSH)-induced melanin production was significantly inhibited by K7G and tilianin in a dose-dependent manner. The effects of these compounds on the signaling pathway of melanogenesis were examined. K7G and tilianin downregulated the expression of microphthalmia-associated transcription factor (MITF) and melanocyte-specific enzymes, i.e., tyrosinase and TRP1. These compounds also inhibited the phosphorylation of cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB) in a dose-dependent manner. In addition, these compounds increased the phosphorylation of extracellular signal-regulated kinase (ERK) but decreased the phosphorylation of c-Jun N-terminal kinase (JNK) in B16 cells. Based on the above results, the anti-melanogenic effects of these compounds are caused by suppression of the MAPK signaling pathway through the down-regulation of α-MSH-induced CREB accumulation. This finding suggests that K7G and tilianin may be good candidates for further research to develop therapeutic agents for hyperpigmentation diseases. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Mining Chromatographic Enantioseparation Data Using Matched Molecular Pair Analysis
Molecules 2016, 21(10), 1297; doi:10.3390/molecules21101297
Received: 13 July 2016 / Revised: 14 September 2016 / Accepted: 16 September 2016 / Published: 29 September 2016
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Abstract
We apply matched molecular pair (MMP) analysis to data from ChirBase, which contains literature reports of chromatographic enantioseparations. For the 19 chiral stationary phases we examined, we were able to identify 289 sets of pairs where there is a statistically significant and consistent
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We apply matched molecular pair (MMP) analysis to data from ChirBase, which contains literature reports of chromatographic enantioseparations. For the 19 chiral stationary phases we examined, we were able to identify 289 sets of pairs where there is a statistically significant and consistent difference in enantioseparation due to a small chemical change. In many cases these changes highlight enantioselectivity differences between pairs or small families of closely related molecules that have for many years been used to probe the mechanisms of chromatographic chiral recognition; for example, the comparison of N-H vs. N-Me analytes to determine the criticality of an N-H hydrogen bond in chiral molecular recognition. In other cases, statistically significant MMPs surfaced by the analysis are less familiar or somewhat puzzling, sparking a need to generate and test hypotheses to more fully understand. Consequently, mining of appropriate datasets using MMP analysis provides an important new approach for studying and understanding the process of chromatographic enantioseparation. Full article
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Open AccessArticle Identification of the Main Intermediate Precursor of l-Ergothioneine Biosynthesis in Human Biological Specimens
Molecules 2016, 21(10), 1298; doi:10.3390/molecules21101298
Received: 18 August 2016 / Revised: 10 September 2016 / Accepted: 23 September 2016 / Published: 28 September 2016
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Abstract
A capillary electrophoresis coupled to tandem mass spectrometry (CE–MS/MS) has been used to make a qualitative determination of hercynine—the main precursor of l-ergothioneine biosynthesis—in some key human biological specimens, such as urine, whole blood, plasma, and saliva. From semiquantitative analysis results, the
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A capillary electrophoresis coupled to tandem mass spectrometry (CE–MS/MS) has been used to make a qualitative determination of hercynine—the main precursor of l-ergothioneine biosynthesis—in some key human biological specimens, such as urine, whole blood, plasma, and saliva. From semiquantitative analysis results, the highest concentrations of hercynine were detected in saliva and whole blood, whereas much lower concentrations were measured in urine and plasma. Whole blood was the biological matrix with the highest concentration of l-ergothioneine followed by plasma, saliva, and urine. The antioxidant effects attributed to l-ergothioneine, along with its peculiar antioxidant mechanism, offer a possible explanation for the presence of the hercynine, as well as its concentration, in the considered biological matrices. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle New Diphenol and Isocoumarins from the Aerial Part of Lawsonia inermis and Their Inhibitory Activities against NO Production
Molecules 2016, 21(10), 1299; doi:10.3390/molecules21101299
Received: 17 August 2016 / Revised: 22 September 2016 / Accepted: 23 September 2016 / Published: 28 September 2016
Cited by 5 | PDF Full-text (1334 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Lawsonia inermis Linn (Lythraceae), also known as henna, is a small shrub or tree distributed throughout Taiwan’s Lanyu Island, in North Africa, and in Australia. Its leaves are used as a folk medicine for the treatment of external hemorrhage and fingernail abscesses. Investigation
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Lawsonia inermis Linn (Lythraceae), also known as henna, is a small shrub or tree distributed throughout Taiwan’s Lanyu Island, in North Africa, and in Australia. Its leaves are used as a folk medicine for the treatment of external hemorrhage and fingernail abscesses. Investigation of the ethyl acetate (EtOAc)-soluble fractions from methanol extract of the aerial part of Lawsonia inermis has led to the isolation of a new diphenol, (Z)-4,4′-(prop-1-ene-1,3-diyl)diphenol (1), two new isocoumarin carbonates, inermiscarbonates A (2) and B (3), and six known compounds, 4′-hydroxyflavanone (4), apigenine (5), kampferol (6), luteolin (7), quercetin (8), and (-)-catechin (9). Their structures were determined by detailed analysis of spectroscopic data and comparison with the data of known analogues. Compounds 1 and 49 were evaluated for the inhibition of nitric oxide production in lipopolysaccharide (LPS)-stimulated product of nitrite in RAW 264.7 cells with IC50 values of 5.63, 15.72, 8.67, 6.67, 6.17, 7.61, and 14.52 μg/mL, respectively. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Flavonoid Interaction with a Chitinase from Grape Berry Skin: Protein Identification and Modulation of the Enzymatic Activity
Molecules 2016, 21(10), 1300; doi:10.3390/molecules21101300
Received: 1 September 2016 / Revised: 20 September 2016 / Accepted: 22 September 2016 / Published: 28 September 2016
Cited by 2 | PDF Full-text (2725 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the present study, an antibody raised against a peptide sequence of rat bilitranslocase (anti-peptide Ab) was tested on microsomal proteins obtained from red grape berry skin. Previously, this antibody had demonstrated to recognize plant membrane proteins associated with flavonoid binding and transport.
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In the present study, an antibody raised against a peptide sequence of rat bilitranslocase (anti-peptide Ab) was tested on microsomal proteins obtained from red grape berry skin. Previously, this antibody had demonstrated to recognize plant membrane proteins associated with flavonoid binding and transport. Immuno-proteomic assays identified a number of proteins reacting with this particular antibody, suggesting that the flavonoid binding and interaction may be extended not only to carriers of these molecules, but also to enzymes with very different functions. One of these proteins is a pathogenesis-related (PR) class IV chitinase, whose in vitro chitinolytic activity was modulated by two of the most representative flavonoids of grape, quercetin and catechin, as assessed by both spectrophotometric and fluorimetric assays in grape microsomes and commercial enzyme preparations. The effect of these flavonoids on the catalysis and its kinetic parameters was also evaluated, evidencing that they determine a hormetic dose-dependent response. These results highlight the importance of flavonoids not only as antioxidants or antimicrobial effectors, but also as modulators of plant growth and stress response. Implications of the present suggestion are here discussed in the light of environment and pesticide-reduction concerns. Full article
(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)
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Open AccessArticle Catalytic Synthesis of a New Series of Alkyl Uronates and Evaluation of Their Physicochemical Properties
Molecules 2016, 21(10), 1301; doi:10.3390/molecules21101301
Received: 27 July 2016 / Revised: 13 September 2016 / Accepted: 22 September 2016 / Published: 28 September 2016
PDF Full-text (2795 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Large quantities (>3 g) of a new series of alkyl uronates were synthesized in two steps from commercial methyl hexopyranosides. Firstly, several tens of grams of free methyl α-d-glucopyranoside were selectively and quantitatively oxidized into corresponding sodium uronate using 2,2,6,6-tetramethyl-1-piperidinyloxy free
[...] Read more.
Large quantities (>3 g) of a new series of alkyl uronates were synthesized in two steps from commercial methyl hexopyranosides. Firstly, several tens of grams of free methyl α-d-glucopyranoside were selectively and quantitatively oxidized into corresponding sodium uronate using 2,2,6,6-tetramethyl-1-piperidinyloxy free radical (TEMPO)-catalyzed oxidation. Hydrophobic chains of different length were then introduced by acid-mediated esterification with fatty alcohols (ethyl to lauryl alcohol) leading to the desired alkyl glucuronates with moderate to good yields (49%–72%). The methodology was successfully applied to methyl α-d-mannopyranoside and methyl β-d-galactopyranoside. Physicochemical properties, such as critical micelle concentration (CMC), equilibrium surface tension at CMC (γcmc), solubility, and Krafft temperature were measured, and the effect of structural modifications on surface active properties and micelle formation was discussed. Full article
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Open AccessArticle Traceability of Satsuma Mandarin (Citrus unshiu Marc.) Honey through Nectar/Honey-Sac/Honey Pathways of the Headspace, Volatiles, and Semi-Volatiles: Chemical Markers
Molecules 2016, 21(10), 1302; doi:10.3390/molecules21101302
Received: 29 August 2016 / Revised: 23 September 2016 / Accepted: 23 September 2016 / Published: 29 September 2016
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Abstract
Headspace solid-phase microextraction (HS-SPME) and ultrasonic solvent extraction (USE), followed by GC-MS/FID, were applied for monitoring the nectar (NE)/honey-sac (HoS)/honey (HO) pathways of the headspace, volatiles, and semi-volatiles. The major NE (4 varieties of Citrus unshiu) headspace compounds were linalool, α-terpineol, 1
[...] Read more.
Headspace solid-phase microextraction (HS-SPME) and ultrasonic solvent extraction (USE), followed by GC-MS/FID, were applied for monitoring the nectar (NE)/honey-sac (HoS)/honey (HO) pathways of the headspace, volatiles, and semi-volatiles. The major NE (4 varieties of Citrus unshiu) headspace compounds were linalool, α-terpineol, 1H-indole, methyl anthranilate, and phenylacetonitrile. Corresponding extracts contained, among others, 1H-indole, methyl anthranilate, 1,3-dihydro-2H-indol-2-one and caffeine. The major HoS headspace compounds were linalool, α-terpineol, 1,8-cineole, 1H-indole, methyl anthranilate, and cis-jasmone. Characteristic compounds from HoS extract were caffeine, 1H-indole, 1,3-dihydro-2H-indol-2-one, methyl anthranilate, and phenylacetonitrile. However, HO headspace composition was significantly different in comparison to NE and HoS with respect to phenylacetaldehyde and linalool derivatives abundance that appeared as the consequence of the hive conditions and the bee enzyme activity. C. unshiu honey traceability is determined by chemical markers: phenylacetaldehyde, phenylacetonitrile, linalool and its derivatives, as well as 1H-indole, 1,3-dihydro-2H-indol-2-one, and caffeine. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Increasing the Level of IRS-1 and Insulin Pathway Sensitivity by Natural Product Carainterol A
Molecules 2016, 21(10), 1303; doi:10.3390/molecules21101303
Received: 1 September 2016 / Revised: 21 September 2016 / Accepted: 23 September 2016 / Published: 29 September 2016
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Abstract
Carainterol A is a eudesmane sesquiterpenoid extracted from Caragana intermedia. We have reported that carainterol A showed potent glucose consumption activity in C2C12 muscle cells and the db/db mouse model. However, the mechanism of the hypoglycemic effect of carainterol
[...] Read more.
Carainterol A is a eudesmane sesquiterpenoid extracted from Caragana intermedia. We have reported that carainterol A showed potent glucose consumption activity in C2C12 muscle cells and the db/db mouse model. However, the mechanism of the hypoglycemic effect of carainterol A remains elusive. In this article, we present a network pharmacology approach to predict the target and signaling pathway of carainterol A which was subsequently validated in HepG2 cells. It was demonstrated that carainterol A could increase the protein levels of IRS-1 and the downstream protein kinase AKT phosphorylation at a low micromolar level. These findings suggest that carainterol A can be a valuable lead compound and a promising chemical probe for the insulin signaling pathway. Full article
(This article belongs to the Section Natural Products)
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Open AccessCommunication Nucleophilic Substitution on 2-Monosubstituted Quinoxalines Giving 2,3-Disubstituted Quinoxalines: Investigating the Effect of the 2-Substituent
Molecules 2016, 21(10), 1304; doi:10.3390/molecules21101304
Received: 30 August 2016 / Revised: 15 September 2016 / Accepted: 23 September 2016 / Published: 30 September 2016
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Abstract
An investigation on the effect of substituent at the 2-position of mono-substituted quinoxalines in the synthesis of di-substituted quinoxaline derivatives via nucleophilic substitution reactions, is reported. Di-substituted quinoxalines bearing aryl-alky, aryl-aryl, aryl-heteroaryl, aryl-alkynyl, and amino-alkyl substituents were prepared in moderate to good yields.
[...] Read more.
An investigation on the effect of substituent at the 2-position of mono-substituted quinoxalines in the synthesis of di-substituted quinoxaline derivatives via nucleophilic substitution reactions, is reported. Di-substituted quinoxalines bearing aryl-alky, aryl-aryl, aryl-heteroaryl, aryl-alkynyl, and amino-alkyl substituents were prepared in moderate to good yields. 2-Monosubstituted quinoxalines bearing a phenyl and butyl substituent reacted readily with alkyl-, aryl-, heteroaryl- and alkynyl- nucluephiles, giving di-substituted quinoxalines. 2-Monosubstituted quinoxalines bearing an amine and alkynyl substituent only reacted with alkyl nucleophiles. Oxidative rearomatization to give 2,3-disubstituted quinoxaline products occurred in atmospheric O2. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Antidermatophytic Action of Resorcinol Derivatives: Ultrastructural Evidence of the Activity of Phenylethyl Resorcinol against Microsporum gypseum
Molecules 2016, 21(10), 1306; doi:10.3390/molecules21101306
Received: 14 July 2016 / Revised: 25 September 2016 / Accepted: 27 September 2016 / Published: 30 September 2016
Cited by 1 | PDF Full-text (1736 KB) | HTML Full-text | XML Full-text
Abstract
In this work, we evaluated the antidermatophytic activities of three resorcinol derivatives that have a history of use in dermo-cosmetic applications to discover molecules with multiple dermatological activities (i.e., multi-target drugs), thereby reducing the cost and time necessary for new drug development. The
[...] Read more.
