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4 pages, 170 KiB

Open AccessEditorial

Special Issue: Natural Products: Anticancer and Beyond

by Qingbin Cui, Dong-Hua Yang and Zhe-Sheng Chen

Molecules 2018, 23(6), 1246; https://doi.org/10.3390/molecules23061246 - 23 May 2018

Cited by 23 | Viewed by 3553

Abstract

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Research

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12 pages, 638 KiB

Open AccessArticle

Evaluating the Intoxicating Degree of Liquor Products with Combinations of Fusel Alcohols, Acids, and Esters

by Jia Xie, Xiao-Fei Tian, Song-Gui He, Yun-Lu Wei, Bin Peng and Zhen-Qiang Wu

Molecules 2018, 23(6), 1239; https://doi.org/10.3390/molecules23061239 - 23 May 2018

Cited by 33 | Viewed by 4053

Abstract

To investigate the effects of fusel alcohols on the intoxicating degree of liquor products, formulated liquors (FLs) were prepared by blending 1-propanol, isobutanol, and isoamyl alcohol with ethanol, organic acids, and corresponding ethyl esters to simulate the formula of traditional Chinese liquors. The [...] Read more.

To investigate the effects of fusel alcohols on the intoxicating degree of liquor products, formulated liquors (FLs) were prepared by blending 1-propanol, isobutanol, and isoamyl alcohol with ethanol, organic acids, and corresponding ethyl esters to simulate the formula of traditional Chinese liquors. The prepared FLs were submitted for evaluation of their intoxicating degree (ID). The results showed that the fusel alcohols had a biphasic effect on the IDs of the FLs, depending on the comprehensive coordination of the characteristic minor components. The importance of the suitable ratio of alcohols/acids/esters (RAAE) on the IDs was also revealed. Under an optimal ratio level, the fusel alcohols exhibited negligible effects on the IDs of the FLs. Moreover, the ratio of isoamyl alcohol to isobutanol (IA/IB) showed a strong positive correlation to the IDs of the FLs. This study lays a foundation for the potential application in producing low-ID liquor. Full article

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12 pages, 2915 KiB

Open AccessArticle

Substructural Connectivity Fingerprint and Extreme Entropy Machines—A New Method of Compound Representation and Analysis

by Krzysztof Rataj, Wojciech Czarnecki, Sabina Podlewska, Agnieszka Pocha and Andrzej J. Bojarski

Molecules 2018, 23(6), 1242; https://doi.org/10.3390/molecules23061242 - 23 May 2018

Cited by 6 | Viewed by 4567

Abstract

Key-based substructural fingerprints are an important element of computer-aided drug design techniques. The usefulness of the fingerprints in filtering compound databases is invaluable, as they allow for the quick rejection of molecules with a low probability of being active. However, this method is [...] Read more.

Key-based substructural fingerprints are an important element of computer-aided drug design techniques. The usefulness of the fingerprints in filtering compound databases is invaluable, as they allow for the quick rejection of molecules with a low probability of being active. However, this method is flawed, as it does not consider the connections between substructures. After changing the connections between particular chemical moieties, the fingerprint representation of the compound remains the same, which leads to difficulties in distinguishing between active and inactive compounds. In this study, we present a new method of compound representation—substructural connectivity fingerprints (SCFP), providing information not only about the presence of particular substructures in the molecule but also additional data on substructure connections. Such representation was analyzed by the recently developed methodology—extreme entropy machines (EEM). The SCFP can be a valuable addition to virtual screening tools, as it represents compound structure with greater detail and more specificity, allowing for more accurate classification. Full article

(This article belongs to the Section Analytical Chemistry)

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18 pages, 2949 KiB

Open AccessArticle

Production of Minor Ginenosides from Panax notoginseng by Microwave Processing Method and Evaluation of Their Blood-Enriching and Hemostatic Activity

by Huiying Liu, Jun Pan, Ye Yang, Xiuming Cui and Yuan Qu

Molecules 2018, 23(6), 1243; https://doi.org/10.3390/molecules23061243 - 23 May 2018

Cited by 15 | Viewed by 3867

Abstract

A green solvent extraction technology involving a microwave processing method was used to increase the content of minor ginsenosides from Panax notoginseng. This article aims to investigate the optimization of preparation of the minor ginsenosides by this microwave processing method using single-factor [...] Read more.

A green solvent extraction technology involving a microwave processing method was used to increase the content of minor ginsenosides from Panax notoginseng. This article aims to investigate the optimization of preparation of the minor ginsenosides by this microwave processing method using single-factor experiments and response surface methodology (RSM), and discuss the blood-enriching activity and hemostatic activity of the extract of microwave processed P. notoginseng (EMPN) The RSM for production of the minor ginsenosides was based on a three-factor and three-level Box-Behnken design. When the optimum conditions of microwave power, temperature and time were 495.03 W, 150.68 °C and 20.32 min, respectively, results predicted that the yield of total minor ginsenosides (Y₉) would be 93.13%. The actual value of Y₉ was very similar to the predicted value. In addition, the pharmacological results of EMPN in vivo showed that EMPN had the effect of enriching blood in N-acetylphenylhydrazine (APH) and cyclophosphamide (CTX)-induced blood deficient mice because of the increasing content of white blood cells (WBCs) and hemoglobin (HGB) in blood. Hemostatic activity in vitro of EMPN showed that it had significantly shortened the clotting time in PT testing (p < 0.05). The hemostatic effect of EMPN was mainly caused by its components of Rh₄, 20(S)-Rg₃ and 20(R)-Rg₃. This microwave processing method is simple and suitable to mass-produce the minor ginsenosides from P. notoginseng. Full article

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

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15 pages, 3394 KiB

Open AccessArticle

Phosphate-Based Ultrahigh Molecular Weight Polyethylene Fibers for Efficient Removal of Uranium from Carbonate Solution Containing Fluoride Ions

by Rong Li, Yuna Li, Maojiang Zhang, Zhe Xing, Hongjuan Ma and Guozhong Wu

Molecules 2018, 23(6), 1245; https://doi.org/10.3390/molecules23061245 - 23 May 2018

Cited by 26 | Viewed by 3472

Abstract

This work provides a cost-effective approach for preparing functional polymeric fibers used for removing uranium (U(VI)) from carbonate solution containing NaF. Phosphate-based ultrahigh molecular weight polyethylene (UHMWPE-g-PO₄) fibers were developed by grafting of glycidyl methacrylate, and ring-opening reaction using phosphoric acid. [...] Read more.

This work provides a cost-effective approach for preparing functional polymeric fibers used for removing uranium (U(VI)) from carbonate solution containing NaF. Phosphate-based ultrahigh molecular weight polyethylene (UHMWPE-g-PO₄) fibers were developed by grafting of glycidyl methacrylate, and ring-opening reaction using phosphoric acid. Uranium (U(VI)) adsorption capacity of UHMWPE-g-PO₄ fibers was dependent on the density of phosphate groups (D_PO, mmol∙g⁻¹). UHMWPE-g-PO₄ fibers with a D_PO of 2.01 mmol∙g⁻¹ removed 99.5% of U(VI) from a Na₂CO₃ solution without the presence of NaF. In addition, when NaF concentration was 3 g∙L⁻¹, 150 times larger than that of U(VI), the U(VI) removal ratio was still able to reach 92%. The adsorption process was proved to follow pseudo-second-order kinetics and Langmuir isotherm model. The experimental maximum U(VI) adsorption capacity (Q_max) of UHMWPE-g-PO₄ fibers reached 110.7 mg∙g⁻¹, which is close to the calculated Q_max (117.1 mg∙g⁻¹) by Langmuir equation. Compared to F⁻, Cl⁻, NO₃⁻, and SO₄²⁻ did not influence U(VI) removal ratio, but, H₂PO₄⁻ and CO₃²⁻ significantly reduced U(VI) removal ratio in the order of F⁻ > H₂PO₄⁻ > CO₃²⁻. Cyclic U(VI) sorption-desorption tests suggested that UHMWPE-g-PO₄ fibers were reusable. These results support that UHMWPE-g-PO₄ fibers can efficiently remove U(VI) from carbonate solutions containing NaF. Full article

(This article belongs to the Special Issue Radiation Chemistry for New Materials and Applications)

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16 pages, 3765 KiB

Open AccessArticle

Exploring New Antioxidant and Mineral Compounds from Nymphaea alba Wild-Grown in Danube Delta Biosphere

by Mihaela Cudalbeanu, Ioana Otilia Ghinea, Bianca Furdui, Durand Dah-Nouvlessounon, Robert Raclea, Teodor Costache, Iulia Elena Cucolea, Florentina Urlan and Rodica Mihaela Dinica

Molecules 2018, 23(6), 1247; https://doi.org/10.3390/molecules23061247 - 23 May 2018

Cited by 37 | Viewed by 6466

Abstract

Nymphaea alba is an aquatic flowering plant from the Nymphaeaceae family that has been used for hundreds of years in traditional herbal medicine. The plant is characterized by different phytochemicals, depending on the geographical location. Herein, we have carried out, for the first [...] Read more.

Nymphaea alba is an aquatic flowering plant from the Nymphaeaceae family that has been used for hundreds of years in traditional herbal medicine. The plant is characterized by different phytochemicals, depending on the geographical location. Herein, we have carried out, for the first time, the separation and HPLC-MS/MS identification of some antioxidant compounds, such as polyphenols and flavonoids from N. alba extracts from the Danube Delta Biosphere, and investigated their possible antiradical properties. An ultrasonic method has been exhaustively used for the extraction of the antioxidant compounds from the different anatomic parts of N. alba (fruit, flower, leaf, stem, and root). The extracts that were obtained using ultrasound irradiation showed a large polyphenol (19.42 mg EqGA/100 mg extract) and flavonoid (0.97 mg EqQ/100 mg extract) content. The fruit and flower extracts showed the highest antioxidant activity index (AAI). Among the 27 phytochemical compounds identified in all of the N. alba extracts, rutin and p-coumaric acid were found as the major components. The content of macroelements and microelements in N. alba extracts were compared, and it was found that their concentrations depend on the different anatomic parts of the plant. This research contributes to the study of Nymphaeaceae family, being the first exhaustive phytochemical study of N. alba from a wild population in Romania. Full article

(This article belongs to the Section Natural Products Chemistry)

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20 pages, 8172 KiB

Open AccessArticle

Characterization of the Complete Chloroplast Genomes of Buddleja colvilei and B. sessilifolia: Implications for the Taxonomy of Buddleja L.

by Jia Ge, Lei Cai, Gui-Qi Bi, Gao Chen and Weibang Sun

Molecules 2018, 23(6), 1248; https://doi.org/10.3390/molecules23061248 - 23 May 2018

Cited by 21 | Viewed by 9019

Abstract

Buddleja colvilei Hook.f. & Thomson (Scrophulariaceae) is a threatened alpine plant with a distribution throughout the Himalayas, also used as an ornamental plant. The name Buddleja sessilifolia B.S. Sun ex S.Y. Pao was assigned in 1983 to a plant distributed throughout the Gaoligong [...] Read more.

Buddleja colvilei Hook.f. & Thomson (Scrophulariaceae) is a threatened alpine plant with a distribution throughout the Himalayas, also used as an ornamental plant. The name Buddleja sessilifolia B.S. Sun ex S.Y. Pao was assigned in 1983 to a plant distributed throughout the Gaoligong Mountains, but the name was later placed in synonymy with B. colvilei in the Flora of China. In this study we sequenced the complete chloroplast (cp) genomes of two individuals of B. colvilei and three individuals of B. sessilifolia from across the range. Both molecular and morphological analysis support the revision of B. sessilifolia. The phylogenetic analysis constructed with the whole cp genomes, the large single-copy regions (LSC), small single-copy regions (SSC), inverted repeat (IR) and the nuclear genes 18S/ITS1/5.8S/ITS2/28S all supported B. sessilifolia as a distinct species. Additionally, coalescence-based species delimitation methods (bGMYC, bPTP) using the whole chloroplast datasets also supported B. sessilifolia as a distinct species. The results suggest that the B. sessilifolia lineage was early diverging among the Asian Buddleja species. Overall gene contents were similar and gene arrangements were found to be highly conserved in the two species, however, fixed differences were found between the two species. A total of 474 single nucleotide polymorphisms (SNPs) were identified between the two species. The Principal Coordinate Analysis of the morphological characters resolved two groups and supported B. sessilifolia as a distinct species. Discrimination of B. colvilei and B. sessilifolia using morphological characters and the redescription of B. sessilifolia are detailed here. Full article

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20 pages, 2002 KiB

Open AccessArticle

Design, Synthesis and Antitumor Evaluation of Novel Pyrazolopyrimidines and Pyrazoloquinazolines

by Mohamed El-Naggar, Ashraf S. Hassan, Hanem M. Awad and Mohamed F. Mady

Molecules 2018, 23(6), 1249; https://doi.org/10.3390/molecules23061249 - 23 May 2018

Cited by 47 | Viewed by 4385

Abstract

A series of N-aryl-7-aryl-pyrazolo[1,5-a]pyrimidines 18a–u and N-aryl-pyrazolo[1,5-a]quinazolines 25a–c were designed and synthesized via the reaction of 5-aminopyrazoles 11a–c with enaminones 12a–g or 19, respectively. The new compounds were [...] Read more.

A series of N-aryl-7-aryl-pyrazolo[1,5-a]pyrimidines 18a–u and N-aryl-pyrazolo[1,5-a]quinazolines 25a–c were designed and synthesized via the reaction of 5-aminopyrazoles 11a–c with enaminones 12a–g or 19, respectively. The new compounds were screened for their in vitro antitumor activity toward liver (HepG-2) and breast (MCF-7) human cancer cells using 3-[4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide MTT assay. From the results, it was found that all compounds showed dose-dependent cytotoxic activities against both HepG-2 and MCF-7 cells. Two compounds 18o and 18a were selected for further investigations. Cell cycle analysis of liver (HepG-2) cells treated with 18o and breast (MCF-7) cells treated with 18a showed cell cycle arrest at G2/M phase and pro-apoptotic activity as indicated by annexin V-FITC staining. Full article

(This article belongs to the Section Medicinal Chemistry)

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19 pages, 4408 KiB

Open AccessArticle

Indole Derivatives as Cyclooxygenase Inhibitors: Synthesis, Biological Evaluation and Docking Studies

by Mashooq Ahmad Bhat, Mohamed A. Al-Omar, Mohammad Raish, Mushtaq Ahmad Ansari, Hatem A. Abuelizz, Ahmed H. Bakheit and Ahmed M. Naglah

Molecules 2018, 23(6), 1250; https://doi.org/10.3390/molecules23061250 - 24 May 2018

Cited by 40 | Viewed by 5193

Abstract

A new series of 2-(5-methoxy-2-methyl-1H-indol-3-yl)-N′-[(E)-(substituted phenyl) methylidene] acetohydrazide derivatives (S1–S18) were synthesized and evaluated for their anti-inflammatory activity, analgesic activity, ulcerogenic activity, lipid peroxidation, ulcer index and cyclooxygenase expression activities. All the synthesized [...] Read more.

A new series of 2-(5-methoxy-2-methyl-1H-indol-3-yl)-N′-[(E)-(substituted phenyl) methylidene] acetohydrazide derivatives (S1–S18) were synthesized and evaluated for their anti-inflammatory activity, analgesic activity, ulcerogenic activity, lipid peroxidation, ulcer index and cyclooxygenase expression activities. All the synthesized compounds were in good agreement with spectral and elemental analysis. Three synthesized compounds (S3, S7 and S14) have shown significant anti-inflammatory activity as compared to the reference drug indomethacin. Compound S3 was further tested for ulcerogenic index and cyclooxygenase (COX) expression activity. It was selectively inhibiting COX-2 expression and providing the gastric sparing activity. Docking studies have revealed the potential of these compounds to bind with COX-2 enzyme. Compound S3 formed a hydrogen bond between OH of Tyr 355 and NH₂ of Arg 120 with carbonyl group and this hydrogen bond was similar to that formed by indomethacin. This study provides insight for compound S3, as a new lead compound as anti-inflammatory agent and selective COX-2 inhibitor. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 12538 KiB

Open AccessArticle

T59, a New Compound Reconstructed from Curcumin, Induces Cell Apoptosis through Reactive Oxygen Species Activation in Human Lung Cancer Cells

by Zhendong Zhao, Yanjun Yang, Weihai Liu and Ziqian Li

Molecules 2018, 23(6), 1251; https://doi.org/10.3390/molecules23061251 - 24 May 2018

Cited by 10 | Viewed by 4129

Abstract

Curcumin is acknowledged for its antioxidant, anti-inflammatory, anti-cancer, and wound-healing properties. However, the biological activity and the molecular mechanisms of T59, which is a new derivative of curcumin, are not fully understood. The present study was aimed to determine the cytoxicity role of [...] Read more.

Curcumin is acknowledged for its antioxidant, anti-inflammatory, anti-cancer, and wound-healing properties. However, the biological activity and the molecular mechanisms of T59, which is a new derivative of curcumin, are not fully understood. The present study was aimed to determine the cytoxicity role of T59 in human lung cancer and the molecular mechanisms. Cytotoxicity and cell apoptosis effects induced by T59 were determined by MTT, AO staining, Annexin V, and JC-1. Compared with curcumin, T59 exerted more effective cytotoxicity and cell apoptosis effects in A549 and H1975. With the decreasing level of the mitochondrion membrane potential, the generation of reactive oxygen species (ROS) was increased and induced by T59. Furthermore, the expressions of cleaved-caspase-3 and Bax were increased, which were reversed by NAC mainly through the PI3K/AKT signaling pathway. Our results suggested that T59 has the potential for further investigation and study to act as an anti-cancer therapeutic against human lung cancer. Full article

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11 pages, 1891 KiB

Open AccessFeature PaperArticle

Carbon Nanohorn Suprastructures on a Paper Support as a Sorptive Phase

by Julia Ríos-Gómez, Beatriz Fresco-Cala, María Teresa García-Valverde, Rafael Lucena and Soledad Cárdenas

Molecules 2018, 23(6), 1252; https://doi.org/10.3390/molecules23061252 - 24 May 2018

Cited by 38 | Viewed by 4518

Abstract

This article describes a method for the modification of paper with single-wall carbon nanohorns (SWCNHs) to form stable suprastructures. The SWCNHs form stable dahlia-like aggregates in solution that are then self-assembled into superior structures if the solvent is evaporated. Dipping paper sections into [...] Read more.

This article describes a method for the modification of paper with single-wall carbon nanohorns (SWCNHs) to form stable suprastructures. The SWCNHs form stable dahlia-like aggregates in solution that are then self-assembled into superior structures if the solvent is evaporated. Dipping paper sections into a dispersion of SWCNHs leads to the formation of a thin film that can be used for microextraction purposes. The coated paper can be easily handled with a simple pipette tip, paving the way for disposable extraction units. As a proof of concept, the extraction of antidepressants from urine and their determination by direct infusion mass spectrometry is studied. Limits of detection (LODs) were 10 ng/L for desipramine, amitriptyline, and mianserin, while the precision, expressed as a relative standard deviation, was 7.2%, 7.3%, and 9.8%, respectively. Full article

(This article belongs to the Special Issue Solid Phase Extraction: State of the Art and Future Perspectives)

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13 pages, 1754 KiB

Open AccessArticle

Optimization of Production Conditions for Protoplasts and Polyethylene Glycol-Mediated Transformation of Gaeumannomyces tritici

by Mei Wang, Jie Zhang, Lanying Wang, Lirong Han, Xing Zhang and Juntao Feng

Molecules 2018, 23(6), 1253; https://doi.org/10.3390/molecules23061253 - 24 May 2018

Cited by 13 | Viewed by 5419

Abstract

Take-all, caused by Gaeumannomyces tritici, is one of the most important wheat root diseases worldwide, as it results in serious yield losses. In this study, G. tritici was transformed to express the hygromycin B phosphotransferase using a combined protoplast and polyethylene glycol [...] Read more.

Take-all, caused by Gaeumannomyces tritici, is one of the most important wheat root diseases worldwide, as it results in serious yield losses. In this study, G. tritici was transformed to express the hygromycin B phosphotransferase using a combined protoplast and polyethylene glycol (PEG)-mediated transformation technique. Based on a series of single-factor experimental results, three major factors—temperature, enzyme lysis time, and concentration of the lysing enzyme—were selected as the independent variables, which were optimized using the response surface methodology. A higher protoplast yield of 9.83 × 10⁷ protoplasts/mL was observed, and the protoplast vitality was also high, reaching 96.27% after optimization. Protoplasts were isolated under the optimal conditions, with the highest transformation frequency (46–54 transformants/μg DNA). Polymerase chain reaction and Southern blotting detection indicated that the genes of hygromycin phosphotransferase were successfully inserted into the genome of G. tritici. An optimised PEG-mediated protoplast transformation system for G. tritici was established. The techniques and procedures described will lay the foundation for establishing a good mutation library of G. tritici and could be used to transform other fungi. Full article

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14 pages, 5715 KiB

Open AccessArticle

Synthesis, Design, and Structure–Activity Relationship of the Pyrimidone Derivatives as Novel Selective Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase

by Le Xu, Wenjie Li, Yanyan Diao, Hongxia Sun, Honglin Li, Lili Zhu, Hongchang Zhou and Zhenjiang Zhao

Molecules 2018, 23(6), 1254; https://doi.org/10.3390/molecules23061254 - 24 May 2018

Cited by 15 | Viewed by 5123

Abstract

The inhibition of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) potentially represents a new treatment option for malaria, as P. falciparum relies entirely on a de novo pyrimidine biosynthetic pathway for survival. Herein, we report a series of pyrimidone derivatives as novel inhibitors [...] Read more.

The inhibition of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) potentially represents a new treatment option for malaria, as P. falciparum relies entirely on a de novo pyrimidine biosynthetic pathway for survival. Herein, we report a series of pyrimidone derivatives as novel inhibitors of PfDHODH. The most potent compound, 26, showed high inhibition activity against PfDHODH (IC₅₀ = 23 nM), with >400-fold species selectivity over human dihydroorotate dehydrogenase (hDHODH). The brand-new inhibitor scaffold targeting PfDHODH reported in this work may lead to the discovery of new antimalarial agents. Full article

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17 pages, 6321 KiB

Open AccessArticle

A Gelatin Hydrogel-Containing Nano-Organic PEI–Ppy with a Photothermal Responsive Effect for Tissue Engineering Applications

by Mantosh Kumar Satapathy, Batzaya Nyambat, Chih-Wei Chiang, Chih-Hwa Chen, Pei-Chun Wong, Po-Hsien Ho, Pei-Ru Jheng, Thierry Burnouf, Ching-Li Tseng and Er-Yuan Chuang

Molecules 2018, 23(6), 1256; https://doi.org/10.3390/molecules23061256 - 24 May 2018

Cited by 62 | Viewed by 10582

Abstract

The introduction and designing of functional thermoresponsive hydrogels have been recommended as recent potential therapeutic approaches for biomedical applications. The development of bioactive materials such as thermosensitive gelatin-incorporated nano-organic materials with a porous structure and photothermally triggerable and cell adhesion properties may potentially [...] Read more.

The introduction and designing of functional thermoresponsive hydrogels have been recommended as recent potential therapeutic approaches for biomedical applications. The development of bioactive materials such as thermosensitive gelatin-incorporated nano-organic materials with a porous structure and photothermally triggerable and cell adhesion properties may potentially achieve this goal. This novel class of photothermal hydrogels can provide an advantage of hyperthermia together with a reversibly transformable hydrogel for tissue engineering. Polypyrrole (Ppy) is a bioorganic conducting polymeric substance and has long been used in biomedical applications owing to its brilliant stability, electrically conductive features, and excellent absorbance around the near-infrared (NIR) region. In this study, a cationic photothermal triggerable/guidable gelatin hydrogel containing a polyethylenimine (PEI)–Ppy nanocomplex with a porous microstructure was established, and its physicochemical characteristics were studied through dynamic light scattering, scanning electronic microscopy, transmission electron microscopy, an FTIR; and cellular interaction behaviors towards fibroblasts incubated with a test sample were examined via MTT assay and fluorescence microscopy. Photothermal performance was evaluated. Furthermore, the in vivo study was performed on male Wistar rat full thickness excisions model for checking the safety and efficacy of the designed gelatin–PEI–Ppy nanohydrogel system in wound healing and for other biomedical uses in future. This photothermally sensitive hydrogel system has an NIR-triggerable property that provides local hyperthermic temperature by PEI–Ppy nanoparticles for tissue engineering applications. Features of the designed hydrogel may fill other niches, such as being an antibacterial agent, generation of free radicals to further improve wound healing, and remodeling of the promising photothermal therapy for future tissue engineering applications. Full article

(This article belongs to the Collection Nanomedicine)

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13 pages, 2301 KiB

Open AccessFeature PaperArticle

The Conversion of 5,5′-Bi(1,2,3-dithiazolylidenes) into Isothiazolo[5,4-d]isothiazoles

by Lidia S. Konstantinova, Ilia V. Baranovsky, Vlada V. Strunyasheva, Andreas S. Kalogirou, Vadim V. Popov, Konstantin A. Lyssenko, Panayiotis A. Koutentis and Oleg A. Rakitin

Molecules 2018, 23(6), 1257; https://doi.org/10.3390/molecules23061257 - 24 May 2018

Cited by 7 | Viewed by 4105

Abstract

Thermolysis of 4,4′-dichloro-, 4,4′-diaryl-, and 4,4′-di(thien-2-yl)-5,5′-bi(1,2,3-dithiazol-ylidenes) affords the respective 3,6-dichloro-, 3,6-diaryl- and 3,6-di(thien-2-yl)isothiazolo[5,4-d]-isothiazoles in low to high yields. The transformation of the 4,4′-diaryl- and 4,4′-di(thien-2-yl)-5,5′-bi(1,2,3-dithiazolylidenes) occurs at lower temperatures in the presence of the thiophiles triphenylphosphine or tetraethylammonium iodide. Optimized reaction [...] Read more.

Thermolysis of 4,4′-dichloro-, 4,4′-diaryl-, and 4,4′-di(thien-2-yl)-5,5′-bi(1,2,3-dithiazol-ylidenes) affords the respective 3,6-dichloro-, 3,6-diaryl- and 3,6-di(thien-2-yl)isothiazolo[5,4-d]-isothiazoles in low to high yields. The transformation of the 4,4′-diaryl- and 4,4′-di(thien-2-yl)-5,5′-bi(1,2,3-dithiazolylidenes) occurs at lower temperatures in the presence of the thiophiles triphenylphosphine or tetraethylammonium iodide. Optimized reaction conditions and a mechanistic rationale for the thiophile-mediated ring transformation are presented. Full article

(This article belongs to the Special Issue Recent Advances in Nitrogen-Containing Aromatic Heterocycles)

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14 pages, 1850 KiB

Open AccessArticle

Establishment and Phytochemical Analysis of a Callus Culture from Ageratina pichinchensis (Asteraceae) and Its Anti-Inflammatory Activity

by Mariana Sánchez-Ramos, Silvia Marquina Bahena, Antonio Romero-Estrada, Antonio Bernabé-Antonio, Francisco Cruz-Sosa, Judith Gonzálesssz-Christen, Juan José Acevedo-Fernández, Irene Perea-Arango and Laura Alvarez

Molecules 2018, 23(6), 1258; https://doi.org/10.3390/molecules23061258 - 25 May 2018

Cited by 30 | Viewed by 4870

Abstract

A protocol was established to produce bioactive compounds in a callus culture of Ageratina pichinchensis by using 1 mg L⁻¹ NAA with 0.1 mg L⁻¹ KIN. The phytochemical study of the EtOAc extract obtained from the callus biomass, allowed the isolation [...] Read more.

A protocol was established to produce bioactive compounds in a callus culture of Ageratina pichinchensis by using 1 mg L⁻¹ NAA with 0.1 mg L⁻¹ KIN. The phytochemical study of the EtOAc extract obtained from the callus biomass, allowed the isolation and characterization of eleven secondary metabolites, of which dihydrobenzofuran (5) and 3-epilupeol (7), showed important anti-inflammatory activity. Compound 5 inhibits in vitro the secretion of NO (IC₅₀ = 36.96 ± 1.06 μM), IL-6 (IC₅₀ = 73.71 ± 3.21 μM), and TNF-α (IC₅₀ = 73.20 ± 5.99 μM) in RAW (Murine macrophage cells) 264.7 macrophages, as well as the activation of NF-κB (40% at 150 μM) in RAW-blue macrophages, while compound 7 has been described that inhibit the in vivo TPA-induced ear edema, and the in vitro production of NO, and the PLA2 enzyme activity. In addition, quantitative GC-MS analysis showed that the anti-inflammatory metabolites 5 and 7 were not detected in the wild plant. Overall, our results indicated that A. pichinchensis can be used as an alternative biotechnological resource for obtaining anti-inflammatory compounds. This is the first report of the anti-inflammatory activity of compound 5 and its production in a callus culture of A. pichinchensis. Full article

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13 pages, 1041 KiB

Open AccessArticle

Hydrophobic Amino Acid Content in Onions as Potential Fingerprints of Geographical Origin: The Case of Rossa da Inverno sel. Rojo Duro

by Federica Ianni, Antonella Lisanti, Maura Marinozzi, Emidio Camaioni, Lucia Pucciarini, Andrea Massoli, Roccaldo Sardella, Luciano Concezzi and Benedetto Natalini

Molecules 2018, 23(6), 1259; https://doi.org/10.3390/molecules23061259 - 25 May 2018

Cited by 13 | Viewed by 4404

Abstract

In this study, we were interested in comparing the amino acid profile in a specific variety of onion, Rossa da inverno sel. Rojo Duro, produced in two different Italian sites: the Cannara (Umbria region) and Imola (Emilia Romagna region) sites. Onions were [...] Read more.

In this study, we were interested in comparing the amino acid profile in a specific variety of onion, Rossa da inverno sel. Rojo Duro, produced in two different Italian sites: the Cannara (Umbria region) and Imola (Emilia Romagna region) sites. Onions were cultivated in a comparable manner, mostly in terms of the mineral fertilization, seeding, and harvesting stages, as well as good weed control. Furthermore, in both regions, the plants were irrigated by the water sprinkler method and subjected to similar temperature and weather conditions. A further group of Cannara onions that were grown by micro-irrigation was also evaluated. After the extraction of the free amino acid mixture, an ion-pairing reversed-phase (IP-RP) HPLC method allowed for the separation and the evaporative light scattering detection of almost all the standard proteinogenic amino acids. However, only the peaks corresponding to leucine (Leu), phenylalanine (Phe), and tryptophan (Trp), were present in all the investigated samples and they were unaffected from the matrix interfering peaks. The use of the beeswarm/box plots revealed that the content of Leu and Phe were markedly influenced by the geographical origin of the onions (with *** p << 0.001 for Phe), but not by the irrigation procedure. The applied HPLC method was validated in terms of the specificity, the linearity (a logarithm transformation was applied for the method linearization), the limit of detection (LOD) and limit of quantification (LOQ), the accuracy (≥90% for inter-day Recovery percentage), and the precision (≤10.51 for the inter-day RSD percentage), before the quantitative assay of Leu, Phe, and Trp in the onion samples. These preliminary findings are a good starting point for considering the quantity of the specific amino acids in the Rossa da inverno sel. Rojo Duro variety as a fingerprint of its geographical origin. Full article

(This article belongs to the Special Issue Qualitative and Quantitative Analysis of Bioactive Natural Products 2018)

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7 pages, 2040 KiB

Open AccessArticle

High Conversion of Styrene, Ethylene, and Hydrogen to Linear Monoalkylbenzenes

by David Hermann Lamparelli, Antonio Ricca, Vincenzo Palma and Leone Oliva

Molecules 2018, 23(6), 1260; https://doi.org/10.3390/molecules23061260 - 25 May 2018

Viewed by 3298

Abstract

1-Alkylbenzenes as a precursor of surfactants, can be produced from ethylene, styrene, and hydrogen. These intermediates, lacking tertiary carbons, are environmentally more benign than commercial ones that bear the aromatic ring linked to an internal carbon of the aliphatic chain. The one-pot synthesis [...] Read more.

1-Alkylbenzenes as a precursor of surfactants, can be produced from ethylene, styrene, and hydrogen. These intermediates, lacking tertiary carbons, are environmentally more benign than commercial ones that bear the aromatic ring linked to an internal carbon of the aliphatic chain. The one-pot synthesis of highly linear 1-alkylbenzenes (LABs) through the homogeneous catalysis of olefin poly-insertion from cheap and largely available reagents can be carried out with a high turnover and selectivity. A purposely designed reactor that allows for the fine control of the three components feed, along with temperature, plays a key role in this achievement. A turnover of 194 g of LABs per mmol of catalyst per hour can be obtained with the simultaneous removal of polyethylene as a by-product. Full article

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

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29 pages, 6327 KiB

Open AccessCommunication

Monitoring the Chemical Profile in Agarwood Formation within One Year and Speculating on the Biosynthesis of 2-(2-Phenylethyl)Chromones

by Ge Liao, Wen-Hua Dong, Jin-Ling Yang, Wei Li, Jun Wang, Wen-Li Mei and Hao-Fu Dai

Molecules 2018, 23(6), 1261; https://doi.org/10.3390/molecules23061261 - 25 May 2018

Cited by 52 | Viewed by 5527

Abstract

Agarwood is highly valued for its uses as incense, perfume, and medicine. However, systematic analyses of dynamic changes of secondary metabolites during the process of agarwood formation have not yet been reported. In this study, agarwood was produced by transfusing the agarwood inducer [...] Read more.

Agarwood is highly valued for its uses as incense, perfume, and medicine. However, systematic analyses of dynamic changes of secondary metabolites during the process of agarwood formation have not yet been reported. In this study, agarwood was produced by transfusing the agarwood inducer into the trunk of Aquilaria sinensis, and changing patterns of chemical constituents, especially 2-(2-phenylethyl)chromones (PECs), in wood samples collected from the 1st to 12th month, were analyzed by GC-EI-MS and UPLC-ESI-MS/MS methods. Aromatic compounds, steroids, fatty acids/esters, sesquiterpenoids, and PECs were detected by GC-MS, in which PECs were the major constituents. Following this, UPLC-MS was used for further comprehensive analysis of PECs, from which we found that 2-(2-phenylethyl)chromones of flindersia type (FTPECs) were the most abundant, while PECs with epoxidated chromone moiety were detected with limited numbers and relatively low content. Speculation on the formation of major FTPECs was fully elucidated in our context. The key step of FTPECs biosynthesis is possibly catalyzed by type III polyketide synthases (PKSs) which condensate dihydro-cinnamoyl-CoA analogues and malonyl-CoA with 2-hydroxy-benzoyl-CoA to produce 2-(2-phenyethyl)chromone scaffold, or with 2,5-dihydroxybenzoyl-CoA to form FTPECS with 6-hydroxy group, which may serve as precursors for further reactions catalyzed by hydroxylase or O-methyltransferase (OMT) to produce FTPECs with diverse substitution patterns. It is the first report that systematically analyzed dynamic changes of secondary metabolites during the process of agarwood formation and fully discussed the biosynthetic pathway of PECs. Full article

(This article belongs to the Section Analytical Chemistry)

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18 pages, 649 KiB

Open AccessArticle

Profile of Polyphenolic and Essential Oil Composition of Polish Propolis, Black Poplar and Aspens Buds

by Piotr Okińczyc, Antoni Szumny, Jakub Szperlik, Anna Kulma, Roman Franiczek, Beata Żbikowska, Barbara Krzyżanowska and Zbigniew Sroka

Molecules 2018, 23(6), 1262; https://doi.org/10.3390/molecules23061262 - 25 May 2018

Cited by 45 | Viewed by 5530

Abstract

In this work, we studied similarities and differences between 70% ethanol in water extract (70EE) and essential oils (EOs) obtained from propolis, black poplars (Populus nigra L.) and aspens (P. tremula L.) to ascertain which of these is a better indicator [...] Read more.

In this work, we studied similarities and differences between 70% ethanol in water extract (70EE) and essential oils (EOs) obtained from propolis, black poplars (Populus nigra L.) and aspens (P. tremula L.) to ascertain which of these is a better indicator of the plant species used by bees to collect propolis precursors. Composition of 70EE was analyzed by UPLC-PDA-MS, while GC-MS was used to research the EOs. Principal component analyses (PCA) and calculations of Spearman’s coefficient rank were used for statistical analysis. Statistical analysis exhibited correlation between chemical compositions of propolis and Populus buds’ 70EE. In the case of EOs, results were less clear. Compositions of black poplars, aspens EOs and propolises have shown more variability than 70EE. Different factors such as higher instability of EOs compared to 70EE, different degradation pattern of benzyl esters to benzoic acid, differences in plant metabolism and bees’ preferences may be responsible for these phenomena. Our research has therefore shown that 70EE of propolis reflected the composition of P. nigra or complex aspen–black poplar origin. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 1171 KiB

Open AccessArticle

Sporulosol, a New Ketal from the Fungus Paraconiothyrium sporulosum

by Chen Zhao, Peinan Fu, Yang Zhang, Xingzhong Liu, Fengxia Ren and Yongsheng Che

Molecules 2018, 23(6), 1263; https://doi.org/10.3390/molecules23061263 - 25 May 2018

Cited by 15 | Viewed by 3887

Abstract

Sporulosol (1), a new ketal, together with four known compounds, has been isolated from the liquid fermentation cultures of a wetland-soil-derived fungus, Paraconiothyrium sporulosum. Its structure was elucidated primarily by NMR experiments, and was further confirmed by X-ray crystallography. Sporulosol [...] Read more.

Sporulosol (1), a new ketal, together with four known compounds, has been isolated from the liquid fermentation cultures of a wetland-soil-derived fungus, Paraconiothyrium sporulosum. Its structure was elucidated primarily by NMR experiments, and was further confirmed by X-ray crystallography. Sporulosol was obtained as a racemic mixture and the resolved two enantiomers racemized immediately after chiral separation. Sporulosol appears to be the first ketal derived from a 6H-benzo[c]chromen-6-one and a benzofuranone unit. The compound showed modest cytotoxicity toward the human tumor cell line T24, with an IC₅₀ value of 18.2 µM. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 1237 KiB

Open AccessArticle

Determination of Chlortetracycline Residues, Antimicrobial Activity and Presence of Resistance Genes in Droppings of Experimentally Treated Broiler Chickens

by Javiera Cornejo, Karina Yevenes, Constanza Avello, Ekaterina Pokrant, Aldo Maddaleno, Betty San Martin and Lisette Lapierre

Molecules 2018, 23(6), 1264; https://doi.org/10.3390/molecules23061264 - 25 May 2018

Cited by 24 | Viewed by 5820

Abstract

Tetracyclines are important antimicrobial drugs for poultry farming that are actively excreted via feces and urine. Droppings are one of the main components in broiler bedding, which is commonly used as an organic fertilizer. Therefore, bedding becomes an unintended carrier of antimicrobial residues [...] Read more.

Tetracyclines are important antimicrobial drugs for poultry farming that are actively excreted via feces and urine. Droppings are one of the main components in broiler bedding, which is commonly used as an organic fertilizer. Therefore, bedding becomes an unintended carrier of antimicrobial residues into the environment and may pose a highly significant threat to public health. For this depletion study, 60 broiler chickens were treated with 20% chlortetracycline (CTC) under therapeutic conditions. Concentrations of CTC and 4-epi-CTC were then determined in their droppings. Additionally, this work also aimed to detect the antimicrobial activity of these droppings and the phenotypic susceptibility to tetracycline in E. coli isolates, as well as the presence of tet(A), tet(B), and tet(G) resistance genes. CTC and 4-epi-CTC concentrations that were found ranged from 179.5 to 665.8 µg/kg. Based on these data, the depletion time for chicken droppings was calculated and set at 69 days. All samples presented antimicrobial activity, and a resistance to tetracyclines was found in bacterial strains that were isolated from these samples. Resistance genes tet(A) and tet(B) were also found in these samples. Full article

(This article belongs to the Special Issue Trends in Veterinary Drug Analysis: Multiresidue and Omic Approaches)

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10 pages, 1652 KiB

Open AccessArticle

Depsidomycins B and C: New Cyclic Peptides from a Ginseng Farm Soil-Derived Actinomycete

by Yun Kwon, Woong Sub Byun, Byung-Yong Kim, Myoung Chong Song, Munhyung Bae, Yeo Joon Yoon, Jongheon Shin, Sang Kook Lee and Dong-Chan Oh

Molecules 2018, 23(6), 1266; https://doi.org/10.3390/molecules23061266 - 25 May 2018

Cited by 13 | Viewed by 4355

Abstract

LC/MS-based chemical profiling of a ginseng farm soil-derived actinomycete strain, Streptomyces sp. BYK1371, enabled the discovery of two new cyclic heptapeptides, depsidomycins B and C (1 and 2), each containing two piperazic acid units and a formyl group at their N [...] Read more.

LC/MS-based chemical profiling of a ginseng farm soil-derived actinomycete strain, Streptomyces sp. BYK1371, enabled the discovery of two new cyclic heptapeptides, depsidomycins B and C (1 and 2), each containing two piperazic acid units and a formyl group at their N-terminus. The structures of 1 and 2 were elucidated by a combination of spectroscopic and chemical analyses. These new compounds were determined to possess d-leucine, d-threonine, d-valine, and S-piperazic acid based on the advanced Marfey’s method and a GITC (2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl isothiocyanate) derivatization of their hydrolysates, followed by LC/MS analysis. Depsidomycins B and C displayed significant antimetastatic activities against metastatic breast cancer cells (MDA-MB-231). Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 293 KiB

Open AccessArticle

Nutrients Composition in Fit Snacks Made from Ostrich, Beef and Chicken Dried Meat

by Żaneta Zdanowska-Sąsiadek, Joanna Marchewka, Jarosław Olav Horbańczuk, Agnieszka Wierzbicka, Paulina Lipińska, Artur Jóźwik, Atanas G. Atanasov, Łukasz Huminiecki, Aleksander Sieroń, Karolina Sieroń, Nina Strzałkowska, Adrian Stelmasiak, Stefaan De Smet, Thomas Van Hecke and Louwrens C. Hoffman

Molecules 2018, 23(6), 1267; https://doi.org/10.3390/molecules23061267 - 25 May 2018

Cited by 32 | Viewed by 6873

Abstract

The aim of the study was to compare three types of meat snacks made from ostrich, beef, and chicken meat in relation to their nutrients content including fat, fatty acids, heme iron, and peptides, like anserine and carnosine, from which human health may [...] Read more.

The aim of the study was to compare three types of meat snacks made from ostrich, beef, and chicken meat in relation to their nutrients content including fat, fatty acids, heme iron, and peptides, like anserine and carnosine, from which human health may potentially benefit. Dry meat samples were produced, from one type of muscle, obtained from ostrich (m. ambiens), beef (m. semimembranosus), and broiler chicken meat (m. pectoralis major). The composition of dried ostrich, beef, and chicken meat, with and without spices was compared. We show that meat snacks made from ostrich, beef, and chicken meat were characterized by high concentration of nutrients including proteins, minerals (heme iron especially in ostrich, than in beef), biologically active peptides (carnosine—in beef, anserine—in ostrich then in chicken meat). The, beneficial to human health, n-3 fatty acids levels differed significantly between species. Moreover, ostrich jerky contained four times less fat as compared to beef and half of that in chicken. In conclusion we can say that dried ostrich, beef, and chicken meat could be a good source of nutritional components. Full article

13 pages, 5160 KiB

Open AccessArticle

Theoretical Investigations on Mechanisms and Pathways of C₂H₅O₂ with BrO Reaction in the Atmosphere

by Chenggang Lu, Yizhen Tang, Wei Zhang, Xunshuai Qu and Zhihao Fu

Molecules 2018, 23(6), 1268; https://doi.org/10.3390/molecules23061268 - 25 May 2018

Cited by 1 | Viewed by 3765

Abstract

In this work, feasible mechanisms and pathways of the C₂H₅O₂ + BrO reaction in the atmosphere were investigated using quantum chemistry methods, i.e., QCISD(T)/6-311++G(2df,2p)//B3LYP/6-311++G(2df,2p) levels of theory. Our result indicates that the title reaction occurs on both the [...] Read more.

In this work, feasible mechanisms and pathways of the C₂H₅O₂ + BrO reaction in the atmosphere were investigated using quantum chemistry methods, i.e., QCISD(T)/6-311++G(2df,2p)//B3LYP/6-311++G(2df,2p) levels of theory. Our result indicates that the title reaction occurs on both the singlet and triplet potential energy surfaces (PESs). Kinetically, singlet C₂H₅O₃Br and C₂H₅O₂BrO were dominant products under the atmospheric conditions below 300 K. CH₃CHO₂ + HOBr, CH₃CHO + HOBrO, and CH₃CHO + HBrO₂ are feasible to a certain extent thermodynamically. Because of high energy barriers, all products formed on the triplet PES are negligible. Moreover, time-dependent density functional theory (TDDFT) calculation implies that C₂H₅O₃Br and C₂H₅O₂BrO will photolyze under the sunlight. Full article

(This article belongs to the Special Issue Theoretical Investigations of Reaction Mechanisms)

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8 pages, 2869 KiB

Open AccessCommunication

Dicyanamide Bridged Cu(II)36-Metallacrown-6 Complex with 1,4,7-Triisopropyl-1,4,7-Triazacyclononane and Binding Properties with DNA

by Yong-Sheng Yang, Li-Jun Liu, Hai-Yan Ju, Xiu-Ying Liu, Yu-Guang Li and Shi-Ping Yan

Molecules 2018, 23(6), 1269; https://doi.org/10.3390/molecules23061269 - 25 May 2018

Cited by 5 | Viewed by 3630

Abstract

A novel 36-metallacrown-6 complex [CuL(N(CN)₂)(PF₆)]₆∙0.5H₂O 1 was achieved using a tridendate ligand, 1,4,7-triisopropyl-1,4,7-triazacyclononane (L), and a flexible ligand, dicyanamide in MeOH. The μ_1,5 bridging models of the dicyanamide ligand linked the macrocycle to form [...] Read more.

A novel 36-metallacrown-6 complex [CuL(N(CN)₂)(PF₆)]₆∙0.5H₂O 1 was achieved using a tridendate ligand, 1,4,7-triisopropyl-1,4,7-triazacyclononane (L), and a flexible ligand, dicyanamide in MeOH. The μ_1,5 bridging models of the dicyanamide ligand linked the macrocycle to form in a specific size with the chair conformation. The anion was important to form this 36-metallacrown-6 complex, as change was obtained with the larger anion BPh₄⁻, binuclear copper compound 2. The magnetic property indicates that slightly ferromagnetic interactions resulted from a superexchange mechanism. DNA binding properties were also studied. UV and fluorescence spectra showed that complex 1 could bind with DNA. Full article

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

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11 pages, 1825 KiB

Open AccessArticle

An Electron-Transporting Thiazole-Based Polymer Synthesized Through Direct (Hetero)Arylation Polymerization

by Patricia Chávez, Ibrahim Bulut, Sadiara Fall, Olzhas A. Ibraikulov, Christos L. Chochos, Jérémy Bartringer, Thomas Heiser, Patrick Lévêque and Nicolas Leclerc

Molecules 2018, 23(6), 1270; https://doi.org/10.3390/molecules23061270 - 25 May 2018

Cited by 6 | Viewed by 5056

Abstract

In this work, a new n-type polymer based on a thiazole-diketopyrrolopyrrole unit has been synthesized through direct (hetero)arylation polycondensation. The molar mass has been optimized by systematic variation of the the monomer concentration. Optical and electrochemical properties have been studied. They clearly [...] Read more.

In this work, a new n-type polymer based on a thiazole-diketopyrrolopyrrole unit has been synthesized through direct (hetero)arylation polycondensation. The molar mass has been optimized by systematic variation of the the monomer concentration. Optical and electrochemical properties have been studied. They clearly suggested that this polymer possess a high electron affinity together with a very interesting absorption band, making it a good non-fullerene acceptor candidate. As a consequence, its charge transport and photovoltaic properties in a blend with the usual P3HT electron-donating polymer have been investigated. Full article

(This article belongs to the Special Issue Direct (Hetero)Arylation: A New Tool for Organic Electronics)

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14 pages, 1384 KiB

Open AccessArticle

Enzymatic Synthesis of a Novel Pterostilbene α-Glucoside by the Combination of Cyclodextrin Glucanotransferase and Amyloglucosidase

by José L. González-Alfonso, David Rodrigo-Frutos, Efres Belmonte-Reche, Pablo Peñalver, Ana Poveda, Jesús Jiménez-Barbero, Antonio O. Ballesteros, Yoshihiko Hirose, Julio Polaina, Juan C. Morales, María Fernández-Lobato and Francisco J. Plou

Molecules 2018, 23(6), 1271; https://doi.org/10.3390/molecules23061271 - 25 May 2018

Cited by 26 | Viewed by 7532

Abstract

The synthesis of a novel α-glucosylated derivative of pterostilbene was performed by a transglycosylation reaction using starch as glucosyl donor, catalyzed by cyclodextrin glucanotransferase (CGTase) from Thermoanaerobacter sp. The reaction was carried out in a buffer containing 20% (v/v) [...] Read more.

The synthesis of a novel α-glucosylated derivative of pterostilbene was performed by a transglycosylation reaction using starch as glucosyl donor, catalyzed by cyclodextrin glucanotransferase (CGTase) from Thermoanaerobacter sp. The reaction was carried out in a buffer containing 20% (v/v) DMSO to enhance the solubility of pterostilbene. Due to the formation of several polyglucosylated products with CGTase, the yield of monoglucoside was increased by the treatment with a recombinant amyloglucosidase (STA1) from Saccharomyces cerevisiae (var. diastaticus). This enzyme was not able to hydrolyze the linkage between the glucose and pterostilbene. The monoglucoside was isolated and characterized by combining ESI-MS and 2D-NMR methods. Pterostilbene α-d-glucopyranoside is a novel compound. The α-glucosylation of pterostilbene enhanced its solubility in water to approximately 0.1 g/L. The α-glucosylation caused a slight loss of antioxidant activity towards ABTS˙⁺ radicals. Pterostilbene α-d-glucopyranoside was less toxic than pterostilbene for human SH-S5Y5 neurons, MRC5 fibroblasts and HT-29 colon cancer cells, and similar for RAW 264.7 macrophages. Full article

(This article belongs to the Section Green Chemistry)

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10 pages, 1630 KiB

Open AccessCommunication

Antibodies towards Tyrosine Amyloid-Like Fibrils Allow Toxicity Modulation and Cellular Imaging of the Assemblies

by Dor Zaguri, Topaz Kreiser, Shira Shaham-Niv and Ehud Gazit

Molecules 2018, 23(6), 1273; https://doi.org/10.3390/molecules23061273 - 26 May 2018

Cited by 35 | Viewed by 4950

Abstract

The amino acid tyrosine forms cytotoxic amyloid-like fibrils by molecular self-assembly. However, the production of antibodies towards tyrosine assemblies, reflecting their presentation to the immune system, was not demonstrated yet. Here, we describe the production of antibodies that specifically recognize tyrosine in its [...] Read more.

The amino acid tyrosine forms cytotoxic amyloid-like fibrils by molecular self-assembly. However, the production of antibodies towards tyrosine assemblies, reflecting their presentation to the immune system, was not demonstrated yet. Here, we describe the production of antibodies that specifically recognize tyrosine in its fibrillated form. The antibodies were demonstrated to specifically bind self-assembled tyrosine, in contrast to its non-aggregated form or disintegrated fibrils. The antibodies could be used for immunostaining of tyrosine fibrils in cultured cells. Furthermore, confocal microscopy allowed a demonstration of the intracellular presence of the metabolite amyloids in a neuroblastoma cell model. Finally, pre-incubation of tyrosine fibrils with the antibodies resulted in significant reduction in their cytotoxicity. Taken together, we provide an experimental proof for the immunogenicity of tyrosine amyloid fibrillary assemblies. These specific antibodies against tyrosine structures could be further used as a research tool to study the dynamics, toxicity and cellular localization of the assemblies. Full article

(This article belongs to the Special Issue 25th Anniversary of the Amyloid Hypothesis and Alzheimer Disease)

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15 pages, 6401 KiB

Open AccessArticle

Betaine Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats via Inhibiting Inflammatory Response

by Jia-mei Yang, Ru Zhou, Min Zhang, Huan-ran Tan and Jian-qiang Yu

Molecules 2018, 23(6), 1274; https://doi.org/10.3390/molecules23061274 - 26 May 2018

Cited by 49 | Viewed by 5655

Abstract

Background: Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, leading to right ventricular failure and death. Recent studies have suggested that chronic inflammatory processes are involved in the pathogenesis of PAH. Several studies have demonstrated that betaine possesses outstanding anti-inflammatory [...] Read more.

Background: Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, leading to right ventricular failure and death. Recent studies have suggested that chronic inflammatory processes are involved in the pathogenesis of PAH. Several studies have demonstrated that betaine possesses outstanding anti-inflammatory effects. However, whether betaine exerts protective effects on PAH by inhibiting inflammatory responses in the lungs needs to be explored. To test our hypothesis, we aimed to investigate the effects of betaine on monocrotaline-induced PAH in rats and attempted to further clarify the possible mechanisms. Methods: PAH was induced by monocrotaline (50 mg/kg) and oral administration of betaine (100, 200, and 400 mg/kg/day). The mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricle hypertrophy index were used to evaluate the development of PAH. Hematoxylin and eosin staining and Masson staining were performed to measure the extents of vascular remodeling and proliferation in fibrous tissue. Monocyte chemoattractant protein-1 (MCP-1) and endothelin-1 (ET-1) were also detected by immunohistochemical staining. Nuclear factor-κB (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) were assessed by Western blot. Results: This study showed that betaine improved the abnormalities in right ventricular systolic pressure, mean pulmonary arterial pressure, right ventricle hypertrophy index, and pulmonary arterial remodeling induced by monocrotaline compared with the PAH group. The levels of MCP-1 and ET-1 also decreased. Western blot indicated that the protein expression levels of NF-κB, TNF-α, and IL-1β significantly decreased (p < 0.01). Conclusion: Our study demonstrated that betaine attenuated PAH through its anti-inflammatory effects. Hence, the present data may offer novel targets and promising pharmacological perspectives for treating monocrotaline-induced PAH. Full article

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16 pages, 2738 KiB

Open AccessArticle

O-Linked N-Acetylglucosamine Transiently Elevates in HeLa Cells during Mitosis

by Viktória Fisi, Emese Kátai, József Orbán, Silvia Dossena, Attila Miseta and Tamás Nagy

Molecules 2018, 23(6), 1275; https://doi.org/10.3390/molecules23061275 - 26 May 2018

Cited by 6 | Viewed by 5937

Abstract

O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins. O-GlcNAc modification influences many cellular mechanisms, including carbohydrate metabolism, signal transduction and protein degradation. Multiple studies also showed that cell [...] Read more.

O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins. O-GlcNAc modification influences many cellular mechanisms, including carbohydrate metabolism, signal transduction and protein degradation. Multiple studies also showed that cell cycle might be modulated by O-GlcNAc. Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial. In this study, we analysed the dynamic changes of overall O-GlcNAc levels in HeLa cells using double thymidine block. O-GlcNAc levels in G₁, S, G₂ and M phase were measured. We observed that O-GlcNAc levels are significantly increased during mitosis in comparison to the other cell cycle phases. However, this change could only be detected when mitotic cells were enriched by harvesting round shaped cells from the G₂/M fraction of the synchronized cells. Our data verify that O-GlcNAc is elevated during mitosis, but also emphasize that O-GlcNAc levels can significantly change in a short period of time. Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies. Full article

(This article belongs to the Special Issue Functional Roles of Protein O-Glycosylation)

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13 pages, 2418 KiB

Open AccessArticle

The Chloroplast Genome of Lilium henrici: Genome Structure and Comparative Analysis

by Hai-Ying Liu, Yan Yu, Yi-Qi Deng, Juan Li, Zi-Xuan Huang and Song-Dong Zhou

Molecules 2018, 23(6), 1276; https://doi.org/10.3390/molecules23061276 - 26 May 2018

Cited by 48 | Viewed by 6354

Abstract

Lilium henrici Franchet, which belongs to the family Liliaceae, is an endangered plant native to China. The wild populations of L. henrici have been largely reduced by habitat degradation or loss. In our study, we determined the whole chloroplast genome sequence for L. [...] Read more.

Lilium henrici Franchet, which belongs to the family Liliaceae, is an endangered plant native to China. The wild populations of L. henrici have been largely reduced by habitat degradation or loss. In our study, we determined the whole chloroplast genome sequence for L. henrici and compared its structure with other Lilium (including Nomocharis) species. The chloroplast genome of L. henrici is a circular structure and 152,784 bp in length. The large single copy and small single copy is 82,429 bp and 17,533 bp in size, respectively, and the inverted repeats are 26,411 bp in size. The L. henrici chloroplast genome contains 116 different genes, including 78 protein coding genes, 30 tRNA genes, 4 rRNA genes, and 4 pseudogenes. There were 51 SSRs detected in the L. henrici chloroplast genome sequence. Genic comparison among L. henrici with other Lilium (including Nomocharis) chloroplast genomes shows that the sequence lengths and gene contents show little variation, the only differences being in three pseudogenes. Phylogenetic analysis revealed that N. pardanthina was a sister species to L. henrici. Overall, this study, providing L. henrici genomic resources and the comparative analysis of Lilium chloroplast genomes, will be beneficial for the evolutionary study and phylogenetic reconstruction of the genus Lilium, molecular barcoding in population genetics. Full article

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11 pages, 1657 KiB

Open AccessArticle

N-oxide alkaloids from Crinum amabile (Amaryllidaceae)

by Luciana R. Tallini, Laura Torras-Claveria, Warley De Souza Borges, Marcel Kaiser, Francesc Viladomat, José Angelo S. Zuanazzi and Jaume Bastida

Molecules 2018, 23(6), 1277; https://doi.org/10.3390/molecules23061277 - 26 May 2018

Cited by 25 | Viewed by 5523

Abstract

Natural products play an important role in the development of new drugs. In this context, the Amaryllidaceae alkaloids have attracted considerable attention in view of their unique structural features and various biological activities. In this study, twenty-three alkaloids were identified from Crinum amabile [...] Read more.

Natural products play an important role in the development of new drugs. In this context, the Amaryllidaceae alkaloids have attracted considerable attention in view of their unique structural features and various biological activities. In this study, twenty-three alkaloids were identified from Crinum amabile by GC-MS and two new structures (augustine N-oxide and buphanisine N-oxide) were structurally elucidated by NMR. Anti-parasitic and cholinesterase (AChE and BuChE) inhibitory activities of six alkaloids isolated from this species, including the two new compounds, are described herein. None of the alkaloids isolated from C. amabile gave better results than the reference drugs, so it was possible to conclude that the N-oxide group does not increase their therapeutic potential. 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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9 pages, 1162 KiB

Open AccessArticle

Serum Protein Electrophoretic Pattern in Neonatal Calves Treated with Clinoptilolite

by Simona Marc, Danijela Kirovski, Călin Mircu, Ioan Hutu, Gabriel Otavă, Cristina Paul, Oana Maria Boldura and Camelia Tulcan

Molecules 2018, 23(6), 1278; https://doi.org/10.3390/molecules23061278 - 26 May 2018

Cited by 10 | Viewed by 4476

Abstract

The objective of our study was to determine the effects of clinoptilolite supplemented in colostrum on the blood serum protein electrophoretic pattern of new-born calves. Methods: Romanian Black and White new-born calves involved in the study were divided into 3 groups: the control [...] Read more.

The objective of our study was to determine the effects of clinoptilolite supplemented in colostrum on the blood serum protein electrophoretic pattern of new-born calves. Methods: Romanian Black and White new-born calves involved in the study were divided into 3 groups: the control group (C) that received colostrum without clinoptilolite, and experimental groups I (E1) and II (E2) that received colostrum supplemented with 0.5% and 2% clinoptilolite, respectively. The concentration of total protein and protein fractions (albumin, α1-globulin, α2-globulin, β-globulin and γ-globulin) were analyzed by electrophoresis on cellulose acetate. Results: At hour 30 after birth, concentrations of γ-globulins, β-globulin and total protein in E1 group of calves were higher than in control group by 42.11% (p < 0.05), 28.48% (p > 0.05) and 18.52% (p > 0.05), respectively, and were higher, but not significantly, in group E2 compared to the control group. This was in accordance with a significant lower albumin/globulin ratio in groups E1 and E2 (29.35%, p < 0.05 and 35.87%, p < 0.05, respectively) than in control group at 30 h postpartum, which indicates an obvious increase of the globulins fraction in experimental groups. The conclusion: Clinoptilolite was effective in improving passive transfer in new-born calves, but it was more effective if added in colostrum with a dose of 0.5% than with a dose of 2%. Full article

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9 pages, 936 KiB

Open AccessArticle

Four New Lignans from Kadsura Interior and Their Bioactivity

by Jiu-Shi Liu, Jin Zhang, Yao-Dong Qi, Xiao-Guang Jia, Ben-Gang Zhang and Hai-Tao Liu

Molecules 2018, 23(6), 1279; https://doi.org/10.3390/molecules23061279 - 26 May 2018

Cited by 5 | Viewed by 4030

Abstract

A phytochemical investigation of the stems of Kadsura interior has led to an isolation of four new lignans, named kadsutherin E–H (1–4), together with two known lignans (5–6). The structures of the four new compounds [...] Read more.

