Molecules

16 pages, 365 KiB

Open AccessArticle

K₂CO₃-Mediated Synthesis of Functionalised 4-Substituted-2-amino-3-cyano-4H-chromenes via Michael-Cyclization Reactions

by Yanyang He^1,†, Rong Hu^1,†, Rongsheng Tong², Fengqiong Li¹, Jianyou Shi^2,* and Mei Zhang^1,*

¹ Key Laboratory of Standardization of Chinese Herbal Medicines of Ministry of Education, State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China

² Pharmaceutical Department of Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, Chengdu 610072, China

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 19253-19268; https://doi.org/10.3390/molecules191219253 - 25 Nov 2014

Cited by 25 | Viewed by 8793

Abstract

An efficient approach for the synthesis of functionalized 4-substituted-2-amino-3-cyano-4H-chromenes moderate to high yields (up to 98%) has been achieved via a tandem K₂CO₃catalyzed conjugate addition-cyclization reaction of malononitrile and a range of Knoevenagel adducts previously formed from [...] Read more.

An efficient approach for the synthesis of functionalized 4-substituted-2-amino-3-cyano-4H-chromenes moderate to high yields (up to 98%) has been achieved via a tandem K₂CO₃catalyzed conjugate addition-cyclization reaction of malononitrile and a range of Knoevenagel adducts previously formed from oxindole, pyrazolone, nitromethane, N,N-dimethylbarbituric acid or indanedione. This methodology differs from the previous classical methods in its simplicity and ready availability of the catalyst. Full article

(This article belongs to the Section Organic Chemistry)

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23 pages, 1981 KiB

Open AccessArticle

Inter-Dye Distance Distributions Studied by a Combination of Single-Molecule FRET-Filtered Lifetime Measurements and a Weighted Accessible Volume (wAV) Algorithm

by Henning Höfig^1,2,†, Matteo Gabba^2,*,†, Simón Poblete^3,†, Daryan Kempe¹ and Jörg Fitter^1,2,*

¹ Physikalisches Institut (IA), RWTH Aachen University, Otto-Blumenthal-Straße, 52074 Aachen, Germany

² Institute of Complex Systems (ICS-5), Molecular Biophysics, Forschungszentrum Jülich, Wilhelm-Johnen-Straße, 52428 Jülich, Germany

³ Institute of Complex Systems (ICS-2), Theoretical Soft Matter and Biophysics, Forschungszentrum Jülich, Wilhelm-Johnen-Straße, 52428 Jülich, Germany

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 19269-19291; https://doi.org/10.3390/molecules191219269 - 25 Nov 2014

Cited by 30 | Viewed by 8832

Abstract

Förster resonance energy transfer (FRET) is an important tool for studying the structural and dynamical properties of biomolecules. The fact that both the internal dynamics of the biomolecule and the movements of the biomolecule-attached dyes can occur on similar timescales of nanoseconds is [...] Read more.

Förster resonance energy transfer (FRET) is an important tool for studying the structural and dynamical properties of biomolecules. The fact that both the internal dynamics of the biomolecule and the movements of the biomolecule-attached dyes can occur on similar timescales of nanoseconds is an inherent problem in FRET studies. By performing single-molecule FRET-filtered lifetime measurements, we are able to characterize the amplitude of the motions of fluorescent probes attached to double-stranded DNA standards by means of flexible linkers. With respect to previously proposed experimental approaches, we improved the precision and the accuracy of the inter-dye distance distribution parameters by filtering out the donor-only population with pulsed interleaved excitation. A coarse-grained model is employed to reproduce the experimentally determined inter-dye distance distributions. This approach can easily be extended to intrinsically flexible proteins allowing, under certain conditions, to decouple the macromolecule amplitude of motions from the contribution of the dye linkers. Full article

(This article belongs to the Special Issue Single Molecule Techniques)

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58 pages, 466 KiB

Open AccessReview

Natural Cinnamic Acids, Synthetic Derivatives and Hybrids with Antimicrobial Activity

by Juan David Guzman

Departamento de Química y Biología, División de Ciencias Básicas, Universidad del Norte, Km. 5 vía Puerto Colombia, Barranquilla 081007, Colombia

Molecules 2014, 19(12), 19292-19349; https://doi.org/10.3390/molecules191219292 - 25 Nov 2014

Cited by 342 | Viewed by 23136

Abstract

Antimicrobial natural preparations involving cinnamon, storax and propolis have been long used topically for treating infections. Cinnamic acids and related molecules are partly responsible for the therapeutic effects observed in these preparations. Most of the cinnamic acids, their esters, amides, aldehydes and alcohols, [...] Read more.

Antimicrobial natural preparations involving cinnamon, storax and propolis have been long used topically for treating infections. Cinnamic acids and related molecules are partly responsible for the therapeutic effects observed in these preparations. Most of the cinnamic acids, their esters, amides, aldehydes and alcohols, show significant growth inhibition against one or several bacterial and fungal species. Of particular interest is the potent antitubercular activity observed for some of these cinnamic derivatives, which may be amenable as future drugs for treating tuberculosis. This review intends to summarize the literature data on the antimicrobial activity of the natural cinnamic acids and related derivatives. In addition, selected hybrids between cinnamic acids and biologically active scaffolds with antimicrobial activity were also included. A comprehensive literature search was performed collating the minimum inhibitory concentration (MIC) of each cinnamic acid or derivative against the reported microorganisms. The MIC data allows the relative comparison between series of molecules and the derivation of structure-activity relationships. Full article

(This article belongs to the Special Issue Cinnamic Acids Hybrids with Biological Interest)

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11 pages, 859 KiB

Open AccessArticle

Optimization of Supercritical Fluid Extraction of Oil from the Fruit of Gardenia jasminoides and Its Antidepressant Activity

by Weiwei Tao^1,2,3, Hailou Zhang^1,2, Wenda Xue^1,2, Li Ren^1,2, Baomei Xia^1,2, Xin Zhou^1,2, Haoxin Wu^1,2, Jinao Duan³ and Gang Chen^1,2,*

¹ Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China

² Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China

³ National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China

Molecules 2014, 19(12), 19350-19360; https://doi.org/10.3390/molecules191219350 - 25 Nov 2014

Cited by 61 | Viewed by 9255

Abstract

A response surface methodology was applied to optimize the variables affecting the supercritical ﬂuid carbon dioxide extraction of oil from the fruit of Gardenia jasminoides using the Box–Behnken design. The optimum extraction parameters were an extraction temperature of 49.94 °C, an extraction pressure [...] Read more.

A response surface methodology was applied to optimize the variables affecting the supercritical ﬂuid carbon dioxide extraction of oil from the fruit of Gardenia jasminoides using the Box–Behnken design. The optimum extraction parameters were an extraction temperature of 49.94 °C, an extraction pressure of 29.89 MPa and an extraction time of 93.82 min. Through a GC/MS analysis, we revealed 16 major components of the oil extract, which showed potent antidepressant effects in both of two behavior despair models in mice: tail suspension test and forced swimming test. Our results suggest that the oil extract of Gardenia jasminoides prepared using the supercritical ﬂuid carbon dioxide extraction may contain effective constituents to be used for depression therapy. Full article

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15 pages, 1296 KiB

Open AccessArticle

EOP, a Newly Synthesized Ethyl Pyruvate Derivative, Attenuates the Production of Inflammatory Mediators via p38, ERK and NF-κB Pathways in Lipopolysaccharide-Activated BV-2 Microglial Cells

by Soon Min¹, Sandeep Vasant More¹, Ju-Young Park², Sae-Bom Jeon³, Shin Young Park¹, Eun-Jung Park³, Sung-Hwa Yoon² and Dong-Kug Choi^1,*

¹ Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Korea

² Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea

³ Branch of Immune and Cell Therapy, National Cancer Center, Goyang 410-769, Korea

Molecules 2014, 19(12), 19361-19375; https://doi.org/10.3390/molecules191219361 - 25 Nov 2014

Cited by 17 | Viewed by 7899

Abstract

Microglia-induced neuroinflammation is an important pathological mechanism influencing various neurodegenerative disorders. Excess activation of microglia produces a myriad of proinflammatory mediators that decimate neurons. Hence, therapeutic strategies aimed to suppress the activation of microglia might lead to advancements in the treatment of neurodegenerative [...] Read more.

Microglia-induced neuroinflammation is an important pathological mechanism influencing various neurodegenerative disorders. Excess activation of microglia produces a myriad of proinflammatory mediators that decimate neurons. Hence, therapeutic strategies aimed to suppress the activation of microglia might lead to advancements in the treatment of neurodegenerative diseases. In this study, we synthesized a novel ethyl pyruvate derivative, named EOP (S-ethyl 2-oxopropanethioate) and studied its effects on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) in rat primary microglia and mouse BV-2 microglia. EOP significantly decreased the production of NO, inducible nitric oxide synthase, cyclooxygenase and other proinflammatory cytokines, such as interleukin (IL)-6, IL-1β and tumor necrosis factor-α, in LPS-stimulated BV-2 microglia. The phosphorylation levels of extracellular regulated kinase, p38 mitogen-activated protein kinase, and nuclear translocation of NF-κB were also inhibited by EOP in LPS-activated BV-2 microglial cells. Overall, our observations indicate that EOP might be a promising therapeutic agent to diminish the development of neurodegenerative diseases associated with microglia activation. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 253 KiB

Open AccessReview

Potential Role of Sulfur-Containing Antioxidant Systems in Highly Oxidative Environments

by Emmanuel Mukwevho^1,*,†, Zané Ferreira^2,† and Ademola Ayeleso^2,†

¹ Department of Biochemistry, North West University, Private Bag X2046, Mmabatho 2735, South Africa

² Department of Biochemistry, University of Johannesburg, P.O. Box 524, Auckland Park 2006, South Africa

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 19376-19389; https://doi.org/10.3390/molecules191219376 - 25 Nov 2014

Cited by 113 | Viewed by 12651

Abstract

All forms of life maintain a reducing environment (homeostasis) within their cells. Perturbations in the normal redox state can lead to an oxidative environment which has deleterious effects, especially in health. In biological systems, metabolic activities are dependent mainly on mitochondrial oxidative phosphorylation, [...] Read more.

All forms of life maintain a reducing environment (homeostasis) within their cells. Perturbations in the normal redox state can lead to an oxidative environment which has deleterious effects, especially in health. In biological systems, metabolic activities are dependent mainly on mitochondrial oxidative phosphorylation, a metabolic pathway that uses energy released by the oxidation of nutrients to produce ATP. In the process of oxidative phosphorylation, electrons are transferred from electron donors to electron acceptors such as oxygen in redox reactions and often results to the generation of reactive species. Reactive oxygen species consist of a class of radical and non-radical oxygen derivatives. The imbalance between the reactive oxygen species and antioxidant defence systems leads to oxidative burden and hence, damage biological molecules. Antioxidants help to prevent or fix the deleterious effects of reactive species. Sulfur is an important element in biological systems. This atom is usually integrated into proteins as the redox-active cysteine residue and in molecules such as glutathione, thioredoxin and glutaredoxin which are vital antioxidant molecules and are therefore essential for life. This review covers the role of sulfur containing antioxidant systems in oxidative environments. Full article

(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)

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17 pages, 2491 KiB

Open AccessArticle

Enzymatic Cellulose Hydrolysis: Enzyme Reusability and Visualization of β-Glucosidase Immobilized in Calcium Alginate

by Chien-Tai Tsai and Anne S. Meyer^*

Center for Bioprocess Engineering, Department of Chemical and Biochemical Engineering, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark

Molecules 2014, 19(12), 19390-19406; https://doi.org/10.3390/molecules191219390 - 25 Nov 2014

Cited by 57 | Viewed by 9417

Abstract

The high cellulase enzyme dosages required for hydrolysis of cellulose is a major cost challenge in lignocellulosic ethanol production. One method to decrease the enzyme dosage and increase biocatalytic productivity is to re-use β-glucosidase (BG) via immobilization. In the present research, glutaraldehyde cross-linked [...] Read more.

The high cellulase enzyme dosages required for hydrolysis of cellulose is a major cost challenge in lignocellulosic ethanol production. One method to decrease the enzyme dosage and increase biocatalytic productivity is to re-use β-glucosidase (BG) via immobilization. In the present research, glutaraldehyde cross-linked BG was entrapped in calcium alginate gel particles. More than 60% of the enzyme activity could be recovered under optimized conditions, and glutaraldehyde cross-linking decreased leakage of BG from the calcium alginate particles. The immobilized BG aggregates were visualized by confocal laser scanning microscopy (CLSM). The CLSM images, which we believe are the first to be published, corroborate that more BG aggregates were entrapped in the matrix when the enzymes were cross-linked by glutaraldehyde as opposed to when they are not cross-linked. The particles with the immobilized BG were recycled for cellulase catalyzed hydrolysis of Avicel. No significant loss in BG activity was observed for up to 20 rounds of reaction recycle steps of the BG particles of 48 h each, verifying a significant stabilization of the BG by immobilization. Similar high glucose yields were obtained by one round of enzymatic hydrolysis of hydrothermally pretreated barley straw during a 72 h reaction with immobilized BG and free BG. Full article

(This article belongs to the Special Issue Enzyme Immobilization)

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28 pages, 3574 KiB

Open AccessReview

Shedding Light on Protein Folding, Structural and Functional Dynamics by Single Molecule Studies

by Krutika Bavishi¹ and Nikos S. Hatzakis^2,*

¹ Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, Center for Synthetic Biology "bioSYNergy", Villum Research Center "Plant Plasticity", University of Copenhagen, Thorvaldsenvej 40, DK-1871 Frederiksberg C, Denmark

² Bio-Nanotechnology Laboratory, Department of Chemistry, Nano-Science Center, Lundbeck Foundation Center Biomembranes in Nanomedicine, University of Copenhagen, 2100 Copenhagen, Denmark

Molecules 2014, 19(12), 19407-19434; https://doi.org/10.3390/molecules191219407 - 25 Nov 2014

Cited by 17 | Viewed by 10713

Abstract

The advent of advanced single molecule measurements unveiled a great wealth of dynamic information revolutionizing our understanding of protein dynamics and behavior in ways unattainable by conventional bulk assays. Equipped with the ability to record distribution of behaviors rather than the mean property [...] Read more.

The advent of advanced single molecule measurements unveiled a great wealth of dynamic information revolutionizing our understanding of protein dynamics and behavior in ways unattainable by conventional bulk assays. Equipped with the ability to record distribution of behaviors rather than the mean property of a population, single molecule measurements offer observation and quantification of the abundance, lifetime and function of multiple protein states. They also permit the direct observation of the transient and rarely populated intermediates in the energy landscape that are typically averaged out in non-synchronized ensemble measurements. Single molecule studies have thus provided novel insights about how the dynamic sampling of the free energy landscape dictates all aspects of protein behavior; from its folding to function. Here we will survey some of the state of the art contributions in deciphering mechanisms that underlie protein folding, structural and functional dynamics by single molecule fluorescence microscopy techniques. We will discuss a few selected examples highlighting the power of the emerging techniques and finally discuss the future improvements and directions. Full article

(This article belongs to the Special Issue Single Molecule Techniques)

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25 pages, 3452 KiB

Open AccessArticle

Synthesis, Anticancer and Antibacterial Activity of Salinomycin N-Benzyl Amides

by Michał Antoszczak¹

, Ewa Maj², Agnieszka Napiórkowska³

, Joanna Stefańska⁴, Ewa Augustynowicz-Kopeć³, Joanna Wietrzyk²

, Jan Janczak⁵, Bogumil Brzezinski¹ and Adam Huczyński^1,*

¹ Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89 b, 61-614 Poznań, Poland

² Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland

³ Department of Microbiology, Institute of Tuberculosis and Pulmonary Diseases, Płocka 26, 01-138 Warsaw, Poland

⁴ Department of Pharmaceutical Microbiology, University of Warsaw, Oczki 3, 02-007 Warsaw, Poland

⁵ Institute of Low Temperature and Structure Research, Polish Academy of Sciences, P.O. Box 1410, 50-950 Wrocław, Poland

Molecules 2014, 19(12), 19435-19459; https://doi.org/10.3390/molecules191219435 - 25 Nov 2014

Cited by 52 | Viewed by 10177

Abstract

A series of 12 novel monosubstituted N-benzyl amides of salinomycin (SAL) was synthesized for the first time and characterized by NMR and FT-IR spectroscopic methods. Molecular structures of three salinomycin derivatives in the solid state were determined using single crystal [...] Read more.

A series of 12 novel monosubstituted N-benzyl amides of salinomycin (SAL) was synthesized for the first time and characterized by NMR and FT-IR spectroscopic methods. Molecular structures of three salinomycin derivatives in the solid state were determined using single crystal X-ray method. All compounds obtained were screened for their antiproliferative activity against various human cancer cell lines as well as against the most problematic bacteria strains such as methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), and Mycobacterium tuberculosis. Novel salinomycin derivatives exhibited potent anticancer activity against drug-resistant cell lines. Additionally, two N-benzyl amides of salinomycin revealed interesting antibacterial activity. The most active were N-benzyl amides of SAL substituted at -ortho position and the least anticancer active derivatives were those substituted at the -para position. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 494 KiB

Open AccessCommunication

Polylactide Conjugates of Camptothecin with Different Drug Release Abilities

by Ewa Oledzka^1,†, Paweł Horeglad^2,†, Zuzanna Gruszczyńska¹, Andrzej Plichta³, Grzegorz Nałęcz-Jawecki⁴ and Marcin Sobczak^1,5,*,†

¹ Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, Warsaw 02-097, Poland

² Centre of New Technologies, University of Warsaw, Banacha 2c, Warsaw 02-097, Poland

³ Chair of Polymer Chemistry and Technology, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, Warsaw 00-664, Poland

⁴ Department of Environmental Health Science, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, Warsaw 02-097, Poland

⁵ Chair of Chemistry, Department of Organic Chemistry, Faculty of Materials Science and Design, Kazimierz Pulaski University of Technology and Humanities in Radom, Chrobrego 27, Radom 26-600, Poland

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 19460-19470; https://doi.org/10.3390/molecules191219460 - 25 Nov 2014

Cited by 16 | Viewed by 7808

Abstract

Camptothecin-polylactide conjugates (CMPT-PLA) were synthesized by covalent incorporation of CMPT into PLA of different microstructure, i.e., atactic PLA and atactic-block-isotactically enriched PLA (P_m = 0.79) via urethane bonds. The kinetic release of CPMT from CMPT-PLA conjugates, tested in [...] Read more.

Camptothecin-polylactide conjugates (CMPT-PLA) were synthesized by covalent incorporation of CMPT into PLA of different microstructure, i.e., atactic PLA and atactic-block-isotactically enriched PLA (P_m = 0.79) via urethane bonds. The kinetic release of CPMT from CMPT-PLA conjugates, tested in vitro under different conditions, is possible in both cases and notably, strongly dependent on PLA microstructure. It shows that release properties of drug-PLA conjugates can be tailored by controlled design of the PLA microstructure, and allow in the case of CMPT-PLA conjugates for the development of highly controlled biodegradable CMPT systems—important delivery systems for anti-cancer agents. Full article

(This article belongs to the Special Issue Prodrugs)

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20 pages, 2819 KiB

Open AccessArticle

Development of an Ionic Liquid-Based Microwave-Assisted Method for the Extraction and Determination of Taxifolin in Different Parts of Larix gmelinii

by Zaizhi Liu^1,†, Jia Jia^2,†, Fengli Chen¹, Fengjian Yang^1,*, Yuangang Zu¹ and Lei Yang^1,*

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

² Pharmacy & Medical Laboratory Department, Daqing Medical College, Daqing 163312, China

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 19471-19490; https://doi.org/10.3390/molecules191219471 - 25 Nov 2014

Cited by 20 | Viewed by 6818

Abstract

An ionic liquid-based microwave-assisted extraction method (ILMAE) was successfully applied for the extraction of taxifolin from Larix gmelinii. Different kinds of 1-alkyl-3-methylimidazolium ionic liquids with different kinds of cations and anions were studied and 1-butyl-3-methylimidazolium bromide was chosen as the optimal solvent [...] Read more.

An ionic liquid-based microwave-assisted extraction method (ILMAE) was successfully applied for the extraction of taxifolin from Larix gmelinii. Different kinds of 1-alkyl-3-methylimidazolium ionic liquids with different kinds of cations and anions were studied and 1-butyl-3-methylimidazolium bromide was chosen as the optimal solvent for taxifolin extraction. The optimal conditions of ILMAE were determined by single factor experiments and Box-Behnken design as follows: [C₄mim]Br concentration of 1.00 M, soaking time of 2 h, liquid-solid ratio of 15:1 mL/g, microwave irradiation power of 406 W, microwave irradiation time of 14 min. No degradation of taxifolin had been observed under the optimum conditions as evidenced from the stability studies performed with standard taxifolin. Compared with traditional solvent and methods, ILMAE provided higher extraction yield, lower energy and time consumption. The distribution of taxifolin in different parts of larch and the influences of age, orientation, and season on the accumulation of taxifolin were analyzed for the sufficient utilization of L. gmelinii. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 267 KiB

Open AccessArticle

Synthesis of Chiral Chalcone Derivatives Catalyzed by the Chiral Cinchona Alkaloid Squaramide

by Dandan Xie^†, Ying Xie^†, Yan Ding, Jian Wu and Deyu Hu^*

¹ State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi District, Guiyang 550025, China

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 19491-19500; https://doi.org/10.3390/molecules191219491 - 25 Nov 2014

Cited by 8 | Viewed by 5549

Abstract

An effective method has been developed for the preparation of novel chiral chalcone derivatives under mild conditions from the easily accessible starting materials nitromethane and chalcone derivatives 2. The corresponding products were obtained in moderate yields with excellent enantioselectivities (up to 99%). Full article

(This article belongs to the Section Organic Chemistry)

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15 pages, 1401 KiB

Open AccessArticle

Goniolactone C, a Styryl Lactone Derivative, Inhibits PDGF-BB-Induced Vascular Smooth Muscle Cell Migration and Proliferation via PDGFR/ERK Signaling

by Lan Sun^1,2, Rui Zhao^1,3, Xi Lan⁴, Ruoyun Chen¹, Si Wang¹ and Guanhua Du^1,2,*

¹ Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China

² Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Beijing 100050, China

³ State Key Laboratory for Bioactive Substances and Functions of Natural Medicines, Beijing 100050, China

⁴ Department of Anesthesiology and Critical Care medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA

Molecules 2014, 19(12), 19501-19515; https://doi.org/10.3390/molecules191219501 - 26 Nov 2014

Cited by 16 | Viewed by 6713

Abstract

Platelet-derived growth factor-BB (PDGF-BB) and its downstream effector, extracellular signal-regulated kinase 1/2 (ERK1/2) MAP kinase, initiate a multitude of biological effects, including vascular smooth muscle cell (VSMC) proliferation and migration, which are critical events in the initiation and development of restenosis following percutaneous [...] Read more.

Platelet-derived growth factor-BB (PDGF-BB) and its downstream effector, extracellular signal-regulated kinase 1/2 (ERK1/2) MAP kinase, initiate a multitude of biological effects, including vascular smooth muscle cell (VSMC) proliferation and migration, which are critical events in the initiation and development of restenosis following percutaneous transluminal coronary angioplasty (PTCA). Styryl lactones are natural products that have been demonstrated to possess anti-proliferative activities. Goniolactone C is a styryl lactone derivative that was first extracted from Goniothalamus cheliensis Hu. In the present study, we investigated the effects of goniolactone C on VSMC migration and proliferation. We found that goniolactone C preferentially interacted with cellular systems that rely on PDGF signaling but not those that rely on epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) signaling. Goniolactone C strongly inhibited PDGF-BB-induced VSMC migration and proliferation. goniolactone C-mediated inhibition of VSMC proliferation was associated with cell cycle arrest, while goniolactone C-mediated inhibition of VSMC migration was associated with the suppression of adhesion molecule expression. In addition, goniolactone C directly inhibited PDGFR-β kinase activity, thereby blocking the downstream effector of PDGF-BB. Thus, the results of the present study suggest a novel adjunctive pharmacological strategy that may be used to prevent angioplasty-related restenosis. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 633 KiB

Open AccessArticle

Concise and Straightforward Asymmetric Synthesis of a Cyclic Natural Hydroxy-Amino Acid

by Mario J. Simirgiotis^1,*

, Javier Vallejos², Carlos Areche³ and Beatriz Sepúlveda⁴

¹ Laboratorio de Productos Naturales, Facultad de Ciencias Básicas, Universidad de Antofagasta, Avenida Universidad de Antofagasta 02800, Casilla 170, Antofagasta 1240000, Chile

² Departamento de Química, Universidad Católica del Norte, Av. Angamos 610, Antofagasta 1240000, Chile

³ Departamento de Química, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago 7800024, Chile

⁴ Departamento de Ciencias Químicas, Universidad Andrés Bello, Campus Viña del Mar, Quillota 980, Viña del Mar 2520000, Chile

Molecules 2014, 19(12), 19516-19531; https://doi.org/10.3390/molecules191219516 - 26 Nov 2014

Cited by 2 | Viewed by 7420

Abstract

An enantioselective total synthesis of the natural amino acid (2S,4R,5R)-4,5-di-hydroxy-pipecolic acid starting from D-glucoheptono-1, 4-lactone is presented. The best sequence employed as a key step the intramolecular nucleophilic displacement by an amino function of a 6-O [...] Read more.

