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Molecules, Volume 21, Issue 9 (September 2016)

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Cover Story This study presents information about the chemical and bioactive properties of nine wild edible [...] Read more.
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Editorial

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Open AccessEditorial Special Issue “Biomaterials and Bioprinting”
Molecules 2016, 21(9), 1231; doi:10.3390/molecules21091231
Received: 9 September 2016 / Accepted: 10 September 2016 / Published: 14 September 2016
Cited by 1 | PDF Full-text (143 KB) | HTML Full-text | XML Full-text
Abstract
The emergence of bioprinting in recent years represents a marvellous advancement in 3D printing technology. It expands the range of 3D printable materials from the world of non-living materials into the world of living materials. Biomaterials play an important role in this paradigm
[...] Read more.
The emergence of bioprinting in recent years represents a marvellous advancement in 3D printing technology. It expands the range of 3D printable materials from the world of non-living materials into the world of living materials. Biomaterials play an important role in this paradigm shift. This Special Issue focuses on biomaterials and bioprinting and contains eight articles covering a number of recent topics in this emerging area. Full article
(This article belongs to the Special Issue Biomaterials and Bioprinting)
Open AccessEditorial Does a Graphical Abstract Bring More Visibility to Your Paper?
Molecules 2016, 21(9), 1247; doi:10.3390/molecules21091247
Received: 14 September 2016 / Accepted: 15 September 2016 / Published: 18 September 2016
Cited by 3 | PDF Full-text (164 KB) | HTML Full-text | XML Full-text
Abstract
A graphical abstract (GA) represents a piece of artwork that is intended to summarize the main findings of an article for readers at a single glance. Many publishers currently encourage authors to supplement their articles with GAs, in the hope that such a
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A graphical abstract (GA) represents a piece of artwork that is intended to summarize the main findings of an article for readers at a single glance. Many publishers currently encourage authors to supplement their articles with GAs, in the hope that such a convenient visual summary will facilitate readers with a clearer outline of papers that are of interest and will result in improved overall visibility of the respective publication. To test this assumption, we statistically compared publications with or without GA published in Molecules between March 2014 and March 2015 with regard to several output parameters reflecting visibility. Contrary to our expectations, manuscripts published without GA performed significantly better in terms of PDF downloads, abstract views, and total citations than manuscripts with GA. To the best of our knowledge, this is the first empirical study on the effectiveness of GA for attracting attention to scientific publications. Full article
(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)
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Research

Jump to: Editorial, Review, Other

Open AccessArticle DNA Three Way Junction Core Decorated with Amino Acids-Like Residues-Synthesis and Characterization
Molecules 2016, 21(9), 1082; doi:10.3390/molecules21091082
Received: 5 July 2016 / Revised: 8 August 2016 / Accepted: 10 August 2016 / Published: 23 August 2016
PDF Full-text (1251 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Construction and physico-chemical behavior of DNA three way junction (3WJ) functionalized by protein-like residues (imidazole, alcohol and carboxylic acid) at unpaired positions at the core is described. One 5′-C(S)-propargyl-thymidine nucleotide was specifically incorporated on each strand to react through a post
[...] Read more.
Construction and physico-chemical behavior of DNA three way junction (3WJ) functionalized by protein-like residues (imidazole, alcohol and carboxylic acid) at unpaired positions at the core is described. One 5′-C(S)-propargyl-thymidine nucleotide was specifically incorporated on each strand to react through a post synthetic CuACC reaction with either protected imidazolyl-, hydroxyl- or carboxyl-azide. Structural impacts of 5′-C(S)-functionalization were investigated to evaluate how 3WJ flexibility/stability is affected. Full article
(This article belongs to the collection New Frontiers in Nucleic Acid Chemistry)
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Open AccessArticle Elucidation of Differential Accumulation of 1-Phenylethanol in Flowers and Leaves of Tea (Camellia sinensis) Plants
Molecules 2016, 21(9), 1106; doi:10.3390/molecules21091106
Received: 1 August 2016 / Revised: 16 August 2016 / Accepted: 19 August 2016 / Published: 23 August 2016
Cited by 2 | PDF Full-text (1977 KB) | HTML Full-text | XML Full-text
Abstract
1-Phenylethanol (1PE) is a major aromatic volatile in tea (Camellia sinensis) flowers, whereas it occurs in a much smaller amounts in leaves. Enzymes involved in the formation of 1PE in plants and the reason why 1PE differentially accumulates in plants is
[...] Read more.
1-Phenylethanol (1PE) is a major aromatic volatile in tea (Camellia sinensis) flowers, whereas it occurs in a much smaller amounts in leaves. Enzymes involved in the formation of 1PE in plants and the reason why 1PE differentially accumulates in plants is unknown. In the present study, enzymes in the last step leading from acetophenone to 1PE were isolated from tea flowers by traditional biochemical chromatography. The two types of partially purified enzymes were proposed to be responsible for formations of (R)-1PE and (S)-1PE, respectively. Tea leaves also contained such enzymes having equivalent activities with flowers. Stable isotope labeling experiments indicated that weak transformation from l-phenylalanine to acetophenone in leaves mainly resulted in little occurrence of 1PE in leaves. This study provided an example that differential distribution of some metabolites in plant tissues was not only determined by enzyme(s) in the last step of metabolite formation, but also can be due to substrate availability. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
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Open AccessArticle Neuroprotective Effects of a Standardized Flavonoid Extract from Safflower against a Rotenone-Induced Rat Model of Parkinson’s Disease
Molecules 2016, 21(9), 1107; doi:10.3390/molecules21091107
Received: 22 April 2016 / Revised: 16 June 2016 / Accepted: 16 August 2016 / Published: 24 August 2016
Cited by 7 | PDF Full-text (4336 KB) | HTML Full-text | XML Full-text
Abstract
Parkinson’s disease (PD) is a major age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra par compacta (SNpc). Rotenone is a neurotoxin that is routinely used to model PD to aid in understanding the mechanisms of neuronal death.
[...] Read more.
Parkinson’s disease (PD) is a major age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra par compacta (SNpc). Rotenone is a neurotoxin that is routinely used to model PD to aid in understanding the mechanisms of neuronal death. Safflower (Carthamus tinctorius. L.) has long been used to treat cerebrovascular diseases in China. This plant contains flavonoids, which have been reported to be effective in models of neurodegenerative disease. We previously reported that kaempferol derivatives from safflower could bind DJ-1, a protein associated with PD, and that a flavonoid extract from safflower exhibited neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD. In this study, a standardized safflower flavonoid extract (SAFE) was isolated from safflower and found to primarily contain flavonoids. The aim of the current study was to confirm the neuroprotective effects of SAFE in rotenone-induced Parkinson rats. The results showed that SAFE treatment increased body weight and improved rearing behavior and grip strength. SAFE (35 or 70 mg/kg/day) treatment reversed the decreased protein expression of tyrosine hydroxylase, dopamine transporter and DJ-1 and increased the levels of dopamine and its metabolite. In contrast, acetylcholine levels were decreased. SAFE treatment also led to partial inhibition of PD-associated changes in extracellular space diffusion parameters. These changes were detected using a magnetic resonance imaging (MRI) tracer-based method, which provides novel information regarding neuronal loss and astrocyte activation. Thus, our results indicate that SAFE represents a potential therapeutic herbal treatment for PD. Full article
(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)
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Open AccessArticle Marine Toxin Okadaic Acid Affects the Immune Function of Bay Scallop (Argopecten irradians)
Molecules 2016, 21(9), 1108; doi:10.3390/molecules21091108
Received: 15 July 2016 / Revised: 12 August 2016 / Accepted: 18 August 2016 / Published: 24 August 2016
Cited by 2 | PDF Full-text (1298 KB) | HTML Full-text | XML Full-text
Abstract
Okadaic acid (OA) is produced by dinoflagellates during harmful algal blooms and is a diarrhetic shellfish poisoning toxin. This toxin is particularly problematic for bivalves that are cultured for human consumption. This study aimed to reveal the effects of exposure to OA on
[...] Read more.
Okadaic acid (OA) is produced by dinoflagellates during harmful algal blooms and is a diarrhetic shellfish poisoning toxin. This toxin is particularly problematic for bivalves that are cultured for human consumption. This study aimed to reveal the effects of exposure to OA on the immune responses of bay scallop, Argopecten irradians. Various immunological parameters were assessed (total hemocyte counts (THC), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), lactate dehydrogenase (LDH), and nitric oxide (NO) in the hemolymph of scallops at 3, 6, 12, 24, and 48 h post-exposure (hpe) to different concentrations of OA (50, 100, and 500 nM). Moreover, the expression of immune-system-related genes (CLT-6, FREP, HSP90, MT, and Cu/ZnSOD) was also measured. Results showed that ROS, MDA, and NO levels and LDH activity were enhanced after exposure to different concentrations of OA; however, both THC and GSH decreased between 24–48 hpe. The expression of immune-system-related genes was also assessed at different time points during the exposure period. Overall, our results suggest that exposure to OA had negative effects on immune system function, increased oxygenic stress, and disrupted metabolism of bay scallops. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Stability, Antioxidant Capacity and Degradation Kinetics of Pelargonidin-3-glucoside Exposed to Ultrasound Power at Low Temperature
Molecules 2016, 21(9), 1109; doi:10.3390/molecules21091109
Received: 29 April 2016 / Revised: 5 August 2016 / Accepted: 10 August 2016 / Published: 24 August 2016
PDF Full-text (1195 KB) | HTML Full-text | XML Full-text
Abstract
As an alternative preservation method to thermal treatment, ultrasound is a novel non-thermal processing technology that can significantly avoid undesirable nutritional changes. However, recently literature indicated that anthocyanin degradation occurred when high amplitude ultrasound was applied to juice. This work mainly studied the
[...] Read more.
As an alternative preservation method to thermal treatment, ultrasound is a novel non-thermal processing technology that can significantly avoid undesirable nutritional changes. However, recently literature indicated that anthocyanin degradation occurred when high amplitude ultrasound was applied to juice. This work mainly studied the effect of ultrasound on the stability and antioxidant capacity of pelargonidin-3-glucoside (Pg-3-glu) and the correlation between anthocyanin degradation and •OH generation in a simulated system. Results indicated that the spectral intensities of Pg-3-glu decreased with increasing ultrasound power (200–500 W) and treatment time (0–60 min). The degradation trend was consistent with first-order reaction kinetics (R2 > 0.9100). Further study showed that there was a good linear correlation between Pg-3-glu degradation and •OH production (R2 = 0.8790), which indicated the important role of •OH in the degradation of anthocyanin during ultrasound exposure. Moreover, a decrease in the antioxidant activity of solution(s) containing Pg-3-glu as evaluated by the DPPH and FRAP methods was observed after ultrasound treatment. Full article
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Open AccessArticle In Vivo Metabolite Profiling of a Purified Ellagitannin Isolated from Polygonum capitatum in Rats
Molecules 2016, 21(9), 1110; doi:10.3390/molecules21091110
Received: 24 July 2016 / Revised: 17 August 2016 / Accepted: 19 August 2016 / Published: 24 August 2016
PDF Full-text (1382 KB) | HTML Full-text | XML Full-text
Abstract
Ellagitannin is a common compound in food and herbs, but there are few detailed studies on the metabolism of purified ellagitannins. FR429 is a purified ellagitannin with antitumor potential, which is from Polygonum capitatum Buch.-Ham.ex D. Don. The present study was designed to
[...] Read more.
Ellagitannin is a common compound in food and herbs, but there are few detailed studies on the metabolism of purified ellagitannins. FR429 is a purified ellagitannin with antitumor potential, which is from Polygonum capitatum Buch.-Ham.ex D. Don. The present study was designed to investigate the metabolic profiles of FR429 in rats in vivo. Using liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MSn-IT-TOF), total eight metabolites were found in rat bile and urine after intravenous administration of FR429, but could not be detected in plasma. These metabolites were ellagic acid, mono-methylated FR429, ellagic acid methyl ether glucuronide, ellagic acid methyl ether diglucuronide, ellagic acid dimethyl ether glucuronide, and ellagic acid dimethyl ether diglucuronide. It was concluded that methylation and subsequent glucuronidation were the major metabolic pathways of FR429 in rats in vivo. This is the first report on the in vivo metabolism of the purified ellagitannin in rats. Full article
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Open AccessArticle Ball Milling Assisted Solvent and Catalyst Free Synthesis of Benzimidazoles and Their Derivatives
Molecules 2016, 21(9), 1111; doi:10.3390/molecules21091111
Received: 31 July 2016 / Revised: 13 August 2016 / Accepted: 15 August 2016 / Published: 24 August 2016
Cited by 1 | PDF Full-text (1177 KB) | HTML Full-text | XML Full-text
Abstract
Benzoic acid and o-phenylenediamine efficiently reacted under the green solvent-free Ball Milling method. Several reaction parameters were investigated such as rotation frequency; milling balls weight and milling time. The optimum reaction condition was milling with 56.6 g weight of balls at 20
[...] Read more.
Benzoic acid and o-phenylenediamine efficiently reacted under the green solvent-free Ball Milling method. Several reaction parameters were investigated such as rotation frequency; milling balls weight and milling time. The optimum reaction condition was milling with 56.6 g weight of balls at 20 Hz frequency for one hour milling time. The study was extended for synthesis of a series of benzimidazol-2-one or benzimidazol-2-thione using different aldehydes; carboxylic acids; urea; thiourea or ammonium thiocyanate with o-phenylenediamine. Moreover; the alkylation of benzimidazolone or benzimidazolthione using ethyl chloroacetate was also studied. Full article
(This article belongs to the Special Issue Mechanochemistry)
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Open AccessCommunication Three New Isoprenylated Flavonoids from the Root Bark of Morus alba
Molecules 2016, 21(9), 1112; doi:10.3390/molecules21091112
Received: 12 July 2016 / Revised: 16 August 2016 / Accepted: 19 August 2016 / Published: 24 August 2016
Cited by 2 | PDF Full-text (797 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phytochemical investigation of the root bark of Morus alba has led to the isolation and identification of three new isoprenylated flavonoids, namely sanggenon U (1), sanggenon V (2), and sanggenon W (3), along with four known isoprenylated
[...] Read more.
Phytochemical investigation of the root bark of Morus alba has led to the isolation and identification of three new isoprenylated flavonoids, namely sanggenon U (1), sanggenon V (2), and sanggenon W (3), along with four known isoprenylated flavonoids: euchrenone a7 (4), sanggenon J (5), kuwanon E (6), and kuwanon S (7). All compounds were isolated by repeated silica gel (SiO2), octadecyl SiO2 (ODS), and Sephadex LH-20 open column chromatography. The structure of the compounds were determined based on spectroscopic analyses, including nuclear magnetic resonance (NMR), mass spectrometry (MS), circular dichroism (CD), and infrared (IR). In addition, compounds 14 were isolated for the first time from the root bark of M. alba in this study. Full article
(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)
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Open AccessArticle Efficient Synthesis of Fully Substituted Pyrrolidine-Fused 3-Spirooxindoles via 1,3-Dipolar Cycloaddition of Aziridine and 3-Ylideneoxindole
Molecules 2016, 21(9), 1113; doi:10.3390/molecules21091113
Received: 26 July 2016 / Revised: 12 August 2016 / Accepted: 18 August 2016 / Published: 24 August 2016
PDF Full-text (1465 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Drug-like spirocyclic scaffolds have been prepared by fusing fully functionalized pyrrolidine with oxindoles in an approach based on 1,3-dipolar cycloaddition. Reaction between aziridine and 3-ylideneoxindole generated diverse spirooxindole-pyrrolidines in good yield (up to 95%) with high diastereoselectivity (up to >20:1). The reaction also
[...] Read more.
Drug-like spirocyclic scaffolds have been prepared by fusing fully functionalized pyrrolidine with oxindoles in an approach based on 1,3-dipolar cycloaddition. Reaction between aziridine and 3-ylideneoxindole generated diverse spirooxindole-pyrrolidines in good yield (up to 95%) with high diastereoselectivity (up to >20:1). The reaction also proceeded smoothly with several other synthetically useful activated trisubstituted olefins. The mild reaction conditions, short reaction times, and high tolerance for various substitutions make this approach attractive for constructing pharmacologically interesting spiro-architectures. Full article
(This article belongs to the Special Issue Pericyclic Reactions)
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Open AccessArticle Identification of a New Morpholine Scaffold as a P2Y12 Receptor Antagonist
Molecules 2016, 21(9), 1114; doi:10.3390/molecules21091114
Received: 29 June 2016 / Revised: 11 August 2016 / Accepted: 22 August 2016 / Published: 24 August 2016
PDF Full-text (2034 KB) | HTML Full-text | XML Full-text
Abstract
The P2Y12 receptor is critical for platelet activation and is an attractive drug target for the prevention of atherothrombotic events. Despite the proven antithrombotic efficacy of P2Y12 inhibitors, these thienopyridine scaffolds are prodrugs that lack important features of the ideal antithrombotic agent. For
[...] Read more.
The P2Y12 receptor is critical for platelet activation and is an attractive drug target for the prevention of atherothrombotic events. Despite the proven antithrombotic efficacy of P2Y12 inhibitors, these thienopyridine scaffolds are prodrugs that lack important features of the ideal antithrombotic agent. For this reason, ticagrelor—a new chemical class of P2Y12 receptor antagonist—was developed, but it can cause shortness of breath and various types of bleeding. Moreover, ticagrelor is a cytochrome P450 3A4 substrate/inhibitor and, therefore, caution should be exercised when it is used concomitantly with strong CYP3A4 inducers/inhibitors. There is a need for novel P2Y12 receptor antagonist scaffolds that are reversible and have high efficacy without associated side effects. Here, we describe a novel antagonist containing a morpholine moiety that was identified by screening libraries of commercially available compounds. The molecule, Compound E, acted on P2Y12, but not P2Y1 and P2Y13, and exhibited pharmacological characteristics that were distinct from those of ticagrelor, acting instead on P2Y12 via an allosteric mechanism. These results provide a basis for the development/optimization of a new class of P2Y12 antagonists. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Ionic Liquids as Solvents for Rhodium and Platinum Catalysts Used in Hydrosilylation Reaction
Molecules 2016, 21(9), 1115; doi:10.3390/molecules21091115
Received: 28 June 2016 / Revised: 8 August 2016 / Accepted: 12 August 2016 / Published: 24 August 2016
Cited by 3 | PDF Full-text (2700 KB) | HTML Full-text | XML Full-text | Correction
Abstract
A group of imidazolium and pyridinium based ionic liquids has been synthetized, and their ability to dissolve and activate the catalysts used in hydrosilylation reaction of 1-octane and 1,1,1,3,5,5,5-heptamethyltrisiloxane was investigated. An organometallic catalyst as well as inorganic complexes of platinum and rhodium
[...] Read more.
A group of imidazolium and pyridinium based ionic liquids has been synthetized, and their ability to dissolve and activate the catalysts used in hydrosilylation reaction of 1-octane and 1,1,1,3,5,5,5-heptamethyltrisiloxane was investigated. An organometallic catalyst as well as inorganic complexes of platinum and rhodium dissolved in ionic liquids were used, forming liquid solutions not miscible with the substrates or with the products of the reaction. The results show that application of such a simple biphasic catalytic system enables reuse of ionic liquid phase with catalysts in multiple reaction cycles reducing the costs and decreasing the amount of catalyst needed per mole of product. Full article
(This article belongs to the Special Issue Organic Reaction in Green Solvents)
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Open AccessArticle Bioactive 2(1H)-Pyrazinones and Diketopiperazine Alkaloids from a Tunicate-Derived Actinomycete Streptomyces sp.