In this work, we evaluated the antidermatophytic activities of three resorcinol derivatives that have a history of use in dermo-cosmetic applications to discover molecules with multiple dermatological activities (i.e., multi-target drugs), thereby reducing the cost and time necessary for new drug development. The antidermatophytic activities of the three skin lighteners were evaluated relative to the known antifungal drug fluconazole on nine dermatophytes responsible for the most common dermatomycoses: Microsporum gypseum, Microsporum canis, Trichophyton violaceum, Arthroderma cajetani, Trichophyton mentagrophytes, Epidermophyton floccosum, Nannizzia gypsea, Trichophyton rubrum and Trichophyton tonsurans. Among the three tested resorcinols, only two showed promising properties, with the ability to inhibit the growth of all tested dermatophytes; additionally, the IC50 values of these two resorcinols against the nine dermatophytes confirmed their good antifungal activity, particularly for phenylethyl resorcinol against M. gypseum. Ultrastructural alterations exhibited by the fungus were observed using scanning electron microscopy and transmission electron microscopy and reflected a dose-dependent response to treatment with the activation of defence and self-preservation strategies. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Quantitative and Qualitative Analysis of Flavonoids and Phenolic Acids in Snow Chrysanthemum (Coreopsis tinctoria Nutt.) by HPLC-DAD and UPLC-ESI-QTOF-MS
Molecules 2016, 21(10), 1307; doi:10.3390/molecules21101307
Received: 26 August 2016 / Revised: 22 September 2016 / Accepted: 25 September 2016 / Published: 30 September 2016
Cited by 4 | PDF Full-text (2750 KB) | HTML Full-text | XML Full-text
Abstract
A simple, accurate and reliable high performance liquid chromatography coupled with photodiode array detection (HPLC-DAD) method was developed and then successfully applied for simultaneous quantitative analysis of eight compounds, including chlorogenic acid (1), (R/S)-flavanomarein (2),
[...] Read more.
A simple, accurate and reliable high performance liquid chromatography coupled with photodiode array detection (HPLC-DAD) method was developed and then successfully applied for simultaneous quantitative analysis of eight compounds, including chlorogenic acid (1), (R/S)-flavanomarein (2), butin-7-O-β-d-glucopyranoside (3), isookanin (4), taxifolin (5), 5,7,3′,5′-tetrahydroxyflavanone-7-O-β-d-glucopyranoside (6), marein (7) and okanin (8), in 23 batches of snow chrysanthemum of different seed provenance and from various habitats. The results showed total contents of the eight compounds in the samples with seed provenance from Keliyang (Xinjiang, China), are higher than in samples from the other five provenances by 52.47%, 15.53%, 19.78%, 21.17% and 5.06%, respectively, which demonstrated that provenance has a great influence on the constituents in snow chrysanthemum. Meanwhile, an ultra performance liquid chromatography coupled with electrospray ionization and quadrupole time-of-flight-mass spectrometry (UPLC-ESI-QTOF-MS) was also employed to rapidly separate and identify flavonoids and phenolic acids in snow chrysanthemum from Keliyang. As a result, a total of 30 constituents, including 26 flavonoids and four phenolic acids, were identified or tentatively identified based on the exact mass information, the fragmentation characteristics, and retention times of eight reference standards. This work may provide an efficient approach to comprehensively evaluate the quality of snow chrysanthemum. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Re-188 Enhances the Inhibitory Effect of Bevacizumab in Non-Small-Cell Lung Cancer
Molecules 2016, 21(10), 1308; doi:10.3390/molecules21101308
Received: 18 July 2016 / Revised: 24 September 2016 / Accepted: 25 September 2016 / Published: 30 September 2016
Cited by 2 | PDF Full-text (10698 KB) | HTML Full-text | XML Full-text
Abstract
The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, plus chemotherapy or biological therapy can prolong
[...] Read more.
The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC), we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model. Cytotoxic assay data showed that, after 188ReO4 or 188Re-bevacizumab at different concentration for 4 and 24 h, a time- and radioactivity does-dependent reduction in cell viability occurred. Also, an apoptosis assay conformed great apoptosis in the 188Re-bevacizumab group compared with controls and other treatment groups. In vivo, tumor volumes in the 188Re-bevacizumab (11.1 MBq/mice) group were not reduced but growth was delayed compared with other groups. Thus, 188Re-bevacizumab enhanced the therapeutic effect of bevacizumab, suggesting a potential therapeutic strategy for NSCLC treatment. Full article
(This article belongs to the Special Issue Molecular Imaging Probes)
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Open AccessCommunication Synthesis of a 1-Aryl-2,2-chlorosilyl(phospha)silene Coordinated by an N-Heterocyclic Carbene
Molecules 2016, 21(10), 1309; doi:10.3390/molecules21101309
Received: 30 August 2016 / Revised: 22 September 2016 / Accepted: 24 September 2016 / Published: 30 September 2016
Cited by 4 | PDF Full-text (2144 KB) | HTML Full-text | XML Full-text
Abstract
Phosphasilenes, P=Si doubly bonded compounds, have received considerable attention due to their unique physical and chemical properties. We report on the synthesis and structure of a chlorophosphasilene coordinated by an N-heterocyclic carbene (NHC), which has the potential of functionalization at the Si–Cl
[...] Read more.
Phosphasilenes, P=Si doubly bonded compounds, have received considerable attention due to their unique physical and chemical properties. We report on the synthesis and structure of a chlorophosphasilene coordinated by an N-heterocyclic carbene (NHC), which has the potential of functionalization at the Si–Cl moiety. Treatment of a silylphosphine, ArPH–SiCl2RSi (Ar = bulky aryl group, RSi = Si(SiMe3)3) with two equivalents of Im-Me4 (1,3,4,5-tetramethylimidazol-2-ylidene) afforded the corresponding NHC-coordinated phosphasilene, ArP=SiClRSi(Im-Me4) as a stable compound. Bonding properties of the P=Si bond coordinated to an NHC will be discussed on the basis of theoretical calculations. Full article
(This article belongs to the Special Issue Advances in Silicon Chemistry)
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Open AccessArticle Real-Time Detection of a Self-Replicating RNA Enzyme
Molecules 2016, 21(10), 1310; doi:10.3390/molecules21101310
Received: 6 September 2016 / Revised: 25 September 2016 / Accepted: 27 September 2016 / Published: 30 September 2016
Cited by 1 | PDF Full-text (1215 KB) | HTML Full-text | XML Full-text
Abstract
A system was developed to detect the self-replication of an RNA enzyme in real time. The enzyme is an RNA ligase that undergoes exponential amplification at a constant temperature and can be made to operate in a ligand-dependent manner. The real-time system is
[...] Read more.
A system was developed to detect the self-replication of an RNA enzyme in real time. The enzyme is an RNA ligase that undergoes exponential amplification at a constant temperature and can be made to operate in a ligand-dependent manner. The real-time system is based on a fluorimetric readout that directly couples the ligation event to an increase in florescence signal that can be monitored using standard instrumentation. The real-time system can also operate entirely with l-RNA, which is not susceptible to degradation by ribonucleases that are present in biological samples. The system is analogous to real-time PCR, but with the potential to detect small molecules, proteins, and other targets that can be recognized by a suitable aptamer. The ligand-dependent self-replication of RNA has potential applications in molecular diagnostics and biosensing that benefit from the rapid, precise, and real-time detection of various target molecules. Full article
(This article belongs to the Special Issue Ribozymes and RNA Catalysis)
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Open AccessArticle Chlorella sorokiniana Extract Improves Short-Term Memory in Rats
Molecules 2016, 21(10), 1311; doi:10.3390/molecules21101311
Received: 1 August 2016 / Revised: 21 September 2016 / Accepted: 23 September 2016 / Published: 29 September 2016
Cited by 1 | PDF Full-text (1628 KB) | HTML Full-text | XML Full-text
Abstract
Increasing evidence shows that eukaryotic microalgae and, in particular, the green microalga Chlorella, can be used as natural sources to obtain a whole variety of compounds, such as omega (ω)-3 and ω-6 polyunsatured fatty acids (PUFAs). Although either beneficial or toxic effects
[...] Read more.
Increasing evidence shows that eukaryotic microalgae and, in particular, the green microalga Chlorella, can be used as natural sources to obtain a whole variety of compounds, such as omega (ω)-3 and ω-6 polyunsatured fatty acids (PUFAs). Although either beneficial or toxic effects of Chlorella sorokiniana have been mainly attributed to its specific ω-3 and ω-6 PUFAs content, the underlying molecular pathways remain to be elucidated yet. Here, we investigate the effects of an acute oral administration of a lipid extract of Chlorella sorokiniana, containing mainly ω-3 and ω-6 PUFAs, on cognitive, emotional and social behaviour in rats, analysing possible underlying neurochemical alterations. Our results showed improved short-term memory in Chlorella sorokiniana-treated rats compared to controls, without any differences in exploratory performance, locomotor activity, anxiety profile and depressive-like behaviour. On the other hand, while the social behaviour of Chlorella sorokiniana-treated animals was significantly decreased, no effects on aggressivity were observed. Neurochemical investigations showed region-specific effects, consisting in an elevation of noradrenaline (NA) and serotonin (5-HT) content in hippocampus, but not in the prefrontal cortex and striatum. In conclusion, our results point towards a beneficial effect of Chlorella sorokiniana extract on short-term memory, but also highlight the need of caution in the use of this natural supplement due to its possible masked toxic effects. Full article
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Open AccessArticle 2-(2-Phenylethyl)chromone Derivatives of Agarwood Originating from Gyrinops salicifolia
Molecules 2016, 21(10), 1313; doi:10.3390/molecules21101313
Received: 1 September 2016 / Accepted: 26 September 2016 / Published: 3 October 2016
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Abstract
Three new2-(2-phenylethyl)chromone derivatives (1–3) and a new2-(2-phenylethenyl)chromone derivative (4), together with two known 2-(2-phenylethyl)chromone derivatives (5–6), were isolated from agarwood originating from Gyrinops salicifolia Ridl. The structures of compounds 1–4 were elucidated by comprehensive spectroscopic techniques (UV, IR, 1D and 2D-NMR) and MS
[...] Read more.
Three new2-(2-phenylethyl)chromone derivatives (1–3) and a new2-(2-phenylethenyl)chromone derivative (4), together with two known 2-(2-phenylethyl)chromone derivatives (5–6), were isolated from agarwood originating from Gyrinops salicifolia Ridl. The structures of compounds 1–4 were elucidated by comprehensive spectroscopic techniques (UV, IR, 1D and 2D-NMR) and MS analysis, as well as by comparison with the literature. Compounds 1, 2, and 5 showed moderate cytotoxicity against human tumor K562, BEL-7402, and SGC-7901 cell lines with IC50 values of 5.76 to 20.1 µM. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis of Polymer-Lipid Nanoparticles by Microfluidic Focusing for siRNA Delivery
Molecules 2016, 21(10), 1314; doi:10.3390/molecules21101314
Received: 16 July 2016 / Revised: 13 August 2016 / Accepted: 20 September 2016 / Published: 17 October 2016
Cited by 2 | PDF Full-text (3450 KB) | HTML Full-text | XML Full-text
Abstract
Polyethylenimine (PEI) as a cationic polymer is commonly used as a carrier for gene delivery. PEI-800 is less toxic than PEI-25K but it is also less efficient. A novel nanocarrier was developed by combining PEI-800 with a pH-sensitive lipid to form polymer-lipid hybrid
[...] Read more.
Polyethylenimine (PEI) as a cationic polymer is commonly used as a carrier for gene delivery. PEI-800 is less toxic than PEI-25K but it is also less efficient. A novel nanocarrier was developed by combining PEI-800 with a pH-sensitive lipid to form polymer-lipid hybrid nanoparticles (P/LNPs). They were synthesized by microfluidic focusing (MF). Two microfluidic devices were used to synthesize P/LNPs loaded with VEGF siRNA. A series of P/LNPs with different particle sizes and distributions were obtained by altering the flow rate and geometry of microfluidic chips, and introducing sonication. Furthermore, the P/LNPs can be loaded with VEGF siRNA efficiently and were stable in serum for 12 h. Finally, P/LNPs produced by the microfluidic chip showed greater cellular uptake as well as down-regulation of VEGF protein level in both A549 and MCF-7 with reduced cellular toxicity. All in all, the P/LNPs produced by MF method were shown to be a safe and efficient carrier for VEGF siRNA, with potential application for siRNA therapeutics. Full article
(This article belongs to the Special Issue Nucleic Acid-based Drug)
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Open AccessArticle SimCP3—An Advanced Homologue of SimCP2 as a Solution-Processed Small Molecular Host Material for Blue Phosphorescence Organic Light-Emitting Diodes
Molecules 2016, 21(10), 1315; doi:10.3390/molecules21101315
Received: 5 September 2016 / Revised: 24 September 2016 / Accepted: 27 September 2016 / Published: 30 September 2016
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Abstract
We have overcome the synthetic difficulty of 9,9′,9′′,9′′′,9′′′′,9′′′′′-((phenylsilanetriyl)tris(benzene-5,3,1-triyl))hexakis(9H-carbazole) (SimCP3) an advanced homologue of previously known SimCP2 as a solution-processed, high triplet gap energy host material for a blue phosphorescence dopant. A series of organic light-emitting diodes based on blue phosphorescence dopant
[...] Read more.