A phytochemical investigation of the stems of Kadsura interior has led to an isolation of four new lignans, named kadsutherin E–H (1–4), together with two known lignans (5–6). The structures of the four new compounds were established on the basis of comprehensive spectroscopic analyses. Compounds 1–6 exhibited inhibition against adenosine diphosphate (ADP) induced platelet aggregation. Among the isolated compounds, kadsutherin F (2) showed the strongest anti-platelet aggregation activity with an inhibition of 49.47%. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 3978 KiB

Open AccessArticle

Synthesis of 8-Fluoro-3,4-dihydroisoquinoline and Its Transformation to 1,8-Disubstituted Tetrahydroisoquinolines

by Csilla Hargitai, Tamás Nagy, Judit Halász, Gyula Simig and Balázs Volk

Molecules 2018, 23(6), 1280; https://doi.org/10.3390/molecules23061280 - 26 May 2018

Cited by 3 | Viewed by 5787

Abstract

A simple procedure for the synthesis of 8-fluoro-3,4-dihydroisoquinoline is described below, based on a directed ortho-lithiation reaction. This key intermediate was then applied in various transformations. Fluorine–amine exchange afforded the corresponding 8-amino-3,4-dihydroisoquinolines, suitable starting compounds for the synthesis of 1-substituted 8-amino-tetrahydroisoquinolines. On [...] Read more.

A simple procedure for the synthesis of 8-fluoro-3,4-dihydroisoquinoline is described below, based on a directed ortho-lithiation reaction. This key intermediate was then applied in various transformations. Fluorine–amine exchange afforded the corresponding 8-amino-3,4-dihydroisoquinolines, suitable starting compounds for the synthesis of 1-substituted 8-amino-tetrahydroisoquinolines. On the other hand, reduction and alkylation reactions of 8-fluoro-3,4-dihydroisoquinoline led to novel 1,2,3,4-tetrahydroisoquinoline derivatives that can be used as building blocks in the synthesis of potential central nervous system drug candidates. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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27 pages, 11608 KiB

Open AccessArticle

Hyperbranched Polyglycerol Derivatives as Prospective Copper Nanotransporter Candidates

by Mohiuddin Quadir, Susanne Fehse, Gerhard Multhaup and Rainer Haag

Molecules 2018, 23(6), 1281; https://doi.org/10.3390/molecules23061281 - 26 May 2018

Cited by 9 | Viewed by 4906

Abstract

Hyperbranched polyglycerol (hPG) has been used as a multivalent scaffold to develop a series of nanocarriers capable of high-affinity encapsulation of copper (Cu). A rationally selected set of Cu-complexing motifs has been conjugated to hPG hydroxyl groups to render the constructs potentially usable [...] Read more.

Hyperbranched polyglycerol (hPG) has been used as a multivalent scaffold to develop a series of nanocarriers capable of high-affinity encapsulation of copper (Cu). A rationally selected set of Cu-complexing motifs has been conjugated to hPG hydroxyl groups to render the constructs potentially usable as exogenous sources of Cu for addressing different pathological conditions associated with Cu-deficiency. We have utilized a newly discovered route to attach Cu-binding domains exclusively within a hPG core by selective differentiation between the primary and secondary hydroxyl groups of the polyol. These hPG-derivatives were found to form a stable complex with Cu ions depending on the type of immobilized ligands and corresponding degree of functionalization. In addition, these Cu-bearing nano-complexes demonstrated moderately cationic surface charge resulting in adjustable protein-binding characteristics and low cellular toxicity profile. We envision that these Cu-loaded hPG nanocarriers can be used as a stable platform to transport the metal ion across the systemic circulation to supply bioavailable quantity of Cu in disease-afflicted tissues. 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, 1543 KiB

Open AccessArticle

Antifeedant Effects of Essential Oil, Extracts, and Isolated Sesquiterpenes from Pilgerodendron uviferum (D. Don) Florin Heartwood on Red Clover Borer Hylastinus obscurus (Coleoptera: Curculionidae)

by Javier Espinoza, Alejandro Urzúa, Leonardo Bardehle, Andrés Quiroz, Javier Echeverría and Marcia González-Teuber

Molecules 2018, 23(6), 1282; https://doi.org/10.3390/molecules23061282 - 27 May 2018

Cited by 16 | Viewed by 4059

Abstract

The beetle Hylastinus obscurus Marsham (Coleoptera: Curculionidae), endemic to Europe and Northern Africa, is one of the most important red clover pests in Chile. As commercial insecticides are less effective against this pest, plant secondary metabolites have been considered as an alternative for [...] Read more.

The beetle Hylastinus obscurus Marsham (Coleoptera: Curculionidae), endemic to Europe and Northern Africa, is one of the most important red clover pests in Chile. As commercial insecticides are less effective against this pest, plant secondary metabolites have been considered as an alternative for its control. Here, we have investigated the chemical composition of essential oil (EO), petroleum ether extract (PEE), and dichloromethane extract (DCME) from Pilgerodendron uviferum heartwood. Additionally, the effects of EO and extracts on the feeding behavior (% of weight shift) of H. obscurus have been evaluated. The composition of EO, PEE, and DCME were analyzed using gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). The results showed the presence of a similar mixture of sesquiterpenes in the essential oil and in both of the extracts, which accounted for circa 60% of the total mixture. Sesquiterpenes were further isolated using chromatographic methods and were structurally characterized by optical rotation, GC–MS, FTIR, and 1D and 2D NMR experiments. The physicochemical properties of the isolated sesquiterpenes, including lipophilicity and vapor pressure, were also determined. The sesquiterpenes were identified as the following: (−)-trans-calamenene (1), cadalene (2), (−)-cubenol (3), (−)-epi-cubenol (4), (−)-torreyol (5), and (−)-15-copaenol (6). The antifeedant activity of EO, extracts, and isolated sesquiterpenes were evaluated using artificial diets in a non-choice test. Relative to the control, the EO, DCME extract, and the isolated sesquiterpenes, namely, (−)-trans-calamenene (1), cadalene (2), and (5) torreyol, were found to be the most effective treatments against H. obscurus. Our study showed that the compounds occurring in P. uviferum heartwood were effective in reducing the adult growth of H. obscurus. The physicochemical properties of the isolated sesquiterpenes might have been associated with antifeedant effects. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 3060 KiB

Open AccessArticle

A Modified GC-MS Analytical Procedure for Separation and Detection of Multiple Classes of Carbohydrates

by Yong-Gang Xia, Hui-Min Sun, Tian-Long Wang, Jun Liang, Bing-You Yang and Hai-Xue Kuang

Molecules 2018, 23(6), 1284; https://doi.org/10.3390/molecules23061284 - 27 May 2018

Cited by 35 | Viewed by 6760

Abstract

A modified GC-MS analytical procedure based on trimethylsilyl-dithioacetal (TMSD) derivatization has been established for a simultaneous determination of thirteen carbohydrates. Different from previous approaches, the current GC-MS method was featured by a powerful practicability for simultaneous detection of aldoses, uronic acids, ketoses, and [...] Read more.

A modified GC-MS analytical procedure based on trimethylsilyl-dithioacetal (TMSD) derivatization has been established for a simultaneous determination of thirteen carbohydrates. Different from previous approaches, the current GC-MS method was featured by a powerful practicability for simultaneous detection of aldoses, uronic acids, ketoses, and amino sugars; simplifying GC-MS chromatograms and producing a single peak for each derivatized sugar, as well as high resolution, sensitivity, and repeatability. An additional liquid-liquid extraction from derivatization mixtures was performed not only to increase the detection sensitivity of amino sugars but also to decrease the by-products of derivatization. Contrarily, three amino sugars were detected at a very low intensity or not detected at all. The effect of time on monosaccharide- mercaptalated reaction was systematically investigated. The effect of trimethylsilylation on the formation of TMSD was also optimized. The established GC-MS based on TMSD derivatization was suitable for complex carbohydrate analysis and has been successfully applied for the detection of free carbohydrates in water extracts of Anemarrhena asphodeloides roots and determination of monosaccharides in Glossy ganoderma polysaccharides. Full article

(This article belongs to the Section Analytical Chemistry)

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11 pages, 1753 KiB

Open AccessFeature PaperArticle

Scabiosa stellata L. Phenolic Content Clarifies Its Antioxidant Activity

by Naima Rahmouni, Diana C. G. A. Pinto, Noureddine Beghidja, Samir Benayache and Artur M. S. Silva

Molecules 2018, 23(6), 1285; https://doi.org/10.3390/molecules23061285 - 27 May 2018

Cited by 20 | Viewed by 4761

Abstract

The phenolic profile of Scabiosa stellata L., a species used in Moroccan traditional medicine, is disclosed. To obtain that profile the species extract was analyzed by ultra-high-performance chromatography coupled to photodiode-array detection and electrospray ionization/ion trap mass spectrometry (UHPLC-DAD-ESI/MSⁿ). Twenty-five phenolic [...] Read more.

The phenolic profile of Scabiosa stellata L., a species used in Moroccan traditional medicine, is disclosed. To obtain that profile the species extract was analyzed by ultra-high-performance chromatography coupled to photodiode-array detection and electrospray ionization/ion trap mass spectrometry (UHPLC-DAD-ESI/MSⁿ). Twenty-five phenolic compounds were identified from which isoorientin and 4-O-caffeoylquinic acid can be highlighted because they are the major ones. The antioxidant activity was significantly controlled by the fraction type, with the n-butanol fraction showing the highest antioxidant activity (FRS₅₀ = 64.46 µg/mL in the DPPH assay, FRS₅₀ = 27.87 µg/mL in the ABTS assay and EC₅₀ = 161.11 µg/mL in the reducing power assay). A phytochemical study of the n-butanol fraction was performed, and some important flavone glycosides were isolated. Among them the tamarixetin derivatives—the less common ones—can be emphasized. This phytochemical study and polyphenolic profile can be correlated with S. stellata extracts in vitro antioxidant activity. Moreover, it can be regarded as an evidence of its medicinal use and can incentivize its consumption. Full article

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

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15 pages, 3009 KiB

Open AccessArticle

Expression Analysis of Oxalate Metabolic Pathway Genes Reveals Oxalate Regulation Patterns in Spinach

by Xiaofeng Cai, Chenhui Ge, Chenxi Xu, Xiaoli Wang, Shui Wang and Quanhua Wang

Molecules 2018, 23(6), 1286; https://doi.org/10.3390/molecules23061286 - 27 May 2018

Cited by 33 | Viewed by 7219

Abstract

Spinach (Spinacia oleracea L.) is one of most important leafy vegetables because of its high nutritional value and high oxalate content, which can be toxic with negative effects on human nutrition. Ammonium and nitrate can effectively regulate oxalate accumulation, although the mechanisms [...] Read more.

Spinach (Spinacia oleracea L.) is one of most important leafy vegetables because of its high nutritional value and high oxalate content, which can be toxic with negative effects on human nutrition. Ammonium and nitrate can effectively regulate oxalate accumulation, although the mechanisms underlying the oxalate biosynthesis and regulation are still undetermined in plants. In the present study, we identified 25 putative genes that are involved in the oxalate biosynthetic and degradation pathway, before analyzing the oxalate content and the expression levels of the corresponding proteins under normal growth conditions, with or without ammonium and nitrate treatments, using high and low oxalate-accumulated spinach genotypes. The two cultivars exhibited different profiles of total oxalate and soluble oxalate accumulation. The high oxalate concentrations in spinach were as a result of the high transcription levels of the genes that are involved in oxalate biosynthesis under normal growth conditions, such as SoGLO2, SoGLO3, three SoOXACs, SoMLS, SoMDH1, SoMDH2, and SoMDH4. The results revealed that the ammonium and nitrate were able to control the oxalate content in leaves, possibly because of the different transcription levels of the genes. The oxalate content is regulated by complex regulatory mechanisms and is varied in the different varieties of spinach. The results from this research may be used to assist the investigation of the mechanism of oxalate regulation and breeding for reduced oxalate content in spinach. Full article

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18 pages, 20893 KiB

Open AccessArticle

The Growth Proliferation, Apoptotic Prevention, and Differentiation Induction of the Gelatin Hydrolysates from Three Sources to Human Fetal Osteoblasts (hFOB 1.19 Cells)

by Ming Lu and Xin-Huai Zhao

Molecules 2018, 23(6), 1287; https://doi.org/10.3390/molecules23061287 - 28 May 2018

Cited by 16 | Viewed by 4399

Abstract

Gelatins from the skin of bovine, porcine, and tilapia were hydrolyzed to three degrees of hydrolysis (DH) by alcalase, neutrase, and papain, respectively. These hydrolysates at 0.02–0.1 g/L promoted the growth of human fetal osteoblasts by 101.4–135.7%, while higher DH or using papain [...] Read more.

Gelatins from the skin of bovine, porcine, and tilapia were hydrolyzed to three degrees of hydrolysis (DH) by alcalase, neutrase, and papain, respectively. These hydrolysates at 0.02–0.1 g/L promoted the growth of human fetal osteoblasts by 101.4–135.7%, while higher DH or using papain and tilapia gelatins resulted in higher proliferation. The hydrolysates from porcine and tilapia gelatins at 0.05 g/L prevented induced apoptosis (decreasing total apoptotic proportions from 28.4% or 35.2% to 10.3–17.5% or 16.0–23.6%), and had differentiation induction (increasing alkaline phosphatase activity by 126.9–246.7% in early differentiation stage, or enhancing osteocalcin production by 4.1–22.5% in later differentiation stage). These hydrolysates had a similar amino acid profile; however, tilapia gelatin hydrolysates by papain with DH 15.4% mostly displayed higher activity than others. Tilapia gelatin hydrolysate could up-regulate β-catenin, Wnt 3a, Wnt 10b, cyclin D1, and c-Myc expression at mRNA levels by 1.11–3.60 folds, but down-regulate GSK 3β expression by 0.98 fold. Of note, β-catenin in total cellular and nuclear protein was up-regulated by 1.14–1.16 folds but unchanged in cytoplasmic protein, Wnt 10b, cyclin D1, and c-Myc expression were up-regulated by 1.27–1.95 folds, whilst GSK 3β expression was down-regulated by 0.87 fold. Activation of Wnt/β-catenin pathway is suggested to mediate cell proliferation and differentiation. Full article

(This article belongs to the Special Issue Gelatin: Chemistry, Characterization, Application)

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10 pages, 4994 KiB

Open AccessArticle

Antiproliferative Phenothiazine Hybrids as Novel Apoptosis Inducers against MCF-7 Breast Cancer

by Jun-Xia Zhang, Jiao-Mei Guo, Ting-Ting Zhang, Hong-Jun Lin, Nai-Song Qi, Zhen-Guo Li, Ji-Chun Zhou and Zhen-Zhong Zhang

Molecules 2018, 23(6), 1288; https://doi.org/10.3390/molecules23061288 - 28 May 2018

Cited by 16 | Viewed by 4038

Abstract

We designed a series of novel phenothiazine-1,2,3-triazole hybrids by the molecular hybridization strategy and evaluated their antiproliferative activity against three cancer cell lines (MDA-MB-231, MDA-MB-468 and MCF-7). For the structure-activity relationships, the importance of 1,2,3-triazole and substituents on phenyl ring was explored. Among [...] Read more.

We designed a series of novel phenothiazine-1,2,3-triazole hybrids by the molecular hybridization strategy and evaluated their antiproliferative activity against three cancer cell lines (MDA-MB-231, MDA-MB-468 and MCF-7). For the structure-activity relationships, the importance of 1,2,3-triazole and substituents on phenyl ring was explored. Among these phenothiazine-1,2,3-triazole hybrids, compound 9f showed the most potent inhibitory effect against MCF-7 cells, with an IC₅₀ value of 0.8 μM. Importantly, compound 9f could induce apoptosis against MCF-7 cells by regulating apoptosis-related proteins (Bcl-2, Bax, Bad, Parp, and DR5). These potent phenothiazine-1,2,3-triazole hybrids as novel apoptosis inducers might be used as antitumor agents in the future. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 2763 KiB

Open AccessArticle

Benzothiadiazole and B-Aminobutyricacid Induce Resistance to Ectropis Obliqua in Tea Plants (Camellia Sinensis (L.) O. Kuntz)

by Huan Li, Ying Yu, Zhenzhen Li, Emmanuel Arkorful, Yiyang Yang, Xinqiu Liu, Xinghui Li and Ronglin Li

Molecules 2018, 23(6), 1290; https://doi.org/10.3390/molecules23061290 - 28 May 2018

Cited by 10 | Viewed by 4056

Abstract

In order to investigate the effect of benzothiadiazole (BTH) and β-aminobutyric acid (BABA) on the resistance of tea plants (Camellia sinensis) to tea geometrid (Ectropis obliqua), three levels each of benzothiadiazole (BTH) and β-aminobutyric acid (BABA) were sprayed on 10-year-old [...] Read more.

In order to investigate the effect of benzothiadiazole (BTH) and β-aminobutyric acid (BABA) on the resistance of tea plants (Camellia sinensis) to tea geometrid (Ectropis obliqua), three levels each of benzothiadiazole (BTH) and β-aminobutyric acid (BABA) were sprayed on 10-year-old tea plants. Generally PPO and PAL activities increased with low concentrations of BTH and BABA treatments. Quantitative RT-PCR revealed a 1.43 and 2.72-fold increase in PPO gene expression, and 3.26 and 3.99-fold increase in PAL gene expression with 75 mg/L BTH and 400 mg/L BABA respectively. Analysis of hydrolysis of synthetic substrates also revealed that chymotrypsin-like enzyme activity present in larval midgut extracts was not significantly inhibited by BTH and BABA. However, proteinase activity was found to be inversely proportional to the age of tea geometrid. Larvae pupation rate decreased by 8.10, 10.81 and 21.62% when tea geometrid were fed with leaves treated with 25, 50 and 75 mg/L BTH solutions, while 100, 200 and 400 mg/L BABA solutions decreased same by 8.10, 16.21 and 13.51% respectively. Also, larvae development period delayed to 23.33 and 26.33 days with 75 mg/L BTH and 400 mg/L BABA treatments respectively. The results in this study; therefore, suggest that benzothiadiazole (BTH) and β-aminobutyric acid (BABA) play a role in inducing resistance in tea plants to tea geometrid, with the optimal effect achieved at BTH-3 (75 mg/L) and BABA-3 (400 mg/L), respectively. Full article

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10 pages, 1077 KiB

Open AccessArticle

Aspergoterpenins A–D: Four New Antimicrobial Bisabolane Sesquiterpenoid Derivatives from an Endophytic Fungus Aspergillus versicolor

by Zhi-Yong Guo, Ming-Hui Tan, Cheng-Xiong Liu, Meng-Meng Lv, Zhang-Shuang Deng, Fei Cao, Kun Zou and Peter Proksch

Molecules 2018, 23(6), 1291; https://doi.org/10.3390/molecules23061291 - 28 May 2018

Cited by 35 | Viewed by 5675

Abstract

Aspergoterpenins A–D (1–4), four new bisabolane sesquiterpenoid derivatives, were obtained from the endophytic fungus, Aspergillus versicolor, together with eight known compounds (5–12), and their structures were elucidated by a comprehensive analysis of their [...] Read more.

Aspergoterpenins A–D (1–4), four new bisabolane sesquiterpenoid derivatives, were obtained from the endophytic fungus, Aspergillus versicolor, together with eight known compounds (5–12), and their structures were elucidated by a comprehensive analysis of their NMR (Nuclear Magnetic Resonance), MS (Mass Spectrum) and CD (Circular Dichroism) spectra. Aspergoterpenin A (1) was the first example with a characteristic ketal bridged-ring part in the degraded natural bisabolane-type sesquiterpene structures. The compounds 1–12 displayed no significant activities against four cancer cell lines (A549, Caski, HepG2 and MCF-7). Further, the antimicrobial activities to Erwinia carotovora sub sp. Carotovora were evaluated, and the results showed that compounds 1–12 displayed antimicrobial activities with MIC values ranging from 15.2 to 85.2 μg/mL. Full article

(This article belongs to the Collection Bioactive Compounds)

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9 pages, 282 KiB

Open AccessArticle

Expectation-Maximization Model for Substitution of Missing Values Characterizing Greenness of Organic Solvents

by Gabriela Łuczyńska, Francisco Pena-Pereira, Marek Tobiszewski and Jacek Namieśnik

Molecules 2018, 23(6), 1292; https://doi.org/10.3390/molecules23061292 - 28 May 2018

Cited by 9 | Viewed by 3573

Abstract

Organic solvents are ubiquitous in chemical laboratories and the Green Chemistry trend forces their detailed assessments in terms of greenness. Unfortunately, some of them are not fully characterized, especially in terms of toxicological endpoints that are time consuming and expensive to be determined. [...] Read more.

Organic solvents are ubiquitous in chemical laboratories and the Green Chemistry trend forces their detailed assessments in terms of greenness. Unfortunately, some of them are not fully characterized, especially in terms of toxicological endpoints that are time consuming and expensive to be determined. Missing values in the datasets are serious obstacles, as they prevent the full greenness characterization of chemicals. A featured method to deal with this problem is the application of Expectation-Maximization algorithm. In this study, the dataset consists of 155 solvents that are characterized by 13 variables is treated with Expectation-Maximization algorithm to predict missing data for toxicological endpoints, bioavailability, and biodegradability data. The approach may be particularly useful for substitution of missing values of environmental, health, and safety parameters of new solvents. The presented approach has high potential to deal with missing values, while assessing environmental, health, and safety parameters of other chemicals. Full article

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

11 pages, 3498 KiB

Open AccessArticle

Electrodegradation of Resorcinol on Pure and Catalyst-Modified Ni Foam Anodes, Studied under Alkaline and Neutral pH Conditions

by Tomasz Mikolajczyk, Boguslaw Pierozynski, Lech Smoczynski and Wieslaw Wiczkowski

Molecules 2018, 23(6), 1293; https://doi.org/10.3390/molecules23061293 - 28 May 2018

Cited by 7 | Viewed by 4442

Abstract

This work reports on the kinetics of electrochemical degradation of the resorcinol molecule, examined on nickel foam-based electrodes in contact with 0.1 M NaOH and 0.5 M Na₂SO₄ supporting electrolytes. The electrooxidation of resorcinol was examined on as-received, as well [...] Read more.

This work reports on the kinetics of electrochemical degradation of the resorcinol molecule, examined on nickel foam-based electrodes in contact with 0.1 M NaOH and 0.5 M Na₂SO₄ supporting electrolytes. The electrooxidation of resorcinol was examined on as-received, as well as on Pd-modified, nickel foam catalyst materials, produced via spontaneous deposition of trace amounts of palladium element. Electrochemical (cyclic voltammetry and a.c. impedance) experiments were carried out by means of a three-compartment, pyrex glass electrochemical cell, whereas continuous resorcinol electrooxidation tests were conducted galvanostatically (or potentistatically) with a laboratory-size, single-cell electrolyzer unit. In addition, quantitative determination of resorcinol and its possible electrodegradation products was performed by means of instrumental HPLC: High-Performance Liquid Chromatography/MS: Mass Spectrometry methodology. Also, SEM (Scanning Electron Microscopy) and EDX (Energy Dispersive X-ray spectroscopy) techniques were employed for Ni foam (Pd-modified Ni foam) surface characterizations. Full article

(This article belongs to the Section Physical Chemistry)

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13 pages, 3646 KiB

Open AccessArticle

Viability, Enzymatic and Protein Profiles of Pseudomonas aeruginosa Biofilm and Planktonic Cells after Monomeric/Gemini Surfactant Treatment

by Anna Koziróg, Anna Otlewska and Bogumił Brycki

Molecules 2018, 23(6), 1294; https://doi.org/10.3390/molecules23061294 - 28 May 2018

Cited by 18 | Viewed by 4468

Abstract

This study set out to investigate the biological activity of monomeric surfactants dodecyltrimethylammonium bromide (DTAB) and the next generation gemini surfactant hexamethylene-1,6-bis-(N,N-dimethyl-N-dodecylammonium bromide) (C6) against the environmental strain Pseudomonas aeruginosa PB_1. Minimal inhibitory concentrations (MIC) were determined [...] Read more.

This study set out to investigate the biological activity of monomeric surfactants dodecyltrimethylammonium bromide (DTAB) and the next generation gemini surfactant hexamethylene-1,6-bis-(N,N-dimethyl-N-dodecylammonium bromide) (C6) against the environmental strain Pseudomonas aeruginosa PB_1. Minimal inhibitory concentrations (MIC) were determined using the dilution method. The viability of the planktonic cells and biofilm was assessed using the plate count method. Enzymatic profile was determined using the API-ZYM system. Proteins were extracted from the biofilm and planktonic cells and analysed using SDS-PAGE. The MIC of the gemini surfactants was 70 times lower than that of its monomeric analogue. After 4 h of treatment at MIC (0.0145 mM for C6 and 1.013 mM for DTAB), the number of viable planktonic cells was reduce by less than 3 logarithm units. At the concentration ≥MIC, a reduction in the number of viable cells was observed in mature biofilms (p < 0.05). Treatment for 4 h with gemini surfactant at 20 MIC caused complete biofilm eradication. At sub-MIC, the concentration of some enzymes reduced and their protein profiles changed. The results of this study show that due to its superior antibacterial activity, gemini compound C6 can be applied as an effective microbiocide against P. aeruginosa in both planktonic and biofilm forms. Full article

(This article belongs to the Special Issue Antibacterial Materials and Coatings 2018)

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11 pages, 2305 KiB

Open AccessArticle

Changes in Photosynthetic Pigments, Total Phenolic Content, and Antioxidant Activity of Salvia coccinea Buc’hoz Ex Etl. Induced by Exogenous Salicylic Acid and Soil Salinity

by Monika Grzeszczuk, Piotr Salachna and Edward Meller

Molecules 2018, 23(6), 1296; https://doi.org/10.3390/molecules23061296 - 29 May 2018

Cited by 55 | Viewed by 6370

Abstract

Salvia coccinea (Lamiaceae) is a promising source of potential antioxidants, and its extracts can be used in pharmaceutical industry, as well as in food products and cosmetics. Salicylic acid (SA) affects many physiological and metabolic processes in vascular plants under salinity stress. The [...] Read more.

Salvia coccinea (Lamiaceae) is a promising source of potential antioxidants, and its extracts can be used in pharmaceutical industry, as well as in food products and cosmetics. Salicylic acid (SA) affects many physiological and metabolic processes in vascular plants under salinity stress. The aim of this study was to investigate the response of S. coccinea to either SA, or sodium chloride (NaCl), or a combination of both. The plants were sprayed with a solution of 0.5 or 1.0 mM SA and watered with 0, 100, 200, or 300 mM NaCl. Exogenous application of SA increased the number of branches, fresh herbal weight, and total chlorophyll content vs control plants. Salinity-exposed plants showed reduced growth, content of photosynthetic pigments total polyphenols, and antioxidant activity. However, foliar application of SA relieved the adverse effects of 100 mM NaCl, as demonstrated by increased number of branches, greater fresh herbal weight, higher content of total chlorophyll, total carotenoids, and total polyphenols, as well as antioxidant potential, detected using ferric-reducing ability of plasma (FRAP) and 2.2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), compared with untreated plants. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 1328 KiB

Open AccessArticle

Beneficial Effects of Green Tea Catechins on Neurodegenerative Diseases

by Monira Pervin, Keiko Unno, Tomokazu Ohishi, Hiroki Tanabe, Noriyuki Miyoshi and Yoriyuki Nakamura

Molecules 2018, 23(6), 1297; https://doi.org/10.3390/molecules23061297 - 29 May 2018

Cited by 216 | Viewed by 24020

Abstract

Tea is one of the most consumed beverages in the world. Green tea, black tea, and oolong tea are made from the same plant Camellia sinensis (L.) O. Kuntze. Among them, green tea has been the most extensively studied for beneficial effects on [...] Read more.

Tea is one of the most consumed beverages in the world. Green tea, black tea, and oolong tea are made from the same plant Camellia sinensis (L.) O. Kuntze. Among them, green tea has been the most extensively studied for beneficial effects on diseases including cancer, obesity, diabetes, and inflammatory and neurodegenerative diseases. Several human observational and intervention studies have found beneficial effects of tea consumption on neurodegenerative impairment, such as cognitive dysfunction and memory loss. These studies supported the basis of tea’s preventive effects of Parkinson’s disease, but few studies have revealed such effects on Alzheimer’s disease. In contrast, several human studies have not reported these favorable effects with regard to tea. This discrepancy may be due to incomplete adjustment of confounding factors, including the method of quantifying consumption, beverage temperature, cigarette smoking, alcohol consumption, and differences in genetic and environmental factors, such as race, sex, age, and lifestyle. Thus, more rigorous human studies are required to understand the neuroprotective effect of tea. A number of laboratory experiments demonstrated the benefits of green tea and green tea catechins (GTCs), such as epigallocatechin gallate (EGCG), and proposed action mechanisms. The targets of GTCs include the abnormal accumulation of fibrous proteins, such as Aβ and α-synuclein, inflammation, elevated expression of pro-apoptotic proteins, and oxidative stress, which are associated with neuronal cell dysfunction and death in the cerebral cortex. Computational molecular docking analysis revealed how EGCG can prevent the accumulation of fibrous proteins. These findings suggest that GTCs have the potential to be used in the prevention and treatment of neurodegenerative diseases and could be useful for the development of new drugs. Full article

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

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11 pages, 2492 KiB

Open AccessArticle

The Selectivity of Polymers Imprinted with Amines

by Zsanett Dorkó, Anett Nagy-Szakolczai, Blanka Tóth and George Horvai

Molecules 2018, 23(6), 1298; https://doi.org/10.3390/molecules23061298 - 29 May 2018

Cited by 11 | Viewed by 4593

Abstract

One of the main reasons for making molecularly imprinted polymers (MIPs) has been that MIPs interact selectively with a specific target compound. This claim is investigated here with the example of a widely used type of noncovalent MIP, the MIP for the beta [...] Read more.

One of the main reasons for making molecularly imprinted polymers (MIPs) has been that MIPs interact selectively with a specific target compound. This claim is investigated here with the example of a widely used type of noncovalent MIP, the MIP for the beta blocker propranolol. Adsorption isotherms of this MIP and of a nonimprinted control polymer (NIP), respectively, have been measured with a series of compounds in the porogen solvent acetonitrile. The results, visualized as “selectivity ladders”, show that the MIP binds propranolol and many other amines better than the NIP does, but the selectivity of the MIP is actually inferior to that of the NIP. The selectivity of either polymer for propranolol is modest against many amines, but is remarkable with respect to other compounds. The contribution of imprinting towards selectivity can be better appreciated when three MIPs, made with different amine templates, are compared among themselves. Each MIP is seen to bind its own template slightly better than the other two MIPs do. In media different from the porogen, the selectivity patterns may change substantially. Propranolol seems to have properties that make it stand high on the selectivity scale in different solvents, albeit for different reasons. Full article

(This article belongs to the Special Issue Synthesis and Applications of Molecularly Imprinted Polymers)

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14 pages, 1371 KiB

Open AccessArticle

Flavor Compounds in Pixian Broad-Bean Paste: Non-Volatile Organic Acids and Amino Acids

by Hongbin Lin, Xiaoyu Yu, Jiaxing Fang, Yunhao Lu, Ping Liu, Yage Xing, Qin Wang, Zhenming Che and Qiang He

Molecules 2018, 23(6), 1299; https://doi.org/10.3390/molecules23061299 - 29 May 2018

Cited by 109 | Viewed by 6909

Abstract

Non-volatile organic acids and amino acids are important flavor compounds in Pixian broad-bean paste, which is a traditional Chinese seasoning product. In this study, non-volatile organic acids, formed in the broad-bean paste due to the metabolism of large molecular compounds, are qualitatively and [...] Read more.

Non-volatile organic acids and amino acids are important flavor compounds in Pixian broad-bean paste, which is a traditional Chinese seasoning product. In this study, non-volatile organic acids, formed in the broad-bean paste due to the metabolism of large molecular compounds, are qualitatively and quantitatively determined by high-performance liquid chromatography (HPLC). Amino acids, mainly produced by hydrolysis of soybean proteins, were determined by the amino acid automatic analyzer. Results indicated that seven common organic acids and eighteen common amino acids were found in six Pixian broad-bean paste samples. The content of citric acid was found to be the highest in each sample, between 4.1 mg/g to 6.3 mg/g, and malic acid were between 2.1 mg/g to 3.6 mg/g ranked as the second. Moreover, fumaric acid was first detected in fermented bean pastes albeit with a low content. For amino acids, savory with lower sour taste including glutamine (Gln), glutamic acid (Glu), aspartic acid (Asp) and asparagines (Asn) were the most abundant, noted to be 6.5 mg/g, 4.0 mg/g, 6.4 mg/g, 4.9 mg/g, 6.2 mg/g and 10.2 mg/g, and bitter taste amino acids followed. More importantly, as important flavor materials in Pixian broad-bean paste, these two groups of substances are expected to be used to evaluate and represent the flavor quality of Pixian broad-bean paste. Moreover, the results revealed that citric acid, glutamic acid, methionine and proline were the most important flavor compounds. These findings are agreat contribution for evaluating the quality and further assessment of Pixian broad-bean paste. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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13 pages, 1946 KiB

Open AccessArticle

Enhanced Enzymatic Hydrolysis and Structural Features of Corn Stover by NaOH and Ozone Combined Pretreatment

by Wenhui Wang, Chunyan Zhang, Shisheng Tong, Zhongyi Cui and Ping Liu

Molecules 2018, 23(6), 1300; https://doi.org/10.3390/molecules23061300 - 29 May 2018

Cited by 30 | Viewed by 4019

Abstract

A two-step pretreatment using NaOH and ozone was performed to improve the enzymatic hydrolysis, compositions and structural characteristics of corn stover. Comparison between the unpretreated and pretreated corn stover was also made to illustrate the mechanism of the combined pretreatment. A pretreatment with [...] Read more.

A two-step pretreatment using NaOH and ozone was performed to improve the enzymatic hydrolysis, compositions and structural characteristics of corn stover. Comparison between the unpretreated and pretreated corn stover was also made to illustrate the mechanism of the combined pretreatment. A pretreatment with 2% (w/w) NaOH at 80 °C for 2 h followed by ozone treatment for 25 min with an initial pH 9 was found to be the optimal procedure and the maximum efficiency (91.73%) of cellulose enzymatic hydrolysis was achieved. Furthermore, microscopic observation of changes in the surface structure of the samples showed that holes were formed and lignin and hemicellulose were partially dissolved and removed. X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) and Cross-Polarization Magic Angle Spinning Carbon-13 Nuclear Magnetic Resonance (CP/MAS ¹³C-NMR) were also used to characterize the chemical structural changes after the combined pretreatment. The results were as follows: part of the cellulose I structure was destroyed and then reformed into cellulose III, the cellulose crystal indices were also changed; a wider space between the crystal layer was observed; disruption of hydrogen bonds in cellulose and disruption of ester bonds in hemicellulose; cleavage of bonds linkage in lignin-carbohydrate complexes; removal of methoxy in lignin and hemicellulose. As a result, all these changes effectively reduced recalcitrance of corn stover and promoted subsequent enzymatic hydrolysis of cellulose. Full article

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

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12 pages, 1086 KiB

Open AccessCommunication

MAO-A Inhibitory Potential of Terpene Constituents from Ginger Rhizomes—A Bioactivity Guided Fractionation

by Wirginia Kukula-Koch, Wojciech Koch, Lidia Czernicka, Kazimierz Głowniak, Yoshinori Asakawa, Akemi Umeyama, Zbigniew Marzec and Takashi Kuzuhara

Molecules 2018, 23(6), 1301; https://doi.org/10.3390/molecules23061301 - 29 May 2018

Cited by 26 | Viewed by 6366

Abstract

Background: In the search for novel antidepressive drug candidates, bioguided fractionation of nonpolar constituents present in the oleoresin from ginger rhizomes (Zingiber officinale Roscoe, Zingiberaceae) was performed. This particular direction of the research was chosen due to the existing reports on the [...] Read more.

Background: In the search for novel antidepressive drug candidates, bioguided fractionation of nonpolar constituents present in the oleoresin from ginger rhizomes (Zingiber officinale Roscoe, Zingiberaceae) was performed. This particular direction of the research was chosen due to the existing reports on the antidepressive properties of ginger total extract. The search for individual metabolites acting as MAO-A inhibitors, which correspond to the apparent effect of the total extract, is the subject of this work. Methods: Hexane extracts from ginger rhizomes were fractionated by using column chromatography (including silica gel impregnated with silver nitrate) and semi-preparative high-performance chromatography. For the activity assessment, an in vitro monoamine oxidase A (MAO-A) inhibition luminescence assay was performed on 10 purified terpenes: 1,8-cineole, α-citronellal, geraniol, β-sesquiphellandrene, γ-terpinen, geranyl acetate, isobornyl acetate, terpinen-4-ol, (E,E)-α-farnesene, and α-zingiberene. Results: Geraniol and (−)-terpinen-4-ol were found to be the strongest enzyme inhibitors with inhibition of 44.1% and 42.5%, respectively, at a concentration of 125 µg/mL. No differences in the inhibition potential were observed for the different groups of terpenes: sesquiterpenes, monoterpenes, or sesquiterpene alcohols; however, the two most active compounds contained a hydroxyl moiety. Conclusions: Terpene constituents from ginger’s extract were found to exhibit moderate inhibitory properties against the MAO-A enzyme in in vitro tests. Full article

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

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17 pages, 3323 KiB

Open AccessArticle

Antioxidant Activity and Spectroscopic Characteristics of Extractable and Non-Extractable Phenolics from Terminalia sericea Burch. ex DC.

by Chinedu Anokwuru, Muendi Sigidi, Marlaine Boukandou, Peter Tshisikhawe, Afsatou Traore and Natasha Potgieter

Molecules 2018, 23(6), 1303; https://doi.org/10.3390/molecules23061303 - 29 May 2018

Cited by 25 | Viewed by 5157

Abstract

The aim of this study was to determine the antioxidant activity of the extractable and non-extractable phenolics of Terminalia. Sericea Burch. Ex DC. Free, ester bound, ether or glycoside bound and insoluble phenolics were extracted from the fruit, leaves, stem, and root samples. [...] Read more.

The aim of this study was to determine the antioxidant activity of the extractable and non-extractable phenolics of Terminalia. Sericea Burch. Ex DC. Free, ester bound, ether or glycoside bound and insoluble phenolics were extracted from the fruit, leaves, stem, and root samples. Follin Ciocalteu was used to estimate the phenolic content while DPPH (2,2-diphenyl-1-picrylhydrazyl) assay was used to determine the antioxidant activity. The data obtained were subjected to multivariate analysis for relationships. The result indicated that the highest average total phenolic contents and antioxidant activities were found in the free (14.8 mgGAE/g; IC₅₀ 6.8 μg/mL) and ester bound (15.1 mgGAE/g; IC₅₀ 6.4 μg/mL) extractable phenolics. There was a strong negative correlation between TPC and DPPH (r = −0.828). Agglomerative hierarchical clustering revealed three clusters. Cluster one contained the insoluble and glycoside phenolics while cluster 2 contained only free phenolic acid of the root. The third cluster was predominantly free and ester bound phenolic extracts. The principal component analysis score plot indicated two major clusters with factor 1 (F1) explaining 61% of the variation. The nuclear magnetic resonance spectroscopy spectra indicated that gallic acid and resveratrol are the major phenolic compounds present in the root. This study has demonstrated that extractable phenolics contributed more to the antioxidant activities compared to the non-extractables. Full article

(This article belongs to the Special Issue Extractable and Non-Extractable Antioxidants)

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15 pages, 1612 KiB

Open AccessArticle

Exploring the Dual Inhibitory Activity of Novel Anthranilic Acid Derivatives towards α-Glucosidase and Glycogen Phosphorylase Antidiabetic Targets: Design, In Vitro Enzyme Assay, and Docking Studies

by Saleh Ihmaid

Molecules 2018, 23(6), 1304; https://doi.org/10.3390/molecules23061304 - 29 May 2018

Cited by 6 | Viewed by 3990

Abstract

A few new anthranilate diamide derivatives, 3a–e, 5a–c and 7a–d, were designed, synthesized, and evaluated for their inhibitory activity against two interesting antidiabetic targets, α-glucosidase and glycogen phosphorylase enzymes. Different instrumental analytical tools were applied [...] Read more.

A few new anthranilate diamide derivatives, 3a–e, 5a–c and 7a–d, were designed, synthesized, and evaluated for their inhibitory activity against two interesting antidiabetic targets, α-glucosidase and glycogen phosphorylase enzymes. Different instrumental analytical tools were applied in identification and conformation of their structures like; ¹³C NMR, ¹H NMR and elemental analysis. The screening of the novel compounds showed potent inhibitory activity with nanomolar concentration values. The most active compounds (5c) and (7b) showed the highest inhibitory activity against α-glucosidase and glycogen phosphorylase enzymes IC₅₀ = 0.01247 ± 0.01 µM and IC₅₀ = 0.01372 ± 0.03 µM, respectively. In addition, in vivo testing of the highly potent α-glucosidase inhibitor (7b) on rats with DTZ-induced diabetes was done and showed significant reduction of blood glucose levels compared to the reference drug. Furthermore, a molecular docking study was performed to help understand the binding interactions of the most active analogs with these two enzymes. The data obtained from the molecular modeling were correlated with those obtained from the biological screening. These data showed considerable antidiabetic activity for these newly synthesized compounds. Full article

(This article belongs to the Section Medicinal Chemistry)

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9 pages, 1136 KiB

Open AccessArticle

Separation and Quantification of Four Main Chiral Glucosinolates in Radix Isatidis and Its Granules Using High-Performance Liquid Chromatography/Diode Array Detector Coupled with Circular Dichroism Detection

by Yanhong Shi, Cheng Zheng, Jinhang Li, Li Yang, Zhengtao Wang and Rui Wang

Molecules 2018, 23(6), 1305; https://doi.org/10.3390/molecules23061305 - 29 May 2018

Cited by 14 | Viewed by 4091

Abstract

As chemical drugs, separation and quantification of the specific enantiomer from the chiral compounds in herbal medicines are becoming more important. To clarify the chemical characterization of chiral glucosinolates—the antiviral active ingredients of Radix Isatidis, an optimized efficient method of HPLC-UV-CD was [...] Read more.

As chemical drugs, separation and quantification of the specific enantiomer from the chiral compounds in herbal medicines are becoming more important. To clarify the chemical characterization of chiral glucosinolates—the antiviral active ingredients of Radix Isatidis, an optimized efficient method of HPLC-UV-CD was developed to simultaneously separate and quantify the four main chiral glucosinolates: progoitrin, epiprogoitrin, and R,S-goitrin. The first step was to determine progoitrin, epiprogoitrin, and R,S-goitrin using HPLC-UV, and then determine the R-goitrin and S-goitrin by coupling with CD detection. Subsequently, through the linear relations between anisotropy factor (g factor) and the percent optical purity of R-goitrin, the contents of R-goitrin and S-goitrin from the R,S-goitrin mixture were calculated separately. Furthermore, the chemical composition features of the four chiral glucosinolates in 37 samples from crude drugs, decoction pieces, and granules of R. Isatidis were conducted. The total content of the four glucosinolates was obviously higher in crude drugs, and the variance character of each glucosinolate contents was different. In summary, the accurate measurement method reported here allows for better control of the internal quality of R. Isatidis and its granules and provides a powerful approach for the analysis of other chiral components in traditional Chinese medicines. Full article

(This article belongs to the Section Analytical Chemistry)

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16 pages, 3892 KiB

Open AccessArticle

Synthesis of 2-Deoxybrassinosteroids Analogs with 24-nor, 22(S)-23-Dihydroxy-Type Side Chains from Hyodeoxycholic Acid

by Rodrigo Carvajal, Cesar González, Andrés F. Olea, Mauricio Fuentealba and Luis Espinoza

Molecules 2018, 23(6), 1306; https://doi.org/10.3390/molecules23061306 - 29 May 2018

Cited by 11 | Viewed by 4111

Abstract

Natural brassinosteroids are widespread in the plant kingdom and it is known that they play an important role in regulating plant growth. In this study, two new brassinosteroid analogs with shorter side chains but keeping the diol function were synthesized. Thus, the synthesis [...] Read more.

Natural brassinosteroids are widespread in the plant kingdom and it is known that they play an important role in regulating plant growth. In this study, two new brassinosteroid analogs with shorter side chains but keeping the diol function were synthesized. Thus, the synthesis of 2-deoxybrassinosteroids analogs of the 3α-hydroxy-24-nor, 22,23-dihydroxy-5α-cholestane side chain type is described. The starting material is a derivative from hyodeoxycholic acid (4), which was obtained with an overall yield of 59% following a previously reported five step route. The side chain of this intermediate was modified by oxidative decarboxylation to get a terminal olefin at the C22-C23 position (compound 20) and subsequent dihydroxylation of the olefin. The resulting epimeric mixture of 21a, 21b was separated and the absolute configuration at the C22 carbon for the main product 21a was elucidated by single crystal X-ray diffraction analysis of the benzoylated derivative 22. Finally, lactonization of 21a through a Baeyer-Villiger oxidation of triacetylated derivative 23, using CF₃CO₃H/CHCl₃ as oxidant system, leads to lactones 24 and 25 in 35% and 14% yields, respectively. Deacetylation of these compounds leads to 2-deoxybrassinosteroids 18 and 19 in 86% and 81% yields. Full structural characterization of all synthesized compounds was achieved using their 1D, 2D NMR, and HRMS data. Full article

(This article belongs to the Section Organic Chemistry)

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13 pages, 398 KiB

Open AccessArticle

Small Universal Bacteria and Plasmid Computing Systems

by Xun Wang, Pan Zheng, Tongmao Ma and Tao Song

Molecules 2018, 23(6), 1307; https://doi.org/10.3390/molecules23061307 - 29 May 2018

Cited by 16 | Viewed by 6537

Abstract

Bacterial computing is a known candidate in natural computing, the aim being to construct “bacterial computers” for solving complex problems. In this paper, a new kind of bacterial computing system, named the bacteria and plasmid computing system (BP system), is proposed. We investigate [...] Read more.

Bacterial computing is a known candidate in natural computing, the aim being to construct “bacterial computers” for solving complex problems. In this paper, a new kind of bacterial computing system, named the bacteria and plasmid computing system (BP system), is proposed. We investigate the computational power of BP systems with finite numbers of bacteria and plasmids. Specifically, it is obtained in a constructive way that a BP system with 2 bacteria and 34 plasmids is Turing universal. The results provide a theoretical cornerstone to construct powerful bacterial computers and demonstrate a concept of paradigms using a “reasonable” number of bacteria and plasmids for such devices. Full article

(This article belongs to the Special Issue Molecular Computing and Bioinformatics)

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12 pages, 794 KiB

Open AccessArticle

Parametrization of Combined Quantum Mechanical and Molecular Mechanical Methods: Bond-Tuned Link Atoms

by Xin-Ping Wu, Laura Gagliardi and Donald G. Truhlar

Molecules 2018, 23(6), 1309; https://doi.org/10.3390/molecules23061309 - 30 May 2018

Cited by 12 | Viewed by 5315

Abstract

Combined quantum mechanical and molecular mechanical (QM/MM) methods are the most powerful available methods for high-level treatments of subsystems of very large systems. The treatment of the QM−MM boundary strongly affects the accuracy of QM/MM calculations. For QM/MM calculations having covalent bonds cut [...] Read more.

Combined quantum mechanical and molecular mechanical (QM/MM) methods are the most powerful available methods for high-level treatments of subsystems of very large systems. The treatment of the QM−MM boundary strongly affects the accuracy of QM/MM calculations. For QM/MM calculations having covalent bonds cut by the QM−MM boundary, it has been proposed previously to use a scheme with system-specific tuned fluorine link atoms. Here, we propose a broadly parametrized scheme where the parameters of the tuned F link atoms depend only on the type of bond being cut. In the proposed new scheme, the F link atom is tuned for systems with a certain type of cut bond at the QM−MM boundary instead of for a specific target system, and the resulting link atoms are call bond-tuned link atoms. In principle, the bond-tuned link atoms can be as convenient as the popular H link atoms, and they are especially well adapted for high-throughput and accurate QM/MM calculations. Here, we present the parameters for several kinds of cut bonds along with a set of validation calculations that confirm that the proposed bond-tuned link-atom scheme can be as accurate as the system-specific tuned F link-atom scheme. Full article

(This article belongs to the Special Issue Combined Quantum Mechanical and Molecular Mechanical Methods and Simulations)

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14 pages, 3693 KiB

Open AccessArticle

Subcritical Water-Carbon Dioxide Pretreatment of Oil Palm Mesocarp Fiber for Xylooligosaccharide and Glucose Production

by Norlailiza Ahmad, Mohd Rafein Zakaria, Mohd Zulkhairi Mohd Yusoff, Shinji Fujimoto, Hiroyuki Inoue, Hidayah Ariffin, Mohd Ali Hassan and Yoshihoto Shirai

Molecules 2018, 23(6), 1310; https://doi.org/10.3390/molecules23061310 - 30 May 2018

Cited by 22 | Viewed by 5057

Abstract

The present work aimed to investigate the pretreatment of oil palm mesocarp fiber (OPMF) in subcritical H₂O-CO₂ at a temperature range from 150–200 °C and 20–180 min with CO₂ pressure from 3–5 MPa. The pretreated solids and liquids from [...] Read more.

The present work aimed to investigate the pretreatment of oil palm mesocarp fiber (OPMF) in subcritical H₂O-CO₂ at a temperature range from 150–200 °C and 20–180 min with CO₂ pressure from 3–5 MPa. The pretreated solids and liquids from this process were separated by filtration and characterized. Xylooligosaccharides (XOs), sugar monomers, acids, furans and phenols in the pretreated liquids were analyzed by using HPLC. XOs with a degree of polymerization X2–X4 comprising xylobiose, xylotriose, xylotetraose were analyzed by using HPAEC-PAD. Enzymatic hydrolysis was performed on cellulose-rich pretreated solids to observe xylose and glucose production. An optimal condition for XOs production was achieved at 180 °C, 60 min, 3 MPa and the highest XOs obtained was 81.60 mg/g which corresponded to 36.59% of XOs yield from total xylan of OPMF. The highest xylose and glucose yields obtained from pretreated solids were 29.96% and 84.65%, respectively at cellulase loading of 10 FPU/g-substrate. Full article

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

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12 pages, 1908 KiB

Open AccessArticle

Enantiomerically Enriched 1,2-P,N-Bidentate Ferrocenyl Ligands for 1,3-Dipolar Cycloaddition and Transfer Hydrogenation Reactions

by Irina A. Utepova, Polina O. Serebrennikova, Marina S. Streltsova, Alexandra A. Musikhina, Tatiana G. Fedorchenko, Oleg N. Chupakhin and Andrey P. Antonchick

Molecules 2018, 23(6), 1311; https://doi.org/10.3390/molecules23061311 - 30 May 2018

Cited by 8 | Viewed by 4235

Abstract

Novel complexes of 1,2-P,N-bidentate ferrocenyl ligands with AgOAc or with [RuCl₂(PPh₃)₃] as catalysts have been studied in asymmetric synthesis. The catalytic activity of these systems have been studied in [3+2]-cycloaddition of azomethine ylides with olefins and the asymmetric transfer hydrogenation of ketones. Full article

(This article belongs to the Special Issue Ferrocene and Ferrocene-Containing Compounds)

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19 pages, 4043 KiB

Open AccessArticle

Knowledge-Based Neuroendocrine Immunomodulation (NIM) Molecular Network Construction and Its Application

by Tongxing Wang, Lu Han, Xiaorui Zhang, Rongrong Wu, Xiaorui Cheng, Wenxia Zhou and Yongxiang Zhang

Molecules 2018, 23(6), 1312; https://doi.org/10.3390/molecules23061312 - 30 May 2018

Cited by 8 | Viewed by 4643

Abstract

Growing evidence shows that the neuroendocrine immunomodulation (NIM) network plays an important role in maintaining and modulating body function and the homeostasis of the internal environment. The disequilibrium of NIM in the body is closely associated with many diseases. In the present study, [...] Read more.

Growing evidence shows that the neuroendocrine immunomodulation (NIM) network plays an important role in maintaining and modulating body function and the homeostasis of the internal environment. The disequilibrium of NIM in the body is closely associated with many diseases. In the present study, we first collected a core dataset of NIM signaling molecules based on our knowledge and obtained 611 NIM signaling molecules. Then, we built a NIM molecular network based on the MetaCore database and analyzed the signaling transduction characteristics of the core network. We found that the endocrine system played a pivotal role in the bridge between the nervous and immune systems and the signaling transduction between the three systems was not homogeneous. Finally, employing the forest algorithm, we identified the molecular hub playing an important role in the pathogenesis of rheumatoid arthritis (RA) and Alzheimer’s disease (AD), based on the NIM molecular network constructed by us. The results showed that GSK3B, SMARCA4, PSMD7, HNF4A, PGR, RXRA, and ESRRA might be the key molecules for RA, while RARA, STAT3, STAT1, and PSMD14 might be the key molecules for AD. The molecular hub may be a potentially druggable target for these two complex diseases based on the literature. This study suggests that the NIM molecular network in this paper combined with the forest algorithm might provide a useful tool for predicting drug targets and understanding the pathogenesis of diseases. Therefore, the NIM molecular network and the corresponding online tool will not only enhance research on complex diseases and system biology, but also promote the communication of valuable clinical experience between modern medicine and Traditional Chinese Medicine (TCM). Full article

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13 pages, 3293 KiB

Open AccessArticle

Molecular Docking of Potential Inhibitors of Broccoli Myrosinase

by J. Román, A. Castillo and A. Mahn

Molecules 2018, 23(6), 1313; https://doi.org/10.3390/molecules23061313 - 30 May 2018

Cited by 21 | Viewed by 6832

Abstract

Glucosinolates are secondary metabolites occurring in Brassicaceae plants whose hydrolysis may yield isothiocyanates, widely recognized as health-promoting compounds. Myrosinase catalyzes this conversion. The chemical mechanism involves an unstable intermediary (thiohydroxamate-O-sulfonate) that spontaneously decomposes into isothiocyanates or other non-bioactive compounds depending on [...] Read more.

Glucosinolates are secondary metabolites occurring in Brassicaceae plants whose hydrolysis may yield isothiocyanates, widely recognized as health-promoting compounds. Myrosinase catalyzes this conversion. The chemical mechanism involves an unstable intermediary (thiohydroxamate-O-sulfonate) that spontaneously decomposes into isothiocyanates or other non-bioactive compounds depending on pH and cofactors. At acidic pH, non-bioactive compounds such as nitriles and thiocyanates are formed, while at neutral pH isothiocyanates are obtained. Broccoli myrosinase has been poorly studied so far. Recently, its amino acidic sequence was elucidated, and a structural model was built. The aim of this work was to study the molecular interaction of broccoli myrosinase with different ligands at acidic pH to propose possible inhibitors that prevent formation of undesirable compounds at acidic pH, and that at neutral pH dissociate from the enzyme, allowing formation of isothiocyanates. The interaction between broccoli myrosinase and 40 ligands was studied by molecular docking simulations. Both the enzyme and each inhibitor were set at pH 3.0. Amygdaline and arbutin showed the highest affinity to broccoli myrosinase in this condition. The residues that stabilize the complexes agree with those that stabilize the substrate (Gln207, Glu429, Tyr352, and Ser433). Accordingly, amygdaline and arbutin would perform as competitive inhibitors of myrosinase at pH 3.0. Full article

(This article belongs to the Special Issue Molecular Docking/Screening for Food Science)

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17 pages, 3909 KiB

Open AccessArticle

UPLC-HRMS-Based Plasma Metabolomic Profiling of Novel Biomarkers by Treatment with KDZI in Cerebral Ischemia Reperfusion Rats

by Chunguo Wang, Chenyue Liu, Min Wang, Quantao Ma, Yaqi Li, Ting Wang and Baosheng Zhao

Molecules 2018, 23(6), 1315; https://doi.org/10.3390/molecules23061315 - 30 May 2018

Cited by 17 | Viewed by 4314

Abstract

Kudiezi injection (KDZI), also known as Diemailing injection, is a traditional Chinese medicine injection of the composite plant Ixeris sonchifolia Hance (also known as Kudiezi), and has been widely used to treat coronary heart disease, angina pectoris, and cerebral infarction, but its pharmacological [...] Read more.

Kudiezi injection (KDZI), also known as Diemailing injection, is a traditional Chinese medicine injection of the composite plant Ixeris sonchifolia Hance (also known as Kudiezi), and has been widely used to treat coronary heart disease, angina pectoris, and cerebral infarction, but its pharmacological mechanisms remain unclear. This study is designed to explore the effects of KDZI on middle cerebral artery occlusion and reperfusion (MCAO/R) rats, and to identify metabolic features of cerebral ischemia reperfusion by using a nontargeted metabolic profiling method based on ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). In this process, 32 potential biomarkers were found in plasma. KDZI significantly upregulated the levels of taurochenodesoxycholic acid, leucine, l-phenylalanine, l-tryptophan, arachidonic acid (ARA), and phosphatidyl ethanolamines (PE), phosphatidyl cholines (PC) and downregulated the levels of l-valine and 5-hydroxyindole-3-acetic acid (5-HIAA) in plasma. The results indicated that the mechanisms of KDZI on MCAO/R were related to the mechanisms of amino acid and lipid metabolism. Full article

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13 pages, 2946 KiB

Open AccessArticle

Gold Nanoparticles as a Photothermal Agent in Cancer Therapy: The Thermal Ablation Characteristic Length

by Thomas Grosges and Dominique Barchiesi

Molecules 2018, 23(6), 1316; https://doi.org/10.3390/molecules23061316 - 31 May 2018

Cited by 26 | Viewed by 4247

Abstract

In cancer therapy, the thermal ablation of diseased cells by embedded nanoparticles is one of the known therapies. It is based on the absorption of the energy of the illuminating laser by nanoparticles. The resulting heating of nanoparticles kills the cell where these [...] Read more.

In cancer therapy, the thermal ablation of diseased cells by embedded nanoparticles is one of the known therapies. It is based on the absorption of the energy of the illuminating laser by nanoparticles. The resulting heating of nanoparticles kills the cell where these photothermal agents are embedded. One of the main constraints of this therapy is preserving the surrounding healthy cells. Therefore, two parameters are of interest. The first one is the thermal ablation characteristic length, which corresponds to an action distance around the nanoparticles for which the temperature exceeds the ablation threshold. This critical geometric parameter is related to the expected conservation of the body temperature in the surroundings of the diseased cell. The second parameter is the temperature that should be reached to achieve active thermal agents. The temperature depends on the power of the illuminating laser, on the size of nanoparticles and on their physical properties. The purpose of this paper is to propose behavior laws under the constraints of both the body temperature at the boundary of the cell to preserve surrounding cells and an acceptable range of temperature in the target cell. The behavior laws are deduced from the finite element method, which is able to model aggregates of nanoparticles. We deduce sensitivities to the laser power and to the particle size. We show that the tuning of the temperature elevation and of the distance of action of a single nanoparticle is not significantly affected by variations of the particle size and of the laser power. Aggregates of nanoparticles are much more efficient, but represent a potential risk to the surrounding cells. Fortunately, by tuning the laser power, the thermal ablation characteristic length can be controlled. Full article

(This article belongs to the Special Issue Photothermal Agents in Therapy)

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14 pages, 4051 KiB

Open AccessArticle

Characterization of Goat Milk Hydrolyzed by Cell Envelope Proteinases from Lactobacillus plantarum LP69: Proteolytic System Optimization, Bioactivity, and Storage Stability Evaluation

by Guowei Shu, Jie Huang, Li Chen, Ni Lei and He Chen

Molecules 2018, 23(6), 1317; https://doi.org/10.3390/molecules23061317 - 31 May 2018

Cited by 15 | Viewed by 3562

Abstract

Despite the widespread application of lactic acid bacterium in dairy production through its contribution to acidification, development of sensorial properties, and health-promoting effects, relatively little information is available on the cell envelope proteinases (CEPs) of Lactobacillus plantarum, especially on the proteolytic system [...] Read more.

