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Molecules, Volume 21, Issue 12 (December 2016)

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Description "Microtubule targeting agents, some of the most effective drugs used in the treatment of cancer, [...] Read more.
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Editorial

Jump to: Research, Review, Other

Open AccessEditorial Dr. Kenneth A. Jacobson: First Winner of the Tu Youyou Award, in Honor of the Co-Recipient of the 2015 Nobel Prize in Physiology or Medicine
Molecules 2016, 21(12), 1656; doi:10.3390/molecules21121656
Received: 29 November 2016 / Revised: 29 November 2016 / Accepted: 29 November 2016 / Published: 1 December 2016
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Open AccessEditorial Special Issue “Ring-Opening Polymerization”
Molecules 2016, 21(12), 1720; doi:10.3390/molecules21121720
Received: 5 December 2016 / Revised: 8 December 2016 / Accepted: 8 December 2016 / Published: 14 December 2016
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(This article belongs to the Special Issue Ring-Opening Polymerization)
Open AccessEditorial Special Issue: “Molecules against Alzheimer”
Molecules 2016, 21(12), 1736; doi:10.3390/molecules21121736
Received: 9 December 2016 / Revised: 12 December 2016 / Accepted: 12 December 2016 / Published: 16 December 2016
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Abstract
This Special Issue, entitled “Molecules against Alzheimer”, gathers a number of original articles, short communications, and review articles on recent research efforts toward the development of novel drug candidates, diagnostic agents and therapeutic approaches for Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder
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This Special Issue, entitled “Molecules against Alzheimer”, gathers a number of original articles, short communications, and review articles on recent research efforts toward the development of novel drug candidates, diagnostic agents and therapeutic approaches for Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder and a leading cause of death worldwide. This Special Issue contains many interesting examples describing the design, synthesis, and pharmacological profiling of novel compounds that hit one or several key biological targets, such as cholinesterases, β-amyloid formation or aggregation, monoamine oxidase B, oxidative stress, biometal dyshomeostasis, mitochondrial dysfunction, serotonin and/or melatonin systems, the Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase, or nuclear erythroid 2-related factor. The development of novel AD diagnostic agents based on tau protein imaging and the use of lithium or intranasal insulin for the prevention or the symptomatic treatment of AD is also covered in some articles of the Special Issue. Full article
(This article belongs to the Special Issue Molecules against Alzheimer)
Open AccessEditorial Natural Products in Anti-Obesity Therapy
Molecules 2016, 21(12), 1750; doi:10.3390/molecules21121750
Received: 16 December 2016 / Revised: 16 December 2016 / Accepted: 17 December 2016 / Published: 20 December 2016
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Abstract Obesity is regulated by genetic, endocrine, metabolic, neurological, pharmacological, environmental, and nutritional factors. [...]
Full article
(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)
Open AccessEditorial Recent Advances in Olefin Metathesis
Molecules 2016, 21(12), 1751; doi:10.3390/molecules21121751
Received: 19 December 2016 / Revised: 19 December 2016 / Accepted: 20 December 2016 / Published: 21 December 2016
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Abstract Olefin metathesis is one of the most significant developments of the last 20 years in the fields of organic chemistry, polymers synthesis, and materials science [1–7]. [...]
Full article
(This article belongs to the Special Issue Olefin Metathesis)

Research

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Open AccessArticle Combating Ebola with Repurposed Therapeutics Using the CANDO Platform
Molecules 2016, 21(12), 1537; doi:10.3390/molecules21121537
Received: 29 July 2016 / Revised: 23 October 2016 / Accepted: 28 October 2016 / Published: 25 November 2016
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Abstract
Ebola virus disease (EVD) is extremely virulent with an estimated mortality rate of up to 90%. However, the state-of-the-art treatment for EVD is limited to quarantine and supportive care. The 2014 Ebola epidemic in West Africa, the largest in history, is believed to
[...] Read more.
Ebola virus disease (EVD) is extremely virulent with an estimated mortality rate of up to 90%. However, the state-of-the-art treatment for EVD is limited to quarantine and supportive care. The 2014 Ebola epidemic in West Africa, the largest in history, is believed to have caused more than 11,000 fatalities. The countries worst affected are also among the poorest in the world. Given the complexities, time, and resources required for a novel drug development, finding efficient drug discovery pathways is going to be crucial in the fight against future outbreaks. We have developed a Computational Analysis of Novel Drug Opportunities (CANDO) platform based on the hypothesis that drugs function by interacting with multiple protein targets to create a molecular interaction signature that can be exploited for rapid therapeutic repurposing and discovery. We used the CANDO platform to identify and rank FDA-approved drug candidates that bind and inhibit all proteins encoded by the genomes of five different Ebola virus strains. Top ranking drug candidates for EVD treatment generated by CANDO were compared to in vitro screening studies against Ebola virus-like particles (VLPs) by Kouznetsova et al. and genetically engineered Ebola virus and cell viability studies by Johansen et al. to identify drug overlaps between the in virtuale and in vitro studies as putative treatments for future EVD outbreaks. Our results indicate that integrating computational docking predictions on a proteomic scale with results from in vitro screening studies may be used to select and prioritize compounds for further in vivo and clinical testing. This approach will significantly reduce the lead time, risk, cost, and resources required to determine efficacious therapies against future EVD outbreaks. Full article
(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)
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Open AccessArticle Synthesis and Structure-Activity Relationships of a Series of Aporphine Derivatives with Antiarrhythmic Activities and Acute Toxicity
Molecules 2016, 21(12), 1555; doi:10.3390/molecules21121555
Received: 18 October 2016 / Revised: 7 November 2016 / Accepted: 7 November 2016 / Published: 28 November 2016
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Abstract
Some aporphine alkaloids, such as crebanine, were found to present arrhythmic activity and also higher toxicity. A series of derivatives were synthesized by using three kinds of aporphine alkaloids (crebanine, isocorydine, and stephanine) as lead compounds. Chemical methods, including ring-opening reaction, bromination, methylation,
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Some aporphine alkaloids, such as crebanine, were found to present arrhythmic activity and also higher toxicity. A series of derivatives were synthesized by using three kinds of aporphine alkaloids (crebanine, isocorydine, and stephanine) as lead compounds. Chemical methods, including ring-opening reaction, bromination, methylation, acetylation, quaternization, and dehydrogenation, were adopted. Nineteen target derivatives were evaluated for their antiarrhythmic potential in the mouse model of ventricular fibrillation (VF), induced by CHCl3, and five of the derivatives were investigated further in the rat model of arrhythmia, induced by BaCl2. Meanwhile, preliminary structure-activity/toxicity relationship analyses were carried out. Significantly, N-acetamidesecocrebanine (1d), three bromo-substituted products of crebanine (2a, 2b, 2c), N-methylcrebanine (2d), and dehydrostephanine (4a) displayed antiarrhythmic effects in the CHCl3-induced model. Among them, 7.5 mg/kg of 2b was able to significantly reduce the incidence of VF induced by CHCl3 (p < 0.05), increase the number of rats that resumed sinus rhythm from arrhythmia, induced by BaCl2 (p < 0.01), and the number of rats that maintained sinus rhythm for more than 20 min (p < 0.01). Therefore, 2b showed remarkably higher antiarrhythmic activity and a lower toxicity (LD50 = 59.62 mg/kg, mice), simultaneously, indicating that 2b could be considered as a promising candidate in the treatment of arrhythmia. Structural-activity analysis suggested that variationsin antiarrhythmic efficacy and toxicity of aporphines were related to the C-1,C-2-methylenedioxy group on ring A, restricted ring B structural conformation, N-quaternization of ring B, levoduction of 6a in ring C, and the 8-, 9-, 10-methoxy groups on ring D on the skeleton. Full article
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Open AccessArticle Effects of Polysaccharide Elicitors from Endophytic Fusarium oxysporum Fat9 on the Growth, Flavonoid Accumulation and Antioxidant Property of Fagopyrum tataricum Sprout Cultures
Molecules 2016, 21(12), 1590; doi:10.3390/molecules21121590
Received: 20 September 2016 / Revised: 12 November 2016 / Accepted: 16 November 2016 / Published: 25 November 2016
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Abstract
The purpose of this study was to evaluate the effects of four different fungal polysaccharides, named water-extracted mycelia polysaccharide (WPS), sodium hydroxide-extracted mycelia polysaccharide (SPS), hydrochloric-extracted mycelia polysaccharide (APS), and exo-polysaccharide (EPS) obtained from the endophytic Fusarium oxysporum Fat9 on the sprout growth,
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The purpose of this study was to evaluate the effects of four different fungal polysaccharides, named water-extracted mycelia polysaccharide (WPS), sodium hydroxide-extracted mycelia polysaccharide (SPS), hydrochloric-extracted mycelia polysaccharide (APS), and exo-polysaccharide (EPS) obtained from the endophytic Fusarium oxysporum Fat9 on the sprout growth, flavonoid accumulation, and antioxidant capacity of tartary buckwheat. Without visible changes in the appearance of the sprouts, the exogenous polysaccharide elicitors strongly stimulated sprout growth and flavonoid production, and the stimulation effect was closely related with the polysaccharide (PS) species and its treatment dosage. With application of 200 mg/L of EPS, 200 mg/L of APS, 150 mg/L of WPS, or 100 mg/L of SPS, the total rutin and quercetin yields of buckwheat sprouts were significantly increased to 41.70 mg/(100 sprouts), 41.52 mg/(100 sprouts), 35.88 mg/(100 sprouts), and 32.95 mg/(100 sprouts), respectively. This was about 1.11 to 1.40-fold compared to the control culture of 31.40 mg/(100 sprouts). Moreover, the antioxidant capacity of tartary buckwheat sprouts was also enhanced after treatment with the four PS elicitors. Furthermore, the present study revealed the polysaccharide elicitation that caused the accumulation of functional flavonoid by stimulating the phenylpropanoid pathway. The application of beneficial fungal polysaccharide elicitors may be an effective approach to improve the nutritional and functional characteristics of tartary buckwheat sprouts. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Improvement of Transmembrane Transport Mechanism Study of Imperatorin on P-Glycoprotein-Mediated Drug Transport
Molecules 2016, 21(12), 1606; doi:10.3390/molecules21121606
Received: 20 September 2016 / Revised: 16 November 2016 / Accepted: 16 November 2016 / Published: 24 November 2016
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Abstract
P-glycoprotein (P-gp) affects the transport of many drugs; including puerarin and vincristine. Our previous study demonstrated that imperatorin increased the intestinal absorption of puerarin and vincristine by inhibiting P-gp-mediated drug efflux. However; the underlying mechanism was not known. The present study investigated the
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P-glycoprotein (P-gp) affects the transport of many drugs; including puerarin and vincristine. Our previous study demonstrated that imperatorin increased the intestinal absorption of puerarin and vincristine by inhibiting P-gp-mediated drug efflux. However; the underlying mechanism was not known. The present study investigated the mechanism by which imperatorin promotes P-gp-mediated drug transport. We used molecular docking to predict the binding force between imperatorin and P-gp and the effect of imperatorin on P-gp activity. P-gp efflux activity and P-gp ATPase activity were measured using a rhodamine 123 (Rh-123) accumulation assay and a Pgp-Glo™ assay; respectively. The fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to assess cellular membrane fluidity in MDCK-MDR1 cells. Western blotting was used to analyze the effect of imperatorin on P-gp expression; and P-gp mRNA levels were assessed by qRT-PCR. Molecular docking results demonstrated that the binding force between imperatorin and P-gp was much weaker than the force between P-gp and verapamil (a P-gp substrate). Imperatorin activated P-gp ATPase activity; which had a role in the inhibition of P-gp activity. Imperatorin promoted Rh-123 accumulation in MDCK-MDR1 cells and decreased cellular membrane fluidity. Western blotting demonstrated that imperatorin inhibited P-gp expression; and qRT-PCR revealed that imperatorin down-regulated P-gp (MDR1) gene expression. Imperatorin decreased P-gp-mediated drug efflux by inhibiting P-gp activity and the expression of P-gp mRNA and protein. Our results suggest that imperatorin could down-regulate P-gp expression to overcome multidrug resistance in tumors. Full article
(This article belongs to the Special Issue Can Membrane Transporters Contribute to Drug Discovery?)
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Open AccessArticle Extraction of Opuntia dillenii Haw. Polysaccharides and Their Antioxidant Activities
Molecules 2016, 21(12), 1612; doi:10.3390/molecules21121612
Received: 3 October 2016 / Revised: 10 November 2016 / Accepted: 16 November 2016 / Published: 24 November 2016
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Abstract
Use of natural polysaccharides in medicine and food has wide interest in research. In this study, we extracted and purified some polysaccharides from cactus Opuntia dillenii Haw. (ODP). Some preliminary functions of these products were characterized. Under the optimal purification conditions, the yield
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Use of natural polysaccharides in medicine and food has wide interest in research. In this study, we extracted and purified some polysaccharides from cactus Opuntia dillenii Haw. (ODP). Some preliminary functions of these products were characterized. Under the optimal purification conditions, the yield of ODP extracted from the 2–4 month-old Opuntia dillenii Haw. (T-ODP) was 30.60% ± 0.40%, higher than that of ODP from the 5–10 month-old materials (O-ODP) (18.97% ± 0.58%). The extracted ODP was purified by DEAE sepharose fast flow anion exchange and Sephacryl S-400 chromatography with four fractions obtained (ODP-Ia, ODP-Ib, ODP-IIa and ODP-IIb). Analysis with UV-vis chromatography indicated that ODP-Ia and ODP-IIa were relatively homogeneous molecules with a molecular weight of 339 kD and 943 kD, respectively. Results of infrared spectroscopy indicated that ODP, ODP-Ia, and ODP-IIa were acidic polysaccharides. Further, the antioxidant activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) radical, hydroxyl radicals, and superoxide radical in vitro demonstrated that the T-ODP exhibited higher antioxidant activity than the O-ODP, and the purified fraction (ODP-Ia) was superior to the ODP. These results will offer a theoretical basis for further research on the structure-function relationship of ODP and the rational utilization of Opuntia dillenii Haw. Full article
(This article belongs to the Special Issue Natural Polysaccharides)
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Open AccessArticle Screening for Triterpenoid Saponins in Plants Using Hyphenated Analytical Platforms
Molecules 2016, 21(12), 1614; doi:10.3390/molecules21121614
Received: 14 October 2016 / Revised: 15 November 2016 / Accepted: 19 November 2016 / Published: 24 November 2016
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Abstract
Recently the number of studies investigating triterpenoid saponins has drastically increased due to their diverse and potentially attractive biological activities. Currently the literature contains chemical structures of few hundreds of triterpenoid saponins of plant and animal origin. Triterpenoid saponins consist of a triterpene
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Recently the number of studies investigating triterpenoid saponins has drastically increased due to their diverse and potentially attractive biological activities. Currently the literature contains chemical structures of few hundreds of triterpenoid saponins of plant and animal origin. Triterpenoid saponins consist of a triterpene aglycone with one or more sugar moieties attached to it. However, due to similar physico-chemical properties, isolation and identification of a large diversity of triterpenoid saponins remain challenging. This study demonstrates a methodology to screen saponins using hyphenated analytical platforms, GC-MS, LC-MS/MS, and LC-SPE-NMR/MS, in the example of two different phenotypes of the model plant Barbarea vulgaris (winter cress), glabrous (G) and pubescent (P) type that are known to differ by their insect resistance. The proposed methodology allows for detailed comparison of saponin profiles from intact plant extracts as well as saponin aglycone profiles from hydrolysed samples. Continuously measured 1D proton NMR data during LC separation along with mass spectrometry data revealed significant differences, including contents of saponins, types of aglycones and numbers of sugar moieties attached to the aglycone. A total of 49 peaks were tentatively identified as saponins from both plants; they are derived from eight types of aglycones and with 2–5 sugar moieties. Identification of two previously known insect-deterrent saponins, hederagenin cellobioside and oleanolic acid cellobioside, demonstrated the applicability of the methodology for relatively rapid screening of bioactive compounds. Full article
(This article belongs to the Special Issue Triterpenes and Triterpenoids 2016)
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Open AccessArticle A Novel Lighting OLED Panel Design
Molecules 2016, 21(12), 1615; doi:10.3390/molecules21121615
Received: 15 September 2016 / Revised: 9 November 2016 / Accepted: 13 November 2016 / Published: 25 November 2016
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Abstract
A novel OLED (organic light emitting diode) lighting panel, which uses a special layout design, can reduce the photolithography cycles and process costs and is more reliable. It only needs two steps of photolithography cycles, which include an ITO (InSnO compound transparent oxide)
[...] Read more.
A novel OLED (organic light emitting diode) lighting panel, which uses a special layout design, can reduce the photolithography cycles and process costs and is more reliable. It only needs two steps of photolithography cycles, which include an ITO (InSnO compound transparent oxide) pattern and insulator pattern. There is no need for the metal bus pattern of the ordinary design. The OLED device structure is a type of red–green–blue (RGB)-stacked emitting layer that has a good color index and greater adjustability, which improves the performance of the device. This novel design has the same equipment and material requirement compared to the ordinary design, and it is very beneficial in terms of high volume and low-cost production. It uses a hyper driving method because the entire OLED lighting panel is divided into many sub-emitting units; if one of the sub-emitting units is burned out, it has no effect on the adjacent sub-emitting unit, so the reliability is markedly better than the ordinary design. Full article
(This article belongs to the Special Issue Organic Light Emitting Diodes)
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Open AccessArticle Evaluation and Comparison of the Inhibition Effect of Astragaloside IV and Aglycone Cycloastragenol on Various UDP-Glucuronosyltransferase (UGT) Isoforms
Molecules 2016, 21(12), 1616; doi:10.3390/molecules21121616
Received: 8 October 2016 / Revised: 8 November 2016 / Accepted: 22 November 2016 / Published: 29 November 2016
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Abstract
As one of the main active ingredients from Radix Astragali (RA), orally dosed astragaloside IV (AST) is easily transformed to sapogenin-cycloastragenol (CAG) by deglycosylation in the gastrointestinal tract. Because the potential adverse effects of AST and CAG remain unclear, the present study in
[...] Read more.
