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Molecules, Volume 22, Issue 6 (June 2017)

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Cover Story The increasing popularity of porphyrinoids in a variety of biomedical and technical applications is [...] Read more.
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Open AccessArticle Total Synthesis and Pharmacological Investigation of Cordyheptapeptide A
Molecules 2017, 22(6), 682; doi:10.3390/molecules22060682
Received: 23 March 2017 / Revised: 17 April 2017 / Accepted: 18 April 2017 / Published: 27 May 2017
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Abstract
The present investigation reports the synthesis of a phenylalanine-rich N-methylated cyclopeptide, cordyheptapeptide A (8), previously isolated from the insect pathogenic fungus Cordyceps sp. BCC 1788, accomplished through the coupling of N-methylated tetrapeptide and tripeptide fragments followed by cyclization of
[...] Read more.
The present investigation reports the synthesis of a phenylalanine-rich N-methylated cyclopeptide, cordyheptapeptide A (8), previously isolated from the insect pathogenic fungus Cordyceps sp. BCC 1788, accomplished through the coupling of N-methylated tetrapeptide and tripeptide fragments followed by cyclization of the linear heptapeptide unit. Structure elucidation of the newly synthesized cyclopolypeptide was performed by means of FT-IR, 1H-NMR, 13C-NMR, and fast atom bombardment mass spectrometry (FABMS), and screened for its antibacterial, antidermatophytic, and cytotoxic potential. According to the antimicrobial activity results, the newly synthesized N-Methylated cyclopeptide exhibited potent antibacterial activity against Gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae and antifungal activity against dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 μg/mL, in comparison to the reference drugs, gatifloxacin and griseofulvin. In addition, cyclopolypeptide 8 displayed suitable levels of cytotoxicity against Dalton’s lymphoma ascites (DLA) and Ehrlich’s ascites carcinoma (EAC) cell lines. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle New Mild and Simple Approach to Isothiocyanates: A Class of Potent Anticancer Agents
Molecules 2017, 22(6), 773; doi:10.3390/molecules22060773
Received: 18 March 2017 / Revised: 22 April 2017 / Accepted: 27 April 2017 / Published: 1 June 2017
Cited by 2 | PDF Full-text (3637 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In our current work, acetyl chloride-mediated synthesis of phenethyl isothiocyanate (PEITC) derivatives proves to be convenient and provides the expected products at good to excellent yields. Biological evaluation and structure-activity relationship analysis found that the novel compound 7 showed the best anticancer activity
[...] Read more.
In our current work, acetyl chloride-mediated synthesis of phenethyl isothiocyanate (PEITC) derivatives proves to be convenient and provides the expected products at good to excellent yields. Biological evaluation and structure-activity relationship analysis found that the novel compound 7 showed the best anticancer activity against human cancer cell line Panc1 and HGC27 compared with PEITC. Compounds 6 and 7 induced more apoptosis in pancreatic cancer cells but less toxicity in non-cancer cells. Further biological study demonstrated that 7 substantially increased intracellular reactive oxygen species (ROS) and depleted glutathione (GSH), leading to an oxidative stress to kill cancer cell. Full article
(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)
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Open AccessArticle Secondary Sulfonamides as Effective Lactoperoxidase Inhibitors
Molecules 2017, 22(6), 793; doi:10.3390/molecules22060793
Received: 28 February 2017 / Revised: 27 April 2017 / Accepted: 9 May 2017 / Published: 24 May 2017
Cited by 3 | PDF Full-text (702 KB) | HTML Full-text | XML Full-text
Abstract
Secondary sulfonamides (4a8h) incorporating acetoxybenzamide, triacetoxybenzamide, hydroxybenzamide, and trihydroxybenzamide and possessing thiazole, pyrimidine, pyridine, isoxazole and thiadiazole groups were synthesized. Lactoperoxidase (LPO, E.C.1.11.1.7), as a natural antibacterial agent, is a peroxidase enzyme secreted from salivary, mammary, and other mucosal
[...] Read more.
Secondary sulfonamides (4a8h) incorporating acetoxybenzamide, triacetoxybenzamide, hydroxybenzamide, and trihydroxybenzamide and possessing thiazole, pyrimidine, pyridine, isoxazole and thiadiazole groups were synthesized. Lactoperoxidase (LPO, E.C.1.11.1.7), as a natural antibacterial agent, is a peroxidase enzyme secreted from salivary, mammary, and other mucosal glands. In the present study, the in vitro inhibitory effects of some secondary sulfonamide derivatives (4a8h) were examined against LPO. The obtained results reveal that secondary sulfonamide derivatives (4a8h) are effective LPO inhibitors. The Ki values of secondary sulfonamide derivatives (4a8h) were found in the range of 1.096 × 10−3 to 1203.83 µM against LPO. However, the most effective inhibition was found for N-(sulfathiazole)-3,4,5-triacetoxybenzamide (6a), with Ki values of 1.096 × 10−3 ± 0.471 × 10−3 µM as non-competitive inhibition. Full article
(This article belongs to the Special Issue Sulfonamides)
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Open AccessArticle Production of Recombinant Antimicrobial Polymeric Protein Beta Casein-E 50-52 and Its Antimicrobial Synergistic Effects Assessment with Thymol
Molecules 2017, 22(6), 822; doi:10.3390/molecules22060822
Received: 24 March 2017 / Revised: 8 May 2017 / Accepted: 11 May 2017 / Published: 31 May 2017
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Abstract
Accelerating emergence of antimicrobial resistance among food pathogens and consumers’ increasing demands for preservative-free foods are two contemporary challenging aspects within the food industry. Antimicrobial packaging and the use of natural preservatives are promising solutions. In the present study, we used beta-casein—one
[...] Read more.
Accelerating emergence of antimicrobial resistance among food pathogens and consumers’ increasing demands for preservative-free foods are two contemporary challenging aspects within the food industry. Antimicrobial packaging and the use of natural preservatives are promising solutions. In the present study, we used beta-casein—one of the primary self-assembly proteins in milk with a high polymeric film production capability—as a fusion partner for the recombinant expression of E 50-52 antimicrobial peptide in Escherichia coli. The pET21a-BCN-E 50-52 construct was transformed to E. coli BL21 (DE3), and protein expression was induced under optimized conditions. Purified protein obtained from nickel affinity chromatography was refolded under optimized dialysis circumstances and concentrated to 1600 µg/mL fusion protein by ultrafiltration. Antimicrobial activities of recombinant BCN-E 50-52 performed against Escherichia coli, Salmonella typhimurium, Listeria monocytogenes, Staphylococcus aureus, Aspergillus flavus, and Candida albicans. Subsequently, the synergistic effects of BCN-E 50-52 and thymol were assayed. Results of checkerboard tests showed strong synergistic activity between two compounds. Time–kill and growth kinetic studies indicated a sharp reduction of cell viability during the first period of exposure, and SEM (scanning electron microscope) results validated the severe destructive effects of BCN E 50-52 and thymol in combination on bacterial cells. Full article
(This article belongs to the Special Issue Bioactive Natural Peptides As A Pipeline For Therapeutics)
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Open AccessArticle Green Synthesis of Zinc Oxide Nanoparticles for Enhanced Adsorption of Lead Ions from Aqueous Solutions: Equilibrium, Kinetic and Thermodynamic Studies
Molecules 2017, 22(6), 831; doi:10.3390/molecules22060831
Received: 20 April 2017 / Revised: 11 May 2017 / Accepted: 15 May 2017 / Published: 8 June 2017
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Abstract
In the present study, ZnO nanoparticles (NPs) were synthesized in zerumbone solution by a green approach and appraised for their ability to absorb Pb(II) ions from aqueous solution. The formation of as-synthesized NPs was established by X-ray diffraction (XRD), Transmission Electron Microscopy (TEM),
[...] Read more.
In the present study, ZnO nanoparticles (NPs) were synthesized in zerumbone solution by a green approach and appraised for their ability to absorb Pb(II) ions from aqueous solution. The formation of as-synthesized NPs was established by X-ray diffraction (XRD), Transmission Electron Microscopy (TEM), and UV–visible studies. The XRD and TEM analyses revealed high purity and wurtzite hexagonal structure of ZnO NPs with a mean size of 10.01 ± 2.6 nm. Batch experiments were performed to investigate the impact of process parameters viz. Pb(II) concentration, pH of solution, adsorbent mass, solution temperature, and contact time variations on the removal efficiency of Pb(II). The adsorption isotherm data provided that the adsorption process was mainly monolayer on ZnO NPs. The adsorption process follows pseudo-second-order reaction kinetic. The maximum removal efficiencies were 93% at pH 5. Thermodynamic parameters such as enthalpy change (ΔH0), free energy change (ΔG0), and entropy change (ΔS0) were calculated; the adsorption process was spontaneous and endothermic. The good efficiency of the as-synthesized NPs makes them attractive for applications in water treatment, for removal of heavy metals from aqueous system. Full article
(This article belongs to the Section Green Chemistry)
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Open AccessArticle Endophytic Bacteria Isolated from Panax ginseng Improves Ginsenoside Accumulation in Adventitious Ginseng Root Culture
Molecules 2017, 22(6), 837; doi:10.3390/molecules22060837
Received: 7 April 2017 / Revised: 17 May 2017 / Accepted: 17 May 2017 / Published: 23 May 2017
Cited by 1 | PDF Full-text (3295 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ginsenoside is the most important secondary metabolite of ginseng. Natural sources of wild ginseng have been overexploited. Although root culture could reduce the length of the growth cycle of ginseng, the number of ginsenosides is fewer and their contents are lower in adventitious
[...] Read more.
Ginsenoside is the most important secondary metabolite of ginseng. Natural sources of wild ginseng have been overexploited. Although root culture could reduce the length of the growth cycle of ginseng, the number of ginsenosides is fewer and their contents are lower in adventitious roots of ginseng than that in ginseng cultivated in the field. In this study, we investigated the effects of endophytic bacterial elicitors on biomass and ginsenoside production in adventitious roots cultures of Panax ginseng. Endophyte LB 5-3 as an elicitor could increase biomass and ginsenoside accumulation in ginseng adventitious root culture. After 6 days elicitation with a 10.0 mL of strain LB 5-3, the content of total ginsenoside was 2.026 mg g−1 which was four times more than that in unchallenged roots. The combination of methyl jasmonate and strain LB 5-3 had a negative effect on ginseng adventitious root growth and ginsenoside production. The genomic DNA of strain LB 5-3 was sequenced, and was found to be most closely related to Bacillus altitudinis (KX230132.1). The challenged ginseng adventitious root extracts exerted inhibitory effect against the HepG2 cells, which IC50 value was 0.94 mg mL−1. Full article
(This article belongs to the Special Issue Current Trends in Ginseng Research)
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Open AccessArticle Immunomodulatory Effect of Agave tequilana Evaluated on an Autoimmunity Like-SLE Model Induced in Balb/c Mice with Pristane
Molecules 2017, 22(6), 848; doi:10.3390/molecules22060848
Received: 5 April 2017 / Revised: 5 May 2017 / Accepted: 7 May 2017 / Published: 25 May 2017
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Abstract
In this work, the immunomodulatory activity of the acetone extract and the fructans obtained from Agave tequilana were evaluated, on the systemic autoimmunity type-SLE model generated by the administration of 2,6,10,14-tetramethylpentadecane (TMPD, also known as pristane) on Balb/c female mice. The systemic autoimmunity
[...] Read more.
In this work, the immunomodulatory activity of the acetone extract and the fructans obtained from Agave tequilana were evaluated, on the systemic autoimmunity type-SLE model generated by the administration of 2,6,10,14-tetramethylpentadecane (TMPD, also known as pristane) on Balb/c female mice. The systemic autoimmunity type-SLE was observed seven months after the application of TMPD, in which the animals from the negative control group (animals with damage and without any other treatment) developed articular inflammation, proteinuria, an increment of the antinuclear antibody titters and tissue pro-inflammatory cytokines levels (IL-1β, IL-6, TNF-α e IFN-γ) as well as the anti-inflammatory cytokine IL-10. The administration of the different treatments and the extracts of A. tequilana, provoked the decrease of: articular inflammation, the development of proteinuria, ssDNA/dsDNA antinuclear antibody titters and cytokines IL-1β, IL-6, TNF-α, IFN-γ and IL-10. The phytochemical analysis of the acetone extract identified the presence of the following compounds: β-sitosterol glycoside; 3,7,11,15-tetramethyl-2-hexadecen-1-ol (phytol); octadecadienoic acid-2,3-dihydroxypropyl ester; stigmasta-3,5-dien-7-one; cycloartenone and cycloartenol. Therefore, A. tequilana contains active compounds with the capacity to modify the evolution of the systemic autoimmunity type-SLE on a murine model. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Phloroglucinols with Antioxidant Activities Isolated from Lysidice rhodostegia
Molecules 2017, 22(6), 855; doi:10.3390/molecules22060855
Received: 31 March 2017 / Accepted: 17 May 2017 / Published: 23 May 2017
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Abstract
Two new phloroglucinols, lysidisides X and Y (1 and 2), and two known compounds, 2-(2-methylbutyryl)phloroglucinol 1-O-β-d-glucopyranoside (3) and (E)-resveratrol 3-(6″-galloyl)-O-β-d-glucopyranoside (4), have been isolated from the roots
[...] Read more.
Two new phloroglucinols, lysidisides X and Y (1 and 2), and two known compounds, 2-(2-methylbutyryl)phloroglucinol 1-O-β-d-glucopyranoside (3) and (E)-resveratrol 3-(6″-galloyl)-O-β-d-glucopyranoside (4), have been isolated from the roots of Lysidice rhodostegia. The structures of 1 and 2 were elucidated primarily by NMR experiments. Their absolute configurations were deduced via circular dichroism (CD) data and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 exhibited significant antioxidative activities with IC50 values of 12.0 and 11.8 µM, respectively. Full article
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Open AccessArticle 14,15-Secopregnane-Type Glycosides with 5α:9α-Peroxy and Δ6,8(14)-diene Linkages from the Roots of Cynanchum stauntonii
Molecules 2017, 22(6), 860; doi:10.3390/molecules22060860
Received: 21 April 2017 / Revised: 18 May 2017 / Accepted: 19 May 2017 / Published: 23 May 2017
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Abstract
Three new 14,15-secopregnane-type glycosides, stauntosides UA, UA1, and UA2, were isolated from the roots of Cynanchum stauntonii. The three compounds share the first reported and same basic structural features of 3β-hydroxy-14:16,15:20,18:20-triepoxy-5α:9α-peroxy-14,15-secopregnane-6,8(14)-diene named as stauntogenin G as the aglycones.
[...] Read more.
Three new 14,15-secopregnane-type glycosides, stauntosides UA, UA1, and UA2, were isolated from the roots of Cynanchum stauntonii. The three compounds share the first reported and same basic structural features of 3β-hydroxy-14:16,15:20,18:20-triepoxy-5α:9α-peroxy-14,15-secopregnane-6,8(14)-diene named as stauntogenin G as the aglycones. The structures of the new compounds were characterized on the basis of extensive spectroscopic analyses, mainly 1D and 2D NMR and MS methods and chemical analysis. The isolation and identification of the new compounds graced the structural diversity of pregnane-type steroids from C. stauntonii. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Daucosterol Inhibits the Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells via Wnt/β-Catenin Signaling
Molecules 2017, 22(6), 862; doi:10.3390/molecules22060862
Received: 17 March 2017 / Revised: 15 May 2017 / Accepted: 20 May 2017 / Published: 2 June 2017
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Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The purpose of this study was to determine the effects of daucosterol on HCC by investigating Wnt/β-catenin signaling. In this study, HepG2 and SMMC-7721 cells were treated with varying concentrations
[...] Read more.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The purpose of this study was to determine the effects of daucosterol on HCC by investigating Wnt/β-catenin signaling. In this study, HepG2 and SMMC-7721 cells were treated with varying concentrations of daucosterol, and the corresponding inhibitory effects on HCC cells were examined via CCK-8 assays. Cell migration and invasion abilities were detected via transwell assays. β-Catenin and phospho (p)-β-catenin levels were analyzed via western blotting. Our results showed that daucosterol reduced the proliferation, migration, and invasion capacities of HCC cells in a concentration-dependent manner. In addition, daucosterol reduced the levels of β-catenin and p-β-catenin in HepG2 and SMMC-7721 cells. Furthermore, the Wnt signaling pathway inhibitor SB-216763 was used to treat HepG2 and SMMC-7721 cells with daucosterol. Our results showed that co-treatment with daucosterol and SB-216763 abolished the effects of daucosterol on cell inhibition ratios, cell migration, and cell invasion. These findings indicated that daucosterol inhibited cell migration and invasion in HCC cells via the Wnt/β-catenin signaling pathway. Therefore, our study highlights the use of daucosterol as a promising therapeutic strategy for HCC treatment. Full article
(This article belongs to the Special Issue Cancer Chemoprevention)
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Open AccessArticle Anti-Inflammatory Activity of a Polymeric Proanthocyanidin from Serjania schiedeana
Molecules 2017, 22(6), 863; doi:10.3390/molecules22060863
Received: 7 April 2017 / Revised: 15 May 2017 / Accepted: 16 May 2017 / Published: 26 May 2017
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Abstract
The ethyl acetate extract (SsAcOEt) from Serjania schiedeana, select fractions (F-6, F-12, F-13, F-14), and one isolated compound, were evaluated in 12-O-tetradecanoylphorbol 13-acetate (TPA) ear edema and kaolin/carrageenan (KC)-induced monoarthritis assays. SsEtOAc induced edema inhibition of 90% (2.0 mg/ear), fractions
[...] Read more.
The ethyl acetate extract (SsAcOEt) from Serjania schiedeana, select fractions (F-6, F-12, F-13, F-14), and one isolated compound, were evaluated in 12-O-tetradecanoylphorbol 13-acetate (TPA) ear edema and kaolin/carrageenan (KC)-induced monoarthritis assays. SsEtOAc induced edema inhibition of 90% (2.0 mg/ear), fractions showed activity within a range of 67–89%. Due to the fact F-14 showed the highest effect, it was separated, yielding a proanthocyanidin-type called epicatechin–(4β → 8)–epicatechin–(4β → 8, 2β → O → 7) epicatechin (ETP). This compound (2.0 mg/ear) provoked 72% of edema inhibition (ED50 = 0.25 mg/ear, Emax = 52.9%). After 9 days of treatment, joint inflammation was decreasing, and on the last day, SsEtOAc (400 mg/kg), F-14 and ETP (10 mg/kg), SsEtOAc (200 mg/kg), methotrexate (MTX) 1.0 mg/kg and meloxicam (MEL) 1.5 mg/kg, produced an inhibition articulate edema of 94, 62, 36, 21, 80, and 54%, respectively. In the joint, pro-inflammatory molecules were elevated in animals without treatment (vehicle group, VEH). Treatments from S. schiedeana induced a decrease in the concentration of interleukin (IL)-1β, IL-17, and IL-6, and SsEtOAc at a higher dose diminished tumor necrosis factor (TNF-α). IL-10 and IL-4 were fewer in the VEH group in comparison with healthy mice; the animals with treatments from S. schiedeana induced an increment in the levels of these cytokines in joint and spleen. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Encapsulation of the Antioxidant R-(+)-α-Lipoic Acid in Permethylated α- and β-Cyclodextrins: Thermal and X-ray Structural Characterization of the 1:1 Inclusion Complexes
Molecules 2017, 22(6), 866; doi:10.3390/molecules22060866
Received: 9 January 2017 / Revised: 16 May 2017 / Accepted: 16 May 2017 / Published: 23 May 2017
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Abstract
The naturally occurring compound α-lipoic acid (ALA) is implicated in manifold critical biological roles and its potent antioxidant properties and potential for treatment of various diseases have led to its widespread use as a dietary supplement. However, shortcomings of poor aqueous solubility and
[...] Read more.