An enantioselective total synthesis of the natural amino acid (2S,4R,5R)-4,5-di-hydroxy-pipecolic acid starting from D-glucoheptono-1, 4-lactone is presented. The best sequence employed as a key step the intramolecular nucleophilic displacement by an amino function of a 6-O-p-toluene-sulphonyl derivative of a methyl D-arabino-hexonate and involved only 12 steps with an overall yield of 19%. The structures of the compounds synthesized were elucidated on the basis of comprehensive spectroscopic (NMR and MS) and computational analysis. Full article

(This article belongs to the Section Organic Chemistry)

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17 pages, 253 KiB

Open AccessArticle

Evaluation of the Chemical and Antioxidant Properties of Wild and Cultivated Mushrooms of Ghana

by Mary Obodai¹

, Isabel C.F.R. Ferreira^2,*

, Ângela Fernandes², Lillian Barros^2,*, Deborah L. Narh Mensah¹, Matilda Dzomeku¹, Arailde F. Urben³, Juanita Prempeh¹ and Richard K. Takli¹

¹ CSIR-Food Research Institute, P.O. Box M20, Accra, Ghana

² Mountain Research Centre (CIMO), ESA, Polytechnic Institute of Bragança, Campus de Santa Apolónia, apartado 1172, Bragança 5301-855, Portugal

³ Embrapa Recursos Genéticos e Biotecnologia—PqEB—Parque Estação Biológica, Final Av. W5 Norte, Caixa Postal 02372, CEP:70770-900 Brasília, DF, Brazil

Molecules 2014, 19(12), 19532-19548; https://doi.org/10.3390/molecules191219532 - 26 Nov 2014

Cited by 71 | Viewed by 8537

Abstract

Knowledge of the chemical composition of both wild and cultivated edible mushrooms in Ghana is limited. This study reports their nutritional value, composition in lipophilic and hydrophilic molecules, minerals and antioxidant properties. The samples were found to be nutritionally rich in carbohydrates, ranging [...] Read more.

Knowledge of the chemical composition of both wild and cultivated edible mushrooms in Ghana is limited. This study reports their nutritional value, composition in lipophilic and hydrophilic molecules, minerals and antioxidant properties. The samples were found to be nutritionally rich in carbohydrates, ranging from 64.14 ± 0.93 g in Pleurotus ostreatus strain EM-1 to 80.17 ± 0.34 g in Lentinus squarrosulus strain LSF. The highest level of proteins (28.40 ± 0.86 g) was recorded in the mentioned P. ostreatus strain. Low fat contents were registered in the samples, with Auricularia auricula recording the lowest value. High levels of potassium were also observed with the following decreasing order of elements: K > P ~ Na > Mg > Ca. High levels of antioxidants were also observed, thus making mushrooms suitable to be used as functional foods or nutraceutical sources. Furthermore, this study provides new information regarding chemical properties of mushrooms from Ghana, which is very important for the biodiversity characterization of this country. Full article

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

8 pages, 220 KiB

Open AccessArticle

Resveratrol Trimers from Seed Cake of Paeonia rockii

by Pu Liu, Yiran Wang, Jiayu Gao, Zongyuan Lu, Weiping Yin^* and Ruixue Deng^*

Chemical Engineering & Pharmaceutical College, Henan University of Science and Technology, Research Center on Wild Natural Resources of FUNIU Mountain, Luoyang 471023, China

Molecules 2014, 19(12), 19549-19556; https://doi.org/10.3390/molecules191219549 - 26 Nov 2014

Cited by 23 | Viewed by 7008

Abstract

In the course of screening natural products for antibacterial activities, a total acetone extract of the seed cake of Paeonia rockii showed significant effects against bacterial strains. Bioactivity-guided fractionation of the EtOAc-soluble fraction of the total acetone extract resulted in the isolation [...] Read more.

In the course of screening natural products for antibacterial activities, a total acetone extract of the seed cake of Paeonia rockii showed significant effects against bacterial strains. Bioactivity-guided fractionation of the EtOAc-soluble fraction of the total acetone extract resulted in the isolation and identification of five resveratrol trimers, including rockiiol C (1), gnetin H (2), suffruticosol A (3), suffruticosol B (4) and suffruticosol C (5). The relative configuration of these compounds was elucidated mainly by comprehensive 1D and 2D-NMR experiments. Compound 1 was a new compound. All isolated compounds exhibited strong antibacterial activities against Gram-positive bacteria. Full article

(This article belongs to the Special Issue Resveratrol)

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16 pages, 504 KiB

Open AccessArticle

Some Observations on the Development of Superior Photocatalytic Systems for Application to Water Purification by the “Adsorb and Shuttle” or the Interphase Charge Transfer Mechanisms

by Cooper Langford^1,*, Maryam Izadifard^2,†, Emad Radwan^3,† and Gopal Achari⁴

¹ Department of Chemistry, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4, Canada

² Department of Chemistry University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4, Canada

³ Department of Water Pollution Research, National Research Centre, Cairo 12311, Egypt

⁴ Department of Civil Engineering, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4, Canada

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 19557-19572; https://doi.org/10.3390/molecules191219557 - 26 Nov 2014

Cited by 16 | Viewed by 5964

Abstract

Adsorb and shuttle (A/S) and interfacial charge transfer are the two major strategies for overcoming recombination in photocatalysis in this era of nanoparticle composites. Their relationships are considered here. A review of key literature is accompanied by a presentation of three new experiments [...] Read more.

Adsorb and shuttle (A/S) and interfacial charge transfer are the two major strategies for overcoming recombination in photocatalysis in this era of nanoparticle composites. Their relationships are considered here. A review of key literature is accompanied by a presentation of three new experiments within the overall aim of assessing the relation of these strategies. The cases presented include: A/S by a high silica zeolite/TiO₂ composite, charge transfer (CT) between phases in a TiO₂/WO₃ composite and both A/S and CT by composites of TiO₂ with powered activated carbon (AC) and single-walled carbon nanotubes (SWCNT). The opportunities presented by the two strategies for moving toward photocatalysts that could support applications for the removal of contaminants from drinking water or that lead to a practical adsorbent for organics that could be regenerated photocatalytically link this discussion to ongoing research here. Full article

(This article belongs to the Special Issue Photocatalysis)

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15 pages, 2758 KiB

Open AccessArticle

Influence of Post-Treatment Operations on Structural Properties and Photocatalytic Activity of Octahedral Anatase Titania Particles Prepared by an Ultrasonication-Hydrothermal Reaction

by Zhishun Wei, Ewa Kowalska^*

and Bunsho Ohtani

Catalysis Research Center, Hokkaido University, Sapporo 001-0021, Japan

Molecules 2014, 19(12), 19573-19587; https://doi.org/10.3390/molecules191219573 - 26 Nov 2014

Cited by 23 | Viewed by 6291

Abstract

The influence of changes in structural and physical properties on the photocatalytic activity of octahedral anatase particles (OAPs), exposing eight equivalent {101} facets, caused by calcination (2 h) in air or grinding (1 h) in an agate mortar was studied with samples prepared [...] Read more.

The influence of changes in structural and physical properties on the photocatalytic activity of octahedral anatase particles (OAPs), exposing eight equivalent {101} facets, caused by calcination (2 h) in air or grinding (1 h) in an agate mortar was studied with samples prepared by ultrasonication (US; 1 h)–hydrothermal reaction (HT; 24 h, 433 K). Calcination in air at temperatures up to 1173 K induced particle shape changes, evaluated by aspect ratio (AR; d₀₀₁/d₁₀₁ = depth vertical to anatase {001} and {101} facets estimated by the Scherrer equation with data obtained from X-ray diffraction (XRD) patterns) and content of OAP and semi-OAP particles, without transformation into rutile. AR and OAP content, as well as specific surface area (SSA), were almost unchanged by calcination at temperatures up to 673 K and were then decreased by elevating the calcination temperature, suggesting that calcination at a higher temperature caused dull-edging and particle sintering, the latter also being supported by the analysis of particle size using XRD patterns and scanning electron microscopic (SEM) images. Time-resolved microwave conductivity (TRMC) showed that the maximum signal intensity (I_max), corresponding to a product of charge-carrier density and mobility, and signal-decay rate, presumably corresponding to reactivity of charge carriers, were increased with increase in AR, suggesting higher photocatalytic activity of OAPs than that of dull-edged particles. Grinding also decreased the AR, indicating the formation of dull-edged particles. The original non-treated samples showed activities in the oxidative decomposition of acetic acid (CO₂ system) and dehydrogenation of methanol (H₂ system) comparable to and lower than those of a commercial anatase titania (Showa Denko Ceramics FP-6), respectively. The activities of calcined and ground samples for the CO₂ system and H₂ system showed almost linear relations with AR and I_max, respectively, suggesting that those activities may depend on different properties. Full article

(This article belongs to the Special Issue Photocatalysis)

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6 pages, 183 KiB

Open AccessEditorial

Special Issue: Redox Active Natural Products and Their Interaction with Cellular Signalling Pathways

by Claus Jacob

Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, Campus B 2.1, D-66123 Saarbruecken, Germany

Molecules 2014, 19(12), 19588-19593; https://doi.org/10.3390/molecules191219588 - 26 Nov 2014

Cited by 12 | Viewed by 6434

Abstract

During the last decade, research into natural products has experienced a certain renaissance. The urgent need for more and more effective antibiotics in medicine, the demand for ecologically friendly plant protectants in agriculture, “natural” cosmetics and the issue of a sustainable and healthy [...] Read more.

During the last decade, research into natural products has experienced a certain renaissance. The urgent need for more and more effective antibiotics in medicine, the demand for ecologically friendly plant protectants in agriculture, “natural” cosmetics and the issue of a sustainable and healthy nutrition in an ageing society have fuelled research into Nature’s treasure chest of “green gold”. Here, redox active secondary metabolites from plants, fungi, bacteria and other (micro-)organisms often have been at the forefront of the most interesting developments. These agents provide powerful means to interfere with many, probably most cellular signaling pathways in humans, animals and lower organisms, and therefore can be used to protect, i.e., in form of antioxidants, and to frighten off or even kill, i.e., in form of repellants, antibiotics, fungicides and selective, often catalytic “sensor/effector” anticancer agents. Interestingly, whilst natural product research dates back many decades, in some cases even centuries, and compounds such as allicin and various flavonoids have been investigated thoroughly in the past, it has only recently become possible to investigate their precise interactions and mode(s) of action inside living cells. Here, fluorescent staining and labelling on the one side, and appropriate detection, either qualitatively under the microscope or quantitatively in flow cytometers and plate readers, on the other, enable researchers to obtain the various pieces of information necessary to construct a fairly complete puzzle of how such compounds act and interact in living cells. Complemented by the more traditional activity assays and Western Blots, and increasingly joined by techniques such as proteomics, chemogenetic screening and mRNA profiling, these cell based bioanalytical techniques form a powerful platform for “intracellular diagnostics”. In the case of redox active compounds, especially of Reactive Sulfur Species (RSS), such techniques have recently unraveled concepts such as the “cellular thiolstat”, yet considerably more research is required in order to gain a full understanding of why and how such compounds act—often selectively—in different organisms. Full article

(This article belongs to the Special Issue Redox Active Natural Products and Their Interaction with Cellular Signalling Pathways)

16 pages, 1101 KiB

Open AccessArticle

The Effect of Lycii Radicis Cortex Extract on Bone Formation in Vitro and in Vivo

by Eunkuk Park^1,2,†

, Hyun-Seok Jin^1,2,†, Doo-Yeoun Cho^3,4,†, Jeonghyun Kim^1,2, Mun-Chang Kim^1,2, Chun Whan Choi⁵, Yilan Jin¹, Ji-Won Lee⁶, Jin-Hyok Park⁷, Yoon-Sok Chung⁸, Dam Huh^7,* and Seon-Yong Jeong^1,2,*

¹ Department of Medical Genetics, Ajou University School of Medicine, Suwon 443-721, Korea

² Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 443-721, Korea

³ Department of Family Practice and Community Health, Ajou University School of Medicine, Suwon 443-721, Korea

⁴ Clinical Trial Center, Ajou University Medical Center, Suwon 443-721, Korea

⁵ Natural Products Research Institute, Gyeonggi Institute of Science & Technology Promotion, Suwon 443-721, Korea

⁶ Korea Food Research Institute, Seongnam 463-746, Korea

⁷ Dongwoodang Pharmacy Co., Ltd., Yeongchen 770-864, Korea

⁸ Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon 443-721, Korea

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 19594-19609; https://doi.org/10.3390/molecules191219594 - 26 Nov 2014

Cited by 20 | Viewed by 9417

Abstract

Osteoporosis is a common skeletal disease caused by decreased bone mass; it enhances the risk of bone fracture. This study aimed to discover novel herbal extract(s) for the treatment of osteoporosis. We screened 64 ethanol extracts of edible plants native to Korea for [...] Read more.

Osteoporosis is a common skeletal disease caused by decreased bone mass; it enhances the risk of bone fracture. This study aimed to discover novel herbal extract(s) for the treatment of osteoporosis. We screened 64 ethanol extracts of edible plants native to Korea for their ability to increase the cellular proliferation and differentiation of two osteoblastic cell lines: C3H10T1/2 and MC3T3-E1. We selected a Lycii Radicis Cortex (LRC), Lycium Chinese root bark as the primary candidate. Treatment with LRC extract showed enhanced alkaline phosphatase activity and increased expression of bone metabolic markers Alpl, Runx2, and Bglap genes in both osteoblastic cell lines. There was no effect on the osteoclastic differentiation of primary-cultured monocytes from the mouse bone marrows. Furthermore, the study examined the effect of LRC extract in vivo in ovariectomizd (OVX) mice for 8 weeks and 16 weeks, respectively. Bone mineral density (BMD) was significantly higher in LRC extract-administered group than in the non-LRC-administered OVX control group. The results indicated that LRC extract prevented the OVX-induced BMD loss in mice via promoting the differentiation of osteoblast linage cells. These results suggest that LRC extract may be a good natural herbal medicine candidate for the treatment of osteoporosis. Full article

(This article belongs to the Section Medicinal Chemistry)

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23 pages, 605 KiB

Open AccessReview

Recent Advances in the Chemical Composition of Propolis

by Shuai Huang¹, Cui-Ping Zhang¹, Kai Wang¹

, George Q. Li^2,* and Fu-Liang Hu^1,*

¹ College of Animal Sciences, Zhejiang University, Hangzhou 310058, China

² Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia

Molecules 2014, 19(12), 19610-19632; https://doi.org/10.3390/molecules191219610 - 26 Nov 2014

Cited by 616 | Viewed by 33108

Abstract

Propolis is a honeybee product with broad clinical applications. Current literature describes that propolis is collected from plant resins. From a systematic database search, 241 compounds were identified in propolis for the first time between 2000 and 2012; and they belong to such [...] Read more.

Propolis is a honeybee product with broad clinical applications. Current literature describes that propolis is collected from plant resins. From a systematic database search, 241 compounds were identified in propolis for the first time between 2000 and 2012; and they belong to such diverse chemical classes as flavonoids, phenylpropanoids, terpenenes, stilbenes, lignans, coumarins, and their prenylated derivatives, showing a pattern consistent with around 300 previously reported compounds. The chemical characteristics of propolis are linked to the diversity of geographical location, plant sources and bee species. Full article

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

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15 pages, 254 KiB

Open AccessArticle

Formation of Combustible Hydrocarbons and H₂ during Photocatalytic Decomposition of Various Organic Compounds under Aerated and Deaerated Conditions

by Sylwia Mozia^*, Aleksandra Kułagowska and Antoni W. Morawski

Institute of Chemical and Environment Engineering, West Pomeranian University of Technology, ul. Pułaskiego 10, 70–322 Szczecin, Poland

Molecules 2014, 19(12), 19633-19647; https://doi.org/10.3390/molecules191219633 - 26 Nov 2014

Cited by 14 | Viewed by 6285

Abstract

A possibility of photocatalytic production of useful aliphatic hydrocarbons and H₂ from various organic compounds, including acetic acid, methanol, ethanol and glucose, over Fe-modified TiO₂ is discussed. In particular, the influence of the reaction atmosphere (N₂, air) was investigated. [...] Read more.

A possibility of photocatalytic production of useful aliphatic hydrocarbons and H₂ from various organic compounds, including acetic acid, methanol, ethanol and glucose, over Fe-modified TiO₂ is discussed. In particular, the influence of the reaction atmosphere (N₂, air) was investigated. Different gases were identified in the headspace volume of the reactor depending on the substrate. In general, the evolution of the gases was more effective in air compared to a N₂ atmosphere. In the presence of air, the gaseous phase contained CO₂, CH₄ and H₂, regardless of the substrate used. Moreover, formation of C₂H₆ and C₃H₈ in the case of acetic acid and C₂H₆ in the case of ethanol was observed. In case of acetic acid and methanol an increase in H₂ evolution under aerated conditions was observed. It was concluded that the photocatalytic decomposition of organic compounds with simultaneous generation of combustible hydrocarbons and hydrogen could be a promising method of “green energy” production. Full article

(This article belongs to the Special Issue Photocatalysis)

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17 pages, 866 KiB

Open AccessArticle

Microwave-Assisted Synthesis of Novel 2H-Chromene Derivatives Bearing Phenylthiazolidinones and Their Biological Activity Assessment

by Islam H. El Azab^1,2,*

, Mohamed M. Youssef³ and Mahmoud A. Amin^2,4

¹ Chemistry Department, Faculty of Science, Aswan University, Aswan 81528, Egypt

² Chemistry Department, Faculty of Science, Taif University, Al-Haweiah, P.O. Box 888, Taif 21974, Saudi Arabia

³ Chemistry Department, Faculty of Science, Cairo University, Giza 12613, Egypt

⁴ Chemistry Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt

Molecules 2014, 19(12), 19648-19664; https://doi.org/10.3390/molecules191219648 - 26 Nov 2014

Cited by 38 | Viewed by 9674 | Correction

Abstract

6-Hydroxy-2-oxo-2H-chromene-4-carbaldehyde (2), 6-chloro-2-oxo-2H-chromene-4-carbaldehyde (3) and 6-hydrazinyl-4-methyl-2H-chromen-2-one (5) were prepared as single-pharmacophore motif key intermediates. Compounds 2, 3 and 5 were incorporated in a series of multicomponent reactions (MCRs), under microwave [...] Read more.

6-Hydroxy-2-oxo-2H-chromene-4-carbaldehyde (2), 6-chloro-2-oxo-2H-chromene-4-carbaldehyde (3) and 6-hydrazinyl-4-methyl-2H-chromen-2-one (5) were prepared as single-pharmacophore motif key intermediates. Compounds 2, 3 and 5 were incorporated in a series of multicomponent reactions (MCRs), under microwave assistance as well as conventional chemical synthesis processes, to afford a series of three and/or four-pharmacophoric-motif conjugates 8a,b, 11, 13, 16, 17, 19 and 20 in good yields. The newly synthesized compounds were characterized by IR, NMR, ¹³C-NMR, MS and elemental analyses. Finally the synthesized compounds have been screened for their biological activity whereupon they exhibited remarkable antimicrobial activity on different classes of bacteria and the fungus. Full article

(This article belongs to the Section Organic Chemistry)

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13 pages, 298 KiB

Open AccessArticle

Facile Synthesis of Bis(indolyl)methanes Catalyzed by α-Chymotrypsin

by Zong-Bo Xie^†, Da-Zhao Sun^†, Guo-Fang Jiang and Zhang-Gao Le^*

¹ Department of Applied Chemistry, East China Institute of Technology, Nanchang 330013, China

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 19665-19677; https://doi.org/10.3390/molecules191219665 - 27 Nov 2014

Cited by 40 | Viewed by 8137

Abstract

A mild and efficient method catalyzed by α-chymotrypsin was developed for the synthesis of bis(indolyl)methanes through a cascade process between indole and aromatic aldehydes. In the ethanol aqueous solution, a green medium, a wide range of aromatic aldehydes could react with indole to [...] Read more.

A mild and efficient method catalyzed by α-chymotrypsin was developed for the synthesis of bis(indolyl)methanes through a cascade process between indole and aromatic aldehydes. In the ethanol aqueous solution, a green medium, a wide range of aromatic aldehydes could react with indole to afford the desired products with moderate to good yields (from 68% to 95%) using a little α-chymotrypsin as catalyst. Full article

(This article belongs to the Special Issue Enzyme-Catalyzed Reactions)

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18 pages, 870 KiB

Open AccessArticle

Mechanisms Underlying Vasorelaxation Induced in Rat Aorta by Galetin 3,6-Dimethyl Ether, a Flavonoid from Piptadenia stipulacea (Benth.) Ducke

by Cibério L. Macêdo^1,*,†, Luiz H. C. Vasconcelos^1,*,†, Ana C. De C. Correia¹, Italo R. R. Martins¹, Daysianne P. De Lira², Bárbara V. De O. Santos^1,3, Fabiana De A. Cavalcante^1,4 and Bagnólia A. Da Silva^1,3

¹ Programa de Pós-graduação em Produtos Naturais e Sintéticos Bioativos, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, PB 58051-900, Brazil

² Departamento de Farmácia, Faculdade Santa Maria (FSM), Cajazeiras, PB 58900-000, Brazil

³ Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, PB 58051-970, Brazil

⁴ Departamento de Fisiologia e Patologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, PB 58051-970, Brazil

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 19678-19695; https://doi.org/10.3390/molecules191219678 - 27 Nov 2014

Cited by 15 | Viewed by 7901

Abstract

In this study, we investigated the relaxant action of galetin 3,6-dimethyl ether (FGAL) on rat aorta. The flavonoid relaxed both PMA‑ and phenylephrine (Phe)-induced contractions (pD₂ = 5.36 ± 0.11 and 4.17 ± 0.10, respectively), suggesting the involvement of PKC and Phe [...] Read more.

In this study, we investigated the relaxant action of galetin 3,6-dimethyl ether (FGAL) on rat aorta. The flavonoid relaxed both PMA‑ and phenylephrine (Phe)-induced contractions (pD₂ = 5.36 ± 0.11 and 4.17 ± 0.10, respectively), suggesting the involvement of PKC and Phe pathways or α₁ adrenergic receptor blockade. FGAL inhibited and rightward shifted Phe-induced cumulative contraction‑response curves, indicating a noncompetitive antagonism of α₁ adrenergic receptors. The flavonoid was more potent in relaxing 30 mM KCl- than 80 mM KCl-induced contractions (pD₂ = 5.50 ± 0.22 and 4.37 ± 0.12). The vasorelaxant potency of FGAL on Phe-induced contraction was reduced in the presence of 10 mM TEA⁺. Furthermore, in the presence of apamin, glibenclamide, BaCl₂ or 4-AP, FGAL-induced relaxation was attenuated, indicating the participation of small conductance calcium-activated K⁺ channels (SK_Ca), ATP-sensitive K⁺ channels (K_ATP), inward rectifier K⁺ channels (K_ir) and voltage-dependent K⁺ channels (K_V), respectively. FGAL inhibited and rightward shifted CaCl₂-induced cumulative contraction-response curves in both depolarizing medium (high K⁺) and in the presence of verapamil and phenylephrine, suggesting inhibition of Ca²⁺ influx through voltage-gated calcium channels (Ca_V) and receptor operated channels (ROCs), respectively. Likewise, FGAL inhibited Phe-induced contractions in Ca²⁺-free medium, indicating inhibition of Ca²⁺ release from the sarcoplasmic reticulum (SR). FGAL potentiated the relaxant effect of aminophylline and sildenafil but not milrinone, suggesting the involvement of phosphodiesterase V (PDE V). Thus, the FGAL vasorelaxant mechanism involves noncompetitive antagonism of α₁ adrenergic receptors, the non-selective opening of K⁺ channels, inhibition of Ca²⁺ influx through Ca_V or ROCs and the inhibition of intracellular Ca²⁺ release. Additionally, there is the involvement of cyclic nucleotide pathway, particularly through PDE V inhibition. Full article

(This article belongs to the Collection Bioactive Compounds)

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12 pages, 1157 KiB

Open AccessArticle

Cloning and Characterisation of the Gene Encoding 3-Hydroxy-3-Methylglutaryl-CoA Synthase in Tripterygium wilfordii

by Yu-Jia Liu¹, Yu-Jun Zhao¹, Meng Zhang¹, Ping Su¹, Xiu-Juan Wang¹, Xia-Nan Zhang¹, Wei Gao^1,* and Lu-Qi Huang^2,*

¹ School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China

² National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

Molecules 2014, 19(12), 19696-19707; https://doi.org/10.3390/molecules191219696 - 27 Nov 2014

Cited by 28 | Viewed by 6669

Abstract

Tripterygium wilfordii is a traditional Chinese medical plant used to treat rheumatoid arthritis and cancer. The main bioactive compounds of the plant are diterpenoids and triterpenoids. 3-Hydroxy-3-methylglutaryl-CoA synthase (HMGS) catalyses the reaction of acetoacetyl-CoA to 3-hydroxy-3-methylglutaryl-CoA, which is the first committed enzyme in [...] Read more.