As one of the main active ingredients from Radix Astragali (RA), orally dosed astragaloside IV (AST) is easily transformed to sapogenin-cycloastragenol (CAG) by deglycosylation in the gastrointestinal tract. Because the potential adverse effects of AST and CAG remain unclear, the present study in this article was carried out to investigate the inhibition effects of AST and CAG on UDP-glucuronosyltransferases (UGTs) to explore potential clinical toxicity. An in vitro UGTs incubation mixture was employed to study the inhibition of AST and CAG towards UGT isoforms. Concentrations of 100 μM for each compound were used to initially screen the inhibitory efficiency. Deglycosylation of AST to CAG could strongly increase the inhibitory effects towards almost all of the tested UGT isoforms, with an IC50 of 0.84 μM and 11.28 μM for UGT1A8 and UGT2B7, respectively. Ulteriorly, the inhibition type and kinetics of CAG towards UGT1A8 and UGT2B7 were evaluated depending on the initial screening results. Data fitting using Dixon and Lineweaver–Burk plots demonstrated that CAG competitively inhibited UGT1A8 and noncompetitively inhibited UGT2B7. From the second plot drawn with the slopes from the Lineweaver–Burk plot versus the concentrations of CAG, the inhibition constant (Ki) was calculated to be 0.034 μM and 20.98 μM for the inhibition of UGT1A8 and UGT2B7, respectively. Based on the [I]/Ki standard ([I]/Ki < 0.1, low possibility; 1 > [I]/Ki > 0.1, medium possibility; [I]/Ki > 1, high possibility), it was successfully predicted here that an in vivo herb–drug interaction between AST/CAG and drugs mainly undergoing UGT1A8- or UGT2B7-catalyzed metabolism might occur when the plasma concentration of CAG is above 0.034 μM and 20.98 μM, respectively. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle Charge Transfer Enhancement in the D-π-A Type Porphyrin Dyes: A Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TD-DFT) Study
Molecules 2016, 21(12), 1618; doi:10.3390/molecules21121618
Received: 4 November 2016 / Revised: 19 November 2016 / Accepted: 21 November 2016 / Published: 25 November 2016
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Abstract
The electronic geometries and optical properties of two D-π-A type zinc porphyrin dyes (NCH3-YD2 and TPhe-YD) were systematically investigated by density functional theory (DFT) and time-dependent density functional theory (TD-DFT) to reveal the origin of significantly altered charge transfer enhancement by
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The electronic geometries and optical properties of two D-π-A type zinc porphyrin dyes (NCH3-YD2 and TPhe-YD) were systematically investigated by density functional theory (DFT) and time-dependent density functional theory (TD-DFT) to reveal the origin of significantly altered charge transfer enhancement by changing the electron donor of the famous porphyrin-based sensitizer YD2-o-C8. The molecular geometries and photophysical properties of dyes before and after binding to the TiO2 cluster were fully investigated. From the analyses of natural bond orbital (NBO), extended charge decomposition analysis (ECDA), and electron density variations (Δρ) between the excited state and ground state, it was found that the introduction of N(CH3)2 and 1,1,2-triphenylethene groups enhanced the intramolecular charge-transfer (ICT) character compared to YD2-o-C8. The absorption wavelength and transition possess character were significantly influenced by N(CH3)2 and 1,1,2-triphenylethene groups. NCH3-YD2 with N(CH3)2 groups in the donor part is an effective way to improve the interactions between the dyes and TiO2 surface, light having efficiency (LHE), and free energy change (ΔGinject), which is expected to be an efficient dye for use in dye-sensitized solar cells (DSSCs). Full article
(This article belongs to the Special Issue Dye‐Sensitized Solar Cells)
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Open AccessArticle A New Two-Photon Ratiometric Fluorescent Probe for Detecting Alkaline Phosphatase in Living Cells
Molecules 2016, 21(12), 1619; doi:10.3390/molecules21121619
Received: 19 October 2016 / Revised: 20 November 2016 / Accepted: 22 November 2016 / Published: 25 November 2016
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Abstract
Alkaline phosphatase (ALP) is an important diagnostic indicator of many human diseases. To quantitatively track ALP in biosystems, herein, for the first time, we report an efficient two-photon ratiometric fluorescent probe, termed probe 1 and based on classic naphthalene derivatives with a donor–π–acceptor
[...] Read more.
Alkaline phosphatase (ALP) is an important diagnostic indicator of many human diseases. To quantitatively track ALP in biosystems, herein, for the first time, we report an efficient two-photon ratiometric fluorescent probe, termed probe 1 and based on classic naphthalene derivatives with a donor–π–acceptor (D–π–A) structure and deprotection of the phosphoric acid moiety by ALP. The presence of ALP causes the cleave of the phosphate group from naphthalene derivatives and the phosphate group changes the ability of the intramolecular charge transfer (ICT) and remarkably alters the probe’s photophysical properties, thus an obvious ratiometric signal with an isoemissive point is observed. The fluorescence intensity ratio displayed a linear relationship against the concentration of ALP in the concentration range from 20 to 180 U/L with the limit of detection of 2.3 U/L. Additionally, the probe 1 is further used for fluorescence imaging of ALP in living cells under one-photon excitation (405 nm) or two-photon excitation (720 nm), which showed a high resolution imaging, thus demonstrating its practical application in biological systems. Full article
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Open AccessArticle Hydrodechlorination of Tetrachloromethane over Palladium Catalysts Supported on Mixed MgF2-MgO Carriers
Molecules 2016, 21(12), 1620; doi:10.3390/molecules21121620
Received: 1 November 2016 / Revised: 18 November 2016 / Accepted: 22 November 2016 / Published: 25 November 2016
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Abstract
Pd/MgO, Pd/MgF2 and Pd/MgO-MgF2 catalysts were investigated in the reaction of CCl4 hydrodechlorination. All the catalysts deactivated in time on stream, but the degree of deactivation varied from catalyst to catalyst. The MgF2-supported palladium with relatively large metal
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Pd/MgO, Pd/MgF2 and Pd/MgO-MgF2 catalysts were investigated in the reaction of CCl4 hydrodechlorination. All the catalysts deactivated in time on stream, but the degree of deactivation varied from catalyst to catalyst. The MgF2-supported palladium with relatively large metal particles appeared the best catalyst, characterized by good activity and selectivity to C2-C5 hydrocarbons. Investigation of post-reaction catalyst samples allowed to find several details associated with the working state of hydrodechlorination catalysts. The role of support acidity was quite complex. On the one hand, a definite, although not very high Lewis acidity of MgF2 is beneficial for shaping high activity of palladium catalysts. The MgO-MgF2 support characterized by stronger Lewis acidity than MgF2 contributes to very good catalytic activity for a relatively long reaction period (~5 h) but subsequent neutralization of stronger acid centers (by coking) eliminates them from the catalyst. On the other hand, the role of acidity evolution, which takes place when basic supports (like MgO) are chlorided during HdCl reactions, is difficult to assess because different events associated with distribution of chlorided support species, leading to partial or even full blocking of the surface of palladium, which plays the role of active component in HdCl reactions. Full article
(This article belongs to the Special Issue Nano-sized Metal Fluorides: Novel Approaches to Lewis Acid Catalysts)
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Open AccessArticle Immobilization of Neutral Protease from Bacillus subtilis for Regioselective Hydrolysis of Acetylated Nucleosides: Application to Capecitabine Synthesis
Molecules 2016, 21(12), 1621; doi:10.3390/molecules21121621
Received: 10 September 2016 / Revised: 19 November 2016 / Accepted: 21 November 2016 / Published: 25 November 2016
Cited by 2 | PDF Full-text (2030 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This paper describes the immobilization of the neutral protease from Bacillus subtilis and its application in the regioselective hydrolysis of acetylated nucleosides, including building blocks useful for the preparation of anticancer products. Regarding the immobilization study, different results have been obtained depending on
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This paper describes the immobilization of the neutral protease from Bacillus subtilis and its application in the regioselective hydrolysis of acetylated nucleosides, including building blocks useful for the preparation of anticancer products. Regarding the immobilization study, different results have been obtained depending on the immobilization procedure. Epoxy hydrophobic carriers gave a poorly stable derivative that released almost 50% of the immobilized protein under the required reaction conditions. On the contrary, covalent immobilization on a differently activated hydrophilic carrier (agarose) resulted in very stable enzyme derivatives. In an attempt to explain the obtained enzyme immobilization results, the hypothetical localization of lysines on the enzyme surface was predicted in a 3D structure model of B. subtilis protease N built in silico by using the structure of Staphylococcus aureus metalloproteinase as the template. The immobilized enzyme shown a high regioselectivity in the hydrolysis of different peracetylated nucleosides. A stable enzyme derivative was obtained and successfully used in the development of efficient preparative bioprocesses for the hydrolysis of acetylated nucleosides, giving new intermediates for the synthesis of capecitabine in high yield. Full article
(This article belongs to the Special Issue Enzyme Immobilization 2016)
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Open AccessArticle In Vitro Chemopreventive Properties of Green Tea, Rooibos and Honeybush Extracts in Skin Cells
Molecules 2016, 21(12), 1622; doi:10.3390/molecules21121622
Received: 30 October 2016 / Revised: 20 November 2016 / Accepted: 21 November 2016 / Published: 25 November 2016
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Abstract
The chemopreventive properties of the herbal teas rooibos (Aspalathus linearis) and honeybush (Cyclopia spp.) have been demonstrated on mouse skin in vivo but the underlying mechanisms are not clear. The aim of the current study was to determine the anti-proliferative
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The chemopreventive properties of the herbal teas rooibos (Aspalathus linearis) and honeybush (Cyclopia spp.) have been demonstrated on mouse skin in vivo but the underlying mechanisms are not clear. The aim of the current study was to determine the anti-proliferative and pro-apoptotic activity of methanol and aqueous extracts of rooibos and two Cyclopia species in different skin cells, using green tea (Camellia sinensis) as a benchmark. Extracts were also characterised for their major individual polyphenols by high performance liquid chromatography and spectroscopically for the total polyphenol (TP) groups. The methanol extract of rooibos, containing higher levels of polyphenols than its aqueous extract, displayed similar activity to green tea as it selectively targeted premalignant cells by inhibiting cell proliferation at lower concentrations whilst inducing apoptosis via membrane depolarisation at higher concentrations. Specific roles of the major rooibos dihydrochalcones and flavanol/proanthocyanidin-type (FLAVA) compounds are likely to be involved. The aqueous extracts of the Cyclopia species were more active against cell proliferation and at inducing apoptosis which was associated with a higher FLAVA content and a reduced TP/FLAVA ratio. In contrast, their methanol extracts exhibited a cytoprotective effect against apoptosis which was related to their monomeric xanthone and flavanone content. The underlying chemopreventive properties of green tea and the herbal teas appear to be associated with diverse and complex monomeric/polymeric polyphenolic cell interactions. Full article
(This article belongs to the Special Issue Catechins and Human Health: Current State of the Science)
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Open AccessArticle Research on the Relationships between Endogenous Biomarkers and Exogenous Toxic Substances of Acute Toxicity in Radix Aconiti
Molecules 2016, 21(12), 1623; doi:10.3390/molecules21121623
Received: 13 October 2016 / Revised: 13 November 2016 / Accepted: 21 November 2016 / Published: 25 November 2016
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Abstract
Radix Aconiti, a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently,
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Radix Aconiti, a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were available to find the relationships between these endogenous biomarkers and exogenous toxic substances. Therefore, in this study, toxic substances of Radix Aconiti have been found using UPLC-Q-TOF-MS technology. Then, we used biochemical indicators as a bridge to find the relationships between biomarkers and toxic substances of Radix Aconiti through Pearson correlation analysis and canonical correlation analysis (CCA). Finally, the CCA results showed that LysoPC(22:5) is related to 14-acetyl-talatisamine, mesaconitine, talatisamine and deoxyaconitine in varying degrees; l-acetylcarnitine is negatively correlated with deoxyaconitine and demethyl-14-acetylkaracoline; shikimic acid has a good correlation with karacoline, demethyl-14-acetylkaracoline and deoxyaconitine; and valine is correlated with talatisamine and deoxyaconitine. Research on these relationships provides an innovative way to interpret the toxic mechanism of traditional Chinese medicine, and plays a positive role in the overall study of TCM toxicity. Full article
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Open AccessCommunication Effect of Thermoultrasound on the Antioxidant Compounds and Fatty Acid Profile of Blackberry (Rubus fruticosus spp.) Juice
Molecules 2016, 21(12), 1624; doi:10.3390/molecules21121624
Received: 7 October 2016 / Revised: 19 November 2016 / Accepted: 23 November 2016 / Published: 29 November 2016
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Abstract
Blackberry (Rubus fruticosus spp.) fruit has high antioxidant activity due to its significant content of anthocyanins and antioxidant compounds. Among emerging technologies for food preservation, thermoultrasound is a technique that reduces microbial loads and releases compounds with antioxidant properties. The objective of
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Blackberry (Rubus fruticosus spp.) fruit has high antioxidant activity due to its significant content of anthocyanins and antioxidant compounds. Among emerging technologies for food preservation, thermoultrasound is a technique that reduces microbial loads and releases compounds with antioxidant properties. The objective of this study was to determine the antioxidant content and fatty acid profile of blackberry juice subjected to thermoultrasound treatment in comparison to pasteurized juice. Blackberry juice and n-hexane extracts from a control (untreated juice), pasteurized, and thermoultrasonicated samples were evaluated for antioxidant activity, fatty acid profile, and antioxidant content. The juice treated with thermoultrasound exhibited significantly (p < 0.05) higher levels of total phenols (1011 mg GAE/L), anthocyanins (118 mg Cy-3-GlE/L); antioxidant activity by ABTS (44 mg VCEAC/L) and DPPH (2665 µmol TE/L) in comparison to the control and pasteurized samples. Oil extract from thermoultrasound juice also had the highest antioxidant activity (177.5 mg VCEAC/L and 1802.6 µmol TE/L). The fatty acid profile of the n-hexane extracts showed the presence of myristic, linolenic, stearic, oleic, and linoleic acids and was not affected by the treatments except for stearic acid, whose amount was particularly higher in the control. Our results demonstrated that thermoultrasound can be an alternative technology to pasteurization that maintains and releases antioxidant compounds and preserves the fatty acids of fruit juice. Full article
(This article belongs to the Special Issue Sonochemistry and Green Chemistry Applications)
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Open AccessArticle A Method for Determining the Content of Glycoproteins in Biological Samples
Molecules 2016, 21(12), 1625; doi:10.3390/molecules21121625
Received: 22 October 2016 / Revised: 22 November 2016 / Accepted: 22 November 2016 / Published: 26 November 2016
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Abstract
The glycoprotein purified from the mycelium extract of Tremella fuciformis was marked with iodine through the iodine substitution reaction. The content of iodine, which is indicative of the amount of the marked tremella glycoprotein (ITG), was detected with Inductively coupled plasma mass spectrometry
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The glycoprotein purified from the mycelium extract of Tremella fuciformis was marked with iodine through the iodine substitution reaction. The content of iodine, which is indicative of the amount of the marked tremella glycoprotein (ITG), was detected with Inductively coupled plasma mass spectrometry (ICP-MS). The method was found to be stable, sensitive, and accurate at detecting the content of iodine-substituted glycoprotein, and was used in the quantitative analysis of biological samples, including blood and organs. Different biological samples were collected from rats after oral administration of ITG, and were tested for iodine content by ICP-MS to calculate the amount of ITG in the samples. The results suggested that ICP-MS is a sensitive, stable, and accurate method for detection of iodinated glycoproteins in blood and organs. Full article
(This article belongs to the Special Issue Natural Polysaccharides)
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Open AccessArticle Inhibition of Urease by Disulfiram, an FDA-Approved Thiol Reagent Used in Humans
Molecules 2016, 21(12), 1628; doi:10.3390/molecules21121628
Received: 8 October 2016 / Revised: 18 November 2016 / Accepted: 21 November 2016 / Published: 26 November 2016
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Abstract
Urease is a nickel-dependent amidohydrolase that catalyses the decomposition of urea into carbamate and ammonia, a reaction that constitutes an important source of nitrogen for bacteria, fungi and plants. It is recognized as a potential antimicrobial target with an impact on medicine, agriculture,
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Urease is a nickel-dependent amidohydrolase that catalyses the decomposition of urea into carbamate and ammonia, a reaction that constitutes an important source of nitrogen for bacteria, fungi and plants. It is recognized as a potential antimicrobial target with an impact on medicine, agriculture, and the environment. The list of possible urease inhibitors is continuously increasing, with a special interest in those that interact with and block the flexible active site flap. We show that disulfiram inhibits urease in Citrullus vulgaris (CVU), following a non-competitive mechanism, and may be one of this kind of inhibitors. Disulfiram is a well-known thiol reagent that has been approved by the FDA for treatment of chronic alcoholism. We also found that other thiol reactive compounds (l-captopril and Bithionol) and quercetin inhibits CVU. These inhibitors protect the enzyme against its full inactivation by the thiol-specific reagent Aldrithiol (2,2′-dipyridyl disulphide, DPS), suggesting that the three drugs bind to the same subsite. Enzyme kinetics, competing inhibition experiments, auto-fluorescence binding experiments, and docking suggest that the disulfiram reactive site is Cys592, which has been proposed as a “hinge” located in the flexible active site flap. This study presents the basis for the use of disulfiram as one potential inhibitor to control urease activity. Full article
(This article belongs to the Section Theoretical Chemistry)
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Open AccessArticle Design, Synthesis and Biological Evaluation of Novel Primaquine-Cinnamic Acid Conjugates of the Amide and Acylsemicarbazide Type
Molecules 2016, 21(12), 1629; doi:10.3390/molecules21121629
Received: 18 October 2016 / Revised: 16 November 2016 / Accepted: 24 November 2016 / Published: 28 November 2016
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Abstract
In this paper design and synthesis of a scaffold comprising primaquine (PQ) motif and cinnamic acid derivatives (CADs) bound directly (compounds 3ak) or via a spacer (compounds 7ak) are reported. In the first series of compounds, PQ
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In this paper design and synthesis of a scaffold comprising primaquine (PQ) motif and cinnamic acid derivatives (CADs) bound directly (compounds 3ak) or via a spacer (compounds 7ak) are reported. In the first series of compounds, PQ and various CADs were connected by amide bonds and in the second series by acylsemicarbazide functional groups built from the PQ amino group, CONHNH spacer and the carbonyl group originating from the CADs. PQ-CAD amides 3ak were prepared by a simple one-step condensation reaction of PQ with a series of CAD chlorides (method A) or benzotriazolides 2 (method B). The synthesis of acylsemicarbazides 7ak included activation of PQ with benzotriazole, preparation of PQ-semicarbazide 6 and its condensation with CAD chlorides 4. All synthesized PQ-CAD conjugates were evaluated for their anticancer, antiviral and antioxidative activities. Almost all compounds from series 3 were selective towards the MCF-7 cell line and active at micromolar concentrations. The o-fluoro derivative 3h showed high activity against HeLa, MCF-7 and in particular against the SW 620 cell line, while acylsemicarbazide 7f with a benzodioxole ring and 7c, 7g and especially 7j with methoxy-, chloro- or trifluoromethyl-substituents in the para position showed high selectivity and high inhibitory activity against MCF-7 cell line at micromolar (7c, 7f, 7g) and nanomolar (7j) levels. Acylsemicarbazide derivatives with trifluoromethyl group(s) 7i, 7j and 7k showed specific activity against human coronavirus (229E) at concentrations which did not alter the normal cell morphology. The same compounds exerted the most potent reducing activity in the DPPH test, together with 7d and 7g, while methoxy (compounds 7ce), benzodioxole (7f), p-Cl (7g) and m-CF3 (7i) acylsemicarbazides and amide 3f presented the highest LP inhibition (83%–89%). The dimethoxy derivative 7d was the most potent LOX inhibitor (IC50 = 10 μΜ). The performed biological tests gave evidence of acylsemicarbazide functional group as superior binding group in PQ-CAD conjugates. Full article
