Molecules

Editorial

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2 pages, 130 KiB

Open AccessEditorial

A Serendipitous Journey Leading to My Love of Dendritic Patterns and Chemistry

by Donald A. Tomalia

Molecules 2018, 23(4), 824; https://doi.org/10.3390/molecules23040824 - 4 Apr 2018

Cited by 1 | Viewed by 3415

Abstract

As the oldest of four Midwestern boys who were offsprings of an accountant and a housewife, each with less than a formal high school degree, we were blessed to have such parents.[...] Full article

(This article belongs to the Special Issue Dendrimers: A Themed Issue in Honor of Professor Donald A. Tomalia on the Occasion of His 80th Birthday)

3 pages, 156 KiB

Open AccessEditorial

Lewis Pair Polymerization for New Reactivity and Structure in Polymer Synthesis

by Jiawei Chen, Miao Hong and Eugene Y.-X. Chen

Molecules 2018, 23(4), 915; https://doi.org/10.3390/molecules23040915 - 16 Apr 2018

Cited by 2 | Viewed by 3840

Abstract

n/a Full article

(This article belongs to the Special Issue Lewis Pair Polymerization for New Reactivity and Structure in Polymer Synthesis)

2 pages, 145 KiB

Open AccessEditorial

Biomedical Applications of Polylactide (PLA) and Its Copolymers

by Gaetano Giammona and Emanuela Fabiola Craparo

Molecules 2018, 23(4), 980; https://doi.org/10.3390/molecules23040980 - 23 Apr 2018

Cited by 22 | Viewed by 4143

Abstract

n/a Full article

(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

Research

Jump to: Editorial, Review, Other

14 pages, 726 KiB

Open AccessArticle

Efficient Synthesis and Bioactivity of Novel Triazole Derivatives

by Boyang Hu, Hanqing Zhao, Zili Chen, Chen Xu, Jianzhuang Zhao and Wenting Zhao

Molecules 2018, 23(4), 709; https://doi.org/10.3390/molecules23040709 - 21 Mar 2018

Cited by 12 | Viewed by 5179

Abstract

Triazole pesticides are organic nitrogen-containing heterocyclic compounds, which contain 1,2,3-triazole ring. In order to develop potential glucosamine-6-phosphate synthase (GlmS) inhibitor fungicides, forty compounds of triazole derivatives were synthesized in an efficient way, thirty nine of them were new compounds. The structures of all [...] Read more.

Triazole pesticides are organic nitrogen-containing heterocyclic compounds, which contain 1,2,3-triazole ring. In order to develop potential glucosamine-6-phosphate synthase (GlmS) inhibitor fungicides, forty compounds of triazole derivatives were synthesized in an efficient way, thirty nine of them were new compounds. The structures of all the compounds were confirmed by high resolution mass spectrometer (HRMS), ¹H-NMR and ¹³C-NMR. The fungicidal activities results based on means of mycelium growth rate method indicated that some of the compounds exhibited good fungicidal activities against P. CapasiciLeonian, Sclerotinia sclerotiorum (Lib.) de Bary, Pyricularia oryzae Cav. and Fusarium oxysporum Schl. F.sp. vasinfectum (Atk.) Snyd. & Hans. at the concentration of 50 µg/mL, especially the inhibitory rates of compounds 1-d and 1-f were over 80%. At the same time, the preliminary studies based on the Elson-Morgan method indicated that the compounds exhibited some inhibitory activity toward glucosamine-6-phosphate synthase (GlmS). These compounds will be further studied as potential antifungal lead compounds. The structure-activity relationships (SAR) were discussed in terms of the effects of the substituents on both the benzene and the sugar ring. Full article

(This article belongs to the Section Organic Chemistry)

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17 pages, 6250 KiB

Open AccessArticle

Synthesis of Benzofuran-2-One Derivatives and Evaluation of Their Antioxidant Capacity by Comparing DPPH Assay and Cyclic Voltammetry

by Martina Miceli, Elia Roma, Paolo Rosa, Marta Feroci, M. Antonietta Loreto, Daniela Tofani and Tecla Gasperi

Molecules 2018, 23(4), 710; https://doi.org/10.3390/molecules23040710 - 21 Mar 2018

Cited by 14 | Viewed by 4698

Abstract

The present work aimed to synthesise promising antioxidant compounds as a valuable alternative to the currently expensive and easily degradable molecules that are employed as stabilizers in industrial preparation. Taking into account our experience concerning domino Friedel-Crafts/lactonization reactions, we successfully improved and extended [...] Read more.

The present work aimed to synthesise promising antioxidant compounds as a valuable alternative to the currently expensive and easily degradable molecules that are employed as stabilizers in industrial preparation. Taking into account our experience concerning domino Friedel-Crafts/lactonization reactions, we successfully improved and extended the previously reported methodology toward the synthesis of 3,3-disubstituted-3H-benzofuran-2-one derivatives 9–20 starting from polyphenols 1–6 as substrates and either diethylketomalonate (7) or 3,3,3-trifluoromethyl pyruvate (8) as electrophilic counterpart. The antioxidant capacity of the most stable compounds (9–11 and 15–20) was evaluated by both DPPH assay and Cyclic Voltammetry analyses performed in alcoholic media (methanol) as well as in aprotic solvent (acetonitrile). By comparing the recorded experimental data, a remarkable activity can be attributed to few of the tested lactones. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 2110 KiB

Open AccessArticle

Theoretical Investigation of the Formation Mechanism of NH₃ and HCN during Pyrrole Pyrolysis: The Effect of H₂O

by Ji Liu, Qiang Lu, Xiao-yan Jiang, Bin Hu, Xiao-lei Zhang, Chang-qing Dong and Yong-ping Yang

Molecules 2018, 23(4), 711; https://doi.org/10.3390/molecules23040711 - 21 Mar 2018

Cited by 27 | Viewed by 5537

Abstract

Coal is a major contributor to the global emission of nitrogen oxides (NO_x). The NO_x formation during coal utilization typically derives from the thermal decomposition of N-containing compounds (e.g., pyrrolic groups). NH₃ and HCN are common precursors of NO [...] Read more.

Coal is a major contributor to the global emission of nitrogen oxides (NO_x). The NO_x formation during coal utilization typically derives from the thermal decomposition of N-containing compounds (e.g., pyrrolic groups). NH₃ and HCN are common precursors of NO_x from the decomposition of N-containing compounds. The existence of H₂O has significant influences on the pyrrole decomposition and NO_x formation. In this study, the effects of H₂O on pyrrole pyrolysis to form NO_x precursors HCN and NH₃ are investigated using the density functional theory (DFT) method. The calculation results indicate that the presence of H₂O can lead to the formation of both NH₃ and HCN during pyrrole pyrolysis, while only HCN is formed in the absence of H₂O. The initial interaction between pyrrole and H₂O determines the N products. NH₃ will be formed when H₂O attacks the C₂ position of pyrrole with its hydroxyl group. On the contrary, HCN will be generated instead of NH₃ when H₂O attacks the C₃ position of pyrrole with its hydroxyl group. In addition, the DFT calculations clearly indicate that the formation of NH₃ will be promoted by H₂O, whereas the formation of HCN is inhibited. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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12 pages, 2951 KiB

Open AccessArticle

Digestibility of Bovine Serum Albumin and Peptidomics of the Digests: Effect of Glycation Derived from α-Dicarbonyl Compounds

by Bulei Sheng, Lotte Bach Larsen, Thao T. Le and Di Zhao

Molecules 2018, 23(4), 712; https://doi.org/10.3390/molecules23040712 - 21 Mar 2018

Cited by 29 | Viewed by 5580

Abstract

α-Dicarbonyl compounds, which are widely generated during sugar fragmentation and oil oxidation, are important precursors of advanced glycation end products (AGEs). In this study, the effect of glycation derived from glyoxal (GO), methylglyoxal (MGO) and diacetyl (DA) on the in vitro digestibility of [...] Read more.

α-Dicarbonyl compounds, which are widely generated during sugar fragmentation and oil oxidation, are important precursors of advanced glycation end products (AGEs). In this study, the effect of glycation derived from glyoxal (GO), methylglyoxal (MGO) and diacetyl (DA) on the in vitro digestibility of bovine serum albumin (BSA) was investigated. Glycation from α-dicarbonyl compounds reduced digestibility of BSA in both gastric and intestinal stage of digestion according to measurement of degree of hydrolysis. Changes in peptide composition of digests induced by glycation were displayed, showing absence of peptides, occurrence of new peptides and formation of peptide-AGEs, based on the results obtained using liquid chromatography electron-spray-ionization tandem mass spectrometry (LC-ESI-MS/MS). Crosslinked glycation structures derived from DA largely reduced the sensitivity of glycated BSA towards digestive proteases based on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results. Network structures were found to remain in the digests of glycated samples by transmission electron microscope (TEM), thus the impact of AGEs in unabsorbed digests on the gut flora should be an interest for further studies. Full article

(This article belongs to the Section Analytical Chemistry)

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11 pages, 4063 KiB

Open AccessArticle

Utilizing a Spiro Core with Acridine- and Phenothiazine-Based New Hole Transporting Materials for Highly Efficient Green Phosphorescent Organic Light-Emitting Diodes

by Ramanaskanda Braveenth, Il-Ji Bae, Ji-Hun Han, Wu Qiong, Guk Seon, Kanthasamy Raagulan, Kihun Yang, Young Hee Park, Miyoung Kim and Kyu Yun Chai

Molecules 2018, 23(4), 713; https://doi.org/10.3390/molecules23040713 - 21 Mar 2018

Cited by 9 | Viewed by 4808

Abstract

Two new hole transporting materials, 2,7-bis(9,9-diphenylacridin-10(9H)-yl)-9,9′ spirobi[fluorene] (SP1) and 2,7-di(10H-phenothiazin-10-yl)-9,9′-spirobi[fluorene] (SP2), were designed and synthesized by using the Buchwald–Hartwig coupling reaction with a high yield percentage of over 84%. Both of the materials exhibited high glass transition temperatures of [...] Read more.

Two new hole transporting materials, 2,7-bis(9,9-diphenylacridin-10(9H)-yl)-9,9′ spirobi[fluorene] (SP1) and 2,7-di(10H-phenothiazin-10-yl)-9,9′-spirobi[fluorene] (SP2), were designed and synthesized by using the Buchwald–Hartwig coupling reaction with a high yield percentage of over 84%. Both of the materials exhibited high glass transition temperatures of over 150 °C. In order to understand the device performances, we have fabricated green phosphorescent organic light-emitting diodes (PhOLEDs) with SP1 and SP2 as hole transporting materials. Both of the materials revealed improved device properties, in particular, the SP2-based device showed excellent power (34.47 lm/W) and current (38.41 cd/A) efficiencies when compare with the 4,4′-bis(N-phenyl-1-naphthylamino)biphenyl (NPB)-based reference device (30.33 lm/W and 32.83 cd/A). The external quantum efficiency (EQE) of SP2 was 13.43%, which was higher than SP1 (13.27%) and the reference material (11.45%) with a similar device structure. The SP2 hole transporting material provides an effective charge transporting path from anode to emission layer, which is explained by the device efficiencies. Full article

(This article belongs to the Special Issue Advances in Spiro Compounds)

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17 pages, 876 KiB

Open AccessArticle

Development and Validation of a HPLC-ESI-MS/MS Method for Simultaneous Quantification of Fourteen Alkaloids in Mouse Plasma after Oral Administration of the Extract of Corydalis yanhusuo Tuber: Application to Pharmacokinetic Study

by Weijuan Du, Lisha Jin, Liping Li, Wei Wang, Su Zeng, Huidi Jiang and Hui Zhou

Molecules 2018, 23(4), 714; https://doi.org/10.3390/molecules23040714 - 21 Mar 2018

Cited by 24 | Viewed by 5198

Abstract

The tuber of Corydalis yanhusuo is a famous traditional Chinese medicine and found to have potent pharmacological effects, such as antinociceptive, antitumor, antibacterial, anti-inflammatory, and anti-depressive activities. Although there are several methods to be developed for the analysis and detection of the bioactive [...] Read more.

The tuber of Corydalis yanhusuo is a famous traditional Chinese medicine and found to have potent pharmacological effects, such as antinociceptive, antitumor, antibacterial, anti-inflammatory, and anti-depressive activities. Although there are several methods to be developed for the analysis and detection of the bioactive ingredients’ alkaloids, so far, only few prominent alkaloids could be quantified, and in vitro and in vivo changes of comprehensive alkaloids after oral administration are still little known. In this study, we first developed a simple and sensitive high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to quantify the comprehensive alkaloids of extracts of C. yanhusuo in mouse plasma, using nitidine chloride as an internal standard. As results, at least fourteen alkaloids, including an aporphine (oxoglaucine), a protopine (protopine), five tertiary alkaloids (corydaline, tetrahydroberberine, tetrahydropalmatine, tetrahydrocolumbamine, and tetrahydrocoptisine) and seven quaternary alkaloids (columbamine, palmatine, berberine, epiberberine, coptisine, jatrorrhizine, and dehydrocorydaline) could be well quantified simultaneously in mouse plasma. The lower limits of quantification were greater than, or equal to, 0.67 ng/mL, and the average matrix effects ranged from 96.4% to 114.3%. The mean extraction recoveries of quality control samples were over 71.40%, and the precision and accuracy were within the acceptable limits. All the analytes were shown to be stable under different storage conditions. Then the established method was successfully applied to investigate the pharmacokinetics of these alkaloids after oral administration of the extract of Corydalis yanhusuo in mice. To the best of our knowledge, this is the first document to report the comprehensive and simultaneous analyses of alkaloids of C. yanhusuo in mouse plasma. It was efficient and useful for comprehensive pharmacokinetic and metabolomic analyses of these complex alkaloids after drug administration. Full article

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13 pages, 3264 KiB

Open AccessArticle

Selection and Characterization of Single-Stranded DNA Aptamers Binding Human B-Cell Surface Protein CD20 by Cell-SELEX

by Mansoureh Haghighi, Hossein Khanahmad and Abbasali Palizban

Molecules 2018, 23(4), 715; https://doi.org/10.3390/molecules23040715 - 21 Mar 2018

Cited by 29 | Viewed by 5284

Abstract

The B-lymphocyte antigen (CD20) is a suitable target for single-stranded (ss) nucleic acid oligomer (aptamers). The aim of study was selection and characterization of a ssDNA aptamer against CD20 using Cell-Systematic Evolution of Ligands by Exponential Enrichment (Cell-SELEX). The cDNA clone of CD20 [...] Read more.

The B-lymphocyte antigen (CD20) is a suitable target for single-stranded (ss) nucleic acid oligomer (aptamers). The aim of study was selection and characterization of a ssDNA aptamer against CD20 using Cell-Systematic Evolution of Ligands by Exponential Enrichment (Cell-SELEX). The cDNA clone of CD20 (pcDNA-CD20) was transfected to human embryonic kidney (HEK293T) cells. Ten rounds of Cell-SELEX was performed on recombinant HEK-CD20 cells. The final eluted ssDNA pool was amplified and ligated in T/A vector for cloning. The plasmids of positive clones were extracted, sequenced and the secondary structures of the aptamers predicted using DNAMAN^® software. The sequencing results revealed 10 different types; three of them had the highest thermodynamic stability, named AP-1, AP-2 and AP-3. The AP-1 aptamer was the most thermodynamically stable one (ΔGAP-1 = −10.87 kcal/mol) with the highest binding affinity to CD20 (96.91 ± 4.5 nM). Since, the CD20 is a suitable target for recognition of B-Cell. The selected aptamers could be comparable to antibodies with many advantages. The AP-1, AP-2 and AP-3 could be candidate instead of antibodies for diagnostic and therapeutic applications in immune deficiency, autoimmune diseases, leukemia and lymphoma. Full article

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11 pages, 1268 KiB

Open AccessArticle

Synthesis of Some Novel Thiadiazole Derivative Compounds and Screening Their Antidepressant-Like Activities

by Nafiz Öncü Can, Özgür Devrim Can, Derya Osmaniye and Ümide Demir Özkay

Molecules 2018, 23(4), 716; https://doi.org/10.3390/molecules23040716 - 21 Mar 2018

Cited by 30 | Viewed by 4876

Abstract

Novel thiadiazole derivatives were synthesized through the reaction of acetylated 2-aminothiadiazole and piperazine derivatives. The chemical structures of the compounds were clarified by Infrared Spectroscopy (IR), ¹H Nuclear Magnetic Resonance Spectroscopy (¹H-NMR), ¹³C Nuclear Magnetic Resonance Spectroscopy (¹³ [...] Read more.

Novel thiadiazole derivatives were synthesized through the reaction of acetylated 2-aminothiadiazole and piperazine derivatives. The chemical structures of the compounds were clarified by Infrared Spectroscopy (IR), ¹H Nuclear Magnetic Resonance Spectroscopy (¹H-NMR), ¹³C Nuclear Magnetic Resonance Spectroscopy (¹³C-NMR) and Electronspray Ionisation Mass Spectroscopy (ESI-MS) spectroscopic methods. Antidepressant-like activities were evaluated by the tail-suspension (TST) and modified forced swimming (MFST) methods. Besides, possible influence of the test compounds on motor activities of the animals were examined by activity cage tests. In the TST, administration of the compounds 2c, 2d, 2e, 2f, 2g and 2h significantly decreased the immobility time of mice regarding the control values. Further, in the MFST, the same compounds reduced the total number of immobility behaviors while increasing swimming performance. However, no change was observed in the total number of climbing behaviors. These data suggested that compounds 2c, 2d, 2e, 2f, 2g and 2h possess notable antidepressant-like activities. Reference drug fluoxetine (10 mg/kg) was also exhibited its antidepressant activity, as expected. No significant difference was seen between the locomotor activity values of the test groups signifying that observed antidepressant-like activities are specific. Theoretical calculation of absorption, distribution, metabolism, excretion (ADME) properties for the obtained compounds were performed and obtained data supported the antidepressant-like potential of these novel thiadiazole derivatives. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 4273 KiB

Open AccessArticle

Heterophyllin B Ameliorates Lipopolysaccharide-Induced Inflammation and Oxidative Stress in RAW 264.7 Macrophages by Suppressing the PI3K/Akt Pathways

by Chunjing Yang, Longtai You, Xingbin Yin, Yi Liu, Xin Leng, Wenping Wang, Na Sai and Jian Ni

Molecules 2018, 23(4), 717; https://doi.org/10.3390/molecules23040717 - 21 Mar 2018

Cited by 25 | Viewed by 5702

Abstract

Heterophyllin B (HB), an active cyclic peptide, is a compound existing in the ethyl acetate extract of Pseudostellaria heterophylla (Miq.) Pax and exhibited the activity of inhibiting the production of NO and cytokines, such as IL-1β and IL-6, in LPS-stimulated RAW 264.7 macrophages. [...] Read more.

Heterophyllin B (HB), an active cyclic peptide, is a compound existing in the ethyl acetate extract of Pseudostellaria heterophylla (Miq.) Pax and exhibited the activity of inhibiting the production of NO and cytokines, such as IL-1β and IL-6, in LPS-stimulated RAW 264.7 macrophages. In addition, HB suppressed the production of ROS and the apoptosis induced by LPS in RAW 264.7 macrophages. The underlying mechanism was investigated in the LPS-induced RAW 264.7 cells. The results showed that HB decreased the level of IL-1β and IL-6 expression by qRT-PCR analysis. HB up-regulated the relative ratio of p-AKT/AKT and p-PI3K/PI3K as indicated by western blot analysis. In summary, HB inhibited the LPS-induced inflammation and apoptosis through the PI3K/Akt signaling pathways and represented a potential therapeutic target for treatment of inflammatory diseases. Full article

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9 pages, 1056 KiB

Open AccessArticle

Amaryllidaceae Alkaloids as Potential Glycogen Synthase Kinase-3β Inhibitors

by Daniela Hulcová, Kateřina Breiterová, Tomáš Siatka, Kamila Klímová, Lara Davani, Marcela Šafratová, Anna Hošťálková, Angela De Simone, Vincenza Andrisano and Lucie Cahlíková

Molecules 2018, 23(4), 719; https://doi.org/10.3390/molecules23040719 - 21 Mar 2018

Cited by 26 | Viewed by 5758

Abstract

Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine protein kinase that was originally identified as an enzyme involved in the control of glycogen metabolism. It plays a key role in diverse physiological processes including metabolism, the cell cycle, and gene expression by regulating [...] Read more.

Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine protein kinase that was originally identified as an enzyme involved in the control of glycogen metabolism. It plays a key role in diverse physiological processes including metabolism, the cell cycle, and gene expression by regulating a wide variety of well-known substances like glycogen synthase, tau-protein, and β-catenin. Recent studies have identified GSK-3β as a potential therapeutic target in Alzheimer´s disease, bipolar disorder, stroke, more than 15 types of cancer, and diabetes. GSK-3β is one of the most attractive targets for medicinal chemists in the discovery, design, and synthesis of new selective potent inhibitors. In the current study, twenty-eight Amaryllidaceae alkaloids of various structural types were studied for their potency to inhibit GSK-3β. Promising results have been demonstrated by alkaloids of the homolycorine-{9-O-demethylhomolycorine (IC₅₀ = 30.00 ± 0.71 µM), masonine (IC₅₀ = 27.81 ± 0.01 μM)}, and lycorine-types {caranine (IC₅₀ = 30.75 ± 0.04 μM)}. Full article

(This article belongs to the Collection Bioactive Compounds)

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10 pages, 752 KiB

Open AccessArticle

New Metabolites Isolated from a Laurencia obtusa Population Collected in Corsica

by Hélène Esselin, Félix Tomi, Ange Bighelli and Sylvain Sutour

Molecules 2018, 23(4), 720; https://doi.org/10.3390/molecules23040720 - 21 Mar 2018

Cited by 8 | Viewed by 3446

Abstract

The chemical investigation of an ethyl acetate extract (EtOAc) obtained from Laurencia obtusa, collected in Corsica, allowed for the identification of three new compounds (1, 2, and 4) and six known compounds. Compounds 1 to 4 were isolated [...] Read more.

The chemical investigation of an ethyl acetate extract (EtOAc) obtained from Laurencia obtusa, collected in Corsica, allowed for the identification of three new compounds (1, 2, and 4) and six known compounds. Compounds 1 to 4 were isolated and fully characterized by a detailed spectroscopic analysis. Compounds 1 and 2 are two C₁₅-acetogenins sharing the same ring system: a tetrahydropyran linked by a methylene to a tetrahydrofuran ring. Compound 1 exhibits a bromoallene unit whereas compound 2 possesses an uncommon α-bromo-α,β-unsaturated aldehyde terminal unit. Compound 4 is the first diterpene exhibiting a 19(4

\to

3)abeo-labdane skeleton isolated from a Laurencia species. Isolation of concinndiol (compound 3) together with compound 4 suggests a common biosynthetic origin. Additionally, five known compounds, namely sagonenyne, laurene, α-bromocuparene, microcladallene A, and β-snyderol were identified in chromatographic fractions by NMR analysis using a computerized method that was developed in our laboratory. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 5689 KiB

Open AccessArticle

Copper(II) Thiosemicarbazone Complexes and Their Proligands upon UVA Irradiation: An EPR and Spectrophotometric Steady-State Study

by Michal Hricovíni, Milan Mazúr, Angela Sîrbu, Oleg Palamarciuc, Vladimir B. Arion and Vlasta Brezová

Molecules 2018, 23(4), 721; https://doi.org/10.3390/molecules23040721 - 21 Mar 2018

Cited by 14 | Viewed by 6822

Abstract

X- and Q-band electron paramagnetic resonance (EPR) spectroscopy was used to characterize polycrystalline Cu(II) complexes that contained sodium 5-sulfonate salicylaldehyde thiosemicarbazones possessing a hydrogen, methyl, ethyl, or phenyl substituent at the terminal nitrogen. The ability of thiosemicarbazone proligands to generate superoxide radical anions [...] Read more.

X- and Q-band electron paramagnetic resonance (EPR) spectroscopy was used to characterize polycrystalline Cu(II) complexes that contained sodium 5-sulfonate salicylaldehyde thiosemicarbazones possessing a hydrogen, methyl, ethyl, or phenyl substituent at the terminal nitrogen. The ability of thiosemicarbazone proligands to generate superoxide radical anions and hydroxyl radicals upon their exposure to UVA irradiation in aerated aqueous solutions was evidenced by the EPR spin trapping technique. The UVA irradiation of proligands in neutral or alkaline solutions and dimethylsulfoxide (DMSO) caused a significant decrease in the absorption bands of aldimine and phenolic chromophores. Mixing of proligand solutions with the equimolar amount of copper(II) ions resulted in the formation of 1:1 Cu(II)-to-ligand complex, with the EPR and UV-Vis spectra fully compatible with those obtained for the dissolved Cu(II) thiosemicarbazone complexes. The formation of the complexes fully inhibited the photoinduced generation of reactive oxygen species, and only subtle changes were found in the electronic absorption spectra of the complexes in aqueous and DMSO solutions upon UVA steady-state irradiation. The dark redox activity of copper(II) complexes and proligand/Cu(II) aqueous solutions towards hydrogen peroxide which resulted in the generation of hydroxyl radicals, was confirmed by spin trapping experiments. Full article

(This article belongs to the Section Inorganic Chemistry)

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14 pages, 2527 KiB

Open AccessFeature PaperArticle

Nutraceutical Potential of Phenolics from ′Brava′ and ′Mansa′ Extra-Virgin Olive Oils on the Inhibition of Enzymes Associated to Neurodegenerative Disorders in Comparison with Those of ′Picual′ and ′Cornicabra′

by María Figueiredo-González, Patricia Reboredo-Rodríguez, Carmen González-Barreiro, Alegría Carrasco-Pancorbo, Jesús Simal-Gándara and Beatriz Cancho-Grande

Molecules 2018, 23(4), 722; https://doi.org/10.3390/molecules23040722 - 21 Mar 2018

Cited by 19 | Viewed by 5287

Abstract

The increasing interest in the Mediterranean diet is based on the protective effects against several diseases, including neurodegenerative disorders. Polyphenol-rich functional foods have been proposed to be unique supplementary and nutraceutical treatments for these disorders. Extra-virgin olive oils (EVOOs) obtained from ′Brava′ and [...] Read more.

The increasing interest in the Mediterranean diet is based on the protective effects against several diseases, including neurodegenerative disorders. Polyphenol-rich functional foods have been proposed to be unique supplementary and nutraceutical treatments for these disorders. Extra-virgin olive oils (EVOOs) obtained from ′Brava′ and ′Mansa′, varieties recently identified from Galicia (northwestern Spain), were selected for in vitro screening to evaluate their capacity to inhibit key enzymes involved in Alzheimer′s disease (AD) (acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and 5-lipoxygenase (5-LOX)), major depressive disorder (MDD) and Parkinson′s disease (PD) (monoamine oxidases: hMAO-A and hMAO-B respectively). ′Brava′ oil exhibited the best inhibitory activity against all enzymes, when they are compared to ′Mansa′ oil: BuChE (IC₅₀ = 245 ± 5 and 591 ± 23 mg·mL⁻¹), 5-LOX (IC₅₀ = 45 ± 7 and 106 ± 14 mg·mL⁻¹), hMAO-A (IC₅₀ = 30 ± 1 and 72 ± 10 mg·mL⁻¹) and hMAO-B (IC₅₀ = 191 ± 8 and 208 ± 14 mg·mL⁻¹), respectively. The inhibitory capacity of the phenolic extracts could be associated with the content of secoiridoids, lignans and phenolic acids. Full article

(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)

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14 pages, 3093 KiB

Open AccessArticle

Food Additive Sodium Benzoate (NaB) Activates NFκB and Induces Apoptosis in HCT116 Cells

by Betul Yilmaz and Arzu Zeynep Karabay

Molecules 2018, 23(4), 723; https://doi.org/10.3390/molecules23040723 - 22 Mar 2018

Cited by 17 | Viewed by 7125

Abstract

NaB, the metabolite of cinnamon and sodium salt of benzoic acid is a commonly used food and beverage preservative. Various studies have investigated NaB for its effects on different cellular models. However, the effects of NaB on cancer cell viability signaling is substantially [...] Read more.

NaB, the metabolite of cinnamon and sodium salt of benzoic acid is a commonly used food and beverage preservative. Various studies have investigated NaB for its effects on different cellular models. However, the effects of NaB on cancer cell viability signaling is substantially unknown. In this study, the effects of NaB on viability parameters and NFκB, one of the most important regulators in apoptosis, were examined in HCT116 colon cancer cells. Cell culture, light microscopy, spectrophotometry, flow cytometry, and western blot were used as methods to determine cell viability, caspase-3 activity, NFκB, Bcl-xl, Bim, and PARP proteins, respectively. NaB (6.25 mM–50 mM) treatment inhibited cell viability by inducing apoptosis, which was evident with increased Annexin V-PE staining and caspase-3 activity. NFκB activation accompanied the induction of apoptosis in NaB treated cells. Inhibition of NFκB with BAY 11-7082 did not show a pronounced effect on cell viability but induced a more apoptotic profile, which was confirmed by increased PARP fragmentation and caspase-3 activity. This effect was mostly evident at 50 mM concentration of NaB. Bcl-xl levels were not affected by NaB or BAY 11-7082/NaB treatment; whereas, total Bim increased with NaB treatment. Inhibition of NFκB activity further increased Bim levels. Overall, these results suggest that NaB induces apoptosis and activates NFκB in HCT116 colon cancer cells. Activation of NFκB emerges as target in an attempt to protect cells against apoptosis. Full article

(This article belongs to the Section Chemical Biology)

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22 pages, 5738 KiB

Open AccessArticle

Development of Phaleria macrocarpa (Scheff.) Boerl Fruits Using Response Surface Methodology Focused on Phenolics, Flavonoids and Antioxidant Properties

by Khurul Ain Mohamed Mahzir, Siti Salwa Abd Gani, Uswatun Hasanah Zaidan and Mohd Izuan Effendi Halmi

Molecules 2018, 23(4), 724; https://doi.org/10.3390/molecules23040724 - 22 Mar 2018

Cited by 14 | Viewed by 6853

Abstract

In this study, the optimal conditions for the extraction of antioxidants from the Buah Mahkota Dewa fruit (Phaleria macrocarpa) was determined by using Response Surface Methodology (RSM). The optimisation was applied using a Central Composite Design (CCD) to investigate the effect of [...] Read more.

In this study, the optimal conditions for the extraction of antioxidants from the Buah Mahkota Dewa fruit (Phaleria macrocarpa) was determined by using Response Surface Methodology (RSM). The optimisation was applied using a Central Composite Design (CCD) to investigate the effect of three independent variables, namely extraction temperature (°C), extraction time (minutes) and extraction solvent to-feed ratio (% v/v) on four responses: free radical scavenging activity (DPPH), ferric ion reducing power assay (FRAP), total phenolic content (TPC) and total flavonoid content (TFC). The optimal conditions for the antioxidants extraction were found to be 64 °C extraction temperature, 66 min extraction time and 75% v/v solvent to-feed ratio giving the highest percentage yields of DPPH, FRAP, TPC and TFC of 86.85%, 7.47%, 292.86 mg/g and 3.22 mg/g, respectively. Moreover, the data were subjected to Response Surface Methodology (RSM) and the results showed that the polynomial equations for all models were significant, did not show lack of fit, and presented adjusted determination coefficients (R²) above 99%, proving that the yield of phenolic, flavonoid and antioxidants activities obtained experimentally were close to the predicted values and the suitability of the model employed in RSM to optimise the extraction conditions. Hence, in this study, the fruit from P. macrocarpa could be considered to have strong antioxidant ability and can be used in various cosmeceutical or medicinal applications. Full article

(This article belongs to the Special Issue Natural Flavonoids: Structure Elucidation, Distribution and Applications)

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18 pages, 2927 KiB

Open AccessArticle

New Findings in Prunus padus L. Fruits as a Source of Natural Compounds: Characterization of Metabolite Profiles and Preliminary Evaluation of Antioxidant Activity

by Dario Donno, Maria Gabriella Mellano, Marta De Biaggi, Isidoro Riondato, Ernest Naivonirina Rakotoniaina and Gabriele Loris Beccaro

Molecules 2018, 23(4), 725; https://doi.org/10.3390/molecules23040725 - 22 Mar 2018

Cited by 39 | Viewed by 5207

Abstract

European bird cherry (Prunus padus L.) has been known since the Middle Ages for its medical/food use and high health-promoting value. This study aimed to assess the potential of these fruits as a source of bioactive compounds through the characterization of its [...] Read more.

European bird cherry (Prunus padus L.) has been known since the Middle Ages for its medical/food use and high health-promoting value. This study aimed to assess the potential of these fruits as a source of bioactive compounds through the characterization of its physicochemical traits, nutraceutical properties, phytochemical composition via HPLC fingerprint, and antioxidant capacity. Fully ripened fruits of Prunus padus L. (Colorata cv) were collected in mid-July 2017 in Chieri, north-western Italy. The TPC (194.22 ± 32.83 mg_GAE/100 g_FW) and TAC (147.42 ± 0.58 mg_C3G/100 g_FW) values were obtained from the analyzed extracts. The most important phytochemical class was organic acids (48.62 ± 2.31%), followed by polyphenols (35.34 ± 1.80%), monoterpenes (9.36 ± 0.64%), and vitamin C (6.68 ± 0.22%). In this research the most important flavonols selected as marker were quercitrin (16.37 ± 3.51 mg/100 g_FW) and quercetin (11.86 ± 2.36 mg/100 g_FW). Data were reported based on fresh weight. Moreover, fresh fruits showed a mean antioxidant activity value of 17.78 ± 0.84 mmol Fe²⁺·kg⁻¹. Even though the seeds and leaves contain cyanogenic glycosides, this study showed that these fruits could be a natural source of bioactive compounds with high antioxidant properties, due to the contents of organic and phenolic acids, catechins, and a synergetic effect of vitamin C and flavonoids. Full article

(This article belongs to the Collection Advances in Liquid Separation Techniques for Food and Pharmaceutical Analysis)

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14 pages, 3298 KiB

Open AccessArticle

Reparative Effects of Astaxanthin-Hyaluronan Nanoaggregates against Retrorsine-CCl₄-Induced Liver Fibrosis and Necrosis

by Yi Jhen Wu, Yu Chiuan Wu, I-Fen Chen, Yi-Lung Wu, Chin Wen Chuang, Han Hsiang Huang and Shyh Ming Kuo

Molecules 2018, 23(4), 726; https://doi.org/10.3390/molecules23040726 - 22 Mar 2018

Cited by 22 | Viewed by 4904

Abstract

Astaxanthin (Asta), a xanthophyll carotenoid, has been reported to be a strong antioxidative agent and has anti-inflammatory, antitumor and free radical-scavenging activities. However, inadequate stability and water solubility results in its low bioavailability. This study incorporated Asta into hydrophilic hyaluronan nanoparticles (HAn) to [...] Read more.

Astaxanthin (Asta), a xanthophyll carotenoid, has been reported to be a strong antioxidative agent and has anti-inflammatory, antitumor and free radical-scavenging activities. However, inadequate stability and water solubility results in its low bioavailability. This study incorporated Asta into hydrophilic hyaluronan nanoparticles (HAn) to produce Asta-HAn aggregates (AHAna) using an electrostatic field system and investigated the restorative effects of AHAna on retrorsine-CCl₄-induced liver fibrosis in rats in vivo. Transmission electron microscopy (TEM) revealed that the prepared HAn were approximately 15 ± 2.1 nm in diameter and after the incorporation of Asta into HAn, the size increased to 210–500 nm. The incorporation efficiency of Asta was approximately 93% and approximately 54% of Asta was released after incubation for 18 h. Significant reductions in alanine aminotransferase and aspartate aminotransferase levels were observed after the rats were intraperitoneally injected with AHAna. Histopathological findings revealed the greatest reduction in hepatic fibrosis and hepatocyte necrosis in the rats after 2 weeks of intraperitoneal injection with AHAna, which is consistent with the data acquired from serum biochemical analysis. The restorative effects on liver damage displayed by AHAna in vivo demonstrated that Asta aggregated through HAn incorporation exerts therapeutic effects on liver fibrosis and necrosis. Full article

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10 pages, 593 KiB

Open AccessArticle

Heterogeneity of Circulating Tumor Cells in Neoadjuvant Chemotherapy of Breast Cancer

by Evgeniya V. Kaigorodova, Olga E. Savelieva, Liubov A. Tashireva, Natalia A. Tarabanovskaya, Elena I. Simolina, Evgeny V. Denisov, Elena M. Slonimskaya, Evgeny L. Choynzonov and Vladimir M. Perelmuter

Molecules 2018, 23(4), 727; https://doi.org/10.3390/molecules23040727 - 22 Mar 2018

Cited by 31 | Viewed by 4653

Abstract

The biological properties of circulating tumor cells (CTCs), and their dynamics during neoadjuvant chemotherapy are important, both for disease progression prediction and therapeutic target determination, with the aim of preventing disease progression. The aim of our study was to estimate of different CTC [...] Read more.

The biological properties of circulating tumor cells (CTCs), and their dynamics during neoadjuvant chemotherapy are important, both for disease progression prediction and therapeutic target determination, with the aim of preventing disease progression. The aim of our study was to estimate of different CTC subsets in breast cancer during the NACT (neoadjuvant chemotherapy). The prospective study includes 27 patients with invasive breast cancer, T2-4N0-3M0, aged 32 to 60 years. Venous heparinized blood samples, taken before and after biopsy, after each courses of chemotherapy (on days 3–7), and before surgical intervention, served as the material for this study. Different subsets of circulating tumor cells were determined on the basis of the expression of EpCAM, CD45, CD44, CD24, and N-Cadherin using flow cytometry. As the result of this study, it has been observed that significant changes in the quantity of the different subsets of circulating tumor cells in patients’ blood were observed after carrying out the 3rd course of NACT. NACT causes significant changes in the quantity of six CTC subsets, with various combinations of stemness and epithelial-mesenchymal transition (EMT) properties. Full article

(This article belongs to the Special Issue Molecular Imaging and Treatment Monitoring of Cancer)

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13 pages, 8192 KiB

Open AccessArticle

Simultaneous Screening of Major Flame Retardants and Plasticizers in Polymer Materials Using Pyrolyzer/Thermal Desorption Gas Chromatography Mass Spectrometry (Py/TD–GC–MS)

by Hiroyuki Yanagisawa, Yukihiko Kudo, Katsuhiro Nakagawa, Haruhiko Miyagawa, Fumitaka Maruyama and Shigehiko Fujimaki

Molecules 2018, 23(4), 728; https://doi.org/10.3390/molecules23040728 - 22 Mar 2018

Cited by 25 | Viewed by 7139

Abstract

This study was conducted with the aim of achieving the simultaneous screening of various additives in polymer materials by utilizing a solvent-free pyrolyzer/thermal desorption gas chromatography mass spectrometry (Py/TD-GC–MS) method. As a first step to achieve this goal, simultaneous screening has been examined [...] Read more.

This study was conducted with the aim of achieving the simultaneous screening of various additives in polymer materials by utilizing a solvent-free pyrolyzer/thermal desorption gas chromatography mass spectrometry (Py/TD-GC–MS) method. As a first step to achieve this goal, simultaneous screening has been examined by selecting major substances representing plasticizers and flame retardants, such as short chain chlorinated paraffins (SCCPs), decabromodiphenyl ether (DecaBDE), hexabromocyclododecane (HBCDD), and di(2-ethylhexyl) phthalate (DEHP). A quantitative MS analysis was performed to check for the peak areas and sensitivities. Since Py/TD-GC–MS is fraught with the risk of thermal degradation of the sample, temperatures during the analytical process were finely tuned for securing reliable results. The instrumental sensitivity was confirmed by the S/N ratio on each component. The detection limits of all components were less than 50 mg/kg, which are sufficiently lower than the regulatory criteria. With regard to reproducibility, a relative standard deviation (RSD) of about 5% was confirmed by employing a spike recovery test on a polystyrene polymer solution containing mixed standard solution (ca. 1000 mg/kg). In conclusion, the results obtained in this study indicate that Py/TD-GC–MS is applicable for the screening of major flame retardants and plasticizers in real samples with sufficient reproducibility at regulatory levels. Full article

(This article belongs to the Special Issue Functional Molecular Materials)

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13 pages, 2405 KiB

Open AccessArticle

Effects of Limited Hydrolysis and High-Pressure Homogenization on Functional Properties of Oyster Protein Isolates

by Cuiping Yu, Yue Cha, Fan Wu, Xianbing Xu and Ming Du

Molecules 2018, 23(4), 729; https://doi.org/10.3390/molecules23040729 - 22 Mar 2018

Cited by 17 | Viewed by 4014

Abstract

In this study, the effects of limited hydrolysis and/or high-pressure homogenization (HPH) treatment in acid conditions on the functional properties of oyster protein isolates (OPI) were studied. Protein solubility, surface hydrophobicity, particle size distribution, zeta potential, foaming, and emulsifying properties were evaluated. The [...] Read more.

In this study, the effects of limited hydrolysis and/or high-pressure homogenization (HPH) treatment in acid conditions on the functional properties of oyster protein isolates (OPI) were studied. Protein solubility, surface hydrophobicity, particle size distribution, zeta potential, foaming, and emulsifying properties were evaluated. The results showed that acid treatment led to the dissociation and unfolding of OPI. Subsequent treatment such as limited proteolysis, HPH, and their combination remarkably improved the functional properties of OPI. Acid treatment produced flexible aggregates, as well as reduced particle size and solubility. On the contrary, limited hydrolysis increased the solubility of OPI. Furthermore, HPH enhanced the effectiveness of the above treatments. The emulsifying and foaming properties of acid- or hydrolysis-treated OPI significantly improved. In conclusion, a combination of acid treatment, limited proteolysis, and HPH improved the functional properties of OPI. The improvements in the functional properties of OPI could potentiate the use of oyster protein and its hydrolysates in the food industry. Full article

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17 pages, 1757 KiB

Open AccessArticle

Effects of Ultrasound Assisted Extraction in Conjugation with Aid of Actinidin on the Molecular and Physicochemical Properties of Bovine Hide Gelatin

by Tanbir Ahmad, Amin Ismail, Siti A. Ahmad, Khalilah A. Khalil, Teik K. Leo, Elmutaz A. Awad, Jurhamid C. Imlan and Awis Q. Sazili

Molecules 2018, 23(4), 730; https://doi.org/10.3390/molecules23040730 - 22 Mar 2018

Cited by 26 | Viewed by 6034

Abstract

Actinidin was used to pretreat the bovine hide and ultrasonic wave (53 kHz and 500 W) was used for the time durations of 2, 4 and 6 h at 60 °C to extract gelatin samples (UA2, UA4 and UA6, respectively). Control (UAC) gelatin [...] Read more.

Actinidin was used to pretreat the bovine hide and ultrasonic wave (53 kHz and 500 W) was used for the time durations of 2, 4 and 6 h at 60 °C to extract gelatin samples (UA2, UA4 and UA6, respectively). Control (UAC) gelatin was extracted using ultrasound for 6 h at 60 °C without enzyme pretreatment. There was significant (p < 0.05) increase in gelatin yield as the time duration of ultrasound treatment increased with UA6 giving the highest yield of 19.65%. Gel strength and viscosity of UAC and UA6 extracted gelatin samples were 627.53 and 502.16 g and 16.33 and 15.60 mPa.s, respectively. Longer duration of ultrasound treatment increased amino acids content of the extracted gelatin and UAC exhibited the highest content of amino acids. Progressive degradation of polypeptide chains was observed in the protein pattern of the extracted gelatin as the time duration of ultrasound extraction increased. Fourier transform infrared (FTIR) spectroscopy depicted loss of molecular order and degradation in UA6. Scanning electron microscopy (SEM) revealed protein aggregation and network formation in the gelatin samples with increasing time of ultrasound treatment. The study indicated that ultrasound assisted gelatin extraction using actinidin exhibited high yield with good quality gelatin. Full article

(This article belongs to the Special Issue Innovative Extraction Techniques and Hyphenated Instrument Configuration for Complex Matrices Analysis)

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12 pages, 2988 KiB

Open AccessArticle

Synthesis and Physicochemical Evaluation of Entecavir-Fatty Acid Conjugates in Reducing Food Effect on Intestinal Absorption

by Hyuck Jun Jung, Myoung Jin Ho, Sungwan Ahn, Young Taek Han and Myung Joo Kang

Molecules 2018, 23(4), 731; https://doi.org/10.3390/molecules23040731 - 22 Mar 2018

Cited by 10 | Viewed by 5217

Abstract

The oral bioavailability of entecavir (EV), an anti-viral agent commonly prescribed to treat hepatitis B infections, is drastically reduced under a post-prandial state. This is primarily due to its low permeability in the gastrointestinal tract. To reduce the food effect on the intestinal [...] Read more.

The oral bioavailability of entecavir (EV), an anti-viral agent commonly prescribed to treat hepatitis B infections, is drastically reduced under a post-prandial state. This is primarily due to its low permeability in the gastrointestinal tract. To reduce the food effect on the intestinal absorption of the nucleotide analogue, four lipidic prodrugs were synthesized via the esterification of the primary alcohol of EV with fatty acids (hexanoic acid, octanoic acid, decanoic acid, and dodecanoic acid). EV-3-dodecanoate (or EV-C12) exhibited high solubility in a fed state simulated intestinal fluid (78.8 μg/mL), with the acceptable calculated logP value (3.62) and the lowest hydrolysis rate (22.5% for 12 h in simulated gastric fluid, pH 1.2). Therefore, it was chosen as a candidate to improve intestinal absorption of EV, especially under a fed state condition. Physical characterization using scanning electron microscopy, a differential scanning calorimeter, and X-ray powder diffraction revealed that EV-C12 had a rectangular-shaped crystalline form, with a melting point of about 170 °C. In a release test in biorelevant media, such as fasted and fed state-simulated intestinal and/or gastric fluid, more than 90% of the prodrug was released within 2 h in all media tested. These data suggest that this lipidic prodrug might have the potential to alleviate the negative food effect on the intestinal absorption of EV with increased therapeutic efficacy and patient compliance. Full article

(This article belongs to the Section Medicinal Chemistry)

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18 pages, 6183 KiB

Open AccessArticle

Functional Characterization of the Saccharomyces cerevisiae Equilibrative Nucleoside Transporter 1 (ScENT1)

by Rebba C. Boswell-Casteel, Jennifer M. Johnson and Franklin A. Hays

Molecules 2018, 23(4), 732; https://doi.org/10.3390/molecules23040732 - 22 Mar 2018

Cited by 3 | Viewed by 4242

Abstract

Equilibrative nucleoside transporters (ENTs) are polytopic membrane transporters responsible for the translocation of nucleosides, nucleobases—to a lesser extent—and nucleoside analog therapeutics across cellular membranes. ENTs function in a diffusion controlled bidirectional manner and are thought to utilize an alternating access transport mechanism. However, [...] Read more.

Equilibrative nucleoside transporters (ENTs) are polytopic membrane transporters responsible for the translocation of nucleosides, nucleobases—to a lesser extent—and nucleoside analog therapeutics across cellular membranes. ENTs function in a diffusion controlled bidirectional manner and are thought to utilize an alternating access transport mechanism. However, a detailed understanding of ENT function at the molecular level has remained elusive. ScENT1 (formerly known as Function Unknown Now 26 or FUN26) is the only known ENT ortholog endogenously expressed in S. cerevisiae, and a proteoliposome assay system was used to study homogenously overexpressed and purified ScENT1 (wildtype relative to L390A and F249I mutants). L390 and F249 are highly conserved residues and were found to alter transporter function. L390A produced a reduction of mean transport activity while F249I increased mean substrate translocation relative to wildtype protein. However, both mutations resulted in transport of UTP—a novel gain of function for any ENT. These residues were then mapped onto an ab initio model of FUN26 which suggests they function in substrate translocation (L390) or cytoplasmic gating (F249). Furthermore, wildtype, L390A, and F249I were found to be sensitive to the presence of alcohols. Ethanol attenuated ScENT1-mediated transport of uridine by ~50%. These findings further demonstrate functional similarities between ScENT1 and human ENT isoforms and support identification of FUN26 as ScENT1, the first ENT isoform in S. cerevisiae. Full article

(This article belongs to the Special Issue Nucleoside and Nucleotide Analogues)

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11 pages, 3243 KiB

Open AccessFeature PaperArticle

Theoretical Insights into the Solvent Polarity Effect on the Quality of Self-Assembled N-Octadecanethiol Monolayers on Cu (111) Surfaces

by Jun Hu, Shijun He, Yaozhong Zhang, Haixia Ma, Xiaoli Zhang and Zhong Chen

Molecules 2018, 23(4), 733; https://doi.org/10.3390/molecules23040733 - 22 Mar 2018

Cited by 4 | Viewed by 4933

Abstract

The effect of solvent polarity on the quality of self-assembled n-octadecanethiol (C₁₈SH) on Cu surfaces was systematically analyzed using first-principles calculations. The results indicate that the adsorption energy for C₁₈SH on a Cu surface is −3.37 eV, which [...] Read more.

The effect of solvent polarity on the quality of self-assembled n-octadecanethiol (C₁₈SH) on Cu surfaces was systematically analyzed using first-principles calculations. The results indicate that the adsorption energy for C₁₈SH on a Cu surface is −3.37 eV, which is higher than the adsorption energies of the solvent molecules. The higher adsorption energy of dissociated C₁₈SH makes the monolayer self-assembly easier on a Cu (111) surface through competitive adsorption. Furthermore, the adsorption energy per unit area for C₁₈SH decreases from −3.24 eV·Å⁻² to −3.37 eV·Å⁻² in solvents with an increased dielectric constant of 1 to 78.54. Detailed energy analysis reveals that the electrostatic energy gradually increases, while the kinetic energy decreases with increasing dielectric constant. The increased electrostatic energies are mainly attributable to the disappearance of electrostatic interactions on the sulfur end of C₁₈SH. The decreased kinetic energy is mainly due to the generated push force in the polar solvent, which limits the mobility of C₁₈SH. A molecular dynamics simulation also confirms that the -CH₃ site has a great interaction with CH₃(CH₂)₄CH₃ molecules and a weak interaction with CH₃CH₂OH molecules. The different types of interactions help to explain why the surface coverage of C₁₈SH on Cu in a high-polarity ethanol solution is significantly larger than that in a low-polarity n-hexane solution at the stabilized stage. Full article

(This article belongs to the Section Physical Chemistry)

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15 pages, 3471 KiB

Open AccessArticle

A Metabolomics Approach Uncovers Differences between Traditional and Commercial Dairy Products in Buryatia (Russian Federation)

by Lin Pan, Jie Yu, Zhihui Mi, Lanxin Mo, Hao Jin, Caiqing Yao, Dongyan Ren and Bilige Menghe

Molecules 2018, 23(4), 735; https://doi.org/10.3390/molecules23040735 - 22 Mar 2018

Cited by 24 | Viewed by 5019

Abstract

Commercially available and traditional dairy products differ in terms of their manufacturing processes. In this study, commercially available and traditionally fermented cheese, yogurt, and milk beverages were analyzed and compared. The metabolomic technique of ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF) in [...] Read more.

Commercially available and traditional dairy products differ in terms of their manufacturing processes. In this study, commercially available and traditionally fermented cheese, yogurt, and milk beverages were analyzed and compared. The metabolomic technique of ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF) in the MS^E mode was used in combination with statistical methods, including univariate analysis and chemometric analysis, to determine the differences in metabolite profiles between commercially and traditionally fermented dairy products. The experimental results were analyzed statistically and showed that traditional and commercial dairy products were well differentiated in both positive and negative ion modes, with significant differences observed between the samples. After screening for metabolite differences, we detected differences between traditional milk beverages and yogurt and their commercial counterparts in terms of the levels of compounds such as l-lysine, l-methionine, l-citrulline, l-proline, l-serine, l-valine and l-homocysteine, and of short peptides such as Asp-Arg, Gly-Arg, His-Pro, Pro-Asn. The greatest difference between commercially available and traditional cheese was in the short peptide composition, as commercially available and traditional cheese is rich in short peptides. Full article

(This article belongs to the Section Metabolites)

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13 pages, 1460 KiB

Open AccessArticle

Facilitating Anti-Cancer Combinatorial Drug Discovery by Targeting Epistatic Disease Genes

by Yuan Quan, Meng-Yuan Liu, Ye-Mao Liu, Li-Da Zhu, Yu-Shan Wu, Zhi-Hui Luo, Xiu-Zhen Zhang, Shi-Zhong Xu, Qing-Yong Yang and Hong-Yu Zhang

Molecules 2018, 23(4), 736; https://doi.org/10.3390/molecules23040736 - 23 Mar 2018

Cited by 11 | Viewed by 4500

Abstract

Due to synergistic effects, combinatorial drugs are widely used for treating complex diseases. However, combining drugs and making them synergetic remains a challenge. Genetic disease genes are considered a promising source of drug targets with important implications for navigating the drug space. Most [...] Read more.

Due to synergistic effects, combinatorial drugs are widely used for treating complex diseases. However, combining drugs and making them synergetic remains a challenge. Genetic disease genes are considered a promising source of drug targets with important implications for navigating the drug space. Most diseases are not caused by a single pathogenic factor, but by multiple disease genes, in particular, interacting disease genes. Thus, it is reasonable to consider that targeting epistatic disease genes may enhance the therapeutic effects of combinatorial drugs. In this study, synthetic lethality gene pairs of tumors, similar to epistatic disease genes, were first targeted by combinatorial drugs, resulting in the enrichment of the combinatorial drugs with cancer treatment, which verified our hypothesis. Then, conventional epistasis detection software was used to identify epistatic disease genes from the genome wide association studies (GWAS) dataset. Furthermore, combinatorial drugs were predicted by targeting these epistatic disease genes, and five combinations were proven to have synergistic anti-cancer effects on MCF-7 cells through cell cytotoxicity assay. Combined with the three-dimensional (3D) genome-based method, the epistatic disease genes were filtered and were more closely related to disease. By targeting the filtered gene pairs, the efficiency of combinatorial drug discovery has been further improved. Full article

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15 pages, 22251 KiB

Open AccessArticle

The Melatonin Signaling Pathway in a Long-Term Memory In Vitro Study

by Jin-Young Sung, Ji-Hyun Bae, Jong-Ha Lee, Yoon-Nyun Kim and Dae-Kwang Kim

Molecules 2018, 23(4), 737; https://doi.org/10.3390/molecules23040737 - 23 Mar 2018

Cited by 18 | Viewed by 7612

Abstract

The activation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) via phosphorylation in the hippocampus is an important signaling mechanism for enhancing memory processing. Although melatonin is known to increase CREB expression in various animal models, the signaling mechanism between melatonin and [...] Read more.

The activation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) via phosphorylation in the hippocampus is an important signaling mechanism for enhancing memory processing. Although melatonin is known to increase CREB expression in various animal models, the signaling mechanism between melatonin and CREB has been unknown in vitro. Thus, we confirmed the signaling pathway between the melatonin receptor 1 (MT1) and CREB using melatonin in HT-22 cells. Melatonin increased MT1 and gradually induced signals associated with long-term memory processing through phosphorylation of Raf, ERK, p90RSK, CREB, and BDNF expression. We also confirmed that the calcium, JNK, and AKT pathways were not involved in this signaling pathway by melatonin in HT-22 cells. Furthermore, we investigated whether melatonin regulated the expressions of CREB-BDNF associated with long-term memory processing in aged HT-22 cells. In conclusion, melatonin mediated the MT1-ERK-p90RSK-CREB-BDNF signaling pathway in the in vitro long-term memory processing model and increased the levels of p-CREB and BDNF expression in melatonin-treated cells compared to untreated HT-22 cells in the cellular aged state. Therefore, this paper suggests that melatonin induces CREB signaling pathways associated with long-term memory processing in vitro. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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15 pages, 39497 KiB

Open AccessFeature PaperArticle

Encapsulation of Curcumin-Loaded Liposomes for Colonic Drug Delivery in a pH-Responsive Polymer Cluster Using a pH-Driven and Organic Solvent-Free Process

by Vincenzo De Leo, Francesco Milano, Erminia Mancini, Roberto Comparelli, Livia Giotta, Angelo Nacci, Francesco Longobardi, Antonella Garbetta, Angela Agostiano and Lucia Catucci

Molecules 2018, 23(4), 739; https://doi.org/10.3390/molecules23040739 - 23 Mar 2018

Cited by 87 | Viewed by 7916

Abstract

The present study aimed to develop and optimize liposome formulation for the colonic delivery of biologically active compounds. A strategy to facilitate such targeting is to formulate liposomes with a polymer coating sensitive to the pH shifts in the gastrointestinal tract. To this [...] Read more.

The present study aimed to develop and optimize liposome formulation for the colonic delivery of biologically active compounds. A strategy to facilitate such targeting is to formulate liposomes with a polymer coating sensitive to the pH shifts in the gastrointestinal tract. To this end, liposomes encapsulating curcumin—chosen as the biologically active compound model—and coated with the pH-responsive polymer Eudragit S100 were prepared and characterized. Curcumin was encapsulated into small unilamellar vesicles (SUVs) by the micelle-to-vesicle transition method (MVT) in a simple and organic solvent-free way. Curcumin-loaded liposomes were coated with Eudragit S100 by a fast and easily scalable pH-driven method. The prepared liposomes were evaluated for size, surface morphology, entrapment efficiency, stability, in vitro drug release, and curcumin antioxidant activity. In particular, curcumin-loaded liposomes displayed size lower than 100 nm, encapsulation efficiency of 98%, high stability at both 4 °C and 25 °C, high in vitro antioxidant activity, and a cumulative release that was completed within 200 min. A good Eudragit S100 coating which did not alter the properties of the curcumin-loaded liposomes was obtained. The present work therefore provides a fast and solvent-free method to prepare pH-responsive polymer-coated liposomes for the colonic delivery of biologically active compounds. Full article

(This article belongs to the Special Issue Chemical Transformation of Renewable Material for Green Chemistry)

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18 pages, 1891 KiB

Open AccessArticle

Design, Synthesis, and SAR of Novel 2-Glycinamide Cyclohexyl Sulfonamide Derivatives against Botrytis cinerea

by Nan Cai, Caixiu Liu, Zhihui Feng, Xinghai Li, Zhiqiu Qi, Mingshan Ji, Peiwen Qin, Wasim Ahmed and Zining Cui

Molecules 2018, 23(4), 740; https://doi.org/10.3390/molecules23040740 - 23 Mar 2018

Cited by 12 | Viewed by 4603

Abstract

N-(2-trifluoromethyl-4-chlorophenyl)-2-oxocyclohexyl sulfonamide (chesulfamide) is in the limelight as a novel fungicide, and has fungicidal activity against Botrytis cinerea. For exploring more novel structures, 33 new compounds were synthesized by N-alkylation and acid–amine coupling reactions with chesulfamide as the core moiety, [...] Read more.

N-(2-trifluoromethyl-4-chlorophenyl)-2-oxocyclohexyl sulfonamide (chesulfamide) is in the limelight as a novel fungicide, and has fungicidal activity against Botrytis cinerea. For exploring more novel structures, 33 new compounds were synthesized by N-alkylation and acid–amine coupling reactions with chesulfamide as the core moiety, and their structures were characterized and established by ¹H-NMR, ¹³C-NMR, MS, and elemental analysis. The structure of (1R,2S)-2-(2-(N-(4-chloro-2-trifluoromethylphenyl)sulfamoyl)-cyclohexylamino)-N-(2-trifluoromethylphenyl) acetamide (II-19) was defined by X-ray single crystal diffraction. The in vivo and in vitro fungicidal activities against B. cinerea were evaluated. The bioassay results of mycelial growth demonstrated that most compounds exhibited excellent inhibitory activity against B. cinerea at 50 μg mL⁻¹, and 7 compounds showed lower EC₅₀ values than boscalid (EC₅₀ = 4.46 μg mL⁻¹) against B. cinerea (CY-09). In cucumber pot experiment, the inhibitory rates of four compounds (II-4, II-5, II-12, and II-13) against B. cinerea were 90.48, 93.45, 92.86, and 91.07, which were better than cyprodinil (88.69%), the best performing of all controls. In tomato pot experiment, the control efficacy of two analogs (II-8 and II-15) were 87.98 and 87.97% at 200 μg mL⁻¹, which were significantly higher than boscalid (78.10%). Most compounds have an excellent fungicidal effect on B. cinerea, with potential as a lead compound for developing new pesticides. Full article

(This article belongs to the Section Medicinal Chemistry)

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20 pages, 4100 KiB

Open AccessArticle

Effects of Lysozyme on the Activity of Ionic of Fluoroquinolone Species

by Hugo Alejandro Perez, Ana Yanina Bustos, María Pía Taranto, María De los Angeles Frías and Ana Estela Ledesma

Molecules 2018, 23(4), 741; https://doi.org/10.3390/molecules23040741 - 23 Mar 2018

Cited by 12 | Viewed by 3721

Abstract

Fluoroquinolones (FQs) constitute an important class of biologically active broad-spectrum antibacterial drugs that are which are in contact with many biological fluids under different acidity conditions. We studied the reactivity of ciprofloxacin (Cpx) and levofloxacin (Lev) and their interaction with lysozyme (Lyz) at [...] Read more.

Fluoroquinolones (FQs) constitute an important class of biologically active broad-spectrum antibacterial drugs that are which are in contact with many biological fluids under different acidity conditions. We studied the reactivity of ciprofloxacin (Cpx) and levofloxacin (Lev) and their interaction with lysozyme (Lyz) at different pH values, using UV-visible absorption, fluorescence, infrared spectroscopies supported by DFT calculation and docking. In addition, by antimicrobial assays, the biological consequences of the interaction were evaluated. DFT calculation predicted that the FQ cationic species present at acid pH have lower stabilization energies, with an electric charge rearrangement because of their interactions with solvent molecules. NBO and frontier orbital calculations evidenced the role of two charged centers, NH₂⁺ and COO⁻, for interactions by electronic delocalization effects. Both FQs bind to Lyz via a static quenching with a higher interaction in neutral medium. The interaction induces a structural rearrangement in β-sheet content while in basic pH a protective effect against the denaturation of Lyz was inferred. The analysis of thermodynamic parameters and docking showed that hydrophobic, electrostatic forces and hydrogen bond are the responsible of Cpx-Lyz and Lev-Lyz associations. Antimicrobial assays evidenced an antagonist effect of Lyz in acid medium while in neutral medium the FQs’ activities were not modified by Lyz. Full article

(This article belongs to the Section Physical Chemistry)

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12 pages, 5072 KiB

Open AccessArticle

Identification, Characterization, and Expression Analysis of a FMRFamide-Like Peptide Gene in the Common Chinese Cuttlefish (Sepiella japonica)

by Ying Li, Zihao Cao, Haifeng Li, Huihui Liu, Zhenming Lü and Changfeng Chi

Molecules 2018, 23(4), 742; https://doi.org/10.3390/molecules23040742 - 23 Mar 2018

Cited by 7 | Viewed by 4209

Abstract

The peptide FMRFamide is one of the well-known peptides involved in multiple physiological processes in the phylum Mollusca. In this study, a FMRFamide gene (GenBank accession No. KJ933411) was identified in a cuttlefish species called Sepiella japonica and was designated as SjFMRFamide. The [...] Read more.

The peptide FMRFamide is one of the well-known peptides involved in multiple physiological processes in the phylum Mollusca. In this study, a FMRFamide gene (GenBank accession No. KJ933411) was identified in a cuttlefish species called Sepiella japonica and was designated as SjFMRFamide. The total length of the SjFMRFamide sequence was found to be 1880 bp while the open reading frame contained 996 bp encoding a protein of 331 amino acid residues with a predicted isoelectric point (pI) and molecular weight (MW) of 9.18 and 38.8 kDa along with a 333 bp 5′-untranslated region (UTR) and 551 bp 3′-UTR. The deduced SjFMRFamide precursor protein contains one signal peptide and expresses four kinds FMRFamide-related peptides including a single copy of FLRFamide, ALSGDAFLRFamide, and FIRFamide and multiple copies of FMRFamide. Results of phylogenetic relation analysis strongly indicated that the sequence of this gene shares high identity with the genes of known FMRFamides. Spatial expression analysis indicated the highest mRNA expression of SjFMRFamide in the brain of male and female cuttlefishes among the eight tissues analyzed. An in situ hybridization assay of the brain indicated that SjFMRFamide was transcribed in several functional lobes, which suggests that it might be related to many physiological regulatory mechanisms. This is the first study describing FMRFamide in S. japonica and the results may contribute to future studies of neuropeptide evolution or may prove useful for the development of aquaculture methods for this cuttlefish species. Full article

(This article belongs to the Section Molecular Diversity)

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14 pages, 1731 KiB

Open AccessArticle

Potential of Cellulose Functionalized with Carboxylic Acid as Biosorbent for the Removal of Cationic Dyes in Aqueous Solution

by Lucinaldo Dos Santos Silva, Jhonatam De Oliveira Carvalho, Roosevelt Delano De Sousa Bezerra, Mateus Soares Da Silva, Francisco José Lustosa Ferreira, Josy Anteveli Osajima and Edson Cavalcanti Da Silva Filho

Molecules 2018, 23(4), 743; https://doi.org/10.3390/molecules23040743 - 23 Mar 2018

Cited by 49 | Viewed by 5521

Abstract

In the last decade, adsorption has been used to minimize the pollution caused by dyes, which represents a serious environmental problem. In this context, this work reports the preparation of phthalic anhydride-modified cellulose (PhCel), through the reaction of cellulose (Cel) with phthalic anhydride [...] Read more.

