Molecules

36 pages, 823 KiB

Open AccessReview

Anti-Diabetic Potential of Noni: The Yin and the Yang

by Pratibha V. Nerurkar^*, Phoebe W. Hwang and Erik Saksa

Laboratory of Metabolic Disorders and Alternative Medicine, Department of Molecular Biosciences and Bioengineering, College of Tropical Agriculture and Human Resources, University of Hawaii at Manoa, Honolulu, HI 96822, USA

Molecules 2015, 20(10), 17684-17719; https://doi.org/10.3390/molecules201017684 - 25 Sep 2015

Cited by 45 | Viewed by 19505

Abstract

Escalating trends of chronic diseases such as type-2 diabetes (T2D) have sparked a renewed interest in complementary and alternative medicine, including herbal products. Morinda citrifolia (noni) has been used for centuries by Pacific Islanders to treat various ailments. Commercial noni fruit juice has [...] Read more.

Escalating trends of chronic diseases such as type-2 diabetes (T2D) have sparked a renewed interest in complementary and alternative medicine, including herbal products. Morinda citrifolia (noni) has been used for centuries by Pacific Islanders to treat various ailments. Commercial noni fruit juice has been marketed as a dietary supplement since 1996. In 2003, the European Commission approved Tahitian noni juice as a novel food by the Health and Consumer Protection Directorate General. Among noni’s several health benefits, others and we have demonstrated the anti-diabetic effects of fermented noni fruit juice in animal models. Unfortunately, noni’s exciting journey from Polynesian medicine to the research bench does not reach its final destination of successful clinical outcomes when translated into commercial products. Noni products are perceived to be safe due to their “natural” origin. However, inadequate evidence regarding bioactive compounds, molecular targets, mechanism of action, pharmacokinetics, long-term safety, effective dosages, and/or unanticipated side effects are major roadblocks to successful translation “from bench side to bedside”. In this review we summarize the anti-diabetic potential of noni, differences between traditional and modern use of noni, along with beneficial clinical studies of noni products and challenges in clinical translation of noni’s health benefits. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

15 pages, 1343 KiB

Open AccessArticle

Hinokitiol Exerts Anticancer Activity through Downregulation of MMPs 9/2 and Enhancement of Catalase and SOD Enzymes: In Vivo Augmentation of Lung Histoarchitecture

by Chien-Hsun Huang^1,2, Thanasekaran Jayakumar³, Chao-Chien Chang⁴, Tsorng-Harn Fong⁵, Shing-Hwa Lu², Philip Aloysius Thomas⁶, Cheuk-Sing Choy^3,7,* and Joen-Rong Sheu^1,3,*

¹ Graduate Institute of Medical Sciences, Taipei Medical University, Taipei 110, Taiwan

² Division of Urology, Department of Surgery, Taipei City Hospital, Zhongxiao Branch, Taipei 115, Taiwan

³ Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei 110, Taiwan

⁴ Department of Cardiology, Cathay General Hospital, Taipei 106, Taiwan

⁵ Department of Anatomy, Taipei Medical University, No. 250 Wu-Hsing Street, Taipei 110, Taiwan

⁶ Department of Microbiology, Institute of Ophthalmology, Joseph Eye Hospital, Tiruchirappalli 620001, Tamil Nadu, India

⁷ Department of Emergency, Min-Sheng General Hospital, Taoyuan 330, Taiwan

Molecules 2015, 20(10), 17720-17734; https://doi.org/10.3390/molecules201017720 - 25 Sep 2015

Cited by 27 | Viewed by 8248

Abstract

Melanoma is extremely resistant to chemotherapy and the death rate is increasing hastily worldwide. Extracellular matrix promotes the migration and invasion of tumor cells through the production of matrix metalloproteinase (MMP)-2 and -9. Evidence has shown that natural dietary antioxidants are capable of [...] Read more.

Melanoma is extremely resistant to chemotherapy and the death rate is increasing hastily worldwide. Extracellular matrix promotes the migration and invasion of tumor cells through the production of matrix metalloproteinase (MMP)-2 and -9. Evidence has shown that natural dietary antioxidants are capable of inhibiting cancer cell growth. Our recent studies showed that hinokitiol, a natural bioactive compound, inhibited vascular smooth muscle cell proliferation and platelets aggregation. The present study is to investigate the anticancer efficacy of hinokitiol against B16-F10 melanoma cells via modulating tumor invasion factors MMPs, antioxidant enzymes in vitro. An in vivo mice model of histological investigation was performed to study the patterns of elastic and collagen fibers. Hinokitiol inhibited the expression and activity of MMPs-2 and -9 in B16-F10 melanoma cells, as measured by western blotting and gelatin zymography, respectively. An observed increase in protein expression of MMPs 2/9 in melanoma cells was significantly inhibited by hinokitiol. Notably, hinokitiol (1–5 μM) increased the activities of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) from the reduction in melanoma cells. Also, hinokitiol (2–10 µM) concentration dependently reduced in vitro Fenton reaction induced hydroxyl radical (OH·) formation. An in vivo study showed that hinokitiol treatment increased elastic fibers (EF), collagens dispersion, and improved alveolar alterations in the lungs of B16/F10 injected mice. Overall, our findings propose that hinokitiol may be a potent anticancer candidate through down regulation of MMPs 9/2, reduction of OH· production and enhancement of antioxidant enzymes SOD and CAT. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 764 KiB

Open AccessCommunication

Identification of Minor Benzoylated 4-Phenylcoumarins from a Mammea neurophylla Bark Extract

by Bach Tai Dang^1,†, Caroline Rouger^1,†, Marc Litaudon², Pascal Richomme¹, Denis Séraphin¹ and Séverine Derbré^1,*

¹ EA 921 SONAS, Université D'Angers, SFR QUASAV 4207, Campus du Végétal, 42, rue Georges Morel, Beaucouzé 49070, France

² Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, 1, av. de la Terrasse, Gif-sur-Yvette 91198, France

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 17735-17746; https://doi.org/10.3390/molecules201017735 - 25 Sep 2015

Cited by 7 | Viewed by 7418

Abstract

Through dereplication analysis, seven known Mammea coumarins were identified in a fraction obtained from Mammea neurophylla dichloromethane bark extract selected for its ability to prevent advanced glycation end-product (AGE) formation. Among them, a careful examination of the NMR dataset of pedilanthocoumarin B led [...] Read more.

Through dereplication analysis, seven known Mammea coumarins were identified in a fraction obtained from Mammea neurophylla dichloromethane bark extract selected for its ability to prevent advanced glycation end-product (AGE) formation. Among them, a careful examination of the NMR dataset of pedilanthocoumarin B led to a structural revision. Inspection of LC-DAD-MSⁿ chromatograms allowed us to predict the presence of four new compounds, which were further isolated. Using spectroscopic methods (¹H-, ¹³C- and 2D-NMR, HRMS, UV), these compounds were identified as new benzoyl substituted 4-phenylcoumarins (iso-pedilanthocoumarin B and neurophyllol C) and 4-(1-acetoxypropyl)coumarins cyclo F (ochrocarpins H and I). Full article

(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)

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13 pages, 1425 KiB

Open AccessArticle

Protective Effect of Plantago major Extract against t-BOOH-Induced Mitochondrial Oxidative Damage and Cytotoxicity

by Joyce C. Mello¹, Mariano V. D. Gonzalez², Vivian W. R. Moraes¹, Tatiana Prieto¹, Otaciro R. Nascimento³ and Tiago Rodrigues^1,*

¹ Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP 09210-170, Brazil

² Centro Interdisciplinar de Investigação Bioquímica, Universidade de Mogi das Cruzes, Mogi das Cruzes, SP 08780-911, Brazil

³ Grupo de Biofísica Molecular "Sergio Mascarenhas", Departamento de Física e Ciência Interdisciplinar, Instituto de Física de São Carlos, Universidade de São Paulo (USP), São Carlos, SP 13566-590, Brazil

Molecules 2015, 20(10), 17747-17759; https://doi.org/10.3390/molecules201017747 - 25 Sep 2015

Cited by 16 | Viewed by 7852

Abstract

Plantago major L. produces several chemical substances with anti-inflammatory and analgesic activities and its use in the treatment of oral and throat inflammation in popular medicine is well described. In this study, the antioxidant potential of the Plantago major hydroethanolic extract was screened [...] Read more.

Plantago major L. produces several chemical substances with anti-inflammatory and analgesic activities and its use in the treatment of oral and throat inflammation in popular medicine is well described. In this study, the antioxidant potential of the Plantago major hydroethanolic extract was screened and its protective action was evaluated against t-BOOH-induced oxidative stress. The extract was obtained by fractionated percolation using 50% ethanolic solution and, after drying, suspended in dimethyl sulfoxide. The chromatographic profile of crude extract was obtained with the identification of some phytochemical markers and the total phenols and flavonoids were quantified. The scavenger activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals was determined and the antioxidant activity in biological systems was evaluated in isolated rat liver mitochondria and HepG2 cells. The extract exhibited a significant free radical scavenger activity at 0.1 mg/mL, and decreased the ROS (reactive oxygen species) generation in succinate-energized mitochondria. Such an effect was associated with the preservation of the intrinsic antioxidant defenses (reduced glutathione and NAD(P)H) against the oxidation by t-BOOH, and also to the protection of membranes from lipid oxidation. The cytoprotective effect of PmHE against t-BOOH induced cell death was also shown. These findings contribute to the understanding of the health benefits attributed to P. major. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 792 KiB

Open AccessArticle

Enhanced Bioaccessibility of Crocetin Sugar Esters from Saffron in Infusions Rich in Natural Phenolic Antioxidants

by Stella A. Ordoudi

, Anastasia Kyriakoudi and Maria Z. Tsimidou^*

Laboratory of Food Chemistry and Technology, School of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece

Molecules 2015, 20(10), 17760-17774; https://doi.org/10.3390/molecules201017760 - 25 Sep 2015

Cited by 24 | Viewed by 6653

Abstract

The present study aims to examine whether and to what extent the bioaccessibility of the major saffron apocarotenoids, namely crocetin sugar esters (CRTSEs), is affected by the presence of strong water-soluble antioxidants, ingredients of the herbs found in commercial tea blends with saffron. [...] Read more.

The present study aims to examine whether and to what extent the bioaccessibility of the major saffron apocarotenoids, namely crocetin sugar esters (CRTSEs), is affected by the presence of strong water-soluble antioxidants, ingredients of the herbs found in commercial tea blends with saffron. An in vitro digestion model was applied to infusions from these products to investigate the possible changes. All of the studied infusions were rich in total phenols (9.9–22.5 mg caffeic acid equivalents/100 mg dry infusion) and presented strong DPPH radical scavenging activity regardless of the composition of the corresponding herbal blends. RP-HPLC-DAD and LC-MS analysis enabled the grouping of the infusions into hydroxycinnamic acid-rich and in flavan-3-ol-rich ones. CRTSEs in herbal tea infusions were found to be significantly more bioaccessible (66.3%–88.6%) than those in the reference saffron infusion (60.9%). The positive role of strong phenolic antioxidants (caffeic acid, rosmarinic acid) on the stability of CRTSEs was also evidenced in model binary mixtures. On the contrary, cinnamic acid, exerting no antioxidant activity, did not have such an effect. Our findings suggest that strong radical scavengers may protect the crocetin sugar esters from oxidation during digestion when present in excess. Full article

(This article belongs to the Special Issue Saffron (Crocus sativus, L.): Omics and Other Techniques in Authenticity, Quality and Bioactivity Studies)

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14 pages, 3512 KiB

Open AccessArticle

In Vitro Antioxidant Activities and in Vivo Anti-Hypoxic Activity of the Edible Mushroom Agaricus bisporus (Lange) Sing. Chaidam

by Hong-Ji Li¹, Hai-Yan Chen², Lin-Lin Fan¹, Zhi-Hua Jiao¹, Qi-He Chen^1,* and Ying-Chun Jiao^3,*

¹ Department of Food Science and Nutrition, Zhejiang University, Hangzhou 310058, China

² College of Chemistry and Biology Science, Lishui University, Lishui 323000, China

³ Agriculture and Animal Husbandry College, Qinghai University, Xining 810016, China

Molecules 2015, 20(10), 17775-17788; https://doi.org/10.3390/molecules201017775 - 25 Sep 2015

Cited by 22 | Viewed by 6682

Abstract

With the rising awareness of a healthy lifestyle, natural functional foods have gained much interest as promising alternatives to synthetic functional drugs. Recently, wild Agaricus bisporus (Lange) Sing. Chaidam has been found and artificially cultivated for its thick fresh body and excellent taste, [...] Read more.

With the rising awareness of a healthy lifestyle, natural functional foods have gained much interest as promising alternatives to synthetic functional drugs. Recently, wild Agaricus bisporus (Lange) Sing. Chaidam has been found and artificially cultivated for its thick fresh body and excellent taste, with its antioxidant and anti-hypoxic abilities unknown. In this work, the antioxidant potential of its methanolic, 55% ethanolic, aqueous extracts and crude polysaccharide was evaluated in different systems. The results showed that polysaccharide was the most effective in scavenging ability on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radicals, metal chelating activity and reducing power, with EC₅₀ values of 0.02, 2.79, 1.29, and 1.82 mg/mL, respectively. Therefore, we further studied the anti-hypoxic activity of crude polysaccharide. The results turned out that polysaccharide (300 mg/kg) prolonged the survival time, decreased the blood urea nitrogen and lactic acid content as well as increased the liver glycogen significantly, compared with the blank control and the commercialized product Hongjingtian (p < 0.05). With such excellent activities, we purified the polysaccharide and analyzed its molecular weight (120 kDa) as well as monosaccharide components (glucose, fructose and mannose). This study indicated that wild Agaricus bisporus (Lange) Sing. Chaidam had strong potential to be exploited as an effective natural functional food to relieve oxidative and hypoxia stresses Full article

(This article belongs to the Special Issue Dietary Bioactive Compounds: Metabolism, Mechanisms and Translational Significance for Health and Prevention of Diseases)

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18 pages, 6484 KiB

Open AccessArticle

Is Promiscuous CALB a Good Scaffold for Designing New Epoxidases?

by Isabel Bordes¹, José Recatalá¹, Katarzyna Świderek^1,2,*

and Vicent Moliner^1,*

¹ Departament de Química Física i Analítica, Universitat Jaume I, Castellón 12071, Spain

² Institute of Applied Radiation Chemistry, Lodz University of Technology, Lodz 90-924, Poland

Molecules 2015, 20(10), 17789-17806; https://doi.org/10.3390/molecules201017789 - 25 Sep 2015

Cited by 9 | Viewed by 7960

Abstract

Candida Antarctica lipase B (CALB) is a well-known enzyme, especially because of its promiscuous activity. Due to its properties, CALB was widely used as a benchmark for designing new catalysts for important organic reactions. The active site of CALB is very similar to [...] Read more.

Candida Antarctica lipase B (CALB) is a well-known enzyme, especially because of its promiscuous activity. Due to its properties, CALB was widely used as a benchmark for designing new catalysts for important organic reactions. The active site of CALB is very similar to that of soluble epoxide hydrolase (sEH) formed by a nucleophile-histidine-acid catalytic triad and an oxyanion hole typical for molecular structures derived from processes of α/β hydrolases. In this work we are exploring these similarities and proposing a Ser105Asp variant of CALB as a new catalyst for epoxide hydrolysis. In particular, the hydrolysis of the trans-diphenylpropene oxide (t-DPPO) is studied by means of quantum cluster models mimicking the active site of both enzymes. Our results, based on semi-empirical and DFT calculations, suggest that mutant Ser105Asp CALB is a good protein scaffold to be used for the bio-synthesis of chiral compounds. Full article

(This article belongs to the Special Issue Phase-Transfer Catalysis)

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11 pages, 1833 KiB

Open AccessArticle

Glucuronoyl Esterase Screening and Characterization Assays Utilizing Commercially Available Benzyl Glucuronic Acid Ester

by Hampus Sunner^1,2, Maria-Despoina Charavgi³, Lisbeth Olsson^1,2, Evangelos Topakas³ and Paul Christakopoulos^4,*

¹ Industrial Biotechnology, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg SE-412 96, Sweden

² Wallenberg Wood Science Centre, Teknikringen 56-58, Stockholm SE-100 44, Sweden

³ Biotechnology Laboratory, School of Chemical Engineering, National Technical University of Athens, 5 Iroon Polytechniou Str., Zografou Campus, Athens 15780, Greece

⁴ Biochemical Process Engineering, Division of Chemical Engineering, Department of Civil, Environmental and Natural Resources Engineering, Luleå University of Technology, Luleå SE-971 87, Sweden

Molecules 2015, 20(10), 17807-17817; https://doi.org/10.3390/molecules201017807 - 25 Sep 2015

Cited by 19 | Viewed by 6662

Abstract

Research on glucuronoyl esterases (GEs) has been hampered by the lack of enzyme assays based on easily obtainable substrates. While benzyl d-glucuronic acid ester (BnGlcA) is a commercially available substrate that can be used for GE assays, several considerations regarding substrate instability, limited [...] Read more.

Research on glucuronoyl esterases (GEs) has been hampered by the lack of enzyme assays based on easily obtainable substrates. While benzyl d-glucuronic acid ester (BnGlcA) is a commercially available substrate that can be used for GE assays, several considerations regarding substrate instability, limited solubility and low apparent affinities should be made. In this work we discuss the factors that are important when using BnGlcA for assaying GE activity and show how these can be applied when designing BnGlcA-based GE assays for different applications: a thin-layer chromatography assay for qualitative activity detection, a coupled-enzyme spectrophotometric assay that can be used for high-throughput screening or general activity determinations and a HPLC-based detection method allowing kinetic determinations. The three-level experimental procedure not merely facilitates routine, fast and simple biochemical characterizations but it can also give rise to the discovery of different GEs through an extensive screening of heterologous Genomic and Metagenomic expression libraries. Full article

(This article belongs to the Special Issue Biocatalytic Lignin Modification)

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30 pages, 4465 KiB

Open AccessReview

Phenolics and Polyphenolics from Melastomataceae Species

by Diana Marcela Ocampo Serna^1,2 and José Hipólito Isaza Martínez^1,*

¹ Grupo de Investigación en Productos Naturales y Alimentos (GIPNA), Departamento de Química, Facultad de Ciencias Naturales y Exactas, Universidad del Valle, Edificio 320, Oficina 2096, Ciudad Universitaria-Meléndez, Calle 13 No. 100-00, Cali 760032, Colombia

² Departamento de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Caldas, Calle 65 No. 26-10, Manizales 170004, Colombia

Molecules 2015, 20(10), 17818-17847; https://doi.org/10.3390/molecules201017818 - 25 Sep 2015

Cited by 33 | Viewed by 12481

Abstract

The Melastomataceae family, the seventh largest flowering plants, has been studied in several fronts of natural product chemistry, including terpenoids, simple phenolics, flavonoids, quinones, lignans and their glycosides, as well as a vast range of tannins or polyphenols. This review concerns the phenolic [...] Read more.

The Melastomataceae family, the seventh largest flowering plants, has been studied in several fronts of natural product chemistry, including terpenoids, simple phenolics, flavonoids, quinones, lignans and their glycosides, as well as a vast range of tannins or polyphenols. This review concerns the phenolic and polyphenolic metabolites described in the literature for several genera of this family, the mode of isolation and purification, and the structure elucidation of these new natural products that has been achieved by extensive spectral analyses, including ESI-MS, ¹H-, ¹³C-NMR spectra and two-dimensional experiments, COSY, TOCSY, J-resolved, NOESY, HMQC, DEPT, and HMBC, as well as chemical and enzymatic degradations and the chemotaxonomic meaning. Finally, a general biogenetic pathway map for ellagitannins is proposed on the bases of the most plausible free radical C-O oxidative coupling. Full article

(This article belongs to the Special Issue Recent Advances in Plant Phenolics)

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12 pages, 984 KiB

Open AccessArticle

Bioassay-Guided Isolation and Identification of Xanthine Oxidase Inhibitory Constituents from the Leaves of Perilla frutescens

by Li-Na Huo¹, Wei Wang^1,*

, Chun-Yu Zhang², Hai-Bo Shi³, Yang Liu¹, Xiao-Hong Liu¹, Bing-Hua Guo¹, Dong-Mei Zhao¹ and Hua Gao¹

¹ College of Pharmacy, Qingdao University, Qingdao 266021, Shandong, China

² Health Education Institute of Changchun, Changchun 130021, Jilin, China

³ Institute of Changbai Mountain Resources, Jilin Academy of Chinese Medicine Sciences, Changchun 130012, Jilin, China

Molecules 2015, 20(10), 17848-17859; https://doi.org/10.3390/molecules201017848 - 25 Sep 2015

Cited by 60 | Viewed by 10180

Abstract

Activity-directed fractionation and purification processes were employed to identify xanthine oxidase (XO) inhibitory compounds from the leaves of Perilla frutescens. The total extract was evaluated in vitro on XO inhibitory activity and in vivo in an experimental model with potassium oxonate-induced hyperuricemia [...] Read more.

Activity-directed fractionation and purification processes were employed to identify xanthine oxidase (XO) inhibitory compounds from the leaves of Perilla frutescens. The total extract was evaluated in vitro on XO inhibitory activity and in vivo in an experimental model with potassium oxonate-induced hyperuricemia in mice which was used to evaluate anti-hyperuricemic activity. The crude extract showed expressive urate-lowering activity results. Solvent partitioning of the total extract followed by macroporous resin column chromatography of the n-butanol extract yielded four extracts and eluted parts. Among them, only the 70% ethanol eluted part of the n-butanol extract showed strong activity and therefore was subjected to separation and purification using various chromatographic techniques. Five compounds showing potent activity were identified by comparing their spectral data with literature values to be caffeic acid, vinyl caffeate, rosmarinic acid, methyl rosmarinate, and apigenin. These results indicate that pending further study, these compounds could be used as novel natural product agents for the treatment of hyperuricemia. Full article

(This article belongs to the Collection Bioactive Compounds)

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12 pages, 1035 KiB

Open AccessArticle

Amination of Aryl Halides and Esters Using Intensified Continuous Flow Processing

by Thomas M. Kohl^*, Christian H. Hornung and John Tsanaktsidis

CSIRO Manufacturing Flagship, Bag 10, Clayton South, Victoria 3169, Australia

Molecules 2015, 20(10), 17860-17871; https://doi.org/10.3390/molecules201017860 - 25 Sep 2015

Cited by 7 | Viewed by 8291

Abstract

Significant process intensification of the amination reactions of aryl halides and esters has been demonstrated using continuous flow processing. Using this technology traditionally difficult amination reactions have been performed safely at elevated temperatures. These reactions were successfully conducted on laboratory scale coil reactor [...] Read more.

Significant process intensification of the amination reactions of aryl halides and esters has been demonstrated using continuous flow processing. Using this technology traditionally difficult amination reactions have been performed safely at elevated temperatures. These reactions were successfully conducted on laboratory scale coil reactor modules with 1 mm internal diameter (ID) and on a preparatory scale tubular reactor with 6 mm ID containing static mixers. Full article

(This article belongs to the Special Issue Recent Advances in Flow Chemistry)

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11 pages, 1839 KiB

Open AccessArticle

Methanolic Extract of Ganoderma lucidum Induces Autophagy of AGS Human Gastric Tumor Cells

by Filipa S. Reis^1,2,3,4

, Raquel T. Lima^1,2,5, Patricia Morales³

, Isabel C. F. R. Ferreira^4,*

and M. Helena Vasconcelos^1,2,6,*

¹ Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4099-002, Portugal

² Cancer Drug Resistance Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho, 45, Porto 4200-135, Portugal

³ Departamento de Nutrición y Bromatología II, Facultad de Farmacia, Universidad Complutense de Madrid (UCM), Pza Ramón y Cajal, s/n, E-28040 Madrid, Spain

⁴ Mountain Research Center (CIMO), ESA, Polytechnic Institute of Bragança, Apartado 1172, Bragança 5301-855, Portugal

⁵ Department of Pathology and Oncology, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, Porto 4200-319, Portugal

⁶ Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira n.° 228, Porto 4050-313, Portugal

Molecules 2015, 20(10), 17872-17882; https://doi.org/10.3390/molecules201017872 - 29 Sep 2015

Cited by 45 | Viewed by 9167

Abstract

Ganoderma lucidum is one of the most widely studied mushroom species, particularly in what concerns its medicinal properties. Previous studies (including those from some of us) have shown some evidence that the methanolic extract of G. lucidum affects cellular autophagy. However, it was [...] Read more.

Ganoderma lucidum is one of the most widely studied mushroom species, particularly in what concerns its medicinal properties. Previous studies (including those from some of us) have shown some evidence that the methanolic extract of G. lucidum affects cellular autophagy. However, it was not known if it induces autophagy or decreases the autophagic flux. The treatment of a gastric adenocarcinoma cell line (AGS) with the mushroom extract increased the formation of autophagosomes (vacuoles typical from autophagy). Moreover, the cellular levels of LC3-II were also increased, and the cellular levels of p62 decreased, confirming that the extract affects cellular autophagy. Treating the cells with the extract together with lysossomal protease inhibitors, the cellular levels of LC3-II and p62 increased. The results obtained proved that, in AGS cells, the methanolic extract of G. lucidum causes an induction of autophagy, rather than a reduction in the autophagic flux. To our knowledge, this is the first study proving that statement. Full article

(This article belongs to the Collection Bioactive Compounds)

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20 pages, 3377 KiB

Open AccessArticle

Phytotoxic Potential and Biological Activity of Three Synthetic Coumarin Derivatives as New Natural-Like Herbicides

by Fabrizio Araniti¹

, Raffaella Mancuso^2,*

, Antonio Lupini¹, Salvatore V. Giofrè³, Francesco Sunseri¹

, Bartolo Gabriele²

and Maria Rosa Abenavoli^1,*

¹ Dipartimento AGRARIA, Università Mediterranea di Reggio Calabria, Reggio Calabria 89124, Italy

² Laboratory of Industrial and Synthetic Organic Chemistry (LISOC), Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, Via P. Bucci 12/C, Arcavacata di Rende (Cosenza) 87036, Italy

³ Dipartimento di Scienze del Farmaco e dei Prodotti per la Salute, Università di Messina, Via SS Annunziata, Messina 98168, Italy

Molecules 2015, 20(10), 17883-17902; https://doi.org/10.3390/molecules201017883 - 29 Sep 2015

Cited by 47 | Viewed by 7727

Abstract

Coumarin is a natural compound well known for its phytotoxic potential. In the search for new herbicidal compounds to manage weeds, three synthetic derivatives bearing the coumarin scaffold (1–3), synthesized by a carbonylative organometallic approach, were in vitro assayed [...] Read more.

Coumarin is a natural compound well known for its phytotoxic potential. In the search for new herbicidal compounds to manage weeds, three synthetic derivatives bearing the coumarin scaffold (1–3), synthesized by a carbonylative organometallic approach, were in vitro assayed on germination and root growth of two noxious weeds, Amaranthus retroflexus and Echinochloa crus-galli. Moreover, the synthetic coumarins 1–3 were also in vitro assayed on seedlings growth of the model species Arabidopsis thaliana to identify the possible physiological targets. All molecules strongly affected seed germination and root growth of both weeds. Interestingly, the effects of synthetic coumarins on weed germination were higher than template natural coumarin, pointing out ED₅₀ values ranging from 50–115 µM. Moreover, all synthetic coumarins showed a strong phytotoxic potential on both Arabidopsis shoot and root growth, causing a strong reduction in shoot fresh weight (ED₅₀ values ≤ 60 µM), accompanied by leaf development and a decrease in pigment content. Furthermore, they caused a strong alteration in root growth (ED₅₀ values ≤ 170 µM) and morphology with evident alterations in root tip anatomy. Taken together, our results highlight the promising potential herbicidal activity of these compounds. Full article

(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)

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10 pages, 696 KiB

Open AccessArticle

Activity of Polyphenolic Compounds against Candida glabrata

by Ricardo Salazar-Aranda^1,†, Graciela Granados-Guzmán^1,†, Jonathan Pérez-Meseguer¹, Gloria M. González² and Noemí Waksman De Torres^1,*

¹ Departamento de Química Analítica, Facultad de Medicina, Universidad Autónoma de Nuevo León, Madero y Aguirre Pequeño, Col. Mitras Centro. Monterrey, N.L. C.P. 64460, Mexico

² Departamento de Microbiología, Facultad de Medicina, Universidad Autónoma de Nuevo León, Madero y Aguirre Pequeño, Col. Mitras Centro. Monterrey, N.L. C.P. 64460, Mexico

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 17903-17912; https://doi.org/10.3390/molecules201017903 - 29 Sep 2015

Cited by 52 | Viewed by 6570

Abstract

Opportunistic mycoses increase the morbidity and mortality of immuno-compromised patients. Five Candida species have been shown to be responsible for 97% of worldwide cases of invasive candidiasis. Resistance of C. glabrata and C. krusei to azoles has been reported, and new, improved antifungal [...] Read more.