The naturally occurring compound α-lipoic acid (ALA) is implicated in manifold critical biological roles and its potent antioxidant properties and potential for treatment of various diseases have led to its widespread use as a dietary supplement. However, shortcomings of poor aqueous solubility and low thermal stability have hampered its development as a medicinal agent, prompting the use of cyclodextrins (CDs) to address these problems. The paucity of published structural data on the nature of the interactions between ALA and CDs motivated the present study, which describes the synthesis and X-ray structural elucidation of crystalline inclusion complexes between the biologically relevant R-(+)-α-lipoic acid (RALA) and the host molecules permethylated α-CD (TMA) and permethylated β-CD (TMB). Single crystal X-ray diffraction of TMA·RALA·6H2O and TMB·RALA revealed significantly different orientations of the RALA molecule within the TMA and TMB cavities, but in both cases the guest molecule is fully encapsulated by the respective parent host molecules and residues of CD molecules of neighboring complex units. While pure RALA melted at 46–48 °C, combined thermal analysis techniques indicated that on heating the respective complexes, the release of RALA occurred at significantly higher onset temperatures, in the range 150–170 °C. Full article
(This article belongs to the Special Issue Cyclodextrin Chemistry)
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Open AccessArticle On Forgotten Topological Indices of Some Dendrimers Structure
Molecules 2017, 22(6), 867; doi:10.3390/molecules22060867
Received: 10 April 2017 / Revised: 15 May 2017 / Accepted: 15 May 2017 / Published: 24 May 2017
Cited by 1 | PDF Full-text (838 KB) | HTML Full-text | XML Full-text
Abstract
A series of previously conducted experiments pertaining to various chemicals and drugs uncover a natural linkage between the molecular structures and the bio-medical and pharmacological characteristics. The forgotten topological index computed for the molecular structures of various chemical compounds and drugs has proven
[...] Read more.
A series of previously conducted experiments pertaining to various chemicals and drugs uncover a natural linkage between the molecular structures and the bio-medical and pharmacological characteristics. The forgotten topological index computed for the molecular structures of various chemical compounds and drugs has proven significant in medical and pharmaceutical fields by predicting biological features of new chemical compounds and drugs. A topological index can be considered as the transformation of chemical structure into a real number. Dendrimers are highly-branched star-shaped macromolecules with nanometer-scale dimensions. Dendrimers are defined by three components: a central core, an interior dendritic structure (the branches), and an exterior surface with functional surface groups. In this paper, we determine forgotten topological indices of poly(propyl) ether imine, porphyrin, and zinc–porphyrin dendrimers. Full article
(This article belongs to the Section Theoretical Chemistry)
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Open AccessArticle Design and Synthesis of Dendrimers with Facile Surface Group Functionalization, and an Evaluation of Their Bactericidal Efficacy
Molecules 2017, 22(6), 868; doi:10.3390/molecules22060868
Received: 5 May 2017 / Revised: 18 May 2017 / Accepted: 18 May 2017 / Published: 24 May 2017
Cited by 2 | PDF Full-text (1697 KB) | HTML Full-text | XML Full-text
Abstract
We report a versatile divergent methodology to construct dendrimers from a tetrafunctional core, utilizing the robust copper(I) catalyzed alkyne-azide cycloaddition (CuAAC, “click”) reaction for both dendrimer synthesis and post-synthesis functionalization. Dendrimers of generations 1–3 with 8–32 protected or free OH and acetylene surface
[...] Read more.
We report a versatile divergent methodology to construct dendrimers from a tetrafunctional core, utilizing the robust copper(I) catalyzed alkyne-azide cycloaddition (CuAAC, “click”) reaction for both dendrimer synthesis and post-synthesis functionalization. Dendrimers of generations 1–3 with 8–32 protected or free OH and acetylene surface groups, were synthesized using building blocks that included acetylene- or azide-terminated molecules with carboxylic acid or diol end groups, respectively. The acetylene surface groups were subsequently used to covalently link cationic amino groups. A preliminary evaluation indicated that the generation one dendrimer with terminal NH3+ groups was the most effective bactericide, and it was more potent than several previously studied dendrimers. Our results suggest that size, functional end groups and hydrophilicity are important parameters to consider in designing efficient antimicrobial dendrimers. Full article
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Open AccessArticle In Silico Study and Bioprospection of the Antibacterial and Antioxidant Effects of Flavone and Its Hydroxylated Derivatives
Molecules 2017, 22(6), 869; doi:10.3390/molecules22060869
Received: 28 March 2017 / Revised: 14 May 2017 / Accepted: 20 May 2017 / Published: 24 May 2017
PDF Full-text (2014 KB) | HTML Full-text | XML Full-text
Abstract
Flavonoid compounds are widely used as natural protective species, which can act as anti-inflammatory, antioxidant, anticoagulant, antihypertensive and antitumor agents. This study set out to investigate the probable pharmacological activities, along with the antibacterial and antioxidant effects, of flavone and its hydroxy derivatives:
[...] Read more.
Flavonoid compounds are widely used as natural protective species, which can act as anti-inflammatory, antioxidant, anticoagulant, antihypertensive and antitumor agents. This study set out to investigate the probable pharmacological activities, along with the antibacterial and antioxidant effects, of flavone and its hydroxy derivatives: 3-hydroxyflavone, 5-hydroxyflavone and 6-hydroxyflavone. To do so, we investigated their pharmacological characteristics, using in silico tests that indicate likelihood of activity or inactivity, with the PASS online software, and the antimicrobial potential against Gram positive and Gram negative bacteria was also analyzed, including bacteria of clinical importance. We also tested for oxidant and antioxidant potential in these molecules in the presence of reactive oxygen species (ROS) and phenylhydrazine (Ph). The results revealed the following characteristics: pharmacological activities for the flavonoids as agonists of cell membrane integrity and as permeability inhibitors, as antagonists of anaphylatoxin receptors, as inhibitors of both kinase and peroxidase, and as having both antimutagenic capacity and vaso-protective potential. All of the flavonoids exhibited moderate antibacterial activity against Gram positive and Gram negative strains, with the flavones being bactericidal at 200 μg/mL for the strains of P. aeruginosa ATCC 8027, S. aureus ATCC 25619 and E. coli 104; the other flavonoids revealed bacteriostatic action. The substances did not promote erythrocyte oxidation and behaved as sequestrators and antioxidants of hydrogen peroxide (H2O2) and phenylhydrazine (Ph). It was concluded that the analyzed compounds have various pharmacological activities in accordance with the predictions of PASS online, as their antibacterial and antioxidant activities were confirmed. The study also helps to consolidate the use of computational chemistry in silico tools to guide new drug search and discovery protocols. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Preparation, Characterization, and Antioxidant Activity Evaluation of Liposomes Containing Water-Soluble Hydroxytyrosol from Olive
Molecules 2017, 22(6), 870; doi:10.3390/molecules22060870
Received: 15 April 2017 / Revised: 19 May 2017 / Accepted: 19 May 2017 / Published: 24 May 2017
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Abstract
Due to the multiple hydroxyl groups in its structure, hydroxytyrosol (HT) is very sensitive to air and light and has very strong instability and hydrophilicity that affect its biological activity. This study attempted to prepare liposomes containing water-soluble HT to improve the bioavailability
[...] Read more.
Due to the multiple hydroxyl groups in its structure, hydroxytyrosol (HT) is very sensitive to air and light and has very strong instability and hydrophilicity that affect its biological activity. This study attempted to prepare liposomes containing water-soluble HT to improve the bioavailability and biocompatibility of the target drug. The preparation process factors (temperature, mass ratio of phospholipid (PL) and cholesterol (CH), Tween-80 volume, HT mass) were studied and response surface methodology (RSM) was applied to optimize the conditions. The results demonstrated that by using a temperature of 63 °C, mass ratio of PL and CH 4.5:1, HT mass 5 mg and Tween-80 volume of 6 mL, HT liposomes with an encapsulation efficiency (EE) of 45.08% were prepared. It was found that the particle sizes of the HT liposomes were well distributed in the range of 100–400 nm. Compared to free HT, prepared HT liposomes had better stability and a distinct slow release effect in vitro. Besides, HT liposomes presented better DPPH radical scavenging activity than free HT, which could be due to the fact that HT was encapsulated fully inside the liposomes. In addition, the encapsulation mechanism of HT was evaluated. In summary, the results indicated that HT liposome could enhance the antioxidant activity and was a promising formulation for prolonging the biological activity time of the target drug. Full article
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Open AccessArticle Biosynthesis of ZnO Nanoparticles by a New Pichia kudriavzevii Yeast Strain and Evaluation of Their Antimicrobial and Antioxidant Activities
Molecules 2017, 22(6), 872; doi:10.3390/molecules22060872
Received: 25 April 2017 / Revised: 17 May 2017 / Accepted: 19 May 2017 / Published: 24 May 2017
Cited by 3 | PDF Full-text (7032 KB) | HTML Full-text | XML Full-text
Abstract
The potential ability of a new yeast strain, Pichia kudriavzevii, in the synthesis of zinc oxide nanoparticles (ZnO-NPs) through a green method was explored in this study. The effect of reaction time (12, 24 and 36 h) on the structure of the
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The potential ability of a new yeast strain, Pichia kudriavzevii, in the synthesis of zinc oxide nanoparticles (ZnO-NPs) through a green method was explored in this study. The effect of reaction time (12, 24 and 36 h) on the structure of the resulting ZnO nanoparticles was investigated. From the XRD and TEM results, the ZnO-NPs with a hexagonal wurtzite structure and a particle crystal size of ~10–61 nm was formed at different reaction times. Combing XRD, TEM, and PL results, it was revealed that the sample prepared at intermediate duration (24 h) has the most favorable nanosized structure with the lowest defect concentration. The biomedical properties of ZnO-NPs as free radical scavenging activity, cytotoxicity and antibacterial agents were characterized. Biosynthesized ZnO-NPs showed strong DPPH free radical scavenging and a dose dependent toxicity with non-toxic effects on Vero cells for concentrations below 190 µg/mL. Desirable bactericidal activity was shown by the ZnO-NPs on Gram-positive bacteria (Bacillus subtilis, Staphylococcus epidermidis and Staphylococcus aurous) and Gram-negative bacteria (Escherichia coli and Serratia marcescens). A maximum inhibition zone of ~19 mm was observed for Staphylococcus epidermidis at a concentration of 100 µg/mL for sample prepared at 24 h. The results from this study reveal that ZnO-NPs possesses potential for many medical and industrial applications. Full article
(This article belongs to the Section Green Chemistry)
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Open AccessArticle Impact of Maturity of Malay Cherry (Lepisanthes alata) Leaves on the Inhibitory Activity of Starch Hydrolases
Molecules 2017, 22(6), 873; doi:10.3390/molecules22060873
Received: 24 April 2017 / Revised: 20 May 2017 / Accepted: 23 May 2017 / Published: 24 May 2017
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Abstract
Aqueous extracts of young (7-day-old) Malay cherry (Lepisanthes alata) leaves were incorporated into wheat and rice flours to evaluate their inhibitory activities against α-amylase and α-glucosidase. HPLC-ESI/MS2 results showed that the active components in young leaves were proanthocyanidins with lower
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Aqueous extracts of young (7-day-old) Malay cherry (Lepisanthes alata) leaves were incorporated into wheat and rice flours to evaluate their inhibitory activities against α-amylase and α-glucosidase. HPLC-ESI/MS2 results showed that the active components in young leaves were proanthocyanidins with lower mean degrees of polymerisation (≤10). The IC50 of the aqueous extracts of young leaves were 2.50 ± 0.03 and 12.91 ± 0.29 µg/mL, against α-amylase and α-glucosidase, which make them less active compared to the mature leaves. In contrast, total proanthocyanidins in aqueous extracts decreased as the leaves matured, indicating that the compounds in the mature leaves have much higher activity. However, there was no significant difference in the digestibility of wheat noodles incorporated with the aqueous extracts from either young or mature leaves. Interestingly, with regard to rice noodles, their digestibility was mostly reduced by incorporating aqueous extracts of young leaves compared to using mature leaves. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Isolation of Monoterpene Dihydrochalcones from Piper montealegreanum Yuncker (Piperaceae)
Molecules 2017, 22(6), 874; doi:10.3390/molecules22060874
Received: 5 April 2017 / Revised: 18 May 2017 / Accepted: 23 May 2017 / Published: 9 June 2017
Cited by 1 | PDF Full-text (1253 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four new compounds were isolated from the branches of Piper montealegreanum Yuncker, a shrub found in the Amazon rainforest, including two new dihydrochalcones named claricine (1) and maisine (2), a cinnamic acid derivative 3 and a phenylalkanoid 4,
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Four new compounds were isolated from the branches of Piper montealegreanum Yuncker, a shrub found in the Amazon rainforest, including two new dihydrochalcones named claricine (1) and maisine (2), a cinnamic acid derivative 3 and a phenylalkanoid 4, along with a porphyrin identified as the known compound phaeophytin a (5). The structures were established using spectroscopic experiments, including 1D and 2D NMR and HRESIMS experiments, performed on the two monoterpene dihydrochalcones and their monoacetyl derivatives. The structural diversity of these substances is very important for the Piper genus chemotaxonomy. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Structure Modification of an Active Azo-Compound as a Route to New Antimicrobial Compounds
Molecules 2017, 22(6), 875; doi:10.3390/molecules22060875
Received: 4 May 2017 / Revised: 19 May 2017 / Accepted: 22 May 2017 / Published: 25 May 2017
Cited by 1 | PDF Full-text (1209 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Some novel (phenyl-diazenyl)phenols 3ag were designed and synthesized to be evaluated for their antimicrobial activity. A previously synthesized molecule, active against bacteria and fungi, was used as lead for modifications and optimization of the structure, by introduction/removal or displacement of hydroxyl
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Some novel (phenyl-diazenyl)phenols 3ag were designed and synthesized to be evaluated for their antimicrobial activity. A previously synthesized molecule, active against bacteria and fungi, was used as lead for modifications and optimization of the structure, by introduction/removal or displacement of hydroxyl groups on the azobenzene rings. The aim of this work was to evaluate the consequent changes of the antimicrobial activity and to validate the hypothesis that, for these compounds, a plausible mechanism could involve an interaction with protein receptors, rather than an interaction with membrane. All newly synthesized compounds were analyzed by 1H-NMR, DSC thermal analysis and UV-Vis spectroscopy. The in vitro minimal inhibitory concentrations (MIC) of each compound was determined against Gram-positive and Gram-negative bacteria and Candida albicans. Compounds 3b and 3g showed the highest activity against S. aureus and C. albicans, with remarkable MIC values of 10 µg/mL and 3 µg/mL, respectively. Structure-activity relationship studies were capable to rationalize the effect of different substitutions on the phenyl ring of the azobenzene on antimicrobial activity. Full article
(This article belongs to the Special Issue Antibacterial Materials and Coatings)
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Open AccessArticle Identification of Anthocyanin Composition and Functional Analysis of an Anthocyanin Activator in Solanum nigrum Fruits
Molecules 2017, 22(6), 876; doi:10.3390/molecules22060876
Received: 3 May 2017 / Revised: 22 May 2017 / Accepted: 22 May 2017 / Published: 25 May 2017
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Abstract
Solanum nigrum fruits have been conventionally used in beverages due to their nutritional substances such as minerals, vitamins, amino acids, proteins, sugars, polyphenols, and anthocyanins. The characterization of components and regulatory mechanism of anthocyanins in S. nigrum fruits have rarely been reported. In
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Solanum nigrum fruits have been conventionally used in beverages due to their nutritional substances such as minerals, vitamins, amino acids, proteins, sugars, polyphenols, and anthocyanins. The characterization of components and regulatory mechanism of anthocyanins in S. nigrum fruits have rarely been reported. In this study, we determined that the peel and flesh of S. nigrum fruits shared similar HPLC profiles but different contents and total antioxidant activities for anthocyanins. After an efficient purification method, mainly including extraction with pH 1.0 distilled water and then desorption with pH 1.0 95% ethanol after a DM-130 resin adsorption step to obtain more pure anthocyanin extracts, the purity of anthocyanins extracted from S. nigrum fruits reached 56.1%. Moreover, eight anthocyanins from S. nigrum fruit were identified with HPLC-MS/MS for the first time. A typical R2R3-MYB transcription factor gene, SnMYB, was also cloned for the first time by rapid amplification of cDNA ends (RACE)-PCR from S. nigrum. Moreover, the contents of anthocyanins were shown to correlate well (r = 0.93) with the expression levels of SnMYB gene during the fruit’s developmental stages. Most significantly, SnMYB gene successfully produced high anthocyanin content (1.03 mg/g) when SnMYB gene was transiently expressed in tobacco leaves. Taken together, S. nigrum fruits are a promising resource for anthocyanin extraction, and SnMYB gene is an activator that positively regulates anthocyanin biosynthesis in S. nigrum. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Design, Synthesis, and Biological Activities of Novel Pyrazole Oxime Compounds Containing a Substituted Pyridyl Moiety
Molecules 2017, 22(6), 878; doi:10.3390/molecules22060878
Received: 16 April 2017 / Revised: 20 May 2017 / Accepted: 23 May 2017 / Published: 25 May 2017
Cited by 1 | PDF Full-text (707 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this paper, in order to find novel biologically active pyrazole oximes, a series of pyrazole oxime compounds bearing a substituted pyridyl unit were prepared. Bioassays showed that some target compounds were found to have good acaricidal activity against Tetranychus cinnabarinus at a
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In this paper, in order to find novel biologically active pyrazole oximes, a series of pyrazole oxime compounds bearing a substituted pyridyl unit were prepared. Bioassays showed that some target compounds were found to have good acaricidal activity against Tetranychus cinnabarinus at a concentration of 500 μg/mL, compound 9q especially displayed potent acaricidal activity against T. cinnabarinus when the concentration was reduced to 100 μg/mL. Interestingly, most target compounds possessed excellent insecticidal activities against Oriental armyworm at 500 μg/mL. Moreover, some compounds were active against Aphis medicaginis and Nilaparvata lugens at 500 μg/mL. Additionally, compounds 9b, 9g, 9l, 9p, 9q, 9r, 9s, 9t, 9u, and 9v displayed significant antiproliferative activities against HepG2 cells with IC50 values of 1.53–17.27 μM, better than that of the control 5-fluorouracil (IC50 = 35.67 μM). Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Floral Scent Chemistry of Luculia yunnanensis (Rubiaceae), a Species Endemic to China with Sweetly Fragrant Flowers
Molecules 2017, 22(6), 879; doi:10.3390/molecules22060879
Received: 27 March 2017 / Revised: 22 May 2017 / Accepted: 23 May 2017 / Published: 25 May 2017
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Abstract
Luculia plants are famed ornamentals with sweetly fragrant flowers. Luculia yunnanensis Hu is an endemic plant from Yunnan Province, China. Headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) was used to identify the volatile organic compounds (VOCs) of the different flower development stages of L.