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Open AccessArticle Simultaneous Determination of Four Tanshinones by UPLC-TQ/MS and Their Pharmacokinetic Application after Administration of Single Ethanol Extract of Danshen Combined with Water Extract in Normal and Adenine-Induced Chronic Renal Failure Rats
Molecules 2016, 21(12), 1630; doi:10.3390/molecules21121630
Received: 19 October 2016 / Revised: 24 November 2016 / Accepted: 25 November 2016 / Published: 28 November 2016
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Abstract
Salvia miltiorrhiza, one of the major traditional Chinese medicines, is commonly used and the main active ingredients—tanshinones—possess the ability to improve renal function. In this paper, the UPLC-TQ/MS method of simultaneously determining four tanshinones—tanshinone IIA, dihydrotanshinone I, tanshinone I, and cryptotanshinone—was established
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Salvia miltiorrhiza, one of the major traditional Chinese medicines, is commonly used and the main active ingredients—tanshinones—possess the ability to improve renal function. In this paper, the UPLC-TQ/MS method of simultaneously determining four tanshinones—tanshinone IIA, dihydrotanshinone I, tanshinone I, and cryptotanshinone—was established and applied to assess the pharmacokinetics in normal and chronic renal failure (CRF) rat plasma. The pharmacokinetics of tanshinones in rats were studied after separately intragastric administration of Salvia miltiorrhiza ethanol extract (SMEE) (0.65 g/kg), SMEE (0.65 g/kg) combined with Salvia miltiorrhiza water extract (SMWE) (1.55 g/kg). The results showed Cmax and AUC0–t of tanshinone IIA, tanshinone I, cryptotanshinone reduced by 50%~80% and CLz/F increased by 2~4 times (p < 0.05) in model group after administrated with SMEE. Nevertheless, after intragastric administration of a combination of SMWE and SMEE, the Cmax and AUC0–t of four tanshinones were upregulated and CLz/F was downregulated, which undulated similarity from the model group to the normal group with compatibility of SMEE and SMWE. These results hinted that SMWE could improve the bioavailability of tanshinones in CRF rats, which provides scientific information for further exploration the mechanism of the combination of SMWE and SMEE and offers a reference for clinical administration of Salvia miltiorrhiza. Full article
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Open AccessArticle Antifungal Activity of Oleuropein against Candida albicans—The In Vitro Study
Molecules 2016, 21(12), 1631; doi:10.3390/molecules21121631
Received: 1 November 2016 / Revised: 21 November 2016 / Accepted: 24 November 2016 / Published: 28 November 2016
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Abstract
In the present study we investigated activity of oleuropein, a complex phenol present in large quantities in olive tree products, against opportunistic fungal pathogen Candida albicans. Oleuropein was found to have in vitro antifungal activity with a minimal inhibitory concentration (MIC) value
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In the present study we investigated activity of oleuropein, a complex phenol present in large quantities in olive tree products, against opportunistic fungal pathogen Candida albicans. Oleuropein was found to have in vitro antifungal activity with a minimal inhibitory concentration (MIC) value of 12.5 mg·mL−1. Morphological changes in the nuclei after staining with fluorescent DNA-binding dyes revealed that apoptosis was a primary mode of cell death in the analyzed samples treated with subinhibitory concentrations of oleuropein. Our results suggest that this antifungal agent targets virulence factors essential for establishment of the fungal infection. We noticed that oleuropein modulates morphogenetic conversion and inhibits filamentation of C. albicans. The hydrophobicity assay showed that oleuropein in sub-MIC values has significantly decreased, in both aerobic and anaerobic conditions, the cellular surface hydrophobicity (CSH) of C. albicans, a factor associated with adhesion to epithelial cells. It was also demonstrated that the tested compound inhibits the activity of SAPs, cellular enzymes secreted by C. albicans, which are reported to be related to the pathogenicity of the fungi. Additionally, we detected that oleuropein causes a reduction in total sterol content in the membrane of C. albicans cells, which might be involved in the mechanism of its antifungal activity. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessArticle Expression, Purification, and Characterization of Interleukin-11 Orthologues
Molecules 2016, 21(12), 1632; doi:10.3390/molecules21121632
Received: 10 November 2016 / Revised: 22 November 2016 / Accepted: 24 November 2016 / Published: 29 November 2016
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Abstract
Interleukin-11 (IL-11) is a multifunctional cytokine implicated in several normal and pathological processes. The decoding of IL-11 function and development of IL-11-targeted drugs dictate the use of laboratory animals and need of the better understanding of species specificity of IL-11 signaling. Here, we
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Interleukin-11 (IL-11) is a multifunctional cytokine implicated in several normal and pathological processes. The decoding of IL-11 function and development of IL-11-targeted drugs dictate the use of laboratory animals and need of the better understanding of species specificity of IL-11 signaling. Here, we present a method for the recombinant interleukin-11 (rIL-11) production from the important model animals, mouse and macaque. The purified mouse and macaque rIL-11 interact with extracellular domain of human IL-11 receptor subunit α and activate STAT3 signaling in HEK293 cells co-expressing human IL-11 receptors with efficacies resembling those of human rIL-11. Hence, the evolutionary divergence does not impair IL-11 signaling. Furthermore, compared to human rIL-11 its macaque orthologue is 8-fold more effective STAT3 activator, which favors its use for treatment of thrombocytopenia as a potent substitute for human rIL-11. Compared to IL-6, IL-11 signaling exhibits lower species specificity, likely due to less conserved intrinsic disorder propensity within IL-6 orthologues. The developed express method for preparation of functionally active macaque/mouse rIL-11 samples is suited for exploration of the molecular mechanisms underlying IL-11 action and for development of the drug candidates for therapy of oncologic/hematologic/inflammatory diseases related to IL-11 signaling. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Enhanced Antimicrobial and Anticancer Activity of Silver and Gold Nanoparticles Synthesised Using Sargassum incisifolium Aqueous Extracts
Molecules 2016, 21(12), 1633; doi:10.3390/molecules21121633
Received: 26 October 2016 / Revised: 22 November 2016 / Accepted: 23 November 2016 / Published: 2 December 2016
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Abstract
A detailed, methodical approach was used to synthesise silver and gold nanoparticles using two differently prepared aqueous extracts of the brown algae Sargassum incisifolium. The efficiency of the extracts in producing nanoparticles were compared to commercially available brown algal fucoidans, a major
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A detailed, methodical approach was used to synthesise silver and gold nanoparticles using two differently prepared aqueous extracts of the brown algae Sargassum incisifolium. The efficiency of the extracts in producing nanoparticles were compared to commercially available brown algal fucoidans, a major constituent of brown algal aqueous extracts. The nanoparticles were characterised using TEM, XRD and UV/Vis spectroscopy and zeta potential measurements. The rate of nanoparticle formation was assessed using UV/Vis spectroscopy and related to the size, shape and morphology of the nanoparticles as revealed by TEM. The antioxidant, reducing power and total polyphenolic contents of the aqueous extracts and fucoidans were determined, revealing that the aqueous extracts with the highest contents produced smaller, spherical, more monodisperse nanoparticles at a faster rate. The nanoparticles were assessed against two gram-negative bacteria, two gram-positive bacteria and one yeast strain. In contrast to the literature, the silver nanoparticles produced using the aqueous extracts were particularly toxic to Gram-negative bacteria, while the gold nanoparticles lacked activity. The cytotoxic activity of the nanoparticles was also evaluated against cancerous (HT-29, MCF-7) and non-cancerous (MCF-12a) cell lines. The silver nanoparticles displayed selectivity, since the MCF-12a cell line was found to be resistant to the nanoparticles, while the cancerous HT-29 cell line was found to be sensitive (10% viability). The gold nanoparticles displayed negligible toxicity. Full article
(This article belongs to the Special Issue Gold Nanoparticles for Biomedical Applications)
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Open AccessArticle Synthesis and Pharmacological Evaluation of New 3,4-Dihydroisoquinolin Derivatives Containing Heterocycle as Potential Anticonvulsant Agents
Molecules 2016, 21(12), 1635; doi:10.3390/molecules21121635
Received: 2 November 2016 / Accepted: 25 November 2016 / Published: 29 November 2016
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Abstract
Two novel series of 3,4-dihydroisoquinolin with heterocycle derivatives (4at and 9ae) were synthesized and evaluated for their anticonvulsant activity using maximal electroshock (MES) test and pentylenetetrazole (PTZ)-induced seizure test. All compounds were characterized by IR, 1H-NMR,
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Two novel series of 3,4-dihydroisoquinolin with heterocycle derivatives (4at and 9ae) were synthesized and evaluated for their anticonvulsant activity using maximal electroshock (MES) test and pentylenetetrazole (PTZ)-induced seizure test. All compounds were characterized by IR, 1H-NMR, 13C-NMR, and mass spectral data. Among them, 9-(exyloxy)-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinolin-3(2H)-one (9a) showed significant anticonvulsant activity in MES tests with an ED50 value of 63.31 mg/kg and it showed wide margins of safety with protective index (PI > 7.9). It showed much higher anticonvulsant activity than that of valproate. It also demonstrated potent activity against PTZ-induced seizures. A docking study of compound 9a in the benzodiazepine (BZD)-binding site of γ-aminobutyric acidA (GABAA) receptor confirmed possible binding of compound 9a with the BZD receptors. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessCommunication Controlled Synthesis of Atomically Layered Hexagonal Boron Nitride via Chemical Vapor Deposition
Molecules 2016, 21(12), 1636; doi:10.3390/molecules21121636
Received: 17 August 2016 / Revised: 19 November 2016 / Accepted: 24 November 2016 / Published: 29 November 2016
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Abstract
Hexagonal boron nitrite (h-BN) is an attractive material for many applications including electronics as a complement to graphene, anti-oxidation coatings, light emitters, etc. However, the synthesis of high-quality h-BN is still a great challenge. In this work, via controlled chemical vapor deposition, we
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Hexagonal boron nitrite (h-BN) is an attractive material for many applications including electronics as a complement to graphene, anti-oxidation coatings, light emitters, etc. However, the synthesis of high-quality h-BN is still a great challenge. In this work, via controlled chemical vapor deposition, we demonstrate the synthesis of h-BN films with a controlled thickness down to atomic layers. The quality of as-grown h-BN is confirmed by complementary characterizations including high-resolution transition electron microscopy, atomic force microscopy, Raman spectroscopy and X-ray photo-electron spectroscopy. This work will pave the way for production of large-scale and high-quality h-BN and its applications as well. Full article
(This article belongs to the Special Issue Boron Nitride: Synthesis and Application)
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Open AccessArticle Synthesis and Biological Evaluation of Novel Aromatic Imide-Polyamine Conjugates
Molecules 2016, 21(12), 1637; doi:10.3390/molecules21121637
Received: 1 October 2016 / Revised: 17 November 2016 / Accepted: 23 November 2016 / Published: 30 November 2016
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Abstract
Three types of conjugates in which aromatic imide scaffolds were coupled to diverse amine/polyamine motifs were synthesized, and their antitumor activities were evaluated in vitro and in vivo. Results showed that the conjugate 11e of 1,8-naphthilimide with spermine had pronounced effects on inhibiting
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Three types of conjugates in which aromatic imide scaffolds were coupled to diverse amine/polyamine motifs were synthesized, and their antitumor activities were evaluated in vitro and in vivo. Results showed that the conjugate 11e of 1,8-naphthilimide with spermine had pronounced effects on inhibiting tumor cell proliferation and inducing tumor cell apoptosis via ROS-mediated mitochondrial pathway. The in vivo assays on three H22 tumor transplant models revealed that compound 11e exerted potent ability in preventing lung cancer metastasis and extending lifespan. Furthermore, the efficacy of 11e in inhibiting tumor growth and improving body weight index were better than that of positive control, amonafide. Our study demonstrates that compound 11e is a valuable lead compound for further investigation. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Multi-Layer Identification of Highly-Potent ABCA1 Up-Regulators Targeting LXRβ Using Multiple QSAR Modeling, Structural Similarity Analysis, and Molecular Docking
Molecules 2016, 21(12), 1639; doi:10.3390/molecules21121639
Received: 31 October 2016 / Revised: 21 November 2016 / Accepted: 26 November 2016 / Published: 29 November 2016
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Abstract
In this study, in silico approaches, including multiple QSAR modeling, structural similarity analysis, and molecular docking, were applied to develop QSAR classification models as a fast screening tool for identifying highly-potent ABCA1 up-regulators targeting LXRβ based on a series of new flavonoids. Initially,
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In this study, in silico approaches, including multiple QSAR modeling, structural similarity analysis, and molecular docking, were applied to develop QSAR classification models as a fast screening tool for identifying highly-potent ABCA1 up-regulators targeting LXRβ based on a series of new flavonoids. Initially, four modeling approaches, including linear discriminant analysis, support vector machine, radial basis function neural network, and classification and regression trees, were applied to construct different QSAR classification models. The statistics results indicated that these four kinds of QSAR models were powerful tools for screening highly potent ABCA1 up-regulators. Then, a consensus QSAR model was developed by combining the predictions from these four models. To discover new ABCA1 up-regulators at maximum accuracy, the compounds in the ZINC database that fulfilled the requirement of structural similarity of 0.7 compared to known potent ABCA1 up-regulator were subjected to the consensus QSAR model, which led to the discovery of 50 compounds. Finally, they were docked into the LXRβ binding site to understand their role in up-regulating ABCA1 expression. The excellent binding modes and docking scores of 10 hit compounds suggested they were highly-potent ABCA1 up-regulators targeting LXRβ. Overall, this study provided an effective strategy to discover highly potent ABCA1 up-regulators. Full article
(This article belongs to the Special Issue Biomolecular Simulations)
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Open AccessArticle Combined Use of Zoledronic Acid Augments Ursolic Acid-Induced Apoptosis in Human Osteosarcoma Cells through Enhanced Oxidative Stress and Autophagy
Molecules 2016, 21(12), 1640; doi:10.3390/molecules21121640
Received: 25 October 2016 / Revised: 16 November 2016 / Accepted: 25 November 2016 / Published: 30 November 2016
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Abstract
Ursolic acid (UA), a naturally occurring pentacyclic triterpene acid found in many medicinal herbs and edible plants, triggers apoptosis in several tumor cell lines but not in human bone cancer cells. Most recently, we have demonstrated that UA exposure reduces the viability of
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Ursolic acid (UA), a naturally occurring pentacyclic triterpene acid found in many medicinal herbs and edible plants, triggers apoptosis in several tumor cell lines but not in human bone cancer cells. Most recently, we have demonstrated that UA exposure reduces the viability of human osteosarcoma MG-63 cells through enhanced oxidative stress and apoptosis. Interestingly, an inhibitor of osteoclast-mediated bone resorption, zoledronic acid (ZOL), also a third-generation nitrogen-containing bisphosphonate, is effective in the treatment of bone metastases in patients with various solid tumors. In this present study, we found that UA combined with ZOL to significantly suppress cell viability, colony formation, and induce apoptosis in two lines of human osteosarcoma cells. The pre-treatment of the antioxidant had reversed the oxidative stress and cell viability inhibition in the combined treatment, indicating that oxidative stress is important in the combined anti-tumor effects. Moreover, we demonstrated that ZOL combined with UA significantly induced autophagy and co-administration of autophagy inhibitor reduces the growth inhibitory effect of combined treatment. Collectively, these data shed light on the pathways involved in the combined effects of ZOL and UA that might serve as a potential therapy against osteosarcoma. Full article
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Open AccessArticle Docetaxel-Loaded Self-Assembly Stearic Acid-Modified Bletilla striata Polysaccharide Micelles and Their Anticancer Effect: Preparation, Characterization, Cellular Uptake and In Vitro Evaluation
Molecules 2016, 21(12), 1641; doi:10.3390/molecules21121641
Received: 18 October 2016 / Revised: 21 November 2016 / Accepted: 25 November 2016 / Published: 2 December 2016
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Abstract
Poorly soluble drugs have low bioavailability after oral administration, thereby hindering effective drug delivery. A novel drug-delivery system of docetaxel (DTX)-based stearic acid (SA)-modified Bletilla striata polysaccharides (BSPs) copolymers was successfully developed. Particle size, zeta potential, encapsulation efficiency (EE), and loading capacity (LC)
[...] Read more.
Poorly soluble drugs have low bioavailability after oral administration, thereby hindering effective drug delivery. A novel drug-delivery system of docetaxel (DTX)-based stearic acid (SA)-modified Bletilla striata polysaccharides (BSPs) copolymers was successfully developed. Particle size, zeta potential, encapsulation efficiency (EE), and loading capacity (LC) were determined. The DTX release percentage in vitro was determined using high performance liquid chromatography (HPLC). The hemolysis and in vitro anticancer activity were studied. Cellular uptake and apoptotic rate were measured using flow cytometry assay. Particle size, zeta potential, EE and LC were 125.30 ± 1.89 nm, −26.92 ± 0.18 mV, 86.6% ± 0.17%, and 14.8% ± 0.13%, respectively. The anticancer activities of DTX-SA-BSPs copolymer micelles against HepG2, HeLa, SW480, and MCF-7 (83.7% ± 1.0%, 54.5% ± 4.2%, 48.5% ± 4.2%, and 59.8% ± 1.4%, respectively) were superior to that of docetaxel injection (39.2% ± 1.1%, 44.5% ± 5.3%, 38.5% ± 5.4%, and 49.8% ± 2.9%, respectively) at 0.5 μg/mL drug concentration. The DTX release percentage of DTX-SA-BSPs copolymer micelles and docetaxel injection were 66.93% ± 1.79% and 97.06% ± 1.56% in two days, respectively. Cellular uptake of DTX-FITC-SA-BSPs copolymer micelles in cells had a time-dependent relation. Apoptotic rate of DTX-SA-BSPs copolymer micelles and docetaxel injection were 73.48% and 69.64%, respectively. The SA-BSPs copolymer showed good hemocompatibility. Therefore, SA-BSPs copolymer can be used as a carrier for delivering hydrophobic drugs. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Investigation on Fluorescence Quenching Mechanism of Perylene Diimide Dyes by Graphene Oxide
Molecules 2016, 21(12), 1642; doi:10.3390/molecules21121642
Received: 15 September 2016 / Revised: 21 November 2016 / Accepted: 23 November 2016 / Published: 30 November 2016
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Abstract
Perylene diimide derivatives were used as probes to investigate the effect of the molecular structures on the fluorescence quenching mechanism in a perylene diimide/graphene oxide system. The electrons transferred from the excited state of dyes to the conductive band of graphene oxide with
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Perylene diimide derivatives were used as probes to investigate the effect of the molecular structures on the fluorescence quenching mechanism in a perylene diimide/graphene oxide system. The electrons transferred from the excited state of dyes to the conductive band of graphene oxide with different concentrations were determined by fluorescence spectra. The results indicated that the quenching efficiency of perylene diimides by graphene oxide was not only dependent on the difference between the lowest unoccupied molecular orbital level of dyes and the conduction band of the graphene oxide, but also mainly on the difference in the molecular structures. Full article
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Open AccessArticle Drug Release by Direct Jump from Poly(ethylene-glycol-b-ε-caprolactone) Nano-Vector to Cell Membrane
Molecules 2016, 21(12), 1643; doi:10.3390/molecules21121643
Received: 24 October 2016 / Revised: 15 November 2016 / Accepted: 18 November 2016 / Published: 30 November 2016
PDF Full-text (2499 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Drug delivery by nanovectors involves numerous processes, one of the most important being its release from the carrier. This point still remains unclear. The current work focuses on this point using poly(ethyleneglycol-b-ε-caprolactone) micelles containing either pheophorbide-a (Pheo-a) as a fluorescent probe and a
[...] Read more.