Tripterygium wilfordii is a traditional Chinese medical plant used to treat rheumatoid arthritis and cancer. The main bioactive compounds of the plant are diterpenoids and triterpenoids. 3-Hydroxy-3-methylglutaryl-CoA synthase (HMGS) catalyses the reaction of acetoacetyl-CoA to 3-hydroxy-3-methylglutaryl-CoA, which is the first committed enzyme in the mevalonate (MVA) pathway. The sequence information of HMGS in Tripterygium wilfordii is a basic resource necessary for studying the terpenoids in the plant. In this paper, full-length cDNA encoding HMGS was isolated from Tripterygium wilfordii (abbreviated TwHMGS, GenBank accession number: KM978213). The full length of TwHMGS is 1814 bp, and the gene encodes a protein with 465 amino acids. Sequence comparison revealed that TwHMGS exhibits high similarity to HMGSs of other plants. The tissue expression patterns revealed that the expression level of TwHMGS is highest in the stems and lowest in the roots. Induced expression of TwHMGS can be induced by MeJA, and the expression level is highest 4 h after induction. The functional complement assays in the YML126C knockout yeast demonstrated that TwHMGS participates in yeast terpenoid biosynthesis. Full article

(This article belongs to the Section Molecular Diversity)

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10 pages, 276 KiB

Open AccessArticle

Unstable Simple Volatiles and Gas Chromatography-Tandem Mass Spectrometry Analysis of Essential Oil from the Roots Bark of Oplopanax Horridus Extracted by Supercritical Fluid Extraction

by Li Shao^1,2, Mei-Hua Bao^1,2, Dong-Sheng Ouyang^3,4, Chong-Zhi Wang⁵, Chun-Su Yuan⁵, Hong-Hao Zhou^3,4 and Wei-Hua Huang^3,4,*

¹ Department of Human Anatomy, Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha 410219, China

² Department of Pharmacognosy, School of Pharmacy, Changsha Medical University, Changsha 410219, China

³ Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China

⁴ Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China

⁵ Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago, 5841 South Maryland Avenue, MC 4028, Chicago, IL 60637, USA

Molecules 2014, 19(12), 19708-19717; https://doi.org/10.3390/molecules191219708 - 27 Nov 2014

Cited by 7 | Viewed by 7097

Abstract

Volatile oil from the root bark of Oplopanax horridus is regarded to be responsible for the clinical uses of the title plant as a respiratory stimulant and expectorant. Therefore, a supercritical fluid extraction method was first employed to extract the volatile oil from [...] Read more.

Volatile oil from the root bark of Oplopanax horridus is regarded to be responsible for the clinical uses of the title plant as a respiratory stimulant and expectorant. Therefore, a supercritical fluid extraction method was first employed to extract the volatile oil from the roots bark of O. horridus, which was subsequently analyzed by GC/MS. Forty-eight volatile compounds were identified by GC/MS analysis, including (S,E)-nerolidol (52.5%), τ-cadinol (21.6%) and S-falcarinol (3.6%). Accordingly, the volatile oil (100 g) was subjected to chromatographic separation and purification. As a result, the three compounds, (E)-nerolidol (2 g), τ-cadinol (62 mg) and S-falcarinol (21 mg), were isolated and purified from the volatile oil, the structures of which were unambiguously elucidated by detailed spectroscopic analysis including 1D- and 2D-NMR techniques. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 607 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Novel 10-Substituted-7-ethyl-10-hydroxycamptothecin (SN-38) Prodrugs

by Mo Zhou^1,†, Meixia Liu^1,†, Xinhua He¹, Hong Yu², Di Wu³, Yishan Yao¹, Shiyong Fan¹, Ping Zhang¹, Weiguo Shi^1,* and Bohua Zhong^1,*

¹ Beijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, China

² Cell Biology Laboratory of Jilin Province Tumor Institute, No 1018 Huguang Road, Changchun 130012, China

³ Tumor Centre, No.1 Hospital, Jilin University, 71 Xin-Min Street, Changchun 130012, China

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 19718-19731; https://doi.org/10.3390/molecules191219718 - 27 Nov 2014

Cited by 13 | Viewed by 8882

Abstract

In an attempt to improve the antitumor activity and reduce the side effects of irinotecan (2), novel prodrugs of SN-38 (3) were prepared by conjugating amino acids or dipeptides to the 10-hydroxyl group of SN-38 via a carbamate linkage. [...] Read more.

In an attempt to improve the antitumor activity and reduce the side effects of irinotecan (2), novel prodrugs of SN-38 (3) were prepared by conjugating amino acids or dipeptides to the 10-hydroxyl group of SN-38 via a carbamate linkage. The synthesized compounds completely generated SN-38 in pH 7.4 buffer or in human plasma, while remaining stable under acidic conditions. All prodrug compounds demonstrated much greater in vitro antitumor activities against HeLa cells and SGC-7901 cells than irinotecan. The most active compounds, 5h, 7c, 7d, and 7f, exhibited IC₅₀ values that were 1000 times lower against HeLa cells and 30 times lower against SGC-7901 cells than those of irinotecan, and the inhibitory activities of these prodrugs against acetylcholinesterase (AchE) were significantly reduced, with IC₅₀ values more than 6.8 times greater than that of irinotecan. In addition, compound 5e exhibited the same level of tumor growth inhibitory activity as irinotecan (CPT-11) in a human colon xenograft model in vivo. Full article

(This article belongs to the Special Issue Prodrugs)

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19 pages, 1255 KiB

Open AccessArticle

Photocatalysis for Renewable Energy Production Using PhotoFuelCells

by Robert Michal^1,†, Stavroula Sfaelou¹ and Panagiotis Lianos^1,2,*

¹ Department of Chemical Engineering, University of Patras, University Campus, Patras 26500, Greece

² FORTH/ICE-HT, Stadiou Str., Platani, P.O. Box 1414, Patras 26504, Greece

^† Permanent address: Department of Inorganic Chemistry, Faculty of Natural Sciences, Comenius University, Mlynská Dolina, 84215 Bratislava, Slovakia

Molecules 2014, 19(12), 19732-19750; https://doi.org/10.3390/molecules191219732 - 27 Nov 2014

Cited by 45 | Viewed by 9031

Abstract

The present work is a short review of our recent studies on PhotoFuelCells, that is, photoelectrochemical cells which consume a fuel to produce electricity or hydrogen, and presents some unpublished data concerning both electricity and hydrogen production. PhotoFuelCells have been constructed using nanoparticulate [...] Read more.

The present work is a short review of our recent studies on PhotoFuelCells, that is, photoelectrochemical cells which consume a fuel to produce electricity or hydrogen, and presents some unpublished data concerning both electricity and hydrogen production. PhotoFuelCells have been constructed using nanoparticulate titania photoanodes and various cathode electrodes bearing a few different types of electrocatalyst. In the case where the cell functioned with an aerated cathode, the cathode electrode was made of carbon cloth carrying a carbon paste made of carbon black and dispersed Pt nanoparticles. When the cell was operated in the absence of oxygen, the electrocatalyst was deposited on an FTO slide using a special commercial carbon paste, which was again enriched with Pt nanoparticles. Mixing of Pt with carbon paste decreased the quantity of Pt necessary to act as electrocatalyst. PhotoFuelCells can produce electricity without bias and with relatively high open-circuit voltage when they function in the presence of fuel and with an aerated cathode. In that case, titania can be sensitized in the visible region by CdS quantum dots. In the present work, CdS was deposited by the SILAR method. Other metal chalcogenides are not functional as sensitizers because the combined photoanode in their presence does not have enough oxidative power to oxidize the fuel. Concerning hydrogen production, it was found that it is difficult to produce hydrogen in an alkaline environment even under bias, however, this is still possible if losses are minimized. One way to limit losses is to short-circuit anode and cathode electrode and put them close together. This is achieved in the “photoelectrocatalytic leaf”, which was presently demonstrated capable of producing hydrogen even in a strongly alkaline environment. Full article

(This article belongs to the Special Issue Photocatalysis)

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18 pages, 2918 KiB

Open AccessArticle

Post-Polymerization Modification of Poly(L-glutamic acid) with D-(+)-Glucosamine

by Peter Perdih, Sašo Čebašek, Alenka Možir and Ema Žagar^*

National Institute of Chemistry, Laboratory for Polymer Chemistry and Technology, Hajdrihova 19, SI-1000 Ljubljana, Slovenia

Molecules 2014, 19(12), 19751-19768; https://doi.org/10.3390/molecules191219751 - 27 Nov 2014

Cited by 16 | Viewed by 12253

Abstract

Carboxyl functional groups of poly(L-glutamic acid) (PGlu) were modified with a D-(+)-glucosamine (GlcN) by amidation using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) as a coupling reagent. The coupling reaction was performed in aqueous medium without protection of hydroxyl functional groups of D-(+)-glucosamine. Poly(L-glutamic acid) and GlcN [...] Read more.

Carboxyl functional groups of poly(L-glutamic acid) (PGlu) were modified with a D-(+)-glucosamine (GlcN) by amidation using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) as a coupling reagent. The coupling reaction was performed in aqueous medium without protection of hydroxyl functional groups of D-(+)-glucosamine. Poly(L-glutamic acid) and GlcN functionalized polyglutamates (P(Glu-GlcN)) were thoroughly characterized by 1D and 2D NMR spectroscopy and SEC-MALS to gain detailed information on their structure, composition and molar mass characteristics. The results reveal successful functionalization with GlcN through the amide bond and also to a minor extent through ester bond formation in position 1 of GlcN. In addition, a ratio between the α- and β-form of glucosamine substituent coupled to polyglutamate repeating units as well as the content of residual dimethoxy triazinyl active ester moiety in the samples were evaluated. Full article

(This article belongs to the Special Issue Ring-Opening Polymerization)

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67 pages, 4070 KiB

Open AccessReview

Bioinspired Syntheses of Dimeric Hydroxycinnamic Acids (Lignans) and Hybrids, Using Phenol Oxidative Coupling as Key Reaction, and Medicinal Significance Thereof

by George E. Magoulas and Dionissios Papaioannou^*

Department of Chemistry, University of Patras, Patras 26504, Greece

Molecules 2014, 19(12), 19769-19835; https://doi.org/10.3390/molecules191219769 - 28 Nov 2014

Cited by 27 | Viewed by 14519

Abstract

Lignans are mainly dimers of 4-hydroxycinnamic acids (HCAs) and reduced analogs thereof which are produced in Nature through phenol oxidative coupling (POC) as the primary C-C or C-O bond-forming reaction under the action of the enzymes peroxidases and laccases. They present a large [...] Read more.

Lignans are mainly dimers of 4-hydroxycinnamic acids (HCAs) and reduced analogs thereof which are produced in Nature through phenol oxidative coupling (POC) as the primary C-C or C-O bond-forming reaction under the action of the enzymes peroxidases and laccases. They present a large structural variety and particularly interesting biological activities, therefore, significant efforts has been devoted to the development of efficient methodologies for the synthesis of lignans isolated from natural sources, analogs and hybrids with other biologically interesting small molecules. We summarize in the present review those methods which mimic Nature for the assembly of the most common lignan skeleta by using either enzymes or one-electron inorganic oxidants to effect POC of HCAs and derivatives, such as esters and amides, or cross-POC of pairs of HCAs or HCAs with 4-hydrocycinnamyl alcohols. We, furthermore, provide outlines of mechanistic schemes accounting for the formation of the coupled products and, where applicable, indicate their potential application in medicine. Full article

(This article belongs to the Special Issue Cinnamic Acids Hybrids with Biological Interest)

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9 pages, 260 KiB

Open AccessArticle

Novel Polyprenylated Phloroglucinols from Hypericum sampsonii

by Jih-Jung Chen^1,2

, Hong-Jhang Chen³ and Yun-Lian Lin^3,4,*

¹ Department of Pharmacy, Tajen University, Pingtung 907, Taiwan

² Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung 907, Taiwan

³ National Research Institute of Chinese Medicine, Taipei 112, Taiwan

⁴ School of Pharmacy, National Taiwan University, Taipei 100, Taiwan

Molecules 2014, 19(12), 19836-19844; https://doi.org/10.3390/molecules191219836 - 28 Nov 2014

Cited by 11 | Viewed by 6685

Abstract

Hypericum sampsonii Hance (Clusiaceae) is a folk medicine used in Taiwan to treat blood stasis, relieve swelling, and as an anti-hepatitis drug. Two new polyprenylated phloroglucinol derivatives, hypersampsone R (1) and hypersampsone S (2), and a known prenylated benzophenone, [...] Read more.

Hypericum sampsonii Hance (Clusiaceae) is a folk medicine used in Taiwan to treat blood stasis, relieve swelling, and as an anti-hepatitis drug. Two new polyprenylated phloroglucinol derivatives, hypersampsone R (1) and hypersampsone S (2), and a known prenylated benzophenone, hyperibone K (3) were isolated from the aerial parts of H. sampsonii. Their structures were determined by extensive 1D and 2D NMR, and MS spectral analyses. Full article

(This article belongs to the Section Natural Products Chemistry)

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23 pages, 4397 KiB

Open AccessArticle

Profiling of Concanavalin A-Binding Glycoproteins in Human Hepatic Stellate Cells Activated with Transforming Growth Factor-β1

by Yannan Qin^1,†, Yaogang Zhong^2,†, Ganglong Yang², Tianran Ma², Liyuan Jia², Chen Huang¹ and Zheng Li^2,*

¹ Department of Genetics and Molecular Biology, Xi'an Jiaotong University College of Medicine, Xi'an 710061, Shaanxi, China

² Laboratory for Functional Glycomics, College of Life Sciences, Northwest University, Xi'an 710069, Shaanxi, China

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 19845-19867; https://doi.org/10.3390/molecules191219845 - 28 Nov 2014

Cited by 16 | Viewed by 10470

Abstract

Glycoproteins play important roles in maintaining normal cell functions depending on their glycosylations. Our previous study indicated that the abundance of glycoproteins recognized by concanavalin A (ConA) was increased in human hepatic stellate cells (HSCs) following activation by transforming growth factor-β1 (TGF-β1); however, [...] Read more.

Glycoproteins play important roles in maintaining normal cell functions depending on their glycosylations. Our previous study indicated that the abundance of glycoproteins recognized by concanavalin A (ConA) was increased in human hepatic stellate cells (HSCs) following activation by transforming growth factor-β1 (TGF-β1); however, little is known about the ConA-binding glycoproteins (CBGs) of HSCs. In this study, we employed a targeted glycoproteomics approach using lectin-magnetic particle conjugate-based liquid chromatography-tandem mass spectrometry to compare CBG profiles between LX-2 HSCs with and without activation by TGF-β1, with the aim of discovering novel CBGs and determining their possible roles in activated HSCs. A total of 54 and 77 proteins were identified in the quiescent and activated LX-2 cells, respectively. Of the proteins identified, 14.3% were glycoproteins and 73.3% were novel potential glycoproteins. Molecules involved in protein processing in the endoplasmic reticulum (e.g., calreticulin) and calcium signaling (e.g., 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase β-2 [PLCB2]) were specifically identified in activated LX-2 cells. Additionally, PLCB2 expression was upregulated in the cytoplasm of the activated LX-2 cells, as well as in the hepatocytes and sinusoidal cells of liver cirrhosis tissues. In conclusion, the results of this study may aid future investigations to find new molecular mechanisms involved in HSC activation and antifibrotic therapeutic targets. Full article

(This article belongs to the Collection Advances in Glycosciences)

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12 pages, 1998 KiB

Open AccessArticle

New Biscoumarin Derivatives: Synthesis, Crystal Structure, Theoretical Study and Antibacterial Activity against Staphylococcus aureus

by Di Qu^1,†, Jing Li^2,†, Xiao-Hui Yang², Zi-Dan Zhang³, Xiao-Xing Luo¹, Ming-Kai Li^1,* and Xia Li^4,*

¹ Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, China

² School of Chemistry and Chemical Engineering, Xi'an University, Xi'an 710065, China

³ Department of Physics, School of Science, Tianjin University, Tianjin 300072, China

⁴ Department of Neurosurgery, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 19868-19879; https://doi.org/10.3390/molecules191219868 - 28 Nov 2014

Cited by 19 | Viewed by 6403

Abstract

Five novel biscoumarins 1–5 were synthesized and characterized. In these compounds, two classical asymmetrical intramolecular O–H···O hydrogen bonds were used to stabilize the whole structures and the HB energies were performed with the density functional theory (DFT) [B3LYP/6-31G*] method. The five [...] Read more.

Five novel biscoumarins 1–5 were synthesized and characterized. In these compounds, two classical asymmetrical intramolecular O–H···O hydrogen bonds were used to stabilize the whole structures and the HB energies were performed with the density functional theory (DFT) [B3LYP/6-31G*] method. The five compounds were evaluated for their in vitro antibacterial activities against Staphylococcus aureus (S. aureus ATCC 29213), methicillin-resistant S. aureus (MRSA XJ 75302), vancomycin-intermediate S. aureus (Mu50 ATCC 700699), and USA 300 (Los Angeles County clone, LAC) by the means of minimum inhibitory concentration and time-kill curves. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 813 KiB

Open AccessArticle

Isolation and Characterization of a Novel Lectin from the Edible Mushroom Stropharia rugosoannulata

by Weiwei Zhang¹, Guoting Tian², Xueran Geng¹, Yongchang Zhao², Tzi Bun Ng³, Liyan Zhao⁴ and Hexiang Wang^1,*

¹ State Key Laboratory for Agrobiotechnology and Department of Microbiology, China Agricultural University, Beijing 100193, China

² Institute of Biotechnology and Germplasmic Resource, Yunnan Academy of Agricultural Science, Kunming 650223, China

³ School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China

⁴ College of Food Science and Technology, Nanjing Agricultural University, Weigang, Nanjing 210095, China

Molecules 2014, 19(12), 19880-19891; https://doi.org/10.3390/molecules191219880 - 28 Nov 2014

Cited by 49 | Viewed by 8179

Abstract

To date, only a few steroids have been isolated from the mushroom Stropharia rugosoannulata which can be cultivated. In this paper, a novel lectin (SRL) with a molecular weight of 38 kDa, and a unique IKSGVYRIVSWQGALGPEAR N-terminal sequence was isolated from S. rugosoannulata [...] Read more.

To date, only a few steroids have been isolated from the mushroom Stropharia rugosoannulata which can be cultivated. In this paper, a novel lectin (SRL) with a molecular weight of 38 kDa, and a unique IKSGVYRIVSWQGALGPEAR N-terminal sequence was isolated from S. rugosoannulata, which represents the first protein isolated from the mushroom. The purification methods included (NH₄)₂SO₄ precipitation, ion exchange chromatography on CM-cellulose, Q-Sepharose, and SP-Sepharose, and gel- filtration on Superdex-75. The lectin was adsorbed on all three types of ion exchangers and was purified more than 450-fold. The lectin was stable below 70 °C (with half of the activity preserved at 80 °C), and in the presence of NaOH and HCl solutions up to a concentration of 12.5 mM and 25 mM, respectively. The hemagglutinating activity of SRL was inhibited by inulin. Cd²⁺ and Hg²⁺ ions strongly reduced the hemagglutinating activity at concentrations from 1.25 mM to 10 mM. SRL exhibited anti-proliferative activity toward both hepatoma Hep G2 cells and leukemia L1210 cells, with an IC₅₀ of 7 μM and 19 μM, respectively. The activity of HIV-1 reverse transcriptase could also be inhibited by SRL, with an IC₅₀ of 10 μM. Full article

(This article belongs to the Special Issue Lectins)

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15 pages, 610 KiB

Open AccessArticle

Maslinic Acid Induces Mitochondrial Apoptosis and Suppresses HIF-1α Expression in A549 Lung Cancer Cells under Normoxic and Hypoxic Conditions

by Te-Chun Hsia^1,2, Wen-Hu Liu³, Wen-Wei Qiu⁴, Jian Luo⁵ and Mei-Chin Yin^6,7,*

¹ Department of Respiratory Therapy, China Medical University, Taichung 40402, Taiwan

² Department of Internal Medicine, China Medical University Hospital, Taichung 40402, Taiwan

³ Department of Nutrition, Chung Shan Medical University, Taichung 40201, Taiwan

⁴ Institute of Medicinal Chemistry and Department of Chemistry, East China Normal University, Shanghai 200241, China

⁵ Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China

⁶ Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan

⁷ Department of Nutrition, China Medical University, Taichung 40402, Taiwan

Molecules 2014, 19(12), 19892-19906; https://doi.org/10.3390/molecules191219892 - 28 Nov 2014

Cited by 28 | Viewed by 7521

Abstract

The apoptotic effects of maslinic acid (MA) at 4, 8, 16, 32 and 64 μmol/L on human lung cancer A549 cells under normoxic and hypoxic conditions were examined. MA at 4–64 and 16–64 μmol/L lowered Bcl-2 expression under normoxic and hypoxic conditions, respectively [...] Read more.

The apoptotic effects of maslinic acid (MA) at 4, 8, 16, 32 and 64 μmol/L on human lung cancer A549 cells under normoxic and hypoxic conditions were examined. MA at 4–64 and 16–64 μmol/L lowered Bcl-2 expression under normoxic and hypoxic conditions, respectively (p < 0.05). This agent at 4–64 μmol/L decreased Na⁺-K⁺-ATPase activity and increased caspase-3 expression under normoxic conditions, but at 8–64 μmol/L it caused these changes under hypoxic conditions (p < 0.05). MA up-regulated caspase-8, cytochrome c and apoptosis-inducing factor expression under normoxic and hypoxic conditions at 8–64 μmol/L and 32–64 μmol/L, respectively (p < 0.05). MA down-regulated hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), survivin and inducible nitric oxide synthase (iNOS) expression under normoxic and hypoxic conditions at 8–64 and 16–64 μmol/L, respectively (p < 0.05). After cells were pre-treated with YC-1, an inhibitor of HIF-1α, MA failed to affect the protein expression of HIF-1α, VEGF, survivin and iNOS (p > 0.05). MA at 8-64 and 32-64 μmol/L reduced reactive oxygen species and nitric oxide levels under both conditions (p < 0.05). These findings suggest that maslinic acid, a pentacyclic triterpenic acid, exerted its cytotoxic activities toward A549 cells by mediating mitochondrial apoptosis and the HIF-1α pathway. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 265 KiB

Open AccessArticle

The Epoxidation of Limonene over the TS-1 and Ti-SBA-15 Catalysts

by Agnieszka Wróblewska

Institute of Organic Chemical Technology, West Pomeranian University of Technology Szczecin, Pułaskiego 10, Szczecin 70-322, Poland

Molecules 2014, 19(12), 19907-19922; https://doi.org/10.3390/molecules191219907 - 28 Nov 2014

Cited by 66 | Viewed by 11114

Abstract

Limonene belongs to a group of very important intermediates used in the production of fine chemicals. This monoterpene compound can be obtained from peels of oranges or lemon which are a (biomass) waste from the orange juice industry. Thus, limonene is a renewable, [...] Read more.

Limonene belongs to a group of very important intermediates used in the production of fine chemicals. This monoterpene compound can be obtained from peels of oranges or lemon which are a (biomass) waste from the orange juice industry. Thus, limonene is a renewable, easy available and a relatively cheap compound. This work presents preliminary studies on the process of limonene epoxidation over zeolite type catalysts such as: TS-1 and Ti-SBA-15. In these studies methanol was used as a solvent and as an oxidizing agent a 60 wt % hydrogen peroxide solution was applied. The activity of each catalyst was investigated for four chosen temperatures (0 °C, 40 °C, 80 °C and 120 °C). The reaction time was changed from 0.5 to 24 h. For each catalyst the most beneficial conditions (the appropriate temperature and the reaction time) have been established. The obtained results were compared and the most active catalyst was chosen. These studies have also shown different possible ways of limonene transformation, not only in the direction of 1,2-epoxylimonene and its corresponding diol, but also in direction of carveol, carvone and perillyl alcohol—compounds with a lot of applications. The possible mechanisms of formation of the allylic oxidation products were proposed. Full article

(This article belongs to the Special Issue Zeolite Chemistry)

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12 pages, 255 KiB

Open AccessArticle

Antibacterial and EGFR-Tyrosine Kinase Inhibitory Activities of Polyhydroxylated Xanthones from Garcinia succifolia

by Susawat Duangsrisai^1,2, Kiattawee Choowongkomon³, Lucinda J. Bessa^1,4, Paulo M. Costa^1,4

, Nurmuhammat Amat⁵ and Anake Kijjoa^1,4,*

¹ ICBAS—Instituto de Ciências Biomédicas Abel Salazar—Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal

² Department of Botany, Faculty of Science, Kasetsart University, Paholyothin Road, Chatuchuck, Bangkok 10900, Thailand

³ Department of Biochemistry, Faculty of Science, Kasetsart University, Paholyothin Road, Chatuchuck, Bangkok 10900, Thailand

⁴ Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), Universidade do Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal

⁵ Traditional Uighur Medicine Department, Xinjiang Medical University, 393 Medical University Road, Urumqi 830011, Xinjiang, China

Molecules 2014, 19(12), 19923-19934; https://doi.org/10.3390/molecules191219923 - 28 Nov 2014

Cited by 22 | Viewed by 7955

Abstract

Chemical investigation of the methanol extract of the wood of Garcinia succifolia Kurz (Clusiaceae) led to the isolation of 1,5-dihydroxyxanthone (1), 1,7-dihydroxyxanthone (2), 1,3,7-trihydroxyxanthone (3), 1,5,6-trihydroxyxanthone (4), 1,6,7-trihydroxyxanthone (5), and 1,3,6,7-tetrahydroxyxanthone (6 [...] Read more.