In the last decade, adsorption has been used to minimize the pollution caused by dyes, which represents a serious environmental problem. In this context, this work reports the preparation of phthalic anhydride-modified cellulose (PhCel), through the reaction of cellulose (Cel) with phthalic anhydride (Ph). The efficiency of the reaction was observed by elemental analysis, Fourier Transform Infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and thermogravimetry/derivative thermogravimetry (TG/DTG). The adsorbent matrix (Cel and PhCel) was used in the removal of crystal violet (CV) and methylene blue (MB) dyes in aqueous medium. In the kinetic study, the experimental data obtained had the best fit to the pseudo-first-order model. In general, the isotherms obtained at different temperatures had a best fit to the model proposed by Langmuir, and the CV and MB adsorption process in adsorbent matrixes can be favored strictly by hydrogen bonds and/or electrostatic interactions for Cel and electrostatic interactions for PhCel. Full article

(This article belongs to the Special Issue Cellulose Chemical Modifications—Towards Sustainable Materials)

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13 pages, 11387 KiB

Open AccessFeature PaperArticle

Investigating the Interaction of Ascorbic Acid with Anthocyanins and Pyranoanthocyanins

by Jacob E. Farr and M. Monica Giusti

Molecules 2018, 23(4), 744; https://doi.org/10.3390/molecules23040744 - 23 Mar 2018

Cited by 47 | Viewed by 6057

Abstract

Juices colored by anthocyanins experience color loss related to fortification with ascorbic acid (AA), thought to be the result of condensation at Carbon-4 of anthocyanins. To further understand this mechanism, pyranoanthocyanins, having a fourth-ring covalently occupying Carbon-4, were synthesized to compare its reactivity [...] Read more.

Juices colored by anthocyanins experience color loss related to fortification with ascorbic acid (AA), thought to be the result of condensation at Carbon-4 of anthocyanins. To further understand this mechanism, pyranoanthocyanins, having a fourth-ring covalently occupying Carbon-4, were synthesized to compare its reactivity with AA against that of anthocyanins. Pyranoanthocyanins were synthesized by combining chokeberry anthocyanins with pyruvic acid. AA (250–1000 mg/L) was added to either chokeberry extract, cyanidin-3-galactoside, or 5-Carboxypyranocyanidin-3-galactoside. Samples were stored in the dark for 5 days at 25 °C and spectra (380–700 nm), color (CIE-L*c*h*), and composition changes (HPLC-MS/MS) were monitored. Extensive bleaching occurred for cyanidin-3-galactoside and chokeberry colored solutions, with a decrease in half-lives from 22.8 to 0.3 days for Cyanidin-3-galactoside when 1000 mg/L AA was added. 5-Carboxypyranocyanidin-3-galactoside solution better maintained color with limited loss in absorbance, due to the formation of colored degradation products (λ_vis-max = 477 to 487 nm), and half-life decrease from 40.8 to 2.7 days, an 8–13-fold improvement compared to anthocyanins. This suggested alternative sites of reactivity with AA. Carbon-4 may be the preferred site for AA-pigment interactions, but it was not the only location. With Carbon-4 blocked, 5-Carboxypyranocyanidin-3-galactoside reacted with AA to form new pigments and reduce bleaching. Full article

(This article belongs to the Special Issue Advances in Anthocyanin Research 2018)

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14 pages, 9588 KiB

Open AccessArticle

PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP

by Miji Yeom, HansongI Lee, Seoungwoo Shin, Deokhoon Park and Eunsun Jung

Molecules 2018, 23(4), 745; https://doi.org/10.3390/molecules23040745 - 23 Mar 2018

Cited by 14 | Viewed by 6533

Abstract

Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1) and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by [...] Read more.

Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1) and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian clock in mouse skin. However, the molecular link between circadian clock and MMP-1 has little been investigated. We found PERIOD protein, a morning clock component, represses the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy. Treatment with siPer3 alleviated the suppression of MMP-1 expression induced by forskolin. Results revealed PER3 suppresses the expression of MMP-1 via cAMP signaling pathway. Additionally, we screened for an activator of PER that could repress the expression of MMP-1 using HaCaT cell line containing PER promoter-luciferase reporter gene. Results showed Lespedeza capitate extract (LCE) increased PER promoter activity. LCE inhibited the expression of MMP-1 and its effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can repress the expression of MMP-1 through PER. Since circadian clock component PER can regulate MMP-1 expression, it might be a new molecular mechanism to develop therapeutics to alleviate skin aging and skin cancer. Full article

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14 pages, 8353 KiB

Open AccessArticle

Synthesis, Characterization, and Antifungal Activity of Novel Benzo[4,5]imidazo[1,2-d][1,2,4]triazine Derivatives

by Ling-Xia Li, Jian Jiao, Xiao-Bin Wang, Min Chen, Xin-Can Fu, Wei-Jie Si and Chun-Long Yang

Molecules 2018, 23(4), 746; https://doi.org/10.3390/molecules23040746 - 23 Mar 2018

Cited by 19 | Viewed by 4781

Abstract

A series of novel fused heterocyclic compounds bearing benzo[4,5]imidazo[1,2-d][1,2,4]triazine 4a–4w were designed and conveniently synthesized via the intermediates 2-(halogenated alkyl)-1H-benzo[d]imidazoles 2a, 2b, and 2-((1-(substituted phenyl)hydrazinyl)alkyl)-1H-benzo[d]imidazoles 3a–3g. [...] Read more.

A series of novel fused heterocyclic compounds bearing benzo[4,5]imidazo[1,2-d][1,2,4]triazine 4a–4w were designed and conveniently synthesized via the intermediates 2-(halogenated alkyl)-1H-benzo[d]imidazoles 2a, 2b, and 2-((1-(substituted phenyl)hydrazinyl)alkyl)-1H-benzo[d]imidazoles 3a–3g. The structures of all target compounds were characterized by FT-IR, ¹H NMR, ¹³C NMR, and EI-MS, of which, the structure of compound 4n was further determined by the single crystal X-ray diffraction. The crystal structure of 4n was crystallized in the triclinic crystal system, space group P

\bar{1}

with a = 9.033 (6) Å, b = 10.136 (7) Å, c = 10.396 (7) Å, α = 118.323 (7)°, β = 91.750 (8)°, γ = 104.198 (7)°, Z = 2, V = 800.2 (9) Å³; total R indices: R₁ = 0.0475, wR₂ = 0.1284. The antifungal activity of title compounds 4a–4w in vitro against the phytopathogenic fungi Botrytis cinerea (B. cinerea), Rhizoctonia solani (R. solani) and Colletotrichum capsici (C. capsici) were evaluated, the bioassay results demonstrated that most of the title compounds exhibited obvious fungicidal activities at 50 μg/mL. This work indicated that benzo[4,5]imidazo[1,2-d][1,2,4]triazine derivatives could be considered as a new leading structure in searching for novel agricultural fungicides. Full article

(This article belongs to the Section Molecular Diversity)

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11 pages, 3399 KiB

Open AccessArticle

Design, Synthesis, and Biological Evaluation of Axitinib Derivatives

by Na Wei, Jianqing Liang, Shengming Peng, Qiang Sun, Qiuyun Dai and Mingxin Dong

Molecules 2018, 23(4), 747; https://doi.org/10.3390/molecules23040747 - 23 Mar 2018

Cited by 11 | Viewed by 5673

Abstract

Axitinib is an approved kinase inhibitor for the therapy of advanced metastatic renal cell carcinoma (RCC). It prevents angiogenesis, cellular adhesion, and induces apoptosis of cancer cells. Here, nine axitinib derivatives were designed by replacing the C=C moiety with the N=N group, and [...] Read more.

Axitinib is an approved kinase inhibitor for the therapy of advanced metastatic renal cell carcinoma (RCC). It prevents angiogenesis, cellular adhesion, and induces apoptosis of cancer cells. Here, nine axitinib derivatives were designed by replacing the C=C moiety with the N=N group, and the substituted benzene or pyrrole analogs were considered to replace the pyridine ring. Biological activity results showed that most of nascent derivatives exhibited favorable VEGFR-2 kinase inhibitory activities, and TM6, 7, 9, and 11 behaved more potent anti-proliferative activities than axitinib. This novel series of compounds shows a potential for the treatment of solid tumors and other diseases where angiogenesis plays an important role. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 13355 KiB

Open AccessArticle

Expression of Pinellia pedatisecta Lectin Gene in Transgenic Wheat Enhances Resistance to Wheat Aphids

by Xiaoliang Duan, Qiling Hou, Guoyu Liu, Xiaomeng Pang, Zhenli Niu, Xiao Wang, Yufeng Zhang, Baoyun Li and Rongqi Liang

Molecules 2018, 23(4), 748; https://doi.org/10.3390/molecules23040748 - 24 Mar 2018

Cited by 25 | Viewed by 4490

Abstract

Wheat aphids are major pests during the seed filling stage of wheat. Plant lectins are toxic to sap-sucking pests such as wheat aphids. In this study, Pinellia pedatisecta agglutinin (ppa), a gene encoding mannose binding lectin, was cloned, and it shared [...] Read more.

Wheat aphids are major pests during the seed filling stage of wheat. Plant lectins are toxic to sap-sucking pests such as wheat aphids. In this study, Pinellia pedatisecta agglutinin (ppa), a gene encoding mannose binding lectin, was cloned, and it shared 92.69% nucleotide similarity and 94% amino acid similarity with Pinellia ternata agglutinin (pta). The ppa gene, driven by the constitutive and phloem-specific ribulose bisphosphate carboxylase small subunit gene (rbcs) promoter in pBAC-rbcs-ppa expression vector, was transferred into the wheat cultivar Baofeng104 (BF104) by particle bombardment transformation. Fifty-four T₀ transgenic plants were generated. The inheritance and expression of the ppa gene were confirmed by PCR and RT-PCR analysis respectively, and seven homozygous transgenic lines were obtained. An aphid bioassay on detached leaf segments revealed that seven ppa transgenic wheat lines had lower aphid growth rates and higher inhibition rates than BF104. Furthermore, two-year aphid bioassays in isolated fields showed that aphid numbers per tiller of transgenic lines were significantly decreased, compared with wild type BF104. Therefore, ppa could be a strong biotechnological candidate to produce aphid-resistant wheat. Full article

(This article belongs to the Special Issue Lectins: From Basic Science to Application for Glycobiology, Cell Biology, and Medicine)

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13 pages, 30897 KiB

Open AccessArticle

Molecular Mechanisms of Melatonin Protection from Gastric Mucosal Apoptotic Injury in Experimental Burns

by Minka Hristova, Maria Tzaneva, Ganka Bekyarova, Dariya Chivchibashi, Nadezhda Stefanova and Yoana Kiselova-Kaneva

Molecules 2018, 23(4), 749; https://doi.org/10.3390/molecules23040749 - 24 Mar 2018

Cited by 6 | Viewed by 4682

Abstract

Melatonin, a basic secretory pineal gland product, is a nontoxic, multifunctional molecule. It has antioxidant and anti-apoptotic activities and protects tissues from injury. The objective of the present study was to determine the molecular mechanism of melatonin anti-apoptotic effect on gastric injury in [...] Read more.

Melatonin, a basic secretory pineal gland product, is a nontoxic, multifunctional molecule. It has antioxidant and anti-apoptotic activities and protects tissues from injury. The objective of the present study was to determine the molecular mechanism of melatonin anti-apoptotic effect on gastric injury in a rat burn model. We hypothesized that melatonin gastric protection may be related to the activation of transcription erythroid 2-related factor 2 (Nrf2). Using a 30% total body surface area (TBSA) rat burn model, melatonin (10 mg/kg, i.p.) was injected immediately and 12 h after thermal skin injury. Via light immunohistochemistry, we determined the tissue level of 4-hydroxy-2-nonenal (4-HNE) as a marker of lipid peroxidation, Bcl-2 and Bax as apoptosis-related proteins, and Nrf2. Results are presented as medians (interquartile range (IQR)). Thermal trauma in burned animals, compared with the controls, increased the expression of pro-apoptotic Bax protein (1.37 (0.94–1.47)), decreased anti-apoptotic Bcl-2 protein (1.16 (1.06–1.23), p < 0.001) in epithelial cells, and elevated Bax/Bcl-2 ratios (p < 0.05). Tissue 4-HNE and Nrf2 levels were increased following severe burns (1.55 (0.98–1.61) and 1.16 (1.01–1.25), p < 0.05, respectively). Melatonin significantly decreased 4-HNE (0.87 (0.74–0.96), p < 0.01) and upregulated Nrf2 (1.55 (1.52–1.65), p < 0.001) levels. It also augmented Bax (1.68 (1.5–1.8), p < 0.001) and Bcl-2 expressions (1.96 (1.89–2.01), p < 0.0001), but reduced Bax/Bcl-2 ratios (p < 0.05). Our results suggest that experimental thermal trauma induces oxidative gastric mucosal injury. Melatonin manifests a gastroprotective effect through Nrf2 activation, lipid peroxidation attenuation, and Bax/Bcl-2 ratio modification as well. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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18 pages, 15232 KiB

Open AccessFeature PaperArticle

Economy of Catalyst Synthesis—Convenient Access to Libraries of Di- and Tetranaphtho Azepinium Compounds

by Sorachat Tharamak, Christian Knittl-Frank, Auraya Manaprasertsak, Anchulee Pengsook, Lydia Suchy, Philipp Schuller, Barbara Happl, Alexander Roller and Michael Widhalm

Molecules 2018, 23(4), 750; https://doi.org/10.3390/molecules23040750 - 24 Mar 2018

Cited by 2 | Viewed by 5250

Abstract

Efficient optimization procedures in chiral catalysis are usually linked to a straightforward strategy to access groups of structurally similar catalysts required for fine-tuning. The ease of building up such ligand libraries can be increased when the structure-modifying step (introduction of a substituent) is [...] Read more.

Efficient optimization procedures in chiral catalysis are usually linked to a straightforward strategy to access groups of structurally similar catalysts required for fine-tuning. The ease of building up such ligand libraries can be increased when the structure-modifying step (introduction of a substituent) is done at a later stage of the synthesis. This is demonstrated for the extended family of di- and tetranaphtho azepinium compounds, widely used as chiral phase transfer catalysts (PTC). Using 2,6-diiodo-4,5-dihydro-3H-dinaphtho[2,1-c:1′,2′-e]azepine and 4,8-diiodo-6,7-dihydro-5H-dibenzo[c,e]azepine, respectively, as key intermediates, 18 spiro-azepinium compounds were synthesized in a total yield of 25–42% over 6–7 steps from 1,1′-binaphthyl-2,2′-dicarboxylic acid or diphenic acid, respectively. The replacement of iodo groups with aryl substituents was performed as the last or the penultimate step of the synthesis. Full article

(This article belongs to the Special Issue Enantioselective Catalysis)

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16 pages, 19517 KiB

Open AccessArticle

Multifunctional Fischer Aminocarbene Complexes as Hole or Electron Transporting Layers in Organic Solar Cells

by Pablo Vidal-García, María Elena Sánchez-Vergara, Ricardo Corona-Sánchez, Omar Jiménez-Sandoval, Efraín Gutiérrez-Rivas Mercado, Rubén A. Toscano and Cecilio Álvarez-Toledano

Molecules 2018, 23(4), 751; https://doi.org/10.3390/molecules23040751 - 24 Mar 2018

Cited by 2 | Viewed by 3819

Abstract

A new series of Fischer carbenes have been synthetized and examined as hole-transporting or electron-transporting layers (HTLs or ETLs) in the fabrication of organic solar cells (OSCs). The synthesis of three Fischer aminocarbene complexes with the general formula [Cr(CO)₅{C(NHCH₂)Ar}] [...] Read more.

A new series of Fischer carbenes have been synthetized and examined as hole-transporting or electron-transporting layers (HTLs or ETLs) in the fabrication of organic solar cells (OSCs). The synthesis of three Fischer aminocarbene complexes with the general formula [Cr(CO)₅{C(NHCH₂)Ar}] (Ar = 2-pyridyl (3a), 3-pyridyl (3b) and 4-pyridyl (3c)) is reported. The molecular structure of complex 3b has been confirmed by X-ray analysis. In order to study the possible applications of the three Fischer aminocarbenes in OSCs, thin films of these complexes were prepared using a vacuum deposition process. These organometallic films were chemically and morphologically characterized by IR spectroscopy, SEM, AFM and XRD. According to the IR and Tauc analysis, the vacuum deposition process generates thin films free of impurities with an activation energy of 4.0, 2.7 and 2.1 eV for 3a, 3b y 3c, respectively. The UV-vis spectra of the amorphous aminocarbene films show that they are practically transparent to the visible radiation of the electromagnetic spectrum. This is due to the fact that their absorption is located mainly in the ultraviolet range. Two OSCs with bulk-heterojunction configuration were manufactured in order to prove the use of the aminocarbenes as ETL o HTL. The aminocarbene [Cr(CO)₅{C(NHCH₂) 4-pyridyl}] (3c) proved to be suitable as ETL with a fill factor (FF) of 0.23 and a short circuit current density (J_SC) of 1.037 mA/cm². Full article

(This article belongs to the Special Issue Functional Molecular Materials)

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9 pages, 10991 KiB

Open AccessArticle

Rhamnellosides A and B, ω-Phenylpentaene Fatty Acid Amide Diglycosides from the Fruits of Rhamnella franguloides

by Kyo Bin Kang, Ming Gao, Geum Jin Kim, Hyukjae Choi and Sang Hyun Sung

Molecules 2018, 23(4), 752; https://doi.org/10.3390/molecules23040752 - 24 Mar 2018

Cited by 3 | Viewed by 3340

Abstract

Two new ω-phenylpentaene fatty acid amide diglycosides, rhamnellosides A (1) and B (2), were isolated from the fruits of Rhamnella franguloides (Rhamnaceae). These compounds were prioritized using LC-MS/MS molecular networking dereplication based on our previous discovery of 2-acetoxy-ω-phenylpentaene fatty [...] Read more.

Two new ω-phenylpentaene fatty acid amide diglycosides, rhamnellosides A (1) and B (2), were isolated from the fruits of Rhamnella franguloides (Rhamnaceae). These compounds were prioritized using LC-MS/MS molecular networking dereplication based on our previous discovery of 2-acetoxy-ω-phenylpentaene fatty acid triglycosides berchemiosides A−C from a phylogenetically related species, Berchemia berchemiifolia. The structures of the isolated compounds were elucidated by spectroscopic analyses in combination with chemical derivatization. The pentaene groups of 1 and 2 were found to have (6E, 8E, 10Z, 12Z, 14E)-geometry, which is the same as that found in berchemioside A. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 4673 KiB

Open AccessArticle

Physicochemical Characterization and Antioxidant Activity of Humic Acids Isolated from Peat of Various Origins

by Maria V. Zykova, Igor A. Schepetkin, Mikhail V. Belousov, Sergey V. Krivoshchekov, Lyudmila A. Logvinova, Kristina A. Bratishko, Mekhman S. Yusubov, Sergey V. Romanenko and Mark T. Quinn

Molecules 2018, 23(4), 753; https://doi.org/10.3390/molecules23040753 - 24 Mar 2018

Cited by 65 | Viewed by 6515

Abstract

Although humic acids (HAs) from peat exhibit various therapeutic properties, there is little information available concerning their physicochemical and antioxidant properties. To address this issue, nine different types of peat, including oligotrophic, mesotrophic, and minerotrophic peat samples, were used for isolation of HA [...] Read more.

Although humic acids (HAs) from peat exhibit various therapeutic properties, there is little information available concerning their physicochemical and antioxidant properties. To address this issue, nine different types of peat, including oligotrophic, mesotrophic, and minerotrophic peat samples, were used for isolation of HA fractions by basic (HAb) and pyrophosphate (HAp) extractions. Physical parameters of the HAs were analyzed by UV-Vis, fluorescent, infrared (IR), and electron paramagnetic resonance (EPR) spectroscopy. Average M_r of the fractions ranged from 17.2 to 39.7 kDa, while their humification index (HIX) varied from 0.49 to 1.21. HAp fractions had a higher content of aromatic structures compared to HAb fractions. Moreover, HAp fractions had a significantly higher content of phenolic OH groups (3.6 ± 0.5 mmol/g) versus HAb (3.1 ± 0.5 mmol/g). All HA fractions exhibited antioxidant activity in radical scavenging and electrochemical assays, and their EPR signal had a single line with g = 2.0035, which is consistent with semiquinone type radicals. Furthermore, the HIX was found to be important in determining the number of semiquinone-type free radicals in the HA structures. Overall, these data provide a molecular basis to explain at least part of the beneficial therapeutic properties of peat-derived HAs. Full article

(This article belongs to the Special Issue The Antioxidant Capacities of Natural Products)

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11 pages, 8402 KiB

Open AccessCommunication

Effect of Double Bond Position on 2-Phenyl-benzofuran Antioxidants: A Comparative Study of Moracin C and Iso-Moracin C

by Xican Li, Hong Xie, Ruicai Zhan and Dongfeng Chen

Molecules 2018, 23(4), 754; https://doi.org/10.3390/molecules23040754 - 24 Mar 2018

Cited by 23 | Viewed by 4181

Abstract

Two 2-phenyl-benzofurans, moracin C {2-[3′,5′-dihydroxy-4′-(3-methlbut-2-enyl)phenyl]-6-hydroxybenzofuran} and its isomer iso-moracin C{2-[3′,5′-dihydroxy-4′-(3-methlbut-1-enyl)phenyl]-6-hydroxybenzofuran}, were comparatively studied using redox-related antioxidant assays and non-redox antioxidant assays. Moracin C always resulted in higher IC₅₀ values than iso-moracin C in the redox-related antioxidant assays, including •O₂ [...] Read more.

Two 2-phenyl-benzofurans, moracin C {2-[3′,5′-dihydroxy-4′-(3-methlbut-2-enyl)phenyl]-6-hydroxybenzofuran} and its isomer iso-moracin C{2-[3′,5′-dihydroxy-4′-(3-methlbut-1-enyl)phenyl]-6-hydroxybenzofuran}, were comparatively studied using redox-related antioxidant assays and non-redox antioxidant assays. Moracin C always resulted in higher IC₅₀ values than iso-moracin C in the redox-related antioxidant assays, including •O₂⁻-inhibition, Cu²⁺-reducing power, DPPH•-inhibition, and ABTS⁺•-inhibition assays. In the non-redox antioxidant assay, moracin C and iso-moracin C underwent similar radical-adduct-formation (RAF), evidenced by the peaks at m/z 704 and m/z 618 in HPLC-MS spectra. In conclusion, both moracin C and iso-moracin C can act as 2-phenyl-benzofuran antioxidants; their antioxidant mechanisms may include redox-related ET and H⁺-transfer, and non-redox RAF. A double bond at the conjugation position can enhance the redox-related antioxidant potential, but hardly affects the RAF potential. Full article

(This article belongs to the Special Issue The Antioxidant Capacities of Natural Products)

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13 pages, 14975 KiB

Open AccessArticle

Co₂ and Co₃ Mixed Cluster Secondary Building Unit Approach toward a Three-Dimensional Metal-Organic Framework with Permanent Porosity

by Meng-Yao Chao, Wen-Hua Zhang and Jian-Ping Lang

Molecules 2018, 23(4), 755; https://doi.org/10.3390/molecules23040755 - 25 Mar 2018

Cited by 24 | Viewed by 6192

Abstract

Large and permanent porosity is the primary concern when designing metal-organic frameworks (MOFs) for specific applications, such as catalysis and drug delivery. In this article, we report a MOF Co₁₁(BTB)₆(NO₃)₄(DEF)₂(H₂O)₁₄ [...] Read more.

Large and permanent porosity is the primary concern when designing metal-organic frameworks (MOFs) for specific applications, such as catalysis and drug delivery. In this article, we report a MOF Co₁₁(BTB)₆(NO₃)₄(DEF)₂(H₂O)₁₄ (1, H₃BTB = 1,3,5-tris(4-carboxyphenyl)benzene; DEF = N,N-diethylformamide) via a mixed cluster secondary building unit (SBU) approach. MOF 1 is sustained by a rare combination of a linear trinuclear Co₃ and two types of dinuclear Co₂ SBUs in a 1:2:2 ratio. These SBUs are bridged by BTB ligands to yield a three-dimensional (3D) non-interpenetrated MOF as a result of the less effective packing due to the geometrically contrasting SBUs. The guest-free framework of 1 has an estimated density of 0.469 g cm⁻³ and exhibits a potential solvent accessible void of 69.6% of the total cell volume. The activated sample of 1 exhibits an estimated Brunauer-Emmett-Teller (BET) surface area of 155 m² g⁻¹ and is capable of CO₂ uptake of 58.61 cm³ g⁻¹ (2.63 mmol g⁻¹, 11.6 wt % at standard temperature and pressure) in a reversible manner at 195 K, showcasing its permanent porosity. Full article

(This article belongs to the Special Issue Functional Molecular Materials)

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12 pages, 1789 KiB

Open AccessArticle

Synthesis and Evaluation of the Anticonvulsant Activities of 4-(2-(Alkylthio)benzo[d]oxazol-5-yl)-2,4-dihydro-3H-1,2,4-triazol-3-ones

by Ming-Xia Song, Zhen-Yuan Wang, Shi-Hui He, Sheng-Wang Yu, Shi-Long Chen, Dong-Fu Guo, Wen-Hao Zhao and Xian-Qing Deng

Molecules 2018, 23(4), 756; https://doi.org/10.3390/molecules23040756 - 25 Mar 2018

Cited by 11 | Viewed by 3517

Abstract

In this study, a novel series of 4-(2-(alkylthio)benzo[d]oxazol-5-yl)-2,4-dihydro-3H-1,2,4-triazol-3-ones (4a–m) was designed and synthesized. The anticonvulsant activities of these compounds were evaluated by using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models in [...] Read more.

In this study, a novel series of 4-(2-(alkylthio)benzo[d]oxazol-5-yl)-2,4-dihydro-3H-1,2,4-triazol-3-ones (4a–m) was designed and synthesized. The anticonvulsant activities of these compounds were evaluated by using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models in mice. The neurotoxicity of these compounds was evaluated using the rotarod neurotoxicity test. The majority of compounds showed anti-MES activities at 100 or 300 mg/kg. Compound 4g was considered to be the most promising, based on its potency against MES- and PTZ-induced seizures with ED₅₀ values of 23.7 and 18.9 mg/kg, respectively. The TD₅₀ value of 4g was 284.0 mg/kg, which resulted in a higher protective index (PI = TD₅₀/ED₅₀) value than that of carbamazepine and valproate. In an ELISA test, compound 4g significantly increased the γ-aminobutyric acid (GABA) content in mouse brain. In addition, pretreatment with thiosemicarbazide (an inhibitor of the GABA synthesizing enzyme) significantly decreased the activity of 4g in the MES model, which suggests that the mechanism through which compound 4g elicits its anticonvulsive action is at least in part through increasing the GABA level in the brain. Full article

(This article belongs to the Section Medicinal Chemistry)

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9 pages, 20067 KiB

Open AccessArticle

Long-Time Relaxation of Stress-Induced Birefringence of Microcrystalline Alkali Halide Crystals

by Hiroki Ueno, Ryoga Arakane, Yoshihisa Matsumoto, Tomoki Tsumura, Akihito Kitazaki, Toru Takahashi, Shotaro Hirao, Yasushi Ohga and Takunori Harada

Molecules 2018, 23(4), 757; https://doi.org/10.3390/molecules23040757 - 25 Mar 2018

Cited by 3 | Viewed by 4833

Abstract

Alkali halide single crystals are most commonly used as the diluent matrix in the tablet method or disk technique for spectroscopic measurements. However, stress-induced birefringence (SIB) of alkali halides as well as intrinsic birefringence manifest during the disk formation process. Thus, the true [...] Read more.

Alkali halide single crystals are most commonly used as the diluent matrix in the tablet method or disk technique for spectroscopic measurements. However, stress-induced birefringence (SIB) of alkali halides as well as intrinsic birefringence manifest during the disk formation process. Thus, the true chiroptical measurement is disturbed by optical anisotropies (OA) containing SIB and intrinsic birefringence, except in the case of optical homogeneity. SIB is generally larger than intrinsic birefringence and has a value of several thousand millidegrees in the ultraviolet-visible wavelength range, although this varies with disk type. Here, to investigate the SIB origin, alkali halide crystals were examined using polarized light, X-ray diffraction, Fourier-transform infrared, and electron backscattering diffraction spectroscopic measurements. It was found that, after stress release, the SIB exhibited nonlinear long-time relaxation, which roughly converged within several hours, with the only time-invariant intrinsic birefringence remaining being due to OA. This behavior was strongly related to an increase in the quasi-amorphous domain and the generation of an air gap between the crystallite boundaries and their pellets. Further, a straightforward correlation was found between amorphization and an increase in the disk water content caused by deliquescence. Thus, the OA of alkali halide single crystals was found to have two different origins yielding intrinsic birefringence and SIB. Full article

(This article belongs to the Special Issue Recent Advances in Chiroptical Spectroscopy)

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15 pages, 7792 KiB

Open AccessArticle

UHPLC-MS/MS Quantification Combined with Chemometrics for Comparative Analysis of Different Batches of Raw, Wine-Processed, and Salt-Processed Radix Achyranthis Bidentatae

by Liu Yang, Hai Jiang, Meiling Yan, Xudong Xing, Xinyue Guo, Bingyou Yang, Qiuhong Wang and Haixue Kuang

Molecules 2018, 23(4), 758; https://doi.org/10.3390/molecules23040758 - 26 Mar 2018

Cited by 14 | Viewed by 4576

Abstract

An accurate and reliable method using ultra-high performance liquid chromatography combined with triple quadrupole tandem mass spectrometry (UHPLC–MS/MS) was established for simultaneous quantification of five major bioactive analytes in raw, wine-processed, and salt-processed Radix Achyranthis bidentatae (RAB). The results showed that this method [...] Read more.

An accurate and reliable method using ultra-high performance liquid chromatography combined with triple quadrupole tandem mass spectrometry (UHPLC–MS/MS) was established for simultaneous quantification of five major bioactive analytes in raw, wine-processed, and salt-processed Radix Achyranthis bidentatae (RAB). The results showed that this method exhibited desirable sensitivity, precision, stability, and repeatability. The overall intra-day and inter-day variations (RSD) were in the range of 1.57–2.46 and 1.51–3.00%, respectively. The overall recoveries were 98.58–101.48% with a relative standard deviation (RSD) of 0.01–1.86%. In addition, the developed approach was applied to 21 batches of raw, wine-processed, and salt-processed samples of RAB. Hierarchical clustering analysis (HCA), principal component analysis (PCA), heat map, and boxplot analysis were performed to evaluate the quality of raw, wine-processed, and salt-processed RAB collected from different regions. The chemometrics combined with the quantitative analysis based on UHPLC–MS/MS results indicated that the content of five analytes increased significantly in processed RAB compared to raw RAB. Full article

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17 pages, 20782 KiB

Open AccessArticle

Intraconversion of Polar Ginsenosides, Their Transformation into Less-Polar Ginsenosides, and Ginsenoside Acetylation in Ginseng Flowers upon Baking and Steaming

by Xiang Li, Fan Yao, Hang Fan, Ke Li, Liwei Sun and Yujun Liu

Molecules 2018, 23(4), 759; https://doi.org/10.3390/molecules23040759 - 26 Mar 2018

Cited by 21 | Viewed by 5510

Abstract

Heating is a traditional method used in ginseng root processing, however, there aren’t reports on differences resulting from baking and steaming. Moreover, ginseng flowers, with 5.06 times more total saponins than ginseng root, are not fully taken advantage of for their ginsenosides. Transformation [...] Read more.

Heating is a traditional method used in ginseng root processing, however, there aren’t reports on differences resulting from baking and steaming. Moreover, ginseng flowers, with 5.06 times more total saponins than ginseng root, are not fully taken advantage of for their ginsenosides. Transformation mechanisms of ginsenosides in ginseng flowers upon baking and steaming were thus explored. HPLC using authentic standards of 20 ginsenosides and UPLC-QTOF-MS/MS were used to quantify and identify ginsenosides, respectively, in ginseng flowers baked or steamed at different temperatures and durations. Results show that baking and steaming caused a 3.2-fold increase in ginsenoside species existed in unheated ginseng flowers (20/64 ginsenosides) and transformation of a certain amount of polar ginsenosides into numerous less polar ginsenosides. Among the 20 ginsenosides with standards, polar ginsenosides were abundant in ginseng flowers baked or steamed at lower temperatures, whereas less polar ginsenosides occurred and were enriched at higher temperatures. Furthermore, the two types of heating treatments could generate mostly similar ginsenosides, but steaming was much efficient than baking in transforming polar- into less polar ginsenosides, with steaming at 120 °C being comparably equivalent to baking at 150 °C. Moreover, both the two heating methods triggered ginsenoside acetylation and thus caused formation of 16 acetylginsenosides. Finally, a new transformation mechanism concerning acetyl-ginsenosides formation was proposed. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 2768 KiB

Open AccessFeature PaperArticle

Zn(OAc)₂-Catalyzing Ring-Opening Polymerization of N-Carboxyanhydrides for the Synthesis of Well-Defined Polypeptides

by Yanzhao Nie, Xinmei Zhi, Haifeng Du and Jing Yang

Molecules 2018, 23(4), 760; https://doi.org/10.3390/molecules23040760 - 26 Mar 2018

Cited by 17 | Viewed by 7397

Abstract

Despite notable progress, the fabrication of well-defined polypeptides via controlled ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCAs) using convenient catalysts under mild conditions in a relatively short polymerization time is still challenging. Herein, an easily obtained catalyst system composed of zinc [...] Read more.

Despite notable progress, the fabrication of well-defined polypeptides via controlled ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCAs) using convenient catalysts under mild conditions in a relatively short polymerization time is still challenging. Herein, an easily obtained catalyst system composed of zinc acetate and aniline was explored to mediate the fast ROP of γ-benzyl-l-glutamate-N-carboxyanhydride (BLG-NCA) monomer, to produce poly(γ-benzyl-l-glutamates) (PBLGs) with controllable molecular weights and narrow dispersity. Considering the excellent cooperative action of zinc acetate and a broad scope of aniline derivatives with different functional groups to control ROP of BLG-NCA, this method may offer a useful platform enabling the rapid generation of end-functionalized PBLG and block copolymers for numerous biomedical applications. Full article

(This article belongs to the Special Issue Lewis Pair Polymerization for New Reactivity and Structure in Polymer Synthesis)

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13 pages, 2739 KiB

Open AccessArticle

Synthesis, Molecular Docking Studies, In Vitro Antimicrobial and Antifungal Activities of Novel Dipeptide Derivatives Based on N-(2-(2-Hydrazinyl-2-oxoethylamino)-2-oxoethyl)-Nicotinamide

by Gaber Moustafa, Hemat Khalaf, Ahmed Naglah, Asma Al-Wasidi, Nawal Al-Jafshar and Hassan Awad

Molecules 2018, 23(4), 761; https://doi.org/10.3390/molecules23040761 - 27 Mar 2018

Cited by 39 | Viewed by 5377

Abstract

A series of linear dipeptide derivatives (4–10) were prepared and evaluated as antimicrobial agents via the synthesis of N-(2-(2-hydrazinyl-2-oxoethylamino)-2-oxoethyl) nicotinamide (4). Compound 4 was reacted with 4-chlorobenzaldehyde or 4-hydroxybenzaldehyde, to give the hydrazones 5 and 6 [...] Read more.

A series of linear dipeptide derivatives (4–10) were prepared and evaluated as antimicrobial agents via the synthesis of N-(2-(2-hydrazinyl-2-oxoethylamino)-2-oxoethyl) nicotinamide (4). Compound 4 was reacted with 4-chlorobenzaldehyde or 4-hydroxybenzaldehyde, to give the hydrazones 5 and 6, respectively. On the other hand, Compound 4 was coupled with phenylisocyanate or methylisothiocyanate to give Compounds 7 and 8, respectively. The latter compounds (7 and 8) were coupled with chloroacetic acid to give oxazolidine (9) and thiazolidine (10), respectively. The newly synthesized dipeptide compounds were confirmed by means of their spectral data. The antimicrobial activity of the newly synthesized compounds 4–10 was evaluated by agar well diffusion, and they showed good activity. Compounds 4, 5, and 9 gave the most promising activity in this study. Most of the tested compounds possessed MIC values ranging from 50 to 500 µg/mL. Furthermore, docking studies were carried out on enoyl reductase from E. coli and cytochrome P450 14 α-sterol demethylase (Cyp51) from Candida albicans active sites. The MolDock scores of the seven tested compounds ranged between −117 and −171 and between −107 and −179, respectively. Full article

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20 pages, 28072 KiB

Open AccessArticle

Synthesis of Polyheterocyclic Pyrrolo[3,4-b]pyridin-5-ones via a One-Pot (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization/S_N2) Process. A Suitable Alternative towards Novel Aza-Analogues of Falipamil

by Angel Zamudio-Medina, Ailyn N. García-González, Genesis K. Herrera-Carrillo, Daniel Zárate-Zárate, Adriana Benavides-Macías, Joaquín Tamariz, Ilich A. Ibarra, Alejandro Islas-Jácome and Eduardo González-Zamora

Molecules 2018, 23(4), 763; https://doi.org/10.3390/molecules23040763 - 27 Mar 2018

Cited by 6 | Viewed by 5583

Abstract

We describe the one-pot synthesis of twenty polyheterocyclic pyrrolo[3,4-b]pyridin-5-ones via a cascade process (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization) in 20 to 95% overall yields, as well as four pharmacologically promising analogues via an improved cascade process (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization/S_N2): [...] Read more.

We describe the one-pot synthesis of twenty polyheterocyclic pyrrolo[3,4-b]pyridin-5-ones via a cascade process (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization) in 20 to 95% overall yields, as well as four pharmacologically promising analogues via an improved cascade process (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization/S_N2): two piperazine-linked pyrrolo[3,4-b]pyridin-5-ones in 33 and 34%, and a couple of Falipamil aza-analogues in 30 and 35% overall yields. It is worth highlighting the good substrate scope found, because final products are furnished with alkyl, aryl, and heterocyclic substituents. The use of chain-ring tautomerizable isocyanides (as key reagents for the Ugi-type three component reaction) allowed for a rapid and efficient assembly of the polysubstituted oxindoles, which were used in situ toward the complex products, conferring features like robustness, sustainability, and the one-pot approach to this synthetic methodology. Full article

(This article belongs to the Section Organic Chemistry)

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16 pages, 3208 KiB

Open AccessArticle

A Visible Light-Driven Minisci-Type Reaction with N-Hydroxyphthalimide Esters

by Lisa Marie Kammer, Aliyaah Rahman and Till Opatz

Molecules 2018, 23(4), 764; https://doi.org/10.3390/molecules23040764 - 27 Mar 2018

Cited by 45 | Viewed by 13535

Abstract

A visible light-promoted protocol for the redox-neutral coupling of N-hydroxyphthalimide esters with different N-heterocyclic compounds is described. The reaction proceeds through an alkyl radical intermediate generated by reductive decarboxylation of N-hydroxyphthalimide esters. In contrast to the original Minisci protocol, polyalkylation [...] Read more.

A visible light-promoted protocol for the redox-neutral coupling of N-hydroxyphthalimide esters with different N-heterocyclic compounds is described. The reaction proceeds through an alkyl radical intermediate generated by reductive decarboxylation of N-hydroxyphthalimide esters. In contrast to the original Minisci protocol, polyalkylation can largely be avoided. Mechanistic investigations revealed a radical chain mechanism which in some cases can proceed even if no photocatalyst is added. This valuable and functional group-tolerant reaction produces substituted heterocycles in moderate to excellent yield. The use of inexpensive starting materials and LEDs as the light source are key features of this C–C bond formation. Full article

(This article belongs to the Special Issue Radical Chemistry)

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17 pages, 978 KiB

Open AccessArticle

Performance of Different Immobilized Lipases in the Syntheses of Short- and Long-Chain Carboxylic Acid Esters by Esterification Reactions in Organic Media

by Lionete Nunes De Lima, Adriano Aguiar Mendes, Roberto Fernandez-Lafuente, Paulo Waldir Tardioli and Raquel De Lima Camargo Giordano

Molecules 2018, 23(4), 766; https://doi.org/10.3390/molecules23040766 - 27 Mar 2018

Cited by 30 | Viewed by 5076

Abstract

Short-chain alkyl esters and sugar esters are widely used in the food, pharmaceutical and cosmetic industries due to their flavor and emulsifying characteristics, respectively. Both compounds can be synthesized via biocatalysis using lipases. This work aims to compare the performance of commercial lipases [...] Read more.

Short-chain alkyl esters and sugar esters are widely used in the food, pharmaceutical and cosmetic industries due to their flavor and emulsifying characteristics, respectively. Both compounds can be synthesized via biocatalysis using lipases. This work aims to compare the performance of commercial lipases covalently attached to dry acrylic beads functionalized with oxirane groups (lipases from Candida antarctica type B—IMMCALB-T2-350, Pseudomonas fluorescens—IMMAPF-T2-150, and Thermomyces lanuginosus—IMMTLL-T2-150) and a home-made biocatalyst (lipase from Pseudomonas fluorescens adsorbed onto silica coated with octyl groups, named PFL-octyl-silica) in the syntheses of short- and long-chain carboxylic acid esters. Esters with flavor properties were synthetized by esterification of acetic and butyl acids with several alcohols (e.g., ethanol, 1-butanol, 1-hexanol, and isoamyl alcohol), and sugar esters were synthetized by esterification of oleic and lauric acids with fructose and lactose. All biocatalysts showed similar performance in the syntheses of short-chain alkyl esters, with conversions ranging from 88.9 to 98.4%. However, in the syntheses of sugar esters the performance of PFL-octyl-silica was almost always lower than the commercial IMMCALB-T2-350, whose conversion was up to 96% in the synthesis of fructose oleate. Both biocatalysts showed high operational stability in organic media, thus having great potential for biotransformations. Full article

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20 pages, 20290 KiB

Open AccessArticle

Computational Simulation Studies on the Binding Selectivity of 1-(1H-Benzimidazol-5-yl)-5-aminopyrazoles in Complexes with FGFR1 and FGFR4

by You-Lu Pan, Yan-Ling Liu and Jian-Zhong Chen

Molecules 2018, 23(4), 767; https://doi.org/10.3390/molecules23040767 - 27 Mar 2018

Cited by 6 | Viewed by 4104

Abstract

Fibroblast growth factor receptor 1 (FGFR1) has become a potential target for the treatment of cancer. Designing FGFR1-selective inhibitors remains fundamental to the development of anti-cancer drugs because of highly sequential homology among FGFR subtypes. In present work, four inhibitors were examined with [...] Read more.

Fibroblast growth factor receptor 1 (FGFR1) has become a potential target for the treatment of cancer. Designing FGFR1-selective inhibitors remains fundamental to the development of anti-cancer drugs because of highly sequential homology among FGFR subtypes. In present work, four inhibitors were examined with intermolecular interaction patterns with FGFR1 and FGFR4, respectively, for the exploration of binding mechanisms by applying a combined approach of computational techniques, including flexible docking, binding site analyses, electronic structure computations, molecular dynamic simulations, and binding free energy predictions. Molecular simulation-predicted binding conformations and pharmacophoric features of these molecules in the active pocket of either FGFR1 or FGFR4. MMPB(GB)SA-calculated binding free energies were accordant with the ordering of their tested potency values. Furthermore, in silico mutations of two residues (FGFR1: Tyr563 and Ser565) were also performed to check their impact on ligand binding by applying MD simulations and binding free energy calculations. The present studies may provide a structural understanding of the FGFR1-selective mechanism. The viewpoints from computational simulations would be valuable guidelines for the development of novel FGFR1-selective inhibitors. Full article

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8 pages, 5301 KiB

Open AccessCommunication

E-p-Methoxycinnamoyl-α-l-rhamnopyranosyl Ester, a Phenylpropanoid Isolated from Scrophularia buergeriana, Increases Nuclear Factor Erythroid-Derived 2-Related Factor 2 Stability by Inhibiting Ubiquitination in Human Keratinocytes

by Jiwon Jeong, Lilik Duwi Wahyudi, Young-Sam Keum, Heejung Yang and Jung-Hwan Kim

Molecules 2018, 23(4), 768; https://doi.org/10.3390/molecules23040768 - 27 Mar 2018

Cited by 9 | Viewed by 3710

Abstract

The nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a key regulator of gene expression during oxidative stress and drug detoxification. Thus, identifying Nrf2 activators to protect from possible cell damage is necessary. In this study, we investigated whether E-p-methoxycinnamoyl-α-l [...] Read more.

The nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a key regulator of gene expression during oxidative stress and drug detoxification. Thus, identifying Nrf2 activators to protect from possible cell damage is necessary. In this study, we investigated whether E-p-methoxycinnamoyl-α-l-rhamnopyranosyl ester (MCR), a phenylpropanoid isolated from Scrophularia buergeriana, can activate Nrf2 signaling in human keratinocytes (HaCaT). First, we determined the dose- and time-dependent effects of MCR on the expression and activity of Nrf2. The antioxidant response element-luciferase reporter assay and western blot analysis results showed that MCR markedly induced Nrf2 activity and its protein expression, respectively. Further, MCR increased both the mRNA and protein levels of heme-oxygenase-1, one of the Nrf2 target genes, in the cells. Interestingly, we found that Nrf2 stability was remarkably enhanced by MCR. Furthermore, ubiquitin-dependent proteasomal degradation of Nrf2 was significantly reduced by MCR. Thus, MCR might afford skin protection by enhancing Nrf2 stability or by blocking its proteasomal degradation. Full article

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13 pages, 5739 KiB

Open AccessArticle

Charge-Controlled Synthetic Hyaluronan-Based Cell Matrices

by Patricia S. Hegger, Julia Kupka, Burcu Baykal Minsky, Sabine Laschat and Heike Boehm

Molecules 2018, 23(4), 769; https://doi.org/10.3390/molecules23040769 - 27 Mar 2018

Cited by 5 | Viewed by 4428

Abstract

The extracellular matrix (ECM) represents a highly charged and hydrated network in which different cells in vertebrate tissues are embedded. Hydrogels as minimal ECM mimetics with a controlled chemistry offer the opportunity to vary material properties by varying the negative network charge. In [...] Read more.

The extracellular matrix (ECM) represents a highly charged and hydrated network in which different cells in vertebrate tissues are embedded. Hydrogels as minimal ECM mimetics with a controlled chemistry offer the opportunity to vary material properties by varying the negative network charge. In this paper, a synthetic biology model of the ECM based on natural and highly negatively charged polyelectrolyte hyaluronic acid (HA) is characterized with specific emphasis on its charge-related bioactivity. Therefore, the thiol-Michael addition click reaction is used to produce HA hydrogels with defined network structure and charge density. The presented hydrogels show enzymatic degradability and cell attachment. These properties depend on both covalent and electrostatic interactions within the hydrogel network. Furthermore, no unspecific or specific attachment of proteins to the presented hydrogels is observed. In addition, these fundamental insights into charge-related ECM behavior and the influence of electrostatic properties could also lead to innovations in existing biomedical products. Full article

(This article belongs to the Special Issue Hyaluronic Acid and its Derivatives for Biomedical Applications)

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8 pages, 784 KiB

Open AccessArticle

A New Lignanamide from the Root of Lycium yunnanense Kuang and Its Antioxidant Activity

by Xin-Heng Zheng, Yuan-Peng Huang, Qiu-Ping Liang, Wei Xu, Ting Lan and Guang-Xiong Zhou

Molecules 2018, 23(4), 770; https://doi.org/10.3390/molecules23040770 - 27 Mar 2018

Cited by 16 | Viewed by 3825

Abstract

A new lignanamide (1), lyciumamide K, together with four known analogues (2–5), was isolated from the root of Lycium yunnanense Kuang. Based on HR-ESI-MS, NMR spectral data and quantum chemistry ECD calculations, the structure of this new [...] Read more.

A new lignanamide (1), lyciumamide K, together with four known analogues (2–5), was isolated from the root of Lycium yunnanense Kuang. Based on HR-ESI-MS, NMR spectral data and quantum chemistry ECD calculations, the structure of this new compound was confirmed, including its absolute configuration. Evaluation of the antioxidant activity of compounds 1–5 in the oxygen radical absorption capacity (ORAC) assay showed that they all exhibited significant antioxidant activities. Particularly, compound 1 showed the best activity with ORAC values (U/mol) of 7.90 ± 0.52. Thus, the new lignanamide may be a good source of bioavtive and protective compounds. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 2571 KiB

Open AccessArticle

Stereoselective Syntheses and Application of Chiral Bi- and Tridentate Ligands Derived from (+)-Sabinol

by Yerbolat Tashenov, Mathias Daniels, Koen Robeyns, Luc Van Meervelt, Wim Dehaen, Yerlan M. Suleimen and Zsolt Szakonyi

Molecules 2018, 23(4), 771; https://doi.org/10.3390/molecules23040771 - 27 Mar 2018

Cited by 9 | Viewed by 4703

Abstract

A library of bidentate diols, as well as tridentate triols and aminodiols, derived from (+)-sabinol, was synthesized in a stereoselective manner. Sabinol was transformed into allylic trichloroacetamide via Overman rearrangement of the corresponding trichloroacetimidate. After changing the protecting group to Boc, the enamine [...] Read more.

A library of bidentate diols, as well as tridentate triols and aminodiols, derived from (+)-sabinol, was synthesized in a stereoselective manner. Sabinol was transformed into allylic trichloroacetamide via Overman rearrangement of the corresponding trichloroacetimidate. After changing the protecting group to Boc, the enamine was subjected to stereospecific dihydroxylation with OsO₄/NMO, resulting in the (1R,2R,3R,5R)-aminodiol diastereomer. The obtained primary aminodiol was transformed to a secondary analogue. The ring closure of the N-benzyl-substituted aminodiol with formaldehyde was investigated and regioselective formation of the spiro-oxazolidine ring was observed. Hydroboration or dihydroxylation of sabinol or its benzyl ether with OsO₄/NMO resulted in the formation of sabinane-based diols and triols following a highly stereospecific reaction. Treatment of sabinol with m-CPBA afforded O-benzoyl triol as a diastereoisomer of the directly dihydroxylated product, instead of the expected epoxy alcohol. The resulting aminodiols, diol, and triols were applied as chiral catalysts in the reaction of diethylzinc and benzaldehyde from moderate to good selectivity. Full article

(This article belongs to the Special Issue Enantioselective Catalysis)

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16 pages, 45362 KiB

Open AccessArticle

In Silico Discovery of a Substituted 6-Methoxy-quinalidine with Leishmanicidal Activity in Leishmania infantum

by Strahinja Stevanović, Andrej Perdih, Milan Senćanski, Sanja Glišić, Margarida Duarte, Ana M. Tomás, Filipa V. Sena, Filipe M. Sousa, Manuela M. Pereira and Tom Solmajer

Molecules 2018, 23(4), 772; https://doi.org/10.3390/molecules23040772 - 27 Mar 2018

Cited by 24 | Viewed by 5767

Abstract

There is an urgent need for the discovery of new antileishmanial drugs with a new mechanism of action. Type 2 NADH dehydrogenase from Leishmania infantum (LiNDH2) is an enzyme of the parasite’s respiratory system, which catalyzes the electron transfer from NADH [...] Read more.

There is an urgent need for the discovery of new antileishmanial drugs with a new mechanism of action. Type 2 NADH dehydrogenase from Leishmania infantum (LiNDH2) is an enzyme of the parasite’s respiratory system, which catalyzes the electron transfer from NADH to ubiquinone without coupled proton pumping. In previous studies of the related NADH: ubiquinone oxidoreductase crystal structure from Saccharomyces cerevisiae, two ubiquinone-binding sites (UQ_I and UQ_II) were identified and shown to play an important role in the NDH-2-catalyzed oxidoreduction reaction. Based on the available structural data, we developed a three-dimensional structural model of LiNDH2 using homology detection methods and performed an in silico virtual screening campaign to search for potential inhibitors targeting the LiNDH2 ubiquinone-binding site 1—UQ_I. Selected compounds displaying favorable properties in the computational screening experiments were assayed for inhibitory activity in the structurally similar recombinant NDH-2 from S. aureus and leishmanicidal activity was determined in the wild-type axenic amastigotes and promastigotes of L. infantum. The identified compound, a substituted 6-methoxy-quinalidine, showed promising nanomolar leishmanicidal activity on wild-type axenic promastigotes and amastigotes of L. infantum and the potential for further development. Full article

(This article belongs to the Special Issue COST CM1307: Targeted Chemotherapy towards Diseases Caused by Endoparasites—Proceedings in Medicinal and Natural Product Chemistry)

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10 pages, 1551 KiB

Open AccessArticle

Lentinoids A–D, New Natural Products Isolated from Lentinus strigellus

by Roger Vásquez, Nivia Rios, Godofredo Solano and Luis Cubilla-Rios

Molecules 2018, 23(4), 773; https://doi.org/10.3390/molecules23040773 - 28 Mar 2018

Cited by 10 | Viewed by 4640

Abstract

Four novel lentinoids (1–4), along with the known compounds striguellone A (5), isopanepoxydone (6) and panepoxydone (7), were isolated as part of our studies on Lentinus strigellus. The structures of 1– [...] Read more.

Four novel lentinoids (1–4), along with the known compounds striguellone A (5), isopanepoxydone (6) and panepoxydone (7), were isolated as part of our studies on Lentinus strigellus. The structures of 1–4 have been established by 1D- and 2D-NMR and MS analysis. Compounds (1–3) and (5–7) were tested against Listeria monocytogenes, Enterococcus faecalis, Pseudomonas aeruginosa and Klebsiella pneumoniae. These compounds showed inhibition diameters ranging from 7.5–9.5 mm, however, when the minimum inhibitory concentration (MIC) was determined, only compound 1 showed a significant activity of 200 μg/mL. Intermediates for the biosynthesis of the oxygenated cyclohexenyl derivatives isolated from lentinoid fungi (genera Lentinus and Panus) are proposed. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 4129 KiB

Open AccessArticle

In Vitro Anti-Toxoplasma gondii and Antimicrobial Activity of Amides Derived from Cinnamic Acid

by Graziela Rangel Silveira, Karoline Azerêdo Campelo, Gleice Rangel Silveira Lima, Lais Pessanha Carvalho, Solange Silva Samarão, Olney Vieira-da-Motta, Leda Mathias, Carlos Roberto Ribeiro Matos, Ivo José Curcino Vieira, Edesio José Tenório de Melo and Edmilson José Maria

Molecules 2018, 23(4), 774; https://doi.org/10.3390/molecules23040774 - 28 Mar 2018

Cited by 17 | Viewed by 5041

Abstract

Most cinnamic acids, their esters, amides, aldehydes, and alcohols present several therapeutic actions through anti-inflammatory, antitumor, and inhibitory activity against a great variety of microorganisms. In this work, eight amines derived from cinnamic acid were synthesized and tested against host cells infected with [...] Read more.

Most cinnamic acids, their esters, amides, aldehydes, and alcohols present several therapeutic actions through anti-inflammatory, antitumor, and inhibitory activity against a great variety of microorganisms. In this work, eight amines derived from cinnamic acid were synthesized and tested against host cells infected with Toxoplasma gondii and the bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and three strains of Staphylococcus aureus. Compounds 3 and 4 showed the best result against intracellular T. gondii, presenting antiparasitic activity at low concentrations (0.38 and 0.77 mM). The antibacterial activity of these compounds was also evaluated by the agar microdilution method, and amides 2 and 5 had a minimum inhibitory concentration of 250 µg mL⁻¹ against two strains of S. aureus (ATCC 25923 and bovine strain LSA 88). These also showed synergistic action along with a variety of antibiotics, demonstrating that amines derived from cinnamic acid have potential as pharmacological agents. Full article

(This article belongs to the Collection Antibiotics & Superbugs: New Strategies to Combat Antimicrobial Resistance)

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12 pages, 6140 KiB

Open AccessFeature PaperArticle

PEG 400/Cerium Ammonium Nitrate Combined with Microwave-Assisted Synthesis for Rapid Access to Beta-Amino Ketones. An Easy-to-Use Protocol for Discovering New Hit Compounds

by Giacomo Rossino, Maria Valeria Raimondi, Marta Rui, Marcello Di Giacomo, Daniela Rossi and Simona Collina

Molecules 2018, 23(4), 775; https://doi.org/10.3390/molecules23040775 - 28 Mar 2018

Cited by 6 | Viewed by 5793

Abstract

Compound libraries are important requirement in target-based drug discovery. In the present work, a small focused compound library based on β-aminoketone scaffold has been prepared combining microwave-assisted organic synthesis (MAOS) with polymer-assisted solution phase synthesis (PASPS) and replacing reaction workup standard purification procedures [...] Read more.

Compound libraries are important requirement in target-based drug discovery. In the present work, a small focused compound library based on β-aminoketone scaffold has been prepared combining microwave-assisted organic synthesis (MAOS) with polymer-assisted solution phase synthesis (PASPS) and replacing reaction workup standard purification procedures with solid phase extraction (SPE). Specifically, the effects of solvent, such as dioxane, dimethylformamide (DMF), polyethylene glycol 400 (PEG 400), temperature, irradiation time, stoichiometric ratio of reagents, and catalysts (HCl, acetic acid, cerium ammonium nitrate (CAN)) were investigated to maximize both conversion and yield. The optimized protocol generally afforded the desired products in satisfying yields and purities. The designed library is a part of our current research on sigma 1 receptor modulators, a valuable tool for the identification of novel potential hit compounds. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 6275 KiB

Open AccessArticle

Synthesis and Antiproliferative Activity of Minor Hops Prenylflavonoids and New Insights on Prenyl Group Cyclization

by Jarosław Popłoński, Eliza Turlej, Sandra Sordon, Tomasz Tronina, Agnieszka Bartmańska, Joanna Wietrzyk and Ewa Huszcza

Molecules 2018, 23(4), 776; https://doi.org/10.3390/molecules23040776 - 28 Mar 2018

Cited by 22 | Viewed by 5824

Abstract

Synthesis of minor prenylflavonoids found in hops and their non-natural derivatives were performed. The antiproliferative activity of the obtained compounds against some human cancer cell lines was investigated. Using xanthohumol isolated from spent hops as a lead compound, a series of minor hop [...] Read more.

Synthesis of minor prenylflavonoids found in hops and their non-natural derivatives were performed. The antiproliferative activity of the obtained compounds against some human cancer cell lines was investigated. Using xanthohumol isolated from spent hops as a lead compound, a series of minor hop prenylflavonoids and synthetic derivatives were obtained by isomerization, cyclisation, oxidative-cyclisation, oxidation, reduction and demethylation reactions. Three human cancer cell lines—breast (MCF-7), prostate (PC-3) and colon (HT-29)—were used in antiproliferative assays, with cisplatin as a control compound. Five minor hop prenyl flavonoids and nine non-natural derivatives of xanthohumol have been synthetized. Syntheses of xanthohumol K, its dihydro- and tetrahydro-derivatives and 1″,2″,α,β-tetrahydroxanthohumol C were described for the first time. All of the minor hops prenyl flavonoids exhibited strong to moderate antiproliferative activity in vitro. The minor hops flavonoids xanthohumol C and 1″,2″-dihydroxanthohumol K and non-natural 2,3-dehydroisoxanthohumol exhibited the activity comparable to cisplatin. Results described in the article suggest that flavonoids containing chromane- and chromene-like moieties, especially chalcones, are potent antiproliferative agents. The developed new efficient, regioselective cyclisation reaction of the xanthohumol prenyl group to 1″,2″-dihydroxantohumol K may be used in the synthesis of other compounds with the chromane moiety. Full article

(This article belongs to the Special Issue Chalcone: A Privileged Structure in Medicinal Chemistry)

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14 pages, 973 KiB

Open AccessArticle

Synthesis of Novel Amino Acid–Fipronil Conjugates and Study on Their Phloem Loading Mechanism

by Qingqing Sheng, Xinxin Liu, Yun Xie, Fei Lin, Zhixiang Zhang, Chen Zhao and Hanhong Xu

Molecules 2018, 23(4), 778; https://doi.org/10.3390/molecules23040778 - 28 Mar 2018

Cited by 11 | Viewed by 4444

Abstract

To develop a new pesticide with phloem mobility, a series of new amino acid–fipronil conjugates were designed and synthesized based on derivatization at the 3-position of the pyrazole ring of fipronil. Experiments using a Ricinus communis seedling system showed that all tested conjugates [...] Read more.

To develop a new pesticide with phloem mobility, a series of new amino acid–fipronil conjugates were designed and synthesized based on derivatization at the 3-position of the pyrazole ring of fipronil. Experiments using a Ricinus communis seedling system showed that all tested conjugates were phloem mobile except for the isoleucine–fipronil conjugate, and that the serine–fipronil conjugate (4g) exhibited the highest concentration in phloem sap (52.00 ± 5.80 μM). According to prediction with log Cf values and uptake experiments with Xenopus oocytes, the phloem loading process of conjugate 4g involved both passive diffusion and an active carrier system (RcANT15). In particular, compared with for a previously reported glycinergic–fipronil conjugate (GlyF), passive diffusion played a more important role for conjugate 4g in the enhancement of phloem mobility. This study suggests that associating a nutrient at a different position of an existing pesticide structure could still be effective in obtaining phloem-mobile derivatives, but the distinct physicochemical properties of resultant conjugates may lead to different phloem loading mechanisms. Full article

(This article belongs to the Section Chemical Biology)

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9 pages, 242 KiB

Open AccessArticle

Sensory Characteristics of Various Concentrations of Phenolic Compounds Potentially Associated with Smoked Aroma in Foods

by Hongwei Wang and Edgar Chambers IV

Molecules 2018, 23(4), 780; https://doi.org/10.3390/molecules23040780 - 28 Mar 2018

Cited by 19 | Viewed by 4777

Abstract

This research describes the sensory odor characteristics of 19 phenolic compounds (11 phenol derivatives, six guaiacol derivatives, and two syringol derivatives) that have been associated with smoked aroma in previous literature. Seven concentrations varying from 1 to 100,000 ppm of each chemical were [...] Read more.

This research describes the sensory odor characteristics of 19 phenolic compounds (11 phenol derivatives, six guaiacol derivatives, and two syringol derivatives) that have been associated with smoked aroma in previous literature. Seven concentrations varying from 1 to 100,000 ppm of each chemical were examined. A highly trained descriptive panel used a recently published lexicon for smoky aroma and flavor and found that smoked aroma compounds have many different attributes that make up smokiness. Musty/dusty, musty/earthy, pungent, acid, smoky, woody, burnt, ashy, cedar, creosote or petroleum-like collectively imparted smoked aroma. Most of the phenolic compounds were described as having smoky characteristics at low concentrations, generally at 1 and 10 ppm, except 3,4-dimethylphenol at 5000 ppm. 2,6-Dimethylphenol was not associated with smoky characteristics. This research is the first to evaluate a set of phenolic compounds for their sensory characteristics using a professionally developed set of sensory attributes. Full article

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18 pages, 41705 KiB

Open AccessArticle

Ectopic Overexpression of a Novel R2R3-MYB, NtMYB2 from Chinese Narcissus Represses Anthocyanin Biosynthesis in Tobacco

by Muhammad Anwar, Guiqing Wang, Jiacheng Wu, Saquib Waheed, Andrew C. Allan and Lihui Zeng

Molecules 2018, 23(4), 781; https://doi.org/10.3390/molecules23040781 - 28 Mar 2018

Cited by 45 | Viewed by 6499

Abstract

R2R3 MYB transcription factors play key functions in the regulation of secondary metabolites. In the present study, a R2R3 MYB transcriptional factor NtMYB2 was identified from Chinese narcissus (Narcissus tazetta L. var. Chinensis Roem) and functionally characterized. NtMYB2 belongs to subgroup 4 [...] Read more.