Drug delivery by nanovectors involves numerous processes, one of the most important being its release from the carrier. This point still remains unclear. The current work focuses on this point using poly(ethyleneglycol-b-ε-caprolactone) micelles containing either pheophorbide-a (Pheo-a) as a fluorescent probe and a phototoxic agent or fluorescent copolymers. This study showed that the cellular uptake and the phototoxicity of loaded Pheo-a are ten times higher than those of the free drug and revealed a very low cellular penetration of the fluorescence-labeled micelles. Neither loaded nor free Pheo-a displayed the same cellular localization as the labeled micelles. These results imply that the drug entered the cells without its carrier and probably without a disruption, as suggested by their stability in cell culture medium. These data allowed us to propose that Pheo-a directly migrates from the micelle to the cell without disruption of the vector. This mechanism will be discussed. Full article
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Open AccessArticle Alpha- and Beta-Cyclodextrin Inclusion Complexes with 5-Fluorouracil: Characterization and Cytotoxic Activity Evaluation
Molecules 2016, 21(12), 1644; doi:10.3390/molecules21121644
Received: 10 November 2016 / Revised: 24 November 2016 / Accepted: 25 November 2016 / Published: 1 December 2016
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Abstract
Cyclodextrins are natural macrocyclic oligosaccharides able to form inclusion complexes with a wide variety of guests, affecting their physicochemical and pharmaceutical properties. In order to obtain an improvement of the bioavailability and solubility of 5-fluorouracil, a pyrimidine analogue used as chemotherapeutic agent in
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Cyclodextrins are natural macrocyclic oligosaccharides able to form inclusion complexes with a wide variety of guests, affecting their physicochemical and pharmaceutical properties. In order to obtain an improvement of the bioavailability and solubility of 5-fluorouracil, a pyrimidine analogue used as chemotherapeutic agent in the treatment of the colon, liver, and stomac cancers, the drug was complexed with alpha- and beta-cyclodextrin. The inclusion complexes were prepared in the solid state by kneading method and characterized by Fourier transform-infrared (FT-IR) spectroscopy and X-ray powder diffractometry. In solution, the 1:1 stoichiometry for all the inclusion complexes was established by the Job plot method and the binding constants were determined at different pHs by UV-VIS titration. Furthermore, the cytotoxic activity of 5-fluorouracil and its complexation products were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on MCF-7 (breast cancer cell line), Hep G2 (hepatocyte carcinoma cell line), Caco-2 (colon adenocarcinoma cell line), and A-549 (alveolar basal epithelial carcinoma cell line). The results showed that both inclusion complexes increased the 5-fluorouracil capability of inhibiting cell growth. In particular, 5-fluorouracil complexed with beta-cyclodextrin had the highest cytotoxic activity on MCF-7; with alpha-cyclodextrin the highest cytotoxic activity was observed on A-549. The IC50 values were equal to 31 and 73 µM at 72 h, respectively. Our results underline the possibility of using these inclusion complexes in pharmaceutical formulations for improving 5-fluorouracil therapeutic efficacy. Full article
(This article belongs to the Special Issue Cyclodextrin Chemistry)
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Open AccessCommunication Excited-State Dynamics of Melamine and Its Lysine Derivative Investigated by Femtosecond Transient Absorption Spectroscopy
Molecules 2016, 21(12), 1645; doi:10.3390/molecules21121645
Received: 1 November 2016 / Revised: 24 November 2016 / Accepted: 24 November 2016 / Published: 30 November 2016
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Abstract
Melamine may have been an important prebiotic information carrier, but its excited-state dynamics, which determine its stability under UV radiation, have never been characterized. The ability of melamine to withstand the strong UV radiation present on the surface of the early Earth is
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Melamine may have been an important prebiotic information carrier, but its excited-state dynamics, which determine its stability under UV radiation, have never been characterized. The ability of melamine to withstand the strong UV radiation present on the surface of the early Earth is likely to have affected its abundance in the primordial soup. Here, we studied the excited-state dynamics of melamine (a proto-nucleobase) and its lysine derivative (a proto-nucleoside) using the transient absorption technique with a UV pump, and UV and infrared probe pulses. For melamine, the excited-state population decays by internal conversion with a lifetime of 13 ps without coupling significantly to any photochemical channels. The excited-state lifetime of the lysine derivative is slightly longer (18 ps), but the dominant deactivation pathway is otherwise the same as for melamine. In both cases, the vast majority of excited molecules return to the electronic ground state on the aforementioned time scales, but a minor population is trapped in a long-lived triplet state. Full article
(This article belongs to the Special Issue Experimental and Computational Photochemistry of Bioorganic Molecules)
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Open AccessArticle A Simple Precursor for Highly Functionalized Fused Imidazo[4,5-b]pyridines and Imidazo[4,5-b]-1,8-naphthyridine
Molecules 2016, 21(12), 1646; doi:10.3390/molecules21121646
Received: 23 September 2016 / Revised: 21 November 2016 / Accepted: 23 November 2016 / Published: 1 December 2016
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Abstract
1-alkyl aryl-5-amino-4-(cyanoformimidoyl)imidazoles 4 were reacted with malononitrile and 2-amino-1,1,3-propenetricarbonitrile under mild experimental conditions, which led to 5-amino-3-(substituted benzyl)-6,7-dicyano-3H-imidazo[4,5-b]pyridines 5 and 6,8-diamino-3-(4-substituted benzyl)-3H-imidazo[4,5-b]-1,8-naphthyridine-7,9-dicarbonitrile 6, respectively, when the reaction was carried out in the absence of
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1-alkyl aryl-5-amino-4-(cyanoformimidoyl)imidazoles 4 were reacted with malononitrile and 2-amino-1,1,3-propenetricarbonitrile under mild experimental conditions, which led to 5-amino-3-(substituted benzyl)-6,7-dicyano-3H-imidazo[4,5-b]pyridines 5 and 6,8-diamino-3-(4-substituted benzyl)-3H-imidazo[4,5-b]-1,8-naphthyridine-7,9-dicarbonitrile 6, respectively, when the reaction was carried out in the absence of a base, or to 5,7-diamino-3-(4-alkyl aryl)-3H-imidazo[4,5-b]pyridine-6-carbonitrile 8, and 6,8,9-triamino-3-(4-substitutedbenzyl)-3H-imidazo[4,5-b]-1,8-naphthyridine-7-carbonitrile 10 in the presence of 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU). Both reactions evolved from an adduct formed by nucleophilic attack of the malononitrile anion or 2-amino-1,1,3-propenetricarbonitrile anion to the carbon of the cyanoformimidoyl substituent. In the case of the malononitrile anion, a 5-amino-1-alkyl aryl-4-(1-amino-2,2-dicyanovinyl)imidazole 7 was isolated when this reaction was carried out in the presence of DBU. The structure of compound 7 was confirmed by spectroscopic methods, and cyclized intramolecularly to 8 by heating in ethanol/triethyl amine. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Pathway Analysis and Metabolites Identification by Metabolomics of Etiolation Substrate from Fresh-Cut Chinese Water Chestnut (Eleocharis tuberosa)
Molecules 2016, 21(12), 1648; doi:10.3390/molecules21121648
Received: 9 October 2016 / Revised: 20 November 2016 / Accepted: 21 November 2016 / Published: 1 December 2016
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Abstract
Fresh-cut Chinese water chestnuts (CWC) turn yellow after being peeled, reducing their shelf life and commercial value. Metabolomics, the systematic study of the full complement of small molecular metabolites, was useful for clarifying the mechanism of fresh-cut CWC etiolation and developing methods to
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Fresh-cut Chinese water chestnuts (CWC) turn yellow after being peeled, reducing their shelf life and commercial value. Metabolomics, the systematic study of the full complement of small molecular metabolites, was useful for clarifying the mechanism of fresh-cut CWC etiolation and developing methods to inhibit yellowing. In this study, metabolic alterations associated with etiolation at different growth stages (0 day, 2 days, 3 days, 4 days, 5 days) from fresh-cut CWC were investigated using LC–MS and analyzed by pattern recognition methods (principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal projection to latent structures-discriminant analysis (OPLS-DA)). The metabolic pathways of the etiolation molecules were elucidated. The main metabolic pathway appears to be the conversion of phenylalanine to p-coumaroyl-CoA, followed by conversion to naringenin chalcone, to naringenin, and naringenin then following different pathways. Firstly, it can transform into apigenin and its derivatives; secondly, it can produce eriodictyol and its derivatives; and thirdly it can produce dihydrokaempferol, quercetin, and myricetin. The eriodictyol can be further transformed to luteolin, cyanidin, dihydroquercetin, dihydrotricetin, and others. This is the first reported use of metabolomics to study the metabolic pathways of the etiolation of fresh-cut CWC. Full article
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Open AccessArticle A Molecular Electron Density Theory Study of the Chemical Reactivity of Cis- and Trans-Resveratrol
Molecules 2016, 21(12), 1650; doi:10.3390/molecules21121650
Received: 14 October 2016 / Revised: 22 November 2016 / Accepted: 28 November 2016 / Published: 1 December 2016
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Abstract
The chemical reactivity of resveratrol isomers with the potential to play a role as inhibitors of the nonenzymatic glycation of amino acids and proteins, both acting as antioxidants and as chelating agents for metallic ions such as Cu, Al and Fe, have been
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The chemical reactivity of resveratrol isomers with the potential to play a role as inhibitors of the nonenzymatic glycation of amino acids and proteins, both acting as antioxidants and as chelating agents for metallic ions such as Cu, Al and Fe, have been studied by resorting to the latest family of Minnesota density functionals. The chemical reactivity descriptors have been calculated through Molecular Electron Density Theory encompassing Conceptual DFT. The active sites for nucleophilic and electrophilic attacks have been chosen by relating them to the Fukui function indices, the dual descriptor f ( 2 ) ( r ) and the electrophilic and nucleophilic Parr functions. The validity of “Koopmans’ theorem in DFT” has been assessed by means of a comparison between the descriptors calculated through vertical energy values and those arising from the HOMO and LUMO values. Full article
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Open AccessArticle Catalytic Performance of a New 1D Cu(II) Coordination Polymer {Cu(NO3)(H2O)}(HTae)(4,4′-Bpy) for Knoevenagel Condensation
Molecules 2016, 21(12), 1651; doi:10.3390/molecules21121651
Received: 20 October 2016 / Revised: 18 November 2016 / Accepted: 23 November 2016 / Published: 1 December 2016
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Abstract
The {Cu(NO3)(H2O)}(HTae)(4,4′-Bpy) (H2Tae = 1,1,2,2-tetraacetylethane, 4,4′-Bpy = 4,4′-Dipyridyl) 1D coordination polymer has been obtained by slow evaporation. The crystal structure consists of parallel and oblique {Cu(HTae)(4,4′-Bpy)} zig-zag metal–organic chains stacked along the [100] crystallographic direction. Copper(II) ions
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The {Cu(NO3)(H2O)}(HTae)(4,4′-Bpy) (H2Tae = 1,1,2,2-tetraacetylethane, 4,4′-Bpy = 4,4′-Dipyridyl) 1D coordination polymer has been obtained by slow evaporation. The crystal structure consists of parallel and oblique {Cu(HTae)(4,4′-Bpy)} zig-zag metal–organic chains stacked along the [100] crystallographic direction. Copper(II) ions are in octahedral coordination environment linked to two nitrogen atoms of two bridging 4,4′-Bpy and to two oxygen atoms of one HTae molecule in the equatorial plane. The occupation of the axial positions varies from one copper atom to another, with different combinations of water molecules and nitrate anions, giving rise to a commensurate super-structure. By means of the thermal removal of water molecules, copper coordinatively unsaturated centres are obtained. These open metal sites could act as Lewis acid active sites in several heterogeneous catalytic reactions. The dehydrated compound, CuHTaeBpy_HT, has been tested as a heterogeneous recoverable catalyst for Knoevenagel condensation reactions. The catalyst is active and heterogeneous for the condensation of aldehydes with malononitrile at 60 °C using a molar ratio catalyst:substrate of 3 % and toluene as solvent. The catalyst suffers a partial loss of activity when reusing it, but can be reused at least four times. Full article
(This article belongs to the Special Issue Transition Metal Catalysis 2016)
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Open AccessArticle Multi-Residue Analysis of Pesticide Residues in Crude Pollens by UPLC-MS/MS
Molecules 2016, 21(12), 1652; doi:10.3390/molecules21121652
Received: 6 November 2016 / Revised: 24 November 2016 / Accepted: 24 November 2016 / Published: 1 December 2016
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Abstract
A multi-residue method for the determination of 54 pesticide residues in pollens has been developed and validated. The proposed method was applied to the analysis of 48 crude pollen samples collected from eight provinces of China. The recovery of analytes ranged from 60%
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A multi-residue method for the determination of 54 pesticide residues in pollens has been developed and validated. The proposed method was applied to the analysis of 48 crude pollen samples collected from eight provinces of China. The recovery of analytes ranged from 60% to 136% with relative standard deviations (RSDs) below 30%. Of the 54 targeted compounds, 19 pesticides were detected. The major detection rates of each compound were 77.1% for carbendazim, 58.3% for fenpropathrin, 56.3% for chlorpyrifos, 50.0% for fluvalinate, 31.3% for chlorbenzuron, and 29.2% for triadimefon in crude pollen samples. The maximum values of each pesticide were 4516 ng/g for carbendazim, 162.8 ng/g for fenpropathrin, 176.6 ng/g for chlorpyrifos, 316.2 ng/g for fluvalinate, 437.2 ng/g for chlorbenzuron, 79.00 ng/g for triadimefon, and so on. This study provides basis for the research on the risks to honeybee health. Full article
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Open AccessArticle A Novel Two-Step Liquid-Liquid Extraction Procedure Combined with Stationary Phase Immobilized Human Serum Albumin for the Chiral Separation of Cetirizine Enantiomers along with M and P Parabens
Molecules 2016, 21(12), 1654; doi:10.3390/molecules21121654
Received: 11 October 2016 / Revised: 27 November 2016 / Accepted: 29 November 2016 / Published: 7 December 2016
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Abstract
The research into the separation of drug enantiomers is closely related to the safety and efficiency of the drugs. The aim of this study was to develop a simple and validated HPLC method to analyze cetirizine enantiomers. In the case of liquid dosage
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The research into the separation of drug enantiomers is closely related to the safety and efficiency of the drugs. The aim of this study was to develop a simple and validated HPLC method to analyze cetirizine enantiomers. In the case of liquid dosage forms, besides the active substance in large amounts there are usually also inactive ingredients such as methyl- and propylparaben. Unfortunately, these compounds can interfere with the analyte, inter alia during chiral separation of the analyte enantiomers. The proposed innovative two-step liquid-liquid extraction procedure allowed for the determination of cetirizine enantiomers (along with M and P parabens) also in liquid dosage forms. The main focus of this study was the chromatographic activity of cetirizine dihydrochloride on the proteinate-based chiral stationary phase. The chromatographic separation of cetirizine enantiomers was performed on an immobilized human serum albumin (HSA) column for the first time. Measurements were performed at a wavelength of 227 nm. Under optimal conditions, baseline separation of two enantiomers was obtained with 1.43 enantioseparation factor (α) and 1.82 resolution (Rs). Finally, the proposed method was successfully applied to the selected pharmaceutical formulations. Full article
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Open AccessArticle Expedient Organocatalytic Syntheses of 4-Substituted Pyrazolidines and Isoxazolidines
Molecules 2016, 21(12), 1655; doi:10.3390/molecules21121655
Received: 9 November 2016 / Revised: 24 November 2016 / Accepted: 28 November 2016 / Published: 1 December 2016
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Abstract
The efficient organocatalytic synthesis of heterocyclic systems of biological relevance is a subject of growing interest. We have found that the pyrrolidine/benzoic acid-catalyzed reaction of α-substituted propenals such as methacrolein, 2-benzylpropenal and 2-(n-hexyl)propenal with activated hydrazines takes place in very good
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The efficient organocatalytic synthesis of heterocyclic systems of biological relevance is a subject of growing interest. We have found that the pyrrolidine/benzoic acid-catalyzed reaction of α-substituted propenals such as methacrolein, 2-benzylpropenal and 2-(n-hexyl)propenal with activated hydrazines takes place in very good yields (83%–99.6%) under very mild conditions to afford 4-substituted pyrazolidin-3-ols (as diastereomer mixtures); subsequent oxidation with PCC affords the corresponding-4-substituted-3-pyrazolidinones in essentially quantitative yields. In a similar way, 4-substituted isoxazolidinones are obtained with N-Cbz-hydroxylamine as a reagent. The use of chiral diarylprolinol trimethylsilyl ethers as catalysts allows the synthesis of several of these compounds in optically active form, in some cases with excellent enantioselectivity (up to 96:4 er). A preliminary evaluation of the biological activity shows that some of these compounds exhibit interesting antibacterial and antifungal activities. Full article
(This article belongs to the collection Recent Advances in Organocatalysis)
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Open AccessArticle A Computational Study of Structure and Reactivity of N-Substitued-4-Piperidones Curcumin Analogues and Their Radical Anions
Molecules 2016, 21(12), 1658; doi:10.3390/molecules21121658
Received: 21 October 2016 / Revised: 25 November 2016 / Accepted: 28 November 2016 / Published: 2 December 2016
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Abstract
In this work, a computational study of a series of N-substitued-4-piperidones curcumin analogues is presented. The molecular structure of the neutral molecules and their radical anions, as well as their reactivity, are investigated. N-substituents include methyl and benzyl groups, while substituents
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In this work, a computational study of a series of N-substitued-4-piperidones curcumin analogues is presented. The molecular structure of the neutral molecules and their radical anions, as well as their reactivity, are investigated. N-substituents include methyl and benzyl groups, while substituents on the aromatic rings cover electron-donor and electron-acceptor groups. Substitutions at the nitrogen atom do not significantly affect the geometry and frontier molecular orbitals (FMO) energies of these molecules. On the other hand, substituents on the aromatic rings modify the distribution of FMO. In addition, they influence the capability of these molecules to attach an additional electron, which was studied through adiabatic (AEA) and vertical electron affinities (VEA), as well as vertical detachment energy (VDE). To study electrophilic properties of these structures, local reactivity indices, such as Fukui (f+) and Parr (P+) functions, were calculated, and show the influence of the aromatic rings substituents on the reactivity of α,β-unsaturated ketones towards nucleophilic attack. This study has potential implications for the design of curcumin analogues based on a 4-piperidone core with desired reactivity. Full article
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Open AccessArticle Supercritical CO2 Foaming of Radiation Cross-Linked Isotactic Polypropylene in the Presence of TAIC
Molecules 2016, 21(12), 1660; doi:10.3390/molecules21121660
Received: 17 October 2016 / Revised: 27 November 2016 / Accepted: 29 November 2016 / Published: 7 December 2016
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Abstract
Since the maximum foaming temperature window is only about 4 °C for supercritical CO2 (scCO2) foaming of pristine polypropylene, it is important to raise the melt strength of polypropylene in order to more easily achieve scCO2
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Since the maximum foaming temperature window is only about 4 °C for supercritical CO2 (scCO2) foaming of pristine polypropylene, it is important to raise the melt strength of polypropylene in order to more easily achieve scCO2 foaming. In this work, radiation cross-linked isotactic polypropylene, assisted by the addition of a polyfunctional monomer (triallylisocyanurate, TAIC), was employed in the scCO2 foaming process in order to understand the benefits of radiation cross-linking. Due to significantly enhanced melt strength and the decreased degree of crystallinity caused by cross-linking, the scCO2 foaming behavior of polypropylene was dramatically changed. The cell size distribution, cell diameter, cell density, volume expansion ratio, and foaming rate of radiation-cross-linked polypropylene under different foaming conditions were analyzed and compared. It was found that radiation cross-linking favors the foamability and formation of well-defined cell structures. The optimal absorbed dose with the addition of 2 wt % TAIC was 30 kGy. Additionally, the foaming temperature window was expanded to about 8 °C, making the handling of scCO2 foaming of isotactic polypropylene much easier. Full article