We have overcome the synthetic difficulty of 9,9′,9′′,9′′′,9′′′′,9′′′′′-((phenylsilanetriyl)tris(benzene-5,3,1-triyl))hexakis(9H-carbazole) (SimCP3) an advanced homologue of previously known SimCP2 as a solution-processed, high triplet gap energy host material for a blue phosphorescence dopant. A series of organic light-emitting diodes based on blue phosphorescence dopant iridium (III) bis(4,6-difluorophenylpyridinato)picolate, FIrpic, were fabricated and tested to demonstrate the validity of solution-processed SimCP3 in the device fabrication. Full article
(This article belongs to the Special Issue Organic Light Emitting Diodes)
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Open AccessArticle A Set of 20 New SSR Markers Developed and Evaluated in Mandevilla Lindl.
Molecules 2016, 21(10), 1316; doi:10.3390/molecules21101316
Received: 12 August 2016 / Revised: 15 September 2016 / Accepted: 22 September 2016 / Published: 30 September 2016
PDF Full-text (2837 KB) | HTML Full-text | XML Full-text
Abstract
Mandevilla is an ornamental crop with a bright future worldwide because of its high commercial acceptance and added value. However, as with most ornamental species, there are few molecular tools to support cultivar breeding and innovation. In this work, we report the development
[...] Read more.
Mandevilla is an ornamental crop with a bright future worldwide because of its high commercial acceptance and added value. However, as with most ornamental species, there are few molecular tools to support cultivar breeding and innovation. In this work, we report the development and analysis of 20 new Simple Sequence Repeat (SSR) markers in Mandevilla. Microsatellites were isolated from two enriched small-insert genomic libraries of Mandevilla × amabilis. The diversity parameters estimated after their amplification in a group of 11 commercial genotypes illustrate the effect of two opposite drifts: the high relatedness of cultivars belonging to the same commercial group and the high divergence of other cultivars, especially M. × amabilis. Based on their different band patterns, six genotypes were uniquely distinguished, and two groups of sport mutations remained undistinguishable. The amplification of the SSRs in three wild species suggested the existence of unexploited diversity available to be introgressed into the commercial pool. This is the first report of available microsatellites in Mandevilla. The development process has provided some clues concerning the genome structure of the species, and the SSRs obtained will help to create new products and to protect existing and upcoming plant innovations. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle A Potential Mechanism for the Anti-Apoptotic Property of Koumine Involving Mitochondrial Pathway in LPS-Mediated RAW 264.7 Macrophages
Molecules 2016, 21(10), 1317; doi:10.3390/molecules21101317
Received: 16 July 2016 / Revised: 19 September 2016 / Accepted: 21 September 2016 / Published: 1 October 2016
Cited by 1 | PDF Full-text (3423 KB) | HTML Full-text | XML Full-text
Abstract
Koumine is a kind of alkaloid extracted from Gelsemium elegans (G. elegans). Benth, which has shown promise as an anti-tumor, anxiolytic, and analgesic agent. In our present study, the effect of koumine on lipopolysaccharide (LPS)-mediated RAW 264.7 cell apoptosis was evaluated.
[...] Read more.
Koumine is a kind of alkaloid extracted from Gelsemium elegans (G. elegans). Benth, which has shown promise as an anti-tumor, anxiolytic, and analgesic agent. In our present study, the effect of koumine on lipopolysaccharide (LPS)-mediated RAW 264.7 cell apoptosis was evaluated. MTT assays showed that koumine obviously increased cell viability in LPS-mediated RAW 264.7 macrophages. Preincubation with koumine ameliorated LPS-medicated apoptosis by decreasing reactive oxygen species (ROS) production, which resulted in a significant decrease in the levels of nitric oxide (NO) and inducible nitric oxide synthase (iNOS). In addition, koumine-pretreated RAW 264.7 macrophages exhibited reduction of LPS-induced levels of TNF-α, IL-1β, and IL-6 mRNA. Furthermore, pretreatment with koumine suppressed LPS-mediated p53 activation, loss of mitochondrial membrane potential, caspase-3 activation, decrease of Bcl-2 expression, and elevation of Bax and caspase-3 expressions, suggesting that koumine might act directly on RAW 264.7 cells to inhibit LPS-induced apoptosis. It seems as though the mechanism that koumine possesses is the anti-apoptotic effect mediated by suppressing production of ROS, activation of p53, and mitochondrial apoptotic pathways in RAW 264 cells. Koumine could potentially serve as a protective effect against LPS-induced apoptosis. Full article
(This article belongs to the Special Issue Natural Products and Inflammation)
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Open AccessArticle Growing and Etching MoS2 on Carbon Nanotube Film for Enhanced Electrochemical Performance
Molecules 2016, 21(10), 1318; doi:10.3390/molecules21101318
Received: 5 September 2016 / Revised: 25 September 2016 / Accepted: 28 September 2016 / Published: 30 September 2016
Cited by 2 | PDF Full-text (3346 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this work we directly synthesized molybdenum disulfide (MoS2) nanosheets on carbon nanotube film (MoS2@CNT) via a two-step chemical vapor deposition method (CVD). By etching the obtained MoS2@CNT into 10% wt HNO3, the morphology of
[...] Read more.
In this work we directly synthesized molybdenum disulfide (MoS2) nanosheets on carbon nanotube film (MoS2@CNT) via a two-step chemical vapor deposition method (CVD). By etching the obtained MoS2@CNT into 10% wt HNO3, the morphology of MoS2 decorated on CNT bundles was modulated, resulting in more catalytic active MoS2 edges being exposed for significantly enhanced electrochemical performance. Our results revealed that an 8 h acid etching sample exhibited the best performance for the oxygen evolution reaction, i.e., the current density reached 10 mA/cm2 under 375 mV over-potential, and the tafel slope was as low as 94 mV/dec. The enhanced behavior was mainly originated from the more catalytic sites in MoS2 induced by the acid etching treatment and the higher conductivity from the supporting CNT films. Our study provides a new route to produce two-dimensional layers on CNT films with tunable morphology, and thus may open a window for exploring its promising applications in the fields of catalytic-, electronic-, and electrochemical-related fields. Full article
(This article belongs to the Special Issue Carbon Nanotubes: Advances and Applications)
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Open AccessArticle Molecular Electron Density Theory: A Modern View of Reactivity in Organic Chemistry
Molecules 2016, 21(10), 1319; doi:10.3390/molecules21101319
Received: 1 July 2016 / Revised: 27 September 2016 / Accepted: 28 September 2016 / Published: 30 September 2016
Cited by 24 | PDF Full-text (2641 KB) | HTML Full-text | XML Full-text
Abstract
A new theory for the study of the reactivity in Organic Chemistry, named Molecular Electron Density Theory (MEDT), is proposed herein. MEDT is based on the idea that while the electron density distribution at the ground state is responsible for physical and chemical
[...] Read more.
A new theory for the study of the reactivity in Organic Chemistry, named Molecular Electron Density Theory (MEDT), is proposed herein. MEDT is based on the idea that while the electron density distribution at the ground state is responsible for physical and chemical molecular properties, as proposed by the Density Functional Theory (DFT), the capability for changes in electron density is responsible for molecular reactivity. Within MEDT, the reactivity in Organic Chemistry is studied through a rigorous quantum chemical analysis of the changes of the electron density as well as the energies associated with these changes along the reaction path in order to understand experimental outcomes. Studies performed using MEDT allow establishing a modern rationalisation and to gain insight into molecular mechanisms and reactivity in Organic Chemistry. Full article
(This article belongs to the Section Theoretical Chemistry)
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Open AccessArticle Fermentation Results and Chemical Composition of Agricultural Distillates Obtained from Rye and Barley Grains and the Corresponding Malts as a Source of Amylolytic Enzymes and Starch
Molecules 2016, 21(10), 1320; doi:10.3390/molecules21101320
Received: 21 July 2016 / Revised: 26 September 2016 / Accepted: 28 September 2016 / Published: 1 October 2016
Cited by 1 | PDF Full-text (1388 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this study was to determine the efficiency of rye and barley starch hydrolysis in mashing processes using cereal malts as a source of amylolytic enzymes and starch, and to establish the volatile profile of the obtained agricultural distillates. In addition,
[...] Read more.
The objective of this study was to determine the efficiency of rye and barley starch hydrolysis in mashing processes using cereal malts as a source of amylolytic enzymes and starch, and to establish the volatile profile of the obtained agricultural distillates. In addition, the effects of the pretreatment method of unmalted cereal grains on the physicochemical composition of the prepared mashes, fermentation results, and the composition of the obtained distillates were investigated. The raw materials used were unmalted rye and barley grains, as well as the corresponding malts. All experiments were first performed on a semi-technical scale, and then verified under industrial conditions in a Polish distillery. The fermentable sugars present in sweet mashes mostly consisted of maltose, followed by glucose and maltotriose. Pressure-thermal treatment of unmalted cereals, and especially rye grains, resulted in higher ethanol content in mashes in comparison with samples subjected to pressureless liberation of starch. All agricultural distillates originating from mashes containing rye and barley grains and the corresponding malts were characterized by low concentrations of undesirable compounds, such as acetaldehyde and methanol. The distillates obtained under industrial conditions contained lower concentrations of higher alcohols (apart from 1-propanol) than those obtained on a semi-technical scale. Full article
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Open AccessArticle Anti-Inflammatory Effects of Aspalathus linearis and Cyclopia spp. Extracts in a UVB/Keratinocyte (HaCaT) Model Utilising Interleukin-1α Accumulation as Biomarker
Molecules 2016, 21(10), 1323; doi:10.3390/molecules21101323
Received: 7 August 2016 / Revised: 16 September 2016 / Accepted: 26 September 2016 / Published: 2 October 2016
Cited by 3 | PDF Full-text (753 KB) | HTML Full-text | XML Full-text
Abstract
Ultraviolet B (UVB) radiation is one of the major predisposing risk factors of skin cancer. The anticancer and photoprotective effects of unoxidized rooibos (Aspalathus linearis) and honeybush (Cyclopia) herbal teas, containing high levels of dihydrochalones and xanthones, respectively, have
[...] Read more.
Ultraviolet B (UVB) radiation is one of the major predisposing risk factors of skin cancer. The anticancer and photoprotective effects of unoxidized rooibos (Aspalathus linearis) and honeybush (Cyclopia) herbal teas, containing high levels of dihydrochalones and xanthones, respectively, have been demonstrated in skin cancer models in vivo. In the current study, the anti-inflammatory effects of methanol and aqueous extracts of these herbal teas were investigated in a UVB/HaCaT keratinocyte model with intracellular interleukin-1α (icIL-1α) accumulation as a biomarker. Extracts of green tea (Camellia sinensis) served as benchmark. Both extracts of green tea and rooibos, as well as the aqueous extract of C. intermedia, enhanced UVB-induced inhibition of cell viability, proliferation and induction of apoptosis, facilitating the removal of icIL-1α. The underlying mechanisms may involve mitochondrial dysfunction exhibiting pro-oxidant responses via polyphenol-iron interactions. The methanol extracts of honeybush, however, protected against UVB-induced reduction of cell growth parameters, presumably via antioxidant mechanisms that prevented the removal of highly inflamed icIL-1α-containing keratinocytes via apoptosis. The dual antioxidant and/or pro-oxidant role of the polyphenolic herbal tea constituents should be considered in developing preventive strategies against UVB-induced skin carcinogenesis. The indirect removal of UVB damaged keratinocytes by herbal tea extracts via apoptosis may find application in the prevention of photo-induced inflammation. Full article
(This article belongs to the Special Issue Natural Products and Inflammation)
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Open AccessArticle Effect of Raw Material, Pressing and Glycosidase on the Volatile Compound Composition of Wine Made From Goji Berries
Molecules 2016, 21(10), 1324; doi:10.3390/molecules21101324
Received: 2 August 2016 / Revised: 27 September 2016 / Accepted: 28 September 2016 / Published: 2 October 2016
Cited by 1 | PDF Full-text (650 KB) | HTML Full-text | XML Full-text
Abstract
This study investigated the effect of raw material, pressing, and glycosidase on the aromatic profile of goji berry wine. The free-run and the pressed juice of dried and fresh goji berries were used for wine production, whereas glycosidase was applied to wine after
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This study investigated the effect of raw material, pressing, and glycosidase on the aromatic profile of goji berry wine. The free-run and the pressed juice of dried and fresh goji berries were used for wine production, whereas glycosidase was applied to wine after fermentation. Dried goji berry fermented wine exhibited much stronger fruity, floral, caramel, and herbaceous odors due to higher levels of esters, β-ionone and methionol. However, fresh berry fermented wine possessed stronger chemical notes due to higher levels of 4-ethylphenol. Pressing treatment reduced the fruity and caramel odors in these fermented wines, and fresh berry free-run juice fermented wine exhibited the least floral aroma. Glycosidase addition did not alter the aromatic composition of wines. The principal component analysis indicated that goji raw material played a primary role in differentiating the aromatic profiles of the wines due to the difference on the content of 20 esters, nine benzenes, eight aldehydes/ketones, three acids, two alcohols and six other volatiles. The content differences on isopentyl alcohol, styrene, benzyl alcohol, 1-octanol, (E)-5-decen-1-ol, 1-hexanol, and β-cyclocitral resulted in the segregation of the wines with and without the pressing treatment, especially for fresh berry fermented wine. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Transformation of Tertiary Benzyl Alcohols into the Vicinal Halo-Substituted Derivatives Using N-Halosuccinimides
Molecules 2016, 21(10), 1325; doi:10.3390/molecules21101325
Received: 31 August 2016 / Revised: 23 September 2016 / Accepted: 27 September 2016 / Published: 2 October 2016
Cited by 1 | PDF Full-text (985 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The efficiency of direct conversion of tertiary alcohols bearing a β-hydrogen atom to vicinal halohydrins—chlorohydrins and bromohydrins—under green reaction conditions was tested preliminarily on model tertiary benzyl alcohols. Tertiary alcohols were successfully directly halogenated to vicinal halohydrins with N-halosuccinimide in aqueous media.
