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Molecules, Volume 22, Issue 7 (July 2017)

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Cover Story A new multifunctional composite, based on hydroxyapatite porous granules doped with selenite ions, [...] Read more.
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Editorial

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Open AccessEditorial Special Issue: Chitin, Chitosan and Related Enzymes
Molecules 2017, 22(7), 1066; doi:10.3390/molecules22071066
Received: 19 June 2017 / Revised: 20 June 2017 / Accepted: 20 June 2017 / Published: 27 June 2017
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Abstract
Chitin and chitosan are very abundant natural polymers with distinctive properties, such as bioactivity, biocompatibility and biodegradability, that have inspired a number of basic and applied studies, mostly in biotechnology, medicine, food preservation and agriculture.[...] Full article
(This article belongs to the Special Issue Chitin, Chitosan and Related Enzymes)
Open AccessFeature PaperEditorial Special Issue: Frontiers in Antimicrobial Drug Discovery and Design
Molecules 2017, 22(7), 1127; doi:10.3390/molecules22071127
Received: 4 July 2017 / Accepted: 4 July 2017 / Published: 6 July 2017
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Abstract
Since the discovery of Penicillin, antibiotics have saved millions of lives every year.[...] Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
Open AccessFeature PaperEditorial Special Issue: Adenosine Receptors
Molecules 2017, 22(7), 1220; doi:10.3390/molecules22071220
Received: 16 July 2017 / Accepted: 18 July 2017 / Published: 20 July 2017
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Abstract
Nearly 90 years ago, Drury and Szent-Györgyi revealed that adenosine produced profound hypotension and bradycardia, and it affected kidney function in mammals [1]. [...]
Full article
(This article belongs to the Special Issue Adenosine Receptors)

Research

Jump to: Editorial, Review, Other

Open AccessArticle Chemical Composition, Antibacterial and Antifungal Activities of Crude Dittrichia viscosa (L.) Greuter Leaf Extracts
Molecules 2017, 22(7), 942; doi:10.3390/molecules22070942
Received: 12 May 2017 / Revised: 31 May 2017 / Accepted: 3 June 2017 / Published: 30 June 2017
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Abstract
The small amount of data regarding the antifungal activity of Dittrichia viscosa (L.) Greuter against dermatophytes, Malassezia spp. and Aspergillus spp., associated with the few comparative studies on the antimicrobial activity of methanolic, ethanolic, and butanolic extracts underpins the study herein presented. The
[...] Read more.
The small amount of data regarding the antifungal activity of Dittrichia viscosa (L.) Greuter against dermatophytes, Malassezia spp. and Aspergillus spp., associated with the few comparative studies on the antimicrobial activity of methanolic, ethanolic, and butanolic extracts underpins the study herein presented. The total condensed tannin (TCT), phenol (TPC), flavonoid (TFC), and caffeoylquinic acid (CQC) content of methanol, butanol, and ethanol (80% and 100%) extracts of D. viscosa were assessed and their bactericidal and fungicidal activities were evaluated. The antibacterial, anti-Candida and anti-Malassezia activities were evaluated by using the disk diffusion method, whereas the anti-Microsporum canis and anti-Aspergillus fumigatus activities were assessed by studying the toxicity effect of the extracts on vegetative growth, sporulation and germination. The methanolic extract contained the highest TPC and CQC content. It contains several phytochemicals mainly caffeoylquinic acid derivatives as determined by liquid chromatography with photodiode array and electrospray ionisation mass spectrometric detection (LC/PDA/ESI-MS) analysis. All extracts showed an excellent inhibitory effect against bacteria and Candida spp., whereas methanolic extract exhibited the highest antifungal activities against Malassezia spp., M. canis and A. fumigatus strains. The results clearly showed that all extracts, in particular the methanolic extract, might be excellent antimicrobial drugs for treating infections that are life threatening (i.e., Malassezia) or infections that require mandatory treatments (i.e., M. canis or A. fumigatus). Full article
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Open AccessArticle Studies on the Two Thymine Residues in the Catalytic Core of 10-23 DNAzyme: The Impact on the Catalysis of Their 5-Substituted Functional Groups
Molecules 2017, 22(7), 1011; doi:10.3390/molecules22071011
Received: 26 May 2017 / Revised: 9 June 2017 / Accepted: 15 June 2017 / Published: 22 June 2017
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Abstract
In the 15-mer catalytic core of 10-23 DNAzyme, each residue contributes to the catalytic conformation differently. Here, the critically conserved T4 and the least conserved T8 were modified on their 5-position with hydroxyl, imidazolyl, and amino groups with a hydrogen-bonding ability. These external
[...] Read more.
In the 15-mer catalytic core of 10-23 DNAzyme, each residue contributes to the catalytic conformation differently. Here, the critically conserved T4 and the least conserved T8 were modified on their 5-position with hydroxyl, imidazolyl, and amino groups with a hydrogen-bonding ability. These external functional groups induced new interactions within the catalytic core, resulting in both negative and positive effects on the catalytic activity of 10-23 DNAzyme, and the different linkages could be used to modulate the effect of the functional groups. The conservation of T4 and T8 could be recognized at the level of the nucleobase, but at the level of the functional group, T4 is not completely conserved. Their 5-methyl groups could be modified for a better performance in terms of the DNAzyme. Full article
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Open AccessArticle Synthesis and In Vitro Anti-Influenza Virus Evaluation of Novel Sialic Acid (C-5 and C-9)-Pentacyclic Triterpene Derivatives
Molecules 2017, 22(7), 1018; doi:10.3390/molecules22071018
Received: 16 May 2017 / Revised: 16 June 2017 / Accepted: 16 June 2017 / Published: 22 June 2017
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Abstract
The emergence of drug resistant variants of the influenza virus has led to a great need to identify novel and effective antiviral agents. In our previous study, a series of sialic acid (C-2 and C-4)-pentacyclic triterpene conjugates have been synthesized, and a five-fold
[...] Read more.
The emergence of drug resistant variants of the influenza virus has led to a great need to identify novel and effective antiviral agents. In our previous study, a series of sialic acid (C-2 and C-4)-pentacyclic triterpene conjugates have been synthesized, and a five-fold more potent antiviral activity was observed when sialic acid was conjugated with pentacyclic triterpene via C-4 than C-2. It was here that we further reported the synthesis and anti-influenza activity of novel sialic acid (C-5 and C-9)-pentacyclic triterpene conjugates. Their structures were confirmed by ESI-HRMS, 1H-NMR, and 13C-NMR spectroscopic analyses. Two conjugates (26 and 42) showed strong cytotoxicity to MDCK cells in the CellTiter-Glo assay at a concentration of 100 μM. However, they showed no significant cytotoxicity to HL-60, Hela, and A549 cell lines in MTT assay under the concentration of 10 μM (except compound 42 showed weak cytotoxicity to HL-60 cell line (10 μM, ~53%)). Compounds 20, 28, 36, and 44 displayed weak potency to influenza A/WSN/33 (H1N1) virus (100 μM, ~20–30%), and no significant anti-influenza activity was found for the other conjugates. The data suggested that both the C-5 acetylamide and C-9 hydroxy of sialic acid were important for its binding with hemagglutinin during viral entry into host cells, while C-4 and C-2 hydroxy were not critical for the binding process and could be replaced with hydrophobic moieties. The research presented herein had significant implications for the design of novel antiviral inhibitors based on a sialic acid scaffold. Full article
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Open AccessFeature PaperArticle Albumin and Hyaluronic Acid-Coated Superparamagnetic Iron Oxide Nanoparticles Loaded with Paclitaxel for Biomedical Applications
Molecules 2017, 22(7), 1030; doi:10.3390/molecules22071030
Received: 22 May 2017 / Accepted: 16 June 2017 / Published: 22 June 2017
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Abstract
Super paramagnetic iron oxide nanoparticles (SPION) were augmented by both hyaluronic acid (HA) and bovine serum albumin (BSA), each covalently conjugated to dopamine (DA) enabling their anchoring to the SPION. HA and BSA were found to simultaneously serve as stabilizing polymers of Fe
[...] Read more.
Super paramagnetic iron oxide nanoparticles (SPION) were augmented by both hyaluronic acid (HA) and bovine serum albumin (BSA), each covalently conjugated to dopamine (DA) enabling their anchoring to the SPION. HA and BSA were found to simultaneously serve as stabilizing polymers of Fe3O4·DA-BSA/HA in water. Fe3O4·DA-BSA/HA efficiently entrapped and released the hydrophobic cytotoxic drug paclitaxel (PTX). The relative amount of HA and BSA modulates not only the total solubility but also the paramagnetic relaxation properties of the preparation. The entrapping of PTX did not influence the paramagnetic relaxation properties of Fe3O4·DA-BSA. Thus, by tuning the surface structure and loading, we can tune the theranostic properties of the system. Full article
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Open AccessArticle Use of Chitosan-PVA Hydrogels with Copper Nanoparticles to Improve the Growth of Grafted Watermelon
Molecules 2017, 22(7), 1031; doi:10.3390/molecules22071031
Received: 16 May 2017 / Revised: 18 June 2017 / Accepted: 19 June 2017 / Published: 22 June 2017
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Abstract
Modern agriculture requires alternative practices that improve crop growth without negatively affecting the environment, as resources such as water and arable land grow scarcer while the human population continues to increase. Grafting is a cultivation technique that allows the plant to be more
[...] Read more.
Modern agriculture requires alternative practices that improve crop growth without negatively affecting the environment, as resources such as water and arable land grow scarcer while the human population continues to increase. Grafting is a cultivation technique that allows the plant to be more efficient in its utilization of water and nutrients, while nanoscale material engineering provides the opportunity to use much smaller quantities of consumables compared to conventional systems but with similar or superior effects. On those grounds, we evaluated the effects of chitosan-polyvinyl alcohol hydrogel with absorbed copper nanoparticles (Cs-PVA-nCu) on leaf morphology and plant growth when applied to grafted watermelon cultivar ‘Jubilee’ plants. Stomatal density (SD), stomatal index (SI), stoma length (SL), and width (SW) were evaluated. The primary stem and root length, the stem diameter, specific leaf area, and fresh and dry weights were also recorded. Our results demonstrate that grafting induces modifications to leaf micromorphology that favorably affect plant growth, with grafted plants showing better vegetative growth in spite of their lower SD and SI values. Application of Cs-PVA-nCu was found to increase stoma width, primary stem length, and root length by 7%, 8% and 14%, respectively. These techniques modestly improve plant development and growth. Full article
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Open AccessArticle Effect of Solution pH on the Adsorption of Paracetamol on Chemically Modified Activated Carbons
Molecules 2017, 22(7), 1032; doi:10.3390/molecules22071032
Received: 13 April 2017 / Accepted: 13 June 2017 / Published: 22 June 2017
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Abstract
Paracetamol adsorption in acidic, neutral and basic media on three activated carbons with different chemistry surfaces was studied. A granular activated carbon (GAC) was prepared from coconut shell; starting from this sample, an oxidized activated carbon (GACo) was obtained by treating the GAC
[...] Read more.
Paracetamol adsorption in acidic, neutral and basic media on three activated carbons with different chemistry surfaces was studied. A granular activated carbon (GAC) was prepared from coconut shell; starting from this sample, an oxidized activated carbon (GACo) was obtained by treating the GAC with a boiling solution of 6 M nitric acid, so to generate a greater number of oxygenated surface groups. In addition, a reduced activated carbon (GACr) was obtained by heating the GAC at 1173 K, to remove the oxygenated surface groups. Paracetamol adsorption was higher for GACr due to the lower presence of oxygenated surface functional groups. Moreover, adsorption was highest at neutral pH. The magnitude of the interactions between paracetamol molecules and activated carbons was studied by measuring the immersion enthalpies of activated carbons in solution of paracetamol at different concentrations and pH values and by calculating the interaction enthalpy. The highest value was obtained for GACr in a paracetamol solution of 1000 mg L−1 at pH 7, confirming that paracetamol adsorption is favoured on basic activated carbons at pH values near to neutrality. Finally, the Gibbs energy changes confirmed the latter result, allowing explaining the different magnitudes of the interactions between paracetamol and activated carbons, as a function of solution pH. Full article
(This article belongs to the Section Green Chemistry)
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Open AccessArticle Total Flavonoids of Drynariae Rhizoma Prevent Bone Loss Induced by Hindlimb Unloading in Rats
Molecules 2017, 22(7), 1033; doi:10.3390/molecules22071033
Received: 27 April 2017 / Revised: 12 June 2017 / Accepted: 15 June 2017 / Published: 22 June 2017
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Abstract
Drynariae Rhizoma is a kidney-tonifying herb that has a long history in clinical practice for the treatment of bone fractures and joint diseases in China. Flavonoids are considered to be its major active ingredients and are reported to ease bone loss in ovariectomized
[...] Read more.
Drynariae Rhizoma is a kidney-tonifying herb that has a long history in clinical practice for the treatment of bone fractures and joint diseases in China. Flavonoids are considered to be its major active ingredients and are reported to ease bone loss in ovariectomized rats. However, the beneficial effects of the total flavonoids of Drynariae Rhizoma on osteoporosis caused by microgravity or mechanical inactivity remain unknown. This study assessed the effects of total Drynariae Rhizoma flavonoids (DRTF, Qihuang, Beijing, China, national medicine permit No. Z20030007, number of production: 04080081, content of DRTF ≥80%) against bone loss induced by simulated microgravity. A hindlimb unloading tail-suspended rat model was established to determine the effect of DRTF on bone mineral density (BMD), biomechanical strength and trabecular bone microarchitecture. Twenty-eight male Sprague–Dawley rats were divided into four groups: the baseline, control, hindlimb unloading with vehicle (HLU), and hindlimb unloading treated with DRTF (HLU–DRTF, 75 mg/kg/day) groups. Oral DRTF was administered for 4 weeks. The underlying mechanisms of the DRTF actions on disuse-induced osteoporosis are discussed. The results showed that DRTF treatment significantly increased the BMD and mechanical strength of tail-suspended rats. Enhanced bone turnover markers with HLU treatment were attenuated by DRTF administration. Deterioration of trabecular bone induced by HLU was prevented through elevated bone volume/tissue volume (BV/TV), trabecular number (Tb. N), trabecular thickness (Tb. Th) and decreased trabecular separation (Tb. Sp). The present study provides the first evidence that DRTF prevents bone loss induced by HLU treatment, indicating its potential application in the treatment of disuse-induced osteoporosis. Full article
(This article belongs to the Special Issue Natural Products and Chronic Diseases)
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Open AccessArticle Herb-Drug Interaction between the Traditional Hepatoprotective Formulation and Sorafenib on Hepatotoxicity, Histopathology and Pharmacokinetics in Rats
Molecules 2017, 22(7), 1034; doi:10.3390/molecules22071034
Received: 4 June 2017 / Accepted: 19 June 2017 / Published: 22 June 2017
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Abstract
Sorafenib has been used as a standard therapy for advanced hepatocellular carcinoma (HCC). In Asia, patients with HCC are potentially treated with the combination of sorafenib and Chinese herbal medicines to improve the efficiency and reduce the side effects of sorafenib. However, limited
[...] Read more.
Sorafenib has been used as a standard therapy for advanced hepatocellular carcinoma (HCC). In Asia, patients with HCC are potentially treated with the combination of sorafenib and Chinese herbal medicines to improve the efficiency and reduce the side effects of sorafenib. However, limited information about the herb-drug interactions is available. We hypothesize that the Chinese herbal medicine may exert hepatoprotective effects on the sorafenib-treated group. The aim of this study is to investigate the pharmacokinetic mechanism of drug-drug interactions of sorafenib including interacting with hepatoprotective formulation, Long-Dan-Xie-Gan-Tang formulation (LDXGT) and with two cytochrome P450 3A4 (CYP3A4) inhibitors, grapefruit juice and ketoconazole. Liver enzyme levels and histopathology of liver slices were used to evaluate sorafenib-induced hepatotoxicity and the potential hepatoprotective effects of the LDXGT formulation on subjects treated with the combination of sorafenib and the herbal medicine. In this study, a validated HPLC-photodiode array analytical system was developed for the pharmacokinetic study of sorafenib in rats. As the result of the pharmacokinetic data, pretreatment with the LDXGT formulation did not significantly interact with sorafenib compared with sorafenib oral administration alone. Furthermore, grapefruit juice and ketoconazole did not significantly affect sorafenib metabolism. Furthermore, pretreatment with variable, single or repeat doses of the LDXGT formulation did not suppress or exacerbate the sorafenib-induced hepatotoxicity and histopathological alterations. According to these results, the LDXGT formulation is safe, but has no beneficial effects on sorafenib-induced hepatotoxicity. A detailed clinical trial should be performed to further evaluate the efficacy or adverse effects of the LDXGT formulation in combination with sorafenib in humans. Full article
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Open AccessArticle Exogenous Feeding of Fructose and Phenylalanine Further Improves Betulin Production in Suspended Betula platyphylla Cells under Nitric Oxide Treatment
Molecules 2017, 22(7), 1035; doi:10.3390/molecules22071035
Received: 6 May 2017 / Revised: 18 June 2017 / Accepted: 18 June 2017 / Published: 30 June 2017
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Abstract
The aim of this study was to assay by NMR the metabolites which contribute to betulin production. 8-day-old suspended birch (Betula platyphylla) cells were treated by sodium nitroprusside (SNP) treatment, an NO donor, and 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (cPTIO), an NO-specific scavenger. The results
[...] Read more.
The aim of this study was to assay by NMR the metabolites which contribute to betulin production. 8-day-old suspended birch (Betula platyphylla) cells were treated by sodium nitroprusside (SNP) treatment, an NO donor, and 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (cPTIO), an NO-specific scavenger. The results showed that betulin production was increased by five times after SNP treatment, similar with that of the control under cPTIO treatment. Forty one metabolites were detected after SNP treatment or cPTIO treatment. Among them, 10 were found to significantly contribute to the differences observed between controls and treated cell culture samples. To validate the contribution of the above 10 metabolites to betulin production, myo-inositol, fructose and phenylalanine based on correlation analysis between the content of 12 metabolites and betulin were used to feed birch suspension cell cultures under SNP treatment. Exogenous feeding of fructose or phenylalanine further enhanced the betulin production under SNP treatment, but myo-inositol had the opposite result. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle Molecular Structure–Affinity Relationship of Flavonoids in Lotus Leaf (Nelumbo nucifera Gaertn.) on Binding to Human Serum Albumin and Bovine Serum Albumin by Spectroscopic Method
Molecules 2017, 22(7), 1036; doi:10.3390/molecules22071036
Received: 3 May 2017 / Revised: 20 June 2017 / Accepted: 20 June 2017 / Published: 23 June 2017
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Abstract
Lotus leaf has gained growing popularity as an ingredient in herbal formulations due to its various activities. As main functional components of lotus leaf, the difference in structure of flavonoids affected their binding properties and activities. In this paper, the existence of 11
[...] Read more.