(This article belongs to the Special Issue Sub- and Supercritical Fluids and Green Chemistry)
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Open AccessArticle Janus Compounds, 5-Chloro-N4-methyl-N4-aryl-9H-pyrimido[4,5-b]indole-2,4-diamines, Cause Both Microtubule Depolymerizing and Stabilizing Effects
Molecules 2016, 21(12), 1661; doi:10.3390/molecules21121661
Received: 17 October 2016 / Revised: 23 November 2016 / Accepted: 28 November 2016 / Published: 2 December 2016
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Abstract
While evaluating a large library of compounds designed to inhibit microtubule polymerization, we identified four compounds that have unique effects on microtubules. These compounds cause mixed effects reminiscent of both microtubule depolymerizers and stabilizers. Immunofluorescence evaluations showed that each compound initially caused microtubule
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While evaluating a large library of compounds designed to inhibit microtubule polymerization, we identified four compounds that have unique effects on microtubules. These compounds cause mixed effects reminiscent of both microtubule depolymerizers and stabilizers. Immunofluorescence evaluations showed that each compound initially caused microtubule depolymerization and, surprisingly, with higher concentrations, microtubule bundles were also observed. There were subtle differences in the propensity to cause these competing effects among the compounds with a continuum of stabilizing and destabilizing effects. Tubulin polymerization experiments confirmed the differential effects and, while each of the compounds increased the initial rate of tubulin polymerization at high concentrations, total tubulin polymer was not enhanced at equilibrium, likely because of the dueling depolymerization effects. Modeling studies predict that the compounds bind to tubulin within the colchicine site and confirm that there are differences in their potential interactions that might underlie their distinct effects on microtubules. Due to their dual properties of microtubule stabilization and destabilization, we propose the name Janus for these compounds after the two-faced Roman god. The identification of synthetically tractable, small molecules that elicit microtubule stabilizing effects is a significant finding with the potential to identify new mechanisms of microtubule stabilization. Full article
(This article belongs to the Special Issue Tubulin Inhibitors)
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Open AccessArticle Activity of Eribulin in a Primary Culture of Well-Differentiated/Dedifferentiated Adipocytic Sarcoma
Molecules 2016, 21(12), 1662; doi:10.3390/molecules21121662
Received: 30 August 2016 / Revised: 16 November 2016 / Accepted: 29 November 2016 / Published: 3 December 2016
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Abstract
Eribulin mesylate is a novel, non-taxane, synthetic microtubule inhibitor showing antitumor activity in a wide range of tumors including soft tissue sarcomas (STS). Eribulin has been recently approved for the treatment of metastatic liposarcoma (LPS) patients previously treated with anthracyclines. This work investigated
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Eribulin mesylate is a novel, non-taxane, synthetic microtubule inhibitor showing antitumor activity in a wide range of tumors including soft tissue sarcomas (STS). Eribulin has been recently approved for the treatment of metastatic liposarcoma (LPS) patients previously treated with anthracyclines. This work investigated the mechanism of action of this innovative antitubulin agent in well-differentiated/dedifferentiated LPS (ALT/DDLPS) which represents one of the most common adipocytic sarcoma histotypes. A primary culture of ALT/DDLPS from a 54-year-old patient was established. The anticancer activity of eribulin on the patient-derived primary culture was assessed by MTT and tunel assays. Eribulin efficacy was compared to other drugs approved for the treatment of STS. Cell migration and morphology were examined after exposure to eribulin to better understand the drug mechanism of action. Finally, Western blot analysis of apoptosis and migration proteins was performed. The results showed that eribulin exerts its antiproliferative effect by the arrest of cell motility and induction of apoptosis. Our results highlighted the activity of eribulin in the treatment of ALT/DDLPS patients. Full article
(This article belongs to the Special Issue Tubulin Inhibitors)
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Open AccessArticle Synthesis, Antiphospholipase A2, Antiprotease, Antibacterial Evaluation and Molecular Docking Analysis of Certain Novel Hydrazones
Molecules 2016, 21(12), 1664; doi:10.3390/molecules21121664
Received: 21 October 2016 / Revised: 20 November 2016 / Accepted: 28 November 2016 / Published: 2 December 2016
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Abstract
Some novel hydrazone derivatives 6ao were synthesized from the key intermediate 4-Chloro-N-(2-hydrazinocarbonyl-phenyl)-benzamide 5 and characterized using IR, 1H-NMR, 13C-NMR, mass spectroscopy and elemental analysis. The inhibitory potential against two secretory phospholipase A2 (sPLA2), three
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Some novel hydrazone derivatives 6ao were synthesized from the key intermediate 4-Chloro-N-(2-hydrazinocarbonyl-phenyl)-benzamide 5 and characterized using IR, 1H-NMR, 13C-NMR, mass spectroscopy and elemental analysis. The inhibitory potential against two secretory phospholipase A2 (sPLA2), three protease enzymes and eleven bacterial strains were evaluated. The results revealed that all compounds showed preferential inhibition towards hGIIA isoform of sPLA2 rather than DrG-IB with compounds 6l and 6e being the most active. The tested compounds exhibited excellent antiprotease activity against proteinase K and protease from Bacillus sp. with compound 6l being the most active against both enzymes. Furthermore, the maximum zones of inhibition against bacterial growth were exhibited by compounds; 6a, 6m, and 6o against P. aeruginosa; 6a, 6b, 6d, 6f, 6l, 6m, 6n, and 6o against Serratia; 6k against S. mutans; and compounds 6a, 6d, 6e, 6m, and 6n against E. feacalis. The docking simulations of hydrazones 6ao with GIIA sPLA2, proteinase K and hydrazones 6ae with glutamine-fructose-6-phosphate transaminase were performed to obtain information regarding the mechanism of action. Full article
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Open AccessArticle Bioactivities of a New Pyrrolidine Alkaloid from the Root Barks of Orixa japonica
Molecules 2016, 21(12), 1665; doi:10.3390/molecules21121665
Received: 26 October 2016 / Revised: 23 November 2016 / Accepted: 29 November 2016 / Published: 2 December 2016
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Abstract
A new pyrrolidine alkaloid named (Z)-3-(4-hydroxybenzylidene)-4-(4-hydroxyphenyl)-1-methylpyrrolidin-2-one was isolated from the ethanol extract of the root barks of Orixa japonica. The structure of the new alkaloid was elucidated on the basis of NMR and MS analysis. The compound exhibited larvicidal activity against
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A new pyrrolidine alkaloid named (Z)-3-(4-hydroxybenzylidene)-4-(4-hydroxyphenyl)-1-methylpyrrolidin-2-one was isolated from the ethanol extract of the root barks of Orixa japonica. The structure of the new alkaloid was elucidated on the basis of NMR and MS analysis. The compound exhibited larvicidal activity against the fourth instar larvae of Aedes aegypti (LC50 = 232.09 μg/mL), Anopheles sinensis (LC50 = 49.91 μg/mL), and Culex pipiens pallens (LC50 = 161.10 μg/mL). The new alkaloid also possessed nematicidal activity against Bursaphelenchus xylophilus (LC50 = 391.50 μg/mL) and Meloidogynein congnita (LC50 = 134.51 μg/mL). The results indicate that the crude ethanol extract of O. japonica root barks and its isolated pyrrolidine alkaloid have potential for development into natural larvicides and nematicides. Full article
(This article belongs to the Special Issue Diversity of Alkaloids)
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Open AccessArticle Assessment of the Potential Energy Hypersurfaces in Thymine within Multiconfigurational Theory: CASSCF vs. CASPT2
Molecules 2016, 21(12), 1666; doi:10.3390/molecules21121666
Received: 15 October 2016 / Revised: 30 November 2016 / Accepted: 1 December 2016 / Published: 3 December 2016
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Abstract
The present study provides new insights into the topography of the potential energy hypersurfaces (PEHs) of the thymine nucleobase in order to rationalize its main ultrafast photochemical decay paths by employing two methodologies based on the complete active space self-consistent field (CASSCF) and
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The present study provides new insights into the topography of the potential energy hypersurfaces (PEHs) of the thymine nucleobase in order to rationalize its main ultrafast photochemical decay paths by employing two methodologies based on the complete active space self-consistent field (CASSCF) and the complete active space second-order perturbation theory (CASPT2) methods: (i) CASSCF optimized structures and energies corrected with the CASPT2 method at the CASSCF geometries and (ii) CASPT2 optimized geometries and energies. A direct comparison between these strategies is drawn, yielding qualitatively similar results within a static framework. A number of analyses are performed to assess the accuracy of these different computational strategies under study based on a variety of numerical thresholds and optimization methods. Several basis sets and active spaces have also been calibrated to understand to what extent they can influence the resulting geometries and subsequent interpretation of the photochemical decay channels. The study shows small discrepancies between CASSCF and CASPT2 PEHs, displaying a shallow planar or twisted 1(ππ*) minimum, respectively, and thus featuring a qualitatively similar scenario for supporting the ultrafast bi-exponential deactivation registered in thymine upon UV-light exposure. A deeper knowledge of the PEHs at different levels of theory provides useful insight into its correct characterization and subsequent interpretation of the experimental observations. The discrepancies displayed by the different methods studied here are then discussed and framed within their potential consequences in on-the-fly non-adiabatic molecular dynamics simulations, where qualitatively diverse outcomes are expected. Full article
(This article belongs to the Special Issue Experimental and Computational Photochemistry of Bioorganic Molecules)
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Open AccessArticle Identification and Characterisation of the Antimicrobial Peptide, Phylloseptin-PT, from the Skin Secretion of Phyllomedusa tarsius, and Comparison of Activity with Designed, Cationicity-Enhanced Analogues and Diastereomers
Molecules 2016, 21(12), 1667; doi:10.3390/molecules21121667
Received: 24 October 2016 / Revised: 23 November 2016 / Accepted: 1 December 2016 / Published: 3 December 2016
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Abstract
Antimicrobial peptides belonging to the phylloseptin family are mainly found in phyllomedusine frogs. These peptides not only possess potent antimicrobial activity but exhibit low toxicity against eukaryotic cells. Therefore, they are considered as promising drug candidates for a number of diseases. In a
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Antimicrobial peptides belonging to the phylloseptin family are mainly found in phyllomedusine frogs. These peptides not only possess potent antimicrobial activity but exhibit low toxicity against eukaryotic cells. Therefore, they are considered as promising drug candidates for a number of diseases. In a recent study, potent antimicrobial activity was correlated with the conserved structures and cationic amphiphilic characteristics of members of this peptide family. A phylloseptin peptide precursor was discovered here in the skin secretion of Phyllomedusa tarsius and the mature peptide was validated by MS/MS sequencing, and was subsequently named phylloseptin-PT. The chemically-synthesized and purified phylloseptin-PT displayed activity against Staphylococcus aureus and Candida albicans. Nevertheless, a range of cationicity-enhanced peptide analogues of phylloseptin-PT, which contained amino acid substitutions at specific sites, exhibited significant increases in antimicrobial activity compared to native phylloseptin-PT. In addition, alternative conformers which were designed and chemically-synthesized with d-lysine, showed potent antimicrobial activity and enhanced bioavailability. These data indicate that phylloseptins may represent potential candidates for next-generation antibiotics. Thus, rational design through modification of natural antimicrobial peptide templates could provide an accelerated path to overcoming obstacles en-route to their possible clinical applications. Full article
(This article belongs to the Special Issue Bioactive Natural Peptides As A Pipeline For Therapeutics)
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Open AccessArticle Xanthines Studied via Femtosecond Fluorescence Spectroscopy
Molecules 2016, 21(12), 1668; doi:10.3390/molecules21121668
Received: 14 October 2016 / Revised: 25 November 2016 / Accepted: 29 November 2016 / Published: 3 December 2016
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Abstract
Xanthines represent a wide class of compounds closely related to the DNA bases adenine and guanine. Ubiquitous in the human body, they are capable of replacing natural bases in double helices and give rise to four-stranded structures. Although the use of their fluorescence
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Xanthines represent a wide class of compounds closely related to the DNA bases adenine and guanine. Ubiquitous in the human body, they are capable of replacing natural bases in double helices and give rise to four-stranded structures. Although the use of their fluorescence for analytical purposes was proposed, their fluorescence properties have not been properly characterized so far. The present paper reports the first fluorescence study of xanthine solutions relying on femtosecond spectroscopy. Initially, we focus on 3-methylxanthine, showing that this compound exhibits non-exponential fluorescence decays with no significant dependence on the emission wavelength. The fluorescence quantum yield (3 × 10−4) and average decay time (0.9 ps) are slightly larger than those found for the DNA bases. Subsequently, we compare the dynamical fluorescence properties of seven mono-, di- and tri-methylated derivatives. Both the fluorescence decays and fluorescence anisotropies vary only weakly with the site and the degree of methylation. These findings are in line with theoretical predictions suggesting the involvement of several conical intersections in the relaxation of the lowest singlet excited state. Full article
(This article belongs to the Special Issue Experimental and Computational Photochemistry of Bioorganic Molecules)
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Open AccessArticle Decomposition of Intermolecular Interactions in the Crystal Structure of Some Diacetyl Platinum(II) Complexes: Combined Hirshfeld, AIM, and NBO Analyses
Molecules 2016, 21(12), 1669; doi:10.3390/molecules21121669
Received: 23 October 2016 / Revised: 29 November 2016 / Accepted: 30 November 2016 / Published: 6 December 2016
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Abstract
Intermolecular interactions play a vital role in crystal structures. Therefore, we conducted a topological study, using Hirshfeld surfaces and atom in molecules (AIM) analysis, to decompose and analyze, respectively, the different intermolecular interactions in six hydrazone-diacetyl platinum(II) complexes. Using AIM and natural bond
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Intermolecular interactions play a vital role in crystal structures. Therefore, we conducted a topological study, using Hirshfeld surfaces and atom in molecules (AIM) analysis, to decompose and analyze, respectively, the different intermolecular interactions in six hydrazone-diacetyl platinum(II) complexes. Using AIM and natural bond orbital (NBO) analyses, we determined the type, nature, and strength of the interactions. All the studied complexes contain C-H⋯O interactions, and the presence of bond critical points along the intermolecular paths underlines their significance. The electron densities (ρ(r)) at the bond critical points (0.0031–0.0156 e/a03) fall within the typical range for H-bonding interactions. Also, the positive values of the Laplacian of the electron density (∇2ρ(r)) revealed the depletion of electronic charge on the interatomic path, another characteristic feature of closed-shell interactions. The ratios of the absolute potential energy density to the kinetic energy density (|V(r)|/G(r)) and ρ(r) are highest for the O2⋯H15-N3 interaction in [Pt(COMe)2(2-pyCMe=NNH2)] (1); hence, this interaction has the highest covalent character of all the O⋯H intermolecular interactions. Interestingly, in [Pt(COMe)2(H2NN=CMe-CMe=NNH2)] (3), there are significant N-H⋯Pt interactions. Using the NBO method, the second-order interaction energies, E(2), of these interactions range from 3.894 to 4.061 kJ/mol. Furthermore, the hybrid Pt orbitals involved in these interactions are comprised of dxy, dxz, and s atomic orbitals. Full article
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Open AccessArticle Clarification of the Antagonistic Effect of the Lipopeptides Produced by Bacillus amyloliquefaciens BPD1 against Pyricularia oryzae via In Situ MALDI-TOF IMS Analysis
Molecules 2016, 21(12), 1670; doi:10.3390/molecules21121670
Received: 7 November 2016 / Revised: 29 November 2016 / Accepted: 1 December 2016 / Published: 3 December 2016
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Abstract
This study tried to clarify the antagonistic effect of the lipopeptides secreted by Bacillus amyloliquefaciens strain BPD1 (Ba-BPD1) against Pyricularia oryzae Cavara (PO). To determine the major antifungal lipopeptides effective against PO, single and dual cultures were carried out in solid-state media. The
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This study tried to clarify the antagonistic effect of the lipopeptides secreted by Bacillus amyloliquefaciens strain BPD1 (Ba-BPD1) against Pyricularia oryzae Cavara (PO). To determine the major antifungal lipopeptides effective against PO, single and dual cultures were carried out in solid-state media. The matrix-assisted laser desorption/ionization–time of flight imaging mass spectrometry (MALDI-TOF IMS) was used to identify the most effective lipopeptide in situ. Meanwhile, the morphology of pathogen fungi treated with lipopeptides was observed via the SEM. Of the three lipopeptide families, surfactin, iturin, and fengycin, the last was identified as the most effective for inhibiting mycelium growth and conidial germination of PO. The conidia and hyphae of fengycin-treated PO were shown to become deformed and tumorous under exposure. This study provides insights into the antagonistic effect of Ba-BPD1 against fungal phytopathogens. Such insights are helpful in the development of reagents for biological control applications. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle Extraction and Quantification of Bioactive Tyrian Purple Precursors: A Comparative and Validation Study from the Hypobranchial Gland of a Muricid Dicathais orbita
Molecules 2016, 21(12), 1672; doi:10.3390/molecules21121672
Received: 6 October 2016 / Revised: 21 November 2016 / Accepted: 28 November 2016 / Published: 5 December 2016
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Abstract
Muricidae are marine molluscs known for the production of Tyrian purple and bioactive precursor compounds. A validation study for the extraction and analysis of secondary metabolites found in the hypobranchial gland of the muricid Dicathais orbita is reported, using high performance liquid chromatography–mass
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Muricidae are marine molluscs known for the production of Tyrian purple and bioactive precursor compounds. A validation study for the extraction and analysis of secondary metabolites found in the hypobranchial gland of the muricid Dicathais orbita is reported, using high performance liquid chromatography–mass spectrometry (HPLC-MS) with diode array detector (DAD). Quantification of the dominant secondary metabolites from D. orbita is described, followed by a comparison of solvent extraction procedures and stability studies. The intra- and inter-day relative standard deviation (RSD) for tyrindoxyl sulphate was 0.46% and 0.17%, respectively. The quantification was linear for standards murexine, 6-bromoisatin, and tyrindoxyl sulphate. The limits of detection were 0.03, 0.004, and 0.07 mg/mL, respectively, and the limits of quantification were 0.09, 0.01, and 0.22 mg/mL, respectively. The results showed that alcoholic solvents were better for extracting choline ester and indoxyl sulphate ultimate precursors, while chloroform was more suitable for the extraction of the intermediate precursors. Multivariate analysis revealed significant differences in extract composition according to the solvent used. Stability testing showed an increase of the oxidative compounds 6-bromoisatin and putative tyrindoxyl S-oxide sulphate in the ethanol extracts while more degradation products were seen in the chloroform extracts after months of cold storage. The validated method was found to be simple, reproducible, precise, and suitable for quantification of the secondary metabolites of muricid molluscs for dye precursor and nutraceutical quality control, as well as applications in marine chemical ecology. Full article
(This article belongs to the Special Issue Diversity of Alkaloids)
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Open AccessArticle Using Light Microscopy and Liquid Chromatography Tandem Mass Spectrometry for Qualitative and Quantitative Control of a Combined Three-Herb Formulation in Different Preparations
Molecules 2016, 21(12), 1673; doi:10.3390/molecules21121673
Received: 10 November 2016 / Revised: 1 December 2016 / Accepted: 1 December 2016 / Published: 6 December 2016
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Abstract
Artemisia capillaries Thunb, Gardenia jasminoides Ellis, and Rheum officinale Baill have been combined to treat jaundice for thousands of years. Studies have revealed that these herbs induce anti-hepatic fibrosis and anti-hepatic apoptosis and alleviate hepatic oxidative stress. This study aims to determine the