[...] Read more.
The efficiency of direct conversion of tertiary alcohols bearing a β-hydrogen atom to vicinal halohydrins—chlorohydrins and bromohydrins—under green reaction conditions was tested preliminarily on model tertiary benzyl alcohols. Tertiary alcohols were successfully directly halogenated to vicinal halohydrins with N-halosuccinimide in aqueous media. The efficiency of the reaction in water was significantly improved in the presence of sodium dodecyl sulphate as the surfactant. Full article
(This article belongs to the Special Issue Organic Reaction in Green Solvents)
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Open AccessCommunication Quantitative Determination of 3-O-Acetyl-11-Keto-βBoswellic Acid (AKBA) and Other Boswellic Acids in Boswellia sacra Flueck (syn. B. carteri Birdw) and Boswellia serrata Roxb
Molecules 2016, 21(10), 1329; doi:10.3390/molecules21101329
Received: 29 July 2016 / Accepted: 1 October 2016 / Published: 6 October 2016
Cited by 3 | PDF Full-text (433 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Boswellia serrata and Boswellia sacra (syn. B. carteri) are important medicinal plants widely used for their content of bioactive lipophilic triterpenes. The qualitative and quantitative determination of boswellic acids (BAs) is important for their use in dietary supplements aimed to provide a support
[...] Read more.
Boswellia serrata and Boswellia sacra (syn. B. carteri) are important medicinal plants widely used for their content of bioactive lipophilic triterpenes. The qualitative and quantitative determination of boswellic acids (BAs) is important for their use in dietary supplements aimed to provide a support for osteoarthritic and inflammatory diseases. We used High Performance Liquid Chromatography (HPLC)-Diode Array Detector (DAD) coupled to ElectroSpray Ionization and tandem Mass Spectrometry (ESI-MS/MS) for the qualitative and quantitative determination of BAs extracted from the gum resins of B. sacra and B. serrata. Limit of detection (LOD), limit of quantification (LOQ), and Matrix Effect were assessed in order to validate quantitative data. Here we show that the BAs quantitative determination was 491.20 g·kg−1 d. wt (49%) in B. sacra and 295.25 g·kg−1 d. wt (30%) in B. serrata. Lower percentages of BAs content were obtained when BAs were expressed on the gum resin weight (29% and 16% for B. sacra and B. serrata, respectively). The content of Acetyl-11-Keto-β-Boswellic Acid (AKBA) was higher in B. sacra (70.81 g·kg−1 d. wt; 7%) than in B. serrata (7.35 g·kg−1 d. wt; 0.7%). Our results show that any claim of BAs content in either B. sacra or B. serrata gum resins equal to or higher than 70% or AKBA contents of 30% are simply unrealistic or based on a wrong quantitative determination. Full article
(This article belongs to the Special Issue Triterpenes and Triterpenoids 2016)
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Open AccessCommunication Synthesis of Thioethers by InI3-Catalyzed Substitution of Siloxy Group Using Thiosilanes
Molecules 2016, 21(10), 1330; doi:10.3390/molecules21101330
Received: 6 September 2016 / Accepted: 3 October 2016 / Published: 6 October 2016
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Abstract
The substitution of a siloxy group using thiosilanes smoothly occurred in the presence of InI3 catalyst to yield the corresponding thioethers. InI3 was a specifically effective catalyst in this reaction system, while other typical Lewis acids such as BF3⋅OEt
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The substitution of a siloxy group using thiosilanes smoothly occurred in the presence of InI3 catalyst to yield the corresponding thioethers. InI3 was a specifically effective catalyst in this reaction system, while other typical Lewis acids such as BF3⋅OEt2, AlCl3, and TiCl4 were ineffective. Various silyl ethers such as primary alkyl, secondary alkyl, tertiary alkyl, allylic, benzylic, and propargylic types were applicable. In addition, bulky OSitBuMe2 and OSiiPr3 groups, other than the OSiMe3 group, were successfully substituted. The substitution reaction of enantiopure secondary benzylic silyl ether yielded the corresponding racemic thioether product, which suggested that the reaction of tertiary alkyl, secondary alkyl, benzylic, and propargylic silyl ethers would proceed via a SN1 mechanism. Full article
(This article belongs to the Special Issue Advances in Silicon Chemistry)
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Open AccessArticle Inhibition of Uterine Contractility by Thalidomide Analogs via Phosphodiesterase-4 Inhibition and Calcium Entry Blockade
Molecules 2016, 21(10), 1332; doi:10.3390/molecules21101332
Received: 5 August 2016 / Revised: 21 September 2016 / Accepted: 30 September 2016 / Published: 7 October 2016
Cited by 2 | PDF Full-text (3367 KB) | HTML Full-text | XML Full-text
Abstract
Uterine relaxation is crucial during preterm labor. Phosphodiesterase-4 (PDE-4) inhibitors have been proposed as tocolytics. Some thalidomide analogs are PDE-4 inhibitors. The aim of this study was to assess the uterus-relaxant properties of two thalidomide analogs, methyl
3-(4-nitrophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4NO2PDPMe) and methyl
3-(4-aminophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4APDPMe)
[...] Read more.
Uterine relaxation is crucial during preterm labor. Phosphodiesterase-4 (PDE-4) inhibitors have been proposed as tocolytics. Some thalidomide analogs are PDE-4 inhibitors. The aim of this study was to assess the uterus-relaxant properties of two thalidomide analogs, methyl
3-(4-nitrophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4NO2PDPMe) and methyl
3-(4-aminophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4APDPMe) and were compared to rolipram in functional studies of spontaneous phasic, K+-induced tonic, and Ca2+-induced contractions in isolated pregnant human myometrial tissues. The accumulation of cAMP was quantified in HeLa cells. The presence of PDE-4B2 and phosphorylated myosin light-chain (pMLC), in addition to the effect of thalidomide analogs on oxytocin-induced pMLC, were assessed in human uterine myometrial cells (UtSMCs). Thalidomide analogs had concentration-dependent inhibitory effects on spontaneous and tonic contractions and inhibited Ca2+-induced responses. Tonic contraction was equipotently inhibited by 4APDPMe and rolipram (IC50 = 125 ± 13.72 and 98.45 ± 8.86 µM, respectively). Rolipram and the thalidomide analogs inhibited spontaneous and tonic contractions equieffectively. Both analogs increased cAMP accumulation in a concentration-dependent manner (p < 0.05) and induced changes in the subcellular localization of oxytocin-induced pMLC in UtSMCs. The inhibitory effects of thalidomide analogs on the contractions of pregnant human myometrium tissue may be due to their PDE-4 inhibitory effect and novel mechanism as calcium-channel blockers. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Relationship between the Ingestion of a Polyphenol-Rich Drink, Hepcidin Hormone, and Long-Term Training
Molecules 2016, 21(10), 1333; doi:10.3390/molecules21101333
Received: 29 June 2016 / Revised: 28 September 2016 / Accepted: 1 October 2016 / Published: 8 October 2016
Cited by 3 | PDF Full-text (842 KB) | HTML Full-text | XML Full-text
Abstract
The effects of polyphenol-rich foods on the iron status of athletes, as well as the effect of physical training on the hormone hepcidin, implicated in iron metabolism, are not clear. We investigated the influence on iron metabolism of a long-term training intervention of
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The effects of polyphenol-rich foods on the iron status of athletes, as well as the effect of physical training on the hormone hepcidin, implicated in iron metabolism, are not clear. We investigated the influence on iron metabolism of a long-term training intervention of 120 days, measuring the hepcidin concentration in the plasma of 16 elite triathletes, and the effect of the ingestion of 200 mL of either aronia-citrus juice or a placebo drink for 45 days, in a crossover design. The highest plasma hepcidin concentrations were observed at the beginning of the study (116 ± 63 nM) and levels steadily decreased until the end of the intervention (final value 10 ± 7.5 nM). Long-term training might reduce inflammation and, hence, could be responsible for the decrease in hepcidin in triathletes. Polyphenols from aronia-citrus juice did not interfere in iron absorption, as we did not observe significant differences between the intake of the placebo drink or juice with regard to hepcidin levels. Further studies are required to ascertain the time and conditions necessary to restore hepcidin levels, which reflect the iron status of triathletes. Full article
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Open AccessArticle Targeted Delivery of siRNA to Transferrin Receptor Overexpressing Tumor Cells via Peptide Modified Polyethylenimine
Molecules 2016, 21(10), 1334; doi:10.3390/molecules21101334
Received: 15 September 2016 / Revised: 30 September 2016 / Accepted: 4 October 2016 / Published: 10 October 2016
Cited by 5 | PDF Full-text (2813 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The use of small interference RNA (siRNA) to target oncogenes is a promising treatment approach for cancer. However, siRNA cancer therapies are hindered by poor delivery of siRNA to cancer cells. Transferrin receptor (TfR) is overexpressed in many types of tumor cells and
[...] Read more.
The use of small interference RNA (siRNA) to target oncogenes is a promising treatment approach for cancer. However, siRNA cancer therapies are hindered by poor delivery of siRNA to cancer cells. Transferrin receptor (TfR) is overexpressed in many types of tumor cells and therefore is a potential target for the selective delivery of siRNA to cancer cells. Here, we used the TfR binding peptide HAIYPRH (HAI peptide) conjugated to cationic polymer branched polyethylenimine (bPEI), optimized the coupling strategy, and the TfR selective delivery of siRNA was evaluated in cells with high (H1299) and low TfR expression (A549 and H460). The HAI-bPEI conjugate exhibited chemico-physical properties in terms of size, zeta-potential, and siRNA condensation efficiency similar to unmodified bPEI. Confocal microscopy and flow cytometry results revealed that HAI-bPEI selectively delivered siRNA to H1299 cells compared with A549 or H460 cells. Moreover, HAI-bPEI achieved more efficient glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene knockdown in H1299 cells compared with bPEI alone. However, despite optimization of the targeting peptide and coupling strategy, HAI-bPEI can only silence reporter gene enhanced green fluorescent protein (eGFP) at the protein level when chloroquine is present, indicating that further optimization of the conjugate is required. In conclusion, the HAI peptide may be useful to target TfR overexpressing tumors in targeted gene and siRNA delivery approaches. Full article
(This article belongs to the Special Issue Nucleic Acid-based Drug)
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Open AccessArticle Optimization Extraction, Preliminary Characterization and Antioxidant Activities of Polysaccharides from Semen Juglandis
Molecules 2016, 21(10), 1335; doi:10.3390/molecules21101335
Received: 18 August 2016 / Revised: 23 September 2016 / Accepted: 29 September 2016 / Published: 9 October 2016
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Abstract
The optimization extraction process, preliminary characterization and antioxidant activities of polysaccharides from Semen Juglandis (SJP) were studied in this paper. Based on the Box-Behnken experimental design and response surface methodology, the optimal extraction conditions for the SJP extraction were obtained as follows: temperature
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The optimization extraction process, preliminary characterization and antioxidant activities of polysaccharides from Semen Juglandis (SJP) were studied in this paper. Based on the Box-Behnken experimental design and response surface methodology, the optimal extraction conditions for the SJP extraction were obtained as follows: temperature 88 °C, extraction time 125 min and ratio of liquid to solid 31 mL/g. Under these conditions, experimental extraction yield of SJP was (5.73 ± 0.014)% (n = 5), similar to the predicted value of 5.78%. Furtherly, the purified SJP obtained from SJP extract by DEAE-52 and Sephacryl S-100 chromatography was analyzed to be rhamnose, galacturonic acid, galactose, arabinose and fucose in the molar ratio of 1:6.34:1.38:3.21:1.56. And the weight-average molecular weight and radius of gyration of the purified SJP in 0.1 M NaCl were determined to be 2.76 × 104 g/mol and 122 nm by SEC-MALLS, respectively. More importantly, it exhibited appreciable antioxidant activities compared to the standard Vc, such as DPPH radical scavenging activity (IC50 0.21 mg/mL), strong reducing power, ABTS radical scavenging activity (IC50 0.29 mg/mL), and hydroxyl radical scavenging activity (IC50 0.38 mg/mL). These results indicate that SJP may be useful for developing functional health products or natural antioxidant. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis of Pyrazole-Thiobarbituric Acid Derivatives: Antimicrobial Activity and Docking Studies
Molecules 2016, 21(10), 1337; doi:10.3390/molecules21101337
Received: 18 August 2016 / Revised: 25 September 2016 / Accepted: 30 September 2016 / Published: 9 October 2016
Cited by 2 | PDF Full-text (4913 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A one-pot reaction was described that results in various pyrazole-thiobarbituric acid derivatives as new pharmacophore agents. These new heterocycles were synthesized in high yields with a broad substrate scope under mild reaction conditions in water mediated by NHEt2. The molecular structures
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A one-pot reaction was described that results in various pyrazole-thiobarbituric acid derivatives as new pharmacophore agents. These new heterocycles were synthesized in high yields with a broad substrate scope under mild reaction conditions in water mediated by NHEt2. The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques. The new compounds were evaluated for their antibacterial and antifungal activity. Compounds 4h and 4l were the most active compounds against C. albicans with MIC = 4 µg/L. Compound 4c exhibited the best activity against S. aureus and E. faecalis with MIC = 16 µg/L. However, compounds 4l and 4o were the most active against B. subtilis with MIC = 16 µg/L. Molecular docking studies for the final compounds and standard drugs were performed using the OpenEye program. Full article
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Open AccessArticle Design, Synthesis and Evaluation of Novel Tacrine-Ferulic Acid Hybrids as Multifunctional Drug Candidates against Alzheimer’s Disease
Molecules 2016, 21(10), 1338; doi:10.3390/molecules21101338
Received: 2 August 2016 / Revised: 4 October 2016 / Accepted: 7 October 2016 / Published: 11 October 2016
Cited by 1 | PDF Full-text (1531 KB) | HTML Full-text | XML Full-text
Abstract
Five novel tacrine-ferulic acid hybrid compounds (8ae) were synthesized and their structures were identified on the basis of a detailed spectroscopic analysis. The activities of inhibiting acetyl cholinesterase (AChE) and butyryl cholinesterase (BuChE), reducing self-induced β-amyloid (Aβ) aggregation and
[...] Read more.