R2R3 MYB transcription factors play key functions in the regulation of secondary metabolites. In the present study, a R2R3 MYB transcriptional factor NtMYB2 was identified from Chinese narcissus (Narcissus tazetta L. var. Chinensis Roem) and functionally characterized. NtMYB2 belongs to subgroup 4 of the R2R3 MYB transcription factor family that are related to repressor MYBs involved in the regulation of anthocyanin and flavonoids. Transient expression confirmed that NtMYB2 strongly reduced the red pigmentation induced by MYB- anthocyanin activators in agro-infiltrated tobacco leaves. Ectopic expression of NtMYB2 in tobacco significantly reduced the pigmentation and altered the floral phenotypes in transgenic tobacco flowers. Gene expression analysis suggested that NtMYB2 repressed the transcript levels of structural genes involved in anthocyanin biosynthesis pathway, especially the UFGT gene. NtMYB2 gene is expressed in all examined narcissus tissues; the levels of transcription in petals and corona is higher than other tissues and the transcription level at the bud stage was highest. These results show that NtMYB2 is involved in the regulation of anthocyanin biosynthesis pathway and may act as a repressor by down regulating the transcripts of key enzyme genes in Chinese narcissus. Full article

(This article belongs to the Section Molecular Diversity)

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11 pages, 672 KiB

Open AccessCommunication

Catalytic Annulation of Epoxides with Heterocumulenes by the Indium-Tin System

by Itaru Suzuki, Akira Imakuni, Akio Baba and Ikuya Shibata

Molecules 2018, 23(4), 782; https://doi.org/10.3390/molecules23040782 - 28 Mar 2018

Cited by 6 | Viewed by 4586

Abstract

In the synthesis of five-membered heterocycles by the annulation of epoxides with heterocumulenes such as carbon dioxide and isocyanates, we developed the indium-tin catalytic system and synthesized various cyclic adducts including novel types products under mild reaction conditions. Full article

(This article belongs to the Special Issue Indium in Organic Synthesis)

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20 pages, 6591 KiB

Open AccessArticle

Computational Modeling of In Vitro Swelling of Mitochondria: A Biophysical Approach

by Vladimir I. Makarov, Igor Khmelinskii and Sabzali Javadov

Molecules 2018, 23(4), 783; https://doi.org/10.3390/molecules23040783 - 28 Mar 2018

Cited by 20 | Viewed by 6907

Abstract

Swelling of mitochondria plays an important role in the pathogenesis of human diseases by stimulating mitochondria-mediated cell death through apoptosis, necrosis, and autophagy. Changes in the permeability of the inner mitochondrial membrane (IMM) of ions and other substances induce an increase in the [...] Read more.

Swelling of mitochondria plays an important role in the pathogenesis of human diseases by stimulating mitochondria-mediated cell death through apoptosis, necrosis, and autophagy. Changes in the permeability of the inner mitochondrial membrane (IMM) of ions and other substances induce an increase in the colloid osmotic pressure, leading to matrix swelling. Modeling of mitochondrial swelling is important for simulation and prediction of in vivo events in the cell during oxidative and energy stress. In the present study, we developed a computational model that describes the mechanism of mitochondrial swelling based on osmosis, the rigidity of the IMM, and dynamics of ionic/neutral species. The model describes a new biophysical approach to swelling dynamics, where osmotic pressure created in the matrix is compensated for by the rigidity of the IMM, i.e., osmotic pressure induces membrane deformation, which compensates for the osmotic pressure effect. Thus, the effect is linear and reversible at small membrane deformations, allowing the membrane to restore its normal form. On the other hand, the membrane rigidity drops to zero at large deformations, and the swelling becomes irreversible. As a result, an increased number of dysfunctional mitochondria can activate mitophagy and initiate cell death. Numerical modeling analysis produced results that reasonably describe the experimental data reported earlier. Full article

(This article belongs to the Special Issue Biology of Reactive Oxygen and Nitrogen Species: Redox Signaling, Metabolic Effects, Cellular Functions and Oxidative Damage)

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13 pages, 7465 KiB

Open AccessArticle

Investigation of Absorption Routes of Meloxicam and Its Salt Form from Intranasal Delivery Systems

by Csilla Bartos, Rita Ambrus, Anita Kovács, Róbert Gáspár, Anita Sztojkov-Ivanov, Árpád Márki, Tamás Janáky, Ferenc Tömösi, Gábor Kecskeméti and Piroska Szabó-Révész

Molecules 2018, 23(4), 784; https://doi.org/10.3390/molecules23040784 - 28 Mar 2018

Cited by 19 | Viewed by 5142

Abstract

The aim of this article was to study the trans-epithelial absorption to reach the blood and to target the brain by axonal transport using nasal formulations with nanonized meloxicam (nano MEL spray) and its salt form known as meloxicam potassium monohydrate (MELP spray). [...] Read more.

The aim of this article was to study the trans-epithelial absorption to reach the blood and to target the brain by axonal transport using nasal formulations with nanonized meloxicam (nano MEL spray) and its salt form known as meloxicam potassium monohydrate (MELP spray). The physicochemical properties and the mucoadhesivity of nasal formulations were controlled. In vitro and in vivo studies were carried out. These forms were first investigated in “nose-to-brain” relation. It was found that the in vitro study and in vivo study did not show any significant correlation. In vitro experiments demonstrated faster dissolution rate and higher diffusion of MELP from the spray compared with the nano MEL spray. The administration of the nano MEL spray resulted in faster absorption and constant plasma concentration of the drug after five minutes of administration as compared to MELP. The axonal transport of the drug was justified. MEL appeared in the brain tissues after the first five minutes of administration in the case of both spray forms, but its amount was too small in comparison with the total plasma concentration. The application of the nano MEL spray resulted in the same AUC in the brain as the intravenous injection. The “nose-to-blood” results predicted the nasal applicability of MEL and MELP in pain management. The “nose-to-brain” pathway requires further study. Full article

(This article belongs to the Collection Poorly Soluble Drugs)

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15 pages, 50678 KiB

Open AccessArticle

Comparative Evaluation of the Antioxidant and Anti-Alzheimer’s Disease Potential of Coumestrol and Puerarol Isolated from Pueraria lobata Using Molecular Modeling Studies

by Prashamsa Koirala, Su Hui Seong, Hyun Ah Jung and Jae Sue Choi

Molecules 2018, 23(4), 785; https://doi.org/10.3390/molecules23040785 - 28 Mar 2018

Cited by 21 | Viewed by 5785

Abstract

The current study assesses the antioxidant effects of two similar isoflavonoids isolated from Pueraria lobata, coumestrol and puerarol, along with the cholinergic and amyloid-cascade pathways to mitigate Alzheimer’s disease (AD). Antioxidant activity was evaluated via 1,1-diphenyl-2-picryhydrazyl (DPPH) and peroxynitrite (ONOO⁻) [...] Read more.

The current study assesses the antioxidant effects of two similar isoflavonoids isolated from Pueraria lobata, coumestrol and puerarol, along with the cholinergic and amyloid-cascade pathways to mitigate Alzheimer’s disease (AD). Antioxidant activity was evaluated via 1,1-diphenyl-2-picryhydrazyl (DPPH) and peroxynitrite (ONOO⁻) scavenging ability further screened via ONOO⁻-mediated nitrotyrosine. Similarly, acetyl- and butyrylcholinesterase (AChE/BChE) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities were assessed together with docking and kinetic studies. Considering DPPH and ONOO⁻ scavenging activity, coumestrol (EC₅₀ values of 53.98 and 1.17 µM) was found to be more potent than puerarol (EC₅₀ values of 82.55 and 6.99 µM) followed by dose dependent inhibition of ONOO⁻-mediated nitrotyrosine. Coumestrol showed pronounced AChE and BChE activity with IC₅₀ values of 42.33 and 24.64 µM, respectively, acting as a dual cholinesterase (ChE) inhibitor. Despite having weak ChE inhibitory activity, puerarol showed potent BACE1 inhibition (28.17 µM). Kinetic studies of coumestrol showed AChE and BChE inhibition in a competitive and mixed fashion, whereas puerarol showed mixed inhibition for BACE1. In addition, docking simulations demonstrated high affinity and tight binding capacity towards the active site of the enzymes. In summary, we undertook a comparative study of two similar isoflavonoids differing only by a single aliphatic side chain and demonstrated that antioxidant agents coumestrol and puerarol are promising, potentially complementary therapeutics for AD. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 1717 KiB

Open AccessArticle

ω-Methylsulfanylalkyl Glucosinolates: A General Synthetic Pathway

by Manolis Mavratzotis, Stéphanie Cassel, Sabine Montaut and Patrick Rollin

Molecules 2018, 23(4), 786; https://doi.org/10.3390/molecules23040786 - 28 Mar 2018

Cited by 3 | Viewed by 4913

Abstract

A general pathway was devised to synthesize ω-methylsulfanylalkyl glucosinolates, which represent an important class of structurally homogeneous plant secondary metabolites. The required thiofunctionalized hydroximoyl chlorides were obtained from the corresponding α,ω-nitroalkyl methylsulfide precursors, involving as the key-step, a nitronate chlorination strategy. A coupling [...] Read more.

A general pathway was devised to synthesize ω-methylsulfanylalkyl glucosinolates, which represent an important class of structurally homogeneous plant secondary metabolites. The required thiofunctionalized hydroximoyl chlorides were obtained from the corresponding α,ω-nitroalkyl methylsulfide precursors, involving as the key-step, a nitronate chlorination strategy. A coupling reaction with 1-thio-beta-d-glucopyranose, followed by O-sulfation of the intermediate thiohydroximate and final deprotection of the sugar moiety afforded the target compounds. Full article

(This article belongs to the Special Issue Focusing on Sulfur in Medicinal Chemistry)

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11 pages, 1721 KiB

Open AccessArticle

Differences in the Effects of EGCG on Chromosomal Stability and Cell Growth between Normal and Colon Cancer Cells

by Juan Ni, Xihan Guo, Han Wang, Tao Zhou and Xu Wang

Molecules 2018, 23(4), 788; https://doi.org/10.3390/molecules23040788 - 29 Mar 2018

Cited by 34 | Viewed by 4853

Abstract

The tea catechin epigallocatechin-3-gallate (EGCG) proved to be the most potent physiologically active tea compound in vitro. It possesses antioxidant as well as pro-oxidant properties. EGCG has the effect of inducing apoptosis of tumor cells and inhibiting cell proliferation. Whether this effect is [...] Read more.

The tea catechin epigallocatechin-3-gallate (EGCG) proved to be the most potent physiologically active tea compound in vitro. It possesses antioxidant as well as pro-oxidant properties. EGCG has the effect of inducing apoptosis of tumor cells and inhibiting cell proliferation. Whether this effect is associated with the antioxidant or pro-oxidative effects of EGCG affecting the genome stability of normal and cancer cells has not been confirmed. Here, we selected Human normal colon epithelial cells NCM460 and colon adenocarcinoma cells COLO205 to investigate the effects of EGCG (0–40 μg/mL) on the genome stability and cell growth status. Chromosomal instability (CIN), nuclear division index (NDI), and apoptosis was measured by cytokinesis-block micronucleus assay (CBMN), and the expression of core genes in mismatch repair (hMLMLH1 and hMSH2) was examined by RT-qPCR. We found that EGCG significantly reduced CIN and apoptosis rate of NCM460 at all concentrations (5–40 μg/mL) and treatment time, EGCG at 5 μg/mL promoted cell division; EGCG could significantly induce chromosome instability in COLO205 cells and trigger apoptosis and inhibition of cell division. These results suggest that EGCG exhibits different genetic and cytological effects in normal and colon cancer cells. Full article

(This article belongs to the Special Issue Dietary Antioxidants: Evidence of Protective Effects against Chronic Disease)

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14 pages, 3018 KiB

Open AccessArticle

Development of Polyclonal Antibody against Clenbuterol for Immunoassay Application

by Nurul Ain A. Talib, Faridah Salam and Yusran Sulaiman

Molecules 2018, 23(4), 789; https://doi.org/10.3390/molecules23040789 - 29 Mar 2018

Cited by 6 | Viewed by 8110

Abstract

Development of an immunoassay for clenbuterol (CLB) detection required an anti-CLB antibody as an important bioreceptor. In this study, we report our work on production and purification of a rabbit-derived polyclonal anti-CLB antibody. The antibody was then purified by nProtein A Sepharose affinity [...] Read more.

Development of an immunoassay for clenbuterol (CLB) detection required an anti-CLB antibody as an important bioreceptor. In this study, we report our work on production and purification of a rabbit-derived polyclonal anti-CLB antibody. The antibody was then purified by nProtein A Sepharose affinity column and the antibody purity was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The activities of purified antibody were evaluated based on high antibody titer determined from enzyme-linked immunosorbent assay (ELISA). The sensitivity and selectivity of this antibody was evaluated and exhibits negligible cross-reactivity to antibiotics other than β-agonist families. Evaluation of the antibody as bioreceptor in immunoassay was performed using direct competitive ELISA and exhibited linear calibration plot (R² = 0.9484). The antibody was used to detect the content of CLB in spiked milk samples and the recovery of more than 92% indicating significant performance as bioreceptor for the development of a rapid and simple immunoassay. Full article

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14 pages, 5828 KiB

Open AccessArticle

Dissipation and Migration of Pyrethroids in Auricularia polytricha Mont. from Cultivation to Postharvest Processing and Dietary Risk

by Jin-Jing Xiao, Jin-Sheng Duan, Yan-Can Wu, Yan-Hong Shi, Qing-Kui Fang, Min Liao, Ri-Mao Hua and Hai-Qun Cao

Molecules 2018, 23(4), 791; https://doi.org/10.3390/molecules23040791 - 29 Mar 2018

Cited by 3 | Viewed by 3815

Abstract

In order to ensure raw consumption safety the dissipation behavior, migration, postharvest processing, and dietary risk assessment of five pyrethroids in mushroom (Auricularia polytricha Mont.) cultivated under Chinese greenhouse-field conditions. Half-lives (t_1/2) of pyrethroids in fruiting body and substrate [...] Read more.

In order to ensure raw consumption safety the dissipation behavior, migration, postharvest processing, and dietary risk assessment of five pyrethroids in mushroom (Auricularia polytricha Mont.) cultivated under Chinese greenhouse-field conditions. Half-lives (t_1/2) of pyrethroids in fruiting body and substrate samples were 3.10–5.26 and 17.46–40.06 d, respectively. Fenpropathrin dissipated rapidly in fruiting bodies (t_1/2 3.10 d); bifenthrin had the longest t_1/2. At harvest, pyrethroid residues in A. polytricha (except fenpropathrin) were above the respective maximum residue limits (MRLs). Some migration of lambda-cyhalothrin was observed in the substrate-fruit body system. In postharvest-processing, sun-drying and soaking reduced pyrethroid residues by 25–83%. We therefore recommend that consumers soak these mushrooms in 0.5% NaHCO₃ at 50 °C for 90 min. Pyrethroids exhibit a particularly low PF value of 0.08–0.13%, resulting in a negligible exposure risk upon mushroom consumption. This study provides guidance for the safe application of pyrethroids to edible fungi, and for the establishment of MRLs in mushrooms to reduce pesticide exposure in humans. Full article

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15 pages, 2045 KiB

Open AccessArticle

UHPLC-MS Metabolome Fingerprinting: The Isolation of Main Compounds and Antioxidant Activity of the Andean Species Tetraglochin ameghinoi (Speg.) Speg.

by Lorena Luna, Mario J. Simirgiotis, Beatriz Lima, Jorge Bórquez, Gabriela E. Feresin and Alejandro Tapia

Molecules 2018, 23(4), 793; https://doi.org/10.3390/molecules23040793 - 29 Mar 2018

Cited by 9 | Viewed by 4306

Abstract

The seriated extracts of petroleum ether (PE-E), dichloromethane (DCM-E) and methanol extracts (MeOH-E) from the aerial parts of the native South American plant Tetraglochin ameghinoi (Rosaceae), were evaluated regarding their antioxidant and antibacterial activities. The antioxidant properties were evaluated by free radical scavenging [...] Read more.

The seriated extracts of petroleum ether (PE-E), dichloromethane (DCM-E) and methanol extracts (MeOH-E) from the aerial parts of the native South American plant Tetraglochin ameghinoi (Rosaceae), were evaluated regarding their antioxidant and antibacterial activities. The antioxidant properties were evaluated by free radical scavenging methods (DPPH and TEAC), ferric-reducing antioxidant power (FRAP) and lipoperoxidation in erythrocytes (LP), while the antibacterial activity was performed against Gram-positive and Gram-negative bacteria according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The chemical and biological analyses of this plant are very important since this bush is currently used in traditional medicine as a cholagogue and digestive. The polar MeOH-E showed the highest antioxidant activities (17.70 µg/mL in the DPPH assay, 381.43 ± 22.38 mM TE/g extract in the FRAP assay, 387.76 ± 91.93 mg TE/g extract in the TEAC assay and 93.23 + 6.77% in the LP assay) and it was selected for chromatographic isolation of its components. These components were found to be four acetophenones, including the new phloracetophenone glucoside: 4′,6′,-dihydroxy-2′-O-(6″-acetyl)-β-d-glucopyranosylacetophenone or IUPAC name: (6-(2-acetyl-3,5-dihydroxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)methyl acetate, whose structure was elucidated by NMR and MS methods. In addition, twenty-six compounds, including five of these acetophenone derivatives, two sugars, six flavonoids, eleven phenolic acids and two triterpenes, were identified based on UHPLC-OT-MS and PDA analysis on the MeOH-E. The results support the medicinal use of the plant. Full article

(This article belongs to the Special Issue The Antioxidant Capacities of Natural Products)

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12 pages, 1315 KiB

Open AccessArticle

The Effects of Plant-Derived Oleanolic Acid on Selected Parameters of Glucose Homeostasis in a Diet-Induced Pre-Diabetic Rat Model

by Mlindeli Gamede, Lindokuhle Mabuza, Phikelelani Ngubane and Andile Khathi

Molecules 2018, 23(4), 794; https://doi.org/10.3390/molecules23040794 - 29 Mar 2018

Cited by 46 | Viewed by 6611

Abstract

Prolonged exposure to high energy diets has been implicated in the development of pre-diabetes, a long-lasting condition that precedes type 2 diabetes mellitus (T2DM). A combination of pharmacological and dietary interventions is used to prevent the progression of pre-diabetes to T2DM. However, poor [...] Read more.

Prolonged exposure to high energy diets has been implicated in the development of pre-diabetes, a long-lasting condition that precedes type 2 diabetes mellitus (T2DM). A combination of pharmacological and dietary interventions is used to prevent the progression of pre-diabetes to T2DM. However, poor patient compliance leads to negligence of the dietary intervention and thus reduced drug efficiency. Oleanolic acid (OA) has been reported to possess anti-diabetic effects in type 1 diabetic rats. However, the effects of this compound on pre-diabetes have not yet been established. Consequently, this study sought to evaluate the effects OA on a diet-induced pre-diabetes rat model. Pre-diabetic male Sprague Dawley rats were treated with OA in both the presence and absence of dietary intervention for a period of 12 weeks. The administration of OA with and without dietary intervention resulted in significantly improved glucose homeostasis through reduced caloric intake, body weights, plasma ghrelin concentration and glycated haemoglobin by comparison to the pre-diabetic control. These results suggest that OA may be used to manage pre-diabetes as it was able to restore glucose homeostasis and prevented the progression to overt type 2 diabetes. Full article

(This article belongs to the Special Issue Chemical Biology of Sterols, Triterpenoids and Other Natural Products: A Themed Issue in Honor of Professor W. David Nes on the Occasion of His 65th Birthday)

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13 pages, 37282 KiB

Open AccessArticle

On-Demand Bioadhesive Dendrimers with Reduced Cytotoxicity

by Feng Gao, Ivan Djordjevic, Oleksandr Pokholenko, Haobo Zhang, Junying Zhang and Terry W. J. Steele

Molecules 2018, 23(4), 796; https://doi.org/10.3390/molecules23040796 - 30 Mar 2018

Cited by 22 | Viewed by 6502

Abstract

Tissue adhesives based on polyamidoamine (PAMAM) dendrimer, grafted with UV-sensitive aryldiazirine (PAMAM-g-diazirine) are promising new candidates for light active adhesion on soft tissues. Diazirine carbene precursors form interfacial and intermolecular covalent crosslinks with tissues after UV light activation that requires no premixing or [...] Read more.

Tissue adhesives based on polyamidoamine (PAMAM) dendrimer, grafted with UV-sensitive aryldiazirine (PAMAM-g-diazirine) are promising new candidates for light active adhesion on soft tissues. Diazirine carbene precursors form interfacial and intermolecular covalent crosslinks with tissues after UV light activation that requires no premixing or inclusion of free radical initiators. However, primary amines on the PAMAM dendrimer surface present a potential risk due to their cytotoxic and immunological effects. PAMAM-g-diazirine formulations with cationic pendant amines converted into neutral amide groups were evaluated. In vitro toxicity is reduced by an order of magnitude upon amine capping while retaining bioadhesive properties. The in vivo immunological response to PAMAM-g-diazirine formulations was found to be optimal in comparison to standard poly(lactic-co-glycolic acid) (PLGA) thin films. Full article

(This article belongs to the Special Issue Dendrimers: A Themed Issue in Honor of Professor Donald A. Tomalia on the Occasion of His 80th Birthday)

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10 pages, 15267 KiB

Open AccessArticle

A Co-Precursor Approach Coupled with a Supercritical Modification Method for Constructing Highly Transparent and Superhydrophobic Polymethylsilsesquioxane Aerogels

by Chaoshuai Lei, Junning Li, Chencheng Sun, Hailong Yang, Tao Xia, Zijun Hu and Yue Zhang

Molecules 2018, 23(4), 797; https://doi.org/10.3390/molecules23040797 - 30 Mar 2018

Cited by 10 | Viewed by 4487

Abstract

Polymethylsilsesquioxane (PMSQ) aerogels obtained from methyltrimethoxysilane (MTMS) are well-known high-performance porous materials. Highly transparent and hydrophobic PMSQ aerogel would play an important role in transparent vacuum insulation panels. Herein, the co-precursor approach and supercritical modification method were developed to prepare the PMSQ aerogels [...] Read more.

Polymethylsilsesquioxane (PMSQ) aerogels obtained from methyltrimethoxysilane (MTMS) are well-known high-performance porous materials. Highly transparent and hydrophobic PMSQ aerogel would play an important role in transparent vacuum insulation panels. Herein, the co-precursor approach and supercritical modification method were developed to prepare the PMSQ aerogels with high transparency and superhydrophobicity. Firstly, benefiting from the introduction of tetramethoxysilane (TMOS) in the precursor, the pore structure became more uniform and the particle size was decreased. As the TMOS content increased, the light transmittance increased gradually from 54.0% to 81.2%, whereas the contact angle of water droplet decreased from 141° to 99.9°, ascribed to the increase of hydroxyl groups on the skeleton surface. Hence, the supercritical modification method utilizing hexamethyldisilazane was also introduced to enhance the hydrophobic methyl groups on the aerogel’s surface. As a result, the obtained aerogels revealed superhydrophobicity with a contact angle of 155°. Meanwhile, the developed surface modification method did not lead to any significant changes in the pore structure resulting in the superhydrophobic aerogel with a high transparency of 77.2%. The proposed co-precursor approach and supercritical modification method provide a new horizon in the fabrication of highly transparent and superhydrophobic PMSQ aerogels. Full article

(This article belongs to the Special Issue Chemistry of Aerogels and Their Applications)

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9 pages, 860 KiB

Open AccessArticle

Steroidal Constituents from Roots and Rhizomes of Smilacina japonica

by Yuwen Cui, Xinjie Yang, Dongdong Zhang, Yuze Li, Li Zhang, Bei Song, Zhenggang Yue, Xiaomei Song and Haifeng Tang

Molecules 2018, 23(4), 798; https://doi.org/10.3390/molecules23040798 - 30 Mar 2018

Cited by 16 | Viewed by 3904

Abstract

Four new steroidal constituents (1–4) along with two known steroidal glycosides (5 and 6) were isolated from the roots and rhizomes of Smilacina japonica. Analysis of their physicochemical properties and spectroscopic profiles identified the compounds as [...] Read more.

Four new steroidal constituents (1–4) along with two known steroidal glycosides (5 and 6) were isolated from the roots and rhizomes of Smilacina japonica. Analysis of their physicochemical properties and spectroscopic profiles identified the compounds as (25S)-5α-spirostan-9(11)-en-3β, 17α-diol (1); (25S)-5α-spirostan-9(11)-en-3β, 12β-diol (2); (25S)-5α-spirostan-9(11)-en-3β, 17α-diol-3-O-β-d-glucopyranoside (3); (25S)-5α-spirostan-9(11)-en-3β, 17α-diol-3-O-β-d-glucopyranosyl-(1→2)-[β-d-glucopyranosyl-(1→3)]-β-d-galactopyranoside (4); japonicoside B (5); and japonicoside C (6). All six compounds showed cytotoxic activity against SMMC-7712, Bel-7402, A549, H460, and K562 human cancer cells. Full article

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18 pages, 8054 KiB

Open AccessArticle

Exogenous Melatonin Confers Cadmium Tolerance by Counterbalancing the Hydrogen Peroxide Homeostasis in Wheat Seedlings

by Jun Ni, Qiaojian Wang, Faheem Afzal Shah, Wenbo Liu, Dongdong Wang, Shengwei Huang, Songling Fu and Lifang Wu

Molecules 2018, 23(4), 799; https://doi.org/10.3390/molecules23040799 - 30 Mar 2018

Cited by 141 | Viewed by 8249

Abstract

Melatonin has emerged as a research highlight regarding its important role in regulating plant growth and the adaptation to the environmental stresses. In this study, we investigated how melatonin prevented the cadmium toxicity to wheat seedlings. The results demonstrated that cadmium induced the [...] Read more.

Melatonin has emerged as a research highlight regarding its important role in regulating plant growth and the adaptation to the environmental stresses. In this study, we investigated how melatonin prevented the cadmium toxicity to wheat seedlings. The results demonstrated that cadmium induced the expression of melatonin biosynthesis-related genes and cause a significant increase of endogenous melatonin level. Melatonin treatment drastically alleviated the cadmium toxicity, resulting in increased plant height, biomass accumulation, and root growth. Cadmium and senescence treatment significantly increased the endogenous level of hydrogen peroxide, which was strictly counterbalanced by melatonin. Furthermore, melatonin treatment caused a significant increase of GSH (reduced glutathione) content and the GSH/GSSG (oxidized glutathione) ratio. The activities of two key antioxidant enzymes, ascorbate peroxidase (APX) and superoxide dismutase (SOD), but not catalase (CAT) and peroxidase (POD), were specifically improved by melatonin. Additionally, melatonin not only promoted the primary root growth, but also drastically enhanced the capacity of the seedling roots to degrade the exogenous hydrogen peroxide. These results suggested that melatonin played a key role in maintaining the hydrogen peroxide homeostasis, via regulation of the antioxidant systems. Conclusively, this study revealed a crucial protective role of melatonin in the regulation of cadmium resistance in wheat. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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11 pages, 5408 KiB

Open AccessArticle

High Level Expression and Purification of the Clinically Active Antimicrobial Peptide P-113 in Escherichia coli

by Kuang-Ting Cheng, Chih-Lung Wu, Bak-Sau Yip, Hui-Yuan Yu, Hsi-Tsung Cheng, Ya-Han Chih and Jya-Wei Cheng

Molecules 2018, 23(4), 800; https://doi.org/10.3390/molecules23040800 - 30 Mar 2018

Cited by 18 | Viewed by 4700

Abstract

P-113, which was originally derived from the human saliva protein histatin 5, is a histidine-rich antimicrobial peptide with the sequence AKRHHGYKRKFH. P-113 is currently undergoing phase II clinical trial as a pharmaceutical agent to fight against fungal infections in HIV patients with oral [...] Read more.

P-113, which was originally derived from the human saliva protein histatin 5, is a histidine-rich antimicrobial peptide with the sequence AKRHHGYKRKFH. P-113 is currently undergoing phase II clinical trial as a pharmaceutical agent to fight against fungal infections in HIV patients with oral candidiasis. Previously, we developed a new procedure for the high-yield expression and purification of hG31P, an analogue and antagonist of human CXCL8. Moreover, we have successfully removed lipopolysaccharide (LPS, endotoxin) associated with hG31P in the expression with Escherichia coli. In this paper, we have used hG31P as a novel fusion protein for the expression and purification of P-113. The purity of the expressed P-113 is more than 95% and the yield is 4 mg P-113 per liter of E. coli cell culture in Luria-Bertani (LB) medium. The antimicrobial activity of the purified P-113 was tested. Furthermore, we used circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy to study the structural properties of P-113. Our results indicate that using hG31P as a fusion protein to obtain large quantities of P-113 is feasible and is easy to scale up for commercial production. An effective way of producing enough P-113 for future clinical studies is evident in this study. Full article

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13 pages, 14389 KiB

Open AccessArticle

Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic Peptide CIGB-552 and Its Relationship with Tumor Cell Line Sensitivity

by Soledad Astrada, Julio Raúl Fernández Massó, Maribel G. Vallespí and Mariela Bollati-Fogolín

Molecules 2018, 23(4), 801; https://doi.org/10.3390/molecules23040801 - 30 Mar 2018

Cited by 10 | Viewed by 4218

Abstract

CIGB-552 is a twenty-amino-acid novel synthetic peptide that has proven to be effective in reducing tumor size and increasing lifespan in tumor-bearing mice. Such capability is conferred by its cell-penetrating peptide character, which allows it to enter cells and elicit a pro-apoptotic effect [...] Read more.

CIGB-552 is a twenty-amino-acid novel synthetic peptide that has proven to be effective in reducing tumor size and increasing lifespan in tumor-bearing mice. Such capability is conferred by its cell-penetrating peptide character, which allows it to enter cells and elicit a pro-apoptotic effect through its major mediator, COMMD1 protein. Cell-penetrating peptides are able to use different internalization mechanisms, such as endocytosis or direct transduction through the plasma membrane. Although CIGB-552 cytotoxicity has been evaluated in several non-tumor- and tumor-derived cell lines, no data regarding the relationship between cell line sensitivity, cell penetrating capacity, the internalization mechanisms involved, COMMD1 expression levels, or its subcellular localization has yet been produced. Here, we present the results obtained from a comparative analysis of CIGB-552 sensitivity, internalization capacity and the mechanisms involved in three human tumor-derived cell lines from different origins: mammary gland, colon and lung (MCF-7, HT-29 and H460, respectively). Furthermore, cell surface markers relevant for internalization processes such as phosphatidylserine, as well as CIGB-552 target COMMD1 expression/localization, were also evaluated. We found that both endocytosis and transduction are involved in CIGB-552 internalization in the three cell lines evaluated. However, CIGB-552 incorporation efficiency and contribution of each mechanism is cell-line dependent. Finally, sensitivity was directly correlated with high internalization capacity in those cell lines where endocytosis had a major contribution on CIGB-552 internalization. Full article

(This article belongs to the Special Issue Peptide Therapeutics)

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14 pages, 9672 KiB

Open AccessArticle

Expression Stabilities of Ten Candidate Reference Genes for RT-qPCR in Zanthoxylum bungeanum Maxim

by Xitong Fei, Qianqian Shi, Tuxi Yang, Zhaoxue Fei and Anzhi Wei

Molecules 2018, 23(4), 802; https://doi.org/10.3390/molecules23040802 - 30 Mar 2018

Cited by 48 | Viewed by 3798

Abstract

Real-time reverse transcription quantitative PCR has become a common method for studying gene expression, however, the optimal selection of stable reference genes is a prerequisite for obtaining accurate quantification of transcript abundance. Suitable reference genes for RT-qPCR have not yet been identified for [...] Read more.

Real-time reverse transcription quantitative PCR has become a common method for studying gene expression, however, the optimal selection of stable reference genes is a prerequisite for obtaining accurate quantification of transcript abundance. Suitable reference genes for RT-qPCR have not yet been identified for Chinese prickly ash (Zanthoxylum bungeanum Maxim.). Chinese prickly ash is the source of an important food seasoning in China. In recent years, Chinese prickly ash has also been developed as a medicinal plant. The expression stabilities of ten genes (18S, 28S, EF, UBA, UBQ, TIF, NTB, TUA, RPS, and TIF5A) were evaluated in roots, stems, leaves, flowers and fruits at five developmental stages and also under stress from cold, drought, and salt. To do this we used three different statistical algorithms: geNorm, NormFinder and BestKeeper. Among the genes investigated, UBA and UBQ were found to be most stable for the different cultivars and different tissues examined, UBQ and TIF for fruit developmental stage. Meanwhile, EF and TUA were most stable under cold treatment, EF and UBQ under drought treatment and NTB and RPS under salt treatment. UBA and UBQ for all samples evaluated were most stably expressed, but 18S, TUA and RPS were found to be generally unreliable as reference genes. Our results provide a basis for the future selection of reference genes for biological research with Chinese prickly ash, under a variety of conditions. Full article

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15 pages, 10783 KiB

Open AccessArticle

Identification and Comparison of Constituents of Aurantii Fructus and Aurantii Fructus Immaturus by UFLC-DAD-Triple TOF-MS/MS

by Yang Bai, Yuying Zheng, Wenjing Pang, Wei Peng, Hao Wu, Hongliang Yao, Panlin Li, Wen Deng, Jinle Cheng and Weiwei Su

Molecules 2018, 23(4), 803; https://doi.org/10.3390/molecules23040803 - 30 Mar 2018

Cited by 34 | Viewed by 5451

Abstract

Although Aurantii Fructus (AF) and Aurantii Fructus Immaturus (AFI) are both the fruits of the same rutaceae plant at different stages of growth, they exert similar yet distinct clinical effects. The chemical composition is crucial for quality control as well as therapeutic application. [...] Read more.

Although Aurantii Fructus (AF) and Aurantii Fructus Immaturus (AFI) are both the fruits of the same rutaceae plant at different stages of growth, they exert similar yet distinct clinical effects. The chemical composition is crucial for quality control as well as therapeutic application. To address this concern, it is significant to evaluate the similarities and differences of the constituents in both AF and AFI. The extract of AF and AFI were comprehensively analyzed by ultra fast liquid chromatography-photodiode array detector-triple-time of flight-tandem mass spectrometry (UFLC-DAD-Triple TOF-MS/MS). Among the 40 compounds detected, 19 metabolites were detected in both the AF and AFI; whereas 13 compounds were only detected in AF and five constituents were exclusively detected in AFI. In particular, even in AFI, three compounds were only identified in AFI (Citrus aurantium’ L. and its cultivar). Among the 18 compounds confirmed by standard database, 13 compounds were reported in AF and AFI for the first time. Furthermore, the distinction was also revealed by the content of naringin, hesperidin, neohesperidin, and synephrine. The study directly contributed to the similarities and differences of AF and AFI. Herein, similarities and the differences in chemical profiles of AF and AFI could explain the current clinical applications. Full article

(This article belongs to the Section Analytical Chemistry)

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16 pages, 27897 KiB

Open AccessArticle

Synthesis and Fluorescence Properties of a New Heterotrinuclear Co(II)-Ce(III)Complex Constructed from a bis(salamo)-Type Tetraoxime Ligand

by Lu-Mei Pu, Qing Zhao, Ling-Zhi Liu, Han Zhang, Hai-Tao Long and Wen-Kui Dong

Molecules 2018, 23(4), 804; https://doi.org/10.3390/molecules23040804 - 31 Mar 2018

Cited by 4 | Viewed by 5102

Abstract

[Co₂(L)Ce(OAc)₃(CH₃CH₂OH)]·1.5CH₃OH∙0.5CH₂Cl₂, a heterotrinuclear Co(II)-Ce(III) bis(salamo)-type complex with a symmetric bi(salamo)-type ligand H₄L and an acyclic naphthalenediol moiety, was designed, synthesized and characterized by elemental analyses, FT-IR, UV-Vis [...] Read more.

[Co₂(L)Ce(OAc)₃(CH₃CH₂OH)]·1.5CH₃OH∙0.5CH₂Cl₂, a heterotrinuclear Co(II)-Ce(III) bis(salamo)-type complex with a symmetric bi(salamo)-type ligand H₄L and an acyclic naphthalenediol moiety, was designed, synthesized and characterized by elemental analyses, FT-IR, UV-Vis and fluorescence spectroscopy and X-ray crystallography. The X-ray crystallographic investigation revealed the heterotrinuclear complex consisted of two Co(II) atoms, one Ce(III) atom, one (L)^4‒ unit, three μ₂-acetate ions, one coordinated ethanol molecule, one and half crystallization methanol molecule and half crystallization dichloromethane molecule. Two Co(II) atoms located in the N₂O₂ coordination spheres, are both hexacoordinated, with slightly distorted octahedral geometries. The Ce(III) atom is nine-coordinated and located in the O₆ cavity possesses a single square antiprismatic geometry. In addition, supramolecular interactions exist in the Co(II)-Ce(III) complex. Two infinite 2D supramolecular structures are built via intermolecular O–H···O, C–H···O and C–H···π interactions, respectively. Full article

(This article belongs to the Special Issue Metal Complexes of Biological Ligands)

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18 pages, 60645 KiB

Open AccessArticle

Protective Effect of Polyphenol-Rich Extract from Bee Pollen in a High-Fat Diet

by Anna Rzepecka-Stojko, Agata Kabała-Dzik, Robert Kubina, Krzysztof Jasik, Maciej Kajor, Dorota Wrześniok and Jerzy Stojko

Molecules 2018, 23(4), 805; https://doi.org/10.3390/molecules23040805 - 31 Mar 2018

Cited by 20 | Viewed by 8100

Abstract

We have studied a preventive effect of polyphenol-rich bee pollen ethanol extract (EEP) against histological changes in the liver and cardiac blood vessels, abnormalities of lipid profile, and the levels of oxidized low density lipoproteins (ox-LDL), asymmetric dimethylarginine (ADMA), angiotensin-converting enzyme (ACE), and [...] Read more.

We have studied a preventive effect of polyphenol-rich bee pollen ethanol extract (EEP) against histological changes in the liver and cardiac blood vessels, abnormalities of lipid profile, and the levels of oxidized low density lipoproteins (ox-LDL), asymmetric dimethylarginine (ADMA), angiotensin-converting enzyme (ACE), and angiotensin II (ANG II) caused by a high-fat diet in C₅₇BL₆ mice. Supplementing the diet with EEP in the doses of 0.1 g/kg body mass (BM) and 1 g/kg BM resulted in a decrease of total cholesterol by 31% and 35%, respectively. It also decreased the level of low density lipoproteins by 67% and 90%, respectively. No differences in the levels of high density lipoprotein and triacylglycerols were observed. EEP reduced the level of ox-LDL by 33% and 47%, ADMA by 13% and 51%, ACE by 17% and 30%, as well as ANG II by 11% and 15% in a dose-dependent manner, which proves a protective effect of EEP in a high-fat diet. EEP reduces and/or prevents hepatic steatosis and degenerative changes caused by a high-fat diet in C₅₇BL₆ mice, which indicates its hepatoprotective effect. EEP used with standard feed does not disturb a normal concentration of the assayed parameters. Full article

(This article belongs to the Special Issue The Antioxidant Capacities of Natural Products)

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15 pages, 14753 KiB

Open AccessArticle

High Glucose-Induced Cardiomyocyte Death May Be Linked to Unbalanced Branched-Chain Amino Acids and Energy Metabolism

by Xi Zhang, Qiuting Lin, Jiuxia Chen, Tingting Wei, Chen Li, Liangcai Zhao, Hongchang Gao and Hong Zheng

Molecules 2018, 23(4), 807; https://doi.org/10.3390/molecules23040807 - 1 Apr 2018

Cited by 23 | Viewed by 5410

Abstract

High glucose-induced cardiomyocyte death is a common symptom in advanced-stage diabetic patients, while its metabolic mechanism is still poorly understood. The aim of this study was to explore metabolic changes in high glucose-induced cardiomyocytes and the heart of streptozotocin-induced diabetic rats by ¹ [...] Read more.

High glucose-induced cardiomyocyte death is a common symptom in advanced-stage diabetic patients, while its metabolic mechanism is still poorly understood. The aim of this study was to explore metabolic changes in high glucose-induced cardiomyocytes and the heart of streptozotocin-induced diabetic rats by ¹H-NMR-based metabolomics. We found that high glucose can promote cardiomyocyte death both in vitro and in vivo studies. Metabolomic results show that several metabolites exhibited inconsistent variations in vitro and in vivo. However, we also identified a series of common metabolic changes, including increases in branched-chain amino acids (BCAAs: leucine, isoleucine and valine) as well as decreases in aspartate and creatine under high glucose condition. Moreover, a reduced energy metabolism could also be a common metabolic characteristic, as indicated by decreases in ATP in vitro as well as AMP, fumarate and succinate in vivo. Therefore, this study reveals that a decrease in energy metabolism and an increase in BCAAs metabolism could be implicated in high glucose-induced cardiomyocyte death. Full article

(This article belongs to the Section Metabolites)

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16 pages, 4661 KiB

Open AccessArticle

²⁷Al NMR Study of the pH Dependent Hydrolysis Products of Al₂(SO₄)₃ in Different Physiological Media

by Svend Berger, Jürgen Nolde, Timucin Yüksel, Wolfgang Tremel and Mihail Mondeshki

Molecules 2018, 23(4), 808; https://doi.org/10.3390/molecules23040808 - 2 Apr 2018

Cited by 6 | Viewed by 5888

Abstract

Soluble inorganic aluminium compounds like aluminium sulfate or aluminium chloride have been challenged by the European Chemical Agency to induce germ cell mutagenicity. Before conducting mutagenicity tests, the hydrolysis products in water and in physiological solutions should be determined as a function of [...] Read more.

Soluble inorganic aluminium compounds like aluminium sulfate or aluminium chloride have been challenged by the European Chemical Agency to induce germ cell mutagenicity. Before conducting mutagenicity tests, the hydrolysis products in water and in physiological solutions should be determined as a function of the concentration and pH. We used different ²⁷Al NMR spectroscopic techniques (heteronuclear Overhauser effect spectroscopy (HOESY), exchange spectroscopy (EXSY), diffusion ordered (DOSY)) in this work to gain the information to study the aluminium species in solutions with Al₂(SO₄)₃ concentrations of 50.0, 5.0, and 0.5 g/L and their pH and time dependent transformation. At low pH, three different species were present in all physiological solutions and water: [Al(OH)_n(H₂O)_{6 − n}]^{(3 − n)+} (n = 0–2), [Al(H₂O)₅SO₄]⁺, and [Al₂(OH)₂(H₂O)₈]⁴⁺. Increasing pH reduced the amounts of the two monomer species, with a complete loss at pH 5 for solutions with a concentration of 50.0 g/L and at pH 4 for solutions with a concentration of 5.0 g/L. The dimer species [Al₂(OH)₂(H₂O)₈]⁴⁺ is present in a pH range between 3 and 6. Less symmetric oligomeric and probably asymmetric aluminium species are formed at pH of 5 and 6. The pH value is the driving force for the formation of aluminium species in all media, whereas the specific medium had only minor effect. No conclusive information could be obtained at pH 7 due to signal loss related to fast quadrupole relaxation of asymmetric aluminium species. A slight reduction of the content of the symmetric aluminium species due to the formation of oligomeric species was observed over a period of 6 weeks. Reference ²⁷Al NMR experiments conducted on saturated water solutions of AlCl₃ and those with a concentration of 50 g/L show that the type of salt/counter ion at the same concentration and pH influences the hydrolysis products formed. Full article

(This article belongs to the Section Inorganic Chemistry)

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13 pages, 5990 KiB

Open AccessArticle

VpStyA1/VpStyA2B of Variovorax paradoxus EPS: An Aryl Alkyl Sulfoxidase Rather than a Styrene Epoxidizing Monooxygenase

by Dirk Tischler, Ringo Schwabe, Lucas Siegel, Kristin Joffroy, Stefan R. Kaschabek, Anika Scholtissek and Thomas Heine

Molecules 2018, 23(4), 809; https://doi.org/10.3390/molecules23040809 - 2 Apr 2018

Cited by 20 | Viewed by 3819

Abstract

Herein we describe the first representative of an E2-type two-component styrene monooxygenase of proteobacteria. It comprises a single epoxidase protein (VpStyA1) and a two domain protein (VpStyA2B) harboring an epoxidase (A2) and a FAD-reductase (B) domain. It was annotated [...] Read more.

Herein we describe the first representative of an E2-type two-component styrene monooxygenase of proteobacteria. It comprises a single epoxidase protein (VpStyA1) and a two domain protein (VpStyA2B) harboring an epoxidase (A2) and a FAD-reductase (B) domain. It was annotated as VpStyA1/VpStyA2B of Variovorax paradoxus EPS. VpStyA2B serves mainly as NADH:FAD-oxidoreductase. A K_m of 33.6 ± 4.0 µM for FAD and a k_cat of 22.3 ± 1.1 s⁻¹ were determined and resulted in a catalytic efficiency (k_cat K_m⁻¹) of 0.64 s⁻¹ μM⁻¹. To investigate its NADH:FAD-oxidoreductase function the linker between A2- and B-domain (AREAV) was mutated. One mutant (AAAAA) showed 18.7-fold higher affinity for FAD (k_cat K_m⁻¹ of 5.21 s⁻¹ μM⁻¹) while keeping wildtype NADH-affinity and -oxidation activity. Both components, VpStyA2B and VpStyA1, showed monooxygenase activity on styrene of 0.14 U mg⁻¹ and 0.46 U mg⁻¹, as well as on benzyl methyl sulfide of 1.62 U mg⁻¹ and 3.11 U mg⁻¹, respectively. The high sulfoxidase activity was the reason to test several thioanisole-like substrates in biotransformations. VpStyA1 showed high substrate conversions (up to 95% in 2 h) and produced dominantly (S)-enantiomeric sulfoxides of all tested substrates. The AAAAA-mutant showed a 1.6-fold increased monooxygenase activity. In comparison, the GQWCSQY-mutant did neither show monooxygenase nor efficient FAD-reductase activity. Hence, the linker between the two domains of VpStyA2B has effects on the reductase as well as on the monooxygenase performance. Overall, this monooxygenase represents a promising candidate for biocatalyst development and studying natural fusion proteins. Full article

(This article belongs to the Special Issue Flavoenzymes)

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15 pages, 5947 KiB

Open AccessArticle

Coumarin Content, Morphological Variation, and Molecular Phylogenetics of Melilotus

by Jiyu Zhang, Hongyan Di, Kai Luo, Zulfi Jahufer, Fan Wu, Zhen Duan, Alan Stewart, Zhuanzhuan Yan and Yanrong Wang

Molecules 2018, 23(4), 810; https://doi.org/10.3390/molecules23040810 - 2 Apr 2018

Cited by 27 | Viewed by 5493

Abstract

Melilotus albus and Melilotus officinalis are widely used in forage production and herbal medicine due to the biological activity of their coumarins, which have many biological and pharmacological activities, including anti-HIV and anti-tumor effects. To comprehensively evaluate M. albus and M. officinalis coumarin [...] Read more.

Melilotus albus and Melilotus officinalis are widely used in forage production and herbal medicine due to the biological activity of their coumarins, which have many biological and pharmacological activities, including anti-HIV and anti-tumor effects. To comprehensively evaluate M. albus and M. officinalis coumarin content (Cou), morphological variation, and molecular phylogeny, we examined the Cou, five morphological traits and the molecular characterization based on the trnL-F spacer and internal transcribed spacer (ITS) regions of 93 accessions. Significant (p < 0.05) variation was observed in the Cou and all five morphological traits in both species. Analysis of population differentiation (Pst) of the phenotypic traits showed that powdery mildew resistance (PMR) had the greatest Pst, meaning that this trait demonstrated the largest genetic differentiation among the accessions. The Pst values of dry matter yield (DMY) and Cou were relatively high. Biplot analysis identified accessions with higher DMY and higher and lower Cou. Analysis of molecular sequence variation identified seven haplotypes of the trnL-F spacer and 13 haplotypes of the ITS region. Based on haplotype and sequence analyses, the genetic variation of M. officinalis was higher than that of M. albus. Additionally, ITS sequence analysis showed that the variation among accessions was larger than that among species across three geographical areas: Asia, Europe, and North America. Similarly, variation among accessions for both the trnL-F and ITS sequences were larger than the differences between the geographical areas. Our results indicate that there has been considerable gene flow between the two Melilotus species. Our characterization of Cou and the morphological and genetic variations of these two Melilotus species may provide useful insights into germplasm improvement to enhance DMY and Cou. Full article

(This article belongs to the Collection Herbal Medicine Research)

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14 pages, 12033 KiB

Open AccessArticle

Combination of Superheated Steam with Laccase Pretreatment Together with Size Reduction to Enhance Enzymatic Hydrolysis of Oil Palm Biomass

by Nur Fatin Athirah Ahmad Rizal, Mohamad Faizal Ibrahim, Mohd Rafein Zakaria, Ezyana Kamal Bahrin, Suraini Abd-Aziz and Mohd Ali Hassan

Molecules 2018, 23(4), 811; https://doi.org/10.3390/molecules23040811 - 2 Apr 2018

Cited by 18 | Viewed by 4480

Abstract

The combination of superheated steam (SHS) with ligninolytic enzyme laccase pretreatment together with size reduction was conducted in order to enhance the enzymatic hydrolysis of oil palm biomass into glucose. The oil palm empty fruit bunch (OPEFB) and oil palm mesocarp fiber (OPMF) [...] Read more.

The combination of superheated steam (SHS) with ligninolytic enzyme laccase pretreatment together with size reduction was conducted in order to enhance the enzymatic hydrolysis of oil palm biomass into glucose. The oil palm empty fruit bunch (OPEFB) and oil palm mesocarp fiber (OPMF) were pretreated with SHS and ground using a hammer mill to sizes of 2, 1, 0.5 and 0.25 mm before pretreatment using laccase to remove lignin. This study showed that reduction of size from raw to 0.25 mm plays important role in lignin degradation by laccase that removed 38.7% and 39.6% of the lignin from OPEFB and OPMF, respectively. The subsequent saccharification process of these pretreated OPEFB and OPMF generates glucose yields of 71.5% and 63.0%, which represent a 4.6 and 4.8-fold increase, respectively, as compared to untreated samples. This study showed that the combination of SHS with laccase pretreatment together with size reduction could enhance the glucose yield. Full article

(This article belongs to the Special Issue Efficient Technology for the Pretreatment of Biomass)

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15 pages, 7399 KiB

Open AccessArticle

Oligo-Alginate with Low Molecular Mass Improves Growth and Physiological Activity of Eucomis autumnalis under Salinity Stress

by Piotr Salachna, Monika Grzeszczuk, Edward Meller and Marcin Soból

Molecules 2018, 23(4), 812; https://doi.org/10.3390/molecules23040812 - 2 Apr 2018

Cited by 58 | Viewed by 6975

Abstract

Biopolymers have become increasingly popular as biostimulators of plant growth. One of them, oligo-alginate, is a molecule that regulates plant biological processes and may be used in horticultural practice as a plant growth regulator. Biostimulators are mainly used to improve plant tolerance to [...] Read more.

Biopolymers have become increasingly popular as biostimulators of plant growth. One of them, oligo-alginate, is a molecule that regulates plant biological processes and may be used in horticultural practice as a plant growth regulator. Biostimulators are mainly used to improve plant tolerance to abiotic stresses, including salinity. The aim of the study was to assess the effects of salinity and oligo-alginate of various molecular masses on the growth and physiological activity of Eucomis autumnalis. The species is an ornamental and medicinal plant that has been used for a long time in the traditional medicine of South Africa. The bulbs of E. autumnalis were coated using depolymerized sodium alginate of molecular mass 32,000; 42,000, and 64,000 g mol⁻¹. All of these oligo-alginates fractions stimulated plant growth, and the effect was the strongest for the fraction of 32,000 g mol⁻¹. This fraction was then selected for the second stage of the study, when plants were exposed to salt stress evoked by the presence of 100 mM NaCl. We found that the oligo-alginate coating mitigated the negative effects of salinity. Plants treated with the oligomer and watered with NaCl showed smaller reduction in the weight of the above-ground parts and bulbs, pigment content and antioxidant activity as compared with those not treated with the oligo-alginate. The study demonstrated for the first time that low molecular mass oligo-alginate may be used as plant biostimulator that limits negative effects of salinity in E. autumnalis. Full article

(This article belongs to the Special Issue Advances in Biodegradable Polymers)

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13 pages, 10452 KiB

Open AccessArticle

Synthesis, Structural Characterization and Antimicrobial Activity of Cu(II) and Fe(III) Complexes Incorporating Azo-Azomethine Ligand

by Mohammad Azam, Saud I. Al-Resayes, Saikh Mohammad Wabaidur, Mohammad Altaf, Bhaskar Chaurasia, Mahboob Alam, Satyendra Nath Shukla, Pratiksha Gaur, Nader Talmas M. Albaqami, Mohammad Shahidul Islam and Soonheum Park

Molecules 2018, 23(4), 813; https://doi.org/10.3390/molecules23040813 - 2 Apr 2018

Cited by 37 | Viewed by 5176

Abstract

We are reporting a novel azo-azomethine ligand, HL and its complexes with Cu(II) and Fe(III) ions. The ligand and its complexes are characterized by various physico-chemical techniques using C,H,N analyses, FT-IR, ¹H-NMR, ESI-MS and UV-Vis studies. TGA analyses reveal complexes are sufficiently [...] Read more.

We are reporting a novel azo-azomethine ligand, HL and its complexes with Cu(II) and Fe(III) ions. The ligand and its complexes are characterized by various physico-chemical techniques using C,H,N analyses, FT-IR, ¹H-NMR, ESI-MS and UV-Vis studies. TGA analyses reveal complexes are sufficiently stable and undergo two-step degradation processes. The redox behavior of the complexes was evaluated by cyclic voltammetry. Furthermore, the ligand and its complexes were tested for antimicrobial activity against bacterial and fungal strains by determining inhibition zone, minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). The complexes showed moderate antimicrobial activity when tested against Gram +ve and Gram −ve bacterial strains. To obtain insights into the structure of ligand, DFT studies are recorded. The results obtained are quite close to the experimental results. In addition, the energy gap, chemical hardness, softness, electronegativity, electrophilic index and chemical potential were calculated using HOMO, LUMO energy value of ligand. Full article

(This article belongs to the Section Inorganic Chemistry)

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13 pages, 2702 KiB

Open AccessArticle

Antioxidant Activities of Phenolic Metabolites from Flemingia philippinensis Merr. et Rolfe and Their Application to DNA Damage Protection

by Jeong Yoon Kim, Yan Wang, Yeong Hun Song, Zia Uddin, Zuo Peng Li, Yeong Jun Ban and Ki Hun Park

Molecules 2018, 23(4), 816; https://doi.org/10.3390/molecules23040816 - 2 Apr 2018

Cited by 13 | Viewed by 5426

Abstract

F. philippinensis Merr. et Rolfe has been cultivated on a large scale and is widely consumed by local inhabitants as an important nutraceutical, especially against rheumatism which has a deep connection with antioxidants. In this study, a total of 18 different phenolic [...] Read more.

F. philippinensis Merr. et Rolfe has been cultivated on a large scale and is widely consumed by local inhabitants as an important nutraceutical, especially against rheumatism which has a deep connection with antioxidants. In this study, a total of 18 different phenolic metabolite compounds in F. philippinensis were isolated and identified, and evaluated for their antioxidant and DNA damage protection potential. The antioxidant activity of the 18 identified compounds was screened using DPPH, ORAC, hydroxyl and superoxide radical scavenging assays. The antioxidant potential of the compounds was found to differ by functionality and skeleton. However, most compounds showed a good antioxidant potential. In particular, seven of the identified compounds, namely, compounds 2, 3, 6, 10, 11, 15 and 16, showed significant protective effects on pBR322 plasmid DNA against the mutagenic and toxic effects of Fenton’s reaction. The most active compound, compound 2, displayed a dose-dependent DNA damage protection potential in the range of 7.5~60.0 μM. The DNA damage protective effect of the identified compounds was significantly correlated with the hydroxyl radical scavenging activity. Compounds that exhibited effective (IC₅₀ = 5.4~12.5 μg/mL) hydroxyl radical scavenging activity were found to be the ones with higher DNA damage protection potential. Full article

(This article belongs to the Special Issue The Antioxidant Capacities of Natural Products)

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15 pages, 16287 KiB

Open AccessArticle

Discovery of a Manduca sexta Allatotropin Antagonist from a Manduca sexta Allatotropin Receptor Homology Model

by Zhen-Peng Kai, Jing-Jing Zhu, Xi-Le Deng, Xin-Ling Yang and Shan-Shan Chen

Molecules 2018, 23(4), 817; https://doi.org/10.3390/molecules23040817 - 3 Apr 2018

Cited by 4 | Viewed by 3759

Abstract

Insect G protein coupled receptors (GPCRs) have important roles in modulating biology, physiology and behavior. They have been identified as candidate targets for next-generation insecticides, yet these targets have been relatively poorly exploited for insect control. In this study, we present a pipeline [...] Read more.

Insect G protein coupled receptors (GPCRs) have important roles in modulating biology, physiology and behavior. They have been identified as candidate targets for next-generation insecticides, yet these targets have been relatively poorly exploited for insect control. In this study, we present a pipeline of novel Manduca sexta allatotropin (Manse-AT) antagonist discovery with homology modeling, docking, molecular dynamics simulation and structure-activity relationship. A series of truncated and alanine-replacement analogs of Manse-AT were assayed for the stimulation of juvenile hormone biosynthesis. The minimum sequence required to retain potent biological activity is the C-terminal amidated octapeptide Manse-AT (6–13). We identified three residues essential for bioactivity (Thr⁴, Arg6 and Phe⁸) by assaying alanine-replacement analogs of Manse-AT (6–13). Alanine replacement of other residues resulted in reduced potency but bioactivity was retained. The 3D structure of the receptor (Manse-ATR) was built and the binding pocket was identified. The binding affinities of all the analogs were estimated by calculating the free energy of binding. The calculated binding affinities corresponded to the biological activities of the analogs, which supporting our localization of the binding pocket. Then, based on the docking and molecular dynamics studies of Manse-AT (10–13), we described it can act as a potent Manse-AT antagonist. The antagonistic effect on JH biosynthesis of Manse-AT (10–13) validated our hypothesis. The IC₅₀ value of antagonist Manse-AT (10–13) is 0.9 nM. The structure-activity relationship of antagonist Manse-AT (10–13) was also studied for the further purpose of investigating theoretically the structure factors influencing activity. These data will be useful for the design of new Manse-AT agonist and antagonist as potential pest control agents. Full article

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11 pages, 22473 KiB

Open AccessArticle

Extraction and Analysis of Gigantol from Dendrobium officinale with Response Surface Methodology

by Siyan Zheng, Yingpeng Zhu, Chunyan Jiao, Mengyao Shi, Lianping Wei, Yang Zhou, Qing Jin and Yongping Cai

Molecules 2018, 23(4), 818; https://doi.org/10.3390/molecules23040818 - 3 Apr 2018

Cited by 16 | Viewed by 4448

Abstract

In order to optimize the extraction of gigantol from Dendrobium officinale, the influence of methanol concentration, ultrasonic temperature, and liquid ratio on extraction efficiency was analysed by the response surface analysis method. The results show that the extraction rate reached a maximum [...] Read more.

In order to optimize the extraction of gigantol from Dendrobium officinale, the influence of methanol concentration, ultrasonic temperature, and liquid ratio on extraction efficiency was analysed by the response surface analysis method. The results show that the extraction rate reached a maximum when the methanol concentration was 92.98%, the solid-liquid ratio was 27.2 mL/g, and the extraction temperature was 41.41 °C. The content of gigantol of Dendrobium officinale in leaves was significantly higher than that in stems, reaching 4.7942 μg/g. The content of gigantol in Dendrobium huoshanensis Fengdou was significantly higher than that of other species of Fengdou. This experiment has practical significance for improving the utilization rate of Dendrobium officinale, and provides a reference for the study of the pharmacological and biological activity of gigantol. Full article

(This article belongs to the Special Issue Bioactives from Bioprocessing: Sources and Production)

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11 pages, 17865 KiB

Open AccessArticle

Role of Phenolic Acids from the Rhizosphere Soils of Panax notoginseng as a Double-Edge Sword in the Occurrence of Root-Rot Disease

by Ya-Meng Zhao, Yong-Xian Cheng, Yu-Nan Ma, Chuan-Jiao Chen, Fu-Rong Xu and Xian Dong

Molecules 2018, 23(4), 819; https://doi.org/10.3390/molecules23040819 - 3 Apr 2018

Cited by 40 | Viewed by 4259

Abstract

Chemical agents in the rhizosphere soils of plants might have an influence on root-rot disease, which therefore might reveal the mechanism of root rot in Panax notoginseng (P. notoginseng). With this hypothesis the alterations of phenolic acids (PAs) in the rhizosphere [...] Read more.

Chemical agents in the rhizosphere soils of plants might have an influence on root-rot disease, which therefore might reveal the mechanism of root rot in Panax notoginseng (P. notoginseng). With this hypothesis the alterations of phenolic acids (PAs) in the rhizosphere soils of P. notoginseng after pathogen infection were determined. The effects of PAs on the growth of Fusarium oxysporum (F. oxysporum), a fungal pathogenic factor for P. notoginseng, as well as production of fusaric acid, a wilting agent for the plants, were also examined. The results indicate the presence of five PAs (ferulic acid, syringic acid, p-hydroxybenzoic acid, p-coumaric acid, and vanillic acid) in the rhizosphere soils of P. notoginseng, whose contents in the rhizosphere soils of healthy plants are higher than those of the diseased ones. Further we found that individual PA could inhibit the mycelium growth and spore production of F. oxysporum, but stimulate fusaric acid production as well, disclosing the double-edge sword role of PAs in the occurrence of root rot of P. notoginseng and paving the way for the intervention of P. notoginseng root rot via balancing PAs. Full article

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17 pages, 30721 KiB

Open AccessArticle

Effect of Red and Blue Light on Anthocyanin Accumulation and Differential Gene Expression in Strawberry (Fragaria × ananassa)

by Yunting Zhang, Leiyu Jiang, Yali Li, Qing Chen, Yuntian Ye, Yong Zhang, Ya Luo, Bo Sun, Xiaorong Wang and Haoru Tang

Molecules 2018, 23(4), 820; https://doi.org/10.3390/molecules23040820 - 3 Apr 2018

Cited by 108 | Viewed by 10492

Abstract

Light conditions can cause quantitative and qualitative changes in anthocyanin. However, little is known about the underlying mechanism of light quality-regulated anthocyanin accumulation in fruits. In this study, light-emitting diodes (LEDs) were applied to explore the effect of red and blue light on [...] Read more.

Light conditions can cause quantitative and qualitative changes in anthocyanin. However, little is known about the underlying mechanism of light quality-regulated anthocyanin accumulation in fruits. In this study, light-emitting diodes (LEDs) were applied to explore the effect of red and blue light on strawberry coloration. The results showed contents of total anthocyanins (TA), pelargonidin 3-glucoside (Pg3G) and pelargonidin 3-malonylglucoside (Pg3MG) significantly increased after blue and red light treatment. Pg3G was the major anthocyanin component in strawberry fruits, accounting for more than 80% of TA, whereas Pg3MG accounted for a smaller proportion. Comparative transcriptome analysis was conducted using libraries from the treated strawberries. A total of 1402, 5034, and 3764 differentially-expressed genes (DEGs) were identified in three pairwise comparisons (red light versus white light, RL-VS-WL; blue light versus white light, BL-VS-WL; blue light versus red light, BL-VS-RL), respectively. Photoreceptors and light transduction components remained dynamic to up-regulate the expression of regulatory factors and structural genes related to anthocyanin biosynthesis under red and white light, whereas most genes had low expression levels that were not consistent with the highest total anthocyanin content under blue light. Therefore, the results indicated that light was an essential environmental factor for anthocyanin biosynthesis before the anthocyanin concentration reached saturation in strawberry fruits, and blue light could quickly stimulate the accumulation of anthocyanin in the fruit. In addition, red light might contribute to the synthesis of proanthocyanidins by inducing LAR and ANR. Full article

(This article belongs to the Section Metabolites)

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13 pages, 1851 KiB

Open AccessArticle

Synthesis of Novel C-2- or C-15-Labeled BODIPY—Estrone Conjugates

by Ildikó Bacsa, Csilla Konc, Anna Boglárka Orosz, Gábor Kecskeméti, Réka Rigó, Csilla Özvegy-Laczka and Erzsébet Mernyák

Molecules 2018, 23(4), 821; https://doi.org/10.3390/molecules23040821 - 3 Apr 2018

Cited by 7 | Viewed by 4657

Abstract

Novel BODIPY–estrone conjugates were synthesized via Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC). Estrone-alkynes or an estrone-azide as starting compounds were synthesized via Michael addition or Sonogashira reaction as key steps. Fluorescent dyes based on BODIPY-core were provided by azide or alkyne functional groups. Fluorescent labeling [...] Read more.

Novel BODIPY–estrone conjugates were synthesized via Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC). Estrone-alkynes or an estrone-azide as starting compounds were synthesized via Michael addition or Sonogashira reaction as key steps. Fluorescent dyes based on BODIPY-core were provided by azide or alkyne functional groups. Fluorescent labeling of estrone was efficiently achieved at the C-2 or C-15 position. The newly-elaborated coupling procedures might have a broad applicability in the synthesis of fluorescent-labeled estrone conjugates suitable for biological assays. Full article

(This article belongs to the Section Organic Chemistry)

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20 pages, 7363 KiB

Open AccessArticle

Synthesis, Structural Studies and Biological Evaluation of Connections of Thiosemicarbazide, 1,2,4-Triazole and 1,3,4-Thiadiazole with Palmitic Acid

by Michał Jóźwiak, Karolina Stępień, Małgorzata Wrzosek, Wioletta Olejarz, Grażyna Kubiak-Tomaszewska, Anna Filipowska, Wojciech Filipowski and Marta Struga

Molecules 2018, 23(4), 822; https://doi.org/10.3390/molecules23040822 - 3 Apr 2018

Cited by 10 | Viewed by 4049

Abstract

Thirty new derivatives of palmitic acid were efficiently synthesized. All obtained compounds can be divided into three groups of derivatives: Thiosemicarbazides (compounds 1–10), 1,2,4-triazoles (compounds 1a–10a) and 1,3,4-thiadiazoles (compounds 1b–10b) moieties. ¹H-NMR, ¹³ [...] Read more.