Despite the widespread application of lactic acid bacterium in dairy production through its contribution to acidification, development of sensorial properties, and health-promoting effects, relatively little information is available on the cell envelope proteinases (CEPs) of Lactobacillus plantarum, especially on the proteolytic system and the production of bioactivity peptides. In this study, CEPs from a novel L. plantarum LP69 were involved in goat milk hydrolysis and generated a product with high activity that showed a degree of hydrolysis of 15.68 ± 0.74%, Angiotensin I-Converting Enzyme (ACE)-inhibitory rate of 83.25 ± 1.05%, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging rate of 64.91 ± 1.27%, and hydroxyl radical scavenging rate of 89.17 ± 1.13%. The optimized hydrolysis conditions were time of 4.5 h, temperature of 41 °C, initial pH of 8.5, and enzyme to substrate ratio (E/S) of 12% (w/w) by orthogonal experiments. Application of a stabilizer greatly promoted milk stability. A well-designed stabilizer consists of 0.05% carrageenan, 0.15% gellan gum, and 0.15% sucrose esters, which significantly raised the milk stability coefficient, R, from 70.67% to 98.57%. The storage stability of milk was evaluated during 84 days at room temperature or 4 °C. Our study depicts the contribution of CEPs from L. plantarum LP69 in goat milk, exploring a new way for the development of a functional milk product. Full article

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17 pages, 17502 KiB

Open AccessArticle

Design, Synthesis, and Evaluation of a New Series of Thiazole-Based Anticancer Agents as Potent Akt Inhibitors

by Mehlika Dilek Altıntop, Belgin Sever, Gülşen Akalın Çiftçi and Ahmet Özdemir

Molecules 2018, 23(6), 1318; https://doi.org/10.3390/molecules23061318 - 31 May 2018

Cited by 57 | Viewed by 4766

Abstract

In an attempt to develop potent anticancer agents targeting Akt, new thiazole derivatives (1–10) were synthesized and investigated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma, and NIH/3T3 (healthy) mouse embryonic fibroblast cell lines. The [...] Read more.

In an attempt to develop potent anticancer agents targeting Akt, new thiazole derivatives (1–10) were synthesized and investigated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma, and NIH/3T3 (healthy) mouse embryonic fibroblast cell lines. The most potent compounds were also investigated for their effects on apoptosis and Akt pathway. The most promising anticancer agent was found to be 2-[2-((4-(4-cyanophenoxy)phenyl)methylene)hydrazinyl]-4-(4-cyanophenyl)thiazole (6), due to its selective inhibitory effects on A549 and C6 cells with IC₅₀ values of 12.0 ± 1.73 µg/mL and 3.83 ± 0.76 µg/mL, respectively. Furthermore, compound 6 increased early and late apoptotic cell population (32.8%) in C6 cell line more than cisplatin (28.8%) and significantly inhibited the Akt enzyme. The molecular docking study was performed to predict the possible binding modes of compounds A, 6, and 8 inside the active site of Akt (PDB code: 4EJN). Molecular docking simulations were found to be in accordance with in vitro studies and, hence, supported the biological activity. A computational study for the prediction of absorption, distribution, metabolism and excretion (ADME) properties of all compounds was also performed. On the basis of Lipinski’s rule of five, the compounds were expected to be potential orally bioavailable agents. Full article

(This article belongs to the Section Medicinal Chemistry)

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9 pages, 3051 KiB

Open AccessArticle

Photo-Oxidation of Bisphenol A in Aqueous Solutions at Near Neutral pH by a Fe(III)-Carboxylate Complex with Oxalacetic Acid as a Benign Molecule

by Jing Xu, Chuxuan Zhao, Tianbei Wang, Shaojie Yang and Zizheng Liu

Molecules 2018, 23(6), 1319; https://doi.org/10.3390/molecules23061319 - 31 May 2018

Cited by 7 | Viewed by 3561

Abstract

The photo-oxidation of organic pollutants as induced by ferric-carboxylate complexes was known to be a photo-Fenton-like process. The use of a carboxylate ligand with higher efficiency and lower toxicity at near neutral pH is of high interest to researchers. In this work, photo-oxidation [...] Read more.

The photo-oxidation of organic pollutants as induced by ferric-carboxylate complexes was known to be a photo-Fenton-like process. The use of a carboxylate ligand with higher efficiency and lower toxicity at near neutral pH is of high interest to researchers. In this work, photo-oxidation of bisphenol A (BPA) induced by a ferric-oxalacetic acid complex in aqueous solutions was investigated under 395 nm LED lamps. The results showed that the rate of BPA degradation increased in the order pH 10.0 << 8.0 < 6.5 < 4.0 within the first 10 min. More than 90% of BPA was successfully oxidized with Fe(III)/oxalacetic acid with a ratio of 1:5 at pH 6.5, which was primarily attributed to the generated hydroxyl radical. Iron in the Fe(III)-oxalacetic acid system was reused by simple addition of oxalacetic acid to the reaction mixture. Compared to common carboxylate ligands (pyruvic acid, oxalic acid, and citric acid), oxalacetic acid is more efficient and environmentally friendly for the Fe(III)-carboxylate complex-based photo-Fenton-like process at near neutral pH. Full article

(This article belongs to the Section Photochemistry)

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15 pages, 4685 KiB

Open AccessFeature PaperArticle

Computational Insight into the Effect of Natural Compounds on the Destabilization of Preformed Amyloid-β(1–40) Fibrils

by Francesco Tavanti, Alfonso Pedone and Maria Cristina Menziani

Molecules 2018, 23(6), 1320; https://doi.org/10.3390/molecules23061320 - 31 May 2018

Cited by 29 | Viewed by 5016

Abstract

One of the principal hallmarks of Alzheimer’s disease (AD) is related to the aggregation of amyloid-β fibrils in an insoluble form in the brain, also known as amyloidosis. Therefore, a prominent therapeutic strategy against AD consists of either blocking the amyloid aggregation and/or [...] Read more.

One of the principal hallmarks of Alzheimer’s disease (AD) is related to the aggregation of amyloid-β fibrils in an insoluble form in the brain, also known as amyloidosis. Therefore, a prominent therapeutic strategy against AD consists of either blocking the amyloid aggregation and/or destroying the already formed aggregates. Natural products have shown significant therapeutic potential as amyloid inhibitors from in vitro studies as well as in vivo animal tests. In this study, the interaction of five natural biophenols (curcumin, dopamine, (-)-epigallocatechin-3-gallate, quercetin, and rosmarinic acid) with amyloid-β(1–40) fibrils has been studied through computational simulations. The results allowed the identification and characterization of the different binding modalities of each compounds and their consequences on fibril dynamics and aggregation. It emerges that the lateral aggregation of the fibrils is strongly influenced by the intercalation of the ligands, which modulates the double-layered structure stability. Full article

(This article belongs to the Special Issue Molecular Modeling in Drug Design)

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16 pages, 3657 KiB

Open AccessArticle

Effect on White Grape Must of Multiflora Bee Pollen Addition during the Alcoholic Fermentation Process

by Antonio Amores-Arrocha, Ana Roldán, Ana Jiménez-Cantizano, Ildefonso Caro and Víctor Palacios

Molecules 2018, 23(6), 1321; https://doi.org/10.3390/molecules23061321 - 31 May 2018

Cited by 17 | Viewed by 5378

Abstract

The aim of the present study was to compare and analyze the impact of using bee pollen doses (0.1, 0.25, 1, 5, 10 and 20 g/L) as activator in the alcoholic fermentation process of Palomino fino and Riesling wines. In this regard, its [...] Read more.

The aim of the present study was to compare and analyze the impact of using bee pollen doses (0.1, 0.25, 1, 5, 10 and 20 g/L) as activator in the alcoholic fermentation process of Palomino fino and Riesling wines. In this regard, its influence on the musts composition, the fermentative kinetics, the evolution of the populations of Saccharomyces cerevisiae, the evolution of yeast-assimilable nitrogen and physico-chemical characteristics of final wines has been analyzed. Bee pollen addition produces significant increases in yeast-assimilable nitrogen and maximum yeasts population and exponential velocity reached during alcoholic fermentation. Bee pollen showed an important effect on yeast survival during the death phase. Final wines showed significantly increase in volatile acidity above doses higher than 10 g/L and Comisión Internacional de L’Eclairage parameters (CIELab), color intensity and Abs 420 nm, from 1 g/L. Therefore, pollen could be used as fermentative activator for the alcoholic fermentation of white wines applying doses below of 1 g/L. Full article

(This article belongs to the Collection Wine Chemistry)

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13 pages, 727 KiB

Open AccessArticle

Development and Validation of a HPLC-MS/MS Method for Simultaneous Determination of Twelve Bioactive Compounds in Epimedium: Application to a Pharmacokinetic Study in Rats

by Mengjie Sun, Yanwei Yin, Juan Wei, Xiaopeng Chen, Huizi Ouyang, Yanxu Chang, Xiumei Gao and Jun He

Molecules 2018, 23(6), 1322; https://doi.org/10.3390/molecules23061322 - 31 May 2018

Cited by 25 | Viewed by 4393

Abstract

A rapid and reliable HPLC-MS/MS method has been developed and validated for the simultaneous quantification of twelve bioactive compounds (baohuoside II, baohuoside I, sagittatoside A, sagittatoside B, magnoflorine, epimedin A, epimedin B, epimedin C, chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid and icariin) in [...] Read more.

A rapid and reliable HPLC-MS/MS method has been developed and validated for the simultaneous quantification of twelve bioactive compounds (baohuoside II, baohuoside I, sagittatoside A, sagittatoside B, magnoflorine, epimedin A, epimedin B, epimedin C, chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid and icariin) in rat plasma. The collected plasma samples were prepared by protein precipitate with acetonitrile. The twelve compounds were separated on a CORTECS^®C18 column (4.6 mm × 150 mm, 2.7 μm) with a gradient mobile phase system of 0.1% (v/v) formic acid and acetonitrile at a flow rate of 0.3 mL/min. All of the analytes were quantitated using electrospray ionization (ESI) in negative ion mode with selected reaction monitoring (SRM). The intra- and inter-day accuracy ranged from −5.6% to 13.0%, and the precisions of the analytes were less than 10.9%. The mean recoveries of the analytes were in the range of 60.66% to 99.77% and the matrix effect ranged from 93.08% to 119.84%. Stability studies proved that the analytes were stable under the tested conditions, with a relative standard deviation (RSD) lower than 11.7%. The developed method was successfully applied to evaluating the pharmacokinetic study of twelve bioactive compounds after oral administration of Epimedium extract in rat. Full article

(This article belongs to the Section Analytical Chemistry)

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14 pages, 5661 KiB

Open AccessArticle

Plate-Focusing Based on a Meta-Molecule of Dendritic Structure in the Visible Frequency

by Suna Cheng, Di An, Huan Chen and Xiaopeng Zhao

Molecules 2018, 23(6), 1323; https://doi.org/10.3390/molecules23061323 - 31 May 2018

Cited by 2 | Viewed by 3468

Abstract

To study the potential application of metasurfaces in lens technology, we propose a dendritic meta-molecule surface (also referred to as a dendritic metasurface) and realize the focusing effect in the visible spectrum through simulations and experiments. Using asymmetric dendritic structures, this metasurface can [...] Read more.

To study the potential application of metasurfaces in lens technology, we propose a dendritic meta-molecule surface (also referred to as a dendritic metasurface) and realize the focusing effect in the visible spectrum through simulations and experiments. Using asymmetric dendritic structures, this metasurface can achieve distinct broadband anomalous reflection and refraction. When the metasurface is rotated by 180° around the z axis, anomalous reflection and refraction in vertically incident optical waves are in opposite directions. Considering this feature, a metasurface is designed to achieve a prominent plate-focusing effect. Samples with a transmission peak of green light at 555 nm, yellow light at 580 nm, and red light at 650 nm were prepared using bottom-up electrochemical deposition, and the focus intensity of approximately 10% and focal length of almost 600 µm were experimentally demonstrated. Full article

(This article belongs to the Special Issue Metallic Nanoparticles: From Synthesis, Structure-Property Relationships to Applications)

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14 pages, 4679 KiB

Open AccessArticle

Sphingolipidomic Profiling of Rat Serum by UPLC-Q-TOF-MS: Application to Rheumatoid Arthritis Study

by Fanghui Qu, Hongyang Zhang, Min Zhang and Ping Hu

Molecules 2018, 23(6), 1324; https://doi.org/10.3390/molecules23061324 - 31 May 2018

Cited by 22 | Viewed by 4808

Abstract

Sphingolipids (SPLs) are biologically important molecules, but the structural diversity and complexity of SPLs brings significant analytical challenges for their study. In this paper, we have developed an UPLC-Q-TOF-MS-based sphingolipidomic approach for the comprehensive identification and quantification of SPLs in rat serum. A [...] Read more.

Sphingolipids (SPLs) are biologically important molecules, but the structural diversity and complexity of SPLs brings significant analytical challenges for their study. In this paper, we have developed an UPLC-Q-TOF-MS-based sphingolipidomic approach for the comprehensive identification and quantification of SPLs in rat serum. A total of 120 SPLs covering seven subcategories were identified for the first time. Method validations including linearity, sensitivity, reproducibility, and recovery were also evaluated. This method was exemplarily applied to characterize the SPL alterations in rheumatoid arthritis (RA) rats and the intervention effects of indomethacin (IDM). Partial least squares-discriminant analysis (PLS-DA) showed that the model group was well separated from the control group, whereas the IDM-treated group exhibited a trend to recover the controls. Twenty-six significantly changed SPL markers were explored, and the levels of ceramides (Cers) and their metabolites were found to be reversed by IDM treatment. These results indicate that IDM exerts anti-arthritic effects through the suppression of Cer-mediated COX-2 activation and resulting PEG₂ liberation. The present study demonstrates a promising potential of this method for the understanding of RA and the anti-arthritic mechanisms of relevant drugs. Full article

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14 pages, 10157 KiB

Open AccessArticle

Study on the Structure of Ginseng Glycopeptides with Anti-Inflammatory and Analgesic Activity

by Haoming Luo, Difu Zhu, Ying Wang, Yinghong Chen, Ruizhi Jiang, Peng Yu and Zhidong Qiu

Molecules 2018, 23(6), 1325; https://doi.org/10.3390/molecules23061325 - 31 May 2018

Cited by 24 | Viewed by 4120

Abstract

Panax ginseng is well known for its medicinal functions. As a class of important compound of ginseng, ginsenoside is widely studied around the world. In addition, ginseng glycopeptides also showed good biological activity, but researches in this field are rarely reported. In this [...] Read more.

Panax ginseng is well known for its medicinal functions. As a class of important compound of ginseng, ginsenoside is widely studied around the world. In addition, ginseng glycopeptides also showed good biological activity, but researches in this field are rarely reported. In this study, ginseng glycopeptides (Gg) were first prepared from Panax ginseng by reflux extracted with 85% ethanol and the following purification with Sephadex G-15 column. Then, the inflammatory pain models induced by carrageenan and the rat pain models induced by Faure Marin were established for research on mechanism of analgesic activities. It is showed that Gg had an obvious inhibiting effect on inflammation and a significant reduction on the Malondialdehyde (MDA) of inflammatory foot tissue. And there were significant differences between moderate to high dose of Gg and model group in Interleukin 1β (IL-1β), Interleukin 2 (IL-2), Interleukin 4 (IL-4), Tumor necrosis factor α (TNF-α) and Histamine. The two models can be preliminarily determined that the analgesic effect of Gg may be peripheral, which mechanism may be related to the dynamic balance between proinflammatory cytokines (TNF-α, IL-1β) and anti-inflammatory cytokines (IL-2, IL-4, and Interleukin 10 (IL-10)). A series of methods were used to study Gg in physical-chemical properties and linking mode of glycoside. The high-resolution mass spectrometry was used for identification of the structure of Gg. Moreover, the structure of 20 major Gg were investigated and identified. The structural analysis of Gg was benefit for the next study on structure-activity relationship. Full article

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11 pages, 1612 KiB

Open AccessArticle

Enhanced Antioxidant Activity of Bioactives in Colored Grains by Nano-Carriers in Human Lens Epithelial Cells

by Yoon-Mi Lee, Young Yoon, Haelim Yoon, Sooji Song, Hyun-Min Park, Yu Young Lee, Hyunho Shin, Sung Won Hwang and Kyung-Jin Yeum

Molecules 2018, 23(6), 1327; https://doi.org/10.3390/molecules23061327 - 31 May 2018

Cited by 9 | Viewed by 5139

Abstract

The use of phytochemicals for preventing chronic diseases associated with oxidative stress such as cataracts is hindered by their low bioavailability. The effects of nano-carriers on the antioxidant activities of extracts of black rice with giant embryo (BRGEx) and soybeans (SBx) have been [...] Read more.

The use of phytochemicals for preventing chronic diseases associated with oxidative stress such as cataracts is hindered by their low bioavailability. The effects of nano-carriers on the antioxidant activities of extracts of black rice with giant embryo (BRGEx) and soybeans (SBx) have been determined in human lens epithelial B3 cells. Scanning (SEM) and transmission electron microscopy (TEM) demonstrated that rGO (reduced graphene oxide) has a flat surface unlike GO (graphene oxide), which has a distinctive wrinkled structure with defects. UPLC analysis revealed 41.9 μg/100 g of γ-oryzanols in water extract of BRGE, and 111.8 μg /100 g of lutein, 757.7 μg/100 g of γ-tocotrienol, 4071.4 μg/100 g of γ-tocopherol in 40% ethanol extract of soybeans, respectively. Even though a low concentration of BRGEx alone did not show any antioxidant activity in B3 cells, co-treatment of BRGEx with rGO together substantially reduced hydrogen peroxide and methylglyoxal-induced DNA damage, as determined by phosphorylated γH2AX. In addition, SBx with rGO also attenuated DNA damage. Furthermore, intracellular reactive oxygen species were significantly decreased by combining extracts of these colored grains with rGO. These results suggest a potential application of nanocarriers for enhancing the bioavailability of phytochemicals. Full article

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

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16 pages, 3751 KiB

Open AccessArticle

Replacing Standard Reporters from Molecular Cloning Plasmids with Chromoproteins for Positive Clone Selection

by Margarita Daniela Tafoya-Ramírez, Felipe Padilla-Vaca, Ana Patricia Ramírez-Saldaña, Josué Daniel Mora-Garduño, Ángeles Rangel-Serrano, Naurú Idalia Vargas-Maya, Luz Janeth Herrera-Gutiérrez and Bernardo Franco

Molecules 2018, 23(6), 1328; https://doi.org/10.3390/molecules23061328 - 31 May 2018

Cited by 10 | Viewed by 9153

Abstract

Cloning and expression plasmids are the workhorses of modern molecular biology. Despite the pathway paved by synthetic biology, laboratories around the globe still relay on standard cloning techniques using plasmids with reporter proteins for positive clone selection, such as β-galactosidase alpha peptide complementation [...] Read more.

Cloning and expression plasmids are the workhorses of modern molecular biology. Despite the pathway paved by synthetic biology, laboratories around the globe still relay on standard cloning techniques using plasmids with reporter proteins for positive clone selection, such as β-galactosidase alpha peptide complementation for blue/white screening or ccdB, which encodes for a toxic DNA gyrase. These reporters, when interrupted, serve as a positive clone detection system. In the present report, we show that molecular cloning plasmids bearing the coding sequence for a 25.4 kDa protein, AmilCP, encoded by a 685 bp gene, that is well expressed in Escherichia coli, render blue-purple colonies. Using this reporter protein, we developed and tested a cloning system based on the constitutive expression of the non-toxic AmilCP protein, that once interrupted, the loss of purple color serves to facilitate positive clone selection. The main advantage of this system is that is less expensive than other systems since media do not contain chromogenic markers such as X-gal, which is both expensive and cumbersome to prepare and use, or inductors such as IPTG. We also designed an inducible expression plasmid suitable for recombinant protein expression that also contains AmilCP cloning selection marker, a feature not commonly found in protein expression plasmids. The use of chromogenic reporters opens an important avenue for its application in other organisms besides E. coli for clone selection or even for mutant selection. Full article

(This article belongs to the Special Issue Design in Synthetic Biology)

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17 pages, 4243 KiB

Open AccessArticle

Red and Blue Light Promote the Accumulation of Artemisinin in Artemisia annua L.

by Dong Zhang, Wei Sun, Yuhua Shi, Lan Wu, Tianyuan Zhang and Li Xiang

Molecules 2018, 23(6), 1329; https://doi.org/10.3390/molecules23061329 - 31 May 2018

Cited by 53 | Viewed by 5798

Abstract

Artemisinin, which has been isolated from Artemisia annua L., is the most effective antimalarial drug and has saved millions of lives. In addition, artemisinin and its derivatives have anti-tumor, anti-parasitic, anti-fibrosis, and anti-arrhythmic properties, which enhances the demand for these compounds. Improving the [...] Read more.

Artemisinin, which has been isolated from Artemisia annua L., is the most effective antimalarial drug and has saved millions of lives. In addition, artemisinin and its derivatives have anti-tumor, anti-parasitic, anti-fibrosis, and anti-arrhythmic properties, which enhances the demand for these compounds. Improving the content of artemisinin in A. annua is therefore becoming an increasing research interest, as the chemical synthesis of this metabolite is not viable. Ultraviolet B and C irradiation have been reported to improve the artemisinin content in A. annua, but they are harmful to plant growth and development. Therefore, we screened other light sources to examine if they could promote artemisinin content without affecting plant growth and development. We found that red and blue light could enhance artemisinin accumulation by promoting the expression of the genes that were involved in artemisinin biosynthesis, such as amorpha-4,11-diene synthase (ADS) and cytochrome P450 monooxygenase (CYP71AV1) genes. Thus, in addition to being the main light sources for photosynthesis, red and blue light play a key role in plant secondary metabolism, and optimizing the combination of these light might allow for the productionof artemisinin-rich A. annua. Full article

(This article belongs to the Section Metabolites)

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10 pages, 14719 KiB

Open AccessArticle

Detection and Identification of Estrogen Based on Surface-Enhanced Resonance Raman Scattering (SERRS)

by Yang Liu, Yue Chen, Yuanyuan Zhang, Qiangwei Kou, Yongjun Zhang, Yaxin Wang, Lei Chen, Yantao Sun, Honglin Zhang and Young Mee Jung

Molecules 2018, 23(6), 1330; https://doi.org/10.3390/molecules23061330 - 1 Jun 2018

Cited by 38 | Viewed by 6459

Abstract

Many studies have shown that it is important to consider the harmful effects of phenolic hormones on the human body. Traditional UV detection has many limitations, so there is a need to develop new detection methods. We demonstrated a simple and rapid surface-enhanced [...] Read more.

Many studies have shown that it is important to consider the harmful effects of phenolic hormones on the human body. Traditional UV detection has many limitations, so there is a need to develop new detection methods. We demonstrated a simple and rapid surface-enhanced resonance Raman scattering (SERRS) based detection method of trace amounts of phenolic estrogen. As a result of the coupling reaction, there is the formation of strong SERRS activity of azo compound. Therefore, the detection limits are as low as 0.2 × 10⁻⁴ for estrone (E1), estriol (E3), and bisphenol A (BPA). This method is universal because each SERRS fingerprint of the azo dyes a specific hormone. The use of this method is applicable for the testing of phenolic hormones through coupling reactions, and the investigation of other phenolic molecules. Therefore, this new method can be used for efficient detection. Full article

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

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13 pages, 2969 KiB

Open AccessArticle

Monohexosylceramides from Rhizopus Species Isolated from Brazilian Caatinga: Chemical Characterization and Evaluation of Their Anti-Biofilm and Antibacterial Activities

by Edson Rodrigues Vieira, Mariana Ingrid Dutra da Silva Xisto, Milagre Américo Pele, Daniela Sales Alviano, Celuta Sales Alviano, Eliana Barreto-Bergter and Galba Maria De Campos-Takaki

Molecules 2018, 23(6), 1331; https://doi.org/10.3390/molecules23061331 - 1 Jun 2018

Cited by 7 | Viewed by 3988

Abstract

Monohexosylceramides (CMHs) are highly conserved fungal glycosphingolipids playing a role in several cellular processes such as growth, differentiation and morphological transition. In this study, we report the isolation, purification and chemical characterization of CMHs from Rhizopus stolonifer and R. microspores. Using positive [...] Read more.

Monohexosylceramides (CMHs) are highly conserved fungal glycosphingolipids playing a role in several cellular processes such as growth, differentiation and morphological transition. In this study, we report the isolation, purification and chemical characterization of CMHs from Rhizopus stolonifer and R. microspores. Using positive ion mode ESI-MS, two major ion species were observed at m/z 750 and m/z 766, respectively. Both ion species consisted of a glucose/galactose residue attached to a ceramide moiety containing 9-methyl-4,8-sphingadienine with an amidic linkage to a hydroxylated C16:0 fatty acid. The antimicrobial activity of CMH was evaluated against Gram positive and Gram negative bacteria using the agar diffusion assay. CMH from both Rhizopus species inhibited the growth of Bacillus terrae, Micrococcus luteus (M. luteus) and Pseudomonas stutzeri (P. stutzeri) with a MIC₅₀ of 6.25, 6.25 and 3.13 mg/mL, respectively. The bactericidal effect was detected only for M. luteus and P. stutzeri, with MBC values of 25 and 6.25 mg/mL, respectively. Furthermore, the action of CMH on the biofilm produced by methicillin-resistant Staphylococcus aureus (MRSA) was analyzed using 12.5 and 25 mg/mL of CMH from R. microsporus. Total biofilm biomass, biofilm matrix and viability of the cells that form the biofilm structure were evaluated. CMH from R. microsporus was able to inhibit the MRSA biofilm formation in all parameters tested. Full article

(This article belongs to the Section Chemical Biology)

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25 pages, 2753 KiB

Open AccessArticle

Irinotecan and Δ⁹-Tetrahydrocannabinol Interactions in Rat Liver: A Preliminary Evaluation Using Biochemical and Genotoxicity Markers

by Ana Lucić Vrdoljak, Nino Fuchs, Anja Mikolić, Suzana Žunec, Irena Brčić Karačonji, Andreja Jurič, Ljerka Prester, Vedran Micek, Marijana Neuberg, Samir Čanović, Gordan Mršić and Nevenka Kopjar

Molecules 2018, 23(6), 1332; https://doi.org/10.3390/molecules23061332 - 1 Jun 2018

Cited by 10 | Viewed by 5498

Abstract

There is growing interest regarding the use of herbal preparations based on Cannabis sativa for medicinal purposes, despite the poorly understood interactions of their main constituent Δ⁹-tetrahydrocannabinol (THC) with conventional drugs, especially cytostatics. The objective of this pilot study was to [...] Read more.

There is growing interest regarding the use of herbal preparations based on Cannabis sativa for medicinal purposes, despite the poorly understood interactions of their main constituent Δ⁹-tetrahydrocannabinol (THC) with conventional drugs, especially cytostatics. The objective of this pilot study was to prove whether the concomitant intake of THC impaired liver function in male Wistar rats treated with the anticancer drug irinotecan (IRI), and evaluate the toxic effects associated with this exposure. IRI was administered once intraperitoneally (at 100 mg/kg of the body weight (b.w.)), while THC was administered per os repeatedly for 1, 3, and 7 days (at 7 mg/kg b.w.). Functional liver impairments were studied using biochemical markers of liver function (aspartate aminotransferase—AST, alanine aminotransferase—ALP, alkaline phosphatase—AP, and bilirubin) in rats given a combined treatment, single IRI, single THC, and control groups. Using common oxidative stress biomarkers, along with measurement of primary DNA damage in hepatocytes, the degree of impairments caused at the cellular level was also evaluated. THC caused a time-dependent enhancement of acute toxicity in IRI-treated rats, which was confirmed by body and liver weight reduction. Although single THC affected ALP and AP levels more than single IRI, the levels of liver function markers measured after the administration of a combined treatment mostly did not significantly differ from control. Combined exposure led to increased oxidative stress responses in 3- and 7-day treatments, compared to single IRI. Single IRI caused the highest DNA damage at all timepoints. Continuous 7-day oral exposure to single THC caused an increased mean value of comet tail length compared to its shorter treatments. Concomitant intake of THC slightly affected the levels of IRI genotoxicity at all timepoints, but not in a consistent manner. Further studies are needed to prove our preliminary observations, clarify the underlying mechanisms behind IRI and THC interactions, and unambiguously confirm or reject the assumptions made herein. Full article

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28 pages, 7018 KiB

Open AccessArticle

Aromaticity as a Guiding Concept for Spectroscopic Features and Nonlinear Optical Properties of Porphyrinoids

by Tatiana Woller, Paul Geerlings, Frank De Proft, Benoît Champagne and Mercedes Alonso

Molecules 2018, 23(6), 1333; https://doi.org/10.3390/molecules23061333 - 1 Jun 2018

Cited by 46 | Viewed by 7333

Abstract

With their versatile molecular topology and aromaticity, porphyrinoid systems combine remarkable chemistry with interesting photophysical properties and nonlinear optical properties. Hence, the field of application of porphyrinoids is very broad ranging from near-infrared dyes to opto-electronic materials. From previous experimental studies, aromaticity emerges [...] Read more.

With their versatile molecular topology and aromaticity, porphyrinoid systems combine remarkable chemistry with interesting photophysical properties and nonlinear optical properties. Hence, the field of application of porphyrinoids is very broad ranging from near-infrared dyes to opto-electronic materials. From previous experimental studies, aromaticity emerges as an important concept in determining the photophysical properties and two-photon absorption cross sections of porphyrinoids. Despite a considerable number of studies on porphyrinoids, few investigate the relationship between aromaticity, UV/vis absorption spectra and nonlinear properties. To assess such structure-property relationships, we performed a computational study focusing on a series of Hückel porphyrinoids to: (i) assess their (anti)aromatic character; (ii) determine the fingerprints of aromaticity on the UV/vis spectra; (iii) evaluate the role of aromaticity on the NLO properties. Using an extensive set of aromaticity descriptors based on energetic, magnetic, structural, reactivity and electronic criteria, the aromaticity of [4n+2] π-electron porphyrinoids was evidenced as was the antiaromaticity for [4n] π-electron systems. In agreement with previous studies, the absorption spectra of aromatic systems display more intense B and Q bands in comparison to their antiaromatic homologues. The nature of these absorption bands was analyzed in detail in terms of polarization, intensity, splitting and composition. Finally, quantities such as the average polarizability and its anisotropy were found to be larger in aromatic systems, whereas first and second hyperpolarizability are influenced by the interplay between aromaticity, planarity and molecular symmetry. To conclude, aromaticity dictates the photophysical properties in porphyrinoids, whereas it is not the only factor determining the magnitude of NLO properties. Full article

(This article belongs to the Special Issue The Molecular Electron Density Theory: A Modern View of Molecular Reactivity in Organic Chemistry)

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16 pages, 3823 KiB

Open AccessArticle

Statistical Optimization of Medium for Pullulan Production by Aureobasidium pullulans NCPS2016 Using Fructose and Soybean Meal Hydrolysates

by Jinyu Yang, Yanhao Zhang, Shuangzhi Zhao, Qingxin Zhou, Xue Xin and Leilei Chen

Molecules 2018, 23(6), 1334; https://doi.org/10.3390/molecules23061334 - 1 Jun 2018

Cited by 24 | Viewed by 4645

Abstract

Pullulan, with its excellent characteristics of film-forming, water solubility, and biodegradability, is attracting more and more attention in agricultural products preservation. However, high pullulan production cost largely restricts its widely application due to its low production. In order to improve pullulan production by [...] Read more.

Pullulan, with its excellent characteristics of film-forming, water solubility, and biodegradability, is attracting more and more attention in agricultural products preservation. However, high pullulan production cost largely restricts its widely application due to its low production. In order to improve pullulan production by Aureobasidium pullulans NCPS2016, the medium was optimized using single factor experiment and response surface methodology. Based on the single factor experiments, the contents of soybean meal hydrolysates (SMHs), (NH₄)₂SO₄, and K₂HPO₄·3H₂O were considered to be main factors influencing the extracellular polysaccharide (EPS) production, and were further optimized by Box–Behnken design. The optimal content of SMHs of 7.71 g/L, (NH₄)₂SO₄ of 0.35 g/L, and K₂HPO₄·3H₂O of 8.83 g/L were defined. Finally, EPS production of 59.8 g/L was obtained, 39% higher in comparison with the production in the basal medium. The purified EPS produced by NCPS2016 was confirmed to be pullulan. This is the first time fructose is reported to be the optimal carbon source for pullulan production by Aureobasidium pullulans, which is of great significance for the further study of the mechanism of the synthesis of pullulan by NCPS2016. Also, the results here have laid a foundation for reducing the industrial production cost of pullulan. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 2273 KiB

Open AccessArticle

Trapping para-Quinone Methide Intermediates with Ferrocene: Synthesis and Preliminary Biological Evaluation of New Phenol-Ferrocene Conjugates

by Silvia González-Pelayo, Enol López, Javier Borge, Noemí De-los-Santos-Álvarez and Luis A. López

Molecules 2018, 23(6), 1335; https://doi.org/10.3390/molecules23061335 - 1 Jun 2018

Cited by 7 | Viewed by 5357

Abstract

The reaction of para-hydroxybenzyl alcohols with ferrocene in the presence of a catalytic amount of InCl₃ provided ferrocenyl phenol derivatives, an interesting class of organometallic compounds with potential applications in medicinal chemistry. This transformation exhibited a reasonable substrate scope delivering the [...] Read more.

The reaction of para-hydroxybenzyl alcohols with ferrocene in the presence of a catalytic amount of InCl₃ provided ferrocenyl phenol derivatives, an interesting class of organometallic compounds with potential applications in medicinal chemistry. This transformation exhibited a reasonable substrate scope delivering the desired products in synthetically useful yields. Evidence of involvement of a para-quinone methide intermediate in this coupling process was also provided. Preliminary biological evaluation demonstrated that some of the ferrocene derivatives available by this methodology exhibit significant cytotoxicity against several cancer cell lines with IC₅₀ values within the range of 1.07–4.89 μM. Full article

(This article belongs to the Special Issue Ferrocene and Ferrocene-Containing Compounds)

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10 pages, 1229 KiB

Open AccessArticle

Sterepinic Acids A–C, New Carboxylic Acids Produced by a Marine Alga-Derived Fungus

by Takeshi Yamada, Miwa Matsuda, Mayuko Seki, Megumi Hirose and Takashi Kikuchi

Molecules 2018, 23(6), 1336; https://doi.org/10.3390/molecules23061336 - 1 Jun 2018

Cited by 7 | Viewed by 5199

Abstract

Sterepinic acids A–C (1–3), new carboxylic acids with two primary alcohols, have been isolated from a fungal strain of Stereum sp. OUPS-124D-1 attached to the marine alga Undaria pinnatifida. Dihydro-1,5-secovibralactone (4), a new vibralactone derivative, was [...] Read more.

Sterepinic acids A–C (1–3), new carboxylic acids with two primary alcohols, have been isolated from a fungal strain of Stereum sp. OUPS-124D-1 attached to the marine alga Undaria pinnatifida. Dihydro-1,5-secovibralactone (4), a new vibralactone derivative, was isolated from the same fungal metabolites together with known vibralactone A (5), and 1,5-secovibralactone (6). The planar structures of these compounds have been elucidated by spectroscopic analyses using IR, HRFABMS, and NMR spectra. To determine the absolute configuration of the compounds, we used the phenylglycine methyl ester (PGME) method. These compounds exhibited less activity in the cytotoxicity assay against cancer cell lines. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 23061 KiB

Open AccessArticle

Aleuritolic Acid Impaired Autophagic Flux and Induced Apoptosis in Hepatocellular Carcinoma HepG2 Cells

by Hua Yi, Kun Wang, Biaoyan Du, Lina He, Hiuting HO, Maosong Qiu, Yidan Zou, Qiao Li, Junfeng Jin, Yujuan Zhan, Zhongxiang Zhao and Xiaodong Liu

Molecules 2018, 23(6), 1338; https://doi.org/10.3390/molecules23061338 - 2 Jun 2018

Cited by 12 | Viewed by 4970

Abstract

Aleuritolic acid (AA) is a triterpene that is isolated from the root of Croton crassifolius Geisel. In the present study, the cytotoxic effects of AA on hepatocellular carcinoma cells were evaluated. AA exerted dose- and time-dependent cytotoxicity by inducing mitochondria-dependent apoptosis in the [...] Read more.

Aleuritolic acid (AA) is a triterpene that is isolated from the root of Croton crassifolius Geisel. In the present study, the cytotoxic effects of AA on hepatocellular carcinoma cells were evaluated. AA exerted dose- and time-dependent cytotoxicity by inducing mitochondria-dependent apoptosis in the hepatocellular carcinoma cell line, HepG2. Meanwhile, treatment with AA also caused dysregulation of autophagy, as evidenced by enhanced conversion of LC3-I to LC3-II, p62 accumulation, and co-localization of GFP and mCherry-tagged LC3 puncta. Notably, blockage of autophagosome formation by ATG5 knockdown or inhibitors of phosphatidylinositol 3-kinase (3-MA or Ly294002), significantly reversed AA-mediated cytotoxicity. These data indicated that AA retarded the clearance of autophagic cargos, resulting in the production of cytotoxic factors and led to apoptosis in hepatocellular carcinoma cells. Full article

(This article belongs to the Special Issue Qualitative and Quantitative Analysis of Bioactive Natural Products 2018)

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11 pages, 8791 KiB

Open AccessFeature PaperArticle

Indium-Catalyzed Direct Conversion of Lactones into Thiolactones Using a Disilathiane as a Sulfur Source

by Yohei Ogiwara, Ken Takano, Shuhei Horikawa and Norio Sakai

Molecules 2018, 23(6), 1339; https://doi.org/10.3390/molecules23061339 - 2 Jun 2018

Cited by 7 | Viewed by 4994

Abstract

An indium-catalyzed reaction of lactones and a disilathiane leading to thiolactones is described. The direct synthesis of thiolactones from lactones with an appropriate sulfur source is one of the most attractive approaches in organic and pharmaceutical chemistry. In this context, we found an [...] Read more.

An indium-catalyzed reaction of lactones and a disilathiane leading to thiolactones is described. The direct synthesis of thiolactones from lactones with an appropriate sulfur source is one of the most attractive approaches in organic and pharmaceutical chemistry. In this context, we found an indium-catalyzed direct conversion of lactones into thiolactones in the presence of elemental sulfur and a hydrosilane via formation of the disilathiane in situ. On the basis of the previous reaction, the application utilizing the disilathiane as a sulfur source was performed herein for the efficient synthesis of a variety of thiolactone derivatives from lactones by an indium catalyst. Full article

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

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11 pages, 3839 KiB

Open AccessArticle

Pomelo Peel Modified with Citrate as a Sustainable Adsorbent for Removal of Methylene Blue from Aqueous Solution

by Yimei Ren, Chang Cui and Pengjie Wang

Molecules 2018, 23(6), 1342; https://doi.org/10.3390/molecules23061342 - 3 Jun 2018

Cited by 40 | Viewed by 6240

Abstract

An anionic adsorbent was prepared by grafting citrate onto pomelo peel (PPL) to remove methylene blue (MB) from aqueous solution. The PPL and modified pomelo peel (MPPL) were analyzed by Fourier transform infrared spectroscopy (FTIR) and observed by scanning electron microscopy (SEM). The [...] Read more.

An anionic adsorbent was prepared by grafting citrate onto pomelo peel (PPL) to remove methylene blue (MB) from aqueous solution. The PPL and modified pomelo peel (MPPL) were analyzed by Fourier transform infrared spectroscopy (FTIR) and observed by scanning electron microscopy (SEM). The effects of dye concentration, contact time, and pH on adsorption were studied. The FTIR results confirmed that the carboxyl groups were successfully bound to cellulose molecules in PPL via modification with citrate. SEM indicated that the surface of PPL became clean and the porous structure was well maintained after modification. The adsorption capacities of MB onto PPL and MPPL were 81.7 mg/g and 199.2 mg/g, respectively, thus indicating that the addition of anionic groups significantly improved the adsorption performance. The increase in the initial dye concentration and pH of the dye solution promoted the adsorption process. The adsorption equilibrium on MPPL required approximately 3 h. The adsorption of MB on MPPL was well described by a pseudo-second order kinetic model and Langmuir isotherm model. The thermodynamic parameters indicated spontaneous and exothermic adsorption. This study suggests that PPL modified with citrate can be used as a sustainable adsorbent in wastewater purification. Full article

(This article belongs to the Special Issue Chemical Surface Functionalization)

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12 pages, 970 KiB

Open AccessArticle

Synthesis, Antiviral and Cytotoxic Activity of Novel Terpenyl Hybrid Molecules Prepared by Click Chemistry

by Mariano Walter Pertino, Erina Petrera, Laura Edith Alché and Guillermo Schmeda-Hirschmann

Molecules 2018, 23(6), 1343; https://doi.org/10.3390/molecules23061343 - 3 Jun 2018

Cited by 13 | Viewed by 4881

Abstract

Naturally occurring terpenes were combined by click reactions to generate sixteen hybrid molecules. The diterpene imbricatolic acid (IA) containing an azide group was used as starting compound for the synthesis of all the derivatives. The alkyne group in the terpenes cyperenoic acid, dehydroabietinol, [...] Read more.

Naturally occurring terpenes were combined by click reactions to generate sixteen hybrid molecules. The diterpene imbricatolic acid (IA) containing an azide group was used as starting compound for the synthesis of all the derivatives. The alkyne group in the terpenes cyperenoic acid, dehydroabietinol, carnosic acid γ-lactone, ferruginol, oleanolic acid and aleuritolic acid was obtained by esterification using appropriate alcohols or acids. The hybrid compounds were prepared by combining the IA azide function with the different terpene-alkynes under click chemistry conditions. The cytotoxic activity of the terpene hybrids 1–16 was assessed against Vero cells and tumour cell lines (HEP-2, C6 and Raw 264.7). Compounds 1, 2, 3 and 7 showed cytotoxic activity against the tested cell lines. The antiviral activity of the compounds was evaluated against HSV-1 KOS, Field and B2006 strain. For the pairs of hybrid compounds formed between IA-diterpene (compounds 3–8, except for compound 7), a moderate activity was observed against the three HSV-1 strains with an interesting selectivity index (SI ≥10, SI = CC₅₀/CE₅₀) for some compounds. Full article

(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)

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11 pages, 1183 KiB

Open AccessArticle

Design, Synthesis, and Antifungal Activity of Novel Aryl-1,2,3-Triazole-β-Carboline Hybrids

by Xin-Yu Huo, Liang Guo, Xiao-Fei Chen, Yue-Ting Zhou, Jie Zhang, Xiao-Qiang Han and Bin Dai

Molecules 2018, 23(6), 1344; https://doi.org/10.3390/molecules23061344 - 4 Jun 2018

Cited by 33 | Viewed by 4616

Abstract

The copper catalytic azide and terminal alkyne cycloaddition reaction, namely “click chemistry”, gives a new and convenient way to create l,4-disubstitutd-l,2,3-triazoles. In this work, 2-pyrrolecarbaldiminato–Cu(II) complexes were established as efficient catalysts for the three-component 1,3-dipolar cycloaddition reaction of arylboronic acid and sodium azide [...] Read more.

The copper catalytic azide and terminal alkyne cycloaddition reaction, namely “click chemistry”, gives a new and convenient way to create l,4-disubstitutd-l,2,3-triazoles. In this work, 2-pyrrolecarbaldiminato–Cu(II) complexes were established as efficient catalysts for the three-component 1,3-dipolar cycloaddition reaction of arylboronic acid and sodium azide (NaN₃) with terminal alkynes in ethanol at room temperature to 50 °C, 1,4-disubstituted 1,2,3-triazoles were synthesized. Following the optimized protocol, two series of new aryl-1,2,3-triazole-β-carboline hybrids have been designed and synthesized, and the chemical structures were characterized by ¹H NMR, ¹³C NMR, and high-resolution mass spectrometry (HRMS). All of the target compounds were evaluated in vitro for their antifungal activity against Rhizoctorzia solani, Fusarium oxysporum, Botrytis cinerea Pers., sunflower sclerotinia rot, and rape sclerotinia rot by mycelia growth inhibition assay at 50 μg/mL. The antifungal evaluation of the novel hybrids showed that, among the tested compounds, 5a, 5b, 5c, and 9b showed good antifungal activity against sunflower sclerotinia rot. Specifically, compound 9b also exhibited high broad-spectrum fungicidal against all the tested fungi with inhibition rates of 58.3%, 18.52%, 63.07%, 84.47%, and 81.23%. However, for F. oxysporum, all the target compounds showed no in vitro antifungal activities with an inhibition rate lower than 20%. These results provide an encouraging framework that could lead to the development of potent novel antifungal agents. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 1162 KiB

Open AccessArticle

Vermicompost Supplementation Improves the Stability of Bioactive Anthocyanin and Phenolic Compounds in Clinacanthus nutans Lindau

by Zuhaili Yusof, Sujatha Ramasamy, Noor Zalina Mahmood and Jamilah Syafawati Yaacob

Molecules 2018, 23(6), 1345; https://doi.org/10.3390/molecules23061345 - 4 Jun 2018

Cited by 33 | Viewed by 6258

Abstract

This project studied the effect of vermicompost application on the composition of bioactive anthocyanin and phenolic compounds, and the antioxidant activity of Clinacanthus nutans. The correlation between the bioactive constituents and antioxidant capacity was also evaluated. In this project, a field study [...] Read more.

This project studied the effect of vermicompost application on the composition of bioactive anthocyanin and phenolic compounds, and the antioxidant activity of Clinacanthus nutans. The correlation between the bioactive constituents and antioxidant capacity was also evaluated. In this project, a field study was conducted using a randomized complete block design (RCBD) with four treatment groups, including control plants (CC), plants supplied with chemical fertilizer (CF), plants supplied with vermicompost (VC), and plants supplied with mixed fertilizer (MF). The leaves of C. nutans from all treatment groups were harvested, subjected to solvent extraction, and used for quantification of total anthocyanin content (TAC), total phenolic content (TPC), and total flavonoid content (TFC). The initial antioxidant activity of the extracts was evaluated using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, as well as after two and four weeks of storage at −20 °C and 4 °C. Data analysis showed that CC plants contained the highest TAC (2180.14 ± 338.43 µg/g dry weight) and TFC (276.25 ± 3.09 mg QE/g dry weight). On the other hand, CF plants showed the highest TPC (181.53 ± 35.58 mg GAE/g dry weight). Moreover, we found that CC plants had the highest antioxidant potential against DPPH radicals whereas MF plants showed the lowest antioxidant potential. After four weeks of extract storage at −20 °C and 4 °C, the TPC, TFC, TAC, and antioxidant potential of the extracts decreased. Extracts from VC showed the lowest percentage of total phenolic and total flavonoid loss after extract storage at −20 °C and 4 °C compared with other plant extracts. At this juncture, it could be deduced that the application of vermicompost had little effect on the expression of phenolics, flavonoids, or anthocyanin in C. nutans. However, the extract from plants treated with vermicompost (VC and MF) showed better stability compared with CC and CF after extract storage at different temperatures. Full article

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

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11 pages, 1304 KiB

Open AccessFeature PaperArticle

Simultaneous Quantification of Ellagitannins and Related Polyphenols in Geranium thunbergii Using Quantitative NMR

by Februadi Bastian, Yurie Ito, Erika Ogahara, Natsuki Ganeko, Tsutomu Hatano and Hideyuki Ito

Molecules 2018, 23(6), 1346; https://doi.org/10.3390/molecules23061346 - 4 Jun 2018

Cited by 16 | Viewed by 4967

Abstract

Compared to commonly employed liquid chromatography-based methods, quantitative nuclear magnetic resonance (qNMR) is a recently developed method for accurate quantification of natural compounds in extracts. The simultaneous quantification of ellagitannins and the related polyphenols of Geranium thunbergii were studied using qNMR after a [...] Read more.

Compared to commonly employed liquid chromatography-based methods, quantitative nuclear magnetic resonance (qNMR) is a recently developed method for accurate quantification of natural compounds in extracts. The simultaneous quantification of ellagitannins and the related polyphenols of Geranium thunbergii were studied using qNMR after a short-term and long-term decoction. The qNMR fingerprint for quantifying ellagitannin was presented in this work. Geraniin was observed in the short-term decoction as a major component while corilagin was the major component of the long-term decoction. An aqueous acetone extract of G. thunbergii after long-term decoction was extracted with diethyl ether, ethyl acetate, and n-butanol. Corilagin was found as a major constituent in the ethyl acetate and n-butanol extracts. Furthermore, the contents of these polyphenols in G. thunbergii from six locations in Japan and three locations in China were quantified. The contents of geraniin and corilagin in G. thunbergii from Japan were higher than those from China. Our finding raised the possibility that qNMR can be effectively employed as a simple, accurate, and efficient method for quantification of ellagitannins in medicinal plants. 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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8 pages, 1562 KiB

Open AccessArticle

Synthesis of the Sex Pheromone of the Tea Tussock Moth Based on a Resource Chemistry Strategy

by Hong-Li Zhang, Zhi-Feng Sun, Lu-Nan Zhou, Lu Liu, Tao Zhang and Zhen-Ting Du

Molecules 2018, 23(6), 1347; https://doi.org/10.3390/molecules23061347 - 4 Jun 2018

Cited by 17 | Viewed by 4214

Abstract

Synthesis of the sex pheromone of the tea tussock moth in 33% overall yield over 10 steps was achieved. Moreover, the chiral pool concept was applied in the asymmetric synthesis. The synthesis used a chemical available on a large-scale from recycling of wastewater [...] Read more.

Synthesis of the sex pheromone of the tea tussock moth in 33% overall yield over 10 steps was achieved. Moreover, the chiral pool concept was applied in the asymmetric synthesis. The synthesis used a chemical available on a large-scale from recycling of wastewater from the steroid industry. The carbon skeleton was constructed using the C4+C5+C8 strategy. Based on this strategy, the original chiral center was totally retained. Full article

(This article belongs to the Special Issue Synthesis, Study and Utilization of Natural Products)

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13 pages, 2995 KiB

Open AccessArticle

Identfication of Potent LXRβ-Selective Agonists without LXRα Activation by In Silico Approaches

by Meimei Chen, Fafu Yang, Jie Kang, Huijuan Gan, Xuemei Yang, Xinmei Lai and Yuxing Gao

Molecules 2018, 23(6), 1349; https://doi.org/10.3390/molecules23061349 - 4 Jun 2018

Cited by 5 | Viewed by 3962

Abstract

Activating Liver X receptors (LXRs) represents a promising therapeutic option for dyslipidemia. However, activating LXRα may cause undesired lipogenic effects. Discovery of highly LXRβ-selective agonists without LXRα activation were indispensable for dyslipidemia. In this study, in silico approaches were applied to develop highly [...] Read more.

Activating Liver X receptors (LXRs) represents a promising therapeutic option for dyslipidemia. However, activating LXRα may cause undesired lipogenic effects. Discovery of highly LXRβ-selective agonists without LXRα activation were indispensable for dyslipidemia. In this study, in silico approaches were applied to develop highly potent LXRβ-selective agonists based on a series of newly reported 3-(4-(2-propylphenoxy)butyl)imidazolidine-2,4-dione-based LXRα/β dual agonists. Initially, Kohonen and stepwise multiple linear regression SW-MLR were performed to construct models for LXRβ agonists and LXRα agonists based on the structural characteristics of LXRα/β dual agonists, respectively. The obtained LXRβ agonist model gave a good predictive ability (R²_train = 0.837, R²_test = 0.843, Q²_LOO = 0.715), and the LXRα agonist model produced even better predictive ability (R²_train = 0.968, R²_test = 0.914, Q²_LOO = 0.895). Also, the two QSAR models were independent and can well distinguish LXRβ and LXRα activity. Then, compounds in the ZINC database met the lower limit of structural similarity of 0.7, compared to the 3-(4-(2-propylphenoxy)butyl)imidazolidine-2,4-dione scaffold subjected to our QSAR models, which resulted in the discovery of ZINC55084484 with an LXRβ prediction value of pEC₅₀ equal to 7.343 and LXRα prediction value of pEC₅₀ equal to −1.901. Consequently, nine newly designed compounds were proposed as highly LXRβ-selective agonists based on ZINC55084484 and molecular docking, of which LXRβ prediction values almost exceeded 8 and LXRα prediction values were below 0. Full article

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16 pages, 4473 KiB

Open AccessArticle

SLC35B4, an Inhibitor of Gluconeogenesis, Responds to Glucose Stimulation and Downregulates Hsp60 among Other Proteins in HepG2 Liver Cell Lines

by Brigitte Wex, Rémi M. Safi, Gregory Antonios, Perla Z. Zgheib, Dania B. Awad, Firas H. Kobeissy, Rami A. Mahfouz, Marwan M. El-Sabban and Soha N. Yazbek

Molecules 2018, 23(6), 1350; https://doi.org/10.3390/molecules23061350 - 4 Jun 2018

Cited by 4 | Viewed by 5071

Abstract

SLC35B4, solute receptor for UDP-N-acetylglucosamine and UDP-xylose, is associated with diabetes and predisposing conditions. This study investigated the localization of SLC35B4 and compared the differential expression between a knockdown of SLC35B4 and controls in HepG2. Responsiveness to glucose, expression, and [...] Read more.

SLC35B4, solute receptor for UDP-N-acetylglucosamine and UDP-xylose, is associated with diabetes and predisposing conditions. This study investigated the localization of SLC35B4 and compared the differential expression between a knockdown of SLC35B4 and controls in HepG2. Responsiveness to glucose, expression, and localization were assayed using Western blot and immunostaining. Localization was confirmed using a proximity ligation assay. Two-dimensional (2D) gel electrophoresis and MALDI-TOF were used to identify differentially expressed proteins and pathway analysis was performed. SLC35B4 was increased by 60% upon glucose stimulation and localized in Golgi apparatus and endoplasmic reticulum. Presence of SLC35B4 in the Golgi apparatus suggests its involvement in the biosynthesis of glycoconjugate proteins. Four proteins were markedly under-expressed (Hsp60, HspA8, TUBA1A, and ENO1) and linked to the pathogenesis of diabetes or post-translationally modified by O-GlcNAc. Glucose levels activate SLC35B4 expression. This triggers a downstream effect via Hsp60 and other proteins. We hypothesize that the downstream effect on the proteins is mediated via altering the glycosylation pattern inside liver cells. The downstream cascade ultimately alters the ability of cultured liver cells to inhibit endogenous glucose production, and this could play a role in the association of the above-listed genes with the pathogenesis of diabetes. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 7290 KiB

Open AccessArticle

Theoretical Study of the Photolysis Mechanisms of Methylpentaphenyldimetallanes (Ph₃MM′Ph₂Me; M, M′ = Si and Ge)

by Shih-Hao Su and Ming-Der Su

Molecules 2018, 23(6), 1351; https://doi.org/10.3390/molecules23061351 - 4 Jun 2018

Cited by 2 | Viewed by 3839

Abstract

The mechanisms of the photolysis reactions are studied theoretically at the M06-2X/6-311G(d) level of theory, using the four types of group 14 molecules that have the general structure, Ph₃M–M′Ph₂Me (M and M′ = Si and Ge), as model systems. [...] Read more.

The mechanisms of the photolysis reactions are studied theoretically at the M06-2X/6-311G(d) level of theory, using the four types of group 14 molecules that have the general structure, Ph₃M–M′Ph₂Me (M and M′ = Si and Ge), as model systems. This study provides the first theoretical evidence for the mechanisms of these photorearrangements of compounds that contain a M–M′ single bond. The model investigations indicate that the preferred reaction route for the photolysis reactions is, as follows: reactant → Franck-Condon (FC) region → minimum (triplet) → transition state (triplet) → triplet/singlet intersystem crossing → photoproducts (both di-radicals and singlets). The theoretical findings demonstrate that the formation of radicals results from reactions of the triplet states of these reactants. This could be because both the atomic radius and the chemical properties of silicon and germanium are quite similar to each other and compared to other group 14 elements, their photolytic mechanisms are nearly the same. The results for the photolytic mechanisms that are studied in this work are consistent with the available experimental observations and allow for a number of predictions for other group 14 dimetallane analogues to be made. Full article

(This article belongs to the Special Issue Theoretical Investigations of Reaction Mechanisms)

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12 pages, 3809 KiB

Open AccessArticle

Non-Destructive and Rapid Variety Discrimination and Visualization of Single Grape Seed Using Near-Infrared Hyperspectral Imaging Technique and Multivariate Analysis

by Yiying Zhao, Chu Zhang, Susu Zhu, Pan Gao, Lei Feng and Yong He

Molecules 2018, 23(6), 1352; https://doi.org/10.3390/molecules23061352 - 4 Jun 2018

Cited by 46 | Viewed by 4857

Abstract

Hyperspectral images in the spectral range of 874–1734 nm were collected for 14,015, 14,300 and 15,042 grape seeds of three varieties, respectively. Pixel-wise spectra were preprocessed by wavelet transform, and then, spectra of each single grape seed were extracted. Principal component analysis (PCA) [...] Read more.

Hyperspectral images in the spectral range of 874–1734 nm were collected for 14,015, 14,300 and 15,042 grape seeds of three varieties, respectively. Pixel-wise spectra were preprocessed by wavelet transform, and then, spectra of each single grape seed were extracted. Principal component analysis (PCA) was conducted on the hyperspectral images. Scores for images of the first six principal components (PCs) were used to qualitatively recognize the patterns among different varieties. Loadings of the first six PCs were used to identify the effective wavelengths (EWs). Support vector machine (SVM) was used to build the discriminant model using the spectra based on the EWs. The results indicated that the variety of each single grape seed was accurately identified with a calibration accuracy of 94.3% and a prediction accuracy of 88.7%. An external validation image of each variety was used to evaluate the proposed model and to form the classification maps where each single grape seed was explicitly identified as belonging to a distinct variety. The overall results indicated that a hyperspectral imaging (HSI) technique combined with multivariate analysis could be used as an effective tool for non-destructive and rapid variety discrimination and visualization of grape seeds. The proposed method showed great potential for developing a multi-spectral imaging system for practical application in the future. Full article

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

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27 pages, 3522 KiB

Open AccessArticle

Chemotypes and Biomarkers of Seven Species of New Caledonian Liverworts from the Bazzanioideae Subfamily

by Benjamin Métoyer, Nicolas Lebouvier, Edouard Hnawia, Gaëtan Herbette, Louis Thouvenot, Yoshinori Asakawa, Mohammed Nour and Phila Raharivelomanana

Molecules 2018, 23(6), 1353; https://doi.org/10.3390/molecules23061353 - 5 Jun 2018

Cited by 14 | Viewed by 4412

Abstract

Volatile components of seven species of the Bazzanioideae sub-family (Lepidoziaceae) native to New Caledonia, including three endemic species (Bazzania marginata, Acromastigum caledonicum and A. tenax), were analyzed by GC-FID-MS in order to index these plants to known or new chemotypes. [...] Read more.

Volatile components of seven species of the Bazzanioideae sub-family (Lepidoziaceae) native to New Caledonia, including three endemic species (Bazzania marginata, Acromastigum caledonicum and A. tenax), were analyzed by GC-FID-MS in order to index these plants to known or new chemotypes. Detected volatile constituents in studied species were constituted mainly by sesquiterpene, as well as diterpene compounds. All so-established compositions cannot successfully index some of them to known chemotypes but afforded the discovery of new chemotypes such as cuparane/fusicoccane. The major component of B. francana was isolated and characterized as a new zierane-type sesquiterpene called ziera-12(13),10(14)-dien-5-ol (23). In addition, qualitative intraspecies variations of chemical composition were very important particularly for B. francana which possessed three clearly defined different compositions. We report here also the first phytochemical investigation of Acromastigum species. Moreover, crude diethyl ether extract of B. vitatta afforded a new bis(bibenzyl) called vittatin (51), for which a putative biosynthesis was suggested. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 1017 KiB

Open AccessArticle

Quantification of Neoagaro-Oligosaccharide Production through Enzymatic Hydrolysis and Its Anti-Oxidant Activities

by Shu-Ying Xu, Jie Kan, Zhong Hu, Yang Liu, Hong Du, Guang-Chang Pang and Kit-Leong Cheong

Molecules 2018, 23(6), 1354; https://doi.org/10.3390/molecules23061354 - 5 Jun 2018

Cited by 60 | Viewed by 5531

Abstract

Neoagaro-oligosaccharides (NAOS) have health benefits that are related to their amount and degree of polymerization (DP). However, the current methods that are used to quantify enzymatically released NAOS are un-specific and time-consuming. Agar has been extracted from Gelidium amansii and has been degraded [...] Read more.