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Artemisia capillaries Thunb, Gardenia jasminoides Ellis, and Rheum officinale Baill have been combined to treat jaundice for thousands of years. Studies have revealed that these herbs induce anti-hepatic fibrosis and anti-hepatic apoptosis and alleviate hepatic oxidative stress. This study aims to determine the quality and quantity of an herbal formulation (Chinese name: Yin-Chen-Hao-Tang) using physical and chemical examinations. Physical examination of Yin-Chen-Hao-Tang in pharmaceutical herbal products, raw fiber powders, and decoction preparations was performed using Congo red and iodine-potassium staining. A sensitive and validated method employing ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was developed to simultaneously quantify the bioactive compounds scoparone, geniposide, and rhein in the Yin-Chen-Hao-Tang formulation in different preparations. Physical examination indicated that cellulose fibers with irregular round shapes were present in the pharmaceutical herbal products. The developed UHPLC-MS/MS method showed good linearity and was well validated. The quantification results revealed that the decoction preparations had the highest amounts of geniposide and rhein. Scoparone appeared in pharmaceutical herbal products from two manufacturers. This experiment provides a qualitative and quantitative method using physical and chemical examinations to test different preparations of herbal products. The results provide a reference for clinical herbal product preparations and further pharmacokinetic research. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle Synthesis and Antitumor Activity of 5-Bromo-7-azaindolin-2-one Derivatives Containing a 2,4-Dimethyl-1H-pyrrole-3-carboxamide Moiety
Molecules 2016, 21(12), 1674; doi:10.3390/molecules21121674
Received: 11 November 2016 / Revised: 28 November 2016 / Accepted: 30 November 2016 / Published: 6 December 2016
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Abstract
We report herein the design and synthesis of a series of novel 5-bromo-7-azaindolin-2-one derivatives containing a 2,4-dimethyl-1H-pyrrole-3-carboxamide moiety. These newly synthesized derivatives were evaluated for in vitro activity against selected cancer cell lines by MTT assay. Results revealed that some compounds
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We report herein the design and synthesis of a series of novel 5-bromo-7-azaindolin-2-one derivatives containing a 2,4-dimethyl-1H-pyrrole-3-carboxamide moiety. These newly synthesized derivatives were evaluated for in vitro activity against selected cancer cell lines by MTT assay. Results revealed that some compounds exhibit broad-spectrum antitumor potency, and the most active compound 23p (IC50: 2.357–3.012 μM) was found more potent than Sunitinib (IC50: 31.594–49.036 μM) against HepG2, A549 and Skov-3, respectively. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Subcritical Butane Extraction of Wheat Germ Oil and Its Deacidification by Molecular Distillation
Molecules 2016, 21(12), 1675; doi:10.3390/molecules21121675
Received: 11 October 2016 / Revised: 29 November 2016 / Accepted: 30 November 2016 / Published: 7 December 2016
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Abstract
Extraction and deacidification are important stages for wheat germ oil (WGO) production. Crude WGO was extracted using subcritical butane extraction (SBE) and compared with traditional solvent extraction (SE) and supercritical carbon dioxide extraction (SCE) based on the yield, chemical index and fatty acid
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Extraction and deacidification are important stages for wheat germ oil (WGO) production. Crude WGO was extracted using subcritical butane extraction (SBE) and compared with traditional solvent extraction (SE) and supercritical carbon dioxide extraction (SCE) based on the yield, chemical index and fatty acid profile. Furthermore, the effects of the molecular distillation temperature on the quality of WGO were also investigated in this study. Results indicated that WGO extracted by SBE has a higher yield of 9.10% and better quality; at the same time, its fatty acid composition has no significant difference compared with that of SE and SCE. The molecular distillation experiment showed that the acid value, peroxide value and p-anisidine value of WGO were reduced with the increase of the evaporation temperatures, and the contents of the active constituents of tocopherol, polyphenols and phytosterols are simultaneously decreased. Generally, the distillation temperature of 150 °C is an appropriate condition for WGO deacidification with the higher deacidification efficiency of 77.78% and the higher retention rate of active constituents. Full article
(This article belongs to the Special Issue Sub- and Supercritical Fluids and Green Chemistry)
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Open AccessArticle The Traditional Chinese Medicine DangguiBuxue Tang Sensitizes Colorectal Cancer Cells to Chemoradiotherapy
Molecules 2016, 21(12), 1677; doi:10.3390/molecules21121677
Received: 30 September 2016 / Revised: 23 November 2016 / Accepted: 30 November 2016 / Published: 6 December 2016
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Abstract
Chemotherapy is an important treatment modality for colon cancer, and concurrent chemoradiation therapy (CCRT) is the preferred treatment route for patients with stage II and III rectal cancer. We examined whether DangguiBuxue Tang (DBT), a traditional Chinese herbal extract, sensitizes colorectal cancer cells
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Chemotherapy is an important treatment modality for colon cancer, and concurrent chemoradiation therapy (CCRT) is the preferred treatment route for patients with stage II and III rectal cancer. We examined whether DangguiBuxue Tang (DBT), a traditional Chinese herbal extract, sensitizes colorectal cancer cells to anticancer treatments. The polysaccharide-depleted fraction of DBT (DBT-PD) contains greater amounts of astragaloside IV (312.626 µg/g) and ferulic acid (1.404 µg/g) than does the original formula. Treatment of the murine colon carcinoma cell line (CT26) with DBT-PD inhibits growth, whereas treatment with comparable amounts of purified astragaloside IV and ferulic acid showed no significant effect. Concurrent treatment with DBT-PD increases the growth inhibitory effect of 5-fluorouracil up to 4.39-fold. DBT-PD enhances the effect of radiation therapy (RT) with a sensitizer enhancement ratio (SER) of up to 1.3. It also increases the therapeutic effect of CCRT on CT26 cells. Cells treated with DBP-PD showed ultrastructural changes characteristic of autophagy, including multiple cytoplasmic vacuoles with double-layered membranes, vacuoles containing remnants of degraded organelles, marked swelling and vacuolization of mitochondria, and autolysosome-like vacuoles. We conclude that DBT-PD induces autophagy-associated cell death in CT26 cells, and may have potential as a chemotherapy or radiotherapy sensitizer in colorectal cancer treatment. Full article
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Open AccessArticle Virtual-Wall Model for Molecular Dynamics Simulation
Molecules 2016, 21(12), 1678; doi:10.3390/molecules21121678
Received: 11 October 2016 / Revised: 26 November 2016 / Accepted: 29 November 2016 / Published: 9 December 2016
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Abstract
A large number of molecules are usually required to model atomic walls in molecular dynamics simulations. A virtual-wall model is proposed in this study to describe fluid-wall molecular interactions, for reducing the computational time. The infinite repetition of unit cell structures within the
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A large number of molecules are usually required to model atomic walls in molecular dynamics simulations. A virtual-wall model is proposed in this study to describe fluid-wall molecular interactions, for reducing the computational time. The infinite repetition of unit cell structures within the atomic wall causes the periodicity of the force acting on a fluid molecule from the wall molecules. This force is first calculated and then stored in the memory. A fluid molecule appearing in the wall force field is subjected to the force from the wall molecules. The force can then be determined by the position of the molecule relative to the wall. This model avoids excessive calculations of fluid-wall interactions and reduces the computational time drastically. The time reduction is significant for small fluid density and channel height. The virtual-wall model is applied to Poiseuille and Couette flows, and to a flow in a channel with a rough surface. Results of the virtual and atomic wall simulations agree well with each other, thereby indicating the usefulness of the virtual-wall model. The appropriate bin size and cut-off radius in the virtual-wall model are also discussed. Full article
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Open AccessArticle Design of Heterogeneous Hoveyda–Grubbs Second-Generation Catalyst–Lipase Conjugates
Molecules 2016, 21(12), 1680; doi:10.3390/molecules21121680
Received: 4 October 2016 / Revised: 25 November 2016 / Accepted: 30 November 2016 / Published: 6 December 2016
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Abstract
Heterogeneous catalysts have been synthesized by the conjugation of Hoveyda–Grubbs second-generation catalyst with a lipase. The catalytic properties of the organometallic compound in solution were firstly optimized, evaluating the activity of Ru in the ring-closing metathesis of diethyldiallymalonate at 25 °C at different
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Heterogeneous catalysts have been synthesized by the conjugation of Hoveyda–Grubbs second-generation catalyst with a lipase. The catalytic properties of the organometallic compound in solution were firstly optimized, evaluating the activity of Ru in the ring-closing metathesis of diethyldiallymalonate at 25 °C at different solvents and in the presence of different additives. The best result was found using tetrahydrofuran as a solvent. Some additives such as phenylboronic acid or polyetheneglycol slightly improved the activity of the Ru catalyst whereas others, such as pyridine or dipeptides affected it negatively. The organometallic compound immobilized on functionalized-surface materials activated with boronic acid or epoxy groups (around 50–60 µg per mg support) and showed 50% conversion at 24 h in the ring-closing metathesis. Cross-linked enzyme aggregates (CLEA’s) of the Hoveyda–Grubbs second-generation catalyst with Candida antarctica lipase (CAL-B) were prepared, although low Ru catalyst was found to be translated in low conversion. Therefore, a sol–gel preparation of the Hoveyda–Grubbs second-generation and CAL-B was performed. This catalyst exhibited good activity in the metathesis of diethyldiallymalonate in toluene and in aqueous media. Finally, a new sustainable approach was used by the conjugation lipase–Grubbs in solid phase in aqueous media. Two strategies were used: one using lipase previously covalently immobilized on an epoxy-Sepharose support (hydrophilic matrix) and then conjugated with grubbs; and in the second, the free lipase was incubated with organometallic in aqueous solution and then immobilized on epoxy-Sepharose. The different catalysts showed excellent conversion values in the ring-closing metathesis of diethyldiallymalonate in aqueous media at 25 °C. Full article
(This article belongs to the Special Issue Biomolecules Modification)
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Open AccessArticle Pentacoordinate and Hexacoordinate Mn(III) Complexes of Tetradentate Schiff-Base Ligands Containing Tetracyanidoplatinate(II) Bridges and Revealing Uniaxial Magnetic Anisotropy
Molecules 2016, 21(12), 1681; doi:10.3390/molecules21121681
Received: 25 October 2016 / Revised: 30 November 2016 / Accepted: 2 December 2016 / Published: 8 December 2016
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Abstract
Crystal structures and magnetic properties of polymeric and trinuclear heterobimetallic MnIII···PtII···MnIII coordination compounds, prepared from the Ba[Pt(CN)4] and [Mn(L4A/B)(Cl)] (1a/b) precursor complexes, are reported. The polymeric complex [{Mn(L4A)}24-Pt(CN)
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Crystal structures and magnetic properties of polymeric and trinuclear heterobimetallic MnIII···PtII···MnIII coordination compounds, prepared from the Ba[Pt(CN)4] and [Mn(L4A/B)(Cl)] (1a/b) precursor complexes, are reported. The polymeric complex [{Mn(L4A)}24-Pt(CN)4}]n (2a), where H2L4A = N,N’-ethylene-bis(salicylideneiminate), comprises the {Mn(L4A)} moieties covalently connected through the [Pt(CN)4]2− bridges, thus forming a square-grid polymeric structure with the hexacoordinate MnIII atoms. The trinuclear complex [{Mn(L4B)}2{μ-Pt(CN)4}] (2b), where H2L4B = N,N’-benzene-bis(4-aminodiethylene-salicylideneiminate), consists of two [{Mn(L4B)} moieties, involving pentacoordinate MnIII atoms, bridged through the tetracyanidoplatinate (II) bridges to which they are coordinated in a trans fashion. Both complexes possess uniaxial type of magnetic anisotropy, with D (the axial parameter of zero-field splitting) = −3.7(1) in 2a and −2.2(1) cm−1 in 2b. Furthermore, the parameters of magnetic anisotropy 2a and 2b were also thoroughly studied by theoretical complete active space self-consistent field (CASSCF) methods, which revealed that the former is much more sensitive to the ligand field strength of the axial ligands. Full article
(This article belongs to the Section Organometallic Chemistry)
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Open AccessCommunication Synthesis and Determination of Physicochemical Properties of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4-Alkoxyethoxybenzoates
Molecules 2016, 21(12), 1682; doi:10.3390/molecules21121682
Received: 27 September 2016 / Revised: 28 November 2016 / Accepted: 30 November 2016 / Published: 7 December 2016
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Abstract
Nine new dihydrochloride salts of 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-alkoxyethoxybenzoates were designed and synthesized. The physicochemical properties such as lipophilicity index (log kw) and dissociation constant (pKa) were experimentally determined and compared to the software calculated data. The lipophilicity index was
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Nine new dihydrochloride salts of 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-alkoxyethoxybenzoates were designed and synthesized. The physicochemical properties such as lipophilicity index (log kw) and dissociation constant (pKa) were experimentally determined and compared to the software calculated data. The lipophilicity index was determined by means of reversed-phase high performance liquid chromatography (RP-HPLC). The pKa values were determined by means of capillary zone electrophoresis. The “drug-likeness” properties according to the Lipinski Rule of Five and prediction of possible blood–brain barrier penetration were computed and discussed. Full article
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Open AccessArticle Stereoselective Fluorescence Quenching in the Electron Transfer Photooxidation of Nucleobase-Related Azetidines by Cyanoaromatics
Molecules 2016, 21(12), 1683; doi:10.3390/molecules21121683
Received: 15 October 2016 / Revised: 29 November 2016 / Accepted: 1 December 2016 / Published: 7 December 2016
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Abstract
Electron transfer involving nucleic acids and their derivatives is an important field in bioorganic chemistry, specifically in connection with its role in the photo-driven DNA damage and repair. Four-membered ring heterocyclic oxetanes and azetidines have been claimed to be the intermediates involved in
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Electron transfer involving nucleic acids and their derivatives is an important field in bioorganic chemistry, specifically in connection with its role in the photo-driven DNA damage and repair. Four-membered ring heterocyclic oxetanes and azetidines have been claimed to be the intermediates involved in the repair of DNA (6-4) photoproduct by photolyase. In this context, we examine here the redox properties of the two azetidine isomers obtained from photocycloaddition between 6-aza-1,3-dimethyluracil and cyclohexene. Steady-state and time-resolved fluorescence experiments using a series of photoreductants and photooxidants have been run to evaluate the efficiency of the electron transfer process. Analysis of the obtained quenching kinetics shows that the azetidine compounds can act as electron donors. Additionally, it appears that the cis isomer is more easily oxidized than its trans counterpart. This result is in agreement with electrochemical studies performed on both azetidine derivatives. Full article
(This article belongs to the Special Issue Experimental and Computational Photochemistry of Bioorganic Molecules)
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Open AccessCommunication Design, Synthesis, and Biological Evaluation of Novel Benzofuran Derivatives Bearing N-Aryl Piperazine Moiety
Molecules 2016, 21(12), 1684; doi:10.3390/molecules21121684
Received: 6 October 2016 / Revised: 27 November 2016 / Accepted: 1 December 2016 / Published: 9 December 2016
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Abstract
A series of novel hybrid compounds between benzofuran and N-aryl piperazine have been synthesized and screened in vitro for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages and for anticancer activity against three human tumor cell lines. The results demonstrated that derivative 16
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A series of novel hybrid compounds between benzofuran and N-aryl piperazine have been synthesized and screened in vitro for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages and for anticancer activity against three human tumor cell lines. The results demonstrated that derivative 16 not only had inhibitory effect on the generation of NO (IC50 = 5.28 μM), but also showed satisfactory and selective cytotoxic activity against human lung cancer line (A549) and gastric cancer cell (SGC7901) (IC50 = 0.12 μM and 2.75 μM, respectively), which was identified as the most potent anti-inflammatory and anti-tumor agent in this study. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Geometry Constrained N-(5,6,7-Trihydroquinolin-8-ylidene)arylaminopalladium Dichloride Complexes: Catalytic Behavior toward Methyl Acrylate (MA), Methyl Acrylate-co-Norbornene (MA-co-NB) Polymerization and Heck Coupling
Molecules 2016, 21(12), 1686; doi:10.3390/molecules21121686
Received: 11 November 2016 / Revised: 2 December 2016 / Accepted: 3 December 2016 / Published: 7 December 2016
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Abstract
A new pair of plladium complexes (Pd4 and Pd5) ligated with constrained N-(5,6,7-trihydroquinolin-8-ylidene)arylamine ligands have been prepared and well characterized by 1H-, 13C-NMR and FTIR spectroscopies as well as elemental analysis. The molecular structure of Pd4 and Pd5
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A new pair of plladium complexes (Pd4 and Pd5) ligated with constrained N-(5,6,7-trihydroquinolin-8-ylidene)arylamine ligands have been prepared and well characterized by 1H-, 13C-NMR and FTIR spectroscopies as well as elemental analysis. The molecular structure of Pd4 and Pd5 in solid state have also been determined by X-ray diffraction, showing slightly distorted square planar geometry around the palladium metal center. All complexes Pd1Pd5 are revealed highly efficient catalyst in methyl acrylate (MA) polymerization as well as methyl acrylate/norbornene (MA/NB) copolymerization. In the case of MA polymerization, as high as 98.4% conversion with high molecular weight up to 6282 kg·mol−1 was achieved. Likewise, Pd3 complex has good capability to incorporate about 18% NB content into MA polymer chains. Furthermore, low catalyst loadings (0.002 mol %) of Pd4 or Pd5 are able to efficiently mediate the coupling of haloarenes with styrene affording up to 98% conversion. Full article
(This article belongs to the Special Issue Palladium Catalysts 2016)
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Open AccessArticle The Protective Effect of Selenium on Chronic Zearalenone-Induced Reproductive System Damage in Male Mice
Molecules 2016, 21(12), 1687; doi:10.3390/molecules21121687
Received: 11 July 2016 / Revised: 2 December 2016 / Accepted: 5 December 2016 / Published: 7 December 2016
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Abstract
This study aims to explore the protective effect of selenium (Se) on chronic zearalenone (ZEN)-induced reproductive system damage in male mice and the possible protective molecular mechanism against this. The chronic ZEN-induced injury mouse model was established with the continuous intragastric administration of
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This study aims to explore the protective effect of selenium (Se) on chronic zearalenone (ZEN)-induced reproductive system damage in male mice and the possible protective molecular mechanism against this. The chronic ZEN-induced injury mouse model was established with the continuous intragastric administration of 40 mg/kg body mass (B.M.) ZEN for 28 days. Then, interventions with different doses (0.1, 0.2, and 0.4 mg/kg B.M.) of Se were conducted on mice to analyse the changes in organ indexes of epididymis and testis, antioxidant capability of testis, serum level of testosterone, sperm concentration and motility parameters, and the expression levels of apoptosis-associated genes and blood testis barrier- (BTB) related genes. Our results showed that Se could greatly improve the ZEN-induced decrease of epididymis indexes and testis indexes. Results also showed that the decrease in sperm concentration, sperm normality rate, and sperm motility parameters, including percentage of motile sperm (motile), tropism percentage (progressive) and sperm average path velocity (VAP), caused by ZEN were elevated upon administration of the higher dose (0.4 mg/kg) and intermediate dose (0.2 mg/kg) of Se. Selenium also significantly reduced the content of malondialdehyde (MDA) but enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the testis tissue. Further research demonstrated that ZEN increased the level of mRNA expression of BCL2-associated X protein (Bax) and caspase 3 (Casp3), decreased the level of mRNA expression of B cell leukemia/lymphoma 2 (Bcl2), vimentin (Vim) and cadherin 2 (Cdh2), whereas the co-administration of Se reversed these gene expression levels. Our results indicated that high levels of Se could protect against reproductive system damage in male mice caused by ZEN and the mechanism might such be that Se improved mice antioxidant ability, inhibited reproductive cell apoptosis, and increased the decrease of BTB integrity-related genes caused by ZEN. Full article