Thirty new derivatives of palmitic acid were efficiently synthesized. All obtained compounds can be divided into three groups of derivatives: Thiosemicarbazides (compounds 1–10), 1,2,4-triazoles (compounds 1a–10a) and 1,3,4-thiadiazoles (compounds 1b–10b) moieties. ¹H-NMR, ¹³C-NMR and MS methods were used to confirm the structure of derivatives. All obtained compounds were tested in vitro against a number of microorganisms, including Gram-positive cocci, Gram-negative rods and Candida albicans. Compounds 4, 5, 6, 8 showed significant inhibition against C. albicans. The range of MIC values was 50–1.56 μg/mL. The halogen atom, especially at the 3rd position of the phenyl group was significantly important for antifungal activity. The biological activity against Candida albicans and selected molecular descriptors were used as a basis for QSAR models, that have been determined by means of multiple linear regression. The models have been validated by means of the Leave-One-Out Cross Validation. The obtained QSAR models were characterized by high determination coefficients and good prediction power. Full article

(This article belongs to the Section Chemical Biology)

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14 pages, 1125 KiB

Open AccessArticle

Prediction of Protein-Protein Interactions from Amino Acid Sequences Based on Continuous and Discrete Wavelet Transform Features

by Tao Wang, Liping Li, Yu-An Huang, Hui Zhang, Yahong Ma and Xing Zhou

Molecules 2018, 23(4), 823; https://doi.org/10.3390/molecules23040823 - 4 Apr 2018

Cited by 20 | Viewed by 4338

Abstract

Protein-protein interactions (PPIs) play important roles in various aspects of the structural and functional organization of cells; thus, detecting PPIs is one of the most important issues in current molecular biology. Although much effort has been devoted to using high-throughput techniques to identify [...] Read more.

Protein-protein interactions (PPIs) play important roles in various aspects of the structural and functional organization of cells; thus, detecting PPIs is one of the most important issues in current molecular biology. Although much effort has been devoted to using high-throughput techniques to identify protein-protein interactions, the experimental methods are both time-consuming and costly. In addition, they yield high rates of false positive and false negative results. In addition, most of the proposed computational methods are limited in information about protein homology or the interaction marks of the protein partners. In this paper, we report a computational method only using the information from protein sequences. The main improvements come from novel protein sequence representation by combing the continuous and discrete wavelet transforms and from adopting weighted sparse representation-based classifier (WSRC). The proposed method was used to predict PPIs from three different datasets: yeast, human and H. pylori. In addition, we employed the prediction model trained on the PPIs dataset of yeast to predict the PPIs of six datasets of other species. To further evaluate the performance of the prediction model, we compared WSRC with the state-of-the-art support vector machine classifier. When predicting PPIs of yeast, humans and H. pylori dataset, we obtained high average prediction accuracies of 97.38%, 98.92% and 93.93% respectively. In the cross-species experiments, most of the prediction accuracies are over 94%. These promising results show that the proposed method is indeed capable of obtaining higher performance in PPIs detection. Full article

(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)

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9 pages, 472 KiB

Open AccessCommunication

Discovery of Novel Enhancers of Isoniazid Toxicity in Mycobacterium tuberculosis

by Fabian Lentz, Norbert Reiling, Ana Martins, Joseph Molnár and Andreas Hilgeroth

Molecules 2018, 23(4), 825; https://doi.org/10.3390/molecules23040825 - 4 Apr 2018

Cited by 6 | Viewed by 7354

Abstract

The number of effective first-line antibiotics for the treatment of Mycobacterium tuberculosis infection is strongly limited to a few drugs. Due to emerging resistance against those drugs, second- and third-line antibiotics have been established in therapy with certain problems and also increasing mycobacterial [...] Read more.

The number of effective first-line antibiotics for the treatment of Mycobacterium tuberculosis infection is strongly limited to a few drugs. Due to emerging resistance against those drugs, second- and third-line antibiotics have been established in therapy with certain problems and also increasing mycobacterial resistance. An alternative to such novel drugs or combined therapeutic regimes which may reduce resistance development is finding enhancers of mycobacterial drug effectiveness, especially enhancers that counteract causative resistance mechanisms. Such enhancers may reduce the extracellular drug efflux mediated by bacterial efflux pumps and thus enhance the intracellular drug toxicity. We developed novel 1,4-dihydropyridines (DHPs) as potential efflux pump inhibitors with some determined P-gp affinities. The influence on the antituberculotic drug toxicity has been investigated for three prominent antituberculotic drugs. Exclusive and selective toxicity enhancing effects have been detected for isoniazid (INH) which could be related to certain substituent effects of the 1,4-DHPs. So, structure-dependent activities have been found. Thus, promising enhancers could be identified and a suggested efflux pump inhibition is discussed. Full article

(This article belongs to the Collection Antibiotics & Superbugs: New Strategies to Combat Antimicrobial Resistance)

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11 pages, 17521 KiB

Open AccessArticle

Metabolomic Profiling of the White, Violet, and Red Flowers of Rhododendron schlippenbachii Maxim.

by Chang Ha Park, Hyeon Ji Yeo, Nam Su Kim, Ye Eun Park, Soo-Yun Park, Jae Kwang Kim and Sang Un Park

Molecules 2018, 23(4), 827; https://doi.org/10.3390/molecules23040827 - 4 Apr 2018

Cited by 22 | Viewed by 4606

Abstract

Rhododendron schlippenbachii Maxim. is a garden plant that is also used for natural medicines as a consequence of the biological activities of its diverse metabolites. We accordingly profiled two anthocyanins and 40 primary and secondary metabolites in the three different colored flowers. The [...] Read more.

Rhododendron schlippenbachii Maxim. is a garden plant that is also used for natural medicines as a consequence of the biological activities of its diverse metabolites. We accordingly profiled two anthocyanins and 40 primary and secondary metabolites in the three different colored flowers. The major anthocyanins found in the flowers were cyanidins. The red flowers exhibited the highest accumulation of anthocyanins (1.02 ± 0.02 mg/g dry weight). Principal component analysis was applied to the GC‒TOFMS data. The levels of key tricarboxylic acid cycle intermediates in red flowers, such as succinic acid, fumaric acid, and malic acid, were found to be highly significantly different (p < 0.0001) from those in the flowers of other colors. In this study, we aimed to determine metabolite interactions and phenotypic variation among white, violet, and red flowers of R. schlippenbachii by using gas chromatography time-of-flight mass spectrometry (GC‒TOFMS) and high-performance liquid chromatography (HPLC). Full article

(This article belongs to the Section Metabolites)

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12 pages, 3350 KiB

Open AccessArticle

Study of Photochemical Cytosine to Uracil Transition via Ultrafast Photo-Cross-Linking Using Vinylcarbazole Derivatives in Duplex DNA

by Siddhant Sethi, Shigetaka Nakamura and Kenzo Fujimoto

Molecules 2018, 23(4), 828; https://doi.org/10.3390/molecules23040828 - 4 Apr 2018

Cited by 7 | Viewed by 5843

Abstract

Gene therapies, including genome editing, RNAi, anti-sense technology and chemical DNA editing are becoming major methods for the treatment of genetic disorders. Techniques like CRISPR-Cas9, zinc finger nuclease (ZFN) and transcription activator-like effector-based nuclease (TALEN) are a few such enzymatic techniques. Most enzymatic [...] Read more.

Gene therapies, including genome editing, RNAi, anti-sense technology and chemical DNA editing are becoming major methods for the treatment of genetic disorders. Techniques like CRISPR-Cas9, zinc finger nuclease (ZFN) and transcription activator-like effector-based nuclease (TALEN) are a few such enzymatic techniques. Most enzymatic genome editing techniques have their disadvantages. Thus, non-enzymatic and non-invasive technologies for nucleic acid editing has been reported in this study which might possess some advantages over the older methods of DNA manipulation. 3-cyanovinyl carbazole (^CNVK) based nucleic acid editing takes advantage of photo-cross-linking between a target pyrimidine and the ^CNVK to afford deamination of cytosine and convert it to uracil. This method previously required the use of high temperatures but, in this study, it has been optimized to take place at physiological conditions. Different counter bases (inosine, guanine and cytosine) complementary to the target cytosine were used, along with derivatives of ^CNVK (^NH2VK and ^OHVK) to afford the deamination at physiological conditions. Full article

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18 pages, 14118 KiB

Open AccessArticle

Exosome-Mediated Transfer of Cancer Cell Resistance to Antiestrogen Drugs

by Svetlana E. Semina, Alexander M. Scherbakov, Anna A. Vnukova, Dmitry V. Bagrov, Evgeniy G. Evtushenko, Vera M. Safronova, Daria A. Golovina, Ludmila N. Lyubchenko, Margarita V. Gudkova and Mikhail A. Krasil’nikov

Molecules 2018, 23(4), 829; https://doi.org/10.3390/molecules23040829 - 4 Apr 2018

Cited by 52 | Viewed by 7652

Abstract

Exosomes are small vesicles which are produced by the cells and released into the surrounding space. They can transfer biomolecules into recipient cells. The main goal of the work was to study the exosome involvement in the cell transfer of hormonal resistance. The [...] Read more.

Exosomes are small vesicles which are produced by the cells and released into the surrounding space. They can transfer biomolecules into recipient cells. The main goal of the work was to study the exosome involvement in the cell transfer of hormonal resistance. The experiments were performed on in vitro cultured estrogen-dependent MCF-7 breast cancer cells and MCF-7 sublines resistant to SERM tamoxifen and/or biguanide metformin, which exerts its anti-proliferative effect, at least in a part, via the suppression of estrogen machinery. The exosomes were purified by differential ultracentrifugation, cell response to tamoxifen was determined by MTT test, and the level and activity of signaling proteins were determined by Western blot and reporter analysis. We found that the treatment of the parent MCF-7 cells with exosomes from the resistant cells within 14 days lead to the partial resistance of the MCF-7 cells to antiestrogen drugs. The primary resistant cells and the cells with the exosome-induced resistance were characterized with these common features: decrease in ERα activity and parallel activation of Akt and AP-1, NF-κB, and SNAIL1 transcriptional factors. In general, we evaluate the established results as the evidence of the possible exosome involvement in the transferring of the hormone/metformin resistance in breast cancer cells. Full article

(This article belongs to the Special Issue Selective Estrogen Receptor Modulators and Downregulators (SERMs and SERDs): New Possibilities in Developing Next Generation Hormone Therapies for Breast Cancer)

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13 pages, 2114 KiB

Open AccessArticle

Synthesis and Anticandidal Activity of New Imidazole-Chalcones

by Derya Osmaniye, Betul Kaya Cavusoglu, Begum Nurpelin Saglik, Serkan Levent, Ulviye Acar Cevik, Ozlem Atli, Yusuf Ozkay and Zafer Asim Kaplancikli

Molecules 2018, 23(4), 831; https://doi.org/10.3390/molecules23040831 - 4 Apr 2018

Cited by 22 | Viewed by 6516

Abstract

In the present work, 15 new 1-(4-(1H-imidazol-1-yl)phenyl)-3-(4-substituedphenyl)prop-2-en-1-one derivatives (3a–3o) were synthesized to evaluate their antifungal activity. Structures of newly synthesized imidazole derivatives (3a–3o) were characterized by IR, ¹H-NMR, ¹³C-NMR, and LCMSMS [...] Read more.

In the present work, 15 new 1-(4-(1H-imidazol-1-yl)phenyl)-3-(4-substituedphenyl)prop-2-en-1-one derivatives (3a–3o) were synthesized to evaluate their antifungal activity. Structures of newly synthesized imidazole derivatives (3a–3o) were characterized by IR, ¹H-NMR, ¹³C-NMR, and LCMSMS spectroscopic methods. The anticandidal activity of compounds (3a–3o) against C. albicans (ATCC 24433), C. krusei (ATCC 6258), C. parapsilosis (ATCC 22019), and C. glabrata (ATCC 90030) was elucidated according to the EUCAST definitive (EDef 7.1) method. Consistent with the activity studies, 3a–3d were found to be more potent derivatives with their MIC₅₀ values (0.78 µg/mL–3.125 µg/mL) against Candida strains. Compound 3c indicated similar antifungal activity to ketoconazole against all Candida species and was evaluated as the most active derivative in the series. Effects of the most potent derivatives 3a–3d on ergosterol biosynthesis were observed by LC-MS-MS method, which is based on quantification of the ergosterol level in C. krusei. Moreover, these compounds were subjected to a cytotoxicity test for the preliminary toxicological profiles and were found as non-cytotoxic. Furthermore, docking studies for the most active derivative 3c were performed to evaluate its binding modes on lanosterol 14-α-demethylase. In addition to in vitro tests, docking studies also revealed that Compound 3c is a potential ergosterol biosynthesis inhibitor. Full article

(This article belongs to the Special Issue Chalcone: A Privileged Structure in Medicinal Chemistry)

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12 pages, 2376 KiB

Open AccessArticle

Single Nucleotide Polymorphisms in HMGB1 Correlate with Lung Cancer Risk in the Northeast Chinese Han Population

by Min Jiang, Xuelian Li, Xiaowei Quan, Xiaoying Li and Baosen Zhou

Molecules 2018, 23(4), 832; https://doi.org/10.3390/molecules23040832 - 4 Apr 2018

Cited by 10 | Viewed by 6283

Abstract

Lung cancer is the principal cause of cancer-associated deaths. HMGB1 has been reported to be associated with tumorigenesis. This study aimed to investigate the relationship between rs1412125 and rs1360485 polymorphisms in HMGB1 and the risk and survival of lung cancer. 850 cases and [...] Read more.

Lung cancer is the principal cause of cancer-associated deaths. HMGB1 has been reported to be associated with tumorigenesis. This study aimed to investigate the relationship between rs1412125 and rs1360485 polymorphisms in HMGB1 and the risk and survival of lung cancer. 850 cases and 733 controls were included. Logistic regression analysis and survival analysis were performed to investigate the association between SNPs and the risk and survival of lung cancer. Crossover analysis was used to analyze the interaction between SNPs and tobacco exposure. Results indicated that rs1412125 polymorphism was associated with lung cancer risk, especially with the risk of lung adenocarcinoma and small cell lung cancer. Carriers with CT and CC genotypes had a decreased risk of lung cancer (CT + CC vs.TT: adjusted OR = 0.736, p = 0.004). Similar results were obtained in the stratification analysis for non-smokers and female population. For rs1360485 polymorphism, AG and GG genotypes could decrease the risk of lung adenocarcinoma and female lung cancer by 0.771-fold and 0.789-fold. However, no significant interaction between polymorphisms and tobacco exposure or association between SNPs and the survival of lung cancer was observed. This study indicated polymorphisms in HMGB1 may be a novel biomarker for female lung adenocarcinoma risk. Full article

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14 pages, 12997 KiB

Open AccessArticle

Flavonoid 8-O-Glucuronides from the Aerial Parts of Malva verticillata and Their Recovery Effects on Alloxan-Induced Pancreatic Islets in Zebrafish

by Jung-Hwan Ko, Youn Hee Nam, Sun-Woo Joo, Hyoung-Geun Kim, Yeong-Geun Lee, Tong Ho Kang and Nam-In Baek

Molecules 2018, 23(4), 833; https://doi.org/10.3390/molecules23040833 - 4 Apr 2018

Cited by 22 | Viewed by 5950

Abstract

Malva verticillata (Cluster mallow), a leafy vegetable that has been popular in East Asia for a long time, has also been used in herbal teas and medicines. The aqueous fraction of the aerial parts of Malva verticillata, exhibiting a very high quantity [...] Read more.

Malva verticillata (Cluster mallow), a leafy vegetable that has been popular in East Asia for a long time, has also been used in herbal teas and medicines. The aqueous fraction of the aerial parts of Malva verticillata, exhibiting a very high quantity of flavonoids compared to the EtOAc and n-BuOH fractions, exhibited significant recovery effects on pancreatic islets damaged by alloxan in zebrafish larvae. Thus, the bioactive components responsible for this anti-diabetic activity were investigated. A new flavonoid glucuronide (1) and five known flavonoids were isolated from the aqueous fraction. Based on several spectroscopic methods, compound 1 was identified to be nortangeretin-8-O-β-d-glucuronide, and was named malvaflavone A. The A-ring of compound 1 had a 5,6,7,8-tetrahydroxy moiety, which rarely occurs in plant systems. Also 8-O-glucuronide attached to the flavonoid moiety was rarely occurred in plant system. Compounds 1, 3, 4, and 6 significantly improved the pancreatic islet size in zebrafish at 0.1 μM, and compounds 1 and 6 were found to block β-cell K⁺ channels in experiments with diazoxide. In ABTS, ORAC, and SOD assays, compounds 1–5 exhibited high anti-oxidant activities compared with quercetin and BHA (positive controls), indicating that the 8-O-glucuronide attached to the flavonoid moiety is a key structure for the expression of anti-oxidant activity. This is the first report of the isolation of compounds 1–6 from M. verticillata as well evaluated for anti-diabetic and anti-oxidant ativities. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 6725 KiB

Open AccessArticle

Illumination on “Reserving Phloem and Discarding Xylem” and Quality Evaluation of Radix polygalae by Determining Oligosaccharide Esters, Saponins, and Xanthones

by Fan Yang, Huijuan Yu, Xin Chai, Siwei Peng, Junjun Yang, Dan Wu, Jie Du and Yuefei Wang

Molecules 2018, 23(4), 836; https://doi.org/10.3390/molecules23040836 - 5 Apr 2018

Cited by 15 | Viewed by 4240

Abstract

The root of Polygala tenuifolia Willd. or Polygala sibirica L. exhibits protective effects on the central nervous system and is frequently used to treat insomnia, amnesia, and other cognitive dysfunction. In our study, we studied nine bioactive compounds spanning oligosaccharide esters, saponins, and [...] Read more.

The root of Polygala tenuifolia Willd. or Polygala sibirica L. exhibits protective effects on the central nervous system and is frequently used to treat insomnia, amnesia, and other cognitive dysfunction. In our study, we studied nine bioactive compounds spanning oligosaccharide esters, saponins, and xanthones by using a sensitive, efficient, and validated method established on ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry. The quantified result of interesting compounds proved that accumulation of those compounds were found in phloem rather than in xylem. By taking the standardized result of nine compound contents into account, the “Spider-web” analytical result of xylem and phloem from Radix polygalae (RP) unveiled the rationality of RP’s classical use in clinic including discarding the xylem and reserving the phloem. Moreover, the remarkable variation was also revealed from the quantitative result of 45 samples with different diameters from the different origins, which did not significantly correlate with the variation of RP’s diameter. Our study could shed the light on the quality assessment of RP for further research and illustrate the scientific connotation of the processing method of “discarding the xylem and reserving the phloem”. Full article

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18 pages, 1736 KiB

Open AccessArticle

Indium-Catalyzed Annulation of o-Acylanilines with Alkoxyheteroarenes: Synthesis of Heteroaryl[b]quinolines and Subsequent Transformation to Cryptolepine Derivatives

by Kyohei Yonekura, Mika Shinoda, Yuko Yonekura and Teruhisa Tsuchimoto

Molecules 2018, 23(4), 838; https://doi.org/10.3390/molecules23040838 - 5 Apr 2018

Cited by 23 | Viewed by 5835

Abstract

We disclose herein the first synthetic method that is capable of offering heteroaryl[b]quinolines (HA[b]Qs) with structural diversity, which include tricyclic and tetracyclic structures with (benzo)thienyl, (benzo)furanyl, and indolyl rings. The target HA[b]Q is addressed by the annulation [...] Read more.

We disclose herein the first synthetic method that is capable of offering heteroaryl[b]quinolines (HA[b]Qs) with structural diversity, which include tricyclic and tetracyclic structures with (benzo)thienyl, (benzo)furanyl, and indolyl rings. The target HA[b]Q is addressed by the annulation of o-acylanilines and MeO–heteroarenes with the aid of an indium Lewis acid that effectively works to make two different types of the N–C and C–C bonds in one batch. A series of indolo[3,2-b]quinolines prepared here can be subsequently transformed to structurally unprecedented cryptolepine derivatives. Mechanistic studies showed that the N–C bond formation is followed by the C–C bond formation. The indium-catalyzed annulation reaction thus starts with the nucleophilic attack of the NH₂ group of o-acylanilines to the MeO-connected carbon atom of the heteroaryl ring in an S_NAr fashion, and thereby the N–C bond is formed. The resulting intermediate then cyclizes to make the C–C bond through the nucleophilic attack of the heteroaryl-ring-based carbon atom to the carbonyl carbon atom, providing the HA[b]Q after aromatizing dehydration. Full article

(This article belongs to the Special Issue Indium in Organic Synthesis)

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15 pages, 2469 KiB

Open AccessArticle

A Beneficial Role of Rooibos in Diabetes Mellitus: A Systematic Review and Meta-Analysis

by Moe Sasaki, Nami Nishida and Masako Shimada

Molecules 2018, 23(4), 839; https://doi.org/10.3390/molecules23040839 - 6 Apr 2018

Cited by 30 | Viewed by 7822

Abstract

In a rapid increase in cases of diabetes mellitus worldwide, there has been interested in the use of plant-derived polyphenols as nutraceuticals to prevent the onset and progression of diabetes mellitus and its associated complications. Aspalathus linearis, commonly known as rooibos, is [...] Read more.

In a rapid increase in cases of diabetes mellitus worldwide, there has been interested in the use of plant-derived polyphenols as nutraceuticals to prevent the onset and progression of diabetes mellitus and its associated complications. Aspalathus linearis, commonly known as rooibos, is a rich source of uncommon glycosylated plant polyphenols with various critical health-promoting properties, including the prevention and treatment of diabetes mellitus (DM). This study aimed to examine these effects by meta-analyzing the current evidence in diabetic rodent models. Peer-reviewed studies written in English from two databases, PubMed and Embase, were searched up to 28 February 2018. Studies reporting blood glucose levels in diabetic rodents with and without receiving rooibos extracts or their major phenolic compounds are included. Twelve studies enrolling 88 diabetic rodents treated with rooibos extracts or their polyphenols and 85 diabetic control males reported blood glucose levels. The pooled effect size was −0.89 (95% CI: −1.44 to −0.35) with a substantial heterogeneity (I² = 67.0%). This effect was likely to be modified by type of rooibos extracts and their polyphenols and treatment period. Blood glucose levels were significantly lower in diabetic rodent models treated with the phenolic compound rich in rooibos extracts, PPAG. Full article

(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)

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13 pages, 289 KiB

Open AccessArticle

Antibacterial Activity of Emulsified Pomelo (Citrus grandis Osbeck) Peel Oil and Water-Soluble Chitosan on Staphylococcus aureus and Escherichia coli

by Guan-Wen Chen, Yu-Hsin Lin, Chia-Hua Lin and Hsiao-Chin Jen

Molecules 2018, 23(4), 840; https://doi.org/10.3390/molecules23040840 - 6 Apr 2018

Cited by 24 | Viewed by 7092

Abstract

This study utilized pomelo steam distillation to isolate pomelo peel essential oil. The constituents were then analyzed through gas chromatography-mass spectrometry (GC-MS), and the antibacterial activity of the essential oil emulsions at different homogenizer speed conditions and concentrations of water-soluble chitosan (degree of [...] Read more.

This study utilized pomelo steam distillation to isolate pomelo peel essential oil. The constituents were then analyzed through gas chromatography-mass spectrometry (GC-MS), and the antibacterial activity of the essential oil emulsions at different homogenizer speed conditions and concentrations of water-soluble chitosan (degree of acetylation, DA = 54.8%) against S. aureus and E. coli was examined. Analysis of the essential oil composition identified a total of 33 compounds with the main constituent, limonene accounting for 87.5% (940.07 mg/g) of the total. The pomelo peel oil was emulsified through homogenization at 24,000 rpm, resulting in a minimal inhibitory concentration (MIC) for E. coli that was 1.9 times lower than that of the essential oil without homogenization. In addition, a mixture of 0.4% essential oil emulsion and 0.03% water-soluble chitosan had the strongest synergetic antibacterial effect on S. aureus and E. coli at pH 7.4. In comparison with chitosan alone, the MIC value of this mixture was significantly 2.4 and 2.5 times lower. Hence, this study suggests using a mixture of emulsified pomelo peel oil and water-soluble chitosan to develop a novel natural food preservative, and that the processability of food, as well as the economic value of the byproducts of the Taiwan Matou pomelo and chitosan, could be increased. Full article

(This article belongs to the Special Issue Essential Oils as Antimicrobial and Anti-infectious Agents)

13 pages, 10793 KiB

Open AccessArticle

Treatment of Multidrug-Resistant Leukemia Cells by Novel Artemisinin-, Egonol-, and Thymoquinone-Derived Hybrid Compounds

by Lisa Gruber, Sara Abdelfatah, Tony Fröhlich, Christoph Reiter, Volker Klein, Svetlana B. Tsogoeva and Thomas Efferth

Molecules 2018, 23(4), 841; https://doi.org/10.3390/molecules23040841 - 6 Apr 2018

Cited by 23 | Viewed by 5885

Abstract

Two major obstacles for successful cancer treatment are the toxicity of cytostatics and the development of drug resistance in cancer cells during chemotherapy. Acquired or intrinsic drug resistance is responsible for almost 90% of treatment failure. For this reason, there is an urgent [...] Read more.

Two major obstacles for successful cancer treatment are the toxicity of cytostatics and the development of drug resistance in cancer cells during chemotherapy. Acquired or intrinsic drug resistance is responsible for almost 90% of treatment failure. For this reason, there is an urgent need for new anticancer drugs with improved efficacy against cancer cells, and with less toxicity on normal cells. There are impressive examples demonstrating the success of natural plant compounds to fight cancer, such as Vinca alkaloids, taxanes, and anthracyclines. Artesunic acid (ARTA), a drug for malaria treatment, also exerts cytotoxic activity towards cancer cells. Multidrug resistance often results from drug efflux pumps (ABC-transporters) that reduce intracellular drug levels. Hence, it would be interesting to know, whether ARTA could overcome drug resistance of tumor cells, and in what way ABC-transporters are involved. Different derivatives showing improved features concerning cytotoxicity and pharmacokinetic behavior have been developed. Considering both drug sensitivity and resistance, we chose a sensitive and a doxorubicin-resistant leukemia cell line and determined the killing effect of ARTA on these cells. Molecular docking and doxorubicin efflux assays were performed to investigate the interaction of the derivatives with P-glycoprotein. Using single-cell gel electrophoresis (alkaline comet assay), we showed that the derivatives of ARTA induce DNA breakage and accordingly programmed cell death, which represents a promising strategy in cancer treatment. ARTA activated apoptosis in cancer cells by the iron-mediated generation of reactive oxygen species (ROS). In conclusion, ARTA derivatives may bear the potential to be further developed as anticancer drugs. Full article

(This article belongs to the Special Issue Artemisinin: Against Malaria, Cancer and Viruses)

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12 pages, 4431 KiB

Open AccessArticle

Chemical Characterization of an Encapsulated Red Wine Powder and Its Effects on Neuronal Cells

by Diego Rocha-Parra, Jorge Chirife, Clara Zamora and Sonia De Pascual-Teresa

Molecules 2018, 23(4), 842; https://doi.org/10.3390/molecules23040842 - 7 Apr 2018

Cited by 14 | Viewed by 5096

Abstract

Red wine polyphenols are known for their implications for human health protection, although they suffer from high instability. For this reason, a red wine powder was prepared by freeze-drying encapsulation in maltodextrin/arabic gum matrix, and its composition was determined by means of high-performance [...] Read more.

Red wine polyphenols are known for their implications for human health protection, although they suffer from high instability. For this reason, a red wine powder was prepared by freeze-drying encapsulation in maltodextrin/arabic gum matrix, and its composition was determined by means of high-performance liquid chromatography coupled quadrupole time-of-flight mass spectrometry (HPLC-MS-QTOF). More than thirty polyphenols, including anthocyanins, flavanols, flavonols, phenolic acids and stilbenoids, were identified. Some of the main quantified polyphenols were: malvidin-3-O-glucoside, malvidin 3-O-(6″-acetyl-glucose), petunidin-3-O-glucoside, quercetin-3-O-glucuronide, syringenin-3-O-glucoside, epicatechin, gallic acid and syringic acid. The biological activity of this de-alcoholized and encapsulated red wine on human neuroblastoma SH-SY5Y cells was studied. The results showed that the encapsulated red wine powder has active redox properties, as verified by performing reactive oxygen species (ROS) analysis utilizing a neuronal model. This could help explain its action against the neurotoxicity induced by 6-hydroxydopamine (6-OHDA). Full article

(This article belongs to the Special Issue Dietary Antioxidants: Evidence of Protective Effects against Chronic Disease)

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13 pages, 8356 KiB

Open AccessArticle

Oxadiazole-Based Highly Efficient Bipolar Fluorescent Emitters for Organic Light-Emitting Diodes

by Qiong Wu, Ramanaskanda Braveenth, Heng Qiang Zhang, Il-Ji Bae, Miyoung Kim and Kyu Yun Chai

Molecules 2018, 23(4), 843; https://doi.org/10.3390/molecules23040843 - 7 Apr 2018

Cited by 9 | Viewed by 4299

Abstract

In this study, a series of bipolar fluorescence emitters named 2DPAc-OXD, DPAc-OXD, 2PTZ-OXD and PTZ-OXD were designed and synthesized with excellent yields. The characterization of materials was investigated by using nuclear magnetic resonance (NMR) (¹H, ¹³C), mass spectrometry and thermogravimetric [...] Read more.

In this study, a series of bipolar fluorescence emitters named 2DPAc-OXD, DPAc-OXD, 2PTZ-OXD and PTZ-OXD were designed and synthesized with excellent yields. The characterization of materials was investigated by using nuclear magnetic resonance (NMR) (¹H, ¹³C), mass spectrometry and thermogravimetric analysis (TGA). To investigate device efficiencies, two different OLED devices (Device 1, Device 2) were fabricated with two different host materials (Bepp₂, DPEPO). The Device 2 with 2PTZ-OXD as fluorescent emitter exhibited excellent power and current efficiencies of 6.88 Lm/W and 10.10 cd/A, respectively. The external quantum efficiency of 2PTZ-OXD was around 3.99% for Device 2. The overall device properties of phenothiazine donor were better than acridine derivatives. Full article

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12 pages, 3249 KiB

Open AccessArticle

Optimization of the Ultrasonic-Assisted Extraction of Phenolic Compounds from Oryza Sativa L. ‘Violet Nori’ and Determination of the Antioxidant Properties of its Caryopses and Leaves

by Federica Turrini, Raffaella Boggia, Riccardo Leardi, Matilde Borriello and Paola Zunin

Molecules 2018, 23(4), 844; https://doi.org/10.3390/molecules23040844 - 7 Apr 2018

Cited by 16 | Viewed by 4798

Abstract

‘Violet Nori’ is a new spontaneous growing violet rice variety showing a peculiar violet color in its fresh leaves as well. In this paper, the antioxidant properties and the content of total phenols, radical scavengers, and anthocyanins in ‘Violet Nori’ caryopses, flour, and [...] Read more.

‘Violet Nori’ is a new spontaneous growing violet rice variety showing a peculiar violet color in its fresh leaves as well. In this paper, the antioxidant properties and the content of total phenols, radical scavengers, and anthocyanins in ‘Violet Nori’ caryopses, flour, and leaves are explored and compared. Ultrasonic-Assisted Extraction (UAE) is employed for the extraction of phenolic compounds, improving the extraction conditions by Design of Experiments (DoE). The obtained results show that the Radical Scavenging Activities (RSAs), the Total Phenolic Contents (TPCs), and the anthocyanin amounts (1000–1500 μg/g, expressed as cyanidin-3-glucoside) of ‘Violet Nori’ caryopses are higher than those in the other analyzed colored rice samples (300–900 μg/g as cyanidin-3-glucoside), with the exception of the cultivars ‘Artemide’ and ‘Nerone’, which show comparable values of RSAs and TPCs. The study of ‘Violet Nori’ leaves at different plant maturation stages shows that their anthocyanin content is 2–3 times higher than in the caryopses and in the flour, reaching the highest levels at about 60 days from seeding. Thus, the estimated extraction yield of 4 kg anthocyanins/t makes fresh leaves very interesting for the extraction of anthocyanins on an industrial scale, whereas violet caryopses are a very interesting dietetic source of valuable anthocyanins and other antioxidant compounds. Full article

(This article belongs to the Special Issue The Antioxidant Capacities of Natural Products)

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10 pages, 5401 KiB

Open AccessArticle

Preparation of Ruthenium Dithiolene Complex/Polysiloxane Films and Their Responses to CO Gas

by Satoru Tsukada, Takuya Sagawa, Kazuki Yamamoto and Takahiro Gunji

Molecules 2018, 23(4), 845; https://doi.org/10.3390/molecules23040845 - 7 Apr 2018

Cited by 2 | Viewed by 3494

Abstract

To develop advanced materials using metal complexes, it is better to prepare metal complexes contained in composite or hybrid films. To achieve this purpose, we synthesized ruthenium complexes with dihalogen-substituted benzendithiolate ligands, [(η⁶-C₆Me₆)Ru(S₂C₆H [...] Read more.

To develop advanced materials using metal complexes, it is better to prepare metal complexes contained in composite or hybrid films. To achieve this purpose, we synthesized ruthenium complexes with dihalogen-substituted benzendithiolate ligands, [(η⁶-C₆Me₆)Ru(S₂C₆H₂X₂)] (X = F, 3,6-Cl, Br, 4,5-Cl), 1b–1e. We also investigated preparation of 1c or 1e containing polysiloxane composite films and their reactivity to CO gas. All ruthenium complexes 1b–1e reacted with CO gas, and carbonyl ligand adducts 2b–2e were generated. Ruthenium complexes 1b–1e show two strong absorption peaks around 550 and 420 nm. After exposure to CO gas, these absorption peaks were immediately decreased without a peak shift. A similar trend was observed in 1c or 1e containing polysiloxane composite films. These results indicate that 1c and 1e were easily converted into 2c and 2e, both in the solution and the polysiloxane film during CO gas exposure. Full article

(This article belongs to the Special Issue Coordination Chemistry for Devices and Functional Materials)

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19 pages, 47489 KiB

Open AccessArticle

The Complete Chloroplast Genome of Heimia myrtifolia and Comparative Analysis within Myrtales

by Cuihua Gu, Bin Dong, Liang Xu, Luke R. Tembrock, Shaoyu Zheng and Zhiqiang Wu

Molecules 2018, 23(4), 846; https://doi.org/10.3390/molecules23040846 - 8 Apr 2018

Cited by 26 | Viewed by 6130

Abstract

Heimia myrtifolia is an important medicinal plant with several pharmacologically active alkaloids and is also used as an ornamental landscape plant. The purpose of this study is to complete and characterize the chloroplast (cp) genome of H. myrtifolia and compare genomic features to [...] Read more.

Heimia myrtifolia is an important medicinal plant with several pharmacologically active alkaloids and is also used as an ornamental landscape plant. The purpose of this study is to complete and characterize the chloroplast (cp) genome of H. myrtifolia and compare genomic features to other Myrtales species’ cp genomes. The analysis showed that H. myrtifolia has a total length of 159,219 bp with a typical quadripartite structure containing two identical inverted repeats (IRs) of 25,643 bp isolated by one large single copy (LSC) of 88,571 bp and one small single copy (SSC) of 18,822 bp. The H. myrtifolia cp genome contains 129 genes with eight ribosomal RNAs, 30 transfer RNAs, and 78 protein coding genes, in which 17 genes are duplicated in two IR regions. The genome organization including gene type and number and guanine-cytosine (GC) content is analyzed among the 12 cp genomes in this study. Approximately 255 simple sequence repeats (SSRs) and 16 forward, two reverses, and two palindromic repeats were identified in the H. myrtifolia cp genome. By comparing the whole H. myrtifolia cp genome with 11 other Myrtales species, the results showed that the sequence similarity was high between coding regions while sequence divergence was high between intergenic regions. By employing the full cp genomes for phylogenetic analysis, structural and sequence differences were characterized between H. myrtifolia and 11 Myrtales species illustrating what patterns are common in the evolution of cp genomes within the Myrtales. The first entire cp genome in the genus Heimia provides a valuable resource for further studies in these medicinally and ornamentally important taxa. Full article

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9 pages, 10533 KiB

Open AccessArticle

3,3′-Bicarbazole-Based Host Molecules for Solution-Processed Phosphorescent OLEDs

by Jungwoon Kim, Suhan Lee, Jaemin Lee, Eunhee Lim and Byung Jun Jung

Molecules 2018, 23(4), 847; https://doi.org/10.3390/molecules23040847 - 8 Apr 2018

Cited by 10 | Viewed by 5260

Abstract

Solution-processed organic light-emitting diodes (OLEDs) are attractive due to their low-cost, large area displays, and lighting features. Small molecules as well as polymers can be used as host materials within the solution-processed emitting layer. Herein, we report two 3,3′-bicarbazole-based host small molecules, which [...] Read more.

Solution-processed organic light-emitting diodes (OLEDs) are attractive due to their low-cost, large area displays, and lighting features. Small molecules as well as polymers can be used as host materials within the solution-processed emitting layer. Herein, we report two 3,3′-bicarbazole-based host small molecules, which possess a structural isomer relationship. 9,9′-Di-4-n-butylphenyl-9H,9′H-3,3′-bicarbazole (BCz-nBuPh) and 9,9′-di-4-t-butylphenyl-9H,9′H-3,3′-bicarbazole (BCz-tBuPh) exhibited similar optical properties within solutions but different photoluminescence within films. A solution-processed green phosphorescent OLED with the BCz-tBuPh host exhibited a high maximum current efficiency and power efficiency of 43.1 cd/A and 40.0 lm/W, respectively, compared to the device with the BCz-nBuPh host. Full article

(This article belongs to the Section Organic Chemistry)

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12 pages, 9466 KiB

Open AccessArticle

Extracellular Phytase Production by the Wine Yeast S. cerevisiae (Finarome Strain) during Submerged Fermentation

by Grzegorz Kłosowski, Dawid Mikulski and Oliwia Jankowiak

Molecules 2018, 23(4), 848; https://doi.org/10.3390/molecules23040848 - 8 Apr 2018

Cited by 17 | Viewed by 5450

Abstract

One of the key steps in the production of phytases of microbial origin is selection of culture parameters, followed by isolation of the enzyme and evaluation of its catalytic activity. It was found that conditions for S. cerevisiae yeast culture, strain Finarome, giving [...] Read more.

One of the key steps in the production of phytases of microbial origin is selection of culture parameters, followed by isolation of the enzyme and evaluation of its catalytic activity. It was found that conditions for S. cerevisiae yeast culture, strain Finarome, giving the reduction in phytic acid concentration of more than 98% within 24 h of incubation were as follows: pH 5.5, 32 °C, continuous stirring at 80 rpm, the use of mannose as a carbon source and aspartic acid as a source of nitrogen. The highest catalytic activity of the isolated phytase was observed at 37 °C, pH 4.0 and using phytate as substrate at concentration of 5.0 mM. The presence of ethanol in the medium at a concentration of 12% v/v reduces the catalytic activity to above 60%. Properties of phytase derived from S. cerevisiae yeast culture, strain Finarome, indicate the possibility of its application in the form of a cell’s free crude protein isolate for the hydrolysis of phytic acid to improve the efficiency of alcoholic fermentation processes. Our results also suggest a possibility to use the strain under study to obtain a fusant derived with specialized distillery strains, capable of carrying out a highly efficient fermentation process combined with the utilization of phytates. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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13 pages, 17318 KiB

Open AccessArticle

Sinularin Selectively Kills Breast Cancer Cells Showing G2/M Arrest, Apoptosis, and Oxidative DNA Damage

by Hurng-Wern Huang, Jen-Yang Tang, Fu Ou-Yang, Hui-Ru Wang, Pei-Ying Guan, Chiung-Yao Huang, Chung-Yi Chen, Ming-Feng Hou, Jyh-Horng Sheu and Hsueh-Wei Chang

Molecules 2018, 23(4), 849; https://doi.org/10.3390/molecules23040849 - 8 Apr 2018

Cited by 47 | Viewed by 5726 | Correction

Abstract

The natural compound sinularin, isolated from marine soft corals, is antiproliferative against several cancers, but its possible selective killing effect has rarely been investigated. This study investigates the selective killing potential and mechanisms of sinularin-treated breast cancer cells. In 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H- tetrazolium, inner salt [...] Read more.

The natural compound sinularin, isolated from marine soft corals, is antiproliferative against several cancers, but its possible selective killing effect has rarely been investigated. This study investigates the selective killing potential and mechanisms of sinularin-treated breast cancer cells. In 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H- tetrazolium, inner salt (MTS) assay, sinularin dose-responsively decreased the cell viability of two breast cancer (SKBR3 and MDA-MB-231) cells, but showed less effect on breast normal (M10) cells after a 24 h treatment. According to 7-aminoactinomycin D (7AAD) flow cytometry, sinularin dose-responsively induced the G2/M cycle arrest of SKBR3 cells. Sinularin dose-responsively induced apoptosis on SKBR3 cells in terms of a flow cytometry-based annexin V/7AAD assay and pancaspase activity, as well as Western blotting for cleaved forms of poly(ADP-ribose) polymerase (PARP), caspases 3, 8, and 9. These caspases and PARP activations were suppressed by N-acetylcysteine (NAC) pretreatment. Moreover, sinularin dose-responsively induced oxidative stress and DNA damage according to flow cytometry analyses of reactive oxygen species (ROS), mitochondrial membrane potential (MitoMP), mitochondrial superoxide, and 8-oxo-2′-deoxyguanosine (8-oxodG)). In conclusion, sinularin induces selective killing, G2/M arrest, apoptosis, and oxidative DNA damage of breast cancer cells. Full article

(This article belongs to the Special Issue Biological Potential of Marine and Terrestrial Species)

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14 pages, 10207 KiB

Open AccessArticle

Monitoring of the Apple Fruit Moth: Detection of Genetic Variation and Structure Applying a Novel Multiplex Set of 19 STR Markers

by Abdelhameed Elameen, Hans Geir Eiken, Ida Fløystad, Geir Knudsen and Snorre B. Hagen

Molecules 2018, 23(4), 850; https://doi.org/10.3390/molecules23040850 - 8 Apr 2018

Cited by 2 | Viewed by 3902

Abstract

The apple fruit moth Argyresthia conjugella (Lepidoptera, Yponomeutidae) is a seed predator of rowan (Sorbus aucuparia) and is distributed in Europe and Asia. In Fennoscandia (Finland, Norway and Sweden), rowan fruit production is low every 2–4 years, and apple (Malus [...] Read more.

The apple fruit moth Argyresthia conjugella (Lepidoptera, Yponomeutidae) is a seed predator of rowan (Sorbus aucuparia) and is distributed in Europe and Asia. In Fennoscandia (Finland, Norway and Sweden), rowan fruit production is low every 2–4 years, and apple (Malus domestica) functions as an alternative host, resulting in economic loss in apple crops in inter-mast years. We have used Illumina MiSeq sequencing to identify a set of 19 novel tetra-nucleotide short tandem repeats (STRs) in Argyresthia conjugella. Such motifs are recommended for genetic monitoring, which may help to determine the eco-evolutionary processes acting on this pest insect. The 19 STRs were optimized and amplified into five multiplex PCR reactions. We tested individuals collected from Norway and Sweden (n = 64), and detected very high genetic variation (average 13.6 alleles, He = 0.75) compared to most other Lepidoptera species studied so far. Spatial genetic differentiation was low and gene flow was high in the test populations, although two non-spatial clusters could be detected. We conclude that this set of genetic markers may be a useful resource for population genetic monitoring of this economical important insect species. Full article

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20 pages, 3670 KiB

Open AccessArticle

Isolation of Bioactive Compounds from Calicotome villosa Stems

by Josiane Alhage, Hoda Elbitar, Samir Taha, Jean-Paul Guegan, Zeina Dassouki, Thomas Vives and Thierry Benvegnu

Molecules 2018, 23(4), 851; https://doi.org/10.3390/molecules23040851 - 8 Apr 2018

Cited by 12 | Viewed by 5380

Abstract

A phenylethanoid, two steroids, a flavone glucoside and a chalcone have been isolated for the first time from the stems of Calicotome villosa together with a previously isolated flavone glucoside. Their structures were determined by spectroscopic analyses (NMR, HRMS) as basalethanoïd B ( [...] Read more.

A phenylethanoid, two steroids, a flavone glucoside and a chalcone have been isolated for the first time from the stems of Calicotome villosa together with a previously isolated flavone glucoside. Their structures were determined by spectroscopic analyses (NMR, HRMS) as basalethanoïd B (1), β-sitosterol and stigmasterol (2), chrysine-7-O-β-d-glucopyranoside (3), chrysine 7-((6′′-O-acetyl)-O-β-d-glucopyranoside) (4) and calythropsin (5). The crude extracts and the isolated compounds (except 4), were evaluated for their antioxidant, antimicrobial (against two Gram-positive bacterial strains: Staphylococcus aureus, Bacillus cereus, four Gram-negative bacterial strains: Staphylococcus epidermidis, Klebsiella pneumonia, Acinetobacter baumanii, and three yeasts: Candida albicans, Candida tropicalis, and Candida glabrata), hemolytic, antidiabetic, anti-inflammatory and cytotoxic activity. The crude extracts showed good ability to scavenge the free radical DPPH. Methanol stem extract followed by the dichloromethane stem extract showed moderate antimicrobial potency; furthermore, at 1 mg/mL the methanol extract showed an inhibition of C. albicans growth comparable to nystatin. Dichloromethane, methanol, and aqueous extracts inhibited 98%, 90%, and 80% of HeLa cell proliferation at 2 mg/mL respectively. Weak hypoglycemic and hemolytic effects were exhibited by the crude extracts. Among all the tested compounds, compound 3 showed remarkable hypoglycemic potential (93% at 0.1 mg/mL) followed by compound 5 (90% at 0.3 mg/mL). Compound 5 was the most effective in the DPPH^. scavenging assay (100% at 0.1 mg/mL) and cytotoxic assay on HeLa cells (99% and 90% after 24 and 48 h of treatment at 0.1 mg/mL, respectively). No anti-inflammatory effects were displayed by any of the crude extracts or the isolated compounds at any of the tested concentrations. Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 9361 KiB

Open AccessArticle

Effect of Pinocembrin Isolated from Mexican Brown Propolis on Diabetic Nephropathy

by Jessica Granados-Pineda, Norma Uribe-Uribe, Patricia García-López, María Del Pilar Ramos-Godinez, J. Fausto Rivero-Cruz and Jazmin Marlen Pérez-Rojas

Molecules 2018, 23(4), 852; https://doi.org/10.3390/molecules23040852 - 9 Apr 2018

Cited by 37 | Viewed by 6416

Abstract

Propolis is a resinous beehive product that has been used worldwide in traditional medicine to prevent and treat colds, wounds, rheumatism, heart disease and diabetes. Diabetic nephropathy is the final stage of renal complications caused by diabetes and for its treatment there are [...] Read more.

Propolis is a resinous beehive product that has been used worldwide in traditional medicine to prevent and treat colds, wounds, rheumatism, heart disease and diabetes. Diabetic nephropathy is the final stage of renal complications caused by diabetes and for its treatment there are few alternatives. The present study aimed to determine the chemical composition of three propolis samples collected in Chihuahua, Durango and Zacatecas and to evaluate the effect of pinocembrin in a model of diabetic nephropathy in vivo. Previous research demonstrated that propolis of Chihuahua possesses hypoglycemic and antioxidant activities. Two different schemes were assessed, preventive (before renal damage) and corrective (once renal damage is established). In the preventive scheme, pinocembrin treatment avoids death of the rats, improves lipid profile, glomerular filtration rate, urinary protein, avoid increases in urinary biomarkers, oxidative stress and glomerular basement membrane thickness. Whereas, in the corrective scheme, pinocembrin only improves lipid profile without showing improvement in any other parameters, even pinocembrin exacerbated the damage. In conclusion, pinocembrin ameliorates diabetic nephropathy when there is no kidney damage but when it is already present, pinocembrin accelerates kidney damage. Full article

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19 pages, 24199 KiB

Open AccessArticle

Multi-Component Analysis of Ilex Kudingcha C. J. Tseng by a Single Marker Quantification Method and Chemometric Discrimination of HPLC Fingerprints

by Huan Yi, Jie Zhou, Xueying Shang, Zhongxiang Zhao, Qian Peng, Mingjuan Zhu, Chenchen Zhu, Chaozhan Lin, Qide Liu, Qiongfeng Liao and Lei Zhang

Molecules 2018, 23(4), 854; https://doi.org/10.3390/molecules23040854 - 9 Apr 2018

Cited by 22 | Viewed by 4052

Abstract

The quantitative analysis of multiple components with a single marker (QAMS) method was firstly established for simultaneous determination of 18 active components in Ilex kudingcha C. J. Tseng by HPLC. Using rutin, isochlorogenic acid A and kudinoside A as internal refererence substances (IRS), [...] Read more.

The quantitative analysis of multiple components with a single marker (QAMS) method was firstly established for simultaneous determination of 18 active components in Ilex kudingcha C. J. Tseng by HPLC. Using rutin, isochlorogenic acid A and kudinoside A as internal refererence substances (IRS), compatibility results showed that the relative correction factors (RCFs) of all compounds showed good reproducibility under different chromatographic conditions. On the basis of previous studies, the accuracy of the QAMS method was systematically evaluated by investigating the influences of curve intercept, analytes and IRS concentration. The results showed that the concentration (especially at low level) of analytes and curve intercept were the major influencing parameters for the LRG-QAMS method (LRG = linear regression), whereas the influence of IRS concentration seemed more apparent in terms of the AVG-QAMS method (AVG = average). The two approaches were complementary with each other. In addition, hierarchical clustering analysis (HCA), principal components analysis (PCA) and similarity analysis (SA) were performed to differentiate and classify the samples based on the contents of 18 marker compounds. The results of the different chemometric analyses were completely consistent with each other, and could be supported by the quantification results. Full article

(This article belongs to the Section Analytical Chemistry)

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7 pages, 796 KiB

Open AccessArticle

Tricycloalternarene Analogs from a Symbiotic Fungus Aspergillus sp. D and Their Antimicrobial and Cytotoxic Effects

by Huawei Zhang, Ziping Zhao, Jianwei Chen, Xuelian Bai and Hong Wang

Molecules 2018, 23(4), 855; https://doi.org/10.3390/molecules23040855 - 9 Apr 2018

Cited by 16 | Viewed by 3958

Abstract

Bioassay-guided fractionation of the crude extract of fermentation broth of one symbiotic strain Aspergillus sp. D from the coastal plant Edgeworthia chrysantha Lindl. led to isolation of one new meroterpenoid, tricycloalternarene 14b (1), together with four known analogs (2– [...] Read more.

Bioassay-guided fractionation of the crude extract of fermentation broth of one symbiotic strain Aspergillus sp. D from the coastal plant Edgeworthia chrysantha Lindl. led to isolation of one new meroterpenoid, tricycloalternarene 14b (1), together with four known analogs (2–5), tricycloalternarenes 2b (2), 3a (3), 3b (4), and ACTG-toxin F (5). Their chemical structures were unambiguously established on the basis of NMR, mass spectrometry, and optical rotation data analysis, as well as by comparison with literature data. Biological assays indicated that compound 2 exhibited potent in vitro cytotoxicity against human lung adenocarcinoma A549 cell line with an IC₅₀ value of 2.91 μM, and compound 5 had a moderate inhibitory effect on Candida albicans, with an MIC value of 15.63 μM. The results indicated that this symbiotic strain D is an important producer of tricycloalternarene derivatives, with potential therapeutic application in treatment of cancer and pathogen infection. Full article

(This article belongs to the Special Issue Biological Activity of Secondary Metabolites)

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14 pages, 1632 KiB

Open AccessArticle

Quality Assessment of Kumu Injection, a Traditional Chinese Medicine Preparation, Using HPLC Combined with Chemometric Methods and Qualitative and Quantitative Analysis of Multiple Alkaloids by Single Marker

by Ning Wang, Zhi-Yong Li, Xiao-Li Zheng, Qiao Li, Xin Yang and Hui Xu

Molecules 2018, 23(4), 856; https://doi.org/10.3390/molecules23040856 - 9 Apr 2018

Cited by 32 | Viewed by 4775

Abstract

Kumu injection (KMI) is a common-used traditional Chinese medicine (TCM) preparation made from Picrasma quassioides (D. Don) Benn. rich in alkaloids. An innovative technique for quality assessment of KMI was developed using high performance liquid chromatography (HPLC) combined with chemometric methods and qualitative [...] Read more.

Kumu injection (KMI) is a common-used traditional Chinese medicine (TCM) preparation made from Picrasma quassioides (D. Don) Benn. rich in alkaloids. An innovative technique for quality assessment of KMI was developed using high performance liquid chromatography (HPLC) combined with chemometric methods and qualitative and quantitative analysis of multi-components by single marker (QAMS). Nigakinone (PQ-6, 5-hydroxy-4-methoxycanthin-6-one), one of the most abundant alkaloids responsible for the major pharmacological activities of Kumu, was used as a reference substance. Six alkaloids in KMI were quantified, including 6-hydroxy-β-carboline-1-carboxylic acid (PQ-1), 4,5-dimethoxycanthin-6-one (PQ-2), β-carboline-1-carboxylic acid (PQ-3), β-carboline-1-propanoic acid (PQ-4), 3-methylcanthin-5,6-dione (PQ-5), and PQ-6. Based on the outcomes of twenty batches of KMI samples, the contents of six alkaloids were used for further chemometric analysis. By hierarchical cluster analysis (HCA), radar plots, and principal component analysis (PCA), all the KMI samples could be categorized into three groups, which were closely related to production date and indicated the crucial influence of herbal raw material on end products of KMI. QAMS combined with chemometric analysis could accurately measure and clearly distinguish the different quality samples of KMI. Hence, QAMS is a feasible and promising method for the quality control of KMI. Full article

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18 pages, 24178 KiB

Open AccessArticle

Chloroplast Genome of the Folk Medicine and Vegetable Plant Talinum paniculatum (Jacq.) Gaertn.: Gene Organization, Comparative and Phylogenetic Analysis

by Xia Liu, Yuan Li, Hongyuan Yang and Boyang Zhou

Molecules 2018, 23(4), 857; https://doi.org/10.3390/molecules23040857 - 9 Apr 2018

Cited by 24 | Viewed by 5787

Abstract

The complete chloroplast (cp) genome of Talinum paniculatum (Caryophyllale), a source of pharmaceutical efficacy similar to ginseng, and a widely distributed and planted edible vegetable, were sequenced and analyzed. The cp genome size of T. paniculatum is 156,929 bp, with a pair of [...] Read more.

The complete chloroplast (cp) genome of Talinum paniculatum (Caryophyllale), a source of pharmaceutical efficacy similar to ginseng, and a widely distributed and planted edible vegetable, were sequenced and analyzed. The cp genome size of T. paniculatum is 156,929 bp, with a pair of inverted repeats (IRs) of 25,751 bp separated by a large single copy (LSC) region of 86,898 bp and a small single copy (SSC) region of 18,529 bp. The genome contains 83 protein-coding genes, 37 transfer RNA (tRNA) genes, eight ribosomal RNA (rRNA) genes and four pseudogenes. Fifty one (51) repeat units and ninety two (92) simple sequence repeats (SSRs) were found in the genome. The pseudogene rpl23 (Ribosomal protein L23) was insert AATT than other Caryophyllale species by sequence alignment, which located in IRs region. The gene of trnK-UUU (tRNA-Lys) and rpl16 (Ribosomal protein L16) have larger introns in T. paniculatum, and the existence of matK (maturase K) genes, which usually located in the introns of trnK-UUU, rich sequence divergence in Caryophyllale. Complete cp genome comparison with other eight Caryophyllales species indicated that the differences between T. paniculatum and P. oleracea were very slight, and the most highly divergent regions occurred in intergenic spacers. Comparisons of IR boundaries among nine Caryophyllales species showed that T. paniculatum have larger IRs region and the contraction is relatively slight. The phylogenetic analysis among 35 Caryophyllales species and two outgroup species revealed that T. paniculatum and P. oleracea do not belong to the same family. All these results give good opportunities for future identification, barcoding of Talinum species, understanding the evolutionary mode of Caryophyllale cp genome and molecular breeding of T. paniculatum with high pharmaceutical efficacy. Full article

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14 pages, 2882 KiB

Open AccessArticle

Confinement Effects on Chemical Equilibria: Pentacyano(Pyrazine)Ferrate(II) Stability Changes within Nanosized Droplets of Water

by Teofilo Borunda, Alexander J. Myers, J. Mary Fisher, Debbie C. Crans and Michael D. Johnson

Molecules 2018, 23(4), 858; https://doi.org/10.3390/molecules23040858 - 9 Apr 2018

Cited by 2 | Viewed by 4302

Abstract

Nanoscale confinement is known to impact properties of molecules and we observed changes in the reactivity of an iron coordination complex, pentacyano(pyrazine)ferrate(II). The confinement of two coordination complexes in a sodium AOT/isooctane reverse micellar (RM) water droplet was found to dramatically increase the [...] Read more.

Nanoscale confinement is known to impact properties of molecules and we observed changes in the reactivity of an iron coordination complex, pentacyano(pyrazine)ferrate(II). The confinement of two coordination complexes in a sodium AOT/isooctane reverse micellar (RM) water droplet was found to dramatically increase the hydrolysis rate of [Fe(CN)₅pyz]³⁻ and change the monomer-dimer equilibria between [Fe(CN)₅pyz]³⁻ and [Fe₂(CN)₁₀pyz]⁶⁻. Combined UV-Vis and ¹H-NMR spectra of these complexes in RMs were analyzed and the position of the monomer-dimer equilibrium and the relative reaction times were determined at three different RM sizes. The data show that the hydrolysis rates (loss of pyrazine) are dramatically enhanced in RMs over bulk water and increase as the size of the RM decreases. Likewise, the monomer-dimer equilibrium changes to favor the formation of dimer as the RM size decreases. We conclude that the effects of the [Fe(CN)₅pyz]³⁻ stability is related to its solvation within the RM. Full article

(This article belongs to the Special Issue Coordination Chemistry for Devices and Functional Materials)

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17 pages, 7904 KiB

Open AccessFeature PaperArticle

1-(Acylamino)alkylphosphonic Acids—Alkaline Deacylation

by Marek Cypryk, Jozef Drabowicz, Bartlomiej Gostynski, Marcin H. Kudzin, Zbigniew H. Kudzin and Pawel Urbaniak

Molecules 2018, 23(4), 859; https://doi.org/10.3390/molecules23040859 - 9 Apr 2018

Cited by 5 | Viewed by 4233

Abstract

The alkaline deacylation of a representative series of 1-(acylamino)alkylphosphonic acids [(AC)-AA^P: (AC) = Ac, TFA, Bz; AA^P = Gly^P, Ala^P, Val^P, Pgl^P and Phe^P] in an aqueous solution of KOH (2M) [...] Read more.

The alkaline deacylation of a representative series of 1-(acylamino)alkylphosphonic acids [(AC)-AA^P: (AC) = Ac, TFA, Bz; AA^P = Gly^P, Ala^P, Val^P, Pgl^P and Phe^P] in an aqueous solution of KOH (2M) was investigated. The results suggested a two-stage reaction mechanism with a quick interaction of the hydroxyl ion on the carbonyl function of the amide R-C(O)-N(H)- group in the first stage, which leads to instant formation of the intermediary acyl-hydroxyl adducts of R-C(O⁻)₂-N(H)-, visible in the ³¹P NMR spectra. In the second stage, these intermediates decompose slowly by splitting of the RC(O⁻)₂-N(H)- function with the subsequent formation of 1-aminoalkylphosphonate and carboxylate ions. Full article

(This article belongs to the Special Issue Organophosphorus Chemistry 2018)

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12 pages, 4971 KiB

Open AccessArticle

Application of Multiple Regression and Design of Experiments for Modelling the Effect of Monoethylene Glycol in the Calcium Carbonate Scaling Process

by Vinicius Kartnaller, Fabrício Venâncio, Francisca F. do Rosário and João Cajaiba

Molecules 2018, 23(4), 860; https://doi.org/10.3390/molecules23040860 - 10 Apr 2018

Cited by 8 | Viewed by 3318

Abstract

To avoid gas hydrate formation during oil and gas production, companies usually employ thermodynamic inhibitors consisting of hydroxyl compounds, such as monoethylene glycol (MEG). However, these inhibitors may cause other types of fouling during production such as inorganic salt deposits (scale). Calcium carbonate [...] Read more.

To avoid gas hydrate formation during oil and gas production, companies usually employ thermodynamic inhibitors consisting of hydroxyl compounds, such as monoethylene glycol (MEG). However, these inhibitors may cause other types of fouling during production such as inorganic salt deposits (scale). Calcium carbonate is one of the main scaling salts and is a great concern, especially for the new pre-salt wells being explored in Brazil. Hence, it is important to understand how using inhibitors to control gas hydrate formation may be interacting with the scale formation process. Multiple regression and design of experiments were used to mathematically model the calcium carbonate scaling process and its evolution in the presence of MEG. It was seen that MEG, although inducing the precipitation by increasing the supersaturation ratio, actually works as a scale inhibitor for calcium carbonate in concentrations over 40%. This effect was not due to changes in the viscosity, as suggested in the literature, but possibly to the binding of MEG to the CaCO₃ particles’ surface. The interaction of the MEG inhibition effect with the system’s variables was also assessed, when temperature’ and calcium concentration were more relevant. Full article

(This article belongs to the Section Analytical Chemistry)

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14 pages, 4376 KiB

Open AccessArticle

Molecular Cloning and Functional Characterization of a Dihydroflavonol 4-Reductase from Vitis bellula

by Yue Zhu, Qingzhong Peng, Kegang Li and De-Yu Xie

Molecules 2018, 23(4), 861; https://doi.org/10.3390/molecules23040861 - 10 Apr 2018

Cited by 15 | Viewed by 4799

Abstract

Vitis bellula is a new grape crop in southern China. Berries of this species are rich in antioxidative anthocyanins and proanthocyanidins. This study reports cloning and functional characterization of a cDNA encoding a V. bellula dihydroflavonol reductase (VbDFR) involved in the biosynthesis of [...] Read more.

Vitis bellula is a new grape crop in southern China. Berries of this species are rich in antioxidative anthocyanins and proanthocyanidins. This study reports cloning and functional characterization of a cDNA encoding a V. bellula dihydroflavonol reductase (VbDFR) involved in the biosynthesis of anthocyanins and proanthocyanidins. A cDNA including 1014 bp was cloned from young leaves and its open reading frame (ORF) was deduced encoding 337 amino acids, highly similar to V. vinifera DFR (VvDFR). Green florescence protein fusion and confocal microscopy analysis determined the cytosolic localization of VbDFR in plant cells. A soluble recombinant VbDFR was induced and purified from E. coli for enzyme assay. In the presence of NADPH, the recombinant enzyme catalyzed dihydrokaempferol (DHK) and dihydroquercetin (DHQ) to their corresponding leucoanthocyanidins. The VbDFR cDNA was introduced into tobacco plants via Agrobacterium-mediated transformation. The overexpression of VbDFR increased anthocyanin production in flowers. Anthocyanin hydrolysis and chromatographic analysis revealed that transgenic flowers produced pelargonidin and delphinidin, which were not detected in control flowers. These data demonstrated that the overexpression of VbDFR produced new tobacco anthocyanidins. In summary, all data demonstrate that VbDFR is a useful gene to provide three types of substrates for metabolic engineering of anthocyanins and proanthocyanidins in grape crops and other crops. Full article

(This article belongs to the Section Metabolites)

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13 pages, 32184 KiB

Open AccessArticle

Microwave-Assisted Oxalic Acid Pretreatment for the Enhancing of Enzyme Hydrolysis in the Production of Xylose and Arabinose from Bagasse

by Yuhuan Yan, Chunhui Zhang, Qixuan Lin, Xiaohui Wang, Banggui Cheng, Huiling Li and Junli Ren

Molecules 2018, 23(4), 862; https://doi.org/10.3390/molecules23040862 - 10 Apr 2018

Cited by 52 | Viewed by 5689

Abstract

In this study, highly-efficient hydrolysis of bagasse into xylose and arabinose sugars (C5 sugars) was developed by microwave-assisted oxalic acid pretreatment under mild reaction conditions. The effects of acid and hydrolysis conditions on the C5 sugar yields were discussed. The results showed that [...] Read more.