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Luculia plants are famed ornamentals with sweetly fragrant flowers. Luculia yunnanensis Hu is an endemic plant from Yunnan Province, China. Headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) was used to identify the volatile organic compounds (VOCs) of the different flower development stages of L. yunnanensis for the evaluation of floral volatile polymorphism. The results showed that a total of 40 compounds were identified at four different stages. The main aroma-active compounds were 3-carene, α-cubebene, α-copaene, δ-cadinene, and isoledene. Floral scent emission had the tendency to ascend first and descend in succession, reaching its peak level at the initial-flowering stage. The richest diversity of floral volatiles was detected at the full-flowering stage. Principal component analysis (PCA) indicated that the composition and its relative content of floral scent differed at the whole flower development stage. In comparison with the other two species of Luculia (L. pinceana and L. gratissima), the composition and its relative content of floral scent were also different among the tree species. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Yeast Extract Stimulates Ginsenoside Production in Hairy Root Cultures of American Ginseng Cultivated in Shake Flasks and Nutrient Sprinkle Bioreactors
Molecules 2017, 22(6), 880; doi:10.3390/molecules22060880
Received: 24 March 2017 / Accepted: 23 May 2017 / Published: 26 May 2017
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Abstract
One of the most effective strategies to enhance metabolite biosynthesis and accumulation in biotechnological systems is the use of elicitation processes. This study assesses the influence of different concentrations of yeast extract (YE) on ginsenoside biosynthesis in Panax quinquefolium (American ginseng) hairy roots
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One of the most effective strategies to enhance metabolite biosynthesis and accumulation in biotechnological systems is the use of elicitation processes. This study assesses the influence of different concentrations of yeast extract (YE) on ginsenoside biosynthesis in Panax quinquefolium (American ginseng) hairy roots cultivated in shake flasks and in a nutrient sprinkle bioreactor after 3 and 7 days of elicitation. The saponin content was determined using HPLC. The maximum yield (20 mg g−1 d.w.) of the sum of six examined ginsenosides (Rb1, Rb2, Rc, Rd, Re and Rg1) in hairy roots cultivated in shake flasks was achieved after application of YE at 50 mg L−1 concentration and 3 day exposure time. The ginsenoside level was 1.57 times higher than that attained in control medium. The same conditions of elicitation (3 day time of exposure and 50 mg L−1 of YE) also favourably influenced the biosynthesis of studied saponins in bioreactor cultures. The total ginsenoside content was 32.25 mg g−1 d.w. and was higher than that achieved in control medium and in shake flasks cultures. Obtained results indicated that yeast extract can be used to increase ginsenoside production in hairy root cultures of P. quinquefolium. Full article
(This article belongs to the Special Issue Current Trends in Ginseng Research)
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Open AccessArticle Identification of Non-Electrophilic Nrf2 Activators from Approved Drugs
Molecules 2017, 22(6), 883; doi:10.3390/molecules22060883
Received: 5 May 2017 / Revised: 22 May 2017 / Accepted: 24 May 2017 / Published: 26 May 2017
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Abstract
Oxidative damage can lead to a wide range of diseases. Nrf2 is an important transcription factor that regulates many of the cytoprotective enzymes involved in the oxidative stress response. Therefore, targeting the regulation of Nrf2 activation is one logical and effective strategy to
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Oxidative damage can lead to a wide range of diseases. Nrf2 is an important transcription factor that regulates many of the cytoprotective enzymes involved in the oxidative stress response. Therefore, targeting the regulation of Nrf2 activation is one logical and effective strategy to prevent or lower the risk of oxidative stress-related diseases. Until now, most research has focused on electrophilic indirect Nrf2 activators, but the risk of ‘off-target’ effects may be associated with these activators. To find novel small non-electrophilic modulators of Nrf2, we started from chemical agents derived from a connectivity map (cMap) and identified 22 non-electrophilic potential Nrf2-activating drugs through a drug repositioning tactic. By determining the expression changes of antioxidant genes in MCF7 cells that were treated with the potential Nrf2 activators using quantitative real-time polymerase chain reaction RT-PCR (real-time polymerase chain reaction) (qRT-PCR), astemizole was found to have a greater scale of upregulating antioxidant genes NQO1, HO-1, and GCLM than the positive control d,l-sulforaphane, although the testing concentration was lower than that of the control. Astemizole is a good potential redox regulator and deserves more pharmacodynamic experimentation to test and verify its feasibility for use as an Nrf2 activator. Full article
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Open AccessArticle In Vitro Antioxidant Activity of Idebenone Derivative-Loaded Solid Lipid Nanoparticles
Molecules 2017, 22(6), 887; doi:10.3390/molecules22060887
Received: 1 May 2017 / Revised: 22 May 2017 / Accepted: 23 May 2017 / Published: 27 May 2017
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Abstract
Idebenone (IDE) has been proposed for the treatment of neurodegenerative diseases involving mitochondria dysfunctions. Unfortunately, to date, IDE therapeutic treatments have not been as successful as expected. To improve IDE efficacy, in this work we describe a two-step approach: (1) synthesis of IDE
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Idebenone (IDE) has been proposed for the treatment of neurodegenerative diseases involving mitochondria dysfunctions. Unfortunately, to date, IDE therapeutic treatments have not been as successful as expected. To improve IDE efficacy, in this work we describe a two-step approach: (1) synthesis of IDE ester derivatives by covalent linking IDE to other two antioxidants, trolox (IDETRL) and lipoic acid (IDELIP), to obtain a synergic effect; (2) loading of IDE, IDETRL, or IDELIP into solid lipid nanoparticles (SLN) to improve IDE and its esters’ water solubility while increasing and prolonging their antioxidant activity. IDE and its derivatives loaded SLN showed good physico-chemical and technological properties (spherical shape, mean particle sizes 23–25 nm, single peak in the size distribution, ζ potential values −1.76/−2.89 mV, and good stability at room temperature). In vitro antioxidant activity of these SLN was evaluated in comparison with free drugs by means of oxygen radical absorbance capacity (ORAC) test. IDETRL and IDELIP showed a greater antioxidant activity than IDE and encapsulation of IDE and its derivatives into SLN was able to prolong their antioxidant activity. These results suggest that loading IDETRL and IDELIP into SLN could be a useful strategy to improve IDE efficacy. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Effect of Selected Mercapto Flavor Compounds on Acrylamide Elimination in a Model System
Molecules 2017, 22(6), 888; doi:10.3390/molecules22060888
Received: 3 May 2017 / Revised: 3 May 2017 / Accepted: 20 May 2017 / Published: 31 May 2017
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Abstract
The effect of four mercapto flavor compounds (1,2-ethanedithiol, 1-butanethiol, 2-methyl-3-furanthiol, and 2-furanmethanethiol) on acrylamide elimination were investigated in model systems. The obtained results showed that mercaptans assayed were effective in elimination arylamide in a model system. Their reactivities for decreasing acrylamide content depended
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The effect of four mercapto flavor compounds (1,2-ethanedithiol, 1-butanethiol, 2-methyl-3-furanthiol, and 2-furanmethanethiol) on acrylamide elimination were investigated in model systems. The obtained results showed that mercaptans assayed were effective in elimination arylamide in a model system. Their reactivities for decreasing acrylamide content depended on mercaptan’s molecular structure and acrylamide disappearance decreased in the following order: 1,2-ethanedithiol > 2-methyl-3-furanthiol > 1-butanethiol > 2-furanmethanethiol. Mercaptans were added to acrylamide to produce the corresponding 3-(alkylthio) propionamides. This reaction was irreversible and only trace amounts of acrylamide were formed by thermal heating of 3-(alkylthio) propanamide. Although a large amount disappeared, only part of the acrylamide conversed into 3-(alkylthio) propionamides. All of these results constitute a fundamental proof of the complexity of the reactions involved in the removal of free acrylamide in foods. This implies mercapto flavor/aroma may directly or indirectly reduce the level of acrylamide in food processing. This study could be regarded as a pioneer contribution on acrylamide elimination in a model system by the addition of mercapto flavor compounds. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
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Open AccessArticle Comprehensive Characterization for Ginsenosides Biosynthesis in Ginseng Root by Integration Analysis of Chemical and Transcriptome
Molecules 2017, 22(6), 889; doi:10.3390/molecules22060889
Received: 9 April 2017 / Revised: 9 May 2017 / Accepted: 23 May 2017 / Published: 31 May 2017
Cited by 2 | PDF Full-text (1718 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Herbgenomics provides a global platform to explore the genetics and biology of herbs on the genome level. Panax ginseng C.A. Meyer is an important medicinal plant with numerous pharmaceutical effects. Previous reports mainly discussed the transcriptome of ginseng at the organ level. However,
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Herbgenomics provides a global platform to explore the genetics and biology of herbs on the genome level. Panax ginseng C.A. Meyer is an important medicinal plant with numerous pharmaceutical effects. Previous reports mainly discussed the transcriptome of ginseng at the organ level. However, based on mass spectrometry imaging analyses, the ginsenosides varied among different tissues. In this work, ginseng root was separated into three tissues—periderm, cortex and stele—each for five duplicates. The chemical analysis and transcriptome analysis were conducted simultaneously. Gene-encoding enzymes involved in ginsenosides biosynthesis and modification were studied based on gene and molecule data. Eight widely-used ginsenosides were distributed unevenly in ginseng roots. A total of 182,881 unigenes were assembled with an N50 contig size of 1374 bp. About 21,000 of these unigenes were positively correlated with the content of ginsenosides. Additionally, we identified 192 transcripts encoding enzymes involved in two triterpenoid biosynthesis pathways and 290 transcripts encoding UDP-glycosyltransferases (UGTs). Of these UGTs, 195 UGTs (67.2%) were more highly expressed in the periderm, and that seven UGTs and one UGT were specifically expressed in the periderm and stele, respectively. This genetic resource will help to improve the interpretation on complex mechanisms of ginsenosides biosynthesis, accumulation, and transportation. Full article
(This article belongs to the Special Issue Isoprenoid Biosynthesis)
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Open AccessArticle Structural Characterization of Lignin in Fruits and Stalks of Chinese Quince
Molecules 2017, 22(6), 890; doi:10.3390/molecules22060890
Received: 17 March 2017 / Revised: 23 May 2017 / Accepted: 23 May 2017 / Published: 27 May 2017
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Abstract
Chinese quince (Chaenomeles sinensis) is used in food and pharmaceutical products, but it is seldom eaten as a raw fruit due to its astringent, woody flesh. The structural characterization of lignin fractions from Chinese quince was very important to investigate the
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Chinese quince (Chaenomeles sinensis) is used in food and pharmaceutical products, but it is seldom eaten as a raw fruit due to its astringent, woody flesh. The structural characterization of lignin fractions from Chinese quince was very important to investigate the structure-activity relationships of lignin. In this investigation, to characterize the structure of lignin in Chinese quince fruits, the milled wood lignin sample was isolated from the fruits (FMWL) and the chemical structure of FMWL was investigated by sugar analysis, FT-IR, GPC, pyrolysis-GC/MS analysis, UV spectra analysis, thermogravimetric analysis (TGA), and advanced NMR spectroscopic techniques. In addition, the lignin fraction from the stalk of Chinese quince (SMWL) was also prepared for comparison to obtained more information of lignin structure in the fruits. The results showed that the two lignin fractions isolated from fruit and stalk of Chinese quince exhibited different structural features. The two MWL samples were mainly composed of β-O-4 ether bonds, β-5 and β-β′ carbon-carbon linkages in the lignin structural units. Compared to the SMWL, the FMWL fraction had the higher S/G ratio and more carbohydrates linkages. The predominant carbohydrates associated with FMWL and SMWL fractions were glucans-type hemicelluloses and xylan-type hemicelluloses, respectively. Understanding the structure of lignin could give insight into the properties of the lignin and enable the food processing industry to separate lignin more efficiently. Full article
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Open AccessFeature PaperArticle Identification of Novel Vacuolin-1 Analogues as Autophagy Inhibitors by Virtual Drug Screening and Chemical Synthesis
Molecules 2017, 22(6), 891; doi:10.3390/molecules22060891
Received: 26 April 2017 / Revised: 25 May 2017 / Accepted: 25 May 2017 / Published: 27 May 2017
PDF Full-text (3806 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Autophagy is a fundamental cellular degradation process which is essential for cell homeostasis, and dysfunctional autophagy has been associated with a variety of human diseases, such as cancer. Several autophagy chemical modulators have been applied in a number of preclinical or clinical trials
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Autophagy is a fundamental cellular degradation process which is essential for cell homeostasis, and dysfunctional autophagy has been associated with a variety of human diseases, such as cancer. Several autophagy chemical modulators have been applied in a number of preclinical or clinical trials against these autophagy related diseases, especially cancer. Small molecule vacuolin-1 potently and reversibly inhibits both endosomal-lysosomal trafficking and autophagosome-lysosome fusion, yet the molecular mechanisms underlying vacuolin-1 mediated autophagy inhibition remain unknown. Here, we first performed the virtual drug screening and identified 14 vacuolin-1 analogues as autophagy inhibitors. Based on these virtual screening results, we further designed and synthesized 17 vacuolin-1 analogues, and found that 13 of them are autophagy inhibitors and a couple of them are as potent as vacuolin-1. In summary, these studies expanded the pool of useful autophagy inhibitors and reveal the structural-activity relationship of vacuolin-1 analogues, which is useful for future development of vacuolin-1 analogues with high potency and for identification of the molecular targets of vacuolin-1. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle The Cytotoxicity of the Ajoene Analogue BisPMB in WHCO1 Oesophageal Cancer Cells Is Mediated by CHOP/GADD153
Molecules 2017, 22(6), 892; doi:10.3390/molecules22060892
Received: 21 March 2017 / Revised: 23 May 2017 / Accepted: 24 May 2017 / Published: 28 May 2017
PDF Full-text (2743 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Garlic is a food and medicinal plant that has been used in folk medicine since ancient times for its beneficial health effects, which include protection against cancer. Crushed garlic cloves contain an array of small sulfur-rich compounds such as ajoene. Ajoene is able
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Garlic is a food and medicinal plant that has been used in folk medicine since ancient times for its beneficial health effects, which include protection against cancer. Crushed garlic cloves contain an array of small sulfur-rich compounds such as ajoene. Ajoene is able to interfere with biological processes and is cytotoxic to cancer cells in the low micromolar range. BisPMB is a synthetic ajoene analogue that has been shown in our laboratory to have superior cytotoxicity to ajoene. In the current study we have performed a DNA microarray analysis of bisPMB-treated WHCO1 oesophageal cancer cells to identify pathways and processes that are affected by bisPMB. The most significantly enriched biological pathways as assessed by gene ontology, KEGG and ingenuity pathway analysis were those involving protein processing in the endoplasmic reticulum (ER) and the unfolded protein response. In support of these pathways, bisPMB was found to inhibit global protein synthesis and lead to increased levels of ubiquitinated proteins. BisPMB also induced alternate splicing of the transcription factor XBP-1; increased the expression of the ER stress sensor GRP78 and induced expression of the ER stress marker CHOP/GADD153. CHOP expression was found to be central to the cytotoxicity of bisPMB as its silencing with siRNA rendered the cells resistant to bisPMB. The MAPK proteins, JNK and ERK1/2 were activated following bisPMB treatment. However JNK activation was not critical in the cytotoxicity of bisPMB, and ERK1/2 activation was found to play a pro-survival role. Overall the ajoene analogue bisPMB appears to induce cytotoxicity in WHCO1 cells by activating the unfolded protein response through CHOP/GADD153. Full article
(This article belongs to the Special Issue The Chemistry of Alliums)
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Open AccessCommunication Synthesis and Free Radical Scavenging Activity of New Hydroxybenzylidene Hydrazines
Molecules 2017, 22(6), 894; doi:10.3390/molecules22060894
Received: 7 April 2017 / Revised: 25 May 2017 / Accepted: 26 May 2017 / Published: 29 May 2017
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Abstract
Hydroxybenzylidene hydrazines exhibit a wide spectrum of biological activities. Here, we report synthesis and free radical scavenging activity of nine new N-(hydroxybenzylidene)-N′-[2,6-dinitro-4-(trifluoromethyl)]phenylhydrazines. The chemical structures of these compounds were confirmed by 1H-NMR, 13C-NMR, 19F-NMR, IR spectroscopy, LC-MS, and elemental analysis. The prepared compounds
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Hydroxybenzylidene hydrazines exhibit a wide spectrum of biological activities. Here, we report synthesis and free radical scavenging activity of nine new N-(hydroxybenzylidene)-N′-[2,6-dinitro-4-(trifluoromethyl)]phenylhydrazines. The chemical structures of these compounds were confirmed by 1H-NMR, 13C-NMR, 19F-NMR, IR spectroscopy, LC-MS, and elemental analysis. The prepared compounds were tested for their activity to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), galvinoxyl radical (GOR), and 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulphonic acid (ABTS) radicals. The free radical scavenging activity expressed as SC50 values of these compounds varied in a wide range, from a strong to no radical scavenging effect. The most effective radical scavengers were hydroxybenzylidene hydrazines containing three hydroxyl groups in the benzylidene part of their molecules. The prepared compounds were also tested for their activity to inhibit photosynthetic electron transport in spinach chloroplasts. IC50 values of these compounds varied in wide range, from an intermediate to no inhibitory effect.
Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Genealogy of Conjugated Acyclic Polyenes
Molecules 2017, 22(6), 896; doi:10.3390/molecules22060896
Received: 30 April 2017 / Revised: 24 May 2017 / Accepted: 24 May 2017 / Published: 29 May 2017
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Abstract
Based on the total π-electron energies Eπs of Hückel Molecular Orbital (HMO) method for all the possible isomers of conjugated acyclic polyenes (C2nH2n+2) up to n = 7, the structure–stability relation of the possible
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Based on the total π-electron energies Eπs of Hückel Molecular Orbital (HMO) method for all the possible isomers of conjugated acyclic polyenes (C2nH2n+2) up to n = 7, the structure–stability relation of the possible isomers was analyzed. It was shown that the mean length of conjugation L can roughly predict the ordering of stability among isomers, while the Z-index, or Hosoya-index, can almost perfectly reproduce their stability. Further, the genealogy of the conjugated acyclic polyene family was obtained by drawing systematic diagrams connecting these isomers of different n, and governed by several simple rules. Namely, the stability change of a given isomer in the genealogy connecting n and n + 1 polyenes can be classified into three different modes of vinyl addition (elongation, inner and outer branching) and horn growing, i.e., substitution of –HC=CH– moiety with –HC(=CH2)–C(=CH2)H–. By using the Z-index, we can extend this type of discussion to polyene radicals and even to “cross-conjugated” cyclic polyenes containing only one odd-membered cycle, such as radialene and fulvene. Full article
(This article belongs to the Special Issue Cutting-Edge Organic Chemistry in Japan)
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Open AccessArticle Synthesis of Gallic Acid Analogs as Histamine and Pro-Inflammatory Cytokine Inhibitors for Treatment of Mast Cell-Mediated Allergic Inflammation
Molecules 2017, 22(6), 898; doi:10.3390/molecules22060898
Received: 18 April 2017 / Revised: 25 May 2017 / Accepted: 26 May 2017 / Published: 29 May 2017
PDF Full-text (1654 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Gallic acid (3,4,5-trihydroxybenzoic acid), is a natural product found in various foods and herbs that are well known as powerful antioxidants. Our previous report demonstrated that it inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression. In this
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Gallic acid (3,4,5-trihydroxybenzoic acid), is a natural product found in various foods and herbs that are well known as powerful antioxidants. Our previous report demonstrated that it inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression. In this report, various amide analogs of gallic acid have been synthesized by introducing different amines through carbodiimide-mediated amide coupling and Pd/C-catalyzed hydrogenation. These compounds showed a modest to high inhibitory effect on histamine release and pro-inflammatory cytokine expression. Among them, the amide bearing (S)-phenylglycine methyl ester 3d was found to be more active than natural gallic acid. Further optimization yielded several (S)- and (R)-phenylglycine analogs that inhibited histamine release in vitro. Our findings suggest that some gallamides could be used as a treatment for allergic inflammatory diseases. Full article
(This article belongs to the Special Issue Anti-inflammatory Agents)
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Open AccessArticle Influence of Freeze Concentration Technique on Aromatic and Phenolic Compounds, Color Attributes, and Sensory Properties of Cabernet Sauvignon Wine
Molecules 2017, 22(6), 899; doi:10.3390/molecules22060899
Received: 12 April 2017 / Accepted: 26 May 2017 / Published: 2 June 2017
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Abstract
Red wines produced in the Xinjiang region of China possess poor color density, and lack fruity notes and elegance. The freeze concentration technique, as a well-established concentration method for liquid food systems, was applied to the Cabernet Sauvignon (Vitis vinifera L.) wine-making
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Red wines produced in the Xinjiang region of China possess poor color density, and lack fruity notes and elegance. The freeze concentration technique, as a well-established concentration method for liquid food systems, was applied to the Cabernet Sauvignon (Vitis vinifera L.) wine-making process, aiming to investigate its effect on wine quality improvement. Results showed that the freeze concentration treatment did not significantly alter the physicochemical properties of the wine, except for an increase of glycerol and alcoholic content. This technique increased ester contents, as well as decreasing the amount of volatile acids. Higher alcohol contents were also increased, but within an acceptable content range. All taken into consideration, the freeze concentration treated wine showed better fragrance characters according to sensory evaluation. The non-anthocyanin composition was altered by this application, however, the difference disappeared after the aging process. Fortunately, sensory evaluation showed that the treated wine possessed better mouthfeel properties. Anthocyanin contents were enhanced, and effectively stabilized the fresh wine color attributes, resulting in an improvement in appearance of the treated wine. All results considered, it can be concluded that freeze concentration treatment could be a good choice to improve wine quality. Full article
(This article belongs to the collection Wine Chemistry)
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Open AccessArticle Antinociceptive Effect of the Essential Oil from Croton conduplicatus Kunth (Euphorbiaceae)
Molecules 2017, 22(6), 900; doi:10.3390/molecules22060900
Received: 18 April 2017 / Revised: 24 May 2017 / Accepted: 26 May 2017 / Published: 30 May 2017
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Abstract
Medicinal plants have been widely used in the treatment of chronic pain. In this study, we describe the antinociceptive effect of the essential oil from Croton conduplicatus (the EO 25, 50, and 100 mg/kg, i.p.), a medicinal plant native to Brazil. Antinociceptive activity
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Medicinal plants have been widely used in the treatment of chronic pain. In this study, we describe the antinociceptive effect of the essential oil from Croton conduplicatus (the EO 25, 50, and 100 mg/kg, i.p.), a medicinal plant native to Brazil. Antinociceptive activity was investigated by measuring the nociception induced by acetic acid, formalin, hot plate and carrageenan. A docking study was performed with the major constituents of the EO (E-caryophyllene, caryophyllene oxide, and camphor). The EO reduced nociceptive behavior at all doses tested in the acetic acid-induced nociception test (p < 0.05). The same was observed in both phases (neurogenic and inflammatory) of the formalin test. When the hot-plate test was conducted, the EO (50 mg/kg) extended the latency time after 60 min of treatment. The EO also reduced leukocyte migration at all doses, suggesting that its antinociceptive effect involves both central and peripheral mechanisms. Pretreatment with glibenclamide and atropine reversed the antinociceptive effect of the EO on the formalin test, suggesting the involvement of KATP channels and muscarinic receptors. The docking study revealed a satisfactory interaction profile between the major components of the EO and the different muscarinic receptor subtypes (M2, M3, and M4). These results corroborate the medicinal use of C. conduplicatus in folk medicine. Full article
(This article belongs to the Special Issue Essential Oils: Chemistry and Bioactivity)
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Open AccessArticle Expression of Genes Related to Phenylpropanoid Biosynthesis in Different Organs of Ixeris dentata var. albiflora
Molecules 2017, 22(6), 901; doi:10.3390/molecules22060901
Received: 28 February 2017 / Revised: 26 May 2017 / Accepted: 26 May 2017 / Published: 30 May 2017
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Abstract
Members of the genus Ixeris have long been used in traditional medicines as stomachics, sedatives, and diuretics. Phenylalanine ammonia-lyase (PAL), cinnamate-4-hydroxylase (C4H), 4-coumarate: coenzyme-A (CoA) ligase (4CL), chalcone synthase (CHS), and dihydroflavonol 4-reductase (DFR) are important enzymes in the phenylpropanoid pathway. In this
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Members of the genus Ixeris have long been used in traditional medicines as stomachics, sedatives, and diuretics. Phenylalanine ammonia-lyase (PAL), cinnamate-4-hydroxylase (C4H), 4-coumarate: coenzyme-A (CoA) ligase (4CL), chalcone synthase (CHS), and dihydroflavonol 4-reductase (DFR) are important enzymes in the phenylpropanoid pathway. In this study, we analyzed seven genes from Ixeris dentata var. albiflora that are involved in phenylpropanoid biosynthesis, using an Illumina/Solexa HiSeq 2000 platform. The amino acid sequence alignments for IdPALs, IdC4H, Id4CLs, IdCHS, and IdDFR showed high identity to sequences from other plants. We also investigated transcript levels using quantitative real-time PCR, and analyzed the accumulation of phenylpropanoids in different organs of I. dentata var. albiflora using high-performance liquid chromatography. The transcript levels of IdC4H, Id4CL1, IdCHS, and IdDFR were highest in the leaf. The catechin, chlorogenic acid, ferulic acid, and quercetin contents were also highest in the leaf. We suggest that expression of IdC4H, Id4CL1, IdCHS, and IdDFR is associated with the accumulation of phenylpropanoids. Our results may provide baseline information for elucidating the mechanism of phenylpropanoid biosynthesis in different organs of I. dentata var. albiflora. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Characterization of Metabolite Profile in Phyllanthus niruri and Correlation with Bioactivity Elucidated by Nuclear Magnetic Resonance Based Metabolomics
Molecules 2017, 22(6), 902; doi:10.3390/molecules22060902
Received: 13 April 2017 / Revised: 23 May 2017 / Accepted: 25 May 2017 / Published: 30 May 2017
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Abstract
Phyllanthus niruri is an important medicinal plant. To standardize the extract and guarantee its maximum benefit, processing methods optimization ought to be amenable and beneficial. Herein, three dried P. niruri samples, air (AD), freeze (FD) and oven (OD), extracted with various ethanol to
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Phyllanthus niruri is an important medicinal plant. To standardize the extract and guarantee its maximum benefit, processing methods optimization ought to be amenable and beneficial. Herein, three dried P. niruri samples, air (AD), freeze (FD) and oven (OD), extracted with various ethanol to water ratios (0%, 50%, 70%, 80% and 100%) were evaluated for their metabolite changes using proton nuclear magnetic resonance (1H-NMR)-based metabolomics approach. The amino acids analysis showed that FD P. niruri exhibited higher content of most amino acids compared to the other dried samples. Based on principal component analysis (PCA), the FD P. niruri extracted with 80% ethanol contained higher amounts of hypophyllanthin and phenolic compounds based on the loading plot. The partial least-square (PLS) results showed that the phytochemicals, including hypophyllanthin, catechin, epicatechin, rutin, quercetin and chlorogenic, caffeic, malic and gallic acids were correlated with antioxidant and α-glucosidase inhibitory activities, which were higher in the FD material extracted with 80% ethanol. This report optimized the effect of drying and ethanol ratios and these findings demonstrate that NMR-based metabolomics was an applicable approach. The FD P. niruri extracted with 80% ethanol can be used as afunctional food ingredient for nutraceutical or in medicinal preparation. Full article
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Open AccessArticle Combined Treatment with Hyaluronic Acid and Mesalamine Protects Rats from Inflammatory Bowel Disease Induced by Intracolonic Administration of Trinitrobenzenesulfonic Acid
Molecules 2017, 22(6), 904; doi:10.3390/molecules22060904
Received: 21 April 2017 / Revised: 26 May 2017 / Accepted: 28 May 2017 / Published: 30 May 2017
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Abstract
Drugs such as mesalamine (5-ASA) are currently recommended for the treatment of inflammatory bowel disease (IBD). To reduce the frequency of their administration and improve their therapeutic effect, this study investigated the adhesion efficacy, wound healing promotion, and decrease in inflammation in ulcers
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Drugs such as mesalamine (5-ASA) are currently recommended for the treatment of inflammatory bowel disease (IBD). To reduce the frequency of their administration and improve their therapeutic effect, this study investigated the adhesion efficacy, wound healing promotion, and decrease in inflammation in ulcers in the colonic tissue of rats with colitis after combined treatment with hyaluronic acid (HA) and 5-ASA (IBD98-M). HA-fluoresceinamine (FL) conjugates successfully adhered to the mucosal layer and were conjugated in the vascular tissue. In addition, macroscopic and microscopic observations indicated that colonic injuries reduced significantly after treatment with IBD98-M. Compared with PBS and 5-ASA treatment alone, treatment with IBD98-M more effectively reduced bowel inflammation and promoted colonic mucosal healing in TNBS-induced colitis. IBD98-M treatment also reduced myeloperoxidase activity and the expression levels of cyclooxygenase 2 and tumor necrosis factor-αin the colitis tissue. In conclusion, IBD98-M treatment strongly promoted wound healing in colonic injuries and significantly inhibited MPO activity in the inflamed colon tissue of rats. Combined treatment with HA and 5-ASA can accelerate wound healing and reduce inflammatory reaction in rat colitis. Full article
(This article belongs to the Special Issue Anti-inflammatory Agents)
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Open AccessArticle Effect of Montmorillonite Nanogel Composite Fillers on the Protection Performance of Epoxy Coatings on Steel Pipelines
Molecules 2017, 22(6), 905; doi:10.3390/molecules22060905
Received: 20 April 2017 / Revised: 20 April 2017 / Accepted: 28 May 2017 / Published: 2 June 2017
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Abstract
Montmorillonite (MMT) clay mineral is widely used as filler for several organic coatings. Its activity is increased by exfoliation via chemical modification to produce nanomaterials. In the present work, the modification of MMT to form nanogel composites is proposed to increase the dispersion
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Montmorillonite (MMT) clay mineral is widely used as filler for several organic coatings. Its activity is increased by exfoliation via chemical modification to produce nanomaterials. In the present work, the modification of MMT to form nanogel composites is proposed to increase the dispersion of MMT into epoxy matrices used to fill cracks and holes produced by the curing exotherms of epoxy resins. The dispersion of MMT in epoxy improved both the mechanical and anti-corrosion performance of epoxy coatings in aggressive marine environments. In this respect, the MMT surfaces were chemically modified with different types of 2-acrylamido-2-methyl propane sulfonic acid (AMPS) nanogels using a surfactant-free dispersion polymerization technique. The effect of the chemical structure, nanogel content and the interaction with MMT surfaces on the surface morphology, surface charges and dispersion in the epoxy matrix were investigated for use as nano-filler for epoxy coatings. The modified MMT nanogel epoxy composites showed excellent resistance to mechanical damage and salt spray resistance up to 1000 h. The interaction of MMT nanogel composites with the epoxy matrix and good response of AMPS nanogel to sea water improve their ability to act as self-healing materials for epoxy coatings for steel. Full article
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Open AccessArticle Alternative Access to Functionalized 2,8-Ethanonoradamantane Derivatives
Molecules 2017, 22(6), 906; doi:10.3390/molecules22060906
Received: 13 May 2017 / Revised: 24 May 2017 / Accepted: 25 May 2017 / Published: 31 May 2017
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Abstract
7a-(Methoxycarbonyl)-N-methyl-1,3a,5,6,7,7a-hexahydro-4H-1,4,6-(epiethane[1,1,2]triyl)indene-4,9-dicarboximide has been prepared through a modification of a previous synthetic sequence, in which the benzyloxymethyl hydroxyl protecting group has been replaced by methoxymethyl, to avoid the apparent formation of a benzyl ester derivative as a side product. The
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7a-(Methoxycarbonyl)-N-methyl-1,3a,5,6,7,7a-hexahydro-4H-1,4,6-(epiethane[1,1,2]triyl)indene-4,9-dicarboximide has been prepared through a modification of a previous synthetic sequence, in which the benzyloxymethyl hydroxyl protecting group has been replaced by methoxymethyl, to avoid the apparent formation of a benzyl ester derivative as a side product. The overall yield of the new synthetic sequence is comparable to the previous one. Two advantages of the new procedure are: (a) no benzyl ester was formed and (b) a stereoisomeric mixture of syn- and anti-alcohols at the beginning of the synthetic sequence could be separated and the rest of the synthesis could be carried out with the main syn-stereoisomer instead of the corresponding stereoisomeric mixture as it was the case in the previous process. Additionally, several functional 2,8-ethanonoradamantane derivatives have been prepared. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Five New Limonoids from Peels of Satsuma Orange (Citrus reticulata)
Molecules 2017, 22(6), 907; doi:10.3390/molecules22060907
Received: 21 April 2017 / Accepted: 26 May 2017 / Published: 31 May 2017
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Abstract
Five new: 21,23-dihydro-21-hydroxy-23-oxonomilin (1), 21,23-dihydro-23-methoxy-21-oxonomilin (2), 21,23-dihydro-21-hydroxy-23-oxonomilinic acid methyl ester (3), 21,23-dihydro-23-methoxy-21-oxolimonin (4), and 21,23-dihydro-21-oxolimonin (5), and seven known limonoids were isolated from peels of satsuma orange (Citrus reticulata). The isolated
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Five new: 21,23-dihydro-21-hydroxy-23-oxonomilin (1), 21,23-dihydro-23-methoxy-21-oxonomilin (2), 21,23-dihydro-21-hydroxy-23-oxonomilinic acid methyl ester (3), 21,23-dihydro-23-methoxy-21-oxolimonin (4), and 21,23-dihydro-21-oxolimonin (5), and seven known limonoids were isolated from peels of satsuma orange (Citrus reticulata). The isolated compounds were evaluated for their inhibitory effects on macrophage activation by an inhibitory assay of nitric oxide (NO) production. Among them, compound (2) exhibited NO inhibitory activity without cytotoxicity. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis, Characterization and Protonation Behavior of Quinoxaline-Fused Porphycenes
Molecules 2017, 22(6), 908; doi:10.3390/molecules22060908
Received: 13 April 2017 / Revised: 15 May 2017 / Accepted: 24 May 2017 / Published: 31 May 2017
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Abstract
9,10-Quinoxaline-fused porphycenes 1a-H2 and 1b-H2 were synthesized by intramolecular McMurry coupling. As a result of the annulation of the quinoxaline moiety on the porphycene skeleton, 1a-H2 and 1b-H2 display absorption and fluorescence in the near infra-red (NIR) region. Additionally,
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9,10-Quinoxaline-fused porphycenes 1a-H2 and 1b-H2 were synthesized by intramolecular McMurry coupling. As a result of the annulation of the quinoxaline moiety on the porphycene skeleton, 1a-H2 and 1b-H2 display absorption and fluorescence in the near infra-red (NIR) region. Additionally, the quinoxaline moieties of 1a-H2 and 1b-H2 act as electron-withdrawing groups, introducing lower reduction potentials than for pristine porphycene. The protonation occurred at the nitrogen atoms in the cavity of freebase porphycenes and at the quinoxaline moieties for their nickel complexes to give diprotonic species. Full article
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Open AccessArticle Genotypic Variation in Wheat Flour Lysophospholipids
Molecules 2017, 22(6), 909; doi:10.3390/molecules22060909
Received: 24 February 2017 / Revised: 22 May 2017 / Accepted: 26 May 2017 / Published: 31 May 2017
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Abstract
Lysophospholipids (LPLs) are the most abundant polar lipids in wheat endosperm and naturally complex with amylose, affecting starch physicochemical properties. We analyzed LPLs in wheat flour from 58 cultivars which differ by grain hardness using liquid chromatography mass spectrometry (LCMS). There were significant
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Lysophospholipids (LPLs) are the most abundant polar lipids in wheat endosperm and naturally complex with amylose, affecting starch physicochemical properties. We analyzed LPLs in wheat flour from 58 cultivars which differ by grain hardness using liquid chromatography mass spectrometry (LCMS). There were significant differences in LPL content between cultivars, demonstrating that genotype rather than environment contributes most to the total variance in wheat endosperm LPLs. Polar lipids such as LPLs may play a role in grain hardness through their interaction with puroindoline proteins, however, no strong correlation between kernel hardness and LPLs was detected. This may reflect the location of LPLs within the starch granule as opposed to the puroindoline proteins outside starch granules. LPLs may have an indirect relationship with kernel hardness as they could share the same origin as polar lipids that interact with puroindoline on the starch granule surface. Full article
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Open AccessArticle Himatanthus drasticus Leaves: Chemical Characterization and Evaluation of Their Antimicrobial, Antibiofilm, Antiproliferative Activities
Molecules 2017, 22(6), 910; doi:10.3390/molecules22060910
Received: 22 April 2017 / Revised: 25 May 2017 / Accepted: 27 May 2017 / Published: 31 May 2017
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Abstract
Plant-derived products have played a fundamental role in the development of new therapeutic agents. This study aimed to analyze antimicrobial, antibiofilm, cytotoxicity and antiproliferative potentials of the extract and fractions from leaves of Himatanthus drasticus, a plant from the Apocynaceae family. After
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Plant-derived products have played a fundamental role in the development of new therapeutic agents. This study aimed to analyze antimicrobial, antibiofilm, cytotoxicity and antiproliferative potentials of the extract and fractions from leaves of Himatanthus drasticus, a plant from the Apocynaceae family. After harvesting, H. drasticus leaves were macerated and a hydroalcoholic extract (HDHE) and fractions were prepared. Antimicrobial tests, such as agar-diffusion, Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) were carried out against several bacterial species. Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes and Klebsiella pneumoniae were inhibited by at least one extract or fraction in the agar-diffusion assay (inhibition halos from 12 mm to 30 mm). However, the lowest MIC value was found for HDHE against K. pneumoniae. In addition, HDHE and its fractions were able to inhibit biofilm formation at sub-inhibitory concentrations (780 µg/mL and 1.56 µg/mL). As the best activities were found for HDHE, we selected it for further assays. HDHE was able to increase ciprofloxacin (CIP) activity against K. pneumoniae, displaying synergistic (initial concentration CIP + HDHE: 2 µg/mL + 600 µg/mL and 2.5 µg/mL + 500 µg/mL) and additive effects (CIP + HDHE: 3 µg/mL + 400 µg/mL). This action seems to be associated with the alteration in bacterial membrane permeability induced by HDHE (as seen by propidium iodide labeling). This extract was non-toxic for red blood cell or human peripheral blood mononuclear cells (PBMCs). Additionally, it inhibited the lipopolysaccharide-induced proliferation of PBMCs. The following compounds were detected in HDHE using HPLC-ESI-MS analysis: plumieride, plumericin or isoplumericin, rutin, quercetin and derivatives, and chlorogenic acid. Based on these results we suggest that compounds from H. drasticus have antimicrobial and antibiofilm activities against K. pneumoniae and display low cytotoxicity and anti-proliferative action in PBMC stimulated with lipopolysaccharide. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessArticle Rapid Screening and Identification of Diterpenoids in Tinospora sinensis Based on High-Performance Liquid Chromatography Coupled with Linear Ion Trap-Orbitrap Mass Spectrometry
Molecules 2017, 22(6), 912; doi:10.3390/molecules22060912
Received: 20 February 2017 / Revised: 24 May 2017 / Accepted: 25 May 2017 / Published: 31 May 2017
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Abstract
Diterpenoids are considered the major active compounds in Tinospora sinensis in virtue of their special structures and activities. Herein, an analytical method was developed for rapid screening and identification of diterpenoids in T. sinensis using high-performmance liquid chromatography coupled with linear ion trap-Orbitrap
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Diterpenoids are considered the major active compounds in Tinospora sinensis in virtue of their special structures and activities. Herein, an analytical method was developed for rapid screening and identification of diterpenoids in T. sinensis using high-performmance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (HPLC-LTQ-Orbitrap) in negative ion mode. Two diterpenoid reference standards were first analyzed to obtain their characteristic ESI-MS/MS fragmentation patterns. Then, based on the extracted ion chromatogram (EIC) data-mining method and characteristic fragmentation pathways analysis, diterpenoids in T. sinensis were rapidly screened and identified. After that, an important parameter, Clog P, was adopted to discriminate between the isomers of diterpenoids. As a result, 63 diterpenoids were characterized from the extract of T. sinensis, including 10 diterpenoids and 53 diterpenoid glycosides. Among them, 15 compounds were tentatively identified as new compounds. Finally, target isolation of one diterpenoid glycoside named tinosineside A was performed based on the obtained results, which further confirmed the deduced fragmentation patterns and identified diterpenoid profile in T. sinensis. The results demonstrated that the established method could be a rapid, effective analytical tool for screening and characterization of diterpenoids in the complex systems of natural medicines. Full article
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Open AccessArticle Synthesis and Evaluation of Novel 2-Pyrrolidone-Fused (2-Oxoindolin-3-ylidene)methylpyrrole Derivatives as Potential Multi-Target Tyrosine Kinase Receptor Inhibitors
Molecules 2017, 22(6), 913; doi:10.3390/molecules22060913
Received: 29 March 2017 / Revised: 21 May 2017 / Accepted: 29 May 2017 / Published: 31 May 2017
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Abstract
Signaling pathways of VEGFs and PDGFs are crucial in tumor angiogenesis, which is essential in solid tumor progression and metastasis. This study reports our strategy for designing and synthesizing a series of novel 2-pyrrolidone-fused (2-oxoindolin-3-ylidene)methylpyrrole derivatives as potential multi-target tyrosine kinase receptor inhibitors.