Molecules 2016, 21(9), 1116; doi:10.3390/molecules21091116
Received: 8 May 2016 / Revised: 11 August 2016 / Accepted: 16 August 2016 / Published: 24 August 2016
Cited by 4 | PDF Full-text (534 KB) | HTML Full-text | XML Full-text
Abstract
As a part of our ongoing effort to allocate marine microbial bioactive leads, a tunicate-derived actinomycete, Streptomyces sp. Did-27, was investigated. Three new 2(1H)-pyrazinones derivatives, (S)-6-(sec-butyl)-3-isopropylpyrazin-2(1H)-one (1), (S)-3-(sec-butyl)-6-isopropylpyrazin-2(1H
[...] Read more.
As a part of our ongoing effort to allocate marine microbial bioactive leads, a tunicate-derived actinomycete, Streptomyces sp. Did-27, was investigated. Three new 2(1H)-pyrazinones derivatives, (S)-6-(sec-butyl)-3-isopropylpyrazin-2(1H)-one (1), (S)-3-(sec-butyl)-6-isopropylpyrazin-2(1H)-one (2) and (S)-6-(sec-butyl)-3-isobutylpyrazin-2(1H)-one (3), together with the known (1H)-pyrazinones analogues deoxymutaaspergillic acid (4), 3,6-diisobutyl-2(1H)-pyrazinone (5) and 3,6-di-sec-butyl-2(1H)-pyrazinone (6), and the diketopiperazine alkaloids cyclo(6-OH-d-Pro-l-Phe) (7), bacillusamide B (8), cyclo(l-Pro-l-Leu) and cyclo(l-Pro-l-Ile) (10) were isolated from this strain. The structures of the compounds were determined by study of their one- and two-dimensional NMR spectra as well as high-resolution mass spectral determinations. Compound 4 was reported previously as a synthetic product, while compound 6 was reported as 2-hydroxy-3,6-di-sec-butylpyrazine. Herein, we report the complete NMR data for compounds 4 and 6. The compounds were evaluated for their cytotoxic activities against three cell lines. Compound 5 showed potent and selective activity against HCT-116 cell line with IC50 of 1.5 μg/mL, while 110 showed variable cytotoxic activities against these cancer cell lines. These results provide further understanding about the chemistry and bioactivities of the alkylated 2(1H)-pyrazinone derivatives. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Truncation Derivatives of the S-Layer Protein of Sporosarcina ureae ATCC 13881 (SslA): Towards Elucidation of the Protein Domain Responsible for Self-Assembly
Molecules 2016, 21(9), 1117; doi:10.3390/molecules21091117
Received: 30 June 2016 / Revised: 12 August 2016 / Accepted: 19 August 2016 / Published: 24 August 2016
PDF Full-text (3744 KB) | HTML Full-text | XML Full-text
Abstract
The cell surface of Sporosarcina ureae ATCC 13881 is covered by an S-layer (SslA) consisting of identical protein subunits that assemble into lattices exhibiting square symmetry. In this work the self-assembly properties of the recombinant SslA were characterised with an emphasis on the
[...] Read more.
The cell surface of Sporosarcina ureae ATCC 13881 is covered by an S-layer (SslA) consisting of identical protein subunits that assemble into lattices exhibiting square symmetry. In this work the self-assembly properties of the recombinant SslA were characterised with an emphasis on the identification of protein regions responsible for self-assembly. To this end, recombinant mature SslA (aa 31-1097) and three SslA truncation derivatives (one N-terminal, one C-terminal and one CN-terminal) were produced in a heterologous expression system, isolated, purified and their properties analysed by in vitro recrystallisation experiments on a functionalised silicon wafer. As a result, recombinant mature SslA self-assembled into crystalline monolayers with lattices resembling the one of the wild-type SslA. The study identifies the central protein domain consisting of amino acids 341-925 self-sufficient for self-assembly. Neither the first 341 amino acids nor the last 172 amino acids of the protein sequence are required to self-assemble into lattices. Full article
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Open AccessArticle Adaptive Responses to Oxidative Stress in the Filamentous Fungal Shiraia bambusicola
Molecules 2016, 21(9), 1118; doi:10.3390/molecules21091118
Received: 30 June 2016 / Revised: 1 August 2016 / Accepted: 19 August 2016 / Published: 24 August 2016
Cited by 3 | PDF Full-text (2615 KB) | HTML Full-text | XML Full-text
Abstract
Shiraia bambusicola can retain excellent physiological activity when challenged with maximal photo-activated hypocrellin, which causes cellular oxidative stress. The protective mechanism of this fungus against oxidative stress has not yet been reported. We evaluated the biomass and hypocrellin biosynthesis of Shiraia sp. SUPER-H168
[...] Read more.
Shiraia bambusicola can retain excellent physiological activity when challenged with maximal photo-activated hypocrellin, which causes cellular oxidative stress. The protective mechanism of this fungus against oxidative stress has not yet been reported. We evaluated the biomass and hypocrellin biosynthesis of Shiraia sp. SUPER-H168 when treated with high concentrations of H2O2. Hypocrellin production was improved by nearly 27% and 25% after 72 h incubation with 10 mM and 20 mM H2O2, respectively, while the inhibition ratios of exogenous 20 mM H2O2 on wild S. bambusicola and a hypocrellin-deficient strain were 20% and 33%, respectively. Under exogenous oxidative stress, the specific activities of catalase, glutathione reductase, and superoxide dismutase were significantly increased. These changes may allow Shiraia to maintain normal life activities under oxidative stress. Moreover, sufficient glutathione peroxidase was produced in the SUPER-H168 and hypocrellin-deficient strains, to further ensure that S. bambusicola has excellent protective abilities against oxidative stress. This study creates the possibility that the addition of high H2O2 concentrations can stimulate fungal secondary metabolism, and will lead to a comprehensive and coherent understanding of mechanisms against oxidative stresses from high hydrogen peroxide concentrations in the filamentous fungal Shiraia sp. SUPER-H168. Full article
(This article belongs to the Special Issue Biosynthesis of Natural Products)
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Open AccessArticle Quantification of Oxidized and Unsaturated Bile Alcohols in Sea Lamprey Tissues by Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry
Molecules 2016, 21(9), 1119; doi:10.3390/molecules21091119
Received: 18 July 2016 / Revised: 20 August 2016 / Accepted: 22 August 2016 / Published: 24 August 2016
PDF Full-text (1036 KB) | HTML Full-text | XML Full-text
Abstract
A sensitive and reliable method was developed and validated for the determination of unsaturated bile alcohols in sea lamprey tissues using liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The liver, kidney, and intestine samples were extracted with acetonitrile and defatted
[...] Read more.
A sensitive and reliable method was developed and validated for the determination of unsaturated bile alcohols in sea lamprey tissues using liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The liver, kidney, and intestine samples were extracted with acetonitrile and defatted by n-hexane. Gradient UHPLC separation was performed using an Acquity BEH C18 column with a mobile phase of water and methanol containing 20 mM triethylamine. Multiple reaction monitoring modes of precursor-product ion transitions for each analyte was used. This method displayed good linearity, with correlation coefficients greater than 0.99, and was validated. Precision and accuracy (RSD %) were in the range of 0.31%–5.28%, while mean recoveries were between 84.3%–96.3%. With this technique, sea lamprey tissue samples were analyzed for unsaturated bile alcohol analytes. This method is practical and particularly suitable for widespread putative pheromone residue analysis. Full article
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Open AccessArticle Plasma and Urinary Phenolic Profiles after Acute and Repetitive Intake of Wild Blueberry
Molecules 2016, 21(9), 1120; doi:10.3390/molecules21091120
Received: 29 July 2016 / Revised: 17 August 2016 / Accepted: 17 August 2016 / Published: 25 August 2016
Cited by 5 | PDF Full-text (741 KB) | HTML Full-text | XML Full-text
Abstract
Recent studies have shown that blueberries may have cardiovascular and cognitive health benefits. In this work, we investigated the profile of plasma and urine (poly)phenol metabolites after acute and daily consumption of wild blueberries for 30 days in 18 healthy men. The inter-individual
[...] Read more.
Recent studies have shown that blueberries may have cardiovascular and cognitive health benefits. In this work, we investigated the profile of plasma and urine (poly)phenol metabolites after acute and daily consumption of wild blueberries for 30 days in 18 healthy men. The inter-individual variability in plasma and urinary polyphenol levels was also investigated. Blood samples were collected at baseline and 2 h post-consumption on day 1 and day 30. Twenty-four-hour urine was also collected on both days. A total of 61 phenolic metabolites were quantified in plasma at baseline, of which 43 increased after acute or chronic consumption of blueberries over one month. Benzoic and catechol derivatives represented more than 80% of the changes in phenolic profile after 2 h consumption on day 1, whereas hippuric and benzoic derivatives were the major compounds that increased at 0 and 2 h on day 30, respectively. The total (poly)phenol urinary excretion remained unchanged after 30 days of wild blueberry intake. The inter-individual variability ranged between 40%–48% in plasma and 47%–54% in urine. Taken together, our results illustrate that blueberry (poly)phenols are absorbed and extensively metabolized by phase II enzymes and by the gut microbiota, leading to a whole array of metabolites that may be responsible for the beneficial effects observed after blueberry consumption. Full article
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Open AccessArticle Three Novel Triterpenoids from Taraxacum officinale Roots
Molecules 2016, 21(9), 1121; doi:10.3390/molecules21091121
Received: 25 July 2016 / Revised: 19 August 2016 / Accepted: 20 August 2016 / Published: 27 August 2016
Cited by 1 | PDF Full-text (1329 KB) | HTML Full-text | XML Full-text
Abstract
Three novel lupane-, bauerane-, and euphane-type triterpenoids (13), in addition to seven known triterpenoids (410)—18β,19β-epoxy-21β-hydroxylupan-3β-yl acetate (4), 21-oxolup-18-en-3β-yl acetate (5), betulin (6), officinatrione (7), 11α-methoxyolean-12-en-3-one (8
[...] Read more.
Three novel lupane-, bauerane-, and euphane-type triterpenoids (13), in addition to seven known triterpenoids (410)—18β,19β-epoxy-21β-hydroxylupan-3β-yl acetate (4), 21-oxolup-18-en-3β-yl acetate (5), betulin (6), officinatrione (7), 11α-methoxyolean-12-en-3-one (8), eupha-7,24-dien-3-one (9), and 24-oxoeupha-7,24-dien-3β-yl acetate (10)—were isolated from the roots of Taraxacum officinale. Their structures were elucidated on the basis of spectroscopic analyses using 1D and 2D-NMR spectra and electron ionization mass spectrometry (EIMS). The effects of compounds 110 on the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated mouse peritoneal macrophages were evaluated. Compounds 4, 6, and 10 exhibited similar NO inhibitory activities to NG-monomethyl-l-arginine acetate (l-NMMA). These compounds did not exhibit cytotoxicity at an effective concentration. The results of present study suggest that compounds 4, 6, and 10 have potential as anti-inflammatory disease agents. Full article
(This article belongs to the Special Issue Triterpenes and Triterpenoids 2016)
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Open AccessArticle Keratin Protein-Catalyzed Nitroaldol (Henry) Reaction and Comparison with Other Biopolymers
Molecules 2016, 21(9), 1122; doi:10.3390/molecules21091122
Received: 15 July 2016 / Revised: 2 August 2016 / Accepted: 2 August 2016 / Published: 25 August 2016
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Abstract
Here we describe a preliminary investigation on the ability of natural keratin to catalyze the nitroaldol (Henry) reaction between aldehydes and nitroalkanes. Both aromatic and heteroaromatic aldehydes bearing strong or moderate electron-withdrawing groups were converted into the corresponding β-nitroalcohol products in both DMSO
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Here we describe a preliminary investigation on the ability of natural keratin to catalyze the nitroaldol (Henry) reaction between aldehydes and nitroalkanes. Both aromatic and heteroaromatic aldehydes bearing strong or moderate electron-withdrawing groups were converted into the corresponding β-nitroalcohol products in both DMSO and in water in the presence of tetrabutylammonium bromide (TBAB) as a phase transfer catalyst. Negligible background reactions (i.e., negative control experiment in the absence of keratin protein) were observed in these solvent systems. Aromatic aldehydes bearing electron-donating groups and aliphatic aldehydes showed poor or no conversion, respectively. In general, the reactions in water/TBAB required twice the amount of time than in DMSO to achieve similar conversions. Moreover, comparison of the kinetics of the keratin-mediated nitroaldol (Henry) reaction with other biopolymers revealed slower rates for the former and the possibility of fine-tuning the kinetics by appropriate selection of the biopolymer and solvent. Full article
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Open AccessArticle Betulin Phosphonates; Synthesis, Structure, and Cytotoxic Activity
Molecules 2016, 21(9), 1123; doi:10.3390/molecules21091123
Received: 29 July 2016 / Revised: 16 August 2016 / Accepted: 20 August 2016 / Published: 26 August 2016
Cited by 1 | PDF Full-text (1466 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Betulin derivatives are a widely studied group of compounds of natural origin due to their wide spectrum of biological activities. This paper describes new betulin derivatives, containing a phosphonate group. The allyl-vinyl isomerization and synthesis of acetylenic derivatives have been reported. Structural identification
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Betulin derivatives are a widely studied group of compounds of natural origin due to their wide spectrum of biological activities. This paper describes new betulin derivatives, containing a phosphonate group. The allyl-vinyl isomerization and synthesis of acetylenic derivatives have been reported. Structural identification of products as E and Z isomers has been carried out using 1H-, 13C-, 31P-NMR, and crystallographic analysis. The crystal structure in the orthorhombic space group and analysis of crystal packing contacts for 29-diethoxyphosphoryl-28-cyclopropylpropynoyloxy-lup-20E(29)-en-3β-ol 8a are reported. All new compounds were tested in vitro for their antiproliferative activity against human T47D (breast cancer), SNB-19 (glioblastoma), and C32 (melanoma) cell lines. Full article
(This article belongs to the Special Issue Triterpenes and Triterpenoids 2016)
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Open AccessArticle Evaluation of the Effect of Two Volatile Organic Compounds on Barley Pathogens
Molecules 2016, 21(9), 1124; doi:10.3390/molecules21091124
Received: 13 July 2016 / Revised: 22 August 2016 / Accepted: 22 August 2016 / Published: 26 August 2016
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Abstract
This study aimed to determine the effect of Volatile Organic Compounds (VOCs) on some pathogens, these VOCs were emitted during interactions of barley with Fusarium culmorum Schltdl and/or Cochliobolus sativus Shoemaker, two common root rot pathogens. Our work shows that two organic esters:
[...] Read more.
This study aimed to determine the effect of Volatile Organic Compounds (VOCs) on some pathogens, these VOCs were emitted during interactions of barley with Fusarium culmorum Schltdl and/or Cochliobolus sativus Shoemaker, two common root rot pathogens. Our work shows that two organic esters: methyl propanoate (MP) and methyl prop-2-enoate (MA) significantly reduced the development of fungi in vitro. Additional tests showed that the esters significantly inhibited spore germination of these pathogens. The activity of these VOCs on a wide range of fungal and bacterial pathogens was also tested in vitro and showed inhibitory action. The effect of the VOCs on infected barley seeds also showed plantlets growing without disease symptoms. MA and MP seem to have potential value as alternative plant protection compounds against barley bioagressors. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Cytotoxicity of Triterpenoid Alkaloids from Buxus microphylla against Human Tumor Cell Lines
Molecules 2016, 21(9), 1125; doi:10.3390/molecules21091125
Received: 19 July 2016 / Revised: 15 August 2016 / Accepted: 24 August 2016 / Published: 26 August 2016
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Abstract
Three new triterpenoid alkaloids, namely buxmicrophyllines P–R (13), were isolated from the twigs and leaves of Buxus microphylla. Their structures were elucidated on the basis of NMR and MS spectroscopic analyses. Structurally, compounds 13 belong to
[...] Read more.
Three new triterpenoid alkaloids, namely buxmicrophyllines P–R (13), were isolated from the twigs and leaves of Buxus microphylla. Their structures were elucidated on the basis of NMR and MS spectroscopic analyses. Structurally, compounds 13 belong to the 9,10-cycloartane type alkaloids. In addition, compound 3 exhibited moderate cytotoxic activities in vitro against HL-60, SMMC-7221, A-549, MCF-7, and SW480 cell lines (with IC50 values ranging from 4.51 to 15.58 μM). Full article
(This article belongs to the Special Issue Triterpenes and Triterpenoids 2016)
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Open AccessArticle Aspirination of α-Aminoalcohol (Sarpogrelate M1)
Molecules 2016, 21(9), 1126; doi:10.3390/molecules21091126
Received: 3 August 2016 / Revised: 23 August 2016 / Accepted: 24 August 2016 / Published: 25 August 2016
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Abstract
Aspirination of α-aminoalcohol (sarpogrelate M1) has been performed under various general esterification conditions. In most cases, the desired aspirinate ester was obtained at a low yield with unexpected byproducts, the formation of which was mostly derived from the chemical properties of the tertiary
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Aspirination of α-aminoalcohol (sarpogrelate M1) has been performed under various general esterification conditions. In most cases, the desired aspirinate ester was obtained at a low yield with unexpected byproducts, the formation of which was mostly derived from the chemical properties of the tertiary α-amino group. After systematic analysis of those methods, the aspirinated sarpogrelate M1 was prepared using a two-step approach combining salicylate ester formation and acetylation. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Effects of (Oxy-)Fluorination on Various High-Performance Yarns
Molecules 2016, 21(9), 1127; doi:10.3390/molecules21091127
Received: 17 August 2016 / Revised: 17 August 2016 / Accepted: 23 August 2016 / Published: 26 August 2016
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Abstract
In this work, typical high-performance yarns are oxy-fluorinated, such as carbon fibers, ultra-high-molecular-weight polyethylene, poly(p-phenylene sulfide) and poly(p-phenylene terephthalamide). The focus is on the property changes of the fiber surface, especially the wetting behavior, structure and chemical composition. Therefore,
[...] Read more.
In this work, typical high-performance yarns are oxy-fluorinated, such as carbon fibers, ultra-high-molecular-weight polyethylene, poly(p-phenylene sulfide) and poly(p-phenylene terephthalamide). The focus is on the property changes of the fiber surface, especially the wetting behavior, structure and chemical composition. Therefore, contact angle, XPS and tensile strength measurements are performed on treated and untreated fibers, while SEM is utilized to evaluate the surface structure. Different results for the fiber materials are observed. While polyethylene exhibits a relevant impact on both surface and bulk properties, polyphenylene terephthalamide and polyphenylene sulfide are only affected slightly by (oxy-)fluorination. The wetting of carbon fiber needs higher treatment intensities, but in contrast to the organic fibers, even its textile-physical properties are enhanced by the treatment. Based on these findings, the capability of (oxy-)fluorination to improve the adhesion of textiles in fiber-reinforced composite materials can be derived. Full article
(This article belongs to the Special Issue Fluorine Chemistry 2016)
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Open AccessArticle Triterpenes for Well-Balanced Scar Formation in Superficial Wounds
Molecules 2016, 21(9), 1129; doi:10.3390/molecules21091129
Received: 29 July 2016 / Revised: 22 August 2016 / Accepted: 24 August 2016 / Published: 27 August 2016
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Abstract
Triterpenes are demonstrably effective for accelerating re-epithelialisation of wounds and known to improve scar formation for superficial lesions. Among the variety of triterpenes, betuline is of particular medical interest. Topical betuline gel (TBG) received drug approval in 2016 from the European Commission as
[...] Read more.