In this study, highly-efficient hydrolysis of bagasse into xylose and arabinose sugars (C5 sugars) was developed by microwave-assisted oxalic acid pretreatment under mild reaction conditions. The effects of acid and hydrolysis conditions on the C5 sugar yields were discussed. The results showed that oxalic acid performed better than hydrochloric acid and maleic acid, and was a promising alternative to sulfuric acid for xylose production at the same acid concentration. The maximum yields of xylose (95.7%) and arabinose (91.5%) were achieved via the microwave-assisted oxalic acid pretreatment (120 °C, 10 min, 0.4 mol/L, solid–liquid ratio of 1:50 g/mL), indicating that almost all xylan-type hemicelluloses were released from the cell wall and hydrolyzed into C5 sugars. After pretreatment, more than 90% of the cellulose in the residual bagasse was converted to glucose (92.2%) by enzymatic hydrolysis. This approach could realize the highly-efficient hydrolysis of xylan from bagasse into C5 sugars, which would enhance the enzyme hydrolysis of treated bagasse into glucose. Full article

(This article belongs to the Special Issue Platform Chemical: Hydroxymethylfurfural (HMF))

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12 pages, 25485 KiB

Open AccessArticle

Antileishmanial Activity of 2-Methoxy-4H-spiro-[naphthalene-1,2′-oxiran]-4-one (Epoxymethoxy-lawsone): A Promising New Drug Candidate for Leishmaniasis Treatment

by Luiz Filipe Gonçalves Oliveira, Franklin Souza-Silva, Luzia Monteiro De Castro Côrtes, Lea Cysne-Finkelstein, Mirian Cláudia De Souza Pereira, Francisco Odêncio De Oliveira Junior, Rosa Teixeira Pinho, Suzana Corte Real, Saulo Cabral Bourguignon, Vitor Francisco Ferreira and Carlos Roberto Alves

Molecules 2018, 23(4), 864; https://doi.org/10.3390/molecules23040864 - 10 Apr 2018

Cited by 17 | Viewed by 4070

Abstract

Epoxymethoxylawsone is a naphthoquinone derivative promising as drug candidate for the treatment of leishmaniases. In the present work the effectiveness of epoxymethoxylawsone, and meglumine antimoniate on Leishmania (Leishmania) amazonensis parasites and on mice paw lesions of infected BALB/c mice was assessed. [...] Read more.

Epoxymethoxylawsone is a naphthoquinone derivative promising as drug candidate for the treatment of leishmaniases. In the present work the effectiveness of epoxymethoxylawsone, and meglumine antimoniate on Leishmania (Leishmania) amazonensis parasites and on mice paw lesions of infected BALB/c mice was assessed. In an intracellular amastigotes assay, the half-maximal inhibitory concentration (IC₅₀) value for epoxymethoxylawsone was slightly higher (1.7-fold) than that found for meglumine antimoniate. The efficacy of both drugs became more evident after 48 h of exposure when either the oxirane compound and reference drug reached 18-fold and 7.4-fold lower IC₅₀ values (0.40 ± 0.001 µM and 0.60 ± 0.02 µM), respectively. Promastigotes were also affected by epoxymethoxylawsone after 24 h of incubation (IC₅₀ = 45.45 ± 5.0 µM), but with IC₅₀ 6-fold higher than those found for intracellular amastigotes. Cytotoxicity analysis revealed that epoxymethoxylawsone (CC₅₀ = 40.05 ± µM) has 1.7-fold higher effects than meglumine antimoniate (CC₅₀ = 24.14 ± 2.6 µM). Treatment of the paw lesion in infected BALB/c mice with epoxymethoxy-lawsone led to a significant 27% reduction (p < 0.05) of the lesion size, for all administrated doses, compared to the control group. Lesion reduction was also detected after mice treatment with meglumine antimoniate, reaching 31.0% (0.23 mg of Sb(V)/Kg/day and 2.27 mg of Sb(V)/Kg/day) and 64.0% (22.7 mg of Sb(V)/Kg/day). In addition, mice lesion ultrastructural changes were evidenced in amastigotes. The set of data gathered here indicate that epoxymethoxylawsone has pronounced effects on parasites and merits furthering to the preclinical stage. Full article

(This article belongs to the Section Medicinal Chemistry)

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18 pages, 9037 KiB

Open AccessArticle

The Molecular Targets and Anti-Invasive Effects of 2,6-bis-(4-hydroxyl-3methoxybenzylidine) cyclohexanone or BHMC in MDA-MB-231 Human Breast Cancer Cells

by Siti Nor Aini Harun, Daud Ahmad Israf, Chau Ling Tham, Kok Wai Lam, Manraj Singh Cheema and Nur Fariesha Md Hashim

Molecules 2018, 23(4), 865; https://doi.org/10.3390/molecules23040865 - 10 Apr 2018

Cited by 13 | Viewed by 4512

Abstract

In order to metastasize, tumor cells need to migrate and invade the surrounding tissues. It is important to identify compound(s) capable of disrupting the metastasis of invasive cancer cells, especially for hindering invadopodia formation, so as to provide anti-metastasis targeted therapy. Invadopodia are [...] Read more.

In order to metastasize, tumor cells need to migrate and invade the surrounding tissues. It is important to identify compound(s) capable of disrupting the metastasis of invasive cancer cells, especially for hindering invadopodia formation, so as to provide anti-metastasis targeted therapy. Invadopodia are thought to be specialized actin-rich protrusions formed by highly invasive cancer cells to degrade the extracellular matrix (ECM). A curcuminoid analogue known as 2,6-bis-(4-hydroxy-3-methoxybenzylidine)cyclohexanone or BHMC has shown good potential in inhibiting inflammation and hyperalgesia. It also possesses an anti-tumor effects on 4T1 murine breast cancer cells in vivo. However, there is still a lack of empirical evidence on how BHMC works in preventing human breast cancer invasion. In this study, we investigated the effect of BHMC on MDA-MB-231 breast cancer cells and its underlying mechanism of action to prevent breast cancer invasion, especially during the formation of invadopodia. All MDA-MB-231 cells, which were exposed to the non-cytotoxic concentrations of BHMC, expressed the proliferating cell nuclear antigen (PCNA), which indicate that the anti-proliferative effects of BHMC did not interfere in the subsequent experiments. By using a scratch migration assay, transwell migration and invasion assays, we determined that BHMC reduces the percentage of migration and invasion of MDA-MB-231 cells. The gelatin degradation assay showed that BHMC reduced the number of cells with invadopodia. Analysis of the proteins involved in the invasion showed that there is a significant reduction in the expressions of Rho guanine nucleotide exchange factor 7 (β-PIX), matrix metalloproteinase-9 (MMP-9), and membrane type 1 matrix metalloproteinase (MT1-MMP) in the presence of BHMC treatment at 12.5 µM. Therefore, it can be postulated that BHMC at 12.5 µM is the optimal concentration for preventing breast cancer invasion. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 3165 KiB

Open AccessArticle

Light Emission from the Fe²⁺-EGTA-H₂O₂ System: Possible Application for the Determination of Antioxidant Activity of Plant Phenolics

by Michal Nowak, Wieslaw Tryniszewski, Agata Sarniak, Anna Wlodarczyk, Piotr J. Nowak and Dariusz Nowak

Molecules 2018, 23(4), 866; https://doi.org/10.3390/molecules23040866 - 10 Apr 2018

Cited by 5 | Viewed by 4545

Abstract

Oxidative reactions can result in the formation of electronically excited species that undergo radiative decay depending on electronic transition from the excited state to the ground state with subsequent ultra-weak photon emission (UPE). We investigated the UPE from the Fe²⁺-EGTA (ethylene [...] Read more.

Oxidative reactions can result in the formation of electronically excited species that undergo radiative decay depending on electronic transition from the excited state to the ground state with subsequent ultra-weak photon emission (UPE). We investigated the UPE from the Fe²⁺-EGTA (ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid)–H₂O₂ system with a multitube luminometer (Peltier-cooled photon counter, spectral range 380 to 630 nm). The UPE of 92.6 µmol/L Fe²⁺—185.2 µmol/L EGTA—2.6 mmol/L H₂O₂ reached 4319 ± 755 relative light units during 2 min measurement and was about seven times higher (p < 0.001) than the UPE of incomplete systems (Fe²⁺-H₂O₂, EGTA-H₂O₂) and medium alone. Substitution of Fe²⁺ with Cr²⁺, Co²⁺, Mn²⁺ or Cu²⁺ as well as of EGTA with EDTA (ethylenediaminetetraacetic acid) or citrate completely abolished UPE. Experiments with ROS scavengers revealed the dependence of UPE on hydroxyl radicals suggesting occurrence of oxidative attack and cleavage of the ether bond in EGTA backbone structure and formation of triplet excited carbonyl groups with subsequent light emission. Plant phenolics (ferulic, chlorogenic and caffec acids) at concentration 87 µmol/L and ascorbate at 0.46 mmol/L inhibited UPE by 90 ± 4%, 90 ± 5%, 97 ± 2% and 92 ± 1%, respectively. Quenching of UPE from Fe²⁺-EGTA-H₂O₂ system can be used for evaluation of antioxidant activity of phytochemicals. Full article

(This article belongs to the Special Issue The Antioxidant Capacities of Natural Products)

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15 pages, 12057 KiB

Open AccessArticle

N-Confused Porphyrin Immobilized on Solid Supports: Synthesis and Metal Ions Sensing Efficacy

by Sara R. D. Gamelas, Ana T. P. C. Gomes, Nuno M. M. Moura, Maria A. F. Faustino, José A. S. Cavaleiro, Carlos Lodeiro, Marta I. S. Veríssimo, Tiago Fernandes, Ana L. Daniel-da-Silva, M. Teresa S. R. Gomes and Maria G. P. M. S. Neves

Molecules 2018, 23(4), 867; https://doi.org/10.3390/molecules23040867 - 10 Apr 2018

Cited by 19 | Viewed by 6248

Abstract

In this work, the N-confused porphyrin 5,10,15,20-tetraphenyl-2-aza-21-carbaporphyrin (NCTPP) was immobilized on neutral or cationic supports based on silica and on Merrifield resin. The new materials were characterized by appropriate techniques (UV-Vis spectroscopy, SEM, and zeta potential analysis). Piezoelectric quartz crystal gold electrodes [...] Read more.

In this work, the N-confused porphyrin 5,10,15,20-tetraphenyl-2-aza-21-carbaporphyrin (NCTPP) was immobilized on neutral or cationic supports based on silica and on Merrifield resin. The new materials were characterized by appropriate techniques (UV-Vis spectroscopy, SEM, and zeta potential analysis). Piezoelectric quartz crystal gold electrodes were coated with the different hybrids and their ability to interact with heavy metals was evaluated. The preliminary results obtained showed that the new materials can be explored for metal cations detection and the modification of the material surface is a key factor in tuning the metal selectivity. Full article

(This article belongs to the Special Issue Porphyrins and Phthalocyanines: Synthesis, Properties and Applications)

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12 pages, 22395 KiB

Open AccessArticle

Scutellarin Mitigates Aβ-Induced Neurotoxicity and Improves Behavior Impairments in AD Mice

by Yue-Qin Zeng, Yin-Bo Cui, Juan-Hua Gu, Chen Liang and Xin-Fu Zhou

Molecules 2018, 23(4), 869; https://doi.org/10.3390/molecules23040869 - 10 Apr 2018

Cited by 24 | Viewed by 5855

Abstract

Alzheimer’s disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (Aβ) within extracellular spaces of the brain. Aggregation of Aβ has been shown to trigger oxidative stress, inflammation, and neurotoxicity resulting in cognitive dysfunction. In this study, we use models of cerebral [...] Read more.

Alzheimer’s disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (Aβ) within extracellular spaces of the brain. Aggregation of Aβ has been shown to trigger oxidative stress, inflammation, and neurotoxicity resulting in cognitive dysfunction. In this study, we use models of cerebral Aβ amyloidosis to investigate anti-amyloidogenic effects of scutellarin in vitro and in vivo. Our results show that scutellarin, through binding to Aβ42, efficiently inhibits oligomerization as well as fibril formation and reduces Aβ oligomer-induced neuronal toxicity in cell line SH-SY5Y. After nine months of treatment in APP/PS1 double-transgenic mice, scutellarin significantly improves behavior, reduces soluble and insoluble Aβ levels in the brain and plasma, decreases Aβ plaque associated gliosis and levels of proinflammatory cytokines TNF-α and IL-6, attenuates neuroinflammation, displays anti-amyloidogenic effects, and highlights the beneficial effects of intervention on development or progression of AD-like neuropathology. Full article

(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)

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12 pages, 15360 KiB

Open AccessArticle

Effects of Lignans from Schisandra chinensis Rattan Stems against Aβ_1-42-Induced Memory Impairment in Rats and Neurotoxicity in Primary Neuronal Cells

by Bing-You Yang, Wei Han, Hua Han, Yan Liu, Wei Guan, Xiao-Mao Li and Hai-Xue Kuang

Molecules 2018, 23(4), 870; https://doi.org/10.3390/molecules23040870 - 10 Apr 2018

Cited by 13 | Viewed by 3620

Abstract

Oxidative stress, which is caused by Amyloid-β deposition in brain, plays an important role in Alzheimer’s disease. In this study, we found that lignans from Schisandra chinensis rattan stems (rsSCH-L) could reduce the escape latency and the distance travelled by the Aβ_1–42 [...] Read more.

Oxidative stress, which is caused by Amyloid-β deposition in brain, plays an important role in Alzheimer’s disease. In this study, we found that lignans from Schisandra chinensis rattan stems (rsSCH-L) could reduce the escape latency and the distance travelled by the Aβ_1–42 injected rats while the crossing platform time was enhanced in the Morris water maze test. Further research demonstrated that lignans from rsSCH-L attenuated Aβ_1-42-induced neuronal cell injury by increasing the content of SOD and GSH-Px and decreasing the levels of LDH, ROS, and MDA. Moreover, rsSCH-L also inhibited the apoptosis of primary neuronal cells. The mechanisms of the apoptosis were related with the downregulation of caspase-3, caspase-8, Bax, and upregulation of Bcl-2. Taken together, the results show that rsSCH-L can improve cognitive ability in vivo. Meanwhile rsSCH-L exhibit a neuroprotective environment against oxidative stress and apoptosis in vitro. Therefore, rsSCH-L may be a potential therapeutic agent for this neurodegenerative disease. Full article

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11 pages, 12255 KiB

Open AccessArticle

A Novel Colorimetric Fluorescent Probe for SO₂ and Its Application in Living Cells Imaging

by Ming-Yu Wu, Jing Wu, Yue Wang, Yan-Hong Liu and Xiao-Qi Yu

Molecules 2018, 23(4), 871; https://doi.org/10.3390/molecules23040871 - 10 Apr 2018

Cited by 6 | Viewed by 4702

Abstract

A novel chromenylium-based fluorescent probe was exploited for sulphur dioxide (SO₂) detecting. The probe displayed a remarkable fluorescence turn-on response towards SO₂ based on the nucleophilic addition reaction to the carbon-carbon double bond with 105 nm Stock shift. The probe [...] Read more.

A novel chromenylium-based fluorescent probe was exploited for sulphur dioxide (SO₂) detecting. The probe displayed a remarkable fluorescence turn-on response towards SO₂ based on the nucleophilic addition reaction to the carbon-carbon double bond with 105 nm Stock shift. The probe was successfully applied for the quantification of SO₂.The linear detection range was from 0–160 μM with the detection limit as low as 99.27 nM. It also exhibited high selectivity for SO₂ than other reactive species and amino acids. Furthermore, cell staining experiments indicated that the probe was cell membrane permeable and could be used for high-performance imaging of SO₂ in living cells. The superior properties of the probe made it highly promising for use in chemical and biological applications. Full article

(This article belongs to the Section Analytical Chemistry)

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18 pages, 25663 KiB

Open AccessArticle

Effects of Calcination Holding Time on Properties of Wide Band Gap Willemite Semiconductor Nanoparticles by the Polymer Thermal Treatment Method

by Ibrahim Mustapha Alibe, Khamirul Amin Matori, Hj Abdul Aziz Sidek, Yazid Yaakob, Umer Rashid, Ali Mustapha Alibe, Mohd Hafiz Mohd Zaid and Mohammad Zulhasif Ahmad Khiri

Molecules 2018, 23(4), 873; https://doi.org/10.3390/molecules23040873 - 11 Apr 2018

Cited by 36 | Viewed by 6520

Abstract

Willemite is a wide band gap semiconductor used in modern day technology for optoelectronics application. In this study, a new simple technique with less energy consumption is proposed. Willemite nanoparticles (NPs) were produced via a water–based solution consisting of a metallic precursor, polyvinylpyrrolidone [...] Read more.

Willemite is a wide band gap semiconductor used in modern day technology for optoelectronics application. In this study, a new simple technique with less energy consumption is proposed. Willemite nanoparticles (NPs) were produced via a water–based solution consisting of a metallic precursor, polyvinylpyrrolidone (PVP), and underwent a calcination process at 900 °C for several holding times between 1–4 h. The FT–IR and Raman spectra indicated the presence of metal oxide bands as well as the effective removal of PVP. The degree of the crystallization and formation of the NPs were determined by XRD. The mean crystallite size of the NPs was between 18.23–27.40 nm. The morphology, particle shape and size distribution were viewed with HR-TEM and FESEM analysis. The willemite NPs aggregate from the smaller to larger particles with an increase in calcination holding time from 1–4 h with the sizes ranging between 19.74–29.71 nm. The energy values obtained from the experimental band gap decreased with increasing the holding time over the range of 5.39 eV at 1 h to at 5.27 at 4 h. These values match well with band gap obtained from the Mott and Davis model for direct transition. The findings in this study are very promising and can justify the use of these novel materials as a potential candidate for green luminescent optoelectronic applications. Full article

(This article belongs to the Section Nanochemistry)

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15 pages, 21174 KiB

Open AccessArticle

Fucoxanthin and Polyunsaturated Fatty Acids Co-Extraction by a Green Process

by Antoine Delbrut, Pierre Albina, Théo Lapierre, Rémi Pradelles and Eric Dubreucq

Molecules 2018, 23(4), 874; https://doi.org/10.3390/molecules23040874 - 11 Apr 2018

Cited by 45 | Viewed by 5736

Abstract

By their autotrophic nature and their molecular richness, microalgae are serious assets in the context of current environmental and societal challenges. Some species produce both omega-3 long chain polyunsaturated fatty acids (PUFAs) and xanthophylls, two molecular families widely studied for their bioactivities in [...] Read more.

By their autotrophic nature and their molecular richness, microalgae are serious assets in the context of current environmental and societal challenges. Some species produce both omega-3 long chain polyunsaturated fatty acids (PUFAs) and xanthophylls, two molecular families widely studied for their bioactivities in the fields of nutrition and cosmetics. Whereas most studies separately deal with the two families, synergies could be exploited with extracts containing both PUFAs and xanthophylls. The purpose of our work was to determine cost effective and eco-friendly parameters for their co-extraction. The effect of several parameters (solvent, solvent/biomass ratio, temperature, duration) were studied, using two microalgal species, the non-calcifying Haptophyta Tisochrysis lutea, and the diatom Phaeodactylum tricornutum, that presents a silicified frustule. Analyses of PUFAs and fucoxanthin (Fx), the main xanthophyll, allowed to compare kinetics and extraction yields between experimental protocols. Co-extraction yields achieved using 96% ethanol as solvent were 100% for Fx and docosahexaenoic acid (DHA) in one hour from T. lutea biomass, and respectively 95% and 89% for Fx and eicosapentaenoic acid (EPA) in eight hours from P. tricornutum. These conditions are compatible with industrial applications. Full article

(This article belongs to the Special Issue Bioactives from Bioprocessing: Sources and Production)

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15 pages, 12028 KiB

Open AccessArticle

Facile Syntheses and Molecular-Docking of Novel Substituted 3,4-Dimethyl-1H-pyrrole-2-carboxamide/carbohydrazide Analogues with Antimicrobial and Antifungal Properties

by Jitendra D. Bhosale, Rajesh Dabur, Gopal P. Jadhav and R. S. Bendre

Molecules 2018, 23(4), 875; https://doi.org/10.3390/molecules23040875 - 11 Apr 2018

Cited by 10 | Viewed by 5095

Abstract

The article describes the use of facile one-pot, high-yielding reactions to synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamides 3a–m and carbohydrazide analogues 5a–l as potential antifungal and antimicrobial agents. The structural identity and purity of the synthesized compounds were assigned based [...] Read more.

The article describes the use of facile one-pot, high-yielding reactions to synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamides 3a–m and carbohydrazide analogues 5a–l as potential antifungal and antimicrobial agents. The structural identity and purity of the synthesized compounds were assigned based on appropriate spectroscopic techniques. Synthesized compounds were assessed in vitro for antifungal and antibacterial activity. The compounds 5h, 5i and 5j were found to be the most potent against Aspergillus fumigatus, with MIC values of 0.039 mg/mL. The compound 5f bearing a 2, 6-dichloro group on the phenyl ring was found to be the most active broad spectrum antibacterial agent with a MIC value of 0.039 mg/mL. The mode of action of the most promising antifungal compounds (one representative from each series; 3j and 5h) was established by their molecular docking with the active site of sterol 14α-demethylase. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds in the access channel away from catalytic heme iron of the enzyme, which suggested that the tested compounds inhibit this enzyme and would avoid heme iron-related deleterious side effects observed with many existing antifungal compounds. Full article

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12 pages, 26139 KiB

Open AccessArticle

Epigallocatechin Gallate-Modified Gelatin Sponges Treated by Vacuum Heating as a Novel Scaffold for Bone Tissue Engineering

by Yoshitomo Honda, Yoshihiro Takeda, Peiqi Li, Anqi Huang, Satoshi Sasayama, Eiki Hara, Naoya Uemura, Mamoru Ueda, Masanori Hashimoto, Kenji Arita, Naoyuki Matsumoto, Yoshiya Hashimoto, Shunsuke Baba and Tomonari Tanaka

Molecules 2018, 23(4), 876; https://doi.org/10.3390/molecules23040876 - 11 Apr 2018

Cited by 28 | Viewed by 6202

Abstract

Chemical modification of gelatin using epigallocatechin gallate (EGCG) promotes bone formation in vivo. However, further improvements are required to increase the mechanical strength and bone-forming ability of fabricated EGCG-modified gelatin sponges (EGCG-GS) for practical applications in regenerative therapy. In the present study, we [...] Read more.

Chemical modification of gelatin using epigallocatechin gallate (EGCG) promotes bone formation in vivo. However, further improvements are required to increase the mechanical strength and bone-forming ability of fabricated EGCG-modified gelatin sponges (EGCG-GS) for practical applications in regenerative therapy. In the present study, we investigated whether vacuum heating-induced dehydrothermal cross-linking of EGCG-GS enhances bone formation in critical-sized rat calvarial defects. The bone-forming ability of vacuum-heated EGCG-GS (vhEGCG-GS) and other sponges was evaluated by micro-computed tomography and histological staining. The degradation of sponges was assessed using protein assays, and cell morphology and proliferation were verified by scanning electron microscopy and immunostaining using osteoblastic UMR106 cells in vitro. Four weeks after the implantation of sponges, greater bone formation was detected for vhEGCG-GS than for EGCG-GS or vacuum-heated gelatin sponges (dehydrothermal cross-linked sponges without EGCG). In vitro experiments revealed that the relatively low degradability of vhEGCG-GS supports cell attachment, proliferation, and cell–cell communication on the matrix. These findings suggest that vacuum heating enhanced the bone forming ability of EGCG-GS, possibly via the dehydrothermal cross-linking of EGCG-GS, which provides a scaffold for cells, and by maintaining the pharmacological effect of EGCG. Full article

(This article belongs to the Special Issue Catechin in Human Health and Disease)

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14 pages, 2319 KiB

Open AccessArticle

Characteristics of Milk Fermented by Streptococcus thermophilus MGA45-4 and the Profiles of Associated Volatile Compounds during Fermentation and Storage

by Tong Dan, Rulin Jin, Weiyi Ren, Ting Li, Haiyan Chen and Tiansong Sun

Molecules 2018, 23(4), 878; https://doi.org/10.3390/molecules23040878 - 11 Apr 2018

Cited by 44 | Viewed by 4957

Abstract

The lactic acid bacterium Streptococcus thermophilus is a major starter culture for the production of dairy products. In this study, the physiochemical characteristics of milk fermented by the MGA45-4 isolate of S. thermophilus were analyzed. Our data indicate that milk fermented using S. [...] Read more.

The lactic acid bacterium Streptococcus thermophilus is a major starter culture for the production of dairy products. In this study, the physiochemical characteristics of milk fermented by the MGA45-4 isolate of S. thermophilus were analyzed. Our data indicate that milk fermented using S. thermophilus MGA45-4 maintained a high viable cell count (8.86 log10 colony-forming units/mL), and a relatively high pH (4.4), viscosity (834.33 mPa·s), and water holding capacity (40.85%) during 14 days of storage. By analyzing the volatile compound profile using solid-phase microextraction and gas chromatography/mass spectrometry, we identified 73 volatile compounds in the fermented milk product, including five carboxylic acids, 21 aldehydes, 13 ketones, 16 alcohols, five esters, and 13 aromatic carbohydrates. According to the odor activity values, 11 of these volatile compounds were found to play a key role in producing the characteristic flavor of fermented milk, particularly octanal, nonanal, hexanal, 2,3-butanedione, and 1-octen-3-ol, which had the highest odor activity values among all compounds analyzed. These findings thus provide more insights in the chemical/molecular characteristics of milk fermented using S. thermophilus, which may provide a basis for improving dairy product flavor/odor during the process of fermentation and storage. Full article

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20 pages, 1367 KiB

Open AccessArticle

Free and Bound Phenolic Compound Content and Antioxidant Activity of Different Cultivated Blue Highland Barley Varieties from the Qinghai-Tibet Plateau

by Xi-Juan Yang, Bin Dang and Ming-Tao Fan

Molecules 2018, 23(4), 879; https://doi.org/10.3390/molecules23040879 - 11 Apr 2018

Cited by 119 | Viewed by 6726

Abstract

In this study, the polyphenols composition and antioxidant properties of 12 blue highland barley varieties planted on the Qinghai-Tibet Plateau area were measured. The contents of the free, bound and total phenolic acids varied between 166.20–237.60, 170.10–240.75 and 336.29–453.94 mg of gallic acid [...] Read more.

In this study, the polyphenols composition and antioxidant properties of 12 blue highland barley varieties planted on the Qinghai-Tibet Plateau area were measured. The contents of the free, bound and total phenolic acids varied between 166.20–237.60, 170.10–240.75 and 336.29–453.94 mg of gallic acid equivalents per 100 g of dry weight (DW) blue highland barley grains, while the free and bound phenolic acids accounted for 50.09% and 49.91% of the total phenolic acids, respectively. The contents of the free, bound and total flavones varied among 20.61–25.59, 14.91–22.38 and 37.91–47.98 mg of catechin equivalents per 100 g of dry weight (DW) of blue highland barley grains, while the free and bound flavones accounted for 55.90% and 44.10% of the total flavones, respectively. The prominent phenolic compounds in the blue hulless barley grains were gallic acid, benzoic acid, syringic acid, 4-coumaric acid, naringenin, hesperidin, rutin, (+)-catechin and quercetin. Among these, protocatechuic acid, chlorogenic acid and (+)-catechin were the major phenolic compounds in the free phenolics extract. The most abundant bound phenolics were gallic acid, benzoic acid, syringic acid, 4-coumaric acid, benzoic acid, dimethoxybenzoic acid, naringenin, hesperidin, quercetin and rutin. The average contribution of the bound phenolic extract to the DPPH^• free radical scavenging capacity was higher than 86%, that of free phenolic extract to the ABTS^•+ free radical scavenging capacity was higher than 79%, and that of free phenolic (53%) to the FRAP antioxidant activity was equivalent to that of the bound phenol extract (47%). In addition, the planting environment exerts a very important influence on the polyphenol composition, content and antioxidant activity of blue highland barley. The correlation analysis showed that 2,4-hydroxybenzoic acid and protocatechuic acid were the main contributors to the DPPH^• and ABTS^•+ free radical scavenging capacity in the free phenolic extract, while chlorogenic acid, vanillic acid, ferulic acid and quercetin were the main contributors to the free radical scavenging capacity in the bound phenol extract. The study results show that the blue highland barley grains have rich phenolic compounds and high antioxidant activity, as well as significant varietal differences. The free and bound phenolic extracts in the blue hulless barley grains have an equivalent proportion in the total phenol, and co-exist in two forms. They can be used as a potential valuable source of natural antioxidants, and can aid in enhancing the development and daily consumption of foods relating to blue highland barley. Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 27446 KiB

Open AccessArticle

Systematic Analysis of the Pleurotus ostreatus Laccase Gene (PoLac) Family and Functional Characterization of PoLac2 Involved in the Degradation of Cotton-Straw Lignin

by Xiaoyu Jiao, Guoqing Li, Yan Wang, Fan Nie, Xi Cheng, Muhammad Abdullah, Yi Lin and Yongping Cai

Molecules 2018, 23(4), 880; https://doi.org/10.3390/molecules23040880 - 11 Apr 2018

Cited by 36 | Viewed by 5412

Abstract

Fungal laccases play important roles in the degradation of lignocellulose. Although some PoLacs have been reported in several studies, still no comprehensive bioinformatics study of the LAC family in Pleurotus ostreatus has been reported. In this study, we identified 12 laccase genes [...] Read more.

Fungal laccases play important roles in the degradation of lignocellulose. Although some PoLacs have been reported in several studies, still no comprehensive bioinformatics study of the LAC family in Pleurotus ostreatus has been reported. In this study, we identified 12 laccase genes in the whole genome sequence of P. ostreatus and their physical characteristics, gene distribution, phylogenic relationships, gene structure, conserved motifs, and cis-elements were also analyzed. The expression patterns of 12 PoLac genes at different developmental stages and under different culture substrates were also analyzed. The results revealed that PoLac2 and PoLac12 may be involved in the degradation of lignin and the formation of the fruiting body, respectively. Subsequently, we overexpressed PoLac2 in P. ostreatus by the Agrobacterium tumefaciens-mediated transformation (ATMT) method. The transformants’ laccase activity increased in varying degrees, and the gene expression level of PoLac2 in transformants was 2–8 times higher than that of the wild-type strain. Furthermore, the lignin degradation rate by transgenic fungus over 30 days was 2.36–6.3% higher than that of wild-type. Our data show that overexpression of PoLac2 significantly enhanced the lignin degradation of cotton-straw. To our knowledge, this study is the first report to demonstrate the functions of PoLac2 in P. ostreatus. Full article

(This article belongs to the Section Metabolites)

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19 pages, 4419 KiB

Open AccessArticle

Current’s Fluctuations through Molecular Wires Composed of Thiophene Rings

by Judith Helena Ojeda Silva, Juan Camilo Cortés Peñaranda, Jovanny A. Gómez Castaño and Carlos Alberto Duque

Molecules 2018, 23(4), 881; https://doi.org/10.3390/molecules23040881 - 11 Apr 2018

Cited by 6 | Viewed by 3196

Abstract

We study theoretically the electronic transport and quantum fluctuations in single-molecule systems using thiophene rings as integrated elementary functions, as well as the dependence of these properties with the increase of the coupled rings, i.e., as a quantum wire. In order to analyze [...] Read more.

We study theoretically the electronic transport and quantum fluctuations in single-molecule systems using thiophene rings as integrated elementary functions, as well as the dependence of these properties with the increase of the coupled rings, i.e., as a quantum wire. In order to analyze the current flow through these molecular systems, the thiophene rings are considered to be connected to metal contacts, which, in general terms, will be related to the application of voltages (bias voltages or gate voltages) to generate non-equilibrium behavior between the contacts. Due to the nonlinear behavior that is generated when said voltages are applied, it is possible to observe quantum fluctuations in the transport properties of these molecular wires. For the calculation of the transport properties, we applied a tight-binding approach using the Landauer–Büttiker formalism and the Fischer–Lee relationship, by means of a semi-analytic Green’s function method within a real-space renormalization (decimation procedure). Our results showed an excellent agreement with results using a tight-binding model with a minimal number of parameters reported so far for these molecular systems. Full article

(This article belongs to the Section Physical Chemistry)

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14 pages, 46513 KiB

Open AccessArticle

Tracing Actin Filament Bundles in Three-Dimensional Electron Tomography Density Maps of Hair Cell Stereocilia

by Salim Sazzed, Junha Song, Julio A. Kovacs, Willy Wriggers, Manfred Auer and Jing He

Molecules 2018, 23(4), 882; https://doi.org/10.3390/molecules23040882 - 11 Apr 2018

Cited by 13 | Viewed by 5725

Abstract

Cryo-electron tomography (cryo-ET) is a powerful method of visualizing the three-dimensional organization of supramolecular complexes, such as the cytoskeleton, in their native cell and tissue contexts. Due to its minimal electron dose and reconstruction artifacts arising from the missing wedge during data collection, [...] Read more.

Cryo-electron tomography (cryo-ET) is a powerful method of visualizing the three-dimensional organization of supramolecular complexes, such as the cytoskeleton, in their native cell and tissue contexts. Due to its minimal electron dose and reconstruction artifacts arising from the missing wedge during data collection, cryo-ET typically results in noisy density maps that display anisotropic XY versus Z resolution. Molecular crowding further exacerbates the challenge of automatically detecting supramolecular complexes, such as the actin bundle in hair cell stereocilia. Stereocilia are pivotal to the mechanoelectrical transduction process in inner ear sensory epithelial hair cells. Given the complexity and dense arrangement of actin bundles, traditional approaches to filament detection and tracing have failed in these cases. In this study, we introduce BundleTrac, an effective method to trace hundreds of filaments in a bundle. A comparison between BundleTrac and manually tracing the actin filaments in a stereocilium showed that BundleTrac accurately built 326 of 330 filaments (98.8%), with an overall cross-distance of 1.3 voxels for the 330 filaments. BundleTrac is an effective semi-automatic modeling approach in which a seed point is provided for each filament and the rest of the filament is computationally identified. We also demonstrate the potential of a denoising method that uses a polynomial regression to address the resolution and high-noise anisotropic environment of the density map. Full article

(This article belongs to the Special Issue Selected Papers from the 10th Computational Structural Bioinformatics Workshop (CSBW-2017))

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15 pages, 1098 KiB

Open AccessArticle

Preconcentration of Trace Neonicotinoid Insecticide Residues Using Vortex-Assisted Dispersive Micro Solid-Phase Extraction with Montmorillonite as an Efficient Sorbent

by Khwankaew Moyakao, Yanawath Santaladchaiyakit, Supalax Srijaranai and Jitlada Vichapong

Molecules 2018, 23(4), 883; https://doi.org/10.3390/molecules23040883 - 11 Apr 2018

Cited by 24 | Viewed by 7109

Abstract

In this work, we investigated montmorillonite for adsorption of neonicotinoid insecticides in vortex-assisted dispersive micro-solid phase extraction (VA-d-μ-SPE). High-performance liquid chromatography with photodiode array detection was used for quantification and determination of neonicotinoid insecticide residues, including thiamethoxam, clothianidin, imidacloprid, acetamiprid, and thiacloprid. In [...] Read more.

In this work, we investigated montmorillonite for adsorption of neonicotinoid insecticides in vortex-assisted dispersive micro-solid phase extraction (VA-d-μ-SPE). High-performance liquid chromatography with photodiode array detection was used for quantification and determination of neonicotinoid insecticide residues, including thiamethoxam, clothianidin, imidacloprid, acetamiprid, and thiacloprid. In this method, the solid sorbent was dispersed into the aqueous sample solution and vortex agitation was performed to accelerate the extraction process. Finally, the solution was filtered from the solid sorbent with a membrane filter. The parameters affecting the extraction efficiency of the proposed method were optimized, such as amount of sorbent, sample volume, salt addition, type and volume of extraction solvent, and vortex time. The adsorbing results show that montmorillonite could be reused at least 4 times and be used as an effective adsorbent for rapid extraction/preconcentration of neonicotinoid insecticide residues. Under optimum conditions, linear dynamic ranges were achieved between 0.5 and 1000 ng mL⁻¹ with a correlation of determination (R²) greater than 0.99. Limit of detection (LOD) ranged from 0.005 to 0.065 ng mL⁻¹, while limit of quantification (LOQ) ranged from 0.008 to 0.263 ng mL⁻¹. The enrichment factor (EF) ranged from 8 to 176-fold. The results demonstrated that the proposed method not only provided a more simple and sensitive method, but also can be used as a powerful alternative method for the simultaneous determination of insecticide residues in natural surface water and fruit juice samples. Full article

(This article belongs to the Special Issue Green Analytical Chemistry)

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11 pages, 881 KiB

Open AccessArticle

Application of High-Performance Liquid Chromatography Coupled with Linear Ion Trap Quadrupole Orbitrap Mass Spectrometry for Qualitative and Quantitative Assessment of Shejin-Liyan Granule Supplements

by Jifeng Gu, Weijun Wu, Mengwei Huang, Fen Long, Xinhua Liu and Yizhun Zhu

Molecules 2018, 23(4), 884; https://doi.org/10.3390/molecules23040884 - 11 Apr 2018

Cited by 12 | Viewed by 4610

Abstract

A method for high-performance liquid chromatography coupled with linear ion trap quadrupole Orbitrap high-resolution mass spectrometry (HPLC-LTQ-Orbitrap MS) was developed and validated for the qualitative and quantitative assessment of Shejin-liyan Granule. According to the fragmentation mechanism and high-resolution MS data, 54 compounds, including [...] Read more.

A method for high-performance liquid chromatography coupled with linear ion trap quadrupole Orbitrap high-resolution mass spectrometry (HPLC-LTQ-Orbitrap MS) was developed and validated for the qualitative and quantitative assessment of Shejin-liyan Granule. According to the fragmentation mechanism and high-resolution MS data, 54 compounds, including fourteen isoflavones, eleven ligands, eight flavonoids, six physalins, six organic acids, four triterpenoid saponins, two xanthones, two alkaloids, and one licorice coumarin, were identified or tentatively characterized. In addition, ten of the representative compounds (matrine, galuteolin, tectoridin, iridin, arctiin, tectorigenin, glycyrrhizic acid, irigenin, arctigenin, and irisflorentin) were quantified using the validated HPLC-LTQ-Orbitrap MS method. The method validation showed a good linearity with coefficients of determination (r²) above 0.9914 for all analytes. The accuracy of the intra- and inter-day variation of the investigated compounds was 95.0–105.0%, and the precision values were less than 4.89%. The mean recoveries and reproducibilities of each analyte were 95.1–104.8%, with relative standard deviations below 4.91%. The method successfully quantified the ten compounds in Shejin-liyan Granule, and the results show that the method is accurate, sensitive, and reliable. Full article

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24 pages, 10744 KiB

Open AccessArticle

Furan- and Thiophene-2-Carbonyl Amino Acid Derivatives Activate Hypoxia-Inducible Factor via Inhibition of Factor Inhibiting Hypoxia-Inducible Factor-1

by Shin-ichi Kawaguchi, Yuhei Gonda, Takuya Yamamoto, Yuki Sato, Hiroyuki Shinohara, Yohsuke Kobiki, Atsuhiko Ichimura, Takashi Dan, Motohiro Sonoda, Toshio Miyata, Akiya Ogawa and Tadayuki Tsujita

Molecules 2018, 23(4), 885; https://doi.org/10.3390/molecules23040885 - 11 Apr 2018

Cited by 5 | Viewed by 6042

Abstract

Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-α (HIF-α) is a major transcription factor that orchestrates this protective effect. To activate HIF exogenously, without exposing cells to hypoxic conditions, many small-molecule inhibitors targeting prolyl hydroxylase [...] Read more.

Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-α (HIF-α) is a major transcription factor that orchestrates this protective effect. To activate HIF exogenously, without exposing cells to hypoxic conditions, many small-molecule inhibitors targeting prolyl hydroxylase domain-containing protein have been developed. In addition, suppression of factor inhibiting HIF-1 (FIH-1) has also been shown to have the potential to activate HIF-α. However, few small-molecule inhibitors of FIH-1 have been developed. In this study, we synthesized a series of furan- and thiophene-2-carbonyl amino acid derivatives having the potential to inhibit FIH-1. The inhibitory activities of these compounds were evaluated in SK-N-BE(2)c cells by measuring HIF response element (HRE) promoter activity. Several furan- and thiophene-2-carbonyl amino acid derivatives inhibited FIH-1 based on correlations among the docking score of the FIH-1 active site, the chemical structure of the compounds, and biological HIF-α/HRE transcriptional activity. Full article

(This article belongs to the Special Issue Directed Drug Design and Molecular Therapy)

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11 pages, 721 KiB

Open AccessArticle

Maternal Melatonin Therapy Attenuated Maternal High-Fructose Combined with Post-Weaning High-Salt Diets-Induced Hypertension in Adult Male Rat Offspring

by You-Lin Tain, Steve Leu, Wei-Chia Lee, Kay L. H. Wu and Julie Y. H. Chan

Molecules 2018, 23(4), 886; https://doi.org/10.3390/molecules23040886 - 11 Apr 2018

Cited by 17 | Viewed by 3924

Abstract

Consumption of food high in fructose and salt is associated with the epidemic of hypertension. Hypertension can originate from early life. Melatonin, a pleiotropic hormone, regulates blood pressure. We examined whether maternal melatonin therapy can prevent maternal high-fructose combined with post-weaning high-salt diet-induced [...] Read more.

Consumption of food high in fructose and salt is associated with the epidemic of hypertension. Hypertension can originate from early life. Melatonin, a pleiotropic hormone, regulates blood pressure. We examined whether maternal melatonin therapy can prevent maternal high-fructose combined with post-weaning high-salt diet-induced programmed hypertension in adult offspring. Pregnant Sprague-Dawley rats received either a normal diet (ND) or a 60% fructose diet (HF) during pregnancy and the lactation period. Male offspring were on either the ND or a high-salt diet (HS, 1% NaCl) from weaning to 12 weeks of age and were assigned to five groups (n = 8/group): ND/ND, HF/ND, ND/HS, HF/HS, and HF/HS+melatonin. Melatonin (0.01% in drinking water) was administered during pregnancy and lactation. We observed that maternal HF combined with post-weaning HS diets induced hypertension in male adult offspring, which was attenuated by maternal melatonin therapy. The beneficial effects of maternal melatonin therapy on HF/HS-induced hypertension related to regulating several nutrient-sensing signals, including Sirt1, Sirt4, Prkaa2, Prkab2, Pparg, and Ppargc1a. Additionally, melatonin increased protein levels of mammalian targets of rapamycin (mTOR), decreased plasma asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine levels, and increased the l-arginine-to-ADMA ratio. The reprogramming effects by which maternal melatonin therapy protects against hypertension of developmental origin awaits further elucidation. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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8 pages, 2901 KiB

Open AccessArticle

Three New Polyynes from Codonopsis pilosula and Their Activities on Lipid Metabolism

by Xiao-Yu Hu, Fu-Ying Qin, Xi-Feng Lu, Lan-Sheng Zhang and Yong-Xian Cheng

Molecules 2018, 23(4), 887; https://doi.org/10.3390/molecules23040887 - 12 Apr 2018

Cited by 19 | Viewed by 4080

Abstract

Three new polyynes, named choushenpilosulynes A–C (1–3), were isolated from an 85% aqueous EtOH extract of the roots of Codonopsis pilosula cultivated in Xundian County of Yunnan province, China. Their structures, including the absolute configuration of the glucose residue [...] Read more.

Three new polyynes, named choushenpilosulynes A–C (1–3), were isolated from an 85% aqueous EtOH extract of the roots of Codonopsis pilosula cultivated in Xundian County of Yunnan province, China. Their structures, including the absolute configuration of the glucose residue in 1 and 2, were determined by spectroscopic analysis and gas chromatography (GC). In addition, biological evaluation shows that all the compounds can inhibit the expression of the squalene monooxygenase (SQLE) gene in HepG2 cells, suggesting that these compounds may be involved in lipid metabolism. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 30065 KiB

Open AccessArticle

Synthesis, Crystal Structure and DFT Studies of a New Dinuclear Ag(I)-Malonamide Complex

by Saied M. Soliman, Assem Barakat, Mohammad Shahidul Islam and Hazem A. Ghabbour

Molecules 2018, 23(4), 888; https://doi.org/10.3390/molecules23040888 - 11 Apr 2018

Cited by 7 | Viewed by 4032

Abstract

The synthesis and structural aspects of a new dinuclear silver (I) complex with malonamide type ligand (L) is reported. Each Ag ion in the [Ag₂L₂(NO₃)₂]·H₂O complex is coordinated to two [...] Read more.

The synthesis and structural aspects of a new dinuclear silver (I) complex with malonamide type ligand (L) is reported. Each Ag ion in the [Ag₂L₂(NO₃)₂]·H₂O complex is coordinated to two ligands, L, each acting as a bridged ligand via its two pyridine arms; Ag(I) acts as a connector between them. Two types of Ag-ligands close contacts were detected: Ag–N1, Ag–N4 from the two L units, and Ag–O5, Ag—O6 from the two nitrate anions, wherein both the nitrate ions are inside the cage formed by the [Ag₂L₂] unit. The coordination geometry around each Ag(I) is a distorted tetrahedron. The [Ag₂L₂(NO₃)₂] complex units are connected by weak intermolecular C—H…O interactions. The different intermolecular interactions were quantified using Hirshfeld surface analysis. Using two DFT methods (B3LYP and WB97XD), the nature and strength of the Ag–N and Ag–O interactions were described using atoms in molecules (AIM) and natural bond orbital (NBO) analyses. Topological parameters indicated that the strength of the two Ag–N bonds was similar, while that of the two Ag–O interactions were significantly different. Moreover, the Ag–N interactions have a predominant covalent character, while the Ag–O interactions are mainly ionic. The NBO analysis indicated that the most important anti-bonding Ag-orbital in these interactions has an s-orbital character. Full article

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13 pages, 3614 KiB

Open AccessArticle

Continuous Separation of Light Olefin/Paraffin Mixtures on ZIF-4 by Pressure Swing Adsorption and Membrane Permeation

by Maximilian Hovestadt, Sebastian Friebe, Lailah Helmich, Marcus Lange, Jens Möllmer, Roger Gläser, Alexander Mundstock and Martin Hartmann

Molecules 2018, 23(4), 889; https://doi.org/10.3390/molecules23040889 - 11 Apr 2018

Cited by 21 | Viewed by 7187

Abstract

In this study, two zeolitic imidazolate frameworks (ZIFs) called ZIF-4 and ZIF-zni (zni is the network topology) were characterized by sorption studies regarding their paraffin/olefin separation potential. In particular, equilibrated pure and mixed gas adsorption isotherms of ethane and ethene were recorded at [...] Read more.

In this study, two zeolitic imidazolate frameworks (ZIFs) called ZIF-4 and ZIF-zni (zni is the network topology) were characterized by sorption studies regarding their paraffin/olefin separation potential. In particular, equilibrated pure and mixed gas adsorption isotherms of ethane and ethene were recorded at 293 K up to 3 MPa. ZIF-4 exhibits selectivities for ethane in the range of 1.5–3, which is promising for continuous pressure swing adsorption (PSA). ZIF-4 shows high cycle stability with promising separation potential regarding ethane, which results in purification of the more industrial desired olefin. Furthermore, both ZIF materials were implemented in Matrimid to prepare a mixed matrix membrane (MMM) and were used in the continuous separation of a propane/propene mixture. The separation performance of the neat polymer is drastically increased after embedding porous ZIF-4 crystals in the Matrimid matrix, especially at higher feed pressures (3–5 barg). Due to the smaller kinetic diameter of the olefin, the permeability is higher compared to the paraffin. Full article

(This article belongs to the Special Issue Zeolites and Related Nanoporous Materials: Synthesis, Characterization and Applications in Catalysis and Green Chemistry)

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15 pages, 3584 KiB

Open AccessArticle

Effects of BTEX on the Removal of Acetone in a Coaxial Non-Thermal Plasma Reactor: Role Analysis of the Methyl Group

by Liyuan Hou, Xiang Li, Deyuan Xie and Haining Wang

Molecules 2018, 23(4), 890; https://doi.org/10.3390/molecules23040890 - 12 Apr 2018

Cited by 8 | Viewed by 4705

Abstract

The removal of acetone and benzene series (BTEX) under individual and concurrent conditions is carried out in a coaxial nonthermal plasma (NTP) reactor. The results show that the benzene series has a significant negative impact on acetone conversion and CO₂ selectivity under [...] Read more.

The removal of acetone and benzene series (BTEX) under individual and concurrent conditions is carried out in a coaxial nonthermal plasma (NTP) reactor. The results show that the benzene series has a significant negative impact on acetone conversion and CO₂ selectivity under NTP treatment. Furthermore, it is found that p-xylene significantly promotes CO_x selectivity under co-treatment with acetone because of greater CO generation. Based on the results of transient FTIR, MS, and GC-MS, it is seen that quantities of formic acid, formaldehyde, and ring-opening byproducts from benzene series decomposition are reduced, while quantities of aromatic byproducts with carboxyl, phenolic, and aldehyde groups on the benzene ring increase under coexistence conditions. With the help of theoretical calculation and kinetic analysis, hydrogen abstraction from the methyl group and active hydroxyl radical consumption are proposed as critical factors in the BTEX inhibition effect on acetone degradation. Full article

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16 pages, 4546 KiB

Open AccessArticle

New and Old Genes Associated with Primary and Established Responses to Paclitaxel Treatment in Ovarian Cancer Cell Lines

by Monika Świerczewska, Andrzej Klejewski, Maciej Brązert, Dominika Kaźmierczak, Dariusz Iżycki, Michał Nowicki, Maciej Zabel and Radosław Januchowski

Molecules 2018, 23(4), 891; https://doi.org/10.3390/molecules23040891 - 12 Apr 2018

Cited by 18 | Viewed by 4027

Abstract

Development of drug resistance is the main reason for low chemotherapy effectiveness in treating ovarian cancer. Paclitaxel (PAC) is a chemotherapeutic drug used in the treatment of this cancer. We analysed the development of PAC resistance in two ovarian cancer cell lines. Exposure [...] Read more.

Development of drug resistance is the main reason for low chemotherapy effectiveness in treating ovarian cancer. Paclitaxel (PAC) is a chemotherapeutic drug used in the treatment of this cancer. We analysed the development of PAC resistance in two ovarian cancer cell lines. Exposure of drug-sensitive cell lines (A2780 and W1) to PAC was used to determine the primary response. An established response was determined in PAC-resistant sublines of the A2780 and W1 cell lines. qRT-PCR was performed to measure the expression levels of specific genes. We observed decreased expression of the PCDH9, NSBP1, MCTP1 and SEMA3A genes in the PAC-resistant cell lines. Short-term exposure to PAC led to increased expression of the MDR1 and BCRP genes in the A2780 and W1 cell lines. In the A2780 cell line, we also observed increased expression of the C4orf18 gene and decreased expression of the PCDH9 and SEMA3A genes after PAC treatment. In the W1 cell line, short-term treatment with PAC upregulated the expression of the ALDH1A1 gene, a marker of Cancer stem cells (CSCs). Our results suggest that downregulation of the PCDH9, NSBP1, MCTP1 and SEMA3A genes and upregulation of the MDR1, BCRP, C4orf18 and ALDH1A1 genes may be related to PAC resistance. Full article

(This article belongs to the Special Issue Counteracting Drug Resistant Mechanisms in Cancer)

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12 pages, 7752 KiB

Open AccessFeature PaperArticle

Assessing Photosensitizer Targeting Using Meso-Tetra(Carboxyphenyl) Porphyrin

by Upendra Chitgupi, Jonathan F. Lovell and Venugopal Rajendiran

Molecules 2018, 23(4), 892; https://doi.org/10.3390/molecules23040892 - 12 Apr 2018

Cited by 7 | Viewed by 4813

Abstract

Mesotetra(4-carboxyphenyl)porphyrin (mTCPP) is a commercially available small molecule fluorophore and photosensitizer with four free carboxylic acid groups. mTCPP can readily be conjugated with amines for facile attachment of functional groups. In this work, we synthesized and assessed tetravalent, lysine-conjugated mTCPP, for its potential [...] Read more.

Mesotetra(4-carboxyphenyl)porphyrin (mTCPP) is a commercially available small molecule fluorophore and photosensitizer with four free carboxylic acid groups. mTCPP can readily be conjugated with amines for facile attachment of functional groups. In this work, we synthesized and assessed tetravalent, lysine-conjugated mTCPP, for its potential applications in targeted imaging and photodynamic therapy. Fmoc-protected d-lysine or l-lysine was conjugated to mTCPP via amide coupling with the epsilon amine group of lysine, followed by Fmoc deprotection. The resulting compounds did not dissolve well in aqueous solvent, but could be solubilized with the assistance of surfactants, including cholic acid. The l-amino acid transporter (LAT1) can uptake diverse neutral l-amino acids. In vitro studies with U87 cells revealed a non-specific uptake of the hydrophobic Fmoc-protected lysine-conjugated mTCPP precursors, but not d- or l-lysine mTCPP. Likewise, only the Fmoc-protected compounds induced substantial phototoxicty in cells following incubation and irradiation with blue light. These experimental results do not provide evidence to suggest that lysine-mTCPP is able to specifically target cancer cells. However, they do highlight mTCPP as a convenient and accessible framework for assessing molecular targeting of photosensitizers. Full article

(This article belongs to the Special Issue Advances in Photodynamic Therapy 2018)

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10 pages, 16573 KiB

Open AccessArticle

Wound Stress, an Unheeded Factor for Echinacoside Accumulation in Cistanche deserticola Y. C. Ma

by Gaosheng Hu, Tianran Wu, Yue Chang, Xinyi Zhan and Jingming Jia

Molecules 2018, 23(4), 893; https://doi.org/10.3390/molecules23040893 - 12 Apr 2018

Cited by 2 | Viewed by 3539

Abstract

Cistanche deserticola Y. C. Ma, a precious parasitic medicinal herb distributed in desert areas in the Northwest of China, also known as “desert ginseng”, has been used in China for thousands of years for its nourishing effects. The phenylethanoid glycosides (PeGs) have been [...] Read more.

Cistanche deserticola Y. C. Ma, a precious parasitic medicinal herb distributed in desert areas in the Northwest of China, also known as “desert ginseng”, has been used in China for thousands of years for its nourishing effects. The phenylethanoid glycosides (PeGs) have been proven as the main effective compounds due to their neuroprotective effects and were used for quality control. In this study, echinacoside content, a representative PeG, total phenolic content, DPPH scavenging activity, and PAL activity were determined in different tissues of C. deserticola. Our results showed that most indices had a similar pattern of scale > cambium ring > pith and bottom part > middle part > upper part. Besides, stereomicroscopic observation showed that the scale surface was densely covered with physical wounds formed during vertical and broadwise growth in sand. Thus, wound area was quantified and a linear regression analysis was conducted between wound area and PAL activity, total phenolics, and echinacoside content. Our results suggested that physical wounding caused by sand might play an important role in echinacoside biosynthesis which has never been noticed in C. deserticola development. Furthermore, the coexistence of the highest PAL activity and highest echinacoside accumulation in scale tissue might indicate that the biosynthetic site of echinacoside in C. deseticola Y. C. Ma is mainly in the scale tissue. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 25666 KiB

Open AccessArticle

Identification by Molecular Docking of Homoisoflavones from Leopoldia comosa as Ligands of Estrogen Receptors

by Fedora Grande, Bruno Rizzuti, Maria A. Occhiuzzi, Giuseppina Ioele, Teresa Casacchia, Fabrizio Gelmini, Rita Guzzi, Antonio Garofalo and Giancarlo Statti

Molecules 2018, 23(4), 894; https://doi.org/10.3390/molecules23040894 - 12 Apr 2018

Cited by 57 | Viewed by 6612

Abstract

The physiological responses to estrogen hormones are mediated within specific tissues by at least two distinct receptors, ERα and ERβ. Several natural and synthetic molecules show activity by interacting with these proteins. In particular, a number of vegetal compounds known as phytoestrogens shows [...] Read more.

The physiological responses to estrogen hormones are mediated within specific tissues by at least two distinct receptors, ERα and ERβ. Several natural and synthetic molecules show activity by interacting with these proteins. In particular, a number of vegetal compounds known as phytoestrogens shows estrogenic or anti-estrogenic activity. The majority of these compounds belongs to the isoflavones family and the most representative one, genistein, shows anti-proliferative effects on various hormone-sensitive cancer cells, including breast, ovarian and prostate cancer. In this work we describe the identification of structurally related homoisoflavones isolated from Leopoldia comosa (L.) Parl. (L. comosa), a perennial bulbous plant, potentially useful as hormonal substitutes or complements in cancer treatments. Two of these compounds have been selected as potential ligands of estrogen receptors (ERs) and the interaction with both isoforms of estrogen receptors have been investigated through molecular docking on their crystallographic structures. The results provide evidence of the binding of these compounds to the target receptors and their interactions with key residues of the active sites of the two proteins, and thus they could represent suitable leads for the development of novel tools for the dissection of ER signaling and the development of new pharmacological treatments in hormone-sensitive cancers. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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15 pages, 1808 KiB

Open AccessArticle

UFLC-Q-TOF-MS/MS-Based Screening and Identification of Flavonoids and Derived Metabolites in Human Urine after Oral Administration of Exocarpium Citri Grandis Extract

by Xuan Zeng, Weiwei Su, Yuying Zheng, Hong Liu, Panlin Li, Weijian Zhang, Yuting Liang, Yang Bai, Wei Peng and Hongliang Yao

Molecules 2018, 23(4), 895; https://doi.org/10.3390/molecules23040895 - 12 Apr 2018

Cited by 71 | Viewed by 7061

Abstract

Exocarpium Citri grandis (ECG) is an important Traditional Chinese Medicine (TCM) for the treatment of cough and phlegm, and the flavonoids contained were considered the main effective components. To date, the systematic chemical profiling of these flavonoids and derived in vivo metabolites in [...] Read more.

Exocarpium Citri grandis (ECG) is an important Traditional Chinese Medicine (TCM) for the treatment of cough and phlegm, and the flavonoids contained were considered the main effective components. To date, the systematic chemical profiling of these flavonoids and derived in vivo metabolites in human have not been well investigated. ECG was extracted using boiling water and then provided to volunteers for oral administration. Following the ingestion, urine samples were collected from volunteers over 48 h. The extract and urine samples were analyzed using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS) system to screen and identify flavonoids and derived in vivo metabolites. A total of 18 flavonoids were identified in the ECG extract, and 20 metabolites, mainly glucuronide and sulfate conjugates, were screened in urine samples collected post consumption. The overall excretion of naringenin metabolites corresponded to 5.45% of intake and occurred mainly within 4–12 h after the ingestion. Meanwhile, another 29 phenolic catabolites were detected in urine. Obtained data revealed that flavonoids were abundant in the ECG extract, and these components underwent extensive phase II metabolism in humans. These results provided valuable information for further study of the pharmacology and mechanism of action of ECG. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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11 pages, 646 KiB

Open AccessFeature PaperArticle

Radical-Mediated Reactions of α-Bromo Aluminium Thioacetals, α-Bromothioesters, and Xanthates for Thiolactone Synthesis

by Ruairí O. McCourt, Fabrice Dénès and Eoin M. Scanlan

Molecules 2018, 23(4), 897; https://doi.org/10.3390/molecules23040897 - 13 Apr 2018

Cited by 6 | Viewed by 5609

Abstract

Thiolactones have attracted considerable attention in recent years as bioactive natural products, lead compounds for drug discovery, molecular probes, and reagents for polymerisation. We have investigated radical-mediated C-C bond forming reactions as a strategy for thiolactone synthesis. Cyclisation of an α-bromo aluminium thioacetal [...] Read more.

Thiolactones have attracted considerable attention in recent years as bioactive natural products, lead compounds for drug discovery, molecular probes, and reagents for polymerisation. We have investigated radical-mediated C-C bond forming reactions as a strategy for thiolactone synthesis. Cyclisation of an α-bromo aluminium thioacetal was investigated under radical conditions. It was found that at low temperature, a radical fragmentation and rearrangement process occurs. A putative reaction mechanism involving a previously unreported aluminium templated thiol-ene step for the rearrangement process is presented. Cyclisation reactions of α-bromo thioesters and α-xanthate thioesters under radical mediated conditions furnished the desired thiolactones in moderate yields. Full article

(This article belongs to the Special Issue Radical Chemistry)

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7 pages, 855 KiB

Open AccessCommunication

Cardiovascular Mechanisms of Action of Anthocyanins May Be Associated with the Impact of Microbial Metabolites on Heme Oxygenase-1 in Vascular Smooth Muscle Cells

by Emily F. Warner, Ildefonso Rodriguez-Ramiro, Maria A. O’Connell and Colin D. Kay

Molecules 2018, 23(4), 898; https://doi.org/10.3390/molecules23040898 - 13 Apr 2018

Cited by 15 | Viewed by 3509

Abstract

Anthocyanins are reported to have cardio-protective effects, although their mechanisms of action remain elusive. We aimed to explore the effects of microbial metabolites common to anthocyanins and other flavonoids on vascular smooth muscle heme oxygenase-1 (HO-1) expression. Thirteen phenolic metabolites identified by previous [...] Read more.

Anthocyanins are reported to have cardio-protective effects, although their mechanisms of action remain elusive. We aimed to explore the effects of microbial metabolites common to anthocyanins and other flavonoids on vascular smooth muscle heme oxygenase-1 (HO-1) expression. Thirteen phenolic metabolites identified by previous anthocyanin human feeding studies, as well as 28 unique mixtures of metabolites and their known precursor structures were explored for their activity on HO-1 protein expression in rat aortic smooth muscle cells (RASMCs). No phenolic metabolites were active when treated in isolation; however, five mixtures of phenolic metabolites significantly increased HO-1 protein expression (127.4–116.6%, p ≤ 0.03). The present study demonstrates that phenolic metabolites of anthocyanins differentially affect HO-1 activity, often having additive, synergistic or nullifying effects. Full article

(This article belongs to the Special Issue Advances in Anthocyanin Research 2018)

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23 pages, 3214 KiB

Open AccessFeature PaperArticle

Differential Effects of Linkers on the Activity of Amphiphilic Tobramycin Antifungals

by Marina Y. Fosso, Sanjib K. Shrestha, Nishad Thamban Chandrika, Emily K. Dennis, Keith D. Green and Sylvie Garneau-Tsodikova

Molecules 2018, 23(4), 899; https://doi.org/10.3390/molecules23040899 - 13 Apr 2018

Cited by 11 | Viewed by 4057

Abstract

As the threat associated with fungal infections continues to rise and the availability of antifungal drugs remains a concern, it becomes obvious that the need to bolster the antifungal armamentarium is urgent. Building from our previous findings of tobramycin (TOB) derivatives with antifungal [...] Read more.

As the threat associated with fungal infections continues to rise and the availability of antifungal drugs remains a concern, it becomes obvious that the need to bolster the antifungal armamentarium is urgent. Building from our previous findings of tobramycin (TOB) derivatives with antifungal activity, we further investigate the effects of various linkers on the biological activity of these aminoglycosides. Herein, we analyze how thioether, sulfone, triazole, amide, and ether functionalities affect the antifungal activity of alkylated TOB derivatives against 22 Candida, Cryptococcus, and Aspergillus species. We also evaluate their impact on the hemolysis of murine erythrocytes and the cytotoxicity against mammalian cell lines. While the triazole linker appears to confer optimal activity overall, all of the linkers incorporated into the TOB derivatives resulted in compounds that are very effective against the Cryptococcus neoformans species, with MIC values ranging from 0.48 to 3.9 μg/mL. Full article

(This article belongs to the Special Issue Recent Development on the New Applications of Aminoglycosides)

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18 pages, 11675 KiB

Open AccessArticle

Comparative Phytonutrient Analysis of Broccoli By-Products: The Potentials for Broccoli By-Product Utilization

by Mengpei Liu, Lihua Zhang, Suk Lan Ser, Jonathan R. Cumming and Kang-Mo Ku

Molecules 2018, 23(4), 900; https://doi.org/10.3390/molecules23040900 - 13 Apr 2018

Cited by 96 | Viewed by 13989

Abstract

The phytonutrient concentrations of broccoli (Brassica oleracea var. italica) florets, stems, and leaves were compared to evaluate the value of stem and leaf by-products as a source of valuable nutrients. Primary metabolites, including amino acids, organic acids, and sugars, as well as [...] Read more.

The phytonutrient concentrations of broccoli (Brassica oleracea var. italica) florets, stems, and leaves were compared to evaluate the value of stem and leaf by-products as a source of valuable nutrients. Primary metabolites, including amino acids, organic acids, and sugars, as well as glucosinolates, carotenoids, chlorophylls, vitamins E and K, essential mineral elements, total phenolic content, antioxidant activity, and expression of glucosinolate biosynthesis and hydrolysis genes were quantified from the different broccoli tissues. Broccoli florets had higher concentrations of amino acids, glucoraphanin, and neoglucobrassicin compared to other tissues, whereas leaves were higher in carotenoids, chlorophylls, vitamins E and K, total phenolic content, and antioxidant activity. Leaves were also good sources of calcium and manganese compared to other tissues. Stems had the lowest nitrile formation from glucosinolate. Each tissue exhibited specific core gene expression profiles supporting glucosinolate metabolism, with different gene homologs expressed in florets, stems, and leaves, which suggests that tissue-specific pathways function to support primary and secondary metabolic pathways in broccoli. This comprehensive nutrient and bioactive compound profile represents a useful resource for the evaluation of broccoli by-product utilization in the human diet, and as feedstocks for bioactive compounds for industry. Full article

(This article belongs to the Special Issue Chemicals from Food Supply Chain By-Products and Waste Streams)

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11 pages, 11414 KiB

Open AccessArticle

Preconcentration and Determination of Perfluoroalkyl Substances (PFASs) in Water Samples by Bamboo Charcoal-Based Solid-Phase Extraction Prior to Liquid Chromatography–Tandem Mass Spectrometry

by Ze-Hui Deng, Chuan-Ge Cheng, Xiao-Li Wang, Shui-He Shi, Ming-Lin Wang and Ru-Song Zhao

Molecules 2018, 23(4), 902; https://doi.org/10.3390/molecules23040902 - 14 Apr 2018

Cited by 26 | Viewed by 5542

Abstract

In this work, bamboo charcoal was used as solid-phase extraction adsorbent for the enrichment of six perfluoroalkyl acids (PFAAs) in environmental water samples before liquid chromatography–tandem mass spectrometry analysis. The specific porous structure, high specific surface area, high porosity, and stability of bamboo [...] Read more.