Chemical investigation of the methanol extract of the wood of Garcinia succifolia Kurz (Clusiaceae) led to the isolation of 1,5-dihydroxyxanthone (1), 1,7-dihydroxyxanthone (2), 1,3,7-trihydroxyxanthone (3), 1,5,6-trihydroxyxanthone (4), 1,6,7-trihydroxyxanthone (5), and 1,3,6,7-tetrahydroxyxanthone (6). All of the isolated xanthones were evaluated for their antibacterial activity against bacterial reference strains, two Gram-positive (Staphylococcus aureus ATTC 25923, Bacillus subtillis ATCC 6633) and two Gram-negative (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853), and environmental drug-resistant isolates (S. aureus B1, Enteroccoccus faecalis W1, and E. coli G1), as well as for their epidermal growth factor receptor (EGFR) of tyrosine kinase inhibitory activity. Only 1,5,6-trihydroxy-(4), 1,6,7-trihydroxy-(5), and 1,3,6,7-tetrahydroxyxanthones (6) exhibited antibacterial activity against Gram-positive bacteria, however none was active against vancomycin-resistant E. faecalis. Additionally, 1,7-dihydroxyxanthone (2) showed synergism with oxacillin, but not with ampicillin. On the other hand, only 1,5-dihydroxyxanthone (1) and 1,7-dihydroxyxanthone (2) were found to exhibit the EGFR-tyrosine kinase inhibitory activity, with IC₅₀values of 90.34 and 223 nM, respectively. Full article

(This article belongs to the Collection Bioactive Compounds)

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45 pages, 1943 KiB

Open AccessReview

The Azaindole Framework in the Design of Kinase Inhibitors

by Jean-Yves Mérour, Frédéric Buron

, Karen Plé

, Pascal Bonnet

and Sylvain Routier^*

Institut de Chimie Organique et Analytique (ICOA), Université d'Orléans, UMR CNRS 7311, Orléans F-45067, France

Molecules 2014, 19(12), 19935-19979; https://doi.org/10.3390/molecules191219935 - 28 Nov 2014

Cited by 154 | Viewed by 17571

Abstract

This review article illustrates the growing use of azaindole derivatives as kinase inhibitors and their contribution to drug discovery and innovation. The different protein kinases which have served as targets and the known molecules which have emerged from medicinal chemistry and Fragment-Based Drug [...] Read more.

This review article illustrates the growing use of azaindole derivatives as kinase inhibitors and their contribution to drug discovery and innovation. The different protein kinases which have served as targets and the known molecules which have emerged from medicinal chemistry and Fragment-Based Drug Discovery (FBDD) programs are presented. The various synthetic routes used to access these compounds and the chemical pathways leading to their synthesis are also discussed. An analysis of their mode of binding based on X-ray crystallography data gives structural insights for the design of more potent and selective inhibitors. Full article

(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)

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15 pages, 1973 KiB

Open AccessArticle

Anti-Proliferative Effects of Siegesbeckia orientalis Ethanol Extract on Human Endometrial RL-95 Cancer Cells

by Chi-Chang Chang^1,2, Hsia-Fen Hsu³, Kuo-Hung Huang^1,2, Jing-Mei Wu², Shyh-Ming Kuo⁴, Xue-Hua Ling^1,2,3 and Jer-Yiing Houng^1,3,*

¹ Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung 84001, Taiwan

² Department of Obstetrics & Gynecology, E-Da Hospital, E-Da Hospital/I-Shou University, Kaohsiung 82445, Taiwan

³ Department of Nutrition, I-Shou University, Kaohsiung 82445, Taiwan

⁴ Department of Biomedical Engineering, I-Shou University, Kaohsiung 82445, Taiwan

Molecules 2014, 19(12), 19980-19994; https://doi.org/10.3390/molecules191219980 - 1 Dec 2014

Cited by 26 | Viewed by 8849

Abstract

Endometrial cancer is a common malignancy of the female genital tract. This study demonstrates that Siegesbeckia orientalis ethanol extract (SOE) significantly inhibited the proliferation of RL95-2 human endometrial cancer cells. Treating RL95-2 cells with SOE caused cell arrest in the G2/M phase and [...] Read more.

Endometrial cancer is a common malignancy of the female genital tract. This study demonstrates that Siegesbeckia orientalis ethanol extract (SOE) significantly inhibited the proliferation of RL95-2 human endometrial cancer cells. Treating RL95-2 cells with SOE caused cell arrest in the G2/M phase and induced apoptosis of RL95-2 cells by up-regulating Bad, Bak and Bax protein expression and down-regulation of Bcl-2 and Bcl-xL protein expression. Treatment with SOE increased protein expression of caspase-3, -8 and -9 dose-dependently, indicating that apoptosis was through the intrinsic and extrinsic apoptotic pathways. Moreover, SOE was also effective against A549 (lung cancer), Hep G2 (hepatoma), FaDu (pharynx squamous cancer), MDA-MB-231 (breast cancer), and especially on LNCaP (prostate cancer) cell lines. In total, 10 constituents of SOE were identified by Gas chromatography-mass analysis. Caryophyllene oxide and caryophyllene are largely responsible for most cytotoxic activity of SOE against RL95-2 cells. Overall, this study suggests that SOE is a promising anticancer agent for treating endometrial cancer. Full article

(This article belongs to the Collection Bioactive Compounds)

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28 pages, 1373 KiB

Open AccessReview

A Review on Visible Light Active Perovskite-Based Photocatalysts

by Pushkar Kanhere^1,2,* and Zhong Chen^1,2,*

¹ Energy Research Institute @ NTU, 1 CleanTech Loop, Clean Tech One, Singapore 637141, Singapore

² School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore

Molecules 2014, 19(12), 19995-20022; https://doi.org/10.3390/molecules191219995 - 1 Dec 2014

Cited by 526 | Viewed by 29512

Abstract

Perovskite-based photocatalysts are of significant interest in the field of photocatalysis. To date, several perovskite material systems have been developed and their applications in visible light photocatalysis studied. This article provides a review of the visible light (λ > 400 nm) active perovskite-based [...] Read more.

Perovskite-based photocatalysts are of significant interest in the field of photocatalysis. To date, several perovskite material systems have been developed and their applications in visible light photocatalysis studied. This article provides a review of the visible light (λ > 400 nm) active perovskite-based photocatalyst systems. The materials systems are classified by the B site cations and their crystal structure, optical properties, electronic structure, and photocatalytic performance are reviewed in detail. Titanates, tantalates, niobates, vanadates, and ferrites form important photocatalysts which show promise in visible light-driven photoreactions. Along with simple perovskite (ABO₃) structures, development of double/complex perovskites that are active under visible light is also reviewed. Various strategies employed for enhancing the photocatalytic performance have been discussed, emphasizing the specific advantages and challenges offered by perovskite-based photocatalysts. This review provides a broad overview of the perovskite photocatalysts, summarizing the current state of the work and offering useful insights for their future development. Full article

(This article belongs to the Special Issue Photocatalysis)

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11 pages, 298 KiB

Open AccessArticle

Effects of Selected Dietary Secondary Metabolites on Reactive Oxygen Species Production Caused by Iron(II) Autoxidation

by Vladimir Chobot^1,*

, Franz Hadacek²

and Lenka Kubicova¹

¹ Division of Molecular Systems Biology, Department of Ecogenomics and Systems Biology, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria

² Department of Plant Biochemistry, Albrecht-von-Haller Institut, Georg-August-Universität Göttingen, Justus-von-Liebig-Weg 11, D-37077 Göttingen, Germany

Molecules 2014, 19(12), 20023-20033; https://doi.org/10.3390/molecules191220023 - 1 Dec 2014

Cited by 22 | Viewed by 8952

Abstract

Iron is an essential co-factor for many enzymes that catalyze electron transfer reactions. It is well known that so-called “poorly liganded” iron can increase ROS concentrations and trigger oxidative stress that is capable of initiating apoptosis. Conversely, controlled ROS production has been recognized [...] Read more.

Iron is an essential co-factor for many enzymes that catalyze electron transfer reactions. It is well known that so-called “poorly liganded” iron can increase ROS concentrations and trigger oxidative stress that is capable of initiating apoptosis. Conversely, controlled ROS production has been recognized as an integral part of cellular signaling. Elevated ROS concentrations are associated with aging, inflammatory and degenerative diseases. Anti-aging properties have been attributed especially to antioxidant phenolic plant metabolites that represent food additives in our diet. Consequently, this study explores the effects of flavonoids (quercetin and rutin), several phenolic acids (caffeic, chlorogenic, and protocatechuic acid), and the alkaloid caffeine on iron(II) autoxidation and ROS production in comparison to the standard antioxidants ascorbic acid and Trolox. The iron(II) autoxidation assay was carried out in pH 6.0 (plant apoplast and inflamed human tissue) and 7.4 (cell cytoplasm and human blood plasma). The obtained results accentuate phenolic acids as the more specific antioxidants compared to ascorbic acid and Trolox. Flavonoid redox chemistry depends more on the chemical milieu, specifically on pH. In vivo, the presence of iron cannot be ruled out and “wrongly” or “poorly” complexed iron has been pointed out as causative agent of various age-related diseases. Full article

(This article belongs to the Special Issue Natural Antioxidants and Ageing)

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20 pages, 740 KiB

Open AccessArticle

Chemical Composition, Antibacterial and Antioxidant Activities of Six Essentials Oils from the Alliaceae Family

by Dima Mnayer^1,2, Anne-Sylvie Fabiano-Tixier¹, Emmanuel Petitcolas¹, Tayssir Hamieh^2,3

, Nancy Nehme², Christine Ferrant⁴, Xavier Fernandez⁵ and Farid Chemat^1,*

¹ Université d'Avignon et des Pays du Vaucluse, UMR 408, INRA, GREEN extraction Team, Avignon 84000, France

² Faculty of Agricultural Engineering and Veterinary Medicine, Lebanese University, Dekwaneh, Beirut 6573, Lebanon

³ Laboratory of Materials, Catalysis, Environment and Analytical Methods (MCEMA), Faculty of Sciences, Doctoral School of Sciences and Technology (EDST), Lebanese University, Beirut 6573-14, Lebanon

⁴ Ferrant P.H.E, 2 Rue d'Ecottes, Rodelinghem 62610, France

⁵ Institut de Chimie de Nice, UMR 7272, Université de Nice-Sophia Antipolis/CNRS, Parc Valrose, Nice 06108, France

Molecules 2014, 19(12), 20034-20053; https://doi.org/10.3390/molecules191220034 - 1 Dec 2014

Cited by 198 | Viewed by 19747

Abstract

Six essential oils (EOs) from the Alliaceae family, namely garlic (Allium sativum), onion (Allium cepa), leek (Allium porrum), Chinese chive (Allium tuberosum), shallot (Allium ascalonicum) and chive (Allium schoenoprasum) were characterized by GC [...] Read more.

Six essential oils (EOs) from the Alliaceae family, namely garlic (Allium sativum), onion (Allium cepa), leek (Allium porrum), Chinese chive (Allium tuberosum), shallot (Allium ascalonicum) and chive (Allium schoenoprasum) were characterized by GC and GC-MS and evaluated for their functional food properties. Antibacterial properties were tested on five food-borne pathogens: Two Gram-positive Staphylococcus aureus (ATCC 25923), Listeria monocytogenes (ATCC 19115) and three Gram-negative Salmonella Typhimurium (ATCC 14028), Escherichia coli (ATCC 8739) and Campylobacter jejuni (ATCC 33291) bacteria. Antioxidant and radical-scavenging properties were tested by means of Folin-Ciocalteu and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. Garlic, Chinese chive and onion EOs had the highest antibacterial activity whereas shallot and leek EOs were the strongest antioxidants. Heating caused a decrease in the antioxidant activity of these Eos, as shown in the Total Polar Materials (TPM) test. Suggestions on relationships between chemical composition and biological activities are presented. Results show that the EOs could be of value in the food industry as alternatives to synthetic antioxidants. Full article

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

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19 pages, 634 KiB

Open AccessArticle

Resveratrol Modulates the Topoisomerase Inhibitory Potential of Doxorubicin in Human Colon Carcinoma Cells

by Anika Schroeter and Doris Marko^*

Department of Food Chemistry and Toxicology, University of Vienna, Währinger Str. 38, 1090 Wien, Austria

Molecules 2014, 19(12), 20054-20072; https://doi.org/10.3390/molecules191220054 - 1 Dec 2014

Cited by 17 | Viewed by 8126

Abstract

Resveratrol (RSV) is currently being widely discussed as potentially useful for anticancer therapy in combination with classical chemotherapeutics, e.g., the topoisomerase II (TOP II) poison doxorubicin (DOX). However, there is still a lack of knowledge of possible interference at the target enzyme, especially [...] Read more.

Resveratrol (RSV) is currently being widely discussed as potentially useful for anticancer therapy in combination with classical chemotherapeutics, e.g., the topoisomerase II (TOP II) poison doxorubicin (DOX). However, there is still a lack of knowledge of possible interference at the target enzyme, especially since RSV itself has recently been described to act as a TOP poison. We therefore sought to address the question whether RSV affects DOX-induced genotoxic and cytotoxic effects with special emphasis on TOP II in HT-29 colon carcinoma cells. RSV was found to counteract DOX-induced formation of DNA-TOP-intermediates at ≥100 µM for TOP IIα and at 250 µM for TOP IIβ. As a consequence, RSV modulated the DNA-strand breaking potential of DOX by mediating protective effects with an apparent maximum at 100 µM. At higher concentration ranges (≥200 µM) RSV diminished the intracellular concentrations of DOX. Nevertheless, the presence of RSV slightly enhanced the cytotoxic effects of DOX after 1.5 h and 24 h of incubation. Taken together, at least in cell culture RSV was found to affect the TOP-poisoning potential of DOX and to modulate its cytotoxic effectiveness. Thus, further studies are needed to clarify the impact of RSV on the therapeutic effectiveness of DOX under in vivo conditions. Full article

(This article belongs to the Special Issue Resveratrol)

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18 pages, 2890 KiB

Open AccessArticle

Alteration of N-glycans and Expression of Their Related Glycogenes in the Epithelial-Mesenchymal Transition of HCV29 Bladder Epithelial Cells

by Jia Guo¹, Xiang Li², Zengqi Tan¹, Wei Lu¹, Ganglong Yang¹ and Feng Guan^1,*

¹ The Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China

² Wuxi Medical School, Jiangnan University, Wuxi 214122, China

Molecules 2014, 19(12), 20073-20090; https://doi.org/10.3390/molecules191220073 - 1 Dec 2014

Cited by 38 | Viewed by 8364

Abstract

The epithelial-mesenchymal transition (EMT) is an essential step in the proliferation and metastasis of solid tumor cells, and glycosylation plays a crucial role in the EMT process. Certain aberrant glycans have been reported as biomarkers during bladder cancer progression, but global variation of [...] Read more.

The epithelial-mesenchymal transition (EMT) is an essential step in the proliferation and metastasis of solid tumor cells, and glycosylation plays a crucial role in the EMT process. Certain aberrant glycans have been reported as biomarkers during bladder cancer progression, but global variation of N-glycans in this type of cancer has not been previously studied. We examined the profiles of N-glycan and glycogene expression in transforming growth factor-beta (TGFβ)-induced EMT using non-malignant bladder transitional epithelium HCV29 cells. These expression profiles were analyzed by mass spectrometry, lectin microarray analysis, and GlycoV4 oligonucleotide microarray analysis, and confirmed by lectin histochemistry and real-time RT-PCR. The expression of 5 N-glycan-related genes were notably altered in TGFβ-induced EMT. In particular, reduced expression of glycogene man2a1, which encodes α-mannosidase 2, contributed to the decreased proportions of bi-, tri- and tetra-antennary complex N-glycans, and increased expression of hybrid-type N-glycans. Decreased expression of fuca1 gene, which encodes Type 1 α-L-fucosidase, contributed to increased expression of fucosylated N-glycans in TGFβ-induced EMT. Taken together, these findings clearly demonstrate the involvement of aberrant N-glycan synthesis in EMT in these cells. Integrated glycomic techniques as described here will facilitate discovery of glycan markers and development of novel diagnostic and therapeutic approaches to bladder cancer. Full article

(This article belongs to the Special Issue Lectins)

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22 pages, 454 KiB

Open AccessReview

The Chemistry of Curcumin: From Extraction to Therapeutic Agent

by Kavirayani Indira Priyadarsini

Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Mumbai 400085, India

Molecules 2014, 19(12), 20091-20112; https://doi.org/10.3390/molecules191220091 - 1 Dec 2014

Cited by 1187 | Viewed by 102626

Abstract

Curcumin, a pigment from turmeric, is one of the very few promising natural products that has been extensively investigated by researchers from both the biological and chemical point of view. While there are several reviews on the biological and pharmacological effects of curcumin, [...] Read more.

Curcumin, a pigment from turmeric, is one of the very few promising natural products that has been extensively investigated by researchers from both the biological and chemical point of view. While there are several reviews on the biological and pharmacological effects of curcumin, chemistry reviews are comparatively scarcer. In this article, an overview of different aspects of the unique chemistry research on curcumin will be discussed. These include methods for the extraction from turmeric, laboratory synthesis methods, chemical and photochemical degradation and the chemistry behind its metabolism. Additionally other chemical reactions that have biological relevance like nucleophilic addition reactions, and metal chelation will be discussed. Recent advances in the preparation of new curcumin nanoconjugates with metal and metal oxide nanoparticles will also be mentioned. Directions for future investigations to be undertaken in the chemistry of curcumin have also been suggested. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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15 pages, 513 KiB

Open AccessArticle

Assessment of Genetic Diversity in Seed Plants Based on a Uniform π Criterion

by Bin Ai, Ming Kang and Hongwen Huang^*

Key Laboratory of Plant Resources Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China

Molecules 2014, 19(12), 20113-20127; https://doi.org/10.3390/molecules191220113 - 1 Dec 2014

Cited by 13 | Viewed by 6528

Abstract

Despite substantial advances in genotyping techniques and massively accumulated data over the past half century, a uniform measurement of neutral genetic diversity derived by different molecular markers across a wide taxonomical range has not yet been formulated. We collected genetic diversity data on [...] Read more.

Despite substantial advances in genotyping techniques and massively accumulated data over the past half century, a uniform measurement of neutral genetic diversity derived by different molecular markers across a wide taxonomical range has not yet been formulated. We collected genetic diversity data on seed plants derived by AFLP, allozyme, ISSR, RAPD, SSR and nucleotide sequences, converted expected heterozygosity (H_e) to nucleotide diversity (π), and reassessed the relationship between plant genetic diversity and life history traits or extinction risk. We successfully established a uniform π criterion and developed a comprehensive plant genetic diversity database. The mean population-level and species-level π values across seed plants were 0.00374 (966 taxa, 155 families, 47 orders) and 0.00569 (728 taxa, 130 families, 46 orders), respectively. Significant differences were recovered for breeding system (p < 0.001) at the population level and geographic range (p = 0.023) at the species level. Selfing taxa had significantly lower π values than outcrossing and mixed-mating taxa, whereas narrowly distributed taxa had significantly lower π values than widely distributed taxa. Despite significant differences between the two extreme threat categories (critically endangered and least concern), the genetic diversity reduction on the way to extinction was difficult to detect in early stages. Full article

(This article belongs to the Section Molecular Diversity)

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11 pages, 958 KiB

Open AccessArticle

Radiosensitizing Effect of Schinifoline from Zanthoxylum schinifolium Sieb et Zucc on Human Non-Small Cell Lung Cancer A549 Cells: A Preliminary in Vitro Investigation

by Cheng-Fang Wang^1,2, Li Fan¹, Mei Tian¹, Xue-Song Qi¹, Jian-Xiang Liu¹, Jiang-Bin Feng¹, Shu-Shan Du², Xu Su^1,* and Yong-Yan Wang²

¹ China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China

² State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing 100875, China

Molecules 2014, 19(12), 20128-20138; https://doi.org/10.3390/molecules191220128 - 1 Dec 2014

Cited by 20 | Viewed by 6930

Abstract

Schinifoline (SF), a 4-quinolinone derivative, was found in Zanthoxylum schinifolium for the first time. 4-Quinolinone moieties are thought to have cytotoxic activity and are often used as a tubulin polymerization inhibitors, heterogeneous enzyme inhibitors and antiplatelet agents. However, very little information respect to [...] Read more.

Schinifoline (SF), a 4-quinolinone derivative, was found in Zanthoxylum schinifolium for the first time. 4-Quinolinone moieties are thought to have cytotoxic activity and are often used as a tubulin polymerization inhibitors, heterogeneous enzyme inhibitors and antiplatelet agents. However, very little information respect to radiosensitization has focused on SF. This work aimed to investigate the radiosensitizing effect of SF on A549 cells. The cell viability results indicated cytotoxicity of SF on A549 cells, with IC₅₀ values of 33.7 ± 2.4, 21.9 ± 1.9 and 16.8 ± 2.2 μg/mL, respectively, after 6, 12, 24 h treatment with different concentrations, and the 10% or 20% IC₅₀ concentration during 12 h was applied in later experiments. The results of cell proliferative inhibition and clonogenic assay showed that SF enhanced the radiosensitivity of A549 cells when applied before ⁶⁰Co γ-irradiation and this effect was mainly time and concentration dependent. The flow cytometric data indicated that SF treatment before theirradiation increased the G₂/M phase, thus improving the radiosensitivity of A549, leading to cell apoptosis. This paper is the first study that describes the in vitro radiosensitising, cell cycle and apoptotic-inducing effects of schinifoline. Full article

(This article belongs to the Section Medicinal Chemistry)

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18 pages, 657 KiB

Open AccessReview

Curcumin and Chronic Kidney Disease (CKD): Major Mode of Action through Stimulating Endogenous Intestinal Alkaline Phosphatase

by Siddhartha S. Ghosh¹, Todd W. B. Gehr¹ and Shobha Ghosh^2,*

¹ Division of Nephrology, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA

² Division of Pulmonary and Critical Care, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA

Molecules 2014, 19(12), 20139-20156; https://doi.org/10.3390/molecules191220139 - 2 Dec 2014

Cited by 91 | Viewed by 30518

Abstract

Curcumin, an active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa), has significant anti-inflammatory properties. Chronic kidney disease (CKD), an inflammatory disease, can lead to end stage renal disease resulting in dialysis and transplant. Furthermore, it is [...] Read more.

Curcumin, an active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa), has significant anti-inflammatory properties. Chronic kidney disease (CKD), an inflammatory disease, can lead to end stage renal disease resulting in dialysis and transplant. Furthermore, it is frequently associated with other inflammatory disease such as diabetes and cardiovascular disorders. This review will focus on the clinically relevant inflammatory molecules that play a role in CKD and associated diseases. Various enzymes, transcription factors, growth factors modulate production and action of inflammatory molecules; curcumin can blunt the generation and action of these inflammatory molecules and ameliorate CKD as well as associated inflammatory disorders. Recent studies have shown that increased intestinal permeability results in the leakage of pro-inflammatory molecules (cytokines and lipopolysaccharides) from gut into the circulation in diseases such as CKD, diabetes and atherosclerosis. This change in intestinal permeability is due to decreased expression of tight junction proteins and intestinal alkaline phosphatase (IAP). Curcumin increases the expression of IAP and tight junction proteins and corrects gut permeability. This action reduces the levels of circulatory inflammatory biomolecules. This effect of curcumin on intestine can explain why, despite poor bioavailability, curcumin has potential anti-inflammatory effects in vivo and beneficial effects on CKD. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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13 pages, 1764 KiB

Open AccessArticle

Aggregation Behavior of Long-Chain Piperidinium Ionic Liquids in Ethylammonium Nitrate

by Caili Dai, Mingyong Du, Yifei Liu, Shilu Wang, Jianhui Zhao, Ang Chen, Dongxu Peng and Mingwei Zhao^*

State Key Laboratory of Heavy Oil Processing, School of Petroleum Engineering, China University of Petroleum (Huadong), Qingdao 266580, Shandong, China

Molecules 2014, 19(12), 20157-20169; https://doi.org/10.3390/molecules191220157 - 2 Dec 2014

Cited by 13 | Viewed by 6882

Abstract

Micelles formed by the long-chain piperidinium ionic liquids (ILs) N-alkyl-N-methylpiperidinium bromide of general formula C_nPDB (n = 12, 14, 16) in ethylammonium nitrate (EAN) were investigated through surface tension and dissipative particle dynamics (DPD) simulations. Through surface [...] Read more.

Micelles formed by the long-chain piperidinium ionic liquids (ILs) N-alkyl-N-methylpiperidinium bromide of general formula C_nPDB (n = 12, 14, 16) in ethylammonium nitrate (EAN) were investigated through surface tension and dissipative particle dynamics (DPD) simulations. Through surface tension measurements, the critical micelle concentration (cmc), the effectiveness of surface tension reduction (Π_cmc), the maximum excess surface concentration (Г_max) and the minimum area occupied per surfactant molecule (A_min) can be obtained. A series of thermodynamic parameters (DG0 m, DH0 m and DS0 m) of micellization can be calculated and the results showed that the micellization was entropy-driven. In addition, the DPD simulation was performed to simulate the whole aggregation process behavior to better reveal the micelle formation process. Full article

(This article belongs to the Section Organic Chemistry)

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13 pages, 1071 KiB

Open AccessArticle

Potential Mechanism of Action of meso-Dihydroguaiaretic Acid on Mycobacterium tuberculosis H37Rv

by Aldo F. Clemente-Soto¹, Isaías Balderas-Rentería¹, Gildardo Rivera², Aldo Segura-Cabrera², Elvira Garza-González³

and María Del Rayo Camacho-Corona^1,*

¹ Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Av. Universidad s/n, Ciudad Universitaria, San Nicolás de los Garza, Nuevo León 66451, Mexico

² Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Boulevard del Maestro s/n, Col. Narciso Mendoza, Reynosa, Tamaulipas 88710, Mexico

³ Servicio de Gastroenterología y Departamento de Patología Clínica, Hospital, Universitario Dr. José Eleuterio González, Universidad Autónoma de Nuevo León, Madero y Aguirre Pequeño, Mitras Centro, Monterrey, Nuevo León 64460, Mexico

Molecules 2014, 19(12), 20170-20182; https://doi.org/10.3390/molecules191220170 - 2 Dec 2014

Cited by 22 | Viewed by 8312

Abstract

The isolation and characterization of the lignan meso-dihydroguaiaretic acid (MDGA) from Larrea tridentata and its activity against Mycobacterial tuberculosis has been demonstrated, but no information regarding its mechanism of action has been documented. Therefore, in this study we carry out the gene [...] Read more.