Triterpenes are demonstrably effective for accelerating re-epithelialisation of wounds and known to improve scar formation for superficial lesions. Among the variety of triterpenes, betuline is of particular medical interest. Topical betuline gel (TBG) received drug approval in 2016 from the European Commission as the first topical therapeutic agent with the proven clinical benefit of accelerating wound healing. Two self-conducted randomized intra-individual comparison clinical studies with a total of 220 patients involved in TBG treatment of skin graft surgical wounds have been screened for data concerning the aesthetic aspect of wound healing. Three months after surgery wound treatment with TBG resulted in about 30% of cases with more discreet scars, and standard of care in about 10%. Patients themselves appreciate the results of TBG after 3 months even more (about 50%) compared to standard of care (about 10%). One year after surgery, the superiority of TBG counts for about 25% in comparison with about 10%, and from the patients’ point of view, for 25% compared to 4% under standard of care. In the majority of wound treatment cases, there is no difference visible between TBG treatment and standard of care after 1 year of scar formation. However, in comparison, TBG still offers a better chance for discreet scars and therefore happens to be superior in good care of wounds. Full article
(This article belongs to the Special Issue Triterpenes and Triterpenoids 2016)
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Open AccessArticle Characterization of a New Flavone and Tyrosinase Inhibition Constituents from the Twigs of Morus alba L.
Molecules 2016, 21(9), 1130; doi:10.3390/molecules21091130
Received: 24 July 2016 / Revised: 24 August 2016 / Accepted: 24 August 2016 / Published: 2 September 2016
Cited by 2 | PDF Full-text (1033 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The twigs of Morus alba L. were found to show strong tyrosinase inhibition activity, and the responsible active components in the extract were further investigated in this study. A flavone, named morusone (1), and sixteen known compounds 217 were
[...] Read more.
The twigs of Morus alba L. were found to show strong tyrosinase inhibition activity, and the responsible active components in the extract were further investigated in this study. A flavone, named morusone (1), and sixteen known compounds 217 were isolated from M. alba twigs and their structures were identified by interpretation of the corresponding ESI-MS and NMR spectral data. In the tyrosinase inhibitory test, the compounds steppogenin (IC50 0.98 ± 0.01 µM), 2,4,2′,4′-tetrahydroxychalcone (IC50 0.07 ± 0.02 µM), morachalcone A (IC50 0.08 ± 0.02 µM), oxyresveratrol (IC50 0.10 ± 0.01 µM), and moracin M (8.00 ± 0.22 µM) exhibited significant tyrosinase inhibition activities, much stronger than that of the positive control kojic acid. These results suggest that M. alba twig extract should served as a good source of natural tyrosinase inhibitors for use in foods as antibrowning agents or in cosmetics as skin-whitening agents. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle New Deferoxamine Glycoconjugates Produced upon Overexpression of Pathway-Specific Regulatory Gene in the Marine Sponge-Derived Streptomyces albus PVA94-07
Molecules 2016, 21(9), 1131; doi:10.3390/molecules21091131
Received: 1 July 2016 / Revised: 22 August 2016 / Accepted: 24 August 2016 / Published: 27 August 2016
Cited by 1 | PDF Full-text (1016 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Activation of silent biosynthetic gene clusters in Streptomyces bacteria via overexpression of cluster-specific regulatory genes is a promising strategy for the discovery of novel bioactive secondary metabolites. This approach was used in an attempt to activate a cryptic gene cluster in a marine
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Activation of silent biosynthetic gene clusters in Streptomyces bacteria via overexpression of cluster-specific regulatory genes is a promising strategy for the discovery of novel bioactive secondary metabolites. This approach was used in an attempt to activate a cryptic gene cluster in a marine sponge-derived Streptomyces albus PVA94-07 presumably governing the biosynthesis of peptide-based secondary metabolites. While no new peptide-based metabolites were detected in the recombinant strain, it was shown to produce at least four new analogues of deferoxamine with additional acyl and sugar moieties, for which chemical structures were fully elucidated. Biological activity tests of two of the new deferoxamine analogues revealed weak activity against Escherichia coli. The gene knockout experiment in the gene cluster targeted for activation, as well as overexpression of certain genes from this cluster did not have an effect on the production of these compounds by the strain overexpressing the regulator. It seems plausible that the production of such compounds is a response to stress imposed by the production of an as-yet unidentified metabolite specified by the cryptic cluster. Full article
(This article belongs to the Special Issue Genomics-based Discovery of Microbial Natural Products)
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Open AccessArticle Antidiarrheal Thymol Derivatives from Ageratina glabrata. Structure and Absolute Configuration of 10-Benzoyloxy-8,9-epoxy-6-hydroxythymol Isobutyrate
Molecules 2016, 21(9), 1132; doi:10.3390/molecules21091132
Received: 7 July 2016 / Revised: 4 August 2016 / Accepted: 24 August 2016 / Published: 12 September 2016
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Abstract
Chemical investigation of the leaves from Ageratina glabrata yielded four new thymol derivatives, namely: 10-benzoyloxy-8,9-dehydro-6-hydroxythymol isobutyrate (4), 10-benzoyloxy-8,9-dehydrothymol (5), 10-benzoyloxythymol (6) and 10-benzoyloxy-6,8-dihydroxy-9-isobutyryl-oxythymol (7). In addition, (8S)-10-benzoyloxy-8,9-epoxy-6-hydroxythymol isobutyrate (1), together with
[...] Read more.
Chemical investigation of the leaves from Ageratina glabrata yielded four new thymol derivatives, namely: 10-benzoyloxy-8,9-dehydro-6-hydroxythymol isobutyrate (4), 10-benzoyloxy-8,9-dehydrothymol (5), 10-benzoyloxythymol (6) and 10-benzoyloxy-6,8-dihydroxy-9-isobutyryl-oxythymol (7). In addition, (8S)-10-benzoyloxy-8,9-epoxy-6-hydroxythymol isobutyrate (1), together with other two already known thymol derivatives identified as 10-benzoyloxy-8,9-epoxy-6-methoxythymol isobutyrate (2) and 10-benzoyloxy-8,9-epoxythymol isobutyrate (3) were also obtained. In this paper, we report the structures and complete assignments of the 1H and 13C-NMR data of compounds 17, and the absolute configuration for compound 1, unambiguously established by single crystal X-ray diffraction, and evaluation of the Flack parameter. The in vitro antiprotozoal assay showed that compound 1 and its derivative 1a were the most potent antiamoebic and antigiardial compounds. Both compounds showed selectivity and good antiamoebic activity comparable to emetine and metronidazole, respectively, two antiprotozoal drugs used as positive controls. In relation to anti-propulsive effect, compound 1 and 1a showed inhibitory activity, with activities comparable to quercetin and compound 9, two natural antipropulsive compounds used as positive controls. These data suggest that compound 1 may play an important role in antidiarrheal properties of Ageratina glabrata. Full article
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Open AccessArticle Anti-Influenza Virus Activity and Constituents Characterization of Paeonia delavayi Extracts
Molecules 2016, 21(9), 1133; doi:10.3390/molecules21091133
Received: 21 June 2016 / Revised: 29 July 2016 / Accepted: 23 August 2016 / Published: 26 August 2016
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Abstract
Paeonia delavayi, an endemic species in southwestern China, has been widely used as a traditional remedy for cardiovascular, extravasated blood, stagnated blood and female diseases in traditional Chinese medicine (TCM). However, there are no reports on the anti-influenza virus activity of this species.
[...] Read more.
Paeonia delavayi, an endemic species in southwestern China, has been widely used as a traditional remedy for cardiovascular, extravasated blood, stagnated blood and female diseases in traditional Chinese medicine (TCM). However, there are no reports on the anti-influenza virus activity of this species. Here, the anti-influenza virus activity of P. delavayi root extracts was first evaluated by an influenza virus neuraminidase (NA) inhibition assay. Meantime, constituents in the active extracts were identified using ultra-high performance liquid coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and seven major identified constituents were used to further evaluate the NA inhibitory activity. The results showed that the ethyl acetate fraction (EA) and the ethanol fraction (E) of P. delavayi both presented strong NA inhibitory activity with IC50 values of 75.932 μg/mL and 83.550 μg/mL, respectively. Twenty-seven constituents were characterized in these two active extracts by UPLC-Q-TOF-MS analysis, and seven major identified constituents exhibited high activity against the influenza virus. Among them, Benzoylpaeoniflorin (IC50 = 143.701 µM) and pentagalloylglucose (IC50 = 62.671 µM) exhibited the highest activity against the influenza virus, even far stronger than oseltamivir acid (IC50 = 281.308 µM). This study indicated that P. delavayi was a strong NA inhibitor, but cell-based inhibition, anti-influenza virus activity in vivo and anti-influenza virus mechanism still need to be tested and explored. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Construction and Quality Analysis of Transgenic Rehmannia glutinosa Containing TMV and CMV Coat Protein
Molecules 2016, 21(9), 1134; doi:10.3390/molecules21091134
Received: 21 July 2016 / Revised: 23 August 2016 / Accepted: 24 August 2016 / Published: 27 August 2016
PDF Full-text (6998 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Plant viruses, especially tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) are serious threats to Rehmannia glutinosa which is a “top grade” herb in China. In the present study, TMV- and CMV-resistant Rehmannia glutinosa Libosch. plants were constructed by transforming the protein
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Plant viruses, especially tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) are serious threats to Rehmannia glutinosa which is a “top grade” herb in China. In the present study, TMV- and CMV-resistant Rehmannia glutinosa Libosch. plants were constructed by transforming the protein (CP) genes of TMV and CMV into Rehmannia glutinosa via a modified procedure of Agrobacterium tumefaciens-mediated transformation. Integration and expression of TMV CP and CMV CP transgenes in 2 lines, LBA-1 and LBA-2, were confirmed by PCR, Southern blot and RT-PCR. Both LBA-1 and LBA-2 were resistant to infection of homologous TMV and CMV strains. The quality of transgenic Rehmanniae Radix was evaluated based on fingerprint analysis and components quantitative analysis comparing with control root tubes. These results showed that chemical composition of transgenic Rehmanniae Radix were similar to non-transgenic ones, which demonstrated that the medical quality and biosafety of transgenic Rehmanniae Radix were equivalent to non-transgenic material when consumed as traditional Chinese medicinal (TCM). Full article
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Open AccessArticle Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes
Molecules 2016, 21(9), 1135; doi:10.3390/molecules21091135
Received: 13 July 2016 / Revised: 24 August 2016 / Accepted: 24 August 2016 / Published: 27 August 2016
Cited by 5 | PDF Full-text (1483 KB) | HTML Full-text | XML Full-text
Abstract
Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a
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Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT) through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, β-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2) and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle The Protective Effect of Melittin on Renal Fibrosis in an Animal Model of Unilateral Ureteral Obstruction
Molecules 2016, 21(9), 1137; doi:10.3390/molecules21091137
Received: 16 July 2016 / Revised: 23 August 2016 / Accepted: 24 August 2016 / Published: 27 August 2016
Cited by 2 | PDF Full-text (2722 KB) | HTML Full-text | XML Full-text
Abstract
Renal fibrosis is the principal pathological process underlying the progression of chronic kidney disease that leads to end-stage renal disease. Melittin is a major component of bee venom, and it has anti-bacterial, anti-viral, and anti-inflammatory properties in various cell types. Thus, this study
[...] Read more.
Renal fibrosis is the principal pathological process underlying the progression of chronic kidney disease that leads to end-stage renal disease. Melittin is a major component of bee venom, and it has anti-bacterial, anti-viral, and anti-inflammatory properties in various cell types. Thus, this study examined the therapeutic effects of melittin on the progression of renal fibrosis using the unilateral ureteral obstruction (UUO) model. In addition, the effects of melittin on inflammation and fibrosis in renal fibroblast cells were explored using transforming growth factor-β1 (TGF-β1). Histological observation revealed that UUO induced a considerable increase in the number of infiltrated inflammatory cells. However, melittin treatment markedly reduced these reactions compared with untreated UUO mice. The expression levels of inflammatory cytokines and pro-fibrotic genes were significantly reduced in melittin-treated mice compared with UUO mice. Melittin also effectively inhibited fibrosis-related gene expression in renal fibroblasts NRK-49F cells. These findings suggest that melittin attenuates renal fibrosis and reduces inflammatory responses by the suppression of multiple growth factor-mediated pro-fibrotic genes. In conclusion, melittin may be a useful therapeutic agent for the prevention of fibrosis that characterizes the progression of chronic kidney disease. Full article
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Open AccessArticle Screening for Neuraminidase Inhibitory Activity in Traditional Chinese Medicines Used to Treat Influenza
Molecules 2016, 21(9), 1138; doi:10.3390/molecules21091138
Received: 27 July 2016 / Revised: 16 August 2016 / Accepted: 23 August 2016 / Published: 27 August 2016
Cited by 2 | PDF Full-text (2243 KB) | HTML Full-text | XML Full-text
Abstract
Objective: To screen for influenza virus neuraminidase inhibition and to provide a reference for the clinical treatment of influenza using traditional Chinese medicines (TCM). In this study, 421 crude extracts (solubilized with petroleum ether, ethanol, ethyl acetate, and aqueous solvents) were obtained from
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Objective: To screen for influenza virus neuraminidase inhibition and to provide a reference for the clinical treatment of influenza using traditional Chinese medicines (TCM). In this study, 421 crude extracts (solubilized with petroleum ether, ethanol, ethyl acetate, and aqueous solvents) were obtained from 113 TCM. The medicine extracts were then reacted with oseltamivir, using 2’-(4-methylumbelliferyl)-α-D-N-acetylneuraminic acid (MUNANA) as the substrate, to determine influenza virus neuraminidase activity using a standard fluorimetric assay. It was found that Chinese medicine extracts from Pyrola calliantha, Cynanchum wilfordii, Balanophora involucrata and Paeonia delavayi significantly inhibited neuraminidase activity at a concentration of 40 μg/mL. Dose-dependent inhibitory assays also revealed significant inhibition. The IC50 range of the TCM extracts for influenza virus neuraminidase was approximately 12.66–34.85 μg/mL, respectively. Some Chinese medicines have clear anti-influenza viral effects that may play an important role in the treatment of influenza through the inhibition of viral neuraminidase. The results of this study demonstrated that plant medicines can serve as a useful source of neuraminidase (NA) inhibitors and further investigation into the pharmacologic activities of these extracts is warranted. Full article
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Open AccessArticle Structural Modifications of Deoxycholic Acid to Obtain Three Known Brassinosteroid Analogues and Full NMR Spectroscopic Characterization
Molecules 2016, 21(9), 1139; doi:10.3390/molecules21091139
Received: 22 July 2016 / Revised: 24 August 2016 / Accepted: 25 August 2016 / Published: 27 August 2016
Cited by 1 | PDF Full-text (1384 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An improved synthesis route for obtaining known brassinosteroid analogues, i.e., methyl 2α,3α-dihydroxy-6-oxo-5α-cholan-24-oate (11), methyl 3α-hydroxy-6-oxo-7-oxa-5α-cholan-24-oate (15) and methyl 3α-hydroxy-6-oxa-7-oxo-5α-cholan-24-oate (16), from hyodeoxycholic acid (4) maintaining the native side chain is described. In the alternative procedure,
[...] Read more.