Opportunistic mycoses increase the morbidity and mortality of immuno-compromised patients. Five Candida species have been shown to be responsible for 97% of worldwide cases of invasive candidiasis. Resistance of C. glabrata and C. krusei to azoles has been reported, and new, improved antifungal agents are needed. The current study was designed to evaluatethe activity of various polyphenolic compounds against Candida species. Antifungal activity was evaluated following the M27-A3 protocol of the Clinical and Laboratory Standards Institute, and antioxidant activity was determined using the DPPH assay. Myricetin and baicalein inhibited the growth of all species tested. This effect was strongest against C. glabrata, for which the minimum inhibitory concentration (MIC) value was lower than that of fluconazole. The MIC values against C. glabrata for myricitrin, luteolin, quercetin, 3-hydroxyflavone, and fisetin were similar to that of fluconazole. The antioxidant activity of all compounds was confirmed, and polyphenolic compounds with antioxidant activity had the greatest activity against C. glabrata. The structure and position of their hydroxyl groups appear to influence their activity against C. glabrata. Full article

(This article belongs to the Section Medicinal Chemistry)

16 pages, 3735 KiB

Open AccessArticle

Potent Activities of Roemerine against Candida albicans and the Underlying Mechanisms

by Chaoyu Ma^1,2,†, Faya Du^1,†, Lan Yan^3,†, Gonghao He¹, Jianchang He¹, Chengying Wang⁴, Gaoxiong Rao⁴, Yuanying Jiang^3,* and Guili Xu^1,*

¹ Department of Pharmacy, Kunming General Hospital of Chengdu Military Region, 212 Da-Guan Road, Kunming 650032, China

² School of Pharmacy, Kunming Medical University, 1168 Yu-Hua Road, Kunming 650500, China

³ New Drug Research and Development Center, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

⁴ School of Pharmacy, Yunnan College of Traditional Chinese Medicine, 1076 Yu-Hua Road, Kunming 650500, China

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 17913-17928; https://doi.org/10.3390/molecules201017913 - 29 Sep 2015

Cited by 33 | Viewed by 7342

Abstract

Roemerine (RM) is an aporphine alkaloid isolated from the fresh rattan stem of Fibraurea recisa, and it has been demonstrated to have certain antifungal activity. This study aimed to investigate the antifungal activity of RM and the underlying mechanisms in Candida albicans [...] Read more.

Roemerine (RM) is an aporphine alkaloid isolated from the fresh rattan stem of Fibraurea recisa, and it has been demonstrated to have certain antifungal activity. This study aimed to investigate the antifungal activity of RM and the underlying mechanisms in Candida albicans (C. albicans). The in vitro antifungal activity of RM was evaluated by a series of experiments, including the XTT reduction assay, confocal laser scanning microscopy assay, scanning electron microscope assay. Results showed that 1 μg/mL RM inhibited biofilm formation significantly (p < 0.01) both in Spider medium and Lee’s medium. In addition, RM could inhibit yeast-to-hyphae transition of C. albicans in a dose-dependent manner. The biofilm-specific and hypha-specific genes such as YWP1, SAP5, SAP6, HWP1, ECE1 were up-regulated and EFG1 was down-regulated after 8 μg/mL RM treatment. Furthermore, the toxicity of RM was investigated using C. elegans worms, three cancer cells and one normal cell. The date showed that RM had no significant toxicity. In conclusion, RM could inhibited the formation of C. albicans biofilm in vitro, but it had no fungicidal effect on planktonic C. albicans cells, and the anti-biofilm mechanism may be related to the cAMP pathway. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 1806 KiB

Open AccessArticle

Ionic Liquid-Based Ultrasonic-Assisted Extraction of Secoisolariciresinol Diglucoside from Flaxseed (Linum usitatissimum L.) with Further Purification by an Aqueous Two-Phase System

by Zhi-Jian Tan^1,*, Chao-Yun Wang^1,*, Zi-Zhen Yang², Yong-Jian Yi¹, Hong-Ying Wang¹, Wan-Lai Zhou¹ and Fen-Fang Li²

¹ Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, China

² College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China

Molecules 2015, 20(10), 17929-17943; https://doi.org/10.3390/molecules201017929 - 30 Sep 2015

Cited by 36 | Viewed by 8044

Abstract

In this work, a two-step extraction methodology of ionic liquid-based ultrasonic-assisted extraction (IL-UAE) and ionic liquid-based aqueous two-phase system (IL-ATPS) was developed for the extraction and purification of secoisolariciresinol diglucoside (SDG) from flaxseed. In the IL-UAE step, several kinds of ILs were investigated [...] Read more.

In this work, a two-step extraction methodology of ionic liquid-based ultrasonic-assisted extraction (IL-UAE) and ionic liquid-based aqueous two-phase system (IL-ATPS) was developed for the extraction and purification of secoisolariciresinol diglucoside (SDG) from flaxseed. In the IL-UAE step, several kinds of ILs were investigated as the extractants, to identify the IL that affords the optimum extraction yield. The extraction conditions such as IL concentration, ultrasonic irradiation time, and liquid–solid ratio were optimized using response surface methodology (RSM). In the IL-ATPS step, ATPS formed by adding kosmotropic salts to the IL extract was used for further separation and purification of SDG. The most influential parameters (type and concentration of salt, temperature, and pH) were investigated to obtain the optimum extraction efficiency. The maximum extraction efficiency was 93.35% under the optimal conditions of 45.86% (w/w) IL and 8.27% (w/w) Na₂SO₄ at 22 °C and pH 11.0. Thus, the combination of IL-UAE and IL-ATPS makes up a simple and effective methodology for the extraction and purification of SDG. This process is also expected to be highly useful for the extraction and purification of bioactive compounds from other important medicinal plants. Full article

(This article belongs to the Section Natural Products Chemistry)

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32 pages, 2548 KiB

Open AccessReview

Therapeutic Oligonucleotides Targeting Liver Disease: TTR Amyloidosis

by Christoph Niemietz^†, Gursimran Chandhok^† and Hartmut Schmidt^*

¹ Klinik für Transplantationsmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude A14, D-48149 Münster, Germany

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 17944-17975; https://doi.org/10.3390/molecules201017944 - 30 Sep 2015

Cited by 25 | Viewed by 14695

Abstract

The liver has become an increasingly interesting target for oligonucleotide therapy. Mutations of the gene encoding transthyretin (TTR), expressed in vast amounts by the liver, result in a complex degenerative disease, termed familial amyloid polyneuropathy (FAP). Misfolded variants of TTR are linked to [...] Read more.

The liver has become an increasingly interesting target for oligonucleotide therapy. Mutations of the gene encoding transthyretin (TTR), expressed in vast amounts by the liver, result in a complex degenerative disease, termed familial amyloid polyneuropathy (FAP). Misfolded variants of TTR are linked to the establishment of extracellular protein deposition in various tissues, including the heart and the peripheral nervous system. Recent progress in the chemistry and formulation of antisense (ASO) and small interfering RNA (siRNA) designed for a knockdown of TTR mRNA in the liver has allowed to address the issue of gene-specific molecular therapy in a clinical setting of FAP. The two therapeutic oligonucleotides bind to RNA in a sequence specific manner but exploit different mechanisms. Here we describe major developments that have led to the advent of therapeutic oligonucleotides for treatment of TTR-related disease. Full article

(This article belongs to the Special Issue Frontiers in Nucleic Acid Chemistry)

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25 pages, 2983 KiB

Open AccessArticle

Comparative Studies on Phenolic Composition, Antioxidant, Wound Healing and Cytotoxic Activities of Selected Achillea L. Species Growing in Turkey

by Osman Tuncay Agar¹, Miris Dikmen², Nilgun Ozturk³, Mustafa Abdullah Yilmaz⁴, Hamdi Temel^4,5 and Fatma Pinar Turkmenoglu^1,*

¹ Department of Pharmaceutical Botany, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey

² Department of Pharmacology, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, Turkey

³ Department of Pharmacognosy, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, Turkey

⁴ Dicle University Science and Technology Research and Application Center, Diyarbakır 21280, Turkey

⁵ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Dicle University, Diyarbakir 21280, Turkey

Molecules 2015, 20(10), 17976-18000; https://doi.org/10.3390/molecules201017976 - 30 Sep 2015

Cited by 93 | Viewed by 10745

Abstract

Turkey is one of the most important centers of diversity for the genus Achillea L. in the world. Keeping in mind the immense medicinal importance of phenols, in this study, three species growing in Turkey, A. coarctata Poir. (AC), A. kotschyi Boiss. subsp. [...] Read more.

Turkey is one of the most important centers of diversity for the genus Achillea L. in the world. Keeping in mind the immense medicinal importance of phenols, in this study, three species growing in Turkey, A. coarctata Poir. (AC), A. kotschyi Boiss. subsp. kotschyi (AK) and A. lycaonica Boiss. & Heldr. (AL) were evaluated for their phenolic compositions, total phenolic contents (TPC), antioxidant properties, wound healing potencies on NIH-3T3 fibroblasts and cytotoxic effects on MCF-7 human breast cancer cells. Comprehensive LC-MS/MS analysis revealed that AK was distinctively rich in chlorogenic acid, hyperoside, apigenin, hesperidin, rutin, kaempferol and luteolin (2890.6, 987.3, 797.0, 422.5, 188.1, 159.4 and 121.2 µg analyte/g extract, respectively). The findings exhibited a strong correlation between TPC and both free radical scavenging activity and total antioxidant capacity (TAC). Among studied species, the highest TPC (148.00 mg GAE/g extract) and TAC (2.080 UAE), the strongest radical scavenging (EC₅₀ = 32.63 μg/mL), the most prominent wound healing and most abundant cytotoxic activities were observed with AK. The results suggested that AK is a valuable source of flavonoids and chlorogenic acid with important antioxidant, wound healing and cytotoxic activities. These findings warrant further studies to assess the potential of AK as a bioactive source that could be exploited in pharmaceutical, cosmetics and food industries. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 885 KiB

Open AccessArticle

Cucurbitacins from the Leaves of Citrullus colocynthis (L.) Schrad

by Rachid Chawech^1,2,3, Raoudha Jarraya³, Cynthia Girardi^1,2, Marieke Vansteelandt^1,2, Guillaume Marti^1,2, Imen Nasri^3,4, Claire Racaud-Sultan⁴ and Nicolas Fabre^1,2,*

¹ Université de Toulouse, UPS, Pharma-DEV, UMR 152, Université Toulouse 3, Faculté des Sciences Pharmaceutiques, F-31062 Toulouse cedex 09, France

² Institut de Recherche pour le Développement (IRD), UMR 152 Pharma-DEV, F-31062 Toulouse cedex 09, France

³ Laboratoire de Chimie des Substances Naturelles, Faculté des Sciences de Sfax, Université de Sfax Route de l'aéroport, BP 1171, 3000 Sfax, Tunisie

⁴ INSERM U1043, CNRS U5282, Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan, F-31300 Toulouse, France

Molecules 2015, 20(10), 18001-18015; https://doi.org/10.3390/molecules201018001 - 30 Sep 2015

Cited by 44 | Viewed by 9222

Abstract

Two new tetracyclic cucurbitane-type triterpene glycosides were isolated from an ethyl acetate extract of Citrullus colocynthis leaves together with four known cucurbitacins. Their structures were established on the basis of their spectroscopic data (mainly NMR and mass spectrometry). Evaluation of the in vitro [...] Read more.

Two new tetracyclic cucurbitane-type triterpene glycosides were isolated from an ethyl acetate extract of Citrullus colocynthis leaves together with four known cucurbitacins. Their structures were established on the basis of their spectroscopic data (mainly NMR and mass spectrometry). Evaluation of the in vitro cytotoxic activity of the isolated compounds against two human colon cancer cell lines (HT29 and Caco-2) and one normal rat intestine epithelial cell line (IEC6), revealed that one of the isolated compounds presented interesting specific cytotoxic activity towards colorectal cell lines. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 3358 KiB

Open AccessArticle

Treatment Efficiency of Free and Nanoparticle-Loaded Mitoxantrone for Magnetic Drug Targeting in Multicellular Tumor Spheroids

by Annkathrin Hornung^1,2, Marina Poettler¹, Ralf P. Friedrich¹, Jan Zaloga¹, Harald Unterweger¹, Stefan Lyer¹, Johannes Nowak³, Stefan Odenbach³, Christoph Alexiou¹ and Christina Janko^1,*

¹ Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Glückstraße 10a, 91054 Erlangen, Germany

² Friedrich-Alexander-University Erlangen-Nuremberg (FAU), 91054 Erlangen, Germany

³ Chair of Magnetofluiddynamics, Measuring and Automation Technology, Technische Universität Dresden, 01062 Dresden, Germany

Molecules 2015, 20(10), 18016-18030; https://doi.org/10.3390/molecules201018016 - 30 Sep 2015

Cited by 32 | Viewed by 8233

Abstract

Major problems of cancer treatment using systemic chemotherapy are severe side effects. Magnetic drug targeting (MDT) employing superparamagnetic iron oxide nanoparticles (SPION) loaded with chemotherapeutic agents may overcome this dilemma by increasing drug accumulation in the tumor and reducing toxic side effects in [...] Read more.

Major problems of cancer treatment using systemic chemotherapy are severe side effects. Magnetic drug targeting (MDT) employing superparamagnetic iron oxide nanoparticles (SPION) loaded with chemotherapeutic agents may overcome this dilemma by increasing drug accumulation in the tumor and reducing toxic side effects in the healthy tissue. For translation of nanomedicine from bench to bedside, nanoparticle-mediated effects have to be studied carefully. In this study, we compare the effect of SPION, unloaded or loaded with the cytotoxic drug mitoxantrone (MTO) with the effect of free MTO, on the viability and proliferation of HT-29 cells within three-dimensional multicellular tumor spheroids. Fluorescence microscopy and flow cytometry showed that both free MTO, as well as SPION-loaded MTO (SPION^MTO) are able to penetrate into tumor spheroids and thereby kill tumor cells, whereas unloaded SPION did not affect cellular viability. Since SPION^MTO has herewith proven its effectivity also in complex multicellular tumor structures with its surrounding microenvironment, we conclude that it is a promising candidate for further use in magnetic drug targeting in vivo. Full article

(This article belongs to the Collection Nanomedicine)

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16 pages, 2480 KiB

Open AccessArticle

Plasma Pharmacokinetics of Polyphenols in a Traditional Japanese Medicine, Jumihaidokuto, Which Suppresses Propionibacterium acnes-Induced Dermatitis in Rats

by Takashi Matsumoto^1,*

, Yousuke Matsubara¹, Yasuharu Mizuhara¹, Kyoji Sekiguchi¹, Junichi Koseki¹, Kazuaki Tsuchiya¹, Hiroaki Nishimura², Junko Watanabe¹, Atsushi Kaneko¹, Kazuya Maemura¹, Tomohisa Hattori¹ and Yoshio Kase¹

¹ Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki 300-1192, Japan

² Kampo Formulations Development Center, Production Division, Tsumura & Co., Ibaraki 300-1192, Japan

Molecules 2015, 20(10), 18031-18046; https://doi.org/10.3390/molecules201018031 - 30 Sep 2015

Cited by 21 | Viewed by 8563

Abstract

Most orally administered polyphenols are metabolized, with very little absorbed as aglycones and/or unchanged forms. Metabolic and pharmacokinetic studies are therefore necessary to understand the pharmacological mechanisms of polyphenols. Jumihaidokuto (JHT), a traditional Japanese medicine, has been used for treatment of skin diseases [...] Read more.

Most orally administered polyphenols are metabolized, with very little absorbed as aglycones and/or unchanged forms. Metabolic and pharmacokinetic studies are therefore necessary to understand the pharmacological mechanisms of polyphenols. Jumihaidokuto (JHT), a traditional Japanese medicine, has been used for treatment of skin diseases including inflammatory acne. Because JHT contains various types of bioactive polyphenols, our aim was to clarify the metabolism and pharmacokinetics of the polyphenols in JHT and identify active metabolites contributing to its antidermatitis effects. Orally administered JHT inhibited the increase in ear thickness in rats induced by intradermal injection of Propionibacterium acnes. Quantification by LC-MS/MS indicated that JHT contains various types of flavonoids and is also rich in hydrolysable tannins, such as 1,2,3,4,6-penta-O-galloyl glucose. Pharmacokinetic and antioxidant analyses showed that some flavonoid conjugates, such as genistein 7-O-glucuronide and liquiritigenin 7-O-glucuronide, appeared in rat plasma and had an activity to inhibit hydrogen peroxide-dependent oxidation. Furthermore, 4-O-methylgallic acid, a metabolite of Gallic acid, appeared in rat plasma and inhibited the nitric oxide reaction. JHT has numerous polyphenols; it inhibited dermatitis probably via the antioxidant effect of its metabolites. Our study is beneficial for understanding in vivo actions of orally administered polyphenol drugs. Full article

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

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19 pages, 2785 KiB

Open AccessArticle

Metabolic Profiling of Alpine and Ecuadorian Lichens

by Verena K. Mittermeier¹, Nicola Schmitt¹, Lukas P. M. Volk¹, Juan Pablo Suárez²

, Andreas Beck^3,4,*

and Wolfgang Eisenreich^1,*

¹ Lehrstuhl für Biochemie, Technische Universität München, Lichtenberg-Str. 4, D-85747 Garching, Germany

² Departamento de Ciencias Naturales, Universidad Técnica Particular de Loja, San Cayetano Alto s/n, C.P. 11 01 608 Loja, Ecuador

³ Department of Lichenology and Bryology, Botanische Staatssammlung München, Menzinger Str. 67, D-80638 München, Germany

⁴ GeoBio-Center, Ludwig-Maximilians Universität München, Richard-Wagner-Str. 10, D-80333 München, Germany

Molecules 2015, 20(10), 18047-18065; https://doi.org/10.3390/molecules201018047 - 1 Oct 2015

Cited by 15 | Viewed by 7399

Abstract

Non-targeted ¹H-NMR methods were used to determine metabolite profiles from crude extracts of Alpine and Ecuadorian lichens collected from their natural habitats. In control experiments, the robustness of metabolite detection and quantification was estimated using replicate measurements of Stereocaulon alpinum extracts. The [...] Read more.

Non-targeted ¹H-NMR methods were used to determine metabolite profiles from crude extracts of Alpine and Ecuadorian lichens collected from their natural habitats. In control experiments, the robustness of metabolite detection and quantification was estimated using replicate measurements of Stereocaulon alpinum extracts. The deviations in the overall metabolite fingerprints were low when analyzing S. alpinum collections from different locations or during different annual and seasonal periods. In contrast, metabolite profiles observed from extracts of different Alpine and Ecuadorian lichens clearly revealed genus- and species-specific profiles. The discriminating functions determining cluster formation in principle component analysis (PCA) were due to differences in the amounts of genus-specific compounds such as sticticin from the Sticta species, but also in the amounts of ubiquitous metabolites, such as sugar alcohols or trehalose. However, varying concentrations of these metabolites from the same lichen species e.g., due to different environmental conditions appeared of minor relevance for the overall cluster formation in PCA. The metabolic clusters matched phylogenetic analyses using nuclear ribosomal DNA (nrDNA) internal transcribed spacer (ITS) sequences of lichen mycobionts, as exemplified for the genus Sticta. It can be concluded that NMR-based non-targeted metabolic profiling is a useful tool in the chemo-taxonomy of lichens. The same approach could also facilitate the discovery of novel lichen metabolites on a rapid and systematical basis. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 2153 KiB

Open AccessArticle

Antiproliferative and Apoptotic Activity of Chamaecyparis obtusa Leaf Extract against the HCT116 Human Colorectal Cancer Cell Line and Investigation of the Bioactive Compound by Gas Chromatography-Mass Spectrometry-Based Metabolomics

by Hye-Youn Kim^1,†, Seul-Gi Lee^1,†, Taek-Joo Oh¹, Sa Rang Lim¹, So-Hyun Kim¹, Hong Jin Lee², Young-Suk Kim³ and Hyung-Kyoon Choi^1,*

¹ College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea

² Department of Food Science and Technology, Chung-Ang University, Anseong 456-756, Korea

³ Department of Food Science and Technology, Ewha Womans University, Seoul 120-750, Korea

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 18066-18082; https://doi.org/10.3390/molecules201018066 - 2 Oct 2015

Cited by 23 | Viewed by 7943

Abstract

Chamaecyparis obtusa (CO) belongs to the Cupressaceae family, and it is found widely distributed in Japan and Korea. In this study, the anti-proliferative activities of the methanol and water extracts of CO leaves against a human colorectal cancer cell line (HCT116) were investigated. [...] Read more.

Chamaecyparis obtusa (CO) belongs to the Cupressaceae family, and it is found widely distributed in Japan and Korea. In this study, the anti-proliferative activities of the methanol and water extracts of CO leaves against a human colorectal cancer cell line (HCT116) were investigated. The methanol extract of CO leaves, at a concentration of 1.25 µg/mL, exhibited anti-proliferative activity against HCT116 cells, while displaying no cytotoxicity against Chang liver cells. Comparative global metabolite profiling was performed using gas chromatography-mass spectrometry coupled with multivariate statistical analysis, and it was revealed that anthricin was the major compound contributing to the anti-proliferative activity. The activation of c-Jun N-terminal kinases played a key role in the apoptotic effect of the methanol extract of CO leaves in HCT116 human colon cancer cells. These results suggest that the methanol extract and anthricin derived from CO leaves might be useful in the development of medicines with anti-colorectal cancer activity. Full article

(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)

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12 pages, 758 KiB

Open AccessArticle

Quantification of Coumarins in Aqueous Extract of Pterocaulon balansae (Asteraceae) and Characterization of a New Compound

by Bruna Medeiros-Neves, Francisco Maikon Corrêa De Barros, Gilsane Lino Von Poser and Helder Ferreira Teixeira^*

Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga, 2752, Porto Alegre, RS 90610-000, Brazil

Molecules 2015, 20(10), 18083-18094; https://doi.org/10.3390/molecules201018083 - 2 Oct 2015

Cited by 17 | Viewed by 6447

Abstract

Plants from the genus Pterocaulon are popularly used as antifungal and wound-healing agents. Such activities have been related to coumarins, which are abundant in those plants. Coumarins are soluble in organic solvents, such as hexane and dichloromethane, and some of them are also [...] Read more.

Plants from the genus Pterocaulon are popularly used as antifungal and wound-healing agents. Such activities have been related to coumarins, which are abundant in those plants. Coumarins are soluble in organic solvents, such as hexane and dichloromethane, and some of them are also soluble in hot water. Considering that infusion and decoctions of these plants are used in traditional medicine, the aim of this study was to identify and quantify the coumarins in the aqueous extract of Pterocaulon balansae. The aqueous extract was obtained by dynamic maceration and the compounds were characterized by UPLC-UV-MS analysis. A new coumarin and 5-methoxy-6,7-methylenedioxycoumarin, used for validation of the analytical HPLC method were obtained by partition of the aqueous extract with n-hexane. The HPLC method validated was linear, specific, and precise. Seven coumarins were characterized in the aqueous extract in a range of 0.584–54 mg/g of dry plant material. The main compound, 5,6-dimethoxy-7-(3′-methyl-2′,3′-dihydroxybutyloxy)coumarin, is described for the first time in P. balansae together with a new compound, 5,6-dimethoxy-7-(2′,3′-epoxy-3′-methylbutyloxy)coumarin. Full article

(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)

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12 pages, 717 KiB

Open AccessArticle

Characterization of Non-Anthocyanic Flavonoids in Some Hybrid Red Grape Extracts Potentially Interesting for Industrial Uses

by Mirko De Rosso^†, Annarita Panighel^†, Antonio Dalla Vedova^†, Massimo Gardiman^† and Riccardo Flamini^*

¹ Consiglio per la Ricerca in Agricoltura e l'Analisi dell'Economia Agraria—Centro di Ricerca per la Viticoltura (CREA-VIT), Viale XXVIII Aprile 26, Conegliano (TV) 31015, Italy

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 18095-18106; https://doi.org/10.3390/molecules201018095 - 2 Oct 2015

Cited by 42 | Viewed by 6543

Abstract

Previous studies showed that hybrid grapes often have qualitatively and quantitatively higher polyphenolic contents than the common V. vinifera grape varieties. In general, these compounds are studied for grape chemotaxonomy and for nutraceutical purposes due to their relevant antioxidant activity. Non-anthocyanic flavonoid composition [...] Read more.

Previous studies showed that hybrid grapes often have qualitatively and quantitatively higher polyphenolic contents than the common V. vinifera grape varieties. In general, these compounds are studied for grape chemotaxonomy and for nutraceutical purposes due to their relevant antioxidant activity. Non-anthocyanic flavonoid composition of five red hybrid grape varieties produced by crossing of V. vinifera, V. aestivalis, V. cinerea, V. berlandieri, V. labrusca, V. lincecumii, and V. rupestris were studied by liquid chromatography/high-resolution mass spectrometry. Thirty-one compounds were identified, including methylnaringenin, a tetrahydroxy-dimethoxyflavanone-hexoside, two flavonols (quercetin and a pentahydroxyflavone isomer), 20 glycoside flavonols (four quercetin, two myricetin, two kaempferol, three isorhamnetin, one laricitrin, two syringetin, one kaempferide and two dihydroflavonol derivatives; myricetin-glucoside-glucuronide; myricetin-diglucoside; syringetin-dihexoside), three flavan-3-ols (−)-epicatechin, (+)-catechin, (−)-epicatechin gallate) and four proantocyanidins (procyanidin B1, procyanidin B2, procyanidin B3 or B4/B5, procyanidin T2 or T3/T4/C1). Seibel 19881, Seyve Villard 12-347 and Seyve Villard 29-399 were particularly rich in polyphenols. These findings emphasize that these grapes are especially interesting for the production of antioxidant extracts for nutraceutical and pharmaceutical uses. Full article

(This article belongs to the Section Natural Products Chemistry)

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21 pages, 741 KiB

Open AccessArticle

A Quantum-Based Similarity Method in Virtual Screening

by Mohammed Mumtaz Al-Dabbagh^1,*, Naomie Salim¹, Mubarak Himmat¹, Ali Ahmed^1,2 and Faisal Saeed¹

¹ Faculty of Computing, Universiti Teknologi Malaysia, Skudia 81310, Malaysia

² Faculty of Engineering, Karary University, Khartoum 12304, Sudan

Molecules 2015, 20(10), 18107-18127; https://doi.org/10.3390/molecules201018107 - 2 Oct 2015

Cited by 21 | Viewed by 6318

Abstract

One of the most widely-used techniques for ligand-based virtual screening is similarity searching. This study adopted the concepts of quantum mechanics to present as state-of-the-art similarity method of molecules inspired from quantum theory. The representation of molecular compounds in mathematical quantum space plays [...] Read more.