In this work, bamboo charcoal was used as solid-phase extraction adsorbent for the enrichment of six perfluoroalkyl acids (PFAAs) in environmental water samples before liquid chromatography–tandem mass spectrometry analysis. The specific porous structure, high specific surface area, high porosity, and stability of bamboo charcoal were characterized. Several experimental parameters which considerably affect extraction efficiency were investigated and optimized in detail. The experimental data exhibited low limits of detection (LODs) (0.01–1.15 ng/L), wide linear range (2–3 orders of magnitude and R ≥ 0.993) within the concentration range of 0.1–1000 ng/L, and good repeatability (2.7–5.0%, n = 5 intraday and 4.8–8.3%, n = 5 interday) and reproducibility (5.3–8.0%, n = 3). Bamboo charcoal was successfully used for the enrichment and determination of PFAAs in real environmental water samples. The bamboo charcoal-based solid-phase extraction coupled with liquid chromatography–tandem mass spectrometry analysis possessed great potential in the determination of trace PFAA levels in environmental water samples. Full article

(This article belongs to the Special Issue Solid Phase Extraction: State of the Art and Future Perspectives)

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18 pages, 12961 KiB

Open AccessArticle

Single Laboratory Validation of a Quantitative Core Shell-Based LC Separation for the Evaluation of Silymarin Variability and Associated Antioxidant Activity of Pakistani Ecotypes of Milk Thistle (Silybum Marianum L.)

by Samantha Drouet, Bilal Haider Abbasi, Annie Falguières, Waqar Ahmad, Sumaira, Clothilde Ferroud, Joël Doussot, Jean Raymond Vanier, Eric Lainé and Christophe Hano

Molecules 2018, 23(4), 904; https://doi.org/10.3390/molecules23040904 - 14 Apr 2018

Cited by 34 | Viewed by 6154

Abstract

Fruits of Silybum marianum (L.) Gaernt are the main source of taxifolin derived flavonolignans. Together, these molecules constitute a mixture called silymarin with many useful applications for cosmetic and pharmaceutic industries. Here, a validated method for the separation of the silymarin constituents has [...] Read more.

Fruits of Silybum marianum (L.) Gaernt are the main source of taxifolin derived flavonolignans. Together, these molecules constitute a mixture called silymarin with many useful applications for cosmetic and pharmaceutic industries. Here, a validated method for the separation of the silymarin constituents has been developed to ensure precision and accuracy in their quantification. Each compound was separated with a high reproducibility. Precision and repeatability of the quantification method were validated according to the AOAC recommendations. The method was then applied to study the natural variability of wild accessions of S. marianum. Analysis of the variation in the fruits composition of these 12 accessions from Pakistan evidenced a huge natural diversity. Correlation analysis suggested a synergistic action of the different flavonolignans to reach the maximal antioxidant activity, as determined by cupric ion reducing antioxidant capacity (CUPRAC) and ferric reducing antioxidant power (FRAP) assays. Principal component analysis (PCA) separated the 12 accessions into three distinct groups that were differing from their silymarin contents, whereas hierarchical clustering analysis (HCA) evidenced strong variations in their silymarin composition, leading to the identification of new silybin-rich chemotypes. These results proved that the present method allows for an efficient separation and quantification of the main flavonolignans with potent antioxidant activities. Full article

(This article belongs to the Collection Advances in Liquid Separation Techniques for Food and Pharmaceutical Analysis)

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18 pages, 12369 KiB

Open AccessArticle

Carotenoid Lutein Selectively Inhibits Breast Cancer Cell Growth and Potentiates the Effect of Chemotherapeutic Agents through ROS-Mediated Mechanisms

by Xiaoming Gong, Joshua R. Smith, Haley M. Swanson and Lewis P. Rubin

Molecules 2018, 23(4), 905; https://doi.org/10.3390/molecules23040905 - 14 Apr 2018

Cited by 105 | Viewed by 11324

Abstract

Increasing evidence suggests that dietary carotenoids may reduce the risk of breast cancer. However, anti-breast cancer effects of carotenoids have been controversial, albeit understudied. Here, we investigated the effects of specific carotenoids on a wide range of breast cancer cell lines, and found [...] Read more.

Increasing evidence suggests that dietary carotenoids may reduce the risk of breast cancer. However, anti-breast cancer effects of carotenoids have been controversial, albeit understudied. Here, we investigated the effects of specific carotenoids on a wide range of breast cancer cell lines, and found that among several carotenoids (including β-carotene, lutein, and astaxanthin), lutein significantly inhibits breast cancer cell growth by inducing cell-cycle arrest and caspase-independent cell death, but it has little effect on the growth of primary mammary epithelial cells (PmECs). Moreover, lutein-mediated growth inhibition of breast cancer cells is quantitatively similar to that induced by chemotherapeutic taxanes, paclitaxel and docetaxel, and exposure to lutein plus taxanes additively inhibits breast cancer cell growth. Analysis of mechanisms showed that lutein treatment significantly increases the intracellular reactive oxygen species (ROS) production in triple-negative breast cancer (TNBC) cells, but not in normal PmECs. Lutein-induced growth inhibition is also attenuated by the radical oxygen scavenger N-acetyl cysteine, suggesting a role for ROS generation in the growth inhibitory effect of lutein on TNBC cells. Additionally, we found that the p53 signaling pathway is activated and HSP60 levels are increased by lutein treatment, which may contribute partly to the induction of growth inhibition in TNBC cells. Our findings show that lutein promotes growth inhibition of breast cancer cells through increased cell type-specific ROS generation and alternation of several signaling pathways. Dietary lutein supplementation may be a promising alternative and/or adjunct therapeutic candidate against breast cancer. Full article

(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)

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14 pages, 15105 KiB

Open AccessArticle

Complexes of CO₂ with the Azoles: Tetrel Bonds, Hydrogen Bonds and Other Secondary Interactions

by Janet E. Del Bene, José Elguero and Ibon Alkorta

Molecules 2018, 23(4), 906; https://doi.org/10.3390/molecules23040906 - 14 Apr 2018

Cited by 35 | Viewed by 5213

Abstract

Ab initio MP2/aug’-cc-pVTZ calculations have been performed to investigate the complexes of CO₂ with the azoles pyrrole, pyrazole, imidazole, 1,2,3- and 1,2,4-triazole, tetrazole and pentazole. Three types of complexes have been found on the CO₂:azole potential surfaces. These include ten [...] Read more.

Ab initio MP2/aug’-cc-pVTZ calculations have been performed to investigate the complexes of CO₂ with the azoles pyrrole, pyrazole, imidazole, 1,2,3- and 1,2,4-triazole, tetrazole and pentazole. Three types of complexes have been found on the CO₂:azole potential surfaces. These include ten complexes stabilized by tetrel bonds that have the azole molecule in the symmetry plane of the complex; seven tetrel-bonded complexes in which the CO₂ molecule is perpendicular to the symmetry plane; and four hydrogen-bonded complexes. Eight of the planar complexes are stabilized by Nx···C tetrel bonds and by a secondary interaction involving an adjacent Ny-H bond and an O atom of CO₂. The seven perpendicular CO₂:azole complexes form between CO₂ and two adjacent N atoms of the ring, both of which are electron-pair donors. In three of the four hydrogen-bonded complexes, the proton-donor Nz-H bond of the ring is bonded to two C-H bonds, thereby precluding the planar and perpendicular complexes. The fourth hydrogen-bonded complex forms with the strongest acid pentazole. Binding energies, charge-transfer energies and changes in CO₂ stretching and bending frequencies upon complex formation provide consistent descriptions of these complexes. Coupling constants across tetrel bonds are negligibly small, but ^2hJ(Ny-C) across Nz-H···C hydrogen bonds are larger and increase as the number of N atoms in the ring increases. Full article

(This article belongs to the Special Issue Tetrel Bonds)

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18 pages, 29645 KiB

Open AccessArticle

PKIDB: A Curated, Annotated and Updated Database of Protein Kinase Inhibitors in Clinical Trials

by Fabrice Carles, Stéphane Bourg, Christophe Meyer and Pascal Bonnet

Molecules 2018, 23(4), 908; https://doi.org/10.3390/molecules23040908 - 15 Apr 2018

Cited by 133 | Viewed by 12766

Abstract

The number of protein kinase inhibitors (PKIs) approved worldwide continues to grow steadily, with 39 drugs approved in the period between 2001 and January 2018. PKIs on the market have been the subject of many reviews, and structure-property relationships specific to this class [...] Read more.

The number of protein kinase inhibitors (PKIs) approved worldwide continues to grow steadily, with 39 drugs approved in the period between 2001 and January 2018. PKIs on the market have been the subject of many reviews, and structure-property relationships specific to this class of drugs have been inferred. However, the large number of PKIs under development is often overlooked. In this paper, we present PKIDB (Protein Kinase Inhibitor Database), a monthly-updated database gathering approved PKIs as well as PKIs currently in clinical trials. The database compiles currently 180 inhibitors ranging from phase 0 to 4 clinical trials along with annotations extracted from seven public resources. The distribution and property ranges of standard physicochemical properties are presented. They can be used as filters to better prioritize compound selection for future screening campaigns. Interestingly, more than one-third of the kinase inhibitors violate at least one Lipinski’s rule. A Principal Component Analysis (PCA) reveals that Type-II inhibitors are mapped to a distinct chemical space as compared to orally administrated drugs as well as to other types of kinase inhibitors. Using a Principal Moment of Inertia (PMI) analysis, we show that PKIs under development tend to explore new shape territories as compared to approved PKIs. In order to facilitate the analysis of the protein space, the kinome tree has been annotated with all protein kinases being targeted by PKIs. Finally, we analyzed the pipeline of the pharmaceutical companies having PKIs on the market or still under development. We hope that this work will assist researchers in the kinase field in identifying and designing the next generation of kinase inhibitors for still untargeted kinases. The PKIDB database is freely accessible from a website at http://www.icoa.fr/pkidb and can be easily browsed through a user-friendly spreadsheet-like interface. Full article

(This article belongs to the Special Issue Kinase Inhibitors)

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15 pages, 3240 KiB

Open AccessArticle

Pharmacokinetic–Pharmacodynamic Model for the Testosterone-Suppressive Effect of Leuprolide in Normal and Prostate Cancer Rats

by Dong-Seok Lee, Sook-Jin Kim, Go-Wun Choi, Yong-Bok Lee and Hea-Young Cho

Molecules 2018, 23(4), 909; https://doi.org/10.3390/molecules23040909 - 15 Apr 2018

Cited by 7 | Viewed by 5828

Abstract

This study developed the pharmacokinetic (PK)–pharmacodynamic (PD) model of the testosterone-suppressive effect of leuprolide for evaluation of the sustained release (SR) depot and leuprolide solution in rats with or without prostate cancer. Six groups of rats were divided by the routes of administration [...] Read more.

This study developed the pharmacokinetic (PK)–pharmacodynamic (PD) model of the testosterone-suppressive effect of leuprolide for evaluation of the sustained release (SR) depot and leuprolide solution in rats with or without prostate cancer. Six groups of rats were divided by the routes of administration (intravenous and subcutaneous injection) and kinds of formulation (vehicle, leuprolide solution, and SR depot). The PK profile after subcutaneous injection of leuprolide solution could be well-described by the one-compartment model. The absorption rate constant, the total body clearance, and the volume of distribution were estimated at 16.67 h⁻¹, 514.46 mL/h, and 487.40 mL. Using PK parameters in the solution-administered group, the PK model for the SR depot was developed. The PK–PD model was constructed by describing the testosterone-suppressive effect of leuprolide using the feedback turnover model. The response of testosterone after administration of each formulation was well described using this PK–PD model for the estimation of PD parameters (EC₅₀, E_max, h) and systemic parameters (k_in, k_out, k_{f on}, k_{f off}). The developed PK–PD model containing an inhibitory feedback system could successfully describe the testosterone-suppressive effect of leuprolide in the type of formulation. The PK–PD model developed would be useful for evaluating the formulation of similar drugs whose effect is regulated through the feedback mechanism. Full article

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17 pages, 785 KiB

Open AccessArticle

Evaluating Molecular Properties Involved in Transport of Small Molecules in Stratum Corneum: A Quantitative Structure-Activity Relationship for Skin Permeability

by Chen-Peng Chen, Chan-Cheng Chen, Chia-Wen Huang and Yen-Ching Chang

Molecules 2018, 23(4), 911; https://doi.org/10.3390/molecules23040911 - 15 Apr 2018

Cited by 65 | Viewed by 9569

Abstract

The skin permeability (Kp) defines the rate of a chemical penetrating across the stratum corneum. This value is widely used to quantitatively describe the transport of molecules in the outermost layer of epidermal skin and indicate the significance of skin absorption. [...] Read more.

The skin permeability (Kp) defines the rate of a chemical penetrating across the stratum corneum. This value is widely used to quantitatively describe the transport of molecules in the outermost layer of epidermal skin and indicate the significance of skin absorption. This study defined a Kp quantitative structure-activity relationship (QSAR) based on 106 chemical substances of Kp measured using human skin and interpreted the molecular interactions underlying transport behavior of small molecules in the stratum corneum. The Kp QSAR developed in this study identified four molecular descriptors that described the molecular cyclicity in the molecule reflecting local geometrical environments, topological distances between pairs of oxygen and chlorine atoms, lipophilicity, and similarity to antineoplastics in molecular properties. This Kp QSAR considered the octanol-water partition coefficient to be a direct influence on transdermal movement of molecules. Moreover, the Kp QSAR identified a sub-domain of molecular properties initially defined to describe the antineoplastic resemblance of a compound as a significant factor in affecting transdermal permeation of solutes. This finding suggests that the influence of molecular size on the chemical’s skin-permeating capability should be interpreted with other relevant physicochemical properties rather than being represented by molecular weight alone. Full article

(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products 2018)

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7 pages, 3768 KiB

Open AccessArticle

Electrochemical Aptamer-Based Sensors for Rapid Point-of-Use Monitoring of the Mycotoxin Ochratoxin A Directly in a Food Stream

by Jacob Somerson and Kevin W. Plaxco

Molecules 2018, 23(4), 912; https://doi.org/10.3390/molecules23040912 - 15 Apr 2018

Cited by 37 | Viewed by 6560

Abstract

The ability to measure the concentration of specific small molecules continuously and in real-time in complex sample streams would impact many areas of agriculture, food safety, and food production. Monitoring for mycotoxin taint in real time during food processing, for example, could improve [...] Read more.

The ability to measure the concentration of specific small molecules continuously and in real-time in complex sample streams would impact many areas of agriculture, food safety, and food production. Monitoring for mycotoxin taint in real time during food processing, for example, could improve public health. Towards this end, we describe here an inexpensive electrochemical DNA-based sensor that supports real-time monitor of the mycotoxin ochratoxin A in a flowing stream of foodstuffs. Full article

(This article belongs to the Special Issue Nucleic Acid Aptamers)

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15 pages, 21559 KiB

Open AccessArticle

Poly(vinyl Chloride) Photostabilization in the Presence of Schiff Bases Containing a Thiadiazole Moiety

by Naser Shaalan, Nawres‎‏ Laftah, Gamal A. El-Hiti, Mohammad Hayal Alotaibi, Raad Muslih, Dina S. Ahmed and Emad Yousif

Molecules 2018, 23(4), 913; https://doi.org/10.3390/molecules23040913 - 15 Apr 2018

Cited by 47 | Viewed by 4330

Abstract

Five Schiff bases containing a thiadiazole moiety have been used as poly(vinyl chloride) photostabilizers at low concentrations. The efficiency of Schiff bases as photostabilizers was investigated using various techniques, for example, the changes in poly(vinyl chloride) infrared spectra, molecular weight, chain scission quantum [...] Read more.

Five Schiff bases containing a thiadiazole moiety have been used as poly(vinyl chloride) photostabilizers at low concentrations. The efficiency of Schiff bases as photostabilizers was investigated using various techniques, for example, the changes in poly(vinyl chloride) infrared spectra, molecular weight, chain scission quantum yield, and surface morphology were monitored upon irradiation with an ultraviolet light. Evidently, all the additives used inhibited poly(vinyl chloride) photodegradation at a significant level. The most efficient Schiff base exhibited a high level of aromaticity and contained a hydroxyl group. It seems possible that such photostabilization could be due to the direct absorption of ultraviolet radiation by the additives. In addition, Schiff bases could act as radical scavengers and proton transfer facilitators to stabilize the polymeric materials. Full article

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11 pages, 1157 KiB

Open AccessFeature PaperCommunication

One-Pot, Highly Stereoselective Synthesis of Dithioacetal-α,α-Diglycosides

by Maria F. Céspedes Dávila, Jérémy P. Schneider, Amélie Godard, Damien Hazelard and Philippe Compain

Molecules 2018, 23(4), 914; https://doi.org/10.3390/molecules23040914 - 15 Apr 2018

Cited by 10 | Viewed by 5086

Abstract

A one-step access to dithioacetal-α,α-diglycosides is reported. The synthetic strategy is based on the thioacetalization of aldehydes or ketones via highly stereoselective ring-opening of 1,6 anhydrosugars with bis(trimethylsilyl)sulfide. Full article

(This article belongs to the Special Issue Glycomimetics: Design, Synthesis and Therapeutic Applications)

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12 pages, 6167 KiB

Open AccessArticle

Cultivar and Harvest Month Influence the Nutrient Content of Opuntia spp. Cactus Pear Cladode Mucilage Extracts

by Alba Du Toit, Maryna De Wit and Arno Hugo

Molecules 2018, 23(4), 916; https://doi.org/10.3390/molecules23040916 - 16 Apr 2018

Cited by 40 | Viewed by 4909

Abstract

Mucilage extracted from cactus pear cladodes is a hydrocolloid gum. It is a novel, natural, low-kilojoule, cost-effective texture-modifying ingredient in functional food products. Yet, the cultivar with the most optimal nutrient content and the preferred harvest times are as yet unknown. For this [...] Read more.

Mucilage extracted from cactus pear cladodes is a hydrocolloid gum. It is a novel, natural, low-kilojoule, cost-effective texture-modifying ingredient in functional food products. Yet, the cultivar with the most optimal nutrient content and the preferred harvest times are as yet unknown. For this reason, mucilage from three Opuntia ficus-indica (Algerian, Morado and Gymno-Carpo) and one Opuntia robusta (Robusta) cultivar were investigated to determine their nutrient content over six months. Nutrients that contribute energy (10.2 kJ/g) were low. The mineral content was high (ash 17.7/100 g), particularly calcium (3.0 g/100 g) and phosphorous (109.5 mg/kg). Low insoluble acid-detergent fibre (1.4 g/kg) and neutral-detergent fibre (2.1 g/kg) values indicated that mucilage was mostly soluble fibre. Calcium oxalate crystals were not detected in dried mucilage. Opuntia robusta powders had higher protein, extractable fat and potassium content, while Opuntia ficus-indica mucilage powders had higher polyunsaturated (Linoleic and α-Linolenic acid) fat content. O. robusta Robusta mucilage, harvested after the fruit harvest (February) had the lowest energy content and the highest mineral and protein content. Mucilage powders were highly soluble, low-kilojoule and mineral-rich. This is a functional ingredient that is produced from an easily cultivated crop, as cactus pears grow in areas with poor soil, extremely high daytime temperatures and limited water supplies. Full article

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16 pages, 31187 KiB

Open AccessArticle

A Comparative Genomic Survey Provides Novel Insights into Molecular Evolution of l-Aromatic Amino Acid Decarboxylase in Vertebrates

by Yanping Li, Yunyun Lv, Chao Bian, Xinxin You, Li Deng and Qiong Shi

Molecules 2018, 23(4), 917; https://doi.org/10.3390/molecules23040917 - 16 Apr 2018

Cited by 7 | Viewed by 4306

Abstract

Melatonin is a pleiotropic molecule with various important physiological roles in vertebrates. l-aromatic amino acid decarboxylase (AAAD) is the second enzyme for melatonin synthesis. By far, a clear-cut gene function of AAAD in the biosynthesis of melatonin has been unclear in vertebrates. [...] Read more.

Melatonin is a pleiotropic molecule with various important physiological roles in vertebrates. l-aromatic amino acid decarboxylase (AAAD) is the second enzyme for melatonin synthesis. By far, a clear-cut gene function of AAAD in the biosynthesis of melatonin has been unclear in vertebrates. Here, we provide novel insights into the evolution of AAAD based on 77 vertebrate genomes. According to our genome-wide alignments, we extracted a total of 151 aaad nucleotide sequences. A phylogenetic tree was constructed on the basis of these sequences and corresponding protein alignments, indicating that tetrapods and diploid bony fish genomes contained one aaad gene and a new aaad-like gene, which formed a novel AAAD family. However, in tetraploid teleosts, there were two copies of the aaad gene due to whole genome duplication. A subsequent synteny analysis investigated 81 aaad sequences and revealed their collinearity and systematic evolution. Interestingly, we discovered that platypus (Ornithorhynchus anatinus), Atlantic cod (Guadus morhua), Mexican tetra (Astyanax mexicanus), and a Sinocyclocheilus cavefish (S. anshuiensis) have long evolutionary branches in the phylogenetic topology. We also performed pseudogene identification and selection pressure analysis; however, the results revealed a deletion of 37 amino acids in Atlantic cod and premature stop codons in the cave-restricted S. anshuiensis and A. mexicanus, suggesting weakening or disappearing rhythms in these cavefishes. Selective pressure analysis of aaad between platypus and other tetrapods showed that rates of nonsynonymous (Ka) and synonymous (Ks) substitutions were higher when comparing the platypus to other representative tetrapods, indicating that, in this semiaquatic mammal, the aaad gene experienced selection during the process of evolution. In summary, our current work provides novel insights into aaad genes in vertebrates from a genome-wide view. Full article

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12 pages, 1646 KiB

Open AccessCommunication

The Stability of Medicinal Plant microRNAs in the Herb Preparation Process

by Wenyan Xie and Matthias F. Melzig

Molecules 2018, 23(4), 919; https://doi.org/10.3390/molecules23040919 - 16 Apr 2018

Cited by 31 | Viewed by 4827

Abstract

Herbal medicine is now globally accepted as a valid alternative system of pharmaceutical therapies. Various studies around the world have been initiated to develop scientific evidence-based herbal therapies. Recently, the therapeutic potential of medicinal plant derived miRNAs has attracted great attraction. MicroRNAs have [...] Read more.

Herbal medicine is now globally accepted as a valid alternative system of pharmaceutical therapies. Various studies around the world have been initiated to develop scientific evidence-based herbal therapies. Recently, the therapeutic potential of medicinal plant derived miRNAs has attracted great attraction. MicroRNAs have been indicated as new bioactive ingredients in medicinal plants. However, the stability of miRNAs during the herbal preparation process and their bioavailability in humans remain unclear. Viscum album L. (European mistletoe) has been widely used in folk medicine for the treatment of cancer and cardiovascular diseases. Our previous study has indicated the therapeutic potential of mistletoe miRNAs by using bioinformatics tools. To evaluate the stability of these miRNAs, various mistletoe extracts that mimic the clinical medicinal use as well as traditional folk medicinal use were prepared. The mistletoe miRNAs including miR166a-3p, miR159a, miR831-5p, val-miR218 and val-miR11 were quantified by stem-loop qRT-PCR. As a result, miRNAs were detectable in the majority of the extracts, indicating that consumption of medicinal plant preparations might introduce miRNAs into mammals. The factors that might cause miRNA degradation include ultrasonic treatment, extreme heat, especially RNase treatment, while to be associated with plant molecules (e.g., proteins, exosomes) might be an efficient way to protect miRNAs against degradation. Our study confirmed the stability of plant derived miRNAs during herb preparations, suggesting the possibility of functionally intact medicinal plant miRNAs in mammals. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 3793 KiB

Open AccessArticle

In Vitro Inhibitory Effects of Synthetic Cannabinoid EAM-2201 on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

by Tae Yeon Kong, Soon-Sang Kwon, Jae Chul Cheong, Hee Seung Kim, Jin Young Kim and Hye Suk Lee

Molecules 2018, 23(4), 920; https://doi.org/10.3390/molecules23040920 - 16 Apr 2018

Cited by 7 | Viewed by 4201

Abstract

EAM-2201, a synthetic cannabinoid, is a potent agonist of the cannabinoid receptors that is widely abused as an illicit recreational drug in combination with other drugs. To evaluate the potential of EAM-2201 as a perpetrator of drug–drug interactions, the inhibitory effects of EAM-2201 [...] Read more.

EAM-2201, a synthetic cannabinoid, is a potent agonist of the cannabinoid receptors that is widely abused as an illicit recreational drug in combination with other drugs. To evaluate the potential of EAM-2201 as a perpetrator of drug–drug interactions, the inhibitory effects of EAM-2201 on major drug-metabolizing enzymes, cytochrome P450s (CYPs) and uridine 5′-diphospho-glucuronosyltransferases (UGTs) were evaluated in pooled human liver microsomes using liquid chromatography–tandem mass spectrometry (LC-MS/MS). EAM-2201 at doses up to 50 µM negligibly inhibited the activities of eight major human CYPs (1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4) and five UGTs (1A1, 1A4, 1A6, 1A9 and 2B7) in human liver microsomes. EAM-2201 exhibited time-dependent inhibition of CYP2C8-catalyzed amodiaquine N-deethylation, CYP2C9-catalyzed diclofenac 4′-hydroxylation, CYP2C19-catalyzed [S]-mephenytoin 4′-hydroxylation and CYP3A4-catalyzed midazolam 1′-hydroxylation with K_i values of 0.54 µM (k_inact: 0.0633 min⁻¹), 3.0 µM (k_inact: 0.0462 min⁻¹), 3.8 µM (k_inact: 0.0264 min⁻¹) and 4.1 µM (k_inact: 0.0250 min⁻¹), respectively and competitively inhibited UGT1A3-catalyzed chenodeoxycholic acid 24-acyl-glucuronidation, with a K_i value of 2.4 µM. Based on these in vitro results, we conclude that EAM-2201 has the potential to trigger in vivo pharmacokinetic drug interactions when co-administered with substrates of CYP2C8, CYP2C9, CYP2C19, CYP3A4 and UGT1A3. Full article

(This article belongs to the Special Issue Emerging Topics in (Endo)Cannabinoid Signalling)

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13 pages, 6957 KiB

Open AccessArticle

Gold Nanoparticles Grafted with PLL-b-PNIPAM: Interplay on Thermal/pH Dual-Response and Optical Properties

by Hui-Juan Li, Peng-Yun Li, Li-Ying Li, Abdul Haleem and Wei-Dong He

Molecules 2018, 23(4), 921; https://doi.org/10.3390/molecules23040921 - 16 Apr 2018

Cited by 13 | Viewed by 5127

Abstract

Narrowly distributed poly(l-lysine-b-N-isopropylacrylamide) (PLL-b-PNIPAM) was prepared through ring-opening polymerization of ε-benzyloxycarbonyl-l-lysine N-carboxy-α-amino anhydride and atom transfer radical polymerization of NIPAM, followed with the removal of ε-benzyloxycarbonyl group. Then gold nanoparticles (AuNPs) grafted [...] Read more.

Narrowly distributed poly(l-lysine-b-N-isopropylacrylamide) (PLL-b-PNIPAM) was prepared through ring-opening polymerization of ε-benzyloxycarbonyl-l-lysine N-carboxy-α-amino anhydride and atom transfer radical polymerization of NIPAM, followed with the removal of ε-benzyloxycarbonyl group. Then gold nanoparticles (AuNPs) grafted with PLL-b-PNIPAM (PNIPAM-PLL-AuNPs) were obtained by the reduction of chloroauric acid with sodium citrate in the presence of PLL-b-PNIPAM. PNIPAM-PLL-AuNPs and its precursors were thoroughly characterized by proton magnetic resonance spectroscope, Fourier transform infrared spectroscope, UV-vis spectroscope, transmission electron microscopy, dynamic light scattering, thermogravimetric analysis, and circular dichroism. The obtained PNIPAM-PLL-AuNPs exhibited high colloid stability even at strong alkaline (pH = 12) and acidic (pH = 2) conditions. The thermal and pH dual-responsive behaviors of the grafting PLL-b-PNIPAM chains was observed to be affected by AuNPs, while not for the secondary structure of PLL chains. Correspondingly, the surface plasmon resonance (SPR) of AuNPs was found to be sensitive to both pH value and temperature. A blue shift in the SPR happened both with increasing pH value and increasing temperature. The stimuli-response was reversible in heating-cooling cycles. The gold nanoparticles with both pH and temperature response may have potential applications in biomedical areas and biosensors. Full article

(This article belongs to the Special Issue Stimuli-Responsive Polymeric Materials)

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16 pages, 10302 KiB

Open AccessArticle

Time-Course Investigation of Small Molecule Metabolites in MAP-Stored Red Blood Cells Using UPLC-QTOF-MS

by Yong Zhou, Zhiyun Meng, Hui Gan, Ying Zheng, Xiaoxia Zhu, Zhuona Wu, Jian Li, Ruolan Gu and Guifang Dou

Molecules 2018, 23(4), 923; https://doi.org/10.3390/molecules23040923 - 16 Apr 2018

Cited by 5 | Viewed by 4060

Abstract

Red blood cells (RBCs) are routinely stored for 35 to 42 days in most countries. During storage, RBCs undergo biochemical and biophysical changes known as RBC storage lesion, which is influenced by alternative storage additive solutions (ASs). Metabolomic studies have been completed on [...] Read more.

Red blood cells (RBCs) are routinely stored for 35 to 42 days in most countries. During storage, RBCs undergo biochemical and biophysical changes known as RBC storage lesion, which is influenced by alternative storage additive solutions (ASs). Metabolomic studies have been completed on RBCs stored in a number of ASs, including SAGM, AS-1, AS-3, AS-5, AS-7, PAGGGM, and MAP. However, the reported metabolome analysis of laboratory-made MAP-stored RBCs was mainly focused on the time-dependent alterations in glycolytic intermediates during storage. In this study, we investigated the time-course of alterations in various small molecule metabolites in RBCs stored in commercially used MAP for 49 days using ultra-high performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-QTOF-MS). These alterations indicated that RBC storage lesion is related to multiple pathways including glycolysis, pentose phosphate pathway, glutathione homeostasis, and purine metabolism. Thus, our findings might be useful for understanding the complexity of metabolic mechanisms of RBCs in vitro aging and encourage the deployment of systems biology methods to blood products in transfusion medicine. Full article

(This article belongs to the Section Bioorganic Chemistry)

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17 pages, 47356 KiB

Open AccessArticle

Immunohistochemical Evidence from APP-Transgenic Mice for Glutaminyl Cyclase as Drug Target to Diminish pE-Abeta Formation

by Maike Hartlage-Rübsamen, Alexandra Bluhm, Anke Piechotta, Miriam Linnert, Jens-Ulrich Rahfeld, Hans-Ulrich Demuth, Inge Lues, Peer-Hendrik Kuhn, Stefan F. Lichtenthaler, Steffen Roßner and Corinna Höfling

Molecules 2018, 23(4), 924; https://doi.org/10.3390/molecules23040924 - 17 Apr 2018

Cited by 12 | Viewed by 5977

Abstract

Oligomeric assemblies of neurotoxic amyloid beta (Abeta) peptides generated by proteolytical processing of the amyloid precursor protein (APP) play a key role in the pathogenesis of Alzheimer’s disease (AD). In recent years, a substantial heterogeneity of Abeta peptides with distinct biophysical and cell [...] Read more.

Oligomeric assemblies of neurotoxic amyloid beta (Abeta) peptides generated by proteolytical processing of the amyloid precursor protein (APP) play a key role in the pathogenesis of Alzheimer’s disease (AD). In recent years, a substantial heterogeneity of Abeta peptides with distinct biophysical and cell biological properties has been demonstrated. Among these, a particularly neurotoxic and disease-specific Abeta variant is N-terminally truncated and modified to pyroglutamate (pE-Abeta). Cell biological and animal experimental studies imply the catalysis of this modification by the enzyme glutaminyl cyclase (QC). However, direct histopathological evidence in transgenic animals from comparative brain region and cell type-specific expression of transgenic hAPP and QC, on the one hand, and on the formation of pE-Abeta aggregates, on the other, is lacking. Here, using single light microscopic, as well as triple immunofluorescent, labeling, we report the deposition of pE-Abeta only in the brain regions of APP-transgenic Tg2576 mice with detectable human APP and endogenous QC expression, such as the hippocampus, piriform cortex, and amygdala. Brain regions showing human APP expression without the concomitant presence of QC (the anterodorsal thalamic nucleus and perifornical nucleus) do not display pE-Abeta plaque formation. However, we also identified brain regions with substantial expression of human APP and QC in the absence of pE-Abeta deposition (the Edinger-Westphal nucleus and locus coeruleus). In these brain regions, the enzymes required to generate N-truncated Abeta peptides as substrates for QC might be lacking. Our observations provide additional evidence for an involvement of QC in AD pathogenesis via QC-catalyzed pE-Abeta formation. Full article

(This article belongs to the Special Issue 25th Anniversary of the Amyloid Hypothesis and Alzheimer Disease)

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11 pages, 4752 KiB

Open AccessArticle

Pectin from Citrus Canning Wastewater as Potential Fat Replacer in Ice Cream

by Hua Zhang, Jianle Chen, Junhui Li, Chaoyang Wei, Xingqian Ye, John Shi and Shiguo Chen

Molecules 2018, 23(4), 925; https://doi.org/10.3390/molecules23040925 - 17 Apr 2018

Cited by 38 | Viewed by 6183

Abstract

Pectin had been recovered from canning wastewater produced by chemical treatment of segment membrane during preparation of canned citrus in our previous research. The purpose of this study was to characterize the extracted pectin from canning wastewater, and to evaluate its application as [...] Read more.

Pectin had been recovered from canning wastewater produced by chemical treatment of segment membrane during preparation of canned citrus in our previous research. The purpose of this study was to characterize the extracted pectin from canning wastewater, and to evaluate its application as a fat alternative to replace fat in ice cream. The monosaccharide composition and rheological properties of the pectin were determined. The influences of fat reduction and pectin addition on the physicochemical, rheological and sensory properties of low-fat ice cream were determined. The rheological results showed that pectin solutions were typical pseudoplastic fluids. The addition of pectin in ice cream can cause an increase in viscosity, overrun, and hardness, and a decrease in meltdown of the ice cream. When 0.72% pectin (w/w) is incorporated into ice cream, a prototype product of ice cream with 45% lower fat content compared to the control was made. Results indicated that their qualities such as appearance, flavor, and taste were not significantly different. The low-fat ice cream had higher smoothness scores and lower mouth-coating scores. Hence, pectin extracted from citrus canning wastewater can be potentially used as fat replacer in ice cream, which benefits both the environment and the food industry. Full article

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12 pages, 8240 KiB

Open AccessArticle

Biflavonoids Isolated from Selaginella tamariscina and Their Anti-Inflammatory Activities via ERK 1/2 Signaling

by Sun-Yup Shim, Seul-gi Lee and Mina Lee

Molecules 2018, 23(4), 926; https://doi.org/10.3390/molecules23040926 - 17 Apr 2018

Cited by 44 | Viewed by 5363

Abstract

Selaginella tamariscina (S. tamariscina) (Beauv.) Spring (Selaginellaceae) has been used in oriental medicine for the treatment of dysmenorrhea, chronic hepatitis, hyperglycemia, amenorrhea, hematuria, prolapse of the anus and metrorrhagia. In the present study, we isolated two strong anti-inflammatory compounds, the biflavonoids [...] Read more.

Selaginella tamariscina (S. tamariscina) (Beauv.) Spring (Selaginellaceae) has been used in oriental medicine for the treatment of dysmenorrhea, chronic hepatitis, hyperglycemia, amenorrhea, hematuria, prolapse of the anus and metrorrhagia. In the present study, we isolated two strong anti-inflammatory compounds, the biflavonoids hinokiflavone (H) and 7′-O-methyl hinokiflavone (mH), from S. tamariscina and examined their anti-inflammatory activities in lipopolysaccharide (LPS)-mediated murine macrophages (RAW 264.7) and colon epithelial cells (HT-29). H and mH suppressed the production of the inflammatory mediators nitric oxide (NO), interleukin (IL)-6, IL-8, and tumor-necrosis factor (TNF)-α, which are most highly activated in inflammatory bowel disease (IBD). In addition, Western blot analysis revealed that H and mH suppressed the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and the activation of nuclear factor-κB (NF-κB) and extracellular regulated kinases (ERK) 1/2. These results suggest that H and mH are compounds having potent anti-inflammatory effects that could be used to treat such diseases as IBD. Full article

(This article belongs to the Collection Bioactive Compounds)

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18 pages, 2327 KiB

Open AccessArticle

Probing the Inhibitor versus Chaperone Properties of sp²-Iminosugars towards Human β-Glucocerebrosidase: A Picomolar Chaperone for Gaucher Disease

by Teresa Mena-Barragán, M. Isabel García-Moreno, Alen Sevšek, Tetsuya Okazaki, Eiji Nanba, Katsumi Higaki, Nathaniel I. Martin, Roland J. Pieters, José M. García Fernández and Carmen Ortiz Mellet

Molecules 2018, 23(4), 927; https://doi.org/10.3390/molecules23040927 - 17 Apr 2018

Cited by 30 | Viewed by 5563

Abstract

A series of sp²-iminosugar glycomimetics differing in the reducing or nonreducing character, the configurational pattern (d-gluco or l-ido), the architecture of the glycone skeleton, and the nature of the nonglycone substituent has been synthesized and [...] Read more.

A series of sp²-iminosugar glycomimetics differing in the reducing or nonreducing character, the configurational pattern (d-gluco or l-ido), the architecture of the glycone skeleton, and the nature of the nonglycone substituent has been synthesized and assayed for their inhibition properties towards commercial glycosidases. On the basis of their affinity and selectivity towards GH1 β-glucosidases, reducing and nonreducing bicyclic derivatives having a hydroxylation profile of structural complementarity with d-glucose and incorporating an N′-octyl-isourea or -isothiourea segment were selected for further evaluation of their inhibitory/chaperoning potential against human glucocerebrosidase (GCase). The 1-deoxynojirimycin (DNJ)-related nonreducing conjugates behaved as stronger GCase inhibitors than the reducing counterparts and exhibited potent chaperoning capabilities in Gaucher fibroblasts hosting the neuronopathic G188S/G183W mutation, the isothiourea derivative being indeed one of the most efficient chaperone candidates reported up to date (70% activity enhancement at 20 pM). At their optimal concentration, the four selected compounds promoted mutant GCase activity enhancements over 3-fold; yet, the inhibitor/chaperoning balance became unfavorable at much lower concentration for nonreducing as compared to reducing derivatives. Full article

(This article belongs to the Special Issue Glycomimetics: Design, Synthesis and Therapeutic Applications)

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12 pages, 15050 KiB

Open AccessArticle

Theoretical Study of the β-Cyclodextrin Inclusion Complex Formation of Eugenol in Water

by Elena Alvira

Molecules 2018, 23(4), 928; https://doi.org/10.3390/molecules23040928 - 17 Apr 2018

Cited by 16 | Viewed by 4551

Abstract

The interaction between eugenol and β-cyclodextrin in the presence of water is studied by molecular mechanics and dynamics simulations. A force field model is used in molecular mechanics to determine the interaction energy and the complex configuration at the absolute minimum. The van [...] Read more.

The interaction between eugenol and β-cyclodextrin in the presence of water is studied by molecular mechanics and dynamics simulations. A force field model is used in molecular mechanics to determine the interaction energy and the complex configuration at the absolute minimum. The van der Waals term is the main contribution to the total energy, and so directly determines the configuration of the inclusion complex. The formation of inclusion complexes is simulated by molecular dynamics, in which their configurations are deduced from the position probability density that represents the preferred location and orientation of the guest in the simulation. When eugenol approaches from the rims of β-cyclodextrin, it tends to enter the cavity, remain inside for a short period and then exit from it. The guest tends to include the phenyl ring inside the cavity in the most probable configurations. Two inclusion complex configurations are proposed, each with the hydroxyl and methoxyl groups pointing towards one different rim of β-cyclodextrin. The initial guest orientation is the main factor determining these configurations. The model presented in this study reproduces the experimental findings on inclusion complex formation and proposes two possible complex configurations, one previously suggested by different authors. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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13 pages, 18391 KiB

Open AccessArticle

Cloning, Characterization, and Expression Analysis of Three FAD8 Genes Encoding a Fatty Acid Desaturase from Seeds of Paeonia ostii

by Jing Sun, Ming Chen, Mengyuan Zhu, Yu Jiang, Jiasong Meng, Daqiu Zhao and Jun Tao

Molecules 2018, 23(4), 929; https://doi.org/10.3390/molecules23040929 - 17 Apr 2018

Cited by 15 | Viewed by 3823

Abstract

The FAD8 gene catalyzes the conversion of diene fatty acids to triene fatty acids and is a key enzyme that determines the synthesis of alpha-linolenic acid. In this study, the full-length cDNAs of FAD8-1, FAD8-2, and FAD8-3 are cloned from Paeonia [...] Read more.

The FAD8 gene catalyzes the conversion of diene fatty acids to triene fatty acids and is a key enzyme that determines the synthesis of alpha-linolenic acid. In this study, the full-length cDNAs of FAD8-1, FAD8-2, and FAD8-3 are cloned from Paeonia ostii T. Hong & J. X. Zhang and named as PoFAD8-1, PoFAD8-2, and PoFAD8-3. Their open reading frame is 1203 bp, 1152 bp, and 1353 bp which encoded 400, 371, and 450 amino acids. The molecular weights of the amino acids are 46 kDa, 43 kDa, and 51 kDa while the isoelectric points are 7.34, 8.74, and 9.23, respectively. Bioinformatics analysis shows that all three genes are hydrophobic-hydrophobic, PoFAD8-1 has three transmembrane domains, and PoFAD8-2 and PoFAD8-3 have two transmembrane domains. Multiple series alignment and phylogenetic analysis revealed that PoFAD8-1 and PoFAD8-2 are closely related while PoFAD8-3 is more closely related to Paeonia delavayi. Subcellular localization results showed that PoFAD8-1 was located on the ER membrane and PoFAD8-2 and PoFAD8-3 were located on the chloroplast membrane. The relative expression level of PoFAD8-1 in seeds is very high. PoFAD8-2 expressed more in the ovary than the other two genes. PoFAD8-3 was highly expressed in roots, stems, leaves, petals, and ovaries. Full article

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23 pages, 16200 KiB

Open AccessArticle

Chemoresistance to Cancer Treatment: Benzo-α-Pyrene as Friend or Foe?

by Kevin Dzobo, Naseeha Hassen, Dimakatso Alice Senthebane, Nicholas Ekow Thomford, Arielle Rowe, Hendrina Shipanga, Ambroise Wonkam, M. Iqbal Parker, Shaheen Mowla and Collet Dandara

Molecules 2018, 23(4), 930; https://doi.org/10.3390/molecules23040930 - 17 Apr 2018

Cited by 16 | Viewed by 5211

Abstract

Background: Environmental pollution such as exposure to pro-carcinogens including benzo-α-pyrene is becoming a major problem globally. Moreover, the effects of benzo-α-pyrene (BaP) on drug pharmacokinetics, pharmacodynamics, and drug resistance warrant further investigation, especially in cancer outpatient chemotherapy where exposure to environmental pollutants might [...] Read more.

Background: Environmental pollution such as exposure to pro-carcinogens including benzo-α-pyrene is becoming a major problem globally. Moreover, the effects of benzo-α-pyrene (BaP) on drug pharmacokinetics, pharmacodynamics, and drug resistance warrant further investigation, especially in cancer outpatient chemotherapy where exposure to environmental pollutants might occur. Method: We report here on the effects of benzo-α-pyrene on esophageal cancer cells in vitro, alone, or in combination with chemotherapeutic drugs cisplatin, 5-flurouracil, or paclitaxel. As the study endpoints, we employed expression of proteins involved in cell proliferation, drug metabolism, apoptosis, cell cycle analysis, colony formation, migration, and signaling cascades in the WHCO1 esophageal cancer cell line after 24 h of treatment. Results: Benzo-α-pyrene had no significant effect on WHCO1 cancer cell proliferation but reversed the effect of chemotherapeutic drugs by reducing drug-induced cell death and apoptosis by 30–40% compared to drug-treated cells. The three drugs significantly reduced WHCO1 cell migration by 40–50% compared to control and BaP-treated cells. Combined exposure to drugs was associated with significantly increased apoptosis and reduced colony formation. Evaluation of survival signaling cascades showed that although the MEK-ERK and Akt pathways were activated in the presence of drugs, BaP was a stronger activator of the MEK-ERK and Akt pathways than the drugs. Conclusion: The present study suggest that BaP can reverse the effects of drugs on cancer cells via the activation of survival signaling pathways and upregulation of anti-apoptotic proteins such as Bcl-2 and Bcl-xL. Our data show that BaP contribute to the development of chemoresistant cancer cells. Full article

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17 pages, 14063 KiB

Open AccessFeature PaperArticle

Direct (Hetero)Arylation for the Synthesis of Molecular Materials: Coupling Thieno[3,4-c]pyrrole-4,6-dione with Perylene Diimide to Yield Novel Non-Fullerene Acceptors for Organic Solar Cells

by Thomas A. Welsh, Audrey Laventure and Gregory C. Welch

Molecules 2018, 23(4), 931; https://doi.org/10.3390/molecules23040931 - 17 Apr 2018

Cited by 29 | Viewed by 6203

Abstract

Herein we report on the synthesis of an N-annulated perylene diimide (PDI) disubstituted thieno[3,4-c]pyrrole-4,6-dione (TPD) molecular acceptor (PDI–TPD–PDI) by direct heteroarylation (DHA) methods. Three sets of DHA conditions that explore the effects of solvent, temperature, and catalyst were employed to find the [...] Read more.

Herein we report on the synthesis of an N-annulated perylene diimide (PDI) disubstituted thieno[3,4-c]pyrrole-4,6-dione (TPD) molecular acceptor (PDI–TPD–PDI) by direct heteroarylation (DHA) methods. Three sets of DHA conditions that explore the effects of solvent, temperature, and catalyst were employed to find the optimal conditions for the synthesis of two PDI–TPD–PDI derivatives. We then selected one PDI–TPD–PDI for use as a non-fullerene acceptor in organic solar cell devices with the donor polymer PBDB-T. Active layer bulk-heterojunction blends were modified using several post-deposition treatments, including thermal annealing, solvent vapour annealing, and high boiling solvent additives. It was found that active layers cast from o-dichlorobenzene with a 3% v/v diphenylether additive yielded films with adequate phase separation, and subsequently gave the best organic solar cell performance, with power conversion efficiencies greater than 3%. Full article

(This article belongs to the Special Issue Direct (Hetero)Arylation: A New Tool for Organic Electronics)

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15 pages, 26545 KiB

Open AccessArticle

Polysaccharide of Atractylodes macrocephala Koidz (PAMK) Relieves Immunosuppression in Cyclophosphamide-Treated Geese by Maintaining a Humoral and Cellular Immune Balance

by Wanyan Li, Sixuan Guo, Danning Xu, Bingxin Li, Nan Cao, Yunbo Tian and Qingyan Jiang

Molecules 2018, 23(4), 932; https://doi.org/10.3390/molecules23040932 - 17 Apr 2018

Cited by 37 | Viewed by 4820

Abstract

Polysaccharide of Atractylodes macrocephala Koidz (PAMK) has been well recognized as an immune enhancer that can promote lymphocyte proliferation and activate immune cells. The purpose of this study was to evaluate the effects of PAMK on humoral and cellular immune functions in immunosuppressed [...] Read more.

Polysaccharide of Atractylodes macrocephala Koidz (PAMK) has been well recognized as an immune enhancer that can promote lymphocyte proliferation and activate immune cells. The purpose of this study was to evaluate the effects of PAMK on humoral and cellular immune functions in immunosuppressed geese. Geese of the Control group were provided with normal feed, the PAMK group was provided with 400 mg·(kg body weight)⁻¹ PAMK, the cyclophosphamide (CTX) group was injected with 40 mg·(kg body weight)⁻¹ cyclophosphamide, while the CTX+PAMK group received the combination of PAMK and CTX. Spleen development and percentages of leukocytes in peripheral blood were examined. Principal component analysis was conducted to analyze correlations among humoral and cellular immune indicators. The results showed that PAMK alleviated the damage to the spleen, the decrease in T- and B-cell proliferation, the imbalance of leukocytes, and the disturbances of humoral and cellular immunity caused by CTX. Principal component analysis revealed that the relevance of humoral-immunity-related indicators was greater, and the CTX+PAMK group manifested the largest difference from the CTX group but was close to the Control group. In conclusion, PAMK alleviates the immunosuppression caused by CTX in geese, and the protective effect on humoral immunity is more obvious and stable. Full article

(This article belongs to the Section Natural Products Chemistry)

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5 pages, 394 KiB

Open AccessArticle

Huberine, a New Canthin-6-One Alkaloid from the Bark of Picrolemma huberi

by Carlos López, Manuel Pastrana, Alexandra Ríos, Alvaro Cogollo and Adriana Pabón

Molecules 2018, 23(4), 934; https://doi.org/10.3390/molecules23040934 - 17 Apr 2018

Cited by 6 | Viewed by 4204

Abstract

A new alkaloid, Canthin-6-one, Huberine (1), together with three known compounds including 1-Hydroxy-canthin-6-one (2), Canthin-6-one (3) and stigma sterol (4), were isolated from the stem bark of Picrolemma huberi. The isolation was achieved by [...] Read more.

A new alkaloid, Canthin-6-one, Huberine (1), together with three known compounds including 1-Hydroxy-canthin-6-one (2), Canthin-6-one (3) and stigma sterol (4), were isolated from the stem bark of Picrolemma huberi. The isolation was achieved by chromatographic techniques and the purification was performed on a C18 column using acetonitrile/water (90:10, v/v) with 0.1% formic acid as the mobile phase. The structural elucidation was performed via spectroscopic methods, notably 1D- and 2D-NMR, UV, IR, MS and HRMS. The antiplasmodial activity of the compounds was studied. Full article

(This article belongs to the Special Issue Advances in Plant Alkaloid Research)

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10 pages, 4217 KiB

Open AccessFeature PaperArticle

Fluorescent Dendritic Micro-Hydrogels: Synthesis, Analysis and Use in Single-Cell Detection

by Lisa Christadore, Mark W. Grinstaff and Scott E. Schaus

Molecules 2018, 23(4), 936; https://doi.org/10.3390/molecules23040936 - 18 Apr 2018

Cited by 3 | Viewed by 3997

Abstract

Hydrogels are of keen interest for a wide range of medical and biotechnological applications including as 3D substrate structures for the detection of proteins, nucleic acids, and cells. Hydrogel parameters such as polymer wt % and crosslink density are typically altered for a [...] Read more.

Hydrogels are of keen interest for a wide range of medical and biotechnological applications including as 3D substrate structures for the detection of proteins, nucleic acids, and cells. Hydrogel parameters such as polymer wt % and crosslink density are typically altered for a specific application; now, fluorescence can be incorporated into such criteria by specific macromonomer selection. Intrinsic fluorescence was observed at λ_max 445 nm from hydrogels polymerized from lysine and aldehyde- terminated poly(ethylene glycol) macromonomers upon excitation with visible light. The hydrogel’s photochemical properties are consistent with formation of a nitrone functionality. Printed hydrogels of 150 μm were used to detect individual cell adherence via a decreased in fluorescence. The use of such intrinsically fluorescent hydrogels as a platform for cell sorting and detection expands the current repertoire of tools available. Full article

(This article belongs to the Special Issue Dendrimers: A Themed Issue in Honor of Professor Donald A. Tomalia on the Occasion of His 80th Birthday)

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11 pages, 11448 KiB

Open AccessCommunication

Highly Stable Zr(IV)-Based Porphyrinic Metal−Organic Frameworks as an Adsorbent for the Effective Removal of Gatifloxacin from Aqueous Solution

by Jing-Jing Chen, Li-Juan Wang, Gui-Ju Xu, Xia Wang and Ru-Song Zhao

Molecules 2018, 23(4), 937; https://doi.org/10.3390/molecules23040937 - 18 Apr 2018

Cited by 22 | Viewed by 5493

Abstract

Water stable Zr-metal–organic framework nanoparticles (PCN-224 NPs, PCN refers to porous coordination network) have been solvothermally synthesized. PCN-224 NPs show spherical shape with smooth surface and particle size of approximately 200 nm. PCN-224 NPs can be stable in acid and aqueous solutions, as [...] Read more.

Water stable Zr-metal–organic framework nanoparticles (PCN-224 NPs, PCN refers to porous coordination network) have been solvothermally synthesized. PCN-224 NPs show spherical shape with smooth surface and particle size of approximately 200 nm. PCN-224 NPs can be stable in acid and aqueous solutions, as confirmed by powder X-ray diffraction. Gatifloxacin (GTF) adsorption measurements showed that PCN-224 NPs exhibit a high adsorption capacity of 876 mg·g⁻¹. Meanwhile, the adsorption factors, adsorption characteristics, and mechanisms of GTF were investigated in batch adsorption experiments. Full article

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9 pages, 5825 KiB

Open AccessFeature PaperArticle

Dendrimers for Drug Delivery

by Abhay Singh Chauhan

Molecules 2018, 23(4), 938; https://doi.org/10.3390/molecules23040938 - 18 Apr 2018

Cited by 291 | Viewed by 16612

Abstract

Dendrimers have come a long way in the last 25 years since their inception. Originally created as a wonder molecule of chemistry, dendrimer is now in the fourth class of polymers. Dr. Donald Tomalia first published his seminal work on Poly(amidoamine) (PAMAM) dendrimers [...] Read more.

Dendrimers have come a long way in the last 25 years since their inception. Originally created as a wonder molecule of chemistry, dendrimer is now in the fourth class of polymers. Dr. Donald Tomalia first published his seminal work on Poly(amidoamine) (PAMAM) dendrimers in 1985. Application of dendrimers as a drug delivery system started in late 1990s. Dendrimers for drug delivery are employed using two approaches: (i) formulation and (ii) nanoconstruct. In the formulation approach, drugs are physically entrapped in a dendrimer using non-covalent interactions, whereas drugs are covalently coupled on dendrimers in the nanoconstruct approach. We have demonstrated the utility of PAMAM dendrimers for enhancing solubility, stability and oral bioavailability of various drugs. Drug entrapment and drug release from dendrimers can be controlled by modifying dendrimer surfaces and generations. PAMAM dendrimers are also shown to increase transdermal permeation and specific drug targeting. Dendrimer platforms can be engineered to attach targeting ligands and imaging molecules to create a nanodevice. Dendrimer nanotechnology, due to its multifunctional ability, has the potential to create next generation nanodevices. Full article

(This article belongs to the Special Issue Dendrimers: A Themed Issue in Honor of Professor Donald A. Tomalia on the Occasion of His 80th Birthday)

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15 pages, 2535 KiB

Open AccessArticle

Anti-Inflammatory and Antinociceptive Studies of Hydroalcoholic Extract from the Leaves of Phyllanthus brasiliensis (Aubl.) Poir. and Isolation of 5-O-β-d-Glucopyranosyljusticidin B and Six Other Lignans

by Luziane Da C. Borges, Raimundo Negrão-Neto, Sônia Pamplona, Luanna Fernandes, Mayra Barros, Enéas Fontes-Júnior, Cristiane Maia, Consuelo Y. Yoshioka E Silva and Milton Nascimento da Silva

Molecules 2018, 23(4), 941; https://doi.org/10.3390/molecules23040941 - 18 Apr 2018

Cited by 11 | Viewed by 4441

Abstract

The aim of this study was to investigate the chemical composition and the antiinflammatory/antinociceptive properties of the hydroalcoholic extract derived from the leaves of Phyllanthus brasiliensis (HEPB) in rodents. A new arylnaphthalene lignan glycoside, 5-O-β-d-glucopyranosyljusticidin B, together with six [...] Read more.

The aim of this study was to investigate the chemical composition and the antiinflammatory/antinociceptive properties of the hydroalcoholic extract derived from the leaves of Phyllanthus brasiliensis (HEPB) in rodents. A new arylnaphthalene lignan glycoside, 5-O-β-d-glucopyranosyljusticidin B, together with six known lignans, were isolated from HEPB. 1D and 2D NMR experiments and HRMS were used to elucidate the structure of the new compound. HEPB toxicity and antinociceptive activity were evaluated through acute oral toxicity and formalin models in mice, respectively. The anti-inflammatory effects of HEPB were assessed using carrageenan- and dextran-induced paw edema models in rats. HEPB showed low toxicity. Oral administration of HEPB reduced paw edema induced by carrageenan, but not by dextran. HEPB and its fractions from FR6 to FR10 (FR6-10) inhibited the neurogenic and inflammatory phases of formalin-induced linking, demonstrating its antinociceptive activity. These results indicated that lignans from Phyllanthus brasiliensis exerted antinociceptive/anti-inflammatory effects not related to the histaminergic pathway. Full article

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12 pages, 2105 KiB

Open AccessArticle

CpG Methylation Changes G-Quadruplex Structures Derived from Gene Promoters and Interaction with VEGF and SP1

by Kaori Tsukakoshi, Shiori Saito, Wataru Yoshida, Shinichi Goto and Kazunori Ikebukuro

Molecules 2018, 23(4), 944; https://doi.org/10.3390/molecules23040944 - 18 Apr 2018

Cited by 30 | Viewed by 6453

Abstract

G-quadruplex (G4) is a DNA/RNA conformation that consists of two or more G-tetrads resulting from four-guanine bases connected by Hoogsteen-type hydrogen bonds, which is often found in the telomeres of chromatin, as well as in the promoter regions of genes. The function of [...] Read more.

G-quadruplex (G4) is a DNA/RNA conformation that consists of two or more G-tetrads resulting from four-guanine bases connected by Hoogsteen-type hydrogen bonds, which is often found in the telomeres of chromatin, as well as in the promoter regions of genes. The function of G4 in the genomic DNA is being elucidated and some G4-protein interactions have been reported; these are believed to play a role in vital cellular functions. In this study, we focused on CpG methylation, a well-known epigenetic modification of the genomic DNA, especially found in the promoter regions. Although many G4-forming sequences within the genomic DNA harbor CpG sites, the relationship between CpG methylation and the binding properties of associated proteins remains unclear. We demonstrated that the binding ability of vascular endothelial growth factor (VEGF) G4 DNA to VEGF165 protein was significantly decreased by CpG methylation. We identified the binding activity of G4 DNA oligonucleotides derived from gene promoter regions to SP1, a transcription factor that interacts with a G4-forming DNA and is also altered by CpG methylation. The effect of methylation on binding affinity was accompanied by changes in G4 structure and/or topology. Therefore, this study suggested that CpG methylation might be involved in protein binding to G4-forming DNA segments for purposes of transcriptional regulation. Full article

(This article belongs to the Special Issue Nucleic Acid Aptamers)

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14 pages, 5817 KiB

Open AccessArticle

Facile Synthesis of Flexible Methylsilsesquioxane Aerogels with Surface Modifications for Sound- Absorbance, Fast Dye Adsorption and Oil/Water Separation

by Xingzhong Guo, Jiaqi Shan, Zhongzhang Lai, Wei Lei, Ronghua Ding, Yun Zhang and Hui Yang

Molecules 2018, 23(4), 945; https://doi.org/10.3390/molecules23040945 - 18 Apr 2018

Cited by 32 | Viewed by 6234

Abstract

New flexible methylsilsesquioxane (MSQ) aerogels have been facilely prepared by a sol–gel process with methyltrimethoxysilane (MTMS) and dimethyldimethoxysilane (DMDMS) as co-precursors, followed by surface modification and ambient pressure drying. The microstructure, mechanical properties and hydrophobicity of these MSQ aerogels after surface modifications of [...] Read more.

New flexible methylsilsesquioxane (MSQ) aerogels have been facilely prepared by a sol–gel process with methyltrimethoxysilane (MTMS) and dimethyldimethoxysilane (DMDMS) as co-precursors, followed by surface modification and ambient pressure drying. The microstructure, mechanical properties and hydrophobicity of these MSQ aerogels after surface modifications of hexamethyldisiloxane (HMDSO) and/or hexamethyldisilazane (HMDS) were investigated in detail, and the applications of surface-modified MSQ aerogels in sound-absorbance, fast dye adsorption and oil/water separation were evaluated, respectively. The MSQ aerogels surface-modified by HMDS possess flexibility, elasticity and superhydrophobicity, and demonstrate good performance in the mentioned applications. The resultant MSQ aerogel used in sound-absorbance has high frequency (about 6 kHz) acoustic absorptivity of up to 80%, benefiting from its macroporous structure and porosity of 94%, and it also possesses intermediate frequency acoustic absorptivity (about 1 kHz) up to 80% owing to its elasticity. This MSQ aerogel can selectively separate oil from oil/water mixtures with high efficiency due to its superhydrophobicity and superlipophilicity, resulting from a lot of methyl groups, density as low as 0.12 cm³·g⁻¹ and a water contact angle as high as 157°. This MSQ aerogel can be assembled to be a monolithic column applied for fast dye adsorption, and shows selective adsorption for anionic dyes and removal efficiency of methyl orange of up to 95%. Full article

(This article belongs to the Special Issue Chemistry of Aerogels and Their Applications)

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14 pages, 4579 KiB

Open AccessArticle

Zeta Potential of Beta Zeolites: Influence of Structure, Acidity, pH, Temperature and Concentration

by Xuan Liu, Päivi Mäki-Arvela, Atte Aho, Zuzana Vajglova, Vladimir M. Gun’ko, Ivo Heinmaa, Narendra Kumar, Kari Eränen, Tapio Salmi and Dmitry Yu. Murzin

Molecules 2018, 23(4), 946; https://doi.org/10.3390/molecules23040946 - 18 Apr 2018

Cited by 58 | Viewed by 8530

Abstract

Measurements of the zeta potential of solid heterogeneous supports are important for preparation of metal supported catalysts and for shaping zeolites into extrudates. In the current work, different types of heterogeneous support materials such as SiO₂, Al₂O₃, [...] Read more.

Measurements of the zeta potential of solid heterogeneous supports are important for preparation of metal supported catalysts and for shaping zeolites into extrudates. In the current work, different types of heterogeneous support materials such as SiO₂, Al₂O₃, and a range of beta zeolites of different silica- to-alumina ratio were analysed. It was observed that parameters such as temperature, pH and acidity significantly affect the zeta potential. In several instances, depending on the materials’ acidity and microstructure, maxima in zeta potential were observed. The solid materials were thoroughly characterized using XRD, SEM, EDX, TEM, nitrogen physisorption, Al-NMR and FTIR with pyridine before zeta potential measurements. Full article

(This article belongs to the Special Issue Zeolites and Related Nanoporous Materials: Synthesis, Characterization and Applications in Catalysis and Green Chemistry)

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10 pages, 5477 KiB

Open AccessArticle

A Highly Selective and Strong Anti-Interference Host-Guest Complex as Fluorescent Probe for Detection of Amantadine by Indicator Displacement Assay

by Linzhao Zhu, Zhiyong Zhao, Xiongzhi Zhang, Haijun Zhang, Feng Liang and Simin Liu

Molecules 2018, 23(4), 947; https://doi.org/10.3390/molecules23040947 - 18 Apr 2018

Cited by 15 | Viewed by 4355

Abstract

Amantadine (AMA) and its derivatives are illicit veterinary drugs that are hard to detect at very low concentrations. Developing a fast, simple and highly sensitive method for the detection of AMA is highly in demand. Here, we designed an anthracyclic compound (ABAM) that [...] Read more.

Amantadine (AMA) and its derivatives are illicit veterinary drugs that are hard to detect at very low concentrations. Developing a fast, simple and highly sensitive method for the detection of AMA is highly in demand. Here, we designed an anthracyclic compound (ABAM) that binds to a cucurbit[7]uril (CB[7]) host with a high association constant of up to 8.7 × 10⁸ M⁻¹. The host-guest complex was then used as a fluorescent probe for the detection of AMA. Competition by AMA for occupying the cavity of CB[7] allows ABAM to release from the CB[7]-ABAM complex, causing significant fluorescence quenching of ABAM (indicator displacement assay, IDA). The linear range of the method is from 0.000188 to 0.375 μg/mL, and the detection limit can be as low as 6.5 × 10⁻⁵ μg/mL (0.35 nM). Most importantly, due to the high binding affinity between CB[7] and ABAM, this fluorescence host-guest system shows great anti-interference capacity. Thus, we are able to accurately determine the concentration of AMA in various samples, including pharmaceutical formulations. Full article

(This article belongs to the Special Issue Molecules for Biotechnologies)

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12 pages, 1584 KiB

Open AccessArticle

Anthocyanin Composition and Content in Rye Plants with Different Grain Color

by Pavel A. Zykin, Elena A. Andreeva, Anna N. Lykholay, Natalia V. Tsvetkova and Anatoly V. Voylokov

Molecules 2018, 23(4), 948; https://doi.org/10.3390/molecules23040948 - 19 Apr 2018

Cited by 37 | Viewed by 7612

Abstract

The color of grain in cereals is determined mainly by anthocyanin pigments. A large level of genetic diversity for anthocyanin content and composition in the grain of different species was observed. In rye, recessive mutations in six genes (vi1...vi6) lead to the absence [...] Read more.