An improved synthesis route for obtaining known brassinosteroid analogues, i.e., methyl 2α,3α-dihydroxy-6-oxo-5α-cholan-24-oate (11), methyl 3α-hydroxy-6-oxo-7-oxa-5α-cholan-24-oate (15) and methyl 3α-hydroxy-6-oxa-7-oxo-5α-cholan-24-oate (16), from hyodeoxycholic acid (4) maintaining the native side chain is described. In the alternative procedure, the di-oxidized product 6, obtained in the oxidation of methyl hyodeoxycholate 5, was converted almost quantitatively into the target monoketone 7 by stereoselective reduction with NaBH4, increasing the overall yield of this synthetic route to 96.8%. The complete 1H- and 13C-NMR assignments for all compounds synthesized in this work have been made by 1D and 2D heteronuclear correlation gs-HSQC and gs-HMBC techniques. Thus, it was possible to update the spectroscopic information of 1H-NMR and to accomplish a complete assignment of all 13C-NMR signals for analogues 516, which were previously reported only in partial form. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Practical and Efficient Synthesis of α-Aminophosphonic Acids Containing 1,2,3,4-Tetrahydroquinoline or 1,2,3,4-Tetrahydroisoquinoline Heterocycles
Molecules 2016, 21(9), 1140; doi:10.3390/molecules21091140
Received: 25 July 2016 / Revised: 15 August 2016 / Accepted: 25 August 2016 / Published: 31 August 2016
Cited by 1 | PDF Full-text (1279 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We report here a practical and efficient synthesis of α-aminophosphonic acid incorporated into 1,2,3,4-tetrahydroquinoline and 1,2,3,4-tetrahydroisoquinoline heterocycles, which could be considered to be conformationally constrained analogues of pipecolic acid. The principal contribution of this synthesis is the introduction of the phosphonate group in
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We report here a practical and efficient synthesis of α-aminophosphonic acid incorporated into 1,2,3,4-tetrahydroquinoline and 1,2,3,4-tetrahydroisoquinoline heterocycles, which could be considered to be conformationally constrained analogues of pipecolic acid. The principal contribution of this synthesis is the introduction of the phosphonate group in the N-acyliminium ion intermediates, obtained from activation of the quinoline and isoquinoline heterocycles or from the appropriate δ-lactam with benzyl chloroformate. Finally, the hydrolysis of phosphonate moiety with simultaneous cleavage of the carbamate afforded the target compounds. Full article
(This article belongs to the Special Issue Recent Advances in Organophosphorus Chemistry)
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Open AccessArticle Arginine: New Insights into Growth Performance and Urinary Metabolomic Profiles of Rats
Molecules 2016, 21(9), 1142; doi:10.3390/molecules21091142
Received: 17 June 2016 / Revised: 6 August 2016 / Accepted: 25 August 2016 / Published: 29 August 2016
PDF Full-text (1018 KB) | HTML Full-text | XML Full-text
Abstract
Arginine regulates growth performance, nutrient metabolism and health effects, but the underlying mechanism remains unknown. This study aims to investigate the effect of dietary arginine supplementation on rat growth performance and urinary metabolome through 1H-NMR spectroscopy. Twenty rats were randomly assigned to
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Arginine regulates growth performance, nutrient metabolism and health effects, but the underlying mechanism remains unknown. This study aims to investigate the effect of dietary arginine supplementation on rat growth performance and urinary metabolome through 1H-NMR spectroscopy. Twenty rats were randomly assigned to two groups supplemented with 0% or 1.0% l-arginine for 4 weeks. Urine samples were analyzed through NMR-based metabolomics. Arginine supplementation significantly increased the urine levels of 4-aminohippurate, acetate, creatine, creatinine, ethanolamine, formate, hippurate, homogentisate, indoxyl sulfate, and phenylacetyglycine. Conversely, arginine decreased the urine levels of acetamide, β-glucose, cirtulline, ethanol, glycine, isobutyrate, lactate, malonate, methymalonate, N-acetylglutamate, N-methylnicotinamide, and propionate. Results suggested that arginine can alter common systemic metabolic processes, including energy metabolism, amino acid metabolism, and gut microbiota metabolism. Moreover, the results also imply a possible physiological role of the metabolism in mediating the arginine supplementation-supported growth of rats. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle In Vivo Targeted MR Imaging of Endogenous Neural Stem Cells in Ischemic Stroke
Molecules 2016, 21(9), 1143; doi:10.3390/molecules21091143
Received: 20 July 2016 / Revised: 19 August 2016 / Accepted: 26 August 2016 / Published: 29 August 2016
Cited by 2 | PDF Full-text (4777 KB) | HTML Full-text | XML Full-text
Abstract
Acute ischemic stroke remains a leading cause of death and disability. Endogenous neurogenesis enhanced via activation of neural stem cells (NSCs) could be a promising method for stroke treatment. In vivo targeted tracking is highly desirable for monitoring the dynamics of endogenous NSCs
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Acute ischemic stroke remains a leading cause of death and disability. Endogenous neurogenesis enhanced via activation of neural stem cells (NSCs) could be a promising method for stroke treatment. In vivo targeted tracking is highly desirable for monitoring the dynamics of endogenous NSCs in stroke. Previously, we have successfully realized in vivo targeted MR imaging of endogenous NSCs in normal adult mice brains by using anti-CD15 antibody-conjugated superparamagnetic iron oxide nanoparticles (anti-CD15-SPIONs) as the molecular probe. Herein, we explore the performance of this molecular probe in targeted in vivo tracking of activated endogenous NSCs in ischemic stroke. Our study showed that intraventricular injection of anti-CD15-SPIONs could label activated endogenous NSCs in situ seven days after ischemic stroke, which were detected as enlarged areas of hypo-intense signals on MR imaging at 7.0 T. The treatment of cytosine arabinosine could inhibit the activation of endogenous NSCs, which was featured by the disappearance of areas of hypo-intense signals on MR imaging. Using anti-CD15-SPIONs as imaging probes, the dynamic process of activation of endogenous NSCs could be readily monitored by in vivo MR imaging. This targeted imaging strategy would be of great benefit to develop a new therapeutic strategy utilizing endogenous NSCs for ischemic stroke. Full article
(This article belongs to the Special Issue Molecular Imaging Probes)
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Open AccessArticle In Vitro and In Vivo Characterization of Selected Fluorine-18 Labeled Radioligands for PET Imaging of the Dopamine D3 Receptor
Molecules 2016, 21(9), 1144; doi:10.3390/molecules21091144
Received: 10 August 2016 / Revised: 25 August 2016 / Accepted: 26 August 2016 / Published: 29 August 2016
Cited by 4 | PDF Full-text (8745 KB) | HTML Full-text | XML Full-text
Abstract
Cerebral dopamine D3 receptors seem to play a key role in the control of drug-seeking behavior. The imaging of their regional density with positron emission tomography (PET) could thus help in the exploration of the molecular basis of drug addiction. A fluorine-18 labeled
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Cerebral dopamine D3 receptors seem to play a key role in the control of drug-seeking behavior. The imaging of their regional density with positron emission tomography (PET) could thus help in the exploration of the molecular basis of drug addiction. A fluorine-18 labeled D3 subtype selective radioligand would be beneficial for this purpose; however, as yet, there is no such tracer available. The three candidates [18F]1, [18F]2a and [18F]2b were chosen for in vitro and in vivo characterization as radioligands suitable for selective PET imaging of the D3 receptor. Their evaluation included the analysis of radiometabolites and the assessment of non-specific binding by in vitro rat brain autoradiography. While [18F]1 and [18F]2a revealed high non-specific uptake in in vitro rat brain autoradiography, the D3 receptor density was successfully determined on rat brain sections (n = 4) with the candidate [18F]2b offering a Bmax of 20.38 ± 2.67 pmol/g for the islands of Calleja, 19.54 ± 1.85 pmol/g for the nucleus accumbens and 16.58 ± 1.63 pmol/g for the caudate putamen. In PET imaging studies, the carboxamide 1 revealed low signal/background ratios in the rat brain and relatively low uptake in the pituitary gland, while the azocarboxamides [18F]2a and [18F]2b showed binding that was blockable by the D3 receptor ligand BP897 in the ventricular system and the pituitary gland in PET imaging studies in living rats. Full article
(This article belongs to the Special Issue Molecular Imaging Probes)
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Open AccessArticle Cardamonin, a Novel Antagonist of hTRPA1 Cation Channel, Reveals Therapeutic Mechanism of Pathological Pain
Molecules 2016, 21(9), 1145; doi:10.3390/molecules21091145
Received: 12 July 2016 / Revised: 25 August 2016 / Accepted: 25 August 2016 / Published: 29 August 2016
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Abstract
The increasing demand for safe and effective treatments of chronic pain has promoted the investigation of novel analgesic drugs. Some herbals have been known to be able to relieve pain, while the chemical basis and target involved in this process remained to be
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The increasing demand for safe and effective treatments of chronic pain has promoted the investigation of novel analgesic drugs. Some herbals have been known to be able to relieve pain, while the chemical basis and target involved in this process remained to be clarified. The current study aimed to find anti-nociceptive candidates targeting transient receptor potential ankyrin 1 (TRPA1), a receptor that implicates in hyperalgesia and neurogenic inflammation. In the current study, 156 chemicals were tested for blocking HEK293/TRPA1 ion channel by calcium-influx assay. Docking study was conducted to predict the binding modes of hit compound with TRPA1 using Discovery Studio. Cytotoxicity in HEK293 was conducted by Cell Titer-Glo assay. Additionally, cardiotoxicity was assessed via xCELLigence RTCA system. We uncovered that cardamonin selectively blocked TRPA1 activation while did not interact with TRPV1 nor TRPV4 channel. A concentration-dependent inhibitory effect was observed with IC50 of 454 nM. Docking analysis of cardamonin demonstrated a compatible interaction with A-967079-binding site of TRPA1. Meanwhile, cardamonin did not significantly reduce HEK293 cell viability, nor did it impair cardiomyocyte constriction. Our data suggest that cardamonin is a selective TRPA1 antagonist, providing novel insight into the target of its anti-nociceptive activity. Full article
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Open AccessArticle Dimacrolide Sesquiterpene Pyridine Alkaloids from the Stems of Tripterygium regelii
Molecules 2016, 21(9), 1146; doi:10.3390/molecules21091146
Received: 20 July 2016 / Accepted: 3 August 2016 / Published: 29 August 2016
Cited by 2 | PDF Full-text (685 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new dimacrolide sesquiterpene pyridine alkaloids (DMSPAs), dimacroregelines A (1) and B (2), were isolated from the stems of Tripterygium regelii. The structures of both compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses, as well
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Two new dimacrolide sesquiterpene pyridine alkaloids (DMSPAs), dimacroregelines A (1) and B (2), were isolated from the stems of Tripterygium regelii. The structures of both compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. Compounds 1 and 2 are two rare DMSPAs possessing unique 2-(3′-carboxybutyl)-3-furanoic acid units forming the second macrocyclic ring, representing the first example of DMSPAs bearing an extra furan ring in their second macrocyclic ring system. Compound 2 showed inhibitory effects on the proliferation of human rheumatoid arthritis synovial fibroblast cell (MH7A) at a concentration of 20 μM. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases
Molecules 2016, 21(9), 1147; doi:10.3390/molecules21091147
Received: 30 June 2016 / Revised: 17 August 2016 / Accepted: 25 August 2016 / Published: 29 August 2016
Cited by 5 | PDF Full-text (3242 KB) | HTML Full-text | XML Full-text
Abstract
Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases’ activity and expression are regulated by oxidative stress, we sought to
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Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases’ activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5–25 μg/mL) of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively) or their specific components (0.5–25 μmol/L), before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases. Full article
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Open AccessArticle Purification of Flavonoids from Chinese Bayberry (Morella rubra Sieb. et Zucc.) Fruit Extracts and α-Glucosidase Inhibitory Activities of Different Fractionations
Molecules 2016, 21(9), 1148; doi:10.3390/molecules21091148
Received: 6 July 2016 / Revised: 11 August 2016 / Accepted: 26 August 2016 / Published: 31 August 2016
Cited by 3 | PDF Full-text (1807 KB) | HTML Full-text | XML Full-text
Abstract
Chinese bayberry (Morella rubra Sieb. et Zucc.) fruit have a diverse flavonoid composition responsible for the various medicinal activities, including anti-diabetes. In the present study, efficient simultaneous purification of four flavonoid glycosides, i.e., cyanidin-3-O-glucoside (1), myricetin-3-O-rhamnoside
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Chinese bayberry (Morella rubra Sieb. et Zucc.) fruit have a diverse flavonoid composition responsible for the various medicinal activities, including anti-diabetes. In the present study, efficient simultaneous purification of four flavonoid glycosides, i.e., cyanidin-3-O-glucoside (1), myricetin-3-O-rhamnoside (2), quercetin-3-O-galactoside (3), quercetin-3-O-rhamnoside (4), from Chinese bayberry pulp was established by the combination of solid phase extract (SPE) by C18 Sep-Pak® cartridge column chromatography and semi-preparative HPLC (Prep-HPLC), which was followed by HPLC and LC-MS identification. The purified flavonoid glycosides, as well as different fractions of fruit extracts of six bayberry cultivars, were investigated for α-glucosidase inhibitory activities. The flavonol extracts (50% methanol elution fraction) of six cultivars showed strong α-glucosidase inhibitory activities (IC50 = 15.4–69.5 μg/mL), which were higher than that of positive control acarbose (IC50 = 383.2 μg/mL). Four purified compounds 14 exerted α-glucosidase inhibitory activities, with IC50 values of 1444.3 μg/mL, 418.8 μg/mL, 556.4 μg/mL, and 491.8 μg/mL, respectively. Such results may provide important evidence for the potential anti-diabetic activity of different cultivars of Chinese bayberry fruit and the possible bioactive compounds involved. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Panax Notoginseng Saponins as a Novel Nature Stabilizer for Poorly Soluble Drug Nanocrystals: A Case Study with Baicalein
Molecules 2016, 21(9), 1149; doi:10.3390/molecules21091149
Received: 29 June 2016 / Revised: 9 August 2016 / Accepted: 25 August 2016 / Published: 30 August 2016
Cited by 2 | PDF Full-text (2152 KB) | HTML Full-text | XML Full-text
Abstract
This study is aimed at seeking a nature saponin-based stabilizer for drug nanosuspensions. A poorly soluble drug (baicalein, BCL) was used as a model drug. BCL nanosuspensions with particle size of 156 nm were prepared by means of homogenization and converted into BCL
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This study is aimed at seeking a nature saponin-based stabilizer for drug nanosuspensions. A poorly soluble drug (baicalein, BCL) was used as a model drug. BCL nanosuspensions with particle size of 156 nm were prepared by means of homogenization and converted into BCL nanocrystals (BCL-NC) stabilized with panax notoginseng saponins (PNS). It was found that PNS was able to prevent the aggregation of BCL-NS during storage and improve the redispersibility of BCL-NC after freeze-drying and spray-drying, compared with polymer stabilizer PVPK30. The freeze-dried and spray-dried BCL-NC with PNS exhibited excellent performance as evidenced by scanning_electron_microscope (SEM) analysis. It was the reason that PNS possessed the interfacial property (41.69 ± 0.32 mN/m) and electrostatic effect (−40.1 ± 1.6 mV), which could easily adsorb onto the surface of hydrophobic BCL nanocrystals and prevent from its aggregation. It is concluded that PNS can be used as an effective nature stabilizer for production of drug nanocrystals. Full article
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Open AccessArticle Chemical Composition, Antioxidant, and Antibacterial Activity of Wood Vinegar from Litchi chinensis
Molecules 2016, 21(9), 1150; doi:10.3390/molecules21091150
Received: 12 July 2016 / Revised: 16 August 2016 / Accepted: 24 August 2016 / Published: 30 August 2016
Cited by 3 | PDF Full-text (940 KB) | HTML Full-text | XML Full-text
Abstract
The antioxidant and antibacterial activities of wood vinegar from Litchi chinensis, and its components have been studied. The chemical compositions of wood vinegar were analyzed by gas chromatography-mass spectrometry (GC-MS). A total of 17 chemical compounds were identified, representing 83.96% of the
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The antioxidant and antibacterial activities of wood vinegar from Litchi chinensis, and its components have been studied. The chemical compositions of wood vinegar were analyzed by gas chromatography-mass spectrometry (GC-MS). A total of 17 chemical compounds were identified, representing 83.96% of the compositions in the wood vinegar. Three major components, included 2,6-dimethoxyphenol (syringol, 29.54%), 2-methoxyphenol (guaiacol, 12.36%), and 3,5-dimethoxy-4-hydroxytoluene (11.07%), were found in the wood vinegar. Antioxidant activities of the acids were investigated from the aspects of 1,1-Diphyl-2-picrylhydrazyl (DPPH) free radicals scavenging capacity, superoxide anion radical scavenging capacity, and reducing power. The pyroligneous acid exhibited high antioxidant activity which was comparable to the reference standards (vitamin C and butylated hydroxyl toluene) at the same dose with IC50 values of 36.5 ppm calculated by the DPPH radical scavenging assay, 38.38 g Trolox equivalent/100 g DW by the trolox equivalent antioxidant capacity (TEAC) assay, and 67.9 by the reducing power analysis. Antibacterial activity was evaluated using the disc diffusion and microdilution methods against a group of clinically antibiotic resistant isolates. The major components exhibited broad spectrum inhibition against all the bacterial strains with a range of disc inhibition zoon between 15–19 mm. The minimum inhibition concentration and minimum bactericide concentration against the test strains was ranging in 0.95–3.80 μL/100 μL and 1.90–3.80 μL/100 μL, respectively. Most of the antibiotic resistant strains were more susceptible to the wood vinegar than the non-antibiotic resistant strain except the strain of ornithine resistant Staphylococcus aureus. Based on the chemical profile, it was considered that the strongest antioxidant and antibacterial activity of Litchi chinensis wood vinegar was due to its highly phenolic compositions. This study revealed that the Litchi chinensis wood vinegar is valuable to develop as alternative food antioxidant and antibiotics. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle Photostabilizing Efficiency of Poly(vinyl chloride) in the Presence of Organotin(IV) Complexes as Photostabilizers
Molecules 2016, 21(9), 1151; doi:10.3390/molecules21091151
Received: 5 August 2016 / Revised: 24 August 2016 / Accepted: 25 August 2016 / Published: 30 August 2016
Cited by 4 | PDF Full-text (5155 KB) | HTML Full-text | XML Full-text
Abstract
Three organotin complexes containing furosemide as a ligand (L), Ph3SnL, Me2SnL2 and Bu2SnL2, were synthesized and characterized. Octahedral geometry was proposed for the Me2SnL2 and Bu2SnL2, while
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Three organotin complexes containing furosemide as a ligand (L), Ph3SnL, Me2SnL2 and Bu2SnL2, were synthesized and characterized. Octahedral geometry was proposed for the Me2SnL2 and Bu2SnL2, while the Ph3SnL complex has trigonal bipyramid geometry. The synthesized organotin complexes (0.5% by weight) were used as additives to improve the photostability of poly(vinyl chloride), PVC, (40 μm thickness) upon irradiation. The changes imposed on functional groups, weight loss and viscosity average molecular weight of PVC films were monitored. The experimental results show that the rate of photodegradation was reduced in the presence of the organotin additives. The quantum yield of the chain scission was found to be low (9.8 × 10−7) when Ph3SnL was used as a PVC photostabilizer compared to controlled PVC (5.18 × 10−6). In addition, the atomic force microscope images for the PVC films containing Ph3SnL2 after irradiation shows a smooth surface compared to the controlled films. The rate of PVC photostabilization was found to be highest for Ph3SnL followed by Bu2SnL2 and Me2SnL2. It has been suggested that the organotin complexes could act as hydrogen chloride scavengers, ultraviolet absorbers, peroxide decomposers and/or radical scavengers. Full article
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Open AccessArticle Mexicanolide-Type Limonoids from the Roots of Trichilia sinensis
Molecules 2016, 21(9), 1152; doi:10.3390/molecules21091152
Received: 8 August 2016 / Revised: 22 August 2016 / Accepted: 26 August 2016 / Published: 30 August 2016
Cited by 3 | PDF Full-text (629 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four new mexicanolide-type limonoids 14, along with two known limonoids 56, were isolated from the ethanolic extracts of roots of the Traditional Chinese Medicine Trichilia sinensis. Their structures were unambiguously determined by analysis of spectroscopic data,
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Four new mexicanolide-type limonoids 14, along with two known limonoids 56, were isolated from the ethanolic extracts of roots of the Traditional Chinese Medicine Trichilia sinensis. Their structures were unambiguously determined by analysis of spectroscopic data, including 1D and 2D NMR as well as MS, and by comparison with literature data. In addition, the acetylcholinesterase (AChE) inhibitory activity of compounds 16 was evaluated by the Ellman method. All these compounds showed weak AChE inhibitory activity, with the inhibition percentages ranging from 18.5% to 27.8%. Full article
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Open AccessArticle Passerini Reactions on Biocatalytically Derived Chiral Azetidines
Molecules 2016, 21(9), 1153; doi:10.3390/molecules21091153
Received: 28 July 2016 / Revised: 24 August 2016 / Accepted: 26 August 2016 / Published: 30 August 2016
PDF Full-text (861 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The purpose of this study was to explore a series of Passerini reactions on a biocatalytically derived enantiopure azetidine-2-carboxyaldehyde in order to obtain, in a diastereoselective manner, polyfunctionalised derivatives having the potential to be cyclized to chiral bridged bicyclic nitrogen heterocycles. While diastereoselectivity
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The purpose of this study was to explore a series of Passerini reactions on a biocatalytically derived enantiopure azetidine-2-carboxyaldehyde in order to obtain, in a diastereoselective manner, polyfunctionalised derivatives having the potential to be cyclized to chiral bridged bicyclic nitrogen heterocycles. While diastereoselectivity was poor under classical Passerini conditions, a significant increase of diastereoselectivity (up to 76:24) was gained by the use of zinc bromide as promoter. The methodology has a broad scope and yields are always good. Full article
(This article belongs to the Special Issue Diversity Oriented Synthesis 2016)
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Open AccessArticle Development and Validation of a Kit to Measure Drink Antioxidant Capacity Using a Novel Colorimeter
Molecules 2016, 21(9), 1154; doi:10.3390/molecules21091154
Received: 13 July 2016 / Revised: 26 August 2016 / Accepted: 27 August 2016 / Published: 30 August 2016
PDF Full-text (357 KB) | HTML Full-text | XML Full-text
Abstract
Measuring the antioxidant capacity of foods is essential, as a means of quality control to ensure that the final product reaching the consumer will be of high standards. Despite the already existing assays with which the antioxidant activity is estimated, new, faster and
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Measuring the antioxidant capacity of foods is essential, as a means of quality control to ensure that the final product reaching the consumer will be of high standards. Despite the already existing assays with which the antioxidant activity is estimated, new, faster and low cost methods are always sought. Therefore, we have developed a novel colorimeter and combined it with a slightly modified DPPH assay, thus creating a kit that can assess the antioxidant capacity of liquids (e.g., different types of coffee, beer, wine, juices) in a quite fast and low cost manner. The accuracy of the colorimeter was ensured by comparing it to a fully validated Hitachi U-1900 spectrophotometer, and a coefficient was calculated to eliminate the observed differences. In addition, a new, user friendly software was developed, in order to render the procedure as easy as possible, while allowing a central monitoring of the obtained results. Overall, a novel kit was developed, with which the antioxidant activity of liquids can be measured, firstly to ensure their quality and secondly to assess the amount of antioxidants consumed with the respective food. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Facile Access to Stable Silylium Ions Stabilized by N-Heterocyclic Imines
Molecules 2016, 21(9), 1155; doi:10.3390/molecules21091155
Received: 26 July 2016 / Revised: 23 August 2016 / Accepted: 25 August 2016 / Published: 30 August 2016
Cited by 5 | PDF Full-text (2665 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Novel silylium ions with N-heterocyclic imines were successfully synthesized. The reaction of trimethylsilyl imidazolin-2-imine Me3SiNIPr (NIPr = bis(2,6-diisopropylphenyl)-imidazolin-2-imino) with B(C6F5)3 leads to dimeric imino-substituted silylium ions through a methyl group abstraction on the silicon atom.