One of the most widely-used techniques for ligand-based virtual screening is similarity searching. This study adopted the concepts of quantum mechanics to present as state-of-the-art similarity method of molecules inspired from quantum theory. The representation of molecular compounds in mathematical quantum space plays a vital role in the development of quantum-based similarity approach. One of the key concepts of quantum theory is the use of complex numbers. Hence, this study proposed three various techniques to embed and to re-represent the molecular compounds to correspond with complex numbers format. The quantum-based similarity method that developed in this study depending on complex pure Hilbert space of molecules called Standard Quantum-Based (SQB). The recall of retrieved active molecules were at top 1% and top 5%, and significant test is used to evaluate our proposed methods. The MDL drug data report (MDDR), maximum unbiased validation (MUV) and Directory of Useful Decoys (DUD) data sets were used for experiments and were represented by 2D fingerprints. Simulated virtual screening experiment show that the effectiveness of SQB method was significantly increased due to the role of representational power of molecular compounds in complex numbers forms compared to Tanimoto benchmark similarity measure. Full article

(This article belongs to the Special Issue Chemoinformatics)

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16 pages, 764 KiB

Open AccessArticle

Phytochemical and Biological Investigation of Two Diplotaxis Species Growing in Tunisia: D. virgata & D. erucoides

by Nizar Ben Salah^1,2, Hervé Casabianca³, Hichem Ben Jannet⁴, Sophie Chenavas³, Corinne Sanglar³, Aurélie Fildier³ and Nabiha Bouzouita^2,*

¹ Faculté des Sciences de Monastir, Université de Monastir, Avenue de l'Environnement, 5019 Monastir, Tunisia

² Laboratoire de Chimie Organique Structurale, Synthèse et Etude Physicochimique–Faculté des Sciences de Tunis, 2092 El Manar, Tunisia

³ Service Central d'analyse, Institut des Sciences Analytiques, Université de Lyon, UMR 5280 CNRS, Université

⁴ Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité, Equipe, Chimie Médicinale et Produits Naturels, Faculté des Sciences de Monastir, Université de Monastir, Avenue of the Environment, 5019 Monastir, Tunisia

Molecules 2015, 20(10), 18128-18143; https://doi.org/10.3390/molecules201018128 - 5 Oct 2015

Cited by 15 | Viewed by 5648

Abstract

A phytochemical investigation of Diplotaxis virgata D.C. and D. erucoides (L.) D.C. (Brassicaceae) offered to the isolation of two new flavonoids isorhamnetin-3-O-α-l-glucopyranoside (1) and rhamnetin-3,3ʹ-di-O-β-d-glucopyranoside (2), respectively. Their structures have been elucidated from [...] Read more.

A phytochemical investigation of Diplotaxis virgata D.C. and D. erucoides (L.) D.C. (Brassicaceae) offered to the isolation of two new flavonoids isorhamnetin-3-O-α-l-glucopyranoside (1) and rhamnetin-3,3ʹ-di-O-β-d-glucopyranoside (2), respectively. Their structures have been elucidated from the extended spectroscopic methods, including 1D- and 2D-NMR, UV and mass spectrometry analysis and by comparison with literature data. The fatty acid composition of the hexane extracts of the two species was also investigated by using GC-MS. The antioxidant activity of ethanol, ethyl acetate, n-butanol extracts and the isolated compounds from the two species was evaluated using DPPH and ABTS⁺ scavenging assays. All the tested samples showed an efficient radical scavenging ability, with IC₅₀values ranging from 16–40 µg/mL for the DPPH and from 17–44 µg/mL for the ABTS⁺ assays. In addition, the antibacterial activity of the prepared extracts and compounds 1 and 2, determined by well diffusion agar method against two Gram positive and five Gram negative bacteria, was evaluated and the results showed significant effects against all strains used. Full article

(This article belongs to the Section Natural Products Chemistry)

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24 pages, 1920 KiB

Open AccessArticle

Antibacterial Activity, Antioxidant Effect and Chemical Composition of Propolis from the Región del Maule, Central Chile

by Nélida Nina^1,2, Cristina Quispe^1,3, Felipe Jiménez-Aspee¹

, Cristina Theoduloz⁴, Gabriela Egly Feresín⁵

, Beatriz Lima⁵, Elba Leiva² and Guillermo Schmeda-Hirschmann^1,*

¹ Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca 3460000, Chile

² Facultad de Ciencias de la Salud, Programa de Magister en Ciencias Biomédicas, Universidad de Talca, Talca 3460000, Chile

³ Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1110939, Chile

⁴ Laboratorio de Cultivo Celular, Facultad de Ciencias de la Salud, Universidad de Talca, Casilla 747, Talca 3460000, Chile

⁵ Instituto de Biotecnología, Facultad de Ingeniería, Universidad Nacional de San Juan, Av. Libertador General San Martin 1109 (oeste), San Juan 5400, Argentina

Molecules 2015, 20(10), 18144-18167; https://doi.org/10.3390/molecules201018144 - 6 Oct 2015

Cited by 77 | Viewed by 10300

Abstract

Propolis is commercialized in Chile as an antimicrobial agent. It is obtained mainly from central and southern Chile, but is used for the same purposes regardless of its origin. To compare the antimicrobial effect, the total phenolic (TP), the total flavonoid (TF) content [...] Read more.

Propolis is commercialized in Chile as an antimicrobial agent. It is obtained mainly from central and southern Chile, but is used for the same purposes regardless of its origin. To compare the antimicrobial effect, the total phenolic (TP), the total flavonoid (TF) content and the phenolic composition, 19 samples were collected in the main production centers in the Región del Maule, Chile. Samples were extracted with MeOH and assessed for antimicrobial activity against Gram (+) and Gram (−) bacteria. TP and TF content, antioxidant activity by the DPPH, FRAP and TEAC methods were also determined. Sample composition was assessed by HPLD-DAD-ESI-MS/MS. Differential compounds in the samples were isolated and characterized. The antimicrobial effect of the samples showed MICs ranging from 31.5 to > 1000 µg/mL. Propolis from the central valley was more effective as antibacterial than those from the coastal area or Andean slopes. The samples considered of interest (MIC ≤ 62.5 µg/mL) showed effect on Escherichia coli, Pseudomonas sp., Yersinia enterocolitica and Salmonella enteritidis. Two new diarylheptanoids, a diterpene, the flavonoids pinocembrin and chrysin were isolated and elucidated by spectroscopic and spectrometric means. Some 29 compounds were dereplicated by HPLC-MS and tentatively identified, including nine flavones/flavonol derivatives, one flavanone, eight dihydroflavonols and nine phenyl-propanoids. Propolis from the Región del Maule showed large variation in antimicrobial effect, antioxidant activity and composition. So far the presence of diarylheptanoids in samples from the coastal area of central Chile can be considered as a marker of a new type of propolis. Full article

(This article belongs to the Special Issue Recent Advances in Plant Phenolics)

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17 pages, 1086 KiB

Open AccessReview

Duchenne Muscular Dystrophy: From Diagnosis to Therapy

by Maria Sofia Falzarano^1,*, Chiara Scotton¹, Chiara Passarelli² and Alessandra Ferlini^1,*

¹ Unit of Medical Genetics, Department of Medical Sciences, University of Ferrara, Ferrara, 44121 Italy

² Bambino Gesù Hospital, Rome, 00146, Italy

Molecules 2015, 20(10), 18168-18184; https://doi.org/10.3390/molecules201018168 - 7 Oct 2015

Cited by 215 | Viewed by 51939

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked inherited neuromuscular disorder due to mutations in the dystrophin gene. It is characterized by progressive muscle weakness and wasting due to the absence of dystrophin protein that causes degeneration of skeletal and cardiac muscle. The molecular [...] Read more.

Duchenne muscular dystrophy (DMD) is an X-linked inherited neuromuscular disorder due to mutations in the dystrophin gene. It is characterized by progressive muscle weakness and wasting due to the absence of dystrophin protein that causes degeneration of skeletal and cardiac muscle. The molecular diagnostic of DMD involves a deletions/duplications analysis performed by quantitative technique such as microarray-based comparative genomic hybridization (array-CGH), Multiple Ligation Probe Assay MLPA. Since traditional methods for detection of point mutations and other sequence variants require high cost and are time consuming, especially for a large gene like dystrophin, the use of next-generation sequencing (NGS) has become a useful tool available for clinical diagnosis. The dystrophin gene is large and finely regulated in terms of tissue expression, and RNA processing and editing includes a variety of fine tuned processes. At present, there are no effective treatments and the steroids are the only fully approved drugs used in DMD therapy able to slow disease progression. In the last years, an increasing variety of strategies have been studied as a possible therapeutic approach aimed to restore dystrophin production and to preserve muscle mass, ameliorating the DMD phenotype. RNA is the most studied target for the development of clinical strategies and Antisense Oligonucleotides (AONs) are the most used molecules for RNA modulation. The identification of delivery system to enhance the efficacy and to reduce the toxicity of AON is the main purpose in this area and nanomaterials are a very promising model as DNA/RNA molecules vectors. Dystrophinopathies therefore represent a pivotal field of investigation, which has opened novel avenues in molecular biology, medical genetics and novel therapeutic options. Full article

(This article belongs to the Special Issue Towards Understanding the Mechanisms and Curing Of Muscular Dystrophy Diseases)

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16 pages, 1073 KiB

Open AccessArticle

Synthesis and Preliminary Evaluation of N-Oxide Derivatives for the Prevention of Atherothrombotic Events

by Leandro Augusto Rosseto¹, Maria Elisa Lopes Pires², Aylime Castanho Bolognesi Melchior¹, Priscila Longhin Bosquesi¹, Aline Renata Pavan¹, Sisi Marcondes², Man Chin Chung¹ and Jean Leandro dos Santos^1,*

¹ Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, UNESP, Rodovia Araraquara Jaú Km 01, 14801-902, Araraquara, SP, Brazil

² Departmento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, UNICAMP, Rua Tessália Vieira de Camargon.126, 13083-887, Campinas, SP, Brazil

Molecules 2015, 20(10), 18185-18200; https://doi.org/10.3390/molecules201018185 - 7 Oct 2015

Cited by 14 | Viewed by 5977

Abstract

Thrombosis is the main outcome of many cardiovascular diseases. Current treatments to prevent thrombotic events involve the long-term use of antiplatelet drugs. However, this therapy has several limitations, thereby justifying the development of new drugs. A series of N-oxide derivatives (furoxan and [...] Read more.

Thrombosis is the main outcome of many cardiovascular diseases. Current treatments to prevent thrombotic events involve the long-term use of antiplatelet drugs. However, this therapy has several limitations, thereby justifying the development of new drugs. A series of N-oxide derivatives (furoxan and benzofuroxan) were synthesized and characterized as potential antiplatelet/antithrombotic compounds. All compounds (3a,b, 4a,b, 8a,b, 9a,b, 13a,b and 14a,b) inhibited platelet aggregation induced by adenosine-5-diphosphate, collagen, and arachidonic acid. All compounds protected mice from pulmonary thromboembolism induced by a mixture of collagen and epinephrine; however, benzofuroxan derivatives (13a,b and 14a,b) were the most active compounds, reducing thromboembolic events by up to 80%. N-oxide derivative 14a did not induce genotoxicity in vivo. In conclusion, 14a has emerged as a new antiplatelet/antithrombotic prototype useful for the prevention of atherothrombotic events. Full article

(This article belongs to the Section Medicinal Chemistry)

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18 pages, 864 KiB

Open AccessArticle

Synthesis of Some Novel Heterocyclic and Schiff Base Derivatives as Antimicrobial Agents

by Mohamed E. Azab^1,*, Sameh A. Rizk¹ and Abd El-Galil E. Amr^2,3

¹ Department of Chemistry, Faculty of Science, University of Ain Shams, Cairo 11566, Egypt

² Pharmaceutical Chemistry Department, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

³ Applied Organic Chemistry Department, National Research Center, Dokki, Cairo 12622, Egypt

Molecules 2015, 20(10), 18201-18218; https://doi.org/10.3390/molecules201018201 - 7 Oct 2015

Cited by 28 | Viewed by 10132

Abstract

Treatment of 2,3-diaryloxirane-2,3-dicarbonitriles 1a–c with different nitrogen nucleophiles, e.g., hydrazine, methyl hydrazine, phenyl hydrazine, hydroxylamine, thiosemicarbazide, and/or 2-amino-5-phenyl-1,3,4-thiadiazole, afforded pyrazole, isoxazole, pyrrolotriazine, imidazolothiadiazole derivatives 2–5, respectively. Reacting pyrazoles 2a–c with aromatic aldehydes and/or methyl glycinate produced [...] Read more.

Treatment of 2,3-diaryloxirane-2,3-dicarbonitriles 1a–c with different nitrogen nucleophiles, e.g., hydrazine, methyl hydrazine, phenyl hydrazine, hydroxylamine, thiosemicarbazide, and/or 2-amino-5-phenyl-1,3,4-thiadiazole, afforded pyrazole, isoxazole, pyrrolotriazine, imidazolothiadiazole derivatives 2–5, respectively. Reacting pyrazoles 2a–c with aromatic aldehydes and/or methyl glycinate produced Schiff’s bases 7a–d and pyrazolo[3,4-b]-pyrazinone derivative 8, respectively. Treating 7 with ammonium acetate and/or hydrazine hydrate, furnished the imidazolopyrazole and pyrazolotriazine derivatives 9 and 10, respectively. Reaction of 8 with chloroacetic acid and/or diethyl malonate gave tricyclic compound 11 and triketone 12, respectively. On the other hand, compound 1 was reacted with active methylene precursors, e.g., acetylacetone and/or cyclopentanone producing adducts 14a,b which upon fusion with ammonium acetate furnished the 3-pyridone derivatives 15a,b, respectively. Some of newly synthesized compounds were screened for activity against bacterial and fungal strains and most of the newly synthesized compounds showed high antimicrobial activities. The structures of the new compounds were elucidated using IR, ¹H-NMR, ¹³C-NMR and mass spectroscopy. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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18 pages, 895 KiB

Open AccessArticle

Potential of Essential Oils as Penetration Enhancers for Transdermal Administration of Ibuprofen to Treat Dysmenorrhoea

by Jun Chen^1,2,†, Qiu-Dong Jiang^1,2,†, Ye-Ming Wu^1,2,†, Pei Liu¹, Jun-Hong Yao², Qing Lu², Hui Zhang² and Jin-Ao Duan^1,*

¹ Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China

² Pharmaceutical Research Laboratory, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 18219-18236; https://doi.org/10.3390/molecules201018219 - 7 Oct 2015

Cited by 80 | Viewed by 10026

Abstract

The present study was conducted to evaluate and compare five essential oils (EOs) as penetration enhancers (PEs) to improve the transdermal drug delivery (TDD) of ibuprofen to treat dysmenorrhoea. The EOs were prepared using the steam distillation method and their chemical compositions were [...] Read more.

The present study was conducted to evaluate and compare five essential oils (EOs) as penetration enhancers (PEs) to improve the transdermal drug delivery (TDD) of ibuprofen to treat dysmenorrhoea. The EOs were prepared using the steam distillation method and their chemical compositions were identified by GC-MS. The corresponding cytotoxicities were evaluated in epidermal keartinocyte HaCaT cell lines by an MTT assay. Furthermore, the percutaneous permeation studies were carried out to compare the permeation enhancement effect of EOs. Then the therapeutic efficacy of ibuprofen with EOs was evaluated using dysmenorrheal model mice. The data supports a decreasing trend of skin cell viability in which Clove oil >Angelica oil > Chuanxiong oil > Cyperus oil > Cinnamon oil >> Azone. Chuanxiong oil and Angelica oil had been proved to possess a significant permeation enhancement for TDD of ibuprofen. More importantly, the pain inhibitory intensity of ibuprofen hydrogel was demonstrated to be greater with Chuanxiong oil when compared to ibuprofen without EOs (p < 0.05). The contents of calcium ion and nitric oxide (NO) were also significantly changed after the addition of Chuanxiong oil (p < 0.05). In summary, we suggest that Chuanxiong oil should be viewed as the best PE for TDD of ibuprofen to treat dysmenorrhea. Full article

(This article belongs to the Section Medicinal Chemistry)

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9 pages, 759 KiB

Open AccessArticle

Ring Opening Reactions through C-O Bond Cleavage Uniquely Adding Chemical Functionality to Boron Subphthalocyanine

by Catherine Bonnier¹ and Timothy P. Bender^1,2,3,*

¹ Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College St., Toronto M5S 3E5, ON, Canada

² Department of Materials Science and Engineering, University of Toronto, 184 College St., Toronto M5S 3E4, ON, Canada

³ Department of Chemistry, University of Toronto, 80 St. George St., Toronto M5S 3H6, ON, Canada

Molecules 2015, 20(10), 18237-18245; https://doi.org/10.3390/molecules201018237 - 7 Oct 2015

Cited by 6 | Viewed by 6378

Abstract

We are reporting the unexpected reaction between bromo-boron subphthalocyanine (Br-BsubPc) and THF, 1,4-dioxane or γ-butyrolactone that results in the ring opening of the solvent and its addition into the BsubPc moiety. Under heating, the endocyclic C-O bond of the solvent is cleaved and [...] Read more.

We are reporting the unexpected reaction between bromo-boron subphthalocyanine (Br-BsubPc) and THF, 1,4-dioxane or γ-butyrolactone that results in the ring opening of the solvent and its addition into the BsubPc moiety. Under heating, the endocyclic C-O bond of the solvent is cleaved and the corresponding bromoalkoxy-BsubPc derivative is obtained. These novel alkoxy-BsubPc derivatives have remaining alkyl-bromides suitable for further functionalization. The alkoxy-BsubPcs maintain the characteristic strongly absorption in visible spectrum and their fluorescence quantum yields. Full article

(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)

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18 pages, 1477 KiB

Open AccessArticle

Lead Optimization of 2-Cyclohexyl-N-[(Z)-(3-methoxyphenyl/3-hydroxyphenyl) methylidene]hydrazinecarbothioamides for Targeting the HER-2 Overexpressed Breast Cancer Cell Line SKBr-3

by Mashooq A. Bhat^1,*

, Abdullah Al-Dhfyan^2,3, Ahmed M. Naglah^4,5, Azmat Ali Khan¹ and Mohamed A. Al-Omar⁴

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

² Stem Cell & Tissue Re-Engineering Program, Research Center, King Faisal Specialized Hospital & Research Center, MBC-03, P. O. Box 3354, Riyadh 11211, Saudi Arabia

³ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

⁴ Department of Pharmaceutical Chemistry, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

⁵ Peptide Chemistry Department, Chemical Industries Research Division, National Research Centre, Dokki, Cairo 12622, Egypt

Molecules 2015, 20(10), 18246-18263; https://doi.org/10.3390/molecules201018246 - 7 Oct 2015

Cited by 11 | Viewed by 6642

Abstract

Lead derivatives of 2-cyclohexyl-N-[(Z)-(3-methoxyphenyl/3-hydroxyphenyl) methylidene]hydrazinecarbothioamides 1–18 were synthesized, characterized and evaluated in vitro against HER-2 overexpressed breast cancer cell line SKBr-3. All the compounds showed activity against HER-2 overexpressed SKBr-3 cells with IC₅₀ = 17.44 ± [...] Read more.

Lead derivatives of 2-cyclohexyl-N-[(Z)-(3-methoxyphenyl/3-hydroxyphenyl) methylidene]hydrazinecarbothioamides 1–18 were synthesized, characterized and evaluated in vitro against HER-2 overexpressed breast cancer cell line SKBr-3. All the compounds showed activity against HER-2 overexpressed SKBr-3 cells with IC₅₀ = 17.44 ± 0.01 µM to 53.29 ± 0.33 µM. (2Z)-2-(3-Hydroxybenzylidene)-N-(3-methoxyphenyl)hydrazinecarbothioamide (12, IC₅₀ = 17.44 ± 0.01 µM) was found to be most potent compound of this series targeting HER-2 overexpressed breast cancer cells compared to the standard drug 5-fluorouracil (5-FU) (IC₅₀ = 38.58 ± 0.04 µM). Compound 12 inhibited the cellular proliferation via DNA degradation. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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15 pages, 742 KiB

Open AccessArticle

New Non-Toxic Semi-Synthetic Derivatives from Natural Diterpenes Displaying Anti-Tuberculosis Activity

by Priscilla M. Matos¹, Brian Mahoney², Yohan Chan², David P. Day², Mirela M. W. Cabral¹, Carlos H. G. Martins¹, Raquel A. Santos¹, Jairo K. Bastos³, Philip C. Bulman Page² and Vladimir C. G. Heleno^1,*

¹ Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Franca 14404-600, Brazil

² School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK

³ Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14040-903, Brazil

Molecules 2015, 20(10), 18264-18278; https://doi.org/10.3390/molecules201018264 - 7 Oct 2015

Cited by 20 | Viewed by 6432

Abstract

We report herein the synthesis of six diterpene derivatives, three of which are new, generated through known organic chemistry reactions that allowed structural modification of the existing natural products kaurenoic acid (1) and copalic acid (2). The new compounds [...] Read more.

We report herein the synthesis of six diterpene derivatives, three of which are new, generated through known organic chemistry reactions that allowed structural modification of the existing natural products kaurenoic acid (1) and copalic acid (2). The new compounds were fully characterized using high resolution mass spectrometry, infrared spectroscopy, ¹H- and ¹³C-NMR experiments. We also report the evaluation of the anti-tuberculosis potential for all compounds, which showed some promising results for Micobacterium tuberculosis inhibition. Moreover, the toxicity for each of the most active compounds was also assessed. Full article

(This article belongs to the Section Natural Products Chemistry)

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73 pages, 5766 KiB

Open AccessArticle

A Generally Applicable Computer Algorithm Based on the Group Additivity Method for the Calculation of Seven Molecular Descriptors: Heat of Combustion, LogP_O/W, LogS, Refractivity, Polarizability, Toxicity and LogBB of Organic Compounds; Scope and Limits of Applicability

by Rudolf Naef

Department of Chemistry, University of Basel, Basel 4003, Switzerland

Molecules 2015, 20(10), 18279-18351; https://doi.org/10.3390/molecules201018279 - 7 Oct 2015

Cited by 42 | Viewed by 8940

Abstract

A generally applicable computer algorithm for the calculation of the seven molecular descriptors heat of combustion, logP_{octanol/water}, logS (water solubility), molar refractivity, molecular polarizability, aqueous toxicity (protozoan growth inhibition) and logBB (log (c_blood/c_brain)) is presented. The method, [...] Read more.

A generally applicable computer algorithm for the calculation of the seven molecular descriptors heat of combustion, logP_{octanol/water}, logS (water solubility), molar refractivity, molecular polarizability, aqueous toxicity (protozoan growth inhibition) and logBB (log (c_blood/c_brain)) is presented. The method, an extendable form of the group-additivity method, is based on the complete break-down of the molecules into their constituting atoms and their immediate neighbourhood. The contribution of the resulting atom groups to the descriptor values is calculated using the Gauss-Seidel fitting method, based on experimental data gathered from literature. The plausibility of the method was tested for each descriptor by means of a k-fold cross-validation procedure demonstrating good to excellent predictive power for the former six descriptors and low reliability of logBB predictions. The goodness of fit (Q²) and the standard deviation of the 10-fold cross-validation calculation was >0.9999 and 25.2 kJ/mol, respectively, (based on N = 1965 test compounds) for the heat of combustion, 0.9451 and 0.51 (N = 2640) for logP, 0.8838 and 0.74 (N = 1419) for logS, 0.9987 and 0.74 (N = 4045) for the molar refractivity, 0.9897 and 0.77 (N = 308) for the molecular polarizability, 0.8404 and 0.42 (N = 810) for the toxicity and 0.4709 and 0.53 (N = 383) for logBB. The latter descriptor revealing a very low Q² for the test molecules (R² was 0.7068 and standard deviation 0.38 for N = 413 training molecules) is included as an example to show the limits of the group-additivity method. An eighth molecular descriptor, the heat of formation, was indirectly calculated from the heat of combustion data and correlated with published experimental heat of formation data with a correlation coefficient R² of 0.9974 (N = 2031). Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 853 KiB

Open AccessArticle

Characterization and Quantification by LC-MS/MS of the Chemical Components of the Heating Products of the Flavonoids Extract in Pollen Typhae for Transformation Rule Exploration

by Yeqing Chen^1,†, Hongli Yu^1,2,3,†, Hao Wu^1,2,3,*, Yaozong Pan¹, Kuilong Wang¹

, Yangping Jin¹ and Chengchao Zhang¹

¹ School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China

² Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing 210023, China

³ Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing 210023, China

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 18352-18366; https://doi.org/10.3390/molecules201018352 - 8 Oct 2015

Cited by 185 | Viewed by 9698

Abstract

The Traditional Chinese Medicine herbs Pollen Typhae and Pollen Typhae Carbonisatus have been used as a hemostatic medicine promoting blood clotting for thousands of years. In this study, a reliable, highly sensitive method based on LC-MS/MS has been developed for differentiation of the [...] Read more.

The Traditional Chinese Medicine herbs Pollen Typhae and Pollen Typhae Carbonisatus have been used as a hemostatic medicine promoting blood clotting for thousands of years. In this study, a reliable, highly sensitive method based on LC-MS/MS has been developed for differentiation of the heating products of total flavonoids in Pollen Typhae (FPT-N). Twenty three peaks were detected and 18 peaks have been structurally identified by comparing retention times, high resolution mass spectrometry data, and fragment ions with those of the reference substances and/or literature data. Additionally, 15 compounds have been quantified by multiple reaction monitoring in the negative ionization mode. It was found that the contents of the characterized compounds differed greatly from each other in FPT-N samples. Among them, the content of huaicarbon B significantly increased at first, while it decreased after heating for 25 min, which could be considered as the characteristic component for distinguishing FPT-N. The present study provided an approach to rapidly distinguish the differences of FPT-N samples. In addition, the actively summarized characteristic fragmentation might help deducing the structure of unknown flavonols compounds. Furthermore, transformation rules of flavonoids during the heating process in carbonisatus development could contribute to hemostatic therapeutic component exploration. Full article

(This article belongs to the Section Natural Products Chemistry)

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20 pages, 1718 KiB

Open AccessArticle

Synthesis and Spectroscopic Evaluation of Two Novel Glycosylated Zinc(II)-Phthalocyanines

by Felix Bächle, Michael Hanack and Thomas Ziegler^*

Institute of Organic Chemistry, Universität Tübingen, Auf der Morgestelle 18, Tübingen 72076, Germany

Molecules 2015, 20(10), 18367-18386; https://doi.org/10.3390/molecules201018367 - 9 Oct 2015

Cited by 14 | Viewed by 8256

Abstract

In continuation of our work on glycoconjugated phthalocyanines, two new water soluble, non-ionic zinc(II) phthalocyanines have been prepared and fully characterized by means of ¹H-NMR, ¹³C-NMR, MALDI-TOF, ESI-TOF, UV-Vis spectroscopy, emission spectroscopy and fluorescence lifetime measurements. The carbohydrate-containing phthalonitrile precursors were [...] Read more.