Lotus leaf has gained growing popularity as an ingredient in herbal formulations due to its various activities. As main functional components of lotus leaf, the difference in structure of flavonoids affected their binding properties and activities. In this paper, the existence of 11 flavonoids in lotus leaf extract was confirmed by High Performance Liquid Chromatography (HPLC) analysis and 11 flavonoids showed various contents in lotus leaf. The interactions between lotus leaf extract and two kinds of serum albumins (human serum albumin (HSA) and bovine serum albumin (BSA)) were investigated by spectroscopic methods. Based on the fluorescence quenching, the interactions between these flavonoids and serum albumins were further checked in detail. The relationship between the molecular properties of flavonoids and their affinities for serum albumins were analyzed and compared. The hydroxylation on 3 and 3’ position increased the affinities for serum albumins. Moreover, both of the methylation on 3’ position of quercetin and the C2=C3 double bond of apigenin and quercetin decreased the affinities for HSA and BSA. The glycosylation lowered the affinities for HSA and BSA depending on the type of sugar moiety. It revealed that the hydrogen bond force played an important role in binding flavonoids to HSA and BSA. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Enhanced Antibacterial Activity of Ent-Labdane Derivatives of Salvic Acid (7α-Hydroxy-8(17)-ent-Labden-15-Oic Acid): Effect of Lipophilicity and the Hydrogen Bonding Role in Bacterial Membrane Interaction
Molecules 2017, 22(7), 1039; doi:10.3390/molecules22071039
Received: 12 May 2017 / Revised: 16 June 2017 / Accepted: 19 June 2017 / Published: 23 June 2017
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Abstract
In the present study, the antibacterial activity of several ent-labdane derivatives of salvic acid (7α-hydroxy-8(17)-ent-labden-15-oic acid) was evaluated in vitro against the Gram-negative bacterium Escherichia coli and the Gram-positive bacteria Staphylococcus aureus and Bacillus cereus. For all of the
[...] Read more.
In the present study, the antibacterial activity of several ent-labdane derivatives of salvic acid (7α-hydroxy-8(17)-ent-labden-15-oic acid) was evaluated in vitro against the Gram-negative bacterium Escherichia coli and the Gram-positive bacteria Staphylococcus aureus and Bacillus cereus. For all of the compounds, the antibacterial activity was expressed as the minimum inhibitory concentration (MIC) in liquid media and minimum inhibitory amount (MIA) in solid media. Structure activity relationships (SAR) were employed to correlate the effect of the calculated lipophilicity parameters (logPow) on the inhibitory activity. Employing a phospholipidic bilayer (POPG) as a bacterial membrane model, ent-labdane-membrane interactions were simulated utilizing docking studies. The results indicate that (i) the presence of a carboxylic acid in the C-15 position, which acted as a hydrogen-bond donor (HBD), was essential for the antibacterial activity of the ent-labdanes; (ii) an increase in the length of the acylated chain at the C-7 position improved the antibacterial activity until an optimum length of five carbon atoms was reached; (iii) an increase in the length of the acylated chain by more than five carbon atoms resulted in a dramatic decrease in activity, which completely disappeared in acyl chains of more than nine carbon atoms; and (iv) the structural factors described above, including one HBD at C-15 and a hexanoyloxi moiety at C-7, had a good fit to a specific lipophilic range and antibacterial activity. The lipophilicity parameter has a predictive characteristic feature on the antibacterial activity of this class of compounds, to be considered in the design of new biologically active molecules. Full article
(This article belongs to the Special Issue Synthesis and Modification of Natural Product)
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Open AccessArticle On the Reaction of Carbonyl Diphosphonic Acid with Hydroxylamine and O-alkylhydroxylamines: Unexpected Degradation of P-C-P Bridge
Molecules 2017, 22(7), 1040; doi:10.3390/molecules22071040
Received: 21 May 2017 / Revised: 20 June 2017 / Accepted: 21 June 2017 / Published: 23 June 2017
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Abstract
Derivatives of methylenediphosphonic acid possess wide spectra of biological activities and are used in enzymology as research tools as well as in practical medicine. Carbonyl diphosphonic acid is a promising starting building block for synthesis of functionally substituted methylenediphosphonates. Investigation of the interaction
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Derivatives of methylenediphosphonic acid possess wide spectra of biological activities and are used in enzymology as research tools as well as in practical medicine. Carbonyl diphosphonic acid is a promising starting building block for synthesis of functionally substituted methylenediphosphonates. Investigation of the interaction of carbonyl diphosphonic acid with hydroxylamine clearly demonstrates that it is impossible to isolate oxime within the pH range 2–12, while only cyanophosphonic and phosphoric acids are the products of the fast proceeding Beckmann-like fragmentation. In the case of O-alkylhydroxylamines, corresponding alcohols are found in the reaction mixtures in addition to cyanophosphonic and phosphoric acids. Therefore, two residues of phosphonic acid being attached to a carbonyl group provide new properties to this carbonyl group, making its oximes very unstable. This principally differs carbonyl diphosphonic acid from structurally related phosphonoglyoxalic acid and other α-ketophosphonates. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle General Methodologies Toward cis-Fused Quinone Sesquiterpenoids. Enantiospecific Synthesis of the epi-Ilimaquinone Core Featuring Sc-Catalyzed Ring Expansion
Molecules 2017, 22(7), 1041; doi:10.3390/molecules22071041
Received: 1 June 2017 / Revised: 21 June 2017 / Accepted: 21 June 2017 / Published: 24 June 2017
Cited by 1 | PDF Full-text (2921 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A stereocontrolled approach to the cis-decalin framework of clerodane diterpenes and biologically active quinone sesquiterpenes is reported. Starting from an inexpensive optically pure tetrahydroindanone, Birch reductive alkylation builds two new contiguous chiral centers—one of which is quaternary and all-carbon-substituted. Also featured is
[...] Read more.
A stereocontrolled approach to the cis-decalin framework of clerodane diterpenes and biologically active quinone sesquiterpenes is reported. Starting from an inexpensive optically pure tetrahydroindanone, Birch reductive alkylation builds two new contiguous chiral centers—one of which is quaternary and all-carbon-substituted. Also featured is a highly regioselective diazoalkane—carbonyl homologation reaction to prepare the 6,6-bicyclic skeleton. Therein, the utility of Sc(OTf)3 as a mild catalyst for formal 1C insertion in complex settings is demonstrated. Full article
(This article belongs to the Special Issue Asymmetric Synthesis 2017)
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Open AccessArticle Antibacterial Effect of a 4x Cu-TiO2 Coating Simulating Acute Periprosthetic Infection—An Animal Model
Molecules 2017, 22(7), 1042; doi:10.3390/molecules22071042
Received: 23 May 2017 / Revised: 20 June 2017 / Accepted: 20 June 2017 / Published: 23 June 2017
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Abstract
The purpose of our study was to investigate the antibacterial effect of a spacer (Ti6Al4V) coated with 4x Cu-TiO2 in an animal model simulating an acute periprosthetic infection by Staphylococcus aureus. Ti6Al4 bolts contaminated with Staphylococcus aureus were implanted into the
[...] Read more.
The purpose of our study was to investigate the antibacterial effect of a spacer (Ti6Al4V) coated with 4x Cu-TiO2 in an animal model simulating an acute periprosthetic infection by Staphylococcus aureus. Ti6Al4 bolts contaminated with Staphylococcus aureus were implanted into the femoral condyle of rabbits (n = 36) divided into 3 groups. After one week in group 1 (control) the bolts were removed without any replacement. In group2 Ti6Al4V bolts with a 4x Cu-TiO2 coating and in group 3 beads of a gentamicin-PMMA chain were imbedded into the borehole. Microbiological investigation was performed at the primary surgery, at the revision surgery and after scarification of the rabbits 3 weeks after the first surgery. Blood tests were conducted weekly. The initial overall infection rate was 88.9%. In group 2 and 3 a significant decrease of the infection rate was shown in contrast to the control group. The C-reactive protein (CRP) levels declined one week after the first surgery except in the control group where the CRP level even increased. This is the first in vivo study that demonstrated the antibacterial effects of a fourfold Cu-TiO2 coating. For the future, the coating investigated could be a promising option in the treatment of implant-associated infections. Full article
(This article belongs to the Special Issue Antibacterial Materials and Coatings)
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Open AccessArticle Cellular Uptake and Delivery-Dependent Effects of Tb3+-Doped Hydroxyapatite Nanorods
Molecules 2017, 22(7), 1043; doi:10.3390/molecules22071043
Received: 2 May 2017 / Revised: 12 June 2017 / Accepted: 21 June 2017 / Published: 23 June 2017
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Abstract
With the increasing interest in hydroxyapatite (HA) nanostructures for use in biomedicine, the systematic evaluation of their potential effects on biological systems is becoming critically important. In this work, we report the in vitro cellular uptake, in vivo tissue distributions and toxicity of
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With the increasing interest in hydroxyapatite (HA) nanostructures for use in biomedicine, the systematic evaluation of their potential effects on biological systems is becoming critically important. In this work, we report the in vitro cellular uptake, in vivo tissue distributions and toxicity of Tb3+-doped HA (HA-Tb) after short-, intermediate-, and long-term exposure. Transmission electron microscopy analysis indicated that HA-Tb was taken up by cells via vesicle endocytosis. Cell proliferation and cytotoxicity assay, combined with confocal laser scanning microscopy, indicated excellent cell viability with no changes in cell morphology at the examined doses. Three HA-Tb delivery methods (intraperitoneal, intragastric, and intravenous) resulted in similar time-dependent tissue distributions, while intraperitoneal injection produced the highest bioavailability. HA-Tb initially accumulated in livers and intestines of rats (4 h to one day after administration), then became increasingly distributed in the kidney and bladder (seven days), and finally decreased in all tissues after 30 to 90 days. No histopathological abnormalities or lesions related to treatment with HA-Tb were observed. These results suggest that HA-Tb has minimal in vitro and in vivo toxicity, regardless of the delivery mode, time, and dose. The findings provide a foundation for the design and development of HA for biological applications. Full article
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Open AccessArticle Osteoprotective Effect of Radix Scutellariae in Female Hindlimb-Suspended Sprague-Dawley Rats and the Osteogenic Differentiation Effect of Its Major Constituent
Molecules 2017, 22(7), 1044; doi:10.3390/molecules22071044
Received: 31 March 2017 / Revised: 23 May 2017 / Accepted: 15 June 2017 / Published: 3 July 2017
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Abstract
A number of medicinal herbs have demonstrated therapeutic effects for the prevention and treatment of disuse-induced osteoporosis. As a common ingredient in proprietary traditional Chinese medicines, the anti-osteoporosis effects of Radix Scutellariae extract (RSE, 50 mg/kg/day) were evaluated in a hindlimb suspended rat
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A number of medicinal herbs have demonstrated therapeutic effects for the prevention and treatment of disuse-induced osteoporosis. As a common ingredient in proprietary traditional Chinese medicines, the anti-osteoporosis effects of Radix Scutellariae extract (RSE, 50 mg/kg/day) were evaluated in a hindlimb suspended rat model. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry, and the micro-architecture observed by MicroCT assay with bone biomechanical properties evaluated by a three-point bending test. To elucidate potential mechanisms, the osteogenic differentiation effect of baicalin as the most abundant ingredient in RSE was investigated in rat bone marrow derived mesenchymal stem cells (rBMSC). After drug administration for 42 days, tibia-BMD was significantly increased to 0.176 ± 0.007 and 0.183 ± 0.011 g/cm2 and f-BMD was enhanced to 0.200 ± 0.017 and 0.207 ± 0.021 g/cm2 for RSE and ALE treatment, respectively, whereas tibia-BMD and femur-BMD of the HLS group were 0.157 ± 0.009 and 0.176 ± 0.008 g/cm2. Deterioration of bone trabecula microstructure was improved by RSE and ALE with increased morphological parameters such as bone volume fraction, trabecular thickness, and trabecular number, as well as connectivity density compared to the HLS group (p < 0.01). A three-point bending test suggested that bone mechanical strength was also enhanced by RSE and ALE treatments with increased maximum stress, young’s modulus, maximum load, and stiffness compared to those of the HLS group (p < 0.05). Besides, serum TRACP levels were significantly suppressed by RSE and ALE treatments. Furthermore, in vitro studies demonstrated that baicalin significantly increased ALP activities and the formation of mineralized nodules in rBMSC. Conclusively, supplementation of RSE could significantly prevent weightlessness induced osteoporosis, which might attribute to the osteogenic differentiation enhancement effect of baicalin. Full article
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Open AccessArticle Characterization of the Key Aroma Compounds in Chinese Syrah Wine by Gas Chromatography-Olfactometry-Mass Spectrometry and Aroma Reconstitution Studies
Molecules 2017, 22(7), 1045; doi:10.3390/molecules22071045
Received: 5 May 2017 / Revised: 15 June 2017 / Accepted: 20 June 2017 / Published: 24 June 2017
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Abstract
The key aroma compounds and the organoleptic quality of two Chinese Syrah wines from the Yunnan Shangri-La region and Ningxia Helan mountain region were characterized. The most important eighty aroma-active compounds were identified by Gas Chromatography-Olfactometry. In both Syrah samples, ethyl 2-methylpropanoate, ethyl
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The key aroma compounds and the organoleptic quality of two Chinese Syrah wines from the Yunnan Shangri-La region and Ningxia Helan mountain region were characterized. The most important eighty aroma-active compounds were identified by Gas Chromatography-Olfactometry. In both Syrah samples, ethyl 2-methylpropanoate, ethyl 3-methylbutanoate, 3-methylbutyl acetate, 2- and 3-methyl-1-butanol, ethyl hexanoate, ethyl octanoate, 2-phenethyl acetate, methional, 3-methylbutanoic acid, hexanoic acid, octanoic acid, β-damascenone, guaiacol, 2-phenylethanol, trans-whiskylactone, 4-ethylguaiacol, eugenol, 4-ethylphenol, and sotolon were detected to have the highest odor intensities. In the chemical analysis, 72 compounds were quantitated by Stir Bar Sorptive Extraction combined with Gas Chromatography Mass Spectrometry. Based on the Odor Activity Value (OAV), the aromas were reconstituted by combining aroma compounds in the synthetic wine, and sensory descriptive analysis was used to verify the chemical data. Fatty acid ethyl esters, acetate esters, and β-damascenone were found with higher OAVs in the more fruity-smelling sample of Helan Mountain rather than Shangri-La. Full article
(This article belongs to the collection Wine Chemistry)
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Open AccessArticle The Investigation of Electrochemistry Behaviors of Tyrosinase Based on Directly-Electrodeposited Grapheneon Choline-Gold Nanoparticles
Molecules 2017, 22(7), 1047; doi:10.3390/molecules22071047
Received: 27 April 2017 / Accepted: 19 June 2017 / Published: 23 June 2017
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Abstract
A novel catechol (CA) biosensor was developed by embedding tyrosinase (Tyr) onto in situ electrochemical reduction graphene (EGR) on choline-functionalized gold nanoparticle (AuNPs-Ch) film. The results of UV-Vis spectra indicated that Tyr retained its original structure in the film, and an electrochemical investigation
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A novel catechol (CA) biosensor was developed by embedding tyrosinase (Tyr) onto in situ electrochemical reduction graphene (EGR) on choline-functionalized gold nanoparticle (AuNPs-Ch) film. The results of UV-Vis spectra indicated that Tyr retained its original structure in the film, and an electrochemical investigation of the biosensor showed a pair of well-defined, quasi-reversible redox peaks with Epa = −0.0744 V and Epc = −0.114 V (vs. SCE) in 0.1 M, pH 7.0 sodium phosphate-buffered saline at a scan rate of 100 mV/s. The transfer rate constant ks is 0.66 s−1. The Tyr-EGR/AuNPs-Ch showed a good electrochemical catalytic response for the reduction of CA, with the linear range from 0.2 to 270 μM and a detection limit of 0.1 μM (S/N = 3). The apparent Michaelis-Menten constant was estimated to be 109 μM. Full article
(This article belongs to the Section Organometallic Chemistry)
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Open AccessArticle Novel Sulfamide-Containing Compounds as Selective Carbonic Anhydrase I Inhibitors
Molecules 2017, 22(7), 1049; doi:10.3390/molecules22071049
Received: 19 May 2017 / Revised: 12 June 2017 / Accepted: 19 June 2017 / Published: 24 June 2017
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Abstract
The development of isoform selective inhibitors of the carbonic anhydrase (CA; EC 4.2.1.1) enzymes represents the key approach for the successful development of druggable small molecules. Herein we report a series of new benzenesulfamide derivatives (-NH-SO2NH2) bearing the 1-benzhydrylpiperazine
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The development of isoform selective inhibitors of the carbonic anhydrase (CA; EC 4.2.1.1) enzymes represents the key approach for the successful development of druggable small molecules. Herein we report a series of new benzenesulfamide derivatives (-NH-SO2NH2) bearing the 1-benzhydrylpiperazine tail and connected by means of a β-alanyl or nipecotyl spacer. All compounds 6al were investigated in vitro for their ability to inhibit the physiological relevant human (h) CA isoforms such as I, II, IV and IX. Molecular modeling provided further structural support to enzyme inhibition data and structure-activity relationship. In conclusion the hCA I resulted the most inhibited isoform, whereas all the remaining ones showed different inhibition profiles. Full article
(This article belongs to the Special Issue Sulfonamides)
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Open AccessArticle Myrtaceae Plant Essential Oils and their β-Triketone Components as Insecticides against Drosophila suzukii
Molecules 2017, 22(7), 1050; doi:10.3390/molecules22071050
Received: 3 June 2017 / Revised: 15 June 2017 / Accepted: 20 June 2017 / Published: 24 June 2017
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Abstract
Spotted wing drosophila (SWD, Drosophila suzukii (Matsumura), Diptera: Drosophilidae) is recognized as an economically important pest in North America and Europe as well as in Asia. Assessments were made for fumigant and contact toxicities of six Myrtaceae plant essential oils (EOs) and their
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Spotted wing drosophila (SWD, Drosophila suzukii (Matsumura), Diptera: Drosophilidae) is recognized as an economically important pest in North America and Europe as well as in Asia. Assessments were made for fumigant and contact toxicities of six Myrtaceae plant essential oils (EOs) and their components to find new alternative types of insecticides active against SWD. Among the EOs tested, Leptospermum citratum EO, consisting mainly of geranial and neral, exhibited effective fumigant activity. Median lethal dose (LD50; mg/L) values of L. citratum were 2.39 and 3.24 for males and females, respectively. All tested EOs except Kunzea ambigua EO exhibited effective contact toxicity. LD50 (µg/fly) values for contact toxicity of manuka and kanuka were 0.60 and 0.71, respectively, for males and 1.10 and 1.23, respectively, for females. The LD50 values of the other 3 EOs-L. citratum, allspice and clove bud were 2.11–3.31 and 3.53–5.22 for males and females, respectively. The non-polar fraction of manuka and kanuka did not show significant contact toxicity, whereas the polar and triketone fractions, composed of flavesone, isoleptospermone and leptospermone, exhibited efficient activity with the LD50 values of 0.13–0.37 and 0.22–0.57 µg/fly for males and females, respectively. Our results indicate that Myrtaceae plant EOs and their triketone components can be used as alternatives to conventional insecticides. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Structural Characterization of the Low-Molecular-Weight Heparin Dalteparin by Combining Different Analytical Strategies
Molecules 2017, 22(7), 1051; doi:10.3390/molecules22071051
Received: 31 May 2017 / Revised: 20 June 2017 / Accepted: 22 June 2017 / Published: 24 June 2017
Cited by 1 | PDF Full-text (2046 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A number of low molecular weight heparin (LMWH) products are available for clinical use and although all share a similar mechanism of action, they are classified as distinct drugs because of the different depolymerisation processes of the native heparin resulting in substantial pharmacokinetic
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A number of low molecular weight heparin (LMWH) products are available for clinical use and although all share a similar mechanism of action, they are classified as distinct drugs because of the different depolymerisation processes of the native heparin resulting in substantial pharmacokinetic and pharmacodynamics differences. While enoxaparin has been extensively investigated, little information is available regarding the LMWH dalteparin. The present study is focused on the detailed structural characterization of Fragmin® by LC-MS and NMR applied both to the whole drug and to its enzymatic products. For a more in-depth approach, size homogeneous octasaccharide and decasaccharide components together with their fractions endowed with high or no affinity toward antithrombin were also isolated and their structural profiles characterized. The combination of different analytical strategies here described represents a useful tool for the assessment of batch-to-batch structural variability and for comparative evaluation of structural features of biosimilar products. Full article