Neoagaro-oligosaccharides (NAOS) have health benefits that are related to their amount and degree of polymerization (DP). However, the current methods that are used to quantify enzymatically released NAOS are un-specific and time-consuming. Agar has been extracted from Gelidium amansii and has been degraded by AgaXa (a recombinant β-agarase). Polysaccharide analysis using carbohydrate gel electrophoresis (PACE) has been adapted in order to quantify NAOS. In addition, the anti-oxidant activity of the degraded samples has been assessed. We have found that the PACE method provided sensitive, precise, and accurate quantification for each of the six NAOS samples. PACE has revealed that the DP of the enzymatic products from the AgaXa digestion were mainly neoagaro-octaose and neoagaro-decaose. The degraded samples exhibited increased radical-scavenging activity towards 2,2-diphenyl-1-picrylhydrazyl and 2,2-azino-bis(3-ethylbenzothiazoline sulfonic acid) radicals. While the anti-oxidant activity may have been from NAOS activity and contributions from neoagaro-octaose and neoagaro-decaose. The adapted PACE method that has been presented here is promising for large sample analysis during quality control and for characterizing novel β-agarase degradation mechanisms. Full article

(This article belongs to the Special Issue Selected Papers from the 6th International Conference on Biotechnology and Bioengineering (6-ICBB 2017))

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20 pages, 3166 KiB

Open AccessArticle

The Protective Effects of a Synthetic Geranyl Acetophenone in a Cellular Model of TNF-α-Induced Pulmonary Epithelial Barrier Dysfunction

by Tee Yee Sim, Hanis Hazeera Harith, Chau Ling Tham, Nur Fariesha Md Hashim, Khozirah Shaari, Mohd Roslan Sulaiman and Daud Ahmad Israf

Molecules 2018, 23(6), 1355; https://doi.org/10.3390/molecules23061355 - 5 Jun 2018

Cited by 19 | Viewed by 4614

Abstract

Alveolar epithelial barrier dysfunction contributes to lung edema and can lead to acute lung injury (ALI). The features include increased epithelial permeability, upregulation of inflammatory mediators and downregulation of junctional complex molecules; these changes are often induced by inflammation. tHGA is an acetophenone [...] Read more.

Alveolar epithelial barrier dysfunction contributes to lung edema and can lead to acute lung injury (ALI). The features include increased epithelial permeability, upregulation of inflammatory mediators and downregulation of junctional complex molecules; these changes are often induced by inflammation. tHGA is an acetophenone analogue with therapeutic potential in asthma. Its therapeutic potential in ALI is presently unknown. Herein, the effects of tHGA on epithelial barrier dysfunction were determined in TNF-α-induced human alveolar epithelial cells. The anti-inflammatory properties of tHGA were assessed by monocyte adhesion assay and analysis of MCP-1 and ICAM-1 expression. The epithelial barrier function was assessed by paracellular permeability and transepithelial electrical resistance (TEER) assays, and analysis of junctional complex molecules expression. To elucidate the mechanism of action, the effects of tHGA on the NF-κB and MAPK pathways were determined. Gene and protein expression were analyzed by RT-PCR and Western blotting or ELISA, respectively. tHGA suppressed leukocyte adhesion to TNF-α-induced epithelium and reduced MCP-1 and ICAM-1 gene expression and secretion. tHGA also increased TEER readings, reduced epithelial permeability and enhanced expression of junctional complex molecules (zona occludens-1, occludin and E-cadherin) in TNF-α-induced cells. Correspondingly, the NF-κB, ERK and p38 MAPK pathways were also inhibited by tHGA. These findings suggest that tHGA is able to preserve alveolar epithelial barrier function in response to acute inflammation, via its anti-inflammatory activity and stabilization of epithelial barrier integrity, mediated by NF-κB, ERK and p38 MAPK signaling. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 1293 KiB

Open AccessArticle

Biotransformations of Flavones and an Isoflavone (Daidzein) in Cultures of Entomopathogenic Filamentous Fungi

by Monika Dymarska, Tomasz Janeczko and Edyta Kostrzewa-Susłow

Molecules 2018, 23(6), 1356; https://doi.org/10.3390/molecules23061356 - 5 Jun 2018

Cited by 30 | Viewed by 5192

Abstract

Entomopathogenic filamentous fungi of the genus Isaria are effective biocatalysts in the biotransformation of flavonoids as well as steroids. In the present study, the species Isaria fumosorosea and Isaria farinosa isolated from the environment were used. Their catalytic capacity to carry out biotransformations [...] Read more.

Entomopathogenic filamentous fungi of the genus Isaria are effective biocatalysts in the biotransformation of flavonoids as well as steroids. In the present study, the species Isaria fumosorosea and Isaria farinosa isolated from the environment were used. Their catalytic capacity to carry out biotransformations of flavones—unsubstituted, with hydroxy- and amino-substituents as well as a hydroxylated isoflavone—was investigated. Biotransformations of flavone, 5-hydroxyflavone, 6-hydroxyflavone, 7-hydroxyflavone, and daidzein resulted in the formation of O-methylglucosides, in the case of flavone and 5-hydroxyflavone with additional hydroxylations. 7-Aminoflavone was transformed into two acetamido derivatives. The following products were obtained: From flavone–flavone 2′-O-β-d-(4′′-O-methyl)-glucopyranoside, flavone 4′-O-β-d-(4′′-O-methyl)-glucopyranoside and 3′-hydroxyflavone 4′-O-β-d-(4′′-O-methyl)-glucopyranoside; from 5-hydroxyflavone–5-hydroxyflavone 4′-O-β-d-(4′′-O-methyl)-glucopyranoside; from 6-hydroxyflavone–flavone 6-O-β-d-(4′′-O-methyl)-glucopyranoside; from 7-hydroxyflavone–flavone 7-O-β-d-(4′′-O-methyl)-glucopyranoside; from daidzein–daidzein 7-O-β-d-(4′′-O-methyl)-glucopyranoside; and from 7-aminoflavone–7-acetamidoflavone and 7-acetamido-4′-hydroxyflavone. Seven of the products obtained by us have not been previously reported in the literature. Full article

(This article belongs to the Section Bioorganic Chemistry)

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13 pages, 1177 KiB

Open AccessArticle

Roselle Anthocyanins: Antioxidant Properties and Stability to Heat and pH

by Hai-Yao Wu, Kai-Min Yang and Po-Yuan Chiang

Molecules 2018, 23(6), 1357; https://doi.org/10.3390/molecules23061357 - 5 Jun 2018

Cited by 148 | Viewed by 11475

Abstract

Roselle is rich in anthocyanins and is traditionally used to prepare a bright red beverage by decoction. However, heat treatment and different pH environments are often encountered during food processing, and these factors are often detrimental to anthocyanins. Therefore, it is very important [...] Read more.

Roselle is rich in anthocyanins and is traditionally used to prepare a bright red beverage by decoction. However, heat treatment and different pH environments are often encountered during food processing, and these factors are often detrimental to anthocyanins. Therefore, it is very important to understand the influence of pH and heat treatment on anthocyanins for the application of roselle. This study determined the antioxidant properties of roselle extract, explored changes in the color and anthocyanin content in different pH environments, and evaluated the thermal stability of roselle anthocyanins using kinetic equations. The results showed that the roselle extract is rich in anthocyanins and has good antioxidant capacity (DPPH IC50 = 4.06 mg/mL, ABTS IC50 = 3.7 mg/mL). The anthocyanins themselves exhibited a certain degree of heat resistance and good color stability in an acidic environment. In contrast, they degraded very quickly and exhibited significant changes in color in a low-acid environment. The activation energy (Ea) ranges of the anthocyanins in the acidic and low-acid environments were quite different at 55.8–95.7 and 31.4–74.9 kJ/mol, respectively. Thus, it can be concluded that roselle anthocyanins are susceptible to heat treatment in a low-acid environment, affecting their quality and appearance; however, they can serve as a good source of functional ingredients and color in an acidic environment. Full article

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

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22 pages, 3203 KiB

Open AccessArticle

Sequencing and Analysis of Chrysanthemum carinatum Schousb and Kalimeris indica. The Complete Chloroplast Genomes Reveal Two Inversions and rbcL as Barcoding of the Vegetable

by Xia Liu, Boyang Zhou, Hongyuan Yang, Yuan Li, Qian Yang, Yuzhuo Lu and Yu Gao

Molecules 2018, 23(6), 1358; https://doi.org/10.3390/molecules23061358 - 5 Jun 2018

Cited by 21 | Viewed by 4214

Abstract

Chrysanthemum carinatum Schousb and Kalimeris indica are widely distributed edible vegetables and the sources of the Chinese medicine Asteraceae. The complete chloroplast (cp) genome of Asteraceae usually occurs in the inversions of two regions. Hence, the cp genome sequences and structures of [...] Read more.

Chrysanthemum carinatum Schousb and Kalimeris indica are widely distributed edible vegetables and the sources of the Chinese medicine Asteraceae. The complete chloroplast (cp) genome of Asteraceae usually occurs in the inversions of two regions. Hence, the cp genome sequences and structures of Asteraceae species are crucial for the cp genome genetic diversity and evolutionary studies. Hence, in this paper, we have sequenced and analyzed for the first time the cp genome size of C. carinatum Schousb and K. indica, which are 149,752 bp and 152,885 bp, with a pair of inverted repeats (IRs) (24,523 bp and 25,003) separated by a large single copy (LSC) region (82,290 bp and 84,610) and a small single copy (SSC) region (18,416 bp and 18,269), respectively. In total, 79 protein-coding genes, 30 distinct transfer RNA (tRNA) genes, four distinct rRNA genes and two pseudogenes were found not only in C. carinatum Schousb but also in the K. indica cp genome. Fifty-two (52) and fifty-nine (59) repeats, and seventy (70) and ninety (90) simple sequence repeats (SSRs) were found in the C. carinatum Schousb and K. indica cp genomes, respectively. Codon usage analysis showed that leucine, isoleucine, and serine are the most frequent amino acids and that the UAA stop codon was the significantly favorite stop codon in both cp genomes. The two inversions, the LSC region ranging from trnC-GCA to trnG-UCC and the whole SSC region were found in both of them. The complete cp genome comparison with other Asteraceae species showed that the coding area is more conservative than the non-coding area. The phylogenetic analysis revealed that the rbcL gene is a good barcoding marker for identifying different vegetables. These results give an insight into the identification, the barcoding, and the understanding of the evolutionary model of the Asteraceae cp genome. Full article

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11 pages, 1592 KiB

Open AccessArticle

Aspirin Derivative 5-(Bis(3-methylbut-2-enyl)amino)-2-hydroxybenzoic Acid Improves Thermotolerance via Stress Response Proteins in Caenorhabditis elegans

by Xiao-Bing Huang, Gui-Sheng Wu, Lei-Yu Ke, Xiao-Gang Zhou, Yue-Hu Wang and Huai-Rong Luo

Molecules 2018, 23(6), 1359; https://doi.org/10.3390/molecules23061359 - 5 Jun 2018

Cited by 5 | Viewed by 4726

Abstract

Aging is a major risk factor for many prevalent diseases. Pharmacological intervention to improve the health span and extend the lifespan could be a preventive elixir for aging and age-related diseases. The non-steroid anti-inflammation medicine aspirin was reported to delay aging in Caenorhabditis [...] Read more.

Aging is a major risk factor for many prevalent diseases. Pharmacological intervention to improve the health span and extend the lifespan could be a preventive elixir for aging and age-related diseases. The non-steroid anti-inflammation medicine aspirin was reported to delay aging in Caenorhabditis elegans (C. elegans) and mice. We are wondering if the analogues of aspirin could also present antiaging activity. Here, we synthesized several aspirin derivatives and investigated their thermotolerance and antiaging effect in C. elegans. One of the compounds, 5-(bis(3-methylbut-2-en-1-yl)amino)-2-hydroxybenzoic acid, moderately increased the survival of C. elegans under heat stress, but could not extend the lifespan under optimum conditions. This compound could increase the mRNA level of stress response gene gst-4, and the mRNA and protein expression level of heat shock protein hsp-16.2 under heat stress. The failure of activating the transcription factor DAF-16 might explain why this compound could not act as aspirin to extend the lifespan of C. elegans. Our results would help further the investigation of the pharmacological activity of aspirin analogues and the relationship between structures and activity. Full article

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10 pages, 1772 KiB

Open AccessArticle

Development of a Mouse Model of Prostate Cancer Using the Sleeping Beauty Transposon and Electroporation

by Hyun-Ji Choi, Han-Byul Lee, Sunyoung Jung, Hyun-Kyu Park, Woori Jo, Sung-Min Cho, Woo-Jin Kim and Woo-Chan Son

Molecules 2018, 23(6), 1360; https://doi.org/10.3390/molecules23061360 - 5 Jun 2018

Cited by 5 | Viewed by 5205

Abstract

The Sleeping Beauty (SB) transposon system is non-viral and uses insertional mutagenesis, resulting in the permanent expression of transferred genes. Although the SB transposon is a useful method for establishing a mouse tumor model, there has been difficulty in using this method to [...] Read more.

The Sleeping Beauty (SB) transposon system is non-viral and uses insertional mutagenesis, resulting in the permanent expression of transferred genes. Although the SB transposon is a useful method for establishing a mouse tumor model, there has been difficulty in using this method to generate tumors in the prostate. In the present study, electroporation was used to enhance the transfection efficiency of the SB transposon. To generate tumors, three constructs (a c-Myc expression cassette, a HRAS (HRas proto-oncogene, GTPase) expression cassette and a shRNA against p53) contained within the SB transposon plasmids were directly injected into the prostate. Electroporation was conducted on the injection site after the injection of the DNA plasmid. Following the tumorigenesis, the tumors were monitored by animal PET imaging and identified by gross observation. After this, the tumors were characterized by using histological and immunohistochemical techniques. The expression of the targeted genes was analyzed by Real-Time qRT-PCR. All mice subjected to the injection were found to have prostate tumors, which was supported by PSA immunohistochemistry. To our knowledge, this is the first demonstration of tumor induction in the mouse prostate using the electroporation-enhanced SB transposon system in combination with c-Myc, HRAS and p53. This model serves as a valuable resource for the future development of SB-induced mouse models of cancer. Full article

(This article belongs to the Special Issue Gene Delivery)

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15 pages, 743 KiB

Open AccessArticle

Phytochemical Composition, Hepatoprotective, and Antioxidant Activities of Phyllodium pulchellum (L.) Desv

by Ya-Chu Fan, Shi-Jun Yue, Zhong-Long Guo, Lan-Ting Xin, Chao-Yi Wang, Dong-Lin Zhao, Hua-Shi Guan and Chang-Yun Wang

Molecules 2018, 23(6), 1361; https://doi.org/10.3390/molecules23061361 - 5 Jun 2018

Cited by 12 | Viewed by 5281

Abstract

Phyllodiumpulchellum has been traditionally used as a medicinal herb because of its health-promoting effects, such as its hepatoprotective and antioxidant activities. In the present study, the petroleum ether fraction, ethyl acetate fraction, n-butanol fraction, and aqueous fraction were successively obtained from [...] Read more.

Phyllodiumpulchellum has been traditionally used as a medicinal herb because of its health-promoting effects, such as its hepatoprotective and antioxidant activities. In the present study, the petroleum ether fraction, ethyl acetate fraction, n-butanol fraction, and aqueous fraction were successively obtained from the ethanol extract of P. pulchellum. Two fractions, ethyl acetate fraction and n-butanol fraction, were found to display hepatoprotective and antioxidant activities. Further chemical investigation of the active fractions led to the isolation of its main constituents, including 11 flavonoids (1–11) and 8 indole alkaloids (12–19). There were 9 flavonoids (1–9) that were obtained from the ethyl acetate fraction, and 2 flavonoids (10 and 11) and 8 alkaloids (12–19) from the n-butanol fraction. Compounds 1–11 and 16–19 were isolated for the first time from P. pulchellum, and 1, 2, 8, 11, and 18 were obtained from the genus Phyllodium initially. Subsequently, the isolated compounds were evaluated for their in vitro hepatoprotective effects on the human normal hepatocyte cell line L-O2 injured by d-galactosamine and radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH). The flavonoids (−)-epigallocatechin (5) and (−)-epicatechin (6) exhibited prominent hepatoprotective activities with higher cell viability values (65.53% and 62.40% at 10 μM·mL⁻¹, respectively) than the positive control, silymarin (61.85% at 10 μM·mL⁻¹). In addition, compared with the positive control of vitamin C (IC₅₀: 5.14 μg·mL⁻¹), (−)-gallocatechin (3) and (−)-epigallocatechin (5) exhibited stronger antioxidant activities with IC₅₀ values of 3.80 and 3.97 μg·mL⁻¹, respectively. Furthermore, the total flavonoids from P. pulchellum were characterized using a high-performance liquid chromatography-linear ion trap quadrupole-Orbitrap-mass spectrometry (HPLC-LTQ-Orbitrap-MS). In total, 34 flavonoids were tentatively identified, which had not been previously reported from P. pulchellum. In addition, we performed a semi-quantitative analysis of the isolated flavonoids. The contents of compounds 1–11 were 3.88, 17.73, 140.35, 41.93, 27.80, 4.34, 0.01, 0.20, 9.67, 795.85, and 5.23 μg·g⁻¹, respectively. In conclusion, this study revealed that the flavonoids that were isolated from P. pulchellum showed hepatoprotective and antioxidant activities, indicating that, besides alkaloids, the flavonoids should be the potential pharmacodynamic ingredients that are responsible for the hepatoprotective and antioxidant activities of P. pulchellum. Full article

(This article belongs to the Section Natural Products Chemistry)

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18 pages, 6922 KiB

Open AccessArticle

Tubular and Spherical SiO₂ Obtained by Sol Gel Method for Lipase Immobilization and Enzymatic Activity

by Crina Anastasescu, Silviu Preda, Adriana Rusu, Dana Culita, Gabriel Plavan, Stefan Strungaru, Jose Maria Calderon-Moreno, Cornel Munteanu, Catalina Gifu, Mirela Enache, Radu Socoteanu, Daniel Angelescu, Mihai Anastasescu, Mariuca Gartner, Ioan Balint and Maria Zaharescu

Molecules 2018, 23(6), 1362; https://doi.org/10.3390/molecules23061362 - 5 Jun 2018

Cited by 17 | Viewed by 4845

Abstract

A wide range of hybrid biomaterials has been designed in order to sustain bioremediation processes by associating sol-gel SiO₂ matrices with various biologically active compounds (enzymes, antibodies). SiO₂ is a widespread, chemically stable and non-toxic material; thus, the immobilization of enzymes [...] Read more.

A wide range of hybrid biomaterials has been designed in order to sustain bioremediation processes by associating sol-gel SiO₂ matrices with various biologically active compounds (enzymes, antibodies). SiO₂ is a widespread, chemically stable and non-toxic material; thus, the immobilization of enzymes on silica may lead to improving the efficiency of biocatalysts in terms of endurance and economic costs. Our present work explores the potential of different hybrid morphologies, based on hollow tubes and solid spheres of amorphous SiO₂, for enzyme immobilization and the development of competitive biocatalysts. The synthesis protocol and structural characterization of spherical and tubular SiO₂ obtained by the sol gel method were fully investigated in connection with the subsequent immobilization of lipase from Rhizopus orizae. The immobilization is conducted at pH 6, lower than the isoelectric point of lipase and higher than the isoelectric point of silica, which is meant to sustain the physical interactions of the enzyme with the SiO₂ matrix. The morphological, textural and surface properties of spherical and tubular SiO₂ were investigated by SEM, nitrogen sorption, and electrokinetic potential measurements, while the formation and characterization of hybrid organic-inorganic complexes were studied by UV-VIS, FTIR-ATR and fluorescence spectroscopy. The highest degree of enzyme immobilization (as depicted from total organic carbon) was achieved for tubular morphology and the hydrolysis of p-nitrophenyl acetate was used as an enzymatic model reaction conducted in the presence of hybrid lipase–SiO₂ complex. Full article

(This article belongs to the Special Issue Sol-Gel Chemistry. From Molecule to Functional Materials)

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15 pages, 6026 KiB

Open AccessArticle

Localized In Situ Nanoemulgel Drug Delivery System of Quercetin for Periodontitis: Development and Computational Simulations

by Gururaj C. Aithal, Usha Yogendra Nayak, Chetan Mehta, Reema Narayan, Pratibha Gopalkrishna, Sudharsan Pandiyan and Sanjay Garg

Molecules 2018, 23(6), 1363; https://doi.org/10.3390/molecules23061363 - 6 Jun 2018

Cited by 59 | Viewed by 7974

Abstract

This study was aimed at formulating a bioabsorbable, controlled-release, nanoemulgel of Quercetin, a potent antimicrobial and anti-inflammatory agent for the treatment of periodontitis that could improve its solubility and bioavailability. Screening of components was carried out based on the solubility studies. Nanoemulsion containing [...] Read more.

This study was aimed at formulating a bioabsorbable, controlled-release, nanoemulgel of Quercetin, a potent antimicrobial and anti-inflammatory agent for the treatment of periodontitis that could improve its solubility and bioavailability. Screening of components was carried out based on the solubility studies. Nanoemulsion containing cinnamon oil as the oil phase, tween 80 and Carbitol^® as the surfactant-cosurfactant mixture (S_mix) and water as the aqueous phase containing 125 µg/200 µL of Quercetin was prepared by using spontaneous emulsification method. Nanoemulgel was prepared using 23% w/v poloxamer 407 as gel base. Comprehensive evaluation of the formulated nanoemulgel was carried out, and the optimized formulation was studied for drug release using Franz vertical diffusion cells. The formulated nanoemulgelexhibited a remarkable release of 92.4% of Quercetin at the end of 6 h, as compared to that of pure Quercetin-loaded gel (<3% release). The viscosity of the prepared nanoemulgel was found to be 30,647 ± 0.32 cPs at 37 °C. Also, molecular dynamics (MD) simulation was utilized to understand the gelation process and role of each component in the formulation. The present study revealed that the developed nanoemulgel of Quercetin could be a potential delivery system for clinical testing in periodontitis. Full article

(This article belongs to the Special Issue Targeted Drug Delivery and Nanocarriers)

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12 pages, 3313 KiB

Open AccessArticle

The Pentatricopeptide Repeat Gene Family in Salvia miltiorrhiza: Genome-Wide Characterization and Expression Analysis

by Heqin Li, Caili Li, Yuxing Deng, Xuwen Jiang and Shanfa Lu

Molecules 2018, 23(6), 1364; https://doi.org/10.3390/molecules23061364 - 6 Jun 2018

Cited by 8 | Viewed by 3594

Abstract

The pentatricopeptide repeat (PPR) gene family is one of the largest gene families in plants and plays important roles in posttranscriptional regulation. In this study, we combined whole genome sequencing and transcriptomes to systematically investigate PPRs in Salvia miltiorrhiza, which is a [...] Read more.

The pentatricopeptide repeat (PPR) gene family is one of the largest gene families in plants and plays important roles in posttranscriptional regulation. In this study, we combined whole genome sequencing and transcriptomes to systematically investigate PPRs in Salvia miltiorrhiza, which is a well-known material of traditional Chinese medicine and an emerging model system for medicinal plant studies. Among 562 identified SmPPRs, 299 belong to the P subfamily while the others belong to the PLS subfamily. The majority of SmPPRs have only one exon and are localized in the mitochondrion or chloroplast. As many as 546 SmPPRs were expressed in at least one tissue and exhibited differential expression patterns, which indicates they likely play a variety of functions in S. miltiorrhiza. Up to 349 SmPPRs were salicylic acid-responsive and 183 SmPPRs were yeast extract and Ag⁺-responsive, which indicates these genes might be involved in S. miltiorrhiza defense stresses and secondary metabolism. Furthermore, 23 salicylic acid-responsive SmPPRs were co-expressed with phenolic acid biosynthetic enzyme genes only while 16 yeast extract and Ag⁺-responsive SmPPRs were co-expressed with tanshinone biosynthetic enzyme genes only. Two SmPPRs were co-expressed with both phenolic acid and tanshinone biosynthetic enzyme genes. The results provide a useful platform for further investigating the roles of PPRs in S. miltiorrhiza. Full article

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14 pages, 8545 KiB

Open AccessArticle

Stomatal Complex Development and F-Actin Organization in Maize Leaf Epidermis Depend on Cellulose Synthesis

by Emmanuel Panteris, Theonymphi Achlati, Gerasimos Daras and Stamatis Rigas

Molecules 2018, 23(6), 1365; https://doi.org/10.3390/molecules23061365 - 6 Jun 2018

Cited by 8 | Viewed by 4983

Abstract

Cellulose microfibrils reinforce the cell wall for morphogenesis in plants. Herein, we provide evidence on a series of defects regarding stomatal complex development and F-actin organization in Zea mays leaf epidermis, due to inhibition of cellulose synthesis. Formative cell divisions of stomatal complex [...] Read more.

Cellulose microfibrils reinforce the cell wall for morphogenesis in plants. Herein, we provide evidence on a series of defects regarding stomatal complex development and F-actin organization in Zea mays leaf epidermis, due to inhibition of cellulose synthesis. Formative cell divisions of stomatal complex ontogenesis were delayed or inhibited, resulting in lack of subsidiary cells and frequently in unicellular stomata, with an atypical stomatal pore. Guard cells failed to acquire a dumbbell shape, becoming rounded, while subsidiary cells, whenever present, exhibited aberrant morphogenesis. F-actin organization was also affected, since the stomatal complex-specific arrays were scarcely observed. At late developmental stages, the overall F-actin network was diminished in all epidermal cells, although thick actin bundles persisted. Taken together, stomatal complex development strongly depends on cell wall mechanical properties. Moreover, F-actin organization exhibits a tight relationship with the cell wall. Full article

(This article belongs to the Special Issue Polysaccharide-based Materials)

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14 pages, 1654 KiB

Open AccessArticle

Discovering Structural Motifs in miRNA Precursors from the Viridiplantae Kingdom

by Joanna Miskiewicz and Marta Szachniuk

Molecules 2018, 23(6), 1367; https://doi.org/10.3390/molecules23061367 - 6 Jun 2018

Cited by 13 | Viewed by 4734

Abstract

A small non-coding molecule of microRNA (19–24 nt) controls almost every biological process, including cellular and physiological, of various organisms’ lives. The amount of microRNA (miRNA) produced within an organism is highly correlated to the organism’s key processes, and determines whether the system [...] Read more.

A small non-coding molecule of microRNA (19–24 nt) controls almost every biological process, including cellular and physiological, of various organisms’ lives. The amount of microRNA (miRNA) produced within an organism is highly correlated to the organism’s key processes, and determines whether the system works properly or not. A crucial factor in plant biogenesis of miRNA is the Dicer Like 1 (DCL1) enzyme. Its responsibility is to perform the cleavages in the miRNA maturation process. Despite everything we already know about the last phase of plant miRNA creation, recognition of miRNA by DCL1 in pre-miRNA structures of plants remains an enigma. Herein, we present a bioinformatic procedure we have followed to discover structure patterns that could guide DCL1 to perform a cleavage in front of or behind an miRNA:miRNA* duplex. The patterns in the closest vicinity of microRNA are searched, within pre-miRNA sequences, as well as secondary and tertiary structures. The dataset consists of structures of plant pre-miRNA from the Viridiplantae kingdom. The results confirm our previous observations based on Arabidopsis thaliana precursor analysis. Hereby, our hypothesis was tested on pre-miRNAs, collected from the miRBase database to show secondary structure patterns of small symmetric internal loops 1-1 and 2-2 at a 1–10 nt distance from the miRNA:miRNA* duplex. Full article

(This article belongs to the Special Issue Molecular Computing and Bioinformatics)

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11 pages, 2426 KiB

Open AccessArticle

Structure–Activity Relationship and Molecular Docking of Natural Product Library Reveal Chrysin as a Novel Dipeptidyl Peptidase-4 (DPP-4) Inhibitor: An Integrated In Silico and In Vitro Study

by Poonam Kalhotra, Veera C. S. R. Chittepu, Guillermo Osorio-Revilla and Tzayhri Gallardo-Velázquez

Molecules 2018, 23(6), 1368; https://doi.org/10.3390/molecules23061368 - 6 Jun 2018

Cited by 55 | Viewed by 10512

Abstract

Numerous studies indicate that diets with a variety of fruits and vegetables decrease the incidence of severe diseases, like diabetes, obesity, and cancer. Diets contain a variety of bioactive compounds, and their features, like diverge scaffolds, and structural complexity make them the most [...] Read more.

Numerous studies indicate that diets with a variety of fruits and vegetables decrease the incidence of severe diseases, like diabetes, obesity, and cancer. Diets contain a variety of bioactive compounds, and their features, like diverge scaffolds, and structural complexity make them the most successful source of potential leads or hits in the process of drug discovery and drug development. Recently, novel serine protease dipeptidyl peptidase-4 (DPP-4) inhibitors played a role in the management of diabetes, obesity, and cancer. This study describes the development of field template, field-based qualitative structure–activity relationship (SAR) model demonstrating DPP-4 inhibitors of natural origin, and the same model is used to screen virtually focused food database composed of polyphenols as potential DPP-4 inhibitors. Compounds’ similarity to field template, and novelty score “high and very high”, were used as primary criteria to identify novel DPP-4 inhibitors. Molecular docking simulations were performed on the resulting natural compounds using FlexX algorithm. Finally, one natural compound, chrysin, was chosen to be evaluated experimentally to demonstrate the applicability of constructed SAR model. This study provides the molecular insights necessary in the discovery of new leads as DPP-4 inhibitors, to improve the potency of existing DPP-4 natural inhibitors. Full article

(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products 2018)

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11 pages, 2568 KiB

Open AccessArticle

Biosynthesis of Fluorescent β Subunits of C-Phycocyanin from Spirulina subsalsa in Escherichia coli, and Their Antioxidant Properties

by Xian-Jun Wu, Hong Yang, Yu-Ting Chen and Ping-Ping Li

Molecules 2018, 23(6), 1369; https://doi.org/10.3390/molecules23061369 - 6 Jun 2018

Cited by 23 | Viewed by 5620

Abstract

Phycocyanin, which covalently binds phycocyanobilin chromophores, is not only a candidate fluorescent probe for biological imaging, but also a potential antioxidative agent for healthcare. Herein, a plasmid harboring two cassettes was constructed, with cpcB from Spirulina subsalsa in one cassette and the fusion [...] Read more.

Phycocyanin, which covalently binds phycocyanobilin chromophores, is not only a candidate fluorescent probe for biological imaging, but also a potential antioxidative agent for healthcare. Herein, a plasmid harboring two cassettes was constructed, with cpcB from Spirulina subsalsa in one cassette and the fusion gene cpcS::ho1::pcyA in the other, and then expressed in Escherichia coli. PCB-CpcB(C-82), a fluorescent phycocyanin β subunit, was biosynthesized in E. coli, exhibiting an absorption maximum at 620 nm and fluorescence emission maximum at 640 nm. When cpcS was replaced by cpcT, PCB-CpcB(C-153), another fluorescent phycocyanin β subunit, was produced, exhibiting an absorption maximum at 590 nm and fluorescence emission maximum at 620 nm. These two fluorescent biliproteins showed stronger scavenging activity toward hydroxyl and DPPH free radicals than apo-CpcB. The IC₅₀ values for hydroxyl radical scavenging by PCB-CpcB(C-82), PCB-CpcB(C-153), and apo-CpcB were 38.72 ± 2.48 µg/mL, 51.06 ± 6.74 µg/mL, and 81.82 ± 0.67 µg/mL, respectively, and the values for DPPH radical scavenging were 201.00 ± 5.86 µg/mL, 240.34 ± 4.03 µg/mL, and 352.93 ± 26.30 µg/mL, respectively. The comparative antioxidant capacities of the proteins were PCB-CpcB(C-82) > PCB-CpcB(C-153) > apo-CpcB, due to bilin binding. The two fluorescent biliproteins exhibited a significant effect on relieving the growth of E. coli cells injured by H₂O₂. The results of this study suggest that the fluorescent phycocyanin β subunits of S. subsalsa were reconstructed by one expression vector in E. coli, and could be developed as potential antioxidants. Full article

(This article belongs to the Special Issue Synthesis, Study and Utilization of Natural Products)

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15 pages, 4794 KiB

Open AccessArticle

Functional Characterisation of New Sesquiterpene Synthase from the Malaysian Herbal Plant, Polygonum Minus

by Nor Azizun Rusdi, Hoe-Han Goh, Suriana Sabri, Ahmad Bazli Ramzi, Normah Mohd Noor and Syarul Nataqain Baharum

Molecules 2018, 23(6), 1370; https://doi.org/10.3390/molecules23061370 - 6 Jun 2018

Cited by 17 | Viewed by 6034

Abstract

Polygonum minus (syn. Persicaria minor) is a herbal plant that is well known for producing sesquiterpenes, which contribute to its flavour and fragrance. This study describes the cloning and functional characterisation of PmSTPS1 and PmSTPS2, two sesquiterpene synthase genes that [...] Read more.

Polygonum minus (syn. Persicaria minor) is a herbal plant that is well known for producing sesquiterpenes, which contribute to its flavour and fragrance. This study describes the cloning and functional characterisation of PmSTPS1 and PmSTPS2, two sesquiterpene synthase genes that were identified from P. minus transcriptome data mining. The full-length sequences of the PmSTPS1 and PmSTPS2 genes were expressed in the E. coli pQE-2 expression vector. The sizes of PmSTPS1 and PmSTPS2 were 1098 bp and 1967 bp, respectively, with open reading frames (ORF) of 1047 and 1695 bp and encoding polypeptides of 348 and 564 amino acids, respectively. The proteins consist of three conserved motifs, namely, Asp-rich substrate binding (DDxxD), metal binding residues (NSE/DTE), and cytoplasmic ER retention (RxR), as well as the terpene synthase family N-terminal domain and C-terminal metal-binding domain. From the in vitro enzyme assays, using the farnesyl pyrophosphate (FPP) substrate, the PmSTPS1 enzyme produced multiple acyclic sesquiterpenes of β-farnesene, α-farnesene, and farnesol, while the PmSTPS2 enzyme produced an additional nerolidol as a final product. The results confirmed the roles of PmSTPS1 and PmSTPS2 in the biosynthesis pathway of P. minus, to produce aromatic sesquiterpenes. Full article

(This article belongs to the Special Issue Design in Synthetic Biology)

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21 pages, 2967 KiB

Open AccessArticle

Influence of Grape Berry Maturity on Juice and Base Wine Composition and Foaming Properties of Sparkling Wines from the Champagne Region

by Pin-He Liu, Céline Vrigneau, Thomas Salmon, Duc An Hoang, Jean-Claude Boulet, Sandrine Jégou and Richard Marchal

Molecules 2018, 23(6), 1372; https://doi.org/10.3390/molecules23061372 - 6 Jun 2018

Cited by 8 | Viewed by 6397

Abstract

In sparkling wine cool-climate regions like Champagne, it is sometimes necessary to pick the healthy grape clusters that have a relatively low maturity level to avoid the deleterious effects of Botrytis cinerea. In such conditions, we know that classical oenological parameters (sugars, [...] Read more.

In sparkling wine cool-climate regions like Champagne, it is sometimes necessary to pick the healthy grape clusters that have a relatively low maturity level to avoid the deleterious effects of Botrytis cinerea. In such conditions, we know that classical oenological parameters (sugars, pH, total acidity) may change but there is little information concerning the impact of grape berry maturity on wine proteins and foaming properties. Therefore, healthy grapes (Chardonnay and Pinot meunier) in 2015 and 2016 were picked at different maturity levels within the range of common industrial maturity for potential alcohol content 8–11% v/v in the Champagne region. Base wine protein content and foamability, and oenological parameters in grape juice and their corresponding base wines, were investigated. The results showed that base wine protein contents (analyzed by the Bradford method and by electrophoresis) and foamability were higher when the grapes were riper. The Pearson’s correlation test found significant positive correlations (r = 0.890–0.997, p < 0.05) between Chardonnay grape berry maturity degree (MD) and base wine foamability in both vintages. Strong correlations between MD and most of the oenological parameters in grape juice and base wine were also found for the two cultivars. Under the premise of guaranteed grape health, delaying harvest date is an oenological decision capable of improving base wine protein content and foamability. Full article

(This article belongs to the Collection Wine Chemistry)

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8 pages, 1023 KiB

Open AccessCommunication

Room-Temperature Fabricated Thin-Film Transistors Based on Compounds with Lanthanum and Main Family Element Boron

by Peng Xiao, Junhua Huang, Ting Dong, Jianing Xie, Jian Yuan, Dongxiang Luo and Baiquan Liu

Molecules 2018, 23(6), 1373; https://doi.org/10.3390/molecules23061373 - 6 Jun 2018

Cited by 17 | Viewed by 3273

Abstract

For the first time, compounds with lanthanum from the main family element Boron (LaB_x) were investigated as an active layer for thin-film transistors (TFTs). Detailed studies showed that the room-temperature fabricated LaB_x thin film was in the crystalline state with [...] Read more.

For the first time, compounds with lanthanum from the main family element Boron (LaB_x) were investigated as an active layer for thin-film transistors (TFTs). Detailed studies showed that the room-temperature fabricated LaB_x thin film was in the crystalline state with a relatively narrow optical band gap of 2.28 eV. The atom ration of La/B was related to the working pressure during the sputtering process and the atom ration of La/B increased with the increase of the working pressure, which will result in the freer electrons in the LaB_x thin film. LaB_x-TFT without any intentionally annealing steps exhibited a saturation mobility of 0.44 cm²·V⁻¹·s⁻¹, which is a subthreshold swing (SS) of 0.26 V/decade and a I_on/I_off ratio larger than 10⁴. The room-temperature process is attractive for its compatibility with almost all kinds of flexible substrates and the LaB_x semiconductor may be a new choice for the channel materials in TFTs. Full article

(This article belongs to the Section Inorganic Chemistry)

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10 pages, 3100 KiB

Open AccessArticle

Chiral 2-Aminobenzimidazole as Bifunctional Catalyst in the Asymmetric Electrophilic Amination of Unprotected 3-Substituted Oxindoles

by Llorenç Benavent, Alejandro Baeza and Megan Freckleton

Molecules 2018, 23(6), 1374; https://doi.org/10.3390/molecules23061374 - 6 Jun 2018

Cited by 13 | Viewed by 4591

Abstract

The use of readily available chiral trans-cyclohexanediamine-benzimidazole derivatives as bifunctional organocatalysts in the asymmetric electrophilic amination of unprotected 3-substituted oxindoles is presented. Different organocatalysts were evaluated; the most successful one contained a dimethylamino moiety (5). With this catalyst under optimized [...] Read more.

The use of readily available chiral trans-cyclohexanediamine-benzimidazole derivatives as bifunctional organocatalysts in the asymmetric electrophilic amination of unprotected 3-substituted oxindoles is presented. Different organocatalysts were evaluated; the most successful one contained a dimethylamino moiety (5). With this catalyst under optimized conditions, different oxindoles containing a wide variety of substituents at the 3-position were aminated in good yields and with good to excellent enantioselectivities using di-tert-butylazodicarboxylate as the aminating agent. The procedure proved to be also efficient for the amination of 3-substituted benzofuranones, although with moderate results. A bifunctional role of the catalyst, acting as Brønsted base and hydrogen bond donor, is proposed according to the experimental results observed. Full article

(This article belongs to the Special Issue Stereogenic Centers)

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16 pages, 4326 KiB

Open AccessArticle

[¹⁸F]FEPPA a TSPO Radioligand: Optimized Radiosynthesis and Evaluation as a PET Radiotracer for Brain Inflammation in a Peripheral LPS-Injected Mouse Model

by Nicolas Vignal, Salvatore Cisternino, Nathalie Rizzo-Padoin, Carine San, Fortune Hontonnou, Thibaut Gelé, Xavier Declèves, Laure Sarda-Mantel and Benoît Hosten

Molecules 2018, 23(6), 1375; https://doi.org/10.3390/molecules23061375 - 7 Jun 2018

Cited by 37 | Viewed by 7567

Abstract

[¹⁸F]FEPPA is a specific ligand for the translocator protein of 18 kDa (TSPO) used as a positron emission tomography (PET) biomarker for glial activation and neuroinflammation. [¹⁸F]FEPPA radiosynthesis was optimized to assess in a mouse model the cerebral inflammation [...] Read more.

[¹⁸F]FEPPA is a specific ligand for the translocator protein of 18 kDa (TSPO) used as a positron emission tomography (PET) biomarker for glial activation and neuroinflammation. [¹⁸F]FEPPA radiosynthesis was optimized to assess in a mouse model the cerebral inflammation induced by an intraperitoneal injection of Salmonella enterica serovar Typhimurium lipopolysaccharides (LPS; 5 mg/kg) 24 h before PET imaging. [¹⁸F]FEPPA was synthesized by nucleophilic substitution (90 °C, 10 min) with tosylated precursor, followed by improved semi-preparative HPLC purification (retention time 14 min). [¹⁸F]FEPPA radiosynthesis were carried out in 55 min (from EOB). The non-decay corrected radiochemical yield were 34 ± 2% (n = 17), and the radiochemical purity greater than 99%, with a molar activity of 198 ± 125 GBq/µmol at the end of synthesis. Western blot analysis demonstrated a 2.2-fold increase in TSPO brain expression in the LPS treated mice compared to controls. This was consistent with the significant increase of [¹⁸F]FEPPA brain total volume of distribution (V_T) estimated with pharmacokinetic modelling. In conclusion, [¹⁸F]FEPPA radiosynthesis was implemented with high yields. The new purification/formulation with only class 3 solvents is more suitable for in vivo studies. Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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13 pages, 2884 KiB

Open AccessArticle

In Situ Monitoring of the Effect of Ultrasound on the Sulfhydryl Groups and Disulfide Bonds of Wheat Gluten

by Yanyan Zhang, Yinli Li, Suyun Li, Hua Zhang and Haile Ma

Molecules 2018, 23(6), 1376; https://doi.org/10.3390/molecules23061376 - 7 Jun 2018

Cited by 18 | Viewed by 3473

Abstract

Ultrasound treatment can improve enzymolysis efficiency by changing the amounts of sulfhydryl groups (SH) and disulfide bonds (SS) in protein. This paper proposes an in-situ and real-time monitoring method for SH and SS during ultrasound application processes using a miniature near-infrared (NIR) optical [...] Read more.

Ultrasound treatment can improve enzymolysis efficiency by changing the amounts of sulfhydryl groups (SH) and disulfide bonds (SS) in protein. This paper proposes an in-situ and real-time monitoring method for SH and SS during ultrasound application processes using a miniature near-infrared (NIR) optical fiber spectrometer and a chemometrics model to determine the endpoint of ultrasonic treatment. The results show that SH and SS contents fluctuated greatly with the extension of ultrasonic time. The optimal spectral intervals for SH content were 869–947, 1207–1284, 1458–1536 and 2205–2274 nm, the optimal spectral intervals of SS content were 933–992, 1388–1446, 2091–2148 and 2217–2274 nm. According to the optimal spectral intervals, the synergy interval partial least squares (Si-PLS) and error back propagation neural network (BP-ANN) for SH, SS contents were established. The BP-ANN model was better than the Si-PLS model. The correlation coefficient of the prediction set (R_p) and the root mean square error of prediction (RMSEP) for the BP-ANN model of SH were 0.9113 and 0.38 μmol/g, respectively, the R_p² and residual prediction deviation of SH were 0.8305 and 2.91, respectively. For the BP-ANN model of SS, the R_p and the RMSEP were 0.7523 and 6.56 μmol/g, respectively. The R_p² and residual prediction deviation (RPD) of SS were 0.8305 and 2.91, respectively. However, the R_p² and RPD of SS was 0.5660 and 1.64, respectively. This work demonstrated that the miniature NIR combined with BP-ANN algorithms has high potential for in-situ monitoring of SH during the ultrasonic treatment process, while the spectral prediction model of SS needs to be further developed. Full article

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11 pages, 820 KiB

Open AccessArticle

Structure-Activity Relationship of Dialkoxychalcones to Combat Fish Pathogen Saprolegnia australis

by Iván Montenegro, Ociel Muñoz, Joan Villena, Enrique Werner, Marco Mellado, Ingrid Ramírez, Nelson Caro, Susana Flores and Alejandro Madrid

Molecules 2018, 23(6), 1377; https://doi.org/10.3390/molecules23061377 - 7 Jun 2018

Cited by 13 | Viewed by 3299

Abstract

To investigate the anti-Saprolegnia activities of chalconic compounds, nine dialkoxychalcones 2–10, along with their key building block 2′,4′-dihydroxychalcone 1, were evaluated for their potential oomycide activities against Saprolegnia australis strains. The synthesis afforded a series of O-alkylated [...] Read more.

To investigate the anti-Saprolegnia activities of chalconic compounds, nine dialkoxychalcones 2–10, along with their key building block 2′,4′-dihydroxychalcone 1, were evaluated for their potential oomycide activities against Saprolegnia australis strains. The synthesis afforded a series of O-alkylated derivatives with typical chalcone skeletons. Compounds 4–10 were reported for the first time. Interestingly, analogue 8 with the new scaffold demonstrated remarkable in vitro growth-inhibitory activities against Saprolegnia strains, displaying greater anti-oomycete potency than the standard drugs used in the assay, namely fluconazole and bronopol. In contrast, a dramatic loss of activity was observed for O-alkylated derivatives 2, 3, 6, and 7. These findings have highlighted the therapeutic potential of the natural compound 1 scaffold to be exploitable as a drug lead with specific activity against various Saprolegnia strains. Full article

(This article belongs to the Section Organic Chemistry)

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13 pages, 1551 KiB

Open AccessArticle

Effect of Indolic-Amide Melatonin on Blood Cell Population: A Biophysical Gaussian Statistical Analysis

by Roberto Zivieri, Fabio Borziani, Angela Strazzanti, Angela Fragomeni and Nicola Pacini

Molecules 2018, 23(6), 1378; https://doi.org/10.3390/molecules23061378 - 7 Jun 2018

Viewed by 3895

Abstract

The problem of the correlation of indolic molecules with special regard to melatonin and immune processes has been widely investigated. However, there are only few studies focusing on circadian variation of peripheral blood leukocytes. The purpose of this study is thus to understand [...] Read more.

The problem of the correlation of indolic molecules with special regard to melatonin and immune processes has been widely investigated. However, there are only few studies focusing on circadian variation of peripheral blood leukocytes. The purpose of this study is thus to understand the influence of MLT on leukocyte populations and its correlation with leukocyte distribution. This is accomplished by administrating placebo and melatonin to different groups of individuals and by performing a biophysical Gaussian analysis on the number of leukocytes by means of a comparison of their p.m. vs. a.m. variations under the effect of placebo and of melatonin and via a comparison in the morning between leukocytes population of untreated group and MLT group. It is shown that: (a) melatonin has the effect of narrowing the normal distribution concentrating most of the individuals towards the mean value of the observed variation of leukocytes population and (b) the individuals who have not received either placebo or supplement have a leukocyte population that follows a normal distribution. These results confirm the crucial role played by melatonin, as the most representative of indolic amide in biological systems, in the circadian peripheral variations of leukocyte numbers because counts of white blood cells are essential in medical urgency and differential diagnosis situations. Hence, further studies are suggested to account for these physiological variations and for the evaluation of the full involvement of the action of MLT on leukocytes distribution. Full article

(This article belongs to the Special Issue The Biomedical Importance of Indoles and Their Derivatives)

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13 pages, 1154 KiB

Open AccessArticle

Comparison between Multi-Linear- and Radial-Basis-Function-Neural-Network-Based QSPR Models for The Prediction of The Critical Temperature, Critical Pressure and Acentric Factor of Organic Compounds

by Mauro Banchero and Luigi Manna

Molecules 2018, 23(6), 1379; https://doi.org/10.3390/molecules23061379 - 7 Jun 2018

Cited by 18 | Viewed by 4337

Abstract

Critical properties and acentric factor are widely used in phase equilibrium calculations but are difficult to evaluate with high accuracy for many organic compounds. Quantitative Structure-Property Relationship (QSPR) models are a powerful tool to establish accurate correlation between molecular properties and chemical structure. [...] Read more.

Critical properties and acentric factor are widely used in phase equilibrium calculations but are difficult to evaluate with high accuracy for many organic compounds. Quantitative Structure-Property Relationship (QSPR) models are a powerful tool to establish accurate correlation between molecular properties and chemical structure. QSPR multi-linear (MLR) and radial basis-function-neural-network (RBFNN) models have been developed to predict the critical temperature, critical pressure and acentric factor of a database of 306 organic compounds. RBFNN models provided better data correlation and higher predictive capability (an AAD% of 0.92–2.0% for training and 1.7–4.8% for validation sets) than MLR models (an AAD% of 3.2–8.7% for training and 6.2–12.2% for validation sets). The RMSE of the RBFNN models was 20–30% of the MLR ones. The correlation and predictive performances of the models for critical temperature were higher than those for critical pressure and acentric factor, which was the most difficult property to predict. However, the RBFNN model for the acentric factor resulted in the lowest RMSE with respect to previous literature. The close relationship between the three properties resulted from the selected molecular descriptors, which are mostly related to molecular electronic charge distribution or polar interactions between molecules. QSPR correlations were compared with the most frequently used group-contribution methods over the same database of compounds: although the MLR models provided comparable results, the RBFNN ones resulted in significantly higher performance. Full article

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13 pages, 24485 KiB

Open AccessArticle

Anti-Inflammatory Effects of Fargesin on Chemically Induced Inflammatory Bowel Disease in Mice

by Bei Yue, Yi-Jing Ren, Jing-Jing Zhang, Xiao-Ping Luo, Zhi-Lun Yu, Gai-Yan Ren, A-Ning Sun, Chao Deng, Zheng-Tao Wang and Wei Dou

Molecules 2018, 23(6), 1380; https://doi.org/10.3390/molecules23061380 - 7 Jun 2018

Cited by 39 | Viewed by 6100

Abstract

Fargesin is a bioactive lignan from Flos Magnoliae, an herb widely used in the treatment of allergic rhinitis, sinusitis, and headache in Asia. We sought to investigate whether fargesin ameliorates experimental inflammatory bowel disease (IBD) in mice. Oral administration of fargesin significantly [...] Read more.

Fargesin is a bioactive lignan from Flos Magnoliae, an herb widely used in the treatment of allergic rhinitis, sinusitis, and headache in Asia. We sought to investigate whether fargesin ameliorates experimental inflammatory bowel disease (IBD) in mice. Oral administration of fargesin significantly attenuated the symptoms of dextran sulfate sodium (DSS)-induced colitis in mice by decreasing the inflammatory infiltration and myeloperoxidase (MPO) activity, reducing tumor necrosis factor (TNF)-α secretion, and inhibiting nitric oxide (NO) production in colitis mice. The degradation of inhibitory κBα (IκBα), phosphorylation of p65, and mRNA expression of nuclear factor κB (NF-κB) target genes were inhibited by fargesin treatment in the colon of the colitis mice. In vitro, fargesin blocked the nuclear translocation of p-p65, downregulated the protein levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), and dose-dependently inhibited the activity of NF-κB-luciferase in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Taken together, for the first time, the current study demonstrated the anti-inflammatory effects of fargesin on chemically induced IBD might be associated with NF-κB signaling suppression. The findings may contribute to the development of therapies for human IBD by using fargesin or its derivatives. Full article

(This article belongs to the Special Issue Drug Discovery for Neglected Diseases)

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18 pages, 1573 KiB

Open AccessArticle

Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma

by Flávio Rogério Da Nóbrega, Ozlem Ozdemir, Sheila Cristina S. Nascimento Sousa, Joice Nascimento Barboza, Hasan Turkez and Damião Pergentino De Sousa

Molecules 2018, 23(6), 1382; https://doi.org/10.3390/molecules23061382 - 8 Jun 2018

Cited by 18 | Viewed by 5355

Abstract

Piplartine (1) is an alkamide extracted from plants of the genus Piper which shows several pharmacological properties, including antitumor activity. To improve this activity, a series of analogues based on 1 have been synthesized by esterification and amidation using the 3,4,5-trimethoxycinnamic [...] Read more.

Piplartine (1) is an alkamide extracted from plants of the genus Piper which shows several pharmacological properties, including antitumor activity. To improve this activity, a series of analogues based on 1 have been synthesized by esterification and amidation using the 3,4,5-trimethoxycinnamic acid-like starting material. During the study, the moieties 3-(3,4,5-trimethoxyphenyl)acrylate and 3-(3,4,5-trimethoxyphenyl)acrylamide were maintained on esters and amides respectively. Meanwhile, functional changes were exploited, and it was revealed that the presence of two aromatic rings in the side-chain was important to improve the cytotoxic activity against the U87MG cell line, such as the compound (E)-benzhydryl 3-(3,4,5-trimethoxyphenyl)acrylate (10), an ester that exhibited strong cytotoxicity and a similar level of potency to that of paclitaxel, a positive control. Compound 10 had a marked concentration-dependent inhibitory effect on the viability of the U87MG cell line with apoptotic and oxidative processes, showing good potential for altering main molecular pathways to prevent tumor development. Moreover, it has strong bioavailability with non-genotoxic and non-cytotoxic properties on human blood cells. In conclusion, the findings of the present study demonstrated that compound 10 is a promising agent that may find applications combatting diseases associated with oxidative stress and as a prototype for the development of novel drugs used in the treatment of glioblastoma. Full article

(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)

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7 pages, 514 KiB

Open AccessArticle

Four New Sesquiterpenoids from the Roots of Diarthron Tianschanica with Their Antineoplastic Activity

by Dong-Xue Sun, Dan Zhao, Hong-Yan Wei, Xiao-Ling Ma, Lei-Ling Shi and Jing Zhang

Molecules 2018, 23(6), 1383; https://doi.org/10.3390/molecules23061383 - 8 Jun 2018

Cited by 3 | Viewed by 3124

Abstract

Four new sesquiterpenoids, known as diarthronchas A–D (1–4), and one known daphnauranol B (5) were isolated from the methanol extract of the roots of Diarthron tianschanica. The compounds structures were determined on the basis of spectroscopic [...] Read more.

Four new sesquiterpenoids, known as diarthronchas A–D (1–4), and one known daphnauranol B (5) were isolated from the methanol extract of the roots of Diarthron tianschanica. The compounds structures were determined on the basis of spectroscopic data. All of the isolated compounds were profiled for their antineoplastic activity. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 1121 KiB

Open AccessArticle

Comparative Proteomic Analysis of Rana chensinensis Oviduct

by Hang Su, He Zhang, Xinghua Wei, Daian Pan, Li Jing, Daqing Zhao, Yu Zhao and Bin Qi

Molecules 2018, 23(6), 1384; https://doi.org/10.3390/molecules23061384 - 8 Jun 2018

Cited by 9 | Viewed by 6262

Abstract

As one of most important traditional Chinese medicine resources, the oviduct of female Rana chensinensis (Chinese brown frog) was widely used in the treatment of asthenia after sickness or delivery, deficiency in vigor, palpitation, and insomnia. Unlike other vertebrates, the oviduct of Rana [...] Read more.

As one of most important traditional Chinese medicine resources, the oviduct of female Rana chensinensis (Chinese brown frog) was widely used in the treatment of asthenia after sickness or delivery, deficiency in vigor, palpitation, and insomnia. Unlike other vertebrates, the oviduct of Rana chensinensis oviduct significantly expands during prehibernation, in contrast to the breeding period. To explain this phenomenon at the molecular level, the protein expression profiles of Rana chensinensis oviduct during the breeding period and prehibernation were observed using isobaric tags for relative and absolute quantitation (iTRAQ) technique. Then, all identified proteins were used to obtain gene ontology (GO) annotation. Ultimately, KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis was performed to predict the pathway on differentially expressed proteins (DEPs). A total of 4479 proteins were identified, and 312 of them presented different expression profiling between prehibernation and breeding period. Compared with prehibernation group, 86 proteins were upregulated, and 226 proteins were downregulated in breeding period. After KEGG enrichment analysis, 163 DEPs were involved in 6 pathways, which were lysosome, RNA transport, glycosaminoglycan degradation, extracellular matrix (ECM)–receptor interaction, metabolic pathways and focal adhesion. This is the first report on the protein profiling of Rana chensinensis oviduct during the breeding period and prehibernation. Results show that this distinctive physiological phenomenon of Rana chensinensis oviduct was mainly involved in ECM–receptor interaction, metabolic pathways, and focal adhesion. Full article

(This article belongs to the Special Issue Mass Spectrometric Proteomics)

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15 pages, 1771 KiB

Open AccessArticle

Cobalt Complex with Thiazole-Based Ligand as New Pseudomonas aeruginosa Quorum Quencher, Biofilm Inhibitor and Virulence Attenuator

by Anabela Borges, Manuel Simões, Tamara R. Todorović, Nenad R. Filipović and Alfonso T. García-Sosa

Molecules 2018, 23(6), 1385; https://doi.org/10.3390/molecules23061385 - 8 Jun 2018

Cited by 16 | Viewed by 5383

Abstract

Pseudomonas aeruginosa is one of the most dreaded human pathogens, because of its intrinsic resistance to a number of commonly used antibiotics and ability to form sessile communities (biofilms). Innovative treatment strategies are required and that can rely on the attenuation of the [...] Read more.

Pseudomonas aeruginosa is one of the most dreaded human pathogens, because of its intrinsic resistance to a number of commonly used antibiotics and ability to form sessile communities (biofilms). Innovative treatment strategies are required and that can rely on the attenuation of the pathogenicity and virulence traits. The interruption of the mechanisms of intercellular communication in bacteria (quorum sensing) is one of such promising strategies. A cobalt coordination compound (Co(HL)₂) synthesized from (E)-2-(2-(pyridin-2-ylmethylene)hydrazinyl)-4-(p-tolyl)thiazole (HL) is reported herein for the first time to inhibit P. aeruginosa 3-oxo-C12-HSL-dependent QS system (LasI/LasR system) and underling phenotypes (biofilm formation and virulence factors). Its interactions with a possible target, the transcriptional activator protein complex LasR-3-oxo-C12-HSL, was studied by molecular modeling with the coordination compound ligand having stronger predicted interactions than those of co-crystallized ligand 3-oxo-C12-HSL, as well as known-binder furvina. Transition metal group 9 coordination compounds may be explored in antipathogenic/antibacterial drug design. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 2577 KiB

Open AccessArticle

Cytotoxic, Anti-Proliferative and Apoptosis Activity of l-Amino Acid Oxidase from Malaysian Cryptelytrops purpureomaculatus (CP-LAAO) Venom on Human Colon Cancer Cells

by Syafiq Asnawi Zainal Abidin, Pathmanathan Rajadurai, Md. Ezharul Hoque Chowdhury, Iekhsan Othman and Rakesh Naidu

Molecules 2018, 23(6), 1388; https://doi.org/10.3390/molecules23061388 - 8 Jun 2018

Cited by 20 | Viewed by 4979

Abstract

The aim of this study is to investigate the potential anti-cancer activity of l-amino acid oxidase (CP-LAAO) purified from the venom of Cryptelytrops purpureomaculatus on SW480 and SW620 human colon cancer cells. Mass spectrometry guided purification was able to identify and purify [...] Read more.

The aim of this study is to investigate the potential anti-cancer activity of l-amino acid oxidase (CP-LAAO) purified from the venom of Cryptelytrops purpureomaculatus on SW480 and SW620 human colon cancer cells. Mass spectrometry guided purification was able to identify and purify CP-LAAO. Amino acid variations identified from the partial protein sequence of CP-LAAO may suggest novel variants of these proteins. The activity of the purified CP-LAAO was confirmed with o-phenyldiamine (OPD)-based spectrophotometric assay. CP-LAAO demonstrated time- and dose-dependent cytotoxic activity and the EC₅₀ value was determined at 13 µg/mL for both SW480 and SW620 cells. Significant increase of caspase-3 activity, reduction of Bcl-2 levels, as well as morphological changes consistent with apoptosis were demonstrated by CP-LAAO. Overall, these data provide evidence on the potential anti-cancer activity of CP-LAAO from the venom of Malaysian C. purpureomaculatus for therapeutic intervention of human colon cancer. 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, 1957 KiB

Open AccessArticle

Quantification of Glutamate and Aspartate by Ultra-High Performance Liquid Chromatography

by Carlos Agius, Sabine Von Tucher, Brigitte Poppenberger and Wilfried Rozhon

Molecules 2018, 23(6), 1389; https://doi.org/10.3390/molecules23061389 - 8 Jun 2018

Cited by 25 | Viewed by 7104

Abstract

Glutamic and aspartic acid fulfil numerous functions in organisms. They are proteinogenic amino acids, they function as neurotransmitters, and glutamic acid links the citrate cycle with amino acid metabolism. In addition, glutamic acid is a precursor for many bioactive molecules like γ-aminobutyric acid [...] Read more.