In continuation of our work on glycoconjugated phthalocyanines, two new water soluble, non-ionic zinc(II) phthalocyanines have been prepared and fully characterized by means of ¹H-NMR, ¹³C-NMR, MALDI-TOF, ESI-TOF, UV-Vis spectroscopy, emission spectroscopy and fluorescence lifetime measurements. The carbohydrate-containing phthalonitrile precursors were synthesized through a copper-catalyzed azide-alkyne cycloaddition (CuAAC). The 2-methoxyethoxymethyl protecting group (MEM) was used to protect the carbohydrate moieties. It resisted the harsh basic cyclotetramerization conditions and could be easily cleaved under mild acidic conditions. The glycoconjugated zinc(II) phthalocyanines described here have molar extinction coefficents ε_max > 10⁵ m⁻¹ cm⁻¹ and absorption maxima λ > 680 nm, which make them attractive photosensitizers for photo-dynamic therapy. Full article

(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)

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35 pages, 1677 KiB

Open AccessArticle

A Promising PET Tracer for Imaging of α₇ Nicotinic Acetylcholine Receptors in the Brain: Design, Synthesis, and in Vivo Evaluation of a Dibenzothiophene-Based Radioligand

by Rodrigo Teodoro^1,†, Matthias Scheunemann^1,†, Winnie Deuther-Conrad^1,*,†

, Barbara Wenzel¹, Francesca Maria Fasoli², Cecilia Gotti², Mathias Kranz¹

, Cornelius K. Donat¹, Marianne Patt³, Ansel Hillmer⁴, Ming-Qiang Zheng⁴, Dan Peters⁵, Jörg Steinbach¹

, Osama Sabri³, Yiyun Huang⁴

and Peter Brust¹

¹ Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Permoserstraße 15, Leipzig 04318, Germany

² Consiglio Nazionale delle Ricerche, Institute of Neuroscience, Biometra-Institute University of Milan, Via Luigi Vanvitelli 32, Milano 20129, Italy

³ Department of Nuclear Medicine, University Hospital Leipzig, Liebigstraße 18, Leipzig 04103, Germany

⁴ PET Center, Yale University, P.O. Box 208048, 801 Howard Avenue, New Haven, CT 06520-8048, USA

⁵ Dan PET AB, Rosenstigen 7, Malmö SE-21619, Sweden

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 18387-18421; https://doi.org/10.3390/molecules201018387 - 9 Oct 2015

Cited by 13 | Viewed by 9830

Abstract

Changes in the expression of α₇ nicotinic acetylcholine receptors (α₇ nAChRs) in the human brain are widely assumed to be associated with neurological and neurooncological processes. Investigation of these receptors in vivo depends on the availability of imaging agents such as [...] Read more.

Changes in the expression of α₇ nicotinic acetylcholine receptors (α₇ nAChRs) in the human brain are widely assumed to be associated with neurological and neurooncological processes. Investigation of these receptors in vivo depends on the availability of imaging agents such as radioactively labelled ligands applicable in positron emission tomography (PET). We report on a series of new ligands for α₇ nAChRs designed by the combination of dibenzothiophene dioxide as a novel hydrogen bond acceptor functionality with diazabicyclononane as an established cationic center. To assess the structure-activity relationship (SAR) of this new basic structure, we further modified the cationic center systematically by introduction of three different piperazine-based scaffolds. Based on in vitro binding affinity and selectivity, assessed by radioligand displacement studies at different rat and human nAChR subtypes and at the structurally related human 5-HT₃ receptor, we selected the compound 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-fluorodibenzo-[b,d]thiophene 5,5-dioxide (10a) for radiolabeling and further evaluation in vivo. Radiosynthesis of [¹⁸F]10a was optimized and transferred to an automated module. Dynamic PET imaging studies with [¹⁸F]10a in piglets and a monkey demonstrated high uptake of radioactivity in the brain, followed by washout and target-region specific accumulation under baseline conditions. Kinetic analysis of [¹⁸F]10a in pig was performed using a two-tissue compartment model with arterial-derived input function. Our initial evaluation revealed that the dibenzothiophene-based PET radioligand [¹⁸F]10a ([¹⁸F]DBT-10) has high potential to provide clinically relevant information about the expression and availability of α₇ nAChR in the brain. Full article

(This article belongs to the Special Issue Preparation of Radiopharmaceuticals and Their Use in Drug Development)

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15 pages, 1538 KiB

Open AccessArticle

Contribution of Bacillus Isolates to the Flavor Profiles of Vanilla Beans Assessed through Aroma Analysis and Chemometrics

by Fenglin Gu^1,*, Yonggan Chen^1,2,3, Yiming Fang¹, Guiping Wu¹ and Lehe Tan¹

¹ Spice and Beverage Research Institute, CATAS, Wanning 571533, Hainan, China

² College of Bioscience and Technology, Qiongzhou University, Sanya 572022, Hainan, China

³ College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, Hubei, China

Molecules 2015, 20(10), 18422-18436; https://doi.org/10.3390/molecules201018422 - 9 Oct 2015

Cited by 21 | Viewed by 8063

Abstract

Colonizing Bacillus in vanilla (Vanilla planifolia Andrews) beans is involved in glucovanillin hydrolysis and vanillin formation during conventional curing. The flavor profiles of vanilla beans under Bacillus-assisted curing were analyzed through gas chromatography-mass spectrometry, electronic nose, and quantitative sensory analysis. The [...] Read more.

Colonizing Bacillus in vanilla (Vanilla planifolia Andrews) beans is involved in glucovanillin hydrolysis and vanillin formation during conventional curing. The flavor profiles of vanilla beans under Bacillus-assisted curing were analyzed through gas chromatography-mass spectrometry, electronic nose, and quantitative sensory analysis. The flavor profiles were analytically compared among the vanilla beans under Bacillus-assisted curing, conventional curing, and non-microorganism-assisted curing. Vanilla beans added with Bacillus vanillea XY18 and Bacillus subtilis XY20 contained higher vanillin (3.58% ± 0.05% and 3.48% ± 0.10%, respectively) than vanilla beans that underwent non-microorganism-assisted curing and conventional curing (3.09% ± 0.14% and 3.21% ± 0.15%, respectively). Forty-two volatiles were identified from endogenous vanilla metabolism. Five other compounds were identified from exogenous Bacillus metabolism. Electronic nose data confirmed that vanilla flavors produced through the different curing processes were easily distinguished. Quantitative sensory analysis confirmed that Bacillus-assisted curing increased vanillin production without generating any unpleasant sensory attribute. Partial least squares regression further provided a correlation model of different measurements. Overall, we comparatively analyzed the flavor profiles of vanilla beans under Bacillus-assisted curing, indirectly demonstrated the mechanism of vanilla flavor formation by microbes. Full article

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

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27 pages, 1310 KiB

Open AccessArticle

Cladribine Analogues via O⁶-(Benzotriazolyl) Derivatives of Guanine Nucleosides

by Sakilam Satishkumar^1,†, Prasanna K. Vuram^1,†, Siva Subrahmanyam Relangi^2,†, Venkateshwarlu Gurram², Hong Zhou³, Robert J. Kreitman³, Michelle M. Martínez Montemayor⁴, Lijia Yang¹, Muralidharan Kaliyaperumal², Somesh Sharma², Narender Pottabathini² and Mahesh K. Lakshman^1,*

¹ Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USA

² Discovery and Analytical Services, GVK Biosciences Pvt. Ltd., 28A IDA Nacharam, Hyderabad 500076, India

³ Clinical Immunotherapy Section, Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA

⁴ Department of Biochemistry, Universidad Central del Caribe-School of Medicine, P. O. Box 60327, Bayamón, PR 00960, USA

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 18437-18463; https://doi.org/10.3390/molecules201018437 - 9 Oct 2015

Cited by 13 | Viewed by 8853

Abstract

Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest [...] Read more.

Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O⁶-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic leukemia (CLL), cladribine was the most active against all. The bromo analogue of cladribine showed comparable activity to the ribose analogue of cladribine against HCL, but was more active against TCL and CLL. The bromo ribose analogue of cladribine showed activity, but was the least active among the C6-NH₂-containing compounds. Substitution with alkyl groups at the exocyclic amino group appears detrimental to activity, and only the C6 piperidinyl cladribine analogue demonstrated any activity. Against adenocarcinoma MDA-MB-231 cells, cladribine and its ribose analogue were most active. Full article

(This article belongs to the Special Issue Nucleoside Modifications)

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18 pages, 786 KiB

Open AccessReview

Breeding Vegetables with Increased Content in Bioactive Phenolic Acids

by Prashant Kaushik¹

, Isabel Andújar¹, Santiago Vilanova¹, Mariola Plazas¹, Pietro Gramazio¹

, Francisco Javier Herraiz¹, Navjot Singh Brar² and Jaime Prohens^1,*

¹ Instituto de Conservación y Mejora de la Agrodiversidad Valenciana, Universitat Politècnica de València, Camino de Vera 14, Valencia 46022, Spain

² Department of Vegetable Science, Chaudhary Charan Singh Haryana Agricultural University, Hisar 125001, India

Molecules 2015, 20(10), 18464-18481; https://doi.org/10.3390/molecules201018464 - 9 Oct 2015

Cited by 87 | Viewed by 11461

Abstract

Vegetables represent a major source of phenolic acids, powerful antioxidants characterized by an organic carboxylic acid function and which present multiple properties beneficial for human health. In consequence, developing new varieties with enhanced content in phenolic acids is an increasingly important breeding objective. [...] Read more.

Vegetables represent a major source of phenolic acids, powerful antioxidants characterized by an organic carboxylic acid function and which present multiple properties beneficial for human health. In consequence, developing new varieties with enhanced content in phenolic acids is an increasingly important breeding objective. Major phenolic acids present in vegetables are derivatives of cinnamic acid and to a lesser extent of benzoic acid. A large diversity in phenolic acids content has been found among cultivars and wild relatives of many vegetable crops. Identification of sources of variation for phenolic acids content can be accomplished by screening germplasm collections, but also through morphological characteristics and origin, as well as by evaluating mutations in key genes. Gene action estimates together with relatively high values for heritability indicate that selection for enhanced phenolic acids content will be efficient. Modern genomics and biotechnological strategies, such as QTL detection, candidate genes approaches and genetic transformation, are powerful tools for identification of genomic regions and genes with a key role in accumulation of phenolic acids in vegetables. However, genetically increasing the content in phenolic acids may also affect other traits important for the success of a variety. We anticipate that the combination of conventional and modern strategies will facilitate the development of a new generation of vegetable varieties with enhanced content in phenolic acids. Full article

(This article belongs to the Special Issue Recent Advances in Plant Phenolics)

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14 pages, 756 KiB

Open AccessArticle

A Mild and Regioselective Ring-Opening of Aziridines with Acid Anhydride Using TBD or PS-TBD as a Catalyst

by Satoru Matsukawa^* and Yasutaka Mouri

Department of Science Education, Faculty of Education, Ibaraki University, Ibaraki 310-8512, Japan

Molecules 2015, 20(10), 18482-18495; https://doi.org/10.3390/molecules201018482 - 9 Oct 2015

Cited by 10 | Viewed by 8870

Abstract

The ring-opening of N-tosylaziridines with various acid anhydrides catalyzed by 5 mol % of 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) afforded the corresponding β-amino esters in excellent yields under mild reaction conditions. Polymer-supported catalyst, PS-TBD also acts as a good catalyst for this reaction. PS-TBD was [...] Read more.

The ring-opening of N-tosylaziridines with various acid anhydrides catalyzed by 5 mol % of 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) afforded the corresponding β-amino esters in excellent yields under mild reaction conditions. Polymer-supported catalyst, PS-TBD also acts as a good catalyst for this reaction. PS-TBD was easily recovered and reused with minimal loss of activity. Full article

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

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15 pages, 974 KiB

Open AccessArticle

Anti-Inflammatory Constituents from Bidens frondosa

by Jiamei Le^1,2,†, Wenquan Lu^1,†, Xiaojuan Xiong², Zhijun Wu^1,* and Wansheng Chen^1,*

¹ Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China

² College of Chemical and Biological Engineering, Yichun University, Jiangxi 336000, China

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 18496-18510; https://doi.org/10.3390/molecules201018496 - 9 Oct 2015

Cited by 37 | Viewed by 6556

Abstract

A new polyacetylene glucoside (3E,5E,11E)-tridecatriene-7,9-diyne-1,2,13-triol-2-O-β-d-glucopyranoside (1), a new phenylpropanoid glucoside 2′-butoxyethylconiferin (2), and a new flavonoid glycoside 8,3′,4′-trihydroxyflavone-7-O-(6′′-O-p-coumaroyl)-β-d-glucopyranoside (3), have been isolated from [...] Read more.

A new polyacetylene glucoside (3E,5E,11E)-tridecatriene-7,9-diyne-1,2,13-triol-2-O-β-d-glucopyranoside (1), a new phenylpropanoid glucoside 2′-butoxyethylconiferin (2), and a new flavonoid glycoside 8,3′,4′-trihydroxyflavone-7-O-(6′′-O-p-coumaroyl)-β-d-glucopyranoside (3), have been isolated from Bidens frondosa together with fifty-three known compounds 4–56. The structures of these compounds were established by spectroscopic methods. mainly ESIMS, 1D- and 2D-NMR spectroscopic data. and comparison with literature data. Compounds 1–34, 36, 39, 43, 47, 51, and 52 were tested for inhibition of nuclear factor kappa B (NF-κB) in 293-NF-κB-luciferase report cell line induced by lipopolysaccharide (LPS), and compounds 1, 2, 3, 9, 15, 21, 24 and 51 were tested for the production of TNF-α, IL-1β, IL-6, IL-10 in RAW 264.7 macrophages induced by LPS. In conclusion, the isolated compounds 1, 2, 3, 9, 15, 21, 24 and 51 exhibited significant activity in anti-inflammatory activity assays. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 932 KiB

Open AccessArticle

Fluorescent Sensor for PH Monitoring Based on an i-Motif- – Switching Aptamer Containing a Tricyclic Cytosine Analogue (tC)

by Patrycja Bielecka and Bernard Juskowiak^*

Laboratory of Bioanalytical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b 61-614 Poznan, Poland

Molecules 2015, 20(10), 18511-18525; https://doi.org/10.3390/molecules201018511 - 9 Oct 2015

Cited by 26 | Viewed by 8207

Abstract

There are cytosine-rich regions in the genome that bind protons with high specificity. Thus protonated C-rich sequence may undergo folding to tetraplex structures called i-motifs. Therefore, one can regard such specific C-rich oligonucleotides as aptamers that recognize protons and undergo conformational transitions. Proper [...] Read more.

There are cytosine-rich regions in the genome that bind protons with high specificity. Thus protonated C-rich sequence may undergo folding to tetraplex structures called i-motifs. Therefore, one can regard such specific C-rich oligonucleotides as aptamers that recognize protons and undergo conformational transitions. Proper labeling of the aptamer with a fluorescent tag constitutes a platform to construct a pH-sensitive aptasensor. Since the hemiprotonated C-C⁺ base pairs are responsible for the folded tetraplex structure of i-motif, we decided to substitute one of cytosines in an aptamer sequence with its fluorescent analogue, 1,3-diaza-2-oxophenothiazine (tC). In this paper we report on three tC-modified fluorescent probes that contain RET related sequences as a proton recognizing aptamer. Results of the circular dichroism (CD), UV absorption melting experiments, and steady-state fluorescence measurements of these tC-modified i-motif probes are presented and discussed. The pH-induced i-motif formation by the probes resulted in fluorescence quenching of tC fluorophore. Efficiency of quenching was related to the pH variations. Suitability of the sensor for monitoring pH changes was also demonstrated. Full article

(This article belongs to the Special Issue Aptamers: Past, Present, and Future)

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13 pages, 847 KiB

Open AccessArticle

Highly Stable Tetra-Phenolato Titanium(IV) Agent Formulated into Nanoparticles Demonstrates Anti-Tumoral Activity and Selectivity

by Sigalit Meker¹, Ori Braitbard², Katrin Margulis-Goshen¹, Shlomo Magdassi¹, Jacob Hochman² and Edit Y. Tshuva^1,*

¹ The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel

² Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Science, The Hebrew University of Jerusalem, Jerusalem 91904, Israel

Molecules 2015, 20(10), 18526-18538; https://doi.org/10.3390/molecules201018526 - 9 Oct 2015

Cited by 21 | Viewed by 7262

Abstract

Titanium(IV) complexes exhibit high potential as anti-tumor agents, particularly due to their low intrinsic toxicity and cytotoxicity toward cisplatin resistant cells. Nevertheless, Ti(IV) complexes generally undergo rapid hydrolysis that previously hampered their utilization as anticancer drugs. We recently overcame this difficulty by developing [...] Read more.

Titanium(IV) complexes exhibit high potential as anti-tumor agents, particularly due to their low intrinsic toxicity and cytotoxicity toward cisplatin resistant cells. Nevertheless, Ti(IV) complexes generally undergo rapid hydrolysis that previously hampered their utilization as anticancer drugs. We recently overcame this difficulty by developing a highly stable Ti(IV) complex that is based on tetra-phenolato, hexadentate ligand, formulated into organic nanoparticles. Herein we investigated the activity of this complex in vitro and in vivo. Although inactive when tested directly due to poor solubility, when formulated, this complex displayed (a) high cytotoxicity toward cisplatin resistant human ovarian cells, A2780-cp, with resistance factor of 1.1; (b) additive behavior in combination with cisplatin toward ovarian and colon cancer cells; (c) selectivity toward cancer cells as implied by its mild activity toward non-cancerous, fibroblast lung cells, MRC-5; (d) high stability and durability as manifested by the ability to maintain cytotoxicity, even following one week of incubation in 100% aquatic medium solution; and (e) in vivo efficacy toward solid tumors of human colon cancer cells, HT-29, in nude mice without any clinical signs of toxicity. These features support the formulated phenolato Ti(IV) complex being an effective and selective anti-tumoral agent. Full article

(This article belongs to the Collection Poorly Soluble Drugs)

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12 pages, 1840 KiB

Open AccessArticle

Identification and Expression Analysis of Zebrafish (Danio rerio) E-Selectin during Embryonic Development

by Guijin Sun², Kechun Liu^1,*, Xue Wang¹, Xiuhe Liu², Qiuxia He¹ and Chung-Der Hsiao³

¹ Biology Institute, Shandong Academy of Sciences, Jinan 250014, China

² School of Food Science and Engineering, Qilu University of Technology, Jinan 250014, China

³ Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan

Molecules 2015, 20(10), 18539-18550; https://doi.org/10.3390/molecules201018539 - 12 Oct 2015

Cited by 9 | Viewed by 50475

Abstract

In this study, we cloned the full-length cDNA of E-selectin of zebrafish (Danio rerio), analyzed its expression pattern and preliminarily explored its biological function. Zebrafish E-selectin cDNA is 3146 bp and encodes a putative 871 amino acid protein. All structural domains [...] Read more.

In this study, we cloned the full-length cDNA of E-selectin of zebrafish (Danio rerio), analyzed its expression pattern and preliminarily explored its biological function. Zebrafish E-selectin cDNA is 3146 bp and encodes a putative 871 amino acid protein. All structural domains involved in E-selectin function are conserved in the putative protein. Whole-mount in situ hybridization of zebrafish at 24 and 48 h post-fertilization (hpf) revealed E-selectin expression mainly in vascular/endothelial progenitor cells in the posterior trunk and blood cells in the intermediate cell mass and posterior cardinal vein regions. Real-time quantitative RT-PCR analysis detected E-selectin expression at 0.2, 24 and 48 hpf and significantly decreased from 48 to 72 hpf. The expression of E-selectin, tumor necrosis factor-α and interleukin-1β was significantly upregulated at 22 to 72 h after induction with bacterial lipopolysaccharide. Thus, the structure of E-selectin protein is highly conserved among species, and E-selectin may be involved in embryonic development and essential for hematopoiesis and angiogenesis during embryonic development in zebrafish. Furthermore, we provide the first evidence of inflammatory mediators inducing E-selectin expression in non-mammalian vertebrates, which suggests that zebrafish E-selectin may be involved in inflammation and probably has similar biological function to mammalian E-selectin. Full article

(This article belongs to the Section Molecular Diversity)

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14 pages, 792 KiB

Open AccessArticle

Limonoids from the Seeds of Swietenia macrophylla and Their Anti-Inflammatory Activities

by Li-Chai Chen^1,2,†, Hsiang-Ruei Liao^3,†, Pei-Yu Chen², Wen-Lung Kuo⁴, Tsung-Hsien Chang⁵, Ping-Jyun Sung⁶

, Zhi-Hong Wen^1,†

and Jih-Jung Chen^7,8,*

¹ Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan

² Department of Pharmacy, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung 81342, Taiwan

³ Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan

⁴ Chung-Jen Junior College of Nursing, Health Sciences and Management, Chiayi 60077, Taiwan

⁵ Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan

⁶ National Museum of Marine Biology and Aquarium, Pingtung 944, Taiwan

⁷ Department of Pharmacy, Tajen University, Pingtung 90741, Taiwan

⁸ Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung 90741, Taiwan

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 18551-18564; https://doi.org/10.3390/molecules201018551 - 12 Oct 2015

Cited by 34 | Viewed by 6976

Abstract

A new limonoid, swietemacrophin (1), was isolated from the seeds of Swietenia macrophylla, together with five known compounds 2–6. The structure of 1 was determined through extensive 1D/2D-NMR and mass-spectrometric analyses. Swietemacrophin (1), humilinolide F [...] Read more.

A new limonoid, swietemacrophin (1), was isolated from the seeds of Swietenia macrophylla, together with five known compounds 2–6. The structure of 1 was determined through extensive 1D/2D-NMR and mass-spectrometric analyses. Swietemacrophin (1), humilinolide F (2), 3,6-O,O-diacetylswietenolide (3), 3-O-tigloylswietenolide (4), and swietemahonin E (5) exhibited inhibition (IC₅₀ values ≤ 45.44 μM) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). Compounds 1, 4, 5, and swietenine (6) showed potent inhibition with IC₅₀ values ≤ 36.32 μM, against lipopolysaccharide (LPS)-induced nitric oxide (NO) generation. Full article

(This article belongs to the Section Natural Products Chemistry)

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20 pages, 1074 KiB

Open AccessArticle

Synthesis, Fluorescence Properties, and Antiproliferative Potential of Several 3-Oxo-3H-benzo[f]chromene-2-carboxylic Acid Derivatives

by Xiao-Bo Fu^†, Xian-Fu Wang^†, Jia-Nian Chen^*, De-Wen Wu, Ting Li, Xing-Can Shen and Jiang-Ke Qin

¹ State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmacy, Guangxi Normal University, Yucai Road 15, Guilin 541004, China

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 18565-18584; https://doi.org/10.3390/molecules201018565 - 13 Oct 2015

Cited by 9 | Viewed by 6624

Abstract

In this study, two series of 3-oxo-3H-benzo[f]chromene-2-carboxylic acid derivatives (compounds 5a–i and 6a–g) were synthesized. Their in vitro proliferation inhibitory activities against the A549 and NCI-H460 human non-small cell lung cancer (NSCLC) cell lines [...] Read more.

In this study, two series of 3-oxo-3H-benzo[f]chromene-2-carboxylic acid derivatives (compounds 5a–i and 6a–g) were synthesized. Their in vitro proliferation inhibitory activities against the A549 and NCI-H460 human non-small cell lung cancer (NSCLC) cell lines were evaluated. Their photophysical properties were measured. Among these target compounds, 5e exhibited the strongest antiproliferative activity by inducing apoptosis, arresting cell cycle, and elevating intracellular reactive oxygen species (ROS) level, suggesting that it may be a potent antitumor agent. In addition, compound 6g with very low cytotoxicity, demonstrated excellent fluorescence properties, which could be used as an effective fluorescence probe for biological imaging. Full article

(This article belongs to the Section Bioorganic Chemistry)

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12 pages, 1837 KiB

Open AccessArticle

Green Synthesis of Novel Polyaniline Nanofibers: Application in pH Sensing

by Shivani Tanwar and Ja-an Annie Ho^*

BioAnalytical Chemistry and NanoBiomedicine Laboratory, Department of Biochemical Science and Technology, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan

Molecules 2015, 20(10), 18585-18596; https://doi.org/10.3390/molecules201018585 - 13 Oct 2015

Cited by 30 | Viewed by 8731

Abstract

An optically active polyaniline nanomaterial (PANI-Nap), doped with (S)-naproxen, was developed and evaluated as a potent pH sensor. We synthesized the material in one pot by the addition of the dopant, (S)-naproxen, prior to polymerization, followed by the addition [...] Read more.

An optically active polyaniline nanomaterial (PANI-Nap), doped with (S)-naproxen, was developed and evaluated as a potent pH sensor. We synthesized the material in one pot by the addition of the dopant, (S)-naproxen, prior to polymerization, followed by the addition of the oxidizing agent (ammonium persulfate) that causes polymerization of the aniline. This green chemistry approach allowed us to take only 1 h to produce a water-soluble and stable nanomaterial. UV-visible spectroscopy, fluorescence spectroscopy, FT-IR spectroscopy, Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) were used to characterize the designed nanomaterial. This nanomaterial exhibited excellent pH sensing properties and showed long term stability (up to one month) without loss of sensor performance. Full article

(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)

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23 pages, 1131 KiB

Open AccessArticle

Qualitative and Quantitative Analysis of the Major Constituents in Shexiang Tongxin Dropping Pill by HPLC-Q-TOF-MS/MS and UPLC-QqQ-MS/MS

by Daxin Chen^1,2, Shan Lin^1,2, Wen Xu³, Mingqing Huang³, Jianfeng Chu^1,2, Fei Xiao^1,2

, Jiumao Lin^1,2 and Jun Peng^1,2,*

¹ Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian, China

² Fujian Key Laboratory of Integrative Medicine on Geriatric, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian, China

³ College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian, China

Molecules 2015, 20(10), 18597-18619; https://doi.org/10.3390/molecules201018597 - 14 Oct 2015

Cited by 61 | Viewed by 9007

Abstract

Shexiang Tongxin dropping pill (STP) is a traditional Chinese medicine formula that consists of total saponins of ginseng, synthetic Calculus bovis, bear gall, Venenum bufonis, borneol and Salvia miltiorrhiza. STP has been widely used in China and Southeast Asia for [...] Read more.

Shexiang Tongxin dropping pill (STP) is a traditional Chinese medicine formula that consists of total saponins of ginseng, synthetic Calculus bovis, bear gall, Venenum bufonis, borneol and Salvia miltiorrhiza. STP has been widely used in China and Southeast Asia for the treatment of cardiovascular diseases. In this study, a qualitative analytical method using high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was developed for identification of the major constituents in STP. Based on the retention time and MS spectra, 41 components were identified by comparison with reference compounds and literature data. Moreover, using ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry in multiple-reaction monitoring mode, we quantified 13 of the identified constituents (ginsenoside Rg1, ginsenoside Rk3, cinobufagin, arenobufagin, bufalin, resibufogenin, tanshinone IIA, taurine, tauroursodeoxycholic acid, taurocholic acid, cholic acid, deoxycholic acid, and chenodeoxycholic acid). These results suggest that this new approach is applicable for the routine analysis and quality control of STP products and provides fundamental data for further in vivo pharmacokinetical studies. Full article

(This article belongs to the Section Metabolites)

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41 pages, 821 KiB

Open AccessReview

A Systematic Review of the Anxiolytic-Like Effects of Essential Oils in Animal Models

by Damião Pergentino De Sousa¹

, Palloma De Almeida Soares Hocayen², Luciana Nalone Andrade³ and Roberto Andreatini^2,*

¹ Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, CP 5009, João Pessoa-PB, CEP 58051-970, Brazil

² Departamento de Farmacologia, Universidade Federal do Paraná, CP 19031, Curitiba-PR, CEP 81540-970, Brazil

³ Departamento de Fisiologia, Universidade Federal de Sergipe, CEP 49100-000, São Cristóvão-SE, Brazil

Molecules 2015, 20(10), 18620-18660; https://doi.org/10.3390/molecules201018620 - 14 Oct 2015

Cited by 111 | Viewed by 37221

Abstract

The clinical efficacy of standardized essential oils (such as Lavender officinalis), in treating anxiety disorders strongly suggests that these natural products are an important candidate source for new anxiolytic drugs. A systematic review of essential oils, their bioactive constituents, and anxiolytic-like activity [...] Read more.