The isolation and characterization of the lignan meso-dihydroguaiaretic acid (MDGA) from Larrea tridentata and its activity against Mycobacterial tuberculosis has been demonstrated, but no information regarding its mechanism of action has been documented. Therefore, in this study we carry out the gene expression from total RNA obtained from M. tuberculosis H37Rv treated with MDGA using microarray technology, which was validated by quantitative real time polymerase chain reaction. Results showed that the alpha subunit of coenzyme A transferase of M. tuberculosis H37Rv is present in both geraniol and 1-and 2-methylnaphthalene degradation pathways, which are targeted by MDGA. This assumption was supported by molecular docking which showed stable interaction between MDGA with the active site of the enzyme. We propose that inhibition of coenzyme A transferase of M. tuberculosis H37Rv results in the accumulation of geraniol and 1-and 2-methylnaphtalene inside bacteria, causing membrane destabilization and death of the pathogen. The natural product MDGA is thus an attractive template to develop new anti-tuberculosis drugs, because its target is different from those of known anti-tubercular agents. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 284 KiB

Open AccessArticle

Evolution of the Aroma Volatiles of Pear Fruits Supplemented with Fatty Acid Metabolic Precursors

by Gaihua Qin^1,2,3,†, Shutian Tao^1,†, Huping Zhang¹, Wenjiang Huang¹, Juyou Wu¹, Yiliu Xu^3,* and Shaoling Zhang^1,*

¹ Department of Horticulture, Nanjing Agricultural University, Nanjing 210095, China

² Horticultural Research Institute, Anhui Academy of Agricultural Sciences, Hefei 230031, China

³ Key Laboratory of Genetic Improvement and Ecophysiology of Horticultural Crop, Hefei 230031, China

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 20183-20196; https://doi.org/10.3390/molecules191220183 - 2 Dec 2014

Cited by 58 | Viewed by 8213

Abstract

To examine the biochemical metabolism of aroma volatiles derived from fatty acids, pear fruits were incubated in vitro with metabolic precursors of these compounds. Aroma volatiles, especially esters, were significantly increased, both qualitatively and quantitatively, in pear fruits fed on fatty acid metabolic [...] Read more.

To examine the biochemical metabolism of aroma volatiles derived from fatty acids, pear fruits were incubated in vitro with metabolic precursors of these compounds. Aroma volatiles, especially esters, were significantly increased, both qualitatively and quantitatively, in pear fruits fed on fatty acid metabolic precursors. Cultivars having different flavor characteristics had distinctly different aroma volatile metabolisms. More esters were formed in fruity-flavored “Nanguoli” fruits than in green-flavored “Dangshansuli” fruits fed on the same quantities of linoleic acid and linolenic acid. Hexanal and hexanol were more efficient metabolic intermediates for volatile synthesis than linoleic acid and linolenic acid. Hexyl esters were the predominant esters produced by pear fruits fed on hexanol, and their contents in “Dangshansuli” fruits were higher than in “Nanguoli” fruits. Hexyl esters and hexanoate esters were the primary esters produced in pear fruits fed on hexanal, however the content of hexyl ester in “Dangshansuli” was approximately three times that in “Nanguoli”. The higher contents of hexyl esters in “Dangshansuli” may have resulted from a higher level of hexanol derived from hexanal. In conclusion, the synthesis of aroma volatiles was largely dependent on the metabolic precursors presented. Full article

(This article belongs to the Special Issue Aromas and Volatiles of Fruits)

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30 pages, 3855 KiB

Open AccessArticle

Multitarget Molecular Hybrids of Cinnamic Acids

by Aikaterini Peperidou¹, Dorothea Kapoukranidou², Christos Kontogiorgis³ and Dimitra Hadjipavlou-Litina^1,*

¹ Department of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece

² Department of Physiology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece

³ Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Dragana (Campus), Alexandroupolis 68100, Greece

Molecules 2014, 19(12), 20197-20226; https://doi.org/10.3390/molecules191220197 - 2 Dec 2014

Cited by 38 | Viewed by 8612

Abstract

In an attempt to synthesize potential new multitarget agents, 11 novel hybrids incorporating cinnamic acids and paracetamol, 4-/7-hydroxycoumarin, benzocaine, p-aminophenol and m-aminophenol were synthesized. Three hybrids—2e, 2a, 2g—and 3b were found to be multifunctional agents. The hybrid [...] Read more.

In an attempt to synthesize potential new multitarget agents, 11 novel hybrids incorporating cinnamic acids and paracetamol, 4-/7-hydroxycoumarin, benzocaine, p-aminophenol and m-aminophenol were synthesized. Three hybrids—2e, 2a, 2g—and 3b were found to be multifunctional agents. The hybrid 2e derived from the phenoxyphenyl cinnamic acid and m-acetamidophenol showed the highest lipoxygenase (LOX) inhibition and analgesic activity (IC₅₀ = 0.34 μΜ and 98.1%, whereas the hybrid 3b of bromobenzyloxycinnamic acid and hymechromone exhibited simultaneously good LOX inhibitory activity (IC₅₀ = 50 μΜ) and the highest anti-proteolytic activity (IC₅₀= 5 μΜ). The hybrid 2a of phenyloxyphenyl acid with paracetamol showed a high analgesic activity (91%) and appears to be a promising agent for treating peripheral nerve injuries. Hybrid 2g which has an ester and an amide bond presents an interesting combination of anti-LOX and anti-proteolytic activity. The esters were found very potent and especially those derived from paracetamol and m-acetamidophenol. The amides follow. Based on 2D-structure–activity relationships it was observed that both steric and electronic parameters play major roles in the activity of these compounds. Molecular docking studies point to the fact that allosteric interactions might govern the LOX-inhibitor binding. Full article

(This article belongs to the Special Issue Cinnamic Acids Hybrids with Biological Interest)

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30 pages, 1061 KiB

Open AccessReview

Strategies for the Synthesis of Yardsticks and Abaci for Nanometre Distance Measurements by Pulsed EPR

by Silvia Valera and Bela E. Bode^*

EaStCHEM School of Chemistry, Biomedical Sciences Research Complex and Centre of Magnetic Resonance, University of St Andrews, KY16 9ST Fife, UK

Molecules 2014, 19(12), 20227-20256; https://doi.org/10.3390/molecules191220227 - 3 Dec 2014

Cited by 10 | Viewed by 8673

Abstract

Pulsed electron paramagnetic resonance (EPR) techniques have been found to be efficient tools for the elucidation of structure in complex biological systems as they give access to distances in the nanometre range. These measurements can provide additional structural information such as relative orientations, [...] Read more.

Pulsed electron paramagnetic resonance (EPR) techniques have been found to be efficient tools for the elucidation of structure in complex biological systems as they give access to distances in the nanometre range. These measurements can provide additional structural information such as relative orientations, structural flexibility or aggregation states. A wide variety of model systems for calibration and optimisation of pulsed experiments has been synthesised. Their design is based on mimicking biological systems or materials in specific properties such as the distances themselves and the distance distributions. Here, we review selected approaches to the synthesis of chemical systems bearing two or more spin centres, such as nitroxide or trityl radicals, metal ions or combinations thereof and outline their application in pulsed EPR distance measurements. Full article

(This article belongs to the Special Issue Free Radicals and Radical Ions)

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9 pages, 710 KiB

Open AccessArticle

Two New N-Oxide Alkaloids from Stemona cochinchinensis

by Ligen Lin^1,2,*

, Han Bao¹, Anqi Wang¹, Chunping Tang², Pham-Huu Dien³ and Yang Ye^2,*

¹ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China

² State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

³ Department of Organic Chemistry, Faculty of Chemistry, Hanoi National University of Education, Hanoi 100000, Vietnam

Molecules 2014, 19(12), 20257-20265; https://doi.org/10.3390/molecules191220257 - 3 Dec 2014

Cited by 10 | Viewed by 5805

Abstract

Two new N-oxide alkaloids with pyrrolo[1,2-α]azepine skeleton, namely isoneostemocochinine-N-oxide (1) and neostemocochinine-N-oxide (2), as well as three known alkaloids with pyrido[1,2-α]azepine skeletons, were isolated and identified from the roots of Stemona cochinchinensis (Stemonaceae). The structures of these compounds were [...] Read more.

Two new N-oxide alkaloids with pyrrolo[1,2-α]azepine skeleton, namely isoneostemocochinine-N-oxide (1) and neostemocochinine-N-oxide (2), as well as three known alkaloids with pyrido[1,2-α]azepine skeletons, were isolated and identified from the roots of Stemona cochinchinensis (Stemonaceae). The structures of these compounds were elucidated by 1D- and 2D-NMR spectra and other spectroscopic studies. Additionally, the ¹H- and ¹³C-NMR characteristic of N-oxide Stemona alkaloids was summarized. Stemokerrin showed potent anti-tussive activity on citric acid-induced guinea pig model. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 905 KiB

Open AccessArticle

The Regulation of Anthocyanin Synthesis in the Wheat Pericarp

by Olesya Y. Shoeva^1,*, Elena I. Gordeeva¹ and Elena K. Khlestkina^1,2

¹ Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Lavrentjeva ave. 10, Novosibirsk 630090, Russia

² Novosibirsk State University, Pirogova St. 2, Novosibirsk 630090, Russia

Molecules 2014, 19(12), 20266-20279; https://doi.org/10.3390/molecules191220266 - 4 Dec 2014

Cited by 66 | Viewed by 8637

Abstract

Bread wheat producing grain in which the pericarp is purple is considered to be a useful source of dietary anthocyanins. The trait is under the control of the Pp-1 homoealleles (mapping to each of the group 7 chromosomes) and Pp3 (on chromosome 2A). [...] Read more.

Bread wheat producing grain in which the pericarp is purple is considered to be a useful source of dietary anthocyanins. The trait is under the control of the Pp-1 homoealleles (mapping to each of the group 7 chromosomes) and Pp3 (on chromosome 2A). Here, TaMyc1 was identified as a likely candidate for Pp3. The gene encodes a MYC-like transcription factor. In genotypes carrying the dominant Pp3 allele, TaMyc1 was strongly transcribed in the pericarp and, although at a lower level, also in the coleoptile, culm and leaf. The gene was located to chromosome 2A. Three further copies were identified, one mapping to the same chromosome arm as TaMyc1 and the other two mapping to the two other group 2 chromosomes; however none of these extra copies were transcribed in the pericarp. Analysis of the effect of the presence of combinations of Pp3 and Pp-1 genotype on the transcription behavior of TaMyc1 showed that the dominant allele Pp-D1 suppressed the transcription of TaMyc1. Full article

(This article belongs to the Special Issue Anthocyanins)

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15 pages, 741 KiB

Open AccessArticle

Structures of Some Novel α-Glucosyl Diterpene Glycosides from the Glycosylation of Steviol Glycosides

by Indra Prakash^* and Venkata Sai Prakash Chaturvedula^†

¹ Organic Chemistry Department, The Coca-Cola Company, Global Research and Development, One Coca-Cola Plaza, Atlanta, GA 30313, USA

^† Current address: Natural Products Research Group, Wisdom Natural Brands, 1203 W San Pedro Street, Gilbert, AZ 85233, USA

Molecules 2014, 19(12), 20280-20294; https://doi.org/10.3390/molecules191220280 - 4 Dec 2014

Cited by 18 | Viewed by 7427

Abstract

Four new minor diterpene glycosides with a rare α-glucosyl linkage were isolated from a cyclodextrin glycosyltransferase glucosylated stevia extract containing more than 98% steviol glycosides. The new compounds were identified as 13-[(2-O-β-D-glucopyranosyl-3-O-(4-O-α-D-glucopyranosyl)-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid-[(4-O-α-D-glucopyranosyl-β-D-glucopyranosyl) [...] Read more.

Four new minor diterpene glycosides with a rare α-glucosyl linkage were isolated from a cyclodextrin glycosyltransferase glucosylated stevia extract containing more than 98% steviol glycosides. The new compounds were identified as 13-[(2-O-β-D-glucopyranosyl-3-O-(4-O-α-D-glucopyranosyl)-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid-[(4-O-α-D-glucopyranosyl-β-D-glucopyranosyl) ester] (1), 13-[(2-O-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid-[(4-O-(4-O-(4-O-α-D-glucopyranosyl)-α-D-glucopyranosyl)-α-D-glucopyranosyl)-β-D-glucopyranosyl ester] (2), 13-[(2-O-β-D-glucopyranosyl-3-O-(4-O-(4-O-(4-O-α-D-glucopyranosyl)-α-D-glucopyranosyl)-α-D-glucopyranosyl)-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid β-D-glucopyranosyl ester (3), and 13-[(2-O-β-D-glucopyranosyl-3-O-(4-O-(4-O-(4-O-α-D-glucopyranosyl)-α-D-glucopyranosyl)-α-D-glucopyranosyl)-β-D-glucopyranosyl- β-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid-[(4-O-α-D-glucopyranosyl-β-D-glucopyranosyl) ester] (4) on the basis of extensive NMR and mass spectral (MS) data as well as hydrolysis studies. Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 1125 KiB

Open AccessReview

Anticancer Agents Targeted to Sirtuins

by Tomohiro Kozako^1,*, Takayoshi Suzuki², Makoto Yoshimitsu³

, Naomichi Arima³, Shin-ichiro Honda¹ and Shinji Soeda^1,*

¹ Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

² Faculty of Medicine, Kyoto Prefectural University of Medicine, 1-5 Shimogamohangi-Cho, Sakyo-Ku, Kyoto 606-0823, Japan

³ Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan

Molecules 2014, 19(12), 20295-20313; https://doi.org/10.3390/molecules191220295 - 4 Dec 2014

Cited by 60 | Viewed by 11258

Abstract

Sirtuins are nicotinamide adenine dinucleotide⁺-dependent deacetylases of which there are seven isoforms (SIRT1–7). Sirtuin activity is linked to gene expression, lifespan extension, neurodegeneration, and age-related disorders. Numerous studies have suggested that sirtuins could be of great significance with regard to both [...] Read more.

Sirtuins are nicotinamide adenine dinucleotide⁺-dependent deacetylases of which there are seven isoforms (SIRT1–7). Sirtuin activity is linked to gene expression, lifespan extension, neurodegeneration, and age-related disorders. Numerous studies have suggested that sirtuins could be of great significance with regard to both antiaging and tumorigenesis, depending on its targets in specific signaling pathways or in specific cancers. Recent studies have identified small chemical compounds that modulate sirtuins, and these modulators have enabled a greater understanding of the biological function and molecular mechanisms of sirtuins. This review highlights the possibility of sirtuins, especially SIRT1 and SIRT2, for cancer therapy targets, and focuses on the therapeutic potential of sirtuin modulators both in cancer prevention and treatment. 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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11 pages, 3765 KiB

Open AccessArticle

A Novel Extended N-Methyl Monopyrrolotetrathiafulvalene Based on 2-Methylene-4,5-Bis(Methylthio)-1,3-Dithiole

by Ruibin Hou^1,2, Xiaohong Shang¹, Yan Xia¹, Bao Li^3,*

and Dongfeng Li^1,*

¹ School of Chemistry and Life Sciences, Changchun University of Technology, Changchun 130012, China

² Advanced Institute of Materials Science, Changchun University of Technology, Changchun 130012, China

³ State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun 130012, China

Molecules 2014, 19(12), 20314-20324; https://doi.org/10.3390/molecules191220314 - 4 Dec 2014

Cited by 1 | Viewed by 5099

Abstract

The title compound was prepared via a cross-coupling reaction and its crystal structure has been determined. It crystallized in the triclinic space group P-1 with cell parameters: a = 8.552(2) Å, b = 11.310(2) Å, c = 16.150(3) Å, α = 109.55(3)°, [...] Read more.

The title compound was prepared via a cross-coupling reaction and its crystal structure has been determined. It crystallized in the triclinic space group P-1 with cell parameters: a = 8.552(2) Å, b = 11.310(2) Å, c = 16.150(3) Å, α = 109.55(3)°, β = 91.45(3)°, γ = 91.28(3)°, V = 1470.6(5) Å³, Z = 2 at 296 K. There is one molecule in the asymmetric unit. In the crystal structure, the neighboring molecules from dimers by weak intermolecular π···π interactions between the pyrrole and tetrathiafulvalene units. The dimers are further linked through C-H···π interactions to generate one-dimensional chains along the [100] direction. The arrangement of the molecules corresponds to an overlap between the HOMO and LUMO. Full article

(This article belongs to the Section Organic Chemistry)

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15 pages, 8442 KiB

Open AccessArticle

Formulation, Characterization, and in Vivo Evaluation of Celecoxib-PVP Solid Dispersion Nanoparticles Using Supercritical Antisolvent Process

by Eun-Sol Ha^1,†, Gwang-Ho Choo^1,†, In-Hwan Baek² and Min-Soo Kim^1,*

¹ College of Pharmacy, Pusan National University, Busan 609-735, Korea

² College of Pharmacy, Kyungsung University, Busan 608-736, Korea

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 20325-20339; https://doi.org/10.3390/molecules191220325 - 4 Dec 2014

Cited by 52 | Viewed by 11507

Abstract

The aim of this study was to develop celecoxib-polyvinylpyrrolidone (PVP) solid dispersion nanoparticles with and without surfactant using the supercritical antisolvent (SAS) process. The effect of different surfactants such as gelucire 44/14, poloxamer 188, poloxamer 407, Ryoto sugar ester L1695, and d-α-tocopheryl polyethylene [...] Read more.

The aim of this study was to develop celecoxib-polyvinylpyrrolidone (PVP) solid dispersion nanoparticles with and without surfactant using the supercritical antisolvent (SAS) process. The effect of different surfactants such as gelucire 44/14, poloxamer 188, poloxamer 407, Ryoto sugar ester L1695, and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on nanoparticle formation and dissolution as well as oral absorption of celecoxib-PVP K30 solid dispersion nanoparticles was investigated. Spherical celecoxib solid dispersion nanoparticles less than 300 nm in size were successfully developed using the SAS process. Analysis by differential scanning calorimetry and powder X-ray diffraction showed that celecoxib existed in the amorphous form within the solid dispersion nanoparticles fabricated using the SAS process. The celecoxib-PVP-TPGS solid dispersion nanoparticles significantly enhanced in vitro dissolution and oral absorption of celecoxib relative to that of the unprocessed form. The area under the concentration-time curve (AUC_{0→24 h}) and peak plasma concentration (C_max) increased 4.6 and 5.7 times, respectively, with the celecoxib-PVP-TPGS formulation. In addition, in vitro dissolution efficiency was well correlated with in vivo pharmacokinetic parameters. The present study demonstrated that formulation of celecoxib-PVP-TPGS solid dispersion nanoparticles using the SAS process is a highly effective strategy for enhancing the bioavailability of poorly water-soluble celecoxib. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 1951 KiB

Open AccessCommunication

Saikosaponin D Isolated from Bupleurum falcatum Inhibits Selectin-Mediated Cell Adhesion

by Myoung-Jun Jang^1,†, Ye Sol Kim^2,†, Eun Young Bae³, Tae-Seok Oh⁴, Hwa-Jung Choi⁵, Jung-Hee Lee⁵, Hyun-Mee Oh^2,* and Seung Woong Lee^6,*

¹ Enviromental Agriculture Research Division, Gyeonggido Agricultural Reaearch and Extension Services(GARES), Hwaseong, Gyeonggi-do 445-784, Korea

² Bioindustial Process Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup-si, Jeollabuk-do 580-185, Korea

³ LINC project group, University Industry Cooperation, Daejeon University, Daejeon 300-716, Korea

⁴ Department of Plant Resources, Kongju National University, Yesan 340-702, Korea

⁵ Department of Beauty Science, Kwangju Women's University, Gwangju 506-713, Korea

⁶ Department of Chemistry, Mokwon University, Daejeon 302-729, Korea

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 20340-20349; https://doi.org/10.3390/molecules191220340 - 4 Dec 2014

Cited by 15 | Viewed by 7792

Abstract

Three saikosaponins were isolated from the MeOH extract of the roots of Bupleurum falcatum L.: saikosaponins B3 (1); B4 (2); and D (3). Of the three, compound 3 inhibited the interaction of selectins (E, L, and P) [...] Read more.

Three saikosaponins were isolated from the MeOH extract of the roots of Bupleurum falcatum L.: saikosaponins B3 (1); B4 (2); and D (3). Of the three, compound 3 inhibited the interaction of selectins (E, L, and P) and THP-1 cells with IC₅₀ values of 1.8, 3.0 and 4.3 µM, respectively. Also, the aglycone structure 4 of compound 3 showed moderate inhibitory activity on L-selectin-mediated cell adhesion. From these results, we suspect that compound 3 isolated from Bupleurum falcatum roots would be a good candidate for therapeutic strategies to treat inflammation. Full article

(This article belongs to the Collection Bioactive Compounds)

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24 pages, 2315 KiB

Open AccessArticle

Are Vicilins Another Major Class of Legume Lectins?

by Ana C. Ribeiro^1,2

, Sara V. Monteiro³, Belmira M. Carrapiço⁴ and Ricardo B. Ferreira^2,5,*

¹ Faculdade de Farmácia de Lisboa, Lisbon University, Lisboa 1649-003, Portugal

² Centro de Botânica Aplicada à Agricultura, Instituto Superior de Agronomia, Lisbon University, Lisboa 1349-017, Portugal

³ CEV, S.A, Zona Industrial de Cantanhede/Biocant Park, Cantanhede 3060-197, Portugal

⁴ Faculdade de Medicina Veterinária, Lisbon University, Lisboa 1300-477, Portugal

⁵ Instituto de Tecnologia Química e Biológica, New University of Lisbon, Oeiras 2780-157, Portugal

Molecules 2014, 19(12), 20350-20373; https://doi.org/10.3390/molecules191220350 - 5 Dec 2014

Cited by 17 | Viewed by 7607

Abstract

Legume lectins comprise a structurally related, Ca/Mn-dependent, widespread, abundant and well characterized lectin family when compared to the large number of lectins from other sources described in the literature. Strangely enough, no specific function has been assigned to them aside from a possible [...] Read more.

Legume lectins comprise a structurally related, Ca/Mn-dependent, widespread, abundant and well characterized lectin family when compared to the large number of lectins from other sources described in the literature. Strangely enough, no specific function has been assigned to them aside from a possible role in storage and/or defense. Using a recent and fine-tuned methodology capable of specific lectin identification, β-conglutin, Vicia faba vicilin and β-lathyrin, the vicilin storage globulins from Lupinus albus, V. faba and Lathyrus sativus, respectively, were shown to be capable of affinity binding to thoroughly washed erythrocyte membranes and of specific elution with appropriate sugars. Based on this evidence and on sparse data published in the literature, a second family of legume lectins is proposed: the 7S family of storage proteins from leguminous seeds, or family II of legume lectins. These lectins are also structurally related, widespread and well characterized. In addition, they self-aggregate in a Ca/Mg, electrostatic dependent manner and are even more abundant than the family I of legume lectins. Using the same evidence, reserve and defense roles may be attributed to family II of legume lectins. Full article

(This article belongs to the Special Issue Lectins)

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8 pages, 697 KiB

Open AccessArticle

Antiprotozoal Activity of (E)-Cinnamic N-Acylhydrazone Derivatives

by Samir Aquino Carvalho^1,4, Marcel Kaiser², Reto Brun², Edson Ferreira da Silva¹ and Carlos Alberto Manssour Fraga^3,4,*

¹ Instituto de Tecnologia em Fármacos e Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, RJ 21041-250, Brazil

² Swiss Tropical and Public Health Institute (Swiss TPH), Socinstrasse 57, Basel CH-4002, Switzerland

³ Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, P.O. Box 68023, Rio de Janeiro, RJ 21941-902, Brazil

⁴ Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21949-900, Brazil

Molecules 2014, 19(12), 20374-20381; https://doi.org/10.3390/molecules191220374 - 5 Dec 2014

Cited by 15 | Viewed by 6663

Abstract

A series of 14 (E)-cinnamic N-acylhydrazone derivatives, designed through molecular hybridization between the (E)-1-(benzo[d][1,3]dioxol-5-yl)-3-(4-bromophenyl)prop-2-en-1-one and (E)-3-hydroxy-N'-((2-hydroxynaphthalen-1-yl)methylene)-7-methoxy-2-naphthohydrazide, were tested for in vitro antiparasitic activity upon axenic amastigote forms of Leishmania donovani and bloodstream [...] Read more.

A series of 14 (E)-cinnamic N-acylhydrazone derivatives, designed through molecular hybridization between the (E)-1-(benzo[d][1,3]dioxol-5-yl)-3-(4-bromophenyl)prop-2-en-1-one and (E)-3-hydroxy-N'-((2-hydroxynaphthalen-1-yl)methylene)-7-methoxy-2-naphthohydrazide, were tested for in vitro antiparasitic activity upon axenic amastigote forms of Leishmania donovani and bloodstream forms of Trypamosoma brucei rhodesiense. The derivative (2E)-3-(4-hydroxy-3-methoxy-5-nitrophenyl)-N'-[(1E)-phenylmethylene]acrylohydrazide showed moderate antileishmanial activity (IC₅₀ = 6.27 µM) when compared to miltefosine, the reference drug (IC₅₀ = 0.348 µM). However, the elected compound showed an excellent selectivity index; in one case it was not cytotoxic against mammalian L-6 cells. The most active antitrypanosomal compound, the derivative (E)-N'-(3,4-dihydroxybenzylidene)cinnamohydrazide (IC₅₀ = 1.93 µM), was cytotoxic against mammalian L-6 cells. Full article

(This article belongs to the Special Issue Cinnamic Acids Hybrids with Biological Interest)

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9 pages, 701 KiB

Open AccessArticle

Chemical Constituents and Bioactivities of Clinacanthus nutans Aerial Parts

by Shu-Fen Tu^1,†, Rosa Huang Liu^2,†, Yuan-Bin Cheng^1,3

, Yu-Ming Hsu¹, Ying-Chi Du¹, Mohamed El-Shazly^1,4, Yang-Chang Wu^1,5,6,7,* and Fang-Rong Chang^1,3,8,9,10,*

¹ Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

² School of Nutrition, College of Health Care and Management, Chung Shan Medical University, Taichung 40201, Taiwan

³ Research Center for Natural Product and New Drug, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

⁴ Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, Ain-Shams University, Cairo 11566, Egypt

⁵ School of Pharmacy, College of Pharmacy, China Medical University, Taichung 404, Taiwan

⁶ Natural Medicinal Products Research Center, China Medical University Hospital, Taichung 404, Taiwan

⁷ Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan

⁸ Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan

⁹ Research and Development Center of Chinese Herbal Medicines and New Drugs, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

¹⁰ Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80708, Taiwan

^† These authors contributed equally to this work.