Glutamic and aspartic acid fulfil numerous functions in organisms. They are proteinogenic amino acids, they function as neurotransmitters, and glutamic acid links the citrate cycle with amino acid metabolism. In addition, glutamic acid is a precursor for many bioactive molecules like γ-aminobutyric acid (GABA). In tomatoes, glutamic acid accumulates in ripening fruits. Here we present a simple and rapid method for quantification of glutamate and aspartate in tomatoes. A cleared extract is prepared and 2-aminoadipic acid added as internal standard. Subsequently, the amino acids are derivatised with 2,4-dinitro-1-fluorobenzene under alkaline conditions. The derivatives are separated by ultra-high performance liquid chromatography using a phenyl-hexyl column and 50 mM N-methylmorpholine/acetate buffer pH 7.4 containing 12% acetonitrile as eluent and detected by UV absorption at 363 nm. The whole analysis time including separation and column equilibration takes less than 2.8 min with a flow rate of 1 mL/min and less than 1.6 min with a flow rate of 2 mL/min, making this method suitable for high-throughput applications. The method shows excellent reproducibility with intra- and inter-day SDs of approximately 4% for both aspartic and glutamic acid. Using this method we show that the glutamate/aspartate ratio changes significantly during fruit ripening. Full article

(This article belongs to the Section Analytical Chemistry)

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13 pages, 2829 KiB

Open AccessFeature PaperArticle

Synthesis of 2-Mercapto-(2-Oxoindolin-3-Ylidene)Acetonitriles from 3-(4-Chloro-5H-1,2,3-Dithiazol-5-Ylidene)Indolin-2-ones

by Boris Letribot, Régis Delatouche, Hervé Rouillard, Antoine Bonnet, Jean-René Chérouvrier, Lisianne Domon, Thierry Besson and Valérie Thiéry

Molecules 2018, 23(6), 1390; https://doi.org/10.3390/molecules23061390 - 8 Jun 2018

Cited by 5 | Viewed by 6277

Abstract

Alkylidene oxindoles are important functional moieties and building blocks in pharmaceutical and synthetic chemistry. Our interest in biologically active compounds focused our studies on the synthesis of novel oxindoles, bearing on the exocyclic double bond at the C8, CN, and S groups. Extending [...] Read more.

Alkylidene oxindoles are important functional moieties and building blocks in pharmaceutical and synthetic chemistry. Our interest in biologically active compounds focused our studies on the synthesis of novel oxindoles, bearing on the exocyclic double bond at the C8, CN, and S groups. Extending the potential applications of Appel’s salt, we developed a new synthetic approach by investigating the reactions of C5-substituted 2-oxindoles with 4,5-dichloro-1,2,3-dithiazolium chloride (Appel’s salt) to give original (Z)-3-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)indolin-2-one derivatives, and new 2-mercapto-(2-oxoindolin-3-ylidene)acetonitriles via a dithiazole ring-opening reaction. The work described in this article represents further applications of Appel’s salt in the conception of novel heterocyclic rings, in an effort to access original bioactive compounds. Fifteen new compounds were prepared and fully characterized. Full article

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

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13 pages, 725 KiB

Open AccessArticle

Isolation, Structural Elucidation, and α-Glucosidase Inhibitory Activities of Triterpenoid Lactones and Their Relevant Biogenetic Constituents from Ganoderma resinaceum

by Xian-Qiang Chen, Li-Gen Lin, Jing Zhao, Ling-Xiao Chen, Yu-Ping Tang, De-Lun Luo and Shao-Ping Li

Molecules 2018, 23(6), 1391; https://doi.org/10.3390/molecules23061391 - 8 Jun 2018

Cited by 9 | Viewed by 4219

Abstract

Ganoderma resinaceum has been used as an ethnomedicine for lowering blood sugar. To clarify the bioactive chemical constituents contributing to lower blood sugar, chemical investigation on the fruiting bodies of Ganoderma resinaceum was conducted by chromatographic techniques, and led to the isolation of [...] Read more.

Ganoderma resinaceum has been used as an ethnomedicine for lowering blood sugar. To clarify the bioactive chemical constituents contributing to lower blood sugar, chemical investigation on the fruiting bodies of Ganoderma resinaceum was conducted by chromatographic techniques, and led to the isolation of 14 compounds. Their structures were elucidated as triterpenoid lactones (1–4 and 8) and ganoderma acids (5–7 and 9–14) based on the analysis of extensive spectroscopy (mass spectrometry (MS), nuclear magnetic resonance (NMR), infrared (IR), and ultraviolet (UV)) and comparison with literature data. Compounds 3, 5, 6, and 9–14 were evaluated for α-glucosidase inhibitory activity. Compounds 1–7 are new compounds. Compounds 1–4 and 8 were characteristic of an oxaspirolactone moiety, consisting of a five-membered ether ring, a five-membered lactone ring, and a characteristic C-23 spiro carbon. It is rare for natural products that such an oxaspirolactone moiety occurred in the lanostane-type triterpenoids. Compounds 5–7 and 9–14 may be important intermediates of the biosynthetic pathways of 1–4 and 8. Compounds 1 and 2 showed more potent inhibitory activity against α-glucosidase compared with the positive control drug acarbose with IC₅₀ value of 0.75 ± 0.018 mM and 1.64 ± 0.022 mM, respectively. Full article

(This article belongs to the Special Issue Natural Products in Prevention and Treatment of Metabolic Syndrome)

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14 pages, 3344 KiB

Open AccessArticle

Protective Effects on 60Co-γ Radiation Damage of Pine Cone Polyphenols from Pinus koraiensis-Loaded Chitosan Microspheres In Vivo

by Sujuan Shao, Juanjuan Yi, Joe M. Regenstein, Cuilin Cheng, Hua Zhang, Haitian Zhao and Zhenyu Wang

Molecules 2018, 23(6), 1392; https://doi.org/10.3390/molecules23061392 - 8 Jun 2018

Cited by 13 | Viewed by 3621

Abstract

A novel chitosan microsphere for encapsulating pine cone polyphenols (PP) from P. koraiensis was successfully prepared using an emulsion crosslinking technique. The characteristics of pine polyphenol-loaded microspheres (PPM) were determined using scanning electron microscopy (SEM) and a laser particle size detector. It was [...] Read more.

A novel chitosan microsphere for encapsulating pine cone polyphenols (PP) from P. koraiensis was successfully prepared using an emulsion crosslinking technique. The characteristics of pine polyphenol-loaded microspheres (PPM) were determined using scanning electron microscopy (SEM) and a laser particle size detector. It was found that PPMs were spherical in shape with uniform particle size distribution patterns. The drug content and encapsulation rate of the microspheres were 7.47% and 73.6%, respectively, at a Ch/GA mass ratio of 0.7. The animal experiments showed that PPM had a stronger radiation protective effect than PP. PPM significantly increased the immune organ indices, the quantity of marrow DNA, the superoxide dismutase (SOD) activity, the splenocyte proliferation index, and the phagocytosis activity of monocytes. PPM also decreased the numbers of micronuclei in bone marrow cells and malondialdehyde (MDA) levels in plasma in mice exposed to ⁶⁰Co γ-irradiation. In addition, gender differences in biological responses to exposure to radiation were observed. Full article

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10 pages, 1759 KiB

Open AccessArticle

Molecular Identification and Taxonomic Implication of Herbal Species in Genus Corydalis (Papaveraceae)

by Lu Jiang, Meihui Li, Fengxi Zhao, Shanshan Chu, Liangping Zha, Tao Xu, Huasheng Peng and Wei Zhang

Molecules 2018, 23(6), 1393; https://doi.org/10.3390/molecules23061393 - 8 Jun 2018

Cited by 30 | Viewed by 5122

Abstract

Many species of Corydalis (Papaveraceae) have been used as medicinal plants in East Asia, and the most well-known species are Corydalis yanhusuo and C. decumbens in the Pharmacopoeia of China. However, authentication of these species remains problematic because of their high morphological variation. [...] Read more.

Many species of Corydalis (Papaveraceae) have been used as medicinal plants in East Asia, and the most well-known species are Corydalis yanhusuo and C. decumbens in the Pharmacopoeia of China. However, authentication of these species remains problematic because of their high morphological variation. Here, we selected 14 closely related species and five genomic regions (chloroplast: matK, trnG, rbcL, psbA-trnH; nuclear: ITS) to explore the utility of DNA barcoding for authenticating these herbs. In addition, the Poisson tree process (PTP) and automatic barcode gap discovery (ABGD) were also used and compared with DNA barcoding. Our results showed that the ITS region was not suitable for molecular analysis because of its heterogeneous nature in Corydalis. In contrast, matK was an ideal region for species identification because all species could be resolved when matK was used along with the other three chloroplast regions. We found that at least five traditional identified species were lumped into one genetic species by ABGD and PTP methods; thus, highlighting the overestimation of species diversity using the morphological approach. In conclusion, our first attempt of molecular analysis of Corydalis herbs presented here successfully resolved the identification of medicinal species and encouraged their taxonomic re-assessment. Full article

(This article belongs to the Section Molecular Diversity)

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13 pages, 2036 KiB

Open AccessArticle

Anti-Tumorigenic Activity of Chrysin from Oroxylum indicum via Non-Genotoxic p53 Activation through the ATM-Chk2 Pathway

by Mai Nagasaka, Ryoko Hashimoto, Yasumichi Inoue, Kan’ichiro Ishiuchi, Michiyo Matsuno, Yuka Itoh, Muneshige Tokugawa, Nobumichi Ohoka, Daisuke Morishita, Hajime Mizukami, Toshiaki Makino and Hidetoshi Hayashi

Molecules 2018, 23(6), 1394; https://doi.org/10.3390/molecules23061394 - 8 Jun 2018

Cited by 34 | Viewed by 5722

Abstract

The p53 tumor suppressor plays critical roles in cell cycle regulation and apoptotic cell death in response to various cellular stresses, thereby preventing cancer development. Therefore, the activation of p53 through small molecules is an attractive therapeutic strategy for the treatment of cancers [...] Read more.

The p53 tumor suppressor plays critical roles in cell cycle regulation and apoptotic cell death in response to various cellular stresses, thereby preventing cancer development. Therefore, the activation of p53 through small molecules is an attractive therapeutic strategy for the treatment of cancers retaining wild-type p53. We used a library of 700 Myanmar wild plant extracts to identify small molecules that induce p53 transcriptional activity. A cell-based screening method with a p53-responsive luciferase-reporter assay system revealed that an ethanol extract of Oroxylum indicum bark increased p53 transcriptional activity. Chrysin was isolated and identified as the active ingredient in the O. indicum bark extract. A treatment with chrysin increased p53 protein expression and the p53-mediated expression of downstream target genes, and decreased cell viability in MCF7 cells, but not in p53-knockdown MCF7 cells. We also found that chrysin activated the ATM-Chk2 pathway in the absence of DNA damage. Hence, the inactivation of the ATM-Chk2 pathway suppressed p53 activation induced by chrysin. These results suggest the potential of chrysin as an anti-cancer drug through the activation of p53 without DNA damage. Full article

(This article belongs to the Special Issue Transcription Factors as Therapeutic Targets)

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8 pages, 1510 KiB

Open AccessArticle

In Vitro Antioxidant Activities of Phenols and Oleanolic Acid from Mango Peel and Their Cytotoxic Effect on A549 Cell Line

by Xuelian Bai, Tongfei Lai, Ting Zhou, Yicong Li, Xiuting Li and Huawei Zhang

Molecules 2018, 23(6), 1395; https://doi.org/10.3390/molecules23061395 - 8 Jun 2018

Cited by 48 | Viewed by 6043

Abstract

Mango peel, the main by-product of juice processing, possesses appreciable quantities of bioactive phenolic compounds and is worthy of further utilization. The present work reports for the first time the HPLC analysis and in vitro antioxidant evaluation of mango peel phenols (MPPs) and [...] Read more.

Mango peel, the main by-product of juice processing, possesses appreciable quantities of bioactive phenolic compounds and is worthy of further utilization. The present work reports for the first time the HPLC analysis and in vitro antioxidant evaluation of mango peel phenols (MPPs) and their cytotoxic effect on the A549 lung cancer cell line. These results indicated that mango peel has the total phenolic content of 723.2 ± 0.93 mg·kg⁻¹ dry mango peel (DMP), which consisted mainly of vanillic aldehyde, caffeic acid, chlorogenic acid, gallic acid, procyanidin B₂ and oleanolic acid. Antioxidant assays showed that MPPs had strong antioxidant activities, with 92 ± 4.2% of DPPH radical scavenging rate, 79 ± 2.5% of ABTS radical inhibition rate and 4.7 ± 0.5 μM Trolox equivalents per kg⁻¹ DMP of ferric reducing power. Gallic acid possess a stronger antioxidant capacity than other phenols. In vitro cytotoxic tests suggested that mango peel extract (MPE) had an IC₅₀ value of 15 mg·mL⁻¹ and MPPs had a stronger inhibitory effect on the A549 cell line. Oleanolic acid exhibited the strongest cytotoxicity, with an IC₅₀ value of 4.7 μM, which was similar with that of the positive control 5-fluorouracil. Full article

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

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15 pages, 5770 KiB

Open AccessCommunication

The Design and Synthesis of N-Xanthone Benzenesulfonamides as Novel Phosphoglycerate Mutase 1 (PGAM1) Inhibitors

by Penghui Wang, Lulu Jiang, Yang Cao, Deyong Ye and Lu Zhou

Molecules 2018, 23(6), 1396; https://doi.org/10.3390/molecules23061396 - 8 Jun 2018

Cited by 11 | Viewed by 4879

Abstract

Upregulation of phosphoglycerate mutase 1 (PGAM1) has been identified as one common phenomenon in a variety of cancers. Inhibition of PGAM1 provides a new promising therapeutic strategy for cancer treatment. Herein, based on our previous work, a series of new N-xanthone benzenesulfonamides [...] Read more.

Upregulation of phosphoglycerate mutase 1 (PGAM1) has been identified as one common phenomenon in a variety of cancers. Inhibition of PGAM1 provides a new promising therapeutic strategy for cancer treatment. Herein, based on our previous work, a series of new N-xanthone benzenesulfonamides were discovered as novel PGAM1 inhibitors. The representative molecule 15h, with an IC₅₀ of 2.1 μM, showed an enhanced PGAM1 inhibitory activity and higher enzyme inhibitory specificity compared to PGMI-004A, as well as a slightly improved antiproliferative activity. Full article

(This article belongs to the Special Issue Xanthones: Themed Issue in Honor of Professor Madalena Pinto on the Occasion of Her 70th Birthday)

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14 pages, 4419 KiB

Open AccessArticle

Hydrogen-Bonded Organic–Inorganic Hybrid Based on Hexachloroplatinate and Nitrogen Heterocyclic Cations: Their Synthesis, Characterization, Crystal Structures, and Antitumor Activities In Vitro

by Jin Zhao, Fuming Chen, Yutong Han, Huaqing Chen, Zhidong Luo, Hao Tian, Yi Zhao, Aiqing Ma and Longguan Zhu

Molecules 2018, 23(6), 1397; https://doi.org/10.3390/molecules23061397 - 8 Jun 2018

Cited by 7 | Viewed by 4008

Abstract

Three new crystal structures containing [PtCl₆]²⁻, pyridinium and benzimidazole groups have been prepared: [PtCl₆]·(H-bzm)₂·2(H₂O) (1), [PtCl₆]·(H-bipy)₂·2(H₂O) (2), [PtCl₆]·(H-dimethyl-bipy)₂·2(H₂ [...] Read more.

Three new crystal structures containing [PtCl₆]²⁻, pyridinium and benzimidazole groups have been prepared: [PtCl₆]·(H-bzm)₂·2(H₂O) (1), [PtCl₆]·(H-bipy)₂·2(H₂O) (2), [PtCl₆]·(H-dimethyl-bipy)₂·2(H₂O) (3) [H-bzm: benzimidazole cation, H-bipy: 2,2′-bipyridine cation, H-dimethyl-bipy: 4,4′-bimethyl-2,2′-bipyridine cation]. All compounds have been fully characterized by elemental analyses, single-crystal X-ray analyses, IR spectra, TG analyses, and fluorescence studies. Single-crystal X-ray diffraction analysis suggests that the primary synthon contains ⁺N–H···Cl⁻, including ionic bonding and hydrogen bonding interactions. The dimensions are enhanced further by secondary O–H ∙∙Cl and N–H ∙∙O hydrogen bonding interactions between donor and acceptor atoms located at the periphery of these synthons. Moreover, coulombic attractions between the ions play an important role in reinforcing the structures of these complexes. In addition, antitumor activity against human lung adenocarcinoma cell line (A549) and human nasopharyngeal carcinoma cell line (CNE-2) was performed. These complexes all showed inhibition to the two cell lines, while complex 3 exhibited higher efficiency than complexes 1–2. Full article

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18 pages, 3819 KiB

Open AccessArticle

Design, Synthesis, Anticancer Evaluation and Docking Studies of Novel Heterocyclic Derivatives Obtained via Reactions Involving Curcumin

by Rita M. Borik, Nagwa M. Fawzy, Sherifa M. Abu-Bakr and Magdy S. Aly

Molecules 2018, 23(6), 1398; https://doi.org/10.3390/molecules23061398 - 8 Jun 2018

Cited by 50 | Viewed by 6796

Abstract

Curcumin, a widely utilized flavor and coloring agent in food, has been shown to demonstrate powerful antioxidant, antitumor promoting and anti-inflammatory properties in vitro and in vivo. In the present work, synthesis of new heterocyclic derivatives based on Curcumin was studied. Compound 3 [...] Read more.

Curcumin, a widely utilized flavor and coloring agent in food, has been shown to demonstrate powerful antioxidant, antitumor promoting and anti-inflammatory properties in vitro and in vivo. In the present work, synthesis of new heterocyclic derivatives based on Curcumin was studied. Compound 3 was synthesized via the reaction of furochromone carbaldehyde (1) with Curcumin (2) using pipredine as catalyst. Also, novel, 4,9-dimethoxy-5H-furo [3, 2-g] chromen-5-one derivatives 4a–d, 6a–d, 7, 8a–d, 9 and 10 were synthesized by the reactions of furochromone carbaldehyde (1) with different reagents (namely: appropriate amine 3a–d, appropriate hydrazine 5a–d, hydroxylamine hydrochloride, urea/thiourea, malononitrile, malononitrile with hydrazine hydrate). The structure of the synthesized products had been confirmed from their spectroscopic data (IR, ¹H-NMR, ¹³C-NMR and mass spectra). In the present investigation, the newly synthesized products were screened using the MTT colorimetric assay for their in vitro inhibition capacity in two human cancer cell lines (hepatocellular carcinoma (HEPG2) and breast cancer (MCF-7) as well as the normal cell line (human normal melanocyte, HFB4) in comparison to the known anticancer drugs: 5-flurouracil and doxorubicin. The anticancer activity results indicated that the synthesized products 4c and 8b showed growth inhibition activity against HEPG2 cell line and synthesized products 4b and 8a showed growth inhibition activity against MCF-7, but with varying intensities in comparison to the known anticancer drugs, 5-flurouracil and doxorubicin. Cyclin dependent kinase 2 (CDK2), a major cell cycle protein, was identified as a potential molecular target of Curcumin. Furthermore, Curcumin induced G1 cell cycle arrest, which is regulated by CDK2 in cancer cells. Therefore, we used molecular modelling to study in silico the possible inhibitory effect of CDK2 by Curcumin derivatives as a possible mechanism of these compounds as anticancer agents. The molecular docking study revealed that compounds 4b, 8a and 8b were the most effective compounds in inhibiting CDk2, and, this result was in agreement with cytotoxicity assay. Full article

(This article belongs to the Section Medicinal Chemistry)

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18 pages, 3068 KiB

Open AccessArticle

Evaluation of the Antimicrobial Activity and Cytotoxicity of Different Components of Natural Origin Present in Essential Oils

by Sara García-Salinas, Hellen Elizondo-Castillo, Manuel Arruebo, Gracia Mendoza and Silvia Irusta

Molecules 2018, 23(6), 1399; https://doi.org/10.3390/molecules23061399 - 8 Jun 2018

Cited by 143 | Viewed by 9240

Abstract

Even though essential oils (EOs) have been used for therapeutic purposes, there is now a renewed interest in the antimicrobial properties of phytochemicals and EOs in particular. Their demonstrated low levels of induction of antimicrobial resistance make them interesting for bactericidal applications, though [...] Read more.

Even though essential oils (EOs) have been used for therapeutic purposes, there is now a renewed interest in the antimicrobial properties of phytochemicals and EOs in particular. Their demonstrated low levels of induction of antimicrobial resistance make them interesting for bactericidal applications, though their complex composition makes it necessary to focus on the study of their main components to identify the most effective ones. Herein, the evaluation of the antimicrobial action of different molecules present in EOs against planktonic and biofilm-forming Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria was assessed. The bactericidal mechanisms of the different molecules, as well as their cytocompatibility, were also studied. Carvacrol, cinnamaldehyde, and thymol exhibit the highest in vitro antimicrobial activities against E. coli and S. aureus, with membrane disruption the bactericidal mechanism identified. The addition of those compounds (≥0.5 mg/mL) hampers S. aureus biofilm formation and partially eliminates preformed biofilms. The subcytotoxic values of the tested EO molecules (0.015–0.090 mg/mL) are lower than the minimum inhibitory and bactericidal concentrations obtained for bacteria (0.2–0.5 mg/mL) but are higher than that obtained for chlorhexidine (0.004 mg/mL), indicating the reduced cytotoxicity of EOs. Therefore, carvacrol, cinnamaldehyde, and thymol are molecules contained in EOs that could be used against E. coli– and S. aureus–mediated infections without a potential induction of bactericidal resistance and with lower cell toxicity than the conventional widely used chlorhexidine. Full article

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12 pages, 2373 KiB

Open AccessArticle

Comparison of Characteristics and DNAzyme Activity of G4–Hemin Conjugates Obtained via Two Hemin Attachment Methods

by Joanna Kosman, Krzysztof Żukowski and Bernard Juskowiak

Molecules 2018, 23(6), 1400; https://doi.org/10.3390/molecules23061400 - 9 Jun 2018

Cited by 16 | Viewed by 6118

Abstract

Two conjugation methods using different linkers were applied for the investigation of the spectral characteristics and activity of G-quadruplex (G4)–hemin conjugates. For this purpose, two G-quadruplex-forming DNA sequences were selected, and then conjugated to a hemin molecule via either amine coupling or a [...] Read more.

Two conjugation methods using different linkers were applied for the investigation of the spectral characteristics and activity of G-quadruplex (G4)–hemin conjugates. For this purpose, two G-quadruplex-forming DNA sequences were selected, and then conjugated to a hemin molecule via either amine coupling or a click reaction. The products obtained via these two methods differed in their chemistry and the length of the linker between the DNA and hemin molecules. Spectral characteristics revealed that both methods produced conjugates that were more thermally stable than G4/hemin complexes. Despite similar spectral characteristics, the conjugates obtained via these two methods differed in their DNAzyme activity. G4–hemin conjugates obtained through amine coupling exhibited higher activity than conjugates obtained through a click reaction. This was potentially due to the length and chemistry of the linker, which was 30 atoms long following the click reaction, but only six atoms long following amine coupling. A longer connector favors higher flexibility, and hence, reduces the binding of hemin with G4. The aromatic groups present in the linker obtained through the click reaction can also disturb the G4–hemin interaction. However, the conjugation of G4 DNA to hemin via the click reaction was connected to a higher yield, and did not require any sophisticated synthesis equipment. Full article

(This article belongs to the Section Bioorganic Chemistry)

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18 pages, 4713 KiB

Open AccessFeature PaperArticle

New Tetrahydroisoquinoline Derivatives Overcome Pgp Activity in Brain-Blood Barrier and Glioblastoma Multiforme in Vitro

by Iris Chiara Salaroglio, Elena Gazzano, Joanna Kopecka, Konstantin Chegaev, Costanzo Costamagna, Roberta Fruttero, Stefano Guglielmo and Chiara Riganti

Molecules 2018, 23(6), 1401; https://doi.org/10.3390/molecules23061401 - 9 Jun 2018

Cited by 14 | Viewed by 4558

Abstract

P-glycoprotein (Pgp) determines resistance to a broad spectrum of drugs used against glioblastoma multiforme (GB). Indeed, Pgp is highly expressed in GB stem cells and in the brain-blood barrier (BBB), the peculiar endothelium surrounding the brain. Inhibiting Pgp activity in the BBB and [...] Read more.

P-glycoprotein (Pgp) determines resistance to a broad spectrum of drugs used against glioblastoma multiforme (GB). Indeed, Pgp is highly expressed in GB stem cells and in the brain-blood barrier (BBB), the peculiar endothelium surrounding the brain. Inhibiting Pgp activity in the BBB and GB is still an open challenge. Here, we tested the efficacy of a small library of tetrahydroisoquinoline derivatives with an EC₅₀ for Pgp ≤ 50 nM, in primary human BBB cells and in patient-derived GB samples, from which we isolated differentiated/adherent cells (AC, i.e., Pgp-negative/doxorubicin-sensitive cells) and stem cells (neurospheres, NS, i.e., Pgp-positive/doxorubicin-resistant cells). Three compounds used at 1 nM increased the delivery of doxorubicin, a typical substrate of Pgp, across BBB monolayer, without altering the expression and activity of other transporters. The compounds increased the drug accumulation within NS, restoring doxorubicin-induced necrosis and apoptosis, and reducing cell viability. In co-culture systems, the compounds added to the luminal face of BBB increased the delivery of doxorubicin to NS growing under BBB and rescued the drug’s cytotoxicity. Our work identified new ligands of Pgp active at low nanomolar concentrations. These compounds reduce Pgp activity in BBB and GB and improve in vitro chemotherapy efficacy in this tumor. Full article

(This article belongs to the Special Issue Counteracting Drug Resistant Mechanisms in Cancer)

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16 pages, 3137 KiB

Open AccessArticle

Synthesis and Activity against Mycobacterium tuberculosis of Olivacine and Oxygenated Derivatives

by Ulrike Schmidt, Gabriele Theumer, Anne Jäger, Olga Kataeva, Baojie Wan, Scott G. Franzblau and Hans-Joachim Knölker

Molecules 2018, 23(6), 1402; https://doi.org/10.3390/molecules23061402 - 9 Jun 2018

Cited by 14 | Viewed by 4873

Abstract

The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as a key step. In a test for the inhibition of the growth of Mycobacterium tuberculosis, 9-methoxyolivacine [...] Read more.

The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as a key step. In a test for the inhibition of the growth of Mycobacterium tuberculosis, 9-methoxyolivacine showed the most significant inhibitory activity against Mycobacterium tuberculosis, with an MIC₉₀ value of 1.5 μM. Full article

(This article belongs to the Section Organic Chemistry)

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11 pages, 3290 KiB

Open AccessArticle

Correlation between the Potency of Flavonoids on Mushroom Tyrosinase Inhibitory Activity and Melanin Synthesis in Melanocytes

by Worrawat Promden, Wittawat Viriyabancha, Orawan Monthakantirat, Kaoru Umehara, Hiroshi Noguchi and Wanchai De-Eknamkul

Molecules 2018, 23(6), 1403; https://doi.org/10.3390/molecules23061403 - 9 Jun 2018

Cited by 49 | Viewed by 8587

Abstract

Twenty-seven flavonoids isolated from Dalbergia parviflora with vast structural diversity were screened for inhibitory activity against mushroom and murine tyrosinases using l-DOPA as the substrate. Among the flavonoids tested, only four—khrinone (5), cajanin (9), (3RS)-3′-hydroxy-8-methoxy vestitol [...] Read more.

Twenty-seven flavonoids isolated from Dalbergia parviflora with vast structural diversity were screened for inhibitory activity against mushroom and murine tyrosinases using l-DOPA as the substrate. Among the flavonoids tested, only four—khrinone (5), cajanin (9), (3RS)-3′-hydroxy-8-methoxy vestitol (21), and (6aR,11aR)-3,8-dihydroxy-9-methoxy pterocarpan (27)—reacted with mushroom tyrosinase, with IC₅₀ values of 54.0, 67.9, 67.8, and 16.7 μM, respectively, and only compound 27 showed inhibitory activity against murine tyrosinase. With cell-based assays, only compounds 9 and 27 effectively inhibited melanogenesis in B16-F10 melanoma cells (by 34% and 59%, respectively), at a concentration of 15 μM, without being significantly toxic to the cells. However, the crude extract of D. parviflora and some of the flavonoid constituents appeared to increase melanin production in B16-F10 cells, suggesting that there are flavonoids with both inhibitory and stimulatory melanogenesis in the crude extract. Studies on the correlation between the enzyme-based and cell-based assays showed that only the flavonoids with IC₅₀ values below 50 μM against mushroom tyrosinase could inhibit the mammalian tyrosinase, and thus, reduce melanogenesis in B16-F10. Flavonoids with the IC₅₀ values greater than 50 μM, on the other hand, could not inhibit the mammalian tyrosinase, and had either no effect or enhancement of melanogenesis. In conclusion, the tyrosinase enzyme from mushroom is not as selective as the one from mammalian source for the enzyme-based melanogenesis inhibitory screening, and the mammalian cell-based assay appears to be a more reliable model for screening than the enzyme-based one. Full article

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

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13 pages, 4114 KiB

Open AccessArticle

Cellulose Nanofiber Biotemplated Palladium Composite Aerogels

by Fred J. Burpo, Alexander N. Mitropoulos, Enoch A. Nagelli, Jesse L. Palmer, Lauren A. Morris, Madeline Y. Ryu and J. Kenneth Wickiser

Molecules 2018, 23(6), 1405; https://doi.org/10.3390/molecules23061405 - 9 Jun 2018

Cited by 21 | Viewed by 6305

Abstract

Noble metal aerogels offer a wide range of catalytic applications due to their high surface area and tunable porosity. Control over monolith shape, pore size, and nanofiber diameter is desired in order to optimize electronic conductivity and mechanical integrity for device applications. However, [...] Read more.

Noble metal aerogels offer a wide range of catalytic applications due to their high surface area and tunable porosity. Control over monolith shape, pore size, and nanofiber diameter is desired in order to optimize electronic conductivity and mechanical integrity for device applications. However, common aerogel synthesis techniques such as solvent mediated aggregation, linker molecules, sol–gel, hydrothermal, and carbothermal reduction are limited when using noble metal salts. Here, we present the synthesis of palladium aerogels using carboxymethyl cellulose nanofiber (CNF) biotemplates that provide control over aerogel shape, pore size, and conductivity. Biotemplate hydrogels were formed via covalent cross linking using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) with a diamine linker between carboxymethylated cellulose nanofibers. Biotemplate CNF hydrogels were equilibrated in precursor palladium salt solutions, reduced with sodium borohydride, and rinsed with water followed by ethanol dehydration, and supercritical drying to produce freestanding aerogels. Scanning electron microscopy indicated three-dimensional nanowire structures, and X-ray diffractometry confirmed palladium and palladium hydride phases. Gas adsorption, impedance spectroscopy, and cyclic voltammetry were correlated to determine aerogel surface area. These self-supporting CNF-palladium aerogels demonstrate a simple synthesis scheme to control porosity, electrical conductivity, and mechanical robustness for catalytic, sensing, and energy applications. Full article

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

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16 pages, 4781 KiB

Open AccessArticle

Dexamethasone-Loaded, PEGylated, Vertically Aligned, Multiwalled Carbon Nanotubes for Potential Ischemic Stroke Intervention

by Patrick P. Komane, Pradeep Kumar, Thashree Marimuthu, Lisa C. du Toit, Pierre P. D. Kondiah, Yahya E. Choonara and Viness Pillay

Molecules 2018, 23(6), 1406; https://doi.org/10.3390/molecules23061406 - 10 Jun 2018

Cited by 27 | Viewed by 5762

Abstract

The complete synthesis, optimization, purification, functionalization and evaluation of vertically aligned multiwalled carbon nanotubes (VA-MWCNTs) was reported for potential application in dexamethasone delivery to the ischemic brain tissue. The conditions for high yield were optimized and carbon nanotubes functionalized and PEGylated prior to [...] Read more.

The complete synthesis, optimization, purification, functionalization and evaluation of vertically aligned multiwalled carbon nanotubes (VA-MWCNTs) was reported for potential application in dexamethasone delivery to the ischemic brain tissue. The conditions for high yield were optimized and carbon nanotubes functionalized and PEGylated prior to dexamethasone loading. Morphological changes were confirmed by SEM and TEM. Addition of functional groups to MWCNTs was demonstrated by FTIR. Thermal stability reduced following MWCNTs functionalization as demonstrated in TGA. The presence of carbon at 2θ of 25° and iron at 2θ of 45° in MWCNTs was illustrated by XRD. Polydispersive index and zeta potential were found to be 0.261 and −15.0 mV, respectively. Dexamethasone release increased by 55%, 65% and 95% in pH of 7.4, 6.5 and 5.5 respectively as evaluated by UV-VIS. The functionalized VA-MWCNTs were demonstrated to be less toxic in PC-12 cells in the concentration range from 20 to 20,000 µg/mL. These findings have demonstrated the potential of VA-MWCNTs in the enhancement of fast and prolonged release of dexamethasone which could lead to the effective treatment of ischemic stroke. More work is under way for targeting ischemic sites using atrial natriuretic peptide antibody in stroke rats. Full article

(This article belongs to the Special Issue Stimuli-Responsive Polymeric Materials)

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12 pages, 2475 KiB

Open AccessArticle

QSAR Study on Antioxidant Tripeptides and the Antioxidant Activity of the Designed Tripeptides in Free Radical Systems

by Nan Chen, Ji Chen, Bo Yao and Zhengguo Li

Molecules 2018, 23(6), 1407; https://doi.org/10.3390/molecules23061407 - 10 Jun 2018

Cited by 39 | Viewed by 5843

Abstract

In this study, quantitative structure-activity relationship (QSAR) models were determined based on 91 antioxidant tripeptides. We firstly adopted the stepwise regression (SWR) method for selecting key variables without autocorrelation and then utilized multiple linear regression (MLR), support vector machine (SVM), random forest (RF), [...] Read more.

In this study, quantitative structure-activity relationship (QSAR) models were determined based on 91 antioxidant tripeptides. We firstly adopted the stepwise regression (SWR) method for selecting key variables without autocorrelation and then utilized multiple linear regression (MLR), support vector machine (SVM), random forest (RF), and partial least square regression (PLS) to develop predictive QSAR models based on the screened variables. The results demonstrated that all the established models have good reliability (R²_train > 0.86, Q²_train > 0.70) and relatively good predictability (R²_test > 0.88). The contribution of amino acid residues was calculated from the stepwise regression combined with multiple linear regression (SWR-MLR) method model that shows Trp, Tyr, or Cys at C-terminus is favorable for antioxidant activity of tripeptides. Nineteen antioxidant tripeptides were designed based on SWR-MLR models, and the antioxidant activity of these tripeptides were evaluated using three antioxidant assays in free radical systems (1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity, trolox equivalent antioxidant capacity assay, and the ferric reducing antioxidant power assay). The experimental antioxidant activities of these tripeptides were higher than the calculated/predicted activity values of the QSAR models. The QSAR models established can be used to identify and screen novel antioxidant tripeptides with high activity. Full article

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17 pages, 995 KiB

Open AccessArticle

Separation of Active Compounds from Food by-Product (Cocoa Shell) Using Subcritical Water Extraction

by Stela Jokić, Tanja Gagić, Željko Knez, Drago Šubarić and Mojca Škerget

Molecules 2018, 23(6), 1408; https://doi.org/10.3390/molecules23061408 - 11 Jun 2018

Cited by 69 | Viewed by 7128

Abstract

Large amounts of residues are produced in the food industries. The waste shells from cocoa processing are usually burnt for fuel or used as a mulch in gardens to add nutrients to soil and to suppress weeds. The objectives of this work were: [...] Read more.

Large amounts of residues are produced in the food industries. The waste shells from cocoa processing are usually burnt for fuel or used as a mulch in gardens to add nutrients to soil and to suppress weeds. The objectives of this work were: (a) to separate valuable compounds from cocoa shell by applying sustainable green separation process—subcritical water extraction (SWE); (b) identification and quantification of active compounds, sugars and sugar degradation products in obtained extracts using HPLC; (c) characterization of the antioxidant activity of extracts; (d) optimization of separation process using response surface methodology (RSM). Depending on applied extraction conditions, different concentration of theobromine, caffeine, theophylline, epicatechin, catechin, chlorogenic acid and gallic acid were determined in the extracts obtained by subcritical water. Furthermore, mannose, glucose, xylose, arabinose, rhamnose and fucose were detected as well as their important degradation products such as 5-hydroxymethylfurfural (5-HMF), furfural, levulinic acid, lactic acid and formic acid. Full article

(This article belongs to the Section Green Chemistry)

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11 pages, 578 KiB

Open AccessArticle

Effect of Sterilization Process and Storage on the Antioxidative Properties of Runner Bean

by Rafał Wołosiak, Beata Drużyńska, Małgorzata Piecyk, Ewa Majewska and Elwira Worobiej

Molecules 2018, 23(6), 1409; https://doi.org/10.3390/molecules23061409 - 11 Jun 2018

Cited by 15 | Viewed by 4222

Abstract

In this study, we investigated the effect of standard preservation of bean seeds on changes in contents and activity of their selected components: dry matter, ash, different forms of nitrogen, composition of protein fractions; total phenolics and condensed tannins; ability to chelate iron(II) [...] Read more.

In this study, we investigated the effect of standard preservation of bean seeds on changes in contents and activity of their selected components: dry matter, ash, different forms of nitrogen, composition of protein fractions; total phenolics and condensed tannins; ability to chelate iron(II) ions; antiradical activity against ABTS^•+ and DPPH^•; and capability for inhibiting autoxidation and enzymatic oxidation of linoleic acid. The conducted technological process caused various changes in contents of nitrogen forms and partial loss of phenolic compounds. The antiradical and antioxidative activity of the extracts decreased significantly, while an increase was observed in their ability to chelate Fe(II). These changes were due to the migration of active compounds to the brine, and to their structural transformations and degradation. Longer storage of the sterilized product caused restoration of part of the antiradical activity of the seeds. Full article

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

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18 pages, 6197 KiB

Open AccessArticle

Polyphenols from Tamarix nilotica: LC–ESI-MSⁿ Profiling and In Vivo Antifibrotic Activity

by Ahmed Sekkien, Noha Swilam, Sherif S. Ebada, Ahmed Esmat, Ahmed H. El-Khatib, Michael W. Linscheid and Abdel Nasser Singab

Molecules 2018, 23(6), 1411; https://doi.org/10.3390/molecules23061411 - 11 Jun 2018

Cited by 16 | Viewed by 5254

Abstract

Tamarix nilotica (Ehrenb.) Bunge (Tamaricaceae), an indigenous plant to the Middle East region, is well-known as a medicinal plant for treating many human ailments. The current study aimed at exploring the polyphenol profile of the alcohol soluble fraction of aqueous T. nilotica extract, [...] Read more.

Tamarix nilotica (Ehrenb.) Bunge (Tamaricaceae), an indigenous plant to the Middle East region, is well-known as a medicinal plant for treating many human ailments. The current study aimed at exploring the polyphenol profile of the alcohol soluble fraction of aqueous T. nilotica extract, assessing its in vivo antifibrotic activity and the possible underlying mechanism, to unravel the impact of quantitative difference of sulphated polyphenols content on the antifibrotic activity of T. nilotca grown in two different habitats. Polyphenol profiling of T. nilotica extracts was performed using HPLC-HRESI-QTOF-MS-MS. The major polyphenol components included sulphated flavonoids, phenolic acids and free aglycones. The antifibrotic activity was evaluated through carbon tetrachloride-induced liver fibrosis in rats. Biochemical evaluations revealed that both fractions ameliorated the increased levels of hepatic aminotransferases, lipid peroxidation, hydroxyproline, α-smooth muscle actin (α-SMA), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB). Moreover, both fractions reduced catalase activity (CAT) and enhanced hepatic glutathione (GSH) content. Histopathological imaging undoubtedly confirmed such results. In conclusion, the T. nilotica polyphenol-rich fraction exhibited potential antifibrotic activity in rats. Significant alterations in GSH levels were recorded based on the sulphated polyphenol metabolite content. Full article

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8 pages, 1883 KiB

Open AccessArticle

Synthesis and Promotion of the Osteoblast Proliferation Effect of Morroniside Derivatives

by Hua Han, ZhengQing Li, Na Qu, Si Chen and PeiLiang Dong

Molecules 2018, 23(6), 1412; https://doi.org/10.3390/molecules23061412 - 11 Jun 2018

Cited by 6 | Viewed by 3841

Abstract

Sambucus williamsii Hance has been used in fractures for thousands of years, but research on its active components, such as morroniside, until now had not been carried out. In this study, morroniside was taken as the leading compound, and fourteen derivatives were synthesized. [...] Read more.

Sambucus williamsii Hance has been used in fractures for thousands of years, but research on its active components, such as morroniside, until now had not been carried out. In this study, morroniside was taken as the leading compound, and fourteen derivatives were synthesized. The promotion of osteoblast proliferation effect of the derivatives was evaluated on MC3T3-E1 cells. Five derivatives (2, 3, 4, 5, and 14) showed a good proliferation effect on MC3T3-E1 cells, and their promoted expression effects on OC (Osteocalcin) and ALP (Alkaline phosphatase) in MC3T3-E1 cells were measured. Compound 3 was shown to have the strongest proliferation effect (EC₅₀ = 14.78 ± 1.17 μg/mL) and to significantly promote the expression of OC and ALP. Full article

(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products 2018)

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12 pages, 2155 KiB

Open AccessArticle

Structure–Activity Relationship of the Tyrosinase Inhibitors Kuwanon G, Mulberrofuran G, and Albanol B from Morus Species: A Kinetics and Molecular Docking Study

by Prashamsa Koirala, Su Hui Seong, Yajuan Zhou, Srijan Shrestha, Hyun Ah Jung and Jae Sue Choi

Molecules 2018, 23(6), 1413; https://doi.org/10.3390/molecules23061413 - 11 Jun 2018

Cited by 33 | Viewed by 7207

Abstract

Kuwanon G (KG) and benzofuran flavonoids such as mulberrofuran G (MG) and albanol B (AB) isolated from Morus sp. are reported to exhibit anti-Alzheimer’s disease, anti-inflammatory, fungicidal, anti-cancer, anti-bacterial, and anti-tyrosinase properties. We investigated the inhibition of mono- and diphenolase activity of mushroom [...] Read more.

Kuwanon G (KG) and benzofuran flavonoids such as mulberrofuran G (MG) and albanol B (AB) isolated from Morus sp. are reported to exhibit anti-Alzheimer’s disease, anti-inflammatory, fungicidal, anti-cancer, anti-bacterial, and anti-tyrosinase properties. We investigated the inhibition of mono- and diphenolase activity of mushroom tyrosinase by KG, MG, and AB. KG and MG displayed acceptable inhibition activity compared to kojic acid. AB did not show any activity up to 350 µM. MG displayed six-fold higher inhibition of l-tyrosine oxidation (IC₅₀ = 6.35 ± 0.45 µM) compared to kojic acid (IC₅₀ = 36.0 µM). Kinetic studies revealed that KG and MG inhibited monophenolase activity of tyrosinase in a competitive manner. Docking simulations of KG and MG demonstrated favorable binding energies with amino acid residues of the active sites of tyrosinase. Our investigation of the structure-activity relationship of the fused benzofuran flavonoids (MG vs. AB) implicated the methyl cyclohexene ring moiety in tyrosinase inhibition. The enzyme substrate and relative structural analyses demonstrated that KG and MG from Morus sp. could be useful natural tyrosinase inhibitors in foods or cosmetics. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 2260 KiB

Open AccessArticle

(2E,5E)-2,5-Bis(3-hydroxy-4-methoxybenzylidene) cyclopentanone Exerts Anti-Melanogenesis and Anti-Wrinkle Activities in B16F10 Melanoma and Hs27 Fibroblast Cells

by Hee Jin Jung, A Kyoung Lee, Yeo Jin Park, Sanggwon Lee, Dongwan Kang, Young Suk Jung, Hae Young Chung and Hyung Ryong Moon

Molecules 2018, 23(6), 1415; https://doi.org/10.3390/molecules23061415 - 11 Jun 2018

Cited by 18 | Viewed by 5558

Abstract

Ultraviolet (UV) radiation exposure is the primary cause of extrinsic skin aging, which results in skin hyperpigmentation and wrinkling. In this study, we investigated the whitening effect of (2E,5E)-2,5-bis(3-hydroxy-4-methoxybenzylidene)cyclopentanone (BHCP) on B16F10 melanoma and its anti-wrinkle activity on Hs27 [...] Read more.

Ultraviolet (UV) radiation exposure is the primary cause of extrinsic skin aging, which results in skin hyperpigmentation and wrinkling. In this study, we investigated the whitening effect of (2E,5E)-2,5-bis(3-hydroxy-4-methoxybenzylidene)cyclopentanone (BHCP) on B16F10 melanoma and its anti-wrinkle activity on Hs27 fibroblasts cells. BHCP was found to potently inhibit tyrosinase, with 50% inhibition concentration (IC₅₀) values of 1.10 µM and 8.18 µM for monophenolase (l-tyrosine) and diphenolase (l-DOPA), and the enzyme kinetics study revealed that BHCP is a competitive-type tyrosinase inhibitor. Furthermore, BHCP significantly inhibited melanin content and cellular tyrosinase activity, and downregulated the levels of microphthalmia-associated transcription factor (MITF), phosphorylated levels of cAMP response element-binding (CREB) protein, and tyrosinase in α-melanocyte stimulating hormone (α-MSH)-induced B16F10 melanoma cells. Moreover, BHCP inhibited the phosphorylation of p65 and expression of matrix metalloproteinases (MMP-1, MMP-9, MMP-12, and MMP-13) in Hs27 fibroblasts stimulated with UV radiation. Therefore, our results demonstrate that BHCP may be a good candidate for the development of therapeutic agents for diseases associated with hyperpigmentation and wrinkling. Full article

(This article belongs to the Special Issue Design in Synthetic Biology)

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16 pages, 1520 KiB

Open AccessArticle

Comparison between Tetrel Bonded Complexes Stabilized by σ and π Hole Interactions

by Wiktor Zierkiewicz, Mariusz Michalczyk and Steve Scheiner

Molecules 2018, 23(6), 1416; https://doi.org/10.3390/molecules23061416 - 11 Jun 2018

Cited by 50 | Viewed by 5064

Abstract

The σ-hole tetrel bonds formed by a tetravalent molecule are compared with those involving a π-hole above the tetrel atom in a trivalent bonding situation. The former are modeled by TH₄, TH₃F, and TH₂F₂ (T = [...] Read more.

The σ-hole tetrel bonds formed by a tetravalent molecule are compared with those involving a π-hole above the tetrel atom in a trivalent bonding situation. The former are modeled by TH₄, TH₃F, and TH₂F₂ (T = Si, Ge, Sn) and the latter by TH₂=CH₂, THF=CH₂, and TF₂=CH₂, all paired with NH₃ as Lewis base. The latter π-bonded complexes are considerably more strongly bound, despite the near equivalence of the σ and π-hole intensities. The larger binding energies of the π-dimers are attributed to greater electrostatic attraction and orbital interaction. Each progressive replacement of H by F increases the strength of the tetrel bond, whether σ or π. The magnitudes of the maxima of the molecular electrostatic potential in the two types of systems are not good indicators of either the interaction energy or even the full Coulombic energy. The geometry of the Lewis acid is significantly distorted by the formation of the dimer, more so in the case of the σ-bonded complexes, and this deformation intensifies the σ and π holes. Full article

(This article belongs to the Special Issue Tetrel Bonds)

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11 pages, 3758 KiB

Open AccessArticle

Secondary Metabolites from the Root Rot Biocontrol Fungus Phlebiopsis gigantea

by David Kälvö, Audrius Menkis and Anders Broberg

Molecules 2018, 23(6), 1417; https://doi.org/10.3390/molecules23061417 - 12 Jun 2018

Cited by 20 | Viewed by 6377

Abstract

Three cyclopentanoids (phlebiopsin A–C), one glycosylated p-terphenyl (methyl-terfestatin A), and o-orsellinaldehyde were isolated from the biocontrol fungus Phlebiopsis gigantea, and their structures were elucidated by 1D and 2D NMR spectroscopic analysis, as well as by LC-HRMS. The biological activity of [...] Read more.

Three cyclopentanoids (phlebiopsin A–C), one glycosylated p-terphenyl (methyl-terfestatin A), and o-orsellinaldehyde were isolated from the biocontrol fungus Phlebiopsis gigantea, and their structures were elucidated by 1D and 2D NMR spectroscopic analysis, as well as by LC-HRMS. The biological activity of the compounds against the root rot fungus Heterobasidion occidentale, as well as against Fusarium oxysporum and Penicillium canescens, was also investigated, but only o-orsellinaldehyde was found to have any antifungal activity in the concentration range tested. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 970 KiB

Open AccessArticle

Plagiochiline A Inhibits Cytokinetic Abscission and Induces Cell Death

by Nicole S. Stivers, Ashraful Islam, Elsa M. Reyes-Reyes, Lavona K. Casson, José C. Aponte, Abraham J. Vaisberg, Gerald B. Hammond and Paula J. Bates

Molecules 2018, 23(6), 1418; https://doi.org/10.3390/molecules23061418 - 12 Jun 2018

Cited by 5 | Viewed by 4301

Abstract

We previously reported on the isolation and biological activities of plagiochiline A (1), a 2,3-secoaromadendrane-type sesquiterpenoid from the Peruvian medicinal plant, Plagiochila disticha. This compound was found to have antiproliferative effects on a variety of solid tumor cell lines, as [...] Read more.

We previously reported on the isolation and biological activities of plagiochiline A (1), a 2,3-secoaromadendrane-type sesquiterpenoid from the Peruvian medicinal plant, Plagiochila disticha. This compound was found to have antiproliferative effects on a variety of solid tumor cell lines, as well as several leukemia cell lines. Other researchers have also noted the cytotoxicity of plagiochiline A (isolated from different plant species), but there are no prior reports regarding the mechanism for this bioactivity. Here, we have evaluated the effects of plagiochiline A on cell cycle progression in DU145 prostate cancer cells. A cell cycle analysis indicated that plagiochiline A caused a significant increase in the percentage of cells in the G₂/M phase when compared with control cells. When cells were stained and observed by fluorescence microscopy to examine progress through the mitotic phase, we found a significant increase in the proportion of cells with features of late cytokinesis (cells connected by intercellular bridges) in the plagiochiline A-treated samples. These results suggest that plagiochiline A inhibits cell division by preventing completion of cytokinesis, particularly at the final abscission stage. We also determined that plagiochiline A reduces DU145 cell survival in clonogenic assays and that it induces substantial cell death in these cells. Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 3041 KiB

Open AccessArticle

Novel Thiazolidinone/Thiazolo[3,2-a]Benzimidazolone-Isatin Conjugates as Apoptotic Anti-proliferative Agents Towards Breast Cancer: One-Pot Synthesis and In Vitro Biological Evaluation

by Mohamed El-Naggar, Wagdy M. Eldehna, Hadia Almahli, Amr Elgez, Mohamed Fares, Mahmoud M. Elaasser and Hatem A. Abdel-Aziz

Molecules 2018, 23(6), 1420; https://doi.org/10.3390/molecules23061420 - 12 Jun 2018

Cited by 59 | Viewed by 5448

Abstract

In connection with our research program on the development of new isatin-based anticancer candidates, herein we report the synthesis of two novel series of thiazolidinone-isatin conjugates (4a–n) and thiazolo[3,2-a]benzimidazolone-isatin conjugates (7a–d), and in [...] Read more.

In connection with our research program on the development of new isatin-based anticancer candidates, herein we report the synthesis of two novel series of thiazolidinone-isatin conjugates (4a–n) and thiazolo[3,2-a]benzimidazolone-isatin conjugates (7a–d), and in vitro evaluation of their antiproliferative activity towards two breast cancer cell lines; triple negative MDA-MB-231, and MCF-7. Compounds 4m and 7b emerged as the most active congeners against MDA-MB-231 cells (IC₅₀ = 7.6 ± 0.5 and 13.2 ± 1.1 µM, respectively). Compounds 4m and 7b were able to provoke apoptosis in MDA-MB-231 cells, evidenced by the up-regulation of Bax and down-regulation of Bcl-2, besides boosting caspase-3 levels. Hybrid 4m induced a fourfold increase in the percentage of cells at Sub-G₁, with concurrent arrest in G₂-M phase by 2.5-folds. Furthermore, hybrid 4m resulted in a sixfold increase in the percentage of annexin V-FITC positive apoptotic MDA-MB-231 cells as compared with the control. Moreover, the cytotoxic activities of the active conjugates were assessed towards two nontumorigenic cell lines (breast MCF-10A and lung WI-38) where both conjugates 4m and 7b displayed mean tumor selectivity index: 9.6 and 13.9, respectively. Finally, several ADME descriptors were predicted for the active conjugates via a theoretical kinetic study. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 2365 KiB

Open AccessArticle

Synthesis of Both Enantiomers of Chiral Phenylalanine Derivatives Catalyzed by Cinchona Alkaloid Quaternary Ammonium Salts as Asymmetric Phase Transfer Catalysts

by Lei Jin, Shuai Zhao and Xin Chen

Molecules 2018, 23(6), 1421; https://doi.org/10.3390/molecules23061421 - 12 Jun 2018

Cited by 7 | Viewed by 6041

Abstract

A practical synthesis of both enantiomers of unnatural phenylalanine derivatives by using two pseudoenantiomeric phase transfer catalysts is described. Through asymmetric α-alkylation of glycine Schiff base with substituted benzyl bromides and 1-(bromomethyl)naphthalene under the catalysis of O-allyl-N-(9-anthracenmethyl) cinchoninium bromide ( [...] Read more.

A practical synthesis of both enantiomers of unnatural phenylalanine derivatives by using two pseudoenantiomeric phase transfer catalysts is described. Through asymmetric α-alkylation of glycine Schiff base with substituted benzyl bromides and 1-(bromomethyl)naphthalene under the catalysis of O-allyl-N-(9-anthracenmethyl) cinchoninium bromide (1f) and O-allyl-N-(9-anthracenylmethyl)cinchonidium bromide (1i), respectively, a series of both (R)- and (S)-enantiomers of unnatural α-amino acid derivatives were obtained in excellent yields and enantioselectivity. The synthetic method is simple and scalable, and the stereochemistry of the products is fully predictable and controlled: the cinchonine-type phase transfer catalyst 1f resulted in (R)-α-amino acid derivatives, and the cinchonidine-type phase transfer catalyst 1i afforded (S)-α-amino acid derivatives. Full article

(This article belongs to the Collection Recent Advances in Organocatalysis)

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15 pages, 3902 KiB

Open AccessArticle

(-)-Shikimic Acid as a Chiral Building Block for the Synthesis of New Cytotoxic 6-Aza-Analogues of Angucyclinones

by Natalia Quiñones, Santiago Hernández, Luis Espinoza Catalán, Joan Villena, Ivan Brito, Alan R. Cabrera, Cristian O. Salas and Mauricio A. Cuellar

Molecules 2018, 23(6), 1422; https://doi.org/10.3390/molecules23061422 - 12 Jun 2018

Cited by 6 | Viewed by 4642

Abstract

We describe the syntheses of nine new angucyclinone 6-aza-analogues, achieved through a hetero Diels-Alder reaction between the shikimic acid derivative-azadiene 13, with different naphthoquinones. The cytotoxic activity of the new synthesized compounds and five angucyclinones, previously reported, was evaluated in vitro against [...] Read more.

We describe the syntheses of nine new angucyclinone 6-aza-analogues, achieved through a hetero Diels-Alder reaction between the shikimic acid derivative-azadiene 13, with different naphthoquinones. The cytotoxic activity of the new synthesized compounds and five angucyclinones, previously reported, was evaluated in vitro against three cancer cell lines: PC-3 (prostate cancer), HT-29 (colon cancer), MCF-7 (breast cancer), and one non-tumoral cell line, human colon epithelial cells (CCD841 CoN). Our results showed that most 6-azadiene derivatives exhibited significant cytotoxic activities, which was demonstrated by their IC₅₀ values (less than 10 μM), especially for the most sensitive cells, PC-3 and HT-29. From a chemical point of view, depending on the protected group of ring A and the pattern of substitution on ring D, cytotoxicity elicited these compounds, in terms of their potency and selectivity. Therefore, according to these chemical features, the most promising agents for every cancer cell line were 7a, 17, and 19c for PC-3 cells; 7a, 17, and 20 for HT-29 cells, and 19a for MCF-7 cells. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 1356 KiB

Open AccessFeature PaperArticle

Natural Aromatic Compounds as Scaffolds to Develop Selective G-Quadruplex Ligands: From Previously Reported Berberine Derivatives to New Palmatine Analogues

by Marco Franceschin, Lorenzo Cianni, Massimo Pitorri, Emanuela Micheli, Stefano Cacchione, Claudio Frezza, Mauro Serafini, Ming-Hao Hu, Huafi Su, Zhishu Huang, Lianquan Gu and Armandodoriano Bianco

Molecules 2018, 23(6), 1423; https://doi.org/10.3390/molecules23061423 - 12 Jun 2018

Cited by 22 | Viewed by 6256

Abstract

In this paper, the selective interactions of synthetic derivatives of two natural compounds, berberine and palmatine, with DNA G-quadruplex structures were reported. In particular, the previous works on this subject concerning berberine were further presented and discussed, whereas the results concerning palmatine are [...] Read more.

In this paper, the selective interactions of synthetic derivatives of two natural compounds, berberine and palmatine, with DNA G-quadruplex structures were reported. In particular, the previous works on this subject concerning berberine were further presented and discussed, whereas the results concerning palmatine are presented here for the first time. In detail, these palmatine derivatives were developed by inserting seven different small peptide basic chains, giving several new compounds that have never been reported before. The preliminary studies of the interactions of these compounds with various G-quadruplex-forming sequences were carried out by means of various structural and biochemical techniques, which showed that the presence of suitable side chains is very useful for improving the interaction of the ligands with G-quadruplex structures. Thus, these new palmatine derivatives might act as potential anticancer drugs. Full article

(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products 2018)

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10 pages, 1901 KiB

Open AccessFeature PaperArticle

Direct Observation of Hydrangea Blue-Complex Composed of 3-O-Glucosyldelphinidin, Al³⁺ and 5-O-Acylquinic Acid by ESI-Mass Spectrometry

by Takaaki Ito, Kin-ichi Oyama and Kumi Yoshida

Molecules 2018, 23(6), 1424; https://doi.org/10.3390/molecules23061424 - 12 Jun 2018

Cited by 26 | Viewed by 6779

Abstract

The blue sepal color of hydrangea is due to a metal complex anthocyanin composed of 3-O-glucosyldelphinidin (1) and an aluminum ion with the co-pigments 5-O-caffeoylquinic acid (2) and/or 5-O-p-coumaroylquinic acid ( [...] Read more.

The blue sepal color of hydrangea is due to a metal complex anthocyanin composed of 3-O-glucosyldelphinidin (1) and an aluminum ion with the co-pigments 5-O-caffeoylquinic acid (2) and/or 5-O-p-coumaroylquinic acid (3). The three components, namely anthocyanin, Al³⁺ and 5-O-acylquinic acids, are essential for blue color development, but the complex is unstable and only exists in an aqueous solution. Furthermore, the complex did not give analyzable NMR spectra or crystals. Therefore, many trials to determine the detailed chemical structure of the hydrangea-blue complex have not been successful to date. Instead, via experiments mixing 1, Al³⁺ and 2 or 3 in a buffered solution at pH 4.0, we obtained the same blue solution derived from the sepals. However, the ratio was not stoichiometric but fluctuated. To determine the composition of the complex, we tried direct observation of the molecular ion of the complex using electrospray-ionization mass spectrometry. In a very low-concentration buffer solution (2.0 mM) at pH 4.0, we reproduced the hydrangea-blue color by mixing 1, 2 and Al³⁺ in ratios of 1:1:1, 1:2:1 and 1:3:1. All solution gave the same molecular ion peak at m/z = 843, indicating that the blue solution has a ratio of 1:1:1 for the complex. By using 3, the observed mass number was m/z = 827 and the ratio of 1, 3 and Al³⁺ was also 1:1:1. A mixture of 1, 3-O-caffeoylquinic acid (4) and Al³⁺ did not give any blue color but instead was purple, and the intensity of the molecular ion peak at m/z = 843 was very low. These results strongly indicate that the hydrangea blue-complex is composed of a ratio of 1:1:1 for 1, Al³⁺ and 2 or 3. 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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10 pages, 747 KiB

Open AccessArticle

UPLC-ESI-QTOF-MS²-Based Identification and Antioxidant Activity Assessment of Phenolic Compounds from Red Corn Cob (Zea mays L.)

by María Hernández, Janeth Ventura, Cecilia Castro, Víctor Boone, Romeo Rojas, Juan Ascacio-Valdés and Guillermo Martínez-Ávila

Molecules 2018, 23(6), 1425; https://doi.org/10.3390/molecules23061425 - 12 Jun 2018

Cited by 25 | Viewed by 6958

Abstract

In this study, the extraction of phenolic antioxidants from red corn cob was carried out using ultrasound-assisted extraction (UAE). The solid:liquid ratio and extraction time were evaluated when obtaining these bioactive compounds. The total phenolic contents were evaluated using the Folin Ciocalteu method, [...] Read more.