The clinical efficacy of standardized essential oils (such as Lavender officinalis), in treating anxiety disorders strongly suggests that these natural products are an important candidate source for new anxiolytic drugs. A systematic review of essential oils, their bioactive constituents, and anxiolytic-like activity is conducted. The essential oil with the best profile is Lavendula angustifolia, which has already been tested in controlled clinical trials with positive results. Citrus aurantium using different routes of administration also showed significant effects in several animal models, and was corroborated by different research groups. Other promising essential oils are Citrus sinensis and bergamot oil, which showed certain clinical anxiolytic actions; along with Achillea wilhemsii, Alpinia zerumbet, Citrus aurantium, and Spiranthera odoratissima, which, like Lavendula angustifolia, appear to exert anxiolytic-like effects without GABA/benzodiazepine activity, thus differing in their mechanisms of action from the benzodiazepines. The anxiolytic activity of 25 compounds commonly found in essential oils is also discussed. Full article

(This article belongs to the Section Natural Products Chemistry)

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24 pages, 12768 KiB

Open AccessArticle

Resin-Immobilized Palladium Nanoparticle Catalysts for Organic Reactions in Aqueous Media: Morphological Aspects

by Piero Mastrorilli^1,*

, Maria M. Dell’Anna¹, Antonino Rizzuti¹, Matilda Mali¹, Mauro Zapparoli² and Cristina Leonelli³

¹ Dipartimento di Ingegneria Civile, Ambientale, del Territorio, Edile e di Chimica (DICATECh), Politecnico di Bari, via Orabona 4, Bari 70125, Italy

² Centro Interdipartimentale Grandi Strumenti (C.I.G.S.), Università di Modena e Reggio Emilia, via Campi 213\A, Modena 41125, Italy

³ Dipartimento di Ingegneria “Enzo Ferrari”, Università di Modena e Reggio Emilia, via Pietro Vivarelli 10, Modena 41125, Italy

Molecules 2015, 20(10), 18661-18684; https://doi.org/10.3390/molecules201018661 - 14 Oct 2015

Cited by 21 | Viewed by 7438

Abstract

An insight into the nano- and micro-structural morphology of a polymer supported Pd catalyst employed in different catalytic reactions under green conditions is reported. The pre-catalyst was obtained by copolymerization of the metal-containing monomer Pd(AAEMA)₂ [AAEMA⁻ = deprotonated form of 2-(acetoacetoxy) [...] Read more.

An insight into the nano- and micro-structural morphology of a polymer supported Pd catalyst employed in different catalytic reactions under green conditions is reported. The pre-catalyst was obtained by copolymerization of the metal-containing monomer Pd(AAEMA)₂ [AAEMA⁻ = deprotonated form of 2-(acetoacetoxy) ethyl methacrylate] with ethyl methacrylate as co-monomer, and ethylene glycol dimethacrylate as cross-linker. This material was used in water for the Suzuki-Miyaura cross-coupling of aryl bromides, and for the reduction of nitroarenes and quinolines using NaBH₄ or H₂, as reductants. TEM analyses showed that in all cases the pristine Pd(II) species were reduced in situ to Pd(0), which formed metal nanoparticles (NPs, the real active species). The dependence of their average size (2–10 nm) and morphology on different parameters (temperature, reducing agent, presence of a phase transfer agent) is discussed. TEM and micro-IR analyses showed that the polymeric support retained its porosity and stability for several catalytic cycles in all reactions and Pd NPs did not aggregate after reuse. The metal nanoparticle distribution throughout the polymer matrix after several recycles provided precious information about the catalytic mechanism, which was truly heterogeneous in the hydrogenation reactions and of the so-called “release and catch” type in the Suzuki coupling. Full article

(This article belongs to the Special Issue Metal Nanocatalysts in Green Synthesis and Energy Applications)

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19 pages, 2836 KiB

Open AccessArticle

Antimicrobial Activity of Rhoeo discolor Phenolic Rich Extracts Determined by Flow Cytometry

by Rebeca García-Varela^1,2, Rebeca M. García-García¹, Bertha A. Barba-Dávila¹, Oscar R. Fajardo-Ramírez³, Sergio O. Serna-Saldívar¹ and Guy A. Cardineau^1,2,*

¹ Centro de Biotecnología FEMSA, Tecnologico de Monterrey, Campus Monterrey, Ave Eugenio Garza Sada 2501, Monterrey 64849, N.L., Mexico

² Centro de Agrobiotecnología, Tecnologico de Monterrey, Campus Monterrey, Ave Eugenio Garza Sada 2501, Monterrey 64849, N.L., Mexico

³ Centro de Innovación y Transferida en Salud, Escuela de Medicina, Tecnologico de Monterrey, Campus Monterrey, Ave Morones Prieto No. 3000 Pte., Col. Los Doctores, C.P. Monterrey 64710, N.L., Mexico

Molecules 2015, 20(10), 18685-18703; https://doi.org/10.3390/molecules201018685 - 14 Oct 2015

Cited by 26 | Viewed by 15826

Abstract

Traditional medicine has led to the discovery of important active substances used in several health-related areas. Phytochemicals in Rhoeo discolor extracts have proven to have important antimicrobial activity. In the present study, our group determined the antimicrobial effects of extracts of Rhoeo discolor [...] Read more.

Traditional medicine has led to the discovery of important active substances used in several health-related areas. Phytochemicals in Rhoeo discolor extracts have proven to have important antimicrobial activity. In the present study, our group determined the antimicrobial effects of extracts of Rhoeo discolor, a plant commonly used in Mexico for both medicinal and ornamental purposes. We evaluated the in vitro activity of phenolic rich extracts against specifically chosen microorganisms of human health importance by measuring their susceptibility via agar-disc diffusion assay and flow cytometry: Gram-positive Listeria innocua and Streptococcus mutans, Gram-negative Escherichia coli and Pseudomonas aeruginosa, and lastly a fungal pathogen Candida albicans. Ten different extracts were tested in eight different doses on all the microorganisms. Analytical data revealed a high content of phenolic compounds. Both agar-disc diffusion assay and flow cytometry results demonstrated that Pseudomonas aeruginosa was the least affected by extract exposure. However, low doses of these extracts (predominantly polar), in a range from 1 to 4 μg/mL, did produce a statistically significant bacteriostatic and bactericidal effect on the rest of the microorganisms. These results suggest the addition of certain natural extracts from Rhoeo discolor could act as antibacterial and antimycotic drugs or additives for foods and cosmetics. Full article

(This article belongs to the Special Issue Recent Advances in Plant Phenolics)

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13 pages, 743 KiB

Open AccessArticle

Study of the Biotransformation of Tongmai Formula by Human Intestinal Flora and Its Intestinal Permeability across the Caco-2 Cell Monolayer

by Shuai Wu, Wei Xu, Fu-Rong Wang and Xiu-Wei Yang^*

State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing 100191, China

Molecules 2015, 20(10), 18704-18716; https://doi.org/10.3390/molecules201018704 - 15 Oct 2015

Cited by 27 | Viewed by 6834

Abstract

Tongmai formula (TMF) is a well-known Chinese medicinal preparation that contains isoflavones as its major bioactive constituents. As traditional Chinese medicines (TCMs) are usually used by oral administration, their fate inside the intestinal lumen, including their biotransformation by human intestinal flora (HIF) and [...] Read more.

Tongmai formula (TMF) is a well-known Chinese medicinal preparation that contains isoflavones as its major bioactive constituents. As traditional Chinese medicines (TCMs) are usually used by oral administration, their fate inside the intestinal lumen, including their biotransformation by human intestinal flora (HIF) and intestinal absorption deserves study. In this work TMF extract was incubated with human intestinal bacteria under anaerobic conditions and the changes in the twelve main constituents of TMF were then investigated. Their intestinal permeabilities, i.e., the transport capability across the intestinal brush border were investigated with a human colon carcinoma cell line (Caco2) cell monolayer model to predict the absorption mechanism. Meanwhile, rapid HPLC-DAD methods were established for the assay. According to the biotransformation curves of the twelve constituents and the permeability coefficients, the intestinal absorption capacity of the typical compounds was elevated from the levels of 10⁻⁷ cm/s to 10⁻⁵ cm/s from those of the original compounds in TMF. Among them the main isoflavone glycosides puerarin (4), mirificin (6) and daidzin (7) were transformed into the same aglycone, daidzein (10). Therefore it was predicted that the aglycone compounds might be the real active ingredients in TMF. The models used can represent a novel path for the TCM studies. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 2265 KiB

Open AccessArticle

Enzymatic Hydrolysis and Simultaneous Extraction for Preparation of Genipin from Bark of Eucommia ulmoides after Ultrasound, Microwave Pretreatment

by Lili Li^1,2, Yupin Guo³, Lianfei Zhao^1,2, Yuangang Zu^1,2, Huiyan Gu^4,* and Lei Yang^1,2,*

¹ Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China

² State Engineering Laboratory for Bioresource Eco-Utilization, Northeast Forestry University, Harbin 150040, China

³ College of Animal Science and Technology, Hebei North University, Zhangjiakou 075000, China

⁴ School of Forestry, Northeast Forestry University, Harbin 150040, China

Molecules 2015, 20(10), 18717-18731; https://doi.org/10.3390/molecules201018717 - 15 Oct 2015

Cited by 16 | Viewed by 6068

Abstract

A continuous process based on the combination of ultrasounds and/or microwaves pretreatments followed by enzymatic hydrolysis and simultaneous extraction (EHSE) has been proposed to recover genipin from Eucommia ulmoides bark. At first, in the pretreatment step, the mixture of 1.0 g dried bark [...] Read more.

A continuous process based on the combination of ultrasounds and/or microwaves pretreatments followed by enzymatic hydrolysis and simultaneous extraction (EHSE) has been proposed to recover genipin from Eucommia ulmoides bark. At first, in the pretreatment step, the mixture of 1.0 g dried bark powder and 10 mL deionized water were irradiated by microwave under 500 W for 10 min. Then, in hydrolysis step, the optimal conditions were as follows: 0.5 mg/mL of cellulase concentration, 4.0 pH of enzyme solution, 24 h of incubation time and 40 °C of incubation temperature. After incubation, 10 mL ethanol was added to extract genipin for 30 min by ultrasound. After EHSE treatment, the yield of genipin could reach 1.71 μmol/g. Moreover, scanning electron micrographs illustrated that severe structural disruption of plant was obtained by EHSE. The results indicated that the EHSE method provided a good alternative for the preparation of genipin from Eucommia ulmoides bark as well as other herbs. Full article

(This article belongs to the Section Natural Products Chemistry)

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27 pages, 7136 KiB

Open AccessReview

Charting a Path to Success in Virtual Screening

by Stefano Forli

Molecular Graphics Laboratory, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA

Molecules 2015, 20(10), 18732-18758; https://doi.org/10.3390/molecules201018732 - 15 Oct 2015

Cited by 70 | Viewed by 14955

Abstract

Docking is commonly applied to drug design efforts, especially high-throughput virtual screenings of small molecules, to identify new compounds that bind to a given target. Despite great advances and successful applications in recent years, a number of issues remain unsolved. Most of the [...] Read more.

Docking is commonly applied to drug design efforts, especially high-throughput virtual screenings of small molecules, to identify new compounds that bind to a given target. Despite great advances and successful applications in recent years, a number of issues remain unsolved. Most of the challenges and problems faced when running docking experiments are independent of the specific software used, and can be ascribed to either improper input preparation or to the simplified approaches applied to achieve high-throughput speed. Being aware of approximations and limitations of such methods is essential to prevent errors, deal with misleading results, and increase the success rate of virtual screening campaigns. In this review, best practices and most common issues of docking and virtual screening will be discussed, covering the journey from the design of the virtual experiment to the hit identification. Full article

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

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18 pages, 796 KiB

Open AccessReview

Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs

by Roberta Censi and Piera Di Martino^*

School of Pharmacy, University of Camerino, via S. Agostino, 1, Camerino 62032, Italy

Molecules 2015, 20(10), 18759-18776; https://doi.org/10.3390/molecules201018759 - 15 Oct 2015

Cited by 371 | Viewed by 23209

Abstract

Drugs with low water solubility are predisposed to poor and variable oral bioavailability and, therefore, to variability in clinical response, that might be overcome through an appropriate formulation of the drug. Polymorphs (anhydrous and solvate/hydrate forms) may resolve these bioavailability problems, but they [...] Read more.

Drugs with low water solubility are predisposed to poor and variable oral bioavailability and, therefore, to variability in clinical response, that might be overcome through an appropriate formulation of the drug. Polymorphs (anhydrous and solvate/hydrate forms) may resolve these bioavailability problems, but they can be a challenge to ensure physicochemical stability for the entire shelf life of the drug product. Since clinical failures of polymorph drugs have not been uncommon, and some of them have been entirely unexpected, the Food and Drug Administration (FDA) and the International Conference on Harmonization (ICH) has required preliminary and exhaustive screening studies to identify and characterize all the polymorph crystal forms for each drug. In the past, the polymorphism of many drugs was detected fortuitously or through manual time consuming methods; today, drug crystal engineering, in particular, combinatorial chemistry and high-throughput screening, makes it possible to easily and exhaustively identify stable polymorphic and/or hydrate/dehydrate forms of poorly soluble drugs, in order to overcome bioavailability related problems or clinical failures. This review describes the concepts involved, provides examples of drugs characterized by poor solubility for which polymorphism has proven important, outlines the state-of-the-art technologies and discusses the pertinent regulations. Full article

(This article belongs to the Collection Poorly Soluble Drugs)

12 pages, 900 KiB

Open AccessArticle

In Vitro Cytoprotective Effects and Antioxidant Capacity of Phenolic Compounds from the Leaves of Swietenia macrophylla

by Sônia Pamplona^1,†, Paulo Sá^1,†

, Dielly Lopes^2,†, Edmar Costa^2,†, Elizabeth Yamada^2,†, Consuelo E Silva^1,†, Mara Arruda^1,†, Jesus Souza^3,† and Milton Da Silva^1,*,†

¹ Programa de Pós-Graduação em Química, Instituto de Ciências Exatas e Naturais, Campus Universitário do Guamá, Universidade Federal do Pará, Belém-PA 66075-970, Brazil

² Laboratório de Neuropatologia Experimental (LaNEx), Hospital Universitário Barros Barreto, Rua dos Mundurucus, 4487–Guamá. CEP 66073-000. Belém, PA, Brazil

³ Faculdade de Engenharia de Alimentos, Instituto de Tecnologia, Campus Universitário do Guamá, Universidade Federal do Pará, Belém-PA 66075-970, Brazil

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 18777-18788; https://doi.org/10.3390/molecules201018777 - 16 Oct 2015

Cited by 18 | Viewed by 8205

Abstract

Swietenia macrophylla (mahogany) is a highly valued timber species, whereas the leaves are considered to be waste product. A total of 27 phenolic compounds were identified in aqueous extracts from mahogany leaves by comparing retention times and mass spectra data with those of [...] Read more.

Swietenia macrophylla (mahogany) is a highly valued timber species, whereas the leaves are considered to be waste product. A total of 27 phenolic compounds were identified in aqueous extracts from mahogany leaves by comparing retention times and mass spectra data with those of authentic standards using LC-ESI-MS/MS. Polyphenols play an important role in plants as defense mechanisms against pests and pathogens and have potent antioxidant properties. In terms of health applications, interest has increased considerably in naturally occurring antioxidant sources, since they can retard the progress of many important neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. The antioxidant capacities of two aqueous extracts, M1 (decoction) and M2 (infusion), were measured using TEAC and Folin-Ciocalteau methods. Additionally, M1 was used in order to investigate its potential cytoprotective effects on an in vitro model of neurodegeneration, by using primary cerebellar cultures exposed to methyl mercury (MeHg). Under experimental sub-chronic conditions (72 h), concomitant exposure of the same cultures to MeHg and M1 extract resulted in a statistically significant increase in cell viability in all three concentrations tested (10, 50 and 100 μg/mL), strongly suggesting that due to its high content of antioxidant compounds, the M1 extract provides significant cytoprotection against the MeHg-induced in vitro neurotoxicity. Full article

(This article belongs to the Collection Neuroprotection Mediated by Natural Products and Their Chemical Derivatives)

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19 pages, 834 KiB

Open AccessArticle

Phosphonylated Acyclic Guanosine Analogues with the 1,2,3-Triazole Linker

by Iwona E. Głowacka^1,*, Graciela Andrei², Dominique Schols², Robert Snoeck² and Dorota G. Piotrowska¹

¹ Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, 90-151 Lodz, Muszyńskiego 1, Poland

² Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium

Molecules 2015, 20(10), 18789-18807; https://doi.org/10.3390/molecules201018789 - 16 Oct 2015

Cited by 9 | Viewed by 6497

Abstract

A novel series of {4-[(2-amino-6-chloro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates and {4-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates as acyclic analogues of guanosine were synthesized and assessed for antiviral activity against a broad range of DNA and RNA viruses and for their cytostatic activity toward three [...] Read more.

A novel series of {4-[(2-amino-6-chloro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates and {4-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates as acyclic analogues of guanosine were synthesized and assessed for antiviral activity against a broad range of DNA and RNA viruses and for their cytostatic activity toward three cancerous cell lines (HeLa, L1210 and CEM). They were devoid of antiviral activity; however, several phosphonates were found slightly cytostatic against HeLa cells at an IC₅₀ in the 80–210 µM range. Compounds (1R,2S)-17k and (1S,2S)-17k showed the highest inhibitory effects (IC₅₀ = 15–30 µM) against the proliferation of murine leukemia (L1210) and human T-lymphocyte (CEM) cell lines. Full article

(This article belongs to the Section Organic Chemistry)

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19 pages, 968 KiB

Open AccessArticle

Synthesis, Hydrolysis, and Protonation-Promoted Intramolecular Reductive Breakdown of Potential NRTIs: Stavudine α-P-Borano-γ-P-N-l-tryptophanyltriphosphates

by Zhihong Xu^* and Barbara Ramsay Shaw

Shaw Department of Chemistry, Duke University, Durham, NC 27708, USA

Molecules 2015, 20(10), 18808-18826; https://doi.org/10.3390/molecules201018808 - 16 Oct 2015

Cited by 2 | Viewed by 7477

Abstract

Phosphorus-modified prodrugs of dideoxynucleoside triphosphates (ddNTPs) have shown promise as pronucleotide strategies for improving antiviral activity compared to their parent dideoxynucleosides. Borane modified NTPs offer a promising choice as nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). However, the availability of α-P-borano-γ-P-substituted [...] Read more.

Phosphorus-modified prodrugs of dideoxynucleoside triphosphates (ddNTPs) have shown promise as pronucleotide strategies for improving antiviral activity compared to their parent dideoxynucleosides. Borane modified NTPs offer a promising choice as nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). However, the availability of α-P-borano-γ-P-substituted NTP analogs remains limited due to challenges with synthesis and purification. Here, we report the chemical synthesis and stability of a new potential class of NRTI prodrugs: stavudine (d4T) 5′-α-P-borano-γ-P-N-L-tryptophanyltriphosphates. One-pot synthesis of these compounds was achieved via a modified cyclic trimetaphosphate approach. Pure Rp and Sp diastereomers were obtained after HPLC separation. Based on LC-MS analysis, we report degradation pathways, half-lives (5–36 days) and mechanisms arising from structural differences to generate the corresponding borano tri- and di-phosphates, and H-phosphonate, via several parallel routes in buffer at physiologically relevant pH and temperature. Here, the major hydrolysis products, d4T α-P-boranotriphosphate Rp and Sp isomers, were isolated by HPLC and identified with spectral data. We first propose that one of the major degradation products, d4T H-phosphonate, was generated from the d4T pronucleotides via a protonation-promoted intramolecular reduction followed by a second step nucleophilic attack. This report could provide valuable information for pronucleotide-based drug design in terms of selective release of target nucleotides. Full article

(This article belongs to the Special Issue Frontiers in Nucleic Acid Chemistry)

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20 pages, 3079 KiB

Open AccessArticle

Synthesis and Crystallographic Insight into the Structural Aspects of Some Novel Adamantane-Based Ester Derivatives

by C. S. Chidan Kumar^1,2,*, Huey Chong Kwong³, Siau Hui Mah⁴

, Tze Shyang Chia¹, Wan-Sin Loh¹, Ching Kheng Quah^1,*, Gin Keat Lim³, Siddegowda Chandraju⁵ and Hoong-Kun Fun^1,6

¹ Crystallography Unit, School of Physics, Universiti Sains Malaysia, Penang 11800, Malaysia

² Department of Chemistry, Alva’s Institute of Engineering & Technology, Visvesvaraya Technological University, Mijar, Moodbidri 574225, India

³ School of Chemical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia

⁴ School of Biosciences, Taylor’s University, Lakeside Campus, Subang Jaya 47500, Selangor, Malaysia

⁵ Department of Sugar Technology & Chemistry, University of Mysore, Sir M.V. PG Center, Mandya 571402, Karnataka, India

⁶ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

Molecules 2015, 20(10), 18827-18846; https://doi.org/10.3390/molecules201018827 - 16 Oct 2015

Cited by 11 | Viewed by 7065

Abstract

Adamantyl-based compounds are commercially important in the treatments for neurological conditions and type-2 diabetes, aside from their anti-viral abilities. Their values in drug design are chronicled as multi-dimensional. In the present study, a series of 2-(adamantan-1-yl)-2-oxoethyl benzoates, 2(a–q), [...] Read more.

Adamantyl-based compounds are commercially important in the treatments for neurological conditions and type-2 diabetes, aside from their anti-viral abilities. Their values in drug design are chronicled as multi-dimensional. In the present study, a series of 2-(adamantan-1-yl)-2-oxoethyl benzoates, 2(a–q), and 2-(adamantan-1-yl)-2-oxoethyl 2-pyridinecarboxylate, 2r, were synthesized by reacting 1-adamantyl bromomethyl ketone with various carboxylic acids using potassium carbonate in dimethylformamide medium at room temperature. Three-dimensional structures studied using X-ray diffraction suggest that the adamantyl moiety can serve as an efficient building block to synthesize 2-oxopropyl benzoate derivatives with synclinal conformation with a looser-packed crystal packing system. Compounds 2a, 2b, 2f, 2g, 2i, 2j, 2m, 2n, 2o, 2q and 2r exhibit strong antioxidant activities in the hydrogen peroxide radical scavenging test. Furthermore, three compounds, 2p, 2q and 2r, show good anti-inflammatory activities in the evaluation of albumin denaturation. Full article

(This article belongs to the Section Molecular Diversity)

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9 pages, 1773 KiB

Open AccessCommunication

Amine-Functionalized ZnO Nanosheets for Efficient CO₂ Capture and Photoreduction

by Yusen Liao, Zhaoning Hu, Quan Gu and Can Xue^*

School of Materials Science and Engineering, Nanyang Technological University, 639798 Singapore, Singapore

Molecules 2015, 20(10), 18847-18855; https://doi.org/10.3390/molecules201018847 - 16 Oct 2015

Cited by 52 | Viewed by 8207

Abstract

Amine-functionalized ZnO nanosheets were prepared through a one-step hydrothermal method by using monoethanolamine, which has a hydroxyl group, for covalent attachment on ZnO and a primary amine group to supply the amine-functionalization. We demonstrate that the terminal amine groups on ZnO surfaces substantially [...] Read more.

Amine-functionalized ZnO nanosheets were prepared through a one-step hydrothermal method by using monoethanolamine, which has a hydroxyl group, for covalent attachment on ZnO and a primary amine group to supply the amine-functionalization. We demonstrate that the terminal amine groups on ZnO surfaces substantially increase the capability of CO₂ capture via chemisorption, resulting in effective CO₂ activation. As a result, the photogenerated electrons from excited ZnO can more readily reduce the surface-activated CO₂, which thereby enhances the activity for photocatalytic CO₂ reduction. Full article

(This article belongs to the Special Issue Nano-Structural Photocatalytic Materials: Synthesis, Characterization and Applications)

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14 pages, 987 KiB

Open AccessArticle

Maleimides Designed for Self-Assembly and Reactivity on Graphene

by Cristina Mattioli^†, André Gourdon^*,† and NanoSciences Group

¹ Centre d’Elaboration de Matériaux et d’Etudes Structurales, Centre National de la Recherche Scientifique, CEMES-CNRS, 29 rue Jeanne Marvig, BP 94347, 31055, Toulouse Cedex 4, France

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 18856-18869; https://doi.org/10.3390/molecules201018856 - 16 Oct 2015

Cited by 1 | Viewed by 7568

Abstract

Two new maleimide derivatives have been synthesized, prone to self-assemble and react with graphene as dienophiles. Both compounds bear a long alkyl chain on the carbon-carbon double bond position 3. The maleimide 1 bears a second alkyl chain at the nitrogen, while in [...] Read more.

Two new maleimide derivatives have been synthesized, prone to self-assemble and react with graphene as dienophiles. Both compounds bear a long alkyl chain on the carbon-carbon double bond position 3. The maleimide 1 bears a second alkyl chain at the nitrogen, while in compound 2, three maleimide functionalities are linked to a triethynylbenzene core. Full article

(This article belongs to the Section Organic Chemistry)

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16 pages, 1083 KiB

Open AccessArticle

Structure–Activity Relationship of Oligomeric Flavan-3-ols: Importance of the Upper-Unit B-ring Hydroxyl Groups in the Dimeric Structure for Strong Activities

by Yoshitomo Hamada¹, Syota Takano², Yoshihiro Ayano¹, Masahiro Tokunaga², Takahiro Koashi¹, Syuhei Okamoto¹, Syoma Doi¹, Masahiko Ishida², Takashi Kawasaki³, Masahiro Hamada⁴, Noriyuki Nakajima^4,* and Akiko Saito^1,2,*

¹ Graduate School of Engineering, Osaka Electro-Communication University (OECU), 18-8 Hatsu-cho, Neyagawa-shi, Osaka 572-8530, Japan

² Faculty of Engineering, Osaka Electro-Communication University (OECU), 18-8 Hatsu-cho, Neyagawa-shi, Osaka 572-8530, Japan

³ Department of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan

⁴ Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180, Kurokawa, Imizu, Toyama 939-0398, Japan

Molecules 2015, 20(10), 18870-18885; https://doi.org/10.3390/molecules201018870 - 16 Oct 2015

Cited by 16 | Viewed by 6269

Abstract

Proanthocyanidins, which are composed of oligomeric flavan-3-ol units, are contained in various foodstuffs (e.g., fruits, vegetables, and drinks) and are strongly biologically active compounds. We investigated which element of the proanthocyanidin structure is primarily responsible for this functionality. In this study, we elucidate [...] Read more.

Proanthocyanidins, which are composed of oligomeric flavan-3-ol units, are contained in various foodstuffs (e.g., fruits, vegetables, and drinks) and are strongly biologically active compounds. We investigated which element of the proanthocyanidin structure is primarily responsible for this functionality. In this study, we elucidate the importance of the upper-unit of 4–8 condensed dimeric flavan-3-ols for antimicrobial activity against Saccharomyces cerevisiae (S. cerevisiae) and cervical epithelioid carcinoma cell line HeLa S3 proliferation inhibitory activity. To clarify the important constituent unit of proanthocyanidin, we synthesized four dimeric compounds, (−)-epigallocatechin-[4,8]-(+)-catechin, (−)-epigallocatechin-[4,8]-(−)-epigallocatechin, (−)-epigallocatechin-[4,8]-(−)-epigallocatechin-3-O-gallate, and (+)-catechin-[4,8]-(−)-epigallocatechin and performed structure–activity relationship (SAR) studies. In addition to antimicrobial activity against S. cerevisiae and proliferation inhibitory activity on HeLa S3 cells, the correlation of 2,2-diphenyl-l-picrylhydrazyl radical scavenging activity with the number of phenolic hydroxyl groups was low. On the basis of the results of our SAR studies, we concluded that B-ring hydroxyl groups of the upper-unit of the dimer are crucially important for strong and effective activity. Full article

(This article belongs to the Section Natural Products Chemistry)

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21 pages, 1285 KiB

Open AccessReview

Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism

by Dun-Xian Tan^*, Lucien C. Manchester, Eduardo Esteban-Zubero, Zhou Zhou and Russel J. Reiter^*

Department of Cellular and Structural Biology, Health Science Center, University of Texas, San Antonio, TX 78229, USA

Molecules 2015, 20(10), 18886-18906; https://doi.org/10.3390/molecules201018886 - 16 Oct 2015

Cited by 565 | Viewed by 35856

Abstract

Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is [...] Read more.

Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is speculated that the melatonin synthetic machinery in eukaryotes was inherited from bacteria as a result of endosymbiosis. However, melatonin’s synthetic mechanisms in microorganisms are currently unknown. Melatonin metabolism is highly complex with these enzymatic processes having evolved from cytochrome C. In addition to its enzymatic degradation, melatonin is metabolized via pseudoenzymatic and free radical interactive processes. The metabolic products of these processes overlap and it is often difficult to determine which process is dominant. However, under oxidative stress, the free radical interactive pathway may be featured over the others. Because of the complexity of the melatonin degradative processes, it is expected that additional novel melatonin metabolites will be identified in future investigations. The original and primary function of melatonin in early life forms such as in unicellular organisms was as a free radical scavenger and antioxidant. During evolution, melatonin was selected as a signaling molecule to transduce the environmental photoperiodic information into an endocrine message in multicellular organisms and for other purposes as well. As an antioxidant, melatonin exhibits several unique features which differ from the classic antioxidants. These include its cascade reaction with free radicals and its capacity to be induced under moderate oxidative stress. These features make melatonin a potent endogenously-occurring antioxidant that protects organisms from catastrophic oxidative stress. Full article

(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)

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16 pages, 1262 KiB

Open AccessArticle

Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception

by Giuseppe Mancuso, Gigliola Borgonovo, Leonardo Scaglioni and Angela Bassoli^*

DeFENS—Department of Food, Environmental and Nutritional Sciences, University of Milan, via Celoria 2, Milano I-20133, Italy

Molecules 2015, 20(10), 18907-18922; https://doi.org/10.3390/molecules201018907 - 16 Oct 2015

Cited by 38 | Viewed by 10624

Abstract

Ruta graveolens (rue) is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two [...] Read more.

Ruta graveolens (rue) is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two quinolinic alkaloids, a dicoumarin and two long chain ketones. Bitter taste and chemesthetic properties have been evaluated by in vitro assays with twenty receptors of the TAS2R family and four TRP ion channels involved in gustation and nociception. Among the alkaloids, skimmianine was active as a specific agonist of T2R14, whereas kokusaginin did not activate any of the tested receptors. The furanocoumarins activates TAS2R10, 14, and 49 with different degrees of selectivity, as well as the TRPA1 somatosensory ion channel. Rutamarin is an agonist of TRPM5 and TRPV1 and a strong antagonist of TRPM8 ion channels. Full article

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

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44 pages, 1162 KiB

Open AccessReview

Membrane Interactions of Phytochemicals as Their Molecular Mechanism Applicable to the Discovery of Drug Leads from Plants

by Hironori Tsuchiya

Department of Dental Basic Education, Asahi University School of Dentistry, 1851 Hozumi, Mizuho, Gifu 501-0296, Japan

Molecules 2015, 20(10), 18923-18966; https://doi.org/10.3390/molecules201018923 - 16 Oct 2015

Cited by 176 | Viewed by 14859

Abstract

In addition to interacting with functional proteins such as receptors, ion channels, and enzymes, a variety of drugs mechanistically act on membrane lipids to change the physicochemical properties of biomembranes as reported for anesthetic, adrenergic, cholinergic, non-steroidal anti-inflammatory, analgesic, antitumor, antiplatelet, antimicrobial, and [...] Read more.

In addition to interacting with functional proteins such as receptors, ion channels, and enzymes, a variety of drugs mechanistically act on membrane lipids to change the physicochemical properties of biomembranes as reported for anesthetic, adrenergic, cholinergic, non-steroidal anti-inflammatory, analgesic, antitumor, antiplatelet, antimicrobial, and antioxidant drugs. As well as these membrane-acting drugs, bioactive plant components, phytochemicals, with amphiphilic or hydrophobic structures, are presumed to interact with biological membranes and biomimetic membranes prepared with phospholipids and cholesterol, resulting in the modification of membrane fluidity, microviscosity, order, elasticity, and permeability with the potencies being consistent with their pharmacological effects. A novel mechanistic point of view of phytochemicals would lead to a better understanding of their bioactivities, an insight into their medicinal benefits, and a strategic implication for discovering drug leads from plants. This article reviews the membrane interactions of different classes of phytochemicals by highlighting their induced changes in membrane property. The phytochemicals to be reviewed include membrane-interactive flavonoids, terpenoids, stilbenoids, capsaicinoids, phloroglucinols, naphthodianthrones, organosulfur compounds, alkaloids, anthraquinonoids, ginsenosides, pentacyclic triterpene acids, and curcuminoids. The membrane interaction’s applicability to the discovery of phytochemical drug leads is also discussed while referring to previous screening and isolating studies. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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21 pages, 1510 KiB

Open AccessArticle

Effect of Three Training Systems on Grapes in a Wet Region of China: Yield, Incidence of Disease and Anthocyanin Compositions of Vitis vinifera cv. Cabernet Sauvignon

by Mei-Ying Liu¹, Ming Chi¹, Yong-Hong Tang¹, Chang-Zheng Song¹, Zhu-Mei Xi^1,2,* and Zhen-Wen Zhang^1,2,*

¹ College of Enology, Northwest A & F University, Yangling 712100, Shannxi, China

² Shaanxi Engineering Research Center for Viti-Viniculture, Yangling 712100, Shannxi, China

Molecules 2015, 20(10), 18967-18987; https://doi.org/10.3390/molecules201018967 - 19 Oct 2015

Cited by 16 | Viewed by 7898

Abstract

Grapevine training systems determine the suitability for grape varieties in a specific growing region. We evaluated the influence of three training systems, Single Guyot (SG), Spur-pruned Vertical Shoot-Positioned (VSP), and Four-Arm Kniffin (4AK), on the performance of grapes and vines of Vitis vinifera [...] Read more.

Grapevine training systems determine the suitability for grape varieties in a specific growing region. We evaluated the influence of three training systems, Single Guyot (SG), Spur-pruned Vertical Shoot-Positioned (VSP), and Four-Arm Kniffin (4AK), on the performance of grapes and vines of Vitis vinifera L. cv. Cabernet Sauvignon in the 2012 and 2013 growing seasons in a wet region of central China. 4AK was the most productive system in comparison to SG and VSP. SG and VSP had lower disease infections of leaves and berries, especially in the mid- and final stage of berry ripening. Three training systems had no impact on berry maturity. PLS-DA (Partial Least Squares-Discriminant) analysis showed that the relatively dry vintage could well discriminate three training systems, but the wet vintage was not. A wet vintage of 2013 had more accumulation of 3′5′-substituted and acylated anthocyanins, including malvidin-3-O-(6-O-acetyl)-glucoside, malvidin-3-O-glucoside, and petunidin-3-O-(cis-6-O-coumaryl)-glucoside, etc. With regard to the effect of training systems, 4AK grapes had the lowest concentrations of total anthocyanins and individual anthocyanins, SG and VSP differed according to the different vintages, and showed highest concentration of total individual anthocyanins in 2012 and 2013, respectively. Generally, VSP benefited the most, contributing to significantly highest levels of total individual anthocyanins, and major anthocyanin, including malvidin-3-O-glucoside and malvidin-3-O-(6-O-acetyl)-glucoside, and the grapes obtained from VSP presented significantly highest proportion of 3′5′-substituted anthocyanins. With regard to the ratios of 3′5′/3′-substituted, methoxylated/non-methoxylated and acylated/non-acylated anthocyanins, the significantly higher levels were also shown in VSP system. In summary, VSP was the best training system for Cabernet Sauvignon to accumulate relatively stable individual anthocyanins in this wet region of China and potentially in other rainy regions. Full article

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

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14 pages, 1577 KiB

Open AccessArticle

Validated LC-MS/MS Method for the Determination of Scopoletin in Rat Plasma and Its Application to Pharmacokinetic Studies

by Yingchun Zeng¹, Sha Li¹, Xiaohong Wang¹, Tao Gong¹, Xun Sun¹ and Zhirong Zhang^2,*

¹ Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China

² West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China

Molecules 2015, 20(10), 18988-19001; https://doi.org/10.3390/molecules201018988 - 19 Oct 2015

Cited by 48 | Viewed by 7893

Abstract

A rapid, sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometric method was developed and validated for the quantification of scopoletin in rat plasma. After the addition of the internal standard xanthotoxin, plasma samples were pretreated by a simple one-step protein precipitation with acetonitrile-methanol [...] Read more.

A rapid, sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometric method was developed and validated for the quantification of scopoletin in rat plasma. After the addition of the internal standard xanthotoxin, plasma samples were pretreated by a simple one-step protein precipitation with acetonitrile-methanol (2:1, v/v). Chromatographic separation was achieved on a Diamonsil ODS chromatography column using gradient elution with the mobile phase consisting of acetonitrile and 0.1% formic acid. The determination was performed by positive ion electrospray ionization in multiple reaction monitoring mode. The calibration curve was linear over the concentration range of 5–1000 ng/mL (r = 0.9996). The intra- and inter-day precision (RSD%) was less than 6.1%, and the accuracy (RE%) was from −3.0%–2.5%. This method was successfully applied to the pharmacokinetic research of scopoletin in rats after intravenous (5 mg/kg) or oral (5, 10 and 20 mg/kg) administration. The result showed that oral bioavailability with a dose of 5 mg/kg was 6.62% ± 1.72%, 10 mg/kg, 5.59% ± 1.16%, and 20 mg/kg, 5.65% ± 0.75%. Full article

(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)

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12 pages, 1106 KiB

Open AccessArticle

The Occurrence of Propyl Lactate in Chinese Baijius (Chinese Liquors) Detected by Direct Injection Coupled with Gas Chromatography-Mass Spectrometry

by Jihong Wu^1,2, Yang Zheng^1,2, Baoguo Sun^1,2,3, Xiaotao Sun^1,2, Jiyuan Sun^1,2, Fuping Zheng^1,2 and Mingquan Huang^1,2,3,*

¹ School of Food and Chemical Engineering, Beijing Technology and Business University, Beijing 100048, China

² Beijing Key Laboratory of Flavor Chemistry, Beijing Technology and Business University, Beijing 100048, China

³ Beijing Innovation Centre of Food Nutrition and Human Health, Beijing 100048, China

Molecules 2015, 20(10), 19002-19013; https://doi.org/10.3390/molecules201019002 - 19 Oct 2015

Cited by 16 | Viewed by 8421

Abstract

As one of the oldest distillates in the world, flavor compounds of Chinese Baijiu (Chinese liquor) were extremely complex. Propyl lactate was ﬁrstly detected by direct injection and gas chromatography-mass spectrometry (GC-MS) in 72 Chinese Baijius. The objectives were to detect the contents [...] Read more.

As one of the oldest distillates in the world, flavor compounds of Chinese Baijiu (Chinese liquor) were extremely complex. Propyl lactate was ﬁrstly detected by direct injection and gas chromatography-mass spectrometry (GC-MS) in 72 Chinese Baijius. The objectives were to detect the contents of propyl lactate and evaluate its contribution to the aroma of Chinese Baijiu based on odor activity values (OAVs). The levels of propyl lactate in these distillates were determined by internal standard method and selective ion monitoring (SIM), which ranged from 0.050 to 1.900 mg∙L⁻¹ under investigation. Its detection threshold was determined by Three-Alternative Forced-Choice (3-AFC) and curve fitting (CF), which was 0.740 mg∙L⁻¹ in 38% ethanol solution. The contribution of propyl lactate on the aroma of these distillate drinks was evaluated by their odor activity values (OAVs), which varied from 0.066 to 4.440. The OAVs of propyl lactate were found to exceed 1 in 13 Chinese Baijius, including 50° Jingzhi Guniang 5 years (4.440), 52° Jingzhi Guniang 10 years (3.024), Jingyanggang (2.568), Xianghe Ronghe Shaofang (2.313), and 1956 Laolang (1.431), which indicated that propyl lactate was one of odor-active components in these Chinese Baijius. Full article

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

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13 pages, 973 KiB

Open AccessArticle

Oligomeric Procyanidins Interfere with Glycolysis of Activated T Cells. A Novel Mechanism for Inhibition of T Cell Function

by Masao Goto¹, Manabu Wakagi¹, Toshihiko Shoji² and Yuko Takano-Ishikawa^1,*

¹ National Food Research Institute, National Agriculture and Food Research Organization, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan

² Institute of Fruit Tree Science, National Agriculture and Food Research Organization, 2-1 Fujimoto, Tsukuba, Ibaraki 305-8605, Japan

Molecules 2015, 20(10), 19014-19026; https://doi.org/10.3390/molecules201019014 - 20 Oct 2015

Cited by 7 | Viewed by 6975

Abstract

Procyanidins, which are flavonoids that are found in a variety of plant species, reduce or prevent immune disorders, such as allergy and autoimmune diseases, through an unknown mechanism. In the present study, we investigated the effects of procyanidins on the T cell receptor [...] Read more.

Procyanidins, which are flavonoids that are found in a variety of plant species, reduce or prevent immune disorders, such as allergy and autoimmune diseases, through an unknown mechanism. In the present study, we investigated the effects of procyanidins on the T cell receptor (TCR)-mediated responses of CD4⁺ T cells in vitro. Apple procyanidins strongly suppressed the proliferation of splenic CD4⁺ T cells that were stimulated by an anti-CD3ε antibody, as well as splenocytes stimulated by antigen, but did not alter interleukin (IL)-2 secretion from these cells. Furthermore, we found that oligomeric procyanidins strongly suppressed, in a degree of polymerization dependent manner, the proliferation of activated CD4⁺ T cells, as well as their production of effector cytokines, including glycolysis associated-cytokines, without affecting IL-2 secretion. Additionally, we investigated the inhibitory effects of oligomeric procyanidins on the glycolytic activity of activated CD4⁺ T cells. We show that pentameric procyanidin suppressed L-lactate production and glucose uptake in activated CD4⁺ T cells. These results suggest that oligomeric procyanidins suppress the functions of activated CD4⁺ T cells by interfering with glycolysis. Full article

(This article belongs to the Section Natural Products Chemistry)

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3 pages, 606 KiB

Open AccessCorrection

Correction: Gomez, T., et al. Imaging the Ultrafast Photoelectron Transfer Process in Alizarin-TiO₂. Molecules 2015, 20, 13830–13853

by Tatiana Gomez^1,*, Gunter Hermann², Ximena Zarate¹, Jhon Fredy Pérez-Torres² and Jean Christophe Tremblay^2,*

¹ Dirección de Postgrado e Investigación, Universidad Autónoma de Chile, Llano Subercaceaux 2801, San Miguel, Santiago, Chile

² Institut für Chemie und Biochemie, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany

Molecules 2015, 20(10), 19027-19029; https://doi.org/10.3390/molecules201019027 - 20 Oct 2015

Viewed by 3734

Abstract

The author wishes to make the following correction to this paper [1]. Due to mislabeling, please replace: [...] Full article

11 pages, 729 KiB

Open AccessArticle

miRNA Stability in Frozen Plasma Samples

by Francesca Balzano¹

, Marta Deiana², Silvia Dei Giudici³, Annalisa Oggiano³, Angela Baralla¹, Sara Pasella¹, Andrea Mannu¹, Mario Pescatori¹, Baingio Porcu¹, Giuseppe Fanciulli⁴

, Angelo Zinellu¹

, Ciriaco Carru¹

and Luca Deiana^1,2,*

¹ Department of Biomedical Sciences, University of Sassari, vl. San Pietro 43b, Sassari 07100, Italy

² Associazione “L’Isola dei Centenari”, Via Milano 4, Sassari 07100, Italy

³ Istituto Zooprofilattico Sperimentale della Sardegna, Via Vienna 2, Sassari 07100, Italy

⁴ Department of Clinical and Experimental Medicine, University of Sassari, vl. San Pietro 8, Sassari 07100, Italy

Molecules 2015, 20(10), 19030-19040; https://doi.org/10.3390/molecules201019030 - 20 Oct 2015

Cited by 100 | Viewed by 9926

Abstract

MicroRNAs (miRNAs) represent a family of small non-coding ribonucleic acids that post-transcriptionally inhibits the expression of their target messenger RNAs (mRNAs), thereby acting as general gene repressors. In this study we examined the relative quantity and stability of miRNA subjected to a long [...] Read more.

MicroRNAs (miRNAs) represent a family of small non-coding ribonucleic acids that post-transcriptionally inhibits the expression of their target messenger RNAs (mRNAs), thereby acting as general gene repressors. In this study we examined the relative quantity and stability of miRNA subjected to a long period of freezing; we compared the stability of eight miRNAs in the plasma of five human healthy controls before freezing and after six and 12 months of storage at −80 °C. In addition, we examined the plasma frozen for 14 years and the amount of miRNA still available. Using a Life Technologies protocol to amplify and quantify plasma miRNAs from EDTA (Ethylene Diamine Tetraacetic Acid)-treated blood, we analyzed the stability of eight miRNAs, (miR-125b-5p, miR-425-5p, miR-200b-5p, miR-200c-3p, miR-579-3p, miR-212-3p, miR-126-3p, and miR-21-5p). The miRNAs analyzed showed a high stability and long frozen half-life. Full article

(This article belongs to the Section Molecular Diversity)

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10 pages, 1551 KiB

Open AccessArticle

Thermal Influence of CNT on the Polyamide 12 Nanocomposite for Selective Laser Sintering

by Jiaming Bai^1,*, Ruth D. Goodridge², Shangqin Yuan^1,3, Kun Zhou³, Chee Kai Chua³

and Jun Wei¹

¹ Singapore Institute of Manufacturing Technology, 71 Nanyang Drive, 638075 Singapore, Singapore

² Additive Manufacturing and 3D-Printing Research Group, Faculty of Engineering, University of Nottingham, Nottingham NG7 2RD, UK

³ School of Mechanical and Aerospace Engineering, Nanyang Technological University, 639798 Singapore, Singapore

Molecules 2015, 20(10), 19041-19050; https://doi.org/10.3390/molecules201019041 - 20 Oct 2015

Cited by 84 | Viewed by 7456

Abstract

The thermal influence of carbon nanotubes (CNTs) on the PA12 in the laser sintering process was assessed by physical experiments and a three dimensional simulation model. It appears that, by adding the CNTs into the PA12 matrix, the thermal conductivity increased. A double [...] Read more.

The thermal influence of carbon nanotubes (CNTs) on the PA12 in the laser sintering process was assessed by physical experiments and a three dimensional simulation model. It appears that, by adding the CNTs into the PA12 matrix, the thermal conductivity increased. A double ellipsoidal heat flux model was applied to input a three dimensional, continuous moving, volumetric laser heat source. The predicted three dimensional temperature distributions suggested that the laser heat was conducted wider and deeper in the PA12-CNT sample than PA12. Greater heat conduction can reduce the interspace between two successive layers, and result in the increase of the parts’ density and properties. Full article

(This article belongs to the Special Issue Selected papers from the Symposium Polymer Nanocomposites and Functional Organic-Inorganic Hybrids (Suntec, Singapore))

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15 pages, 2302 KiB

Open AccessArticle

Antioxidant Properties of Essential Oil Extracted from Pinus morrisonicola Hay Needles by Supercritical Fluid and Identification of Possible Active Compounds by GC/MS

by Ming-Ching Cheng¹, Wen-Hua Chang¹, Chih-Wei Chen¹, Wen-Wing Li¹, Chin-Yin Tseng¹ and Tuzz-Ying Song^2,*

¹ Department of Health Food, Chung Chou University of Science and Technology, Changhua 51591, Taiwan

² Department of Bioindustry Technology, Dayeh University, Changhua 51591, Taiwan

Molecules 2015, 20(10), 19051-19065; https://doi.org/10.3390/molecules201019051 - 20 Oct 2015

Cited by 17 | Viewed by 8533

Abstract

Pine (Pinus morrisonicola Hay, PM) needles have been used as folk medicine for their antihypertension and lipid-lowering effects. As supercritical fluid extraction (SFE) is considered an ideal technique for the extraction of essential oil from plant materials, the present work investigated the [...] Read more.

Pine (Pinus morrisonicola Hay, PM) needles have been used as folk medicine for their antihypertension and lipid-lowering effects. As supercritical fluid extraction (SFE) is considered an ideal technique for the extraction of essential oil from plant materials, the present work investigated the optimal SFE conditions and the protective effects of different resulting fractions of PM needles on lipid peroxidation and foam cell production in macrophages. Nine PM needle extracts (PME1–9) were obtained in 1%–4% yields using different SFE conditions, of which PME1 had the lowest yield (1.1%) and PME3 the highest (3.9%). PME3 exhibited lower cytotoxic effects and stronger inhibition of lipid peroxidation and formation of foam cell in RAW 264.7 macrophages than those of other PME extracts. PME3-1 purified from PME3 by column and thin layer chromatography inhibited LDL oxidation more effectively than did PME3 in a cell-free system oxidized by Cu²⁺. PME3-1 dose-dependently (25–100 μg/mL) decreased conjugated diene levels and foam cell formation induced by ox-LDL. GC/MS analyses revealed that 1-docosene, neophytadiene, and methyl abietate were increased 5.2-, 1.7- and 4.3-fold in PME3-1 relative to PME3. A new hydrocarbon compound, cedrane-8,13-diol, was identified in PME3-1. Overall, the present study demonstrates the optimal extraction conditions of SFE of PM and identifies the most potent antioxidant fractions and possible active compounds in PM. Full article

(This article belongs to the Collection Bioactive Compounds)

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19 pages, 540 KiB

Open AccessArticle

Synthesis and Evaluation of New Pyrazoline Derivatives as Potential Anticancer Agents

by Muhammed Karabacak^1,†, Mehlika Dilek Altıntop^1,†, Halil İbrahim Çiftçi^2,†, Ryoko Koga², Masami Otsuka², Mikako Fujita³ and Ahmet Özdemir^1,*

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey

² Department of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan

³ Research Institute for Drug Discovery, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 19066-19084; https://doi.org/10.3390/molecules201019066 - 20 Oct 2015

Cited by 89 | Viewed by 11274

Abstract

New pyrazoline derivatives were synthesized and evaluated for their cytotoxic effects on AsPC-1 human pancreatic adenocarcinoma, U87 and U251 human glioblastoma cell lines. 1-[((5-(4-Methylphenyl)-1,3,4-oxadiazol-2-yl)thio)acetyl]-3-(2-thienyl)-5-(4-chlorophenyl)-2-pyrazoline (11) was found to be the most effective anticancer agent against AsPC-1 and U251 cell lines, with [...] Read more.

New pyrazoline derivatives were synthesized and evaluated for their cytotoxic effects on AsPC-1 human pancreatic adenocarcinoma, U87 and U251 human glioblastoma cell lines. 1-[((5-(4-Methylphenyl)-1,3,4-oxadiazol-2-yl)thio)acetyl]-3-(2-thienyl)-5-(4-chlorophenyl)-2-pyrazoline (11) was found to be the most effective anticancer agent against AsPC-1 and U251 cell lines, with IC₅₀ values of 16.8 µM and 11.9 µM, respectively. Tumor selectivity of compound 11 was clearly seen between Jurkat human leukemic T-cell line and human peripheral blood mononuclear cells (PBMC). Due to its promising anticancer activity, compound 11 was chosen for apoptosis/necrosis evaluation and DNA-cleavage analysis in U251 cells. Compound 11-treated U251 cells exhibited apoptotic phenotype at low concentration (1.5 µM). DNA-cleaving efficiency of this ligand was more significant than cisplatin and was clearly enhanced by Fe(II)-H₂O₂-ascorbic acid systems. This result pointed out the relationship between the DNA cleavage and the cell death. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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16 pages, 1302 KiB

Open AccessArticle

Lupanine Improves Glucose Homeostasis by Influencing K_ATP Channels and Insulin Gene Expression

by Mats Wiedemann¹, Carmen M. Gurrola-Díaz², Belinda Vargas-Guerrero², Michael Wink³

, Pedro M. García-López⁴ and Martina Düfer^1,*

¹ Department of Pharmaceutical and Medicinal Chemistry, Münster University, Corrensstraße 48, 48149 Münster, Germany

² Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, Jalisco, Mexico

³ Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg 69120, Germany

⁴ Departamento de Botánica y Zoología, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, 45110 Guadalajara, Jalisco, Mexico

Molecules 2015, 20(10), 19085-19100; https://doi.org/10.3390/molecules201019085 - 20 Oct 2015

Cited by 35 | Viewed by 7364

Abstract

The glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main quinolizidine alkaloids, lupanine, on pancreatic beta cells and in an animal model of type-2 diabetes mellitus. In vitro studies [...] Read more.

The glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main quinolizidine alkaloids, lupanine, on pancreatic beta cells and in an animal model of type-2 diabetes mellitus. In vitro studies were performed with insulin-secreting INS-1E cells or islets of C57BL/6 mice. In the in vivo experiments, hyperglycemia was induced in rats by injecting streptozotocin (65 mg/kg body weight). In the presence of 15 mmol/L glucose, insulin secretion was significantly elevated by 0.5 mmol/L lupanine, whereas the alkaloid did not stimulate insulin release with lower glucose concentrations. In islets treated with l-arginine, the potentiating effect of lupanine already occurred at 8 mmol/L glucose. Lupanine increased the expression of the Ins-1 gene. The potentiating effect on secretion was correlated to membrane depolarization and an increase in the frequency of Ca²⁺ action potentials. Determination of the current through ATP-dependent K⁺ channels (K_ATP channels) revealed that lupanine directly inhibited the channel. The effect was dose-dependent but, even with a high lupanine concentration of 1 mmol/L or after a prolonged exposure time (12 h), the K_ATP channel block was incomplete. Oral administration of lupanine did not induce hypoglycemia. By contrast, lupanine improved glycemic control in response to an oral glucose tolerance test in streptozotocin-diabetic rats. In summary, lupanine acts as a positive modulator of insulin release obviously without a risk for hypoglycemic episodes. Full article

(This article belongs to the Special Issue Proceedings of the the 4th Young Researcher Meeting, Münster, March 13-14, 2015)

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29 pages, 1304 KiB

Open AccessArticle

Synthesis, Molecular Structure, Metabolic Stability and QSAR Studies of a Novel Series of Anticancer N-Acylbenzenesulfonamides

by Beata Żołnowska¹, Jarosław Sławiński^1,*

, Mariusz Belka², Tomasz Bączek², Anna Kawiak^3,4, Jarosław Chojnacki⁵

, Aneta Pogorzelska¹ and Krzysztof Szafrański¹

¹ Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland

² Department of Pharmaceutical Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland

³ Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, ul. Kładki 24, 80-822 Gdańsk, Poland

⁴ Department of Human Physiology, Medical University of Gdańsk, ul. Tuwima 15, 80-210 Gdańsk, Poland

⁵ Department of Inorganic Chemistry, Gdańsk University of Technology, Narutowicza 11/12, 80-233 Gdańsk, Poland

Molecules 2015, 20(10), 19101-19129; https://doi.org/10.3390/molecules201019101 - 21 Oct 2015

Cited by 15 | Viewed by 6533

Abstract

A series of novel N-acyl-4-chloro-5-methyl-2-(R¹-methylthio)benzenesulfonamides 18–47 have been synthesized by the reaction of N-[4-chloro-5-methyl-2-(R¹-methylthio) benzenesulfonyl]cyanamide potassium salts with appropriate carboxylic acids. Some of them showed anticancer activity toward the human cancer cell lines MCF-7, HCT-116 [...] Read more.