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Open AccessArticle Impact of Cluster Zone Leaf Removal on Grapes cv. Regent Polyphenol Content by the UPLC-PDA/MS Method
Molecules 2016, 21(12), 1688; doi:10.3390/molecules21121688
Received: 16 October 2016 / Revised: 24 November 2016 / Accepted: 1 December 2016 / Published: 11 December 2016
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Abstract
Abstract: Leaf removal is known to enhance light exposure of clusters and therefore may affect grape composition. Owing to the risk of decreasing grape quality or sunburn as a consequence of improper sun exposure, it is crucial to determine the optimum leaf removal
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Abstract: Leaf removal is known to enhance light exposure of clusters and therefore may affect grape composition. Owing to the risk of decreasing grape quality or sunburn as a consequence of improper sun exposure, it is crucial to determine the optimum leaf removal techniques adequate for the particular climate conditions of a vineyard area. Defoliation experiments on vine cv. Regent were conducted in two consecutive years (2014 and 2015). The effect of leaf removal treatment on the qualitative and quantitative composition of the polyphenol compounds in the grapes, with reference to the basic weather conditions of the vineyard area, located in Szczecin in the North-Western part of Poland, was assessed. Defoliation was performed manually in the cluster zone at three phenological plant stages: pre-flowering, berry-set and véraison. Leaf removal, especially early defoliation (pre-flowering), enhanced total polyphenol content, including the amount of anthocyanins, flavonols and flavan-3-ols and furthermore, it increased the amount of soluble solids, decreasing the titratable acidity in grapes. On the other hand, the treatments had a reducing impact on the phenolic acids in berries. Defoliation at earlier stages of cluster development appears to be an efficient strategy for improving berry quality in cool climate areas, however, additionally further weather data control is required to determine the effects on berry components. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Methotrexate and Cytarabine—Loaded Nanocarriers for Multidrug Cancer Therapy. Spectroscopic Study
Molecules 2016, 21(12), 1689; doi:10.3390/molecules21121689
Received: 30 September 2016 / Revised: 17 November 2016 / Accepted: 30 November 2016 / Published: 8 December 2016
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Abstract
Determining the properties of nanoparticles obtained by novel methods and defining the scope of their application as drug carriers has important practical significance. This article presents the pioneering studies concerning high degree incorporation of cytarabine (AraC) and methotrexate (MTX) into liposome vesicles. The
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Determining the properties of nanoparticles obtained by novel methods and defining the scope of their application as drug carriers has important practical significance. This article presents the pioneering studies concerning high degree incorporation of cytarabine (AraC) and methotrexate (MTX) into liposome vesicles. The main focus of this study were cytarabine-methotrexate-dipalmitoylphosphatidylcholine (DPPC) interactions observed in the gel and fluid phases of DPPC bilayers. The proposed new method of use the Transmittance2919/2850 ratio presented in our research is sensitive to subtle changes in conformational order resulting from rotations, kinks and bends of the lipid chains. The transition temperatures characterized by Fourier Transform Infrared Spectroscopy (FT-IR) were consistent with the results obtained by Differential Scanning Calorimetry (DSC). Transmission Electron Microscopy (TEM) was used in order to determine the size and shape of the liposomes obtained. The mutual interactions occurring between the drugs studied and the phospholipids were analyzed using the Nuclear Magnetic Resonance (NMR). Full article
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Open AccessArticle Metal-Free Photoredox Catalyzed Cyclization of O-(2,4-Dinitrophenyl)oximes to Phenanthridines
Molecules 2016, 21(12), 1690; doi:10.3390/molecules21121690
Received: 1 November 2016 / Revised: 25 November 2016 / Accepted: 6 December 2016 / Published: 8 December 2016
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Abstract
A metal-free visible-light photoredox-catalyzed intermolecular cyclization reaction of O-2,4-dinitrophenyl oximes to phenanthridines was developed. In this study, the organic dye eosin Y and i-Pr2NEt were used as photocatalyst and terminal reductant, respectively. The oxime substrates were transformed into iminyl
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A metal-free visible-light photoredox-catalyzed intermolecular cyclization reaction of O-2,4-dinitrophenyl oximes to phenanthridines was developed. In this study, the organic dye eosin Y and i-Pr2NEt were used as photocatalyst and terminal reductant, respectively. The oxime substrates were transformed into iminyl radical intermediates by single-electron reduction, which then underwent intermolecular homolytic aromatic substitution (HAS) reactions to give phenanthridine derivatives. Full article
(This article belongs to the Section Photochemistry)
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Open AccessArticle Extract of Monascus purpureus CWT715 Fermented from Sorghum Liquor Biowaste Inhibits Migration and Invasion of SK-Hep-1 Human Hepatocarcinoma Cells
Molecules 2016, 21(12), 1691; doi:10.3390/molecules21121691
Received: 10 November 2016 / Revised: 1 December 2016 / Accepted: 5 December 2016 / Published: 8 December 2016
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Abstract
Liver cancer is the most endemic cancer in a large region of the world. This study investigated the anti-metastatic effects of an extract of Monascus purpureus CWT715 (MP) fermented from sorghum liquor biowaste and its mechanisms of action in highly metastatic human hepatocarcinoma
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Liver cancer is the most endemic cancer in a large region of the world. This study investigated the anti-metastatic effects of an extract of Monascus purpureus CWT715 (MP) fermented from sorghum liquor biowaste and its mechanisms of action in highly metastatic human hepatocarcinoma SK-Hep-1 cells. Kinmen sorghum liquor waste was used as the primary nutrient source to produce metabolites (including pigments) of MP. In the presence of 10 µg/mL MP-fermented broth (MFB), the anti-invasive activity increased with increasing fermentation time reaching a maximum at six days of fermentation. Interestingly, MFB also produced maximal pigment content at six days. Treatment for 24 h with MFB (10–100 µg/mL) obtained from fermentation for six days significantly inhibited cell migration and invasion, and these effects were concentration-dependent. MFB also significantly enhanced nm23-H1 protein expression in a concentration-dependent manner, which was highly correlated with migration and invasion. These results suggest that MFB has significant anti-migration and anti-invasion activities and that these effects are associated with the induction of nm23-H1 protein expression. Full article
(This article belongs to the Special Issue Natural Products and Chronic Diseases)
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Open AccessArticle Bioassay-Guided Isolation of Cytotoxic Isocryptoporic Acids from Cryptoporus volvatus
Molecules 2016, 21(12), 1692; doi:10.3390/molecules21121692
Received: 19 October 2016 / Revised: 3 December 2016 / Accepted: 6 December 2016 / Published: 8 December 2016
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Abstract
The present work constitutes a contribution to the phytochemical investigation of Cryptoporus volvatus aiming to search for effective cytotoxic constituents against tumor cell lines in vivo. Bioassay-guided separation of the ethylacetate extract of C. volvatus afforded four new isocryptoporic acid (ICA) derivatives, ICA-B
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The present work constitutes a contribution to the phytochemical investigation of Cryptoporus volvatus aiming to search for effective cytotoxic constituents against tumor cell lines in vivo. Bioassay-guided separation of the ethylacetate extract of C. volvatus afforded four new isocryptoporic acid (ICA) derivatives, ICA-B trimethyl ester (1), ICA-E (2), ICA-E pentamethyl ester (3), and ICA-G (4), together with nine known cryptoporic acids. These isocryptoporic acids are isomers of the cryptoporic acids with drimenol instead of albicanol as the terpenoid fragment; their structures were elucidated on the basis of spectroscopic evidences (UV, IR, HRMS, and NMR) and comparison with literature values. All isolates show certain cytotoxic activities against five tumor cell lines. Among them, compound 4 showed an comparable activity to that of the positive control cis-platin, while other compounds exhibited weak cytotoxic activities. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Design and Synthesis of Vandetanib Derivatives Containing Nitroimidazole Groups as Tyrosine Kinase Inhibitors in Normoxia and Hypoxia
Molecules 2016, 21(12), 1693; doi:10.3390/molecules21121693
Received: 19 October 2016 / Revised: 4 December 2016 / Accepted: 6 December 2016 / Published: 14 December 2016
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Abstract
Sixteen novel epidermal growth factor receptor (EGFR)/vascular endothelial growth factor (VEGF)-2 inhibitors (nitroimidazole-substituted 4-anilinoquinazoline derivatives (16ap)) were designed and prepared via the introduction of a nitroimidazole group in the piperidine side chain and modification on the aniline moiety of
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Sixteen novel epidermal growth factor receptor (EGFR)/vascular endothelial growth factor (VEGF)-2 inhibitors (nitroimidazole-substituted 4-anilinoquinazoline derivatives (16ap)) were designed and prepared via the introduction of a nitroimidazole group in the piperidine side chain and modification on the aniline moiety of vandetanib. Preliminary biological tests showed that comparing with vandetanib, some target compounds exhibited excellent EGFR inhibitory activities and anti-proliferative over A549/H446 cells in hypoxia. Meanwhile, several of the above compounds demonstrated better bioactivity than vandetanib in VEGF gene expression inhibition. Owing to the excellent IC50 value (1.64 μmol/L), the inhibition ratios of 16f over A549 and H446 cells were 62.01% and 59.86% at the concentration of 0.5 μM in hypoxia, respectively. All of these results indicated that 16f was a potential cancer therapeutic agent in hypoxia and was worthy of further development. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Polyphenols Isolated from Xanthoceras sorbifolia Husks and Their Anti-Tumor and Radical-Scavenging Activities
Molecules 2016, 21(12), 1694; doi:10.3390/molecules21121694
Received: 21 October 2016 / Revised: 4 December 2016 / Accepted: 6 December 2016 / Published: 9 December 2016
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Abstract
Xanthoceras sorbifolia Bunge. is used in traditional medicine in North China. To evaluate the anti-tumor and radical-scavenging activities of X. sorbifolia husks polyphenols and determine their structure-activity relationships, 37 polyphenols 137 were obtained by bioassay-guided fractionation. Two new compounds 1
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Xanthoceras sorbifolia Bunge. is used in traditional medicine in North China. To evaluate the anti-tumor and radical-scavenging activities of X. sorbifolia husks polyphenols and determine their structure-activity relationships, 37 polyphenols 137 were obtained by bioassay-guided fractionation. Two new compounds 12, and compounds 5, 6, 8, 9, 11, 1417, 2125, 2729, 31, 33, 34, 36, and 37 were isolated from the genus Xanthoceras for the first time. Compounds 137 did not show strong cytotoxicity against the four tested tumor cell lines (A549, HepG2, MGC-803, and MFC) compared to paclitaxel and under the conditions tested in the anti-tumor assay, but compounds 3, 4, 7, 8, 10, 1820, 25, 26, 29, 30, 32, and 35 exhibited stronger radical-scavenging activity than ascorbic acid in a 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt assay. This was the first report on the anti-tumor and radical-scavenging activities of the polyphenols isolated from X. sorbifolia husks. Overall, the present study contributed valuable information concerning X. sorbifolia husks use in medicine and pharmacology. Full article
(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products)
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Open AccessArticle Optimized and Automated Radiosynthesis of [18F]DHMT for Translational Imaging of Reactive Oxygen Species with Positron Emission Tomography
Molecules 2016, 21(12), 1696; doi:10.3390/molecules21121696
Received: 18 October 2016 / Revised: 27 November 2016 / Accepted: 2 December 2016 / Published: 9 December 2016
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Abstract
Reactive oxygen species (ROS) play important roles in cell signaling and homeostasis. However, an abnormally high level of ROS is toxic, and is implicated in a number of diseases. Positron emission tomography (PET) imaging of ROS can assist in the detection of these
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Reactive oxygen species (ROS) play important roles in cell signaling and homeostasis. However, an abnormally high level of ROS is toxic, and is implicated in a number of diseases. Positron emission tomography (PET) imaging of ROS can assist in the detection of these diseases. For the purpose of clinical translation of [18F]6-(4-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-5-methyl-5,6-dihydrophenanthridine-3,8-diamine ([18F]DHMT), a promising ROS PET radiotracer, we first manually optimized the large-scale radiosynthesis conditions and then implemented them in an automated synthesis module. Our manual synthesis procedure afforded [18F]DHMT in 120 min with overall radiochemical yield (RCY) of 31.6% ± 9.3% (n = 2, decay-uncorrected) and specific activity of 426 ± 272 GBq/µmol (n = 2). Fully automated radiosynthesis of [18F]DHMT was achieved within 77 min with overall isolated RCY of 6.9% ± 2.8% (n = 7, decay-uncorrected) and specific activity of 155 ± 153 GBq/µmol (n = 7) at the end of synthesis. This study is the first demonstration of producing 2-[18F]fluoroethyl azide by an automated module, which can be used for a variety of PET tracers through click chemistry. It is also the first time that [18F]DHMT was successfully tested for PET imaging in a healthy beagle dog. Full article
(This article belongs to the Special Issue Molecular Imaging Probes)
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Open AccessArticle Structural Determinants of Alkyne Reactivity in Copper-Catalyzed Azide-Alkyne Cycloadditions
Molecules 2016, 21(12), 1697; doi:10.3390/molecules21121697
Received: 2 November 2016 / Revised: 3 December 2016 / Accepted: 5 December 2016 / Published: 9 December 2016
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Abstract
This work represents our initial effort in identifying azide/alkyne pairs for optimal reactivity in copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. In previous works, we have identified chelating azides, in particular 2-picolyl azide, as “privileged” azide substrates with high CuAAC reactivity. In the current work,
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This work represents our initial effort in identifying azide/alkyne pairs for optimal reactivity in copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. In previous works, we have identified chelating azides, in particular 2-picolyl azide, as “privileged” azide substrates with high CuAAC reactivity. In the current work, two types of alkynes are shown to undergo rapid CuAAC reactions under both copper(II)- (via an induction period) and copper(I)-catalyzed conditions. The first type of the alkynes bears relatively acidic ethynyl C-H bonds, while the second type contains an N-(triazolylmethyl)propargylic moiety that produces a self-accelerating effect. The rankings of reactivity under both copper(II)- and copper(I)-catalyzed conditions are provided. The observations on how other reaction parameters such as accelerating ligand, reducing agent, or identity of azide alter the relative reactivity of alkynes are described and, to the best of our ability, explained. Full article
(This article belongs to the Special Issue Recent Advances in CuAAC Click Chemistry)
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Open AccessArticle Evaluation of Chemical Composition and Antileishmanial and Antituberculosis Activities of Essential Oils of Piper Species
Molecules 2016, 21(12), 1698; doi:10.3390/molecules21121698
Received: 17 October 2016 / Revised: 18 November 2016 / Accepted: 2 December 2016 / Published: 12 December 2016
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Abstract
Essential oils from fresh Piperaceae leaves were obtained by hydrodistillation and analyzed by gas chromatography mass spectrometry (GC–MS), and a total of 68 components were identified. Principal components analysis results showed a chemical variability between species, with sesquiterpene compounds predominating in the majority
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Essential oils from fresh Piperaceae leaves were obtained by hydrodistillation and analyzed by gas chromatography mass spectrometry (GC–MS), and a total of 68 components were identified. Principal components analysis results showed a chemical variability between species, with sesquiterpene compounds predominating in the majority of species analyzed. The composition of the essential oil of Piper mosenii was described for the first time. The cytotoxicity of the essential oils was evaluated in peritoneal macrophages and the oils of P. rivinoides, P. arboretum, and P. aduncum exhibited the highest values, with cytotoxic concentration at 50% (CC50) > 200 µg/mL. Both P. diospyrifolium and P. aduncum displayed activity against Leishmania amazonensis, and were more selective for the parasite than for the macrophages, with a selectivity index (SI) of 2.35 and >5.52, respectively. These SI values were greater than the 1 for the standard drug pentamidine. The antileishmanial activity of the essential oils of P. diospyrifolium and P. aduncum was described for the first time. P. rivinoides, P. cernuum, and P. diospyrifolium displayed moderate activity against the Mycobacterium tuberculosis H37Rv bacillus, with a minimum inhibitory concentration (MIC) of 125 µg/mL. These results are relevant and suggests their potential for therapeutic purposes. Nevertheless, further studies are required to explain the exact mechanism of action of these essential oils. Full article
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Open AccessArticle Photostability and Performance of Polystyrene Films Containing 1,2,4-Triazole-3-thiol Ring System Schiff Bases
Molecules 2016, 21(12), 1699; doi:10.3390/molecules21121699
Received: 5 November 2016 / Revised: 6 December 2016 / Accepted: 7 December 2016 / Published: 9 December 2016
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Abstract
Series of 4-(4-substituted benzylideneamino)-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazole-3-thiols were synthesized and their structures were confirmed. The synthesized Schiff bases were used as photostabilizers for polystyrene against photodegradation. Polystyrene polymeric films containing synthesized Schiff bases (0.5% by weight) were irradiated (λmax = 365 nm and
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Series of 4-(4-substituted benzylideneamino)-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazole-3-thiols were synthesized and their structures were confirmed. The synthesized Schiff bases were used as photostabilizers for polystyrene against photodegradation. Polystyrene polymeric films containing synthesized Schiff bases (0.5% by weight) were irradiated (λmax = 365 nm and light intensity = 6.43 × 10−9 ein·dm−3·s−1) at room temperature. The photostabilization effect of 1,2,4-triazole-3-thiols Schiff bases was determined using various methods. All the additives used enhanced the photostability of polystyrene films against irradiation compared with the result obtained in the absence of Schiff base. The Schiff bases can act as photostabilizers for polystyrene through the direct absorption of UV radiation and/or radical scavengers. Full article
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Open AccessArticle Six New Triterpene Derivatives from Aralia chinensis Var. dasyphylloides
Molecules 2016, 21(12), 1700; doi:10.3390/molecules21121700
Received: 27 October 2016 / Revised: 2 December 2016 / Accepted: 2 December 2016 / Published: 9 December 2016
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Abstract
Aralia chinensis var. dasyphylloides is widely distributed in China and used as a traditional herbal medicine for the treatment of digestive and immune system diseases. The present study aimed to search for novel oleanolic-type triterpenoids in low-polarity fractions. Six new triterpene derivatives (
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Aralia chinensis var. dasyphylloides is widely distributed in China and used as a traditional herbal medicine for the treatment of digestive and immune system diseases. The present study aimed to search for novel oleanolic-type triterpenoids in low-polarity fractions. Six new triterpene derivatives (16), together with two known compounds were isolated from the barks of A. chinensis var. dasyphylloides. Their structures were elucidated by 1D- and 2D-NMR spectroscopic analysis and chemical methods. They were identified as 3-oxo-oleana-11,13(18)-dien-28,30-dioic acid (1), 30-hydroxy-3-oxo-oleana-11,13(18)-dien-28-oic acid (2), 3β-hydroxy-oleana-11,13(18)-dien-28-oic acid-28-O-β-d-glucopyranoside (3), 3β,30-dihydroxy-oleana-11,13(18)-dien-28-oic acid-28-O-β-d-glucopyranoside (4), 3β-hydroxy-oleana-11,13(18)-dien-28-oic acid-3-O-β-d-xylopyranosyl-(1 → 2)-β-d-glucopyranoside (5), 3β,29-dihydroxy-oleana-9(11),12-dien-28-oic acid-28-O-β-d-glucopyranoside (6), namely, araliachinolic acids I and II and araliachinosides I–IV. The cytotoxicity of the isolated compounds was tested against HepG2, A549, SGC7901, and MCF7 cell lines, but no apparent activity was observed at a concentration of 50 μM. Full article
(This article belongs to the Special Issue Triterpenes and Triterpenoids 2016)
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Open AccessArticle Could a Proto-Ribosome Emerge Spontaneously in the Prebiotic World?