Five novel tacrine-ferulic acid hybrid compounds (8ae) were synthesized and their structures were identified on the basis of a detailed spectroscopic analysis. The activities of inhibiting acetyl cholinesterase (AChE) and butyryl cholinesterase (BuChE), reducing self-induced β-amyloid (Aβ) aggregation and chelating Cu2+ were evaluated in vitro. Among them, 8c and 8d displayed the higher selectivity in inhibiting AChE over BuChE. Moreover, 8d also showed dramatic inhibition of self-Aβ aggregation, activity of chelating Cu2+ and activity against Aβ-induced neurotoxicity in Neuro-2A cells. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Thymol Mitigates Cadmium Stress by Regulating Glutathione Levels and Reactive Oxygen Species Homeostasis in Tobacco Seedlings
Molecules 2016, 21(10), 1339; doi:10.3390/molecules21101339
Received: 10 August 2016 / Revised: 29 September 2016 / Accepted: 1 October 2016 / Published: 14 October 2016
Cited by 1 | PDF Full-text (5095 KB) | HTML Full-text | XML Full-text
Abstract
Thymol is a famous plant-derived compound that has been widely used in pharmacy due to its antioxidant and antimicrobial properties. However, the modulation of intrinsic plant physiology by thymol remains unclear. It is a significant challenge to confer plant tolerance to Cd (cadmium)
[...] Read more.
Thymol is a famous plant-derived compound that has been widely used in pharmacy due to its antioxidant and antimicrobial properties. However, the modulation of intrinsic plant physiology by thymol remains unclear. It is a significant challenge to confer plant tolerance to Cd (cadmium) stress. In the present study physiological, histochemical, and biochemical methods were applied to investigate thymol-induced Cd tolerance in tobacco (Nicotiana tabacum) seedlings. Thymol was able to alleviate Cd-induced growth inhibition of tobacco seedlings in both dose- and time-dependent manners. Both histochemical detection and in-tube assays suggested that thymol treatment blocked Cd-induced over-generation of reactive oxygen species (ROS), lipid peroxidation, and loss of membrane integrity in both leaves and roots. Thymol decreased Cd-induced cell death that was indicated in vivo by propidium iodide (PI) and trypan blue, respectively. Thymol stimulated glutathione (GSH) biosynthesis by upregulating the expression of γ-glutamylcysteine synthetase 1 (GSH1) in Cd-treated seedlings, which may contribute to the alleviation of Cd-induced oxidative injury. In situ fluorescent detection of intracellular Cd2+ revealed that thymol significantly decreased free Cd2+ in roots, which could be explained by the thymol-stimulated GSH biosynthesis and upregulation of the expression of phyochelatin synthase 1 (PCS1). Taken together, these results suggested that thymol has great potential to trigger plant resistant responses to combat heavy metal toxicity, which may help our understanding of the mechanism for thymol-modulated cell metabolic pathways in response to environmental stimuli. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle A High Content Screening Assay to Identify Compounds with Anti-Epithelial-Mesenchymal Transition Effects from the Chinese Herbal Medicine Tong-Mai-Yang-Xin-Wan
Molecules 2016, 21(10), 1340; doi:10.3390/molecules21101340
Received: 17 August 2016 / Revised: 29 September 2016 / Accepted: 6 October 2016 / Published: 10 October 2016
PDF Full-text (2266 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chronic kidney disease (CKD) is a worldwide health problem with growing prevalence in developing countries. Renal tubular epithelial-mesenchymal transition (EMT) is a critical step and key factor in the development of this condition. Renal tubulointerstitial fibrosis is a basic pathological change at the
[...] Read more.
Chronic kidney disease (CKD) is a worldwide health problem with growing prevalence in developing countries. Renal tubular epithelial-mesenchymal transition (EMT) is a critical step and key factor in the development of this condition. Renal tubulointerstitial fibrosis is a basic pathological change at the later stages of the disease. Therefore, blocking the development of EMT could be a critical factor in curing CKD. We have established a cell-based high-content screening (HCS) method to identify inhibitors of EMT in human proximal tubular epithelial (HK-2) cells by automatic acquisition and processing of dual-fluorescent labeled images. With the aid of chromatographic separation and mass spectrometry, we achieved the rapid and reliable screening of active compounds from the Chinese herbal medicine Tong-Mai-Yang-Xin-Wan (TMYX) for treating EMT. Five fractions were found to exert anti-EMT activity and were further identified by liquid chromatography coupled with tandem mass spectrometry. Glycyrrhizic acid, glyasperin A, and licorisoflavan A were found to inhibit EMT. The proposed approach was successfully applied to screen active compounds from TMYX on TGF-β1-stimulated HK-2 cells and may offer a new means for identifying lead compounds for treating EMT from registered Chinese herbal medicines. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle Resveratrol Ameliorates the Depressive-Like Behaviors and Metabolic Abnormalities Induced by Chronic Corticosterone Injection
Molecules 2016, 21(10), 1341; doi:10.3390/molecules21101341
Received: 14 June 2016 / Revised: 24 September 2016 / Accepted: 6 October 2016 / Published: 13 October 2016
Cited by 4 | PDF Full-text (1869 KB) | HTML Full-text | XML Full-text
Abstract
Chronic glucocorticoid exposure is known to cause depression and metabolic disorders. It is critical to improve abnormal metabolic status as well as depressive-like behaviors in patients with long-term glucocorticoid therapy. This study aimed to investigate the effects of resveratrol on the depressive-like behaviors
[...] Read more.
Chronic glucocorticoid exposure is known to cause depression and metabolic disorders. It is critical to improve abnormal metabolic status as well as depressive-like behaviors in patients with long-term glucocorticoid therapy. This study aimed to investigate the effects of resveratrol on the depressive-like behaviors and metabolic abnormalities induced by chronic corticosterone injection. Male ICR mice were administrated corticosterone (40 mg/kg) by subcutaneous injection for three weeks. Resveratrol (50 and 100 mg/kg), fluoxetine (20 mg/kg) and pioglitazone (10 mg/kg) were given by oral gavage 30 min prior to corticosterone administration. The behavioral tests showed that resveratrol significantly reversed the depressive-like behaviors induced by corticosterone, including the reduced sucrose preference and increased immobility time in the forced swimming test. Moreover, resveratrol also increased the secretion of insulin, reduced serum level of glucose and improved blood lipid profiles in corticosterone-treated mice without affecting normal mice. However, fluoxetine only reverse depressive-like behaviors, and pioglitazone only prevent the dyslipidemia induced by corticosterone. Furthermore, resveratrol and pioglitazone decreased serum level of glucagon and corticosterone. The present results indicated that resveratrol can ameliorate depressive-like behaviors and metabolic abnormalities induced by corticosterone, which suggested that the multiple effects of resveratrol could be beneficial for patients with depression and/or metabolic syndrome associated with long-term glucocorticoid therapy. Full article
(This article belongs to the Special Issue Improvements for Resveratrol Efficacy)
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Open AccessArticle Synthesis of Xylitan Derivatives and Preliminary Evaluation of in Vitro Trypanocidal Activity
Molecules 2016, 21(10), 1342; doi:10.3390/molecules21101342
Received: 4 September 2016 / Revised: 26 September 2016 / Accepted: 30 September 2016 / Published: 10 October 2016
PDF Full-text (1126 KB) | HTML Full-text | XML Full-text
Abstract
A series of novel xylitan derivatives derived from xylitol were synthesized using operationally simple procedures. A xylitan acetonide was the key intermediate used to prepare benzoate, arylsulfonate esters and 1,2,3-triazole derivatives of xylitan. These compounds were evaluated for their in vitro anti-Trypanosoma
[...] Read more.
A series of novel xylitan derivatives derived from xylitol were synthesized using operationally simple procedures. A xylitan acetonide was the key intermediate used to prepare benzoate, arylsulfonate esters and 1,2,3-triazole derivatives of xylitan. These compounds were evaluated for their in vitro anti-Trypanosoma cruzi activity against trypomastigote and amastigote forms of the parasite in T. cruzi-infected cell lineages. Benznidazole was used as positive control against T. cruzi and cytotoxicity was determined in mammalian L929 cells. The arylsulfonate xylitan derivative bearing a nitro group displayed the best activity of all the compounds tested, and was slightly more potent than the reference drug benznidazole. The importance of the isopropylidene ketal moiety was established and the greater lipophilicity of these compounds suggests enhancement in cell penetration. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Modulation of Autophagy by a Thioxanthone Decreases the Viability of Melanoma Cells
Molecules 2016, 21(10), 1343; doi:10.3390/molecules21101343
Received: 9 August 2016 / Revised: 30 September 2016 / Accepted: 1 October 2016 / Published: 10 October 2016
Cited by 2 | PDF Full-text (2657 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
(1) Background: Our previous studies unveiled the hit thioxanthone TXA1 as an inhibitor of P-glycoprotein (drug efflux pump) and of human tumor cells growth, namely of melanoma cells. Since TXA1 is structurally similar to lucanthone (an autophagy inhibitor and apoptosis inducer) and to
[...] Read more.