The color of grain in cereals is determined mainly by anthocyanin pigments. A large level of genetic diversity for anthocyanin content and composition in the grain of different species was observed. In rye, recessive mutations in six genes (vi1...vi6) lead to the absence of anthocyanins in all parts of the plant. Moreover, dominant genes of anthocyanin synthesis in aleurone (gene C) and pericarp (gene Vs) also affect the color of the grain. Reverse phase high-performance liquid chromatography and mass spectrometry were used to study anthocyanins in 24 rye samples. A lack of anthocyanins in the lines with yellow and brown grain was determined. Delphinidin rutinoside and cyanidin rutinoside were found in the green-seeded lines. Six samples with violet grains significantly varied in terms of anthocyanin composition and content. However, the main aglycone was cyanidin or peonidin in all of them. Monosaccharide glucose and disaccharide rutinose served as the glycoside units. Violet-seeded accession forms differ in the ratio of the main anthocyanins and the range of their acylated derivatives. The acyl groups were presented mainly by radicals of malonic and sinapic acids. For the colored forms, a profile of the revealed anthocyanins with the indication of their contents was given. The obtained results are discussed in connection to similar data in rice, barley, and wheat, which will provide a perspective for future investigations. Full article

(This article belongs to the Special Issue Advances in Anthocyanin Research 2018)

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7 pages, 483 KiB

Open AccessArticle

Two Novel Cycloartane-Type Triterpenes from Trichilia casaretti C. DC. (Meliaceae)

by Ivo Jose Curcino Vieira, Elaine Rodrigues Figueiredo, Milena Gonçalves Curcino Vieira, Almir Ribeiro de Carvalho Junior, Michel De Souza Passos, Samyra Imad da Silva Boeno, Otoniel Aquino Azevedo and Raimundo Braz-Filho

Molecules 2018, 23(4), 949; https://doi.org/10.3390/molecules23040949 - 19 Apr 2018

Cited by 8 | Viewed by 3836

Abstract

Two new triterpenes cycloartane-type, named 24-methylencycloartan-12-oxo-3β,22α-diol and trichiliol, were isolated from the leaves of Trichilia casaretti C. DC. together with three known triterpenes—24-methylencycloart-3β,22-diol, 22,25-dihydrocycloart-23(E)-en-3β-ol, and 22(R)-hydroxycycloart-24-en-3-ol. These compounds were characterized on the basis of their spectral data, mainly 1D [...] Read more.

Two new triterpenes cycloartane-type, named 24-methylencycloartan-12-oxo-3β,22α-diol and trichiliol, were isolated from the leaves of Trichilia casaretti C. DC. together with three known triterpenes—24-methylencycloart-3β,22-diol, 22,25-dihydrocycloart-23(E)-en-3β-ol, and 22(R)-hydroxycycloart-24-en-3-ol. These compounds were characterized on the basis of their spectral data, mainly 1D (¹H and ¹³C) and 2D NMR (¹H-¹H-COSY, ¹H-¹H-NOESY, HMQC, HSQC, and HMBC), and mass spectra (EI-MS and HR-ESI-MS), also involving comparison with data from the literature. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 1394 KiB

Open AccessArticle

Talarodiolide, a New 12-Membered Macrodiolide, and GC/MS Investigation of Culture Filtrate and Mycelial Extracts of Talaromyces pinophilus

by Maria Michela Salvatore, Marina DellaGreca, Rosario Nicoletti, Francesco Salvatore, Francesco Vinale, Daniele Naviglio and Anna Andolfi

Molecules 2018, 23(4), 950; https://doi.org/10.3390/molecules23040950 - 19 Apr 2018

Cited by 18 | Viewed by 4318

Abstract

Talarodiolide, a new 12-membered macrodiolide, was isolated and characterized from the culture filtrate of strain LT6 of Talaromyces pinophilus. The structure of (Z)-4,10-dimethyl-1,7-dioxa-cyclododeca-3,9-diene-2,8-dione was assigned essentially based on NMR and MS data. Furthermore, several known compounds were isolated and identified in the [...] Read more.

Talarodiolide, a new 12-membered macrodiolide, was isolated and characterized from the culture filtrate of strain LT6 of Talaromyces pinophilus. The structure of (Z)-4,10-dimethyl-1,7-dioxa-cyclododeca-3,9-diene-2,8-dione was assigned essentially based on NMR and MS data. Furthermore, several known compounds were isolated and identified in the crude extract of the culture filtrate and mycelium of this strain. EI mass spectrum at 70 eV of all isolated metabolites was acquired and compiled in a custom GC/MS library to be employed to detect metabolites in the crude extracts. Full article

(This article belongs to the Special Issue Qualitative and Quantitative Analysis of Bioactive Natural Products 2018)

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9 pages, 880 KiB

Open AccessArticle

Phytotoxic and Antifungal Metabolites from Curvularia crepinii QTYC-1 Isolated from the Gut of Pantala flavescens

by Caiping Yin, Liping Jin, Feifei Sun, Xiao Xu, Mingwei Shao and Yinglao Zhang

Molecules 2018, 23(4), 951; https://doi.org/10.3390/molecules23040951 - 19 Apr 2018

Cited by 14 | Viewed by 3673

Abstract

Four metabolites (1–4), including a new macrolide, O-demethylated-zeaenol (2), and three known compounds, zeaenol (1), adenosine (3), and ergosta-5,7,22-trien-3b-ol (4) were isolated and purified from Curvularia crepinii QTYC-1, a fungus [...] Read more.

Four metabolites (1–4), including a new macrolide, O-demethylated-zeaenol (2), and three known compounds, zeaenol (1), adenosine (3), and ergosta-5,7,22-trien-3b-ol (4) were isolated and purified from Curvularia crepinii QTYC-1, a fungus residing in the gut of Pantala flavescens. The structures of isolated compounds were identified on the basis of extensive spectroscopic analysis and by comparison of the corresponding data with those reported in the literature previously. The new compound 2 showed good phytotoxic activity against Echinochloa crusgalli with an IC₅₀ value of less than 5 µg/mL, which was comparable to that of positive 2,4-dichlorophenoxyacetic acid (2,4-D). Compound 1 exhibited moderate herbicidal activity against E. crusgalli with an IC₅₀ value of 28.8 μg/mL. Furthermore, the new metabolite 2 was found to possess moderate antifungal activity against Valsa mali at the concentration of 100 µg/mL, with the inhibition rate of 50%. These results suggest that the new macrolide 2 and the known compound 1 have potential to be used as biocontrol agents in agriculture. Full article

(This article belongs to the Section Metabolites)

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15 pages, 2415 KiB

Open AccessFeature PaperArticle

Chemical Synthesis and Functional Analysis of VarvA Cyclotide

by Claudio A. Álvarez, Paula A. Santana, Omar Luna, Constanza Cárdenas, Fernando Albericio, María S. Romero and Fanny Guzmán

Molecules 2018, 23(4), 952; https://doi.org/10.3390/molecules23040952 - 19 Apr 2018

Cited by 10 | Viewed by 4276

Abstract

Cyclotides are circular peptides found in various plant families. A cyclized backbone, together with multiple disulfide bonds, confers the peptides’ exceptional stability against protease digestion and thermal denaturation. In addition, the features of these antimicrobial molecules make them suitable for use in animal [...] Read more.

Cyclotides are circular peptides found in various plant families. A cyclized backbone, together with multiple disulfide bonds, confers the peptides’ exceptional stability against protease digestion and thermal denaturation. In addition, the features of these antimicrobial molecules make them suitable for use in animal farming, such as aquaculture. Fmoc solid phase peptide synthesis on 2-chlorotrityl chlorine (CTC) resin using the “tea-bag” approach was conducted to generate the VarvA cyclotide identified previously from Viola arvensis. MALDI-TOF mass spectrometry determined the correct peptide amino acid sequence and the cyclization sites-critical in this multicyclic compound. The cyclotide showed antimicrobial activity against various Gram-negative bacteria, including recurrent pathogens present in Chilean aquaculture. The highest antimicrobial activity was found to be against Flavobacterium psychrophilum. In addition, membrane blebbing on the bacterial surface after exposure to the cyclotide was visualized by SEM microscopy and the Sytox Green permeabilization assay showed the ability to disrupt the bacterial membrane. We postulate that this compound can be proposed for the control of fish farming infections. Full article

(This article belongs to the Special Issue Cyclic Peptides)

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12 pages, 6517 KiB

Open AccessArticle

Search for Partner Proteins of A. thaliana Immunophilins Involved in the Control of Plant Immunity

by Inna A. Abdeeva, Gennady V. Pogorelko, Liliya G. Maloshenok, Maria V. Mokrykova, Oksana V. Fursova and Sergey A. Bruskin

Molecules 2018, 23(4), 953; https://doi.org/10.3390/molecules23040953 - 19 Apr 2018

Cited by 7 | Viewed by 3912

Abstract

The involvement of plant immunophilins in multiple essential processes such as development, various ways of adapting to biotic and abiotic stresses, and photosynthesis has already been established. Previously, research has demonstrated the involvement of three immunophilin genes (AtCYP19-1/ROC3, AtFKBP65/ROF2, and [...] Read more.

The involvement of plant immunophilins in multiple essential processes such as development, various ways of adapting to biotic and abiotic stresses, and photosynthesis has already been established. Previously, research has demonstrated the involvement of three immunophilin genes (AtCYP19-1/ROC3, AtFKBP65/ROF2, and AtCYP57) in the control of plant response to invasion by various pathogens. Current research attempts to identify host target proteins for each of the selected immunophilins. As a result, candidate interactors have been determined and confirmed using a yeast 2-hybrid (Y2H) system for protein–protein interaction assays. The generation of mutant isoforms of ROC3 and AtCYP57 harboring substituted amino acids in the in silico-predicted active sites became essential to achieving significant binding to its target partners. This data shows that ROF2 targets calcium-dependent lipid-binding domain-containing protein (At1g70790; AT1) and putative protein phosphatase (At2g30020; АТ2), whereas ROC3 interacts with GTP-binding protein (At1g30580; ENGD-1) and RmlC-like cupin (At5g39120). The immunophilin AtCYP57 binds to putative pyruvate decarboxylase-1 (Pdc1) and clathrin adaptor complex-related protein (At5g05010). Identified interactors confirm our previous findings that immunophilins ROC3, ROF2, and AtCYP57 are directly involved with stress response control. Further, these findings extend our understanding of the molecular functional pathways of these immunophilins. Full article

(This article belongs to the Section Molecular Diversity)

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13 pages, 7770 KiB

Open AccessArticle

Computational Prediction and Analysis of Associations between Small Molecules and Binding-Associated S-Nitrosylation Sites

by Guohua Huang, Jincheng Li and Chenglin Zhao

Molecules 2018, 23(4), 954; https://doi.org/10.3390/molecules23040954 - 19 Apr 2018

Cited by 5 | Viewed by 4317

Abstract

Interactions between drugs and proteins occupy a central position during the process of drug discovery and development. Numerous methods have recently been developed for identifying drug–target interactions, but few have been devoted to finding interactions between post-translationally modified proteins and drugs. We presented [...] Read more.

Interactions between drugs and proteins occupy a central position during the process of drug discovery and development. Numerous methods have recently been developed for identifying drug–target interactions, but few have been devoted to finding interactions between post-translationally modified proteins and drugs. We presented a machine learning-based method for identifying associations between small molecules and binding-associated S-nitrosylated (SNO-) proteins. Namely, small molecules were encoded by molecular fingerprint, SNO-proteins were encoded by the information entropy-based method, and the random forest was used to train a classifier. Ten-fold and leave-one-out cross validations achieved, respectively, 0.7235 and 0.7490 of the area under a receiver operating characteristic curve. Computational analysis of similarity suggested that SNO-proteins associated with the same drug shared statistically significant similarity, and vice versa. This method and finding are useful to identify drug–SNO associations and further facilitate the discovery and development of SNO-associated drugs. Full article

(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)

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14 pages, 3230 KiB

Open AccessArticle

Formation of Sulforaphane and Iberin Products from Thai Cabbage Fermented by Myrosinase-Positive Bacteria

by Vijitra Luang-In, Sirirat Deeseenthum, Piyachat Udomwong, Worachot Saengha and Matteo Gregori

Molecules 2018, 23(4), 955; https://doi.org/10.3390/molecules23040955 - 19 Apr 2018

Cited by 23 | Viewed by 5686

Abstract

Myrosinase-positive bacteria from local fermented foods and beverages in Thailand with the capacity to metabolize glucosinolate and produce isothiocyanates (ITCs) were isolated and used as selected strains for Thai cabbage fermentation. Enterobacter xiangfangensis 4A-2A3.1 (EX) from fermented fish and Enterococcus casseliflavus SB2X2 (EC) [...] Read more.

Myrosinase-positive bacteria from local fermented foods and beverages in Thailand with the capacity to metabolize glucosinolate and produce isothiocyanates (ITCs) were isolated and used as selected strains for Thai cabbage fermentation. Enterobacter xiangfangensis 4A-2A3.1 (EX) from fermented fish and Enterococcus casseliflavus SB2X2 (EC) from fermented cabbage were the two highest ITC producers among seventeen strains identified by 16S rRNA technique. EC and EX were used to ferment Thai cabbage (Brassica oleracea L. var. capitata) containing glucoiberin, glucoraphanin and 4-hydroxyglucobrassicin at 430.5, 615.1 and 108.5 µmol/100 g DW, respectively for 3 days at 25 °C. Different amounts of iberin nitrile, iberin, sulforaphane and indole 3-acetonitrile were produced by spontaneous, EX- and EC-induced cabbage fermentations, and significantly higher ITCs were detected (p < 0.01) with increased antioxidant activities. Iberin and sulforaphane production in EX-induced treatment peaked on day 2 at 117.4 and 294.1 µmol/100 g DW, respectively, significantly higher than iberin at 51.7 µmol/100 g DW but not significantly higher than sulforaphane at 242.6 µmol/100 g DW in EC-induced treatment at day 2. Maximum health-promoting benefits from this functional food can be obtained from consumption of a liquid portion of the fermented cabbage with higher ITC level along with a solid portion. Full article

(This article belongs to the Collection Bioactive Compounds)

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18 pages, 2547 KiB

Open AccessArticle

Multi-Response Extraction Optimization Based on Anti-Oxidative Activity and Quality Evaluation by Main Indicator Ingredients Coupled with Chemometric Analysis on Thymus quinquecostatus Celak

by Yan-Li Chang, Meng Shen, Xue-Yang Ren, Ting He, Le Wang, Shu-Sheng Fan, Xiu-Huan Wang, Xiao Li, Xiao-Ping Wang, Xiao-Yi Chen, Hong Sui and Gai-Mei She

Molecules 2018, 23(4), 957; https://doi.org/10.3390/molecules23040957 - 19 Apr 2018

Cited by 12 | Viewed by 4467

Abstract

Thymus quinquecostatus Celak is a species of thyme in China and it used as condiment and herbal medicine for a long time. To set up the quality evaluation of T. quinquecostatus, the response surface methodology (RSM) based on its 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical [...] Read more.

Thymus quinquecostatus Celak is a species of thyme in China and it used as condiment and herbal medicine for a long time. To set up the quality evaluation of T. quinquecostatus, the response surface methodology (RSM) based on its 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity was introduced to optimize the extraction condition, and the main indicator components were found through an UPLC-LTQ-Orbitrap MSⁿ method. The ethanol concentration, solid-liquid ratio, and extraction time on optimum conditions were 42.32%, 1:17.51, and 1.8 h, respectively. 35 components having 12 phenolic acids and 23 flavonoids were unambiguously or tentatively identified both positive and negative modes to employ for the comprehensive analysis in the optimum anti-oxidative part. A simple, reliable, and sensitive HPLC method was performed for the multi-component quantitative analysis of T. quinquecostatus using six characteristic and principal phenolic acids and flavonoids as reference compounds. Furthermore, the chemometrics methods (principal components analysis (PCA) and hierarchical clustering analysis (HCA)) appraised the growing areas and harvest time of this herb closely relative to the quality-controlled. This study provided full-scale qualitative and quantitative information for the quality evaluation of T. quinquecostatus, which would be a valuable reference for further study and development of this herb and related laid the foundation of further study on its pharmacological efficacy. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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14 pages, 2102 KiB

Open AccessArticle

Anti-Diabetic Effects of Acankoreagenin from the Leaves of Acanthopanax Gracilistylus Herb in RIN-m5F Cells via Suppression of NF-κB Activation

by Man-Xia Lu, Yang Yang, Qin-Peng Zou, Jiao Luo, Bin-Bei Zhang, Xiang-Qian Liu and Eun-Hee Hwang

Molecules 2018, 23(4), 958; https://doi.org/10.3390/molecules23040958 - 19 Apr 2018

Cited by 20 | Viewed by 5311

Abstract

Diabetes mellitus is a chronic degenerative disease that causes long-term complications and represents a serious public health problem. In this manuscript, acankoreagenin isolated from the leaves of Acanthopanax gracilistylus (LAG) is thought to possess excellent anti-diabetic properties. In vitro, anti-diabetic activities were assessed [...] Read more.

Diabetes mellitus is a chronic degenerative disease that causes long-term complications and represents a serious public health problem. In this manuscript, acankoreagenin isolated from the leaves of Acanthopanax gracilistylus (LAG) is thought to possess excellent anti-diabetic properties. In vitro, anti-diabetic activities were assessed based on the inhibitory activities with α-glucosidase (IC₅₀ 13.01 μM), α-amylase (IC₅₀ 30.81 μM), and PTP1B (IC₅₀ 16.39 μM). Acankoreagenin showed better anti-diabetic effects. Then, an investigation was performed to analyze the insulin secretion effects of the insulin-secreting cell line in RIN-m5F cells. It was found that acankoreagenin could increase the insulin release in RIN-m5F cells. It was also found that acankoreagenin reduced NO production, activity of caspase-3, and the reactive oxygen species levels in the cells injured by processing of cytokines. In western blotting, inactivation of NF-κB signaling was confirmed. Acankoreagenin (20 μM) showed a higher I-κBα expression and lower NF-κB expression than the control group and showed a better expression than the positive control L-NAME (1 mM) (p < 0.05). This study demonstrates the anti-diabetic effects of acankoreagenin in vitro and suggests acankoreagenin might offer therapeutic potential for treating diabetes mellitus. Full article

(This article belongs to the Special Issue Medicinal Plants and Diabetes)

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11 pages, 490 KiB

Open AccessArticle

The Chemical Composition and Metabolic Effects of Attalea phalerata Nut Oil in Hyperlipidemic Rats Induced by a High-Fructose Diet

by Débora Da Silva Baldivia, Eliana Janet Sanjinez-Argandonã, Kátia Ávila Antunes, Izabel Cristina Freitas Moraes, Edson Lucas Dos Santos and Kely De Picoli Souza

Molecules 2018, 23(4), 960; https://doi.org/10.3390/molecules23040960 - 20 Apr 2018

Cited by 5 | Viewed by 4294

Abstract

The fatty acids found in nuts are important regulators of the metabolism. These acids are frequently associated with a reduction of serum cholesterol and body fat and a lower risk of developing cardiovascular disease. In this context, the aim of this study was [...] Read more.

The fatty acids found in nuts are important regulators of the metabolism. These acids are frequently associated with a reduction of serum cholesterol and body fat and a lower risk of developing cardiovascular disease. In this context, the aim of this study was to identify and quantify the nut oil fatty acids from Attalea phalerata and investigate their metabolic effects in rats with hyperlipidemia induced by a diet rich in fructose. Oleic and lauric acids were the major compounds found in the A. phalerata nut oil (APNO). Hyperlipidemic rats treated with APNO showed a reduction in the total serum cholesterol similar to those treated with simvastatin, an increased body temperature by 1 °C, and a reduction in the body weight gain and mesenteric depot of white adipose tissue compared to the hyperlipidemic controls rats. There was an increase in the relative liver weight of rats treated with APNO, without, however, any change in the serum markers of hepatic toxicity. In addition, there was an increase in the moisture and lipid content of the feces of the rats treated with APNO compared to the controls. Together, these results suggest that APNO has potential use in health foods and nutritional supplements to control hypercholesterolemia and obesity. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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12 pages, 3684 KiB

Open AccessFeature PaperCommunication

Catalytic Enantioselective Addition of Organozirconium Reagents to Aldehydes

by Ricard Solà, Marcos Veguillas, María José González-Soria, Nicholas Carter, M. Angeles Fernández-Ibáñez and Beatriz Maciá

Molecules 2018, 23(4), 961; https://doi.org/10.3390/molecules23040961 - 20 Apr 2018

Cited by 4 | Viewed by 5888

Abstract

A catalytic enantioselective addition reaction of alkylzirconium species to aromatic aldehydes is reported. The reaction, facilitated by a chiral nonracemic diol ligand complex with Ti(OⁱPr)₄, proceeds under mild and convenient conditions, and no premade organometallic reagents are required since [...] Read more.

A catalytic enantioselective addition reaction of alkylzirconium species to aromatic aldehydes is reported. The reaction, facilitated by a chiral nonracemic diol ligand complex with Ti(OⁱPr)₄, proceeds under mild and convenient conditions, and no premade organometallic reagents are required since the alkylzirconium nucleophiles are generated in situ by hydrozirconation of alkenes with the Schwartz reagent. The methodology is compatible with functionalized nucleophiles and a broad range of aromatic aldehydes. Full article

(This article belongs to the Special Issue Stereogenic Centers)

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10 pages, 1229 KiB

Open AccessFeature PaperArticle

Direct (Hetero)Arylation Polymerization of a Spirobifluorene and a Dithienyl-Diketopyrrolopyrrole Derivative: New Donor Polymers for Organic Solar Cells

by Pierre Josse, Sergey Dayneko, Yangqian Zhang, Sylvie Dabos-Seignon, Shiming Zhang, Philippe Blanchard, Gregory C. Welch and Clément Cabanetos

Molecules 2018, 23(4), 962; https://doi.org/10.3390/molecules23040962 - 20 Apr 2018

Cited by 12 | Viewed by 5801

Abstract

The synthesis and preliminary evaluation as donor material for organic photovoltaics of the poly(diketopyrrolopyrrole-spirobifluorene) (PDPPSBF) is reported herein. Prepared via homogeneous and heterogeneous direct (hetero)arylation polymerization (DHAP), through the use of different catalytic systems, conjugated polymers with comparable molecular weights were [...] Read more.

The synthesis and preliminary evaluation as donor material for organic photovoltaics of the poly(diketopyrrolopyrrole-spirobifluorene) (PDPPSBF) is reported herein. Prepared via homogeneous and heterogeneous direct (hetero)arylation polymerization (DHAP), through the use of different catalytic systems, conjugated polymers with comparable molecular weights were obtained. The polymers exhibited strong optical absorption out to 700 nm as thin-films and had appropriate electronic energy levels for use as a donor with PC₇₀BM. Bulk heterojunction solar cells were fabricated giving power conversion efficiencies above 4%. These results reveal the potential of such polymers prepared in only three steps from affordable and commercially available starting materials. Full article

(This article belongs to the Special Issue Direct (Hetero)Arylation: A New Tool for Organic Electronics)

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18 pages, 1783 KiB

Open AccessArticle

Magnetic Properties of Metal–Organic Coordination Networks Based on 3d Transition Metal Atoms

by María Blanco-Rey, Ane Sarasola, Corneliu Nistor, Luca Persichetti, Christian Stamm, Cinthia Piamonteze, Pietro Gambardella, Sebastian Stepanow, Mikhail M. Otrokov, Vitaly N. Golovach and Andres Arnau

Molecules 2018, 23(4), 964; https://doi.org/10.3390/molecules23040964 - 20 Apr 2018

Cited by 9 | Viewed by 6721

Abstract

The magnetic anisotropy and exchange coupling between spins localized at the positions of 3d transition metal atoms forming two-dimensional metal–organic coordination networks (MOCNs) grown on a Au(111) metal surface are studied. In particular, we consider MOCNs made of Ni or Mn metal centers [...] Read more.

The magnetic anisotropy and exchange coupling between spins localized at the positions of 3d transition metal atoms forming two-dimensional metal–organic coordination networks (MOCNs) grown on a Au(111) metal surface are studied. In particular, we consider MOCNs made of Ni or Mn metal centers linked by 7,7,8,8-tetracyanoquinodimethane (TCNQ) organic ligands, which form rectangular networks with 1:1 stoichiometry. Based on the analysis of X-ray magnetic circular dichroism (XMCD) data taken at T = 2.5 K, we find that Ni atoms in the Ni–TCNQ MOCNs are coupled ferromagnetically and do not show any significant magnetic anisotropy, while Mn atoms in the Mn–TCNQ MOCNs are coupled antiferromagnetically and do show a weak magnetic anisotropy with in-plane magnetization. We explain these observations using both a model Hamiltonian based on mean-field Weiss theory and density functional theory calculations that include spin–orbit coupling. Our main conclusion is that the antiferromagnetic coupling between Mn spins and the in-plane magnetization of the Mn spins can be explained by neglecting effects due to the presence of the Au(111) surface, while for Ni–TCNQ the metal surface plays a role in determining the absence of magnetic anisotropy in the system. Full article

(This article belongs to the Special Issue Electronic Structure Calculations Applied to Magnetic Phenomena)

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13 pages, 12352 KiB

Open AccessArticle

Investigation on Species Authenticity for Herbal Products of Celastrus Orbiculatus and Tripterygum Wilfordii from Markets Using ITS2 Barcoding

by Jingjing Zhang, Xin Hu, Ping Wang, Bisheng Huang, Wei Sun, Chao Xiong, Zhigang Hu and Shilin Chen

Molecules 2018, 23(4), 967; https://doi.org/10.3390/molecules23040967 - 21 Apr 2018

Cited by 13 | Viewed by 5005

Abstract

Herbal material is both a medicine and a commodity. Accurate identification of herbal materials is necessary to ensure the safety and effectiveness of medication. With this work, we initiated an identification method to investigate the species authenticity for herbal products of Celastrus orbiculatus [...] Read more.

Herbal material is both a medicine and a commodity. Accurate identification of herbal materials is necessary to ensure the safety and effectiveness of medication. With this work, we initiated an identification method to investigate the species authenticity for herbal products of Celastrus orbiculatus and Tripterygum wilfordii utilizing DNA barcoding technology. An ITS2 (internal transcribed spacer two) barcode database including 59 sequences was successfully established to estimate the reliability of species-level identification for Celastrus and Tripterygium. Our findings showed that ITS2 can effectively and clearly distinguish C. orbiculatus, T. wilfordii and its congeners. Then, we investigated the proportions and varieties of adulterant species in the herbal markets. The data from ITS2 region indicated that 13 (62%) of the 21 samples labeled as “Nan-she-teng” and eight (31%) of the 26 samples labeled as “Lei-gong-teng” were authentic; the remaining were adulterants. Of the 47 herbal products, approximately 55% of the product identity were not in accordance with the label. In summary, we support the efficacy of the ITS2 barcode for the traceability of C. orbiculatus and T. wilfordii, and the present study provides one method and reference for the identification of the herbal materials and adulterants in the medicinal markets. Full article

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15 pages, 39278 KiB

Open AccessArticle

Co-Localization of Crotamine with Internal Membranes and Accentuated Accumulation in Tumor Cells

by Nicole Caroline Mambelli-Lisboa, Juliana Mozer Sciani, Alvaro Rossan Brandão Prieto da Silva and Irina Kerkis

Molecules 2018, 23(4), 968; https://doi.org/10.3390/molecules23040968 - 20 Apr 2018

Cited by 18 | Viewed by 6146

Abstract

Crotamine is a highly cationic; cysteine rich, cross-linked, low molecular mass cell penetrating peptide (CPP) from the venom of the South American rattlesnake. Potential application of crotamine in biomedicine may require its large-scale purification. To overcome difficulties related with the purification of natural [...] Read more.

Crotamine is a highly cationic; cysteine rich, cross-linked, low molecular mass cell penetrating peptide (CPP) from the venom of the South American rattlesnake. Potential application of crotamine in biomedicine may require its large-scale purification. To overcome difficulties related with the purification of natural crotamine (nCrot) we aimed in the present study to synthesize and characterize a crotamine analog (sCrot) as well investigate its CPP activity. Mass spectrometry analysis demonstrates that sCrot and nCrot have equal molecular mass and biological function—the capacity to induce spastic paralysis in the hind limbs in mice. sCrot CPP activity was evaluated in a wide range of tumor and non-tumor cell tests performed at different time points. We demonstrate that sCrot-Cy3 showed distinct co-localization patterns with intracellular membranes inside the tumor and non-tumor cells. Time-lapse microscopy and quantification of sCrot-Cy3 fluorescence signalss in living tumor versus non-tumor cells revealed a significant statistical difference in the fluorescence intensity observed in tumor cells. These data suggest a possible use of sCrot as a molecular probe for tumor cells, as well as, for the selective delivery of anticancer molecules into these tumors. Full article

(This article belongs to the Special Issue Natural Toxins/Molecules (and Derivatives) from Animal Venoms: From Basic Research to Therapeutic Applications)

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15 pages, 3287 KiB

Open AccessArticle

Self-Assembly Behavior of Amphiphilic Janus Dendrimers in Water: A Combined Experimental and Coarse-Grained Molecular Dynamics Simulation Approach

by Mariana E. Elizondo-García, Valeria Márquez-Miranda, Ingrid Araya-Durán, Jesús A. Valencia-Gallegos and Fernando D. González-Nilo

Molecules 2018, 23(4), 969; https://doi.org/10.3390/molecules23040969 - 21 Apr 2018

Cited by 8 | Viewed by 6979

Abstract

Amphiphilic Janus dendrimers (JDs) are repetitively branched molecules with hydrophilic and hydrophobic components that self-assemble in water to form a variety of morphologies, including vesicles analogous to liposomes with potential pharmaceutical and medical application. To date, the self-assembly of JDs has not been [...] Read more.

Amphiphilic Janus dendrimers (JDs) are repetitively branched molecules with hydrophilic and hydrophobic components that self-assemble in water to form a variety of morphologies, including vesicles analogous to liposomes with potential pharmaceutical and medical application. To date, the self-assembly of JDs has not been fully investigated thus it is important to gain insight into its mechanism and dependence on JDs’ molecular structure. In this study, the aggregation behavior in water of a second-generation bis-MPA JD was evaluated using experimental and computational methods. Dispersions of JDs in water were carried out using the thin-film hydration and ethanol injection methods. Resulting assemblies were characterized by dynamic light scattering, confocal microscopy, and atomic force microscopy. Furthermore, a coarse-grained molecular dynamics (CG-MD) simulation was performed to study the mechanism of JDs aggregation. The obtaining of assemblies in water with no interdigitated bilayers was confirmed by the experimental characterization and CG-MD simulation. Assemblies with dendrimersome characteristics were obtained using the ethanol injection method. The results of this study establish a relationship between the molecular structure of the JD and the properties of its aggregates in water. Thus, our findings could be relevant for the design of novel JDs with tailored assemblies suitable for drug delivery systems. Full article

(This article belongs to the Special Issue Dendrimers in Medicine)

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11 pages, 3450 KiB

Open AccessArticle

Microbial Oxidation of the Fusidic Acid Side Chain by Cunninghamella echinulata

by Abdel-Rahim S. Ibrahim, Khaled M. Elokely, Daneel Ferreira and Amany E. Ragab

Molecules 2018, 23(4), 970; https://doi.org/10.3390/molecules23040970 - 21 Apr 2018

Cited by 6 | Viewed by 5253

Abstract

Biotransformation of fusidic acid (1) was accomplished using a battery of microorganisms including Cunninghamella echinulata NRRL 1382, which converted fusidic acid (1) into three new metabolites 2–4 and the known metabolite 5. These metabolites were identified [...] Read more.

Biotransformation of fusidic acid (1) was accomplished using a battery of microorganisms including Cunninghamella echinulata NRRL 1382, which converted fusidic acid (1) into three new metabolites 2–4 and the known metabolite 5. These metabolites were identified using 1D and 2D NMR and HRESI-FTMS data. Structural assignment of the compounds was supported via computation of ¹H- and ¹³C-NMR chemical shifts. Compounds 2 and 3 were assigned as the 27-hydroxy and 26-hydroxy derivatives of fusidic acid, respectively. Subsequent oxidation of 3 afforded aldehyde 4 and the dicarboxylic acid 5. Compounds 2, 4 and 5 were screened for antimicrobial activity against different Gram positive and negative bacteria, Mycobacterium smegmatis, M. intercellulare and Candida albicans. The compounds showed lower activity compared to fusidic acid against the tested strains. Molecular docking studies were carried out to assist the structural assignments and predict the binding modes of the metabolites. Full article

(This article belongs to the Special Issue Isolation and Structure Elucidation of Bioactive Compounds (Dedicated to the memory of the late Professor Charles D. Hufford))

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10 pages, 1828 KiB

Open AccessArticle

Evaluation of Manganese Chloride’s Effect on Biosynthetic Properties of In Vitro Cultures of Eschscholzia californica Cham.

by Andrea Balažová, Júlia Urdová, František Bilka, Ivana Holková, Branislav Horváth, Vladimír Forman and Pavel Mučaji

Molecules 2018, 23(4), 971; https://doi.org/10.3390/molecules23040971 - 21 Apr 2018

Cited by 5 | Viewed by 4420

Abstract

The basal production of secondary metabolites in medicinal plants is limited. One of the effective approaches that encourages plants to produce a remarkable amount of precious compounds is an application of elicitors. Our work was focused on the elicitation of Eschscholzia californica Cham. [...] Read more.

The basal production of secondary metabolites in medicinal plants is limited. One of the effective approaches that encourages plants to produce a remarkable amount of precious compounds is an application of elicitors. Our work was focused on the elicitation of Eschscholzia californica Cham. suspension cultures using various concentrations of MnCl₂ (5; 10; 15 mg/L) with the aim of evaluating its effect on sanguinarine, chelerythrine, and macarpine production and gene expression of enzymes involved in the biosynthesis of mentioned secondary metabolites (BBE, 4′-OMT, CYP80B1) or in defense processes (LOX). Suspension cultures were exposed to elicitor for 24, 48, and 72 h. The content of alkaloids in phytomass was determined on the basis of their fluorescence properties. The relative mRNA expression of selected genes was analyzed using the ΔΔCt value method. PCR products were evaluated by melting curve analysis to confirm the specific amplification. Our results demonstrated that Eschscholzia californica Cham. cell suspension cultures evince sensitivity to the presence of MnCl₂ in growth media resulting in the increased production of benzophenanthridine alkaloids and gene expression of selected enzymes. Manganese chloride seems to be a potential elicitor supporting natural biosynthetic properties in plant cell cultures and can be applied for the sustained production of valuable secondary metabolites. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 14761 KiB

Open AccessArticle

The Effects of Chinese Herbal Medicines on the Quorum Sensing-Regulated Virulence in Pseudomonas aeruginosa PAO1

by Yee Meng Chong, Kah Yan How, Wai Fong Yin and Kok Gan Chan

Molecules 2018, 23(4), 972; https://doi.org/10.3390/molecules23040972 - 21 Apr 2018

Cited by 16 | Viewed by 5503

Abstract

The quorum sensing (QS) system has been used by many opportunistic pathogenic bacteria to coordinate their virulence determinants in relation to cell-population density. As antibiotic-resistant bacteria are on the rise, interference with QS has been regarded as a novel way to control bacterial [...] Read more.

The quorum sensing (QS) system has been used by many opportunistic pathogenic bacteria to coordinate their virulence determinants in relation to cell-population density. As antibiotic-resistant bacteria are on the rise, interference with QS has been regarded as a novel way to control bacterial infections. As such, many plant-based natural products have been widely explored for their therapeutic roles. These natural products may contain anti-QS compounds that could block QS signals generation or transmission to combat QS pathogens. In this study, we report the anti-QS activities of four different Chinese herbal plant extracts: Poria cum Radix pini, Angelica dahurica, Rhizoma cibotii and Schizonepeta tenuifolia, on Pseudomonas aeruginosa PAO1. All the plants extracted using hexane, chloroform and methanol were tested and found to impair swarming motility and pyocyanin production in P. aeruginosa PAO1, particularly by Poria cum Radix pini. In addition, all the plant extracts also inhibited violacein production in C. violaceum CV026 up to 50% while bioluminescence activities were reduced in lux-based E. coli biosensors, pSB401 and pSB1075, up to about 57%. These anti-QS properties of the four medicinal plants are the first documentation that demonstrates a potential approach to attenuate pathogens’ virulence determinants. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 7585 KiB

Open AccessArticle

Antioxidant and Cytoprotective Effects of Kukoamines A and B: Comparison and Positional Isomeric Effect

by Xican Li, Jian Lin, Ban Chen, Hong Xie and Dongfeng Chen

Molecules 2018, 23(4), 973; https://doi.org/10.3390/molecules23040973 - 21 Apr 2018

Cited by 27 | Viewed by 5340

Abstract

In this study, two natural phenolic polyamines, kukoamine A and B, were comparatively investigated for their antioxidant and cytoprotective effects in Fenton-damaged bone marrow-derived mesenchymal stem cells (bmMSCs). When compared with kukoamine B, kukoamine A consistently demonstrated higher IC₅₀ values in PTIO•-scavenging [...] Read more.

In this study, two natural phenolic polyamines, kukoamine A and B, were comparatively investigated for their antioxidant and cytoprotective effects in Fenton-damaged bone marrow-derived mesenchymal stem cells (bmMSCs). When compared with kukoamine B, kukoamine A consistently demonstrated higher IC₅₀ values in PTIO•-scavenging (pH 7.4), Cu²⁺-reducing, DPPH•-scavenging, •O₂⁻-scavenging, and •OH-scavenging assays. However, in the PTIO•-scavenging assay, the IC₅₀ values of each kukoamine varied with pH value. In the Fe²⁺-chelating assay, kukoamine B presented greater UV-Vis absorption and darker color than kukoamine A. In the HPLC–ESI–MS/MS analysis, kukoamine A with DPPH• produced radical-adduct-formation (RAF) peaks (m/z 922 and 713). The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay suggested that both kukoamines concentration-dependently increased the viabilities of Fenton-damaged bmMSCs at 56.5–188.4 μM. However, kukoamine A showed lower viability percentages than kukoamine B. In conclusion, the two isomers kukoamine A and B can protect bmMSCs from Fenton-induced damage, possibly through direct or indirect antioxidant pathways, including electron-transfer, proton-transfer, hydrogen atom transfer, RAF, and Fe²⁺-chelating. Since kukoamine B possesses higher potentials than kukoamine A in these pathways, kukoamine B is thus superior to kukoamine A in terms of cytoprotection. These differences can ultimately be attributed to positional isomeric effects. Full article

(This article belongs to the Special Issue The Antioxidant Capacities of Natural Products)

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11 pages, 1498 KiB

Open AccessArticle

Application of the Response Surface Methodology to Optimize the Fermentation Parameters for Enhanced Docosahexaenoic Acid (DHA) Production by Thraustochytrium sp. ATCC 26185

by Kang Wu, Lijian Ding, Peng Zhu, Shuang Li and Shan He

Molecules 2018, 23(4), 974; https://doi.org/10.3390/molecules23040974 - 22 Apr 2018

Cited by 20 | Viewed by 4656

Abstract

The aim of this study was to determine the cumulative effect of fermentation parameters and enhance the production of docosahexaenoic acid (DHA) by Thraustochytrium sp. ATCC 26185 using response surface methodology (RSM). Among the eight variables screened for effects of fermentation parameters on [...] Read more.

The aim of this study was to determine the cumulative effect of fermentation parameters and enhance the production of docosahexaenoic acid (DHA) by Thraustochytrium sp. ATCC 26185 using response surface methodology (RSM). Among the eight variables screened for effects of fermentation parameters on DHA production by Plackett-Burman design (PBD), the initial pH, inoculum volume, and fermentation volume were found to be most significant. The Box-Behnken design was applied to derive a statistical model for optimizing these three fermentation parameters for DHA production. The optimal parameters for maximum DHA production were initial pH: 6.89, inoculum volume: 4.16%, and fermentation volume: 140.47 mL, respectively. The maximum yield of DHA production was 1.68 g/L, which was in agreement with predicted values. An increase in DHA production was achieved by optimizing the initial pH, fermentation, and inoculum volume parameters. This optimization strategy led to a significant increase in the amount of DHA produced, from 1.16 g/L to 1.68 g/L. Thraustochytrium sp. ATCC 26185 is a promising resource for microbial DHA production due to the high-level yield of DHA that it produces, and the capacity for large-scale fermentation of this organism. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 3221 KiB

Open AccessArticle

Study on the Bactericidal Mechanism of Atmospheric-Pressure Low-Temperature Plasma against Escherichia coli and Its Application in Fresh-Cut Cucumbers

by Yan Sun, Zhiwei Zhang and Shiqing Wang

Molecules 2018, 23(4), 975; https://doi.org/10.3390/molecules23040975 - 22 Apr 2018

Cited by 29 | Viewed by 6252

Abstract

Atmospheric-pressure low-temperature plasma (APLTP) was used to study the bactericidal mechanism against Escherichia coli (E. coli) and its application in the sterilization of fresh-cut cucumbers. The morphological changes of E. coli cells subjected to APLTP were observed by scanning electron microscopy [...] Read more.

Atmospheric-pressure low-temperature plasma (APLTP) was used to study the bactericidal mechanism against Escherichia coli (E. coli) and its application in the sterilization of fresh-cut cucumbers. The morphological changes of E. coli cells subjected to APLTP were observed by scanning electron microscopy (SEM). Cell death was evaluated by fluorescence microscopy (FM). Cell membrane permeability was measured by conductivity changes, and the amount of soluble protein leakage in the bacterial supernatant was determined by measurement of protein concentration. Additionally, the effects of APLTP on the physicochemical and sensory quality of fresh-cut cucumber were studied by assessing the changes of moisture content, soluble solid content (SSC), pH value, color, relative conductivity, malondialdehyde (MDA) level, vitamin C (Vc) content, aroma composition and microstructure. The results showed that the E. coli cell morphology was changed due to the charged particles and active components produced by APLTP. The E. coli cell wall and cell membrane ruptured, cell content leaked out, cells lost the ability to reproduce and self-replicate, and the function of cell metabolism was directly affected and led to E. coli inactivation. In addition, there was no significant effect on physicochemical properties and sensory quality of fresh-cut cucumbers. Full article

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8 pages, 1526 KiB

Open AccessArticle

Convenient Synthesis of Thiohydantoins, Imidazole-2-thiones and Imidazo[2,1-b]thiazol-4-iums from Polymer-Supported α-Acylamino Ketones

by Petra Králová, Michal Maloň, Hiroyuki Koshino and Miroslav Soural

Molecules 2018, 23(4), 976; https://doi.org/10.3390/molecules23040976 - 23 Apr 2018

Cited by 7 | Viewed by 4680

Abstract

The preparation of 5-methylene-thiohydantoins using solid-phase synthesis is reported in this paper. After sulfonylation of immobilized Ser (t-Bu)-OH with 4-nitrobenzenesulfonyl chloride followed by alkylation with various bromoketones, the 4-Nos group was removed and the resulting polymer-supported α-acylamino ketones reacted with Fmoc-isothiocyanate. [...] Read more.

The preparation of 5-methylene-thiohydantoins using solid-phase synthesis is reported in this paper. After sulfonylation of immobilized Ser (t-Bu)-OH with 4-nitrobenzenesulfonyl chloride followed by alkylation with various bromoketones, the 4-Nos group was removed and the resulting polymer-supported α-acylamino ketones reacted with Fmoc-isothiocyanate. Cleavage of the Fmoc protecting group was followed by the spontaneous cyclative cleavage releasing the 5-methylene-thiohydantoin derivatives from the polymer support. Reduction with triethylsilane (TES) yielded the corresponding 5-methyl-thiohydantoins. When Fmoc-isothiocyanate was replaced with alkyl isothiocyanates, the trifluoroacetic acid (TFA) mediated cleavage from the polymer support, which was followed by the cyclization reaction and the imidazo[2,1-b]thiazol-4-iums were obtained. Their conversion in deuterated dimethylsulfoxide led to imidazole-2-thiones. Full article

(This article belongs to the Special Issue Solid Phase Synthesis)

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13 pages, 7609 KiB

Open AccessArticle

Novel Inhibitor Discovery of Staphylococcus aureus Sortase B and the Mechanism Confirmation via Molecular Modeling

by Guizhen Wang, Xiyan Wang, Lin Sun, Yawen Gao, Xiaodi Niu and Hongsu Wang

Molecules 2018, 23(4), 977; https://doi.org/10.3390/molecules23040977 - 23 Apr 2018

Cited by 8 | Viewed by 4268

Abstract

SortaseB (SrtB) plays a critical role in Staphylococcus aureus (S. aureus) infections. According to the reports in the literature, SrtB can anchor the IsdC to the cell wall to capture iron from the host to achieve a successful invasion. On the [...] Read more.

SortaseB (SrtB) plays a critical role in Staphylococcus aureus (S. aureus) infections. According to the reports in the literature, SrtB can anchor the IsdC to the cell wall to capture iron from the host to achieve a successful invasion. On the other hand, SrtB could also affect the adhesion of S. aureus to host cells based on previous studies. Here, we report about a novel SrtB inhibitor, coptisine, a natural compound that does not exhibit antibacterial activity but can inhibit the SrtB activity in vitro. A cytotoxicity test indicated that coptisine protects human lung epithelial cells from S. aureus. In addition, coptisine can reduce the adhesion of S. aureus to human lung epithelial cells based on the result of plate colony counting assay. Molecular dynamics simulation revealed that coptisine can bind to the active pocket of SrtB, leading to its activity loss. Through the calculation of binding free energy between ligand and protein, site-directed mutagenesis and fluorescence spectroscopy quenching methods, it was confirmed that residues of Arg115, Asn116, and Ile182 played a vital role in the interaction of SrtB with coptisine. These data provide the theoretical basis for the therapy option to the infections caused by S. aureus. Full article

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11 pages, 942 KiB

Open AccessArticle

Anti-Helicobacter, Antitubercular and Cytotoxic Activities of Scalaranes from the Red Sea Sponge Hyrtios erectus

by Abdulrahman M. Alahdal, Hani Z. Asfour, Safwat A. Ahmed, Ahmad O. Noor, Ahmed M. Al-Abd, Mahmoud A. Elfaky and Sameh S. Elhady

Molecules 2018, 23(4), 978; https://doi.org/10.3390/molecules23040978 - 23 Apr 2018

Cited by 36 | Viewed by 5779

Abstract

The Red Sea specimen of the marine sponge Hyrtios erectus (order Dictyoceratida) was found to contain scalarane-type sesterterpenes. 12-O-deacetyl-12,19-di-epi-scalarin (14), a new scalarane sesterterpenoid, along with fourteen previously-reported scalarane-type sesterterpenes (1–13 and 15) [...] Read more.

The Red Sea specimen of the marine sponge Hyrtios erectus (order Dictyoceratida) was found to contain scalarane-type sesterterpenes. 12-O-deacetyl-12,19-di-epi-scalarin (14), a new scalarane sesterterpenoid, along with fourteen previously-reported scalarane-type sesterterpenes (1–13 and 15) have been isolated. The chemical structures of the isolated compounds were elucidated on the basis of detailed 1D and 2D NMR spectral data and mass spectroscopy, as well as by comparison with reported data. The anti-Helicobacter pylori, antitubercular and cytotoxic activities of all fifteen compounds were evaluated to reveal the potency of Compounds 1, 2, 3, 4, 6, 7 and 10. Amongst these, Compounds 1, 3, 4, 6 and 10 displayed a promising bioactivity profile, possessing potent activities in the antitubercular and anti-H. pylori bioassay. Compounds 2 and 7 showed the most promising cytotoxic profile, while Compounds 1 and 10 showed a moderate cytotoxic profile against MCF-7, HCT-116 and HepG2 cell lines. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 1316 KiB

Open AccessFeature PaperCommunication

In(III)-TMSBr-Catalyzed Cascade Reaction of Diarylalkynes with Acrylates for the Synthesis of Aryldihydronaphthalene Derivatives

by Qiu-Chi Zhang, Wen-Wei Zhang, Liang Shen, Zhi-Liang Shen and Teck-Peng Loh

Molecules 2018, 23(4), 979; https://doi.org/10.3390/molecules23040979 - 23 Apr 2018

Cited by 4 | Viewed by 5365

Abstract

A combined Lewis acid system comprising of two or more Lewis acids occasionally exhibits augmented catalytic activity in organic transformations which are otherwise unrealizable by either of the components exclusively. On the other hand, the efficient construction of multiple new C-C bonds and [...] Read more.

A combined Lewis acid system comprising of two or more Lewis acids occasionally exhibits augmented catalytic activity in organic transformations which are otherwise unrealizable by either of the components exclusively. On the other hand, the efficient construction of multiple new C-C bonds and polycyclic structures in minimal steps remains a subject of great interest in both academia and industry. Herein we report an efficient method to assemble aryldihydronaphthalene derivatives via a cascade reaction of diarylalkynes with acrylates under the catalysis of a combined Lewis acid derived from In(III) salt and TMSBr. Full article

(This article belongs to the Special Issue Indium in Organic Synthesis)

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10 pages, 1494 KiB

Open AccessArticle

Synthesis of a 1,2-Dithienylethene-Containing Donor-Acceptor Polymer via Palladium-Catalyzed Direct Arylation Polymerization (DArP)

by Masayuki Wakioka, Natsumi Yamashita, Hiroki Mori, Yasushi Nishihara and Fumiyuki Ozawa

Molecules 2018, 23(4), 981; https://doi.org/10.3390/molecules23040981 - 23 Apr 2018

Cited by 17 | Viewed by 5937

Abstract

This paper reports the synthesis of D-A polymers containing 1,2-dithienylethene (DTE) units via palladium-catalyzed direct arylation polymerization (DArP). The reaction of dibromoisoindigo (1-Br) and DTE (2-H), in the presence of Pd₂(dba)₃·CHCl [...] Read more.

This paper reports the synthesis of D-A polymers containing 1,2-dithienylethene (DTE) units via palladium-catalyzed direct arylation polymerization (DArP). The reaction of dibromoisoindigo (1-Br) and DTE (2-H), in the presence of Pd₂(dba)₃·CHCl₃ (0.5 mol%), P(2-MeOC₆H₄)₃ (L1) (2 mol%), pivalic acid (1 equiv) as catalyst precursors, and Cs₂CO₃ (3 equiv) as a base affords poly(1-alt-2) with a high molecular weight (M_n up to 44,900). Although, it has been known that monomers, with plural C–H bonds, tend to form insoluble materials via direct arylation at undesirable C–H positions; the reaction of 1-Br and 2-H cleanly proceeds without insolubilization. The resulting polymer has a well-controlled structure and exhibits good charge transfer characteristics in an organic field-effect transistor (OFET), compared to the polymer produced by Migita–Kosugi–Stille cross-coupling polymerization. The DArP product displays an ideal linear relationship in the current–voltage curve, whereas the Migita–Kosugi–Stille product shows a V_G-dependent change in the charge mobility. Full article

(This article belongs to the Special Issue Direct (Hetero)Arylation: A New Tool for Organic Electronics)

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14 pages, 3475 KiB

Open AccessArticle

Development of Triamcinolone Acetonide-Loaded Nanostructured Lipid Carriers (NLCs) for Buccal Drug Delivery Using the Box-Behnken Design

by Pakorn Kraisit and Narong Sarisuta

Molecules 2018, 23(4), 982; https://doi.org/10.3390/molecules23040982 - 23 Apr 2018

Cited by 39 | Viewed by 6059

Abstract

The aim of this present work was to prepare triamcinolone acetonide (TA)-loaded nanostructured lipid carriers (TA-loaded NLCs) for buccal drug delivery systems using the Box-Behnken design. A hot homogenization method was used to prepare the TA-loaded NLCs. Spermaceti (X₁), soybean oil [...] Read more.

The aim of this present work was to prepare triamcinolone acetonide (TA)-loaded nanostructured lipid carriers (TA-loaded NLCs) for buccal drug delivery systems using the Box-Behnken design. A hot homogenization method was used to prepare the TA-loaded NLCs. Spermaceti (X₁), soybean oil (X₂), and Tween 80 (X₃) were used as solid lipid, liquid lipid, and stabilizer, respectively. The particle size of TA-loaded NLCs was lower than 200 nm and the zeta potential displayed the negative charge in all formulations. The percentage encapsulation efficiency (%EE) of the TA-loaded NLCs showed that it was higher than 80% for all formulations. Field emission scanning electron microscope (FESEM) confirmed that the size of TA-loaded NLCs was approximately 100 nm and energy-dispersive X-ray spectroscopy (EDS) confirmed that the TA could be incorporated in the NLC system. The Higuchi model gave the highest value of the R², indicating that this model was a fit for the TA release profiles of TA-loaded NLCs. Confocal laser scanning microscopy (CLSM) was used to observe the drug penetration within the porcine buccal mucosa and Nile red-loaded NLCs showed significantly higher penetration depth at 8 h than at 2 h. Therefore, TA-loaded NLCs could be an efficient carrier for drug delivery through the buccal mucosa. Full article

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12 pages, 4445 KiB

Open AccessArticle

Plasma and Salivary Non-Urate Total Antioxidant Capacity Does Not Depend on Dietary Vitamin C, E, or β-Carotene Intake in Older Subjects

by Anna Gawron-Skarbek, Agnieszka Guligowska, Anna Prymont-Przymińska, Dariusz Nowak and Tomasz Kostka

Molecules 2018, 23(4), 983; https://doi.org/10.3390/molecules23040983 - 23 Apr 2018

Cited by 7 | Viewed by 4307

Abstract

The native Total Antioxidant Capacity (TAC) of plasma and saliva is generally determined by uric acid (UA). Several studies have assessed the impact of habitual dietary antioxidative vitamin intake on TAC, but it remains unknown whether it influences Non-Urate Total Antioxidant Capacity (Nu-TAC), [...] Read more.

The native Total Antioxidant Capacity (TAC) of plasma and saliva is generally determined by uric acid (UA). Several studies have assessed the impact of habitual dietary antioxidative vitamin intake on TAC, but it remains unknown whether it influences Non-Urate Total Antioxidant Capacity (Nu-TAC), i.e., TAC after enzymatic UA elimination. The purpose of this study was to assess whether the intake of antioxidative vitamins C, E, and β-carotene, provided with usual daily food rations, affects plasma and salivary Nu-TAC. The study involved 56 older subjects (aged 66.9 ± 4.3 years), divided into two age- and sex-matched groups: group 1 (n = 28), with lower combined vitamin C, E, and β-carotene intake, and group 2 (n = 28), with higher intake. A 24 h dietary recall was obtained from each individual. Nu-TAC was assessed simultaneously with two methods in plasma (Ferric Reducing Ability of Plasma—Nu-FRAP, 2.2-diphenyl-1-picryl-hydrazyl—Nu-DPPH) and in saliva (Nu-FRAS and Nu-DPPHS test). No differences were found in the Nu-TAC parameters between the groups, either in plasma (Nu-FRAP, Nu-DPPH) or in saliva (Nu-FRAS, Nu-DPPHS) (p > 0.05). No plasma or salivary Nu-TAC indices correlated with dietary vitamin C, E, or β-carotene intake or with other nutrients. Habitual, not extra-supplemented dietary intake does not significantly affect plasma or salivary Nu-TAC. Full article

(This article belongs to the Special Issue Dietary Antioxidants: Evidence of Protective Effects against Chronic Disease)

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16 pages, 1386 KiB

Open AccessArticle

Quantitative Analysis of Four Catechins from Green Tea Extract in Human Plasma Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry for Pharmacokinetic Studies

by Jeong-Eun Park, Tae-Eun Kim and Kwang-Hee Shin

Molecules 2018, 23(4), 984; https://doi.org/10.3390/molecules23040984 - 23 Apr 2018

Cited by 14 | Viewed by 6738

Abstract

Green tea is consumed as a beverage worldwide and has beneficial effects, such as a lower risk of cardiovascular disease and cancer. A quantitative analysis of the beneficial components in plasma is important for understanding the potential health benefits of green tea. Four [...] Read more.

Green tea is consumed as a beverage worldwide and has beneficial effects, such as a lower risk of cardiovascular disease and cancer. A quantitative analysis of the beneficial components in plasma is important for understanding the potential health benefits of green tea. Four catechins—epigallocatechin-3-gallate (EGCG), epicatechin-3-gallate (ECG), epigallocatechin (EGC), and epicatechin (EC)—which account for the majority of the components of green tea, were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In this study, a validated method was optimized to obtain the blood concentrations after the one-time ingestion of 630 mg green tea extract with digoxin and then after the ingestion of 630 mg green tea repeatedly for 15 days. The calibration curve, including the LLOQ, was constructed over 1–500 ng/mL for EGCG, ECG, and EGC and 0.1–50 ng/mL for EC. The method for inter- and intra-validation was applied, acceptable for both accuracy and precision. We successfully developed an appropriate UPLC-MS/MS method for human plasma with good reproducibility and sensitivity. Thus, this method could be applied for future preclinical and clinical studies on EGCG, ECG, EGC, and EC. Full article

(This article belongs to the Collection Advances in Liquid Separation Techniques for Food and Pharmaceutical Analysis)

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15 pages, 1617 KiB

Open AccessArticle

Synthesis and Tuberculostatic Activity Evaluation of Novel Benzazoles with Alkyl, Cycloalkyl or Pyridine Moiety

by Malwina Krause, Henryk Foks, Ewa Augustynowicz-Kopeć, Agnieszka Napiórkowska, Małgorzata Szczesio and Katarzyna Gobis

Molecules 2018, 23(4), 985; https://doi.org/10.3390/molecules23040985 - 23 Apr 2018

Cited by 16 | Viewed by 5983

Abstract

Compounds possessing benzimidazole system exhibit significant antituberculous activity. In order to examine how structure modifications affect tuberculostatic activity, a series of benzazole derivatives were synthesized and screened for their antitubercular activity. The compounds 1–20 were obtained by the reaction between o [...] Read more.

Compounds possessing benzimidazole system exhibit significant antituberculous activity. In order to examine how structure modifications affect tuberculostatic activity, a series of benzazole derivatives were synthesized and screened for their antitubercular activity. The compounds 1–20 were obtained by the reaction between o-diamine, o-aminophenol, or o-aminothiophenol with carboxylic acids or thioamides. The newly synthesized compounds were characterized by IR, ¹H-NMR, ¹³C-NMR spectra, and elemental analysis. Synthesized benzazoles were evaluated for their tuberculostatic activity toward Mycobacterium tuberculosis strains. Quantum chemical calculations were performed to study the molecular geometry and the electronic structure of benzimidazoles GK-151B, 4, 6, and benzoxazole 11, using the Gaussian 03W software (Gaussian, Inc., Wallingford, CT, USA). Three-dimensional structure of benzimidazoles 1–3, MC-9, and GK-151B was determined by ab initio calculation using Gamess-US software. The activity of the received benzimidazoles was moderate or good. All of the benzoxazoles and benzothiazoles demonstrated much lower activity. Benzoxazoles were less active by about 50 times, and benzothiazole by 100 times than the benzimidazole analogs. Quantum chemical calculations showed differences in the distribution of electrostatic potential in the benzazole system of benzimidazoles and benzoxazoles. Three-dimensional structure calculations revealed how the parity of the alkyl substituent at the C2 position impacts the activity. Benzimidazole system is essential for the antituberculosis activity that is associated with the presence of the imine nitrogen atom in N-1 position. Its replacement by an oxygen or sulfur atom results in a decrease of the activity. The parity of the alkyl substituent at the C-2 position also modifies the activity. Full article

(This article belongs to the Collection Antibiotics & Superbugs: New Strategies to Combat Antimicrobial Resistance)

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Review

Jump to: Editorial, Research, Other

14 pages, 486 KiB

Open AccessReview

Expression, Distribution, and Role of C-Type Lectin Receptors in the Human and Animal Middle Ear and Eustachian Tube: A Review

by Su Young Jung, Sung Su Kim, Young Il Kim, Hee Yong Chung, Sang Hoon Kim and Seung Geun Yeo

Molecules 2018, 23(4), 734; https://doi.org/10.3390/molecules23040734 - 22 Mar 2018

Cited by 5 | Viewed by 4897

Abstract

Otitis media (OM) is a group of inflammatory diseases of the middle ear (ME), regardless of cause or pathological mechanism. Among the molecular biological studies assessing the pathology of OM are investigations into the expression of C-type lectin receptors (CLR) in the ME [...] Read more.

Otitis media (OM) is a group of inflammatory diseases of the middle ear (ME), regardless of cause or pathological mechanism. Among the molecular biological studies assessing the pathology of OM are investigations into the expression of C-type lectin receptors (CLR) in the ME and Eustachian tube (ET). To date, nine studies have evaluated CLR expression in the ME and ET. The expression of individual CLRs in mammalian ME and ET varies by species and model of OM. Assessments have shown that the patterns of CLR expression in the ME and ET vary; that CLR expression may vary by type of OM; and that the distribution and levels of expression of CLRs may depend on the presence or absence of inflammation, with variations even within the same species and same tissue. Infection of the ME and ET with various pathogens is a common cause of all types of OM, with host responses to pathogens mediated initially by the innate immune system. CLRs are important factors in the innate immune system because they act as both adhesion molecules and as pathogen recognition receptors. The expression of CLRs in OM tissues suggests that CLRs are associated with the pathogenesis of various types of OM. Full article

(This article belongs to the Special Issue Lectins: From Basic Science to Application for Glycobiology, Cell Biology, and Medicine)

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29 pages, 32575 KiB

Open AccessFeature PaperReview

Recent Developments in Vinylsulfonium and Vinylsulfoxonium Salt Chemistry

by Mukulesh Mondal, Shi Chen and Nessan J. Kerrigan

Molecules 2018, 23(4), 738; https://doi.org/10.3390/molecules23040738 - 23 Mar 2018

Cited by 47 | Viewed by 8045

Abstract

This review describes advances in the literature since 2000 in the area of reactions of vinylsulfonium and vinylsulfoxonium salts, with a particular emphasis on stereoselective examples. Although the chemistry of vinylsulfonium salts was first explored back in the 1950s, and that of vinylsulfoxonium [...] Read more.

This review describes advances in the literature since 2000 in the area of reactions of vinylsulfonium and vinylsulfoxonium salts, with a particular emphasis on stereoselective examples. Although the chemistry of vinylsulfonium salts was first explored back in the 1950s, and that of vinylsulfoxonium salts in the early 1970s, there has been renewed interest in these compounds since the turn of the century. This has been largely due to an increased appreciation for the many synthetic possibilities associated with these valuable electrophiles. The development of improved routes to vinylsulfonium salts allowing for their in situ generation has played a part in accelerating their study. In general, reactions of the two sulfur salt classes follow a similar mechanistic pathway: initial conjugate addition of a nucleophile to the β-position, followed by protonation of an ylide intermediate, and cyclization of tethered anion to afford monocyclic or bicyclic product (e.g., cyclopropane, aziridine, oxazole, oxazolidinone, γ-lactam or γ-lactone). Alternatively, reactions involve formation of an ylide intermediate followed by intramolecular Johnson-Corey-Chaykovsky reaction (epoxidation or cyclopropanation), and subsequent cyclization to afford the desired bicyclic product (e.g., fused bicyclic epoxide or cyclopropane). Full article

(This article belongs to the Section Organic Chemistry)

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26 pages, 3618 KiB

Open AccessReview

Response of Plant Secondary Metabolites to Environmental Factors

by Li Yang, Kui-Shan Wen, Xiao Ruan, Ying-Xian Zhao, Feng Wei and Qiang Wang

Molecules 2018, 23(4), 762; https://doi.org/10.3390/molecules23040762 - 27 Mar 2018

Cited by 1017 | Viewed by 36679

Abstract

Plant secondary metabolites (SMs) are not only a useful array of natural products but also an important part of plant defense system against pathogenic attacks and environmental stresses. With remarkable biological activities, plant SMs are increasingly used as medicine ingredients and food additives [...] Read more.

Plant secondary metabolites (SMs) are not only a useful array of natural products but also an important part of plant defense system against pathogenic attacks and environmental stresses. With remarkable biological activities, plant SMs are increasingly used as medicine ingredients and food additives for therapeutic, aromatic and culinary purposes. Various genetic, ontogenic, morphogenetic and environmental factors can influence the biosynthesis and accumulation of SMs. According to the literature reports, for example, SMs accumulation is strongly dependent on a variety of environmental factors such as light, temperature, soil water, soil fertility and salinity, and for most plants, a change in an individual factor may alter the content of SMs even if other factors remain constant. Here, we review with emphasis how each of single factors to affect the accumulation of plant secondary metabolites, and conduct a comparative analysis of relevant natural products in the stressed and unstressed plants. Expectantly, this documentary review will outline a general picture of environmental factors responsible for fluctuation in plant SMs, provide a practical way to obtain consistent quality and high quantity of bioactive compounds in vegetation, and present some suggestions for future research and development. Full article

(This article belongs to the Special Issue Biological Activity of Secondary Metabolites)

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22 pages, 12189 KiB

Open AccessFeature PaperReview

Small Molecule Catalysts with Therapeutic Potential

by Yannick Ney, Muhammad Jawad Nasim, Ammar Kharma, Lama A. Youssef and Claus Jacob

Molecules 2018, 23(4), 765; https://doi.org/10.3390/molecules23040765 - 27 Mar 2018

Cited by 5 | Viewed by 6340

Abstract

Catalysts are employed in many areas of research and development where they combine high efficiency with often astonishing selectivity for their respective substrates. In biology, biocatalysts are omnipresent. Enzymes facilitate highly controlled, sophisticated cellular processes, such as metabolic conversions, sensing and signalling, and [...] Read more.