In this study, the extraction of phenolic antioxidants from red corn cob was carried out using ultrasound-assisted extraction (UAE). The solid:liquid ratio and extraction time were evaluated when obtaining these bioactive compounds. The total phenolic contents were evaluated using the Folin Ciocalteu method, while the antioxidant activity was measured by ABTS^•+ and DPPH^• assays. The amount of phenolic compounds ranged from 215.17 ± 33.49 to 527.33 ± 103.79 GAE mg/100 g and, overall, high solid:liquid ratios and time periods release more phenolic compounds. Moreover, the red corn cob extracts showed higher radical scavenging capacity according to the results obtained using the ABTS^•+ technique compared to the DPPH^• test. The coupling of liquid chromatography and mass spectrometry assay allowed the determination of 11 phenolic compounds, including phenolic acids and flavonoids. Thus, our results demonstrated for the first time the potential of red corn cob as a source of bioactive compounds, which might be included in food and pharmacological preparations. Full article

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

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13 pages, 1537 KiB

Open AccessArticle

Pubescenosides E–K, Seven New Triterpenoid Saponins from the Roots of Ilex pubescens and Their Anti-Inflammatory Activity

by Xiaoxu Qiao, Mengying Ji, Yunda Yao, Leilei Ma, Jinjun Wu, Guochao Liao, Hua Zhou, Zhongqiu Liu and Peng Wu

Molecules 2018, 23(6), 1426; https://doi.org/10.3390/molecules23061426 - 12 Jun 2018

Cited by 14 | Viewed by 3919

Abstract

Seven new triterpenoid saponins (1–7), together with three known ones (8–10), were isolated from Ilex pubescens. Elucidation of their structures was performed based on high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS), infrared spectra (IR), and [...] Read more.

Seven new triterpenoid saponins (1–7), together with three known ones (8–10), were isolated from Ilex pubescens. Elucidation of their structures was performed based on high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS), infrared spectra (IR), and nuclear magnetic resonance (NMR) spectroscopic data. The anti-inflammatory activity of the isolates toward lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages was investigated. The results demonstrated that compounds 3, 5, and 6 inhibited the expression of inducible nitric oxide synthase (iNOS) protein in comparison with LPS stimulation in RAW264.7 cells. Full article

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15 pages, 3507 KiB

Open AccessArticle

A General Aqueous Silanization Protocol to Introduce Vinyl, Mercapto or Azido Functionalities onto Cellulose Fibers and Nanocelluloses

by Marco Beaumont, Markus Bacher, Martina Opietnik, Wolfgang Gindl-Altmutter, Antje Potthast and Thomas Rosenau

Molecules 2018, 23(6), 1427; https://doi.org/10.3390/molecules23061427 - 12 Jun 2018

Cited by 61 | Viewed by 8113

Abstract

The effective and straight-forward modification of nanostructured celluloses under aqueous conditions or as “never-dried” materials is challenging. We report a silanization protocol in water using catalytic amounts of hydrogen chloride and then sodium hydroxide in a two-step protocol. The acidic step hydrolyzes the [...] Read more.

The effective and straight-forward modification of nanostructured celluloses under aqueous conditions or as “never-dried” materials is challenging. We report a silanization protocol in water using catalytic amounts of hydrogen chloride and then sodium hydroxide in a two-step protocol. The acidic step hydrolyzes the alkoxysilane to obtain water-soluble silanols and the subsequent addition of catalytic amounts of NaOH induces a covalent reaction between cellulose surficial hydroxyl groups and the respective silanols. The developed protocol enables the incorporation of vinyl, thiol, and azido groups onto cellulose fibers and cellulose nanofibrils. In contrast to conventional methods, no curing or solvent-exchange is necessary, thereby the functionalized celluloses remain never-dried, and no agglomeration or hornification occurs in the process. The successful modification was proven by solid state NMR, ATR-IR, and EDX spectroscopy. In addition, the covalent nature of this bonding was shown by gel permeation chromatography of polyethylene glycol grafted nanofibrils. By varying the amount of silane agents or the reaction time, the silane loading could be tuned up to an amount of 1.2 mmol/g. Multifunctional materials were obtained either by prior carboxymethylation and subsequent silanization; or by simultaneously incorporating both vinyl and azido groups. The protocol reported here is an easy, general, and straight-forward avenue for introduction of anchor groups onto the surface of never-dried celluloses, ready for click chemistry post-modification, to obtain multifunctional cellulose substrates for high-value applications. Full article

(This article belongs to the Special Issue The Future for Cellulose Nanomaterials)

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13 pages, 1965 KiB

Open AccessArticle

Innovative Natural Ingredients-Based Multiple Emulsions: The Effect on Human Skin Moisture, Sebum Content, Pore Size and Pigmentation

by Ugne Cizauskaite and Jurga Bernatoniene

Molecules 2018, 23(6), 1428; https://doi.org/10.3390/molecules23061428 - 12 Jun 2018

Cited by 18 | Viewed by 8890

Abstract

The increased interest in natural cosmetics has resulted in a higher market demand for preservative-free products based on herbal ingredients. An innovative W/O/W type emulsions containing herbal extracts were prepared directly; its cation form was induced by an ethanolic rosemary extract and stabilized [...] Read more.

The increased interest in natural cosmetics has resulted in a higher market demand for preservative-free products based on herbal ingredients. An innovative W/O/W type emulsions containing herbal extracts were prepared directly; its cation form was induced by an ethanolic rosemary extract and stabilized using weak herbal gels. Due to the wide phytochemical composition of herbal extracts and the presence of alcohol in the emulsion system, which can cause skin irritation, sensitization or dryness when applied topically, the safety of the investigated drug delivery system is necessary. The aim of our study was to estimate the potential of W/O/W emulsions based on natural ingredients for skin irritation and phototoxicity using reconstructed 3D epidermis models in vitro and to evaluate in vivo its effect on human skin moisture, sebum content and pigmentation by biomedical examination using a dermatoscopic camera and corneometer. According to the results obtained after in vitro cell viability test the investigated emulsion was neither irritant nor phototoxic to human skin keratinocytes. W/O/W emulsion did not cause skin dryness in vivo, despite the fact that it contained ethanol. We can conclude that the emulsion is safe for use as a leave-on product due to the positive effect on human skin characteristics or as a semisolid pharmaceutical base where active compounds could be encapsulated. Full article

(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)

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12 pages, 5949 KiB

Open AccessFeature PaperArticle

Preparation, Characterization and Biological Applications of Biosynthesized Silver Nanoparticles with Chitosan-Fucoidan Coating

by Jayachandran Venkatesan, Sandeep Kumar Singh, Sukumaran Anil, Se-Kwon Kim and Min Suk Shim

Molecules 2018, 23(6), 1429; https://doi.org/10.3390/molecules23061429 - 12 Jun 2018

Cited by 106 | Viewed by 10173

Abstract

Silver nanoparticles (AgNPs) are gaining a great deal of attention in biomedical applications due to their unique physicochemical properties. In this study, green synthesis of AgNPs was developed using seaweed polysaccharide fucoidan. The AgNPs were further coated with chitosan to form an electrolyte [...] Read more.

Silver nanoparticles (AgNPs) are gaining a great deal of attention in biomedical applications due to their unique physicochemical properties. In this study, green synthesis of AgNPs was developed using seaweed polysaccharide fucoidan. The AgNPs were further coated with chitosan to form an electrolyte complex on the surface. The developed chitosan–fucoidan complex-coated AgNPs were characterized using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM). FT-IR results suggested strong polyelectrolyte complexation between fucoidan and chitosan. The developed chitosan–fucoidan complex-coated AgNPs significantly inhibited microbial growth. Moreover, the AgNPs showed efficient anticancer activity in human cervical cancer cells (HeLa). This study demonstrated that chitosan–fucoidan complex-coated AgNPs hold high potential for food and cosmeceutical applications. Full article

(This article belongs to the Special Issue Chitin and Chitosan Derivatives: Biological Activities and Application)

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13 pages, 2664 KiB

Open AccessArticle

Hydroxyl Group and Vasorelaxant Effects of Perillyl Alcohol, Carveol, Limonene on Aorta Smooth Muscle of Rats

by Ana Carolina Cardoso-Teixeira, Francisco Walber Ferreira-da-Silva, Dieniffer Peixoto-Neves, Klausen Oliveira-Abreu, Átila Pereira-Gonçalves, Andrelina Noronha Coelho-de-Souza and José Henrique Leal-Cardoso

Molecules 2018, 23(6), 1430; https://doi.org/10.3390/molecules23061430 - 13 Jun 2018

Cited by 26 | Viewed by 4962

Abstract

The present study used isometric tension recording to investigate the vasorelaxant effect of limonene (LM), carveol (CV), and perillyl alcohol (POH) on contractility parameters of the rat aorta, focusing in particular on the structure-activity relationship. LM, CV, and POH showed a reversible inhibitory [...] Read more.

The present study used isometric tension recording to investigate the vasorelaxant effect of limonene (LM), carveol (CV), and perillyl alcohol (POH) on contractility parameters of the rat aorta, focusing in particular on the structure-activity relationship. LM, CV, and POH showed a reversible inhibitory effect on the contraction induced by electromechanical and pharmacomechanical coupling. In the case of LM, but not CV and POH, this effect was influenced by preservation of the endothelium. POH and CV but not LM exhibited greater pharmacological potency on BayK-8644-induced contraction and on electromechanical coupling than on pharmacomechanical coupling. In endothelium-denuded preparations, the order of pharmacological potency on electrochemical coupling was LM < CV < POH. These compounds inhibited also, with grossly similar pharmacological potency, the contraction induced by phorbol ester dibutyrate. The present results suggest that LM, CV and POH induced relaxant effect on vascular smooth muscle by means of different mechanisms likely to include inhibition of PKC and IP3 pathway. For CV and POH, hydroxylated compounds, it was in electromechanical coupling that the greater pharmacological potency was observed, thus suggesting a relative specificity for a mechanism likely to be important in electromechanical coupling, for example, blockade of voltage-dependent calcium channel. Full article

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16 pages, 4334 KiB

Open AccessArticle

Antischistosomal Properties of Hederacolchiside A1 Isolated from Pulsatilla chinensis

by Naixin Kang, Wenhua Shen, Hongwei Gao, Yulin Feng, Weifeng Zhu, Shilin Yang, Yanli Liu, Qiongming Xu and Di Yu

Molecules 2018, 23(6), 1431; https://doi.org/10.3390/molecules23061431 - 13 Jun 2018

Cited by 24 | Viewed by 4669

Abstract

Background: Schistosomiasis is a major neglected disease for which the current control strategy involves mass treatment with praziquantel, the only available drug. Hence, there is an urgent need to develop new antischistosomal compounds. Methods: The antischistosomal activity of hederacolchiside A1 (HSA) [...] Read more.

Background: Schistosomiasis is a major neglected disease for which the current control strategy involves mass treatment with praziquantel, the only available drug. Hence, there is an urgent need to develop new antischistosomal compounds. Methods: The antischistosomal activity of hederacolchiside A1 (HSA) were determined by total or female worm burden reductions in mice harboring Schistosoma japonicum or S. mansoni. Pathology parameters were detected on HSA against 1-day-old S. japonicum-harboring mice. Moreover, we confirmed the antischistosomal effect of HSA on newly transformed schistosomula (NTS) of S. japonicum in vitro. Results: HSA, a natural product isolated from Pulsatilla chinensis (Bunge) Regel, was initially corroborated to possess promising antischistosomal properties. We demonstrated that HSA had high activity against S. japonicum and S. mansoni less in 11 days old parasites harbored in mice. The antischistosomal effect was even more than the currently used drugs, praziquantel, and artesunate. Furthermore, HSA could ameliorate the pathology parameters in mice harboring 1-day-old juvenile S. japonicum. We also confirmed that HSA-mediated antischistosomal activity is partly due to the morphological changes in the tegument system when NTS are exposed to HSA. Conclusions: HSA may have great potential to be an antischistosomal agent for further research. Full article

(This article belongs to the Special Issue Drug Discovery for Neglected Diseases)

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10 pages, 1005 KiB

Open AccessFeature PaperArticle

Membrane Fatty Acid Composition and Cell Surface Hydrophobicity of Marine Hydrocarbonoclastic Alcanivorax borkumensis SK2 Grown on Diesel, Biodiesel and Rapeseed Oil as Carbon Sources

by Maria Konieczna, Martin Olzog, Daniela J. Naether, Łukasz Chrzanowski and Hermann J. Heipieper

Molecules 2018, 23(6), 1432; https://doi.org/10.3390/molecules23061432 - 13 Jun 2018

Cited by 14 | Viewed by 4887

Abstract

The marine hydrocarbonoclastic bacterium Alcanivorax borkumensis is well known for its ability to successfully degrade various mixtures of n-alkanes occurring in marine oil spills. For effective growth on these compounds, the bacteria possess the unique capability not only to incorporate but also [...] Read more.

The marine hydrocarbonoclastic bacterium Alcanivorax borkumensis is well known for its ability to successfully degrade various mixtures of n-alkanes occurring in marine oil spills. For effective growth on these compounds, the bacteria possess the unique capability not only to incorporate but also to modify fatty intermediates derived from the alkane degradation pathway. High efficiency of both these processes provides better competitiveness for a single bacteria species among hydrocarbon degraders. To examine the efficiency of A. borkumensis to cope with different sources of fatty acid intermediates, we studied the growth rates and membrane fatty acid patterns of this bacterium cultivated on diesel, biodiesel and rapeseed oil as carbon and energy source. Obtained results revealed significant differences in both parameters depending on growth substrate. Highest growth rates were observed with biodiesel, while growth rates on rapeseed oil and diesel were lower than on the standard reference compound (hexadecane). The most remarkable observation is that cells grown on rapeseed oil, biodiesel, and diesel showed significant amounts of the two polyunsaturated fatty acids linoleic acid and linolenic acid in their membrane. By direct incorporation of these external fatty acids, the bacteria save energy allowing them to degrade those pollutants in a more efficient way. Such fast adaptation may increase resilience of A. borkumensis and allow them to strive and maintain populations in more complex hydrocarbon degrading microbial communities. Full article

(This article belongs to the Special Issue The Multiple Roles of Fatty Acids)

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20 pages, 3586 KiB

Open AccessArticle

Application of a JA-Ile Biosynthesis Inhibitor to Methyl Jasmonate-Treated Strawberry Fruit Induces Upregulation of Specific MBW Complex-Related Genes and Accumulation of Proanthocyanidins

by Laura D. Delgado, Paz E. Zúñiga, Nicolás E. Figueroa, Edgar Pastene, Hugo F. Escobar-Sepúlveda, Pablo M. Figueroa, Adrián Garrido-Bigotes and Carlos R. Figueroa

Molecules 2018, 23(6), 1433; https://doi.org/10.3390/molecules23061433 - 13 Jun 2018

Cited by 43 | Viewed by 6918

Abstract

Fleshy fruits are an important source of anthocyanins and proanthocyanidins (PAs), which protect plants against stress, and their consumption provides beneficial effects for human health. In strawberry fruit, the application of exogenous methyl jasmonate (MeJA) upregulates anthocyanin accumulation, although the relationship between the [...] Read more.

Fleshy fruits are an important source of anthocyanins and proanthocyanidins (PAs), which protect plants against stress, and their consumption provides beneficial effects for human health. In strawberry fruit, the application of exogenous methyl jasmonate (MeJA) upregulates anthocyanin accumulation, although the relationship between the jasmonate pathway and anthocyanin and PA biosynthesis in fruits remains to be understood. Anthocyanin and PA accumulation is mainly regulated at the transcriptional level through R2R3-MYB and bHLH transcription factors in different plant species and organs. Here, the effect of jarin-1, a specific inhibitor of bioactive JA (jasmonoyl-isoleucine, JA-Ile) biosynthesis, on anthocyanin and PA accumulation was evaluated during strawberry (Fragaria × ananassa) fruit development using an in vitro ripening system for 48 h. Also, we observed the effects of MeJA and the application of jarin-1 to MeJA-treated fruits (MeJA + jarin-1 treatment). We assessed changes of expression levels for the JA-Ile and MeJA biosynthetic (FaJAR1.2 and FaJMT), JA signaling-related (FaMYC2 and FaJAZ1), MYB-bHLH-WD40 (MBW) complex-related (FabHLH3/33, FaMYB9/10/11, and repressor FaMYB1), and anthocyanin and PA biosynthetic (FaANS, FaUFGT, FaANR, and FaLAR) genes. In addition, the promoter region of MBW complex-related MYB genes was isolated and sequenced. We found a higher redness of strawberry fruit skin and anthocyanin content in MeJA-treated fruits with respect to jarin-1-treated ones concomitant with an upregulation of FaANS and FaUFGT genes. Inversely, the PA content was higher in jarin-1- and MeJA + jarin-1-treated than in MeJA-treated fruits. MeJA + jarin-1 treatment resulted in an upregulation of FaANR and associated transcription factors such as FabHLH33 and FaMYB9/11 along with FaJMT and FaJAR1.2. Finally, we found JA-responsive elements in the promoter regions of FaMYB1/9/10/11 genes. It is proposed that PA biosynthesis-related genes can be upregulated by the application of jarin-1 to MeJA-treated fruit, thus increasing PA accumulation in strawberry. Full article

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

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10 pages, 2332 KiB

Open AccessArticle

Correlation of FT-IR Fingerprint and α-Glucosidase Inhibitory Activity of Salak (Salacca zalacca) Fruit Extracts Utilizing Orthogonal Partial Least Square

by Mohammed S. M. Saleh, Mohammad Jamshed Siddiqui, Siti Zaiton Mat So’ad, Fatimah Opeyemi Roheem, Salima Saidi-Besbes and Alfi Khatib

Molecules 2018, 23(6), 1434; https://doi.org/10.3390/molecules23061434 - 13 Jun 2018

Cited by 22 | Viewed by 6621

Abstract

Salak fruit (Salacca zalacca), commonly known as snake fruit, is used indigenously as food and for medicinal applications in Southeast Asia. This study was conducted to evaluate the α-glucosidase inhibitory activity of salak fruit extracts in correlation to its Fourier transform [...] Read more.

Salak fruit (Salacca zalacca), commonly known as snake fruit, is used indigenously as food and for medicinal applications in Southeast Asia. This study was conducted to evaluate the α-glucosidase inhibitory activity of salak fruit extracts in correlation to its Fourier transform infrared spectroscopy (FT-IR) fingerprint, utilizing orthogonal partial least square. This calibration model was applied to develop a rapid analytical method tool for quality control of this fruit. A total of 36 extracts prepared with different solvent ratios of ethanol–water (100, 80, 60, 40.20, 0% v/v) and their α-glucosidase inhibitory activities determined. The FT-IR spectra of ethanol–water extracts measured in the region of 400 and 4000 cm⁻¹ at a resolution of 4 cm⁻¹. Multivariate analysis with a combination of orthogonal partial least-squares (OPLS) algorithm was used to correlate the bioactivity of the samples with the FT-IR spectral data. The OPLS biplot model identified several functional groups (C–H, C=O, C–N, N–H, C–O, and C=C) which actively induced α-glucosidase inhibitory activity. Full article

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

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24 pages, 6763 KiB

Open AccessArticle

Novel Uridine Glycoconjugates, Derivatives of 4-Aminophenyl 1-Thioglycosides, as Potential Antiviral Compounds

by Ewelina Krol, Gabriela Pastuch-Gawolek, Binay Chaubey, Gabriela Brzuska, Karol Erfurt and Boguslaw Szewczyk

Molecules 2018, 23(6), 1435; https://doi.org/10.3390/molecules23061435 - 13 Jun 2018

Cited by 3 | Viewed by 4539

Abstract

A novel series of uridine glycoconjugates, derivatives of 4-aminophenyl 1-thioglycosides, was designed and synthesized. All compounds were evaluated in vitro for their antiviral activity against hepatitis C virus (HCV) and classical swine fever virus (CSFV), two important human and animal viral pathogens for [...] Read more.

A novel series of uridine glycoconjugates, derivatives of 4-aminophenyl 1-thioglycosides, was designed and synthesized. All compounds were evaluated in vitro for their antiviral activity against hepatitis C virus (HCV) and classical swine fever virus (CSFV), two important human and animal viral pathogens for which new or improved therapeutic options are needed. The antiviral activity of all synthesized compounds was confirmed using pseudo-plaque reduction assays in which a significant arrest of CSFV and HCV growth was observed in the presence of these compounds. Two of the synthesized compounds, 9 and 12, displayed a significant inhibitory effect on HCV and CSFV propagation with IC₅₀ values of 4.9 and 13.5 µM for HCV and 4.2 and 4 µM for CSFV, respectively, with low cytotoxicity. Using various infection and replication models, we have shown that both compounds were able to significantly reduce viral genome replication by up to 90% with IC₅₀ values in the low micromolar range. A structure activity analysis of the synthesized compounds showed that the high antiviral activity was attributed to the hydrophobicity of glycoconjugates and the introduction of elements capable to coordinate metal ions into the spacer connecting the sugar and uridine moiety, which can be useful in the development of new antiviral compounds in the future. Full article

(This article belongs to the Collection Advances in Glycosciences)

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13 pages, 2239 KiB

Open AccessArticle

Synthesis and Evaluation of New Potential Benzo[a]phenoxazinium Photosensitizers for Anticancer Photodynamic Therapy

by Juan Zhang, Wellington Tavares de Sousa Júnior, Victor Carlos Mello da Silva, Mosar Correa Rodrigues, José Athayde Vasconcelos Morais, Jia-Li Song, Zhi-Qiang Cheng, João Paulo Figueiró Longo, Ricardo Bentes Azevedo, Cheng-Shi Jiang, Luís Alexandre Muehlmann and Hua Zhang

Molecules 2018, 23(6), 1436; https://doi.org/10.3390/molecules23061436 - 13 Jun 2018

Cited by 12 | Viewed by 5462

Abstract

The use of photodynamic therapy (PDT) and development of novel photosensitizers (PSs) for cancer treatment have received more and more attention nowadays. In the present work, five benzo[a]phenoxazinium derivatives have been prepared and evaluated for their in vitro anticancer photodynamic activity [...] Read more.

The use of photodynamic therapy (PDT) and development of novel photosensitizers (PSs) for cancer treatment have received more and more attention nowadays. In the present work, five benzo[a]phenoxazinium derivatives have been prepared and evaluated for their in vitro anticancer photodynamic activity for the first time. They are red light absorbers and show low fluorescence quantum yield. Of these compounds, PS4 exhibited a higher quantum yield for reactive oxygen species (ROS) generation. The assays with cells in vitro showed that PS1 and PS4 were not significantly toxic in the dark, but was robustly toxic against the murine breast adenocarcinoma cells 4T1 and normal murine fibroblast cells NIH-3T3 upon photoactivation. More interestingly, PS5 was particularly selective towards 4T1 cancer cells and nearly non-phototoxic to non-cancerous NIH-3T3 cells. The results described in this report suggest that these new benzo[a]phenoxazinium derivatives are potential candidates as PSs for anticancer PDT. Further investigation of benzo[a]phenoxaziniums for anticancer PDT is warranted. Full article

(This article belongs to the Special Issue Advances in Photodynamic Therapy 2018)

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8 pages, 3005 KiB

Open AccessArticle

Wetting Properties of Defective Graphene Oxide: A Molecular Simulation Study

by Ke Xu, Jicheng Zhang, Xiaoli Hao, Chunbo Zhang, Ning Wei and Chao Zhang

Molecules 2018, 23(6), 1439; https://doi.org/10.3390/molecules23061439 - 13 Jun 2018

Cited by 39 | Viewed by 7027

Abstract

In the present work, the wettability of defective graphene oxide (GO) film is studied by molecular dynamics simulations. A water droplet is deposited on the surface of a graphene oxide membrane, and the contact angle is measured by fitting the liquid–vapor interface. Although [...] Read more.

In the present work, the wettability of defective graphene oxide (GO) film is studied by molecular dynamics simulations. A water droplet is deposited on the surface of a graphene oxide membrane, and the contact angle is measured by fitting the liquid–vapor interface. Although pristine graphene has few hydrophobic properties with a contact angle of 95°, graphene oxide presents more hydrophilic properties, due to the stronger hydrogen bonds interactions at the interface. Moreover, the introduction of vacancy defects at the graphene oxide surface decreases the wettability of graphene oxide. We find that the contact angle of graphene oxide increases from 70° to 82°, with a defective concentration from 0% to 10%. Our results will help provide a new method for controlling the wetting properties of GO and its additional capabilities in device design for applications. Full article

(This article belongs to the Special Issue Graphene Nanocomposites)

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12 pages, 1216 KiB

Open AccessArticle

Practical Asymmetric Synthesis of Sitagliptin Phosphate Monohydrate

by Haoling Gao, Jiangang Yu, Chengsheng Ge and Qun Jiang

Molecules 2018, 23(6), 1440; https://doi.org/10.3390/molecules23061440 - 13 Jun 2018

Cited by 14 | Viewed by 8090

Abstract

Optically pure sitagliptin phosphate monohydrate is efficiently and practically synthesized through a chiral hemiacetal as the key intermediate in 54% overall yield starting from (E)-4-(2,4,5-trifluorophenyl)but-2-enal and N-boc-protected hydroxylamine. The chiral hemiacetal fragment is constructed by a tandem aza-Michael/hemiacetal reaction catalyzed [...] Read more.

Optically pure sitagliptin phosphate monohydrate is efficiently and practically synthesized through a chiral hemiacetal as the key intermediate in 54% overall yield starting from (E)-4-(2,4,5-trifluorophenyl)but-2-enal and N-boc-protected hydroxylamine. The chiral hemiacetal fragment is constructed by a tandem aza-Michael/hemiacetal reaction catalyzed by an organocatalyst and the influence of acidity of Brønsted acid on tandem aza-Michael/hemiacetal reaction is researched in detail. Full article

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15 pages, 3225 KiB

Open AccessArticle

Understanding the Molecule-Electrode Interface for Molecular Spintronic Devices: A Computational and Experimental Study

by Lidia Rosado Piquer, Raquel Royo Sánchez, E. Carolina Sañudo and Jorge Echeverría

Molecules 2018, 23(6), 1441; https://doi.org/10.3390/molecules23061441 - 13 Jun 2018

Cited by 7 | Viewed by 3775

Abstract

A triple-decker SYML-Dy2 single-molecule magnet (SMM) was synthetized and grafted onto the surface of iron oxide nanoparticles (IO-NPs) coated by an oleic acid monolayer. The magnetism of the SYML-Dy2 complex, and the hybrid system, NP-Dy2, were studied by a superconducting quantum interference device [...] Read more.

A triple-decker SYML-Dy2 single-molecule magnet (SMM) was synthetized and grafted onto the surface of iron oxide nanoparticles (IO-NPs) coated by an oleic acid monolayer. The magnetism of the SYML-Dy2 complex, and the hybrid system, NP-Dy2, were studied by a superconducting quantum interference device (SQUID). Density functional theory (DFT) calculations were carried out to study both the energetics of the interaction between SYML-Dy2 complex to the organic capping, and the assembly presented by the oleic acid chains. Full article

(This article belongs to the Special Issue Noncovalent Interactions: A Useful Tool for Crystal Design)

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16 pages, 3370 KiB

Open AccessArticle

Antifungal Activity of an Abundant Thaumatin-Like Protein from Banana against Penicillium expansum, and Its Possible Mechanisms of Action

by Wenxiao Jiao, Xiangxin Li, Handong Zhao, Jiankang Cao and Weibo Jiang

Molecules 2018, 23(6), 1442; https://doi.org/10.3390/molecules23061442 - 14 Jun 2018

Cited by 36 | Viewed by 5305

Abstract

Thaumatin-like protein from banana (designated BanTLP) has been purified by employing a simple protocol consisting of diethylaminoethyl Sephadex (DEAE–Sephadex) chromatography, gel filtration on Sephadex G50, and reversed-phase chromatography. The purified protein was identified by MALDI-TOF mass spectrometry, with an estimated molecular weight of [...] Read more.

Thaumatin-like protein from banana (designated BanTLP) has been purified by employing a simple protocol consisting of diethylaminoethyl Sephadex (DEAE–Sephadex) chromatography, gel filtration on Sephadex G50, and reversed-phase chromatography. The purified protein was identified by MALDI-TOF mass spectrometry, with an estimated molecular weight of 22.1 kDa. BanTLP effectively inhibited in vitro spore germination of Penicillium expansum, one of the main postharvest pathogens in fruits. This study further investigated the antifungal properties and underlying mechanisms of BanTLP against P. expansum. Results demonstrated that BanTLP exhibited antifungal activity in a wide pH range (4.0–10.0) at 20–50 °C. Propidium iodide (PI) influx and potassium release confirmed that BanTLP induced membrane disruption of the test pathogen, increasing the membrane permeability and disintegration of the cell. This led to cell death, as evidenced by the assays of thiobarbituric acid-reactive species (TBARS) content, the production of reactive oxygen species (ROS), and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence integrity. Ultrastructural alterations in P. expansum conidia after BanTLP treatment revealed severe damage to the cell wall. These results suggest that BanTLP purified from banana exerts antifungal activity against P. expansum by inducing plasma membrane disturbance and cell wall disorganization. Full article

(This article belongs to the Special Issue Antimicrobial Peptides and Peptidomimetics)

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14 pages, 2396 KiB

Open AccessArticle

Rapid Colorimetric Detection of Cartap Residues by AgNP Sensor with Magnetic Molecularly Imprinted Microspheres as Recognition Elements

by Mao Wu, Huiyun Deng, Yajun Fan, Yunchu Hu, Yaping Guo and Lianwu Xie

Molecules 2018, 23(6), 1443; https://doi.org/10.3390/molecules23061443 - 14 Jun 2018

Cited by 23 | Viewed by 5743

Abstract

The overuse of cartap in tea tree leads to hazardous residues threatening human health. A colorimetric determination was established to detect cartap residues in tea beverages by silver nanoparticles (AgNP) sensor with magnetic molecularly imprinted polymeric microspheres (Fe₃O₄@mSiO₂ [...] Read more.

The overuse of cartap in tea tree leads to hazardous residues threatening human health. A colorimetric determination was established to detect cartap residues in tea beverages by silver nanoparticles (AgNP) sensor with magnetic molecularly imprinted polymeric microspheres (Fe₃O₄@mSiO₂@MIPs) as recognition elements. Using Fe₃O₄ as supporting core, mesoporous SiO₂ as intermediate shell, methylacrylic acid as functional monomer, and cartap as template, Fe₃O₄@mSiO₂@MIPs were prepared to selectively and magnetically separate cartap from tea solution before colorimetric determination by AgNP sensors. The core-shell Fe₃O₄@mSiO₂@MIPs were also characterized by FT-IR, TEM, VSM, and experimental adsorption. The Fe₃O₄@mSiO₂@MIPs could be rapidly separated by an external magnet in 10 s with good reusability (maintained 95.2% through 10 cycles). The adsorption process of cartap on Fe₃O₄@mSiO₂@MIPs conformed to Langmuir adsorption isotherm with maximum adsorption capacity at 0.257 mmol/g and short equilibrium time of 30 min at 298 K. The AgNP colorimetric method semi-quantified cartap ≥5 mg/L by naked eye and quantified cartap 0.1–5 mg/L with LOD 0.01 mg/L by UV-vis spectroscopy. The AgNP colorimetric detection after pretreatment with Fe₃O₄@mSiO₂@MIPs could be successfully utilized to recognize and detect cartap residues in tea beverages. Full article

(This article belongs to the Special Issue Synthesis and Applications of Molecularly Imprinted Polymers)

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14 pages, 1457 KiB

Open AccessArticle

Pentacyclic Triterpenes from Cecropia telenitida Can Function as Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1

by Catalina Mosquera, Aram J. Panay and Guillermo Montoya

Molecules 2018, 23(6), 1444; https://doi.org/10.3390/molecules23061444 - 14 Jun 2018

Cited by 12 | Viewed by 6349

Abstract

Plant extracts from the genus Cecropia have been used by Latin-American traditional medicine to treat metabolic disorders and diabetes. Previous results have shown that roots of Cecropia telenitida contain pentacyclic triterpenes and these molecules display a hypoglycemic effect in an insulin-resistant murine model. [...] Read more.

Plant extracts from the genus Cecropia have been used by Latin-American traditional medicine to treat metabolic disorders and diabetes. Previous results have shown that roots of Cecropia telenitida contain pentacyclic triterpenes and these molecules display a hypoglycemic effect in an insulin-resistant murine model. The pharmacological target of these molecules, however, remains unknown. Several lines of evidence indicate that pentacyclic triterpenes inhibit the 11β-hydroxysteroid dehydrogenase type 1 enzyme, which highlights the potential use of this type of natural product as phytotherapeutic or botanical dietary supplements. The main goal of the study was the evaluation of the inhibitory effect of Cecropia telenitida molecules on 11β-hydroxysteroid dehydrogenase type 1 enzyme activity. A pre-fractionated chemical library was obtained from the roots of Cecropia telenitida using several automated chromatography separation steps and a homogeneous time resolved fluorescence assay was used for the bio-guided isolation of inhibiting molecules. The screening of a chemical library consisting of 125 chemical purified fractions obtained from Cecropia telenitida roots identified one fraction displaying 82% inhibition of the formation of cortisol by the 11β-hydroxysteroid dehydrogenase type 1 enzyme. Furthermore, a molecule displaying IC₅₀ of 0.95 ± 0.09 µM was isolated from this purified fraction and structurally characterized, which confirms that a pentacyclic triterpene scaffold was responsible for the observed inhibition. Our results support the hypothesis that pentacyclic triterpene molecules from Cecropia telenitida can inhibit 11β-hydroxysteroid dehydrogenase type 1 enzyme activity. These findings highlight the potential ethnopharmacological use of plants from the genus Cecropia for the treatment of metabolic disorders and diabetes. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 1470 KiB

Open AccessArticle

Alkaloids from Tetrastigma hemsleyanum and Their Anti-Inflammatory Effects on LPS-Induced RAW264.7 Cells

by Cai Yi Wang, Hyun-Jae Jang, Yoo Kyong Han, Xiang Dong Su, Seung Woong Lee, Mun-Chual Rho, Heng-Shan Wang, Seo Young Yang and Young Ho Kim

Molecules 2018, 23(6), 1445; https://doi.org/10.3390/molecules23061445 - 14 Jun 2018

Cited by 42 | Viewed by 5495

Abstract

Alkaloids 1–10 were isolated from the aerial parts of Tetrastigma hemsleyanum (APTH) and obtained from species of the genus Tetrastigma for the first time. The chemical structures of the isolated compounds were identified by NMR, UV, and MS analyses. Their anti-inflammatory [...] Read more.

Alkaloids 1–10 were isolated from the aerial parts of Tetrastigma hemsleyanum (APTH) and obtained from species of the genus Tetrastigma for the first time. The chemical structures of the isolated compounds were identified by NMR, UV, and MS analyses. Their anti-inflammatory activities were investigated by measuring nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Among all the isolates, compounds 6, 7 and 10 showed potent inhibitory activity against LPS-stimulated NO production in RAW264.7 cells (IC₅₀: 31.9, 25.2 and 6.3 μM, respectively). Furthermore, APTH and S-(−)-trolline (10) inhibited induction of inflammatory cytokines or mediators such as interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) via suppression of nuclear factor κB (NF-κB) translocation into the nucleus. In addition, 10 suppressed extracellular signal-regulated protein kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) phosphorylation in a dose-dependent manner. These results conclusively demonstrated that compound 10 displays anti-inflammatory activity via suppression of NF-κB activation and the ERK-MAPK signaling pathway in LPS-stimulated RAW264.7 cells. Full article

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

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8 pages, 1613 KiB

Open AccessArticle

Organic Fluorescent Compounds that Display Efficient Aggregation-Induced Emission Enhancement and Intramolecular Charge Transfer

by Ruibin Hou, Baohua Zhao, Yan Xia and Dongfeng Li

Molecules 2018, 23(6), 1446; https://doi.org/10.3390/molecules23061446 - 14 Jun 2018

Cited by 13 | Viewed by 4628

Abstract

A series of symmetric sulfone-linked organic fluorescent compounds (1a–c) was synthesized and characterized. V-shaped 1a–c were designed as aggregate of intramolecular charge transfer (ICT) and aggregation-induced emission enhancement (AIEE) processes. The 1a–c emitted intense blue [...] Read more.

A series of symmetric sulfone-linked organic fluorescent compounds (1a–c) was synthesized and characterized. V-shaped 1a–c were designed as aggregate of intramolecular charge transfer (ICT) and aggregation-induced emission enhancement (AIEE) processes. The 1a–c emitted intense blue violet lights in normal solvents. A large red shift of the emission wavelength and dramatic decrease of emission efficiency occurred with increasing solvent polarity. The 1a–c will function well as electron transport and blue light-emitting materials through theoretical calculations. Full article

(This article belongs to the Special Issue Organic Light Emitting Diodes II)

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13 pages, 2042 KiB

Open AccessArticle

4′-Methoxyresveratrol Alleviated AGE-Induced Inflammation via RAGE-Mediated NF-κB and NLRP3 Inflammasome Pathway

by Wenzhe Yu, Mengru Tao, Yueliang Zhao, Xiaoqian Hu and Mingfu Wang

Molecules 2018, 23(6), 1447; https://doi.org/10.3390/molecules23061447 - 14 Jun 2018

Cited by 80 | Viewed by 7137

Abstract

Advanced glycation end products (AGEs) could interact with the receptor for AGE (RAGE) as a sterile danger signal to induce inflammation. 4′-methoxyresveratrol (4′MR), a polyphenol derived from Dipterocarpaceae, has not been studied for its anti-inflammation effects. In the present study, we sought to [...] Read more.

Advanced glycation end products (AGEs) could interact with the receptor for AGE (RAGE) as a sterile danger signal to induce inflammation. 4′-methoxyresveratrol (4′MR), a polyphenol derived from Dipterocarpaceae, has not been studied for its anti-inflammation effects. In the present study, we sought to explore the protective role of 4′MR in AGEs-induced inflammatory model using RAW264.7 macrophages. 4′MR significantly inhibited gene expression of pro-inflammatory cytokines and chemokines, such as interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), as well as two typical pro-inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Besides, 4′MR significantly decreased oxidative stress, demonstrated by levels of ROS production, protein carbonyl and advanced oxidation protein product via down-regulation of NADPH oxidase. Further analysis showed that 4′MR attenuated the RAGE overexpression induced by MGO-BSA. It also blocked the downstream signal of AGE-RAGE, particularly, MAPKs including p38 and JNK, and subsequently reduced NF-κB activation. Additionally, 4′MR significantly abated the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome including NLRP3 and cleaved caspase-1 and reduced the secretion of mature IL-1β. Taken together, our results suggest that the anti-inflammatory effect of 4′MR is mainly through suppressing RAGE-mediated MAPK/NF-κB signaling pathway and NLRP3 inflammasome activation. 4′MR could be a novel therapeutic agent for inflammation-related diseases. Full article

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14 pages, 2172 KiB

Open AccessArticle

High-Throughput Identification of Mammalian Secreted Proteins Using Species-Specific Scheme and Application to Human Proteome

by Jian Zhang, Haiting Chai, Song Guo, Huaping Guo and Yanling Li

Molecules 2018, 23(6), 1448; https://doi.org/10.3390/molecules23061448 - 14 Jun 2018

Cited by 11 | Viewed by 3410

Abstract

Secreted proteins are widely spread in living organisms and cells. Since secreted proteins are easy to be detected in body fluids, urine, and saliva in clinical diagnosis, they play important roles in biomarkers for disease diagnosis and vaccine production. In this study, we [...] Read more.

Secreted proteins are widely spread in living organisms and cells. Since secreted proteins are easy to be detected in body fluids, urine, and saliva in clinical diagnosis, they play important roles in biomarkers for disease diagnosis and vaccine production. In this study, we propose a novel predictor for accurate high-throughput identification of mammalian secreted proteins that is based on sequence-derived features. We combine the features of amino acid composition, sequence motifs, and physicochemical properties to encode collected proteins. Detailed feature analyses prove the effectiveness of the considered features. Based on the differences across various species of secreted proteins, we introduce the species-specific scheme, which is expected to further explore the intrinsic attributes of specific secreted proteins. Experiments on benchmark datasets prove the effectiveness of our proposed method. The test on independent testing dataset also promises a good generalization capability. When compared with the traditional universal model, we experimentally demonstrate that the species-specific scheme is capable of significantly improving the prediction performance. We use our method to make predictions on unreviewed human proteome, and find 272 potential secreted proteins with probabilities that are higher than 99%. A user-friendly web server, named iMSPs (identification of Mammalian Secreted Proteins), which implements our proposed method, is designed and is available for free for academic use at: http://www.inforstation.com/webservers/iMSP/. Full article

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15 pages, 1677 KiB

Open AccessArticle

In-Syringe Micro Solid-Phase Extraction Method for the Separation and Preconcentration of Parabens in Environmental Water Samples

by Geaneth Pertunia Mashile, Anele Mpupa and Philiswa Nosizo Nomngongo

Molecules 2018, 23(6), 1450; https://doi.org/10.3390/molecules23061450 - 14 Jun 2018

Cited by 34 | Viewed by 5654

Abstract

In this study, a simple, rapid and effective in-syringe micro-solid phase extraction (MSPE) method was developed for the separation and preconcetration of parabens (methyl, ethyl, propyl and butyl paraben) in environmental water samples. The parabens were determined and quantified using high performance liquid [...] Read more.

In this study, a simple, rapid and effective in-syringe micro-solid phase extraction (MSPE) method was developed for the separation and preconcetration of parabens (methyl, ethyl, propyl and butyl paraben) in environmental water samples. The parabens were determined and quantified using high performance liquid chromatography and a photo diode array detector (HPLC-PDA). Chitosan-coated activated carbon (CAC) was used as the sorbent in the in-syringe MSPE device. A response surface methodology based on central composite design was used for the optimization of factors (eluent solvent type, eluent volume, number of elution cycles, sample volume, sample pH) affecting the extraction efficiency of the preconcentration procedure. The adsorbent used displayed excellent absorption performance and the adsorption capacity ranged from 227–256 mg g⁻¹. Under the optimal conditions the dynamic linear ranges for the parabens were between 0.04 and 380 µg L⁻¹. The limits of detection and quantification ranged from 6–15 ng L⁻¹ and 20–50 ng L⁻¹, respectively. The intraday (repeatability) and interday (reproducibility) precisions expressed as relative standard deviations (%RSD) were below 5%. Furthermore, the in-syringe MSPE/HPLC procedure was validated using spiked wastewater and tap water samples and the recoveries ranged between from 96.7 to 107%. In conclusion, CAC based in-syringe MSPE method demonstrated great potential for preconcentration of parabens in complex environmental water. Full article

(This article belongs to the Special Issue Solid Phase Extraction: State of the Art and Future Perspectives)

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11 pages, 2956 KiB

Open AccessArticle

Anticoagulant Activities of Indobufen, an Antiplatelet Drug

by Jia Liu, Dan Xu, Nian Xia, Kai Hou, Shijie Chen, Yu Wang and Yunman Li

Molecules 2018, 23(6), 1452; https://doi.org/10.3390/molecules23061452 - 15 Jun 2018

Cited by 32 | Viewed by 6584

Abstract

Indobufen is a new generation of anti-platelet aggregation drug, but studies were not sufficient on its anticoagulant effects. In the present study, the anticoagulant activity of indobufen was determined by monitoring the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time [...] Read more.

Indobufen is a new generation of anti-platelet aggregation drug, but studies were not sufficient on its anticoagulant effects. In the present study, the anticoagulant activity of indobufen was determined by monitoring the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) in rabbit plasma. We evaluated the anticoagulant mechanisms on the content of the platelet factor 3,4 (PF3,4), and the coagulation factor 1, 2, 5, 8, 10 (FI, II, V, VIII, X) in rabbits, as well as the in vivo bleeding time and clotting time in mice. The pharmacodynamic differences between indobufen and warfarin sodium, rivaroxaban, and dabigatran were further studied on thrombus formation and the content of FII and FX in rats. Animal experiments showed that intragastric-administrated indobufen can significantly reduce the APTT, PT, TT, PF3, FI, II, V, VIII, and X plasma contents. Its inhibitory effect on plasma FII was better than thrombin inhibitor dabigatran with effect on FX better than FXa inhibitor rivaroxaban. These results suggest that indobufen has some anticoagulant effects as strong as some conventional anticoagulants. The mechanism may be related to both exogenous and endogenous coagulation system. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 2612 KiB

Open AccessArticle

Anti-Mycobacterium tuberculosis Activity of Esters of Quinoxaline 1,4-Di-N-Oxide

by Isidro Palos, Julieta Luna-Herrera, Edgar E. Lara-Ramírez, Alejandra Loera-Piedra, Emanuel Fernández-Ramírez, Ma. Guadalupe Aguilera-Arreola, Alma D. Paz-González, Antonio Monge, Baojie Wan, Scott Franzblau and Gildardo Rivera

Molecules 2018, 23(6), 1453; https://doi.org/10.3390/molecules23061453 - 15 Jun 2018

Cited by 18 | Viewed by 4273

Abstract

Tuberculosis continues to be a public health problem in the world, and drug resistance has been a major obstacle in its treatment. Quinoxaline 1,4-di-N-oxide has been proposed as a scaffold to design new drugs to combat this disease. To examine the [...] Read more.

Tuberculosis continues to be a public health problem in the world, and drug resistance has been a major obstacle in its treatment. Quinoxaline 1,4-di-N-oxide has been proposed as a scaffold to design new drugs to combat this disease. To examine the efficacy of this compound, this study evaluates methyl, ethyl, isopropyl, and n-propyl esters of quinoxaline 1,4-di-N-oxide derivatives in vitro against Mycobacterium tuberculosis (pansusceptible and monoresistant strains). Additionally, the inhibitory effect of esters of quinoxaline 1,4-di-N-oxide on M. tuberculosis gyrase supercoiling was examined, and a stability analysis by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS) was also carried out. Results showed that eight compounds (T-007, T-018, T-011, T-069, T-070, T-072, T-085 and T-088) had an activity similar to that of the reference drug isoniazid (minimum inhibitory concentration (MIC) = 0.12 µg/mL) with an effect on nonreplicative cells and drug monoresistant strains. Structural activity relationship analysis showed that the steric effect of an ester group at 7-position is key to enhancing its biological effects. Additionally, T-069 showed a high stability after 24 h in human plasma at 37 °C. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 3396 KiB

Open AccessArticle

Phosphoproteomics of Retinoblastoma: A Pilot Study Identifies Aberrant Kinases

by Lakshmi Dhevi Nagarajha Selvan, Ravikanth Danda, Anil K. Madugundu, Vinuth N. Puttamallesh, Gajanan J. Sathe, Uma Maheswari Krishnan, Vikas Khetan, Pukhraj Rishi, Thottethodi Subrahmanya Keshava Prasad, Akhilesh Pandey, Subramanian Krishnakumar, Harsha Gowda and Sailaja V. Elchuri

Molecules 2018, 23(6), 1454; https://doi.org/10.3390/molecules23061454 - 15 Jun 2018

Cited by 11 | Viewed by 5973

Abstract

Retinoblastoma is a malignant tumour of the retina which most often occurs in children. Earlier studies on retinoblastoma have concentrated on the identification of key players in the disease and have not provided information on activated/inhibited signalling pathways. The dysregulation of protein phosphorylation [...] Read more.

Retinoblastoma is a malignant tumour of the retina which most often occurs in children. Earlier studies on retinoblastoma have concentrated on the identification of key players in the disease and have not provided information on activated/inhibited signalling pathways. The dysregulation of protein phosphorylation in cancer provides clues about the affected signalling cascades in cancer. Phosphoproteomics is an ideal tool for the study of phosphorylation changes in proteins. Hence, global phosphoproteomics of retinoblastoma (RB) was carried out to identify signalling events associated with this cancer. Over 350 proteins showed differential phosphorylation in RB compared to control retina. Our study identified stress response proteins to be hyperphosphorylated in RB which included H2A histone family member X (H2AFX) and sirtuin 1. In particular, Ser140 of H2AFX also known as gamma-H2AX was found to be hyperphosphorylated in retinoblastoma, which indicated the activation of DNA damage response pathways. We also observed the activation of anti-apoptosis in retinoblastoma compared to control. These observations showed the activation of survival pathways in retinoblastoma. The identification of hyperphosphorylated protein kinases including Bromodomain containing 4 (BRD4), Lysine deficient protein kinase 1 (WNK1), and Cyclin-dependent kinase 1 (CDK1) in RB opens new avenues for the treatment of RB. These kinases can be considered as probable therapeutic targets for RB, as small-molecule inhibitors for some of these kinases are already in clinical trials for the treatment other cancers. Full article

(This article belongs to the Special Issue CZE/LC-MS-based Proteomics)

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12 pages, 7440 KiB

Open AccessArticle

Synergistic Effects of Resveratrol and Pyrimethanil against Botrytis cinerea on Grape

by Dandan Xu, Ge Yu, Pinggen Xi, Xiangyu Kong, Qi Wang, Lingwang Gao and Zide Jiang

Molecules 2018, 23(6), 1455; https://doi.org/10.3390/molecules23061455 - 15 Jun 2018

Cited by 27 | Viewed by 5905

Abstract

Botrytis cinerea is the pathogen of gray mold disease affecting a wide range of plant hosts, with consequential economic losses worldwide. The increased frequency of fungicide resistance of the pathogen challenges its disease management, and thus the development of alternative control strategies are [...] Read more.

Botrytis cinerea is the pathogen of gray mold disease affecting a wide range of plant hosts, with consequential economic losses worldwide. The increased frequency of fungicide resistance of the pathogen challenges its disease management, and thus the development of alternative control strategies are urgently required. In this study, we showed excellent synergistic interactions between resveratrol and pyrimethanil. Significant synergistic values were recorded by the two-drug combination on the suppression of mycelial growth and conidia germination of B. cinerea. The combination of resveratrol and pyrimethanil caused malformation of mycelia. Moreover, the inoculation assay was conducted on table grape and consistent synergistic suppression of the two-drug combination was found in vivo. Our findings first revealed that the combination of resveratrol and pyrimethanil has synergistic effects against resistant B. cinerea and support the potential use of resveratrol as a promising adjuvant on the control of gray mold. Full article

(This article belongs to the Collection Phytoalexins: Fundamental Aspects and Applications)

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11 pages, 3044 KiB

Open AccessArticle

The Possible Reduction Mechanism of Volatile Sulfur Compounds during Durian Wine Fermentation Verified in Modified Buffers

by Yuyun Lu, Alicia Sarah Yoke Ling Fong, Jian-Yong Chua, Dejian Huang, Pin-Rou Lee and Shao-Quan Liu

Molecules 2018, 23(6), 1456; https://doi.org/10.3390/molecules23061456 - 15 Jun 2018

Cited by 11 | Viewed by 5993

Abstract

Durian fruit is rich in volatile sulfur compounds (VSCs), especially thiols and disulfides, which contribute to its onion-like odor. After fermentation, these VSCs were reduced to trace or undetectable levels in durian wine. The possible reduction mechanism of these VSCs (especially diethyl disulfide [...] Read more.

Durian fruit is rich in volatile sulfur compounds (VSCs), especially thiols and disulfides, which contribute to its onion-like odor. After fermentation, these VSCs were reduced to trace or undetectable levels in durian wine. The possible reduction mechanism of these VSCs (especially diethyl disulfide and ethanethiol) was investigated in a modified buffer in the presence of sulfite at different pH. An interconversion between diethyl disulfide and ethanethiol was found to be dependent on the pH: the higher the pH, the higher production of ethanethiol. It is suggested that, during durian wine fermentation, disulfides endogenous to durian pulp might be firstly converted into their corresponding thiols in the presence of reductant sulfite formed by yeast. The produced thiols as well as the thiols endogenous to the durian pulp were then removed by the mannoproteins of yeast lees. Full article

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22 pages, 1561 KiB

Open AccessArticle

Phosphorus Pentachloride Promoted gem-Dichlorination of 2′- and 3′-Deoxynucleosides

by Fabio Da Paixao Soares, Elisabetta Groaz and Piet Herdewijn

Molecules 2018, 23(6), 1457; https://doi.org/10.3390/molecules23061457 - 15 Jun 2018

Cited by 1 | Viewed by 5138

Abstract

Halogen substitution at various positions of canonical nucleosides has generated a number of bioactive structural variants. Herein, the synthesis of two unique series of sugar modified nucleosides bearing a gem-dichloro group is presented. The synthetic plan entails the controlled addition of phosphorus [...] Read more.

Halogen substitution at various positions of canonical nucleosides has generated a number of bioactive structural variants. Herein, the synthesis of two unique series of sugar modified nucleosides bearing a gem-dichloro group is presented. The synthetic plan entails the controlled addition of phosphorus pentachloride to suitably protected 2′- or 3′-ketodeoxynucleoside intermediates as the key step, facilitating the rapid construction of such functionalized molecules. Under the same reaction conditions, the highest chemoselectivity was observed for the formation of 2′,2′-dichloro-2′,3′-dideoxynucleosides, while a competing 2′,3′-elimination process occurred in the case of the 3′,3′-dichloro counterparts. Full article

(This article belongs to the Special Issue Bioactive Nucleosides and Nucleotides)

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15 pages, 2698 KiB

Open AccessArticle

Density Functional Theory Analysis of Deltamethrin and Its Determination in Strawberry by Surface Enhanced Raman Spectroscopy

by Tao Dong, Lei Lin, Yong He, Pengcheng Nie, Fangfang Qu and Shupei Xiao

Molecules 2018, 23(6), 1458; https://doi.org/10.3390/molecules23061458 - 15 Jun 2018

Cited by 33 | Viewed by 4958

Abstract

Deltamethrin is widely used in pest prevention and control such as red spiders, aphids, and grubs in strawberry. It is important to accurately monitor whether the deltamethrin residue in strawberry exceeds the standard. In this paper, density functional theory (DFT) was used to [...] Read more.

Deltamethrin is widely used in pest prevention and control such as red spiders, aphids, and grubs in strawberry. It is important to accurately monitor whether the deltamethrin residue in strawberry exceeds the standard. In this paper, density functional theory (DFT) was used to theoretically analyze the molecular structure of deltamethrin, gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) were used to enhance the surface enhanced Raman spectroscopy (SERS) detection signal. As a result, the theoretical Raman peaks of deltamethrin calculated by DFT were basically similar to the measured results, and the enhancing effects based on AuNPs was better than that of AgNPs. Moreover, 554, 736, 776, 964, 1000, 1166, 1206, 1593, 1613, and 1735 cm⁻¹ could be determined as deltamethrin characteristic peaks, among which only three Raman peaks (736, 1000, and 1166 cm⁻¹) could be used as the deltamethrin characteristic peaks in strawberry when the detection limit reached 0.1 mg/L. In addition, the 500–1800 cm⁻¹ SERS of deltamethrin were analyzed by the partial least squares (PLS) and backward interval partial least squares (BIPLS). The prediction accuracy of deltamethrin in strawberry (

R_{p}^{2}

= 0.93, RMSE_p = 4.66 mg/L, RPD = 3.59) was the highest when the original spectra were pretreated by multiplicative scatter correction (MSC) and then modeled by BIPLS. In conclusion, the deltamethrin in strawberry could be qualitatively analyzed and quantitatively determined by SERS based on AuNPs enhancement, which provides a new detection scheme for deltamethrin residue determination in strawberry. Full article

(This article belongs to the Section Analytical Chemistry)

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16 pages, 1315 KiB

Open AccessArticle

Pyridine-Ureas as Potential Anticancer Agents: Synthesis and In Vitro Biological Evaluation

by Mohamed El-Naggar, Hadia Almahli, Hany S. Ibrahim, Wagdy M. Eldehna and Hatem A. Abdel-Aziz

Molecules 2018, 23(6), 1459; https://doi.org/10.3390/molecules23061459 - 15 Jun 2018

Cited by 71 | Viewed by 7489

Abstract

In our endeavor towards the development of effective anticancer agents, a novel series of pyridine-ureas 8a–n were synthesized. All the newly prepared derivatives were evaluated in vitro for their growth inhibitory activity towards the proliferation of breast cancer MCF-7 cell line. [...] Read more.

In our endeavor towards the development of effective anticancer agents, a novel series of pyridine-ureas 8a–n were synthesized. All the newly prepared derivatives were evaluated in vitro for their growth inhibitory activity towards the proliferation of breast cancer MCF-7 cell line. Compounds 8e and 8n were found to be the most active congeners against MCF-7 cells (IC₅₀ = 0.22 and 1.88 µM after 48 h treatment; 0.11 and 0.80 µM after 72 h treatment, respectively) with increased activity compared to the reference drug doxorubicin (IC₅₀ = 1.93 µM). Moreover, eight selected pyridines 8b, 8d, 8e, 8i, 8j and 8l–n were evaluated for their in vitro anticancer activity according to the US-NCI protocol. Pyridines 8b and 8e proved to be the most effective anticancer agents in the NCI assay with mean inhibition = 43 and 49%, respectively. Both 8b and 8e exhibited anti-proliferative activity against all tested cancer cell lines from all subpanels growth inhibition (GI for 8b; 12–78%, GI for 8e; 15–91%). Pyridines 8b and 8e were screened in vitro for their inhibitory activity against VEGFR-2. Both compounds inhibited VEGFR-2 at micromolar IC₅₀ values 5.0 ± 1.91 and 3.93 ± 0.73 µM, respectively. The most active pyridines were filtered according to the Lipinski and Veber rules and all of them passed these filters. Finally, several ADME descriptors were predicted for the active pyridines through a theoretical kinetic study. Full article

(This article belongs to the Special Issue Recent Advances in Anticancer Drugs)

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10 pages, 800 KiB

Open AccessArticle

Detection of Protein Complexes Based on Penalized Matrix Decomposition in a Sparse Protein–Protein Interaction Network

by Buwen Cao, Shuguang Deng, Hua Qin, Pingjian Ding, Shaopeng Chen and Guanghui Li

Molecules 2018, 23(6), 1460; https://doi.org/10.3390/molecules23061460 - 15 Jun 2018

Cited by 12 | Viewed by 3985

Abstract

High-throughput technology has generated large-scale protein interaction data, which is crucial in our understanding of biological organisms. Many complex identification algorithms have been developed to determine protein complexes. However, these methods are only suitable for dense protein interaction networks, because their capabilities decrease [...] Read more.

High-throughput technology has generated large-scale protein interaction data, which is crucial in our understanding of biological organisms. Many complex identification algorithms have been developed to determine protein complexes. However, these methods are only suitable for dense protein interaction networks, because their capabilities decrease rapidly when applied to sparse protein–protein interaction (PPI) networks. In this study, based on penalized matrix decomposition (PMD), a novel method of penalized matrix decomposition for the identification of protein complexes (i.e., PMD_pc) was developed to detect protein complexes in the human protein interaction network. This method mainly consists of three steps. First, the adjacent matrix of the protein interaction network is normalized. Second, the normalized matrix is decomposed into three factor matrices. The PMD_pc method can detect protein complexes in sparse PPI networks by imposing appropriate constraints on factor matrices. Finally, the results of our method are compared with those of other methods in human PPI network. Experimental results show that our method can not only outperform classical algorithms, such as CFinder, ClusterONE, RRW, HC-PIN, and PCE-FR, but can also achieve an ideal overall performance in terms of a composite score consisting of F-measure, accuracy (ACC), and the maximum matching ratio (MMR). Full article

(This article belongs to the Special Issue Molecular Computing and Bioinformatics)

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18 pages, 1666 KiB

Open AccessArticle

16S rDNA Profiling to Reveal the Influence of Seed-Applied Biostimulants on the Rhizosphere of Young Maize Plants

by Giovanna Visioli, Anna Maria Sanangelantoni, Teofilo Vamerali, Cristian Dal Cortivo and Massimo Blandino

Molecules 2018, 23(6), 1461; https://doi.org/10.3390/molecules23061461 - 15 Jun 2018

Cited by 54 | Viewed by 6180

Abstract

In an open field trial on two agricultural soils in NW Italy, the impact of two seed-applied biostimulants on the rhizosphere bacterial community of young maize plants was evaluated. The 16S rDNA profiling was carried out on control and treated plant rhizosphere samples [...] Read more.