(1) Background: Our previous studies unveiled the hit thioxanthone TXA1 as an inhibitor of P-glycoprotein (drug efflux pump) and of human tumor cells growth, namely of melanoma cells. Since TXA1 is structurally similar to lucanthone (an autophagy inhibitor and apoptosis inducer) and to N10-substituted phenoxazines (isosteres of thioxanthones, and autophagy inducers), this study aimed at further assessing its cytotoxic mechanism and evaluating its potential as an autophagy modulator in A375-C5 melanoma cells; (2) Methods: Flow cytometry with propidium iodide (PI) for cell cycle profile analysis; Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, flow cytometry with Annexin V/PI labeling and Western blot for apoptosis analysis were conducted. A pharmacophore approach was used for mapping TXA1 onto pharmacophores for autophagy induction. Autophagy analyses included transmission electron microscopy for visualization of autophagic structures, fluorescence microscopy for observation of monodansylcadaverine (MDC) staining, pattern of LC3 expression in the cells and acridine orange staining, and Western blot for autophagic proteins expression; (3) Results: TXA1 induced autophagy of melanoma cells at the GI50 concentration (3.6 μM) and apoptosis at twice that concentration. Following treatment with TXA1, autophagic structures were observed, together with the accumulation of autophagosomes and the formation of autophagolysosomes. An increase in LC3-II levels was also observed, which was reverted by 3-methyladenine (3-MA) (an early stage autophagy-inhibitor) but further increased by E-64d/pepstatin (late-stage autophagy inhibitors). Finally, 3-MA also reverted the effect of TXA1 in cellular viability; (4) Conclusion: TXA1 decreases the viability of melanoma cells by modulation of autophagy and may, therefore, serve as a lead compound for the development of autophagy modulators with antitumor activity. Full article
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Open AccessArticle Picrotoxane Sesquiterpene Glycosides and a Coumarin Derivative from Coriaria nepalensis and Their Neurotrophic Activity
Molecules 2016, 21(10), 1344; doi:10.3390/molecules21101344
Received: 10 September 2016 / Revised: 7 October 2016 / Accepted: 9 October 2016 / Published: 12 October 2016
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Abstract
Two picrotoxane sesquiterpene lactone glycosides, nepalactones A (1) and B (2), and one new coumarin, nepalarin (3), were isolated from the root barks of the poisonous plant Coriaria nepalensis. Their structures were elucidated via HRESIMS and
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Two picrotoxane sesquiterpene lactone glycosides, nepalactones A (1) and B (2), and one new coumarin, nepalarin (3), were isolated from the root barks of the poisonous plant Coriaria nepalensis. Their structures were elucidated via HRESIMS and 1D and 2D NMR spectroscopic analyses, and further verified via transformation methods. In addition, compounds 13 and five semisynthetic congeners (1ae) were assayed for the activity to induce neurite outgrowth in rat pheochromocytoma (PC12) cells. As a result, nepalactone A derivative 1c and nepalarin (3) significantly enhanced nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Ultraviolet B (UVB) Photosensitivities of Tea Catechins and the Relevant Chemical Conversions
Molecules 2016, 21(10), 1345; doi:10.3390/molecules21101345
Received: 13 August 2016 / Revised: 22 September 2016 / Accepted: 6 October 2016 / Published: 10 October 2016
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Abstract
Ultraviolet B (UVB) photosensitivities of eight catechins were screened. In both water and ethanol, epicatechin (EC, 575 μM) and catechin (C, 575 μM) exhibited low photostabilities under 6 h UVB radiation with the generation of yellow photoproducts, while other catechins (epigallocatechin gallate, epigallocatechin,
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Ultraviolet B (UVB) photosensitivities of eight catechins were screened. In both water and ethanol, epicatechin (EC, 575 μM) and catechin (C, 575 μM) exhibited low photostabilities under 6 h UVB radiation with the generation of yellow photoproducts, while other catechins (epigallocatechin gallate, epigallocatechin, epicatechin gallate, gallocatechingallate, gallocatechin, catechin gallate) were relatively UVB-insensitive. Photoisomerization and photolysis were two important UVB-induced reactions to EC whereas photolysis was the dominant reaction for C. The influencing factors of time (2–10 h), solvent (water, ethanol) and substrate concentration (71.875–1150 μM) on UVB-induced chemical conversions of EC and C were investigated, and eight photoproducts were identified through ultra performance liquid chromatography-diode array detection-tandem mass spectrometry (UPLC-DAD-MS/MS) and 1H nuclear magnetic resonance (1H-NMR analysis). Photolysis reaction involved two pathways, including radical reaction and photo-induced electron transfer reaction. The 2,2-diphenylpicrylhydrazyl (DPPH) scavenging abilities of eight catechins did not change upon 6 h UVB irradiation. EC and C are photosensitive catechins among eight catechins causing deep color. Full article
(This article belongs to the Special Issue Polyphenols and Antioxidants–The Chemistry of Tea)
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Open AccessArticle Gallic Acid Content in Taiwanese Teas at Different Degrees of Fermentation and Its Antioxidant Activity by Inhibiting PKCδ Activation: In Vitro and in Silico Studies
Molecules 2016, 21(10), 1346; doi:10.3390/molecules21101346
Received: 31 July 2016 / Revised: 28 September 2016 / Accepted: 6 October 2016 / Published: 12 October 2016
Cited by 2 | PDF Full-text (3120 KB) | HTML Full-text | XML Full-text
Abstract
Teas can be classified according to their degree of fermentation, which has been reported to affect both the bioactive components in the teas and their antioxidative activity. In this study, four kinds of commercial Taiwanese tea at different degrees of fermentation, which include
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Teas can be classified according to their degree of fermentation, which has been reported to affect both the bioactive components in the teas and their antioxidative activity. In this study, four kinds of commercial Taiwanese tea at different degrees of fermentation, which include green (non-fermented), oolong (semi-fermented), black (fully fermented), and Pu-erh (post-fermented) tea, were profiled for catechin levels by using high performance liquid chromatography (HPLC). The result indicated that the gallic acid content in tea was directly proportional to the degree of fermentation in which the lowest and highest gallic acid content were 1.67 and 21.98 mg/g from green and Pu-erh tea, respectively. The antioxidative mechanism of the gallic acid was further determined by in vitro and in silico analyses. In vitro assays included the use of phorbol ester-induced macrophage RAW264.7 cell model for determining the inhibition of reactive oxygen species (ROS) production, and PKCδ and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit (p47) activations. The results showed that only at a concentration of 5.00 μM could gallic acid significantly (p < 0.05) reduce ROS levels in phorbol ester-activated macrophages. Moreover, protein immunoblotting expressed similar results in which activations of PKCδ and p47 were only significantly (p < 0.05) attenuated by 5.00 μM treatment. Lastly, in silico experiments further revealed that gallic acid could block PKCδ activation by occupying the phorbol ester binding sites of the protein. Full article
(This article belongs to the Special Issue Catechins and Human Health: Current State of the Science)
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Open AccessArticle Evaluation of Hydrogel Suppositories for Delivery of 5-Aminolevulinic Acid and Hematoporphyrin Monomethyl Ether to Rectal Tumors
Molecules 2016, 21(10), 1347; doi:10.3390/molecules21101347
Received: 25 August 2016 / Revised: 6 October 2016 / Accepted: 7 October 2016 / Published: 12 October 2016
Cited by 3 | PDF Full-text (2521 KB) | HTML Full-text | XML Full-text
Abstract
We evaluated the potential utility of hydrogels for delivery of the photosensitizing agents 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) to rectal tumors. Hydrogel suppositories containing ALA or HMME were administered to the rectal cavity of BALB/c mice bearing subcutaneous tumors of
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We evaluated the potential utility of hydrogels for delivery of the photosensitizing agents 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) to rectal tumors. Hydrogel suppositories containing ALA or HMME were administered to the rectal cavity of BALB/c mice bearing subcutaneous tumors of SW837 rectal carcinoma cells. For comparison, ALA and HMME were also administered by three common photosensitizer delivery routes; local administration to the skin and intratumoral or intravenous injection. The concentration of ALA-induced protoporphyrin IX or HMME in the rectal wall, skin, and subcutaneous tumor was measured by fluorescence spectrophotometry, and their distribution in vertical sections of the tumor was measured using a fluorescence spectroscopy system. The concentration of ALA-induced protoporphyrin IX in the rectal wall after local administration of suppositories to the rectal cavity was 9.76-fold (1 h) and 5.8-fold (3 h) higher than in the skin after cutaneous administration. The maximal depth of ALA penetration in the tumor was ~3–6 mm at 2 h after cutaneous administration. Much lower levels of HMME were observed in the rectal wall after administration as a hydrogel suppository, and the maximal depth of tumor penetration was <2 mm after cutaneous administration. These data show that ALA more readily penetrates the mucosal barrier than the skin. Administration of ALA as an intrarectal hydrogel suppository is thus a potential delivery route for photodynamic therapy of rectal cancer. Full article
(This article belongs to the Special Issue Photodynamic Therapy)
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Open AccessArticle Synthesis and Antifungal Activity against Fusarium oxysporum of Some Brassinin Analogs Derived from l-tryptophan: A DFT/B3LYP Study on the Reaction Mechanism
Molecules 2016, 21(10), 1349; doi:10.3390/molecules21101349
Received: 14 September 2016 / Revised: 26 September 2016 / Accepted: 8 October 2016 / Published: 11 October 2016
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Abstract
An efficient methodology to obtain novel antifungal analogs of brassinin 1 is described. Starting from l-tryptophan 2, N,N′-dialkylthiourea 4, 4-[(1H-indol-3-yl)methylene]-2-sulfanylidene-1,3-thiazolidin-5-one 5 and alkyl (2S)-3-(1H-indol-3-yl)-2-{[(alkylsulfanyl)carbonothioyl]amino}propanoate 6 type compounds were obtained as main
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An efficient methodology to obtain novel antifungal analogs of brassinin 1 is described. Starting from l-tryptophan 2, N,N′-dialkylthiourea 4, 4-[(1H-indol-3-yl)methylene]-2-sulfanylidene-1,3-thiazolidin-5-one 5 and alkyl (2S)-3-(1H-indol-3-yl)-2-{[(alkylsulfanyl)carbonothioyl]amino}propanoate 6 type compounds were obtained as main products in different ratios depending on the reaction conditions via a tandem dithiocarbamate formation and Michael addition reaction. In order to understand the dependence of the reaction conditions on the mechanism pathway, a DFT/B3LYP study was performed. The results suggested the existence of competitive mechanistic routes which involve the presence of an ionic dithiocarbamate intermediate 9. Antifungal activities of all products were then evaluated against Fusarium oxysporum through mycelial growth inhibition using a microscale amended-medium assay. IC50 values were thus determined for each compound. These results showed that 6-related compounds can be considered as promissory antifungal agents. Full article
(This article belongs to the Special Issue MCRs and Related One-Pot Organic Synthesis)
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Open AccessArticle Protective Effect of the Plant Extracts of Erythroxylum sp. against Toxic Effects Induced by the Venom of Lachesis muta Snake
Molecules 2016, 21(10), 1350; doi:10.3390/molecules21101350
Received: 12 May 2016 / Revised: 3 October 2016 / Accepted: 4 October 2016 / Published: 11 October 2016
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Abstract
Snake venoms are composed of a complex mixture of active proteins that induce toxic effects, such as edema, hemorrhage, and death. Lachesis muta has the highest lethality indices in Brazil. In most cases, antivenom fails to neutralize local effects, leading to disabilities in
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Snake venoms are composed of a complex mixture of active proteins that induce toxic effects, such as edema, hemorrhage, and death. Lachesis muta has the highest lethality indices in Brazil. In most cases, antivenom fails to neutralize local effects, leading to disabilities in victims. Thus, alternative treatments are under investigation, and plant extracts are promising candidates. The objective of this work was to investigate the ability of crude extracts, fractions, or isolated products of Erythroxylum ovalifolium and Erythroxylum subsessile to neutralize some toxic effects of L. muta venom. All samples were mixed with L. muta venom, then in vivo (hemorrhage and edema) and in vitro (proteolysis, coagulation, and hemolysis) assays were performed. Overall, crude extracts or fractions of Erythroxylum spp. inhibited (20%–100%) toxic effects of the venom, but products achieved an inhibition of 4%–30%. However, when venom was injected into mice before the plant extracts, hemorrhage and edema were not inhibited by the samples. On the other hand, an inhibition of 5%–40% was obtained when extracts or products were given before venom injection. These results indicate that the extracts or products of Erythroxylum spp. could be a promising source of molecules able to treat local toxic effects of envenomation by L. muta venom, aiding in the development of new strategies for antivenom treatment. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle A Reliable Method for the Evaluation of the Anaphylactoid Reaction Caused by Injectable Drugs
Molecules 2016, 21(10), 1352; doi:10.3390/molecules21101352
Received: 5 August 2016 / Revised: 9 October 2016 / Accepted: 10 October 2016 / Published: 12 October 2016
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Abstract
Adverse reactions of injectable drugs usually occur at first administration and are closely associated with the dosage and speed of injection. This phenomenon is correlated with the anaphylactoid reaction. However, up to now, study methods based on antigen detection have still not gained
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Adverse reactions of injectable drugs usually occur at first administration and are closely associated with the dosage and speed of injection. This phenomenon is correlated with the anaphylactoid reaction. However, up to now, study methods based on antigen detection have still not gained wide acceptance and single physiological indicators cannot be utilized to differentiate anaphylactoid reactions from allergic reactions and inflammatory reactions. In this study, a reliable method for the evaluation of anaphylactoid reactions caused by injectable drugs was established by using multiple physiological indicators. We used compound 48/80, ovalbumin and endotoxin as the sensitization agents to induce anaphylactoid, allergic and inflammatory reactions. Different experimental animals (guinea pig and nude rat) and different modes of administration (intramuscular, intravenous and intraperitoneal injection) and different times (15 min, 30 min and 60 min) were evaluated to optimize the study protocol. The results showed that the optimal way to achieve sensitization involved treating guinea pigs with the different agents by intravenous injection for 30 min. Further, seven related humoral factors including 5-HT, SC5b-9, Bb, C4d, IL-6, C3a and histamine were detected by HPLC analysis and ELISA assay to determine their expression level. The results showed that five of them, including 5-HT, SC5b-9, Bb, C4d and IL-6, displayed significant differences between anaphylactoid, allergic and inflammatory reactions, which indicated that their combination could be used to distinguish these three reactions. Then different injectable drugs were used to verify this method and the results showed that the chosen indicators exhibited good correlation with the anaphylactoid reaction which indicated that the established method was both practical and reliable. Our research provides a feasible method for the diagnosis of the serious adverse reactions caused by injectable drugs which could be used in the clinical practice. Full article
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Open AccessArticle Tetrandrine Induces Apoptosis of Human Nasopharyngeal Carcinoma NPC-TW 076 Cells through Reactive Oxygen Species Accompanied by an Endoplasmic Reticulum Stress Signaling Pathway
Molecules 2016, 21(10), 1353; doi:10.3390/molecules21101353
Received: 24 August 2016 / Revised: 7 October 2016 / Accepted: 8 October 2016 / Published: 12 October 2016
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Abstract
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy of the head and neck and the incidence is higher in Southeast Asia. Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid, a natural product, and exhibits biological activities including action against many human cancer cell lines. However, the
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Nasopharyngeal carcinoma (NPC) is an epithelial malignancy of the head and neck and the incidence is higher in Southeast Asia. Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid, a natural product, and exhibits biological activities including action against many human cancer cell lines. However, the molecular mechanism of TET-induced cell apoptosis in human NPC cells is still unclear. In the present study, we investigated TET-induced apoptotic cell death and associated possible signal pathways on human nasopharyngeal carcinoma NPC-TW 076 cells in vitro. Phase contrast microscopy was used to examine cell morphology and DAPI staining was used to examine chromatin condensation. Flow cytometry assay was used to measure total viable cells, cell cycle and sub-G1 phase distribution, reactive oxygen species (ROS), Ca2+, and mitochondria membrane potential (ΔΨm) in NPC-TW 076 cells. Results indicate that TET induced cell death through the cell morphological changes, caused G0/G1 phase arrest, increased ROS and Ca2+ production, and finally caused apoptotic cell death in NPC-TW 076 cells. There was no influence on the level of ΔΨm after TET treatment. Western blotting indicated that TET increased endoplasmic reticulum (ER) stress associated protein expression such as GADD153, GRP78, ATF-6α and ATF-6 βwhich indicated that TET induced cell death through ER stress. ER stress is a potential target in cancer treatment, so the ability of TET to induce ER stress response and to activate programming cell death in NPC-TW 076 cells make this molecule become a promising anticancer agent. Full article