A series of novel N-acyl-4-chloro-5-methyl-2-(R¹-methylthio)benzenesulfonamides 18–47 have been synthesized by the reaction of N-[4-chloro-5-methyl-2-(R¹-methylthio) benzenesulfonyl]cyanamide potassium salts with appropriate carboxylic acids. Some of them showed anticancer activity toward the human cancer cell lines MCF-7, HCT-116 and HeLa, with the growth percentages (GPs) in the range from 7% to 46%. Quantitative structure-activity relationship (QSAR) studies on the cytotoxic activity of N-acylsulfonamides toward MCF-7, HCT-116 and HeLa were performed by using topological, ring and charge descriptors based on the stepwise multiple linear regression technique (MLR). The QSAR studies revealed three predictive and statistically significant models for the investigated compounds. The results obtained with these models indicated that the anticancer activity of N-acylsulfonamides depends on topological distances, number of ring system, maximum positive charge and number of atom-centered fragments. The metabolic stability of the selected compounds had been evaluated on pooled human liver microsomes and NADPH, both R¹ and R² substituents of the N-acylsulfonamides simultaneously affected them. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 1640 KiB

Open AccessArticle

Olefin Metathesis Reaction in Water and in Air Improved by Supramolecular Additives

by Jasmine Tomasek¹, Miriam Seßler¹, Harald Gröger²

and Jürgen Schatz^1,*

¹ Organic Chemistry 1, Department of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Henkestraße 42, D-91054 Erlangen, Germany

² Faculty of Chemistry, Bielefeld University, Universitätsstraße 25, 33615 Bielefeld, Germany

Molecules 2015, 20(10), 19130-19141; https://doi.org/10.3390/molecules201019130 - 21 Oct 2015

Cited by 12 | Viewed by 6762

Abstract

A range of water-immiscible commercially available Grubbs-type precatalysts can be used in ring-closing olefin metathesis reaction in high yields. The synthetic transformation is possible in pure water under ambient conditions. Sulfocalixarenes can help to boost the reactivity of the metathesis reaction by [...] Read more.

A range of water-immiscible commercially available Grubbs-type precatalysts can be used in ring-closing olefin metathesis reaction in high yields. The synthetic transformation is possible in pure water under ambient conditions. Sulfocalixarenes can help to boost the reactivity of the metathesis reaction by catalyst activation, improved mass transfer, and solubility of reactants in the aqueous reaction media. Additionally, the use of supramolecular additives allows lower catalyst loadings, but still high activity in pure water under aerobic conditions. Full article

(This article belongs to the Special Issue Olefin Metathesis)

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30 pages, 860 KiB

Open AccessReview

Six-Membered Aromatic Polyazides: Synthesis and Application

by Sergei V. Chapyshev

Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka 142432, Moscow Region, Russian

Molecules 2015, 20(10), 19142-19171; https://doi.org/10.3390/molecules201019142 - 21 Oct 2015

Cited by 29 | Viewed by 10821

Abstract

Aromatic polyazides are widely used as starting materials in organic synthesis and photochemical studies, as well as photoresists in microelectronics and as cross-linking agents in polymer chemistry. Some aromatic polyazides possess high antitumor activity, while many others are of considerable interest as high-energy [...] Read more.

Aromatic polyazides are widely used as starting materials in organic synthesis and photochemical studies, as well as photoresists in microelectronics and as cross-linking agents in polymer chemistry. Some aromatic polyazides possess high antitumor activity, while many others are of considerable interest as high-energy materials and precursors of high-spin nitrenes and C₃N₄ carbon nitride nanomaterials. The use of aromatic polyazides in click-reactions may be a new promising direction in the design of various supramolecular systems possessing interesting chemical, physical and biological properties. This review is devoted to the synthesis, properties and applications of six-membered aromatic compounds containing three and more azido groups in the ring. Full article

(This article belongs to the Special Issue Organic Azides)

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17 pages, 1232 KiB

Open AccessArticle

Iridoids and Flavonoids of Four Siberian Gentians: Chemical Profile and Gastric Stimulatory Effect

by Daniil N. Olennikov^1,*

, Nina I. Kashchenko¹, Nadezhda K. Chirikova² and Larisa M. Tankhaeva¹

¹ Institute of General and Experimental Biology, Siberian Division, Russian Academy of Science, Sakh’yanovoy Str., 6, Ulan-Ude 670047, Russia

² Department of Biochemistry and Biotechnology, North-Eastern Federal University, 58 Belinsky Str., Yakutsk 677027, Russia

Molecules 2015, 20(10), 19172-19188; https://doi.org/10.3390/molecules201019172 - 21 Oct 2015

Cited by 47 | Viewed by 8194

Abstract

Some Gentiana species have been used by the nomadic people of Siberia as bitter teas or appetizers to eliminate digestive disorders (dyspepsia, heartburn, nausea, etc.). We studied the most frequently used gentians: Gentiana algida, G. decumbens, G. macrophylla and G. triflora [...] Read more.

Some Gentiana species have been used by the nomadic people of Siberia as bitter teas or appetizers to eliminate digestive disorders (dyspepsia, heartburn, nausea, etc.). We studied the most frequently used gentians: Gentiana algida, G. decumbens, G. macrophylla and G. triflora. The aim of the present study was to evaluate the phytochemical features and gastrostimulatnt activity of these four gentian herbs. Five iridoids, seven flavones and mangiferin were detected in gentian herbs after analysis by microcolumn-RP-HPLC-UV-ESI-MS. A componential phytochemical profile of the G. decumbens herb is presented for the first time, as well as information about distinct phytochemicals found in gentian herbs. HPLC quantification of the specific compounds of gentian herbs demonstrated the high content of iridoids (24.73–73.53 mg/g) and flavonoids (12.92–78.14 mg/g). The results of biological activity evaluation of four gentian decoctions demonstrated their good ability to stimulate acid-, enzyme- and mucin-forming functions of the stomach attributed to mostly by iridoids and flavonoids. In general, it can be claimed that the gentian decoctions can be used as effective and safe appetizers and are also a good source of biologically active agents. Full article

(This article belongs to the Collection Herbal Medicine Research)

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14 pages, 5398 KiB

Open AccessArticle

Enhanced Visible Light Photocatalytic Activity of Br-Doped Bismuth Oxide Formate Nanosheets

by Xin Feng¹, Wen Cui¹, Junbo Zhong², Xiaoying Liu³, Fan Dong^1,* and Yuxin Zhang^3,*

¹ Chongqing Key Laboratory of Catalysis and Functional Organic Molecules, College of Environment and Resources, Chongqing Technology and Business University, Chongqing 400067, China

² Key Laboratory of Green Catalysis of Sichuan Institutes of High Education, Sichuan University of Science and Technology, Zigong 643000, China

³ National Key Laboratory of Fundamental Science of Micro/Nano-Devices and System Technology, College of Materials Science and Engineering, Chongqing University, Chongqing 400044, China

Molecules 2015, 20(10), 19189-19202; https://doi.org/10.3390/molecules201019189 - 21 Oct 2015

Cited by 14 | Viewed by 6918

Abstract

A facile method was developed to enhance the visible light photocatalytic activity of bismuth oxide formate (BiOCOOH) nanosheets via Br-doping. The as-prepared samples were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, the Brunauer–Emmett–Teller surface area, UV-vis diffuse [...] Read more.

A facile method was developed to enhance the visible light photocatalytic activity of bismuth oxide formate (BiOCOOH) nanosheets via Br-doping. The as-prepared samples were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, the Brunauer–Emmett–Teller surface area, UV-vis diffuse reflectance spectroscopy, photoluminescence spectra, and N₂ adsorption-desorption isotherms measurement. The Br⁻ ions replaced the COOH⁻ ions in the layers of BiOCOOH, result in a decreased layer distance. The photocatalytic activity of the as-prepared materials was evaluated by removal of NO in qir at ppb level. The results showed that the Br-doped BiOCOOH nanosheets showed enhanced visible light photocatalytic activtiy with a NO removal of 37.8%. The enhanced activity can be ascribed to the increased visible light absorption and the promoted charge separation. Full article

(This article belongs to the Special Issue Nano-Structural Photocatalytic Materials: Synthesis, Characterization and Applications)

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18 pages, 1083 KiB

Open AccessArticle

Greener Selective Cycloalkane Oxidations with Hydrogen Peroxide Catalyzed by Copper-5-(4-pyridyl)tetrazolate Metal-Organic Frameworks

by Luísa Martins^1,2,*

, Rajendar Nasani^3,†, Manideepa Saha^3,†, Shaikh Mobin^3,*,†, Suman Mukhopadhyay³ and Armando Pombeiro^2,*

¹ Chemical Engineering Departament, Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, R. Conselheiro Emídio Navarro, 1959-007 Lisboa, Portugal

² Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal

³ Department of Chemistry, School of Basic Sciences, Indian Institute of Technology Indore, IET-DAVV Campus, Khandwa Road, Indore 452017, India

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 19203-19220; https://doi.org/10.3390/molecules201019203 - 21 Oct 2015

Cited by 22 | Viewed by 7100

Abstract

Microwave assisted synthesis of the Cu(I) compound [Cu(µ₄-4-ptz)]_n [1, 4-ptz = 5-(4-pyridyl)tetrazolate]has been performed by employing a relatively easy method and within a shorter period of time compared to its sister compounds. The syntheses of the Cu(II) [...] Read more.

Microwave assisted synthesis of the Cu(I) compound [Cu(µ₄-4-ptz)]_n [1, 4-ptz = 5-(4-pyridyl)tetrazolate]has been performed by employing a relatively easy method and within a shorter period of time compared to its sister compounds. The syntheses of the Cu(II) compounds [Cu₃(µ₃-4-ptz)₄(µ₂-N₃)₂(DMF)₂]_n∙(DMF)_2n (2) and [Cu(µ₂-4-ptz)₂(H₂O)₂]_n (3) using a similar method were reported previously by us. MOFs 1-3 revealed high catalytic activity toward oxidation of cyclic alkanes (cyclopentane, -hexane and -octane) with aqueous hydrogen peroxide, under very mild conditions (at room temperature), without any added solvent or additive. The most efficient system (2/H₂O₂) showed, for the oxidation of cyclohexane, a turnover number (TON) of 396 (TOF of 40 h⁻¹), with an overall product yield (cyclohexanol and cyclohexanone) of 40% relative to the substrate. Moreover, the heterogeneous catalytic systems 1–3 allowed an easy catalyst recovery and reuse, at least for four consecutive cycles, maintaining ca. 90% of the initial high activity and concomitant high selectivity. Full article

(This article belongs to the Special Issue Metal Mediated Activation of Small Molecules)

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15 pages, 2518 KiB

Open AccessArticle

γ-Alumina Nanoparticle Catalyzed Efficient Synthesis of Highly Substituted Imidazoles

by Bandapalli Palakshi Reddy¹, Vijayaparthasarathi Vijayakumar^1,*, Mariadhas Valan Arasu² and Naif Abdullah Al-Dhabi²

¹ Center for Organic and Medicinal Chemistry, VIT University, Vellore 632014, Tamil Nadu, India

² Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia

Molecules 2015, 20(10), 19221-19235; https://doi.org/10.3390/molecules201019221 - 21 Oct 2015

Cited by 14 | Viewed by 5903

Abstract

γ-Alumina nano particle catalyzed multi component reaction of benzil, arylaldehyde and aryl amines afforded the highly substituted 1,2,4,5-tetraaryl imidazoles with good to excellent yield in less reaction time under the sonication as well as the conventional methods. Convenient operational simplicity, mild conditions and [...] Read more.

γ-Alumina nano particle catalyzed multi component reaction of benzil, arylaldehyde and aryl amines afforded the highly substituted 1,2,4,5-tetraaryl imidazoles with good to excellent yield in less reaction time under the sonication as well as the conventional methods. Convenient operational simplicity, mild conditions and the reusability of catalyst were the other advantages of this developed protocol. Full article

(This article belongs to the Section Organic Chemistry)

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16 pages, 1790 KiB

Open AccessArticle

A Self-Adaptive Steered Molecular Dynamics Method Based on Minimization of Stretching Force Reveals the Binding Affinity of Protein–Ligand Complexes

by Junfeng Gu^1,*, Hongxia Li² and Xicheng Wang¹

¹ State Key Laboratory of Structural Analysis for Industrial Equipment, Department of Engineering Mechanics, Dalian University of Technology, Dalian 116023, China

² School of Mechanical Engineering, Dalian University of Technology, Dalian 116023, China

Molecules 2015, 20(10), 19236-19251; https://doi.org/10.3390/molecules201019236 - 22 Oct 2015

Cited by 17 | Viewed by 7238

Abstract

Binding affinity prediction of protein–ligand complexes has attracted widespread interest. In this study, a self-adaptive steered molecular dynamics (SMD) method is proposed to reveal the binding affinity of protein–ligand complexes. The SMD method is executed through adjusting pulling direction to find an optimum [...] Read more.

Binding affinity prediction of protein–ligand complexes has attracted widespread interest. In this study, a self-adaptive steered molecular dynamics (SMD) method is proposed to reveal the binding affinity of protein–ligand complexes. The SMD method is executed through adjusting pulling direction to find an optimum trajectory of ligand dissociation, which is realized by minimizing the stretching force automatically. The SMD method is then used to simulate the dissociations of 19 common protein–ligand complexes which are derived from two homology families, and the binding free energy values are gained through experimental techniques. Results show that the proposed SMD method follows a different dissociation pathway with lower a rupture force and energy barrier when compared with the conventional SMD method, and further analysis indicates the rupture forces of the complexes in the same protein family correlate well with their binding free energy, which reveals the possibility of using the proposed SMD method to identify the active ligand. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 837 KiB

Open AccessArticle

Cytotoxicity of Triterpenes from Green Walnut Husks of Juglans mandshurica Maxim in HepG-2 Cancer Cells

by Yuanyuan Zhou^1,†, Bingyou Yang^1,†, Zhaoxi Liu¹, Yanqiu Jiang¹, Yuxin Liu¹, Lei Fu¹, Xiaoli Wang² and Haixue Kuang^1,*

¹ College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China

² College of Adult Education, Heilongjiang University of Chinese Medicine, Harbin 150040, China

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 19252-19262; https://doi.org/10.3390/molecules201019252 - 22 Oct 2015

Cited by 29 | Viewed by 7286

Abstract

Among the classes of identified natural products, triterpenoids, one of the largest families, have been studied extensively for their diverse structures and variety of biological activities, including antitumor effects. In the present study, a phytochemical study of the green walnut husks of Juglans [...] Read more.

Among the classes of identified natural products, triterpenoids, one of the largest families, have been studied extensively for their diverse structures and variety of biological activities, including antitumor effects. In the present study, a phytochemical study of the green walnut husks of Juglans mandshurica Maxim led to the isolation of a new dammarane triterpene, 12β, 20(R), 24(R)-trihydroxydammar-25-en-3-one (6), together with sixteen known compounds, chiefly from chloroform and ethyl acetate extracts. According to their structural characteristics, these compounds were divided into dammarane-type, oleanane- and ursane-type. Dammarane-type triterpenoids were isolated for the first time from the Juglans genus. As part of our continuing search for biologically active compounds from this plant, all of these compounds were also evaluated for their cytotoxic activities against the growth of human cancer cells lines HepG-2 by the MTT assay. The results were shown that 20(S)-protopanaxadiol, 2α,3β,23-trihydroxyolean-12-en-28-oic acid and 2α,3β,23-trihydroxyurs-12-en-28-oic acid exhibited better cytotoxicity in vitro with IC₅₀ values of 10.32 ± 1.13, 16.13 ± 3.83, 15.97 ± 2.47 μM, respectively. Preliminary structure-activity relationships for these compounds were discussed. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 310 KiB

Open AccessArticle

Novel 2-Thioxanthine and Dipyrimidopyridine Derivatives: Synthesis and Antimicrobial Activity

by Samar El-kalyoubi^1,*

, Fatmah Agili² and Shaker Youssif^3,4

¹ Organic Chemistry Department, Faculty of Pharmacy (Girls), ElAzhar University, Nasr City 11651, Egypt

² Chemistry Department, Faculty of Science, Jazan University, Jazan (Female Section) 45142, Saudi Arabia

³ Medical Chemistry Division, Faculty of Medicine, Jazan University, Jazan 82621, Saudi Arabia

⁴ Chemistry Department, Faculty of Science, Zagazig University, Zagazig 44511, Egypt

Molecules 2015, 20(10), 19263-19276; https://doi.org/10.3390/molecules201019263 - 22 Oct 2015

Cited by 11 | Viewed by 6398 | Correction

Abstract

Several fused imidazolopyrimidines were synthesized starting from 6-amino-1-methyl-2-thiouracil (1) followed by nitrosation, reduction and condensation with different aromatic aldehydes to give Schiff’s base. The dehydrocyclization of Schiff’s bases using iodine/DMF gave Compounds 5a–g. The methylation of 5a– [...] Read more.

Several fused imidazolopyrimidines were synthesized starting from 6-amino-1-methyl-2-thiouracil (1) followed by nitrosation, reduction and condensation with different aromatic aldehydes to give Schiff’s base. The dehydrocyclization of Schiff’s bases using iodine/DMF gave Compounds 5a–g. The methylation of 5a–g using a simple alkylating agent as dimethyl sulfate ((CH₃)₂SO₄) gave either monoalkylated imidazolopyrimidine 6a–g at room temperature or dialkylated derivatives 7a–g on heating 6a–g with ((CH₃)₂SO₄). On the other hand, treatment of 1 with different aromatic aldehydes in absolute ethanol in the presence of conc. hydrochloric acid at room temperature and/or reflux with acetic acid afforded bis-5,5́-diuracylmethylene 8a–e, which cyclized on heating with a mixture of acetic acid/HCl (1:1) to give 9a–e. Compounds 9a–e can be obtained directly by refluxing of Compound 1 with a mixture of acetic acid/HCl. The synthesized new compounds were screened for antimicrobial activity, and the MIC was measured. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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14 pages, 3300 KiB

Open AccessArticle

Antimycobacterial Activities of Endolysins Derived From a Mycobacteriophage, BTCU-1

by Meng-Jiun Lai¹, Chih-Chin Liu², Shinn-Jong Jiang³, Po-Chi Soo¹, Meng-Hsuan Tu¹, Jen-Jyh Lee⁴, Ying-Huei Chen^4,5 and Kai-Chih Chang^1,5,*

¹ Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien 97004, Taiwan

² Department of Bioinformatics, Chung Hua University, Hsin-Chu City 97004, Taiwan

³ Department of Biochemistry, Tzu Chi University, Hualien 97004, Taiwan

⁴ Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Hualien 97004, Taiwan

⁵ Department of Laboratory Medicine, Buddhist Tzu Chi General Hospital, Hualien 97004, Taiwan

Molecules 2015, 20(10), 19277-19290; https://doi.org/10.3390/molecules201019277 - 22 Oct 2015

Cited by 34 | Viewed by 7939

Abstract

The high incidence of Mycobacterium infection, notably multidrug-resistant M. tuberculosis infection, has become a significant public health concern worldwide. In this study, we isolate and analyze a mycobacteriophage, BTCU-1, and a foundational study was performed to evaluate the antimycobacterial activity of BTCU-1 and [...] Read more.

The high incidence of Mycobacterium infection, notably multidrug-resistant M. tuberculosis infection, has become a significant public health concern worldwide. In this study, we isolate and analyze a mycobacteriophage, BTCU-1, and a foundational study was performed to evaluate the antimycobacterial activity of BTCU-1 and its cloned lytic endolysins. Using Mycobacterium smegmatis as host, a mycobacteriophage, BTCU-1, was isolated from soil in eastern Taiwan. The electron microscopy images revealed that BTCU-1 displayed morphology resembling the Siphoviridae family. In the genome of BTCU-1, two putative lytic genes, BTCU-1_ORF7 and BTCU-1_ORF8 (termed lysA and lysB, respectively), were identified, and further subcloned and expressed in Escherichia coli. When applied exogenously, both LysA and LysB were active against M. smegmatis tested. Scanning electron microscopy revealed that LysA and LysB caused a remarkable modification of the cell shape of M. smegmatis. Intracellular bactericidal activity assay showed that treatment of M. smegmatis—infected RAW 264.7 macrophages with LysA or LysB resulted in a significant reduction in the number of viable intracellular bacilli. These results indicate that the endolysins derived from BTCU-1 have antimycobacterial activity, and suggest that they are good candidates for therapeutic/disinfectant agents to control mycobacterial infections. Full article

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

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19 pages, 3055 KiB

Open AccessArticle

Highly Selective Bioconversion of Ginsenoside Rb1 to Compound K by the Mycelium of Cordyceps sinensis under Optimized Conditions

by Wei-Nan Wang, Bing-Xiong Yan, Wen-Di Xu, Ye Qiu, Yun-Long Guo and Zhi-Dong Qiu^*

School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun 130117, China

Molecules 2015, 20(10), 19291-19309; https://doi.org/10.3390/molecules201019291 - 23 Oct 2015

Cited by 23 | Viewed by 8501

Abstract

Compound K (CK), a highly active and bioavailable derivative obtained from protopanaxadiol ginsenosides, displays a wide variety of pharmacological properties, especially antitumor activity. However, the inadequacy of natural sources limits its application in the pharmaceutical industry. In this study, we firstly discovered that [...] Read more.

Compound K (CK), a highly active and bioavailable derivative obtained from protopanaxadiol ginsenosides, displays a wide variety of pharmacological properties, especially antitumor activity. However, the inadequacy of natural sources limits its application in the pharmaceutical industry. In this study, we firstly discovered that Cordyceps sinensis was a potent biocatalyst for the biotransformation of ginsenoside Rb1 into CK. After a series of investigations on the biotransformation parameters, an optimal composition of the biotransformation culture was found to be lactose, soybean powder and MgSO₄ without controlling the pH. Also, an optimum temperature of 30 °C for the biotransformation process was suggested in a range of 25 °C–50 °C. Then, a biotransformation pathway of Rb1 → Rd → F2 → CK was established using high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). Our results demonstrated that the molar bioconversion rate of Rb1 to CK was more than 82% and the purity of CK produced by C. sinensis under the optimized conditions was more than 91%. In conclusion, the combination of C. sinensis and the optimized conditions is applicable for the industrial preparation of CK for medicinal purposes. Full article

(This article belongs to the Section Natural Products Chemistry)

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20 pages, 811 KiB

Open AccessArticle

A CuAAC–Hydrazone–CuAAC Trifunctional Scaffold for the Solid-Phase Synthesis of Trimodal Compounds: Possibilities and Limitations

by Benjamin Fabre, Jan Pícha, Václav Vaněk, Miloš Buděšínský and Jiří Jiráček^*

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo n. 2, 16610 Praha 6, Czech Republic

Molecules 2015, 20(10), 19310-19329; https://doi.org/10.3390/molecules201019310 - 23 Oct 2015

Cited by 19 | Viewed by 7669

Abstract

We present a trifunctional scaffold designed for the solid-phase synthesis of trimodal compounds. This scaffold holds two alkyne arms in a free and TIPS-protected form for consecutive CuAAC (copper(I)-catalyzed azide–alkyne cycloaddition), one Fmoc-protected hydrazide arm for reaction with aldehydes, and one carboxylic acid [...] Read more.

We present a trifunctional scaffold designed for the solid-phase synthesis of trimodal compounds. This scaffold holds two alkyne arms in a free and TIPS-protected form for consecutive CuAAC (copper(I)-catalyzed azide–alkyne cycloaddition), one Fmoc-protected hydrazide arm for reaction with aldehydes, and one carboxylic acid arm with CF₂ groups for attachment to the resin and ¹⁹F-NMR quantification. This scaffold was attached to a resin and derivatized with model azides and aliphatic, electron-rich or electron-poor aromatic aldehydes. We identified several limitations of the scaffold caused by the instability of hydrazones in acidic conditions, in the presence of copper during CuAAC, and when copper accumulated in the resin. We successfully overcame these drawbacks by optimizing synthetic conditions for the derivatization of the scaffold with aromatic aldehydes. Overall, the new trifunctional scaffold combines CuAAC and hydrazone chemistries, offering a broader chemical space for the development of bioactive compounds. Full article

(This article belongs to the Section Organic Chemistry)

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13 pages, 1275 KiB

Open AccessArticle

Poly(Propylene Imine) Dendrimers and Amoxicillin as Dual-Action Antibacterial Agents

by Natalia Wrońska¹, Aleksandra Felczak¹, Katarzyna Zawadzka¹, Martyna Poszepczyńska¹, Sylwia Różalska¹, Maria Bryszewska², Dietmar Appelhans³

and Katarzyna Lisowska^1,*

¹ Department of Industrial Microbiology and Biotechnology, Faculty of Biology and Environmental Protection, University of Lodz, 12/16 Banacha Street, 90-237 Lodz, Poland

² Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143, Pomorska Street, 90-236 Lodz, Poland

³ Leibniz Institute of Polymer Research Dresden, Hohe Street 6, 01069 Dresden, Germany

Molecules 2015, 20(10), 19330-19342; https://doi.org/10.3390/molecules201019330 - 23 Oct 2015

Cited by 24 | Viewed by 11023

Abstract

Besides acting as antimicrobial compounds, dendrimers can be considered as agents that improve the therapeutic effectiveness of existing antibiotics. In this work we present a new approach to using amoxicillin (AMX) against reference strains of common Gram-negative pathogens, alone and in combination with [...] Read more.

Besides acting as antimicrobial compounds, dendrimers can be considered as agents that improve the therapeutic effectiveness of existing antibiotics. In this work we present a new approach to using amoxicillin (AMX) against reference strains of common Gram-negative pathogens, alone and in combination with poly(propylene imine) (PPI) dendrimers, or derivatives thereof, in which 100% of the available hydrogen atoms are substituted with maltose (PPI 100%malG3). The concentrations of dendrimers used remained in the range non-toxic to eukaryotic cells. The results indicate that PPI dendrimers significantly enhance the antibacterial effect of amoxicillin alone, allowing antibiotic doses to be reduced. It is important to reduce doses of amoxicillin because its widespread use in medicine could lead to the development of bacterial resistance and environmental pollution. This is the first report on the combined antibacterial activity of PPI surface-modified maltose dendrimers and amoxicillin. Full article

(This article belongs to the Collection Nanomedicine)

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18 pages, 1234 KiB

Open AccessArticle

Analysis of the Photophysical Behavior and Rotational-Relaxation Dynamics of Coumarin 6 in Nonionic Micellar Environments: The Effect of Temperature

by Cristóbal Carnero Ruiz^*,†, José Manuel Hierrezuelo^† and José Antonio Molina-Bolivar^†

¹ Department of Applied Physics II, Engineering School, University of Malaga, Malaga 29071, Spain

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 19343-19360; https://doi.org/10.3390/molecules201019343 - 23 Oct 2015

Cited by 32 | Viewed by 7694

Abstract

The photodynamics of Coumarin 6 have been investigated in three nonionic micellar assemblies, i.e., n-dodecyl-β-d-maltoside (β-C₁₂G₂), p-tert-octyl-phenoxy polyethylene (9.5) ether (Triton X-100 or TX100) and n-dodecyl-hexaethylene-glycol (C₁₂E₆), to assess their potential [...] Read more.

The photodynamics of Coumarin 6 have been investigated in three nonionic micellar assemblies, i.e., n-dodecyl-β-d-maltoside (β-C₁₂G₂), p-tert-octyl-phenoxy polyethylene (9.5) ether (Triton X-100 or TX100) and n-dodecyl-hexaethylene-glycol (C₁₂E₆), to assess their potential use as encapsulation vehicles for hydrophobic drugs. To evaluate the effect of the micellar size and hydration, the study used a broad temperature range (293.15–323.15 K). The data presented here include steady-state absorption and emission spectra of the probe, dynamic light scattering, together with fluorescence lifetimes and both steady-state, as well as time-resolved fluorescence anisotropies. The time-resolved fluorescence anisotropy data were analyzed on the basis of the well-established two-step model. Our data reveal that the molecular probe in all of the cases is solubilized in the hydration layer of micelles, where it would sense a relatively polar environment. However, the probe was found to undergo a slower rotational reorientation when solubilized in the alkylpolyglycoside surfactant, as a result of a more compact microenvironment around the probe. The behavior of the parameters of the reorientation dynamics with temperature was analyzed on the basis of both micellar hydration and the head-group flexibility of the surfactants. Full article

(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)

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11 pages, 296 KiB

Open AccessArticle

Design, Synthesis, Activity and Docking Study of Sorafenib Analogs Bearing Sulfonylurea Unit

by Chunjiang Wu¹, Min Wang¹, Qidong Tang¹, Rong Luo², Le Chen¹, Pengwu Zheng¹ and Wufu Zhu^1,*

¹ School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China

² Jiangxi Province Institute of Materia Medica, Nanchang 330000, China

Molecules 2015, 20(10), 19361-19371; https://doi.org/10.3390/molecules201019361 - 23 Oct 2015

Cited by 41 | Viewed by 9571

Abstract

Two series of novel sorafenib analogs containing a sulfonylurea unit were synthesized and their chemical structures were confirmed by ¹H-NMR, ¹³C-NMR, MS spectrum and elemental analysis. The synthesized compounds were evaluated for the cytotoxicity against A549, Hela, MCF-7, and PC-3 [...] Read more.