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Novel silylium ions with N-heterocyclic imines were successfully synthesized. The reaction of trimethylsilyl imidazolin-2-imine Me3SiNIPr (NIPr = bis(2,6-diisopropylphenyl)-imidazolin-2-imino) with B(C6F5)3 leads to dimeric imino-substituted silylium ions through a methyl group abstraction on the silicon atom. Meanwhile, the intermolecular imino-coordinated silylium ion is formed by using the less sterically crowded imine Me3SiNItBu (NItBu = bis(tert-butyl)-imidazolin-2-imino). Furthermore, the treatment of dimethylchlorosilane Me2(Cl)SiNIPr with AgOTf affords the contact ion pair Me2(OTf)SiNIPr by substitution of the chloride. A novel complex with the formula [Me2(DMAP)SiNIPr][OTf] was prepared by coordination with 4-dimethylamino-pyridine (DMAP). In the solid state, the DMAP adduct [Me2(DMAP)SiNIPr][OTf] contains a distinct [Me2(DMAP)SiNIPr]+ moiety. Full article
(This article belongs to the Special Issue Advances in Silicon Chemistry)
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Open AccessArticle Synthesis and Biological Evaluation of N- Pyrazolyl Derivatives and Pyrazolopyrimidine Bearing a Biologically Active Sulfonamide Moiety as Potential Antimicrobial Agent
Molecules 2016, 21(9), 1156; doi:10.3390/molecules21091156
Received: 1 August 2016 / Revised: 21 August 2016 / Accepted: 25 August 2016 / Published: 31 August 2016
PDF Full-text (1155 KB) | HTML Full-text | XML Full-text
Abstract
A series of novel pyrazole-5-carboxylate containing N-triazole derivatives 3,4; different heterocyclic amines 7ab and 10ab; pyrazolo[4,3-d]pyrimidine containing sulfa drugs 14a,b; and oxypyrazolo[4,3-d]pyrimidine derivatives 17, 19,
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A series of novel pyrazole-5-carboxylate containing N-triazole derivatives 3,4; different heterocyclic amines 7ab and 10ab; pyrazolo[4,3-d]pyrimidine containing sulfa drugs 14a,b; and oxypyrazolo[4,3-d]pyrimidine derivatives 17, 19, 21 has been synthesized. The structure of the newly synthesized compounds was elucidated on the basis of analytical and spectral analyses. All compounds have been screened for their in vitro antimicrobial activity against three gram-positive and gram-negative bacteria as well as three fungi. The results revealed that compounds 14b and 17 had more potent antibacterial activity against all bacterial strains than reference drug Cefotaxime. Moreover compounds 4, 7b, and 12b showed excellent antifungal activities against Aspergillus niger and Candida albicans in low inhibitory concentrations but slightly less than the reference drug miconazole against Aspergillus flavus. Full article
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Open AccessArticle Identification of Iridoids in Edible Honeysuckle Berries (Lonicera caerulea L. var. kamtschatica Sevast.) by UPLC-ESI-qTOF-MS/MS
Molecules 2016, 21(9), 1157; doi:10.3390/molecules21091157
Received: 2 August 2016 / Revised: 23 August 2016 / Accepted: 26 August 2016 / Published: 1 September 2016
Cited by 3 | PDF Full-text (26838 KB) | HTML Full-text | XML Full-text
Abstract
Iridoid profiles of honeysuckle berry were studied. Compounds were identified by ultra-performance liquid chromatography coupled with electrospray ionization mass spectrometry UPLC-ESI-qTOF-MS/MS in positive and negative ions mode. The MS fragmentation pathways of detected iridoid glycosides were also studied in both modes. In the
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Iridoid profiles of honeysuckle berry were studied. Compounds were identified by ultra-performance liquid chromatography coupled with electrospray ionization mass spectrometry UPLC-ESI-qTOF-MS/MS in positive and negative ions mode. The MS fragmentation pathways of detected iridoid glycosides were also studied in both modes. In the negative ESI mass spectra, iridoids with a methyl ester or lactone structure have preferentially produced adduct [M + HCOOH − H] ions. However, protonated ions of molecular fragments, which were released by glycosidic bond cleavage and following fragmentation of aglycone rings, were more usable for iridoid structure analysis. In addition, the neutral losses of H2O, CO, CO2, CH3OH, acetylene, ethenone and cyclopropynone have provided data confirming the presence of functional substituents in the aglycone. Among the 13 iridoids, 11 were identified in honeysuckle berries for the first time: pentosides of loganic acid (two isomers), pentosides of loganin (three isomers), pentosyl sweroside, and additionally 7-epi-loganic acid, 7-epi-loganin, sweroside, secologanin, and secoxyloganin. The five pentoside derivatives of loganic acid and loganin have not been previously detected in the analyzed species. Honeysuckle berries are a source of iridoids with different structures, compounds that are rarely present in fruits. Full article
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Open AccessArticle Icariin Metabolism by Human Intestinal Microflora
Molecules 2016, 21(9), 1158; doi:10.3390/molecules21091158
Received: 4 August 2016 / Revised: 25 August 2016 / Accepted: 26 August 2016 / Published: 31 August 2016
Cited by 5 | PDF Full-text (2238 KB) | HTML Full-text | XML Full-text
Abstract
Icariin is a major bioactive compound of Epimedii Herba, a traditional oriental medicine exhibiting anti-cancer, anti-inflammatory and anti-osteoporosis activities. Recently, the estrogenic activities of icariin drew significant attention, but the published scientific data seemed not to be so consistent. To provide fundamental information
[...] Read more.
Icariin is a major bioactive compound of Epimedii Herba, a traditional oriental medicine exhibiting anti-cancer, anti-inflammatory and anti-osteoporosis activities. Recently, the estrogenic activities of icariin drew significant attention, but the published scientific data seemed not to be so consistent. To provide fundamental information for the study of the icaritin metabolism, the biotransformation of icariin by the human intestinal bacteria is reported for the first time. Together with human intestinal microflora, the three bacteria Streptococcus sp. MRG-ICA-B, Enterococcus sp. MRG-ICA-E, and Blautia sp. MRG-PMF-1 isolated from human intestine were reacted with icariin under anaerobic conditions. The metabolites including icariside II, icaritin, and desmethylicaritin, but not icariside I, were produced. The MRG-ICA-B and E strains hydrolyzed only the glucose moiety of icariin, and icariside II was the only metabolite. However, the MRG-PMF-1 strain metabolized icariin further to desmethylicaritin via icariside II and icaritin. From the results, along with the icariin metabolism by human microflora, it was evident that most icariin is quickly transformed to icariside II before absorption in the human intestine. We propose the pharmacokinetics of icariin should focus on metabolites such as icariside II, icaritin and desmethylicaritin to explain the discrepancy between the in vitro bioassay and pharmacological effects. Full article
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Open AccessArticle Analysis of Sheng-Mai-San, a Ginseng-Containing Multiple Components Traditional Chinese Herbal Medicine Using Liquid Chromatography Tandem Mass Spectrometry and Physical Examination by Electron and Light Microscopies
Molecules 2016, 21(9), 1159; doi:10.3390/molecules21091159
Received: 15 June 2016 / Revised: 15 August 2016 / Accepted: 25 August 2016 / Published: 1 September 2016
PDF Full-text (4654 KB) | HTML Full-text | XML Full-text
Abstract
Sheng-Mai-San is a multi-component traditional Chinese herbal preparation. Due to the fact granulated additives, such as starch, carboxymethyl cellulose, lactose and raw herbal powder may alter the content of the bioactive markers in the herbal products, a developed ultra-high performance liquid chromatography tandem
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Sheng-Mai-San is a multi-component traditional Chinese herbal preparation. Due to the fact granulated additives, such as starch, carboxymethyl cellulose, lactose and raw herbal powder may alter the content of the bioactive markers in the herbal products, a developed ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was used to measure the herbal biomarkers of ginsenoside Rb1, Rb2, Rc, Rd, Re, Rg1, Rh1, compound K, ophiopogonin D and schizandrin from the Sheng-Mai-San herbal formulation. Besides, scanning electron microscopy (SEM) was used to observe the morphology of the herbal granular powders. Light microscopy with Congo red and iodine-KI reagent staining was used to identify the cellulose fiber and cornstarch added to pharmaceutical herbal products. The swelling power (SP), water solubility index (WSI), and crude fiber analysis were used to determine the contents of cellulose fiber and cornstarch in pharmaceutical herbal products. In this study, we developed a novel skill to assess the quantification of appended cornstarch in pharmaceutical herbal products using Aperio ImageScope software. Compared with the traditional cornstarch analysis, our analysis method is a rapid, simple and conversion process which could be applied to detect the percentage of added cornstarch in unknown powder products. The various range of the herbal content for the five pharmaceutical manufacturers varied by up to several hundreds-fold. The physical examination reveals that the morphology of the herbal pharmaceutical products is rough and irregular with sharp layers. This study provides a reference standard operating procedure guide for the quality control of the Chinese herbal pharmaceutical products of Sheng-Mai-San. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis of a Potent Aminopyridine-Based nNOS-Inhibitor by Two Recent No-Carrier-Added 18F-Labelling Methods
Molecules 2016, 21(9), 1160; doi:10.3390/molecules21091160
Received: 3 August 2016 / Revised: 24 August 2016 / Accepted: 25 August 2016 / Published: 1 September 2016
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Abstract
Nitric oxide (NO), an important multifunctional signaling molecule, is produced by three isoforms of NO-synthase (NOS) and has been associated with neurodegenerative disorders. Selective inhibitors of the subtypes iNOS (inducible) or nNOS (neuronal) are of great interest for decoding neurodestructive key factors, and
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Nitric oxide (NO), an important multifunctional signaling molecule, is produced by three isoforms of NO-synthase (NOS) and has been associated with neurodegenerative disorders. Selective inhibitors of the subtypes iNOS (inducible) or nNOS (neuronal) are of great interest for decoding neurodestructive key factors, and 18F-labelled analogues would allow investigating the NOS-function by molecular imaging with positron emission tomography. Especially, the highly selective nNOS inhibitor 6-((3-((3-fluorophenethylamino)methyl)phenoxy)methyl)-4-methylpyridin-2-amine (10) lends itself as suitable compound to be 18F-labelled in no-carrier-added (n.c.a.) form. For preparation of the 18F-labelled nNOS-Inhibitor [18F]10 a “build-up” radiosynthesis was developed based on a corresponding iodonium ylide as labelling precursor. The such activated phenethyl group of the compound was efficiently and regioselectively labelled with n.c.a. [18F]fluoride in 79% radiochemical yield (RCY). After conversion by reductive amination and microwave assisted displacement of the protecting groups, the desired nNOS-inhibitor was obtained in about 15% total RCY. Alternatively, for a simplified “late-stage” 18F-labelling procedure a corresponding boronic ester precursor was synthesized and successfully used in a newer, copper(II) mediated n.c.a. 18F-fluoro-deboroniation reaction, achieving the same total RCY. Thus, both methods proved comparatively suited to provide the highly selective NOS-inhibitor [18F]10 as probe for preclinical in vivo studies. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Extracts from Traditional Chinese Medicinal Plants Inhibit Acetylcholinesterase, a Known Alzheimer’s Disease Target
Molecules 2016, 21(9), 1161; doi:10.3390/molecules21091161
Received: 10 August 2016 / Revised: 24 August 2016 / Accepted: 27 August 2016 / Published: 31 August 2016
Cited by 4 | PDF Full-text (847 KB) | HTML Full-text | XML Full-text
Abstract
Inhibition of acetylcholinesterase (AChE) is a common treatment for early stages of the most general form of dementia, Alzheimer’s Disease (AD). In this study, methanol, dichloromethane and aqueous crude extracts from 80 Traditional Chinese Medical (TCM) plants were tested for their in vitro
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Inhibition of acetylcholinesterase (AChE) is a common treatment for early stages of the most general form of dementia, Alzheimer’s Disease (AD). In this study, methanol, dichloromethane and aqueous crude extracts from 80 Traditional Chinese Medical (TCM) plants were tested for their in vitro anti-acetylcholinesterase activity based on Ellman’s colorimetric assay. All three extracts of Berberis bealei (formerly Mahonia bealei), Coptis chinensis and Phellodendron chinense, which contain numerous isoquinoline alkaloids, substantially inhibited AChE. The methanol and aqueous extracts of Coptis chinensis showed IC50 values of 0.031 µg/mL and 2.5 µg/mL, therefore having an up to 100-fold stronger AChE inhibitory activity than the already known AChE inhibitor galantamine (IC50 = 4.33 µg/mL). Combinations of individual alkaloids berberine, coptisine and palmatine resulted in a synergistic enhancement of ACh inhibition. Therefore, the mode of AChE inhibition of crude extracts of Coptis chinensis, Berberis bealei and Phellodendron chinense is probably due to of this synergism of isoquinoline alkaloids. All extracts were also tested for their cytotoxicity in COS7 cells and none of the most active extracts was cytotoxic at the concentrations which inhibit AChE. Based on these results it can be stated that some TCM plants inhibit AChE via synergistic interaction of their secondary metabolites. The possibility to isolate pure lead compounds from the crude extracts or to administer these as nutraceuticals or as cheap alternative to drugs in third world countries make TCM plants a versatile source of natural inhibitors of AChE. Full article
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Open AccessArticle Comparison of the Essential Oil Composition of Selected Impatiens Species and Its Antioxidant Activities
Molecules 2016, 21(9), 1162; doi:10.3390/molecules21091162
Received: 18 July 2016 / Revised: 24 August 2016 / Accepted: 26 August 2016 / Published: 1 September 2016
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Abstract
The present paper describes the chemical composition of the essential oils obtained by hydrodistillation from four Impatiens species, Impatiens glandulifera Royle, I. parviflora DC., I. balsamina L. and I. noli-tangere L. The GC and GC-MS methods resulted in identification of 226 volatile compounds
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The present paper describes the chemical composition of the essential oils obtained by hydrodistillation from four Impatiens species, Impatiens glandulifera Royle, I. parviflora DC., I. balsamina L. and I. noli-tangere L. The GC and GC-MS methods resulted in identification of 226 volatile compounds comprising from 61.7%–88.2% of the total amount. The essential oils differed significantly in their composition. Fifteen compounds were shared among the essential oils of all investigated Impatiens species. The majority of these constituents was linalool (0.7%–15.1%), hexanal (0.2%–5.3%) and benzaldehyde (0.1%–10.2%). Moreover, the antioxidant activity of the essential oils was investigated using different methods. The chemical composition of the essential oils and its antioxidant evaluation are reported for the first time from the investigated taxon. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Evaluation of the Enantiomer Specific Biokinetics and Radiation Doses of [18F]Fluspidine—A New Tracer in Clinical Translation for Imaging of σ1 Receptors
Molecules 2016, 21(9), 1164; doi:10.3390/molecules21091164
Received: 28 July 2016 / Revised: 22 August 2016 / Accepted: 26 August 2016 / Published: 1 September 2016
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Abstract
The enantiomers of [18F]fluspidine, recently developed for imaging of σ1 receptors, possess distinct pharmacokinetics facilitating their use in different clinical settings. To support their translational potential, we estimated the human radiation dose of (S)-(−)-[18F]fluspidine and (
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The enantiomers of [18F]fluspidine, recently developed for imaging of σ1 receptors, possess distinct pharmacokinetics facilitating their use in different clinical settings. To support their translational potential, we estimated the human radiation dose of (S)-(−)-[18F]fluspidine and (R)-(+)-[18F]fluspidine from ex vivo biodistribution and PET/MRI data in mice after extrapolation to the human scale. In addition, we validated the preclinical results by performing a first-in-human PET/CT study using (S)-(−)-[18F]fluspidine. Based on the respective time-activity curves, we calculated using OLINDA the particular organ doses (ODs) and effective doses (EDs). The ED values of (S)-(−)-[18F]fluspidine and (R)-(+)-[18F]fluspidine differed significantly with image-derived values obtained in mice with 12.9 μSv/MBq and 14.0 μSv/MBq (p < 0.025), respectively. A comparable ratio was estimated from the biodistribution data. In the human study, the ED of (S)-(−)-[18F]fluspidine was calculated as 21.0 μSv/MBq. Altogether, the ED values for both [18F]fluspidine enantiomers determined from the preclinical studies are comparable with other 18F-labeled PET imaging agents. In addition, the first-in-human study confirmed that the radiation risk of (S)-(−)-[18F]fluspidine imaging is within acceptable limits. However, as already shown for other PET tracers, the actual ED of (S)-(−)-[18F]fluspidine in humans was underestimated by preclinical imaging which needs to be considered in other first-in-human studies. Full article
(This article belongs to the Special Issue Molecular Imaging Probes)
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Open AccessArticle Single-Walled Carbon-Nanotubes-Based Organic Memory Structures
Molecules 2016, 21(9), 1166; doi:10.3390/molecules21091166
Received: 1 August 2016 / Revised: 24 August 2016 / Accepted: 29 August 2016 / Published: 2 September 2016
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Abstract
The electrical behaviour of organic memory structures, based on single-walled carbon-nanotubes (SWCNTs), metal–insulator–semiconductor (MIS) and thin film transistor (TFT) structures, using poly(methyl methacrylate) (PMMA) as the gate dielectric, are reported. The drain and source electrodes were fabricated by evaporating 50 nm gold, and
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The electrical behaviour of organic memory structures, based on single-walled carbon-nanotubes (SWCNTs), metal–insulator–semiconductor (MIS) and thin film transistor (TFT) structures, using poly(methyl methacrylate) (PMMA) as the gate dielectric, are reported. The drain and source electrodes were fabricated by evaporating 50 nm gold, and the gate electrode was made from 50 nm-evaporated aluminium on a clean glass substrate. Thin films of SWCNTs, embedded within the insulating layer, were used as the floating gate. SWCNTs-based memory devices exhibited clear hysteresis in their electrical characteristics (capacitance–voltage (CV) for MIS structures, as well as output and transfer characteristics for transistors). Both structures were shown to produce reliable and large memory windows by virtue of high capacity and reduced charge leakage. The hysteresis in the output and transfer characteristics, the shifts in the threshold voltage of the transfer characteristics, and the flat-band voltage shift in the MIS structures were attributed to the charging and discharging of the SWCNTs floating gate. Under an appropriate gate bias (1 s pulses), the floating gate is charged and discharged, resulting in significant threshold voltage shifts. Pulses as low as 1 V resulted in clear write and erase states. Full article
(This article belongs to the Special Issue Organic Memory Devices)
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Open AccessArticle Tetranortriterpenes and Limonoids from the Roots of Aphanamixis polystachya
Molecules 2016, 21(9), 1167; doi:10.3390/molecules21091167
Received: 22 June 2016 / Revised: 12 August 2016 / Accepted: 26 August 2016 / Published: 2 September 2016
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Abstract
Phytochemical investigation of the acetone extract from the roots of Aphanamixis polystachya resulted in isolation of four new tetranortriterpenes (14) in addition to one protolimonoid (methyl-1ξ,7R-diacetoxy-23R,25-dihydroxy-20S,24R-21,24-epoxy-3,4-seco-apotirucall-4(28),14(15)-diene-3-oate (5)), five known
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Phytochemical investigation of the acetone extract from the roots of Aphanamixis polystachya resulted in isolation of four new tetranortriterpenes (14) in addition to one protolimonoid (methyl-1ξ,7R-diacetoxy-23R,25-dihydroxy-20S,24R-21,24-epoxy-3,4-seco-apotirucall-4(28),14(15)-diene-3-oate (5)), five known limonoids (rohituka 3 (6), rohituka 7 (7), nymania 1 (8), rubrin G (9), prieurianin (10)) and a steroid (2,3-dihydroxy-5-pregnan-16-one (11)). Their structures were determined by spectroscopic analyses, including 2D-NMR (COSY, HMQC, HMBC, and NOESY) and high-resolution electrospray ionization mass spectrometry (HRESIMS). Cytotoxic and anti-inflammatory activities of these compounds were evaluated. Compounds 4 and 5 showed significant inhibition against superoxide generation and elastase release by human neutrophils in response to (formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B) (FMLP/CB). Full article
(This article belongs to the Special Issue Triterpenes and Triterpenoids 2016)
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Open AccessArticle 13C-NMR-Based Metabolomic Profiling of Typical Asian Soy Sauces
Molecules 2016, 21(9), 1168; doi:10.3390/molecules21091168
Received: 5 July 2016 / Revised: 29 August 2016 / Accepted: 30 August 2016 / Published: 2 September 2016
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Abstract
It has been a strong consumer interest to choose high quality food products with clear information about their origin and composition. In the present study, a total of 22 Asian soy sauce samples have been analyzed in terms of 13C-NMR spectroscopy. Spectral