In an open field trial on two agricultural soils in NW Italy, the impact of two seed-applied biostimulants on the rhizosphere bacterial community of young maize plants was evaluated. The 16S rDNA profiling was carried out on control and treated plant rhizosphere samples collected at the 4-leaf stage and on bulk soil. In both soils, the rhizospheres were significantly enriched in Proteobacteria, Actinobacteria, and Bacteriodetes, while the abundances of Acidobacteria, Cloroflexi and Gemmatimonadetes decreased compared with bulk soil. Among the culturable bacteria genera that showed an increase by both biostimulants, most are known to be beneficial for nutrient uptake, such as Opitutus, Chryseolinea, Terrimonas, Rhodovastum, Cohnella, Pseudoduganella and the species Anaeromyxobacter dehalogenans; others are known to be involved in root growth, such as Niastella, Labrys, Chloroflexia and Thermomonas; or in plant defence, such as Ohtaekwangia, Quadrisphaera, Turneriella, and Actinoallomurus. Both biostimulants were also found to stimulate gen. Nannocystis, a potential biocompetitive agent against aflatoxigenic Aspergillus moulds. Under controlled conditions, both biostimulants enhanced the shoot and root biomass at the 4–5 leaf stage. We conclude that the biostimulants do not decrease the biodiversity of the microbial community rhizosphere of young maize plants, but stimulate rare bacterial taxa, some involved in plant growth and pathogen resistance, a result that may have implications in improving crop management. Full article

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16 pages, 6064 KiB

Open AccessArticle

Preparation and Characterization of α-Zinc Molybdate Catalyst: Efficient Sorbent for Methylene Blue and Reduction of 3-Nitrophenol

by Hicham Oudghiri-Hassani, Souad Rakass, Mostafa Abboudi, Ahmed Mohmoud and Fahd Al Wadaani

Molecules 2018, 23(6), 1462; https://doi.org/10.3390/molecules23061462 - 15 Jun 2018

Cited by 45 | Viewed by 6152

Abstract

Zinc molybdate (ZnMoO₄) was prepared by thermal decomposition of an oxalate complex under a controlled temperature of 500 °C. Analyses of the oxalate complex were carried out using Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). On the other hand, [...] Read more.

Zinc molybdate (ZnMoO₄) was prepared by thermal decomposition of an oxalate complex under a controlled temperature of 500 °C. Analyses of the oxalate complex were carried out using Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). On the other hand, analyses of the synthesized zinc molybdate were carried out by X-ray diffraction (XRD), transmission electron microscopy (TEM), and Brunauer-Emmett-Teller technique (BET). The efficiency of the synthesized catalyst was tested with the reduction reaction of 3-nitrophenol (3-NP), and was also applied as a sorbent for methylene blue dye (MB) in aqueous solutions. The catalytic test of zinc molybdate shows a very high activity. The concentration reduction progress and adsorption of the dye were followed by an ultraviolet-visible (UV-vis) spectrophotometer. Full article

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13 pages, 1643 KiB

Open AccessArticle

Preparation of Enzyme-Activated Thapsigargin Prodrugs by Solid-Phase Synthesis

by Tomas Zimmermann, Søren Brøgger Christensen and Henrik Franzyk

Molecules 2018, 23(6), 1463; https://doi.org/10.3390/molecules23061463 - 15 Jun 2018

Cited by 10 | Viewed by 5062

Abstract

Since cells in solid tumors divide less rapidly than cells in the bone marrow or cells of the immune system, mitotic inhibitors often cause severe side effects when used for treatment of diseases like prostate cancer and breast cancer. One approach to overcome [...] Read more.

Since cells in solid tumors divide less rapidly than cells in the bone marrow or cells of the immune system, mitotic inhibitors often cause severe side effects when used for treatment of diseases like prostate cancer and breast cancer. One approach to overcome this problem involves attempts at developing drugs based on general cytotoxins, like calicheamicin and thapsigargin, which kill cells at all phases of the cell cycle. However, such toxins can only be used when efficient targeting to the malignant tissue is possible. In the case of thapsigargin, selectivity for tumor-associated cells is achieved by conjugating the drug to a peptide that is only cleaved in the vicinity of tumors to release the cytotoxic drug or an analog with retained activity. Solid-phase synthesis protocols were developed for preparation of three already validated prodrugs of thapsigargin: one prodrug cleavable by human kallikrein 2, one prodrug cleavable by prostate-specific antigen, and one prodrug cleavable by prostate-specific membrane antigen. Full article

(This article belongs to the Special Issue Solid Phase Synthesis)

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12 pages, 1696 KiB

Open AccessArticle

The Effects of Thiamine on Breast Cancer Cells

by Xiaowen Liu, Sophia Montissol, Amy Uber, Sarah Ganley, Anne V. Grossestreuer, Katherine Berg, Stanley Heydrick and Michael W. Donnino

Molecules 2018, 23(6), 1464; https://doi.org/10.3390/molecules23061464 - 16 Jun 2018

Cited by 31 | Viewed by 9647

Abstract

(1) Background: Thiamine is an important cofactor for multiple metabolic processes. Its role in cancer has been debated for years. Our aim is to determine if thiamine can convert the cellular metabolic state of breast cancer cells from anaerobic to aerobic, thus reducing [...] Read more.

(1) Background: Thiamine is an important cofactor for multiple metabolic processes. Its role in cancer has been debated for years. Our aim is to determine if thiamine can convert the cellular metabolic state of breast cancer cells from anaerobic to aerobic, thus reducing their growth. (2) Methods: Breast cancer (MCF7) and non-tumorigenic (MCF10A) cell lines were treated with various doses of thiamine and assessed for changes in cell growth. The mechanism of this relationship was identified through the measurement of enzymatic activity and metabolic changes. (3) Results: A high dose of thiamine reduced cell proliferation in MCF7 (63% decrease, p < 0.0001), but didn’t affect apoptosis and the cell-cycle profile. Thiamine had a number of effects in MCF7; it (1) reduced extracellular lactate levels in growth media, (2) increased cellular pyruvate dehydrogenase (PDH) activities and the baseline and maximum cellular oxygen consumption rates, and (3) decreased non-glycolytic acidification, glycolysis, and glycolytic capacity. MCF10A cells preferred mitochondrial respiration instead of glycolysis. In contrast, MCF7 cells were more resistant to mitochondrial respiration, which may explain the inhibitory effect of thiamine on their proliferation. (4) Conclusions: The treatment of MCF7 breast cancer cells with 1 μg/mL and 2 μg/mL of thiamine for 24 h significantly reduced their proliferation. This reduction is associated with a reduction in glycolysis and activation of the PDH complex in breast cancer cells. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 1687 KiB

Open AccessArticle

Combining Albumin-Binding Properties and Interaction with Pemetrexed to Improve the Tissue Distribution of Radiofolates

by Cristina Müller, Patrycja Guzik, Klaudia Siwowska, Susan Cohrs, Raffaella M. Schmid and Roger Schibli

Molecules 2018, 23(6), 1465; https://doi.org/10.3390/molecules23061465 - 16 Jun 2018

Cited by 9 | Viewed by 3871

Abstract

Folic-acid-based radioconjugates have been developed for nuclear imaging of folate receptor (FR)-positive tumors; however, high renal uptake was unfavorable in view of a therapeutic application. Previously, it was shown that pre-injection of pemetrexed (PMX) increased the tumor-to-kidney ratio of radiofolates several-fold. In this [...] Read more.

Folic-acid-based radioconjugates have been developed for nuclear imaging of folate receptor (FR)-positive tumors; however, high renal uptake was unfavorable in view of a therapeutic application. Previously, it was shown that pre-injection of pemetrexed (PMX) increased the tumor-to-kidney ratio of radiofolates several-fold. In this study, PMX was combined with the currently best performing radiofolate ([¹⁷⁷Lu]cm13), which is outfitted with an albumin-binding entity. Biodistribution studies were carried out in mice bearing KB or IGROV-1 tumor xenografts, both FR-positive tumor types. SPECT/CT was performed with control mice injected with [¹⁷⁷Lu]folate only and with mice that received PMX in addition. Control mice showed high uptake of radioactivity in KB and IGROV-1 tumor xenografts, but retention in the kidneys was also high, resulting in tumor-to-kidney ratios of ~0.85 (4 h p.i.) and ~0.60 (24 h p.i.) or ~1.17 (4 h p.i.) and ~1.11 (24 h p.i.) respectively. Pre-injection of PMX improved the tumor-to-kidney ratio to values of ~1.13 (4 h p.i.) and ~0.92 (24 h p.i.) or ~1.79 (4 h p.i.) and ~1.59 (24 h p.i.), respectively, due to reduced uptake in the kidneys. It was found that a second injection of PMX—3 h or 7 h after administration of the radiofolate—improved the tumor-to-kidney ratio further to ~1.03 and ~0.99 or ~1.78 and ~1.62 at 24 h p.i. in KB and IGROV-1 tumor-bearing mice, respectively. SPECT/CT scans readily visualized the tumor xenografts, whereas accumulation of radioactivity in the kidneys was reduced in mice that received PMX. In this study, it was shown that PMX had a positive impact in terms of reducing the kidney uptake of albumin-binding radiofolates; hence, the administration of PMX resulted in ~1.3–1.7-fold higher tumor-to-kidney ratios. This is, however, a rather moderate effect in comparison to the previously shown effect of PMX on conventional radiofolates (without albumin binder), which led to 5–6-fold increased tumor-to-kidney ratios. An explanation for this result may be the different pharmacokinetic profiles of PMX and long-circulating radiofolates, respectively. Despite the promising potential of this concept, it is believed that a clinical translation would be challenging, particularly when PMX had to be injected more than once. Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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17 pages, 4437 KiB

Open AccessArticle

Cobalt(II) Complexes with N,N,N-Scorpionates and Bidentate Ligands: Comparison of Hydrotris(3,5-dimethylpyrazol-1-yl)borate Tp* vs. Phenyltris(4,4-dimethyloxazolin-2-yl)borate To^M to Control the Structural Properties and Reactivities of Cobalt Centers

by Toshiki Nishiura, Takahiro Uramoto, Yuichiro Takiyama, Jun Nakazawa and Shiro Hikichi

Molecules 2018, 23(6), 1466; https://doi.org/10.3390/molecules23061466 - 16 Jun 2018

Cited by 7 | Viewed by 5450

Abstract

Scorpionate ligands Tp* (hydrotris(3,5-dimethylpyrazol-1-yl)borate) and To^M (tris(4,4-dimethyloxazolin-2-yl)phenylborate) complexes of cobalt(II) with bidentate ligands were synthesized. Both Tp* and To^M coordinate to cobalt(II) in a tridentate fashion when the bidentate ligand is the less hindered acetylacetonate. In crystal structures, the geometry of [...] Read more.

Scorpionate ligands Tp* (hydrotris(3,5-dimethylpyrazol-1-yl)borate) and To^M (tris(4,4-dimethyloxazolin-2-yl)phenylborate) complexes of cobalt(II) with bidentate ligands were synthesized. Both Tp* and To^M coordinate to cobalt(II) in a tridentate fashion when the bidentate ligand is the less hindered acetylacetonate. In crystal structures, the geometry of cobalt(II) supported by the N₃O₂ donor set in the Tp* complex is a square-pyramid, whereas that in the To^M complex is close to a trigonal-bipyramid. Both Tp*- and To^M-acac complexes exhibit solvatochromic behavior, although the changing structural equilibria of these complexes in MeCN are quite different. In the bis(1-methylimidazol-2-yl)methylphenylborate (L^Ph) complexes, Tp* retains the tridentate (к³) mode, whereas To^M functions as the bidentate (к²) ligand, giving the tetrahedral cobalt(II) complex. The bowl-shaped cavity derived from the six methyl groups on To^M lead to susceptibility to the bulkiness of the opposite bidentate ligand. The entitled scorpionate compounds mediate hydrocarbon oxidation with organic peroxides. Allylic oxidation of cyclohexene occurs mainly on the reaction with tert-butyl hydroperoxide (TBHP), although the catalytic efficiency of the scorpionate ligand complexes is lower than that of Co(OAc)₂ and Co(acac)₂. On cyclohexane oxidation with meta-chloroperbenzoic acid (mCPBA), both To^M and Tp* complexes function as catalysts for hydroxylation. The higher electron-donating To^M complexes show faster initial reaction rates compared to the corresponding Tp* complexes. Full article

(This article belongs to the Special Issue Scorpionate Ligands: Ever-Young Chemistry Tools)

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20 pages, 4388 KiB

Open AccessArticle

Identification and Characterization of Flavonoid Biosynthetic Enzyme Genes in Salvia miltiorrhiza (Lamiaceae)

by Yuxing Deng, Caili Li, Heqin Li and Shanfa Lu

Molecules 2018, 23(6), 1467; https://doi.org/10.3390/molecules23061467 - 16 Jun 2018

Cited by 76 | Viewed by 9057

Abstract

Flavonoids are a class of important secondary metabolites with a broad spectrum of pharmacological functions. Salvia miltiorrhiza Bunge (Danshen) is a well-known traditional Chinese medicinal herb with a broad diversity of flavonoids. However, flavonoid biosynthetic enzyme genes have not been systematically and comprehensively [...] Read more.

Flavonoids are a class of important secondary metabolites with a broad spectrum of pharmacological functions. Salvia miltiorrhiza Bunge (Danshen) is a well-known traditional Chinese medicinal herb with a broad diversity of flavonoids. However, flavonoid biosynthetic enzyme genes have not been systematically and comprehensively analyzed in S. miltiorrhiza. Through genome-wide prediction and molecular cloning, twenty six flavonoid biosynthesis-related gene candidates were identified, of which twenty are novel. They belong to nine families potentially encoding chalcone synthase (CHS), chalcone isomerase (CHI), flavone synthase (FNS), flavanone 3-hydroxylase (F3H), flavonoid 3′-hydroxylase (F3′H), flavonoid 3′,5′-hydroxylase (F3′5′H), flavonol synthase (FLS), dihydroflavonol 4-reductase (DFR), and anthocyanidin synthase (ANS), respectively. Analysis of intron/exon structures, features of deduced proteins and phylogenetic relationships revealed the conservation and divergence of S. miltiorrhiza flavonoid biosynthesis-related proteins and their homologs from other plant species. These genes showed tissue-specific expression patterns and differentially responded to MeJA treatment. Through comprehensive and systematic analysis, fourteen genes most likely to encode flavonoid biosynthetic enzymes were identified. The results provide valuable information for understanding the biosynthetic pathway of flavonoids in medicinal plants. Full article

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18 pages, 2167 KiB

Open AccessArticle

Determination of the Phenolic Profile and Antioxidant Properties of Salvia viridis L. Shoots: A Comparison of Aqueous and Hydroethanolic Extracts

by Izabela Grzegorczyk-Karolak and Anna K. Kiss

Molecules 2018, 23(6), 1468; https://doi.org/10.3390/molecules23061468 - 17 Jun 2018

Cited by 56 | Viewed by 7133

Abstract

Salvia viridis L. is an annual herb used in Mediterranean medicine. The purpose of this study was to determine the polyphenol profile of aqueous (decoction and infusion) and hydroethanolic extracts of aerial parts of field-grown S.viridis and to evaluate their antioxidant activity. [...] Read more.

Salvia viridis L. is an annual herb used in Mediterranean medicine. The purpose of this study was to determine the polyphenol profile of aqueous (decoction and infusion) and hydroethanolic extracts of aerial parts of field-grown S.viridis and to evaluate their antioxidant activity. The polyphenol profiling was performed via UPLC-DAD/ESI-MS. Additionally, the total polyphenol content in extracts tested were determined by UV-Vis spectrophotometry using the Folin-Ciocalteu assay. The antioxidant effect was evaluated by the FRAP, DPPH, ABTS, O₂^•− scavenging and TBARS methods. The hydroethanolic extract gave the highest content of total phenolic compounds, followed by the infusion. The UPLC-DAD/ESI-MS analysis of extracts showed a total of 19 phenolic compounds identified as flavonoids (four compounds), phenylethanoids (eight compounds) and phenolic acids (seven compounds). Rosmarinic acid was the predominant phenolic acid, verbascoside was the predominant phenylethanoid, while apigenin glucuronide or methylluteolin glucuronide, depending on the sample, were the predominant flavonoids in the analyzed extracts. The presence of a high polyphenol level indicated a high antioxidant activity of both the infusion and the hydroalcoholic extract. These results indicate that S. viridis is a rich resource of phenolic compounds and can be used in dietary applications with the potential to reduce oxidative stress. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 3001 KiB

Open AccessArticle

Anti-Proliferation Effect of Theasaponin E₁ on the ALDH-Positive Ovarian Cancer Stem-Like Cells

by Ling-Yan Jia, Hui-Long Xia, Zhi-Da Chen, Casey Compton, Heather Bucur, Devendra A. Sawant, Gary O. Rankin, Bo Li, You-Ying Tu and Yi Charlie Chen

Molecules 2018, 23(6), 1469; https://doi.org/10.3390/molecules23061469 - 17 Jun 2018

Cited by 7 | Viewed by 5303

Abstract

Ovarian cancer has the highest mortality rate of all gynecological malignancies and the five-year death rate of patients has remained high in the past five decades. Recently, with the rise of cancer stem cells (CSCs) theory, an increasing amount of research has suggested [...] Read more.

Ovarian cancer has the highest mortality rate of all gynecological malignancies and the five-year death rate of patients has remained high in the past five decades. Recently, with the rise of cancer stem cells (CSCs) theory, an increasing amount of research has suggested that CSCs give rise to tumor recurrence and metastasis. Theasaponin E₁ (TSE₁), which was isolated from green tea (Camellia sinensis) seeds, has been proposed to be an effective compound for tumor treatment. However, studies on whether TSE₁ takes effect through CSCs have rarely been reported. In this paper, ALDH-positive (ALDH+) ovarian cancer stem-like cells from two platinum-resistant ovarian cancer cell lines A2780/CP70 and OVCAR-3 were used to study the anti-proliferation effect of TSE₁ on CSCs. The ALDH+ cells showed significantly stronger sphere forming vitality and stronger cell migration capability. In addition, the stemness marker proteins CD44, Oct-4, Nanog, as well as Bcl-2 and MMP-9 expression levels of ALDH+ cells were upregulated compared with the original tumor cells, indicating that they have certain stem cell characteristics. At the same time, the results showed that TSE₁ could inhibit cell proliferation and suspension sphere formation in ALDH+ cells. Our data suggests that TSE₁ as a natural compound has the potential to reduce human ovarian cancer mortality. However, more research is still needed to find out the molecular mechanism of TSE₁-mediated inhibition of ALDH+ cells and possible drug applications on the disease. Full article

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12 pages, 2169 KiB

Open AccessArticle

Modulation of Rat Hepatic CYP1A and 2C Activity by Honokiol and Magnolol: Differential Effects on Phenacetin and Diclofenac Pharmacokinetics In Vivo

by Sang-Bum Kim, Kyu-Sang Kim, Heon-Min Ryu, Seong-Ho Hong, Bo-Kyoung Kim, Dae-Duk Kim, Jin Woo Park and In-Soo Yoon

Molecules 2018, 23(6), 1470; https://doi.org/10.3390/molecules23061470 - 17 Jun 2018

Cited by 11 | Viewed by 5491

Abstract

Honokiol (2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol) and magnolol (4-Allyl-2-(5-allyl-2-hydroxy-phenyl)phenol) are the major active polyphenol constituents of Magnolia officinalis (Magnoliaceae) bark, which has been widely used in traditional Chinese medicine (Houpu Tang) for the treatment of various diseases, including anxiety, stress, gastrointestinal disorders, infection, and asthma. The aim [...] Read more.

Honokiol (2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol) and magnolol (4-Allyl-2-(5-allyl-2-hydroxy-phenyl)phenol) are the major active polyphenol constituents of Magnolia officinalis (Magnoliaceae) bark, which has been widely used in traditional Chinese medicine (Houpu Tang) for the treatment of various diseases, including anxiety, stress, gastrointestinal disorders, infection, and asthma. The aim of this study was to investigate the direct effects of honokiol and magnolol on hepatic CYP1A and 2C-mediated metabolism in vitro using rat liver microsomes and in vivo using the Sprague-Dawley rat model. Honokiol and magnolol inhibited in vitro CYP1A activity (probe substrate: phenacetin) more potently than CYP2C activity (probe substrate: diclofenac): The mean IC₅₀ values of honokiol for the metabolism of phenacetin and diclofenac were 8.59 μM and 44.7 μM, while those of magnolol were 19.0 μM and 47.3 μM, respectively. Notably, the systemic exposure (AUC and C_max) of phenacetin, but not of diclofenac, was markedly enhanced by the concurrent administration of intravenous honokiol or magnolol. The differential effects of the two phytochemicals on phenacetin and diclofenac in vivo pharmacokinetics could at least be partly attributed to their lower IC₅₀ values for the inhibition of phenacetin metabolism than for diclofenac metabolism. In addition, the systemic exposure, CL, and V_ss of honokiol and magnolol tended to be similar between the rat groups receiving phenacetin and diclofenac. These findings improve our understanding of CYP-mediated drug interactions with M. officinalis and its active constituents. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 2556 KiB

Open AccessFeature PaperArticle

Poly(alkylidenimine) Dendrimers Functionalized with the Organometallic Moiety [Ru(η⁵-C₅H₅)(PPh₃)₂]⁺ as Promising Drugs Against Cisplatin-Resistant Cancer Cells and Human Mesenchymal Stem Cells

by Marisol Gouveia, João Figueira, Manuel G. Jardim, Rita Castro, Helena Tomás, Kari Rissanen and João Rodrigues

Molecules 2018, 23(6), 1471; https://doi.org/10.3390/molecules23061471 - 17 Jun 2018

Cited by 35 | Viewed by 6521

Abstract

Here and for the first time, we show that the organometallic compound [Ru(η⁵-C₅H₅)(PPh₃)₂Cl] (RuCp) has potential to be used as a metallodrug in anticancer therapy, and further present a new approach for the [...] Read more.

Here and for the first time, we show that the organometallic compound [Ru(η⁵-C₅H₅)(PPh₃)₂Cl] (RuCp) has potential to be used as a metallodrug in anticancer therapy, and further present a new approach for the cellular delivery of the [Ru(η⁵-C₅H₅)(PPh₃)₂]⁺ fragment via coordination on the periphery of low-generation poly(alkylidenimine) dendrimers through nitrile terminal groups. Importantly, both the RuCp and the dendrimers functionalized with [Ru(η⁵-C₅H₅)(PPh₃)₂]⁺ fragments present remarkable toxicity towards a wide set of cancer cells (Caco-2, MCF-7, CAL-72, and A2780 cells), including cisplatin-resistant human ovarian carcinoma cell lines (A2780cisR cells). Also, RuCp and the prepared metallodendrimers are active against human mesenchymal stem cells (hMSCs), which are often found in the tumor microenvironment where they seem to play a role in tumor progression and drug resistance. 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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12 pages, 2005 KiB

Open AccessArticle

Identification of a 3-Alkylpyridinium Compound from the Red Sea Sponge Amphimedon chloros with In Vitro Inhibitory Activity against the West Nile Virus NS3 Protease

by Aubrie O’Rourke, Stephan Kremb, Brendan M. Duggan, Salim Sioud, Najeh Kharbatia, Misjudeen Raji, Abdul-Hamid Emwas, William H. Gerwick and Christian R. Voolstra

Molecules 2018, 23(6), 1472; https://doi.org/10.3390/molecules23061472 - 18 Jun 2018

Cited by 17 | Viewed by 5548

Abstract

Viruses are underrepresented as targets in pharmacological screening efforts, given the difficulties of devising suitable cell-based and biochemical assays. In this study we found that a pre-fractionated organic extract of the Red Sea sponge Amphimedon chloros was able to inhibit the West Nile [...] Read more.

Viruses are underrepresented as targets in pharmacological screening efforts, given the difficulties of devising suitable cell-based and biochemical assays. In this study we found that a pre-fractionated organic extract of the Red Sea sponge Amphimedon chloros was able to inhibit the West Nile Virus NS3 protease (WNV NS3). Using liquid chromatography–mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy, the identity of the bioactive compound was determined as a 3-alkylpyridinium with m/z = 190.16. Diffusion Ordered Spectroscopy (DOSY) NMR and NMR relaxation rate analysis suggest that the bioactive compound forms oligomers of up to 35 kDa. We observed that at 9.4 μg/mL there was up to 40–70% inhibitory activity on WNV NS3 protease in orthogonal biochemical assays for solid phase extracts (SPE) of A. chloros. However, the LC-MS purified fragment was effective at inhibiting the protease up to 95% at an approximate amount of 2 µg/mL with negligible cytotoxicity to HeLa cells based on a High-Content Screening (HCS) cytological profiling strategy. To date, 3-alkylpyridinium type natural products have not been reported to show antiviral activity since the first characterization of halitoxin, or 3-alkylpyridinium, in 1978. This study provides the first account of a 3-alkylpyridinium complex that exhibits a proposed antiviral activity by inhibiting the NS3 protease. We suggest that the here-described compound can be further modified to increase its stability and tested in a cell-based assay to explore its full potential as a potential novel antiviral capable of inhibiting WNV replication. Full article

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

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11 pages, 1777 KiB

Open AccessArticle

Synthesis, Insecticidal, Fungicidal Activities and Structure–Activity Relationships of Tschimganin Analogs

by Yueting Zhou, Chunjuan Wang, Fang Xin, Xiaoqiang Han, Jie Zhang and Ke Sun

Molecules 2018, 23(6), 1473; https://doi.org/10.3390/molecules23061473 - 18 Jun 2018

Cited by 9 | Viewed by 5994

Abstract

For the first time, a novel series of tschimganin analogs were designed, synthesized, and evaluated for their insecticidal and fungicidal activities. Their structures were characterized by ¹H-NMR, ¹³C-NMR and HRMS. Some of these compounds displayed excellent insecticidal and fungicidal activities, suggesting [...] Read more.

For the first time, a novel series of tschimganin analogs were designed, synthesized, and evaluated for their insecticidal and fungicidal activities. Their structures were characterized by ¹H-NMR, ¹³C-NMR and HRMS. Some of these compounds displayed excellent insecticidal and fungicidal activities, suggesting that they have potential to be used as bifunctional agrochemicals. Compound 3d and 3g with electron donating groups showed better inhibitory activity and growth inhibition activity towards Helicoverpa armigera (Hübner). The properties and positions of the substituents on the benzene ring have an important influence on the acaricidal activity of tschimganin analogs. Topomer comparative molecular field analysis (CoMFA) was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds against Tetranychus turkestani Ugarov et Nikolski. It was indicated that higher electronegativity was beneficial for acaricidal activity. Moreover, compound 3r having a 2-hydroxy-3,5- dinitrophenyl moiety displayed a fungicidal spectrum as broad as azoxystrobin against these phytopathogens. Full article

(This article belongs to the Section Medicinal Chemistry)

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17 pages, 3499 KiB

Open AccessArticle

Vasodilator Activity of Compounds Isolated from Plants Used in Mexican Traditional Medicine

by Francisco J. Luna-Vázquez, César Ibarra-Alvarado, María Del Rayo Camacho-Corona, Alejandra Rojas-Molina, J. Isela Rojas-Molina, Abraham García and Moustapha Bah

Molecules 2018, 23(6), 1474; https://doi.org/10.3390/molecules23061474 - 18 Jun 2018

Cited by 23 | Viewed by 7166

Abstract

Arterial hypertension is one of the main risk factors in the development of cardiovascular diseases. Therefore, it is important to look for new drugs to treat hypertension. In this study, we carried out the screening of 19 compounds (triterpenes, diterpenes, sesquiterpenes, lignans, and [...] Read more.

Arterial hypertension is one of the main risk factors in the development of cardiovascular diseases. Therefore, it is important to look for new drugs to treat hypertension. In this study, we carried out the screening of 19 compounds (triterpenes, diterpenes, sesquiterpenes, lignans, and flavonoids) isolated from 10 plants used in Mexican traditional medicine to determine whether they elicited vascular smooth muscle relaxation and, therefore, could represent novel anti-hypertension drug candidates. The vasorelaxant activity of these compounds was evaluated on the isolated rat aorta assay and the results obtained from this evaluation showed that three compounds induced a significant vasodilatory effect: meso-dihydroguaiaretic acid [half maximal effective concentration (EC₅₀), 49.9 ± 11.2 µM; maximum effect (Emax), 99.8 ± 2.7%]; corosolic acid (EC₅₀, 108.9 ± 6.7 µM; Emax, 96.4 ± 4.2%); and 5,8,4′-trihydroxy-3,7-dimethoxyflavone (EC₅₀, 122.3 ± 7.6 µM; Emax, 99.5 ± 5.4%). Subsequently, involvement of the NO/cyclic guanosine monophosphate (cGMP) and H₂S/ATP-sensitive potassium channel (K_ATP) pathways on the vasodilator activity of these compounds was assessed. The results derived from this analysis showed that the activation of both pathways contributes to the vasorelaxant effect of corosolic acid. On the other hand, the vasodilator effect of meso-dihydroguaiaretic acid and 5,8,4′-trihydroxy-3,7-dimethoxyflavone, partly involves stimulation of the NO/cGMP pathway. However, these compounds also showed an important endothelium-independent vasorelaxant effect, whose mechanism of action remains to be clarified. This study indicates that meso-dihydroguaiaretic acid, corosolic acid, and 5,8,4′-trihydroxy-3,7-dimethoxyflavone could be used as lead compounds for the synthesis of new derivatives with a higher potency to be developed as drugs for the prevention and treatment of cardiovascular diseases. Full article

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11 pages, 3057 KiB

Open AccessArticle

Desmoglein1 Deficiency Is a Potential Cause of Cutaneous Eruptions Induced by Shuanghuanglian Injection

by Yidan Zhang, Xiujun Zhang, Shanshan Fan, Lili Song, Zhen Yang, Pengwei Zhuang and Yanjun Zhang

Molecules 2018, 23(6), 1477; https://doi.org/10.3390/molecules23061477 - 19 Jun 2018

Cited by 6 | Viewed by 3867

Abstract

Cutaneous eruption is a common drug-adverse reaction, characterised by keratinocytes inflammation and apoptosis. Shuanghuanglian injeciton (SHLI) is a typical Chinese medicine injection, which is used to treat influenza. It has been reported that SHLI has the potential to induce cutaneous adverse eruptions. However, [...] Read more.

Cutaneous eruption is a common drug-adverse reaction, characterised by keratinocytes inflammation and apoptosis. Shuanghuanglian injeciton (SHLI) is a typical Chinese medicine injection, which is used to treat influenza. It has been reported that SHLI has the potential to induce cutaneous adverse eruptions. However, the mechanisms remain unclear. Since desmoglein 1 (DSG1) shows a crucial role in maintaining skin barrier function and cell susceptibility, we assume that DSG1 plays a critical role in the cutaneous eruptions induced by SHLI. In our study, retinoic acid (RA) was selected to downregulate the DSG1 expression, and lipopolysaccharide (LPS) was first used to identify the susceptibility of the DSG1-deficiency Hacat cells. Then, SHLI was administrated to normal or DSG1-deficient Hacat cells and mice. The inflammatory factors and apoptosis rate were evaluated by RT-PCR and flow cytometry. The skin pathological morphology was observed by hematoxylin and eosin (HE) staining. Our results show that treated only with SHLI could not cause IL-4 and TNF-α mRNA increases in normal Hacat cells. However, in the DSG1-deficient Hacat cells or mice, SHLI induced an extreme increase of IL-4 and TNF-α mRNA levels, as well as in the apoptosis rate. The skin tissue showed a local inflammatory cell infiltration when treated with SHIL in the DSG1-deficient mice. Thus, we concluded that DSG1 deficiency was a potential causation of SHLI induced eruptions. These results indicated that keratinocytes with DSG1 deficiency were likely to induce the cutaneous eruptions when stimulated with other medicines. Full article

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15 pages, 2965 KiB

Open AccessArticle

Parthenolide Inhibits STAT3 Signaling by Covalently Targeting Janus Kinases

by Man Liu, Chengqian Xiao, Mingwei Sun, Minjia Tan, Lihong Hu and Qiang Yu

Molecules 2018, 23(6), 1478; https://doi.org/10.3390/molecules23061478 - 19 Jun 2018

Cited by 45 | Viewed by 6470

Abstract

Aberrant activations of the STAT3 (signal transducer and activator of transcription 3) signaling pathway are associated with cancer and inflammatory diseases. Three of the four Janus kinases, JAK1, JAK2, and Tyk2, are the major upstream kinases of STAT3 in responses to cytokine stimulations. [...] Read more.

Aberrant activations of the STAT3 (signal transducer and activator of transcription 3) signaling pathway are associated with cancer and inflammatory diseases. Three of the four Janus kinases, JAK1, JAK2, and Tyk2, are the major upstream kinases of STAT3 in responses to cytokine stimulations. Among them, JAK2 is the key kinase in the IL-6-induced STAT3 phosphorylation. Here we report the mechanisms of a natural compound parthenolide from the medicinal herb Feverfew in regulating the JAK/STAT3 signaling. We found that parthenolide was a potent inhibitor of JAKs. It covalently modified the Cys178, Cys243, Cys335, and Cys480 of JAK2 and suppressed its kinase activity. It also interacted with other JAKs in a similar fashion. The binding of parthenolide to JAKs was selective. It preferentially bound to the JAKs, but not to the abundant proteins, such as tubulin and actin. Parthenolide also induced reactive oxygen species (ROS), but the increased ROS did not seem to contribute to the inhibition of JAK/STAT3 signaling. Furthermore, parthenolide inhibited the IL-6-induced cancer cell migration and preferentially inhibited the growth of cancer cells that had constitutively activated STAT3. Our study suggests a novel strategy to inactivate JAKs and provides a promising anti-inflammation and anticancer drug candidate. Full article

(This article belongs to the Section Chemical Biology)

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21 pages, 1219 KiB

Open AccessArticle

Analysis of the Volatile Profile of Core Chinese Mango Germplasm by Headspace Solid-Phase Microextraction Coupled with Gas Chromatography-Mass Spectrometry

by Xiao-Wei Ma, Mu-Qing Su, Hong-Xia Wu, Yi-Gang Zhou and Song-Biao Wang

Molecules 2018, 23(6), 1480; https://doi.org/10.3390/molecules23061480 - 19 Jun 2018

Cited by 23 | Viewed by 5950

Abstract

Despite abundant published research on the volatile characterization of mango germplasm, the aroma differentiation of Chinese cultivars remains unclear. Using headspace solid phase microextraction (HS-SPME) coupled with gas chromatography–mass spectrometry (GC-MS), the composition and relative content of volatiles in 37 cultivars representing the [...] Read more.

Despite abundant published research on the volatile characterization of mango germplasm, the aroma differentiation of Chinese cultivars remains unclear. Using headspace solid phase microextraction (HS-SPME) coupled with gas chromatography–mass spectrometry (GC-MS), the composition and relative content of volatiles in 37 cultivars representing the diversity of Chinese mango germplasm were investigated. Results indicated that there are distinct differences in the components and content of volatile compounds among and within cultivars. In total, 114 volatile compounds, including 23 monoterpenes, 16 sesquiterpenes, 29 non-terpene hydrocarbons, 25 esters, 11 aldehydes, five alcohols and five ketones, were identified. The total volatile content among cultivars ranged from 211 to 26,022 μg/kg fresh weight (FW), with 123-fold variation. Terpene compounds were the basic background volatiles, and 34 cultivars exhibited abundant monoterpenes. On the basis of hierarchical cluster analysis (HCA) and principal component analysis (PCA), terpinolene and α-pinene were important components constituting the aroma of Chinese mango cultivars. Most obviously, a number of mango cultivars with high content of various aroma components were observed, and they can serve as potential germplasms for both breeding and direct use. Full article

(This article belongs to the Special Issue Solid-Phase Microextraction)

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9 pages, 1437 KiB

Open AccessArticle

Ponasterone A and F, Ecdysteroids from the Arctic Bryozoan Alcyonidium gelatinosum

by Kine Østnes Hansen, Johan Isaksson, Eirin Glomsaker, Jeanette Hammer Andersen and Espen Hansen

Molecules 2018, 23(6), 1481; https://doi.org/10.3390/molecules23061481 - 19 Jun 2018

Cited by 14 | Viewed by 5982

Abstract

A new ecdysteroid, ponasterone F (1) and the previously reported compound ponasterone A (2) were isolated from specimens of the Arctic marine bryozoan Alcyonidium gelatinosum collected at Hopenbanken, off the coast of Edgeøya, Svalbard. The structure of 1 was [...] Read more.

A new ecdysteroid, ponasterone F (1) and the previously reported compound ponasterone A (2) were isolated from specimens of the Arctic marine bryozoan Alcyonidium gelatinosum collected at Hopenbanken, off the coast of Edgeøya, Svalbard. The structure of 1 was elucidated, and the structure of 2 confirmed by spectroscopic methods including 1D and 2D NMR and analysis of HR-MS data. The compounds were evaluated for their ability to affect bacterial survival and cell viability, as well as their agonistic activities towards the estrogen receptors α and β. The compounds were not active in these assays. Compound 2 is an arthropod hormone controlling molting and are known to act as an allelochemical when produced by plants. Even though its structure has been previously reported, this is the first time a ponasterone has been isolated from a bryozoan. A. gelatinosum produced 1 and 2 in concentrations surpassing those expected of hormonal molecules, indicating their function as defence molecules against molting predators. This work adds to the chemical diversity reported from marine bryozoans and expanded our knowledge of the chemical modifications of the ponasterones. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 4533 KiB

Open AccessArticle

Compound K Induces Endoplasmic Reticulum Stress and Apoptosis in Human Liver Cancer Cells by Regulating STAT3

by Xuan Zhang, Silin Zhang, Qitong Sun, Wenjun Jiao, Yan Yan and Xuewu Zhang

Molecules 2018, 23(6), 1482; https://doi.org/10.3390/molecules23061482 - 19 Jun 2018

Cited by 61 | Viewed by 6957

Abstract

The ginsenoside compound K (20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol; CK) is an intestinal bacterial metabolite of ginseng protopanaxadiol saponin that has been reported to induce apoptosis in many cancer cells; however, the precise mechanisms of its activity in human hepatocellular carcinoma [...] Read more.

The ginsenoside compound K (20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol; CK) is an intestinal bacterial metabolite of ginseng protopanaxadiol saponin that has been reported to induce apoptosis in many cancer cells; however, the precise mechanisms of its activity in human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we demonstrated that CK inhibited the growth and colony formation of HepG2 and SMMC-7721 cells, phenotypes that were mediated by inducing apoptosis. Meanwhile, CK showed lower toxicity in normal hepatoma cells. After treating HepG2 and SMMC-7721 cells with CK, p-STAT3 levels decreased, the three branches of the unfolded protein response were activated, and levels of endoplasmic reticulum stress (ERS)-related proteins were increased. We also revealed that CK decreased the DNA-binding capacity of STAT3. Moreover, silencing STAT3 with CRISPR/Cas9 technology enhanced CK-induced ERS and apoptosis. Finally, we showed that CK inhibited the growth of liver cancer xenografts with little toxicity. Mice bearing human HCC xenografts that were treated with CK showed increased GRP78 expression and decreased p-STAT3 levels. Taken together, these data showed that CK induced ERS and apoptosis by inhibiting p-STAT3 in human liver cancer cells; thus, CK might be a potential therapeutic candidate for human HCC. Full article

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16 pages, 4847 KiB

Open AccessArticle

A Novel Cyclodextrin-Functionalized Hybrid Silicon Wastewater Nano-Adsorbent Material and Its Adsorption Properties

by Jing Li, Chao Qiu, Haoran Fan, Yuxiang Bai, Zhengyu Jin and Jinpeng Wang

Molecules 2018, 23(6), 1485; https://doi.org/10.3390/molecules23061485 - 19 Jun 2018

Cited by 10 | Viewed by 4166

Abstract

A novel cyclodextrin-functionalized hybrid silicon nano-adsorbent material (6-EA-β-CD-Si) was synthesized via the nucleophilic substitution method. The structure was detected by Fourier transform infrared (FT-IR), X-ray, thermogravimetric analysis, and Brunauer-Emmett-Teller (BET) analysis. Results reveal that the BET surface area of 6-EA-β-CD-Si is 240 m [...] Read more.

A novel cyclodextrin-functionalized hybrid silicon nano-adsorbent material (6-EA-β-CD-Si) was synthesized via the nucleophilic substitution method. The structure was detected by Fourier transform infrared (FT-IR), X-ray, thermogravimetric analysis, and Brunauer-Emmett-Teller (BET) analysis. Results reveal that the BET surface area of 6-EA-β-CD-Si is 240 m²/g and the average pore size is 4.16 nm. The adsorption properties of 6-EA-β-CD-Si onto methylene blue (MB) were studied and fitted with adsorption kinetic models. Both the Freundlich adsorption isotherm model and pseudo-second-order model were fitted with well shows that the multi-layer adsorption with chemisorption and physisorption co-existing in the system. The maximum adsorption capacities are 39.37, 39.21, 36.90, and 36.36 mg/g at temperatures 303, 313, 323, and 333 K, respectively. The maximum removal rate of MB could reach 99.5%, indicating the potential application value of 6-EA-β-CD-Si in wastewater treatment. The adsorption mechanisms of 6-EA-β-CD-Si showed that the hydrophobic cave of β-CD plays an important role on the adsorption of MB. Full article

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

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13 pages, 2102 KiB

Open AccessArticle

Upregulation of UDP-Glucuronosyltransferases 1a1 and 1a7 Are Involved in Altered Puerarin Pharmacokinetics in Type II Diabetic Rats

by Songtao Dong, Maofan Zhang, Huimin Niu, Kunyu Jiang, Jialei Jiang, Yinglin Ma, Xin Wang and Shengnan Meng

Molecules 2018, 23(6), 1487; https://doi.org/10.3390/molecules23061487 - 20 Jun 2018

Cited by 14 | Viewed by 4762

Abstract

Puerarin is an isoflavonoid extracted from Pueraria lobata roots, and displays a broad range of pharmacological activities, including antidiabetic activity. However, information about the pharmacokinetics of puerarin in diabetics is scarce. This study was conducted to investigate the difference in pharmacokinetic effects of [...] Read more.

Puerarin is an isoflavonoid extracted from Pueraria lobata roots, and displays a broad range of pharmacological activities, including antidiabetic activity. However, information about the pharmacokinetics of puerarin in diabetics is scarce. This study was conducted to investigate the difference in pharmacokinetic effects of puerarin in normal rats and rats with diabetes mellitus (DM), and the mechanism involved. DM was induced by a combined high-fat diet (HFD) and streptozotocin (STZ) injection. Plasma concentrations of puerarin in DM, HFD, and control rats were determined after intravenous (20 mg/kg) and oral administration (500 mg/kg) of puerarin, and pharmacokinetic parameters were estimated. The messenger RNA (mRNA) and protein expression levels of Ugt1a1 and Ugt1a7 in rat livers and intestines were measured using qRT-PCR and western blot, respectively. The area under the concentration–time curve and the clearance of puerarin in the DM rats statistically differed from those in the control rats (p <0.05) with both administration routes. The hepatic and intestinal gene and protein expressions of Ugt1a1 and Ugt1a7 were significantly increased in the DM rats (p <0.05). Therefore, the metabolic changes in diabetes could alter the pharmacokinetics of puerarin. This change could be caused by upregulated uridine diphosphate (UDP)-glucuronosyltransferase activity, which may enhance puerarin clearance, and alter its therapeutic effects. Full article

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

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19 pages, 5184 KiB

Open AccessArticle

Insights into Resistance Mechanisms of Inhibitors to Mps1 C604Y Mutation via a Comprehensive Molecular Modeling Study

by Yuan Chen, Wenquan Yu, Cui-cui Jiang and Jin-gui Zheng

Molecules 2018, 23(6), 1488; https://doi.org/10.3390/molecules23061488 - 20 Jun 2018

Cited by 3 | Viewed by 4157

Abstract

Mono-polar spindle 1 (Mps1/TTK) represents a protein kinase reported to be vital for cell division processes and is generally regarded as an attractive target for the treatment of hepatocellular carcinoma, breast carcinoma, and colon cancer. However, the C604Y mutation has been linked to [...] Read more.

Mono-polar spindle 1 (Mps1/TTK) represents a protein kinase reported to be vital for cell division processes and is generally regarded as an attractive target for the treatment of hepatocellular carcinoma, breast carcinoma, and colon cancer. However, the C604Y mutation has been linked to acquired resistance. Recently, three potential small-molecule inhibitors of Mps1 (i.e., reversine, NMS-P715, and its derivative Cpd-5) were reported for the C604Y mutation that exhibit significant resistance to NMS-P715 and Cpd-5, but retain affinity for reversine. In this study, classical molecular dynamic (MD) simulations, accelerated MD (aMD) simulations, and umbrella sampling (US) simulations were performed to illustrate the resistance mechanisms of inhibitors to Mps1. The classical MD simulations combined with free energy calculations revealed that reversine features similar binding affinity characteristics to both Mps1^WT and Mps1^C604Y, but both NMS-P715 and Cpd-5 feature much higher binding affinities to Mps1^WT than to Mps1^C604Y. The major variations were shown to be controlled by electrostatic energy and the conformational change of A-loop-induced entropy increased. The large conformational changes of Mps1^C604Y bound to NMS-P715 and Cpd-5 were also observed in aMD simulations. The US simulation results further suggest that reversine and Cpd-5 both exhibit similar dissociation processes from both Mps1^WT and Mps1^C604Y, but Cpd-5 and NMS-P715 were found to dissociate more easily from Mps1^C604Y than from Mps1^WT, thus a reduced residence time was responsible for the inhibitors resistance to the C604Y mutation. The physical principles provided by the present study may provide important clues for the discovery and rational design of novel inhibitors to combat the C604Y mutation of Mps1. Full article

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

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10 pages, 2614 KiB

Open AccessArticle

Mouse β-Defensin 3, A Defensin Inhibitor of Both Its Endogenous and Exogenous Potassium Channels

by Yaoyun Zhang, Yonghui Zhao, Hongyue Liu, Weiwei Yu, Fan Yang, Wenhua Li, Zhijian Cao and Yingliang Wu

Molecules 2018, 23(6), 1489; https://doi.org/10.3390/molecules23061489 - 20 Jun 2018

Cited by 6 | Viewed by 4531

Abstract

The human defensins are recently discovered to inhibit potassium channels, which are classical targets of the animal toxins. Whether other vertebrate defensins are potassium channel inhibitors remains unknown. In this work, we reported that the mouse β-defensin 3 (mBD3) was a novel inhibitor [...] Read more.

The human defensins are recently discovered to inhibit potassium channels, which are classical targets of the animal toxins. Whether other vertebrate defensins are potassium channel inhibitors remains unknown. In this work, we reported that the mouse β-defensin 3 (mBD3) was a novel inhibitor of both endogenous and exogenous potassium channels. The structural analysis showed that mBD3 is the most identical to human Kv1.3 channel-sensitive human β-defensin 2 (hBD2). However, the pharmacological profiles indicated that the recombinant mBD3 (rmBD3) weakly inhibited the mouse and human Kv1.3 channels. Different from the pharmacological features of human β-defensins, mBD3 more selectively inhibited the mouse Kv1.6 and human KCNQ1/KCNE1 channels with IC₅₀ values of 0.6 ± 0.4 μM and 1.2 ± 0.8 μM, respectively. The site directed mutagenesis experiments indicated that the extracellular pore region of mouse Kv1.6 channel was the interaction site of rmBD3. In addition, the minor effect on the channel conductance-voltage relationship curves implied that mBD3 might bind the extracellular transmembrane helices S1-S2 linker and/or S3-S4 linker of mouse Kv1.6 channel. Together, these findings not only revealed mBD3 as a novel inhibitor of both endogenous and exogenous potassium channels, but also provided a clue to investigate the role of mBD3-Kv1.6 channel interaction in the physiological and pathological field in the future. 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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20 pages, 6411 KiB

Open AccessArticle

Metabolomic Analysis of Biochemical Changes in the Serum and Urine of Freund’s Adjuvant-Induced Arthritis in Rats after Treatment with Silkworm Excrement

by Tianyao Zheng, Shulan Su, Xinxin Dai, Liwen Zhang, Jin-Ao Duan and Zhen Ou-Yang

Molecules 2018, 23(6), 1490; https://doi.org/10.3390/molecules23061490 - 20 Jun 2018

Cited by 25 | Viewed by 4979

Abstract

Silkworm excrement (SE), is used as a traditional antirheumatic medicine in China. The present study was designed to investigate the therapeutic efficacy of water fraction of SE (ST) and ethanol fraction of SE (CT) at two different doses on adjuvant induced arthritis (AA) [...] Read more.

Silkworm excrement (SE), is used as a traditional antirheumatic medicine in China. The present study was designed to investigate the therapeutic efficacy of water fraction of SE (ST) and ethanol fraction of SE (CT) at two different doses on adjuvant induced arthritis (AA) rats. Arthritis severity was evaluated by body weight, paw thickness, histological changes and index of paws oedema and spleen. Serum samples were collected for estimation of biochemical indicators and cytokines. In addition, a metabonomic method based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) had been established to investigate the holistic efficacy of SE by serum and urine. Multivariate statistical approaches, such as partial least-squares discriminant analysis (PLS-DA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) were built to evaluate the therapeutic effects of SE and find potential biomarkers and metabolic pathways. Administration with SE significantly ameliorated the AA severity, including body weight loss, paw swelling, histological changes and the levels of biochemical index. 33 endogenous metabolites had been identified (10 in serum and 23 in urine) in the AA rats. Urinary and serum metabolic profiling revealed that the metabolites underpin the metabolic pathway including nicotinate and nicotinamide metabolism; pentose and glucuronate interconversions; TCA cycle; beta-Alanine metabolism; purine metabolism and glycolysis or gluconeogenesis. The altered metabolites could be regulated closer to normal level after SE intervention. The results suggested SE possesses substantial anti-arthritic activity and demonstrated that metabonomics is a powerful tool to gain insight in the mechanism of SE formula in therapy. Full article

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12 pages, 2088 KiB

Open AccessArticle

Expression, Purification, and Characterization of a Novel Hybrid Peptide with Potent Antibacterial Activity

by Xubiao Wei, Rujuan Wu, Lulu Zhang, Baseer Ahmad, Dayong Si and Rijun Zhang

Molecules 2018, 23(6), 1491; https://doi.org/10.3390/molecules23061491 - 20 Jun 2018

Cited by 38 | Viewed by 6827

Abstract

The hybrid peptide cecropin A (1–8)–LL37 (17–30) (C–L), derived from the sequence of cecropin A (C) and LL-37 (L), showed significantly increased antibacterial activity and minimized hemolytic activity than C and L alone. To obtain high-level production of C–L, the deoxyribonucleic acid sequence [...] Read more.

The hybrid peptide cecropin A (1–8)–LL37 (17–30) (C–L), derived from the sequence of cecropin A (C) and LL-37 (L), showed significantly increased antibacterial activity and minimized hemolytic activity than C and L alone. To obtain high-level production of C–L, the deoxyribonucleic acid sequence encoding C–L with preferred codons was cloned into pET-SUMO to construct a fusion expression vector, and overexpressed in Escherichia coli (E. coli) BL21 (DE3). The maximum fusion protein (92% purity) was obtained with the yield of 89.14 mg/L fermentation culture after purification with Ni-NTA Sepharose column. The hybrid C–L was cleaved from the fusion protein by SUMO-protease, and 17.54 mg/L pure active C–L was obtained. Furthermore, the purified C–L showed identical antibacterial and hemolytic activity to synthesized C–L. Stability analysis results exhibited that the activity of C–L changed little below 80 °C for 20 min, but when the temperature exceeded 80 °C, a significant decrease was observed. Varying the pH from 5.0 to 10.0 did not appear to influence the activity of C–L, however, pH below 4.0 decreased the antibacterial activity of C–L rapidly. Under the challenge of several proteases (pepsin, trypsin, and proteinase K), the functional activity of C–L was maintained over 50%. In summary, this study not only supplied an effective approach for high-level production of hybrid peptide C–L, but paved the way for its further exploration in controlling infectious diseases of farm animals or even humans. Full article

(This article belongs to the Section Chemical Biology)

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13 pages, 2749 KiB

Open AccessArticle

Identification of 2′,4′-Dihydroxychalcone as an Antivirulence Agent Targeting HlyU, a Master Virulence Regulator in Vibrio vulnificus

by Saba Imdad, Nayab Batool, Subhra Pradhan, Akhilesh Kumar Chaurasia and Kyeong Kyu Kim

Molecules 2018, 23(6), 1492; https://doi.org/10.3390/molecules23061492 - 20 Jun 2018

Cited by 10 | Viewed by 5306

Abstract

The emergence of antimicrobial resistance and rapid acclimation allows Vibrio vulnificus to rapidly propagate in the host. This problematic pathological scenario can be circumvented by employing an antivirulence strategy, treating Vibrio infections without hindering the bacterial growth. We developed a genome-integrated orthogonal inhibitor [...] Read more.

The emergence of antimicrobial resistance and rapid acclimation allows Vibrio vulnificus to rapidly propagate in the host. This problematic pathological scenario can be circumvented by employing an antivirulence strategy, treating Vibrio infections without hindering the bacterial growth. We developed a genome-integrated orthogonal inhibitor screening platform in E. coli to identify antivirulence agents targeting a master virulence regulator of V. vulnificus. We identified 2′,4′-dihydroxychalcone (DHC) from the natural compound library and verified that it decreases the expression of the major toxin network which is equivalent to the ∆hlyU deletion mutant. 2′,4′-DHC also reduced the hemolytic activity of V. vulnificus which was tested as an example of virulence phenotype. The electrophoretic mobility shift assay confirmed that 2′,4′-DHC specifically targeted HlyU and inhibited its binding to P_rtxA1 promoter. Under in vivo conditions, a single dose of 2′,4′-DHC protected ~50% wax-worm larvae from V. vulnificus infection at a non-toxic concentration to both V. vulnificus and wax-worm larvae. In the current study, we demonstrated that an orthogonal reporter system is suitable for the identification of antivirulence compounds with accuracy, and identified 2′,4′-DHC as a potent antivirulence agent that specifically targets the HlyU virulence transcriptional regulator and significantly reduces the virulence and infection potential of V. vulnificus. Full article

(This article belongs to the Section Chemical Biology)

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11 pages, 2517 KiB

Open AccessFeature PaperArticle

Cytotoxic Triterpenes from Salacia crassifolia and Metabolite Profiling of Celastraceae Species

by Laila S. Espindola, Renata G. Dusi, Daniel P. Demarque, Raimundo Braz-Filho, Pengcheng Yan, Heidi R. Bokesch, Kirk R. Gustafson and John A. Beutler

Molecules 2018, 23(6), 1494; https://doi.org/10.3390/molecules23061494 - 20 Jun 2018

Cited by 21 | Viewed by 5842

Abstract

The new pentacyclic triterpene 11β-hydroxypristimerin (1), along with the known metabolites pristimerin (2), 6-oxopristimerol (3) and vitideasin (4), were isolated from a Salacia crassifolia root wood extract, following a bioassay-guided fractionation approach. Both [...] Read more.

The new pentacyclic triterpene 11β-hydroxypristimerin (1), along with the known metabolites pristimerin (2), 6-oxopristimerol (3) and vitideasin (4), were isolated from a Salacia crassifolia root wood extract, following a bioassay-guided fractionation approach. Both the extract and the purified triterpenes displayed pronounced cytotoxic activity against human cancer cell lines. The NCI-60 cell line screen revealed that compound 2 was the most active, with a mean GI₅₀ of 0.17 μM, while compound 1 had a mean GI₅₀ of 8.7 μM. A COMPARE analysis of the screening results showed that pristimerin is likely to be the main compound responsible for the cytotoxic activity of the extract (mean GI₅₀ of 0.3 μg·mL⁻¹). A targeted search for pristimerin and related derivatives using LC-MS/MS revealed the presence of pristimerin (2) and 6-oxopristimerol (3) in all Celastraceae species examined and in all plant parts tested, while vitideasin (4) was only detected in the genus Salacia. Full article

(This article belongs to the Special Issue Antitumoral Properties of Natural Products)

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14 pages, 1923 KiB

Open AccessArticle

Evaluation of the Effects of Isolated Lignin on Cellulose Enzymatic Hydrolysis of Corn Stover Pretreatment by NaOH Combined with Ozone

by Shuo Fang, Wenhui Wang, Shisheng Tong, Chunyan Zhang and Ping Liu

Molecules 2018, 23(6), 1495; https://doi.org/10.3390/molecules23061495 - 20 Jun 2018

Cited by 27 | Viewed by 5373

Abstract

In this experiment, corn stover was treated with optimal combined pretreatment conditions: 2% NaOH at 80 °C treated 2 h combined with initial pH 9 at the ozone concentration of 78 mg/mL treated 25 min. The effect of lignin removal rate on the [...] Read more.

In this experiment, corn stover was treated with optimal combined pretreatment conditions: 2% NaOH at 80 °C treated 2 h combined with initial pH 9 at the ozone concentration of 78 mg/mL treated 25 min. The effect of lignin removal rate on the enzymatic hydrolysis degree of cellulose during the treatment process was studied. At the same time, the lignin in the optimal pretreated corn stover was separated and extracted by enzymatic acidolysis, and its structure and connection were characterized. The results showed that the alkali combined with ozone pretreatment improved the enzymatic hydrolysis degree of the cellulose while exfoliating and degrading the macromolecular lignin into small molecules. The stable crosslink structure of the lignin-cellulose-hemicellulose was destroyed, and the lignocellulosic structure changed in favor of the enzymatic hydrolysis of the cellulose. Full article

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16 pages, 802 KiB

Open AccessArticle

Constituents of Essential Oil and Lipid Fraction from the Aerial Part of Bupleurum scorzonerifolium Willd. (Apiaceae) from Different Habitats

by Zhargal Alexandrovich Tykheev, Svetlana Vasilievna Zhigzhitzhapova, Faqi Zhang, Vasiliy Vladimirovich Taraskin, Oleg Arnoldovich Anenkhonov, Larisa Dorzhievna Radnaeva and Shilong Chen

Molecules 2018, 23(6), 1496; https://doi.org/10.3390/molecules23061496 - 20 Jun 2018

Cited by 24 | Viewed by 4696

Abstract

The essential oils and lipid fraction extracted from the aerial parts of Bupleurum scorzonerifolium were determined by a GC-MS method. In total, up to 67 components were identified. cis-β-Ocimene, trans-β-ocimene, limonene, α-pinene, α-copaene, β-elemene, [...] Read more.

The essential oils and lipid fraction extracted from the aerial parts of Bupleurum scorzonerifolium were determined by a GC-MS method. In total, up to 67 components were identified. cis-β-Ocimene, trans-β-ocimene, limonene, α-pinene, α-copaene, β-elemene, and caryophyllene oxide were recognized as consistent components of the essential oil extracted from the aerial parts of B. scorzonerifolium, regardless of the habitat. The content of these components varied from traces to a significant amount. The volume of the lipid fraction varied from 2.73 to 9.38%. In total, 23 components were identified, including 20 fatty acids, two sterols, and one ketone. The major fatty acid components identified were 16:0, 18:2n9, and 18:1n9. The total content of these fatty acids reached up to 76.19%. The lipid fraction of the aerial parts of B. scorzonerifolium predominantly contained MUFA and PUFA, which confirmed the pharmacological value of the species. The main factors affecting the composition of essential oils and lipid fractions of B. scorzonerifolium are environmental ones that determine the moisture supply to the plants in semiarid and arid areas. Full article

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23 pages, 7132 KiB

Open AccessArticle

Synthesis, Structure, Chemical Stability, and In Vitro Cytotoxic Properties of Novel Quinoline-3-Carbaldehyde Hydrazones Bearing a 1,2,4-Triazole or Benzotriazole Moiety

by Martyna Korcz, Franciszek Sączewski, Patrick J. Bednarski and Anita Kornicka

Molecules 2018, 23(6), 1497; https://doi.org/10.3390/molecules23061497 - 20 Jun 2018

Cited by 35 | Viewed by 7605

Abstract

A small library of novel quinoline-3-carbaldehyde hydrazones (Series 1), acylhydrazones (Series 2), and arylsulfonylhydrazones (Series 3) bearing either a 1,2,4-triazole or benzotriazole ring at position 2 was prepared, characterized by elemental analyses and IR, NMR, and MS spectra, and then subjected to in [...] Read more.