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Signaling pathways of VEGFs and PDGFs are crucial in tumor angiogenesis, which is essential in solid tumor progression and metastasis. This study reports our strategy for designing and synthesizing a series of novel 2-pyrrolidone-fused (2-oxoindolin-3-ylidene)methylpyrrole derivatives as potential multi-target tyrosine kinase receptor inhibitors. The target compounds were obtained by condensation of 5-substituted oxindoles with N-substituted 2-pyrrolidone aldehyde 7 in satisfactory yields. Of these, 11 and 12 had the highest potency and, compared to sunitinib, showed: (1) significant increase in anti-proliferation of various cancer cells with a favorable selective index (SI); (2) higher inhibitory potency against both VEGFR-2 and PDGFRβ. The molecular modeling results showed that, in terms of VEGFR-2 binding, the synthesized products had a similar binding mode to sunitinib but with tighter interaction. Full article
(This article belongs to the Special Issue Kinase Inhibitors)
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Open AccessArticle Some Physical Properties of Protein Moiety of Alkali-Extracted Tea Polysaccharide Conjugates Were Shielded by Its Polysaccharide
Molecules 2017, 22(6), 914; doi:10.3390/molecules22060914
Received: 25 February 2017 / Revised: 8 May 2017 / Accepted: 10 May 2017 / Published: 31 May 2017
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Abstract
Polysaccharide conjugates were alkali-extracted from green tea (TPC-A). Although it contained 11.80% covalently binding proteins, TPC-A could not bind to the Coomassie Brilliant Blue dyes G250 and R250. TPC-A had no expected characteristic absorption peak of protein in the UV-vis spectrum scanning in
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Polysaccharide conjugates were alkali-extracted from green tea (TPC-A). Although it contained 11.80% covalently binding proteins, TPC-A could not bind to the Coomassie Brilliant Blue dyes G250 and R250. TPC-A had no expected characteristic absorption peak of protein in the UV-vis spectrum scanning in the range of 200–700 nm. The UV-vis wavelength of 280 nm was not suitable to detect the presence of the protein portion of TPC-A. The zeta potential of TPC-A merely presented the negative charge properties of polysaccharides instead of the acid–base property of its protein section across the entire pH range. Furthermore, TPC-A was more stable when the pH of solution exceeded 4.0. In addition, no precipitation or haze was generated in the TPC-A/(−)-epigallocatechin gallate (EGCG) mixtures during 12 h storage. TPC-A has emulsifying activity, which indicated that its protein moiety formed hydrophobic groups. Thus, it was proposed that some physical properties of TPC-A protein were shielded by its olysaccharide, since the protein moiety was wrapped by its polysaccharide chains. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle UHPLC-TQ-MS Coupled with Multivariate Statistical Analysis to Characterize Nucleosides, Nucleobases and Amino Acids in Angelicae Sinensis Radix Obtained by Different Drying Methods
Molecules 2017, 22(6), 918; doi:10.3390/molecules22060918
Received: 19 April 2017 / Revised: 21 May 2017 / Accepted: 30 May 2017 / Published: 1 June 2017
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Abstract
To explore the nutrients in roots of Angelica sinensis (Angelicae Sinensis Radix, ASR), a medicinal and edible plant, and evaluate its nutritional value, a rapid and reliable UHPLC-TQ-MS method was established and used to determine the potential nutritional compounds, including nucleosides, nucleobases and
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To explore the nutrients in roots of Angelica sinensis (Angelicae Sinensis Radix, ASR), a medicinal and edible plant, and evaluate its nutritional value, a rapid and reliable UHPLC-TQ-MS method was established and used to determine the potential nutritional compounds, including nucleosides, nucleobases and amino acids, in 50 batches of ASR samples obtained using two drying methods. The results showed that ASR is a healthy food rich in nucleosides, nucleobases and amino acids, especially arginine. The total average content of nucleosides and nucleobases in all ASR samples was 3.94 mg/g, while that of amino acids reached as high as 61.79 mg/g. Principle component analysis showed that chemical profile differences exist between the two groups of ASR samples prepared using different drying methods, and the contents of nutritional compounds in samples dried with the tempering-intermittent drying processing method (TIDM) were generally higher than those dried using the traditional solar processing method. The above results suggest that ASR should be considered an ideal healthy food and TIDM could be a suitable drying method for ASR when taking nucleosides, nucleobases and amino acids as the major consideration for their known human health benefits. Full article
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Open AccessFeature PaperArticle Stable ABTS Immobilized in the MIL-100(Fe) Metal-Organic Framework as an Efficient Mediator for Laccase-Catalyzed Decolorization
Molecules 2017, 22(6), 920; doi:10.3390/molecules22060920
Received: 4 April 2017 / Revised: 31 May 2017 / Accepted: 31 May 2017 / Published: 2 June 2017
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Abstract
The successful encapsulation of 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), a well-known laccase mediator, within a mesoporous metal-organic framework sample (i.e., MIL-100(Fe)) was achieved using a one-pot hydrothermal synthetic method. The as-prepared ABTS@MIL-100(Fe) was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared
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The successful encapsulation of 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), a well-known laccase mediator, within a mesoporous metal-organic framework sample (i.e., MIL-100(Fe)) was achieved using a one-pot hydrothermal synthetic method. The as-prepared ABTS@MIL-100(Fe) was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, nitrogen sorption, and cyclic voltammetry (CV). Our ABTS@MIL-100(Fe)-based electrode exhibited an excellent electrochemical response, indicating that MIL-100(Fe) provides an appropriate microenvironment for the immobilization and electroactivity of ABTS molecules. ABTS@MIL-100(Fe) was then evaluated as an immobilized laccase mediator for dye removal using indigo carmine (IC) as a model dye. Through the application of laccase in combination with a free (ABTS) or immobilized (ABTS@MIL-100(Fe)) mediator, decolorization yields of 95% and 94%, respectively, were obtained for IC after 50 min. In addition, following seven reuse cycles of ABTS@MIL-100(Fe) for dye treatment, a decolorization yield of 74% was obtained. Dye decolorization occurred through the breakdown of the chromophoric group by the Laccase/ABTS@MIL-100(Fe) system, and a catalytic mechanism was proposed. We therefore expect that the stability, reusability, and validity of ABTS@MIL-100(Fe) as a laccase mediator potentially render it a promising tool for dye removal, in addition to reducing the high running costs and potential toxicity associated with synthetic mediators. Full article
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Open AccessArticle New Pinane Derivatives Found in Essential Oils of Calocedrus decurrens
Molecules 2017, 22(6), 921; doi:10.3390/molecules22060921
Received: 5 May 2017 / Revised: 31 May 2017 / Accepted: 31 May 2017 / Published: 2 June 2017
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Abstract
The main objective of this study was to determine the chemical composition of essential oils (EOs) obtained from leaf, old branches, and young branches of a coniferous species Calocedrus decurrens acclimated to Corsica. The analytical investigation was conducted by GC(RI), GC-MS, pc-GC, and
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The main objective of this study was to determine the chemical composition of essential oils (EOs) obtained from leaf, old branches, and young branches of a coniferous species Calocedrus decurrens acclimated to Corsica. The analytical investigation was conducted by GC(RI), GC-MS, pc-GC, and NMR. C. decurrens leaf, old branches, and young branches EOs contained α-pinene (11.2; 56.6; 22.3%), myrcene (13.4; 8.4; 9.7%), Δ-3-carene (31.3; 5.2; 11.1%), limonene (6.4; 5.1; 5.5%), terpinolene (6.9; 1.5; 3.2%), and pin-2-en-8-ol (4.2; 4.5; 10.4%) as major components, respectively. Special attention was paid to purifying and identifying four unusual pinane derivatives: pin-2-en-8-ol, pin-2-en-8-yl Acetate, pin-2-en-8-al, and methyl pin-2-en-8-oate. The last two are reported for the first time. Full article
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Open AccessArticle Characterization of Aliphatic Polyesters Synthesized via Enzymatic Ring-Opening Polymerization in Ionic Liquids
Molecules 2017, 22(6), 923; doi:10.3390/molecules22060923
Received: 24 April 2017 / Revised: 31 May 2017 / Accepted: 31 May 2017 / Published: 2 June 2017
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Abstract
To evaluate the effects of ionic liquids (ILs) on the microstructural features of aliphatic polyesters for biomedical applications, a series of copolymers were synthesized by lipase ring opening polymerization of rac-lactide (rac-LA) and ε-caprolactone (CL). The chemical structures of resulting
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To evaluate the effects of ionic liquids (ILs) on the microstructural features of aliphatic polyesters for biomedical applications, a series of copolymers were synthesized by lipase ring opening polymerization of rac-lactide (rac-LA) and ε-caprolactone (CL). The chemical structures of resulting polymers were characterized by 1H- and 13C-NMR and the average molecular weight (Mn) and dispersity index were characterized by gel permeation chromatography. The structure of the copolymers confirms the presence of linear polymer chains with end-functional hydroxyl groups allowing covalent coupling of the therapeutic agents. Chain microstructure of copolymers indicates the presence of both random and block copolymers depending on the synthesis conditions. Moreover, it was found that CL is the most active co-monomer during copolymerization which enhances the polymerizability of rac-LA and allows to obtain higher Mn of the copolymers. The results demonstrate that ILs could be promising solvents in synthesis of aliphatic esters for biomedical applications. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Phytochemical Quantification and the In Vitro Acetylcholinesterase Inhibitory Activity of Phellodendron chinense and Its Components
Molecules 2017, 22(6), 925; doi:10.3390/molecules22060925
Received: 10 April 2017 / Revised: 23 May 2017 / Accepted: 30 May 2017 / Published: 2 June 2017
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Abstract
The dried bark of Phellodendron chinense has been used as a traditional herbal medicine to remove damp heat, relieve consumptive fever, and cure dysentery and diarrhea. In the present study, we performed quantitative analyses of the two components of P. chinense, phellodendrine
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The dried bark of Phellodendron chinense has been used as a traditional herbal medicine to remove damp heat, relieve consumptive fever, and cure dysentery and diarrhea. In the present study, we performed quantitative analyses of the two components of P. chinense, phellodendrine and berberine, using high-performance liquid chromatography. A 70% ethanol extract of P. chinense was prepared and the two components were separated on a C-18 analytical column using a gradient solvent system of acetonitrile and 0.1% (v/v) aqueous trifluoroacetic acid. The ultraviolet wavelength used for detection was 200 nm for phellodendrine and 226 nm for berberine. The analytical method established here showed high linearity (correlation coefficient, ≥0.9991). The amount of phellodendrine and berberine used was 22.255 ± 0.123 mg/g and 269.651 ± 1.257 mg/g, respectively. Moreover, we performed an in vitro acetylcholinesterase (AChE) activity assay and an amyloid-β aggregation test to examine the biological properties of phellodendrine and berberine as therapeutic drugs for Alzheimer’s disease. Phellodendrine and berberine inhibited AChE activity in a dose-dependent manner (IC50 = 36.51 and 0.44 μM, respectively). In contrast, neither phellodendrine nor berberine had an effect on amyloid-β aggregation. The P. chinense extract and phellodendrine, but not berberine, exhibited antioxidant activity by increasing radical scavenging activity. Moreover, P. chinense demonstrated a neuroprotective effect in hydrogen peroxide-treated HT22 hippocampal cells. Overall, our findings suggest that P. chinense has potential as an anti-Alzheimer’s agent via the suppression of the enzymatic activity of acetylcholinesterase and the stimulation of antioxidant activity. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Cu Nanoparticles in Hydrogels of Chitosan-PVA Affects the Characteristics of Post-Harvest and Bioactive Compounds of Jalapeño Pepper
Molecules 2017, 22(6), 926; doi:10.3390/molecules22060926
Received: 31 March 2017 / Revised: 24 May 2017 / Accepted: 31 May 2017 / Published: 2 June 2017
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Abstract
Peppers are consumed all over the world due to the flavor, aroma, and color that they add to food. Additionally, they play a role in human health, as they contain a high concentration of bioactive compounds and antioxidants. The treatments used were an
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Peppers are consumed all over the world due to the flavor, aroma, and color that they add to food. Additionally, they play a role in human health, as they contain a high concentration of bioactive compounds and antioxidants. The treatments used were an absolute control, Cs-PVA, and four treatments with 0.02, 0.2, 2, and 10 mg (nCu) g−1 (Cs-PVA). The application of Cu nanoparticles in chitosan-PVA hydrogels increases the content of capsaicin by up to 51% compared to the control. This application also increases the content of antioxidants ABTS [2,2′-azino-bis (3-ethylbenzothiazolin-6-sulfonic acid)] and DPPH (2,2-diphenyl-1-picrylhydrazyl), total phenols and flavonoids (4%, 6.6%, 5.9%, and 12.7%, respectively) in jalapeño pepper fruits stored for 15 days at room temperature; under refrigeration, it increases DPPH antioxidants, total phenols, and flavonoids (23.9%, 1.54%, and 17.2%, respectively). The application of Cu nanoparticles in chitosan-PVA hydrogels, even when applied to the substrate, not only has an effect on the development of the jalapeño pepper crop, but also modifies the post-harvest characteristics of the jalapeño pepper fruits. Full article
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Open AccessArticle Simultaneous Quantification of Multiple Representative Components in the Xian-Ling-Gu-Bao Capsule by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry
Molecules 2017, 22(6), 927; doi:10.3390/molecules22060927
Received: 19 April 2017 / Revised: 25 May 2017 / Accepted: 1 June 2017 / Published: 2 June 2017
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Abstract
Xian-Ling-Gu-Bao capsule (XLGB), a famous traditional Chinese medicine prescription, is extensively used for the treatment of osteoporosis in China. However, few studies on the holistic quality control of XLGB have been reported. In this study, a reliable method using 18 representative components in
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Xian-Ling-Gu-Bao capsule (XLGB), a famous traditional Chinese medicine prescription, is extensively used for the treatment of osteoporosis in China. However, few studies on the holistic quality control of XLGB have been reported. In this study, a reliable method using 18 representative components in XLGB was successfully established and applied to evaluate 34 batches of XLGB samples by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS). The choice of quantitative markers mostly followed four principles, i.e., absorbed components in plasma, bioactive compounds with in vitro anti-osteoporosis activity, those derived from multiple individual medicinal herbs in XLGB with multiple representative structure types, and quantitative chemical markers in the Chinese Pharmacopoeia. The results showed chemical consistency was good except for individual batches. Multivariate statistical analysis indicated that asperosaponin VI from Radix Dipsaci, epimedin C, magnoflorine, and icariin from Herba Epimedii as well as timosaponin BII from Rhizoma Anemarrhenae varied significantly in multiple samples, which hinted an assay for these four components should be completed during all of the manufacturing processes. Taken together, this study provided a feasible method for holistic quality control of XLGB by multiple chemical markers, which could play a vital role in guaranteeing the safety, effectiveness, and controllability of administering the capsules as a medication in clinics. Full article
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Open AccessArticle Variability in the Content of Trans-Resveratrol, Trans-ε-Viniferin and R2-Viniferin in Grape Cane of Seven Vitis vinifera L. Varieties during a Three-Year Study
Molecules 2017, 22(6), 928; doi:10.3390/molecules22060928
Received: 21 April 2017 / Revised: 25 May 2017 / Accepted: 31 May 2017 / Published: 3 June 2017
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Abstract
Grape canes are a waste product from viticulture that show potential as an industrially extractable source of stilbenes, which are valuable for medical and other purposes. In this work, grape canes collected in three consecutive years (2014–2016) at six different places in South
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Grape canes are a waste product from viticulture that show potential as an industrially extractable source of stilbenes, which are valuable for medical and other purposes. In this work, grape canes collected in three consecutive years (2014–2016) at six different places in South Moravia, Czech Republic were extracted, and the contents of trans-resveratrol, trans-ε-viniferin, and r2-viniferin were determined by high-performance liquid chromatography. The study included three blue grape varieties of Vitis vinifera L. (Cabernet Moravia, Blaufränkisch, and Piwi variety Laurot) and four white grape varieties (Chardonnay, Green Veltliner, Piwi variety Hibernal, and Piwi variety Malverina). From the viewpoint of producing extracts with high stilbenes content, the Hibernal variety is clearly the best. The mean amounts of the stilbenes for this variety at all localities and for all three years were 4.99 g/kg for trans-resveratrol, 3.24 g/kg for trans-ε-viniferin, and 1.73 g/kg for r2-viniferin. The influence of vintage, locality, and variety on the amounts of stilbenes was studied using PCA analysis. In contrast to expectations, there was no strong impact of locality on stilbenes content. The differences were varietal for most varieties, regardless of the area of cultivation. Laurot and Hibernal varieties did differ significantly in that respect, however, as they exhibited clear dependence on location. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Curcumin Inhibits LIN-28A through the Activation of miRNA-98 in the Lung Cancer Cell Line A549
Molecules 2017, 22(6), 929; doi:10.3390/molecules22060929
Received: 29 March 2017 / Revised: 4 May 2017 / Accepted: 25 May 2017 / Published: 3 June 2017
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Abstract
Metastasis is common in lung cancer and is associated with poor clinical outcomes and increased mortality. Curcumin is a natural anti-cancer agent that inhibits the metastasis of various cancers by modulating the expression of micro (mi) RNAs such as miR-98, which acts as
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Metastasis is common in lung cancer and is associated with poor clinical outcomes and increased mortality. Curcumin is a natural anti-cancer agent that inhibits the metastasis of various cancers by modulating the expression of micro (mi) RNAs such as miR-98, which acts as a tumor suppressor. This study investigated the effect of curcumin on miR-98 expression and in vitro cell line growth and invasiveness in lung cancer. Curcumin treatment enhanced the expression of miR-98 and reduced that of the miR-98 target gene LIN28A as well as matrix metalloproteinase (MMP) 2 and MMP9 in vitro and in vivo. MiR-98 overexpression suppressed lung cancer cell migration and invasion by inhibiting LIN28A-induced MMP2 and MMP9 expression. Meanwhile, LIN28A level was downregulated by overexpression of miR-98 mimic. Induction of miR-98 by curcumin treatment suppressed MMP2 and MMP9 by targeting LIN28A. These findings provide insight into the mechanisms by which curcumin suppresses lung cancer cell line growth in vitro and in vivo and invasiveness in vitro. Full article
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Open AccessArticle Laurus nobilis: Composition of Essential Oil and Its Biological Activities
Molecules 2017, 22(6), 930; doi:10.3390/molecules22060930
Received: 10 May 2017 / Revised: 30 May 2017 / Accepted: 1 June 2017 / Published: 3 June 2017
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Abstract
Laurus nobilis is native to the southern Mediterranean region and cultivated mainly in Europe and the USA as an ornamental and medicinal plant. The chemical composition of the essential oil (EO) from leaves of L. nobilis, collected in Southern Italy, was studied by