Molecules 2016, 21(12), 1701; doi:10.3390/molecules21121701
Received: 20 September 2016 / Revised: 21 November 2016 / Accepted: 24 November 2016 / Published: 9 December 2016
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Abstract
An indispensable prerequisite for establishing a scenario of life emerging by natural processes is the requirement that the first simple proto-molecules could have had a realistic probability of self-assembly from random molecular polymers in the prebiotic world. The vestige of the proto-ribosome, which
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An indispensable prerequisite for establishing a scenario of life emerging by natural processes is the requirement that the first simple proto-molecules could have had a realistic probability of self-assembly from random molecular polymers in the prebiotic world. The vestige of the proto-ribosome, which is believed to be still embedded in the contemporary ribosome, is used to assess the feasibility of such spontaneous emergence. Three concentric structural elements of different magnitudes, having a dimeric nature derived from the symmetrical region of the ribosomal large subunit, were suggested to constitute the vestige of the proto-ribosome. It is assumed to have materialized spontaneously in the prebiotic world, catalyzing non-coded peptide bond formation and simple elongation. Probabilistic and energetic considerations are applied in order to evaluate the suitability of the three contenders for being the initial proto-ribosome. The analysis points to the simplest proto-ribosome, comprised of a dimer of tRNA-like molecules presently embedded in the core of the symmetrical region, as the only one having a realistic statistical likelihood of spontaneous emergence from random RNA chains. Hence it offers a feasible starting point for a continuous evolutionary path from the prebiotic matter, through natural processes, into the intricate modern translation system. Full article
(This article belongs to the Special Issue Ribozymes and RNA Catalysis)
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Open AccessArticle Enhanced Stilbene Production and Excretion in Vitis vinifera cv Pinot Noir Hairy Root Cultures
Molecules 2016, 21(12), 1703; doi:10.3390/molecules21121703
Received: 14 October 2016 / Revised: 2 December 2016 / Accepted: 7 December 2016 / Published: 10 December 2016
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Abstract
Stilbenes are defense molecules produced by grapevine in response to stresses including various elicitors and signal molecules. Together with their prominent role in planta, stilbenes have been the center of much attention in recent decades due to their pharmaceutical properties. With the aim
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Stilbenes are defense molecules produced by grapevine in response to stresses including various elicitors and signal molecules. Together with their prominent role in planta, stilbenes have been the center of much attention in recent decades due to their pharmaceutical properties. With the aim of setting up a cost-effective and high purity production of resveratrol derivatives, hairy root lines were established from Vitis vinifera cv Pinot Noir 40024 to study the organ-specific production of various stilbenes. Biomass increase and stilbene production by roots were monitored during flask experiments. Although there was a constitutive production of stilbenes in roots, an induction of stilbene synthesis by methyl jasmonate (MeJA) after 18 days of growth led to further accumulation of ε-viniferin, δ-viniferin, resveratrol and piceid. The use of 100 µM MeJA after 18 days of culture in the presence of methyl-β-cyclodextrins (MCDs) improved production levels, which reached 1034µg/g fresh weight (FW) in roots and 165 mg/L in the extracellular medium, corresponding to five-and 570-foldincrease in comparison to control. Whereas a low level of stilbene excretion was measured in controls, addition of MeJA induced excretion of up to 37% of total stilbenes. The use of MCDs increased the excretion phenomenon even more, reaching up to 98%. Our results demonstrate the ability of grapevine hairy roots to produce various stilbenes. This production was significantly improved in response to elicitation by methyl jasmonate and/or MCDs. This supports the interest of using hairy roots as a potentially valuable system for producing resveratrol derivatives. Full article
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Open AccessCommunication Sugar-Annulated Oxazoline Ligands: A Novel Pd(II) Complex and Its Application in Allylic Substitution
Molecules 2016, 21(12), 1704; doi:10.3390/molecules21121704
Received: 25 October 2016 / Revised: 1 December 2016 / Accepted: 7 December 2016 / Published: 10 December 2016
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Abstract
Two novel carbohydrate-derived pyridyl (PYOX)- and cyclopropyl (CYBOX)-substituted oxazoline ligands were prepared from d-glucosamine hydrochloride and 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-β-d-glucopyranose hydrochloride in two steps, respectively. The sugar-annulated PYOX ligand formed a stable metal complex with Pd(II), which was fully characterized by
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Two novel carbohydrate-derived pyridyl (PYOX)- and cyclopropyl (CYBOX)-substituted oxazoline ligands were prepared from d-glucosamine hydrochloride and 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-β-d-glucopyranose hydrochloride in two steps, respectively. The sugar-annulated PYOX ligand formed a stable metal complex with Pd(II), which was fully characterized by NMR spectroscopy and X-ray crystallography. NMR and X-ray analysis revealed a change of the conformation in the sugar moiety upon complexation with the palladium(II) species. Both glycosylated ligands resulted in high asymmetric induction (up to 98% ee) upon application as chiral ligands in the Pd-catalyzed allylic alkylation of rac-1,3-diphenylallyl acetate with dimethyl malonate (Tsuji-Trost reaction). Both ligands provided mainly the (R)-enantiomer of the alkylation product. Full article
(This article belongs to the Special Issue Asymmetric Synthesis 2017)
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Open AccessArticle Interactions of Bovine Serum Albumin with Anti-Cancer Compounds Using a ProteOn XPR36 Array Biosensor and Molecular Docking
Molecules 2016, 21(12), 1706; doi:10.3390/molecules21121706
Received: 14 October 2016 / Revised: 28 November 2016 / Accepted: 30 November 2016 / Published: 10 December 2016
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Abstract
The aim of the work was to determine the interactions of a set of anti-cancer compounds with bovine serum albumin (BSA) using a ProteOn XPR36 array biosensor and molecular docking studies. The results revealed that a total of six anti-cancer compounds: gallic acid,
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The aim of the work was to determine the interactions of a set of anti-cancer compounds with bovine serum albumin (BSA) using a ProteOn XPR36 array biosensor and molecular docking studies. The results revealed that a total of six anti-cancer compounds: gallic acid, doxorubicin, acteoside, salvianolic acid B, echinacoside, and vincristine were able to reversibly bind to the immobilized BSA. The sensorgrams of these six compounds were globally fit to a Langmuir 1:1 interaction model for binding kinetics analysis. There were significant differences in their affinity for BSA, with doxorubicin, the weakest binding compound having 1000-fold less affinity than salvianolic acid B, the strongest binding compound. However, compounds with a similar KD often exhibited markedly different kinetics due to the differences in ka and kd. Molecular docking experiments demonstrated that acteoside was partially located within sub-domain IIA of BSA, whereas gallic acid bound to BSA deep within its sub-domain IIIA. In addition, the interactions between these compounds and BSA were dominated by hydrophobic forces and hydrogen bonds. Understanding the detailed information of these anti-cancer compounds can provide important insights into optimizing the interactions and activity of potential compounds during drug development. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessFeature PaperArticle Expression of 3-Mercaptopyruvate Sulfurtransferase in the Mouse
Molecules 2016, 21(12), 1707; doi:10.3390/molecules21121707
Received: 15 November 2016 / Revised: 6 December 2016 / Accepted: 7 December 2016 / Published: 11 December 2016
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Abstract
3-Mercaptopyruvate sulfurtransferase (MST) is one of the principal enzymes for the production of hydrogen sulfide and polysulfides in mammalians, and emerging evidence supports the physiological significance of MST. As a fundamental study of the physiology and pathobiology of MST, it is necessary to
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3-Mercaptopyruvate sulfurtransferase (MST) is one of the principal enzymes for the production of hydrogen sulfide and polysulfides in mammalians, and emerging evidence supports the physiological significance of MST. As a fundamental study of the physiology and pathobiology of MST, it is necessary to establish the tissue distribution of MST in mice. In the present study, the expression of MST in various organs of adult and fetal mice was analyzed by Western blotting and enzyme-immunohistochemistry. Moreover, the histology of MST gene–deficient mice was examined. Western blotting revealed that all organs examined had MST. The brain, liver, kidneys testes, and endocrine organs contained large amounts of MST, but the lungs, spleen, thymus, and small intestine did not. Immunohistochemically, the MST expression pattern varies in a cell-specific manner. In the brain, neural and glial cells are positively stained; in the lung, bronchiolar cells are preferentially stained; in the liver, hepatocytes around central veins are more strongly stained; renal convoluted cells are strongly stained; and pancreatic islets are strongly stained. Fetal tissues were studied, and MST expression was found to be similar before and after birth. Histological observation revealed no remarkable findings in MST gene–deficient mice. The present study revealed fundamental information regarding the MST expression of various organs in adult and fetal mice, and the morphological phenotype of MST gene–deficient mice. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)
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Open AccessArticle Zerumbone, a Bioactive Sesquiterpene, Ameliorates Diabetes-Induced Retinal Microvascular Damage through Inhibition of Phospho-p38 Mitogen-Activated Protein Kinase and Nuclear Factor-κB Pathways
Molecules 2016, 21(12), 1708; doi:10.3390/molecules21121708
Received: 28 October 2016 / Revised: 7 December 2016 / Accepted: 9 December 2016 / Published: 11 December 2016
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Abstract
Zerumbone ameliorates retinal damage by blocking advanced glycation end products and their receptor system in streptozotocin-diabetic rats. Because of the multiple factors involved in diabetic retinopathy (DR) etiology, the mechanisms of zerumbone that are mainly responsible for its ameliorative effect on DR need
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Zerumbone ameliorates retinal damage by blocking advanced glycation end products and their receptor system in streptozotocin-diabetic rats. Because of the multiple factors involved in diabetic retinopathy (DR) etiology, the mechanisms of zerumbone that are mainly responsible for its ameliorative effect on DR need to be further clarified. In the present study, zerumbone (20 mg or 40 mg/kg) or fenofibric acid (100 mg/kg) was orally administered to diabetic rats by intragastric gavage once daily for three consecutive months. Zerumbone displayed similar characteristics to fenofibric acid in reducing retinal vascular permeability and leukostasis in diabetic rats. Fundus photographs showed that large retinal vessel diameters were decreased in zerumbone-treated diabetic rats. Zerumbone not only down-regulated the gene expression of retinal angiogenic parameters, but also reduced the expression of inflammatory cytokines and chemokines in the retina of diabetic rats. Moreover, zerumbone reduced the p38 MAPK phosphorylation and abrogated the nuclear translocation of NF-κB p65 in the retina of diabetic rats. In conclusion, treatment of diabetic rats with zerumbone attenuates the severity of retinal inflammation and angiogenesis, via inhibition of p38 MAPK and NF-κB signaling pathways. These benefits of zerumbone for DR appear to be linked to its antihyperglycemic and antihyperlipidemic effects. Full article
(This article belongs to the Special Issue Natural Products and Chronic Diseases)
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Open AccessArticle Functional Analysis of the Fusarielin Biosynthetic Gene Cluster
Molecules 2016, 21(12), 1710; doi:10.3390/molecules21121710
Received: 3 November 2016 / Revised: 5 December 2016 / Accepted: 5 December 2016 / Published: 13 December 2016
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Abstract
Fusarielins are polyketides with a decalin core produced by various species of Aspergillus and Fusarium. Although the responsible gene cluster has been identified, the biosynthetic pathway remains to be elucidated. In the present study, members of the gene cluster were deleted individually
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Fusarielins are polyketides with a decalin core produced by various species of Aspergillus and Fusarium. Although the responsible gene cluster has been identified, the biosynthetic pathway remains to be elucidated. In the present study, members of the gene cluster were deleted individually in a Fusarium graminearum strain overexpressing the local transcription factor. The results suggest that a trans-acting enoyl reductase (FSL5) assists the polyketide synthase FSL1 in biosynthesis of a polyketide product, which is released by hydrolysis by a trans-acting thioesterase (FSL2). Deletion of the epimerase (FSL3) resulted in accumulation of an unstable compound, which could be the released product. A novel compound, named prefusarielin, accumulated in the deletion mutant of the cytochrome P450 monooxygenase FSL4. Unlike the known fusarielins from Fusarium, this compound does not contain oxygenized decalin rings, suggesting that FSL4 is responsible for the oxygenation. Full article
(This article belongs to the Special Issue Polyketides)
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Open AccessArticle Plasma Processing with Fluorine Chemistry for Modification of Surfaces Wettability
Molecules 2016, 21(12), 1711; doi:10.3390/molecules21121711
Received: 6 October 2016 / Revised: 29 November 2016 / Accepted: 5 December 2016 / Published: 13 December 2016
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Abstract
Using plasma in conjunction with fluorinated compounds is widely encountered in material processing. We discuss several plasma techniques for surface fluorination: deposition of fluorocarbon thin films either by magnetron sputtering of polytetrafluoroethylene targets, or by plasma-assisted chemical vapor deposition using tetrafluoroethane as a
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Using plasma in conjunction with fluorinated compounds is widely encountered in material processing. We discuss several plasma techniques for surface fluorination: deposition of fluorocarbon thin films either by magnetron sputtering of polytetrafluoroethylene targets, or by plasma-assisted chemical vapor deposition using tetrafluoroethane as a precursor, and modification of carbon nanowalls by plasma treatment in a sulphur hexafluoride environment. We showed that conformal fluorinated thin films can be obtained and, according to the initial surface properties, superhydrophobic surfaces can be achieved. Full article
(This article belongs to the Special Issue Fluorine Chemistry 2016)
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Open AccessArticle Long-Term Stability of New Co-Amorphous Drug Binary Systems: Study of Glass Transitions as a Function of Composition and Shelf Time
Molecules 2016, 21(12), 1712; doi:10.3390/molecules21121712
Received: 24 October 2016 / Revised: 29 November 2016 / Accepted: 7 December 2016 / Published: 14 December 2016
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Abstract
The amorphous state is of particular interest in the pharmaceutical industry due to the higher solubility that amorphous active pharmaceutical ingredients show compared to their respective crystalline forms. Due to their thermodynamic instability, drugs in the amorphous state tend to recrystallize; in order
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The amorphous state is of particular interest in the pharmaceutical industry due to the higher solubility that amorphous active pharmaceutical ingredients show compared to their respective crystalline forms. Due to their thermodynamic instability, drugs in the amorphous state tend to recrystallize; in order to avoid crystallization, it has been a common strategy to add a second component to hinder the crystalline state and form a thermally stable co-amorphous system, that is to say, an amorphous binary system which retains its amorphous structure. The second component can be a small molecule excipient (such as a sugar or an aminoacid) or a second drug, with the advantage that a second active pharmaceutical ingredient could be used for complementary or combined therapeutic purposes. In most cases, the compositions studied are limited to 1:1, 2:1 and 1:2 molar ratios, leaving a gap of information about phase transitions and stability on the amorphous state in a wider range of compositions. In the present work, a study of novel co–amorphous formulations in which the selection of the active pharmaceutical ingredients was made according to the therapeutic effect is presented. Resistance against crystallization and behavior of glass transition temperature ( T g were studied through calorimetric measurements as a function of composition and shelf time. It was found that binary formulations with T g temperatures higher than those of pure components presented long-term thermal stability. In addition, significant increments of T g values, of as much as 15 C, were detected as a result of glass relaxation at room temperature during storage time; this behavior of glass transition has not been previously reported for co-amorphous drugs. Based on these results, it can be concluded that monitoring behavior of T g and relaxation processes during the first weeks of storage leads to a more objective evaluation of the thermomechanical stability of an amorphous formulation. Full article
(This article belongs to the collection Poorly Soluble Drugs)
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Open AccessArticle Hypervalent Iodine(III)-Induced Domino Oxidative Cyclization for the Synthesis of Cyclopenta[b]furans
Molecules 2016, 21(12), 1713; doi:10.3390/molecules21121713
Received: 17 November 2016 / Revised: 12 December 2016 / Accepted: 14 December 2016 / Published: 21 December 2016
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Abstract A new strategy for cyclopenta[b]furan synthesis mediated by hypervalent iodine(III) has been described. The approach employs diacetoxyiodobenzene-induced initial dehydrogenation to a putative trienone intermediate and triggered sequential cycloisomerization to form the cyclo-penta[b]furan targets. Full article
(This article belongs to the Special Issue Hypervalent Iodine Chemistry)
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Open AccessArticle A Novel Synthesis of Fused Uracils: Indenopyrimidopyridazines, Pyrimidopyridazines, and Pyrazolopyrimidines for Antimicrobial and Antitumor Evalution
Molecules 2016, 21(12), 1714; doi:10.3390/molecules21121714
Received: 17 October 2016 / Revised: 6 December 2016 / Accepted: 8 December 2016 / Published: 14 December 2016
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Abstract
A variety of different compounds of fused uracils were prepared simply by the heating of 6-hydrazinyl-1-methyl-, 6-hydrazinyl-1-propyl-, or 6-hydrazinyl-1,3-dipropyluracil under reflux with ninhydrin, isatin, benzylidene malononitrile, benzylylidene ethyl cyanoacetate, benzil, and phenacyl bromide derivatives. The newly synthesized compounds were completely screened for antimicrobial
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A variety of different compounds of fused uracils were prepared simply by the heating of 6-hydrazinyl-1-methyl-, 6-hydrazinyl-1-propyl-, or 6-hydrazinyl-1,3-dipropyluracil under reflux with ninhydrin, isatin, benzylidene malononitrile, benzylylidene ethyl cyanoacetate, benzil, and phenacyl bromide derivatives. The newly synthesized compounds were completely screened for antimicrobial and antitumor activity. Full article
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Open AccessArticle Synthesis, Antifungal Evaluation and In Silico Study of N-(4-Halobenzyl)amides
Molecules 2016, 21(12), 1716; doi:10.3390/molecules21121716
Received: 28 October 2016 / Revised: 8 December 2016 / Accepted: 9 December 2016 / Published: 13 December 2016
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Abstract
A collection of 32 structurally related N-(4-halobenzyl)amides were synthesized from cinnamic and benzoic acids through coupling reactions with 4-halobenzylamines, using (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) as a coupling agent. The compounds were identified by spectroscopic methods such as infrared, 1H- and 13C-
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A collection of 32 structurally related N-(4-halobenzyl)amides were synthesized from cinnamic and benzoic acids through coupling reactions with 4-halobenzylamines, using (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) as a coupling agent. The compounds were identified by spectroscopic methods such as infrared, 1H- and 13C- Nuclear Magnetic Resonance (NMR) and high-resolution mass spectrometry. The compounds were then submitted to antimicrobial tests by the minimum inhibitory concentration method (MIC) and nystatin was used as a control in the antifungal assays. The purpose of the tests was to evaluate the influence of structural changes in the cinnamic and benzoic acid substructures on the inhibitory activity against strains of Candida albicans, Candida tropicalis, and Candida krusei. A quantitative structure-activity relationship (QSAR) study with KNIME v. 3.1.0 and Volsurf v. 1.0.7 softwares were realized, showing that descriptors DRDRDR, DRDRAC, L4LgS, IW4 and DD2 influence the antifungal activity of the haloamides. In general, 10 benzamides revealed fungal sensitivity, especially a vanillic amide which enjoyed the lowest MIC. The results demonstrate that a hydroxyl group in the para position, and a methoxyl at the meta position enhance antifungal activity for the amide skeletal structure. In addition, the double bond as a spacer group appears to be important for the activity of amide structures. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Scoparone Inhibits LPS-Simulated Inflammatory Response by Suppressing IRF3 and ERK in BV-2 Microglial Cells
Molecules 2016, 21(12), 1718; doi:10.3390/molecules21121718
Received: 30 October 2016 / Revised: 2 December 2016 / Accepted: 7 December 2016 / Published: 14 December 2016
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Abstract
Microglia activation and the release of various inflammatory cytokines are largely related to neurological diseases, including Parkinson’s, Alzheimer’s, and other brain diseases. The suppression of microglial cells using natural bioactive compounds has become increasingly important for brain therapy owing to the expected beneficial
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Microglia activation and the release of various inflammatory cytokines are largely related to neurological diseases, including Parkinson’s, Alzheimer’s, and other brain diseases. The suppression of microglial cells using natural bioactive compounds has become increasingly important for brain therapy owing to the expected beneficial effect of lower toxicity. Scoparone (6,7-dimethoxycoumarin), a major bioactive compound found in various plant parts, including the inner shell of chestnut (Castanea crenata), was evaluated on lipopolysaccharide (LPS)-activated BV-2 microglia cells. The results indicated that scoparone suppresses the LPS-stimulated increase of neuroinflammatory responses and inhibited the pro-inflammatory cytokine production in the BV-2 microglial cells. A mechanistic study showed that scoparone specifically inhibited the LPS-stimulated activation via a major regulation of IRF-3 and a regulation of ERK, whereby the phosphorylation in the BV-2 microglial cells is blocked. These data suggest that scoparone has anti-neuroinflammatory effects in LPS-activated BV-2 microglial cells, and could possibly be used in the development of novel drugs for the prevention and treatment of neuroinflammatory diseases. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Design, Synthesis and Biological Evaluation of Stilbene Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B
Molecules 2016, 21(12), 1722; doi:10.3390/molecules21121722
Received: 26 October 2016 / Revised: 7 December 2016 / Accepted: 12 December 2016 / Published: 16 December 2016
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Abstract
By imitating the scaffold of lithocholic acid (LCA), a natural steroidal compound displaying Protein Tyrosine Phosphatase 1B (PTP1B) inhibitory activity, a series of stilbene derivatives containing phenyl-substituted isoxazoles were designed and synthesized. The structures of the title compounds were confirmed by 1H-NMR,
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By imitating the scaffold of lithocholic acid (LCA), a natural steroidal compound displaying Protein Tyrosine Phosphatase 1B (PTP1B) inhibitory activity, a series of stilbene derivatives containing phenyl-substituted isoxazoles were designed and synthesized. The structures of the title compounds were confirmed by 1H-NMR, 13C-NMR and HRMS. Activities of the title compounds were evaluated on PTP1B and the homologous enzyme TCPTP by using a colorimetric assay. Most of the target compounds had good activities against PTP1B. Among them, compound 29 (IC50 = 0.91 ± 0.33 μM), characterized by a 5-(2,3-dichlorophenyl) isoxazole moiety, exhibited an activity about 14-fold higher than the lead compound LCA and a 4.2-fold selectivity over TCPTP. Compound 29 was identified as a competitive inhibitor of PTP1B with a Ki value of 0.78 μM in enzyme kinetic studies. Full article
(This article belongs to the Section Medicinal Chemistry)
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