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Open AccessArticle Augmented Anticancer Effects of Cantharidin with Liposomal Encapsulation: In Vitro and In Vivo Evaluation
Molecules 2017, 22(7), 1052; doi:10.3390/molecules22071052
Received: 16 May 2017 / Revised: 20 June 2017 / Accepted: 21 June 2017 / Published: 24 June 2017
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Abstract
PEGylated liposomes have received much attention as pharmaceutical carriers to deliver chemotherapeutic agents for therapeutic purpose. The aim of this study was to prepare and characterize PEGylated liposome of cantharidin and investigate its therapeutic effect on human hepatocellular carcinoma treatment in vitro and
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PEGylated liposomes have received much attention as pharmaceutical carriers to deliver chemotherapeutic agents for therapeutic purpose. The aim of this study was to prepare and characterize PEGylated liposome of cantharidin and investigate its therapeutic effect on human hepatocellular carcinoma treatment in vitro and in vivo. Liposomal cantharidin was evaluated for their anticancer effects in vitro using human hepatocellular carcinoma HepG2 cells and in vivo using HepG2-bearing nude mice compared to free drug. PEGylated liposome of cantharidin had a particle size of 129.9 nm and a high encapsulation efficacy of approximately 88.9%. The liposomal cantharidin had a higher anti-proliferative effect vis-à-vis free cantharidin in inducing G2/M cell cycle arrest and apoptosis. Liposomal cantharidin killed more HepG2 cancer cells at the same concentration equivalent to free cantharidin. Further study in vivo also showed that liposomal cantharidin achieved a higher tumor growth inhibition efficacy than free drug on hepatocellular carcinoma. As our study exhibited enhanced cytotoxicity against HepG2 cells and augmented tumor inhibitory effects in vivo, the results validate the potential value of cantharidin-liposome in improving the therapeutic efficacy of cantharidin for liver cancer. Full article
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Open AccessArticle Eu@C72: Computed Comparable Populations of Two Non-IPR Isomers
Molecules 2017, 22(7), 1053; doi:10.3390/molecules22071053
Received: 18 May 2017 / Revised: 14 June 2017 / Accepted: 21 June 2017 / Published: 24 June 2017
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Abstract
Relative concentrations of six isomeric Eu@C72—one based on the IPR C72 cage (i.e., obeying the isolated-pentagon rule, IPR), two cages with a pentagon–pentagon junction (symmetries C2 and C2v), a cage with one heptagon, a cage with
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Relative concentrations of six isomeric Eu@C 72 —one based on the IPR C 72 cage (i.e., obeying the isolated-pentagon rule, IPR), two cages with a pentagon–pentagon junction (symmetries C 2 and C 2 v ), a cage with one heptagon, a cage with two heptagons, and a cage with two pentagon–pentagon fusions—are DFT computed using the Gibbs energy in a broad temperature interval. It is shown that the two non-IPR isomers with one pentagon–pentagon junction prevail at any relevant temperature and exhibit comparable populations. The IPR-satisfying structure is disfavored by both energy and entropy. Full article
(This article belongs to the Special Issue Endohedral Metallofullerenes)
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Open AccessArticle Rational Design of Cyclic Antimicrobial Peptides Based on BPC194 and BPC198
Molecules 2017, 22(7), 1054; doi:10.3390/molecules22071054
Received: 29 May 2017 / Revised: 20 June 2017 / Accepted: 22 June 2017 / Published: 24 June 2017
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Abstract
A strategy for the design of antimicrobial cyclic peptides derived from the lead compounds c(KKLKKFKKLQ) (BPC194) and c(KLKKKFKKLQ) (BPC198) is reported. First, the secondary β-structure of BPC194 and BPC198 was analyzed by carrying out molecular dynamics (MD) simulations. Then,
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A strategy for the design of antimicrobial cyclic peptides derived from the lead compounds c(KKLKKFKKLQ) (BPC194) and c(KLKKKFKKLQ) (BPC198) is reported. First, the secondary β-structure of BPC194 and BPC198 was analyzed by carrying out molecular dynamics (MD) simulations. Then, based on the sequence pattern and the β-structure of BPC194 or BPC198, fifteen analogues were designed and synthesized on solid-phase. The best peptides (BPC490, BPC918, and BPC924) showed minimum inhibitory concentration (MIC) values <6.2 μM against Pseudomonas syringae pv. syringae and Xanthomonas axonopodis pv. vesicatoria, and an MIC value of 12.5 to 25 μM against Erwinia amylovora, being as active as BPC194 and BPC198. Interestingly, these three analogues followed the structural pattern defined from the MD simulations of the parent peptides. Thus, BPC490 maintained the parallel alignment of the hydrophilic pairs K1–K8, K2–K7, and K4–K5, whereas BPC918 and BPC924 included the two hydrophilic interactions K3–Q10 and K5–K8. In short, MD simulations have proved to be very useful for ascertaining the structural features of cyclic peptides that are crucial for their biological activity. Such approaches could be further employed for the development of new antibacterial cyclic peptides. Full article
(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)
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Open AccessArticle Improved Method for Reliable HMW-GS Identification by RP-HPLC and SDS-PAGE in Common Wheat Cultivars
Molecules 2017, 22(7), 1055; doi:10.3390/molecules22071055
Received: 7 June 2017 / Revised: 22 June 2017 / Accepted: 22 June 2017 / Published: 24 June 2017
Cited by 1 | PDF Full-text (1294 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The accurate identification of alleles for high-molecular weight glutenins (HMW-GS) is critical for wheat breeding programs targeting end-use quality. RP-HPLC methods were optimized for separation of HMW-GS, resulting in enhanced resolution of 1By and 1Dx subunits. Statistically significant differences in retention times (RTs)
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The accurate identification of alleles for high-molecular weight glutenins (HMW-GS) is critical for wheat breeding programs targeting end-use quality. RP-HPLC methods were optimized for separation of HMW-GS, resulting in enhanced resolution of 1By and 1Dx subunits. Statistically significant differences in retention times (RTs) for subunits corresponding to HMW-GS alleles were determined using 16 standard wheat cultivars with known HMW-GS compositions. Subunits that were not identified unambiguously by RP-HPLC were distinguished by SDS-PAGE or inferred from association with linked subunits. The method was used to verify the allelic compositions of 32 Korean wheat cultivars previously determined using SDS-PAGE and to assess the compositions of six new Korean cultivars. Three cultivars contained subunits that were identified incorrectly in the earlier analysis. The improved RP-HPLC method combined with conventional SDS-PAGE provides for accurate, efficient and reliable identification of HMW-GS and will contribute to efforts to improve wheat end-use quality. Full article
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Open AccessArticle Solvent-Free Microwave-Assisted Extraction of Polyphenols from Olive Tree Leaves: Antioxidant and Antimicrobial Properties
Molecules 2017, 22(7), 1056; doi:10.3390/molecules22071056
Received: 27 May 2017 / Revised: 16 June 2017 / Accepted: 19 June 2017 / Published: 24 June 2017
Cited by 5 | PDF Full-text (4241 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Response surface methodology (RSM) and artificial neural networks (ANN) were evaluated and compared in order to decide which method was the most appropriate to predict and optimize total phenolic content (TPC) and oleuropein yields in olive tree leaf (Olea europaea) extracts,
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Response surface methodology (RSM) and artificial neural networks (ANN) were evaluated and compared in order to decide which method was the most appropriate to predict and optimize total phenolic content (TPC) and oleuropein yields in olive tree leaf (Olea europaea) extracts, obtained after solvent-free microwave-assisted extraction (SFMAE). The SFMAE processing conditions were: microwave irradiation power 250–350 W, extraction time 2–3 min, and the amount of sample 5–10 g. Furthermore, the antioxidant and antimicrobial activities of the olive leaf extracts, obtained under optimal extraction conditions, were assessed by several in vitro assays. ANN had better prediction performance for TPC and oleuropein yields compared to RSM. The optimum extraction conditions to recover both TPC and oleuropein were: irradiation power 250 W, extraction time 2 min, and amount of sample 5 g, independent of the method used for prediction. Under these conditions, the maximal yield of oleuropein (0.060 ± 0.012 ppm) was obtained and the amount of TPC was 2.480 ± 0.060 ppm. Moreover, olive leaf extracts obtained under optimum SFMAE conditions showed antibacterial activity against S. aureus and S. epidermidis, with a minimum inhibitory concentration (MIC) value of 1.25 mg/mL. Full article
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Open AccessArticle Influence of Pyranose and Spacer Arm Structures on Phloem Mobility and Insecticidal Activity of New Tralopyril Derivatives
Molecules 2017, 22(7), 1058; doi:10.3390/molecules22071058
Received: 22 May 2017 / Revised: 20 June 2017 / Accepted: 20 June 2017 / Published: 25 June 2017
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Abstract
Six new conjugates were designed and synthesized by introducing glucose, methyl glucuronate or glucuronic acid moieties on tralopyril. Phytotoxicity and phloem mobility results demonstrated that the introduction of glucose, methyl glucuronate or glucuronic acid moieties can simultaneously solve the tough phytotoxicity problem and
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Six new conjugates were designed and synthesized by introducing glucose, methyl glucuronate or glucuronic acid moieties on tralopyril. Phytotoxicity and phloem mobility results demonstrated that the introduction of glucose, methyl glucuronate or glucuronic acid moieties can simultaneously solve the tough phytotoxicity problem and phloem mobility transformation of tralopyril. Conjugates 12 and 18 containing the glucuronic acid moiety exhibited higher phloem mobility than conjugates 9, 11, 15 and 17. Conjugates 15, 17 and 18 with methoxymethyl groups on the tralopyril pyrrole nitrogen atom showed activity against Plutella xylostella, while conjugates 9, 11 and 12 with a methene group on the pyrrole N showed no activity. Cabbage roots were incubated in a buffered solution containing conjugates 15, 17 and 18 at 4 mM for 72 h. Only 18 showed systemic insecticidal activity with 100% mortalityagainst P. xylostella, while 15 and 17 showed lower activity andchlorfenapyr showed no activity. The glucuronic acid promoiety imparted more phloem mobility to tralopyril than glucose and methyl glucuronate. The methoxymethyl group bond on the tralopyril skeleton was the key factor in determining the insecticidal activity of the conjugates. A promising systemic proinsecticide containing glucuronic acid and tralopyril moieties was proposed. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Calculation of Five Thermodynamic Molecular Descriptors by Means of a General Computer Algorithm Based on the Group-Additivity Method: Standard Enthalpies of Vaporization, Sublimation and Solvation, and Entropy of Fusion of Ordinary Organic Molecules and Total Phase-Change Entropy of Liquid Crystals
Molecules 2017, 22(7), 1059; doi:10.3390/molecules22071059
Received: 22 May 2017 / Revised: 22 June 2017 / Accepted: 22 June 2017 / Published: 25 June 2017
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Abstract
The calculation of the standard enthalpies of vaporization, sublimation and solvation of organic molecules is presented using a common computer algorithm on the basis of a group-additivity method. The same algorithm is also shown to enable the calculation of their entropy of fusion
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The calculation of the standard enthalpies of vaporization, sublimation and solvation of organic molecules is presented using a common computer algorithm on the basis of a group-additivity method. The same algorithm is also shown to enable the calculation of their entropy of fusion as well as the total phase-change entropy of liquid crystals. The present method is based on the complete breakdown of the molecules into their constituting atoms and their immediate neighbourhood; the respective calculations of the contribution of the atomic groups by means of the Gauss-Seidel fitting method is based on experimental data collected from literature. The feasibility of the calculations for each of the mentioned descriptors was verified by means of a 10-fold cross-validation procedure proving the good to high quality of the predicted values for the three mentioned enthalpies and for the entropy of fusion, whereas the predictive quality for the total phase-change entropy of liquid crystals was poor. The goodness of fit (Q2) and the standard deviation (σ) of the cross-validation calculations for the five descriptors was as follows: 0.9641 and 4.56 kJ/mol (N = 3386 test molecules) for the enthalpy of vaporization, 0.8657 and 11.39 kJ/mol (N = 1791) for the enthalpy of sublimation, 0.9546 and 4.34 kJ/mol (N = 373) for the enthalpy of solvation, 0.8727 and 17.93 J/mol/K (N = 2637) for the entropy of fusion and 0.5804 and 32.79 J/mol/K (N = 2643) for the total phase-change entropy of liquid crystals. The large discrepancy between the results of the two closely related entropies is discussed in detail. Molecules for which both the standard enthalpies of vaporization and sublimation were calculable, enabled the estimation of their standard enthalpy of fusion by simple subtraction of the former from the latter enthalpy. For 990 of them the experimental enthalpy-of-fusion values are also known, allowing their comparison with predictions, yielding a correlation coefficient R2 of 0.6066. Full article
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Open AccessArticle In silico Study of the Pharmacologic Properties and Cytotoxicity Pathways in Cancer Cells of Various Indolylquinone Analogues of Perezone
Molecules 2017, 22(7), 1060; doi:10.3390/molecules22071060
Received: 30 May 2017 / Revised: 16 June 2017 / Accepted: 19 June 2017 / Published: 25 June 2017
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Abstract
Several indolylquinone analogues of perezone, a natural sesquiterpene quinone, were characterized in this work by theoretical methods. In addition, some physicochemical, toxicological and metabolic properties were predicted using bioinformatics software. The predicted physicochemical properties are in agreement with the solubility and cLogP values,
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Several indolylquinone analogues of perezone, a natural sesquiterpene quinone, were characterized in this work by theoretical methods. In addition, some physicochemical, toxicological and metabolic properties were predicted using bioinformatics software. The predicted physicochemical properties are in agreement with the solubility and cLogP values, the penetration across the cell membrane, and absorption values, as well as with a possible apoptosis-activated mechanism of cytotoxic action. The toxicological predictions suggest no mutagenic, tumorigenic or reproductive effects of the four target molecules. Complementarily, the results of a performed docking study show high scoring values and hydrogen bonding values in agreement with the cytotoxicity IC50 value ranking, i.e: indolylmenadione > indolylperezone > indolylplumbagine > indolylisoperezone. Consequently, it is possible to suggest an appropriate apoptotic pathway for each compound. Finally, potential metabolic pathways of the molecules were proposed. Full article
(This article belongs to the Special Issue The Biomedical Importance of Indoles and Their Derivatives)
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Open AccessArticle Magnetic Solid-phase Extraction with Fe3O4/Molecularly Imprinted Polymers Modified by Deep Eutectic Solvents and Ionic Liquids for the Rapid Purification of Alkaloid Isomers (Theobromine and Theophylline) from Green Tea
Molecules 2017, 22(7), 1061; doi:10.3390/molecules22071061
Received: 4 June 2017 / Revised: 24 June 2017 / Accepted: 24 June 2017 / Published: 25 June 2017
Cited by 1 | PDF Full-text (9770 KB) | HTML Full-text | XML Full-text
Abstract
Different kinds of deep eutectic solvents (DES) based on choline chloride (ChCl) and ionic liquids (ILs) based on 1-methylimidazole were used to modify Fe3O4/molecularly imprinted polymers (Fe3O4/MIPs), and the resulting materials were applied for the rapid purification of alkaloid isomers (theobromine and theophylline)
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Different kinds of deep eutectic solvents (DES) based on choline chloride (ChCl) and ionic liquids (ILs) based on 1-methylimidazole were used to modify Fe3O4/molecularly imprinted polymers (Fe3O4/MIPs), and the resulting materials were applied for the rapid purification of alkaloid isomers (theobromine and theophylline) from green tea with magnetic solid-phase extraction (M-SPE). The M-SPE procedure was optimized using the response surface methodology (RSM) to analyze the maximum conditions. The materials were characterized by Fourier transform infrared spectroscopy (FI-IR) and field emission scanning electron microscopy (FE-SEM). Compared to the ILs-Fe3O4/MIPs, the DESs-Fe3O4/MIPs were developed for the stronger recognition and higher recoveries of the isomers (theophylline and theobromine) from green tea, particularly DES-7-Fe3O4/MIPs. With RSM, the optimal recovery condition for theobromine and theophylline in the M-SPE were observed with ratio of methanol (80%) as the washing solution, methanol/acetic acid (HAc) (8:2) as the eluent at pH 3, and an eluent volume of 4 mL. The practical recoveries of theobromine and theophylline in green tea were 92.27% and 87.51%, respectively, with a corresponding actual extraction amount of 4.87 mg•g−1 and 5.07 mg•g−1. Overall, the proposed approach with the high affinity of Fe3O4/MIPs might offer a novel method for the purification of complex isomer samples. Full article
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Open AccessArticle Calcineurin Antagonizes AMPK to Regulate Lipolysis in Caenorhabditis elegans
Molecules 2017, 22(7), 1062; doi:10.3390/molecules22071062
Received: 27 May 2017 / Accepted: 22 June 2017 / Published: 26 June 2017
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Abstract
Calcineurin is a calcium- and calmodulin-dependent serine/threonine protein phosphatase, and the target of immunosuppressive agent tacrolimus (TAC). The dysfunction of calcineurin, or clinical applications of tacrolimus, have been reported to be associated with dyslipidemia. The underlying mechanisms of calcineurin and tacrolimus in lipid
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Calcineurin is a calcium- and calmodulin-dependent serine/threonine protein phosphatase, and the target of immunosuppressive agent tacrolimus (TAC). The dysfunction of calcineurin, or clinical applications of tacrolimus, have been reported to be associated with dyslipidemia. The underlying mechanisms of calcineurin and tacrolimus in lipid metabolism are largely unknown. Here, we showed that mutations of tax-6 and cnb-1, which respectively encode the catalytic subunit and the regulatory subunit of calcineurin, together with tacrolimus treatment, consistently led to decreased fat accumulation and delayed growth in the nematode Caenorhabditis elegans. In contrast, disruption of the AMP-activated protein kinase (AMPK) encoded by aak-1 and aak-2 reversed the above effects in worms. Moreover, calcineurin deficiency and tacrolimus treatment consistently activated the transcriptional expression of the lipolytic gene atgl-1, encoding triglyceride lipase. Furthermore, RNAi knockdown of atgl-1 recovered the decreased fat accumulation in both calcineurin deficient and tacrolimus treated worms. Collectively, our results reveal that immunosuppressive agent tacrolimus and their target calcineurin may antagonize AMPK to regulate ATGL and lipolysis, thereby providing potential therapy for the application of immunosuppressive agents. Full article
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Open AccessArticle Pamidronate-Conjugated Biodegradable Branched Copolyester Carriers: Synthesis and Characterization
Molecules 2017, 22(7), 1063; doi:10.3390/molecules22071063
Received: 8 May 2017 / Accepted: 22 June 2017 / Published: 26 June 2017
PDF Full-text (2814 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The need for development of comprehensive therapeutic systems, (e.g., polymer-apatite composites) as a bone substitute material has previously been highlighted in many scientific reports. The aim of this study was to develop a new multifunctional composite based on hydroxyapatite porous granules doped with
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The need for development of comprehensive therapeutic systems, (e.g., polymer-apatite composites) as a bone substitute material has previously been highlighted in many scientific reports. The aim of this study was to develop a new multifunctional composite based on hydroxyapatite porous granules doped with selenite ions (SeO32−) and a biodegradable branched copolymer-bisphosphonate conjugate as a promising bone substitute material for patients with bone tumours or bone metastasis. A series of biodegradable and branched copolymer matrices, adequate for delivery of bisphosphonate in the bone-deficient area were synthesized and physico-chemically and biologically (cyto- and genotoxicity assays) characterized. Branched copolymers were obtained using a hyperbranched bis-MPA polyester-16-hydroxyl initiator and Sn(Oct)2, a (co)catalyst of the ring-opening polymerization (ROP) of l,l-lactide (LLA) and ε-caprolactone (CL). A new amide bond was formed between the hydroxyl end groups of the synthesized copolymer carriers and an amine group of pamidronate (PAM)—the drug inhibiting bone resorption and osteoclast activity in bone. The dependence of the physico-chemical properties of the copolymer matrices on the kinetic release of PAM from the synthesized branched copolymer conjugate-coated hydroxyapatite granules doped with selenite ions was observed. Moreover, the correlation of these results with the hydrolytic degradation data of the synthesized matrices was evidenced. Therefore, the developed composite porous hydroxyapatite doped with SeO32− ions/biodegradable copolymer-PAM conjugate appears most attractive as a bone substitute material for cancer patients. Full article