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Laurus nobilis is native to the southern Mediterranean region and cultivated mainly in Europe and the USA as an ornamental and medicinal plant. The chemical composition of the essential oil (EO) from leaves of L. nobilis, collected in Southern Italy, was studied by GC and GC-MS. In all, 55 compounds were identified, accounting for 91.6% of the total oil. 1,8-Cineole (31.9%), sabinene (12.2%), and linalool (10.2%) were the main components. Antimicrobial and antifungal activities of EO and 1,8-cineole were determined in vitro. The cytotoxicity of the EO was evaluated against SH-SY5Y cell line, as well as the influence of the EO on the expression of adenylate cyclase 1 (ADCY1), suggesting possible oil effects on the Central Nervous System. Full article
(This article belongs to the Special Issue Essential Oils: Chemistry and Bioactivity)
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Open AccessArticle Optimization of Ultrasonic-assisted Extraction of Fatty Acids in Seeds of Brucea Javanica (L.) Merr. from Different Sources and Simultaneous Analysis Using High-Performance Liquid Chromatography with Charged Aerosol Detection
Molecules 2017, 22(6), 931; doi:10.3390/molecules22060931
Received: 3 May 2017 / Revised: 24 May 2017 / Accepted: 1 June 2017 / Published: 4 June 2017
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Abstract
Our research aimed to optimize the oil extraction process and determine the fatty acids in Brucea javanica (L.) Merr. seeds. The extraction technology was optimized using response surface methodology. A Box-Behnken design was employed to investigate the effects of three independent variables on
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Our research aimed to optimize the oil extraction process and determine the fatty acids in Brucea javanica (L.) Merr. seeds. The extraction technology was optimized using response surface methodology. A Box-Behnken design was employed to investigate the effects of three independent variables on an ultrasonic-assisted extraction technique, namely, sonication time (X1: 20–40 min), liquid–solid ratio (X2: 16:1 mL/g–24:1 mL/g), and ethanol concentration (X3: 90%–100%). The optimum conditions of sonication time, liquid–solid ratio, and ethanol concentration were 40 min, 24:1 mL/g, and 100%, respectively. The content of fatty acids and the oil yield were 14.64 mg/g and 16.87%, respectively, which match well with the predicted models. The optimum number of extraction times was eventually identified as two. A new rapid method for the qualitative and quantitative analysis of the fatty acids of B. javanica (L.) Merr. seed oil using HPLC with a charged aerosol detector was described. The fatty acid contents of 14 batches of B. javanica (L.) Merr. seed oil were determined, and the relevance and difference were analyzed by fingerprint analysis. The fingerprint has five common peaks, and the similarity was greater than 0.991. HPLC analysis represents a specialized and rational approach for the quality identification and comprehensive evaluation of B. javanica (L.) Merr. seed oils. Full article
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Open AccessArticle In Vitro Study of the Metabolic Characteristics of Eight Isoquinoline Alkaloids from Natural Plants in Rat Gut Microbiota
Molecules 2017, 22(6), 932; doi:10.3390/molecules22060932
Received: 29 April 2017 / Revised: 28 May 2017 / Accepted: 1 June 2017 / Published: 4 June 2017
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Abstract
Gut microbiota is populated with an immense number of microorganisms, which can be regulated by dietary components and drugs to markedly affect the nutritional and health status of the host. Eight medicinal isoquinoline alkaloids from natural plants were cultured anaerobically with rat gut
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Gut microbiota is populated with an immense number of microorganisms, which can be regulated by dietary components and drugs to markedly affect the nutritional and health status of the host. Eight medicinal isoquinoline alkaloids from natural plants were cultured anaerobically with rat gut microbiota and an LC/MSn-IT-TOF technique was used to identify the resulting metabolites. Palmatine, tetrahydropalmatine, dauricine, and tetrandrine containing nitro-hexatomic isoquinoline rings could be easily transformed by the intestinal flora in vitro and a total of nine demethylated metabolites were detected. However, sinomenine, homoharringtonine, harringtonine, and galanthamine, which all contained benzazepine, could not undergo demethylation. Computer-assisted docking was used to analyze the binding between these compounds and sterol 14α-demethylase. The computational results demonstrated that hydrophobic interactions were the main driving force for binding, but the steric hindrance produced by the benzazepine structure resulted in a weak interaction between the hit compounds and the enzyme. This work illustrated that gut microbiota were important in the metabolism of isoquinoline alkaloids. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Determination and Pharmacokinetic Study of Three Diterpenes in Rat Plasma by UHPLC-ESI-MS/MS after Oral Administration of Rosmarinus officinalis L. Extract
Molecules 2017, 22(6), 934; doi:10.3390/molecules22060934
Received: 9 May 2017 / Revised: 28 May 2017 / Accepted: 29 May 2017 / Published: 4 June 2017
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Abstract
Rosmarinus officinalis L. is commonly used as a spice and flavoring agent. Diterpenes are the main active compounds of R. officinalis. An Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-ESI-MS/MS) method was developed for the determination of carnosol, rosmanol, and carnosic acid
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Rosmarinus officinalis L. is commonly used as a spice and flavoring agent. Diterpenes are the main active compounds of R. officinalis. An Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-ESI-MS/MS) method was developed for the determination of carnosol, rosmanol, and carnosic acid isolated from R. officinalis in rat plasma, and applied to a pharmacokinetic study after oral administration of R. officinalis extract. Sample preparation involved a liquid-liquid extraction of the analytes with ethyl acetate. Butylparaben was employed as an internal standard (I.S.). Chromatographic separation was carried out on a C18 column (ACQUITY UPLC® HSS T3, 1.8 μm, 2.1 mm × 100 mm) with a gradient system consisting of the mobile phase solution A (0.1% formic acid in water) and solution B (acetonitrile) at the flow rate of 0.3 mL/min. The quantification was obtained using multiple reaction monitoring (MRM) mode with electrospray ionization (ESI). The UHPLC-MS/MS assay was validated for linearity, accuracy, precision, extraction recovery, matrix effect and stability. This study described a simple, sensitive and validated UHPLC-MS/MS method for the simultaneous determination of three diterpene compounds in rat plasma after oral administration of R. officinalis extract, and investigated on their pharmacokinetic studies as well. Full article
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Open AccessArticle Anti-Inflammatory Phenolic Acid Esters from the Roots and Rhizomes of Notopterygium incisium and Their Permeability in the Human Caco-2 Monolayer Cell Model
Molecules 2017, 22(6), 935; doi:10.3390/molecules22060935
Received: 8 May 2017 / Revised: 1 June 2017 / Accepted: 2 June 2017 / Published: 4 June 2017
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Abstract
A new ferulic acid ester named 4-methyl-3-trans-hexenylferulate (1), together with eight known phenolic acid esters (29), was isolated from the methanolic extract of the roots and rhizomes of Notopterygium incisium. Their structures were elucidated
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A new ferulic acid ester named 4-methyl-3-trans-hexenylferulate (1), together with eight known phenolic acid esters (29), was isolated from the methanolic extract of the roots and rhizomes of Notopterygium incisium. Their structures were elucidated by extensive spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry. 4-Methoxyphenethyl ferulate (8) NMR data is reported here for the first time. The uptake and transepithelial transport of the isolated compounds 19 were investigated in the human intestinal Caco-2 cell monolayer model. Compounds 2 and 6 were assigned for the well-absorbed compounds, compound 8 was assigned for the moderately absorbed compound, and compounds 1, 3, 4, 5, 7, and 9 were assigned for the poorly absorbed compounds. Moreover, all of the isolated compounds were assayed for the inhibitory effects against nitric oxide (NO) production in the lipopolysaccharide-activated RAW264.7 macrophages model and L-N6-(1-iminoethyl)-lysine (L-NIL) was used as a positive control. Compounds 1, 5, 8, and 9 exhibited potent inhibitory activity on NO production with the half maximal inhibitory concentration (IC50) values of 1.01, 4.63, 2.47, and 2.73 μM, respectively, which were more effective than L-NIL with IC50 values of 9.37 μM. These findings not only enriched the types of anti-inflammatory compounds in N. incisum but also provided some useful information for predicting their oral bioavailability and their suitability as drug leads or promising anti-inflammatory agents. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle New Benzenoid Derivatives and Other Constituents from Lawsonia inermis with Inhibitory Activity against NO Production
Molecules 2017, 22(6), 936; doi:10.3390/molecules22060936
Received: 8 May 2017 / Accepted: 1 June 2017 / Published: 5 June 2017
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Abstract
Three new benzenoid derivatives, lawsoinermone (1), inermidioic acid (2), and inermic acid (3) have been isolated from the aerial part of Lawsonia inermis, together with 11 known compounds (414). The structures of
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Three new benzenoid derivatives, lawsoinermone (1), inermidioic acid (2), and inermic acid (3) have been isolated from the aerial part of Lawsonia inermis, together with 11 known compounds (414). The structures of three new compounds were determined through spectroscopic and MS analyses. Compounds 1, 46, 13 and 14 were evaluated for inhibition of nitric oxide production in LPS-stimulated product of nitrite in RAW 264.7 cells with IC50 values of 6.12, 16.43, 18.98, 9.30, 9.30 and 14.90 μg/mL, respectively. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Levo-Corydalmine Alleviates Neuropathic Cancer Pain Induced by Tumor Compression via the CCL2/CCR2 Pathway
Molecules 2017, 22(6), 937; doi:10.3390/molecules22060937
Received: 14 April 2017 / Revised: 2 May 2017 / Accepted: 2 June 2017 / Published: 6 June 2017
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Abstract
Background: Tumor compression-induced pain (TCIP) is a complex pathological cancer pain. Spinal glial cells play a critical role in maintenance of cancer pain by releasing proinflammatory cytokines and chemokines. In this study, we verified the role of levo-corydalmine (l-CDL)
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Background: Tumor compression-induced pain (TCIP) is a complex pathological cancer pain. Spinal glial cells play a critical role in maintenance of cancer pain by releasing proinflammatory cytokines and chemokines. In this study, we verified the role of levo-corydalmine (l-CDL) on TCIP. Methods: Spontaneous pain, paw withdrawal threshold and latency were assessed using TCIP mouse model. Immunofluorescence was used to identify the reactions of glia. RT-PCR and western blot or ELISA were used to determine mRNA or protein expression of tumor necrosis factor-α (TNF-α), interlukin-1β (IL-1β), CC chemokine ligand 2 (CCL2) and chemotactic cytokine receptor 2 (CCR2) in vivo and in vitro. Results: l-CDL significantly attenuated TCIP hypersensitivity, accompanying with downregulation of TNF-α and IL-1β expression levels and declined astrocytes and microglial activation. It also significantly decreased the expression of the mRNA and protein level for CCL2 and CCR2. Further, l-CDL could suppress TNF-α-induced astrocytes activation and IL-1β expression through downregulating the CCL2/CCR2. Besides, CCL2-induced BV-microglia activation and inflammatory factors secretion were suppressed by l-CDL via CCR2. Conclusions: Suppression of CCL2/CCR2 by l-CDL may contribute to alleviate TCIP, offering an alternative medication for TCIP. Full article
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Open AccessArticle Investigation of the Maillard Reaction between Polysaccharides and Proteins from Longan Pulp and the Improvement in Activities
Molecules 2017, 22(6), 938; doi:10.3390/molecules22060938
Received: 11 May 2017 / Accepted: 31 May 2017 / Published: 5 June 2017
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Abstract
The purpose of this study was to investigate the Maillard reaction between polysaccharides and proteins from longan pulp and the effects of reaction on their in vitro activities. The polysaccharide-protein mixtures of fresh longan pulp (LPPMs) were co-prepared by an alkali extraction–acid precipitation
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The purpose of this study was to investigate the Maillard reaction between polysaccharides and proteins from longan pulp and the effects of reaction on their in vitro activities. The polysaccharide-protein mixtures of fresh longan pulp (LPPMs) were co-prepared by an alkali extraction–acid precipitation method. They were then dry-heated under controlled conditions for monitoring the characterization of the Maillard reaction by the measurement of the free amino group content, ultraviolet-visible spectrum, Fourier transform infrared spectrum and molecular weight distribution. All the physicochemical analyses indicated the development of the Maillard reaction between polysaccharides and proteins. The in vitro activity evaluation indicated that the Maillard reaction could effectively enhance the antioxidant, antitumor and immunostimulating activities of LPPMs. The enhancement of 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and ferric reducing antioxidant power displayed both a positive correlation with the reaction time (p < 0.05). LPPMs dry-heated for three days obtained relatively strong inhibitory activity against HepG2 cells and SGC7901 cells, as well as strong immunostimulating effects on the nitric oxide production and tumor necrosis factor α secretion of macrophages. Maillard-type intermacromolecular interaction is suggested to be an effective and controllable method for improving the functional activities of polysaccharides and proteins from longan pulp. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions)
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Open AccessArticle Pharmacokinetics and Tissue Distribution Kinetics of Puerarin in Rats Using Indirect Competitive ELISA
Molecules 2017, 22(6), 939; doi:10.3390/molecules22060939
Received: 5 May 2017 / Accepted: 1 June 2017 / Published: 5 June 2017
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Abstract
Puerarin (PUE) is a compound isolated from the roots of Pueraria lobata. We studied the pharmacokinetics and tissue distribution kinetics of PUE in Sprague-Dawley rats following intraperitoneal administration of three concentrations. Indirect competitive ELISA based on an anti-PUE monoclonal antibody was used
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Puerarin (PUE) is a compound isolated from the roots of Pueraria lobata. We studied the pharmacokinetics and tissue distribution kinetics of PUE in Sprague-Dawley rats following intraperitoneal administration of three concentrations. Indirect competitive ELISA based on an anti-PUE monoclonal antibody was used to determine the concentration of PUE in the blood, heart, liver, spleen, lung, kidney, hippocampus, cerebral cortex, and striatum. The plasma and tissue distribution kinetic characteristics following a single injection of PUE (20, 40 and 80 mg/kg) were calculated using a non-compartment model. In the high-dose (80 mg/kg) and medium-dose (40 mg/kg) groups, the kinetic profile of PUE in blood and kidney samples showed two absorption peaks, while that of the other tissues showed only one peak. In the low-dose (20 mg/kg) group, there was only one peak, irrespective of the sample type. Pharmacokinetic parameters, such as the area under the curve, Cmax, and Tmax varied according to the administered dose. AUC and Cmax values increased dose-dependently. PUE was widely distributed in areas of the brain such as the hippocampus, cerebral cortex, and striatum, providing a foundation for guiding the use of PUE in the treatment of cerebral ischaemic stroke and neurodegenerative diseases. Full article
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Open AccessArticle Sesquiterpene Variation in West Australian Sandalwood (Santalum spicatum)
Molecules 2017, 22(6), 940; doi:10.3390/molecules22060940
Received: 13 April 2017 / Revised: 4 May 2017 / Accepted: 19 May 2017 / Published: 6 June 2017
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Abstract
West Australian sandalwood (Santalum spicatum) has long been exploited for its fragrant, sesquiterpene-rich heartwood; however sandalwood fragrance qualities vary substantially, which is of interest to the sandalwood industry. We investigated metabolite profiles of trees from the arid northern and southeastern and
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West Australian sandalwood (Santalum spicatum) has long been exploited for its fragrant, sesquiterpene-rich heartwood; however sandalwood fragrance qualities vary substantially, which is of interest to the sandalwood industry. We investigated metabolite profiles of trees from the arid northern and southeastern and semi-arid southwestern regions of West Australia for patterns in composition and co-occurrence of sesquiterpenes. Total sesquiterpene content was similar across the entire sample collection; however sesquiterpene composition was highly variable. Northern populations contained the highest levels of desirable fragrance compounds, α- and β-santalol, as did individuals from the southwest. Southeastern populations were higher in E,E-farnesol, an undesired allergenic constituent, and low in santalols. These trees generally also contained higher levels of α-bisabolol. E,E-farnesol co-occurred with dendrolasin. Contrasting α-santalol and E,E-farnesol chemotypes revealed potential for future genetic tree improvement. Although chemical variation was evident both within and among regions, variation was generally lower within regions. Our results showed distinct patterns in chemical diversity of S. spicatum across its natural distribution, consistent with earlier investigations into sandalwood population genetics. These results are relevant for plantation tree improvement and conservation efforts. Full article
(This article belongs to the Special Issue Isoprenoid Biosynthesis)
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Open AccessArticle Tryptophan Levels during Grape Ripening: Effects of Cultural Practices
Molecules 2017, 22(6), 941; doi:10.3390/molecules22060941
Received: 29 April 2017 / Revised: 5 May 2017 / Accepted: 30 May 2017 / Published: 6 June 2017
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Abstract
Some cultural practices that are carried out during the grape ripening period are associated with vine stress, including leaf removal, grape bunch removal, and vegetable cover crops. Additionally, several nitrogen and sulfur supplements have also been used directly on leaves during the last
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Some cultural practices that are carried out during the grape ripening period are associated with vine stress, including leaf removal, grape bunch removal, and vegetable cover crops. Additionally, several nitrogen and sulfur supplements have also been used directly on leaves during the last stage of the ripening period. In the work described here, five different cultural practices and the reference were applied in three replicates in the same vineyard. The evolution of tryptophan levels was evaluated from just after grape veraison until the harvest date. In some cases, certain specific treatments were also evaluated after the regular harvest date. The cultural techniques that involved the application of nitrogen led to higher levels of tryptophan at the harvest day when compared to other cultural techniques. It was also found that the application of nitrogen without sulfur had a faster effect on the level of tryptophan. It was established that a period of around 20 days is needed for the grapes to show clear differences in tryptophan levels after the application of nitrogen. Full article
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Open AccessArticle Evaluation of the Cardiotoxicity of Evodiamine In Vitro and In Vivo
Molecules 2017, 22(6), 943; doi:10.3390/molecules22060943
Received: 19 May 2017 / Revised: 1 June 2017 / Accepted: 2 June 2017 / Published: 9 June 2017
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Abstract
Evodiamine is a bioactive alkaloid that is specified as a biomarker for the quality assessment of Evodia rutaecarpa (E. rutaecarpa) and for traditional Chinese medicines containing this plant. We previously reported that quantitative structure–activity modeling indicated that evodiamine may cause cardiotoxicity.