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Molecules 2014, 19(12), 20382-20390; https://doi.org/10.3390/molecules191220382 - 5 Dec 2014

Cited by 58 | Viewed by 10528

Abstract

Four new sulfur-containing compounds, named clinamides A-C (1–3), and 2-cis-entadamide A (4), were isolated together with three known compounds from the bioactive ethanol extract of the aerial parts of Clinacanthus nutans. These secondary metabolites [...] Read more.

Four new sulfur-containing compounds, named clinamides A-C (1–3), and 2-cis-entadamide A (4), were isolated together with three known compounds from the bioactive ethanol extract of the aerial parts of Clinacanthus nutans. These secondary metabolites possess sulfur atoms and acrylamide functionalities. The structures of the isolated components were established by interpretation of their spectroscopic data, especially 1D and 2D NMR. Full article

(This article belongs to the Section Natural Products Chemistry)

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33 pages, 972 KiB

Open AccessReview

Alkaloids from Marine Invertebrates as Important Leads for Anticancer Drugs Discovery and Development

by Concetta Imperatore, Anna Aiello, Filomena D'Aniello, Maria Senese and Marialuisa Menna^*

The NeaNat Group, Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, Napoli 80131, Italy

Molecules 2014, 19(12), 20391-20423; https://doi.org/10.3390/molecules191220391 - 5 Dec 2014

Cited by 64 | Viewed by 12392

Abstract

The present review describes research on novel natural antitumor alkaloids isolated from marine invertebrates. The structure, origin, and confirmed cytotoxic activity of more than 130 novel alkaloids belonging to several structural families (indoles, pyrroles, pyrazines, quinolines, and pyridoacridines), together with some of their [...] Read more.

The present review describes research on novel natural antitumor alkaloids isolated from marine invertebrates. The structure, origin, and confirmed cytotoxic activity of more than 130 novel alkaloids belonging to several structural families (indoles, pyrroles, pyrazines, quinolines, and pyridoacridines), together with some of their synthetic analogs, are illustrated. Recent discoveries concerning the current state of the potential and/or development of some of them as new drugs, as well as the current knowledge regarding their modes of action, are also summarized. A special emphasis is given to the role of marine invertebrate alkaloids as an important source of leads for anticancer drug discovery. Full article

(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)

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44 pages, 10286 KiB

Open AccessReview

Molecular Modeling to Study Dendrimers for Biomedical Applications

by Nuno Martinho^1,2,3, Helena Florindo¹, Liana Silva¹, Steve Brocchini², Mire Zloh^3,*

and Teresa Barata^2,*

¹ Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, Lisbon 1649-003, Portugal

² Department of Pharmaceutics, The School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK

³ Department of Pharmacy, University of Hertfordshire, College Lane, Hatfield AL10 9AB, UK

Molecules 2014, 19(12), 20424-20467; https://doi.org/10.3390/molecules191220424 - 8 Dec 2014

Cited by 79 | Viewed by 12776

Abstract

Molecular modeling techniques provide a powerful tool to study the properties of molecules and their interactions at the molecular level. The use of computational techniques to predict interaction patterns and molecular properties can inform the design of drug delivery systems and therapeutic agents. [...] Read more.

Molecular modeling techniques provide a powerful tool to study the properties of molecules and their interactions at the molecular level. The use of computational techniques to predict interaction patterns and molecular properties can inform the design of drug delivery systems and therapeutic agents. Dendrimers are hyperbranched macromolecular structures that comprise repetitive building blocks and have defined architecture and functionality. Their unique structural features can be exploited to design novel carriers for both therapeutic and diagnostic agents. Many studies have been performed to iteratively optimise the properties of dendrimers in solution as well as their interaction with drugs, nucleic acids, proteins and lipid membranes. Key features including dendrimer size and surface have been revealed that can be modified to increase their performance as drug carriers. Computational studies have supported experimental work by providing valuable insights about dendrimer structure and possible molecular interactions at the molecular level. The progress in computational simulation techniques and models provides a basis to improve our ability to better predict and understand the biological activities and interactions of dendrimers. This review will focus on the use of molecular modeling tools for the study and design of dendrimers, with particular emphasis on the efforts that have been made to improve the efficacy of this class of molecules in biomedical applications. Full article

(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)

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14 pages, 1243 KiB

Open AccessArticle

Proton Adsorption Selectivity of Zeolites in Aqueous Media: Effect of Si/Al Ratio of Zeolites

by Moses Wazingwa Munthali^1,*, Mohammed Abdalla Elsheikh², Erni Johan¹ and Naoto Matsue¹

¹ Department of Life Environmental Conservation, Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama 790-8566, Japan

² Department of Soil and Environment Sciences, Faculty of Agriculture, University of Khartoum, Shambat, P.O. Box 32, Khartoum North 13314, Sudan

Molecules 2014, 19(12), 20468-20481; https://doi.org/10.3390/molecules191220468 - 8 Dec 2014

Cited by 82 | Viewed by 9946

Abstract

In addition to their well-known uses as catalysts, zeolites are utilized to adsorb and remove various cations from aqueous system. The adsorption of the cations is ascribed to the negative charge of zeolites derived from isomorphous substitution of Si by Al. The amount [...] Read more.

In addition to their well-known uses as catalysts, zeolites are utilized to adsorb and remove various cations from aqueous system. The adsorption of the cations is ascribed to the negative charge of zeolites derived from isomorphous substitution of Si by Al. The amount of Na⁺ adsorption on 4A, X, Y, Na-P1 and mordenite type zeolites were determined in aqueous media, in a two-cation (Na⁺ and H⁺) system. Although each zeolite has a constant amount of negative charge, the amount of Na⁺ adsorption of each zeolite decreased drastically at low pH−pNa values, where pH−pNa is equal to log{(Na⁺)/(H⁺)}. By using the plot of the amount of Na⁺ adsorption versus pH−pNa, an index of the H⁺ selectivity, which is similar to the pKa of acids, of each zeolite was estimated, and the index tended to increase with decreasing Si/Al ratio of zeolites. These indicate that zeolites with lower Si/Al and higher negative charge density have higher H⁺ adsorption selectivity, and in fact, such a zeolite species (4A and X) adsorbed considerable amount of H⁺ even at weakly alkaline pH region. The adsorption of H⁺ results in the decrease of cation adsorption ability, and may lead to the dissolution of zeolites in aqueous media. Full article

(This article belongs to the Special Issue Zeolite Chemistry)

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16 pages, 1264 KiB

Open AccessArticle

A DFT Study of the Photochemical Dimerization of Methyl 3-(2-Furyl)acrylate and Allyl Urocanate

by Maurizio D'Auria

Dipartimento di Scienze, Università della Basilicata, Viale dell'Ateneo Lucano 10, 85100 Potenza, Italy

Molecules 2014, 19(12), 20482-20497; https://doi.org/10.3390/molecules191220482 - 8 Dec 2014

Cited by 11 | Viewed by 7715

Abstract

A DFT study of the photochemical dimerization of methyl 3-(2-furyl)acrylate is reported. The photochemical reaction gave a mixture of two dimers with high regioselectivity and good stereoselectivity. Calculations showed that benzophenone was able to act as a photosensitizer of the reaction. This compound [...] Read more.

A DFT study of the photochemical dimerization of methyl 3-(2-furyl)acrylate is reported. The photochemical reaction gave a mixture of two dimers with high regioselectivity and good stereoselectivity. Calculations showed that benzophenone was able to act as a photosensitizer of the reaction. This compound populated the first excited triplet state of the substrate. The frontier orbitals interaction between LSOMO of the triplet state and HOMO of the ground state accounted for the observed high regioselectivity. Furthermore, the energy of all the possible triplet biradicals has been calculated, showing that the precursor of the main product was the triplet biradical with the lowest energy. The coupling of the atomic coefficients on the radical centres in the biradical intermediates allowed to justify the observed products. The same behavior was observed in the case of the photochemical dimerization of an urocanate ester and in the dimerization of liquid methyl cinnamate. Full article

(This article belongs to the Section Organic Chemistry)

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23 pages, 1345 KiB

Open AccessArticle

Polyphenolic Profile, Antioxidant and Anti-Inflammatory Activity of Eastern Teaberry (Gaultheria procumbens L.) Leaf Extracts

by Piotr Michel¹

, Anna Dobrowolska¹, Agnieszka Kicel¹, Aleksandra Owczarek¹

, Agnieszka Bazylko²

, Sebastian Granica², Jakub P. Piwowarski² and Monika A. Olszewska^1,*

¹ Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Lodz, 1 Muszyńskiego St., Lodz 90-151, Poland

² Department of Pharmacognosy and Molecular Basis of Phytotherapy, Faculty of Pharmacy, Warsaw Medical University, 1 Banacha St., Warsaw 02-097, Poland

Molecules 2014, 19(12), 20498-20520; https://doi.org/10.3390/molecules191220498 - 8 Dec 2014

Cited by 40 | Viewed by 10062

Abstract

Dry leaf extracts of eastern teaberry (Gaultheria procumbens L.) were evaluated as a source of bioactive phytocompounds through systematic activity testing and phytochemical profiling. The antioxidant efficiency was tested using five complementary in vitro models (DPPH; FRAP; linoleic acid (LA) peroxidation assay; [...] Read more.

Dry leaf extracts of eastern teaberry (Gaultheria procumbens L.) were evaluated as a source of bioactive phytocompounds through systematic activity testing and phytochemical profiling. The antioxidant efficiency was tested using five complementary in vitro models (DPPH; FRAP; linoleic acid (LA) peroxidation assay; O₂^•− and H₂O₂ scavenging tests) in parallel with standard antioxidants. The 75% methanol extract and its diethyl ether, ethyl acetate (EAF), n-butanol and water fractions exhibited the dose-dependent responses in all assays, with the highest capacities found for EAF (DPPH EC₅₀ = 2.9 μg/mL; FRAP = 12.8 mmol Fe²⁺/g; IC₅₀ for LA-peroxidation = 123.9 μg/mL; O₂^•− SC₅₀ = 3.9 μg/mL; H₂O₂ SC₅₀ = 7.2 μg/mL). The EAF had also the highest anti-inflammatory activity in the inhibition tests of lipoxygenase and hyaluronidase (60.14% and 21.83% effects, respectively, at the concentration of 100 μg/mL). Activity parameters of the extracts correlated strongly with the levels of total phenolics (72.4–270.7 mg GAE/g), procyanidins, and phenolic acids, whereas for flavonoids only moderate effects were observed. Comprehensive UHPLC-PDA-ESI-MS³ and HPLC-PDA studies led to the identification of 35 polyphenols with a procyanidin A-type trimer, quercetin 3-O-glucuronide, isomers of caffeoylquinic acids, and (‒)-epicatechin being the dominant components. Significant activity levels, high phenolic contents and high extraction yields (39.4%–42.5% DW for defatted and crude methanol extracts, respectively) indicate the value of eastern teaberry leaves as bioactive products. Full article

(This article belongs to the Special Issue Natural Antioxidants and Ageing)

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15 pages, 779 KiB

Open AccessArticle

Biflavans, Flavonoids, and a Dihydrochalcone from the Stem Wood of Muntingia calabura and Their Inhibitory Activities on Neutrophil Pro-Inflammatory Responses

by Wen-Lung Kuo^1,*, Hsiang-Ruei Liao² and Jih-Jung Chen^3,4,*

¹ Chung-Jen Junior College of Nursing, Health Sciences and Management, Chiayi 600, Taiwan

² Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan

³ Department of Pharmacy, Tajen University, Pingtung 907, Taiwan

⁴ Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung 907, Taiwan

Molecules 2014, 19(12), 20521-20535; https://doi.org/10.3390/molecules191220521 - 8 Dec 2014

Cited by 24 | Viewed by 7901

Abstract

Muntingia calabura (Tiliaceae) is commercially used in healthcare for the improvement of hypertension, myocardial infarction, spasm, and inflammatory conditions. Its fruits can be processed into jam and the leaves can be used for making tea. In the work reported herein a new biflavan, [...] Read more.

Muntingia calabura (Tiliaceae) is commercially used in healthcare for the improvement of hypertension, myocardial infarction, spasm, and inflammatory conditions. Its fruits can be processed into jam and the leaves can be used for making tea. In the work reported herein a new biflavan, (M),(2S),(2''S)-,(P),(2S),(2''S)-7,8,3',4',5',7'',8'',3''',4''',5'''-decamethoxy-5,5'' biflavan (1), a new flavone, 4'-hydroxy-7,8,3',5'-tetramethoxyflavone (2), and a new dihydrochalcone, (R)-2',β-dihydroxy-3',4'-dimethoxydihydrochalcone (3), have been isolated from the stem wood of M. calabura, together with 12 known compounds (4–15). The structures of these new compounds were elucidated by the interpretations of extensive spectroscopic data. Among the isolated compounds, 5-hydroxy-7-methoxyflavone (5), quercetin (6), and (2S)-7-hydroxyflavanone (10) exhibited potent inhibition of fMLP-induced superoxide anion generation by human neutrophils, with IC₅₀ values of 1.77 ± 0.70, 3.82 ± 0.46, and 4.92 ± 1.71 μM, respectively. Full article

(This article belongs to the Collection Bioactive Compounds)

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21 pages, 1393 KiB

Open AccessReview

¹⁸F-Labeled Peptides: The Future Is Bright

by Susan Richter and Frank Wuest^*

Department of Oncology, University of Alberta, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada

Molecules 2014, 19(12), 20536-20556; https://doi.org/10.3390/molecules191220536 - 8 Dec 2014

Cited by 123 | Viewed by 14364

Abstract

Radiolabeled peptides have been the subject of intense research efforts for targeted diagnostic imaging and radiotherapy over the last 20 years. Peptides offer several advantages for receptor imaging and targeted radiotherapy. The low molecular weight of peptides allows for rapid clearance from the [...] Read more.

Radiolabeled peptides have been the subject of intense research efforts for targeted diagnostic imaging and radiotherapy over the last 20 years. Peptides offer several advantages for receptor imaging and targeted radiotherapy. The low molecular weight of peptides allows for rapid clearance from the blood and non-target tissue, which results in favorable target-to-non-target ratios. Moreover, peptides usually display good tissue penetration and they are generally non-immunogenic. A major drawback is their potential low metabolic stability. The majority of currently used radiolabeled peptides for targeted molecular imaging and therapy of cancer is labeled with various radiometals like ^99mTc, ⁶⁸Ga, and ¹⁷⁷Lu. However, over the last decade an increasing number of ¹⁸F-labeled peptides have been reported. Despite of obvious advantages of ¹⁸F like its ease of production in large quantities at high specific activity, the low β⁺ energy (0.64 MeV) and the favorable half-life (109.8 min), ¹⁸F-labeling of peptides remains a special challenge. The first part of this review will provide a brief overview on chemical strategies for peptide labeling with ¹⁸F. A second part will discuss recent technological advances for ¹⁸F-labeling of peptides with special focus on microfluidic technology, automation, and kit-like preparation of ¹⁸F-labeled peptides. Full article

(This article belongs to the Special Issue Peptide Chemistry)

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13 pages, 879 KiB

Open AccessReview

Role of Protease-Inhibitors in Ocular Diseases

by Nicola Pescosolido¹, Andrea Barbato², Antonia Pascarella³, Rossella Giannotti², Martina Genzano² and Marcella Nebbioso^2,*

¹ Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, Policlinico Umberto I, Faculty of Medicine and Odontology, Sapienza University of Rome, piazzale Aldo Moro 5, Rome 00185, Italy

² Department of Sense Organs, Ocular Electrophysiology Center, Policlinico Umberto I, Faculty of Medicine and Odontology, Sapienza University of Rome, piazzale Aldo Moro 5, Rome 00185, Italy

³ Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, piazzale Aldo Moro 5, Rome 00185, Italy

Molecules 2014, 19(12), 20557-20569; https://doi.org/10.3390/molecules191220557 - 8 Dec 2014

Cited by 32 | Viewed by 8857

Abstract

It has been demonstrated that the balance between proteases and protease-inhibitors system plays a key role in maintaining cellular and tissue homeostasis. Indeed, its alteration has been involved in many ocular and systemic diseases. In particular, research has focused on keratoconus, corneal wounds [...] Read more.

It has been demonstrated that the balance between proteases and protease-inhibitors system plays a key role in maintaining cellular and tissue homeostasis. Indeed, its alteration has been involved in many ocular and systemic diseases. In particular, research has focused on keratoconus, corneal wounds and ulcers, keratitis, endophthalmitis, age-related macular degeneration, Sorsby fundus dystrophy, loss of nerve cells and photoreceptors during optic neuritis both in vivo and in vitro models. Protease-inhibitors have been extensively studied, rather than proteases, because they may represent a therapeutic approach for some ocular diseases. The protease-inhibitors mainly involved in the onset of the above-mentioned ocular pathologies are: α2-macroglobulin, α1-proteinase inhibitor (α1-PI), metalloproteinase inhibitor (TIMP), maspin, SERPINA3K, SERPINB13, secretory leukocyte protease inhibitor (SLPI), and calpeptin. This review is focused on the several characteristics of dysregulation of this system and, particularly, on a possible role of proteases and protease-inhibitors in molecular remodeling that may lead to some ocular diseases. Recently, researchers have even hypothesized a possible therapeutic effect of the protease-inhibitors in the treatment of injured eye in animal models. Full article

(This article belongs to the Collection Bioactive Compounds)

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10 pages, 1861 KiB

Open AccessArticle

Resveratrol Inhibits Trophoblast Apoptosis through Oxidative Stress in Preeclampsia-Model Rats

by Yanfen Zou^1,†, Qing Zuo^1,†, Shiyun Huang¹, Xiang Yu², Ziyan Jiang¹, Shan Zou¹, Mingsong Fan¹ and Lizhou Sun^1,*

¹ Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu, China

² Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Road, Xiaguan District, Nanjing 210000, Jiangsu, China

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 20570-20579; https://doi.org/10.3390/molecules191220570 - 9 Dec 2014

Cited by 66 | Viewed by 10797

Abstract

Resveratrol has been shown to be a therapeutic agent for cardiovascular disorders by maintaining a lower redox level in vivo through its anti-oxidant properties. Resveratrol can prevent cells from p53- and reactive oxygen species-dependent apoptosis induced by interleukin-1b. We identified an inhibitory effect [...] Read more.

Resveratrol has been shown to be a therapeutic agent for cardiovascular disorders by maintaining a lower redox level in vivo through its anti-oxidant properties. Resveratrol can prevent cells from p53- and reactive oxygen species-dependent apoptosis induced by interleukin-1b. We identified an inhibitory effect of resveratrol against oxidative stress and apoptosis using the TUNEL assay in NG-Nitro-l-arginine methyl ester-induced preeclampsia in rats. To investigate a possible association between resveratrol and the apoptosis caused by oxidative stress in vitro, assays for superoxide dismutase and malondialdehyde as well as flow cytometric analyses were conducted in HTR-8/SVneo cells after hypoxic treatment with or without resveratrol for 24 h. These data suggest that resveratrol significantly opposes the effects of oxidative stress in vivo and in vitro. Full article

(This article belongs to the Special Issue Resveratrol)

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14 pages, 1333 KiB

Open AccessReview

Au-Nanomaterials as a Superior Choice for Near-Infrared Photothermal Therapy

by Fahmida Jabeen^1,2, Muhammad Najam-ul-Haq^1,2,*, Rabia Javeed¹, Christian W. Huck²

and Guenther K. Bonn²

¹ Division of Analytical Chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800, Pakistan

² Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University, Innrain 80-82. Innsbruck 6020, Austria

Molecules 2014, 19(12), 20580-20593; https://doi.org/10.3390/molecules191220580 - 9 Dec 2014

Cited by 94 | Viewed by 11577

Abstract

Photothermal therapy (PPT) is a platform to fight cancer by using multiplexed interactive plasmonic nanomaterials as probes in combination with the excellent therapeutic performance of near-infrared (NIR) light. With recent rapid developments in optics and nanotechnology, plasmonic materials have potential in cancer diagnosis [...] Read more.

Photothermal therapy (PPT) is a platform to fight cancer by using multiplexed interactive plasmonic nanomaterials as probes in combination with the excellent therapeutic performance of near-infrared (NIR) light. With recent rapid developments in optics and nanotechnology, plasmonic materials have potential in cancer diagnosis and treatment, but there are some concerns regarding their clinical use. The primary concerns include the design of plasmonic nanomaterials which are taken up by the tissues, perform their function and then clear out from the body. Gold nanoparticles (Au NPs) can be developed in different morphologies and functionalized to assist the photothermal therapy in a way that they have clinical value. This review outlines the diverse Au morphologies, their distinctive characteristics, concerns and limitations to provide an idea of the requirements in the field of NIR-based therapeutics. Full article

(This article belongs to the Special Issue Advances of Vibrational Spectroscopic Technologies in Life Sciences)

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19 pages, 4048 KiB

Open AccessArticle

Vapour Phase Hydrogenation of Phenol over Rhodium on SBA-15 and SBA-16

by Liliana Giraldo^1,†, Marlon Bastidas-Barranco^2,† and Juan Carlos Moreno-Piraján^3,*,†

¹ Departamento de Química, Universidad Nacional de Colombia, Bogotá 110911, Colombia

² Departamento de Ingeniería Mecánica, Facultad de Ingeniería, Universidad de la Guajira, Riohacha 440001, Colombia

³ Grupo de Investigación en Sólidos Porosos y Calorimetría, Departamento de Química, Universidad de los Andes, Bogotá 110911, Colombia

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 20594-20612; https://doi.org/10.3390/molecules191220594 - 10 Dec 2014

Cited by 17 | Viewed by 9185

Abstract

In the present work, mesoporous SBA-15 and SBA-16 were synthesised using classical methods, and their physicochemical properties were investigated by X-ray diffraction (XRD), FTIR, TEM and N₂ adsorption–desorption. Rhodium (Rh, 1 wt %) was loaded on the mesoporous SBA-15 and SBA-16 by [...] Read more.

In the present work, mesoporous SBA-15 and SBA-16 were synthesised using classical methods, and their physicochemical properties were investigated by X-ray diffraction (XRD), FTIR, TEM and N₂ adsorption–desorption. Rhodium (Rh, 1 wt %) was loaded on the mesoporous SBA-15 and SBA-16 by an impregnation method. The Rh surface coverage, dispersion and crystallite size were determined by room temperature H₂ chemisorption on reduced samples. The catalytic activity of Rh supported on mesoporous SBA-15 and SBA-16 was evaluated for the first time in the hydrogenation of phenol in vapour phase in a temperature range between 130 and 270 °C at atmospheric pressure. The reaction over Rh/SBA-15 at 180 °C produced cyclohexanone as the major product (about 60%) along with lower amounts of cyclohexanol (about 35%) and cyclohexane (about 15%). The influences of temperature, H₂/phenol ratio, contact time and the nature of the solvent on the catalytic performance were systematically investigated. The Rh/SBA-16 system offered lower phenol conversion compared to Rh/SBA-15, but both have a very high selectivity for cyclohexanone (above 60%). Full article

(This article belongs to the Special Issue Zeolite Chemistry)

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14 pages, 715 KiB

Open AccessArticle

Pharmacokinetics, Tissue Distribution and Excretion of Verticinone from F. hupehensis in Rats

by Xiao Wu^1,3,†, Jian-Guo Sun^2,†, Ying Peng², Yan Liang², Guang-Ji Wang^2,*, Hui Chen¹, Ji-Zhou Wu¹ and Peng Zhang^1,*

¹ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy of Tongji Medical College, Huazhong University of Science and Technology, 13# Hangkong Road, Wuhan 430030, China

² State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24# Tongjiaxiang, Nanjing 210009, China

³ Tianjin Key Laboratory of Quality Control in Chinese Medicine, Tianjin Zhongxin Pharmaceuticals R&D Center, 21# 10th Avenue, Tianjin 300457, China

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 20613-20626; https://doi.org/10.3390/molecules191220613 - 10 Dec 2014

Cited by 9 | Viewed by 6906

Abstract

Verticinone, the main active component in F. hupehensis, exhibits potent antitussive and expectorant effects. Here, a LC-MS method was developed and applied to study the pharmacokinetics, tissue distribution and excretion of verticinone in rats, and its plasma protein binding in vitro. [...] Read more.