(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)
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Open AccessArticle Mechanism Exploration of Arylpiperazine Derivatives Targeting the 5-HT2A Receptor by In Silico Methods
Molecules 2017, 22(7), 1064; doi:10.3390/molecules22071064
Received: 21 April 2017 / Revised: 23 June 2017 / Accepted: 23 June 2017 / Published: 26 June 2017
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Abstract
As a G-protein coupled receptor, the 5-hydroxytryptamine 2A (5-HT2A) receptor is known for its critical role in the cognitive, behavioural and physiological functions, and thus is a primary molecular target to treat psychiatric diseases, including especially depression. With purpose to explore
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As a G-protein coupled receptor, the 5-hydroxytryptamine 2A (5-HT2A) receptor is known for its critical role in the cognitive, behavioural and physiological functions, and thus is a primary molecular target to treat psychiatric diseases, including especially depression. With purpose to explore the structural traits affecting the inhibitory activity, currently a dataset of 109 arylpiperazine derivatives as promising 5-HT2A antagonists was built, based on which the ligand-based three-dimensional quantitative structure-activity relationship (3D-QSAR) study by using both comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches was carried out. The resultant optimal CoMSIA model displays proper validity and predictability with cross-validated correlation coefficient Q2 = 0.587, non-cross-validated correlation coefficient R2ncv = 0.900 and predicted correlation coefficient for the test set of compounds R2pre = 0.897, respectively. Besides, molecular docking was also conducted to investigate the binding mode between these ligands and the active site of the 5-HT2A receptor. Meanwhile, as a docking supplementary tool to study the antagonists’ conformation in the binding cavity, molecular dynamics (MD) simulation was also performed, providing further elucidation about the changes in the ligand-receptor complex. Lastly, some new molecules were also newly-designed based on the above results that are potential arylpiperazine antagonists of 5-HT2A receptor. We hope that the present models and derived information may be of help for facilitating the optimization and design of novel potent antagonists as antidepressant drugs as well as exploring the interaction mechanism of 5-HT2A antagonists. Full article
(This article belongs to the Special Issue Biomolecular Simulations)
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Open AccessArticle UVA, UVB Light Doses and Harvesting Time Differentially Tailor Glucosinolate and Phenolic Profiles in Broccoli Sprouts
Molecules 2017, 22(7), 1065; doi:10.3390/molecules22071065
Received: 14 June 2017 / Revised: 22 June 2017 / Accepted: 22 June 2017 / Published: 26 June 2017
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Abstract
Broccoli sprouts contain health-promoting glucosinolate and phenolic compounds that can be enhanced by applying ultraviolet light (UV). Here, the effect of UVA or UVB radiation on glucosinolate and phenolic profiles was assessed in broccoli sprouts. Sprouts were exposed for 120 min to low
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Broccoli sprouts contain health-promoting glucosinolate and phenolic compounds that can be enhanced by applying ultraviolet light (UV). Here, the effect of UVA or UVB radiation on glucosinolate and phenolic profiles was assessed in broccoli sprouts. Sprouts were exposed for 120 min to low intensity and high intensity UVA (UVAL, UVAH) or UVB (UVBL, UVBH) with UV intensity values of 3.16, 4.05, 2.28 and 3.34 W/m2, respectively. Harvest occurred 2 or 24 h post-treatment; and methanol/water or ethanol/water (70%, v/v) extracts were prepared. Seven glucosinolates and 22 phenolics were identified. Ethanol extracts showed higher levels of certain glucosinolates such as glucoraphanin, whereas methanol extracts showed slight higher levels of phenolics. The highest glucosinolate accumulation occurred 24 h after UVBH treatment, increasing 4-methoxy-glucobrassicin, glucobrassicin and glucoraphanin by ~170, 78 and 73%, respectively. Furthermore, UVAL radiation and harvest 2 h afterwards accumulated gallic acid hexoside I (~14%), 4-O-caffeoylquinic acid (~42%), gallic acid derivative (~48%) and 1-sinapoyl-2,2-diferulolyl-gentiobiose (~61%). Increases in sinapoyl malate (~12%), gallotannic acid (~48%) and 5-sinapoyl-quinic acid (~121%) were observed with UVBH Results indicate that UV-irradiated broccoli sprouts could be exploited as a functional food for fresh consumption or as a source of bioactive phytochemicals with potential industrial applications. Full article
(This article belongs to the Special Issue Recent Advances in Plant Phenolics)
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Open AccessArticle Design, Synthesis and Evaluation of Hesperetin Derivatives as Potential Multifunctional Anti-Alzheimer Agents
Molecules 2017, 22(7), 1067; doi:10.3390/molecules22071067
Received: 11 May 2017 / Revised: 15 June 2017 / Accepted: 25 June 2017 / Published: 26 June 2017
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Abstract
In this study we designed and synthesized a series of new hesperetin derivatives on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of the novel derivatives was also evaluated. Results showed that the synthesized hesperetin derivatives displayed stronger
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In this study we designed and synthesized a series of new hesperetin derivatives on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of the novel derivatives was also evaluated. Results showed that the synthesized hesperetin derivatives displayed stronger inhibitory activity against AChE and higher selectivity than butyrylcholine esterase (BuChE) (selectivity index values from 68 to 305). The Lineweaver-Burk plot and molecular docking study showed that these compounds targeted both the peripheral anionic site (PAS) and catalytic active site (CAS) of AChE. The derivatives also showed a potent self-induced β-amyloid (Aβ) aggregation inhibition and a peroxyl radical absorbance activity. Moreover, compound 4f significantly protected PC12 neurons against H2O2-induced cell death at low concentrations. Cytotoxicity assay showed that the low concentration of the derivatives does not affect the viability of the SH-SY5Y neurons. Thus, these hesperetin derivatives are potential multifunctional agents for further development for the treatment of Alzheimer’s disease. Full article
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Open AccessArticle High-Density Energetic Metal–Organic Frameworks Based on the 5,5′-Dinitro-2H,2′H-3,3′-bi-1,2,4-triazole
Molecules 2017, 22(7), 1068; doi:10.3390/molecules22071068
Received: 22 May 2017 / Revised: 16 June 2017 / Accepted: 23 June 2017 / Published: 26 June 2017
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Abstract
High-energy metal–organic frameworks (MOFs) based on nitrogen-rich ligands are an emerging class of explosives, and density is one of the positive factors that can influence the performance of energetic materials. Thus, it is important to design and synthesize high-density energetic MOFs. In the
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High-energy metal–organic frameworks (MOFs) based on nitrogen-rich ligands are an emerging class of explosives, and density is one of the positive factors that can influence the performance of energetic materials. Thus, it is important to design and synthesize high-density energetic MOFs. In the present work, hydrothermal reactions of Cu(II) with the rigid polynitro heterocyclic ligands 5,5′-dinitro-2H,2′H-3,3′-bi-1,2,4-triazole (DNBT) and 5,5′-dinitro-3,3′-bis-1,2,4-triazole-1-diol (DNBTO) gave two high-density MOFs: [Cu(DNBT)(ATRZ)3]n (1) and [Cu(DNBTO)(ATRZ)2(H2O)2]n (2), where ATRZ represents 4,4′-azo-1,2,4-triazole. The structures were characterized by infrared spectroscopy, elemental analysis, ultraviolet-visible (UV) absorption spectroscopy and single-crystal X-ray diffraction. Their thermal stabilities were also determined by thermogravimetric/differential scanning calorimetry analysis (TG/DSC). The results revealed that complex 1 has a two-dimensional porous framework that possesses the most stable chair conformations (like cyclohexane), whereas complex 2 has a one-dimensional polymeric structure. Compared with previously reported MOFs based on copper ions, the complexes have higher density (ρ = 1.93 g cm−3 for complex 1 and ρ = 1.96 g cm−3 for complex 2) and high thermal stability (decomposition temperatures of 323 °C for complex 1 and 333.3 °C for complex 2), especially because of the introduction of an N–O bond in complex 2. We anticipate that these two complexes would be potential high-energy density materials. Full article
(This article belongs to the Section Organometallic Chemistry)
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Open AccessArticle In Vitro Anti-Leishmanial Activity of Essential Oils Extracted from Vietnamese Plants
Molecules 2017, 22(7), 1071; doi:10.3390/molecules22071071
Received: 4 May 2017 / Revised: 21 June 2017 / Accepted: 22 June 2017 / Published: 27 June 2017
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Abstract
Leishmania mexicana is one of the pathogens causing cutaneous leishmaniasis which is associated with patient morbidity. In our researches for new safe and effective treatments, thirty-seven essential oils (EOs) extracted from Vietnamese plants were screened in vitro for the first time on Leishmania
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Leishmania mexicana is one of the pathogens causing cutaneous leishmaniasis which is associated with patient morbidity. In our researches for new safe and effective treatments, thirty-seven essential oils (EOs) extracted from Vietnamese plants were screened in vitro for the first time on Leishmania mexicana mexicana (Lmm) promastigotes at the maximum concentration of 50 nL/mL. Active EOs were also analyzed for cytotoxicity on mammalian cell lines (WI38, J774) and their selectivity indices (SI) were calculated. Their composition was determined by GC-MS and GC-FID. Our results indicated that EOs extracted from Cinnamomum cassia, Zingiber zerumbet, Elsholtzia ciliata and Amomum aromaticum, possessed a moderate anti-leishmanial activity, with IC50 values of 2.92 ± 0.08, 3.34 ± 0.34, 8.49 ± 0.32 and 9.25 ± 0.64 nL/mL respectively. However, they also showed cytotoxicity with SI < 10. The most promising EO was extracted from Ocimum gratissimum, displaying an IC50 of 4.85 ± 1.65 nL/mL and SI > 10. It contained 86.5% eugenol, which was demonstrated to be effective on Lmm with IC50 of 2.57 ± 0.57 nL/mL and not toxic on mammalian cells, explaining the observed activity. Full article
(This article belongs to the Special Issue Essential Oils: Chemistry and Bioactivity)
Open AccessArticle Labradorins with Antibacterial Activity Produced by Pseudomonas sp.
Molecules 2017, 22(7), 1072; doi:10.3390/molecules22071072
Received: 11 May 2017 / Revised: 11 June 2017 / Accepted: 21 June 2017 / Published: 27 June 2017
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Abstract
The urgent need for new antibacterial drugs has led to renewed interest in microorganisms, which historically have been the main source of previously discovered antibiotics. The present study describes the discovery of two new antibacterial oxazolylindole type alkaloids, labradorins 5 (1)
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The urgent need for new antibacterial drugs has led to renewed interest in microorganisms, which historically have been the main source of previously discovered antibiotics. The present study describes the discovery of two new antibacterial oxazolylindole type alkaloids, labradorins 5 (1) and 6 (2), which were isolated and characterized from two isolates of Pseudomonas sp., along with four previously known tryptophane derived alkaloids. The structures of 1 and 2 were determined by NMR spectroscopy and MS, and confirmed by synthesis. During bioassay-guided isolation using several human bacterial pathogens, 1 and 2 displayed activity towards Staphylococcus aureus and Acinetobacter baumannii. The minimal inhibitory concentrations (MIC) of compounds 1 and 2 against S. aureus were 12 μg·mL−1 and 50 μg·mL−1, respectively, whereas the MICs against A. baumannii were >50 μg·mL−1. The CC50 values of compound 1 towards a liver cell line (HEP-G2) and a T-cell line (MT4) were 30 μg·mL−1 and 20 μg·mL−1, respectively, and for compound 2 were >100 μg·mL−1 and 20 μg·mL−1, respectively. Due to the limited potency of compounds 1 and 2, along with their toxicity, the compounds do not warrant further development towards new antibiotics. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Nortriterpenoids from the Fruiting Bodies of the Mushroom Ganoderma resinaceum
Molecules 2017, 22(7), 1073; doi:10.3390/molecules22071073
Received: 2 June 2017 / Revised: 21 June 2017 / Accepted: 22 June 2017 / Published: 28 June 2017
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Abstract
Ganoderma resinaceum is usually used as ethnomedicine for immune-regulation, hyperglycemia, and liver disease. To date, only a few chemical constituents have been reported from G. resinaceum. In this study, fifteen nortriterpenoids including six new nortriterpenoids (16) and
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Ganoderma resinaceum is usually used as ethnomedicine for immune-regulation, hyperglycemia, and liver disease. To date, only a few chemical constituents have been reported from G. resinaceum. In this study, fifteen nortriterpenoids including six new nortriterpenoids (16) and nine known analogs (715), were separated and purified from the fruiting bodies of G. resinaceum. New compounds were identified as lucidone I (1), lucidone J (2), lucidone K (3), lucidone I (4), ganosineniol B (5), and ganosineniol C (6), based on analysis of extensive spectroscopic data (high resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR), infrared (IR), and ultraviolet (UV)). The known compounds were assigned as lucidone A (7), lucidone B (8), lucidone H (9), lucidone E (10), lucidone F (11), lucidone D (12), lucidone C (13), ganoderense F (14), and ganosineniol A (15), by comparing their spectroscopic data with those reported in the literature. Compounds 3, 4, and 713 were examined for α-glucosidase inhibitory activity and display no significant activity, but the finding may support that the side chain of ganoderma triterpenoids played an important role in α-glucosidase inhibitory activity. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Cell-Free Production of Pentacyclic Triterpenoid Compound Betulinic Acid from Betulin by the Engineered Saccharomyces cerevisiae
Molecules 2017, 22(7), 1075; doi:10.3390/molecules22071075
Received: 1 June 2017 / Revised: 24 June 2017 / Accepted: 26 June 2017 / Published: 27 June 2017
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Abstract
Betulinic acid is a product of plant secondary metabolism which has shown various bioactivities. Several CYP716A subfamily genes were recently characterized encoding multifunctional oxidases capable of C-28 oxidation. CYP716A12 was identified as betulin C-28 oxidase, capable of modifying betulin. This study aimed to
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Betulinic acid is a product of plant secondary metabolism which has shown various bioactivities. Several CYP716A subfamily genes were recently characterized encoding multifunctional oxidases capable of C-28 oxidation. CYP716A12 was identified as betulin C-28 oxidase, capable of modifying betulin. This study aimed to induce the transformation of betulin to betulinic acid by co-expressing enzymes CYP716A12 from Medicago truncatula and ATR1 from Arabidopsis thaliana in Saccharomyces cerevisiae. The microsome protein extracted from the transgenic yeast successfully catalyzed the transformation of betulin to betulinic acid. We also characterized the optimization of cell fragmentation, protein extraction method, and the conversion conditions. Response surface methodology was implemented, and the optimal yield of betulinic acid reached 18.70%. After optimization, the yield and the conversion rate of betulin were increased by 83.97% and 136.39%, respectively. These results may present insights and strategies for the sustainable production of betulinic acid in multifarious transgenic microbes. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Ultrasonic Assisted-Reflux Synergistic Extraction of Camptothecin and Betulinic Acid from Camptotheca acuminata Decne. Fruits
Molecules 2017, 22(7), 1076; doi:10.3390/molecules22071076
Received: 28 May 2017 / Revised: 26 June 2017 / Accepted: 26 June 2017 / Published: 27 June 2017
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Abstract
A novel and efficient ultrasonic assisted-reflux synergistic extraction (UARSE) method for extracting camptothecin (CPT) and betulinic acid (BA) from Camptotheca acuminata Decne. fruits has been developed in this study. The advantages of the ultrasonic and reflux extraction methods have been combined in the
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A novel and efficient ultrasonic assisted-reflux synergistic extraction (UARSE) method for extracting camptothecin (CPT) and betulinic acid (BA) from Camptotheca acuminata Decne. fruits has been developed in this study. The advantages of the ultrasonic and reflux extraction methods have been combined in the UARSE method and used to extract CPT and BA for the first time. The parameters influencing the efficiency of UARSE were optimized using the Box-Behnken design (BBD) to obtain the maximum extraction yield of CPT and BA. The optimal extraction conditions were as follows: 225 W for the ultrasonic power; 24 min for the extraction time; and 32 mL/g for the liquid–solid ratio. The extraction yields obtained by UARSE were 2.386 ± 0.112 mg/g for CPT and 17.192 ± 0.808 mg/g for BA, which were 1.43-fold and 1.33-fold, respectively, higher than by using heating reflux extraction (HRE) and ultrasonic-assisted extraction (UAE). In addition, the 24-min extraction time using UARSE was 80% and 60% less than those provided by HRE and UAE, respectively. Therefore, UARSE can be considered a rapid and efficient method for extracting CPT and BA from the fruits of C. acuminata Decne. Full article
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Open AccessArticle Comparative Analysis of Saponins from Different Phytolaccaceae Species and Their Antiproliferative Activities
Molecules 2017, 22(7), 1077; doi:10.3390/molecules22071077
Received: 5 May 2017 / Accepted: 26 June 2017 / Published: 29 June 2017
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Abstract
The quality and the efficacy of herbal medicine are of great concern especially with the increase in their global use. Medicinal plants of different species or collected from different geographical regions have shown variations in both their contents and pharmacological activities due to
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The quality and the efficacy of herbal medicine are of great concern especially with the increase in their global use. Medicinal plants of different species or collected from different geographical regions have shown variations in both their contents and pharmacological activities due to the differences in the environmental conditions of the collected sites. In this study, roots of Phytolacca acinosa found in different provinces in south China (Sichuan and Shandong) and a species of Phytolacca americana were investigated. To ensure a maximum yield of the major compounds, the extraction method and conditions were optimized. The preeminent method of extraction in this analysis was determined to be the ultrasound-assisted method with specific conditions as follows: ethanol-H2O (1:1, v/v), with a solvent: sample ratio of 1:8, and extraction was performed 3 times, each for 30 min. Under these conditions, samples from the different regions varied both in quantity and quality via the LC-MS analysis. A total of 60 triterpenoid saponins were detected within the three samples, among which 22 were identified as common in the three samples. The amounts of these common triterpenoid saponin identified varied across the samples. Moreover, the analysis led to the detection of some novel compounds that have not yet been reported in this family, while other compounds differ in their fragmentation pathways compared to previous literature. To further divulge the correlations between the bioactivities in these three samples and the quantity and quality of their bioactive components, a cytotoxic analysis was thus carried out with two cancer cell lines, and SGC-7901 and Hep G2, which evidently showed remarkable differences in their anti-proliferative activities with respect to the IC50 value. Samples of P. acinosa from Sichuan showed higher values in both cell lines (27.20 ± 1.60 and 25.59 ± 1.63 µg/mL) compared to those of Shandong and P. americana. For the first time, analysis and comparison of both interspecies and of different species in this family were carried out. This study will significantly contribute to the quality insurance of herbal medicine, especially in the Phytolaccaceae family. Full article
(This article belongs to the Special Issue Diversity of Terpenoids)
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Open AccessArticle Effects on Rotational Dynamics of Azo and Hydrazodicarboxamide-Based Rotaxanes
Molecules 2017, 22(7), 1078; doi:10.3390/molecules22071078
Received: 1 June 2017 / Revised: 26 June 2017 / Accepted: 26 June 2017 / Published: 28 June 2017
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Abstract
The synthesis of novel hydrogen-bonded [2]rotaxanes having two pyridine rings in the macrocycle and azo- and hydrazodicarboxamide-based templates decorated with four cyclohexyl groups is described. The different affinity of the binding sites for the benzylic amide macrocycle and the formation of programmed non-covalent