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Evodiamine is a bioactive alkaloid that is specified as a biomarker for the quality assessment of Evodia rutaecarpa (E. rutaecarpa) and for traditional Chinese medicines containing this plant. We previously reported that quantitative structure–activity modeling indicated that evodiamine may cause cardiotoxicity. However, previous investigations have indicated that evodiamine has beneficial effects in patients with cardiovascular diseases and there are no previous in vitro or in vivo reports of evodiamine-induced cardiotoxicity. The present study investigated the effects of evodiamine on primary cultured neonatal rat cardiomyocytes in vitro, and on zebrafish in vivo. Cell viability was reduced in vitro, where evodiamine had a 24 h 50% inhibitory concentration of 28.44 µg/mL. Cells exposed to evodiamine also showed increased lactate dehydrogenase release and maleic dialdehyde levels, and reduced superoxide dismutase activity. In vivo, evodiamine had a 10% lethal concentration of 354 ng/mL and induced cardiac malfunction, as evidenced by changes in heart rate and circulation, and pericardial malformations. This study indicated that evodiamine could cause cardiovascular side effects involving oxidative stress. These findings suggest that cardiac function should be monitored in patients receiving preparations containing evodiamine. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle Pattern Evolution during Double Liquid-Vapor Phase Transitions under Weightlessness
Molecules 2017, 22(6), 947; doi:10.3390/molecules22060947
Received: 13 May 2017 / Revised: 31 May 2017 / Accepted: 2 June 2017 / Published: 9 June 2017
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Abstract
Phase transition in fluids is ubiquitous in nature and has important applications in areas such as the food industry for volatile oils’ extraction or in nuclear plants for heat transfer. Fundamentals are hampered by gravity effects on Earth. We used direct imaging to
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Phase transition in fluids is ubiquitous in nature and has important applications in areas such as the food industry for volatile oils’ extraction or in nuclear plants for heat transfer. Fundamentals are hampered by gravity effects on Earth. We used direct imaging to record snapshots of phase separation that takes place in sulfur hexafluoride, SF6, under weightlessness conditions on the International Space Station (ISS). The system was already at liquid-vapor equilibrium slightly below the critical temperature and further cooled down by a 0.2-mK temperature quench that produced a new phase separation. Both full view and microscopic views of the direct observation cell were analyzed to determine the evolution of the radii distributions. We found that radii distributions could be well approximated by a lognormal function. The fraction of small radii droplets declined while the fraction of large radii droplets increased over time. Phase separation at the center of the sample cell was visualized using a 12× microscope objective, which corresponds to a depth of focus of about 5 μ m. We found that the mean radii of liquid droplets exhibit a t 1 / 3 evolution, in agreement with growth driven by Brownian coalescence. It was also found that the mean radii of the vapor bubbles inside the liquid majority phase exhibit a t 1 / 2 evolution, which suggest a possible directional motion of vapor bubbles due to the influence of weak remaining gravitational field and/or a composition Marangoni force. Full article
(This article belongs to the Special Issue Sub- and Supercritical Fluids and Green Chemistry)
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Open AccessArticle Two New β-Dihydroagarofuran Sesquiterpenes from Celastrus orbiculatus Thunb and Their Anti-Proliferative Activity
Molecules 2017, 22(6), 948; doi:10.3390/molecules22060948
Received: 10 May 2017 / Revised: 5 June 2017 / Accepted: 5 June 2017 / Published: 9 June 2017
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Abstract
Two new β-dihydroagarofuran-type sesquiterpenes (12) were isolated and identified from the fruit of Celastrus orbiculatus Thunb, together with seventeen known compounds (319). The structures of the isolated new compounds were elucidated based on extensive spectroscopic
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Two new β-dihydroagarofuran-type sesquiterpenes (12) were isolated and identified from the fruit of Celastrus orbiculatus Thunb, together with seventeen known compounds (319). The structures of the isolated new compounds were elucidated based on extensive spectroscopic analyses. The cytotoxic activities of the 19 sesquiterpenes on three cell lines, human acute promyelocytic leukemia HL-60, human leukemic K562, and human colon cancer HCT-116 cells, were evaluated in vitro. Compound 4 exhibited potent cytotoxic activity against HL-60, K562, and HCT116 cell lines with IC50 values of 3.61 μΜ, 17.13 μΜ and 10.15 μΜ, respectively, and the other compounds displayed moderate activity. Full article
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Open AccessArticle Anti-Inflammatory and Antioxidant Properties of Peptides Released from β-Lactoglobulin by High Hydrostatic Pressure-Assisted Enzymatic Hydrolysis
Molecules 2017, 22(6), 949; doi:10.3390/molecules22060949
Received: 19 April 2017 / Revised: 24 May 2017 / Accepted: 5 June 2017 / Published: 7 June 2017
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Abstract
Background: β-lactoglobulin hydrolysates (BLGH) have shown antioxidant, antihypertensive, antimicrobial, and opioid activity. In the current study, an innovative combination of high hydrostatic pressure and enzymatic hydrolysis (HHP–EH) was used to increase the yield of short bioactive peptides, and evaluate the anti-inflammatory and antioxidant
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Background: β-lactoglobulin hydrolysates (BLGH) have shown antioxidant, antihypertensive, antimicrobial, and opioid activity. In the current study, an innovative combination of high hydrostatic pressure and enzymatic hydrolysis (HHP–EH) was used to increase the yield of short bioactive peptides, and evaluate the anti-inflammatory and antioxidant properties of the BLGH produced by the HHP–EH process. Method: BLG was enzymatically hydrolyzed by different proteases at an enzyme-to-substrate ratio of 1:100 under HHP (100 MPa) and compared with hydrolysates obtained under atmospheric pressure (AP-EH at 0.1 MPa). The degree of hydrolysis (DH), molecular weight distribution, and the antioxidant and anti-inflammatory properties of hydrolysates in chemical and cellular models were evaluated. Results: BLGH obtained under HHP–EH showed higher DH than the hydrolysates obtained under AP-EH. Free radical scavenging and the reducing capacity were also significantly stronger in HHP-BLGH compared to AP-BLGH. The BLGH produced by alcalase (Alc) (BLG-Alc) showed significantly higher antioxidant properties among the six enzymes examined in this study. The anti-inflammatory properties of BLG-HHP-Alc were observed in lipopolysaccharide-stimulated macrophage cells by a lower level of nitric oxide production and the suppression of the synthesis of pro-inflammatory cytokines. Peptide sequencing revealed that 38% of the amino acids in BLG-HHP-Alc are hydrophobic and aromatic residues, which contribute to its anti-inflammatory properties. Conclusions: Enzymatic hydrolysis of BLG under HHP produces a higher yield of short bioactive peptides with potential antioxidant and anti-inflammatory effects. Full article
(This article belongs to the Special Issue Natural Products and Chronic Diseases)
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Open AccessArticle Nanocrystalline TiO2 Composite Films for the Photodegradation of Formaldehyde and Oxytetracycline under Visible Light Irradiation
Molecules 2017, 22(6), 950; doi:10.3390/molecules22060950
Received: 3 May 2017 / Revised: 4 June 2017 / Accepted: 6 June 2017 / Published: 14 June 2017
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Abstract
In order to effectively photodegradate organic pollutants, ZnO composite and Co-B codoped TiO2 films were successfully deposited on glass substrates via a modified sol-gel method and a controllable dip-coating technique. Combining with UV–Vis diffuse reflectance spectroscopy (DRS) and photoluminescence spectra (PL) analyses,
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In order to effectively photodegradate organic pollutants, ZnO composite and Co-B codoped TiO2 films were successfully deposited on glass substrates via a modified sol-gel method and a controllable dip-coating technique. Combining with UV–Vis diffuse reflectance spectroscopy (DRS) and photoluminescence spectra (PL) analyses, the multi-modification could not only extend the optical response of TiO2 to visible light region but also decrease the recombination rate of electron-hole pairs. XRD results revealed that the multi-modified TiO2 film had an anatase-brookite biphase heterostructure. FE-SEM results indicated that the multi-modified TiO2 film without cracks was composed of smaller round-like nanoparticles compared to pure TiO2. BET surface area results showed that the specific surface area of pure TiO2 and the multi-modified TiO2 sample was 47.8 and 115.8 m2/g, respectively. By degradation of formaldehyde and oxytetracycline, experimental results showed that the multi-modified TiO2 film had excellent photodegradation performance under visible light irradiation. Full article
(This article belongs to the Special Issue Nanocrystals: Synthesis, Characterization and Applications)
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Open AccessArticle Anti-Inflammatory Activities and Liver Protection of Alisol F and 25-Anhydroalisol F through the Inhibition of MAPK, STAT3, and NF-κB Activation In Vitro and In Vivo
Molecules 2017, 22(6), 951; doi:10.3390/molecules22060951
Received: 22 May 2017 / Revised: 5 June 2017 / Accepted: 5 June 2017 / Published: 8 June 2017
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Abstract
Alisol F and 25-anhydroalisol F isolated from Alisma orientale, were proved to exhibit anti-inflammatory potential in our previous work. In the current study, the anti-inflammatory effects and action mechanisms of alisol F and 25-anhydroalisol F were investigated in vitro. Moreover, the pharmacological
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Alisol F and 25-anhydroalisol F isolated from Alisma orientale, were proved to exhibit anti-inflammatory potential in our previous work. In the current study, the anti-inflammatory effects and action mechanisms of alisol F and 25-anhydroalisol F were investigated in vitro. Moreover, the pharmacological effects of alisol F in lipopolysaccharide (LPS)/d-galactosamine (d-gal)-induced acute liver-injured mice were evaluated. The results demonstrated that alisol F and 25-anhydroalisol F could suppress LPS-induced production of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β), as well as inhibit the mRNA and protein levels of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2). In addition, we investigated the role of alisol F and 25-anhydroalisol F in mediating mitogen-activated protein kinases (MAPKs), signal transducers, and activators of transcription 3 (STAT3) and nuclear factor κB (NF-κB) pathways involved in the inflammation process of LPS-stimulated RAW 264.7 cells. The phosphorylation of ERK, JNK, p38, and STAT3, and the NF-κB signaling pathway, were obviously suppressed in alisol F and 25-anhydroalisol F treated cells. Results obtained from in vitro experiments suggested alisol F obviously improved liver pathological injury by inhibiting the production of TNF-α, IL-1β, and IL-6, and significantly decreasing the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in LPS/d-gal-induced mice. Furthermore, the reduction of phosphorylation of ERK and JNK, as well as suppression of the NF-κB signaling pathway, were also observed in liver tissues of the alisol F-treated mice model. Alisol F and 25-anhydroalisol F may serve as potential leads for development of anti-inflammatory agents for acute liver failure treatment. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Lipophilicity Studies on Thiosemicarbazide Derivatives
Molecules 2017, 22(6), 952; doi:10.3390/molecules22060952
Received: 8 April 2017 / Accepted: 1 June 2017 / Published: 8 June 2017
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Abstract
The lipophilicity of two series of thiosemicarbazide derivatives was assessed by the RP-HPLC method with the RP-18 chromatographic column and the methanol–water mixture as the mobile phase. Distribution coefficients logPHPLC were compared to calculated values generated by commonly used AClogP software and
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The lipophilicity of two series of thiosemicarbazide derivatives was assessed by the RP-HPLC method with the RP-18 chromatographic column and the methanol–water mixture as the mobile phase. Distribution coefficients logPHPLC were compared to calculated values generated by commonly used AClogP software and quantum chemical calculations. The reliability of the predictions was evaluated using the correlation matrix and PCA. For 4-benzoylthiosemicarbazides, a high correlation between theoretical and experimental logP parameters was obtained using the XlogP3 algorithm, while for 4-aryl/(cyclohexyl)thiosemicarbazides, the XlogP2 parameter was strongly correlated with the experimentally obtained logP. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Atom Efficient Preparation of Zinc Selenates for the Synthesis of Selenol Esters under “On Water” Conditions
Molecules 2017, 22(6), 953; doi:10.3390/molecules22060953
Received: 11 May 2017 / Revised: 1 June 2017 / Accepted: 3 June 2017 / Published: 8 June 2017
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Abstract
We describe here an atom efficient procedure to prepare selenol esters in good to excellent yields by reacting [(PhSe)2Zn] or [(PhSe)2Zn]TMEDA with acyl chlorides under “on water” conditions. The method is applicable to a series of aromatic and aliphatic
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We describe here an atom efficient procedure to prepare selenol esters in good to excellent yields by reacting [(PhSe)2Zn] or [(PhSe)2Zn]TMEDA with acyl chlorides under “on water” conditions. The method is applicable to a series of aromatic and aliphatic acyl chlorides and tolerates the presence of other functionalities in the starting material. Full article
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Open AccessArticle Rapid Complexation of Aptamers by Their Specific Antidotes
Molecules 2017, 22(6), 954; doi:10.3390/molecules22060954
Received: 4 May 2017 / Revised: 4 June 2017 / Accepted: 5 June 2017 / Published: 8 June 2017
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Abstract
Nucleic acid ligands, aptamers, harbor the unique characteristics of small molecules and antibodies. The specificity and high affinity of aptamers enable their binding to different targets, such as small molecules, proteins, or cells. Chemical modifications of aptamers allow increased bioavailability. A further great
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Nucleic acid ligands, aptamers, harbor the unique characteristics of small molecules and antibodies. The specificity and high affinity of aptamers enable their binding to different targets, such as small molecules, proteins, or cells. Chemical modifications of aptamers allow increased bioavailability. A further great benefit of aptamers is the antidote (AD)-mediated controllability of their effect. In this study, the AD-mediated complexation and neutralization of the thrombin binding aptamer NU172 and Toll-like receptor 9 (TLR9) binding R10-60 aptamer were determined. Thereby, the required time for the generation of aptamer/AD-complexes was analyzed at 37 °C in human serum using gel electrophoresis. Afterwards, the blocking of aptamers’ effects was analyzed by determining the activated clotting time (ACT) in the case of the NU172 aptamer, or the expression of immune activation related genes IFN-1β, IL-6, CXCL-10, and IL-1β in the case of the R10-60 aptamer. Gel electrophoresis analyses demonstrated the rapid complexation of the NU172 and R10-60 aptamers by complementary AD binding after just 2 min of incubation in human serum. A rapid neutralization of anticoagulant activity of NU172 was also demonstrated in fresh human whole blood 5 min after addition of AD. Furthermore, the TLR9-mediated activation of PMDC05 cells was interrupted after the addition of the R10-60 AD. Using these two different aptamers, the rapid antagonizability of the aptamers was demonstrated in different environments; whole blood containing numerous proteins, cells, and different small molecules, serum, or cell culture media. Thus, nucleic acid ADs are promising molecules, which offer several possibilities for different in vivo applications, such as antagonizing aptamer-based drugs, immobilization, or delivery of oligonucleotides to defined locations. Full article
(This article belongs to the collection Nanomedicine)
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Open AccessArticle From Intermolecular Interactions to Texture in Polycrystalline Surfaces of 1,ω-alkanediols (ω = 10–13)
Molecules 2017, 22(6), 956; doi:10.3390/molecules22060956
Received: 19 April 2017 / Accepted: 5 June 2017 / Published: 8 June 2017
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Abstract
Differences on herringbone molecular arrangement in two forms of long-chain 1,ω-alkanediols (CnH2n+2O2 with n = 10, 11, 12, 13) are explained from the analysis of O-H···O hydrogen-bond sequences in infinite chains and the role of a
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Differences on herringbone molecular arrangement in two forms of long-chain 1,ω-alkanediols (CnH2n+2O2 with n = 10, 11, 12, 13) are explained from the analysis of O-H···O hydrogen-bond sequences in infinite chains and the role of a C-H···O intramolecular hydrogen-bond in stabilization of a gauche defect, as well as the inter-grooving effectiveness on molecular packing. GIXD (Glancing Incidence X-ray Diffraction) experiments were conducted on polycrystalline monophasic samples. Diffracted intensities were treated with the multi-axial March-Dollase method to correlate energetic and geometrical features of molecular interactions with the crystalline morphology and textural pattern of samples. The monoclinic (P21/c, Z = 2) crystals of the even-numbered members (n = 10, 12; DEDOL and DODOL, respectively) are diametrical prisms with combined form {104}/{-104}/{001} and present a two-fold platelet-like preferred orientation, whereas orthorhombic (P212121, Z = 4) odd-numbered members (n = 11, 13; UNDOL and TRDOL, respectively) present a dominant needle-like orientation on direction [101] (fiber texture). We show that crystalline structures of medium complexity and their microstructures can be determined from rapid GIXD experiments from standard radiation, combined with molecular replacement procedure using crystal structures of compounds with higher chain lengths as reference data. Full article
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Open AccessArticle Synthesis and Evaluation of Antimicrobial Activity of [R4W4K]-Levofloxacin and [R4W4K]-Levofloxacin-Q Conjugates
Molecules 2017, 22(6), 957; doi:10.3390/molecules22060957
Received: 15 May 2017 / Revised: 6 June 2017 / Accepted: 6 June 2017 / Published: 8 June 2017
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Abstract
The development of a new class of antibiotics to fight bacterial resistance is a time-consuming effort associated with high-cost and commercial risks. Thus, modification, conjugation or combination of existing antibiotics to enhance their efficacy is a suitable strategy. We have previously reported that
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The development of a new class of antibiotics to fight bacterial resistance is a time-consuming effort associated with high-cost and commercial risks. Thus, modification, conjugation or combination of existing antibiotics to enhance their efficacy is a suitable strategy. We have previously reported that the amphiphilic cyclic peptide [R4W4] had antibacterial activity with a minimum inhibitory concentration (MIC) of 2.97 µg/mL against Methicillin-resistant Staphylococcus aureus (MRSA). Herein, we hypothesized that conjugation or combination of the amphiphilic cyclic peptide [R4W4] with levofloxacin or levofloxacin-Q could improve the antibacterial activity of levofloxacin and levofloxacin-Q. Fmoc/tBu solid-phase chemistry was employed to synthesize conjugates of [R4W4K]-levofloxacin-Q and [R4W4K]-levofloxacin. The carboxylic acid group of levofloxacin or levofloxacin-Q was conjugated with the amino group of β-alanine attached to lysine in the presence of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) and N,N-diisopropylethylamine (DIPEA) for 3 h to afford the products. Antibacterial assays were conducted to determine the potency of conjugates [R4W4K]-levofloxacin-Q and [R4W4K]-levofloxacin against MRSA and Klebsiella pneumoniae. Although levofloxacin-Q was inactive even at a concentration of 128 µg/mL, [R4W4K]-levofloxacin-Q conjugate and the corresponding physical mixture showed MIC values of 8 µg/mL and 32 µg/mL against MRSA and Klebsiella pneumonia, respectively, possibly due to the activity of the peptide. On the other hand, [R4W4K]-levofloxacin conjugate (MIC = 32 µg/mL and MIC = 128 µg/mL) and the physical mixture (MIC = 8 µg/mL and 32 µg/mL) was less active than levofloxacin (MIC = 2 µg/mL and 4 = µg/mL) against MRSA and Klebsiella pneumoniae, respectively. The data showed that the conjugation of levofloxacin with [R4W4K] significantly reduced the antibacterial activity compared to the parent analogs, while [R4W4K]-levofloxacin-Q conjugate was more significantly potent than levofloxacin-Q alone. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessArticle Ovicidal and Insecticidal Activities of Pyriproxyfen Derivatives with an Oxime Ester Group
Molecules 2017, 22(6), 958; doi:10.3390/molecules22060958
Received: 12 May 2017 / Revised: 4 June 2017 / Accepted: 7 June 2017 / Published: 8 June 2017
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Abstract
Based on the structural framework of a pyriproxyfen metabolite, nineteen oxime ester derivatives were synthesized via reaction of the carboxylic acids with 4-(2-(2-pyridinyloxy)ethoxy)benzaldehyde oxime. The corresponding structures were comprehensively characterized by 1H-nuclear magnetic resonance (NMR), 13C-NMR, and electrospray ionization high-resolution mass