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It has been a strong consumer interest to choose high quality food products with clear information about their origin and composition. In the present study, a total of 22 Asian soy sauce samples have been analyzed in terms of 13C-NMR spectroscopy. Spectral data were analyzed by multivariate statistical methods in order to find out the important metabolites causing the discrimination among typical soy sauces from different Asian regions. It was found that significantly higher concentrations of glutamate in Chinese red cooking (CR) soy sauce may be the result of the manual addition of monosodium glutamate (MSG) in the final soy sauce product. Whereas lower concentrations of amino acids, like leucine, isoleucine and valine, observed in CR indicate the different fermentation period used in production of CR soy sauce, on the other hand, the concentration of some fermentation cycle metabolites, such as acetate and sucrose, can be divided into two groups. The concentrations of these fermentation cycle metabolites were lower in CR and Singapore Kikkoman (SK), whereas much higher in Japanese shoyu (JS) and Taiwan (China) light (TL), which depict the influence of climatic conditions. Therefore, the results of our study directly indicate the influences of traditional ways of fermentation, climatic conditions and the selection of raw materials and can be helpful for consumers to choose their desired soy sauce products, as well as for researchers in further authentication studies about soy sauce. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle Atractylodin Inhibits Interleukin-6 by Blocking NPM-ALK Activation and MAPKs in HMC-1
Molecules 2016, 21(9), 1169; doi:10.3390/molecules21091169
Received: 9 June 2016 / Revised: 22 August 2016 / Accepted: 30 August 2016 / Published: 2 September 2016
Cited by 3 | PDF Full-text (2876 KB) | HTML Full-text | XML Full-text | Correction
Abstract
Atractylodin is one of the major constituents of the rhizome of Atractylodes lancea, which is widely used in Korean traditional medicine as a remedy for the treatment of gastritis and gastric ulcers. Despite of a major constituent of widely used botanical to
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Atractylodin is one of the major constituents of the rhizome of Atractylodes lancea, which is widely used in Korean traditional medicine as a remedy for the treatment of gastritis and gastric ulcers. Despite of a major constituent of widely used botanical to treat inflammatory responses little is known about anti-inflammatory effect of atractylodin in the human mast cell (HMC-1). Hence, we evaluated the effect of atractylodin on the release of IL-6, the involvement of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) and mitogen-activated protein kinases (MAPKs) in phorbol-12-myristate-13-acetate and A23187-induced HMC-1. In addition, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), phospholipase C (PLC) gamma 1, and AKT phosphorylation relevant to NPM-ALK signal pathway were assessed. IL-6 levels in the HMC-1 stimulated by phorbol-12-myristate-13-acetate and A23187 were apparently decreased by the treatment of atractylodin. Concurrently, atractylodin not only inhibited the phosphorylation of NPM-ALK, but also suppressed the phosphorylation of JAK2, STAT3, PLC gamma 1, and AKT. Furthermore, the activated mitogen-activated protein kinases (MAPKs) by phorbol-12-myristate-13-acetate and A23187 were inhibited by atractylodin. These results suggested that atractylodin might have a potential regulatory effect on inflammatory mediator expression through blockade of both the phosphorylation of MAPKs and the NPM-ALK signaling pathway. Full article
(This article belongs to the Special Issue Natural Products and Inflammation)
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Open AccessArticle Characterization of Antifungal Natural Products Isolated from Endophytic Fungi of Finger Millet (Eleusine coracana)
Molecules 2016, 21(9), 1171; doi:10.3390/molecules21091171
Received: 13 July 2016 / Revised: 19 August 2016 / Accepted: 27 August 2016 / Published: 3 September 2016
Cited by 2 | PDF Full-text (9478 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Finger millet is an ancient African-Indian crop that is resistant to many pathogens including the fungus, Fusarium graminearum. We previously reported the first isolation of putative fungal endophytes from finger millet and showed that the crude extracts of four strains had anti-
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Finger millet is an ancient African-Indian crop that is resistant to many pathogens including the fungus, Fusarium graminearum. We previously reported the first isolation of putative fungal endophytes from finger millet and showed that the crude extracts of four strains had anti-Fusarium activity. However, active compounds were isolated from only one strain. The objectives of this study were to confirm the endophytic lifestyle of the three remaining anti-Fusarium isolates, to identify the major underlying antifungal compounds, and to initially characterize the mode(s) of action of each compound. Results of confocal microscopy and a plant disease assay were consistent with the three fungal strains behaving as endophytes. Using bio-assay guided fractionation and spectroscopic structural elucidation, three anti-Fusarium secondary metabolites were purified and characterized. These molecules were not previously reported to derive from fungi nor have antifungal activity. The purified antifungal compounds were: 5-hydroxy 2(3H)-benzofuranone, dehydrocostus lactone (guaianolide sesquiterpene lactone), and harpagoside (an iridoide glycoside). Light microscopy and vitality staining were used to visualize the in vitro interactions between each compound and Fusarium; the results suggested a mixed fungicidal/fungistatic mode of action. We conclude that finger millet possesses fungal endophytes that can synthesize anti-fungal compounds not previously reported as bio-fungicides against F. graminearum. Full article
(This article belongs to the Section Natural Products)
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Open AccessCommunication Effects of Substitution on Solid-State Fluorescence in 9-Aryl-9-methyl-9H-9-silafluorenes
Molecules 2016, 21(9), 1173; doi:10.3390/molecules21091173
Received: 15 July 2016 / Revised: 30 August 2016 / Accepted: 31 August 2016 / Published: 3 September 2016
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Abstract
Aromatic groups were incorporated into 9H-9-silafluorene units at the 9-position (mono-9H-silafluorenes) and 9,9′-positions (di-9H-9-silafluorenes). The aryl substituents showed weak conjugation to the 9H-9-silafluorene for 9-aryl substituted ones 17 and a 9,9′-phenylene substituted one
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Aromatic groups were incorporated into 9H-9-silafluorene units at the 9-position (mono-9H-silafluorenes) and 9,9′-positions (di-9H-9-silafluorenes). The aryl substituents showed weak conjugation to the 9H-9-silafluorene for 9-aryl substituted ones 17 and a 9,9′-phenylene substituted one (compound 8) and they exhibited similar absorption and emission spectra. The 9H-9-silafluorene 10 containing a 5,5′-(2,2′-bithiophenyl) group showed a significantly red-shifted absorption and fluorescence maxima in the solid-state. Single-crystal X-ray diffraction studies found J-type aggregated structures formed by intermolecular CH–π interactions (ca. 2.6–2.7 Å). Density functional theory (DFT), time-dependent DFT (TD-DFT), and configuration interaction single (CIS) calculations were conducted to explain the observed optical properties. Full article
(This article belongs to the Special Issue Advances in Silicon Chemistry)
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Open AccessArticle C19-Norditerpenoid Alkaloids from Aconitum szechenyianum and Their Effects on LPS-Activated NO Production
Molecules 2016, 21(9), 1175; doi:10.3390/molecules21091175
Received: 16 July 2016 / Revised: 30 August 2016 / Accepted: 31 August 2016 / Published: 3 September 2016
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Abstract
Three new C19-norditerpenoid alkaloids (13), along with two known C19-norditerpenoid alkaloids (45) have been isolated from Aconitum szechenyianum. Their structures were established by extensive spectroscopic techniques and chemical methods as
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Three new C19-norditerpenoid alkaloids (13), along with two known C19-norditerpenoid alkaloids (45) have been isolated from Aconitum szechenyianum. Their structures were established by extensive spectroscopic techniques and chemical methods as szechenyianine A (1), szechenyianine B (2), szechenyianine C (3), N-deethyl-3-acetylaconitine (4), and N-deethyldeoxyaconitine (5). Additionally, compounds 15 were tested for the inhibition of NO production on LPS-activated RAW264.7 cells with IC50 values of 36.62 ± 6.86, 3.30 ± 0.11, 7.46 ± 0.89, 8.09 ± 1.31, and 11.73 ± 1.94 μM, respectively, while the positive control drug dexamethasone showed inhibitory activity with IC50 value of 8.32 ± 1.45 μM. The structure-activity relationship of aconitine alkaloids were discussed. Full article
(This article belongs to the Special Issue Diversity of Alkaloids)
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Open AccessArticle Palladium(II) Catalyzed Cyclization-Carbonylation-Cyclization Coupling Reaction of (ortho-Alkynyl Phenyl) (Methoxymethyl) Sulfides Using Molecular Oxygen as the Terminal Oxidant
Molecules 2016, 21(9), 1177; doi:10.3390/molecules21091177
Received: 22 July 2016 / Revised: 23 August 2016 / Accepted: 30 August 2016 / Published: 5 September 2016
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Abstract
An efficient PdII/Pd0-p-benzoquinone/hydroquinone-CuCl2/CuCl catalyst system was developed that uses environmentally friendly molecular oxygen as the terminal oxidant to catalyze the cyclization-carbonylation-cyclization coupling reaction (CCC-coupling reaction) of (o-alkynyl phenyl) (methoxymethyl) sulfides. Full article
(This article belongs to the Section Green Chemistry)
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Open AccessArticle Molecular Encapsulation of Histamine H2-Receptor Antagonists by Cucurbit[7]Uril: An Experimental and Computational Study
Molecules 2016, 21(9), 1178; doi:10.3390/molecules21091178
Received: 17 July 2016 / Revised: 31 August 2016 / Accepted: 1 September 2016 / Published: 6 September 2016
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Abstract
The histamine H2-receptor antagonists cimetidine, famotidine and nizatidine are individually encapsulated by macrocyclic cucurbit[7]uril (CB[7]), with binding affinities of 6.57 (±0.19) × 103 M−1, 1.30 (±0.27) × 104 M−1 and 1.05 (±0.33) × 105 M
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The histamine H2-receptor antagonists cimetidine, famotidine and nizatidine are individually encapsulated by macrocyclic cucurbit[7]uril (CB[7]), with binding affinities of 6.57 (±0.19) × 103 M−1, 1.30 (±0.27) × 104 M−1 and 1.05 (±0.33) × 105 M−1, respectively. These 1:1 host-guest inclusion complexes have been experimentally examined by 1H-NMR, UV-visible spectroscopic titrations (including Job plots), electrospray ionization mass spectrometry (ESI-MS), and isothermal titration calorimetry (ITC), as well as theoretically by molecular dynamics (MD) computation. This study may provide important insights on the supramolecular formulation of H2-receptor antagonist drugs for potentially enhanced stability and controlled release based on different binding strengths of these host-guest complexes. Full article
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Open AccessArticle Biphenyl Phytoalexin in Sorbus pohuashanensis Suspension Cell Induced by Yeast Extract
Molecules 2016, 21(9), 1180; doi:10.3390/molecules21091180
Received: 13 July 2016 / Revised: 16 August 2016 / Accepted: 31 August 2016 / Published: 14 September 2016
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Abstract
Biphenyls are unique phytoalexins de novo synthesized in plants in response to pathogen attack. These compounds are found in Maloideae, a subfamily of the Rosaceae. The anti-microbial activities of biphenyls have been reported in a number of studies and they appear to represent
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Biphenyls are unique phytoalexins de novo synthesized in plants in response to pathogen attack. These compounds are found in Maloideae, a subfamily of the Rosaceae. The anti-microbial activities of biphenyls have been reported in a number of studies and they appear to represent an important defense strategy against pathogens common in the Maloideae, such as species in Malus, Pyrus, Sorbus, and Chaenomeles. Here, cell suspension cultures of Sorbus pohuashanensis were established to study biphenyl phytoalexins formation after yeast extract (YE) treatment. An ultra-performance liquid chromatography (UPLC) method coupled with quadrupole time of flight mass spectrometry (Q-TOF-MS) LC−MS/MS was applied to determine the time course of these biphenyl biomarkers accumulation in YE-treated S. pohuashanensis suspension cells. The results of quantitative analyses show the content of Noraucuparin, 2′-Hydroxyaucuparin, and their glycosides initially increased, then decreased over time. The Noraucuparin content reached its highest (225.76 μg·g−1) at 18 h after treatment, 6 hours earlier than that of Noraucuparin 5-O-β-d-glucopyranoside. The content of 2′-Hydroxyaucuparin reached its highest (422.75 μg·g−1) at 30 h after treatment, also earlier than that of its glycoside. The understanding of phytoalexin metabolism in this study may provide a basis for improving Maloideae resistance to pathogens. Full article
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Open AccessArticle Structural Features of Alkaline Extracted Polysaccharide from the Seeds of Plantago asiatica L. and Its Rheological Properties
Molecules 2016, 21(9), 1181; doi:10.3390/molecules21091181
Received: 22 June 2016 / Revised: 20 August 2016 / Accepted: 1 September 2016 / Published: 6 September 2016
Cited by 1 | PDF Full-text (3263 KB) | HTML Full-text | XML Full-text
Abstract
Polysaccharide from the seeds of Plantago asiatica L. has many bioactivities, but few papers report on the structural and rheological characteristics of the alkaline extract. The alkaline extracted polysaccharide was prepared from seeds of P. asiatica L. and named herein as alkaline extracted
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Polysaccharide from the seeds of Plantago asiatica L. has many bioactivities, but few papers report on the structural and rheological characteristics of the alkaline extract. The alkaline extracted polysaccharide was prepared from seeds of P. asiatica L. and named herein as alkaline extracted polysaccharide from seeds of P. asiatica L. (PLAP). Its structural and rheological properties were characterized by monosaccharide composition, methylation, GC-MS and rheometry. PLAP, as an acidic arabinoxylan, was mainly composed of 1,2,4-linked Xylp and 1,3,4-linked Xylp residues. PLAP solution showed pseudoplastic behavior, and weak gelling properties at high concentration. Sodium and especially calcium ions played a significant role in increasing the apparent viscosity and gel strength. Full article
(This article belongs to the Special Issue Natural Polysaccharides)
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Open AccessArticle Stereoselective Reduction of Imines with Trichlorosilane Using Solid-Supported Chiral Picolinamides
Molecules 2016, 21(9), 1182; doi:10.3390/molecules21091182
Received: 28 July 2016 / Revised: 30 August 2016 / Accepted: 1 September 2016 / Published: 6 September 2016
Cited by 1 | PDF Full-text (1375 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The stereoselective reduction of imines with trichlorosilane catalyzed by chiral Lewis bases is a well-established procedure for the synthesis of enantio-enriched amines. Five supported cinchona-based picolinamides have been prepared and their activity tested in a model reaction. The comparison of different supporting materials
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The stereoselective reduction of imines with trichlorosilane catalyzed by chiral Lewis bases is a well-established procedure for the synthesis of enantio-enriched amines. Five supported cinchona-based picolinamides have been prepared and their activity tested in a model reaction. The comparison of different supporting materials revealed that polystyrene gave better results than silica in terms of stereoselectivity. The applicability of the solid-supported catalyst of choice to the reduction of different imines was also demonstrated. Additionally, for the first time, a catalytic reactor containing a polymer-immobilized chiral picolinamide has been employed for the stereoselective reduction of imines with trichlorosilane under continuous flow conditions. Full article
(This article belongs to the Special Issue Recent Advancements in Polymer-Supported Catalysis)
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Open AccessArticle Three Pairs of New Isopentenyl Dibenzo[b,e]oxepinone Enantiomers from Talaromyces flavus, a Wetland Soil-Derived Fungus
Molecules 2016, 21(9), 1184; doi:10.3390/molecules21091184
Received: 12 August 2016 / Revised: 27 August 2016 / Accepted: 2 September 2016 / Published: 7 September 2016
Cited by 1 | PDF Full-text (2054 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three pairs of new isopentenyl dibenzo[b,e]oxepinone enantiomers, (+)-(5S)-arugosin K (1a), (−)-(5R)-arugosin K (1b), (+)-(5S)-arugosin L (2a), (−)-(5R)-arugosin L (2b), (+)-(5S)-arugosin M
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Three pairs of new isopentenyl dibenzo[b,e]oxepinone enantiomers, (+)-(5S)-arugosin K (1a), (−)-(5R)-arugosin K (1b), (+)-(5S)-arugosin L (2a), (−)-(5R)-arugosin L (2b), (+)-(5S)-arugosin M (3a), (−)-(5R)-arugosin M (3b), and a new isopentenyl dibenzo[b,e]oxepinone, arugosin N (4), were isolated from a wetland soil-derived fungus Talaromyces flavus, along with two known biosynthetically-related compounds 5 and 6. Among them, arugosin N (4) and 1,6,10-trihydroxy-8-methyl-2-(3-methyl-2-butenyl)-dibenz[b,e]oxepin-11(6H)-one (CAS: 160585-91-1, 5) were obtained as the tautomeric mixtures. The structures of isolated compounds were determined by detailed spectroscopic analysis. In addition, the absolute configurations of these three pairs of new enantiomers were determined by quantum chemical ECD calculations. Full article
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Open AccessArticle Boronic Acid Group: A Cumbersome False Negative Case in the Process of Drug Design
Molecules 2016, 21(9), 1185; doi:10.3390/molecules21091185
Received: 18 July 2016 / Revised: 23 August 2016 / Accepted: 2 September 2016 / Published: 7 September 2016
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Abstract
Herein we present, an exhaustive docking analysis considering the case of autotaxin (ATX). HA155, a small molecule inhibitor of ATX, is co-crystallized. In order to further extract conclusions on the nature of the bond formed between the ligands and the amino acid residues
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Herein we present, an exhaustive docking analysis considering the case of autotaxin (ATX). HA155, a small molecule inhibitor of ATX, is co-crystallized. In order to further extract conclusions on the nature of the bond formed between the ligands and the amino acid residues of the active site, density functional theory (DFT) calculations were undertaken. However, docking does not provide reproducible results when screening boronic acid derivatives and their binding orientations to protein drug targets. Based on natural bond orbital (NBO) calculations, the formed bond between Ser/Thr residues is characterized more accurately as a polar covalent bond instead of a simple nonpolar covalent one. The presented results are acceptable and could be used in screening as an active negative filter for boron compounds. The hydroxyl groups of amino acids are bonded with the inhibitor’s boron atom, converting its hybridization to sp3. Full article
(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)
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Open AccessArticle Catechins Variously Affect Activities of Conjugation Enzymes in Proliferating and Differentiated Caco-2 Cells
Molecules 2016, 21(9), 1186; doi:10.3390/molecules21091186
Received: 27 July 2016 / Revised: 24 August 2016 / Accepted: 1 September 2016 / Published: 7 September 2016
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Abstract
The knowledge of processes in intestinal cells is essential, as most xenobiotics come into contact with the small intestine first. Caco-2 cells are human colorectal adenocarcinoma that once differentiated, exhibit enterocyte-like characteristics. Our study compares activities and expressions of important conjugation enzymes and
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The knowledge of processes in intestinal cells is essential, as most xenobiotics come into contact with the small intestine first. Caco-2 cells are human colorectal adenocarcinoma that once differentiated, exhibit enterocyte-like characteristics. Our study compares activities and expressions of important conjugation enzymes and their modulation by green tea extract (GTE) and epigallocatechin gallate (EGCG) using both proliferating (P) and differentiated (D) caco-2 cells. The mRNA levels of the main conjugation enzymes were significantly elevated after the differentiation of Caco-2 cells. However, no increase in conjugation enzymes’ activities in differentiated cells was detected in comparison to proliferating ones. GTE/EGCG treatment did not affect the mRNA levels of any of the conjugation enzymes tested in either type of cells. Concerning conjugation enzymes activities, GTE/EGCG treatment elevated glutathione S-transferase (GST) activity by approx. 30% and inhibited catechol-O-methyltransferase (COMT) activity by approx. 20% in differentiated cells. On the other hand, GTE as well as EGCG treatment did not significantly affect the activities of conjugation enzymes in proliferating cells. Administration of GTE/EGCG mediated only mild changes of GST and COMT activities in enterocyte-like cells, indicating a low risk of GTE/EGCG interactions with concomitantly administered drugs. However, a considerable chemo-protective effect of GTE via the pronounced induction of detoxifying enzymes cannot be expected as well. Full article