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The synthesis of novel hydrogen-bonded [2]rotaxanes having two pyridine rings in the macrocycle and azo- and hydrazodicarboxamide-based templates decorated with four cyclohexyl groups is described. The different affinity of the binding sites for the benzylic amide macrocycle and the formation of programmed non-covalent interactions between the interlocked components have an important effect on the dynamic behavior of these compounds. Having this in mind, the chemical interconversion between the azo and hydrazo forms of the [2]rotaxane was investigated to provide a chemically-driven interlocked system enable to switch its circumrotation rate as a function of the oxidation level of the binding site. Different structural modifications were carried out to further functionalize the nitrogen of the pyridine rings, including oxidation, alkylation or protonation reactions, affording interlocked azo-derivatives whose rotation dynamics were also analyzed. Full article
(This article belongs to the Special Issue ECSOC-20)
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Open AccessArticle Spectroscopic Investigation of the Interaction of the Anticancer Drug Mitoxantrone with Sodium Taurodeoxycholate (NaTDC) and Sodium Taurocholate (NaTC) Bile Salts
Molecules 2017, 22(7), 1079; doi:10.3390/molecules22071079
Received: 9 May 2017 / Revised: 14 June 2017 / Accepted: 21 June 2017 / Published: 28 June 2017
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Abstract
The focus of the present work was to investigate the interaction of the anticancer drug mitoxantrone with two bile salts, sodium taurodeoxycholate (NaTDC) and sodium taurocholate (NaTC). Ultraviolet-visible (UV-Vis) absorption and electron paramagnetic resonance (EPR) spectroscopy were used to quantify the interaction and
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The focus of the present work was to investigate the interaction of the anticancer drug mitoxantrone with two bile salts, sodium taurodeoxycholate (NaTDC) and sodium taurocholate (NaTC). Ultraviolet-visible (UV-Vis) absorption and electron paramagnetic resonance (EPR) spectroscopy were used to quantify the interaction and to obtain information on the location of mitoxantrone in bile salt micelles. The presence of submicellar concentrations of both bile salts induces mitoxantrone aggregation and the extent of drug aggregation in NaTDC is higher than in NaTC. For micellar bile salts concentrations, mitoxantrone monomers are entrapped in the micellar core. Binding constants, micelle/water partition coefficients and the corresponding thermodynamic parameters for binding and partitioning processes were estimated using the changes in monomer absorbance in the presence of bile salts. Binding interaction of mitoxantrone is stronger for NaTDC than NaTC micelles, whereas partitioning efficiency is higher for NaTC micelles for all investigated temperatures. Thermodynamic parameters indicate that both binding and partitioning processes are spontaneous and entropy controlled. The spectral behavior and thermodynamic parameters indicate distinct types of mitoxantrone interaction with NaTDC and NaTC micelles supported by the differences in nature and structure of bile salts micelles. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Fabrication and Cytotoxicity of Gemcitabine-Functionalized Magnetite Nanoparticles
Molecules 2017, 22(7), 1080; doi:10.3390/molecules22071080
Received: 30 April 2017 / Revised: 10 June 2017 / Accepted: 21 June 2017 / Published: 28 June 2017
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Abstract
Nanotechnology has been successfully used for the fabrication of targeted anti-cancer drug carriers. This study aimed to obtain Fe3O4nanoparticles functionalized with Gemcitabine to improve the cytotoxic effects of the chemotherapeutic substance on cancer cells. The (un) functionalized magnetite nanoparticles
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Nanotechnology has been successfully used for the fabrication of targeted anti-cancer drug carriers. This study aimed to obtain Fe3O4 nanoparticles functionalized with Gemcitabine to improve the cytotoxic effects of the chemotherapeutic substance on cancer cells. The (un) functionalized magnetite nanoparticles were synthesized using a modified co-precipitation method. The nanoconjugate characterization was performed by XRD, SEM, SAED and HRTEM; the functionalizing of magnetite with anti-tumor substances has been highlighted through TGA. The interaction with biologic media has been studied by means of stability and agglomeration tendency (using DLS and Zeta Potential); also, the release kinetics of the drug in culture media was evaluated. Cytotoxicity of free-Gemcitabine and the obtained nanoconjugate were evaluated on human BT 474 breast ductal carcinoma, HepG2 hepatocellular carcinoma and MG 63 osteosarcoma cells by MTS. In parallel, cellular morphology of these cells were examined through fluorescence microscopy and SEM. The localization of the nanoparticles related to the cells was studied using SEM, EDX and TEM. Hemolysis assay showed no damage of erythrocytes. Additionally, an in vivo biodistribution study was made for tracking where Fe3O4@Gemcitabine traveled in the body of mice. Our results showed that the transport of the drug improves the cytotoxic effects in comparison with the one produced by free Gemcitabine for the BT474 and HepG2 cells. The in vivo biodistribution test proved nanoparticle accumulation in the vital organs, with the exception of spleen, where black-brown deposits have been found. These results indicate that our Gemcitabine-functionalized nanoparticles are a promising targeted system for applications in cancer therapy. Full article
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Open AccessArticle Glycosylation of Recombinant Antigenic Proteins from Mycobacterium tuberculosis: In Silico Prediction of Protein Epitopes and Ex Vivo Biological Evaluation of New Semi-Synthetic Glycoconjugates
Molecules 2017, 22(7), 1081; doi:10.3390/molecules22071081
Received: 25 May 2017 / Revised: 23 June 2017 / Accepted: 23 June 2017 / Published: 29 June 2017
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Abstract
Tuberculosis is still one of the most deadly infectious diseases worldwide, and the use of conjugated antigens, obtained by combining antigenic oligosaccharides, such as the lipoarabinomannane (LAM), with antigenic proteins from Mycobacterium tuberculosis (MTB), has been proposed as a new strategy for developing
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Tuberculosis is still one of the most deadly infectious diseases worldwide, and the use of conjugated antigens, obtained by combining antigenic oligosaccharides, such as the lipoarabinomannane (LAM), with antigenic proteins from Mycobacterium tuberculosis (MTB), has been proposed as a new strategy for developing efficient vaccines. In this work, we investigated the effect of the chemical glycosylation on two recombinant MTB proteins produced in E. coli with an additional seven-amino acid tag (recombinant Ag85B and TB10.4). Different semi-synthetic glycoconjugated derivatives were prepared, starting from mannose and two disaccharide analogs. The glycans were activated at the anomeric position with a thiocyanomethyl group, as required for protein glycosylation by selective reaction with lysines. The glycosylation sites and the ex vivo evaluation of the immunogenic activity of the different neo-glycoproteins were investigated. Glycosylation does not modify the immunological activity of the TB10.4 protein. Similarly, Ag85B maintains its B-cell activity after glycosylation while showing a significant reduction in the T-cell response. The results were correlated with the putative B- and T-cell epitopes, predicted using a combination of in silico systems. In the recombinant TB10.4, the unique lysine is not included in any T-cell epitope. Lys30 of Ag85B, identified as the main glycosylation site, proved to be the most important site involved in the formation of T-cell epitopes, reasonably explaining why its glycosylation strongly influenced the T-cell activity. Furthermore, additional lysines included in different epitopes (Lys103, -123 and -282) are also glycosylated. In contrast, B-cell epitopic lysines of Ag85B were found to be poorly glycosylated and, thus, the antibody interaction of Ag85B was only marginally affected after coupling with mono- or disaccharides. Full article
(This article belongs to the Special Issue Synthesis and Biological Applications of Glycoconjugates)
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Open AccessFeature PaperArticle The C5 Variant of the Butyrylcholinesterase Tetramer Includes a Noncovalently Bound 60 kDa Lamellipodin Fragment
Molecules 2017, 22(7), 1083; doi:10.3390/molecules22071083
Received: 3 June 2017 / Revised: 27 June 2017 / Accepted: 27 June 2017 / Published: 29 June 2017
Cited by 1 | PDF Full-text (2914 KB) | HTML Full-text | XML Full-text
Abstract
Humans with the C5 genetic variant of butyrylcholinesterase (BChE) have 30–200% higher plasma BChE activity, low body weight, and shorter duration of action of the muscle relaxant succinylcholine. The C5 variant has an extra, slow-moving band of BChE activity on native polyacrylamide gel
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Humans with the C5 genetic variant of butyrylcholinesterase (BChE) have 30–200% higher plasma BChE activity, low body weight, and shorter duration of action of the muscle relaxant succinylcholine. The C5 variant has an extra, slow-moving band of BChE activity on native polyacrylamide gel electrophoresis. This band is about 60 kDa larger than wild-type BChE. Umbilical cord BChE in 100% of newborn babies has a C5-like band. Our goal was to identify the unknown, 60 kDa protein in C5. Both wild-type and C5 BChE are under the genetic control of two independent loci, the BCHE gene on Chr 3q26.1 and the RAPH1 (lamellipodin) gene on Chr 2q33. Wild-type BChE tetramers are assembled around a 3 kDa polyproline peptide from lamellipodin. Western blot of boiled C5 and cord BChE showed a positive response with an antibody to the C-terminus of lamellipodin. The C-terminal exon of lamellipodin is about 60 kDa including an N-terminal polyproline. We propose that the unknown protein in C5 and cord BChE is encoded by the last exon of the RAPH1 gene. In 90% of the population, the 60 kDa fragment is shortened to 3 kDa during maturation to adulthood, leaving only 10% of adults with C5 BChE. Full article
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Open AccessArticle Water-soluble Manganese and Iron Mesotetrakis(carboxyl)porphyrin: DNA Binding, Oxidative Cleavage, and Cytotoxic Activities
Molecules 2017, 22(7), 1084; doi:10.3390/molecules22071084
Received: 1 June 2017 / Revised: 26 June 2017 / Accepted: 26 June 2017 / Published: 29 June 2017
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Abstract
Two new water-soluble metal carboxyl porphyrins, manganese (III) meso-tetrakis (carboxyl) porphyrin and iron (III) meso-tetrakis (carboxyl) porphyrin, were synthesized and characterized. Their interactions with ct-DNA were investigated by UV-Vis titration, fluorescence spectra, viscosity measurement and CD spectra. The results showed they
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Two new water-soluble metal carboxyl porphyrins, manganese (III) meso-tetrakis (carboxyl) porphyrin and iron (III) meso-tetrakis (carboxyl) porphyrin, were synthesized and characterized. Their interactions with ct-DNA were investigated by UV-Vis titration, fluorescence spectra, viscosity measurement and CD spectra. The results showed they can strongly bind to ct-DNA via outside binding mode. Electrophoresis experiments revealed that both complexes can cleave pBR322 DNA efficiently in the presence of hydrogen peroxide, albeit 2-Mn exhibited a little higher efficiency. The inhibitor tests suggest the oxidative DNA cleavage by these two complexes may involve hydroxyl radical active intermediates. Notably, 2-Mn exhibited considerable photocytotoxicity against Hep G2 cell via triggering a significant generation of ROS and causing disruption of MMP after irradiation. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessArticle An All-Nanocrystal Biosensing System for In Vitro Detection of STAT3 Oligonucleotides
Molecules 2017, 22(7), 1085; doi:10.3390/molecules22071085
Received: 19 May 2017 / Revised: 26 June 2017 / Accepted: 27 June 2017 / Published: 29 June 2017
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Abstract
Lanthanide-doped nanocrystals have shown great promise in bio-detection due to their outstanding luminescent properties, including large Stokes shift and sharp emission bands. Herein, we describe an in vitro detection of STAT3 by using an all-nanocrystal biosensing system that takes advantage of inter-particle energy
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Lanthanide-doped nanocrystals have shown great promise in bio-detection due to their outstanding luminescent properties, including large Stokes shift and sharp emission bands. Herein, we describe an in vitro detection of STAT3 by using an all-nanocrystal biosensing system that takes advantage of inter-particle energy transfer between two types of lanthanide-doped nanocrystals. We investigate the effect of nanocrystal size on the sensing performance and find that smaller nanocrystals offer a lower detection limit and larger dynamic range. As STAT3 is identified as an oncogene aberrantly activated and expressed in malignant transformation and tumorigenesis, our study thus holds promise for cancer diagnosis and therapy. Full article
(This article belongs to the Special Issue Nanocrystals: Synthesis, Characterization and Applications)
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Open AccessCommunication A Novel Synthesis of the Efficient Anti-Coccidial Drug Halofuginone Hydrobromide
Molecules 2017, 22(7), 1086; doi:10.3390/molecules22071086
Received: 9 June 2017 / Revised: 28 June 2017 / Accepted: 28 June 2017 / Published: 30 June 2017
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Abstract
Background: Halofuginone hydrobromide (1) is recognized as an effective drug against several species of Eimeria (E.) in poultry. In this paper, we describe a convenient and low cost preparation method for the compound, as well as primary validation of its
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Background: Halofuginone hydrobromide (1) is recognized as an effective drug against several species of Eimeria (E.) in poultry. In this paper, we describe a convenient and low cost preparation method for the compound, as well as primary validation of its activity. Methods: First, 7-bromo-6-chloroquinazolin-4(3H)-one (2) was prepared from m-chlorotoluene by a conventional process, and then chloroacetone was creatively introduced in two steps. Finally, halofuginone hydrobromide (1) was obtained from 7-bromo-6-chloro-3-(3-cholroacetonyl) quinazolin-4(3H)-one (4) by a four-step reaction sequence including condensation, cyclization, deprotection and isomerization. The structures of the relative intermediates and target compound were characterized by melting point, IR, MS and 1H-NMR. Besides, the protective effect of compound 1-supplemented chicken diet at doses of 6, 3 and 1.5 mg per 1 kg were evaluated on chickens infected with E. tenella, by reduction in mortality, weight loss, fecal oocyst excretion and gut pathology, respectively. Results: Halofuginone hydrobromide (1) was prepared successfully by and improved and innovative method based on traditional research. Moreover, the synthesized halofuginone hydrobromide significantly exhibited an anti-coccidial property. Conclusions: The fruitful work described in this Communication has resulted in halofuginone hydrobromide, which has a good pharmaceutical development prospects, becoming more available for large-scale production. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis and In Vitro Anticancer Activity of Novel Dehydroabietic Acid-Based Acylhydrazones
Molecules 2017, 22(7), 1087; doi:10.3390/molecules22071087
Received: 28 May 2017 / Revised: 24 June 2017 / Accepted: 26 June 2017 / Published: 29 June 2017
Cited by 5 | PDF Full-text (416 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In order to develop novel chemotherapeutic agents with potent anticancer activities, a series of dehydroabietic acid (DHA) derivatives bearing an acylhydrazone moiety were designed and synthesized by the condensation between dehydroabietic acylhydrazide (3) and a variety of substituted arylaldehydes. The inhibitory activities of
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In order to develop novel chemotherapeutic agents with potent anticancer activities, a series of dehydroabietic acid (DHA) derivatives bearing an acylhydrazone moiety were designed and synthesized by the condensation between dehydroabietic acylhydrazide (3) and a variety of substituted arylaldehydes. The inhibitory activities of these compounds against CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical), and BEL-7402 (liver) human carcinoma cell lines were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro. The screening results revealed that many of the compounds showed moderate to high levels of anticancer activities against the tested cancer cell lines and some displayed similar potent inhibitory activities to the commercial anticancer drug cisplatin, while they exhibited lower cytotoxicity against normal human liver cell (HL-7702). Particularly, compound 4w, N’-(3,5-difluorobenzylidene)-2-(dehydroabietyloxy)acetohydrazide, with an IC50 (50% inhibitory concentration) value of 2.21 μM against HeLa cell, was about 17-fold more active than that of the parent compound, and showed remarkable cytotoxicity with an IC50 value of 14.46 μM against BEL-7402 cell. These results provide an encouraging framework that could lead to the development of potent novel anticancer agents. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle New Heterofunctional Supports Based on Glutaraldehyde-Activation: A Tool for Enzyme Immobilization at Neutral pH
Molecules 2017, 22(7), 1088; doi:10.3390/molecules22071088
Received: 3 May 2017 / Revised: 26 June 2017 / Accepted: 27 June 2017 / Published: 29 June 2017
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Abstract
Immobilization is an exciting alternative to improve the stability of enzymatic processes. However, part of the applied covalent strategies for immobilization uses specific conditions, generally alkaline pH, where some enzymes are not stable. Here, a new generation of heterofunctional supports with application at
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Immobilization is an exciting alternative to improve the stability of enzymatic processes. However, part of the applied covalent strategies for immobilization uses specific conditions, generally alkaline pH, where some enzymes are not stable. Here, a new generation of heterofunctional supports with application at neutral pH conditions was proposed. New supports were developed with different bifunctional groups (i.e., hydrophobic or carboxylic/metal) capable of adsorbing biocatalysts at different regions (hydrophobic or histidine richest place), together with a glutaraldehyde group that promotes an irreversible immobilization at neutral conditions. To verify these supports, a multi-protein model system (E. coli extract) and four enzymes (Candida rugosa lipase, metagenomic lipase, β-galactosidase and β-glucosidase) were used. The immobilization mechanism was tested and indicated that moderate ionic strength should be applied to avoid possible unspecific adsorption. The use of different supports allowed the immobilization of most of the proteins contained in a crude protein extract. In addition, different supports yielded catalysts of the tested enzymes with different catalytic properties. At neutral pH, the new supports were able to adsorb and covalently immobilize the four enzymes tested with different recovered activity values. Notably, the use of these supports proved to be an efficient alternative tool for enzyme immobilization at neutral pH. Full article
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Open AccessArticle Characterization of Polyelectrolyte Complex Formation Between Anionic and Cationic Poly(amino acids) and Their Potential Applications in pH-Dependent Drug Delivery
Molecules 2017, 22(7), 1089; doi:10.3390/molecules22071089
Received: 28 April 2017 / Revised: 15 June 2017 / Accepted: 27 June 2017 / Published: 30 June 2017
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Abstract
Polyelectrolyte complexes (PECs) are self-assembling nano-sized constructs that offer several advantages over traditional nanoparticle carriers including controllable size, biodegradability, biocompatibility, and lack of toxicity, making them particularly appealing as tools for drug delivery. Here, we discuss potential application of PECs for drug delivery
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Polyelectrolyte complexes (PECs) are self-assembling nano-sized constructs that offer several advantages over traditional nanoparticle carriers including controllable size, biodegradability, biocompatibility, and lack of toxicity, making them particularly appealing as tools for drug delivery. Here, we discuss potential application of PECs for drug delivery to the slightly acidic tumor microenvironment, a pH in the range of 6.5–7.0. Poly(l-glutamic acid) (En), poly(l-lysine) (Kn), and a copolymer composed of histidine-glutamic acid repeats ((HE)n) were studied for their ability to form PECs, which were analyzed for size, polydispersity, and pH sensitivity. PECs showed concentration dependent size variation at residue lengths of E51/K55 and E135/K127, however, no complexes were observed when E22 or K21 were used, even in combination with the longer chains. (HE)20/K55 PECs could encapsulate daunomycin, were stable from pH 7.4–6.5, and dissociated completely between pH 6.5–6.0. Conversely, the E51-dauno/K55 PEC dissociated between pH 4.0 and 3.0. These values for pH-dependent particle dissociation are consistent with the pKa’s of the ionizable groups in each formulation and indicate that the specific pH-sensitivity of (HE)20-dauno/K55 PECs is mediated by incorporation of histidine. This response within a pH range that is physiologically relevant to the acidic tumors suggests a potential application of these PECs in pH-dependent drug delivery. Full article
(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)
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Open AccessArticle Polyurethane Foams for Thermal Insulation Uses Produced from Castor Oil and Crude Glycerol Biopolyols
Molecules 2017, 22(7), 1091; doi:10.3390/molecules22071091
Received: 7 April 2017 / Revised: 14 June 2017 / Accepted: 15 June 2017 / Published: 2 July 2017
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Abstract
Rigid polyurethane foams were synthesized using a renewable polyol from the simple physical mixture of castor oil and crude glycerol. The effect of the catalyst (DBTDL) content and blowing agents in the foams’ properties were evaluated. The use of physical blowing agents (cyclopentane