Verticinone, the main active component in F. hupehensis, exhibits potent antitussive and expectorant effects. Here, a LC-MS method was developed and applied to study the pharmacokinetics, tissue distribution and excretion of verticinone in rats, and its plasma protein binding in vitro. A significant gender difference in the pharmacokinetics of verticinone in rats was observed, as its absolute oral bioavailability in male and female rats was 45.8% and 2.74%, respectively. The relative bioavailability of verticinone was significantly lower in female rats as compared to male, following intragastrical (i.g.) and intravenous (i.v.) administration. After successive i.g. administration of verticinone, accumulation was observed in female rats but not in the male ones. The tissue distribution study showed that verticinone had a good tissue penetrability and a high tissue affinity in most studied tissues, except brain. After a 2 mg/kg oral dose, less than 4% of the dose was excreted as unchanged parent compound in male rats, and less than 1% in female rats, which indicated that verticinone was metabolized more extensively in female rats than in male rats. Full article

(This article belongs to the Section Metabolites)

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23 pages, 2296 KiB

Open AccessArticle

Determination and Occurrence of Phenoxyacetic Acid Herbicides and Their Transformation Products in Groundwater Using Ultra High Performance Liquid Chromatography Coupled to Tandem Mass Spectrometry

by Sarah-Louise McManus^1,2, Mary Moloney³, Karl G. Richards^1,*

, Catherine E. Coxon² and Martin Danaher³

¹ Teagasc Environmental Research Centre, Johnstown Castle, Wexford, Ireland

² Department of Geology, Trinity College Dublin, Dublin 2, Ireland

³ Food Safety Department, Teagasc Food Research Centre, Ashtown, Dublin 15, Ireland

Molecules 2014, 19(12), 20627-20649; https://doi.org/10.3390/molecules191220627 - 10 Dec 2014

Cited by 38 | Viewed by 8408

Abstract

A sensitive method was developed and validated for ten phenoxyacetic acid herbicides, six of their main transformation products (TPs) and two benzonitrile TPs in groundwater. The parent compounds mecoprop, mecoprop-p, 2,4-D, dicamba, MCPA, triclopyr, fluroxypr, bromoxynil, bentazone, and 2,3,6-trichlorobenzoic acid (TBA) are included [...] Read more.

A sensitive method was developed and validated for ten phenoxyacetic acid herbicides, six of their main transformation products (TPs) and two benzonitrile TPs in groundwater. The parent compounds mecoprop, mecoprop-p, 2,4-D, dicamba, MCPA, triclopyr, fluroxypr, bromoxynil, bentazone, and 2,3,6-trichlorobenzoic acid (TBA) are included and a selection of their main TPs: phenoxyacetic acid (PAC), 2,4,5-trichloro-phenol (TCP), 4-chloro-2-methylphenol (4C2MP), 2,4-dichlorophenol (DCP), 3,5,6-trichloro-2-pyridinol (T2P), and 3,5-dibromo-4-hydroxybenzoic acid (BrAC), as well as the dichlobenil TPs 2,6-dichlorobenzamide (BAM) and 3,5-dichlorobenzoic acid (DBA) which have never before been determined in Irish groundwater. Water samples were analysed using an efficient ultra-high performance liquid chromatography (UHPLC) method in an 11.9 min separation time prior to detection by tandem mass spectrometry (MS/MS). The limit of detection (LOD) of the method ranged between 0.00008 and 0.0047 µg·L⁻¹ for the 18 analytes. All compounds could be detected below the permitted limits of 0.1 µg·L⁻¹ allowed in the European Union (EU) drinking water legislation [1]. The method was validated according to EU protocols laid out in SANCO/10232/2006 with recoveries ranging between 71% and 118% at the spiked concentration level of 0.06 µg·L⁻¹. The method was successfully applied to 42 groundwater samples collected across several locations in Ireland in March 2012 to reveal that the TPs PAC and 4C2MP were detected just as often as their parent active ingredients (a.i.) in groundwater. Full article

(This article belongs to the Special Issue Pesticide Residues in the Environment and Food Chain: Fate, Bioaccumulation and Toxicology)

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14 pages, 770 KiB

Open AccessArticle

Expanding Current Knowledge on the Chemical Composition and Antioxidant Activity of the Genus Lactarius

by Vanessa Vieira^1,2, Lillian Barros^1,*, Anabela Martins² and Isabel C. F. R. Ferreira^1,2,*

¹ Centro de Investigação de Montanha (CIMO), ESA, Instituto Politécnico de Bragança, Campus de Santa Apolónia, Apartado 1172, 5301-855 Bragança, Portugal

² School of Agriculture, Polytechnic Institute of Bragança, Campus de Santa Apolónia, Ap. 1172, 5301-855 Bragança, Portugal

Molecules 2014, 19(12), 20650-20663; https://doi.org/10.3390/molecules191220650 - 10 Dec 2014

Cited by 12 | Viewed by 7173

Abstract

Despite the presence of toxic compounds in inedible mushrooms, the question whether the chemical nutrients and non-nutrients compositions in edible and inedible Lactarius species are similar remains unanswered. To answer this question, Lactarius citriolens Pouzar and Lactarius turpis (Weinm.) Fr., two inedible species, [...] Read more.

Despite the presence of toxic compounds in inedible mushrooms, the question whether the chemical nutrients and non-nutrients compositions in edible and inedible Lactarius species are similar remains unanswered. To answer this question, Lactarius citriolens Pouzar and Lactarius turpis (Weinm.) Fr., two inedible species, were studied in order to obtain information about their chemical composition and bioactivity. Free sugars, fatty acids, tocopherols, organic and phenolic acids were analysed by chromatographic techniques coupled to different detectors. L. citriolens and L. turpis methanolic extracts were tested regarding antioxidant potential (reducing power, radical scavenging activity and lipid peroxidation inhibition). The composition of macronutrients varied among the two species, but the profiles were similar between them and among other Lactarius species; L. citriolens gave the highest energy contribution, saturated fatty acids and organic acids, while the L. turpis sample was richer in free sugars, mono- and polyunsaturated fatty acids, tocopherols and phenolic compounds. L. turpis methanolic extract showed the highest antioxidant activity. The absence of hepatoxicity of the methanolic extracts was confirmed in porcine liver primary cells (in vitro conditions). The present study provided new information about wild L. citriolens and L. turpis, comparing their chemical composition and antioxidant properties with other Lactarius species, and expanding the knowledge about this genus. Full article

(This article belongs to the Collection Bioactive Compounds)

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7 pages, 666 KiB

Open AccessArticle

Synthesis of Racemic β-Chamigrene, a Spiro[5.5]undecane Sesquiterpene

by Simen Antonsen¹

, Lars Skattebøl² and Yngve Stenstrøm^1,*

¹ IKBM, P.O. Box 5003, NMBU, The Norwegian University of Life Sciences, N-1430 Ås, Norway

² Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo, Norway

Molecules 2014, 19(12), 20664-20670; https://doi.org/10.3390/molecules191220664 - 10 Dec 2014

Cited by 7 | Viewed by 7849

Abstract

The present paper describes a total synthesis of racemic β-chamigrene (1), a sesquiterpene with a spiro[5.5]undecane carbon framework. Compared with previously reported β-chamigrene syntheses, we were able to reduce the total number of reaction steps, which also resulted in a significant [...] Read more.

The present paper describes a total synthesis of racemic β-chamigrene (1), a sesquiterpene with a spiro[5.5]undecane carbon framework. Compared with previously reported β-chamigrene syntheses, we were able to reduce the total number of reaction steps, which also resulted in a significant improvement of the overall yield. The commercially available ketone 6-methylhept-5-en-2-one was transformed by known simple procedures into 3,3-dimethyl-2-methylenecyclohexanone. This reacted with isoprene by a Diels-Alder reaction to give a spiro ketone. An olefination reaction on this compound gave the target molecule. Full article

(This article belongs to the Section Organic Chemistry)

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4 pages, 645 KiB

Open AccessEditorial

Editorial: Special Issue — Enzyme Immobilization

by Roberto Fernandez-Lafuente

Institute of Catalysis and Petrochemistry-CSIC, Campus UAM-CSIC Cantoblanco, Madrid 28049, Spain

Molecules 2014, 19(12), 20671-20674; https://doi.org/10.3390/molecules191220671 - 10 Dec 2014

Cited by 6 | Viewed by 5278

Abstract

Immobilization of enzymes and proteins is a requirement for many industrial enzyme applications, as this facilitates enzyme recovery and reuse. Bearing in mind this necessity, the coupling of immobilization to the improvement of other enzyme features has been pursued by many researchers, and [...] Read more.

Immobilization of enzymes and proteins is a requirement for many industrial enzyme applications, as this facilitates enzyme recovery and reuse. Bearing in mind this necessity, the coupling of immobilization to the improvement of other enzyme features has been pursued by many researchers, and nowadays immobilization is recognized as a tool to improve not only stability, but also enzyme selectivity, specificity, resistance to inhibition or chemical modifiers, etc. To achieve these overall improvements of enzymes’ properties via immobilization, it is necessary to both develop new immobilization systems suitable for these purposes, and to achieve a deeper knowledge of the mechanisms of interaction between enzymes and activated solids. That way, immobilization of enzymes, far being an old-fashioned methodology to just reuse these expensive biocatalysts, is a tool of continuous interest that requires a continuous effort to be exploited in all its potential. This special issue collects 23 papers reporting advances in the field of immobilization of enzymes.[...] Full article

(This article belongs to the Special Issue Enzyme Immobilization)

20 pages, 1231 KiB

Open AccessArticle

Synergistic Radiation Protective Effect of Purified Auricularia auricular-judae Polysaccharide (AAP IV) with Grape Seed Procyanidins

by Haina Bai¹, Zhenyu Wang^1,2,*, Jie Cui^1,*, Keli Yun¹, Hua Zhang¹, Rui Hai Liu³, Ziluan Fan² and Cuilin Cheng¹

¹ School of Food Science and Engineering, Harbin Institute of Technology, 73 HuangHe Road, NanGang District, Harbin 150090, China

² School of Forestry, Northeast Forestry University, 26 HeXing Road, DongLi District, Harbin 150040, China

³ Department of Food Science, Cornell University, Ithaca, NY 14853, USA

Molecules 2014, 19(12), 20675-20694; https://doi.org/10.3390/molecules191220675 - 11 Dec 2014

Cited by 40 | Viewed by 6771

Abstract

The aim of this study was to investigate the synergistic antioxidant potential and protective effect of grape seed procyanidins (GSP) in combination with Auricularia auricular-judae polysaccharides (AAP IV) on radiation injury in splenocytes. Rat splenocyte irradiation resulted in significantly higher apoptosis rate, [...] Read more.

The aim of this study was to investigate the synergistic antioxidant potential and protective effect of grape seed procyanidins (GSP) in combination with Auricularia auricular-judae polysaccharides (AAP IV) on radiation injury in splenocytes. Rat splenocyte irradiation resulted in significantly higher apoptosis rate, malondialdehyde (MDA) (p < 0.005), reactive oxygen species (ROS) (p < 0.01); cell viability, total superoxide dismutase (T-SOD) (p < 0.01), catalase (CAT) (p < 0.01), glutathione peroxidase (GSH-P_X) (p < 0.05), activity and glutathione (GSH) (p < 0.01) levels were significantly reduced, compared with the control group. “GSP + AAP IV” treatment of rat splenocytes at doses of “GSP (0.3 μg/mL) + AAP IV (50 μg/mL)” displayed higher radioprotective and antioxidative effects than the administration of either GSP or AAP IV, as evident by lower levels of MDA (p < 0.001) concentration, as well as higher cell viability and T-SOD (p < 0.05), CAT (p < 0.005), GSH-P_X (p < 0.01) and GSH content compared to the radiation group. In addition, in vivo studies have shown that “GSP + AAP IV” significantly ameliorated the decrease of spleen index (p < 0.005) and spleen GSH (p < 0.005) levels and significantly inhibited the increase of MDA (p < 0.005) levels of spleen with radiation-induced damage, compared with the non-treated group. The in vivo and in vitro results suggested that GSP and AAP IV have a synergistic protective effect against radiation-induced injury by improving the antioxidant and immunomodulation activities. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 1126 KiB

Open AccessArticle

Photochemistry of Benzotriazoles: Generation of 1,3-Diradicals and Intermolecular Cycloaddition as a New Route toward Indoles and Dihydropyrrolo[3,4-b]Indoles

by Nader A. Al-Jalal^*, Maher R. Ibrahim, Nouria A. Al-Awadi, Mohamed H. Elnagdi and Yehia A. Ibrahim

Department of Chemistry, Faculty of Science, Kuwait University, P.O. Box 5969, Safat 13060, Kuwait

Molecules 2014, 19(12), 20695-20708; https://doi.org/10.3390/molecules191220695 - 11 Dec 2014

Cited by 18 | Viewed by 7426

Abstract

Irradiation of benzotriazoles 1a–e at λ = 254 nm in acetonitrile solution generated the corresponding 1,3-diradicals which underwent intermolecular cycloaddition with maleimides to afford the corresponding dihydropyrrolo[3,4-b]indoles and with acetylene derivatives to afford indoles as the major products. This [...] Read more.

Irradiation of benzotriazoles 1a–e at λ = 254 nm in acetonitrile solution generated the corresponding 1,3-diradicals which underwent intermolecular cycloaddition with maleimides to afford the corresponding dihydropyrrolo[3,4-b]indoles and with acetylene derivatives to afford indoles as the major products. This offers an interesting and simple access to such ring systems of potential synthetic and biological interest. The structures of the photoproducts were established spectroscopically and by single crystal X-ray crystallography. Full article

(This article belongs to the Section Organic Chemistry)

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22 pages, 909 KiB

Open AccessArticle

Chemically Synthesized Glycosides of Hydroxylated Flavylium Ions as Suitable Models of Anthocyanins: Binding to Iron Ions and Human Serum Albumin, Antioxidant Activity in Model Gastric Conditions

by Sheiraz Al Bittar¹, Nathalie Mora¹, Michèle Loonis² and Olivier Dangles^1,*

¹ University of Avignon, INRA, UMR408, Avignon 84000, France

² INRA, University of Avignon, UMR408, Avignon 84000, France

Molecules 2014, 19(12), 20709-20730; https://doi.org/10.3390/molecules191220709 - 11 Dec 2014

Cited by 17 | Viewed by 8072

Abstract

Polyhydroxylated flavylium ions, such as 3',4',7-trihydroxyflavylium chloride (P1) and its more water-soluble 7-O-β-d-glucopyranoside (P2), are readily accessible by chemical synthesis and suitable models of natural anthocyanins in terms of color and species distribution in aqueous solution. Owing to their catechol B-ring, [...] Read more.

Polyhydroxylated flavylium ions, such as 3',4',7-trihydroxyflavylium chloride (P1) and its more water-soluble 7-O-β-d-glucopyranoside (P2), are readily accessible by chemical synthesis and suitable models of natural anthocyanins in terms of color and species distribution in aqueous solution. Owing to their catechol B-ring, they rapidly bind Fe^III, weakly interact with Fe^II and promote its autoxidation to Fe^III. Both pigments inhibit heme-induced lipid peroxidation in mildly acidic conditions (a model of postprandial oxidative stress in the stomach), the colorless (chalcone) forms being more potent than the colored forms. Finally, P1 and P2 are moderate ligands of human serum albumin (HSA), their likely carrier in the blood circulation, with chalcones having a higher affinity for HSA than the corresponding colored forms. Full article

(This article belongs to the Special Issue Anthocyanins)

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20 pages, 3141 KiB

Open AccessArticle

Investigation of Dendriplexes by Ion Mobility-Mass Spectrometry

by Emma-Dune Leriche¹, Marie Hubert-Roux¹, Carlos Afonso¹, Catherine M. Lange¹, Martin C. Grossel², Florian Maire¹ and Corinne Loutelier-Bourhis^1,*

¹ Normandie Université, COBRA, UMR6014 and FR3038, Université de Rouen, CNRS, IRCOF, 1 rue Tesnière, 76821 Mont-Saint-Aignan Cedex, France

² School of Chemistry, University of Southampton, Highfield, Hants SO17 1BJ Southampton, UK

Molecules 2014, 19(12), 20731-20750; https://doi.org/10.3390/molecules191220731 - 12 Dec 2014

Cited by 2 | Viewed by 7260

Abstract

Highly branched polyamidoamine (PAMAM) dendrimers presenting biological activities have been envisaged as non-viral gene delivery vectors. They are known to associate with nucleic acid (DNA) in non-covalent complexes via electrostatic interactions. Although their transfection efficiency has been proved, PAMAMs present a significant cytotoxicity [...] Read more.

Highly branched polyamidoamine (PAMAM) dendrimers presenting biological activities have been envisaged as non-viral gene delivery vectors. They are known to associate with nucleic acid (DNA) in non-covalent complexes via electrostatic interactions. Although their transfection efficiency has been proved, PAMAMs present a significant cytotoxicity due to their cationic surface. To overcome such a drawback, different chemical modifications of the PAMAM surface have been reported such as the attachment of hydrophobic residues. In the present work, we studied the complexation of DNA duplexes with different low-generation PAMAM; ammonia-cored G0(N) and G1(N) PAMAM, native or chemically modified with aromatic residues, i.e., phenyl-modified-PAMAM G0(N) and phenylalanine-modified-PAMAM G1(N). To investigate the interactions involved in the PAMAM/DNA complexes, also called dendriplexes, we used electrospray ionization (ESI) coupled to ion mobility spectrometry-mass-spectrometry (IM-MS). ESI is known to allow the study of non-covalent complexes in native conditions while IM-MS is a bidimensional separation technique particularly useful for the characterization of complex mixtures. IM-MS allows the separation of the expected complexes, possible additional non-specific complexes and the free ligands. Tandem mass spectrometry (MS/MS) was also used for the structural characterization. This work highlights the contribution of IM-MS and MS/MS for the study of small dendriplexes. The stoichiometries of the complexes and the equilibrium dissociation constants were determined. The [DNA/native PAMAM] and [DNA/modified-PAMAM] dendriplexes were compared. Full article

(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)

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17 pages, 822 KiB

Open AccessArticle

Bio-Inspired Nitrile Hydration by Peptidic Ligands Based on L-Cysteine, L-Methionine or L-Penicillamine and Pyridine-2,6-dicarboxylic Acid

by Cillian Byrne^†, Kate M. Houlihan^†, Prarthana Devi, Paul Jensen and Peter J. Rutledge^*

¹ School of Chemistry F11, The University of Sydney, Sydney, NSW 2006, Australia

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 20751-20767; https://doi.org/10.3390/molecules191220751 - 12 Dec 2014

Cited by 8 | Viewed by 9702

Abstract

Nitrile hydratase (NHase, EC 4.2.1.84) is a metalloenzyme which catalyses the conversion of nitriles to amides. The high efficiency and broad substrate range of NHase have led to the successful application of this enzyme as a biocatalyst in the industrial syntheses of acrylamide [...] Read more.

Nitrile hydratase (NHase, EC 4.2.1.84) is a metalloenzyme which catalyses the conversion of nitriles to amides. The high efficiency and broad substrate range of NHase have led to the successful application of this enzyme as a biocatalyst in the industrial syntheses of acrylamide and nicotinamide and in the bioremediation of nitrile waste. Crystal structures of both cobalt(III)- and iron(III)-dependent NHases reveal an unusual metal binding motif made up from six sequential amino acids and comprising two amide nitrogens from the peptide backbone and three cysteine-derived sulfur ligands, each at a different oxidation state (thiolate, sulfenate and sulfinate). Based on the active site geometry revealed by these crystal structures, we have designed a series of small-molecule ligands which integrate essential features of the NHase metal binding motif into a readily accessible peptide environment. We report the synthesis of ligands based on a pyridine-2,6-dicarboxylic acid scaffold and L-cysteine, L-S-methylcysteine, L-methionine or L-penicillamine. These ligands have been combined with cobalt(III) and iron(III) and tested as catalysts for biomimetic nitrile hydration. The highest levels of activity are observed with the L-penicillamine ligand which, in combination with cobalt(III), converts acetonitrile to acetamide at 1.25 turnovers and benzonitrile to benzamide at 1.20 turnovers. Full article

(This article belongs to the Special Issue Peptide Chemistry)

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12 pages, 11472 KiB

Open AccessArticle

Up-Regulation of Urotensin II and Its Receptor Contributes to Human Hepatocellular Carcinoma Growth via Activation of the PKC, ERK1/2, and p38 MAPK Signaling Pathways

by Xiao-Tong Yu¹, Peng-Yan Wang², Zheng-Ming Shi³, Kun Dong⁴, Ping Feng¹, Hong-Xia Wang^1,* and Xue-Jiang Wang^1,*

¹ Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No.10 Xitoutiao, You An Men, Beijing 100069, China

² Department of Pathology, Peking Union Medical Hospital, Beijing 100692, China

³ Department of General Surgery, Beijing Jishuitan Hospital, Beijing 100031, China

⁴ Department of Pathology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China

Molecules 2014, 19(12), 20768-20779; https://doi.org/10.3390/molecules191220768 - 12 Dec 2014

Cited by 19 | Viewed by 6512

Abstract

Urotensin II (UII) and its receptor (UTR) have mitogenic effects on tumor growth. Our previous study demonstrated that the UII/UTR system is up-regulated in dithyinitrosamine-induced precancerous rat liver lesions. However, its role in human hepatocellular carcinoma remains unknown. In this study, the mRNA [...] Read more.

Urotensin II (UII) and its receptor (UTR) have mitogenic effects on tumor growth. Our previous study demonstrated that the UII/UTR system is up-regulated in dithyinitrosamine-induced precancerous rat liver lesions. However, its role in human hepatocellular carcinoma remains unknown. In this study, the mRNA and protein expression of UII and its receptor (UTR) in human hepatocellular carcinoma samples and in the BEL-7402 human hepatoma cell line were evaluated. In addition, the effect of exogenous UII on the pathways that regulate proliferation in BEL-7402 cells in vitro were determined. Liver sections were subjected to immunohistochemical staining. mRNA expression was detected by real-time polymerase chain reaction analysis, and protein levels were evaluated by western blotting. Proliferating cells were detected by BrdU incorporation. The expression of UII/UT mRNA and protein significantly increased in human hepatocellular carcinoma samples, and in BEL-7402 cells. Administration with UII increased the phosphorylation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein kinases (p38 MAPK). Furthermore, GF109203x, PD184352, and SB203580 partially abolished UII-induced proliferation of BEL-7402 cells. These results provide the first evidence that up-regulation of the UII/UT system may enhance proliferation of the human hepatoma cell line at least in part via PKC, ERK1/2, and p38 MAPK signaling pathways, and may provide novel therapeutic targets for inhibiting human hepatocellular carcinoma. Full article

(This article belongs to the Section Medicinal Chemistry)

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28 pages, 1338 KiB

Open AccessReview

Prodrug Strategies for Enhancing the Percutaneous Absorption of Drugs

by David D. N'Da

Centre of Excellence for Pharmaceutical Sciences (PHARMACEN), North-West University, Potchefstroom 2520, South Africa

Molecules 2014, 19(12), 20780-20807; https://doi.org/10.3390/molecules191220780 - 12 Dec 2014

Cited by 130 | Viewed by 22664

Abstract

The transdermal application of drugs has attracted increasing interest over the last decade or so, due to the advantages it offers, compared to other delivery methods. The development of an efficient means of transdermal delivery can increase drug concentrations, while reducing their systemic [...] Read more.

The transdermal application of drugs has attracted increasing interest over the last decade or so, due to the advantages it offers, compared to other delivery methods. The development of an efficient means of transdermal delivery can increase drug concentrations, while reducing their systemic distribution, thereby avoiding certain limitations of oral administration. The efficient barrier function of the skin, however, limits the use of most drugs as transdermal agents. This limitation has led to the development of various strategies to enhance drug-skin permeation, including the use of penetration enhancers. This method unfortunately has certain proven disadvantages, such as the increased absorption of unwanted components, besides the drug, which may induce skin damage and irritancy. The prodrug approach to increase the skin’s permeability to drugs represents a very promising alternative to penetration enhancers. The concept involves the chemical modification of a drug into a bioreversible entity that changes both its pharmaceutical and pharmacokinetic characteristics to enhance its delivery through the skin. In this review; we report on the in vitro attempts and successes over the last decade by using the prodrug strategy for the percutaneous delivery of pharmacological molecules. Full article

(This article belongs to the Special Issue Prodrugs)

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13 pages, 794 KiB

Open AccessArticle

Optimization of Ultrasonic-Assisted Extraction of Cordycepin from Cordyceps militaris Using Orthogonal Experimental Design

by Hsiu-Ju Wang¹, Meng-Chun Pan², Chao-Kai Chang³

, Shu-Wei Chang² and Chang-Wei Hsieh^2,*

¹ Department of Hospitality Management, Mingdao University, 369 Wen-Hua Rd, Peetow, Chang-Hua 52345, Taiwan

² Department of Medicinal Botanicals and Health Applications, Da-Yen University, 168 University Rd, Dacun, Chang-Hua 51591, Taiwan

³ Department of BioIndustry Technology, Da-Yeh University, 168 University Rd, Dacun, Chang-Hua 51591, Taiwan

Molecules 2014, 19(12), 20808-20820; https://doi.org/10.3390/molecules191220808 - 12 Dec 2014

Cited by 74 | Viewed by 14898

Abstract

This study reports on the optimization of the extraction conditions of cordycepin from Cordyceps militaris by using ultrasonication. For this purpose, the orthogonal experimental design was used to investigate the effects of factors on the ultrasonic-assisted extraction (UAE). Four factors: extraction time (min), [...] Read more.