Catalysts are employed in many areas of research and development where they combine high efficiency with often astonishing selectivity for their respective substrates. In biology, biocatalysts are omnipresent. Enzymes facilitate highly controlled, sophisticated cellular processes, such as metabolic conversions, sensing and signalling, and are prominent targets in drug development. In contrast, the therapeutic use of catalysts per se is still rather limited. Recent research has shown that small molecule catalytic agents able to modulate the redox state of the target cell bear considerable promise, particularly in the context of inflammatory and infectious diseases, stroke, ageing and even cancer. Rather than being “active” on their own in a more traditional sense, such agents develop their activity by initiating, promoting, enhancing or redirecting reactions between biomolecules already present in the cell, and their activity therefore depends critically on the predisposition of the target cell itself. Redox catalysts, for instance, preferably target cells with a distinct sensitivity towards changes in an already disturbed redox balance and/or increased levels of reactive oxygen species. Indeed, certain transition metal, chalcogen and quinone agents may activate an antioxidant response in normal cells whilst at the same time triggering apoptosis in cancer cells with a different pre-existing “biochemical redox signature” and closer to the internal redox threshold. In pharmacy, catalysts therefore stand out as promising lead structures, as sensor/effector agents which are highly effective, fairly selective, active in catalytic, i.e., often nanomolar concentrations and also very flexible in their structural design. Full article

(This article belongs to the Special Issue Small Molecule Catalysts with Therapeutic Potential)

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24 pages, 32541 KiB

Open AccessReview

Polymer-Mediated Delivery of siRNAs to Hepatocellular Carcinoma: Variables Affecting Specificity and Effectiveness

by Rossella Farra, Francesco Musiani, Francesca Perrone, Maja Čemažar, Urška Kamenšek, Federica Tonon, Michela Abrami, Aleš Ručigaj, Mario Grassi, Gabriele Pozzato, Deborah Bonazza, Fabrizio Zanconati, Giancarlo Forte, Maguie El Boustani, Lucia Scarabel, Marica Garziera, Concetta Russo Spena, Lucia De Stefano, Barbara Salis, Giuseppe Toffoli, Flavio Rizzolio, Gabriele Grassi and Barbara Dapas Show full author list Hide full author list

Molecules 2018, 23(4), 777; https://doi.org/10.3390/molecules23040777 - 28 Mar 2018

Cited by 15 | Viewed by 6886

Abstract

Despite the advances in anticancer therapies, their effectiveness for many human tumors is still far from being optimal. Significant improvements in treatment efficacy can come from the enhancement of drug specificity. This goal may be achieved by combining the use of therapeutic molecules [...] Read more.

Despite the advances in anticancer therapies, their effectiveness for many human tumors is still far from being optimal. Significant improvements in treatment efficacy can come from the enhancement of drug specificity. This goal may be achieved by combining the use of therapeutic molecules with tumor specific effects and delivery carriers with tumor targeting ability. In this regard, nucleic acid-based drug (NABD) and particularly small interfering RNAs (siRNAs), are attractive molecules due to the possibility to be engineered to target specific tumor genes. On the other hand, polymeric-based delivery systems are emerging as versatile carriers to generate tumor-targeted delivery systems. Here we will focus on the most recent findings in the selection of siRNA/polymeric targeted delivery systems for hepatocellular carcinoma (HCC), a human tumor for which currently available therapeutic approaches are poorly effective. In addition, we will discuss the most attracting and, in our opinion, promising siRNA-polymer combinations for HCC in relation to the biological features of HCC tissue. Attention will be also put on the mathematical description of the mechanisms ruling siRNA-carrier delivery, this being an important aspect to improve effectiveness reducing the experimental work. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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18 pages, 3216 KiB

Open AccessReview

Effects of Basal Defoliation on Wine Aromas: A Meta-Analysis

by Yu Wang, Lei He, Qiuhong Pan, Changqing Duan and Jun Wang

Molecules 2018, 23(4), 779; https://doi.org/10.3390/molecules23040779 - 28 Mar 2018

Cited by 22 | Viewed by 5351

Abstract

Basal defoliation, as one of the most common viticulture management practices to modify fruit zone microclimates, has been widely applied aiming at improving wine quality. Wine aroma contributes greatly to wine quality, yet the effects of basal defoliation on wine aromas show discrepancies [...] Read more.

Basal defoliation, as one of the most common viticulture management practices to modify fruit zone microclimates, has been widely applied aiming at improving wine quality. Wine aroma contributes greatly to wine quality, yet the effects of basal defoliation on wine aromas show discrepancies according to previous studies. This study is a meta-analysis performed to dissect the factors related to the influence of basal defoliation on volatile compounds in wine. Timing of basal defoliation plays an important role in the concentration of varietal aromas in wine. Pre-veraison defoliation induces an increase in β-damascenone and linalool as well as a reduction in 3-isobutyl-2-methoxypyrazine (IBMP). The effects of basal defoliation on certain volatile compounds relative to fermentation aromas in wine (1-hexanol, β-phenylethanol, 2-phenylethyl acetate, decanoic acid, and ethyl octanoate) depend on grape maturity. There are also other factors, such as cultivar and climate conditions, that might be responsible for the effect of basal defoliation on wine aromas. The concentrations of isobutanol, isoamyl alcohol, hexanoic acid, and octanoic acid as well as ethyl isobutyrate, ethyl hexanoate, ethyl isovalerate, and ethyl decanoate in wine are not markedly affected by basal defoliation. Due to limited studies included in this meta-analysis, more trials are needed to confirm the current findings. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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21 pages, 3938 KiB

Open AccessReview

Regulating Cdc42 and Its Signaling Pathways in Cancer: Small Molecules and MicroRNA as New Treatment Candidates

by Xing-Hua Xiao, Lin-Chen Lv, Jing Duan, Ye-Meng Wu, Shu-Jin He, Zhen-Zhen Hu and Li-Xia Xiong

Molecules 2018, 23(4), 787; https://doi.org/10.3390/molecules23040787 - 29 Mar 2018

Cited by 43 | Viewed by 8705

Abstract

Despite great improvements in the diagnosis and treatment of neoplasms, metastatic disease is still the leading cause of death in cancer patients, with mortality rates still rising. Given this background, new ways to treat cancer will be important for development of improved cancer [...] Read more.

Despite great improvements in the diagnosis and treatment of neoplasms, metastatic disease is still the leading cause of death in cancer patients, with mortality rates still rising. Given this background, new ways to treat cancer will be important for development of improved cancer control strategies. Cdc42 is a member of the Rho GTPase family and plays an important role in cell-to-cell adhesion, formation of cytoskeletal structures, and cell cycle regulation. It thus influences cellular proliferation, transformation, and homeostasis, as well as the cellular migration and invasion processes underlying tumor formation. Cdc42 acts as a collection point for signal transduction and regulates multiple signaling pathways. Moreover, recent studies show that in most human cancers Cdc42 is abnormally expressed and promoting neoplastic growth and metastasis. Regarding possible new treatments for cancer, miRNA and small molecules targeting Cdc42 and related pathways have been recently found to be effective on cancer. In this review, we analyze the newly recognized regulation mechanisms for Cdc42 and Cdc42-related signal pathways, and particularly new treatments using small molecules and miRNAs to inhibit the abnormal overexpression of Cdc42 that may slow down the metastasis process, improve cancer therapy and lead to novel strategies for development of antineoplastic drugs. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 12488 KiB

Open AccessReview

Occurrence of Functional Molecules in the Flowers of Tea (Camellia sinensis) Plants: Evidence for a Second Resource

by Yiyong Chen, Ying Zhou, Lanting Zeng, Fang Dong, Youying Tu and Ziyin Yang

Molecules 2018, 23(4), 790; https://doi.org/10.3390/molecules23040790 - 29 Mar 2018

Cited by 60 | Viewed by 9381

Abstract

Tea (Camellia sinensis) is an important crop, and its leaves are used to make the most widely consumed beverage, aside from water. People have been using leaves from tea plants to make teas for a long time. However, less attention has [...] Read more.

Tea (Camellia sinensis) is an important crop, and its leaves are used to make the most widely consumed beverage, aside from water. People have been using leaves from tea plants to make teas for a long time. However, less attention has been paid to the flowers of tea plants, which is a waste of an abundant resource. In the past 15 years, researchers have attempted to discover, identify, and evaluate functional molecules from tea flowers, and have made insightful and useful discoveries. Here, we summarize the recent investigations into these functional molecules in tea flowers, including functional molecules similar to those in tea leaves, as well as the preponderant functional molecules in tea flowers. Tea flowers contain representative metabolites similar to those of tea leaves, such as catechins, flavonols, caffeine, and amino acids. The preponderant functional molecules in tea flowers include saponins, polysaccharides, aromatic compounds, spermidine derivatives, and functional proteins. We also review the safety and biological functions of tea flowers. Tea flower extracts are proposed to be of no toxicological concern based on evidence from the evaluation of mutagenicity, and acute and subchronic toxicity in rats. The presence of many functional metabolites in tea flowers indicates that tea flowers possess diverse biological functions, which are mostly related to catechins, polysaccharides, and saponins. Finally, we discuss the potential for, and challenges facing, future applications of tea flowers as a second resource from tea plants. Full article

(This article belongs to the Collection Bioactive Compounds)

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34 pages, 63431 KiB

Open AccessFeature PaperReview

Carbene Transfer Reactions Catalysed by Dyes of the Metalloporphyrin Group

by Mário M. Q. Simões, Daniel T. G. Gonzaga, Mariana F. C. Cardoso, Luana Da S. M. Forezi, Ana T. P. C. Gomes, Fernando De C. Da Silva, Vítor F. Ferreira, Maria G. P. M. S. Neves and José A. S. Cavaleiro

Molecules 2018, 23(4), 792; https://doi.org/10.3390/molecules23040792 - 29 Mar 2018

Cited by 22 | Viewed by 7502

Abstract

Carbene transfer reactions are very important transformations in organic synthesis, allowing the generation of structurally challenging products by catalysed cyclopropanation, cyclopropenation, carbene C-H, N-H, O-H, S-H, and Si-H insertion, and olefination of carbonyl compounds. In particular, chiral and achiral metalloporphyrins have been successfully [...] Read more.

Carbene transfer reactions are very important transformations in organic synthesis, allowing the generation of structurally challenging products by catalysed cyclopropanation, cyclopropenation, carbene C-H, N-H, O-H, S-H, and Si-H insertion, and olefination of carbonyl compounds. In particular, chiral and achiral metalloporphyrins have been successfully explored as biomimetic catalysts for these carbene transfer reactions under both homogeneous and heterogeneous conditions. In this work the use of synthetic metalloporphyrins (MPorph, M = Fe, Ru, Os, Co, Rh, Ir, Sn) as homogeneous or heterogeneous catalysts for carbene transfer reactions in the last years is reviewed, almost exclusively focused on the literature since the year 2010, except when reference to older publications was deemed to be crucial. Full article

(This article belongs to the Special Issue Advanced Functional Dyes)

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48 pages, 652 KiB

Open AccessReview

Antibiotic Use in Agriculture and Its Consequential Resistance in Environmental Sources: Potential Public Health Implications

by Christy Manyi-Loh, Sampson Mamphweli, Edson Meyer and Anthony Okoh

Molecules 2018, 23(4), 795; https://doi.org/10.3390/molecules23040795 - 30 Mar 2018

Cited by 904 | Viewed by 42126

Abstract

Due to the increased demand of animal protein in developing countries, intensive farming is instigated, which results in antibiotic residues in animal-derived products, and eventually, antibiotic resistance. Antibiotic resistance is of great public health concern because the antibiotic-resistant bacteria associated with the animals [...] Read more.

Due to the increased demand of animal protein in developing countries, intensive farming is instigated, which results in antibiotic residues in animal-derived products, and eventually, antibiotic resistance. Antibiotic resistance is of great public health concern because the antibiotic-resistant bacteria associated with the animals may be pathogenic to humans, easily transmitted to humans via food chains, and widely disseminated in the environment via animal wastes. These may cause complicated, untreatable, and prolonged infections in humans, leading to higher healthcare cost and sometimes death. In the said countries, antibiotic resistance is so complex and difficult, due to irrational use of antibiotics both in the clinical and agriculture settings, low socioeconomic status, poor sanitation and hygienic status, as well as that zoonotic bacterial pathogens are not regularly cultured, and their resistance to commonly used antibiotics are scarcely investigated (poor surveillance systems). The challenges that follow are of local, national, regional, and international dimensions, as there are no geographic boundaries to impede the spread of antibiotic resistance. In addition, the information assembled in this study through a thorough review of published findings, emphasized the presence of antibiotics in animal-derived products and the phenomenon of multidrug resistance in environmental samples. This therefore calls for strengthening of regulations that direct antibiotic manufacture, distribution, dispensing, and prescription, hence fostering antibiotic stewardship. Joint collaboration across the world with international bodies is needed to assist the developing countries to implement good surveillance of antibiotic use and antibiotic resistance. Full article

15 pages, 3161 KiB

Open AccessReview

β-Glucans: Multi-Functional Modulator of Wound Healing

by Juraj Majtan and Milos Jesenak

Molecules 2018, 23(4), 806; https://doi.org/10.3390/molecules23040806 - 1 Apr 2018

Cited by 84 | Viewed by 9756

Abstract

β-glucans are derived from a variety of sources including yeast, grain and fungus and belong to the class of drugs known as biological response modifiers. They possess a broad spectrum of biological activities that enhance immunity in humans. One promising area for β-glucans’ [...] Read more.

β-glucans are derived from a variety of sources including yeast, grain and fungus and belong to the class of drugs known as biological response modifiers. They possess a broad spectrum of biological activities that enhance immunity in humans. One promising area for β-glucans’ application is dermatology, including wound care. Topical applications of β-glucans are increasing, especially due to their pluripotent properties. Macrophages, keratinocytes and fibroblasts are considered the main target cells of β-glucans during wound healing. β-glucans enhance wound repair by increasing the infiltration of macrophages, which stimulates tissue granulation, collagen deposition and reepithelialization. β-glucan wound dressings represent a suitable wound healing agent, with great stability and resistance to wound proteases. This review summarizes the current knowledge and progress made on characterizing β-glucans’ wound healing properties in vitro and in vivo and their safety and efficacy in managing non-healing wounds or other chronic dermatological conditions and diseases. Full article

(This article belongs to the Special Issue Advances in Natural Polysaccharides Research)

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26 pages, 1799 KiB

Open AccessReview

Role of Plant-Derived Flavonoids and Their Mechanism in Attenuation of Alzheimer’s and Parkinson’s Diseases: An Update of Recent Data

by Ghulam Hussain, Longbin Zhang, Azhar Rasul, Haseeb Anwar, Muhammad Umar Sohail, Aroona Razzaq, Nimra Aziz, Asghar Shabbir, Muhammad Ali and Tao Sun

Molecules 2018, 23(4), 814; https://doi.org/10.3390/molecules23040814 - 2 Apr 2018

Cited by 85 | Viewed by 9262

Abstract

Neurodegeneration is a progressive loss of neuronal cells in certain regions of the brain. Most of the neurodegenerative disorders (NDDs) share the communal characteristic such as damage or reduction of various cell types typically including astrocytes and microglial activity. Several compounds are being [...] Read more.

Neurodegeneration is a progressive loss of neuronal cells in certain regions of the brain. Most of the neurodegenerative disorders (NDDs) share the communal characteristic such as damage or reduction of various cell types typically including astrocytes and microglial activity. Several compounds are being trialed to treat NDDs but they possess solitary symptomatic advantages along with copious side effects. The finding of more enthralling and captivating compounds to suspend and standstill the pathology of NDDs will be considered as a hallmark of present times. Phytochemicals possess the potential to alternate the synthetic line of therapy against NDDs. The present review explores the potential efficacy of plant-derived flavonoids against most common NDDs including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Flavonoids are biologically active phytochemicals which possess potential pharmacological effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic and anti-oxidant effects and are able to attenuate the pathology of various NDDs through down-regulating the nitric oxide (NO) production, by reducing the tumor necrosis factor-α (TNF-α), by reducing the excitotoxicity of superoxide as well as acting as tyrosine kinase (TK) and monoamine oxidase (MAO) inhibiting enzyme. Full article

(This article belongs to the Section Natural Products Chemistry)

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23 pages, 442 KiB

Open AccessReview

Tryptophan-Rich and Proline-Rich Antimicrobial Peptides

by Awdhesh Kumar Mishra, Jaehyuk Choi, Eunpyo Moon and Kwang-Hyun Baek

Molecules 2018, 23(4), 815; https://doi.org/10.3390/molecules23040815 - 2 Apr 2018

Cited by 125 | Viewed by 10485

Abstract

Due to the increasing emergence of drug-resistant pathogenic microorganisms, there is a world-wide quest to develop new-generation antibiotics. Antimicrobial peptides (AMPs) are small peptides with a broad spectrum of antibiotic activities against bacteria, fungi, protozoa, viruses and sometimes exhibit cytotoxic activity toward cancer [...] Read more.

Due to the increasing emergence of drug-resistant pathogenic microorganisms, there is a world-wide quest to develop new-generation antibiotics. Antimicrobial peptides (AMPs) are small peptides with a broad spectrum of antibiotic activities against bacteria, fungi, protozoa, viruses and sometimes exhibit cytotoxic activity toward cancer cells. As a part of the native host defense system, most AMPs target the membrane integrity of the microorganism, leading to cell death by lysis. These membrane lytic effects are often toxic to mammalian cells and restrict their systemic application. However, AMPs containing predominantly either tryptophan or proline can kill microorganisms by targeting intracellular pathways and are therefore a promising source of next-generation antibiotics. A minimum length of six amino acids is required for high antimicrobial activity in tryptophan-rich AMPs and the position of these residues also affects their antimicrobial activity. The aromatic side chain of tryptophan is able to rapidly form hydrogen bonds with membrane bilayer components. Proline-rich AMPs interact with the 70S ribosome and disrupt protein synthesis. In addition, they can also target the heat shock protein in target pathogens, and consequently lead to protein misfolding. In this review, we will focus on describing the structures, sources, and mechanisms of action of the aforementioned AMPs. Full article

29 pages, 35021 KiB

Open AccessReview

Nanotechnology for Cancer Therapy Based on Chemotherapy

by Chen-Yang Zhao, Rui Cheng, Zhe Yang and Zhong-Min Tian

Molecules 2018, 23(4), 826; https://doi.org/10.3390/molecules23040826 - 4 Apr 2018

Cited by 257 | Viewed by 17879

Abstract

Chemotherapy has been widely applied in clinics. However, the therapeutic potential of chemotherapy against cancer is seriously dissatisfactory due to the nonspecific drug distribution, multidrug resistance (MDR) and the heterogeneity of cancer. Therefore, combinational therapy based on chemotherapy mediated by nanotechnology, has been [...] Read more.

Chemotherapy has been widely applied in clinics. However, the therapeutic potential of chemotherapy against cancer is seriously dissatisfactory due to the nonspecific drug distribution, multidrug resistance (MDR) and the heterogeneity of cancer. Therefore, combinational therapy based on chemotherapy mediated by nanotechnology, has been the trend in clinical research at present, which can result in a remarkably increased therapeutic efficiency with few side effects to normal tissues. Moreover, to achieve the accurate pre-diagnosis and real-time monitoring for tumor, the research of nano-theranostics, which integrates diagnosis with treatment process, is a promising field in cancer treatment. In this review, the recent studies on combinational therapy based on chemotherapy will be systematically discussed. Furthermore, as a current trend in cancer treatment, advance in theranostic nanoparticles based on chemotherapy will be exemplified briefly. Finally, the present challenges and improvement tips will be presented in combination therapy and nano-theranostics. Full article

(This article belongs to the Collection Nanomedicine)

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20 pages, 7808 KiB

Open AccessFeature PaperReview

Applications of Cancer Cell-Specific Aptamers in Targeted Delivery of Anticancer Therapeutic Agents

by Minhee Kim, Dong-Min Kim, Keun-Sik Kim, Woong Jung and Dong-Eun Kim

Molecules 2018, 23(4), 830; https://doi.org/10.3390/molecules23040830 - 4 Apr 2018

Cited by 79 | Viewed by 9476

Abstract

Aptamers are single-stranded oligonucleotides that specifically bind and interact with their corresponding targets, including proteins and cells, through unique three-dimensional structures. Numerous aptamers have been developed to target cancer biomarkers with high specificity and affinity, and some are employed as versatile guiding ligands [...] Read more.

Aptamers are single-stranded oligonucleotides that specifically bind and interact with their corresponding targets, including proteins and cells, through unique three-dimensional structures. Numerous aptamers have been developed to target cancer biomarkers with high specificity and affinity, and some are employed as versatile guiding ligands for cancer-specific drug delivery and anti-cancer therapeutics. In this review, we list the aptamers that target tumor surface biomarkers and summarize the representative applications of aptamers as agonists and antagonists that activate anti-cancer and inactivate pro-cancer biomarkers, respectively. In addition, we describe applications of aptamer-drug or aptamer-oligonucleotide conjugates that can deliver therapeutic agents, including small interfering RNAs, micro RNAs, short hairpin RNAs, and chemotherapeutic molecules, to cancer cells. Moreover, we provide examples of aptamer- conjugated nano-vehicles, in which cancer-targeting oligonucleotide aptamers are conjugated with nano-vehicles such as liposomes, micelles, polymeric nanoparticles, and quantum dots. Conjugation of aptamers with anti-cancer drugs and nano-vehicles will facilitate innovative applications of aptamer-based cancer therapeutics. Full article

(This article belongs to the Special Issue Nucleic Acid Aptamers)

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30 pages, 3961 KiB

Open AccessReview

Fungal Metabolites Antagonists towards Plant Pests and Human Pathogens: Structure-Activity Relationship Studies

by Marco Masi, Paola Nocera, Pierluigi Reveglia, Alessio Cimmino and Antonio Evidente

Molecules 2018, 23(4), 834; https://doi.org/10.3390/molecules23040834 - 5 Apr 2018

Cited by 31 | Viewed by 6518

Abstract

Fungi are able to produce many bioactive secondary metabolites that belong to different classes of natural compounds. Some of these compounds have been selected for their antagonism against pests and human pathogens and structure–activity relationship (SAR) studies have been performed to better understand [...] Read more.

Fungi are able to produce many bioactive secondary metabolites that belong to different classes of natural compounds. Some of these compounds have been selected for their antagonism against pests and human pathogens and structure–activity relationship (SAR) studies have been performed to better understand which structural features are essential for the biological activity. In some cases, these studies allowed for the obtaining of hemisynthetic derivatives with increased selectivity and stability in respect to the natural products as well as reduced toxicity in view of their potential practical applications. This review deals with the SAR studies performed on fungal metabolites with potential fungicidal, bactericidal, insecticidal, and herbicidal activities from 1990 to the present (beginning of 2018). Full article

(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products 2018)

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14 pages, 2179 KiB

Open AccessReview

Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases

by Sathish Sundar Dhilip Kumar, Nicolette Nadene Houreld and Heidi Abrahamse

Molecules 2018, 23(4), 835; https://doi.org/10.3390/molecules23040835 - 5 Apr 2018

Cited by 85 | Viewed by 14355

Abstract

Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric (Curcuma longa) plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the [...] Read more.

Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric (Curcuma longa) plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases. Full article

(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)

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18 pages, 331 KiB

Open AccessReview

Tannins from Acacia mearnsii De Wild. Bark: Tannin Determination and Biological Activities

by Sosuke Ogawa and Yoshikazu Yazaki

Molecules 2018, 23(4), 837; https://doi.org/10.3390/molecules23040837 - 5 Apr 2018

Cited by 78 | Viewed by 18211

Abstract

The bark of Acacia mearnsii De Wild. (black wattle) contains significant amounts of water-soluble components acalled “wattle tannin”. Following the discovery of its strong antioxidant activity, a wattle tannin dietary supplement has been developed and as part of developing new dietary supplements, a [...] Read more.

The bark of Acacia mearnsii De Wild. (black wattle) contains significant amounts of water-soluble components acalled “wattle tannin”. Following the discovery of its strong antioxidant activity, a wattle tannin dietary supplement has been developed and as part of developing new dietary supplements, a literature search was conducted using the SciFinder data base for “Acacia species and their biological activities”. An analysis of the references found indicated that the name of Acacia nilotica had been changed to Vachellia nilotica, even though the name of the genus Acacia originated from its original name. This review briefly describes why and how the name of A. nilotica changed. Tannin has been analyzed using the Stiasny method when the tannin is used to make adhesives and the hide-powder method is used when the tannin is to be used for leather tanning. A simple UV method is also able to be used to estimate the values for both adhesives and leather tanning applications. The tannin content in bark can also be estimated using NIR and NMR. Tannin content estimations using pyrolysis/GC, electrospray mass spectrometry and quantitative ³¹P-NMR analyses have also been described. Tannins consists mostly of polyflavanoids and all the compounds isolated have been updated. Antioxidant activities of the tannin relating to anti-tumor properties, the viability of human neuroblastoma SH-SY5Y cells and also anti-hypertensive effects have been studied. The antioxidant activity of proanthocyanidins was found to be higher than that of flavan-3-ol monomers. A total of fourteen papers and two patents reported the antimicrobial activities of wattle tannin. Bacteria were more susceptible to the tannins than the fungal strains tested. Several bacteria were inhibited by the extract from A. mearnsii bark. The growth inhibition mechanisms of E. coli were investigated. An interaction between extracts from A. mearnsii bark and antibiotics has also been studied. The extracts from A. mearnsii bark inhibit the growth of cyanobacteria. Wattle tannin has the ability to inactivate α-amylase, lipase and glucosidase. In vivo experiments on anti-obesity and anti-diabetes were also reported. Several patents relating to these enzymes for anti-diabetes and anti-obesity are in the literature. In addition, studies on Acacia bark extract regarding its antitermite activities, inhibition of itching in atopic dermatitis and anti-inflammatory effects have also been reported. The growth of bacteria was inhibited by the extract from A. mearnsii bark, and typical intestinal bacteria such as E. coli, K. pneumoniae, P. vulgaris and S. marcescenes was also inhibited in vitro by extracts. Based on these results, the Acacia bark extract may inhibit not only the growth of these typical intestinal bacteria but also the growth of other types of intestinal bacteria such as Clostridium and Bacteroides, a so-called “bad bacteria”. If the tannin extract from A. mearnsii bark inhibits growth of these “bad bacteria” in vivo evaluation, the extracts might be usable as a new dietary supplement, which could control the human intestinal microbiome to keep the body healthy. Full article

(This article belongs to the Special Issue Special Issue Dedicated to Late Professor Takuo Okuda, “Tannins and Related Polyphenols Revisited: Chemistry, Biochemistry and Biological Activities”)

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12 pages, 6278 KiB

Open AccessReview

Dual Effects of Alpha-Hydroxy Acids on the Skin

by Sheau-Chung Tang and Jen-Hung Yang

Molecules 2018, 23(4), 863; https://doi.org/10.3390/molecules23040863 - 10 Apr 2018

Cited by 94 | Viewed by 60838

Abstract

AHAs are organic acids with one hydroxyl group attached to the alpha position of the acid. AHAs including glycolic acid, lactic acid, malic acid, tartaric acid, and citric acid are often used extensively in cosmetic formulations. AHAs have been used as superficial peeling [...] Read more.

AHAs are organic acids with one hydroxyl group attached to the alpha position of the acid. AHAs including glycolic acid, lactic acid, malic acid, tartaric acid, and citric acid are often used extensively in cosmetic formulations. AHAs have been used as superficial peeling agents as well as to ameliorate the appearance of keratoses and acne in dermatology. However, caution should be exercised in relation to certain adverse reactions among patients using products with AHAs, including swelling, burning, and pruritus. Whether AHAs enhance or decrease photo damage of the skin remains unclear, compelling us to ask the question, is AHA a friend or a foe of the skin? The aim of this manuscript is to review the various biological effects and mechanisms of AHAs on human keratinocytes and in an animal model. We conclude that whether AHA is a friend or foe of human skin depends on its concentration. These mechanisms of AHAs are currently well understood, aiding the development of novel approaches for the prevention of UV-induced skin damage. Full article

(This article belongs to the Section Chemical Biology)

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25 pages, 5701 KiB

Open AccessReview

Production of Flocculants, Adsorbents, and Dispersants from Lignin

by Jiachuan Chen, Armin Eraghi Kazzaz, Niloofar AlipoorMazandarani, Zahra Hosseinpour Feizi and Pedram Fatehi

Molecules 2018, 23(4), 868; https://doi.org/10.3390/molecules23040868 - 10 Apr 2018

Cited by 71 | Viewed by 9844

Abstract

Currently, lignin is mainly produced in pulping processes, but it is considered as an under-utilized chemical since it is being mainly used as a fuel source. Lignin contains many hydroxyl groups that can participate in chemical reactions to produce value-added products. Flocculants, adsorbents, [...] Read more.

Currently, lignin is mainly produced in pulping processes, but it is considered as an under-utilized chemical since it is being mainly used as a fuel source. Lignin contains many hydroxyl groups that can participate in chemical reactions to produce value-added products. Flocculants, adsorbents, and dispersants have a wide range of applications in industry, but they are mainly oil-based chemicals and expensive. This paper reviews the pathways to produce water soluble lignin-based flocculants, adsorbents, and dispersants. It provides information on the recent progress in the possible use of these lignin-based flocculants, adsorbents, and dispersants. It also critically discusses the advantages and disadvantages of various approaches to produce such products. The challenges present in the production of lignin-based flocculants, adsorbents, and dispersants and possible scenarios to overcome these challenges for commercial use of these products in industry are discussed. Full article

(This article belongs to the Special Issue Lignin for Energy, Chemicals and Materials)

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20 pages, 3919 KiB

Open AccessReview

The Multifunctional Role of Chitosan in Horticultural Crops; A Review

by Rahat Sharif, Muhammad Mujtaba, Mati Ur Rahman, Abdullah Shalmani, Husain Ahmad, Toheed Anwar, Deng Tianchan and Xiping Wang

Molecules 2018, 23(4), 872; https://doi.org/10.3390/molecules23040872 - 10 Apr 2018

Cited by 180 | Viewed by 14599

Abstract

Chitosan is a naturally occurring compound and is commercially produced from seafood shells. It has been utilized in the induction of the defense system in both pre and post-harvest fruits and vegetables against fungi, bacteria, viruses, and other abiotic stresses. In addition to [...] Read more.

Chitosan is a naturally occurring compound and is commercially produced from seafood shells. It has been utilized in the induction of the defense system in both pre and post-harvest fruits and vegetables against fungi, bacteria, viruses, and other abiotic stresses. In addition to that, chitosan effectively improves the physiological properties of plants and also enhances the shelf life of post-harvest produces. Moreover, chitosan treatment regulates several genes in plants, particularly the activation of plant defense signaling pathways. That includes the elicitation of phytoalexins and pathogenesis-related (PR) protein. Besides that, chitosan has been employed in soil as a plant nutrient and has shown great efficacy in combination with other industrial fertilizers without affecting the soil’s beneficial microbes. Furthermore, it is helpful in reducing the fertilizer losses due to its coating ability, which is important in keeping the environmental pollution under check. Based on exhibiting such excellent properties, there is a striking interest in using chitosan biopolymers in agriculture systems. Therefore, our current review has been centered upon the multiple roles of chitosan in horticultural crops that could be useful in future crop improvement programs. Full article

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31 pages, 501 KiB

Open AccessReview

An Overview of Novel Dietary Supplements and Food Ingredients in Patients with Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease

by Priscila Silva Figueiredo, Aline Carla Inada, Melina Ribeiro Fernandes, Daniela Granja Arakaki, Karine De Cássia Freitas, Rita De Cássia Avellaneda Guimarães, Valter Aragão do Nascimento and Priscila Aiko Hiane

Molecules 2018, 23(4), 877; https://doi.org/10.3390/molecules23040877 - 11 Apr 2018

Cited by 33 | Viewed by 8481

Abstract

Metabolic syndrome (MetS) is characterized by interconnected factors related to metabolic disturbances, and is directly related to the occurrence of some diseases such as cardiovascular diseases and type 2 diabetes. MetS is described as one or both of insulin resistance and visceral adiposity, [...] Read more.

Metabolic syndrome (MetS) is characterized by interconnected factors related to metabolic disturbances, and is directly related to the occurrence of some diseases such as cardiovascular diseases and type 2 diabetes. MetS is described as one or both of insulin resistance and visceral adiposity, considered the initial causes of abnormalities that include hyperglycemia, elevated blood pressure, dyslipidemia, elevated inflammatory markers, and prothrombotic state, as well as polycystic ovarian syndrome in women. Other than in MetS, visceral adiposity and the pro-inflammatory state are also key in the development of non-alcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease in modern society. Both MetS and NAFLD are related to diet and lifestyle, and their treatment may be influenced by dietary pattern changes and the use of certain dietary supplements. This study aimed to review the role of food ingredients and supplements in the management of MetS and NAFLD specifically in human clinical trials. Moreover, bioactive compounds and polyunsaturated fatty acids (PUFAs) may be used as strategies for preventing the onset of and treatment of metabolic disorders, such as MetS and NAFLD, improving the inflammatory state and other comorbidities, such as obesity, dyslipidemias, and cardiovascular diseases (CVD). Full article

(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)

60 pages, 41705 KiB

Open AccessFeature PaperReview

Synthesis and Application of the Transition Metal Complexes of α-Pyridinyl Alcohols, α-Bipyridinyl Alcohols, α,α’-Pyridinyl Diols and α,α’-Bipyridinyl Diols in Homogeneous Catalysis

by Tegene Tole, Johannes Jordaan and Hermanus Vosloo

Molecules 2018, 23(4), 896; https://doi.org/10.3390/molecules23040896 - 12 Apr 2018

Cited by 5 | Viewed by 7041

Abstract

The paper presents a comprehensive survey on the synthetic procedures of transition metal complexes of α-pyridinyl alcoholato, α-bipyridinyl alcoholato, α,α’-pyridinyl dialcoholato and α,α’-bipyridinyl dialcoholato ligands and their coordination chemistry. Greater emphasis is, however, given to the catalytic activity of the complexes [...] Read more.

The paper presents a comprehensive survey on the synthetic procedures of transition metal complexes of α-pyridinyl alcoholato, α-bipyridinyl alcoholato, α,α’-pyridinyl dialcoholato and α,α’-bipyridinyl dialcoholato ligands and their coordination chemistry. Greater emphasis is, however, given to the catalytic activity of the complexes in homogeneous and asymmetric chemical reactions. The multidentate character of the pyridinyl alcohols and/or bipyridinyl diols is of great importance in the complexation with a large number and type of transition metals. The transition metal complexes of pyridinyl alcoholato or bipyridinyl dialcoholato ligands in most cases, and a few pyridinyl alcohols alone, were used as catalysts in homogeneous and chemical asymmetric reactions. In most of the homogeneously catalysed enantioselective chemical reactions, limited numbers and types of pyridinyl alcohols and or bipyridinyl diols were used in the preparation of chiral catalysts that led to a few investigations on the catalytic importance of the pyridinyl alcohols. Full article

(This article belongs to the Special Issue Organometallic Catalysis in Organic Synthesis)

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24 pages, 955 KiB

Open AccessFeature PaperReview

Update on Marine Carbohydrate Hydrolyzing Enzymes: Biotechnological Applications

by Antonio Trincone

Molecules 2018, 23(4), 901; https://doi.org/10.3390/molecules23040901 - 13 Apr 2018

Cited by 27 | Viewed by 5570

Abstract

After generating much interest in the past as an aid in solving structural problems for complex molecules such as polysaccharides, carbohydrate-hydrolyzing enzymes of marine origin still appear as interesting biocatalysts for a range of useful applications in strong interdisciplinary fields such as green [...] Read more.

After generating much interest in the past as an aid in solving structural problems for complex molecules such as polysaccharides, carbohydrate-hydrolyzing enzymes of marine origin still appear as interesting biocatalysts for a range of useful applications in strong interdisciplinary fields such as green chemistry and similar domains. The multifaceted fields in which these enzymes are of interest and the scarce number of original articles in literature prompted us to provide the specialized analysis here reported. General considerations from modern (2016–2017 interval time) review articles are at start of this manuscript; then it is subsequently organized in sections according to particular biopolymers and original research articles are discussed. Literature sources like the Science Direct database with an optimized W/in search, and the Espacenet patent database were used. Full article

(This article belongs to the Section Bioorganic Chemistry)

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7 pages, 1529 KiB

Open AccessFeature PaperReview

Iron Is the Active Site in Nickel/Iron Water Oxidation Electrocatalysts

by Bryan M. Hunter, Jay R. Winkler and Harry B. Gray

Molecules 2018, 23(4), 903; https://doi.org/10.3390/molecules23040903 - 14 Apr 2018

Cited by 70 | Viewed by 8679

Abstract

Efficient catalysis of the oxygen-evolution half-reaction (OER) is a pivotal requirement for the development of practical solar-driven water splitting devices. Heterogeneous OER electrocatalysts containing first-row transition metal oxides and hydroxides have attracted considerable recent interest, owing in part to the high abundance and [...] Read more.

Efficient catalysis of the oxygen-evolution half-reaction (OER) is a pivotal requirement for the development of practical solar-driven water splitting devices. Heterogeneous OER electrocatalysts containing first-row transition metal oxides and hydroxides have attracted considerable recent interest, owing in part to the high abundance and low cost of starting materials. Among the best performing OER electrocatalysts are mixed Fe/Ni layered double hydroxides (LDH). A review of the available experimental data leads to the conclusion that iron is the active site for [NiFe]-LDH-catalyzed alkaline water oxidation. Full article

(This article belongs to the Special Issue Artificial Photosynthesis: Recent Progress in Solar Energy Utilization)

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17 pages, 13575 KiB

Open AccessReview

Liposomal Drug Delivery Systems and Anticancer Drugs

by Temidayo O. B. Olusanya, Rita Rushdi Haj Ahmad, Daniel M. Ibegbu, James R. Smith and Amal Ali Elkordy

Molecules 2018, 23(4), 907; https://doi.org/10.3390/molecules23040907 - 14 Apr 2018

Cited by 422 | Viewed by 28253

Abstract

Cancer is a life-threatening disease contributing to ~3.4 million deaths worldwide. There are various causes of cancer, such as smoking, being overweight or obese, intake of processed meat, radiation, family history, stress, environmental factors, and chance. The first-line treatment of cancer is the [...] Read more.

Cancer is a life-threatening disease contributing to ~3.4 million deaths worldwide. There are various causes of cancer, such as smoking, being overweight or obese, intake of processed meat, radiation, family history, stress, environmental factors, and chance. The first-line treatment of cancer is the surgical removal of solid tumours, radiation therapy, and chemotherapy. The systemic administration of the free drug is considered to be the main clinical failure of chemotherapy in cancer treatment, as limited drug concentration reaches the tumour site. Most of the active pharmaceutical ingredients (APIs) used in chemotherapy are highly cytotoxic to both cancer and normal cells. Accordingly, targeting the tumour vasculatures is essential for tumour treatment. In this context, encapsulation of anti-cancer drugs within the liposomal system offers secure platforms for the targeted delivery of anti-cancer drugs for the treatment of cancer. This, in turn, can be helpful for reducing the cytotoxic side effects of anti-cancer drugs on normal cells. This short-review focuses on the use of liposomes in anti-cancer drug delivery. Full article

(This article belongs to the Special Issue Targeted Drug Delivery and Nanocarriers)

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25 pages, 924 KiB

Open AccessReview

Stryphnodendron Species Known as “Barbatimão”: A Comprehensive Report

by Tatiana M. Souza-Moreira, Geisiany M. Queiroz-Fernandes and Rosemeire C. L. R. Pietro

Molecules 2018, 23(4), 910; https://doi.org/10.3390/molecules23040910 - 15 Apr 2018

Cited by 34 | Viewed by 6750

Abstract

Stryphnodendron spp., popularly known as “barbatimão”, is the native Brazilian tree most often employed to treat wounds and infections. The aim of the present study was to highlight the importance of S. adstringens, as well as other Stryphnodendron species recognized as “barbatimão”, to [...] Read more.

Stryphnodendron spp., popularly known as “barbatimão”, is the native Brazilian tree most often employed to treat wounds and infections. The aim of the present study was to highlight the importance of S. adstringens, as well as other Stryphnodendron species recognized as “barbatimão”, to human health, depicting the relevance of ethnopharmacological knowledge to scientific evidence for uses, related chemical compounds, development of pharmaceutical formulations, and the establishment of toxicity parameters. For this purpose, the literature databases PubMed, Scielo, Lilacs, CAPES Thesis and Google Scholar were searched until 2017. It was observed that stem bark was the primary part of the plant used, mainly as a decoction, for wound healing and treatment of infectious and inflammatory disorders. Confirmed biological activities, including wound healing, anti-inflammatory, antioxidant, and antimicrobial activities, were related to the presence of compounds from tannin class, mostly proanthocyanidins. Toxicity parameters for stem bark were inconclusive, but toxicity was observed to a significant extent when seeds were ingested by cattle or other animals. Due to these important and confirmed biological activities, government policy encourages the phytotherapic use of S. adstringens, and some formulations with stem bark extracts were developed and patented. Furthermore, antiprotozoal, hypoglycemic and antiviral activities were identified as promising. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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18 pages, 3439 KiB

Open AccessFeature PaperReview

Synthesis of Theaflavins and Their Functions

by Masumi Takemoto and Hiroaki Takemoto

Molecules 2018, 23(4), 918; https://doi.org/10.3390/molecules23040918 - 16 Apr 2018

Cited by 92 | Viewed by 9456

Abstract

Numerous epidemiological and interventional clinical studies have consistently reported that black tea is good for human health. The polyphenolic compound, theaflavin, and its galloyl esters (theaflavins) are the primary red pigments in black tea that possess several health benefits, including fat-reducing and glucose-lowering [...] Read more.

Numerous epidemiological and interventional clinical studies have consistently reported that black tea is good for human health. The polyphenolic compound, theaflavin, and its galloyl esters (theaflavins) are the primary red pigments in black tea that possess several health benefits, including fat-reducing and glucose-lowering capabilities and lifestyle-related disease prevention related to anti-obesity, anticancer, anti-atherosclerotic, anti-inflammatory, antiviral, antibacterial, anti-osteoporotic, and anti-dental caries properties. These compounds are produced by key enzymes, such as polyphenol oxidase and peroxidase, from parent green tea catechins present in fresh green tea leaves during the production of black tea leaves or the fermentation of green tea. However, theaflavins are only present in low concentrations in black tea; thus, their extraction from black tea leaves at sufficient levels for use in medical studies has been difficult. To circumvent this issue, different procedures for the synthesis of theaflavins using chemical oxidizing reagents or enzymes have been studied; however, low yields have limited their utility. Recently, however, several biosynthetic methods have been developed for the mass production of theaflavins. Using these methods, the physiological functions of theaflavins in lifestyle-related diseases in mice and humans have also been studied. In this review, we present the synthesis of theaflavins and their health benefits. Full article

(This article belongs to the Special Issue Catechin in Human Health and Disease)

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13 pages, 4235 KiB

Open AccessFeature PaperReview

Recent Developments in C–H Activation for Materials Science in the Center for Selective C–H Activation

by Junxiang Zhang, Lauren J. Kang, Timothy C. Parker, Simon B. Blakey, Christine K. Luscombe and Seth R. Marder

Molecules 2018, 23(4), 922; https://doi.org/10.3390/molecules23040922 - 16 Apr 2018

Cited by 42 | Viewed by 7025

Abstract

Organic electronics is a rapidly growing field driven in large part by the synthesis of π-conjugated molecules and polymers. Traditional aryl cross-coupling reactions such as the Stille and Suzuki have been used extensively in the synthesis of π-conjugated molecules and polymers, but the [...] Read more.

Organic electronics is a rapidly growing field driven in large part by the synthesis of π-conjugated molecules and polymers. Traditional aryl cross-coupling reactions such as the Stille and Suzuki have been used extensively in the synthesis of π-conjugated molecules and polymers, but the synthesis of intermediates necessary for traditional cross-couplings can include multiple steps with toxic and hazardous reagents. Direct arylation through C–H bond activation has the potential to reduce the number of steps and hazards while being more atom-economical. Within the Center for Selective C–H Functionalization (CCHF), we have been developing C–H activation methodology for the synthesis of π-conjugated materials of interest, including direct arylation of difficult-to-functionalize electron acceptor intermediates and living polymerization of π-conjugated polymers through C–H activation. Full article

(This article belongs to the Special Issue Direct (Hetero)Arylation: A New Tool for Organic Electronics)

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15 pages, 4362 KiB

Open AccessReview

HIV Tat/P-TEFb Interaction: A Potential Target for Novel Anti-HIV Therapies

by Kaori Asamitsu, Koh Fujinaga and Takashi Okamoto

Molecules 2018, 23(4), 933; https://doi.org/10.3390/molecules23040933 - 17 Apr 2018

Cited by 26 | Viewed by 6121

Abstract

Transcription is a crucial step in the life cycle of the human immunodeficiency virus type 1 (HIV 1) and is primarily involved in the maintenance of viral latency. Both viral and cellular transcription factors, including transcriptional activators, suppressor proteins and epigenetic factors, are [...] Read more.

Transcription is a crucial step in the life cycle of the human immunodeficiency virus type 1 (HIV 1) and is primarily involved in the maintenance of viral latency. Both viral and cellular transcription factors, including transcriptional activators, suppressor proteins and epigenetic factors, are involved in HIV transcription from the proviral DNA integrated within the host cell genome. Among them, the virus-encoded transcriptional activator Tat is the master regulator of HIV transcription. Interestingly, unlike other known transcriptional activators, Tat primarily activates transcriptional elongation and initiation by interacting with the cellular positive transcriptional elongation factor b (P-TEFb). In this review, we describe the molecular mechanism underlying how Tat activates viral transcription through interaction with P-TEFb. We propose a novel therapeutic strategy against HIV replication through blocking Tat action. Full article

(This article belongs to the Special Issue Transcription Factors as Therapeutic Targets)

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12 pages, 1574 KiB

Open AccessReview

Structural Diversity and Biological Activities of Diterpenoids Derived from Euphorbia fischeriana Steud

by Baiyu Jian, Hao Zhang and Jicheng Liu

Molecules 2018, 23(4), 935; https://doi.org/10.3390/molecules23040935 - 18 Apr 2018

Cited by 30 | Viewed by 4132

Abstract

Diterpenoids are the focus of natural product drug discovery because of their great structural diversity and pronounced biological activities. Euphorbia fischeriana Steud is a Chinese traditional medicinal herb for curing edema, ascites, and cancer. This plant contains rich diterpenoids. Based on the carbon [...] Read more.

Diterpenoids are the focus of natural product drug discovery because of their great structural diversity and pronounced biological activities. Euphorbia fischeriana Steud is a Chinese traditional medicinal herb for curing edema, ascites, and cancer. This plant contains rich diterpenoids. Based on the carbon skeleton and substituents, it can be classified into thirteen subtypes: ent-abietane, daphnane, tigliane, ingenane, ent-atisane, ent-rosane, ent-kaurene, ent-kaurane, secotigliane, lathyrane, ent-pimarene, isopimarene and dimeric. In this paper, we reviewed the chemical structures and biological activities of 90 diterpenoids isolated from this medicinal herb. We hope that this work can serve as a reference for further research of these diterpenoids and lay the foundation for drug discovery. Full article

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18 pages, 1740 KiB

Open AccessReview

Pursuing Intracellular Pathogens with Hyaluronan. From a ‘Pro-Infection’ Polymer to a Biomaterial for ‘Trojan Horse’ Systems

by Elita Montanari, Chiara Di Meo, Angela Oates, Tommasina Coviello and Pietro Matricardi

Molecules 2018, 23(4), 939; https://doi.org/10.3390/molecules23040939 - 18 Apr 2018

Cited by 13 | Viewed by 5204

Abstract

Hyaluronan (HA) is among the most important bioactive polymers in mammals, playing a key role in a number of biological functions. In the last decades, it has been increasingly studied as a biomaterial for drug delivery systems, thanks to its physico-chemical features and [...] Read more.

Hyaluronan (HA) is among the most important bioactive polymers in mammals, playing a key role in a number of biological functions. In the last decades, it has been increasingly studied as a biomaterial for drug delivery systems, thanks to its physico-chemical features and ability to target and enter certain cells. The most important receptor of HA is ‘Cluster of Differentiation 44’ (CD44), a cell surface glycoprotein over-expressed by a number of cancers and heavily involved in HA endocytosis. Moreover, CD44 is highly expressed by keratinocytes, activated macrophages and fibroblasts, all of which can act as ‘reservoirs’ for intracellular pathogens. Interestingly, both CD44 and HA appear to play a key role for the invasion and persistence of such microorganisms within the cells. As such, HA is increasingly recognised as a potential target for nano-carriers development, to pursuit and target intracellular pathogens, acting as a ‘Trojan Horse’. This review describes the biological relationship between HA, CD44 and the entry and survival of a number of pathogens within the cells and the subsequent development of HA-based nano-carriers for enhancing the intracellular activity of antimicrobials. Full article

(This article belongs to the Special Issue Hyaluronic Acid and its Derivatives for Biomedical Applications)

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18 pages, 19663 KiB

Open AccessReview

Panax Notoginseng Saponins: A Review of Its Mechanisms of Antidepressant or Anxiolytic Effects and Network Analysis on Phytochemistry and Pharmacology

by Weijie Xie, Xiangbao Meng, Yadong Zhai, Ping Zhou, Tianyuan Ye, Zhen Wang, Guibo Sun and Xiaobo Sun

Molecules 2018, 23(4), 940; https://doi.org/10.3390/molecules23040940 - 17 Apr 2018

Cited by 98 | Viewed by 14037

Abstract

Panax notoginseng (Burk) F. H. Chen, as traditional Chinese medicine, has a long history of high clinical value, such as anti-inflammatory, anti-oxidation, inhibition of platelet aggregation, regulation of blood glucose and blood pressure, inhibition of neuronal apoptosis, and neuronal protection, and its [...] Read more.

Panax notoginseng (Burk) F. H. Chen, as traditional Chinese medicine, has a long history of high clinical value, such as anti-inflammatory, anti-oxidation, inhibition of platelet aggregation, regulation of blood glucose and blood pressure, inhibition of neuronal apoptosis, and neuronal protection, and its main ingredients are Panax notoginseng saponins (PNS). Currently, Panax notoginseng (Burk) F. H. Chen may improve mental function, have anti-insomnia and anti-depression effects, alleviate anxiety, and decrease neural network excitation. However, the underlying effects and the mechanisms of Panax notoginseng (Burk) F. H. Chen and its containing chemical constituents (PNS) on these depression-related or anxiety-related diseases has not been completely established. This review summarized the antidepressant or anxiolytic effects and mechanisms of PNS and analyzed network targets of antidepressant or anxiolytic actions with network pharmacology tools to provide directions and references for further pharmacological studies and new ideas for clinical treatment of nervous system diseases and drug studies and development. The review showed PNS and its components may exert these effects through regulating neurotransmitter mechanism (5-HT, DA, NE), modulation of the gamma-amino butyric acid (GABA) neurotransmission, glutamatergic system, hypo-thalamus-pituitary-adrenal (HPA) axis, brain-derived neurotrophic factor (BDNF), and its intracellular signaling pathways in the central nervous system; and produce neuronal protection by anti-inflammatory, anti-oxidation, or inhibition of neuronal apoptosis, or platelet aggregation and its intracellular signaling pathways. Network target analysis indicated PNS and its components also may have anti-inflammatory and anti-apoptotic effects, which leads to the preservation of brain nerves, and regulate the activity and secretion of nerve cells, exerting anti-depression and anxiolytic effects, which may provide new directions for further in-depth researches of related mechanisms. Full article

(This article belongs to the Collection Herbal Medicine Research)

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35 pages, 52977 KiB

Open AccessReview

Pectin and Pectin-Based Composite Materials: Beyond Food Texture

by Claudia Lara-Espinoza, Elizabeth Carvajal-Millán, René Balandrán-Quintana, Yolanda López-Franco and Agustín Rascón-Chu

Molecules 2018, 23(4), 942; https://doi.org/10.3390/molecules23040942 - 18 Apr 2018

Cited by 327 | Viewed by 34866

Abstract

Pectins are plant cell wall natural heteropolysaccharides composed mainly of α-1-4 d-galacturonic acid units, which may or may not be methyl esterified, possesses neutral sugars branching that harbor functional moieties. Physicochemical features as pH, temperature, ions concentration, and cosolute presence, affect directly [...] Read more.

Pectins are plant cell wall natural heteropolysaccharides composed mainly of α-1-4 d-galacturonic acid units, which may or may not be methyl esterified, possesses neutral sugars branching that harbor functional moieties. Physicochemical features as pH, temperature, ions concentration, and cosolute presence, affect directly the extraction yield and gelling capacity of pectins. The chemical and structural features of this polysaccharide enables its interaction with a wide range of molecules, a property that scientists profit from to form new composite matrices for target/controlled delivery of therapeutic molecules, genes or cells. Considered a prebiotic dietary fiber, pectins meetmany regulations easily, regarding health applications within the pharmaceutical industry as a raw material and as an agent for the prevention of cancer. Thus, this review lists many emergent pectin-based composite materials which will probably palliate the impact of obesity, diabetes and heart disease, aid to forestall actual epidemics, expand the ken of food additives and food products design. Full article

(This article belongs to the Special Issue Polysaccharide-based Materials)

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48 pages, 21275 KiB

Open AccessFeature PaperReview

Application of the Asymmetric Pictet–Spengler Reaction in the Total Synthesis of Natural Products and Relevant Biologically Active Compounds

by Majid M. Heravi, Vahideh Zadsirjan and Masumeh Malmir

Molecules 2018, 23(4), 943; https://doi.org/10.3390/molecules23040943 - 18 Apr 2018

Cited by 49 | Viewed by 10158

Abstract

Tetrahydroisoquinolines are the framework of numerous natural products predominantly alkaloids, an important and one of the most wide spread families of naturally occurring compounds in the plant kingdom. Tetrahydroisoquinolines are commonly constructed through an old reaction, the so-called Pictet–Spengler Reaction (PSR). In this [...] Read more.

Tetrahydroisoquinolines are the framework of numerous natural products predominantly alkaloids, an important and one of the most wide spread families of naturally occurring compounds in the plant kingdom. Tetrahydroisoquinolines are commonly constructed through an old reaction, the so-called Pictet–Spengler Reaction (PSR). In this reaction, a β-aryl ethylamine undergoes an acid mediated condensation with a suitable aldehyde or ketone, followed by ring closure. In this review, we aim to highlight the applications of the asymmetric variant of this old name reaction in the total synthesis of natural products, chiefly, alkaloids, which exhibit significant biological properties. Full article

(This article belongs to the Special Issue Design in Synthetic Biology)

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20 pages, 2124 KiB

Open AccessReview

HIV Resistance Prediction to Reverse Transcriptase Inhibitors: Focus on Open Data

by Olga Tarasova and Vladimir Poroikov

Molecules 2018, 23(4), 956; https://doi.org/10.3390/molecules23040956 - 19 Apr 2018

Cited by 17 | Viewed by 4749

Abstract

Research and development of new antiretroviral agents are in great demand due to issues with safety and efficacy of the antiretroviral drugs. HIV reverse transcriptase (RT) is an important target for HIV treatment. RT inhibitors targeting early stages of the virus-host interaction are [...] Read more.

Research and development of new antiretroviral agents are in great demand due to issues with safety and efficacy of the antiretroviral drugs. HIV reverse transcriptase (RT) is an important target for HIV treatment. RT inhibitors targeting early stages of the virus-host interaction are of great interest for researchers. There are a lot of clinical and biochemical data on relationships between the occurring of the single point mutations and their combinations in the pol gene of HIV and resistance of the particular variants of HIV to nucleoside and non-nucleoside reverse transcriptase inhibitors. The experimental data stored in the databases of HIV sequences can be used for development of methods that are able to predict HIV resistance based on amino acid or nucleotide sequences. The data on HIV sequences resistance can be further used for (1) development of new antiretroviral agents with high potential for HIV inhibition and elimination and (2) optimization of antiretroviral therapy. In our communication, we focus on the data on the RT sequences and HIV resistance, which are available on the Internet. The experimental methods, which are applied to produce the data on HIV-1 resistance, the known data on their concordance, are also discussed. Full article

(This article belongs to the Special Issue Recent Trends on Enzymes Inhibitors and Activators in Drug Research)

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18 pages, 2805 KiB

Open AccessReview

Using Peptidomimetics and Constrained Peptides as Valuable Tools for Inhibiting Protein–Protein Interactions

by Naomi S. Robertson and David R. Spring

Molecules 2018, 23(4), 959; https://doi.org/10.3390/molecules23040959 - 19 Apr 2018

Cited by 70 | Viewed by 10899

Abstract

Protein–protein interactions (PPIs) are tremendously important for the function of many biological processes. However, because of the structure of many protein–protein interfaces (flat, featureless and relatively large), they have largely been overlooked as potential drug targets. In this review, we highlight the current [...] Read more.

Protein–protein interactions (PPIs) are tremendously important for the function of many biological processes. However, because of the structure of many protein–protein interfaces (flat, featureless and relatively large), they have largely been overlooked as potential drug targets. In this review, we highlight the current tools used to study the molecular recognition of PPIs through the use of different peptidomimetics, from small molecules and scaffolds to peptides. Then, we focus on constrained peptides, and in particular, ways to constrain α-helices through stapling using both one- and two-component techniques. Full article

(This article belongs to the Special Issue Protein-Protein Interactions)

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34 pages, 1517 KiB

Open AccessReview

Modified Fusarium Mycotoxins in Cereals and Their Products—Metabolism, Occurrence, and Toxicity: An Updated Review

by Marcin Bryła, Agnieszka Waśkiewicz, Edyta Ksieniewicz-Woźniak, Krystyna Szymczyk and Renata Jędrzejczak

Molecules 2018, 23(4), 963; https://doi.org/10.3390/molecules23040963 - 20 Apr 2018

Cited by 90 | Viewed by 8660

Abstract

Mycotoxins are secondary fungal metabolites, toxic to humans, animals and plants. Under the influence of various factors, mycotoxins may undergo modifications of their chemical structure. One of the methods of mycotoxin modification is a transformation occurring in plant cells or under the influence [...] Read more.

Mycotoxins are secondary fungal metabolites, toxic to humans, animals and plants. Under the influence of various factors, mycotoxins may undergo modifications of their chemical structure. One of the methods of mycotoxin modification is a transformation occurring in plant cells or under the influence of fungal enzymes. This paper reviews the current knowledge on the natural occurrence of the most important trichothecenes and zearalenone in cereals/cereal products, their metabolism, and the potential toxicity of the metabolites. Only very limited data are available for the majority of the identified mycotoxins. Most studies concern biologically modified trichothecenes, mainly deoxynivalenol-3-glucoside, which is less toxic than its parent compound (deoxynivalenol). It is resistant to the digestion processes within the gastrointestinal tract and is not absorbed by the intestinal epithelium; however, it may be hydrolysed to free deoxynivalenol or deepoxy-deoxynivalenol by the intestinal microflora. Only one zearalenone derivative, zearalenone-14-glucoside, has been extensively studied. It appears to be more reactive than deoxynivalenol-3-glucoside. It may be readily hydrolysed to free zearalenone, and the carbonyl group in its molecule may be easily reduced to α/β-zearalenol and/or other unspecified metabolites. Other derivatives of deoxynivalenol and zearalenone are poorly characterised. Moreover, other derivatives such as glycosides of T-2 and HT-2 toxins have only recently been investigated; thus, the data related to their toxicological profile and occurrence are sporadic. The topics described in this study are crucial to ensure food and feed safety, which will be assisted by the provision of widespread access to such studies and obtained results. Full article

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11 pages, 4568 KiB

Open AccessReview

The Role of Catechins in Cellular Responses to Oxidative Stress

by Jurga Bernatoniene and Dalia Marija Kopustinskiene

Molecules 2018, 23(4), 965; https://doi.org/10.3390/molecules23040965 - 20 Apr 2018

Cited by 410 | Viewed by 22803

Abstract

Catechins are polyphenolic compounds—flavanols of the flavonoid family found in a variety of plants. Green tea, wine and cocoa-based products are the main dietary sources of these flavanols. Catechins have potent antioxidant properties, although in some cases they may act in the cell [...] Read more.

Catechins are polyphenolic compounds—flavanols of the flavonoid family found in a variety of plants. Green tea, wine and cocoa-based products are the main dietary sources of these flavanols. Catechins have potent antioxidant properties, although in some cases they may act in the cell as pro-oxidants. Catechins are reactive oxygen species (ROS) scavengers and metal ion chelators, whereas their indirect antioxidant activities comprise induction of antioxidant enzymes, inhibition of pro-oxidant enzymes, and production of the phase II detoxification enzymes and antioxidant enzymes. Oxidative stress and ROS are implicated in aging and related dysfunctions, such as neurodegenerative disease, cancer, cardiovascular diseases, and diabetes. Due to their antioxidant properties, catechins may be beneficial in preventing and protecting against diseases caused by oxidative stress. This article reviews the biochemical properties of catechins, their antioxidant activity, and the mechanisms of action involved in the prevention of oxidative stress-caused diseases. Full article

(This article belongs to the Special Issue Catechin in Human Health and Disease)

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15 pages, 8741 KiB

Open AccessFeature PaperReview

Dentromers, a Family of Super Dendrimers with Specific Properties and Applications

by Didier Astruc, Christophe Deraedt, Rodrigue Djeda, Catia Ornelas, Xiang Liu, Amalia Rapakousiou, Jaime Ruiz, Yanlan Wang and Qi Wang

Molecules 2018, 23(4), 966; https://doi.org/10.3390/molecules23040966 - 20 Apr 2018

Cited by 21 | Viewed by 6244

Abstract

Dentromers (from dentro, δεντρο: tree in Greek), and meros (μεροσ, in greek: part) are introduced as a family of dendrimers constructed according to successive divergent 1 → 3 branching. The smaller dentromers have 27 terminal branches. With alcohol termini they were originally [...] Read more.

Dentromers (from dentro, δεντρο: tree in Greek), and meros (μεροσ, in greek: part) are introduced as a family of dendrimers constructed according to successive divergent 1 → 3 branching. The smaller dentromers have 27 terminal branches. With alcohol termini they were originally named arborols by Newkome, who pioneered 1 → 3 constructions of dendrimers and dendrons. Giant dentromers have been constructed and decorated in particular with ferrocene and other redox active groups. The synthesis, specific properties, and applications are examined in this mini review article dedicated to Don Tomalia, with an emphasis on dense peripheral packing favoring the functions of encapsulation, redox sensing, and micellar template for catalysis in water and aqueous solvents. Full article

(This article belongs to the Special Issue Dendrimers: A Themed Issue in Honor of Professor Donald A. Tomalia on the Occasion of His 80th Birthday)

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14 pages, 1404 KiB

Open AccessCommentary

Synaptic Alterations in Mouse Models for Alzheimer Disease—A Special Focus on N-Truncated Abeta 4-42

by Katharina Dietrich, Yvonne Bouter, Michael Müller and Thomas A. Bayer

Molecules 2018, 23(4), 718; https://doi.org/10.3390/molecules23040718 - 21 Mar 2018

Cited by 19 | Viewed by 4792

Abstract

This commentary reviews the role of the Alzheimer amyloid peptide Aβ on basal synaptic transmission, synaptic short-term plasticity, as well as short- and long-term potentiation in transgenic mice, with a special focus on N-terminal truncated Aβ_4-42. Aβ_4-42 is highly abundant [...] Read more.

This commentary reviews the role of the Alzheimer amyloid peptide Aβ on basal synaptic transmission, synaptic short-term plasticity, as well as short- and long-term potentiation in transgenic mice, with a special focus on N-terminal truncated Aβ_4-42. Aβ_4-42 is highly abundant in the brain of Alzheimer’s disease (AD) patients. It demonstrates increased neurotoxicity compared to full length Aβ, suggesting an important role in the pathogenesis of AD. Transgenic Tg4-42 mice, a model for sporadic AD, express human Aβ_4-42 in Cornu Ammonis (CA1) neurons, and develop age-dependent hippocampal neuron loss and neurological deficits. In contrast to other transgenic AD mouse models, the Tg4-42 model exhibits synaptic hyperexcitability, altered synaptic short-term plasticity with no alterations in short- and long-term potentiation. The outcomes of this study are discussed in comparison with controversial results from other AD mouse models. Full article

(This article belongs to the Special Issue 25th Anniversary of the Amyloid Hypothesis and Alzheimer Disease)

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