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Rigid polyurethane foams were synthesized using a renewable polyol from the simple physical mixture of castor oil and crude glycerol. The effect of the catalyst (DBTDL) content and blowing agents in the foams’ properties were evaluated. The use of physical blowing agents (cyclopentane and n-pentane) allowed foams with smaller cells to be obtained in comparison with the foams produced with a chemical blowing agent (water). The increase of the water content caused a decrease in density, thermal conductivity, compressive strength, and Young’s modulus, which indicates that the increment of CO2 production contributes to the formation of larger cells. Higher amounts of catalyst in the foam formulations caused a slight density decrease and a small increase of thermal conductivity, compressive strength, and Young’s modulus values. These green foams presented properties that indicate a great potential to be used as thermal insulation: density (23–41 kg·m−3), thermal conductivity (0.0128–0.0207 W·m−1·K−1), compressive strength (45–188 kPa), and Young’s modulus (3–28 kPa). These biofoams are also environmentally friendly polymers and can aggregate revenue to the biodiesel industry, contributing to a reduction in fuel prices. Full article
(This article belongs to the Special Issue Natural Polymers and Biopolymers)
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Open AccessArticle In Vitro Effect of 8-Prenylnaringenin and Naringenin on Fibroblasts and Glioblastoma Cells-Cellular Accumulation and Cytotoxicity
Molecules 2017, 22(7), 1092; doi:10.3390/molecules22071092
Received: 20 March 2017 / Revised: 26 June 2017 / Accepted: 28 June 2017 / Published: 30 June 2017
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Abstract
Gliomas are one of the most aggressive and treatment-resistant types of human brain cancer. Identification and evaluation of anticancer properties of compounds found in plants, such as naringenin (N) and 8-prenylnaringenin (8PN), are among the most promising applications in glioma therapy. The prenyl
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Gliomas are one of the most aggressive and treatment-resistant types of human brain cancer. Identification and evaluation of anticancer properties of compounds found in plants, such as naringenin (N) and 8-prenylnaringenin (8PN), are among the most promising applications in glioma therapy. The prenyl group seems to be crucial to the anticancer activity of flavones, since it may lead to enhanced cell membrane targeting and thus increased intracellular activity. It should be noted that 8PN content in hop cones is 10 to 100 times lower compared to other flavonoids, such as xanthohumol. In the study presented, we used a simple method for the synthesis of 8PN from isoxanthohumol—O-demethylation, with a high yield of 97%. Cellular accumulation and cytotoxicity of naringenin and 8-prenylnaringenin in normal (BJ) and cancer cells (U-118 MG) was also examined. Obtained data indicated that 8-prenylnaringenin exhibited higher cytotoxicity against used cell lines than naringenin, and the effect of both flavones was stronger in U-118 MG cells than in normal fibroblasts. The anticancer properties of 8PN correlated with its significantly greater (37%) accumulation in glioblastoma cells than in normal fibroblasts. Additionally, naringenin demonstrated higher selectivity for glioblastoma cells, as it was over six times more toxic for cancer than normal cells. Our results provide evidence that examined prenylated and non-prenylated flavanones have different biological activities against normal and cancer cell lines, and this property may be useful in designing new anticancer drugs for glioblastoma therapy. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Metal Atom Effect on the Photophysical Properties of Mg(II), Zn(II), Cd(II), and Pd(II) Tetraphenylporphyrin Complexes Proposed as Possible Drugs in Photodynamic Therapy
Molecules 2017, 22(7), 1093; doi:10.3390/molecules22071093
Received: 26 May 2017 / Revised: 22 June 2017 / Accepted: 28 June 2017 / Published: 30 June 2017
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Abstract
The effects of Mg, Zn, Cd, and Pd dications on the photophysical properties of the tetraphenylporphyrin ligand have been explored, considering the corresponding complexes and by using the density functional theory and its time-dependent extension. Results show that absorption wavelengths do not change
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The effects of Mg, Zn, Cd, and Pd dications on the photophysical properties of the tetraphenylporphyrin ligand have been explored, considering the corresponding complexes and by using the density functional theory and its time-dependent extension. Results show that absorption wavelengths do not change significantly when the metal ion changes contrary to what happens to the singlet–triplet energy gaps (ΔES−T) and the spin-orbit matrix elements ΨSnHsoΨTm. The most probable intersystem spin crossing (ISC) pathways for the population of the lowest triplet states have been explored. Our findings can contribute to rationalize the available experimental data and promote the potential therapeutic use of these compounds as photosensitizers in photodynamic therapy (PDT). Full article
(This article belongs to the Special Issue Frontiers in Computational Chemistry for Drug Discovery)
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Open AccessArticle Molecular Docking and Anticonvulsant Activity of Newly Synthesized Quinazoline Derivatives
Molecules 2017, 22(7), 1094; doi:10.3390/molecules22071094
Received: 29 April 2017 / Revised: 13 June 2017 / Accepted: 28 June 2017 / Published: 30 June 2017
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Abstract
A new series of quinazoline-4(3H)-ones are evaluated for anticonvulsant activity. After intraperitoneal (ip) injection to albino mice at a dose of 100 mg/kg body weight, synthesized quinazolin-4(3H)-ones (1–24) were examined in the maximal electroshock (MES) induced seizures and subcutaneous pentylenetetrazole (scPTZ) induced seizure
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A new series of quinazoline-4(3H)-ones are evaluated for anticonvulsant activity. After intraperitoneal (ip) injection to albino mice at a dose of 100 mg/kg body weight, synthesized quinazolin-4(3H)-ones (1–24) were examined in the maximal electroshock (MES) induced seizures and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The Rotarod method was applied to determine the neurotoxicity. Most of the compounds displayed anticonvulsant activity in the scPTZ screen at a dose range of 0.204–0.376 mmol/mL. Out of twenty-four, compounds 8, 13 and 19 proved to be the most active with a remarkable protection (100%) against PTZ induced convulsions and four times more potent activity than ethosuximide. The structure-activity relationship concluded valuable pharmacophoric information, which was confirmed by the molecular docking studies using the target enzyme human carbon anhydrase II (HCA II). The studied quinazoline analogues suggested that the butyl substitution at position 3 has a significant effect on preventing the spread of seizure discharge and on raising the seizure threshold. However, benzyl substitution at position 3 has shown a strong anticonvulsant activity but with less seizure prevention compared to the butyl substitution. Full article
(This article belongs to the Special Issue Polypharmacology and Multitarget Drug Discovery)
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Open AccessFeature PaperArticle Kinetics, Mechanism and Theoretical Studies of Norbornene-Ethylene Alternating Copolymerization Catalyzed by Organopalladium(II) Complexes Bearing Hemilabile α-Amino–pyridine
Molecules 2017, 22(7), 1095; doi:10.3390/molecules22071095
Received: 2 June 2017 / Accepted: 27 June 2017 / Published: 30 June 2017
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Abstract
Cationic methylpalladium complexes bearing hemilabile bidentate α-amino–pyridines can serve as effective precursors for catalytic alternating copolymerization of norbornene (N) and ethylene (E), under mild conditions. The norbornyl palladium complexes in the formula of {[RHNCH2(o-C6H4N)]Pd(C7
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Cationic methylpalladium complexes bearing hemilabile bidentate α-amino–pyridines can serve as effective precursors for catalytic alternating copolymerization of norbornene (N) and ethylene (E), under mild conditions. The norbornyl palladium complexes in the formula of {[RHNCH2(o-C6H4N)]Pd(C7H10Me)(NCMe)}(BF4) (R = iPr (2a), tBu (2b), Ph (2c), 2,6-Me2C6H3 (2d), 2,6-iPr2C6H3 (2e)) were synthesized via single insertion of norbornene into the corresponding methylpalladium complexes 1a1e, respectively. Both square planar methyl and norbornyl palladium complexes exhibit facile equilibria of geometrical isomerization, via sterically-controlled amino decoordination–recoordination of amino–pyridine. Kinetic studies of E-insertion, N-insertion of complexes 1 and 2, and the geometric isomerization reactions have been examined by means of VT-NMR, and found in excellent agreement with the results estimated by DFT calculations. The more facile N-insertion in the cis-isomers, and ready geometric isomerization, cooperatively lead to a new mechanism that accounts for the novel catalytic formation of alternating COC. Full article
(This article belongs to the Special Issue Organometallic Catalysis for Olefin Polymerization/Oligomerization)
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Open AccessArticle Enantioselective Michael Addition of Cyclic β-Diones to α,β-Unsaturated Enones Catalyzed by Quinine-Based Organocatalysts
Molecules 2017, 22(7), 1096; doi:10.3390/molecules22071096
Received: 16 May 2017 / Revised: 25 June 2017 / Accepted: 26 June 2017 / Published: 30 June 2017
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Abstract
An enantioselective (52–98% ee) Michael addition between cyclic β-diones and α,β-unsaturated enones was established in the presence of quinine-based primary amine or squaramide. A variety of cinnamones were smoothly converted into the desired 3,4-dihydropyrans in moderate to high yields (63–99%). Chalcones were also
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An enantioselective (52–98% ee) Michael addition between cyclic β-diones and α,β-unsaturated enones was established in the presence of quinine-based primary amine or squaramide. A variety of cinnamones were smoothly converted into the desired 3,4-dihydropyrans in moderate to high yields (63–99%). Chalcones were also suitable acceptors and gave rise to the expected adducts in satisfactory yields (31–99%). The resulting adducts readily underwent further modification to form fused 4H-pyran or 2,3-dihydrofuran. Full article
(This article belongs to the Special Issue Asymmetric Synthesis 2017)
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Open AccessArticle Evaluation of Marine Microalga Diacronema vlkianum Biomass Fatty Acid Assimilation in Wistar Rats
Molecules 2017, 22(7), 1097; doi:10.3390/molecules22071097
Received: 19 May 2017 / Revised: 22 June 2017 / Accepted: 27 June 2017 / Published: 1 July 2017
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Abstract
Diacronema vlkianum is a marine microalgae for which supposed health promoting effects have been claimed based on its phytochemical composition. The potential use of its biomass as health ingredient, including detox-shakes, and the lack of bioavailability studies were the main concerns. In order
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Diacronema vlkianum is a marine microalgae for which supposed health promoting effects have been claimed based on its phytochemical composition. The potential use of its biomass as health ingredient, including detox-shakes, and the lack of bioavailability studies were the main concerns. In order to evaluate the microalgae-biomass assimilation and its health-benefits, single-dose (CD1-mice) studies were followed by 66-days repeated-dose study in Wistar rats with the highest tested single-dose of microalgae equivalent to 101 mg/kg eicosapentaenoic acid + docosahexaenoic acid (EPA+DHA). Microalgae-supplementation modulated EPA and docosapentaenoic acid enrichment at arachidonic acid content expenditure in erythrocytes and liver, while increasing EPA content of heart and adipose tissues of rats. Those fatty acid (FA) changes confirmed the D. vlkianum-biomass FA assimilation. The principal component analyses discriminated brain from other tissues, which formed two other groups (erythrocytes, liver, and heart separated from kidney and adipose tissues), pointing to a distinct signature of FA deposition for the brain and for the other organs. The improved serum lipid profile, omega-3 index and erythrocyte plasticity support the cardiovascular benefits of D. vlkianum. These results bolster the potential of D. vlkianum-biomass to become a “heart-healthy” food supplement providing a safe and renewable source of bioavailable omega-3 FA. Full article
(This article belongs to the Special Issue Natural Products and Chronic Diseases)
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Open AccessArticle Antibacterial Activities of Pyrenylated Coumarins from the Roots of Prangos hulusii
Molecules 2017, 22(7), 1098; doi:10.3390/molecules22071098
Received: 9 June 2017 / Revised: 25 June 2017 / Accepted: 28 June 2017 / Published: 1 July 2017
Cited by 1 | PDF Full-text (616 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The dichloromethane extract of the roots of Prangos hulusii, a recently described endemic species from Turkey, has yielded nine known and one new prenylated coumarins. The structures were elucidated by spectroscopic methods and direct comparison with the reference compounds where available. The
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The dichloromethane extract of the roots of Prangos hulusii, a recently described endemic species from Turkey, has yielded nine known and one new prenylated coumarins. The structures were elucidated by spectroscopic methods and direct comparison with the reference compounds where available. The root extract and its prenylated coumarins exhibit antimicrobial activity against nine standard and six clinically isolated strains at a concentration between 5 and 125 µg/mL. In particular, the new coumarin, 4′-senecioiloxyosthol (1), displayed 5 µg/mL MIC (Minimum Inhibitory Concentration) value against Bacillus subtilis ATCC 9372, murraol (4) and auraptenol (5) showed 63 µg/mL MIC value against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 9372, and isoimperatorin (9) exhibited 16 µg/mL MIC value. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Synthesis and Evaluation of N-(3-Trifluoroacetyl-indol-7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties
Molecules 2017, 22(7), 1099; doi:10.3390/molecules22071099
Received: 5 June 2017 / Revised: 21 June 2017 / Accepted: 28 June 2017 / Published: 2 July 2017
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Abstract
A series of novel N-((2,5-diaryl-3-trifluoroacetyl)-1H-indol-7-yl)acetamides has been prepared via a successive and one-pot reaction sequence involving initial trifluoroacetic acid-mediated Beckmann rearrangement of the oximes derived from the 1-(2,5-diaryl-1H-indol-7-yl)ethanones, followed by trifluoroacetylation of the incipient N-(2,5-diaryl-1H-indol-7-yl)-acetamides
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A series of novel N-((2,5-diaryl-3-trifluoroacetyl)-1H-indol-7-yl)acetamides has been prepared via a successive and one-pot reaction sequence involving initial trifluoroacetic acid-mediated Beckmann rearrangement of the oximes derived from the 1-(2,5-diaryl-1H-indol-7-yl)ethanones, followed by trifluoroacetylation of the incipient N-(2,5-diaryl-1H-indol-7-yl)-acetamides with trifluoroacetic anhydride. The prepared compounds were evaluated for potential in vitro antiplasmodial properties. Preliminary results from antiplasmodial activity against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum revealed that a combination of 2-(4-flurophenyl)- and 5-(4-fluorophenyl) or 2-(4-flurophenyl)- and 4-fluorostyryl groups in compounds 3(a,f) and 4(a,g), for example, is required for biological activity for both series of compounds. Their possible mode of action against the plasmodial parasite is explained theoretically through molecular docking of the most active compounds against the parasite lactate dehydrogenase (pLDH). These compounds were docked at the entrance of NAD+ in pLDH presumably hindering entry of lactate to cause the observed inhibition effect of pLDH. The four compounds were found to exhibit low toxicity against monkey kidney Vero cells at the highest concentrations tested. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessArticle Phytochemical Analysis and Antimicrobial Activity of Myrcia tomentosa (Aubl.) DC. Leaves
Molecules 2017, 22(7), 1100; doi:10.3390/molecules22071100
Received: 23 May 2017 / Accepted: 29 June 2017 / Published: 4 July 2017
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Abstract
This work describes the isolation and structural elucidation of compounds from the leaves of Myrcia tomentosa (Aubl.) DC. (goiaba-brava) and evaluates the antimicrobial activity of the crude extract, fractions and isolated compounds against bacteria and fungi. Column chromatography was used to fractionate and
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This work describes the isolation and structural elucidation of compounds from the leaves of Myrcia tomentosa (Aubl.) DC. (goiaba-brava) and evaluates the antimicrobial activity of the crude extract, fractions and isolated compounds against bacteria and fungi. Column chromatography was used to fractionate and purify the extract of the M. tomentosa leaves and the chemical structures of the compounds were determined using spectroscopic techniques. The antibacterial and antifungal activities were assessed using the broth microdilution method. The phytochemical investigation isolated 11 compounds: α-bisabolol, α-bisabolol oxide B, α-cadinol, β-sitosterol, n-pentacosane, n-tetracosane, quercetin, kaempferol, avicularin, juglanin and guaijaverin. The crude ethanolic extract and its fractions were tested against 15 bacteria and 9 yeasts. The crude extract inhibited the in vitro growth of yeasts at concentration of 4 to 32 μg/mL. The hexane, dichloromethane, ethyl acetate and aqueous fractions inhibited Candida sp. at concentrations of 4 to 256 μg/mL, whereas the Cryptococcus sp. isolates were inhibited only by the hexane and dichloromethane fractions in minimal inhibitory concentrations (MICs) at 16 to 64 μg/mL. The flavonoid quercetin-3-O-α-arabinofuranose (avicularin) was the most active compound, inhibiting Candida species in concentrations of 2 to 32 μg/mL. The MIC values suggest potential activity of this plant species against yeast. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Sites for Dynamic Protein-Carbohydrate Interactions of O- and C-Linked Mannosides on the E. coli FimH Adhesin
Molecules 2017, 22(7), 1101; doi:10.3390/molecules22071101
Received: 1 June 2017 / Revised: 25 June 2017 / Accepted: 28 June 2017 / Published: 3 July 2017
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Abstract
Antagonists of the Escherichia coli type-1 fimbrial adhesin FimH are recognized as attractive alternatives for antibiotic therapies and prophylaxes against acute and recurrent bacterial infections. In this study α-d-mannopyranosides O- or C-linked with an alkyl, alkene, alkyne, thioalkyl, amide,
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Antagonists of the Escherichia coli type-1 fimbrial adhesin FimH are recognized as attractive alternatives for antibiotic therapies and prophylaxes against acute and recurrent bacterial infections. In this study α-d-mannopyranosides O- or C-linked with an alkyl, alkene, alkyne, thioalkyl, amide, or sulfonamide were investigated to fit a hydrophobic substituent with up to two aryl groups within the tyrosine gate emerging from the mannose-binding pocket of FimH. The results were summarized into a set of structure-activity relationships to be used in FimH-targeted inhibitor design: alkene linkers gave an improved affinity and inhibitory potential, because of their relative flexibility combined with a favourable interaction with isoleucine-52 located in the middle of the tyrosine gate. Of particular interest is a C-linked mannoside, alkene-linked to an ortho-substituted biphenyl that has an affinity similar to its O-mannosidic analog but superior to its para-substituted analog. Docking of its high-resolution NMR solution structure to the FimH adhesin indicated that its ultimate, ortho-placed phenyl ring is able to interact with isoleucine-13, located in the clamp loop that undergoes conformational changes under shear force exerted on the bacteria. Molecular dynamics simulations confirmed that a subpopulation of the C-mannoside conformers is able to interact in this secondary binding site of FimH. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions)
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Open AccessArticle Synthesis and Fungicidal Activity of 1-(Carbamoylmethyl)-2-aryl-3,1-benzoxazines
Molecules 2017, 22(7), 1103; doi:10.3390/molecules22071103
Received: 8 June 2017 / Revised: 25 June 2017 / Accepted: 27 June 2017 / Published: 6 July 2017
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Abstract
A series of new 1-(carbamoylmethyl)-2-aryl-3,1-benzoxazines were prepared in moderate to good yields by BF3·OEt2-catalyzed reactions of aromatic aldehydes with 2-(N-substituted carbamoylmethylamino)benzyl alcohols. The structures of the target compounds were confirmed by IR, 1H-NMR, 13C-NMR, and
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A series of new 1-(carbamoylmethyl)-2-aryl-3,1-benzoxazines were prepared in moderate to good yields by BF3·OEt2-catalyzed reactions of aromatic aldehydes with 2-(N-substituted carbamoylmethylamino)benzyl alcohols. The structures of the target compounds were confirmed by IR, 1H-NMR, 13C-NMR, and elemental analyses. The fungicidal activities of the target compounds against plant fungi were preliminarily evaluated, and some of them exhibited good activity. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle L1210 Cells Overexpressing ABCB1 Drug Transporters Are Resistant to Inhibitors of the N- and O-glycosylation of Proteins
Molecules 2017, 22(7), 1104; doi:10.3390/molecules22071104
Received: 1 June 2017 / Revised: 27 June 2017 / Accepted: 28 June 2017 / Published: 3 July 2017
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Abstract
Overexpression of P-glycoprotein (P-gp, drug transporter) in neoplastic cells is the most frequently observed molecular cause of multidrug resistance. Here, we show that the overexpression of P-gp in L1210 cells leads to resistance to tunicamycin and benzyl 2-acetamido-2-deoxy-α-d-galactopyranoside (GalNAc-α-O-benzyl).