A small library of novel quinoline-3-carbaldehyde hydrazones (Series 1), acylhydrazones (Series 2), and arylsulfonylhydrazones (Series 3) bearing either a 1,2,4-triazole or benzotriazole ring at position 2 was prepared, characterized by elemental analyses and IR, NMR, and MS spectra, and then subjected to in vitro cytotoxicity studies on three human tumor cell lines: DAN-G, LCLC-103H, and SISO. In general, compounds 4, 6, and 8 substituted with a 1,2,4-triazole ring proved to be inactive, whereas the benzotriazole-containing quinolines 5, 7, and 9 elicited pronounced cancer cell growth inhibitory effects with IC₅₀ values in the range of 1.23–7.39 µM. The most potent 2-(1H-benzotriazol-1-yl)-3-[2-(pyridin-2-yl)hydrazonomethyl]quinoline (5e) showed a cytostatic effect on the cancer cell lines, whereas N′-[(2-(1H-benzotriazol-1-yl)quinolin-3-yl)methylene]-benzohydrazide (7a) and N′-[(2-1H-benzotriazol-1-yl)quinolin-3-yl)methylene]-naphthalene-2-sulfonohydrazide (9h) exhibited selective activity against the pancreas cancer DAN-G and cervical cancer SISO cell lines. Based on the determined IC₅₀ values, the compound 5e seems to be leading compound for further development as anticancer agent. Full article

(This article belongs to the Section Medicinal Chemistry)

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Review

Jump to: Editorial, Research, Other

21 pages, 843 KiB

Open AccessReview

Design and Efficacy of Nanogels Formulations for Intranasal Administration

by Blessing A. Aderibigbe and Tobeka Naki

Molecules 2018, 23(6), 1241; https://doi.org/10.3390/molecules23061241 - 23 May 2018

Cited by 57 | Viewed by 7385

Abstract

Nanogels are drug delivery systems that can bypass the blood-brain barrier and deliver drugs to the desired site when administered intranasally. They have been used as a drug delivery platform for the management of brain diseases such as Alzheimer disease, migraine, schizophrenia and [...] Read more.

Nanogels are drug delivery systems that can bypass the blood-brain barrier and deliver drugs to the desired site when administered intranasally. They have been used as a drug delivery platform for the management of brain diseases such as Alzheimer disease, migraine, schizophrenia and depression. nanogels have also been developed as vaccine carriers for the protection of bacterial infections such as influenza, meningitis, pneumonia and as veterinary vaccine carriers for the protection of animals from encephalomyelitis and mouth to foot disease. It has been developed as vaccine carriers for the prevention of lifestyle disease such as obesity. Intranasal administration of therapeutics using nanogels for the management of brain diseases revealed that the drug transportation was via the olfactory nerve pathway resulting in rapid drug delivery to the brain with excellent neuroprotective effect. The application of nanogels as vaccine carriers also induced significant responses associated with protective immunity against selected bacterial and viral infections. This review provides a detailed information on the enhanced therapeutic effects, mechanisms and biological efficacy of nanogels for intranasal administration. Full article

(This article belongs to the Special Issue Targeted Drug Delivery and Nanocarriers)

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18 pages, 1555 KiB

Open AccessFeature PaperReview

Performance Comparisons of Polymer Semiconductors Synthesized by Direct (Hetero)Arylation Polymerization (DHAP) and Conventional Methods for Organic Thin Film Transistors and Organic Photovoltaics

by Arthur D. Hendsbee and Yuning Li

Molecules 2018, 23(6), 1255; https://doi.org/10.3390/molecules23061255 - 24 May 2018

Cited by 23 | Viewed by 5634

Abstract

C-C bond forming reactions are central to the construction of π-conjugated polymers. Classical C-C bond forming reactions such as the Stille and Suzuki coupling reactions have been widely used in the past for this purpose. More recently, direct (hetero)arylation polymerization (DHAP) has earned [...] Read more.

C-C bond forming reactions are central to the construction of π-conjugated polymers. Classical C-C bond forming reactions such as the Stille and Suzuki coupling reactions have been widely used in the past for this purpose. More recently, direct (hetero)arylation polymerization (DHAP) has earned a place in the spotlight with an increasing number of π-conjugated polymers being produced using this atom-economic and more sustainable chemistry. As semiconductors in organic electronics, the device performances of the polymers made by DHAP are of great interest and importance. This review compares the device performances of some representative π-conjugated polymers made using the DHAP method with those made using the conventional C-C bond forming reactions when they are used as semiconductors in organic thin film transistors (OTFTs) and organic photovoltaics (OPVs). Full article

(This article belongs to the Special Issue Direct (Hetero)Arylation: A New Tool for Organic Electronics)

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37 pages, 9583 KiB

Open AccessReview

Whole Cells as Biocatalysts in Organic Transformations

by Fabián Garzón-Posse, Liliana Becerra-Figueroa, José Hernández-Arias and Diego Gamba-Sánchez

Molecules 2018, 23(6), 1265; https://doi.org/10.3390/molecules23061265 - 25 May 2018

Cited by 75 | Viewed by 8134

Abstract

Currently, the power and usefulness of biocatalysis in organic synthesis is undeniable, mainly due to the very high enantiomeric excess reached using enzymes, in an attempt to emulate natural processes. However, the use of isolated enzymes has some significant drawbacks, the most important [...] Read more.

Currently, the power and usefulness of biocatalysis in organic synthesis is undeniable, mainly due to the very high enantiomeric excess reached using enzymes, in an attempt to emulate natural processes. However, the use of isolated enzymes has some significant drawbacks, the most important of which is cost. The use of whole cells has emerged as a useful strategy with several advantages over isolated enzymes; for this reason, modern research in this field is increasing, and various reports have been published recently. This review surveys the most recent developments in the enantioselective reduction of carbon-carbon double bonds and prochiral ketones and the oxidation of prochiral sulfides using whole cells as biocatalytic systems. Full article

(This article belongs to the Special Issue Enantioselective Catalysis)

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13 pages, 3251 KiB

Open AccessReview

The ABP Dendrimer, a Drug-Candidate against Inflammatory Diseases That Triggers the Activation of Interleukin-10 Producing Immune Cells

by Séverine Fruchon and Rémy Poupot

Molecules 2018, 23(6), 1272; https://doi.org/10.3390/molecules23061272 - 25 May 2018

Cited by 20 | Viewed by 4612

Abstract

The ABP dendrimer, which is built on a phosphorus-based scaffold and bears twelve azabisphosphonate groups at its surface, is one of the dendrimers that has been shown to display immuno-modulatory and anti-inflammatory effects towards the human immune system. Its anti-inflammatory properties have been [...] Read more.

The ABP dendrimer, which is built on a phosphorus-based scaffold and bears twelve azabisphosphonate groups at its surface, is one of the dendrimers that has been shown to display immuno-modulatory and anti-inflammatory effects towards the human immune system. Its anti-inflammatory properties have been successfully challenged in animal models of inflammatory disorders. In this review, we trace the discovery and the evaluation of the therapeutic effects of the ABP dendrimer in three different animal models of both acute and chronic inflammatory diseases. We emphasize that its therapeutic effects rely on the enhancement of the production of Interleukin-10, the paradigm of anti-inflammatory cytokines, by different subsets of immune cells, such as monocytes/macrophages and CD4+ T lymphocytes. Full article

(This article belongs to the Special Issue Dendrimers in Medicine)

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13 pages, 5889 KiB

Open AccessReview

Synergy between Experimental and Theoretical Results of Some Reactions of Annelated 1,3-Azaphospholes

by Raj K. Bansal, Raakhi Gupta and Manjinder Kour

Molecules 2018, 23(6), 1283; https://doi.org/10.3390/molecules23061283 - 27 May 2018

Cited by 6 | Viewed by 3895

Abstract

Computational calculations have been used successfully to explain the reactivity of the >C=P- functionality in pyrido-annelated 1,3-azaphospholes. Theoretical investigation at the Density Functional Theory (DFT) level shows that the lone pair of the bridgehead nitrogen atoms is involved in extended conjugation, due to [...] Read more.

Computational calculations have been used successfully to explain the reactivity of the >C=P- functionality in pyrido-annelated 1,3-azaphospholes. Theoretical investigation at the Density Functional Theory (DFT) level shows that the lone pair of the bridgehead nitrogen atoms is involved in extended conjugation, due to which electron density increases considerably in the five-membered azaphosphole ring. The electron density in the azaphosphole is further enhanced by the presence of an ester group at the 3-position making the >C=P- functionality electron-rich. Thus, 1,3-azaphospholo[5,1-a]pyridine, i.e., 2-phosphaindolizine having ester group at the 3-position only does not undergo Diels-Alder (DA) reaction with an electron rich diene, such as 2,3-dimethyl-1,3-butadiene (DMB). However, an ester group at 1-position acts as electron-sink, due to which transfer of the electron density to the >C=P- moiety is checked and DA reaction occurs across the >C=P- functionality. The coordination of the Lewis acid to the carbonyl group at the 3-position raises the activation barrier, while it is lowered remarkably when it is coordinated to the P atom. Furthermore, the attack of 1,3-butadiene on the Si face of the P-coordinated (o-menthoxy)aluminum dichloride complex is a lower activation energy path. Fukui functions could be used to explain relative reactivities of indolizine and 2-phosphaindolizine towards electrophilic substitution reactions. Full article

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

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18 pages, 1558 KiB

Open AccessReview

Strategies for Enhancing the Permeation of CNS-Active Drugs through the Blood-Brain Barrier: A Review

by Isra’ Zeiadeh, Anas Najjar and Rafik Karaman

Molecules 2018, 23(6), 1289; https://doi.org/10.3390/molecules23061289 - 28 May 2018

Cited by 55 | Viewed by 13858

Abstract

Background: The blood brain barrier (BBB) is a dynamic and functional structure which poses a vast challenge in the development of drugs acting on the central nervous system (CNS). While most substances are denied BBB crossing, selective penetration of substances mainly occurs through [...] Read more.

Background: The blood brain barrier (BBB) is a dynamic and functional structure which poses a vast challenge in the development of drugs acting on the central nervous system (CNS). While most substances are denied BBB crossing, selective penetration of substances mainly occurs through diffusion, carrier mediated transport, or receptor mediated transcytosis. Methods: Strategies in enhancing BBB penetration have been reviewed and summarized in accordance with their type of formulation. Highlights in monoclonal antibodies, peptide-vectors, nanoparticles, and simple prodrugs were included. Conclusion: Nanoparticles and simple prodrugs, for example, can be used for efficient BBB penetration through inhibition of efflux mechanisms, however, monoclonal antibodies are the most promising strategy in BBB penetration. Close follow-up of future development in this area should confirm our expectation. Full article

(This article belongs to the Special Issue Targeted Prodrugs)

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24 pages, 1996 KiB

Open AccessFeature PaperReview

In Vitro and In Silico Studies of the Molecular Interactions of Epigallocatechin-3-O-gallate (EGCG) with Proteins That Explain the Health Benefits of Green Tea

by Koichi Saeki, Sumio Hayakawa, Shogo Nakano, Sohei Ito, Yumiko Oishi, Yasuo Suzuki and Mamoru Isemura

Molecules 2018, 23(6), 1295; https://doi.org/10.3390/molecules23061295 - 28 May 2018

Cited by 69 | Viewed by 11323

Abstract

Green tea has been shown to have beneficial effects on many diseases such as cancer, obesity, inflammatory diseases, and neurodegenerative disorders. The major green tea component, epigallocatechin-3-O-gallate (EGCG), has been demonstrated to contribute to these effects through its anti-oxidative and pro-oxidative [...] Read more.

Green tea has been shown to have beneficial effects on many diseases such as cancer, obesity, inflammatory diseases, and neurodegenerative disorders. The major green tea component, epigallocatechin-3-O-gallate (EGCG), has been demonstrated to contribute to these effects through its anti-oxidative and pro-oxidative properties. Furthermore, several lines of evidence have indicated that the binding affinity of EGCG to specific proteins may explain its mechanism of action. This review article aims to reveal how EGCG-protein interactions can explain the mechanism by which green tea/EGCG can exhibit health beneficial effects. We conducted a literature search, using mainly the PubMed database. The results showed that several methods such as dot assays, affinity gel chromatography, surface plasmon resonance, computational docking analyses, and X-ray crystallography have been used for this purpose. These studies have provided evidence to show how EGCG can fit or occupy the position in or near functional sites and induce a conformational change, including a quaternary conformational change in some cases. Active site blocking, steric hindrance by binding of EGCG near an active site or induced conformational change appeared to cause inhibition of enzymatic activity and other biological activities of proteins, which are related to EGCG’s biological oligomer and formation of their toxic aggregates, leading to the prevention of neurodegenerative diseases and amyloidosis. In conclusion, these studies have provided useful information on the action of green tea/catechins and would lead to future studies that will provide further evidence for rational EGCG therapy and use EGCG as a lead compound for drug design. Full article

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

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23 pages, 2127 KiB

Open AccessReview

A Half-Century History of Applications of Antisense Oligonucleotides in Medicine, Agriculture and Forestry: We Should Continue the Journey

by Volodymyr V. Oberemok, Kateryna V. Laikova, Anna I. Repetskaya, Igor M. Kenyo, Mikhail V. Gorlov, Igor N. Kasich, Alisa M. Krasnodubets, Nikita V. Gal’chinsky, Iryna I. Fomochkina, Aleksei S. Zaitsev, Viktoriya V. Bekirova, Eleonora E. Seidosmanova, Ksenia I. Dydik, Anna O. Meshcheryakova, Sergey A. Nazarov, Natalya N. Smagliy, Edie L. Chelengerova, Alina A. Kulanova, Karim Deri, Mikhail V. Subbotkin, Refat Z. Useinov, Maksym N. Shumskykh and Anatoly V. Kubyshkin Show full author list Hide full author list

Molecules 2018, 23(6), 1302; https://doi.org/10.3390/molecules23061302 - 29 May 2018

Cited by 57 | Viewed by 8597

Abstract

Antisense oligonucleotides (ASO), short single-stranded polymers based on DNA or RNA chemistries and synthesized in vitro, regulate gene expression by binding in a sequence-specific manner to an RNA target. The functional activity and selectivity in the action of ASOs largely depends on the [...] Read more.

Antisense oligonucleotides (ASO), short single-stranded polymers based on DNA or RNA chemistries and synthesized in vitro, regulate gene expression by binding in a sequence-specific manner to an RNA target. The functional activity and selectivity in the action of ASOs largely depends on the combination of nitrogenous bases in a target sequence. This simple and natural property of nucleic acids provides an attractive route by which scientists can create different ASO-based techniques. Over the last 50 years, planned and realized applications in the field of antisense and nucleic acid nanotechnologies have produced astonishing results and posed new challenges for further developments, exemplifying the essence of the post-genomic era. Today the majority of ASOs are chemically modified and/or incorporated within nanoparticles to enhance their stability and cellular uptake. This review critically analyzes some successful cases using the antisense approach in medicine to address severe diseases, such as Duchenne muscular dystrophy and spinal muscular atrophy, and suggests some prospective directions for future research. We also examine in detail the elaboration of unmodified insect-specific DNA insecticides and RNA preparations in the areas of agriculture and forestry, a relatively new branch of ASO that allows circumvention of the use of non-selective chemical insecticides. When considering the variety of successful ASO modifications with an efficient signal-to-noise ratio of action, coupled with the affordability of in vitro oligonucleotide synthesis and post-synthesis procedures, we predict that the next half-century will produce a fruitful yield of tools created from effective ASO-based end products. Full article

(This article belongs to the Section Nanochemistry)

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14 pages, 508 KiB

Open AccessReview

The Effect of Light Exposure at Night (LAN) on Carcinogenesis via Decreased Nocturnal Melatonin Synthesis

by Aldo Giudice, Anna Crispo, Maria Grimaldi, Andrea Polo, Sabrina Bimonte, Mario Capunzo, Alfonso Amore, Giovanni D’Arena, Pellegrino Cerino, Alfredo Budillon, Gerardo Botti, Susan Costantini and Maurizio Montella

Molecules 2018, 23(6), 1308; https://doi.org/10.3390/molecules23061308 - 29 May 2018

Cited by 31 | Viewed by 6859

Abstract

In mammals, a master clock is located within the suprachiasmatic nucleus (SCN) of the hypothalamus, a region that receives input from the retina that is transmitted by the retinohypothalamic tract. The SCN controls the nocturnal synthesis of melatonin by the pineal gland that [...] Read more.

In mammals, a master clock is located within the suprachiasmatic nucleus (SCN) of the hypothalamus, a region that receives input from the retina that is transmitted by the retinohypothalamic tract. The SCN controls the nocturnal synthesis of melatonin by the pineal gland that can influence the activity of the clock’s genes and be involved in the inhibition of cancer development. On the other hand, in the literature, some papers highlight that artificial light exposure at night (LAN)-induced circadian disruptions promote cancer. In the present review, we summarize the potential mechanisms by which LAN-evoked disruption of the nocturnal increase in melatonin synthesis counteracts its preventive action on human cancer development and progression. In detail, we discuss: (i) the Warburg effect related to tumor metabolism modification; (ii) genomic instability associated with L1 activity; and (iii) regulation of immunity, including regulatory T cell (Treg) regulation and activity. A better understanding of these processes could significantly contribute to new treatment and prevention strategies against hormone-related cancer types. 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, 6744 KiB

Open AccessFeature PaperReview

Lectin-Based Assay for Glycoform-Specific Detection of α2,6-sialylated Transferrin and Carcinoembryonic Antigen in Tissue and Body Fluid

by Hiromi Ito, Kyoka Hoshi, Takashi Honda and Yasuhiro Hashimoto

Molecules 2018, 23(6), 1314; https://doi.org/10.3390/molecules23061314 - 30 May 2018

Cited by 12 | Viewed by 5049

Abstract

Antibodies are useful for detecting glycoprotein antigens, but a conventional antibody recognizes only a protein epitope rather than a glycan. Thus, glycan isoform detection generally requires time- and labor-consuming processes such as lectin affinity column chromatography followed by sandwich ELISA. We recently found [...] Read more.

Antibodies are useful for detecting glycoprotein antigens, but a conventional antibody recognizes only a protein epitope rather than a glycan. Thus, glycan isoform detection generally requires time- and labor-consuming processes such as lectin affinity column chromatography followed by sandwich ELISA. We recently found antigen-antibody reactions that were inhibited by lectin binding to glycans on the glycoprotein antigen, leading to a convenient glycoform-specific assay. Indeed, Sambucus sieboldiana agglutinin (SSA) lectin, a binder to sialylα2,6galactose residue, inhibited antibody binding to α2,6-sialylated transferrin (Tf) (SSA inhibition). SSA inhibition was not observed with other glycoforms, such as periodate-treated, sialidase-treated and sialidase/galactosidase-treated Tf, suggesting that the assay was glycoform-specific. SSA inhibition was also applicable for visualizing localization of α2,6-sialylated-Tf in a liver section. This is the first immunohistochemical demonstration of glycoform localization in a tissue section. SSA inhibition was utilized for establishing ELISA to quantify α2,6-sialylated carcinoembryonic antigen (CEA), a marker for various cancers. In addition, α2,6-sialylated-CEA was visualized in a colonic adenocarcinoma section by SSA inhibition. The method would further be applicable to a simple and rapid estimation of other α2,6-sialylated glycoproteins and have a potential aid to histopathological diagnosis. 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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27 pages, 4257 KiB

Open AccessReview

Epitopes of MUC1 Tandem Repeats in Cancer as Revealed by Antibody Crystallography: Toward Glycopeptide Signature-Guided Therapy

by Dapeng Zhou, Lan Xu, Wei Huang and Torsten Tonn

Molecules 2018, 23(6), 1326; https://doi.org/10.3390/molecules23061326 - 31 May 2018

Cited by 34 | Viewed by 9489

Abstract

Abnormally O-glycosylated MUC1 tandem repeat glycopeptide epitopes expressed by multiple types of cancer have long been attractive targets for therapy in the race against genetic mutations of tumor cells. Glycopeptide signature-guided therapy might be a more promising avenue than mutation signature-guided therapy. [...] Read more.

Abnormally O-glycosylated MUC1 tandem repeat glycopeptide epitopes expressed by multiple types of cancer have long been attractive targets for therapy in the race against genetic mutations of tumor cells. Glycopeptide signature-guided therapy might be a more promising avenue than mutation signature-guided therapy. Three O-glycosylated peptide motifs, PDTR, GSTA, and GVTS, exist in a tandem repeat HGVTSAPDTRPAPGSTAPPA, containing five O-glycosylation sites. The exact peptide and sugar residues involved in antibody binding are poorly defined. Co-crystal structures of glycopeptides and respective monoclonal antibodies are very few. Here we review 3 groups of monoclonal antibodies: antibodies which only bind to peptide portion, antibodies which only bind to sugar portion, and antibodies which bind to both peptide and sugar portions. The antigenicity of peptide and sugar portions of glyco-MUC1 tandem repeat were analyzed according to available biochemical and structural data, especially the GSTA and GVTS motifs independent from the most studied PDTR. Tn is focused as a peptide-modifying residue in vaccine design, to induce glycopeptide-binding antibodies with cross reactivity to Tn-related tumor glycans, but not glycans of healthy cells. The unique requirement for the designs of antibody in antibody-drug conjugate, bi-specific antibodies, and chimeric antigen receptors are also discussed. Full article

(This article belongs to the Special Issue Conjugate Vaccines from Carbohydrate Antigens)

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10 pages, 640 KiB

Open AccessReview

Role of O-Acetylation in the Immunogenicity of Bacterial Polysaccharide Vaccines

by Francesco Berti, Riccardo De Ricco and Rino Rappuoli

Molecules 2018, 23(6), 1340; https://doi.org/10.3390/molecules23061340 - 2 Jun 2018

Cited by 61 | Viewed by 9206

Abstract

The incidence of infectious diseases caused by several bacterial pathogens such as Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis, has been dramatically reduced over the last 25 years through the use of glycoconjugate vaccines. The structures of the bacterial [...] Read more.

The incidence of infectious diseases caused by several bacterial pathogens such as Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis, has been dramatically reduced over the last 25 years through the use of glycoconjugate vaccines. The structures of the bacterial capsular polysaccharide (CPS) antigens, extracted and purified from microbial cultures and obtained with very high purity, show that many of them are decorated by O-acetyl groups. While these groups are often considered important for the structural identity of the polysaccharides, they play a major role in the functional immune response to some vaccines such as meningococcal serogroup A and Salmonella typhi Vi, but do not seem to be important for many others, such as meningococcal serogroups C, W, Y, and type III Group B Streptococcus. This review discusses the O-acetylation status of CPSs and its role in the immunological responses of these antigens. Full article

(This article belongs to the Special Issue Conjugate Vaccines from Carbohydrate Antigens)

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16 pages, 1381 KiB

Open AccessReview

Receptor–Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment

by Dasiel O. Borroto-Escuela, Manuel Narváez, Patrizia Ambrogini, Luca Ferraro, Ismel Brito, Wilber Romero-Fernandez, Yuniesky Andrade-Talavera, Antonio Flores-Burgess, Carmelo Millon, Belen Gago, Jose Angel Narvaez, Yuji Odagaki, Miklos Palkovits, Zaida Diaz-Cabiale and Kjell Fuxe

Molecules 2018, 23(6), 1341; https://doi.org/10.3390/molecules23061341 - 3 Jun 2018

Cited by 45 | Viewed by 12838

Abstract

Due to the binding to a number of proteins to the receptor protomers in receptor heteromers in the brain, the term “heteroreceptor complexes” was introduced. A number of serotonin 5-HT1A heteroreceptor complexes were recently found to be linked to the ascending 5-HT pathways [...] Read more.

Due to the binding to a number of proteins to the receptor protomers in receptor heteromers in the brain, the term “heteroreceptor complexes” was introduced. A number of serotonin 5-HT1A heteroreceptor complexes were recently found to be linked to the ascending 5-HT pathways known to have a significant role in depression. The 5-HT1A–FGFR1 heteroreceptor complexes were involved in synergistically enhancing neuroplasticity in the hippocampus and in the dorsal raphe 5-HT nerve cells. The 5-HT1A protomer significantly increased FGFR1 protomer signaling in wild-type rats. Disturbances in the 5-HT1A–FGFR1 heteroreceptor complexes in the raphe-hippocampal 5-HT system were found in a genetic rat model of depression (Flinders sensitive line (FSL) rats). Deficits in FSL rats were observed in the ability of combined FGFR1 and 5-HT1A agonist cotreatment to produce antidepressant-like effects. It may in part reflect a failure of FGFR1 treatment to uncouple the 5-HT1A postjunctional receptors and autoreceptors from the hippocampal and dorsal raphe GIRK channels, respectively. This may result in maintained inhibition of hippocampal pyramidal nerve cell and dorsal raphe 5-HT nerve cell firing. Also, 5-HT1A–5-HT2A isoreceptor complexes were recently demonstrated to exist in the hippocampus and limbic cortex. They may play a role in depression through an ability of 5-HT2A protomer signaling to inhibit the 5-HT1A protomer recognition and signaling. Finally, galanin (1–15) was reported to enhance the antidepressant effects of fluoxetine through the putative formation of GalR1–GalR2–5-HT1A heteroreceptor complexes. Taken together, these novel 5-HT1A receptor complexes offer new targets for treatment of depression. Full article

(This article belongs to the Special Issue Protein-Protein Interactions)

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21 pages, 18080 KiB

Open AccessReview

Ball Milling Promoted N-Heterocycles Synthesis

by Taghreed H. El-Sayed, Asmaa Aboelnaga, Mohamed A. El-Atawy and Mohamed Hagar

Molecules 2018, 23(6), 1348; https://doi.org/10.3390/molecules23061348 - 4 Jun 2018

Cited by 41 | Viewed by 7822

Abstract

In the last years, numerous protocols have been published using ball milling for organic synthesis. Compared to other methods such as microwave or ultrasound irradiation and ionic liquids, ball mill chemistry is an economical, and ecofriendly method in organic synthesis that is rather [...] Read more.

In the last years, numerous protocols have been published using ball milling for organic synthesis. Compared to other methods such as microwave or ultrasound irradiation and ionic liquids, ball mill chemistry is an economical, and ecofriendly method in organic synthesis that is rather underrepresented in the knowledge of organic chemists. The aim of this review is to explore the advantages of the application of ball milling in synthesis of N-heterocyclic compounds. Full article

(This article belongs to the Section Green Chemistry)

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23 pages, 733 KiB

Open AccessReview

Bactericidal Properties of Plants-Derived Metal and Metal Oxide Nanoparticles (NPs)

by Sin-Yeang Teow, Magdelyn Mei-Theng Wong, Hooi-Yeen Yap, Suat-Cheng Peh and Kamyar Shameli

Molecules 2018, 23(6), 1366; https://doi.org/10.3390/molecules23061366 - 6 Jun 2018

Cited by 42 | Viewed by 6931

Abstract

Nanoparticles (NPs) are nano-sized particles (generally 1–100 nm) that can be synthesized through various methods. The wide range of physicochemical characteristics of NPs permit them to have diverse biological functions. These particles are versatile and can be adopted into various applications, particularly in [...] Read more.

Nanoparticles (NPs) are nano-sized particles (generally 1–100 nm) that can be synthesized through various methods. The wide range of physicochemical characteristics of NPs permit them to have diverse biological functions. These particles are versatile and can be adopted into various applications, particularly in biomedical field. In the past five years, NPs’ roles in biomedical applications have drawn considerable attentions, and novel NPs with improved functions and reduced toxicity are continuously increasing. Extensive studies have been carried out in evaluating antibacterial potentials of NPs. The promising antibacterial effects exhibited by NPs highlight the potential of developing them into future generation of antimicrobial agents. There are various methods to synthesize NPs, and each of the method has significant implication on the biological action of NPs. Among all synthetic methods, green technology is the least toxic biological route, which is particularly suitable for biomedical applications. This mini-review provides current update on the antibacterial effects of NPs synthesized by green technology using plants. Underlying challenges in developing NPs into future antibacterials in clinics are also discussed at the present review. Full article

(This article belongs to the Special Issue Metallic Nanoparticles: From Synthesis, Structure-Property Relationships to Applications)

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25 pages, 3612 KiB

Open AccessReview

Review on Abyssomicins: Inhibitors of the Chorismate Pathway and Folate Biosynthesis

by Carmen Sadaka, Edmund Ellsworth, Paul Robert Hansen, Richard Ewin, Peter Damborg and Jeffrey L. Watts

Molecules 2018, 23(6), 1371; https://doi.org/10.3390/molecules23061371 - 6 Jun 2018

Cited by 36 | Viewed by 9278

Abstract

Antifolates targeting folate biosynthesis within the shikimate-chorismate-folate metabolic pathway are ideal and selective antimicrobials, since higher eukaryotes lack this pathway and rely on an exogenous source of folate. Resistance to the available antifolates, inhibiting the folate pathway, underlines the need for novel antibiotic [...] Read more.

Antifolates targeting folate biosynthesis within the shikimate-chorismate-folate metabolic pathway are ideal and selective antimicrobials, since higher eukaryotes lack this pathway and rely on an exogenous source of folate. Resistance to the available antifolates, inhibiting the folate pathway, underlines the need for novel antibiotic scaffolds and molecular targets. While para-aminobenzoic acid synthesis within the chorismate pathway constitutes a novel molecular target for antifolates, abyssomicins are its first known natural inhibitors. This review describes the abyssomicin family, a novel spirotetronate polyketide Class I antimicrobial. It summarizes synthetic and biological studies, structural, biosynthetic, and biological properties of the abyssomicin family members. This paper aims to explain their molecular target, mechanism of action, structure–activity relationship, and to explore their biological and pharmacological potential. Thirty-two natural abyssomicins and numerous synthetic analogues have been reported. The biological activity of abyssomicins includes their antimicrobial activity against Gram-positive bacteria and mycobacteria, antitumor properties, latent human immunodeficiency virus (HIV) reactivator, anti-HIV and HIV replication inducer properties. Their antimalarial properties have not been explored yet. Future analoging programs using the structure–activity relationship data and synthetic approaches may provide a novel abyssomicin structure that is active and devoid of cytotoxicity. Abyssomicin J and atrop-o-benzyl-desmethylabyssomicin C constitute promising candidates for such programs. Full article

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14 pages, 1014 KiB

Open AccessReview

Pre-treatment of Oil Palm Biomass for Fermentable Sugars Production

by Nur Fatin Athirah Ahmad Rizal, Mohamad Faizal Ibrahim, Mohd Rafein Zakaria, Suraini Abd-Aziz, Phang Lai Yee and Mohd Ali Hassan

Molecules 2018, 23(6), 1381; https://doi.org/10.3390/molecules23061381 - 7 Jun 2018

Cited by 57 | Viewed by 8590

Abstract

Malaysia is the second largest palm oil producer in the world and this industry generates more than 80 million tonnes of biomass every year. When considering the potential of this biomass to be used as a fermentation feedstock, many studies have been conducted [...] Read more.

Malaysia is the second largest palm oil producer in the world and this industry generates more than 80 million tonnes of biomass every year. When considering the potential of this biomass to be used as a fermentation feedstock, many studies have been conducted to develop a complete process for sugar production. One of the essential processes is the pre-treatment to modify the lignocellulosic components by altering the structural arrangement and/or removing lignin component to expose the internal structure of cellulose and hemicellulose for cellulases to digest it into sugars. Each of the pre-treatment processes that were developed has their own advantages and disadvantages, which are reviewed in this study. Full article

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

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14 pages, 6142 KiB

Open AccessReview

14-3-3: A Case Study in PPI Modulation

by Alice Ballone, Federica Centorrino and Christian Ottmann

Molecules 2018, 23(6), 1386; https://doi.org/10.3390/molecules23061386 - 8 Jun 2018

Cited by 44 | Viewed by 8751

Abstract

In recent years, targeting the complex network of protein–protein interactions (PPIs) has been identified as a promising drug-discovery approach to develop new therapeutic strategies. 14-3-3 is a family of eukaryotic conserved regulatory proteins which are of high interest as potential targets for pharmacological [...] Read more.

In recent years, targeting the complex network of protein–protein interactions (PPIs) has been identified as a promising drug-discovery approach to develop new therapeutic strategies. 14-3-3 is a family of eukaryotic conserved regulatory proteins which are of high interest as potential targets for pharmacological intervention in human diseases, such as cancer and neurodegenerative and metabolic disorders. This viewpoint is built on the “hub” nature of the 14-3-3 proteins, binding to several hundred identified partners, consequently implicating them in a multitude of different cellular mechanisms. In this review, we provide an overview of the structural and biological features of 14-3-3 and the modulation of 14-3-3 PPIs for discovering small molecular inhibitors and stabilizers of 14-3-3 PPIs. Full article

(This article belongs to the Special Issue Protein-Protein Interactions)

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32 pages, 5558 KiB

Open AccessReview

An Overview of Biotransformation and Toxicity of Diterpenes

by Ingrid P. De Sousa, Maria V. Sousa Teixeira and Niege A. Jacometti Cardoso Furtado

Molecules 2018, 23(6), 1387; https://doi.org/10.3390/molecules23061387 - 8 Jun 2018

Cited by 58 | Viewed by 9141

Abstract

Diterpenes have been identified as active compounds in several medicinal plants showing remarkable biological activities, and some isolated diterpenes are produced at commercial scale to be used as medicines, food additives, in the synthesis of fragrances, or in agriculture. There is great interest [...] Read more.

Diterpenes have been identified as active compounds in several medicinal plants showing remarkable biological activities, and some isolated diterpenes are produced at commercial scale to be used as medicines, food additives, in the synthesis of fragrances, or in agriculture. There is great interest in developing methods to obtain derivatives of these compounds, and biotransformation processes are interesting tools for the structural modification of natural products with complex chemical structures. Biotransformation processes also have a crucial role in drug development and/or optimization. The understanding of the metabolic pathways for both phase I and II biotransformation of new drug candidates is mandatory for toxicity and efficacy evaluation and part of preclinical studies. This review presents an overview of biotransformation processes of diterpenes carried out by microorganisms, plant cell cultures, animal and human liver microsomes, and rats, chickens, and swine in vivo and highlights the main enzymatic reactions involved in these processes and the role of diterpenes that may be effectively exploited by other fields. Full article

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

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14 pages, 1328 KiB

Open AccessReview

Cocoa Shell: A By-Product with Great Potential for Wide Application

by Jelena Panak Balentić, Đurđica Ačkar, Stela Jokić, Antun Jozinović, Jurislav Babić, Borislav Miličević, Drago Šubarić and Nika Pavlović

Molecules 2018, 23(6), 1404; https://doi.org/10.3390/molecules23061404 - 9 Jun 2018

Cited by 130 | Viewed by 19825

Abstract

Solving the problem of large quantities of organic waste, which represents an enormous ecological and financial burden for all aspects of the process industry, is a necessity. Therefore, there is an emerged need to find specific solutions to utilize raw materials as efficiently [...] Read more.

Solving the problem of large quantities of organic waste, which represents an enormous ecological and financial burden for all aspects of the process industry, is a necessity. Therefore, there is an emerged need to find specific solutions to utilize raw materials as efficiently as possible in the production process. The cocoa shell is a valuable by-product obtained from the chocolate industry. It is rich in protein, dietary fiber, and ash, as well as in some other valuable bioactive compounds, such as methylxanthines and phenolics. This paper gives an overview of published results related to the cocoa shell, mostly on important bioactive compounds and possible applications of the cocoa shell in different areas. The cocoa shell, due to its nutritional value and high-value bioactive compounds, could become a desirable raw material in a large spectrum of functional, pharmaceutical, or cosmetic products, as well as in the production of energy or biofuels in the near future. Full article

(This article belongs to the Section Natural Products Chemistry)

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26 pages, 2929 KiB

Open AccessReview

Gold-Based Medicine: A Paradigm Shift in Anti-Cancer Therapy?

by Chien Ing Yeo, Kah Kooi Ooi and Edward R. T. Tiekink

Molecules 2018, 23(6), 1410; https://doi.org/10.3390/molecules23061410 - 11 Jun 2018

Cited by 160 | Viewed by 11457

Abstract

A new era of metal-based drugs started in the 1960s, heralded by the discovery of potent platinum-based complexes, commencing with cisplatin [(H₃N)₂PtCl₂], which are effective anti-cancer chemotherapeutic drugs. While clinical applications of gold-based drugs largely relate to [...] Read more.

A new era of metal-based drugs started in the 1960s, heralded by the discovery of potent platinum-based complexes, commencing with cisplatin [(H₃N)₂PtCl₂], which are effective anti-cancer chemotherapeutic drugs. While clinical applications of gold-based drugs largely relate to the treatment of rheumatoid arthritis, attention has turned to the investigation of the efficacy of gold(I) and gold(III) compounds for anti-cancer applications. This review article provides an account of the latest research conducted during the last decade or so on the development of gold compounds and their potential activities against several cancers as well as a summary of possible mechanisms of action/biological targets. The promising activities and increasing knowledge of gold-based drug metabolism ensures that continued efforts will be made to develop gold-based anti-cancer agents. Full article

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

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20 pages, 4025 KiB

Open AccessFeature PaperReview

Prussian Blue Nanoparticles as a Versatile Photothermal Tool

by Giacomo Dacarro, Angelo Taglietti and Piersandro Pallavicini

Molecules 2018, 23(6), 1414; https://doi.org/10.3390/molecules23061414 - 11 Jun 2018

Cited by 89 | Viewed by 13526

Abstract

Prussian blue (PB) is a coordination polymer studied since the early 18th century, historically known as a pigment. PB can be prepared in colloidal form with a straightforward synthesis. It has a strong charge-transfer absorption centered at ~700 nm, with a large tail [...] Read more.

Prussian blue (PB) is a coordination polymer studied since the early 18th century, historically known as a pigment. PB can be prepared in colloidal form with a straightforward synthesis. It has a strong charge-transfer absorption centered at ~700 nm, with a large tail in the Near-IR range. Irradiation of this band results in thermal relaxation and can be exploited to generate a local hyperthermia by irradiating in the so-called bio-transparent Near-IR window. PB nanoparticles are fully biocompatible (PB has already been approved by FDA) and biodegradable, this making them ideal candidates for in vivo use. While papers based on the imaging, drug-delivery and absorbing properties of PB nanoparticles have appeared and have been reviewed in the past decades, a very recent interest is flourishing with the use of PB nanoparticles as photothermal agents in biomedical applications. This review summarizes the syntheses and the optical features of PB nanoparticles in relation to their photothermal use and describes the state of the art of PB nanoparticles as photothermal agents, also in combination with diagnostic techniques. Full article

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

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20 pages, 4292 KiB

Open AccessReview

Polyamidoamine Dendrimers for Enhanced Solubility of Small Molecules and Other Desirable Properties for Site Specific Delivery: Insights from Experimental and Computational Studies

by Daniel M. Shadrack, Hulda S. Swai, Joan J. E. Munissi, Egid B. Mubofu and Stephen S. Nyandoro

Molecules 2018, 23(6), 1419; https://doi.org/10.3390/molecules23061419 - 12 Jun 2018

Cited by 45 | Viewed by 8421

Abstract

Clinical applications of many small molecules are limited due to poor solubility and lack of controlled release besides lack of other desirable properties. Experimental and computational studies have reported on the therapeutic potential of polyamidoamine (PAMAM) dendrimers as solubility enhancers in pre-clinical and [...] Read more.

Clinical applications of many small molecules are limited due to poor solubility and lack of controlled release besides lack of other desirable properties. Experimental and computational studies have reported on the therapeutic potential of polyamidoamine (PAMAM) dendrimers as solubility enhancers in pre-clinical and clinical settings. Besides formulation strategies, factors such as pH, PAMAM dendrimer generation, PAMAM dendrimer concentration, nature of the PAMAM core, special ligand and surface modifications of PAMAM dendrimer have an influence on drug solubility and other recommendable pharmacological properties. This review, therefore, compiles the recently reported applications of PAMAM dendrimers in pre-clinical and clinical uses as enhancers of solubility and other desirable properties such as sustained and controlled release, bioavailability, bio-distribution, toxicity reduction or enhancement, and targeted delivery of small molecules with emphasis on cancer treatment. Full article

(This article belongs to the Special Issue Dendrimers in Medicine)

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12 pages, 708 KiB

Open AccessFeature PaperReview

Recent Advances in Applications of Ionic Liquids in Miniaturized Microextraction Techniques

by Maria Kissoudi and Victoria Samanidou

Molecules 2018, 23(6), 1437; https://doi.org/10.3390/molecules23061437 - 13 Jun 2018

Cited by 74 | Viewed by 5483

Abstract

Green sample preparation is one of the most challenging aspects in green analytical chemistry. In this framework, miniaturized microextraction techniques have been developed and are widely performed due to their numerous positive features such as simplicity, limited need for organic solvents, instrumentation of [...] Read more.

Green sample preparation is one of the most challenging aspects in green analytical chemistry. In this framework, miniaturized microextraction techniques have been developed and are widely performed due to their numerous positive features such as simplicity, limited need for organic solvents, instrumentation of low cost and short time of extraction. Also, ionic liquids (ILs) have unequivocally a “green” character, which they owe to their unique properties including the re-usage, the high reaction efficiency and selectivity in room temperature, the ability to dissolve both organic and inorganic compounds, and thermal stability. In the present review, the recent advances in the application of ionic liquids in miniaturized liquid and solid phase extraction techniques as extractants, intermediate solvents, mediators and desorption solvents are discussed, quoting the advantages and drawbacks of each individual technique. Some of the most important sample preparation techniques covered include solid-phase microextraction (SPME), dispersive liquid-liquid microextraction (DLLME), single-drop microextraction (SDME), stir bar sorptive extraction (SBSE), and stir cake sorptive extraction (SCSE). Full article

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

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11 pages, 7018 KiB

Open AccessReview

Cobalt-Catalyzed (Hetero)arylation of Saturated Cyclic Amines with Grignard Reagents

by Baptiste Barré, Laurine Gonnard, Amandine Guérinot and Janine Cossy

Molecules 2018, 23(6), 1449; https://doi.org/10.3390/molecules23061449 - 14 Jun 2018

Cited by 9 | Viewed by 5643

Abstract

(Hetero)aryl substituted saturated cyclic amines are ubiquitous scaffolds in biologically active molecules. Metal-catalyzed cross-couplings between halogeno N-heterocycles and organometallic species are efficient and modular reactions to access these attractive scaffolds. An overview of our work concerning the cobalt-catalyzed arylation of iodo-substituted cyclic [...] Read more.

(Hetero)aryl substituted saturated cyclic amines are ubiquitous scaffolds in biologically active molecules. Metal-catalyzed cross-couplings between halogeno N-heterocycles and organometallic species are efficient and modular reactions to access these attractive scaffolds. An overview of our work concerning the cobalt-catalyzed arylation of iodo-substituted cyclic amines is presented. Full article

(This article belongs to the Special Issue Frontiers in Metal-Catalysed Cross-Coupling Reactions for the Synthesis and Functionalisation of Heterocycles)

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18 pages, 686 KiB

Open AccessReview

Protein Carriers for Glycoconjugate Vaccines: History, Selection Criteria, Characterization and New Trends

by Francesca Micoli, Roberto Adamo and Paolo Costantino

Molecules 2018, 23(6), 1451; https://doi.org/10.3390/molecules23061451 - 15 Jun 2018

Cited by 92 | Viewed by 11400

Abstract

Currently licensed glycoconjugate vaccines are composed of a carbohydrate moiety covalently linked to a protein carrier. Polysaccharides are T-cell independent antigens able to directly stimulate B cells to produce antibodies. Disease burden caused by polysaccharide-encapsulated bacteria is highest in the first year of [...] Read more.

Currently licensed glycoconjugate vaccines are composed of a carbohydrate moiety covalently linked to a protein carrier. Polysaccharides are T-cell independent antigens able to directly stimulate B cells to produce antibodies. Disease burden caused by polysaccharide-encapsulated bacteria is highest in the first year of life, where plain polysaccharides are not generally immunogenic, limiting their use as vaccines. This limitation has been overcome by covalent coupling carbohydrate antigens to proteins that provide T cell epitopes. In addition to the protein carriers currently used in licensed glycoconjugate vaccines, there is a search for new protein carriers driven by several considerations: (i) concerns that pre-exposure or co-exposure to a given carrier can lead to immune interference and reduction of the anti-carbohydrate immune response; (ii) increasing interest to explore the dual role of proteins as carrier and protective antigen; and (iii) new ways to present carbohydrates antigens to the immune system. Protein carriers can be directly coupled to activated glycans or derivatized to introduce functional groups for subsequent conjugation. Proteins can be genetically modified to pre-determine the site of glycans attachment by insertion of unnatural amino acids bearing specific functional groups, or glycosylation consensus sequences for in vivo expression of the glycoconjugate. A large portion of the new protein carriers under investigation are recombinant ones, but more complex systems such as Outer Membrane Vesicles and other nanoparticles are being investigated. Selection criteria for new protein carriers are based on several aspects including safety, manufacturability, stability, reactivity toward conjugation, and preclinical evidence of immunogenicity of corresponding glycoconjugates. Characterization panels of protein carriers include tests before conjugation, after derivatization when applicable, and after conjugation. Glycoconjugate vaccines based on non-covalent association of carrier systems to carbohydrates are being investigated with promising results in animal models. The ability of these systems to convert T-independent carbohydrate antigens into T-dependent ones, in comparison to traditional glycoconjugates, needs to be assessed in humans. Full article

(This article belongs to the Special Issue Conjugate Vaccines from Carbohydrate Antigens)

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25 pages, 10907 KiB

Open AccessReview

Recent Reports of Solid-Phase Cyclohexapeptide Synthesis and Applications

by Allan M. Prior, Taylor Hori, Ashriel Fishman and Dianqing Sun

Molecules 2018, 23(6), 1475; https://doi.org/10.3390/molecules23061475 - 18 Jun 2018

Cited by 12 | Viewed by 11640

Abstract

Macrocyclic peptides are privileged scaffolds for drug development and constitute a significant portion of macrocyclic drugs on the market today in fields spanning from infectious disease to oncology. Developing orally bioavailable peptide-based drugs remains a challenging task; however, macrocyclization of linear peptides can [...] Read more.

Macrocyclic peptides are privileged scaffolds for drug development and constitute a significant portion of macrocyclic drugs on the market today in fields spanning from infectious disease to oncology. Developing orally bioavailable peptide-based drugs remains a challenging task; however, macrocyclization of linear peptides can be an effective strategy to improve membrane permeability, proteolytic stability, oral bioavailability, and overall drug-like characteristics for this class. Significant advances in solid-phase peptide synthesis (SPPS) have enabled the efficient construction of macrocyclic peptide and peptidomimetic libraries with macrolactamization being performed on-resin or in solution phase. The primary goal of this review is to summarize solid-phase cyclohexapeptide synthesis using the on-resin and solution-phase macrocyclization methodologies published since 2013. We also highlight their broad applications ranging from natural product total synthesis, synthetic methodology development, and medicinal chemistry, to drug development and analyses of conformational and physiochemical properties. Full article

(This article belongs to the Special Issue Solid Phase Synthesis)

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61 pages, 2797 KiB

Open AccessReview

Comparison of Strategies to Overcome Drug Resistance: Learning from Various Kingdoms

by Hiroshi Ogawara

Molecules 2018, 23(6), 1476; https://doi.org/10.3390/molecules23061476 - 18 Jun 2018

Cited by 6 | Viewed by 6595

Abstract

Drug resistance, especially antibiotic resistance, is a growing threat to human health. To overcome this problem, it is significant to know precisely the mechanisms of drug resistance and/or self-resistance in various kingdoms, from bacteria through plants to animals, once more. This review compares [...] Read more.

Drug resistance, especially antibiotic resistance, is a growing threat to human health. To overcome this problem, it is significant to know precisely the mechanisms of drug resistance and/or self-resistance in various kingdoms, from bacteria through plants to animals, once more. This review compares the molecular mechanisms of the resistance against phycotoxins, toxins from marine and terrestrial animals, plants and fungi, and antibiotics. The results reveal that each kingdom possesses the characteristic features. The main mechanisms in each kingdom are transporters/efflux pumps in phycotoxins, mutation and modification of targets and sequestration in marine and terrestrial animal toxins, ABC transporters and sequestration in plant toxins, transporters in fungal toxins, and various or mixed mechanisms in antibiotics. Antibiotic producers in particular make tremendous efforts for avoiding suicide, and are more flexible and adaptable to the changes of environments. With these features in mind, potential alternative strategies to overcome these resistance problems are discussed. This paper will provide clues for solving the issues of drug resistance. Full article

(This article belongs to the Section Natural Products Chemistry)

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51 pages, 2982 KiB

Open AccessReview

Targeting Transcription Factors for Cancer Treatment

by Mélanie Lambert, Samy Jambon, Sabine Depauw and Marie-Hélène David-Cordonnier

Molecules 2018, 23(6), 1479; https://doi.org/10.3390/molecules23061479 - 19 Jun 2018

Cited by 272 | Viewed by 23611

Abstract

Transcription factors are involved in a large number of human diseases such as cancers for which they account for about 20% of all oncogenes identified so far. For long time, with the exception of ligand-inducible nuclear receptors, transcription factors were considered as “undruggable” [...] Read more.

Transcription factors are involved in a large number of human diseases such as cancers for which they account for about 20% of all oncogenes identified so far. For long time, with the exception of ligand-inducible nuclear receptors, transcription factors were considered as “undruggable” targets. Advances knowledge of these transcription factors, in terms of structure, function (expression, degradation, interaction with co-factors and other proteins) and the dynamics of their mode of binding to DNA has changed this postulate and paved the way for new therapies targeted against transcription factors. Here, we discuss various ways to target transcription factors in cancer models: by modulating their expression or degradation, by blocking protein/protein interactions, by targeting the transcription factor itself to prevent its DNA binding either through a binding pocket or at the DNA-interacting site, some of these inhibitors being currently used or evaluated for cancer treatment. Such different targeting of transcription factors by small molecules is facilitated by modern chemistry developing a wide variety of original molecules designed to specifically abort transcription factor and by an increased knowledge of their pathological implication through the use of new technologies in order to make it possible to improve therapeutic control of transcription factor oncogenic functions. Full article

(This article belongs to the Special Issue Transcription Factors as Therapeutic Targets)

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31 pages, 1919 KiB

Open AccessReview

Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity

by Petr Ježek, Martin Jabůrek, Blanka Holendová and Lydie Plecitá-Hlavatá

Molecules 2018, 23(6), 1483; https://doi.org/10.3390/molecules23061483 - 19 Jun 2018

Cited by 68 | Viewed by 11932

Abstract

Fatty acid (FA)-stimulated insulin secretion (FASIS) is reviewed here in contrast to type 2 diabetes etiology, resulting from FA overload, oxidative stress, intermediate hyperinsulinemia, and inflammation, all converging into insulin resistance. Focusing on pancreatic islet β-cells, we compare the physiological FA roles with [...] Read more.

Fatty acid (FA)-stimulated insulin secretion (FASIS) is reviewed here in contrast to type 2 diabetes etiology, resulting from FA overload, oxidative stress, intermediate hyperinsulinemia, and inflammation, all converging into insulin resistance. Focusing on pancreatic islet β-cells, we compare the physiological FA roles with the pathological ones. Considering FAs not as mere amplifiers of glucose-stimulated insulin secretion (GSIS), but as parallel insulin granule exocytosis inductors, partly independent of the K_ATP channel closure, we describe the FA initiating roles in the prediabetic state that is induced by retardations in the glycerol-3-phosphate (glucose)-promoted glycerol/FA cycle and by the impaired GPR40/FFA1 (free FA1) receptor pathway, specifically in its amplification by the redox-activated mitochondrial phospholipase, iPLA2γ. Also, excessive dietary FAs stimulate intestine enterocyte incretin secretion, further elevating GSIS, even at low glucose levels, thus contributing to diabetic hyperinsulinemia. With overnutrition and obesity, the FA overload causes impaired GSIS by metabolic dysbalance, paralleled by oxidative and metabolic stress, endoplasmic reticulum stress and numerous pro-apoptotic signaling, all leading to decreased β-cell survival. Lipotoxicity is exerted by saturated FAs, whereas ω-3 polyunsaturated FAs frequently exert antilipotoxic effects. FA-facilitated inflammation upon the recruitment of excess M1 macrophages into islets (over resolving M2 type), amplified by cytokine and chemokine secretion by β-cells, leads to an inevitable failure of pancreatic β-cells. 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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25 pages, 496 KiB

Open AccessReview

A Review of the Extraction and Determination Methods of Thirteen Essential Vitamins to the Human Body: An Update from 2010

by Yuan Zhang, Wei-e Zhou, Jia-qing Yan, Min Liu, Yu Zhou, Xin Shen, Ying-lin Ma, Xue-song Feng, Jun Yang and Guo-hui Li

Molecules 2018, 23(6), 1484; https://doi.org/10.3390/molecules23061484 - 19 Jun 2018

Cited by 143 | Viewed by 15329

Abstract

Vitamins are a class of essential nutrients in the body; thus, they play important roles in human health. The chemicals are involved in many physiological functions and both their lack and excess can put health at risk. Therefore, the establishment of methods for [...] Read more.

Vitamins are a class of essential nutrients in the body; thus, they play important roles in human health. The chemicals are involved in many physiological functions and both their lack and excess can put health at risk. Therefore, the establishment of methods for monitoring vitamin concentrations in different matrices is necessary. In this review, an updated overview of the main pretreatments and determination methods that have been used since 2010 is given. Ultrasonic assisted extraction, liquid–liquid extraction, solid phase extraction and dispersive liquid–liquid microextraction are the most common pretreatment methods, while the determination methods involve chromatography methods, electrophoretic methods, microbiological assays, immunoassays, biosensors and several other methods. Different pretreatments and determination methods are discussed. Full article

(This article belongs to the Special Issue Modern Sample Preparation Approaches for Separation Science)

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19 pages, 872 KiB

Open AccessReview

Mitochondria-Targeting Small Molecules Effectively Prevent Cardiotoxicity Induced by Doxorubicin

by Wei Shi, Hongkuan Deng, Jianyong Zhang, Ying Zhang, Xiufang Zhang and Guozhen Cui

Molecules 2018, 23(6), 1486; https://doi.org/10.3390/molecules23061486 - 19 Jun 2018

Cited by 26 | Viewed by 7667

Abstract

Doxorubicin (Dox) is a chemotherapeutic agent widely used for the treatment of numerous cancers. However, the clinical use of Dox is limited by its unwanted cardiotoxicity. Mitochondrial dysfunction has been associated with Dox-induced cardiotoxicity. To mitigate Dox-related cardiotoxicity, considerable successful examples of a [...] Read more.

Doxorubicin (Dox) is a chemotherapeutic agent widely used for the treatment of numerous cancers. However, the clinical use of Dox is limited by its unwanted cardiotoxicity. Mitochondrial dysfunction has been associated with Dox-induced cardiotoxicity. To mitigate Dox-related cardiotoxicity, considerable successful examples of a variety of small molecules that target mitochondria to modulate Dox-induced cardiotoxicity have appeared in recent years. Here, we review the related literatures and discuss the evidence showing that mitochondria-targeting small molecules are promising cardioprotective agents against Dox-induced cardiac events. Full article

(This article belongs to the Special Issue Recent Advances in Anticancer Drugs)

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29 pages, 7862 KiB

Open AccessFeature PaperReview

Synthesis and Reactions of α-Hydroxyphosphonates

by Zita Rádai and György Keglevich

Molecules 2018, 23(6), 1493; https://doi.org/10.3390/molecules23061493 - 20 Jun 2018

Cited by 73 | Viewed by 13793

Abstract

This review summarizes the main synthetic routes towards α-hydroxyphosphonates that are known as enzyme inhibitors, herbicides and antioxidants, moreover, a number of representatives express antibacterial or antifungal effect. Special attention is devoted to green chemical aspects. α-Hydroxyphosphonates are also versatile intermediates for other [...] Read more.

This review summarizes the main synthetic routes towards α-hydroxyphosphonates that are known as enzyme inhibitors, herbicides and antioxidants, moreover, a number of representatives express antibacterial or antifungal effect. Special attention is devoted to green chemical aspects. α-Hydroxyphosphonates are also versatile intermediates for other valuable derivatives. O-Alkylation and O-acylation are typical reactions to afford α-alkoxy-, or α-acyloxyphosphonates, respectively. The oxidation of hydroxyphosphonates leads to ketophosphonates. The hydroxy function at the α carbon atom of hydroxyphosphonates may be replaced by a halogen atom. α-Aminophosphonates formed in the nucleophilic substitution reaction of α-hydroxyphosphonates with primary or secondary amines are also potentially bioactive compounds. Another typical reaction is the base-catalyzed rearrangement of α-hydroxy-phosphonates to phosphates. Hydrolysis of the ester function of hydroxyphosphonates leads to the corresponding phosphonic acids. Full article

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

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9 pages, 2514 KiB

Open AccessBrief Report

Straightforward Synthesis of Bifunctional Phosphorus Phenols via Phosphination of In Situ Generated o-Quinone Methides

by Zhangpei Chen, Qinglong Shi, Gongshu Wang, Siwen Chen and Jianshe Hu

Molecules 2018, 23(6), 1240; https://doi.org/10.3390/molecules23061240 - 23 May 2018

Cited by 6 | Viewed by 4038

Abstract

An efficient and practical approach towards bifunctional phosphorus phenols has been developed through a reaction of diphenylphosphine oxide and the o-quinone methides in situ generated from 2-tosylalkyl phenols under basic conditions. This protocol features simple experimental procedures under mild conditions and is [...] Read more.

An efficient and practical approach towards bifunctional phosphorus phenols has been developed through a reaction of diphenylphosphine oxide and the o-quinone methides in situ generated from 2-tosylalkyl phenols under basic conditions. This protocol features simple experimental procedures under mild conditions and is easily scaled up. With this method, a variety of diarylmethyl phosphine oxides can be produced with up to 92% yield. Full article

(This article belongs to the Section Organic Chemistry)

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2 pages, 765 KiB

Open AccessCorrection

Correction: Kim, D.-C.; et al. Steppogenin Isolated from Cudrania tricuspidata Shows Antineuroinflammatory Effects via NF-κB and MAPK Pathways in LPS-Stimulated BV2 and Primary Rat Microglial Cells. Molecules 2017, 22, 2130

by Dong-Cheol Kim, Tran Hong Quang, Hyuncheol Oh and Youn-Chul Kim

Molecules 2018, 23(6), 1244; https://doi.org/10.3390/molecules23061244 - 23 May 2018

Cited by 4 | Viewed by 2240

Abstract

The author wishes to make the following correction to this paper [1].[...] Full article

11 pages, 6386 KiB

Open AccessTechnical Note

Molecular Discrimination of Cynanchum wilfordii and Cynanchum auriculatum by InDel Markers of Chloroplast DNA

by Yonguk Kim, Hakjoon Choi, Jawon Shin, Ara Jo, Kyung-Eun Lee, Seung-Sik Cho, Yong-Pil Hwang and Chulyung Choi

Molecules 2018, 23(6), 1337; https://doi.org/10.3390/molecules23061337 - 1 Jun 2018

Cited by 17 | Viewed by 4832

Abstract

The tuber of Cynanchum wilfordii (Baekshuoh Radix in Korean) is an important medicinal herb in Korea and China; however, it is difficult to differentiate C. wilfordii from a related medicinal herb, C. auriculatum (Baishouwu Radix in Chinese). We sought to [...] Read more.

The tuber of Cynanchum wilfordii (Baekshuoh Radix in Korean) is an important medicinal herb in Korea and China; however, it is difficult to differentiate C. wilfordii from a related medicinal herb, C. auriculatum (Baishouwu Radix in Chinese). We sought to develop a molecular method that could be used to distinguish between the tubers of C. wilfordii and C. auriculatum. We aligned the chloroplast genome sequences (available in the NCBI database) of the two species and identified three species-specific insertion and deletion (InDel) sites in the trnQ-psbK, rps2-rpoC2, and psaJ-rpl33 intergenic spacer (IGS) regions. To confirm the presence of these three InDels and validate their use as markers, we designed three primer pairs to amplify the trnQ-psbK, rps2-rpoC2, and psaJ-rpl33 IGS regions. Polymerase chain reaction (PCR) amplification of the trnQ-psbK IGS region yielded a 249 bp fragment for C. wilfordii, and 419 bp fragment for C. auriculatum, whereas the rps2-rpoC2 IGS primers produced a 629 bp fragment from C. wilfordii and a 282 bp fragment from C. auriculatum. In the psaJ-rpl33 IGS region, allele fragments of 342 and 360 bp in length were amplified from C. wilfordii, whereas 249 and 250 bp fragment were amplified from C. auriculatum. We propose these three InDel markers as a valuable, simple, and efficient tool for identifying these medicinal herbs and will thus reduce adulteration of these herbal materials in commercial markets. Full article

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1 pages, 138 KiB

Open AccessCorrection

Correction: Sun, Y.; et al. Design, Synthesis, and Evaluation of Novel 2-Hydroxypyrrolobenzodiazepine-5,11-dione Analogues as Potent Angiotensin Converting Enzyme (ACE) Inhibitors. Molecules 2017, 22, 1739

by Ying Sun, Yujun Bai, Xirui He, Yajun Bai, Pei Liu, Zefeng Zhao, Xufei Chen and Xiaohui Zheng

Molecules 2018, 23(6), 1438; https://doi.org/10.3390/molecules23061438 - 13 Jun 2018

Cited by 1 | Viewed by 2168

Abstract

The author wishes to make the following corrections to this paper [...] Full article

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