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Open AccessArticle Effect of Exogenous Abscisic Acid and Methyl Jasmonate on Anthocyanin Composition, Fatty Acids, and Volatile Compounds of Cabernet Sauvignon (Vitis vinifera L.) Grape Berries
Molecules 2016, 21(10), 1354; doi:10.3390/molecules21101354
Received: 3 August 2016 / Revised: 4 October 2016 / Accepted: 8 October 2016 / Published: 12 October 2016
Cited by 2 | PDF Full-text (1002 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The anthocyanin composition, fatty acids, and volatile aromas are important for Cabernet Sauvignon grape quality. This study evaluated the effect of exogenous abscisic acid (ABA) and methyl jasmonate (MeJA) on the anthocyanin composition, fatty acids, lipoxygenase activity, and the volatile compounds of Cabernet
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The anthocyanin composition, fatty acids, and volatile aromas are important for Cabernet Sauvignon grape quality. This study evaluated the effect of exogenous abscisic acid (ABA) and methyl jasmonate (MeJA) on the anthocyanin composition, fatty acids, lipoxygenase activity, and the volatile compounds of Cabernet Sauvignon grape berries. Exogenous ABA and MeJA improved the content of total anthocyanins (TAC) and individual anthocyanins. Lipoxygenase (LOX) activity also increased after treatment. Furthermore, 16 fatty acids were detected. The linoleic acid concentration gradually increased with ABA concentration. The fatty acid content decreased with increasing MeJA concentration and then increased again, with the exception of linoleic acid. After exogenous ABA and MeJA treatment, the C6 aroma content increased significantly. Interestingly, the exogenous ABA and MeJA treatments improved mainly the content of 1-hexanol, hexanal, and 2-heptanol. These results provide insight into the effect of plant hormones on wine grapes, which is useful for grape quality improvement. Full article
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Open AccessCommunication Exploiting 1,2,3-Triazolium Ionic Liquids for Synthesis of Tryptanthrin and Chemoselective Extraction of Copper(II) Ions and Histidine-Containing Peptides
Molecules 2016, 21(10), 1355; doi:10.3390/molecules21101355
Received: 29 August 2016 / Revised: 5 October 2016 / Accepted: 9 October 2016 / Published: 13 October 2016
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Abstract
Based on a common structural core of 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyridine, a number of bicyclic triazolium ionic liquids 13 were designed and successfully prepared. In our hands, this optimized synthesis of ionic liquids 1 and 2 requires no chromatographic separation. Also in
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Based on a common structural core of 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyridine, a number of bicyclic triazolium ionic liquids 13 were designed and successfully prepared. In our hands, this optimized synthesis of ionic liquids 1 and 2 requires no chromatographic separation. Also in this work, ionic liquids 1, 2 were shown to be efficient ionic solvents for fast synthesis of tryptanthrin natural product. Furthermore, a new affinity ionic liquid 3 was tailor-synthesized and displayed its effectiveness in chemoselective extraction of both Cu(II) ions and, for the first time, histidine-containing peptides. Full article
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Open AccessArticle Small versus Large Iron Oxide Magnetic Nanoparticles: Hyperthermia and Cell Uptake Properties
Molecules 2016, 21(10), 1357; doi:10.3390/molecules21101357
Received: 6 September 2016 / Revised: 30 September 2016 / Accepted: 6 October 2016 / Published: 13 October 2016
Cited by 3 | PDF Full-text (6503 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Efficient use of magnetic hyperthermia in clinical cancer treatment requires biocompatible magnetic nanoparticles (MNPs), with improved heating capabilities. Small (~34 nm) and large (~270 nm) Fe3O4-MNPs were synthesized by means of a polyol method in polyethylene-glycol (PEG) and ethylene-glycol
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Efficient use of magnetic hyperthermia in clinical cancer treatment requires biocompatible magnetic nanoparticles (MNPs), with improved heating capabilities. Small (~34 nm) and large (~270 nm) Fe3O4-MNPs were synthesized by means of a polyol method in polyethylene-glycol (PEG) and ethylene-glycol (EG), respectively. They were systematically investigated by means of X-ray diffraction, transmission electron microscopy and vibration sample magnetometry. Hyperthermia measurements showed that Specific Absorption Rate (SAR) dependence on the external alternating magnetic field amplitude (up to 65 kA/m, 355 kHz) presented a sigmoidal shape, with remarkable SAR saturation values of ~1400 W/gMNP for the small monocrystalline MNPs and only 400 W/gMNP for the large polycrystalline MNPs, in water. SAR values were slightly reduced in cell culture media, but decreased one order of magnitude in highly viscous PEG1000. Toxicity assays performed on four cell lines revealed almost no toxicity for the small MNPs and a very small level of toxicity for the large MNPs, up to a concentration of 0.2 mg/mL. Cellular uptake experiments revealed that both MNPs penetrated the cells through endocytosis, in a time dependent manner and escaped the endosomes with a faster kinetics for large MNPs. Biodegradation of large MNPs inside cells involved an all-or-nothing mechanism. Full article
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Open AccessArticle Chemical Compositions of Ligusticum chuanxiong Oil and Lemongrass Oil and Their Joint Action against Aphis citricola Van Der Goot (Hemiptera: Aphididae)
Molecules 2016, 21(10), 1359; doi:10.3390/molecules21101359
Received: 6 September 2016 / Revised: 9 October 2016 / Accepted: 10 October 2016 / Published: 12 October 2016
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Abstract
In order to develop novel botanical insecticides, the joint action of Ligusticum chuanxiong oil (LCO) and lemongrass oil (LO) against Aphis citricola van der Goot was determined systematically indoors and outdoors. The chemical profiles of LCO and LO as determined by gas chromatography–mass
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In order to develop novel botanical insecticides, the joint action of Ligusticum chuanxiong oil (LCO) and lemongrass oil (LO) against Aphis citricola van der Goot was determined systematically indoors and outdoors. The chemical profiles of LCO and LO as determined by gas chromatography–mass spectrometry (GC-MS) analysis revealed that the main compounds from LCO were (Z)-ligustilide (44.58%) and senkyunolide A (26.92%), and that of LO were geranial (42.16%) and neral (32.58%), respectively. The mixture of LCO and LO showed significant synergy against A. citricola, with a common-toxicity coefficient (CTC) value of 221.46 at the optimal ratio of LCO to LO (4:1, w:w). Based on the results of solvents and emulsifiers screening, L. chuanxiong oil·Lemongrass oil 20% emulsifiable concentrate (20% LCO·LO EC) was developed, and its stability was confirmed with tests of cold and thermal storage. Field trials indicated that the insecticidal activity of the diluted 20% LCO·LO EC (1000 fold dilution) was comparable to conventional pesticide (20% imidacloprid EC) on A. citricola seven days after application. Thus, the mixture of LCO and LO has the potential to be further developed as a botanical pesticide. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Nujiangexathone A, a Novel Compound Derived from Garcinia nujiangensis, Induces Caspase-Dependent Apoptosis in Cervical Cancer through the ROS/JNK Pathway
Molecules 2016, 21(10), 1360; doi:10.3390/molecules21101360
Received: 19 August 2016 / Revised: 20 September 2016 / Accepted: 29 September 2016 / Published: 12 October 2016
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Abstract
Nujiangexathone A (NJXA), a novel compound derived from Garcinia nujiangensis, has been demonstrated to inhibit the proliferation of several human cancer cell lines. This study is the first to demonstrate the apoptosis inductive activities of NJXA and the possible underlying mechanisms. Our
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Nujiangexathone A (NJXA), a novel compound derived from Garcinia nujiangensis, has been demonstrated to inhibit the proliferation of several human cancer cell lines. This study is the first to demonstrate the apoptosis inductive activities of NJXA and the possible underlying mechanisms. Our results demonstrated that NJXA inhibited colony formation by HeLa and SiHa cells in a dose-dependent manner. An Annexin V-FITC/PI staining assay showed that NJXA strongly triggered apoptosis in a dose-dependent manner. Western blotting analyses showed that NJXA induced the caspase-dependent apoptosis of HeLa and SiHa cells by triggering a series of events, including changes in the levels of Bcl-2 family proteins, cytochrome c release, caspase-3 activation, and chromosome fragmentation. Furthermore, we demonstrated that NJXA induced cell apoptosis by activating the reactive oxygen species (ROS)-mediated JNK signaling pathway. Consistent with this finding, a ROS scavenger, N-acetyl-l-cysteine (NAC, 10 mM), hindered NJXA-induced apoptosis and attenuated the sensitivity of HeLa and SiHa cells to NJXA. In vivo results further confirmed that the tumor inhibitory effect of NJXA was partially through the induction of apoptosis. Taken together, our results demonstrated that NJXA induced the apoptosis of HeLa and SiHa cells through the ROS/JNK signaling pathway, indicating that NJXA could be important candidate for the clinical treatment of cervical cancer. Full article
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Open AccessArticle Three New Butenolides from the Fungus Aspergillus sp. CBS-P-2
Molecules 2016, 21(10), 1361; doi:10.3390/molecules21101361
Received: 10 September 2016 / Revised: 9 October 2016 / Accepted: 10 October 2016 / Published: 13 October 2016
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Abstract
Three new butenolides aspernolides H–J (13) together with seven known ones (410) were isolated from the fungus Aspergillus sp. CBS-P-2. Their chemical structures were established on the basis of 1D- and 2D-NMR spectroscopic data, HR-ESI-MS
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Three new butenolides aspernolides H–J (13) together with seven known ones (410) were isolated from the fungus Aspergillus sp. CBS-P-2. Their chemical structures were established on the basis of 1D- and 2D-NMR spectroscopic data, HR-ESI-MS analysis, and their absolute configuration were determined by circular dichroism (CD) analysis. All the compounds were evaluated for the antioxidant effects by DPPH and ABTS methods, the antitumor activities against four human tumor cell lines (HL-60, ASPC1, HCT-116 and PC-3) and antimicrobial activities. Compounds 410 showed significant activity against DPPH (IC50 = 15.9–34.3 μM) and compounds 110 exhibited significant ABTS free radical scavenging activity (IC50 = 2.8–33.1 μM). Compounds 2, 5 and 11 showed potent cytotoxic activities against HL-60 cell lines with IC50 values of 39.4, 13.2 and 16.3 μM, respectively. Compound 10 showed good antimicrobial activity against Staphylococcus aureus with minimum inhibitory concentration (MIC) of 21.3 μM. Full article
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Open AccessArticle GC-MS Analysis of Membrane-Graded Fulvic Acid and Its Activity on Promoting Wheat Seed Germination
Molecules 2016, 21(10), 1363; doi:10.3390/molecules21101363
Received: 8 July 2016 / Revised: 25 September 2016 / Accepted: 9 October 2016 / Published: 13 October 2016
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Abstract
The chemical composition of fulvic acid (FA) with a molecular weight below 500 (FA-500) was analyzed, and its activity on promoting the seed germination of wheat was studied in this paper. The FA-500 was obtained by membrane separation technology and qualitatively and quantitatively
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The chemical composition of fulvic acid (FA) with a molecular weight below 500 (FA-500) was analyzed, and its activity on promoting the seed germination of wheat was studied in this paper. The FA-500 was obtained by membrane separation technology and qualitatively and quantitatively analyzed by using gas chromatography-mass spectrometry combined with the retention index. Forty-seven constituents were identified, including structures with ester, acid and alcohol groups, which accounted for 95% of the total composition. The highest relative content of compounds was diethyl succinate and diethyl malonate, accounting for 29% and 17% of the total, respectively. Yannong 19 and Luyuan 301 wheat seeds were steeped with the FA-500 solution of different concentration respectively for two hours. Several markers were assessed: germination rate, coleoptile and radicle length, germination index, vitality index and the activity of α-amylase and (α+β) amylase. The results indicated that FA-500 had a significant effect on promoting seed germination within an appropriate concentration range. The best concentration was 0.5‰, and an inhibiting effect would appear with the increase of concentration. In the process of seed germination, FA-500 may affect the growth of the seed through influencing the amylase activity, which was related to respiration. Full article
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Open AccessArticle Solasonine, A Natural Glycoalkaloid Compound, Inhibits Gli-Mediated Transcriptional Activity
Molecules 2016, 21(10), 1364; doi:10.3390/molecules21101364
Received: 28 August 2016 / Revised: 28 September 2016 / Accepted: 9 October 2016 / Published: 14 October 2016
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Abstract
The major obstacle limiting the efficacy of current Smoothened (Smo) inhibitors is the primary and acquired resistance mainly caused by Smo mutations and Gli amplification. In this context, developing Hh inhibitors targeting Gli, the final effector of this signaling pathway, may combat the
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The major obstacle limiting the efficacy of current Smoothened (Smo) inhibitors is the primary and acquired resistance mainly caused by Smo mutations and Gli amplification. In this context, developing Hh inhibitors targeting Gli, the final effector of this signaling pathway, may combat the resistance. In this study we found that solasonine, a natural glycoalkaloid compound, significantly inhibited the hedgehog (Hh) pathway activity. Meanwhile, solasonine may obviously inhibit the alkaline phosphatase (ALP) activity in C3H10T1/2 cells, concomitantly with reductions of the mRNA expression of Gli1 and Ptch1. However, we found that solasonine exhibited no effect on the transcriptional factors activities provoked by TNF-α and PGE2, thus suggesting its selectivity against Hh pathway activity. Furthermore, we identified that solasonine inhibited the Hh pathway activity by acting on its transcriptional factor Gli using a series of complementary data. We also observed that solasonine obviously inhibited the Gli-luciferase activity provoked by ectopic expression of Smo mutants which may cause the resistance to the current Smo inhibitors. Our study suggests that solasonine may significantly inhibit the Hh pathway activity by acting on Gli, therefore indicating the possibility to use solasonine as a lead compound to develop anticancer drugs for combating the resistance of current Smo inhibitors. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle The Electroluminescence Mechanism of Solution-Processed TADF Emitter 4CzIPN Doped OLEDs Investigated by Transient Measurements
Molecules 2016, 21(10), 1365; doi:10.3390/molecules21101365
Received: 12 September 2016 / Revised: 8 October 2016 / Accepted: 11 October 2016 / Published: 14 October 2016
Cited by 2 | PDF Full-text (2192 KB) | HTML Full-text | XML Full-text
Abstract
High efficiency, solution-processed, organic light emitting devices (OLEDs), using a thermally-activated delayed fluorescent (TADF) emitter, 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), are fabricated, and the transient electroluminescence (EL) decay of the device with a structure of [ITO/PEDOT: PSS/4CzIPN 5 wt % doped 4,40-N,N0-dicarbazolylbiphenyl(CBP)/bis-4,6-(3,5-di-4-pyridylphenyl)-2-methylpyrimidine (B4PyMPM)/lithium fluoride (LiF)/Al], is
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High efficiency, solution-processed, organic light emitting devices (OLEDs), using a thermally-activated delayed fluorescent (TADF) emitter, 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), are fabricated, and the transient electroluminescence (EL) decay of the device with a structure of [ITO/PEDOT: PSS/4CzIPN 5 wt % doped 4,40-N,N0-dicarbazolylbiphenyl(CBP)/bis-4,6-(3,5-di-4-pyridylphenyl)-2-methylpyrimidine (B4PyMPM)/lithium fluoride (LiF)/Al], is systematically studied. The results shed light on the dominant operating mechanism in TADF-based OLEDs. Electroluminescence in the host–guest system is mainly produced from the 4CzIPN emitter, rather than the exciplex host materials. Full article
(This article belongs to the Special Issue Organic Light Emitting Diodes)
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Open AccessArticle Synthesis and In Vitro Cytotoxic Properties of Polycarbo-Substituted 4-(Arylamino)quinazolines
Molecules 2016, 21(10), 1366; doi:10.3390/molecules21101366
Received: 30 August 2016 / Revised: 30 September 2016 / Accepted: 6 October 2016 / Published: 14 October 2016
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Abstract
Herein, we describe the synthesis of novel unsymmetrical polycarbo-substituted 4-anilinoquinazolines derived from the 2-aryl-6-bromo-8-iodoquinazolines via one-pot three-step reaction sequences involving initial amination and subsequent double cross-coupling (bis-Suzuki, Sonogashira/Stille or Sonogashira/Suzuki-Miyaura) reactions with different cross coupling partners for the two carbon–carbon bond formation steps.