Two series of novel sorafenib analogs containing a sulfonylurea unit were synthesized and their chemical structures were confirmed by ¹H-NMR, ¹³C-NMR, MS spectrum and elemental analysis. The synthesized compounds were evaluated for the cytotoxicity against A549, Hela, MCF-7, and PC-3 cancer cell lines. Some of the compounds showed moderate cytotoxic activity, especially compounds 1-(2,4-difluorophenylsulfonyl)-3-(4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (6c) and 1-(4-bromophenylsulfonyl)-3-(4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (6f) with the IC₅₀ values against four cancer cell lines ranging from 16.54 ± 1.22 to 63.92 ± 1.81 μM, respectively. Inhibitory rates against vascular endothelial growth factor receptor-2 (VEGFR2/KDR) kinase at 10 μM of target compounds were further carried out in this paper in order to investigate the target of these compounds. Structure-activity relationships (SARs) and docking studies indicated that the sulfonylurea unit was important to these kinds of compounds. None of the substitutions in the phenoxy group and small halogen atoms such as 2,4-difluoro substitution of the aryl group contributed to the activity. The results suggested that sulfonylurea sorafenib analogs are worthy of further study. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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21 pages, 1250 KiB

Open AccessArticle

Purification and Partial Characterization of β-Glucosidase in Chayote (Sechium edule)

by Sergio Espíndola Mateos¹, Carlos Alberto Matías Cervantes¹, Edgar Zenteno³, Marie-Christine Slomianny⁴, Juan Alpuche², Pedro Hernández-Cruz², Ruth Martínez-Cruz², Maria Del Socorro Pina Canseco²

, Eduardo Pérez-Campos^1,2, Manuel Sánchez Rubio¹, Laura Pérez-Campos Mayoral²

and Margarito Martínez-Cruz^1,*

¹ Unidad de Bioquímica e Inmunología, Instituto Tecnológico de Oaxaca, Oaxaca 68030, Mexico

² Centro de Investigación Medicina-UNAM-UABJO, Facultad de Medicina y Cirugía, Universidad Autónoma “Benito Juárez” de Oaxaca, Oaxaca 68050, Mexico

³ Facultad de Medicina de la, Universidad Nacional Autónoma de México, Distrito Federal 04510, Mexico

⁴ Unité Mixte de Recherche CNRS/USTL 8576, Glycobiologie Structurale et Fonctionnelle, Université des Sciences et Technologies de Lille 1, Villeneuve d’Ascq 59655, France

Molecules 2015, 20(10), 19372-19392; https://doi.org/10.3390/molecules201019372 - 23 Oct 2015

Cited by 16 | Viewed by 8702

Abstract

β-Glucosidase (EC 3.2.1.21) is a prominent member of the GH1 family of glycoside hydrolases. The properties of this β-glucosidase appear to include resistance to temperature, urea, and iodoacetamide, and it is activated by 2-ME, similar to other members. β-Glucosidase from chayote (Sechium [...] Read more.

β-Glucosidase (EC 3.2.1.21) is a prominent member of the GH1 family of glycoside hydrolases. The properties of this β-glucosidase appear to include resistance to temperature, urea, and iodoacetamide, and it is activated by 2-ME, similar to other members. β-Glucosidase from chayote (Sechium edule) was purified by ionic-interchange chromatography and molecular exclusion chromatography. Peptides detected by LC-ESI-MS/MS were compared with other β-glucosidases using the BLAST program. This enzyme is a 116 kDa protein composed of two sub-units of 58 kDa and shows homology with Cucumis sativus β-glucosidase (NCBI reference sequence XP_004154617.1), in which seven peptides were found with relative masses ranging from 874.3643 to 1587.8297. The stability of β-glucosidase depends on an initial concentration of 0.2 mg/mL of protein at pH 5.0 which decreases by 33% in a period of 30 h, and then stabilizes and is active for the next 5 days (pH 4.0 gives similar results). One hundred μg/mL β-D-glucose inhibited β-glucosidase activity by more than 50%. The enzyme had a K_m of 4.88 mM with p-NPG and a K_cat of 10,000 min⁻¹. The optimal conditions for the enzyme require a pH of 4.0 and a temperature of 50 °C. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 781 KiB

Open AccessArticle

A Practical Route for the Preparation of 1,4,7-Triazacyclononanyl Diacetates with a Hydroxypyridinonate Pendant Arm

by Yongkang Gai, Zhongping Hu, Zhao Rong, Xiang Ma^* and Guangya Xiang^*

School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Molecules 2015, 20(10), 19393-19405; https://doi.org/10.3390/molecules201019393 - 23 Oct 2015

Cited by 15 | Viewed by 6516

Abstract

The preparation of triazamacrocyclic hydroxypyridinonate (HOPO-TACN) derivatives as potential chelators for metals in biomedical applications was reported. The synthesis is based on a convergent synthetic approach, in which the key intermediate di-tert-butyl-2,2′-(1,4,7-triazonane-1,4-diyl) diacetate was coupled with a hydroxypyridinonate pendant arm. The [...] Read more.

The preparation of triazamacrocyclic hydroxypyridinonate (HOPO-TACN) derivatives as potential chelators for metals in biomedical applications was reported. The synthesis is based on a convergent synthetic approach, in which the key intermediate di-tert-butyl-2,2′-(1,4,7-triazonane-1,4-diyl) diacetate was coupled with a hydroxypyridinonate pendant arm. The method is suitable for rapid syntheses of metal chelator HOPO-TACNs of biomedical interest. Full article

(This article belongs to the Section Organic Chemistry)

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27 pages, 892 KiB

Open AccessReview

Effects of Flavonoids from Food and Dietary Supplements on Glial and Glioblastoma Multiforme Cells

by Marko Vidak^*, Damjana Rozman and Radovan Komel

Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov Trg 2, SI-1000 Ljubljana, Slovenia

Molecules 2015, 20(10), 19406-19432; https://doi.org/10.3390/molecules201019406 - 23 Oct 2015

Cited by 43 | Viewed by 11664

Abstract

Quercetin, catechins and proanthocyanidins are flavonoids that are prominently featured in foodstuffs and dietary supplements, and may possess anti-carcinogenic activity. Glioblastoma multiforme is the most dangerous form of glioma, a malignancy of the brain connective tissue. This review assesses molecular structures of these [...] Read more.

Quercetin, catechins and proanthocyanidins are flavonoids that are prominently featured in foodstuffs and dietary supplements, and may possess anti-carcinogenic activity. Glioblastoma multiforme is the most dangerous form of glioma, a malignancy of the brain connective tissue. This review assesses molecular structures of these flavonoids, their importance as components of diet and dietary supplements, their bioavailability and ability to cross the blood-brain barrier, their reported beneficial health effects, and their effects on non-malignant glial as well as glioblastoma tumor cells. The reviewed flavonoids appear to protect glial cells via reduction of oxidative stress, while some also attenuate glutamate-induced excitotoxicity and reduce neuroinflammation. Most of the reviewed flavonoids inhibit proliferation of glioblastoma cells and induce their death. Moreover, some of them inhibit pro-oncogene signaling pathways and intensify the effect of conventional anti-cancer therapies. However, most of these anti-glioblastoma effects have only been observed in vitro or in animal models. Due to limited ability of the reviewed flavonoids to access the brain, their normal dietary intake is likely insufficient to produce significant anti-cancer effects in this organ, and supplementation is needed. Full article

(This article belongs to the Special Issue Dietary Bioactive Compounds: Metabolism, Mechanisms and Translational Significance for Health and Prevention of Diseases)

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16 pages, 759 KiB

Open AccessReview

The Multiple Roles of Microrna-223 in Regulating Bone Metabolism

by Yong Xie^1,†, Lihai Zhang^1,†, Yanpan Gao², Wei Ge^2,* and Peifu Tang^1,*

¹ Department of Orthopedics, General Hospital of Chinese PLA, Beijing 100853, China

² National Key Laboratory of Medical Molecular Biology, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 19433-19448; https://doi.org/10.3390/molecules201019433 - 23 Oct 2015

Cited by 41 | Viewed by 8596

Abstract

Bone metabolism is a lifelong process for maintaining skeletal system homeostasis, which is regulated by bone-resorbing osteoclasts and bone-forming osteoblasts. Aberrant differentiation of osteoclasts and osteoblasts leads to imbalanced bone metabolism, resulting in ossification and osteolysis diseases. MicroRNAs (miRNAs) are pivotal factors in [...] Read more.

Bone metabolism is a lifelong process for maintaining skeletal system homeostasis, which is regulated by bone-resorbing osteoclasts and bone-forming osteoblasts. Aberrant differentiation of osteoclasts and osteoblasts leads to imbalanced bone metabolism, resulting in ossification and osteolysis diseases. MicroRNAs (miRNAs) are pivotal factors in regulating bone metabolism via post-transcriptional inhibition of target genes. Recent studies have revealed that miR-223 exerts multiple effects on bone metabolism, especially in the processes of osteoclast and osteoblasts differentiation. In this review, we highlight the roles of miR-223 during the processes of osteoclast and osteoblast differentiation, as well as the potential clinical applications of miR-223 in bone metabolism disorders. Full article

(This article belongs to the Section Molecular Diversity)

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14 pages, 795 KiB

Open AccessCommunication

Selective Halogen-Lithium Exchange of 1,2-Dihaloarenes for Successive [2+4] Cycloadditions of Arynes and Isobenzofurans

by Shohei Eda and Toshiyuki Hamura^*

Department of Applied Chemistry for Environment, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan

Molecules 2015, 20(10), 19449-19462; https://doi.org/10.3390/molecules201019449 - 23 Oct 2015

Cited by 17 | Viewed by 10371

Abstract

Successive [2+4] cycloadditions of arynes and isobenzofurans by site-selective halogen-lithium exchange of 1,2-dihaloarenes were developed, allowing the rapid construction of polycyclic compounds which serve as a useful synthetic intermediates for the preparation of various polyacene derivatives. Full article

(This article belongs to the Special Issue Development and Application of Aryne Chemistry in Organic Synthesis)

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26 pages, 10701 KiB

Open AccessArticle

Comparative Study of the Optical and Textural Properties of Tetrapyrrole Macrocycles Trapped Within ZrO₂, TiO₂, and SiO₂ Translucent Xerogels

by Eduardo Salas-Bañales, R. Iris Y. Quiroz-Segoviano, Luis Antonio Díaz-Alejo, Fernando Rojas-González

, Alberto Estrella-González, Antonio Campero and Miguel A. García-Sánchez^*

Department of Chemistry, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Mexico, D.F. 09340, Mexico

Molecules 2015, 20(10), 19463-19488; https://doi.org/10.3390/molecules201019463 - 23 Oct 2015

Cited by 8 | Viewed by 7793

Abstract

The entrapping of physicochemical active molecules inside mesoporous networks is an appealing field of research due to the myriad of potential applications in optics, photocatalysis, chemical sensing, and medicine. One of the most important reasons for this success is the possibility of optimizing [...] Read more.

The entrapping of physicochemical active molecules inside mesoporous networks is an appealing field of research due to the myriad of potential applications in optics, photocatalysis, chemical sensing, and medicine. One of the most important reasons for this success is the possibility of optimizing the properties that a free active species displays in solution but now trapped inside a solid substrate. Additionally it is possible to modulate the textural characteristics of substrates, such as pore size, specific surface area, polarity and chemical affinity of the surface, toward the physical or chemical adhesion of a variety of adsorbates. In the present document, two kinds of non-silicon metal alkoxides, Zr and Ti, are employed to prepare xerogels containing entrapped tetrapyrrolic species that could be inserted beforehand in analogue silica systems. The main goal is to develop efficient methods for trapping or binding tetrapyrrole macrocycles inside TiO₂ and ZrO₂ xerogels, while comparing the properties of these systems against those of the SiO₂ analogues. Once the optimal synthesis conditions for obtaining translucent monolithic xerogels of ZrO₂ and TiO₂ networks were determined, it was confirmed that these substrates allowed the entrapment, in monomeric form, of macrocycles that commonly appear as aggregates within the SiO₂ network. From these experiments, it could be determined that the average pore diameters, specific surface areas, and water sorption capacities depicted by each one of these substrates, are a consequence of their own nature combined with the particular structure of the entrapped tetrapyrrole macrocycle. Furthermore, the establishment of covalent bonds between the intruding species and the pore walls leads to the obtainment of very similar pore sizes in the three different metal oxide (Ti, Zr, and Si) substrates as a consequence of the templating effect of the encapsulated species. Full article

(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)

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37 pages, 1537 KiB

Open AccessReview

Antioxidants of Edible Mushrooms

by Maja Kozarski¹, Anita Klaus², Dragica Jakovljevic³, Nina Todorovic³, Jovana Vunduk², Predrag Petrović⁴, Miomir Niksic², Miroslav M. Vrvic^3,5 and Leo Van Griensven^6,*

¹ Department for Chemistry and Biochemistry, Faculty of Agriculture, University of Belgrade, Nemanjina 6, Belgrade 11080, Serbia

² Department for Industrial Microbiology, Faculty of Agriculture, University of Belgrade, Nemanjina 6, Belgrade 11080, Serbia

³ Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Njegoseva 12, Belgrade 11001, Serbia

⁴ Institute of Chemical Engineering, Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, Belgrade 11060, Serbia

⁵ Faculty of Chemistry, University of Belgrade, Studentski trg 12–16, Belgrade 11000, Serbia

⁶ Plant Research International, Wageningen University and Research Centre, Droevendaalsesteeg 1, Wageningen 6700 AA, The Netherlands

Molecules 2015, 20(10), 19489-19525; https://doi.org/10.3390/molecules201019489 - 27 Oct 2015

Cited by 328 | Viewed by 27457

Abstract

Oxidative stress caused by an imbalanced metabolism and an excess of reactive oxygen species (ROS) lead to a range of health disorders in humans. Our endogenous antioxidant defense mechanisms and our dietary intake of antioxidants potentially regulate our oxidative homeostasis. Numerous synthetic antioxidants [...] Read more.

Oxidative stress caused by an imbalanced metabolism and an excess of reactive oxygen species (ROS) lead to a range of health disorders in humans. Our endogenous antioxidant defense mechanisms and our dietary intake of antioxidants potentially regulate our oxidative homeostasis. Numerous synthetic antioxidants can effectively improve defense mechanisms, but because of their adverse toxic effects under certain conditions, preference is given to natural compounds. Consequently, the requirements for natural, alternative sources of antioxidant foods identified in edible mushrooms, as well as the mechanistic action involved in their antioxidant properties, have increased rapidly. Chemical composition and antioxidant potential of mushrooms have been intensively studied. Edible mushrooms might be used directly in enhancement of antioxidant defenses through dietary supplementation to reduce the level of oxidative stress. Wild or cultivated, they have been related to significant antioxidant properties due to their bioactive compounds, such as polyphenols, polysaccharides, vitamins, carotenoids and minerals. Antioxidant and health benefits, observed in edible mushrooms, seem an additional reason for their traditional use as a popular delicacy food. This review discusses the consumption of edible mushrooms as a powerful instrument in maintaining health, longevity and life quality. Full article

(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)

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14 pages, 1196 KiB

Open AccessArticle

Fluorescence and Docking Studies of the Interaction between Human Serum Albumin and Pheophytin

by Otávio Augusto Chaves^1,†, Ana Paula de O. Amorim^1,†, Larissa H. E. Castro^1,†, Carlos Mauricio R. Sant’Anna^1,†, Márcia C. C. De Oliveira^1,†, Dari Cesarin-Sobrinho^1,†, José Carlos Netto-Ferreira^1,2,† and Aurélio B. B. Ferreira^1,*

¹ Departamento de Química, Universidade Federal Rural do Rio de Janeiro, BR 465, km 47, 23890-000 Seropédica-RJ, Brazil

² Instituto Nacional de Metrologia, Qualidade e Tecnologia-INMETRO, Divisão de Metrologia Química, 25250-020 Duque de Caxias-RJ, Brazil

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 19526-19539; https://doi.org/10.3390/molecules201019526 - 27 Oct 2015

Cited by 91 | Viewed by 11205

Abstract

In the North of Brazil (Pará and Amazonas states) the leaves of the plant Talinum triangulare (popular: cariru) replace spinach as food. From a phytochemical point of view, they are rich in compounds of the group of pheophytins. These substances, related to [...] Read more.

In the North of Brazil (Pará and Amazonas states) the leaves of the plant Talinum triangulare (popular: cariru) replace spinach as food. From a phytochemical point of view, they are rich in compounds of the group of pheophytins. These substances, related to chlorophyll, have photophysical properties that give them potential application in photodynamic therapy. Human serum albumin (HSA) is one of the main endogenous vehicles for biodistribution of molecules by blood plasma. Association constants and thermodynamic parameters for the interaction of HSA with pheophytin from Talinum triangulare were studied by UV-Vis absorption, fluorescence techniques, and molecular modeling (docking). Fluorescence quenching of the HSA’s internal fluorophore (tryptophan) at temperatures 296 K, 303 K, and 310 K, resulted in values for the association constants of the order of 10⁴ L∙mol⁻¹, indicating a moderate interaction between the compound and the albumin. The negative values of ΔG° indicate a spontaneous process; ΔH° = 15.5 kJ∙mol⁻¹ indicates an endothermic process of association and ΔS° = 0.145 kJ∙mol⁻¹∙K⁻¹ shows that the interaction between HSA and pheophytin occurs mainly by hydrophobic factors. The observed Trp fluorescence quenching is static: there is initial non-fluorescent association, in the ground state, HSA:Pheophytin. Possible solution obtained by a molecular docking study suggests that pheophytin is able to interact with HSA by means of hydrogen bonds with three lysine and one arginine residues, whereas the phytyl group is inserted in a hydrophobic pocket, close to Trp-214. Full article

(This article belongs to the Section Photochemistry)

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14 pages, 2287 KiB

Open AccessArticle

Unique Reactivity of Transition Metal Atoms Embedded in Graphene to CO, NO, O₂ and O Adsorption: A First-Principles Investigation

by Minmin Chu, Xin Liu^*

, Yanhui Sui^*, Jie Luo and Changgong Meng^*

School of Chemistry and State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China

Molecules 2015, 20(10), 19540-19553; https://doi.org/10.3390/molecules201019540 - 27 Oct 2015

Cited by 15 | Viewed by 6845

Abstract

Taking the adsorption of CO, NO, O₂ and O as probes, we investigated the electronic structure of transition metal atoms (TM, TM = Fe, Co, Ni, Cu and Zn) embedded in graphene by first-principles-based calculations. We showed that these TM atoms can [...] Read more.

Taking the adsorption of CO, NO, O₂ and O as probes, we investigated the electronic structure of transition metal atoms (TM, TM = Fe, Co, Ni, Cu and Zn) embedded in graphene by first-principles-based calculations. We showed that these TM atoms can be effectively stabilized on monovacancy defects on graphene by forming plausible interactions with the C atoms associated with dangling bonds. These interactions not only give rise to high energy barriers for the diffusion and aggregation of the embedded TM atoms to withstand the interference of reaction environments, but also shift the energy levels of TM-d states and regulate the reactivity of the embedded TM atoms. The adsorption of CO, NO, O₂ and O correlates well with the weight averaged energy level of TM-d states, showing the crucial role of interfacial TM-C interactions on manipulating the reactivity of embedded TM atoms. These findings pave the way for the developments of effective monodispersed atomic TM composites with high stability and desired performance for gas sensing and catalytic applications. Full article

(This article belongs to the Section Medicinal Chemistry)

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17 pages, 936 KiB

Open AccessReview

Starch Modification by Organic Acids and Their Derivatives: A Review

by Đurđica Ačkar^1,†

, Jurislav Babić^1,*

, Antun Jozinović^1,†

, Borislav Miličević^1,†, Stela Jokić^1,†, Radoslav Miličević^2,†, Marija Rajič^1,† and Drago Šubarić^1,†

¹ Department of Food Technology, Faculty of Food Technology, Josip Juraj Strossmayer University of Osijek, Franje Kuhača 20, Osijek 31000, Croatia

² Faculty of Technology Tuzla, University of Tuzla, Univerzitetska 8, Tuzla 75000, Bosnia and Herzegovina

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 19554-19570; https://doi.org/10.3390/molecules201019554 - 27 Oct 2015

Cited by 153 | Viewed by 20653

Abstract

Starch has been an inexhaustible subject of research for many decades. It is an inexpensive, readily-available material with extensive application in the food and processing industry. Researchers are continually trying to improve its properties by different modification procedures and expand its application. What [...] Read more.

Starch has been an inexhaustible subject of research for many decades. It is an inexpensive, readily-available material with extensive application in the food and processing industry. Researchers are continually trying to improve its properties by different modification procedures and expand its application. What is mostly applied in this view are their chemical modifications, among which organic acids have recently drawn the greatest attention, particularly with respect to the application of starch in the food industry. Namely, organic acids naturally occur in many edible plants and many of them are generally recognized as safe (GRAS), which make them ideal modification agents for starch intended for the food industry. The aim of this review is to give a short literature overview of the progress made in the research of starch esterification, etherification, cross-linking, and dual modification with organic acids and their derivatives. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 2280 KiB

Open AccessArticle

Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin

by Andreas Beyer¹, Holger Grohganz²

, Korbinian Löbmann²

, Thomas Rades²

and Claudia S. Leopold^1,*

¹ Division of Pharmaceutical Technology, University of Hamburg, Hamburg 20146, Germany

² Department of Pharmacy, University of Copenhagen, Copenhagen 2100, Denmark

Molecules 2015, 20(10), 19571-19587; https://doi.org/10.3390/molecules201019571 - 27 Oct 2015

Cited by 9 | Viewed by 8233

Abstract

To benefit from the optimized dissolution properties of active pharmaceutical ingredients in their amorphous forms, co-amorphisation as a viable tool to stabilize these amorphous phases is of both academic and industrial interest. Reports dealing with the physical stability and recrystallization behavior of co-amorphous [...] Read more.

To benefit from the optimized dissolution properties of active pharmaceutical ingredients in their amorphous forms, co-amorphisation as a viable tool to stabilize these amorphous phases is of both academic and industrial interest. Reports dealing with the physical stability and recrystallization behavior of co-amorphous systems are however limited to qualitative evaluations based on the corresponding X-ray powder diffractograms. Therefore, the objective of the study was to develop a quantification model based on X-ray powder diffractometry (XRPD), followed by a multivariate partial least squares regression approach that enables the simultaneous determination of up to four solid state fractions: crystalline naproxen, γ-indomethacin, α-indomethacin as well as co-amorphous naproxen-indomethacin. For this purpose, a calibration set that covers the whole range of possible combinations of the four components was prepared and analyzed by XRPD. In order to test the model performances, leave-one-out cross validation was performed and revealed root mean square errors of validation between 3.11% and 3.45% for the crystalline molar fractions and 5.57% for the co-amorphous molar fraction. In summary, even four solid state phases, involving one co-amorphous phase, can be quantified with this XRPD data-based approach. Full article

(This article belongs to the Collection Poorly Soluble Drugs)

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17 pages, 3707 KiB

Open AccessArticle

Elevated Expression and Pro-Inflammatory Activity of IL-36 in Patients with Systemic Lupus Erythematosus

by Man Chu^1,2,†, Chun Kwok Wong^1,2,3,†, Zhe Cai^1,2

, Jie Dong^1,2, Delong Jiao^1,2, Ngar Woon Kam^2,4, Christopher Wai Kei Lam⁵ and Lai Shan Tam^2,4,*

¹ Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China

² Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China

³ State Key Laboratory of Phytochemistry and Plant Resources in West China, Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China

⁴ Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China

⁵ State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau

^† These authors contributed equally to this work.

Molecules 2015, 20(10), 19588-19604; https://doi.org/10.3390/molecules201019588 - 27 Oct 2015

Cited by 52 | Viewed by 8676

Abstract

We investigated the expression and proinflammatory activity of interleukin (IL)-36 in patients with systemic lupus erythematosus (SLE). The expression level of IL-36, its putative receptors and the frequency of CD19⁺CD24^highCD27⁺ regulatory B (Breg) lymphocytes of peripheral blood from [...] Read more.

We investigated the expression and proinflammatory activity of interleukin (IL)-36 in patients with systemic lupus erythematosus (SLE). The expression level of IL-36, its putative receptors and the frequency of CD19⁺CD24^highCD27⁺ regulatory B (Breg) lymphocytes of peripheral blood from 43 SLE patients and 16 normal control (NC) subjects were studied using ELISA and flow cytometry. Plasma cytokines/chemokines and ex vivo productions of cytokine/chemokine from peripheral blood mononuclear cells (PBMC) stimulated with recombinant IL-36 were determined by Luminex multiplex assay. Plasma concentrations of IL-36α, IL-36γ and the proportions of circulating IL-36R-positive CD19⁺ B lymphocytes in total B lymphocytes and PBMC were significantly increased in active SLE patients compared with NC (all p < 0.05). Plasma IL-36α and IL-36γ correlated positively with SLE disease activity and elevated plasma IL-10 concentration (all p < 0.05). The frequencies of circulating Breg lymphocytes in total B lymphocytes and PBMC were significantly decreased in both inactive and active SLE patients compared with NC (all p < 0.01). The frequency of Breg lymphocytes in total B lymphocytes correlated negatively with the proportion of IL-36R-positive B lymphocytes (p < 0.05). IL-36α exerted substantial proinflammatory effect in PBMC from SLE patients by inducing the production of IL-6 and CXCL8. Upon stimulation with IL-36α and IL-36γ, ex vivo productions of IL-6 and CXCL8 were significantly increased in SLE patients compared with NC (all p < 0.05). This cross-sectional study demonstrated that over expression of circulating IL-36α may exert a proinflammatory effect as observed in human SLE. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 873 KiB

Open AccessArticle

A Simple, Effective, Green Method for the Regioselective 3-Acylation of Unprotected Indoles

by Phuong Hoang Tran¹, Hai Ngoc Tran¹, Poul Erik Hansen^2,*, Mai Hoang Ngoc Do¹ and Thach Ngoc Le¹

¹ Department of Organic Chemistry, Faculty of Chemistry, University of Science, Vietnam National University, Ho Chi Minh City 70000, Vietnam

² Department of Science, Systems and Models, Roskilde University, POB 260, Roskilde DK-4000, Denmark

Molecules 2015, 20(10), 19605-19619; https://doi.org/10.3390/molecules201019605 - 27 Oct 2015

Cited by 15 | Viewed by 8334

Abstract

A fast and green method is developed for regioselective acylation of indoles in the 3-position without the need for protection of the NH position. The method is based on Friedel-Crafts acylation using acid anhydrides. The method has been optimized, and Y(OTf)₃ in [...] Read more.

A fast and green method is developed for regioselective acylation of indoles in the 3-position without the need for protection of the NH position. The method is based on Friedel-Crafts acylation using acid anhydrides. The method has been optimized, and Y(OTf)₃ in catalytic amounts is found to be the best catalyst together with the commercially available ionic liquid [BMI]BF₄ (1-butyl-3-methylimidazolium tetrafluoro-borate) as solvent. The reaction is completed in a very short time using monomode microwave irradiation. The catalyst can be reused up to four times without significant loss of activity. A range of substituted indoles are investigated as substrates, and thirteen new compounds have been synthesized. Full article

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

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Molecules, Volume 20, Issue 10 (October 2015) – 108 articles , Pages 17684-19646

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