(This article belongs to the Special Issue Catechins and Human Health: Current State of the Science)
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Open AccessArticle Size-Dependent Photodynamic Anticancer Activity of Biocompatible Multifunctional Magnetic Submicron Particles in Prostate Cancer Cells
Molecules 2016, 21(9), 1187; doi:10.3390/molecules21091187
Received: 7 July 2016 / Revised: 18 August 2016 / Accepted: 31 August 2016 / Published: 6 September 2016
Cited by 3 | PDF Full-text (3810 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, newly designed biocompatible multifunctional magnetic submicron particles (CoFe2O4-HPs-FAs) of well-defined sizes (60, 133, 245, and 335 nm) were fabricated for application as a photosensitizer delivery agent for photodynamic therapy in cancer cells. To provide selective targeting
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In this study, newly designed biocompatible multifunctional magnetic submicron particles (CoFe2O4-HPs-FAs) of well-defined sizes (60, 133, 245, and 335 nm) were fabricated for application as a photosensitizer delivery agent for photodynamic therapy in cancer cells. To provide selective targeting of cancer cells and destruction of cancer cell functionality, basic cobalt ferrite (CoFe2O4) particles were covalently bonded with a photosensitizer (PS), which comprises hematoporphyrin (HP), and folic acid (FA) molecules. The magnetic properties of the CoFe2O4 particles were finely adjusted by controlling the size of the primary CoFe2O4 nanograins, and secondary superstructured composite particles were formed by aggregation of the nanograins. The prepared CoFe2O4-HP-FA exhibited high water solubility, good MR-imaging capacity, and biocompatibility without any in vitro cytotoxicity. In particular, our CoFe2O4-HP-FA exhibited remarkable photodynamic anticancer efficiency via induction of apoptotic death in PC-3 prostate cancer cells in a particle size- and concentration-dependent manner. This size-dependent effect was determined by the specific surface area of the particles because the number of HP molecules increased with decreasing size and increasing surface area. These results indicate that our CoFe2O4-HP-FA may be applicable for photodynamic therapy (PDT) as a PS delivery material and a therapeutic agent for MR-imaging based PDT owing to their high saturation value for magnetization and superparamagnetism. Full article
(This article belongs to the Special Issue Photodynamic Therapy)
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Open AccessArticle Synthesis and Antimicrobial Evaluation of 1-[(2-Substituted phenyl)carbamoyl]naphthalen-2-yl Carbamates
Molecules 2016, 21(9), 1189; doi:10.3390/molecules21091189
Received: 24 August 2016 / Revised: 2 September 2016 / Accepted: 5 September 2016 / Published: 7 September 2016
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Abstract
Series of thirteen 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl carbamates and thirteen 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl carbamates with alkyl/cycloalkyl/arylalkyl chains were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, two methicillin-resistant S. aureus strains, Mycobacterium marinum, and M. kansasii. 1-[(2-Chlorophenyl)carbamoyl]naphthalen-2-yl ethylcarbamate
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Series of thirteen 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl carbamates and thirteen 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl carbamates with alkyl/cycloalkyl/arylalkyl chains were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, two methicillin-resistant S. aureus strains, Mycobacterium marinum, and M. kansasii. 1-[(2-Chlorophenyl)carbamoyl]naphthalen-2-yl ethylcarbamate and 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl ethylcarbamate showed antistaphylococcal (MICs = 42 µM against MRSA) and antimycobacterial (MICs = 21 µM) activity against the tested strains comparable with or higher than that of the standards ampicillin and isoniazid. In the case of bulkier carbamate tails (R > propyl/isopropyl), the activity was similar (MICs ca. 70 µM). Screening of the cytotoxicity of both of the most effective compounds was performed using THP-1 cells, and no significant lethal effect was observed (LD50 >30 µM). The structure-activity relationships are discussed. Full article
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Open AccessArticle Isolation of α-Amylase Inhibitors from Kadsura longipedunculata Using a High-Speed Counter-Current Chromatography Target Guided by Centrifugal Ultrafiltration with LC-MS
Molecules 2016, 21(9), 1190; doi:10.3390/molecules21091190
Received: 9 August 2016 / Revised: 5 September 2016 / Accepted: 5 September 2016 / Published: 7 September 2016
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Abstract
In this study, a high-speed counter-current chromatography (HSCCC) separation method target guided by centrifugal ultrafiltration with high-performance liquid chromatography-mass spectrometry (CU-LC-MS) was proposed. This method was used to analyze α-amylase inhibitors from Kadsura longipedunculata extract. According to previous screening with CU-LC-MS, two screened
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In this study, a high-speed counter-current chromatography (HSCCC) separation method target guided by centrifugal ultrafiltration with high-performance liquid chromatography-mass spectrometry (CU-LC-MS) was proposed. This method was used to analyze α-amylase inhibitors from Kadsura longipedunculata extract. According to previous screening with CU-LC-MS, two screened potential α-amylase inhibitors was successfully isolated from Kadsura longipedunculata extract using HSCCC under the optimized experimental conditions. The isolated two target compounds (with purities of 92.3% and 94.6%) were, respectively, identified as quercetin-3-O-rhamnoside (1) and protocatechuic acid (2) based on the MS, UV, and 1H-NMR spectrometry data. To verify the inhibition of screened compounds, the inhibitory activities of quercetin-3-O-rhamnoside (1) and protocatechuic acid (2) on α-amylase were tested, and it demonstrated that the experimental IC50 values of quercetin-3-O-rhamnoside (1) and protocatechuic acid (2) were 28.8 and 12.5 μmol/L. These results proved that the hyphenated technique using CU-LC-MS and HSCCC was a rapid, competent, and reproductive method to screen and separate potential active compounds, like enzyme inhibitors from the extract of herbal medicines. Full article
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Open AccessArticle Pharmacokinetic Comparison of Scutellarin and Paeoniflorin in Sham-Operated and Middle Cerebral Artery Occlusion Ischemia and Reperfusion Injury Rats after Intravenous Administration of Xin-Shao Formula
Molecules 2016, 21(9), 1191; doi:10.3390/molecules21091191
Received: 24 July 2016 / Revised: 27 August 2016 / Accepted: 29 August 2016 / Published: 7 September 2016
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Abstract
Xin-Shao formula is a folk remedy widely used in China to prevent and cure stroke. Cerebral ischemic reperfusion (I/R) injury often takes place during the treatment of stroke. Information about the pharmacokinetic behavior of the remedy under cerebral I/R injury conditions is lacking.
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Xin-Shao formula is a folk remedy widely used in China to prevent and cure stroke. Cerebral ischemic reperfusion (I/R) injury often takes place during the treatment of stroke. Information about the pharmacokinetic behavior of the remedy under cerebral I/R injury conditions is lacking. The present study aimed to compare the pharmacokinetic properties of scutellarin and paeoniflorin, two major bioactive components of Xin-Shao formula, under physiological state in cerebral I/R injury rats. Neurobehavioral dysfunction was evaluated and cerebral infarcted volume was measured in middle cerebral artery occlusion I/R injury (MCAO) rats. Plasma samples were collected at various time points after a single dose (intravenous, i.v.) of Xin-Shao formula. The levels of plasma scutellarin and paeoniflorin at the designed time points were determined by a UPLC-MS/MS method, and drug concentration versus time plots were constructed to estimate pharmacokinetic parameters. Increase in terminal elimination half-life (t1/2z) and mean residence time (MRT(0–t)) of scutellarin as well as elevation in area under the plasma drug concentration-time curve from 0 h to the terminal time point (AUC(0–t)) and maximum plasma drug concentration (Cmax) of paeoniflorin, along with decreased clearance of paeoniflorin and scutellarin as well as reduced apparent volume of distribution (Vz) of paeoniflorin, were observed in MCAO rats, compared with those in sham-operated animals. The elimination of scutellarin and paeoniflorin were reduced in cerebral I/R injury reduced rats. Full article
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Open AccessArticle Effects of Culture Substrate Made of Poly(N-isopropylacrylamide-co-acrylic acid) Microgels on Osteogenic Differentiation of Mesenchymal Stem Cells
Molecules 2016, 21(9), 1192; doi:10.3390/molecules21091192
Received: 12 July 2016 / Revised: 23 August 2016 / Accepted: 30 August 2016 / Published: 9 September 2016
Cited by 2 | PDF Full-text (9446 KB) | HTML Full-text | XML Full-text
Abstract
Poly(N-isopropylacrylamide) (PNIPAM)-based polymers and gels are widely known and studied for their thermoresponsive property. In the biomaterials category, they are regarded as a potential cell culture substrate, not only because of their biocompatibility, but also their special character of allowing controlled
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Poly(N-isopropylacrylamide) (PNIPAM)-based polymers and gels are widely known and studied for their thermoresponsive property. In the biomaterials category, they are regarded as a potential cell culture substrate, not only because of their biocompatibility, but also their special character of allowing controlled detachment of cells via temperature stimulus. Previous research about PNIPAM-based substrates mostly concentrated on their effects in cell adhesion and proliferation. In this study, however, we investigate the influence of the PNIPAM-based substrate on the differentiation capacity of stem cells. Especially, we choose P(NIPAM-AA) microgels as a culture dish coating and mesenchymal stem cells (MSCs) are cultured on top of the microgels. Interestingly, we find that the morphology of MSCs changes remarkably on a microgel-coated surface, from the original spindle form to a more stretched and elongated cell shape. Accompanied by the alternation in morphology, the expression of several osteogenesis-related genes is elevated even without inducing factors. In the presence of full osteogenic medium, MSCs on a microgel substrate show an enhancement in the expression level of osteopontin and alizarin red staining signals, indicating the physical property of substrate has a direct effect on MSCs differentiation. Full article
(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)
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Open AccessArticle NO-Releasing Enmein-Type Diterpenoid Derivatives with Selective Antiproliferative Activity and Effects on Apoptosis-Related Proteins
Molecules 2016, 21(9), 1193; doi:10.3390/molecules21091193
Received: 12 July 2016 / Revised: 23 August 2016 / Accepted: 2 September 2016 / Published: 8 September 2016
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Abstract
A series of nine enmein-type ent-kaurane diterpenoid and furoxan-based nitric oxide (NO) donor hybrids (10ai) were designed and synthesized from commercially available oridonin (1). These hybrids were evaluated for their antiproliferative activity against Bel-7402, K562, MGC-803,
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A series of nine enmein-type ent-kaurane diterpenoid and furoxan-based nitric oxide (NO) donor hybrids (10ai) were designed and synthesized from commercially available oridonin (1). These hybrids were evaluated for their antiproliferative activity against Bel-7402, K562, MGC-803, and CaEs-17 human cancer cell lines and L-02 normal liver cells. The antiproliferative activity against tumor cells was stronger than the lead compound 1 and parent molecule 9 in most cases. Especially, compound 10f showed the strongest activity against human hepatocarcinoma Bel-7402 cell line with an IC50 of 0.81 μM and could also release 33.7 μmol/L NO at the time point of 60 min. Compounds 10ai also showed cytotoxic selectivity between tumor and normal liver cells with IC50 ranging from 22.1 to 33.9 μM. Furthermore, the apoptotic properties on Bel-7402 cells revealed that 10f could induce S phase cell cycle arrest and apoptosis at low micromolar concentrations. The effects of 10f on apoptosis-related proteins were also investigated. The potent antiproliferative activities and mechanistic studies warrant further preclinical investigations. Full article
(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)
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Open AccessArticle Chemical Composition, Antibacterial Properties and Mechanism of Action of Essential Oil from Clove Buds against Staphylococcus aureus
Molecules 2016, 21(9), 1194; doi:10.3390/molecules21091194
Received: 3 August 2016 / Revised: 30 August 2016 / Accepted: 5 September 2016 / Published: 8 September 2016
Cited by 7 | PDF Full-text (8430 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The essential oil of clove has a wide range of pharmacological and biological activities and is widely used in the medicine, fragrance and flavoring industries. In this work, 22 components of the essential oil obtained from clove buds were identified. Eugenol was the
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The essential oil of clove has a wide range of pharmacological and biological activities and is widely used in the medicine, fragrance and flavoring industries. In this work, 22 components of the essential oil obtained from clove buds were identified. Eugenol was the major component (76.23%). The essential oil exhibited strong antibacterial activity against Staphylococcus aureus ATCC 25923 with a minimum inhibitory concentration (MIC) of 0.625 mg/mL, and the antibacterial effects depended on its concentration and action time. Kill-time assays also confirmed the essential oil had a significant effect on the growth rate of surviving S. aureus. We hypothesized that the essential oil may interact with the cell wall and membrane first. On the one hand it destroys cell wall and membranes, next causing the losses of vital intracellular materials, which finally result in the bacterial death. Besides, essential oil penetrates to the cytoplasmic membrane or enters inside the cell after destruction of cell structure, and then inhibits the normal synthesis of DNA and proteins that are required for bacterial growth. These results suggested that the effects of the clove essential oil on the growth inhibition of S. aureus may be at the molecular level rather than only physical damage. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Comparison of Protein N-Homocysteinylation in Rat Plasma under Elevated Homocysteine Using a Specific Chemical Labeling Method
Molecules 2016, 21(9), 1195; doi:10.3390/molecules21091195
Received: 16 August 2016 / Revised: 2 September 2016 / Accepted: 5 September 2016 / Published: 8 September 2016
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Abstract
Elevated blood concentrations of homocysteine have been well established as a risk factor for cardiovascular diseases and neuropsychiatric diseases, yet the etiologic relationship of homocysteine to these disorders remains poorly understood. Protein N-homocysteinylation has been hypothesized as a contributing factor; however, it
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Elevated blood concentrations of homocysteine have been well established as a risk factor for cardiovascular diseases and neuropsychiatric diseases, yet the etiologic relationship of homocysteine to these disorders remains poorly understood. Protein N-homocysteinylation has been hypothesized as a contributing factor; however, it has not been examined globally owing to the lack of suitable detection methods. We recently developed a selective chemical method to label N-homocysteinylated proteins with a biotin-aldehyde tag followed by Western blotting analysis, which was further optimized in this study. We then investigated the variation of protein N-homocysteinylation in plasma from rats on a vitamin B12 deficient diet. Elevated “total homocysteine” concentrations were determined in rats with a vitamin B12 deficient diet. Correspondingly, overall levels of plasma protein N-homocysteinylation displayed an increased trend, and furthermore, more pronounced and statistically significant changes (e.g., 1.8-fold, p-value: 0.03) were observed for some individual protein bands. Our results suggest that, as expected, a general metabolic correlation exists between “total homocysteine” and N-homocysteinylation, although other factors are involved in homocysteine/homocysteine thiolactone metabolism, such as the transsulfuration of homocysteine by cystathionine β-synthase or the hydrolysis of homocysteine thiolactone by paraoxonase 1 (PON1), may play more significant or direct roles in determining the level of N-homocysteinylation. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessArticle Immobilization of α-Amylase from Anoxybacillus sp. SK3-4 on ReliZyme and Immobead Supports
Molecules 2016, 21(9), 1196; doi:10.3390/molecules21091196
Received: 21 July 2016 / Revised: 4 September 2016 / Accepted: 5 September 2016 / Published: 9 September 2016
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Abstract
α-Amylase from Anoxybacillus sp. SK3-4 (ASKA) is a thermostable enzyme that produces a high level of maltose from starches. A truncated ASKA (TASKA) variant with improved expression and purification efficiency was characterized in an earlier study. In this work, TASKA was purified and
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α-Amylase from Anoxybacillus sp. SK3-4 (ASKA) is a thermostable enzyme that produces a high level of maltose from starches. A truncated ASKA (TASKA) variant with improved expression and purification efficiency was characterized in an earlier study. In this work, TASKA was purified and immobilized through covalent attachment on three epoxide (ReliZyme EP403/M, Immobead IB-150P, and Immobead IB-150A) and an amino-epoxide (ReliZyme HFA403/M) activated supports. Several parameters affecting immobilization were analyzed, including the pH, temperature, and quantity (mg) of enzyme added per gram of support. The influence of the carrier surface properties, pore sizes, and lengths of spacer arms (functional groups) on biocatalyst performances were studied. Free and immobilized TASKAs were stable at pH 6.0–9.0 and active at pH 8.0. The enzyme showed optimal activity and considerable stability at 60 °C. Immobilized TASKA retained 50% of its initial activity after 5–12 cycles of reuse. Upon degradation of starches and amylose, only immobilized TASKA on ReliZyme HFA403/M has comparable hydrolytic ability with the free enzyme. To the best of our knowledge, this is the first report of an immobilization study of an α-amylase from Anoxybacillus spp. and the first report of α-amylase immobilization using ReliZyme and Immobeads as supports. Full article
(This article belongs to the Special Issue Enzyme Immobilization 2016)
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Open AccessArticle Synthesis and Anti-HIV-1 Activity Evaluation for Novel 3a,6a-Dihydro-1H-pyrrolo[3,4-c]pyrazole-4,6-dione Derivatives
Molecules 2016, 21(9), 1198; doi:10.3390/molecules21091198
Received: 9 August 2016 / Revised: 30 August 2016 / Accepted: 30 August 2016 / Published: 8 September 2016
Cited by 1 | PDF Full-text (849 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The search for new molecular constructs that resemble the critical two-metal binding pharmacophore and the halo-substituted phenyl functionality required for HIV-1 integrase (IN) inhibition represents a vibrant area of research within drug discovery. As reported herein, we have modified our recently disclosed 1-[2-(4-fluorophenyl)ethyl]-pyrrole-2,5-dione
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The search for new molecular constructs that resemble the critical two-metal binding pharmacophore and the halo-substituted phenyl functionality required for HIV-1 integrase (IN) inhibition represents a vibrant area of research within drug discovery. As reported herein, we have modified our recently disclosed 1-[2-(4-fluorophenyl)ethyl]-pyrrole-2,5-dione scaffolds to design 35 novel compounds with improved biological activities against HIV-1. These new compounds show single-digit micromolar antiviral potencies against HIV-1 and low toxicity. Among of them, compound 9g and 15i had potent anti-HIV-1 activities (EC50 < 5 μM) and excellent therapeutic index (TI, CC50/EC50 > 100). These two compounds have potential as lead compounds for further optimization into clinical anti-HIV-1 agents. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis and Cytotoxic Activity on Human Cancer Cells of Novel Isoquinolinequinone–Amino Acid Derivatives
Molecules 2016, 21(9), 1199; doi:10.3390/molecules21091199
Received: 25 July 2016 / Revised: 1 September 2016 / Accepted: 2 September 2016 / Published: 8 September 2016
Cited by 1 | PDF Full-text (3538 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A variety of aminoisoquinoline-5,8-quinones bearing α-amino acids moieties were synthesized from 3-methyl-4-methoxycarbonylisoquinoline-5,8-quinone and diverse l- and d-α-amino acid methyl esters. The members of the series were evaluated for their cytotoxic activity against normal and cancer cell lines by using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
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A variety of aminoisoquinoline-5,8-quinones bearing α-amino acids moieties were synthesized from 3-methyl-4-methoxycarbonylisoquinoline-5,8-quinone and diverse l- and d-α-amino acid methyl esters. The members of the series were evaluated for their cytotoxic activity against normal and cancer cell lines by using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. From the current investigation, structure–activity relationships demonstrate that the location and structure of the amino acid fragment plays a significant role in the cytotoxic effects. Moderate to high cytotoxic activity was observed and four members, derived from l-alanine, l-leucine, l-phenylalanine, and d-phenylalanine, were selected as promising compounds by their IC50 ranging from 0.5 to 6.25 μM and also by their good selectivity indexes (≥2.24). Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle LC-MS Supported Studies on the in Vitro Metabolism of both Enantiomers of Flubatine and the in Vivo Metabolism of (+)-[18F]Flubatine—A Positron Emission Tomography Radioligand for Imaging α4β2 Nicotinic Acetylcholine Receptors