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Herein, we describe the synthesis of novel unsymmetrical polycarbo-substituted 4-anilinoquinazolines derived from the 2-aryl-6-bromo-8-iodoquinazolines via one-pot three-step reaction sequences involving initial amination and subsequent double cross-coupling (bis-Suzuki, Sonogashira/Stille or Sonogashira/Suzuki-Miyaura) reactions with different cross coupling partners for the two carbon–carbon bond formation steps. The 4-anilinoquinazolines were evaluated for potential cytotoxicity against three cancer cell lines, namely, human breast adenocarcinoma (MCF-7) cells, human cervical cancer (HeLa) and human lung cancer (A549) cells. The most active compounds, 2b, 2c, 3c, 4a, 4c and 5a, were found to be more selective against the MCF-7 and HeLa cell lines than the human lung carcinoma (A549) cells. We selected compounds 2c, 3c and 7a as representatives for further evaluation for potential to induce apoptosis and/or necrotic properties in the three cancer cell lines. Compound 2c induced apoptosis of MCF-7 cells through cell membrane alteration. Treatment of Hela and A549 cell lines with compounds 3c and 7a, respectively, led to caspase-3 activation in both cell lines. Compound 3c, on the other hand, caused more necrosis than apoptosis induction in the membrane alteration assay. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle In Vitro Study on Anti-Hepatitis C Virus Activity of Spatholobus suberectus Dunn
Molecules 2016, 21(10), 1367; doi:10.3390/molecules21101367
Received: 27 August 2016 / Revised: 7 October 2016 / Accepted: 9 October 2016 / Published: 15 October 2016
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Abstract
Hepatitis C virus (HCV) infects 200 million people worldwide, and 75% of HCV cases progress into chronic infections, which consequently cause cirrhosis and hepatocellular carcinoma. HCV infection is treated with currently considered standard drugs, including direct anti-viral agents (DAAs), alone or in combination
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Hepatitis C virus (HCV) infects 200 million people worldwide, and 75% of HCV cases progress into chronic infections, which consequently cause cirrhosis and hepatocellular carcinoma. HCV infection is treated with currently considered standard drugs, including direct anti-viral agents (DAAs), alone or in combination with peginterferon-α plus ribavirin. However, sustained viral responses vary in different cohorts, and high costs limit the broad use of DAAs. In this study, the ethanol and water extracts of 12 herbs from Lingnan in China were examined in terms of their inhibitory effect on HCV replication. Among the examined extracts, Spatholobus suberectus ethanol extracts suppressed HCV replication. By comparison, Extracts from Fructus lycii, Radix astragali (root), Rubus chingii Hu (fruit), Flos chrysanthemi Indici (flower), Cassia obtusifolia (seed), Lonicera japonica Thunb (flower), Forsythia suspense Thunb (fruit), Poria cocos (sclerotia), Carthamus tinctorius L. (flower), Crataegus pinnatifida Bge. (fruit), and Leonurus japonicas Houtt. (leaf) extracts failed to show a similar activity. Active S. suberectus fractions containing tannins as the major component also inhibited the in vitro translation of HCV RNA. The combination treatments of single compounds, such as epigallocatechin gallate and epicatechin gallate, were not as potent as crude S. suberectus fractions; therefore, crude S. suberectus extract may be a potential alternative treatment against HCV either alone or in combination with other agents. Full article
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Open AccessArticle The Determination of Food Dyes in Vitamins by RP-HPLC
Molecules 2016, 21(10), 1368; doi:10.3390/molecules21101368
Received: 15 August 2016 / Revised: 28 September 2016 / Accepted: 11 October 2016 / Published: 17 October 2016
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Abstract
Reversed-phase high performance liquid chromatography (RP-HPLC) for the determination of five synthetic food dyes (Quinoline Yellow E104, Sunset Yellow E110, Ponceau 4R E124, Tartrazine E102 and Carmine E120) in vitamins was used. The dyes were analyzed within 10 min using a column with
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Reversed-phase high performance liquid chromatography (RP-HPLC) for the determination of five synthetic food dyes (Quinoline Yellow E104, Sunset Yellow E110, Ponceau 4R E124, Tartrazine E102 and Carmine E120) in vitamins was used. The dyes were analyzed within 10 min using a column with stationary phase C 18 (250 mm × 4.6 mm, 5 μm) at 40 °C with isocratic elution, and the mobile phase contained acetonitrile and a mixture of CH3COONa:CH3OH (85:15, v/v) in a ratio of 10:90 (v/v) for yellow-colored capsules and 20:80 (v/v) for red-colored capsules, respectively. A diode-array detector was used to monitor the dyes between 190 and 800 nm. It was established that the analyzed samples contained synthetic dyes in a concentration range from 79.5 ± 0.01 μg/capsule of Ponceau 4R, E124 to 524 ± 0.01 μg/capsule of Tartrazine, E102. The obtained results were compared with existing acceptable daily intakes (ADIs) for individual dyes. This paper provides information about the content of dyes in samples of vitamins. This information is not generally available to consumers. Full article
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Open AccessArticle Coumarin Antifungal Lead Compounds from Millettia thonningii and Their Predicted Mechanism of Action
Molecules 2016, 21(10), 1369; doi:10.3390/molecules21101369
Received: 14 July 2016 / Revised: 5 October 2016 / Accepted: 7 October 2016 / Published: 15 October 2016
Cited by 4 | PDF Full-text (2149 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fungal pathogens continue to pose challenges to humans and plants despite efforts to control them. Two coumarins, robustic acid and thonningine-C isolated from Millettia thonningii, show promising activity against the fungus Candida albicans with minimum fungicidal concentration of 1.0 and 0.5 mg/mL,
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Fungal pathogens continue to pose challenges to humans and plants despite efforts to control them. Two coumarins, robustic acid and thonningine-C isolated from Millettia thonningii, show promising activity against the fungus Candida albicans with minimum fungicidal concentration of 1.0 and 0.5 mg/mL, respectively. Molecular modelling against the putative bio-molecular target, lanosterol 14α-demethylase (CYP51), revealed a plausible binding mode for the active compounds, in which the hydroxyl group binds with a methionine backbone carboxylic group blocking access to the iron catalytic site. This binding disrupts the synthesis of several important sterols for the survival of fungi. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Development of Mushroom-Based Cosmeceutical Formulations with Anti-Inflammatory, Anti-Tyrosinase, Antioxidant, and Antibacterial Properties
Molecules 2016, 21(10), 1372; doi:10.3390/molecules21101372
Received: 5 September 2016 / Revised: 1 October 2016 / Accepted: 11 October 2016 / Published: 14 October 2016
Cited by 5 | PDF Full-text (240 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The cosmetic industry is in a constant search for natural compounds or extracts with relevant bioactive properties, which became valuable ingredients to design cosmeceutical formulations. Mushrooms have been markedly studied in terms of nutritional value and medicinal properties. However, there is still slow
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The cosmetic industry is in a constant search for natural compounds or extracts with relevant bioactive properties, which became valuable ingredients to design cosmeceutical formulations. Mushrooms have been markedly studied in terms of nutritional value and medicinal properties. However, there is still slow progress in the biotechnological application of mushroom extracts in cosmetic formulations, either as antioxidants, anti-aging, antimicrobial, and anti-inflammatory agents or as hyperpigmentation correctors. In the present work, the cosmeceutical potential of ethanolic extracts prepared from Agaricus bisporus, Pleurotus ostreatus, and Lentinula edodes was analyzed in terms of anti-inflammatory, anti-tyrosinase, antioxidant, and antibacterial activities. The extracts were characterized in terms of phenolic acids and ergosterol composition, and further incorporated in a base cosmetic cream to achieve the same bioactive purposes. From the results obtained, the final cosmeceutical formulations presented 85%–100% of the phenolic acids and ergosterol levels found in the mushroom extracts, suggesting that there was no significant loss of bioactive compounds. The final cosmeceutical formulation also displayed all the ascribed bioactivities and as such, mushrooms can further be exploited as natural cosmeceutical ingredients. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Comparative Studies of Interactions between Fluorodihydroquinazolin Derivatives and Human Serum Albumin with Fluorescence Spectroscopy
Molecules 2016, 21(10), 1373; doi:10.3390/molecules21101373
Received: 9 September 2016 / Revised: 5 October 2016 / Accepted: 12 October 2016 / Published: 14 October 2016
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Abstract
In the present study, 3-(fluorobenzylideneamino)-6-chloro-1-(3,3-dimethylbutanoyl)-phenyl-2,3-dihydroquinazolin-4(1H)-one (FDQL) derivatives have been designed and synthesized to study the interaction between fluorine substituted dihydroquinazoline derivatives with human serum albumin (HSA) using fluorescence, circular dichroism and Fourier transform infrared spectroscopy. The results indicated that the FDQL
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In the present study, 3-(fluorobenzylideneamino)-6-chloro-1-(3,3-dimethylbutanoyl)-phenyl-2,3-dihydroquinazolin-4(1H)-one (FDQL) derivatives have been designed and synthesized to study the interaction between fluorine substituted dihydroquinazoline derivatives with human serum albumin (HSA) using fluorescence, circular dichroism and Fourier transform infrared spectroscopy. The results indicated that the FDQL could bind to HSA, induce conformation and the secondary structure changes of HSA, and quench the intrinsic fluorescence of HSA through a static quenching mechanism. The thermodynamic parameters, ΔH, ΔS, and ΔG, calculated at different temperatures, revealed that the binding was through spontaneous and hydrophobic forces and thus played major roles in the association. Based on the number of binding sites, it was considered that one molecule of FDQL could bind to a single site of HSA. Site marker competition experiments indicated that the reactive site of HSA to FDQL mainly located in site II (subdomain IIIA). The substitution by fluorine in the benzene ring could increase the interactions between FDQL and HSA to some extent in the proper temperature range through hydrophobic effect, and the substitution at meta-position enhanced the affinity greater than that at para- and ortho-positions. Full article
(This article belongs to the Special Issue Fluorine Chemistry 2016)
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Open AccessArticle Reactions of an Isolable Dialkylsilylene with Aroyl Chlorides. A New Route to Aroylsilanes
Molecules 2016, 21(10), 1376; doi:10.3390/molecules21101376
Received: 14 September 2016 / Revised: 3 October 2016 / Accepted: 8 October 2016 / Published: 15 October 2016
Cited by 1 | PDF Full-text (3796 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The reactions of isolable dialkylsilylene 1 with aromatic acyl chlorides afforded aroylsilanes 3a3c exclusively. Aroylsilanes 3a3c were characterized by 1H-, 13C-, and 29Si-NMR spectroscopy, high-resolution mass spectrometry (HRMS), and single-crystal molecular structure analysis. The reaction mechanisms
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The reactions of isolable dialkylsilylene 1 with aromatic acyl chlorides afforded aroylsilanes 3a3c exclusively. Aroylsilanes 3a3c were characterized by 1H-, 13C-, and 29Si-NMR spectroscopy, high-resolution mass spectrometry (HRMS), and single-crystal molecular structure analysis. The reaction mechanisms are discussed in comparison with related reaction of 1 with chloroalkanes and chlorosilanes. Full article
(This article belongs to the Special Issue Advances in Silicon Chemistry)
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Open AccessArticle A Novel Tetrahydrocannabinol Electrochemical Nano Immunosensor Based on Horseradish Peroxidase and Double-Layer Gold Nanoparticles
Molecules 2016, 21(10), 1377; doi:10.3390/molecules21101377
Received: 8 September 2016 / Revised: 9 October 2016 / Accepted: 12 October 2016 / Published: 17 October 2016
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Abstract
In the current study, a novel double-layer gold nanoparticles-electrochemical immunosensor electrode immobilized with tetrahydrocannabinol (THC) antibody derived from Balb/c mice was developed. To increase the fixed quantity of antibodies and electrochemical signals, an electrochemical biosensing signal amplification system was utilized with gold nanoparticles-thionine-chitosan