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Overexpression of P-glycoprotein (P-gp, drug transporter) in neoplastic cells is the most frequently observed molecular cause of multidrug resistance. Here, we show that the overexpression of P-gp in L1210 cells leads to resistance to tunicamycin and benzyl 2-acetamido-2-deoxy-α-d-galactopyranoside (GalNAc-α-O-benzyl). Tunicamycin induces both glycosylation depression and ubiquitination improvement of P-gp. However, the latter is not associated with large increases in molecular mass as evidence for polyubiquitination. Therefore, P-gp continues in maturation to an active membrane efflux pump rather than proteasomal degradation. P-gp-positive L1210 cells contain a higher quantity of ubiquitin associated with cell surface proteins than their P-gp-negative counterparts. Thus, P-gp-positive cells use ubiquitin signaling for correct protein folding to a higher extent than P-gp-negative cells. Elevation of protein ubiquitination after tunicamycin treatment in these cells leads to protein folding rather than protein degradation, resulting at least in the partial lack of cell sensitivity to tunicamycin in L1210 cells after P-gp expression. In contrast to tunicamycin, to understand why P-gp-positive cells are resistant to GalNAc-α-O-benzyl, further research is needed. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions)
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Open AccessArticle Subcritical Water Technology for Extraction of Phenolic Compounds from Chlorella sp. Microalgae and Assessment on Its Antioxidant Activity
Molecules 2017, 22(7), 1105; doi:10.3390/molecules22071105
Received: 31 May 2017 / Revised: 21 June 2017 / Accepted: 22 June 2017 / Published: 3 July 2017
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Abstract
Chlorella sp. microalgae is a potential source of antioxidants and natural bioactive compounds used in the food and pharmaceutical industries. In this study, a subcritical water (SW) technology was applied to determine the phenolic content and antioxidant activity of Chlorella sp.
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Chlorella sp. microalgae is a potential source of antioxidants and natural bioactive compounds used in the food and pharmaceutical industries. In this study, a subcritical water (SW) technology was applied to determine the phenolic content and antioxidant activity of Chlorella sp. This study focused on maximizing the recovery of Chlorella sp. phenolic content and antioxidant activity measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay as a function of extraction temperature (100–250 °C), time (5–20 min) and microalgae concentration (5–20 wt. %) using response surface methodology. The optimal operating conditions for the extraction process were found to be 5 min at 163 °C with 20 wt. % microalgae concentration, which resulted in products with 58.73 mg gallic acid equivalent (GAE)/g phenolic content and 68.5% inhibition of the DPPH radical. Under optimized conditions, the experimental values were in close agreement with values predicted by the model. The phenolic content was highly correlated (R² = 0.935) with the antioxidant capacity. Results indicated that extraction by SW technology was effective and that Chlorella sp. could be a useful source of natural antioxidants. Full article
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Open AccessArticle Newly Synthesized Doxorubicin Complexes with Selected Metals—Synthesis, Structure and Anti-Breast Cancer Activity
Molecules 2017, 22(7), 1106; doi:10.3390/molecules22071106
Received: 17 May 2017 / Revised: 30 June 2017 / Accepted: 1 July 2017 / Published: 4 July 2017
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Abstract
Doxorubicin (DOX) is very effective chemotherapeutic agent, however it has several major drawbacks. Therefore the motivation for developing novel drug complexes as anticancer agents with different mechanism of action has arisen. The aim of the present study was to evaluate the influence of
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Doxorubicin (DOX) is very effective chemotherapeutic agent, however it has several major drawbacks. Therefore the motivation for developing novel drug complexes as anticancer agents with different mechanism of action has arisen. The aim of the present study was to evaluate the influence of newly synthesized DOX complexes with selected metals (Mg, Mn, Co, Ni, Fe, Cu, Zn) on apoptosis, cell cycle, viability, proliferation and cytotoxicity in the breast cancer cell line MCF-7. Complexation of DOX with metals has likewise been the subject of our research. The current work showed that the tested bivalent metals at a given pH condition formed metal:DOX complexes in a ratio of 2:1, while iron complexes with DOX in a ratio of 3:1. The studies also showed that selected metal-DOX complexes (Mg-DOX, Mn-DOX, Ni-DOX) at 0.5 µM concentration significantly decreased cell viability and proliferation, however they increased caspase 7 activity. Results also indicated that studied metal-DOX complexes showed high cytotoxicity in MCF-7 cells. Therefore they were chosen for cell cycle check-points and apoptosis/necrosis analysis studied by flow cytometry. Obtained results suggest that doxorubicin complexed by specified metals can be considered as a potential anti-breast cancer agent, which is characterized by a higher efficacy than a parent drug. Full article
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Open AccessArticle The [Mo6Cl14]2− Cluster is Biologically Secure and Has Anti-Rotavirus Activity In Vitro
Molecules 2017, 22(7), 1108; doi:10.3390/molecules22071108
Received: 9 May 2017 / Revised: 26 June 2017 / Accepted: 29 June 2017 / Published: 5 July 2017
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Abstract
The molybdenum cluster [Mo6Cl14]2− is a fluorescent component with potential for use in cell labelling and pharmacology. Biological safety and antiviral properties of the cluster are as yet unknown. Here, we show the effect of acute exposition of
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The molybdenum cluster [Mo6Cl14]2− is a fluorescent component with potential for use in cell labelling and pharmacology. Biological safety and antiviral properties of the cluster are as yet unknown. Here, we show the effect of acute exposition of human cells and red blood cells to the molybdenum cluster and its interaction with proteins and antiviral activity in vitro. We measured cell viability of HepG2 and EA.hy926 cell lines exposed to increasing concentrations of the cluster (0.1 to 250 µM), by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Hemolysis and morphological alterations of red blood cells, obtained from healthy donors, exposed to the cluster (10 to 200 µM) at 37 °C were analyzed. Furthermore, quenching of tryptophan residues of albumin was performed. Finally, plaque formation by rotavirus SA11 in MA104 cells treated with the cluster (100 to 300 µM) were analyzed. We found that all doses of the cluster showed similar cell viability, hemolysis, and morphology values, compared to control. Quenching of tryptophan residues of albumin suggests a protein-cluster complex formation. Finally, the cluster showed antiviral activity at 300 µM. These results indicate that the cluster [Mo6Cl14]2− could be intravenously administered in animals at therapeutic doses for further in vivo studies and might be studied as an antiviral agent. Full article
(This article belongs to the Special Issue Metal Based Drugs: Opportunities and Challenges)
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Open AccessArticle Synthesis and Evaluation of New Oxadiazole, Thiadiazole, and Triazole Derivatives as Potential Anticancer Agents Targeting MMP-9
Molecules 2017, 22(7), 1109; doi:10.3390/molecules22071109
Received: 3 June 2017 / Accepted: 1 July 2017 / Published: 4 July 2017
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Abstract
Matrix metalloproteinases (MMPs) are important proteases involved in tumor progression including angiogenesis, tissue invasion, and migration. Therefore, MMPs have been reported as potential diagnostic and prognostic biomarkers in many types of cancer. New oxadiazole, thiadiazole, and triazole derivatives were synthesized and evaluated for
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Matrix metalloproteinases (MMPs) are important proteases involved in tumor progression including angiogenesis, tissue invasion, and migration. Therefore, MMPs have been reported as potential diagnostic and prognostic biomarkers in many types of cancer. New oxadiazole, thiadiazole, and triazole derivatives were synthesized and evaluated for their anticancer effects on A549 human lung adenocarcinoma and C6 rat glioma cell lines. In order to examine the relationship between their anticancer activity and MMP-9, the compounds were evaluated for their inhibitory effects on MMPs. N-(1,3-Benzodioxol-5-ylmethyl)-2-{[5,[5-(((5,6,7,8-tetrahydronaphthalen-2-yl)oxy)methyl)-1,3,4-oxadiazol-2-yl]thio}acetamide (8) and N-(1,3-benzodioxol-5-ylmethyl)-2-[(5-phenyl-1,3,4-oxadiazol-2-yl)thio]acetamide (9) revealed promising cytotoxic effects on A549 and C6 cell lines similar to cisplatin without causing any toxicity towards NIH/3T3 mouse embryonic fibroblast cell line. Compounds 8 and 9 were also the most effective MMP-9 inhibitors in this series. Moreover, docking studies pointed out that compounds 8 and 9 had good affinity to the active site of the MMP-9 enzyme. The molecular docking and in vitro studies suggest that the MMP-9 inhibitory effects of compounds 8 and 9 may play an important role in lung adenocarcinoma and glioma treatment. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Ranatensin-HL: A Bombesin-Related Tridecapeptide from the Skin Secretion of the Broad-Folded Frog, Hylarana latouchii
Molecules 2017, 22(7), 1110; doi:10.3390/molecules22071110
Received: 8 June 2017 / Revised: 24 June 2017 / Accepted: 29 June 2017 / Published: 4 July 2017
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Abstract
Bombesin-related peptides are a family of peptides whose prototype was discovered in amphibian skin and which exhibit a wide range of biological activities. Since the initial isolation of bombesin from Bombina bombina skin, diverse forms of bombesin-related peptides have been found in the
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Bombesin-related peptides are a family of peptides whose prototype was discovered in amphibian skin and which exhibit a wide range of biological activities. Since the initial isolation of bombesin from Bombina bombina skin, diverse forms of bombesin-related peptides have been found in the skins across Anura. In this study, a novel bombesin-related peptide of the ranatensin subfamily, named ranatensin-HL, was structurally-characterised from the skin secretion of the broad-folded frog, Hylarana latouchii, through combination of molecular cloning and mass spectrometric methodologies. It is composed of 13 amino acid residues, pGlu-RAGNQWAIGHFM-NH2, and resembles an N-terminally extended form of Xenopus neuromedin B. Ranatensin-HL and its C-terminal decapeptide (ranatensin-HL-10) were chemically synthesised and subjected to in vitro smooth muscle assays in which they were found to display moderate stimulatory effects on rat urinary bladder and uterus smooth muscles with EC50 values in the range of 1–10 nM. The prepro-ranatensin-HL was highly homological to a bombesin-like peptide from Rana catesbeiana at both nucleotide and amino acid levels, which might provide a clue for the taxonomic classification of ranid frogs in the future. Full article
(This article belongs to the Special Issue Bioactive Natural Peptides As A Pipeline For Therapeutics)
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Open AccessArticle Substituent Effects on the Stability of Thallium and Phosphorus Triple Bonds: A Density Functional Study
Molecules 2017, 22(7), 1111; doi:10.3390/molecules22071111
Received: 12 June 2017 / Revised: 29 June 2017 / Accepted: 29 June 2017 / Published: 5 July 2017
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Abstract
Three computational methods (M06-2X/Def2-TZVP, B3PW91/Def2-TZVP and B3LYP/LANL2DZ+dp) were used to study the effect of substitution on the potential energy surfaces of RTl≡PR (R = F, OH, H, CH3, SiH3, SiMe(SitBu3)2, SiiPrDis
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Three computational methods (M06-2X/Def2-TZVP, B3PW91/Def2-TZVP and B3LYP/LANL2DZ+dp) were used to study the effect of substitution on the potential energy surfaces of RTl≡PR (R = F, OH, H, CH3, SiH3, SiMe(SitBu3)2, SiiPrDis2, Tbt (=C6H2-2,4,6-(CH(SiMe3)2)3), and Ar* (=C6H3-2,6-(C6H2-2, 4,6-i-Pr3)2)). The theoretical results show that these triply bonded RTl≡PR compounds have a preference for a bent geometry (i.e., ∠R⎼Tl⎼P ≈ 180° and ∠Tl⎼P⎼R ≈ 120°). Two valence bond models are used to interpret the bonding character of the Tl≡P triple bond. One is model [I], which is best described as TlP. This interprets the bonding conditions for RTl≡PR molecules that feature small ligands. The other is model [II], which is best represented as TlP. This explains the bonding character of RTl≡PR molecules that feature large substituents. Irrespective of the types of substituents used for the RTl≡PR species, the theoretical investigations (based on the natural bond orbital, the natural resonance theory, and the charge decomposition analysis) demonstrate that their Tl≡P triple bonds are very weak. However, the theoretical results predict that only bulkier substituents greatly stabilize the triply bonded RTl≡PR species, from the kinetic viewpoint. Full article
(This article belongs to the Section Theoretical Chemistry)
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Open AccessArticle Efficiency of Dinucleosides as the Backbone to Pre-Organize Multi-Porphyrins and Enhance Their Stability as Sandwich Type Complexes with DABCO
Molecules 2017, 22(7), 1112; doi:10.3390/molecules22071112
Received: 10 April 2017 / Accepted: 28 June 2017 / Published: 6 July 2017
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Abstract
Flexible linkers such as uridine or 2′-deoxyuridine pre-organize bis-porphyrins in a face-to-face conformation, thus forming stable sandwich complexes with a bidentate base such as 1,4-diazabicyclo[2.2.2]octane (DABCO). Increased stability can be even greater when a dinucleotide linker is used. Such pre-organization increases the association
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Flexible linkers such as uridine or 2′-deoxyuridine pre-organize bis-porphyrins in a face-to-face conformation, thus forming stable sandwich complexes with a bidentate base such as 1,4-diazabicyclo[2.2.2]octane (DABCO). Increased stability can be even greater when a dinucleotide linker is used. Such pre-organization increases the association constant by one to two orders of magnitude when compared to the association constant of DABCO with a reference porphyrin. Comparison with rigid tweezers shows a better efficiency of nucleosidic dimers. Thus, the choice of rigid spacers is not the only way to pre-organize bis-porphyrins, and well-chosen nucleosidic linkers offer an interesting option for the synthesis of such devices. Full article
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Open AccessArticle Proteomics Analysis Reveals an Important Role for the PPAR Signaling Pathway in DBDCT-Induced Hepatotoxicity Mechanisms
Molecules 2017, 22(7), 1113; doi:10.3390/molecules22071113
Received: 21 May 2017 / Accepted: 28 June 2017 / Published: 6 July 2017
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Abstract
A patented organotin di-n-butyl-di-(4-chlorobenzohydroxamato)tin (DBDCT) with high a antitumor activity was designed, however, its antitumor and toxic mechanisms have not yet been clearly illustrated. Hepatic proteins of DBDCT-treated rats were identified and analyzed using LC–MS/MS with label-free quantitative technology. In total,
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A patented organotin di-n-butyl-di-(4-chlorobenzohydroxamato)tin (DBDCT) with high a antitumor activity was designed, however, its antitumor and toxic mechanisms have not yet been clearly illustrated. Hepatic proteins of DBDCT-treated rats were identified and analyzed using LC–MS/MS with label-free quantitative technology. In total, 149 differentially expressed proteins were successfully identified. Five protein and mRNA expressions were involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, including a scavenger receptor (CD36), adipocyte fatty acid binding protein 4 (FABP4), enoyl-CoA hydratase (EHHADH), acetyl-CoA acyltransferase 1 (ACAA1), and phosphoenolpyruvate carboxykinase (PEPCK) in DBDCT-treated Rat Liver (BRL) cells. PPAR-α and PPAR-λ were also significantly decreased at both protein and mRNA levels. Furthermore, compared with the DBDCT treatment group, a special blocking agent of PPAR-λ T0070907 was used to evaluate the relationship between PPAR-λ and its downstream genes. Our studies indicated that DBDCT may serve as a modulator of PPAR-λ, further up-regulating CD36, FABP4 and EHHADH on the PPAR signal pathway. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Antioxidant Capacity, Anticancer Ability and Flavonoids Composition of 35 Citrus (Citrus reticulata Blanco) Varieties
Molecules 2017, 22(7), 1114; doi:10.3390/molecules22071114
Received: 20 June 2017 / Revised: 3 July 2017 / Accepted: 3 July 2017 / Published: 5 July 2017
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Abstract
Citrus (Citrus reticulate Blanco) is one of the most commonly consumed and widely distributed fruit in the world, which is possessing extensive bioactivities. Present study aimed to fully understand the flavonoids compositions, antioxidant capacities and in vitro anticancer abilities of different citrus
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Citrus (Citrus reticulate Blanco) is one of the most commonly consumed and widely distributed fruit in the world, which is possessing extensive bioactivities. Present study aimed to fully understand the flavonoids compositions, antioxidant capacities and in vitro anticancer abilities of different citrus resources. Citrus fruits of 35 varieties belonging to 5 types (pummelos, oranges, tangerines, mandarins and hybrids) were collected. Combining li quid chromatography combined with electrospray ionization mass spectrometry (LC-ESI-MS/MS) and ultra-performance liquid chromatography combined with diode array detector (UPLC-DAD), a total of 39 flavonoid compounds were identified, including 4 flavones, 9 flavanones and 26 polymethoxylated flavonoids (PMFs). Each citrus fruit was examined and compared by 4 parts, flavedo, albedo, segment membrane and juice sacs. The juice sacs had the lowest total phenolics, following by the segment membrane. Four antioxidant traits including 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC) and cupric reducing antioxidant capacity (CUPRAC) were applied for the antioxidant capacities evaluation. Three gastric cancer cell lines, SGC-7901, BGC-823 and AGS were applied for the cytotoxicity evaluation. According to the results of correlation analysis, phenolics compounds might be the main contributor to the antioxidant activity of citrus extracts, while PMFs existing only in the flavedo might be closely related to the gastric cancer cell line cytotoxicity of citrus extracts. The results of present study might provide a theoretical guidance for the utilization of citrus resources. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Quality Control of the Root and Rhizome of Helminthostachys zeylanica (Daodi-Ugon) by HPLC Using Quercetin and Ugonins as Markers
Molecules 2017, 22(7), 1115; doi:10.3390/molecules22071115
Received: 9 June 2017 / Revised: 26 June 2017 / Accepted: 2 July 2017 / Published: 5 July 2017
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Abstract