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Based on the structural framework of a pyriproxyfen metabolite, nineteen oxime ester derivatives were synthesized via reaction of the carboxylic acids with 4-(2-(2-pyridinyloxy)ethoxy)benzaldehyde oxime. The corresponding structures were comprehensively characterized by 1H-nuclear magnetic resonance (NMR), 13C-NMR, and electrospray ionization high-resolution mass spectrometry (ESI-HRMS). All of the compounds were screened for their insecticidal activities against Plutella xylostella and Myzus persicae, and for their ovicidal activities against Helicoverpa armigera eggs. The results obtained show that most of the oxime ester derivatives displayed moderate to high insecticidal activities and ovicidal activities at a concentration of 600 ug/mL. In particular, the ovicidal activity of compounds 5j, 5o, 5p, 5q, and 5s was determined to be 100%. Importantly, some of the compounds presented even higher biological activities than the reference compound pyriproxyfen. For example, compound 5j displayed an insecticidal activity value of 87.5% against Myzus persicae, whereas the activity value of pyriproxyfen was 68.3% at a concentration of 600 ug/mL. Among the synthesized compounds 5j and 5s exhibited broad biological activity spectra. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle 3D Pharmacophore-Based Virtual Screening and Docking Approaches toward the Discovery of Novel HPPD Inhibitors
Molecules 2017, 22(6), 959; doi:10.3390/molecules22060959
Received: 29 April 2017 / Accepted: 5 June 2017 / Published: 9 June 2017
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Abstract
p-Hydroxyphenylpyruvate dioxygenase (HPPD) is not only the useful molecular target in treating life-threatening tyrosinemia type I, but also an important target for chemical herbicides. A combined in silico structure-based pharmacophore and molecular docking-based virtual screening were performed to identify novel potential HPPD
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p-Hydroxyphenylpyruvate dioxygenase (HPPD) is not only the useful molecular target in treating life-threatening tyrosinemia type I, but also an important target for chemical herbicides. A combined in silico structure-based pharmacophore and molecular docking-based virtual screening were performed to identify novel potential HPPD inhibitors. The complex-based pharmacophore model (CBP) with 0.721 of ROC used for screening compounds showed remarkable ability to retrieve known active ligands from among decoy molecules. The ChemDiv database was screened using CBP-Hypo2 as a 3D query, and the best-fit hits subjected to molecular docking with two methods of LibDock and CDOCKER in Accelrys Discovery Studio 2.5 (DS 2.5) to discern interactions with key residues at the active site of HPPD. Four compounds with top rankings in the HipHop model and well-known binding model were finally chosen as lead compounds with potential inhibitory effects on the active site of target. The results provided powerful insight into the development of novel HPPD inhibitors herbicides using computational techniques. Full article
(This article belongs to the Section Theoretical Chemistry)
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Open AccessArticle Isoprenoids Production from Lipid-Extracted Microalgal Biomass Residues Using Engineered E. coli
Molecules 2017, 22(6), 960; doi:10.3390/molecules22060960
Received: 20 April 2017 / Revised: 1 June 2017 / Accepted: 7 June 2017 / Published: 9 June 2017
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Abstract
Microalgae are recognized as a third generation feedstock for biofuel production due to their rapid growth rates and lignin-free characteristics. In this study, a lipid extracted microalgal biomass residues was used as the raw material to produce isoprene, α-pinene and β-pinene with an
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Microalgae are recognized as a third generation feedstock for biofuel production due to their rapid growth rates and lignin-free characteristics. In this study, a lipid extracted microalgal biomass residues was used as the raw material to produce isoprene, α-pinene and β-pinene with an engineered E. coli strain. We adopted an optimal sulfuric acid hydrolysis method (1:7 ratio of solid to acid solution, 32% (w/v) concentration of sulfuric acid solution at 90 °C for 90 min) to efficiently convert holocellulose into glucose efficiently (6.37 g/L). Futhermore, we explored a novel detoxification strategy (phosphoric acid/calcium hydroxide) to remove inhibitors and notably acetic acid, furfural and 5-hydroxymethylfurfural (5-HMF) were reduced by 5.32%, different number given later 99.19% and 98.22%, respectively. Finally, the fermentation concentrations of isoprene (223.23 mg/L), α-pinene (382.21 μg/L) and β-pinene (17.4 mg/L) were achieved using the detoxified hydrolysate as the carbon source, equivalent to approximately 86.02%, 90.16% and 88.32% of those produced by the engineered E. coli strain fermented on pure glucose, respectively. Full article
(This article belongs to the Special Issue Isoprenoid Biosynthesis)
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Open AccessArticle New Strigolactone Mimics as Exogenous Signals for Rhizosphere Organisms
Molecules 2017, 22(6), 961; doi:10.3390/molecules22060961
Received: 28 April 2017 / Revised: 6 June 2017 / Accepted: 7 June 2017 / Published: 9 June 2017
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Abstract
The importance of strigolactones in plant biology prompted us to synthesize simplified strigolactone mimics effective as exogenous signals for rhizosphere organisms. New strigolactone mimics easily derived from simple and available starting materials in significant amounts were prepared and fully characterized. These compounds contain
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The importance of strigolactones in plant biology prompted us to synthesize simplified strigolactone mimics effective as exogenous signals for rhizosphere organisms. New strigolactone mimics easily derived from simple and available starting materials in significant amounts were prepared and fully characterized. These compounds contain an aromatic or heterocyclic ring, usually present in various bioactive molecules, connected by an ether link to a furan-2-one moiety. The new synthesized strigolactone mimics were confirmed to be active on plant pathogenic fungi and parasitic weed seeds. Full article
(This article belongs to the Special Issue Natural Product Inspired Scaffolds Designs)
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Open AccessArticle Subcritical Water Chromatography with Electrochemical Detection
Molecules 2017, 22(6), 962; doi:10.3390/molecules22060962
Received: 9 May 2017 / Revised: 3 June 2017 / Accepted: 7 June 2017 / Published: 9 June 2017
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Abstract
Reverse phase liquid chromatography (RPLC) is a commonly used separation and analysis technique. RPLC typically employs mixtures of organic solvents and water or aqueous buffers as the mobile phase. With RPLC being used on a global scale, enormous quantities of organic solvents are
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Reverse phase liquid chromatography (RPLC) is a commonly used separation and analysis technique. RPLC typically employs mixtures of organic solvents and water or aqueous buffers as the mobile phase. With RPLC being used on a global scale, enormous quantities of organic solvents are consumed every day. In addition to the purchasing cost of the hazardous solvents, the issue of waste disposal is another concern. At ambient temperature, water is too polar to dissolve many organic substances. Therefore, although water is nontoxic it cannot be used to replace the mobile phase in RPLC since organic analytes will not be eluted. Subcritical water chromatography may be an alternative. The characteristics of water, such as polarity, surface tension, and viscosity, can be altered by manipulating water’s temperature, thus making it behave like an organic solvent. The aim of this study was to evaluate the feasibility of separation using water mobile phase and detection by an electrochemical (EC) detector. The classes of analytes studied were neurotransmitters/metabolites, nucleic acids/heterocyclic bases, and capsaicinoids. Both isothermal and temperature-programmed separations were carried out. The separation temperature ranged from 25 to 100 °C. For separations of all three classes of solutes, the retention time was decreased with increasing temperature, thus shortening the analysis time. The peaks also became narrower as temperature increased. The limit of detection of neurotransmitters/metabolites ranges from 0.112 to 0.224 ppm. Full article
(This article belongs to the Special Issue Sub- and Supercritical Fluids and Green Chemistry)
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Open AccessFeature PaperArticle Self-Assembled Lipid Nanoparticles for Oral Delivery of Heparin-Coated Iron Oxide Nanoparticles for Theranostic Purposes
Molecules 2017, 22(6), 963; doi:10.3390/molecules22060963
Received: 12 May 2017 / Revised: 1 June 2017 / Accepted: 5 June 2017 / Published: 9 June 2017
Cited by 2 | PDF Full-text (5165 KB) | HTML Full-text | XML Full-text
Abstract
Recently, solid lipid nanoparticles (SLNs) have attracted increasing attention owing to their potential as an oral delivery system, promoting intestinal absorption in the lymphatic circulation which plays a role in disseminating metastatic cancer cells and infectious agents throughout the body. SLN features can
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Recently, solid lipid nanoparticles (SLNs) have attracted increasing attention owing to their potential as an oral delivery system, promoting intestinal absorption in the lymphatic circulation which plays a role in disseminating metastatic cancer cells and infectious agents throughout the body. SLN features can be exploited for the oral delivery of theranostics. Therefore, the aim of this work was to design and characterise self-assembled lipid nanoparticles (SALNs) to encapsulate and stabilise iron oxide nanoparticles non-covalently coated with heparin (Fe@hepa) as a model of a theranostic tool. SALNs were characterised for physico-chemical properties (particle size, surface charge, encapsulation efficiency, in vitro stability, and heparin leakage), as well as in vitro cytotoxicity by methyl thiazole tetrazolium (MTT) assay and cell internalisation in CaCo-2, a cell line model used as an indirect indication of intestinal lymphatic absorption. SALNs of about 180 nm, which are stable in suspension and have a high encapsulation efficiency (>90%) were obtained. SALNs were able to stabilise the heparin coating of Fe@hepa, which are typically unstable in physiological environments. Moreover, SALNs–Fe@hepa showed no cytotoxicity, although their ability to be internalised into CaCo-2 cells was highlighted by confocal microscopy analysis. Therefore, the results indicated that SALNs can be considered as a promising tool to orally deliver theranostic Fe@hepa into the lymphatic circulation, although further in vivo studies are needed to comprehend further potential applications. Full article
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Open AccessArticle UV-Curable Aliphatic Silicone Acrylate Organic–Inorganic Hybrid Coatings with Antibacterial Activity
Molecules 2017, 22(6), 964; doi:10.3390/molecules22060964
Received: 31 March 2017 / Revised: 26 May 2017 / Accepted: 7 June 2017 / Published: 9 June 2017
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Abstract
The most effective means to protect against bacterial invasion and to reduce the risk of healthcare-associated infections are antibacterial components synthesis. In this study, a novel process for the synthesis of organic–inorganic hybrid coatings containing silver nanoparticles is presented. Silver nanoparticles and polymer
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The most effective means to protect against bacterial invasion and to reduce the risk of healthcare-associated infections are antibacterial components synthesis. In this study, a novel process for the synthesis of organic–inorganic hybrid coatings containing silver nanoparticles is presented. Silver nanoparticles and polymer formation proceeds simultaneously through the in situ photoreduction of silver salt to silver nanoparticles and UV-crosslinking of bifunctional aliphatic silicone acrylate. The nanocomposite films with 0.5–1.43 wt % of silver nanoparticles concentration were obtained and investigated. The formation of silver nanoparticles in polymer matrix was confirmed via UV-visible spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy, scanning electron spectroscopy, and energy dispersive spectroscopy. Our investigations clearly show the formation of silver nanoparticles in silicone acrylate network. Direct photoreduction of silver salt by UV-radiation in the organic media produced silver nanoparticles exhibiting cubic crystal structure. The size of nanoparticles was determined to be near 20 ± 5 nm. The antibacterial activities of coatings were determined using the disc diffusion and direct contact methods. UV-curable silicone acrylate hybrid coatings exhibited antibacterial activity against harmful bacteria strains. Full article
(This article belongs to the Special Issue Antibacterial Materials and Coatings)
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Open AccessArticle Extraction Optimization, Characterization, and Bioactivities of Polysaccharides from Pinelliae Rhizoma Praeparatum Cum Alumine Employing Ultrasound-Assisted Extraction
Molecules 2017, 22(6), 965; doi:10.3390/molecules22060965
Received: 19 May 2017 / Revised: 5 June 2017 / Accepted: 7 June 2017 / Published: 9 June 2017
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Abstract
In this study, the ultrasound-assisted extraction of polysaccharides (PSA) from Pinelliae Rhizoma Praeparatum Cum Alumine (PRPCA) was optimized by response surface methodology (RSM). The structural characteristics of PSA were analyzed by UV-vis spectroscopy, infrared spectroscopy, scanning electron microscopy, high performance gel permeation chromatography
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In this study, the ultrasound-assisted extraction of polysaccharides (PSA) from Pinelliae Rhizoma Praeparatum Cum Alumine (PRPCA) was optimized by response surface methodology (RSM). The structural characteristics of PSA were analyzed by UV-vis spectroscopy, infrared spectroscopy, scanning electron microscopy, high performance gel permeation chromatography and high performance liquid chromatography, respectively. In addition, antioxidant and antimicrobial activities of PSA were studied by different in vitro assays. Results indicated that the optimal extraction conditions were as follows: the ratio of water to raw of 30 mL/g, extraction time of 46.50 min, ultrasonic temperature of 72.00 °C, and ultrasonic power of 230 W. Under these conditions, the obtained PSA yield (13.21 ± 0.37%) was closely agreed with the predicted yield by the model. The average molecular weights of the PSA were estimated to be 5.34 × 103 and 6.27 × 105 Da. Monosaccharide composition analysis indicated that PSA consisted of mannose, galactose uronic acid, glucose, galactose, arabinose with a molar ratio of 1.83:0.55:75.75:1.94:0.45. Furthermore, PSA exhibited moderate antioxidant and antibacterial activities in vitro. Collectively, this study provides a promising strategy to obtain bioactive polysaccharides from processed products of herbal medicines. Full article
(This article belongs to the Special Issue Natural Polysaccharides)
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Open AccessFeature PaperArticle Dichlorotrifluoromethoxyacetic Acid: Preparation and Reactivity
Molecules 2017, 22(6), 966; doi:10.3390/molecules22060966
Received: 28 April 2017 / Revised: 6 June 2017 / Accepted: 6 June 2017 / Published: 9 June 2017
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Abstract
We describe the first gram scale preparation of the reagent dichlorotrifluoromethoxyacetic acid. This stable compound is obtained in five steps starting from the cheap diethylene glycol. The reactivity of the sodium salt of this fluorinated acid was also tested and allowed the preparation
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We describe the first gram scale preparation of the reagent dichlorotrifluoromethoxyacetic acid. This stable compound is obtained in five steps starting from the cheap diethylene glycol. The reactivity of the sodium salt of this fluorinated acid was also tested and allowed the preparation of new amides. Full article
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Open AccessArticle Anti-Inflammatory and Neuroprotective Constituents from the Peels of Citrus grandis
Molecules 2017, 22(6), 967; doi:10.3390/molecules22060967
Received: 19 April 2017 / Revised: 8 June 2017 / Accepted: 8 June 2017 / Published: 9 June 2017
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Abstract
A series of chromatographic separations performed on the ethanol extracts of the peels of Citrus grandis has led to the characterization of forty compounds, including seventeen coumarins, eight flavonoids, two triterpenoids, four benzenoids, two steroids, one lignan, one amide, and five other compounds,
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A series of chromatographic separations performed on the ethanol extracts of the peels of Citrus grandis has led to the characterization of forty compounds, including seventeen coumarins, eight flavonoids, two triterpenoids, four benzenoids, two steroids, one lignan, one amide, and five other compounds, respectively. The chemical structures of the purified constituents were identified on the basis of spectroscopic elucidation, including 1D- and 2D-NMR, UV, IR, and mass spectrometric analysis. Most of the isolated compounds were examined for their inhibition of superoxide anion generation and elastase release by human neutrophils. Among the isolates, isomeranzin (3), 17,18-dihydroxybergamottin (12), epoxybergamottin (13), rhoifolin (19), vitexicarpin (22) and 4-hydroxybenzaldehyde (29) displayed the most significant inhibition of superoxide anion generation and elastase release with IC50 values ranged from 0.54 to 7.57 μM, and 0.43 to 4.33 μM, respectively. In addition, 7-hydroxy-8-(2′-hydroxy-3′-methylbut-3′-enyl)coumarin (8) and 17,18-dihydroxybergamottin (12) also exhibited the protection of neurons against A-mediated neurotoxicity at 50 μM. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Hemi-Synthesis and Anti-Oomycete Activity of Analogues of Isocordoin
Molecules 2017, 22(6), 968; doi:10.3390/molecules22060968
Received: 25 May 2017 / Revised: 7 June 2017 / Accepted: 8 June 2017 / Published: 10 June 2017
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Abstract
An efficient synthesis of a series of 4′-oxyalkyl-isocordoin analogues (28) is reported for the first time. Their structures were confirmed by 1H-NMR, 13C-NMR, and HRMS. Their anti-oomycete activity was evaluated by mycelium and spores inhibition assay against
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An efficient synthesis of a series of 4′-oxyalkyl-isocordoin analogues (28) is reported for the first time. Their structures were confirmed by 1H-NMR, 13C-NMR, and HRMS. Their anti-oomycete activity was evaluated by mycelium and spores inhibition assay against two selected pathogenic oomycetes strains: Saprolegnia parasitica and Saprolegnia australis. The entire series of isocordoin derivatives (except compound 7) showed high inhibitory activity against these oomycete strains. Among them, compound 2 exhibited strong activity, with minimum inhibitory concentration (MIC) and minimum oomyceticidal concentration (MOC) values of 50 µg/mL and 75 µg/mL, respectively. The results showed that 4′-oxyalkylated analogues of isocordoin could be potential anti-oomycete agents. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Docosahexaenoic Acid Induces Expression of Heme Oxygenase-1 and NAD(P)H:quinone Oxidoreductase through Activation of Nrf2 in Human Mammary Epithelial Cells
Molecules 2017, 22(6), 969; doi:10.3390/molecules22060969
Received: 6 March 2017 / Revised: 4 June 2017 / Accepted: 5 June 2017 / Published: 10 June 2017
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Abstract
Docosahexaenoic acid (DHA), an ω-3 fatty acid abundant in fish oils, has diverse health beneficial effects, such as anti-oxidative, anti-inflammatory, neuroprotective, and chemopreventive activities. In this study, we found that DHA induced expression of two representative antioxidant/cytoprotective enzymes, heme oxygenase-1 (HO-1) and NAD(P)H:quinone
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Docosahexaenoic acid (DHA), an ω-3 fatty acid abundant in fish oils, has diverse health beneficial effects, such as anti-oxidative, anti-inflammatory, neuroprotective, and chemopreventive activities. In this study, we found that DHA induced expression of two representative antioxidant/cytoprotective enzymes, heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase (NQO1), in human mammary epithealial (MCF-10A) cells. DHA-induced upregulation of these enzymes was accompanied by enhanced translocation of the redox-sensitive transcription factor Nrf2 into the nucleus and its binding to antioxidant response element. Nrf2 gene silencing by siRNA abolished the DHA-induced expression of HO-1 and NQO1 proteins. When MCF-10A cells were transfected with mutant constructs in which the cysteine 151 or 288 residue of Keap1 was replaced by serine, DHA-induced expression of HO-1 and NQO1 was markedly reduced. Moreover, DHA activated protein kinase C (PKC)δ and induced Nrf2 phosphorylation. DHA-induced phosphorylation of Nrf2 was abrogated by the pharmacological PKCδ inhibitor rottlerin or siRNA knockdown of its gene expression. The antioxidants N-acetyl-l-cysteine and Trolox attenuated DHA-induced activation of PKCδ, phosphorylation of Nrf2, and and its target protein expression. In conclusion, DHA activates Nrf2, possibly through modification of critical Keap1 cysteine 288 residue and PKCδ-mediated phosphorylation of Nrf2, leading to upregulation of HO-1 and NQO1 expression. Full article
(This article belongs to the Special Issue Cancer Chemoprevention)
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Open AccessArticle Synthesis and Bioactivity Evaluation of N-Arylsulfonylindole Analogs Bearing a Rhodanine Moiety as Antibacterial Agents