Molecules 2016, 21(9), 1200; doi:10.3390/molecules21091200
Received: 8 August 2016 / Revised: 1 September 2016 / Accepted: 2 September 2016 / Published: 8 September 2016
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Abstract
Both enantiomers of [18F]flubatine are promising radioligands for neuroimaging of α4β2 nicotinic acetylcholine receptors (nAChRs) by positron emission tomography (PET). To support clinical studies in patients with early Alzheimer’s disease, a detailed examination of the metabolism in vitro and in vivo
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Both enantiomers of [18F]flubatine are promising radioligands for neuroimaging of α4β2 nicotinic acetylcholine receptors (nAChRs) by positron emission tomography (PET). To support clinical studies in patients with early Alzheimer’s disease, a detailed examination of the metabolism in vitro and in vivo has been performed. (+)- and (−)-flubatine, respectively, were incubated with liver microsomes from mouse and human in the presence of NADPH (β-nicotinamide adenine dinucleotide 2′-phosphate reduced tetrasodium salt). Phase I in vitro metabolites were detected and their structures elucidated by LC-MS/MS (liquid chromatography-tandem mass spectrometry). Selected metabolite candidates were synthesized and investigated for structural confirmation. Besides a high level of in vitro stability, the microsomal incubations revealed some species differences as well as enantiomer discrimination with regard to the formation of monohydroxylated products, which was identified as the main metabolic pathway in this assay. Furthermore, after injection of 250 MBq (+)-[18F]flubatine (specific activity > 350 GBq/μmol) into mouse, samples were prepared from brain, liver, plasma, and urine after 30 min and investigated by radio-HPLC (high performance liquid chromatography with radioactivity detection). For structure elucidation of the radiometabolites of (+)-[18F]flubatine formed in vivo, identical chromatographic conditions were applied to LC-MS/MS and radio-HPLC to compare samples obtained in vitro and in vivo. By this correlation approach, we assigned three of four main in vivo radiometabolites to products that are exclusively C- or N-hydroxylated at the azabicyclic ring system of the parent molecule. Full article
(This article belongs to the Special Issue Molecular Imaging Probes)
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Open AccessArticle Chemical and Antioxidant Properties of Wild Edible Mushrooms from Native Nothofagus spp. Forest, Argentina
Molecules 2016, 21(9), 1201; doi:10.3390/molecules21091201
Received: 18 August 2016 / Revised: 31 August 2016 / Accepted: 6 September 2016 / Published: 8 September 2016
Cited by 3 | PDF Full-text (1320 KB) | HTML Full-text | XML Full-text
Abstract
This study addresses issues regarding chemical and bioactive properties of nine wild edible mushrooms from native Nothofagus forest from Patagonia, Argentina. Macronutrients, sugars, fatty acids, tocopherols, organic acids, phenolic compounds and antioxidant properties were determined. Protein was found in high levels and varied
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This study addresses issues regarding chemical and bioactive properties of nine wild edible mushrooms from native Nothofagus forest from Patagonia, Argentina. Macronutrients, sugars, fatty acids, tocopherols, organic acids, phenolic compounds and antioxidant properties were determined. Protein was found in high levels and varied between 3.35 g/100 g dw in Cyttaria hariotii and 22.29 g/100 g dw in Lepista nuda. All of them presented mannitol and trehalose as main sugars. Mannitol was significantly higher in Ramaria patagonica, although absent in Fistulina endoxantha, whereas trehalose predominated in Aleurodiscus vitellinus, Hydropus dusenii, Cortinarius magellanicus, C. hariotii, Grifola gargal and L. nuda, ranging from 1.15 to 10.26 g/100 g dw; it was absent in R. patagonica. The major fatty acid found was linoleic acid, followed by oleic acid and palmitic acid. All species presented oxalic and fumaric acids, while some also had malic, quinic and citric acids. Tocopherols composition was variable. Cortinarius magellanicus presented significantly higher contents of both α-tocopherol and β-tocopherol. R. patagonica presented the best results in all the antioxidant activity assays (EC50 values ≤ 1 mg/mL) and the highest content of phenolic compounds presenting gallic, p-hydroxybenzoic, p-coumaric and cinnamic acids. This study constitutes the first report on chemical composition and nutritional value of most of these edible mushroom species. Furthermore, it provides important information necessary to characterize and define the use of these species as gastronomic delicacies, functional foods and sources of bioactive compounds. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Characterization of French Coriander Oil as Source of Petroselinic Acid
Molecules 2016, 21(9), 1202; doi:10.3390/molecules21091202
Received: 4 August 2016 / Revised: 31 August 2016 / Accepted: 6 September 2016 / Published: 8 September 2016
Cited by 6 | PDF Full-text (387 KB) | HTML Full-text | XML Full-text
Abstract
Coriander vegetable oil was extracted from fruits of French origin in a 23% yield. The oil was of good quality, with a low amount of free fatty acids (1.8%) and a concurrently high amount of triacylglycerols (98%). It is a rich source of
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Coriander vegetable oil was extracted from fruits of French origin in a 23% yield. The oil was of good quality, with a low amount of free fatty acids (1.8%) and a concurrently high amount of triacylglycerols (98%). It is a rich source of petroselinic acid (C18:1n-12), an important renewable building block, making up 73% of all fatty acids, with also significant amounts of linoleic acid (14%), oleic acid (6%), and palmitic acid (3%). The oil was characterized by a high unsaponifiable fraction, comprising a substantial amount of phytosterols (6.70 g/kg). The main sterol markers were β-sitosterol (35% of total sterols), stigmasterol (24%), and Δ7-stigmastenol (18%). Squalene was detected at an amount of 0.2 g/kg. A considerable amount of tocols were identified (500 mg/kg) and consisted mainly of tocotrienols, with γ-tocotrienol as the major compound. The phospholipid content was low at 0.3%, of which the main phospholipid classes were phosphatidic acid (33%), phosphatidylcholine (25%), phosphatidylinositol (17%), and phosphatidylethanolamine (17%). About 50% of all phospholipids were non-hydratable. The β-carotene content was low at 10 mg/kg, while a significant amount of chlorophyll was detected at about 11 mg/kg. An iron content of 1.4 mg/kg was determined through element analysis of the vegetable oil. The influence of fruit origin on the vegetable oil composition was shown to be very important, particularly in terms of the phospholipids, sterols, and tocols composition. Full article
(This article belongs to the Special Issue Chemicals from Biomass)
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Open AccessArticle Improvement in Flavonoids and Phenolic Acids Production and Pharmaceutical Quality of Sweet Basil (Ocimum basilicum L.) by Ultraviolet-B Irradiation
Molecules 2016, 21(9), 1203; doi:10.3390/molecules21091203
Received: 18 July 2016 / Revised: 30 August 2016 / Accepted: 3 September 2016 / Published: 9 September 2016
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Abstract
Sweet basil (Ocimum basilicum Linnaeus) is aromatic herb that has been utilized in traditional medicine. To improve the phytochemical constituents and pharmaceutical quality of sweet basil leaves, ultraviolet (UV)-B irradiation at different intensities (2.30, 3.60, and 4.80 W/m2) and durations
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Sweet basil (Ocimum basilicum Linnaeus) is aromatic herb that has been utilized in traditional medicine. To improve the phytochemical constituents and pharmaceutical quality of sweet basil leaves, ultraviolet (UV)-B irradiation at different intensities (2.30, 3.60, and 4.80 W/m2) and durations (4, 6, 8, and 10-h) was applied at the post-harvest stage. Total flavonoid content (TFC) and total phenolic content (TPC) were measured using spectrophotometric method, and individual flavonoids and phenolic acids were identified using ultra-high performance liquid chromatography. As a key enzyme for the metabolism of flavonoids, chalcone synthase (CHS) activity, was measured using a CHS assay. Antioxidant activity and antiproliferative activity of extracts against a breast cancer cell line (MCF-7) were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, respectively. UV-B irradiation at an intensity of 3.60 W/m2 increased TFC approximately 0.85-fold and also increased quercetin (0.41-fold), catechin (0.85-fold), kaempferol (0.65-fold) rutin (0.68-fold) and luteolin (1.00-fold) content. The highest TPC and individual phenolic acid (gallic acid, cinnamic acid and ferulic acid) was observed in the 3.60 W/m2 of UV-B treatment. Cinnamic acid and luteolin were not detected in the control plants, production being induced by UV-B irradiation. Production of these secondary metabolites was also significantly influenced by the duration of UV-B irradiation. Irradiation for 8-h led to higher TFC, TPC and individual flavonoids and phenolic acids than for the other durations (4, 8, and 10-h) except for cinnamic acid, which was detected at higher concentration when irradiated for 6-h. Irradiation for 10-h significantly decreased the secondary metabolite production in sweet basil leaves. CHS activity was induced by UV-B irradiation and highest activity was observed at 3.60 W/m2 of UV-B irradiation. UV-B treated leaves presented the highest DPPH activity and antiproliferative activity with a half-maximal inhibitory concentration (IC50) value of 56.0 and 40.8 µg/mL, respectively, over that of the control plants (78.0 and 58.2 µg/mL, respectively). These observations suggest that post-harvest irradiation with UV-B can be considered a promising technique to improve the healthy–nutritional and pharmaceutical properties of sweet basil leaves. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Chemical Analysis of Dietary Constituents in Rosa roxburghii and Rosa sterilis Fruits
Molecules 2016, 21(9), 1204; doi:10.3390/molecules21091204
Received: 21 June 2016 / Revised: 2 September 2016 / Accepted: 3 September 2016 / Published: 9 September 2016
Cited by 2 | PDF Full-text (1450 KB) | HTML Full-text | XML Full-text
Abstract
Both Rosa roxburghii and R. sterilis, belonging to the Rosaceae, are endemic species in Guizhou Province, China. The fruits of these two species are mixed-used as functional food in the region. Aiming to elucidate the phytochemical characteristics of R. roxburghii and R.
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Both Rosa roxburghii and R. sterilis, belonging to the Rosaceae, are endemic species in Guizhou Province, China. The fruits of these two species are mixed-used as functional food in the region. Aiming to elucidate the phytochemical characteristics of R. roxburghii and R. sterilis fruits, the essential oils and constituents in a methanol extract have been analyzed and compared by GC-MS and UFLC/Q-TOF-MS, respectively. As a result, a total of 135 volatile compounds were identified by GC-MS and 91 components were different between R. roxburghii and R. sterilis fruits; a total of 59 compounds in methanol extracts were identified by UFLC/Q-TOF-MS, including 13 organic acids, 12 flavonoids, 11 triterpenes, nine amino acids, five phenylpropanoid derivatives, four condensed tannins, two stilbenes, two benzaldehyde derivatives and one benzoic acid derivative; and nine characteristic compounds were found between R. roxburghii and R. sterilis fruits. This systematic study plays an important role for R. roxburghii and R. sterilis fruits in the product development. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle A Highly Efficient and Reusable Palladium(II)/Cationic 2,2’-Bipyridyl-Catalyzed Stille Coupling in Water
Molecules 2016, 21(9), 1205; doi:10.3390/molecules21091205
Received: 13 August 2016 / Revised: 2 September 2016 / Accepted: 6 September 2016 / Published: 9 September 2016
Cited by 2 | PDF Full-text (542 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A water-soluble PdCl2(NH3)2/cationic 2,2′-bipyridyl system was found to be a highly efficient catalyst for Stille coupling of aryl iodides and bromides with organostannanes. The coupling reaction was conducted at 110 °C in water, under aerobic conditions, in
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A water-soluble PdCl2(NH3)2/cationic 2,2′-bipyridyl system was found to be a highly efficient catalyst for Stille coupling of aryl iodides and bromides with organostannanes. The coupling reaction was conducted at 110 °C in water, under aerobic conditions, in the presence of NaHCO3 as a base to afford corresponding Stille coupling products in good to high yields. When aryltributylstannanes were employed, the reactions proceeded smoothly under a very low catalyst loading (as little as 0.0001 mol %). After simple extraction, the residual aqueous phase could be reused in subsequent runs, making this Stille coupling economical. In the case of tetramethylstannane, however, a greater catalyst loading (1 mol %) and the use of tetraethylammonium iodide as a phase-transfer agent were required in order to obtain satisfactory yields. Full article
(This article belongs to the Special Issue Palladium Catalysts 2016)
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Open AccessArticle Anti-Inflammatory Effects and Mechanisms of Action of Coussaric and Betulinic Acids Isolated from Diospyros kaki in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages
Molecules 2016, 21(9), 1206; doi:10.3390/molecules21091206
Received: 4 August 2016 / Revised: 6 September 2016 / Accepted: 7 September 2016 / Published: 9 September 2016
Cited by 6 | PDF Full-text (3254 KB) | HTML Full-text | XML Full-text
Abstract
Diospyros kaki Thunb. is widely distributed in East Asian countries, its leaves being mainly used for making tea. In this study, coussaric acid (CA) and betulinic acid (BA), both triterpenoid compounds, were obtained from D. kaki leaf extracts through bioassay-guided isolation. CA and
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Diospyros kaki Thunb. is widely distributed in East Asian countries, its leaves being mainly used for making tea. In this study, coussaric acid (CA) and betulinic acid (BA), both triterpenoid compounds, were obtained from D. kaki leaf extracts through bioassay-guided isolation. CA and BA showed anti-inflammatory effects via inhibition of the nuclear factor-κB (NF-κB) pathway, providing important information on their anti-inflammatory mechanism. Furthermore, they markedly inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages, and suppressed tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) levels. Furthermore, they decreased protein expression of inducible nitric oxide synthase and cyclooxygenase-2. Pre-treatment with CA and BA inhibited LPS-induced NF-κB. We further examined the effects of CA and BA on heme oxygenase (HO)-1 expression in RAW 264.7 macrophages: BA induced HO-1 protein expression in a dose-dependent manner, while CA had no effect. We also investigated whether BA treatment induced nuclear translocation of Nrf2. BA inhibited LPS-induced NF-κB-binding activity, as well as pro-inflammatory mediator and cytokine production (e.g., NO, PGE2, TNF-α, IL-1β, IL-6), by partial reversal of this effect by SnPP, an inhibitor of HO-1. These findings further elucidate the anti-inflammatory mechanism of CA and BA isolated from D. kaki. Full article
(This article belongs to the Special Issue Natural Products and Inflammation)
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Open AccessArticle Synthesis and Antimicrobial Characterization of Half-Calycanthaceous Alkaloid Derivatives
Molecules 2016, 21(9), 1207; doi:10.3390/molecules21091207
Received: 3 July 2016 / Revised: 6 September 2016 / Accepted: 6 September 2016 / Published: 9 September 2016
Cited by 1 | PDF Full-text (539 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A total of 29 novel tetrahydropyrroloindol-based calycanthaceous alkaloid derivatives were synthesized from indole-3-acetonitrile in good yields. The synthesized compounds were evaluated against nine strains of bacteria and a wide range of plant pathogen fungi. Bioassay results revealed that majority of the compounds displayed
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A total of 29 novel tetrahydropyrroloindol-based calycanthaceous alkaloid derivatives were synthesized from indole-3-acetonitrile in good yields. The synthesized compounds were evaluated against nine strains of bacteria and a wide range of plant pathogen fungi. Bioassay results revealed that majority of the compounds displayed similar or higher in vitro antimicrobial activities than the positive control. The biological activities also indicated that substituents at R4 and R5 significantly affect the activities. Notably, compound c4 was found to be most active among the tested calycanthaceous analogues and might be a novel potential leading compound for further development as an antifungal agent. The results could pave the way for further design and structural modification of calycanthaceous alkaloids as antimicrobial agents. Full article
(This article belongs to the Special Issue Natural Product Inspired Scaffolds Designs)
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Open AccessArticle Impact of Biohybrid Magnetite Nanoparticles and Moroccan Propolis on Adherence of Methicillin Resistant Strains of Staphylococcus aureus
Molecules 2016, 21(9), 1208; doi:10.3390/molecules21091208
Received: 21 July 2016 / Revised: 28 August 2016 / Accepted: 2 September 2016 / Published: 9 September 2016
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Abstract
Biofilm bacteria are more resistant to antibiotics than planktonic cells. Propolis possesses antimicrobial activity. Generally, nanoparticles containing heavy metals possess antimicrobial and antibiofilm properties. In this study, the ability of adherence of Methicillin Resistant Strains of Staphylococcus aureus (MRSA) to catheters treated with
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Biofilm bacteria are more resistant to antibiotics than planktonic cells. Propolis possesses antimicrobial activity. Generally, nanoparticles containing heavy metals possess antimicrobial and antibiofilm properties. In this study, the ability of adherence of Methicillin Resistant Strains of Staphylococcus aureus (MRSA) to catheters treated with magnetite nanoparticles (MNPs), produced by three methods and functionalized with oleic acid and a hydro-alcoholic extract of propolis from Morocco, was evaluated. The chemical composition of propolis was established by gas chromatography mass spectrometry (GC-MS), and the fabricated nanostructures characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Mossbauer spectroscopy and Fourrier transform infrared spectroscopy (FTIR). The capacity for impairing biofilm formation was dependent on the strain, as well as on the mode of production of MNPs. The co-precipitation method of MNPs fabrication using Fe3+ and Na2SO3 solution and functionalized with oleic acid and propolis was the most effective in the impairment of adherence of all MRSA strains to catheters (p < 0.001). The adherence of the strain MRSA16 was also significantly lower (p < 0.001) when the catheters were treated with the hybrid MNPs with oleic acid produced by a hydrothermal method. The anti-MRSA observed can be attributed to the presence of benzyl caffeate, pinocembrin, galangin, and isocupressic acid in propolis extract, along with MNPs. However, for MRSA16, the impairment of its adherence on catheters may only be attributed to the hybrid MNPs with oleic acid, since very small amount, if any at all of propolis compounds were added to the MNPs. Full article
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Open AccessArticle Detection of 191 Taxifolin Metabolites and Their Distribution in Rats Using HPLC-ESI-IT-TOF-MSn
Molecules 2016, 21(9), 1209; doi:10.3390/molecules21091209
Received: 5 July 2016 / Revised: 4 September 2016 / Accepted: 6 September 2016 / Published: 13 September 2016
Cited by 2 | PDF Full-text (4284 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Taxifolin is a ubiquitous bioactive constituent of foods and herbs. To thoroughly explore its metabolism in vivo, an HPLC-ESI-IT-TOF-MSn method combined with specific metabolite detection strategy was used to detect and identify the metabolites of taxifolin in rats. Of the 191 metabolites
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Taxifolin is a ubiquitous bioactive constituent of foods and herbs. To thoroughly explore its metabolism in vivo, an HPLC-ESI-IT-TOF-MSn method combined with specific metabolite detection strategy was used to detect and identify the metabolites of taxifolin in rats. Of the 191 metabolites tentatively identified, 154 were new metabolites, 69 were new compounds and 32 were dimers. This is the first report of the in vivo biotransformation of a single compound into more than 100 metabolites. Furthermore, acetylamination and pyroglutamic acid conjugation were identified as new metabolic reactions. Seventeen metabolites were found to have various taxifolin-related bioactivities. The potential targets of taxifolin and 63 metabolites were predicted using PharmMapper, with results showing that more than 60 metabolites have the same five targets. Metabolites with the same fragment pattern may have the same pharmacophore. Thus these metabolites may exert the same pharmacological effects as taxifolin through an additive effect on the same drug targets. This observation indicates that taxifolin is bioactive not only in the parent form, but also through its metabolites. These findings enhance understanding of the metabolism and effective forms of taxifolin and may provide further insight of the beneficial effects of taxifolin and its derivatives. Full article
(This article belongs to the Section Metabolites)
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