Daodi-Ugon is the dried root and rhizome of Helminthostachys zeylanica (L.) Hook. and has been used for centuries in the treatment of inflammation, fever, pneumonia, burns, and various disorders. However, the chromatographic methods to determine the phytochemical composition of H. zeylanica have never
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Daodi-Ugon is the dried root and rhizome of Helminthostachys zeylanica (L.) Hook. and has been used for centuries in the treatment of inflammation, fever, pneumonia, burns, and various disorders. However, the chromatographic methods to determine the phytochemical composition of H. zeylanica have never been reported. This study not only aims to develop a valid high-performance liquid chromatography (HPLC) method and to establish a chromatographic fingerprint for the quality control of H. zeylanica, it also establish the proposed content limits of Quercetin, Ugonin J, and Ugonin M. An HPLC method with a RP18 column (250 × 4.6 mm, 5 μm) was developed for the quantitative analysis of Quercetin, Ugonin J, and Ugonin M in H. zeylanica. A simple gradient of (A) methanol/(B) phosphoric acid in water (5–45 min, 70–80% A; 50–55 min, 80–70% A) was used and 360 nm was selected as the detection wavelength. The average contents and proposed content limits for H. zeylanica were calculated with a t-test and a measurement uncertainty test based on 20 batches of authentic H. zeylanica samples. Limits of detection (LOD), quantification (LOQ), linearity, precision, repeatability, stability, and recovery of the developed method were validated. All of the validation results of quantitative determination and fingerprinting methods were satisfactory. The developed method was then applied to assay the contents of Quercetin, Ugonin J, and Ugonin M and to acquire the fingerprints of all of the collected H. zeylanica samples. At the 99% confidence level, the calculated content limits were 56.45, 112.15, and 277.98 mg/kg for Quercetin, Ugonin J, and Ugonin M, respectively. Those validated HPLC quantitative method, fingerprinting profile, and the proposed content limits of three chemical markers that could be used in the quality control of H. zeylanica in the market. Full article
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Open AccessArticle Characterization of Danaparoid Complex Extractive Drug by an Orthogonal Analytical Approach
Molecules 2017, 22(7), 1116; doi:10.3390/molecules22071116
Received: 31 May 2017 / Accepted: 2 July 2017 / Published: 5 July 2017
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Abstract
Danaparoid sodium salt, is the active component of ORGARAN, an anticoagulant and antithrombotic drug constituted of three glycosaminoglycans (GAGs) obtained from porcine intestinal mucosa extracts. Heparan sulfate is the major component, dermatan sulfate and chondroitin sulfate being the minor ones. Currently dermatan sulfate
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Danaparoid sodium salt, is the active component of ORGARAN, an anticoagulant and antithrombotic drug constituted of three glycosaminoglycans (GAGs) obtained from porcine intestinal mucosa extracts. Heparan sulfate is the major component, dermatan sulfate and chondroitin sulfate being the minor ones. Currently dermatan sulfate and chondroitin sulfate are quantified by UV detection of their unsaturated disaccharides obtained by enzymatic depolymerization. Due to the complexity of danaparoid biopolymers and the presence of shared components, an orthogonal approach has been applied using more advanced tools and methods. To integrate the analytical profile, 2D heteronuclear single quantum coherence (HSQC) NMR spectroscopy was applied and found effective to identify and quantify GAG component signals as well as those of some process signatures of danaparoid active pharmaceutical ingredient (API) batches. Analyses of components of both API samples and size separated fractions proceeded through the determination and distribution of the molecular weight (Mw) by high performance size exclusion chromatographic triple detector array (HP-SEC-TDA), chain mapping by LC/MS, and mono- (1H and 13C) and bi-dimensional (HSQC) NMR spectroscopy. Finally, large scale chromatographic isolation and depolymerization of each GAG followed by LC/MS and 2D-NMR analysis, allowed the sequences to be defined and components to be evaluated of each GAG including oxidized residues of hexosamines and uronic acids at the reducing ends. Full article
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Open AccessArticle Isopentyl-Sulfide-Impregnated Nano-MnO2 for the Selective Sorption of Pd(II) from the Leaching Liquor of Ores
Molecules 2017, 22(7), 1117; doi:10.3390/molecules22071117
Received: 11 June 2017 / Revised: 1 July 2017 / Accepted: 2 July 2017 / Published: 6 July 2017
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Abstract
Conventional separation methods are not suitable for recovering palladium present in low concentrations in ore leaching solutions. In this study, a novel isopentyl sulfide (S201)-impregnated α-MnO2 nanorod adsorbent (BISIN) was prepared, characterized, and applied for the selective adsorption and separation
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Conventional separation methods are not suitable for recovering palladium present in low concentrations in ore leaching solutions. In this study, a novel isopentyl sulfide (S201)-impregnated α-MnO2 nanorod adsorbent (BISIN) was prepared, characterized, and applied for the selective adsorption and separation of palladium from the leaching liquor of ores. Batch studies were carried out, and the main adsorption parameters were systematically investigated, in addition to the relevant thermodynamic parameters, isotherms, and kinetic models. The thermodynamic parameters reflected the endothermic and spontaneous nature of the adsorption. Moreover, the experimental results indicated that the Langmuir isotherm model fits the palladium adsorption data well and the adsorption was well described by the pseudo-second-order kinetic model. The main adsorption mechanisms of palladium were elucidated at the molecular level by X-ray crystal structure analysis. Thiourea was found to be an excellent desorption agent, and the palladium-thiourea complex was also confirmed by X-ray crystal structure analysis. The results indicated that almost all of the Pd(II) (>99.0%) is adsorbed on BISIN, whereas less than 2% of the adsorbed Pt(IV), Fe3+, Cu2+, Ni2+, and Co2+ is observed under the optimum conditions. The proposed method can be used for the efficient adsorption and separation of palladium from the leaching liquor of ores. Full article
(This article belongs to the Section Organometallic Chemistry)
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Open AccessArticle Characterization of the Fifth Putative Acetylcholinesterase in the Wolf Spider, Pardosa pseudoannulata
Molecules 2017, 22(7), 1118; doi:10.3390/molecules22071118
Received: 23 June 2017 / Revised: 29 June 2017 / Accepted: 1 July 2017 / Published: 11 July 2017
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Abstract
Background: Acetylcholinesterase (AChE) is an important neurotransmitter hydrolase in invertebrate and vertebrate nervous systems. The number of AChEs is various among invertebrate species, with different functions including the ‘classical’ role in terminating synaptic transmission and other ‘non-classical’ roles. Methods: Using rapid amplification
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Background: Acetylcholinesterase (AChE) is an important neurotransmitter hydrolase in invertebrate and vertebrate nervous systems. The number of AChEs is various among invertebrate species, with different functions including the ‘classical’ role in terminating synaptic transmission and other ‘non-classical’ roles. Methods: Using rapid amplification of cDNA ends (RACE) technology, a new putative AChE-encoding gene was cloned from Pardosa pseudoannulata, an important predatory natural enemy. Sequence analysis and in vitro expression were employed to determine the structural features and biochemical properties of this putative AChE. Results: The cloned AChE contained the most conserved motifs of AChEs family and was clearly clustered with Arachnida AChEs. Determination of biochemical properties revealed that the recombinant enzyme had the obvious preference for the substrate ATC (acetylthiocholine iodide) versus BTC (butyrylthiocholine iodide). The AChE was highly sensitive to AChE-specific inhibitor BW284C51, but not butyrylcholinesterase-specific inhibitor tetraisopropyl pyrophosphoramide (ISO-OMPA). Based on these results, we concluded that a new AChE was identified from P. pseudoannulata and denoted as PpAChE5. Conclusion: Here we report the identification of a new AChE from P. pseudoannulata and increased the AChE number to five in this species. Although PpAChE5 had the biggest Vmax value among five identified AChEs, it showed relatively low affinity with ATC. Similar sensitivity to test insecticides indicated that this AChE might serve as the target for both organophosphorus and carbamate insecticides. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Prediction of Drug–Target Interaction Networks from the Integration of Protein Sequences and Drug Chemical Structures
Molecules 2017, 22(7), 1119; doi:10.3390/molecules22071119
Received: 27 May 2017 / Revised: 27 June 2017 / Accepted: 3 July 2017 / Published: 5 July 2017
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Abstract
Knowledge of drug–target interaction (DTI) plays an important role in discovering new drug candidates. Unfortunately, there are unavoidable shortcomings; including the time-consuming and expensive nature of the experimental method to predict DTI. Therefore, it motivates us to develop an effective computational method to
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Knowledge of drug–target interaction (DTI) plays an important role in discovering new drug candidates. Unfortunately, there are unavoidable shortcomings; including the time-consuming and expensive nature of the experimental method to predict DTI. Therefore, it motivates us to develop an effective computational method to predict DTI based on protein sequence. In the paper, we proposed a novel computational approach based on protein sequence, namely PDTPS (Predicting Drug Targets with Protein Sequence) to predict DTI. The PDTPS method combines Bi-gram probabilities (BIGP), Position Specific Scoring Matrix (PSSM), and Principal Component Analysis (PCA) with Relevance Vector Machine (RVM). In order to evaluate the prediction capacity of the PDTPS, the experiment was carried out on enzyme, ion channel, GPCR, and nuclear receptor datasets by using five-fold cross-validation tests. The proposed PDTPS method achieved average accuracy of 97.73%, 93.12%, 86.78%, and 87.78% on enzyme, ion channel, GPCR and nuclear receptor datasets, respectively. The experimental results showed that our method has good prediction performance. Furthermore, in order to further evaluate the prediction performance of the proposed PDTPS method, we compared it with the state-of-the-art support vector machine (SVM) classifier on enzyme and ion channel datasets, and other exiting methods on four datasets. The promising comparison results further demonstrate that the efficiency and robust of the proposed PDTPS method. This makes it a useful tool and suitable for predicting DTI, as well as other bioinformatics tasks. Full article
(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)
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Open AccessArticle Advantages of an Electrochemical Method Compared to the Spectrophotometric Kinetic Study of Peroxidase Inhibition by Boroxine Derivative
Molecules 2017, 22(7), 1120; doi:10.3390/molecules22071120
Received: 29 May 2017 / Accepted: 3 July 2017 / Published: 5 July 2017
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Abstract
In this study, boroxine derivative (K2[B3O3F4OH]) was tested as an inhibitor of horseradish peroxidase (HRP) by spectrophotometric and electrochemical methods. The activity of horseradish peroxidase was first studied under steady-state kinetic conditions by a spectrophotometric
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In this study, boroxine derivative (K2[B3O3F4OH]) was tested as an inhibitor of horseradish peroxidase (HRP) by spectrophotometric and electrochemical methods. The activity of horseradish peroxidase was first studied under steady-state kinetic conditions by a spectrophotometric method which required the use of guaiacol as a second substrate to measure guaiacol peroxidation. The results of this method have shown that, by changing the concentration of guaiacol as the literature suggests, a different type of inhibition is observed than when changing the concentration of hydrogen peroxide as the substrate. This suggests that guaiacol interferes with the reaction in some way. The electrochemical method involves direct electron transfer of HRP immobilized in Nafion nanocomposite films on a glassy carbon (GC) electrode, creating a sensor with an electro-catalytic response to the reduction of hydrogen peroxide. The electrochemical method simplifies kinetic assays by removing the requirement of reducing substrates. Full article
(This article belongs to the Special Issue Metallopeptides)
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Open AccessArticle Anti-Inflammatory and Anti-Urolithiasis Effects of Polyphenolic Compounds from Quercus gilva Blume
Molecules 2017, 22(7), 1121; doi:10.3390/molecules22071121
Received: 16 June 2017 / Revised: 29 June 2017 / Accepted: 2 July 2017 / Published: 5 July 2017
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Abstract
Quercus gilva Bume (QGB, family Fagaceae) is a tall evergreen oak species tree that grows in warm temperate regions in Korea, Japan, China and Taiwan. Quercus plants have long been the basis of traditional medicines. Their clinical benefits according to traditional medicine include
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Quercus gilva Bume (QGB, family Fagaceae) is a tall evergreen oak species tree that grows in warm temperate regions in Korea, Japan, China and Taiwan. Quercus plants have long been the basis of traditional medicines. Their clinical benefits according to traditional medicine include relief of urolithiasis, tremors and inflammation. In the present study, the anti-urolithiasis activity including anti-inflammatory and anti-oxidative activities, of some phenolic compounds isolated from QGB were described. Seven compounds were isolated and identified as picraquassioside D (1), quercussioside (2), (+)-lyoniresinol-9′α-O-β-d-xylopyranoside (3), (+)-catechin (4), (−)-epicatechin (5), procyanidin B-3 (6), and procyanidin B-4 (7). Compounds 57 showed potent anti-oxidative and anti-inflammatory activities. These compounds were further tested for their inhibition of the gene expression of the inflammatory cytokines. The three compounds 57 showed dose-dependent inhibitory activities on gene expression of COX-2 and IL-1β. In vivo, urolithiasis was induced more effectively in an animal model of acute urolithiasis by the administration of QGB extract. These results indicate the potential of compounds from QGB in the treatment of urolithiasis. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Protective Effect of Quercetin against Oxidative Stress-Induced Cytotoxicity in Rat Pheochromocytoma (PC-12) Cells
Molecules 2017, 22(7), 1122; doi:10.3390/molecules22071122
Received: 7 June 2017 / Revised: 4 July 2017 / Accepted: 4 July 2017 / Published: 6 July 2017
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Abstract
Oxidative stress has been implicated in the pathogenesis of many kinds of neurodegenerative disorders, particularly Parkinson’s disease. Quercetin is a bioflavonoid found ubiquitously in fruits and vegetables, and has antioxidative activity. However, the underlying mechanism of the antioxidative effect of quercetin in neurodegenerative
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Oxidative stress has been implicated in the pathogenesis of many kinds of neurodegenerative disorders, particularly Parkinson’s disease. Quercetin is a bioflavonoid found ubiquitously in fruits and vegetables, and has antioxidative activity. However, the underlying mechanism of the antioxidative effect of quercetin in neurodegenerative diseases has not been well explored. Here, we investigated the antioxidative effect and underlying molecular mechanisms of quercetin on PC-12 cells. We found that PC-12 cells pretreated with quercetin exhibited an increased cell viability and reduced lactate dehydrogenase (LDH) release when exposed to hydrogen peroxide (H2O2). The significantly-alleviated intracellular reactive oxygen species (ROS), malondialdehyde (MDA), and lipoperoxidation of the cell membrane of PC-12 cells induced by H2O2 were observed in the quercetin pretreated group. Furthermore, quercetin pretreatment markedly reduced the apoptosis of PC-12 cells and hippocampal neurons. The inductions of antioxidant enzyme catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in PC-12 cells exposed to H2O2 were significantly reduced by preatment with quercetin. In addition, quercetin pretreatment significantly increased Bcl-2 expression, and reduced Bax, cleaved caspase-3 and p53 expressions. In conclusion, this study demonstrated that quercetin exhibited a protective effect against oxidative stress-induced apoptosis in PC-12 cells. Our findings suggested that quercetin may be developed as a novel therapeutic agent for neurodegenerative diseases induced by oxidative stress. Full article
(This article belongs to the Special Issue Natural Products and Chronic Diseases)
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Open AccessArticle A Purified Serine Protease from Nereis virens and Its Impaction of Apoptosis on Human Lung Cancer Cells
Molecules 2017, 22(7), 1123; doi:10.3390/molecules22071123
Received: 9 June 2017 / Accepted: 3 July 2017 / Published: 7 July 2017
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Abstract
Nereis active protease (NAP) is a novel fibrinolytic active serine protease from the polychaete Nereis virens. In this study, NAP was purified from Nereis virens and the effects of NAP on human lung cancer cells were investigated. Our results indicated that NAP
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Nereis active protease (NAP) is a novel fibrinolytic active serine protease from the polychaete Nereis virens. In this study, NAP was purified from Nereis virens and the effects of NAP on human lung cancer cells were investigated. Our results indicated that NAP inhibited the proliferation and induced apoptosis of H1299 cells in a time- and dose-dependent manner. The loss of mitochondrial membrane potential, the activation of Bax and cleaved-caspase 3/9, the release of cytochrome C, and the suppression of Bcl-2 and poly-ADP ribose polymerase were observed in NAP-treated H1299 cells by flow cytometry and Western blotting. Moreover, the expression levels of Bax and Bcl-2 mRNA were determined by real-time quantitative polymerase chain reaction and the Bax/Bcl-2 expression ratio was increased in the NAP-treated cell lines. The results indicated that NAP-induced apoptosis may be related to mitochondria mediated apoptosis and occurs through caspase-dependent pathways. Then, the effects of NAP on tumor growth in animal models were observed, where 5 or 10 mg/kg of NAP noticeably reduced tumor volume and weight and increased apoptosis as determined by Western blotting when compared to the negative control group. Therefore, our findings suggest that NAP could be a hopeful anticancer medicine for its propensity to inhibit growth and induce of apoptosis in human lung cancer cells. Full article
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