This study reports on the optimization of the extraction conditions of cordycepin from Cordyceps militaris by using ultrasonication. For this purpose, the orthogonal experimental design was used to investigate the effects of factors on the ultrasonic-assisted extraction (UAE). Four factors: extraction time (min), ethanol concentration (%), extraction temperature (°C) and extraction frequency (kHz), were studied. The results showed that the highest cordycepin yield of 7.04 mg/g (86.98% ± 0.23%) was obtained with an extraction time of 60 min, ethanol concentration of 50%, extraction temperature of 65 °C and extraction frequency of 56 kHz. It was found that the cordycepin extraction yield increased with the effect of ultrasonication during the extraction process. Therefore, UAE can be used as an alternative to conventional immersion extraction with respect to the recovery of cordycepin from C. militaris, with the advantages of shorter extraction time and reduced solvent consumption. Full article

(This article belongs to the Section Natural Products Chemistry)

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18 pages, 1875 KiB

Open AccessArticle

Antioxidant Properties of Pyroligneous Acid Obtained by Thermochemical Conversion of Schisandra chinensis Baill

by Chunhui Ma^1,2

, Wei Li²

, Yuangang Zu¹, Lei Yang^1,* and Jian Li^2,*

¹ State Engineering Laboratory for Bioresource Eco-Utilization, Northeast Forestry University, Harbin 150040, China

² College of Material Science and Engineering, Northeast Forestry University, Harbin 150040, China

Molecules 2014, 19(12), 20821-20838; https://doi.org/10.3390/molecules191220821 - 12 Dec 2014

Cited by 28 | Viewed by 8043

Abstract

Sustainable development of renewable resources is a major challenge globally. Biomass is an important renewable energy source and an alternative to fossil fuels. Pyrolysis of biomass is a promising method for simultaneous production of biochar, bio-oil, pyroligneous acid (PA), and gaseous fuels. The [...] Read more.

Sustainable development of renewable resources is a major challenge globally. Biomass is an important renewable energy source and an alternative to fossil fuels. Pyrolysis of biomass is a promising method for simultaneous production of biochar, bio-oil, pyroligneous acid (PA), and gaseous fuels. The purpose of this study was to investigate the pyrolysis process and products yields of Schisandra chinensis fruits with different pyrolysis powers. The obtained PA was extracted with organic solvents, including ethyl formate, dichloromethane, methanol and tetrahydrofuran. The antioxidant activities, including the free radical scavenging activity and ferric reducing power, of the PA extracts were investigated. The synthetic antioxidants butylated hydroxyanisole and butylated hydroxytoluene were used as positive controls. A dichloromethane extract of PA showed excellent antioxidant properties compared to the other extracts. The chemical compositions of the PA extracts were determined by GC-MS, and further proved that the dichloromethane extract had the best antioxidant characteristics among the extracts tested. Full article

(This article belongs to the Section Natural Products Chemistry)

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25 pages, 888 KiB

Open AccessReview

Hybrid Curcumin Compounds: A New Strategy for Cancer Treatment

by Marie-Hélène Teiten¹, Mario Dicato¹ and Marc Diederich^2,*

¹ Laboratory of Molecular and Cellular Biology of Cancer (LBMCC), Hôpital Kirchberg, 9, Rue Edward Steichen, Luxembourg L-2540, Luxembourg

² Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea

Molecules 2014, 19(12), 20839-20863; https://doi.org/10.3390/molecules191220839 - 12 Dec 2014

Cited by 117 | Viewed by 16528

Abstract

Cancer is a multifactorial disease that requires treatments able to target multiple intracellular components and signaling pathways. The natural compound, curcumin, was already described as a promising anticancer agent due to its multipotent properties and huge amount of molecular targets in vitro. [...] Read more.

Cancer is a multifactorial disease that requires treatments able to target multiple intracellular components and signaling pathways. The natural compound, curcumin, was already described as a promising anticancer agent due to its multipotent properties and huge amount of molecular targets in vitro. Its translation to the clinic is, however, limited by its reduced solubility and bioavailability in patients. In order to overcome these pharmacokinetic deficits of curcumin, several strategies, such as the design of synthetic analogs, the combination with specific adjuvants or nano-formulations, have been developed. By taking into account the risk-benefit profile of drug combinations, as well as the knowledge about curcumin’s structure-activity relationship, a new concept for the combination of curcumin with scaffolds from different natural products or components has emerged. The concept of a hybrid curcumin molecule is based on the incorporation or combination of curcumin with specific antibodies, adjuvants or other natural products already used or not in conventional chemotherapy, in one single molecule. The high diversity of such conjugations enhances the selectivity and inherent biological activities and properties, as well as the efficacy of the parental compound, with particular emphasis on improving the efficacy of curcumin for future clinical treatments. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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16 pages, 753 KiB

Open AccessReview

Relevance of the Anti-Inflammatory Properties of Curcumin in Neurodegenerative Diseases and Depression

by Yousef Tizabi^*, Laura L. Hurley, Zakiya Qualls and Luli Akinfiresoye

Department of Pharmacology, College of Medicine, Howard University, Washington, DC 20059, USA

Molecules 2014, 19(12), 20864-20879; https://doi.org/10.3390/molecules191220864 - 12 Dec 2014

Cited by 69 | Viewed by 21659

Abstract

This review is an attempt to summarize our current understanding of curcumin’s potential as a neuroprotectant and an antidepressant. This dual property confers a unique advantage to this herbal medication, believed to be devoid of any major side effects, to combat commonly observed [...] Read more.

This review is an attempt to summarize our current understanding of curcumin’s potential as a neuroprotectant and an antidepressant. This dual property confers a unique advantage to this herbal medication, believed to be devoid of any major side effects, to combat commonly observed co-morbid conditions of a neurodegenerative and a neuropsychiatric disorder. Moreover, in line with the theme of this series, the role of inflammation and stress in these diseases and possible anti-inflammatory effects of curcumin, as well as its interaction with signal transduction proteins as a common denominator in its varied mechanisms of action, are also discussed. Thus, following a brief introduction of curcumin’s pharmacology, we present research suggesting how its anti-inflammatory properties have therapeutic potential in treating a devastating neurological disorder (Parkinson’s disease = PD) and a debilitating neuropsychiatric disorder (major depressive disorder = MDD). It is concluded that curcumin, or better yet, an analog with better and longer bioavailability could be of important therapeutic potential in PD and/or major depression. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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8 pages, 721 KiB

Open AccessArticle

Two New Coumarins from Talaromyces flavus

by Jun-Wei He^1,2,†, Da-Peng Qin^1,†, Hao Gao¹, Run-Qiao Kuang¹, Yang Yu^1,*, Xing-Zhong Liu³ and Xin-Sheng Yao^1,*

¹ Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China

² Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China

³ State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 20880-20887; https://doi.org/10.3390/molecules191220880 - 12 Dec 2014

Cited by 19 | Viewed by 6199

Abstract

Two new coumarins, talacoumarins A (1) and B (2), were isolated from the ethyl acetate extract of the wetland soil-derived fungus Talaromyces flavus BYD07-13. Their structures were elucidated by spectroscopic data (NMR, MS) analyses. The absolute configuration of C-12 [...] Read more.

Two new coumarins, talacoumarins A (1) and B (2), were isolated from the ethyl acetate extract of the wetland soil-derived fungus Talaromyces flavus BYD07-13. Their structures were elucidated by spectroscopic data (NMR, MS) analyses. The absolute configuration of C-12 in 1 was assigned using the modified Mosher’s method, whereas that of C-12 in 2 was deduced via the circular dichroism data of its corresponding [Rh₂(OCOCF₃)₄] complex. Compounds 1 and 2 were evaluated for their anti-Aβ₄₂ aggregation, cytotoxic, and antimicrobial activities. The results showed that the two compounds had moderate anti-Aβ₄₂ aggregation activity, and this is the first report on the Aβ₄₂ inhibitory aggregation activity of coumarins. Full article

(This article belongs to the Section Natural Products Chemistry)

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18 pages, 2157 KiB

Open AccessArticle

Combined Dynamic Light Scattering and Raman Spectroscopy Approach for Characterizing the Aggregation of Therapeutic Proteins

by E. Neil Lewis^*, Wei Qi, Linda H. Kidder, Samiul Amin, Stacy M. Kenyon and Steven Blake

Malvern Biosciences Inc., 7221 Lee Deforest Drive, Suite 300, Columbia, MD 21046, USA

Molecules 2014, 19(12), 20888-20905; https://doi.org/10.3390/molecules191220888 - 12 Dec 2014

Cited by 39 | Viewed by 12008

Abstract

Determination of the physicochemical properties of protein therapeutics and their aggregates is critical for developing formulations that enhance product efficacy, stability, safety and manufacturability. Analytical challenges are compounded for materials: (1) that are formulated at high concentration, (2) that are formulated with a [...] Read more.

Determination of the physicochemical properties of protein therapeutics and their aggregates is critical for developing formulations that enhance product efficacy, stability, safety and manufacturability. Analytical challenges are compounded for materials: (1) that are formulated at high concentration, (2) that are formulated with a variety of excipients, and (3) that are available only in small volumes. In this article, a new instrument is described that measures protein secondary and tertiary structure, as well as molecular size, over a range of concentrations and formulation conditions of low volume samples. Specifically, characterization of colloidal and conformational stability is obtained through a combination of two well-established analytical techniques: dynamic light scattering (DLS) and Raman spectroscopy, respectively. As the data for these two analytical modalities are collected on the same sample at the same time, the technique enables direct correlation between them, in addition to the more straightforward benefit of minimizing sample usage by providing multiple analytical measurements on the same aliquot non-destructively. The ability to differentiate between unfolding and aggregation that the combination of these techniques provides enables insights into underlying protein aggregation mechanisms. The article will report on mechanistic insights for aggregation that have been obtained from the application of this technique to the characterization of lysozyme, which was evaluated as a function of concentration and pH. Full article

(This article belongs to the Special Issue Advances of Vibrational Spectroscopic Technologies in Life Sciences)

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7 pages, 711 KiB

Open AccessArticle

Total Synthesis and Anti-Viral Activities of an Extract of Radix isatidis

by Li-Wei He¹, Hua-Qing Liu², Yu-Qing Chen¹, Jing-Yan Yang¹, Tian-Lin Wang^1,* and Wei Li^1,*

¹ School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China

² The Second Hospital of Nanjing, 1-1 ZhongFu Road, Nanjing 210003, China

Molecules 2014, 19(12), 20906-20912; https://doi.org/10.3390/molecules191220906 - 12 Dec 2014

Cited by 21 | Viewed by 6480

Abstract

Radix isatidis (Banlangen), a famous traditional Chinese medicine, has been used for thousands of years in China due to its anti-viral activity. Through our research, we inferred that the anti-viral activity of Radix isatidis depended on the water-soluble part. Among the components of [...] Read more.

Radix isatidis (Banlangen), a famous traditional Chinese medicine, has been used for thousands of years in China due to its anti-viral activity. Through our research, we inferred that the anti-viral activity of Radix isatidis depended on the water-soluble part. Among the components of this extract, the isoquinoline derivative 1 was isolated for the first time and has shown better anti-viral activity than other constituents. In this study, to solve the problem of sourcing sufficient quantities of compound 1, a total synthesis route is described, and several analogues are also evaluated for their anti-viral activities. Among them, compound 8 shown potent anti-viral activity with an IC₅₀ value of 15.3 µg/mL. The results suggested that isoquinoline derivatives possessed potent anti-viral activity and are worthy further development. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 961 KiB

Open AccessArticle

An Insecticidal Compound Produced by an Insect-Pathogenic Bacterium Suppresses Host Defenses through Phenoloxidase Inhibition

by Ihsan Ullah¹, Abdul Latif Khan², Liaqat Ali², Abdur Rahim Khan¹, Muhammad Waqas¹, In-Jung Lee¹ and Jae-Ho Shin^1,*

¹ School of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University, Daegu 702-701, Korea

² Department of Biological Science and Chemistry, University of Nizwa, Nizwa 616, Oman

Molecules 2014, 19(12), 20913-20928; https://doi.org/10.3390/molecules191220913 - 12 Dec 2014

Cited by 35 | Viewed by 7450

Abstract

A bioassay-guided column chromatographic strategy was adopted in the present study to fractionate the culture extract of Photorhabdus temperata M1021 to identify potential insecticidal and antimicrobial compounds. An ethyl acetate (EtOAc) culture extract of P. temperata was assayed against Galleria mellonella larvae through [...] Read more.

A bioassay-guided column chromatographic strategy was adopted in the present study to fractionate the culture extract of Photorhabdus temperata M1021 to identify potential insecticidal and antimicrobial compounds. An ethyl acetate (EtOAc) culture extract of P. temperata was assayed against Galleria mellonella larvae through intra-hemocoel injection and exhibited 100% insect mortality within 60 h. The EtOAc fraction and an isolated compound exhibited phenoloxidase (PO) inhibition of up to 60% and 63%, respectively. The compound was identified as 1,2-benzenedicarboxylic acid (phthalic acid, PA) by gas chromatography-mass spectrometry and nuclear magnetic resonance. PA exhibited insecticidal activity against G. mellonella in a dose-dependent manner, and 100% insect mortality was observed at 108 h after injection of 1 M PA. In a PO inhibition assay, 0.5 and 1 M concentrations of PA were found to inhibit PO activity by 74% and 82%, respectively; and in a melanotic nodule formation assay, nodule formation was significantly inhibited (27 and 10 nodules) by PA (0.5 and 1 M, respectively). PA was furthermore found to have substantial antioxidant activity and maximum antioxidant activity was 64.7% for 0.5 M PA as compare to control. Antibacterial activity was assessed by The MIC values ranged from 0.1 M to 0.5 M of PA. This study reports a multifunctional PA, a potential insecticidal agent, could a factor of insect mortality along with other toxins produced by P. temperata M1021. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 802 KiB

Open AccessArticle

The Biological Activities of Cinnamon, Geranium and Lavender Essential Oils

by Monika Sienkiewicz^1,*

, Anna Głowacka¹, Edward Kowalczyk², Anna Wiktorowska-Owczarek², Marta Jóźwiak-Bębenista² and Monika Łysakowska³

¹ Environmental Biology Department, Medical University of Lodz, ul Żeligowskiego 7/9, Lodz 90-752, Poland

² Pharmacology and Toxicology Department, Medical University of Lodz, ul Żeligowskiego 7/9, Lodz 90-752, Poland

³ Department of Microbiology and Medical Laboratory Immunology, Medical University of Lodz, ul Pomorska 251, Lodz 92-213, Poland

Molecules 2014, 19(12), 20929-20940; https://doi.org/10.3390/molecules191220929 - 12 Dec 2014

Cited by 56 | Viewed by 14897

Abstract

Acinetobacter sp. represent an important cause of nosocomial infections. Their resistance to some antibiotics, their ability to survive on inanimate surfaces in the hospital environment and their ability to produce biofilms contributes to their virulence. The aim of the study was to determine [...] Read more.

Acinetobacter sp. represent an important cause of nosocomial infections. Their resistance to some antibiotics, their ability to survive on inanimate surfaces in the hospital environment and their ability to produce biofilms contributes to their virulence. The aim of the study was to determine the antibacterial properties of cinnamon, lavender and geranium essential oils against bacteria of the genus Acinetobacter isolated from several clinical materials and from the hospital environment. A comprehensive evaluation of the susceptibility of Acinetobacter sp. clinical strains to recommended antibiotics was performed. The constituents of cinnamon, lavender and geranium essential oils were identified by GC-FID-MS analysis, and their Minimal Inhibitory Concentrations (MICs) against tested clinical strains were determined by the micro-dilution broth method. In addition, the effects of essential oils on the viability of human microvascular endothelial cells (HMEC-1) and glioblastoma cell line (T98G) were evaluated. Cinnamon bark oil was the most active against clinical and environmental strains of Acinetobacter baumannii with MIC values ranging from 0.5 to 2.5 µL/mL. The MIC values for geranium oil were between 7.5 and 9.5 µL/mL, and between 10.5 and 13.0 µL/mL for lavender oil. These essential oils can be best employed in the fight against infections caused by bacteria from Acinetobacter genus as components of formulations for hygiene and disinfection of hospital environment. Full article

(This article belongs to the Collection Bioactive Compounds)

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21 pages, 1680 KiB

Open AccessArticle

Evaluation of the Efficiency of Different Disruption Methods on Yeast Cell Wall Preparation for β-Glucan Isolation

by Anna Bzducha-Wróbel^1,*, Stanisław Błażejak¹, Anna Kawarska¹, Lidia Stasiak-Różańska¹, Iwona Gientka¹ and Ewa Majewska²

¹ Department of Biotechnology, Microbiology and Food Evaluation, Warsaw University of Life Sciences-SGGW, Nowoursynowska 159c, Warsaw 02-776, Poland

² Department of Chemistry, Warsaw University of Life Sciences-SGGW, Nowoursynowska 159c, Warsaw 02-776, Poland

Molecules 2014, 19(12), 20941-20961; https://doi.org/10.3390/molecules191220941 - 15 Dec 2014

Cited by 83 | Viewed by 16282

Abstract

Selected methods for yeast cell disruption were evaluated to establish their suitability for cell wall preparation in the process of β-glucan isolation. The effect of different disruption methods on contents of total saccharides, β-glucans and proteins in the produced cell walls preparations was [...] Read more.

Selected methods for yeast cell disruption were evaluated to establish their suitability for cell wall preparation in the process of β-glucan isolation. The effect of different disruption methods on contents of total saccharides, β-glucans and proteins in the produced cell walls preparations was analyzed. The degree of cell wall purification from intracellular components was established on the basis of the ratio of solubilised material. The investigated methods included: cell exposure to hot water (autoclaving), thermally-induced autolysis, homogenization in a bead mill, sonication and their combinations. Experimental systems were prepared in water (pH 5.0 and pH 7.0) and Tris-HCl buffer (pH 8.0). The Saccharomyces cerevisiae yeast cell wall preparations with the highest degree of cytosol component release and purification of β-glucans were produced by 30 min of cell homogenization with zirconium-glass beads (0.5 mm in diameter). This was confirmed by the highest ratio of solubilised material (approx. 64%–67%). The thus-produced preparations contained ca. 60% of total saccharides, 13%–14% of β(1,3)/(1,6)-glucans, and approx. 35% of crude proteins. Similar results were obtained after autolysis coupled with bead milling as well as with sonication, but the time required for these processes was more than 24 h. Homogenization in a bead mill could be valuable for general isolation procedures because allows one to eliminate the different autolytic activity of various yeast strains. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 744 KiB

Open AccessArticle

Aortic Relaxant Activity of Crataegus gracilior Phipps and Identification of Some of Its Chemical Constituents

by Abigail Hernández-Pérez¹, Moustapha Bah^1,*, César Ibarra-Alvarado¹, José Fausto Rivero-Cruz², Alejandra Rojas-Molina¹, Juana Isela Rojas-Molina¹ and José Alejandro Cabrera-Luna³

¹ Posgrado en Ciencias Químico Biológicas, Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario, Cerro de las Campanas, Querétaro 76010, Qro., Mexico

² Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Circuito exterior, Coyoacán 04510, Mexico D.F., Mexico

³ Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Campus Juriquilla, Avenida de Las Ciencias S/N, Delegación Santa Rosa Jáuregui, Querétaro 76230, Qro., Mexico

Molecules 2014, 19(12), 20962-20974; https://doi.org/10.3390/molecules191220962 - 15 Dec 2014

Cited by 23 | Viewed by 7125

Abstract

This study focused on the assessment of the vasorelaxant activity of the organic and aqueous extracts obtained from leaves and fruits of a Mexican hawthorn (Crataegus gracilior) on isolated rat aorta, and on the purification and identification of some of their [...] Read more.

This study focused on the assessment of the vasorelaxant activity of the organic and aqueous extracts obtained from leaves and fruits of a Mexican hawthorn (Crataegus gracilior) on isolated rat aorta, and on the purification and identification of some of their secondary metabolites by the use of chromatographic and spectroscopic techniques. The results obtained showed that the methanol extract has a significantly more potent and effective vasorelaxant effect than the other tested extracts, with an EC₅₀ = 8.69 ± 4.34 µg/mL and an E_max = 94.6% ± 11.30%, values that are close to that of acetylcholine, the positive control. From the same extract, two major triterpenes were isolated and identified as ursolic and corosolic acids by comparison of their experimental NMR spectroscopic data with those reported in the literature. Chlorogenic acid, rutin, quercetin, kaempferol and (+)-catechin were also identified using HPLC coupled with PDAD. All these compounds have already been proven to possess on their own antihypertensive effect and other benefits on cardiovascular diseases and they can support, at least in part, the traditional use of this plant species. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 755 KiB

Open AccessArticle

Four New Furostanol Saponins from the Rhizomes and Roots of Smilax scobinicaulis and Their Cytotoxicity

by Jing Xu^1,3, Shixiu Feng², Qi Wang¹, Yingli Cao¹, Miao Sun¹ and Cunli Zhang^1,*

¹ College of Life Science, Northwest A&F University, Yangling 712100, Shaanxi, China

² Key Laboratory of Southern Subtropical Plant Diversity, Shenzhen Fairy Lake Botanical Garden, Chinese Academy of Sciences, 160 Xianhu Road, Liantang, Shenzhen 518004, China

³ Shenzhen Boton Flavors & Fragrances Co., Ltd., 19 Daxin Road, Nanshan, Shenzhen 518051, China

Molecules 2014, 19(12), 20975-20987; https://doi.org/10.3390/molecules191220975 - 15 Dec 2014

Cited by 7 | Viewed by 5913

Abstract

Four new furostanol saponins 1–4, along with two known furostanol saponins 5 and 6 and one known spirostanol saponin 7 were isolated from the rhizomes and roots of Smilax scobinicaulis. The structures of the new saponins were elucidated as [...] Read more.

Four new furostanol saponins 1–4, along with two known furostanol saponins 5 and 6 and one known spirostanol saponin 7 were isolated from the rhizomes and roots of Smilax scobinicaulis. The structures of the new saponins were elucidated as 26-O-β-D-glucopyranoside-3β,26-dihydroxy-(25R)-5α-furostan-22-methoxyl-6-one-3-O-α-L-arabinopyranosyl-(1→6)-β-D-glucopyranoside (1), 26-O-β-D-glucopyranoside-3β,26-dihydroxy-(25R)-5α-furostan-22-methoxyl-6-one (2), 26-O-β-D-glucopyranoside-3β,26-dihydroxy-(25R)-5α-furostan-20(22)-en-6-one (3), 26-O-β-D-glucopyranoside-3β,23,26-trihydroxy-(23R, 25R)-5α-furostan-20(22)-en-6-one (4) on the basis of spectroscopic analysis. The isolated saponins were evaluated for cytotoxic activity against two human cancer cell lines including Hela (cervical carcinoma) and SMMC-7221 (hepatocellular carcinoma). Compounds 1 and 7 demonstrated cytotoxicity against the tested cell lines. Full article

(This article belongs to the Section Natural Products Chemistry)

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34 pages, 3572 KiB

Open AccessArticle

Comparative Study of the Structural and Vibroelectronic Properties of Porphyrin and Its Derivatives

by Metin Aydin

Department of Chemistry, Faculty of Art and Sciences, Ondokuz Mayıs University, Samsun 55139, Turkey

Molecules 2014, 19(12), 20988-21021; https://doi.org/10.3390/molecules191220988 - 15 Dec 2014

Cited by 30 | Viewed by 7589

Abstract

Density functional theory (DFT and time-dependent-DFT (TD-DFT) were employed to investigate the vibroelectronic structural properties of porphyrin and some derivatives: unsubstituted porphyrin (TPyr), meso-tetraphenylporphyrin (TPP), meso-tetrakis(p-sulfonatophenyl)porphyrin (TSPP), protonated-TPyr (H₂TPyr), deuterated-H₂TPyr (D₄TPyr), protonated-TPP (H [...] Read more.

Density functional theory (DFT and time-dependent-DFT (TD-DFT) were employed to investigate the vibroelectronic structural properties of porphyrin and some derivatives: unsubstituted porphyrin (TPyr), meso-tetraphenylporphyrin (TPP), meso-tetrakis(p-sulfonatophenyl)porphyrin (TSPP), protonated-TPyr (H₂TPyr), deuterated-H₂TPyr (D₄TPyr), protonated-TPP (H₂TPP) and deuterated-H₂TPP (D₄TPP), protonated TSPP (H₂TSPP), deuterated-H₂TSPP (D₄TSPP), dicationic TSPP (H₆TSPP) and deuterated-H₆TSPP (D₈TSPP). The possible internal conversion (IC) and intersystem crossing (ISC) processes of these compounds were investigated. Finally, the relaxed ground state potential energy surface (PES) (S₀), and singlet (S_n, n = 1–24) and triplet (T_n) excited state PESs of the TSPP molecule were calculated as function of the dihedral angle (C_α-C_m-C_ϕ-C(ph)) rotation. The results of the calculations indicated that while the meso-substitutions caused a significant shift in frequencies when the meso-carbons within the parent-porphine (or TPyr) are involved in the vibrational motion of molecules; the protonation of the N atoms at the porphine/porphyrin core causes a significant blue shift when the H on the N atoms within the pyrroline are dominantly involved in the vibrational motions. The deuteration of N atoms not only caused a red-shift in the frequencies of the corresponding peaks below 1600 cm⁻¹, but also produced new vibrational modes of frequencies in the 2565–2595 cm⁻¹ range caused by the N-D bond stretching. Similarly, the deuteration of O atoms within the sulfonato groups (-SO₃⁻) exhibited a new peak at around 2642 cm⁻¹ due to O-D bond stretching. The measured Raman spectrum of the H₂TSPP is assigned based on the predicted Raman spectra of the compounds studied here and measured Raman spectrum of the TPP (from our previous work). The IR spectrum is assigned based on our calculations and measured IR spectra obtained from the literature. The results of the TD-DFT calculations did not only indicate that the meso-substitution and protonation of the porphyrin bring about a significant read shift in the electronic transitions; but also provided a strong evidence for the IC from the Soret band to Q-bands beside possibility of the ISC process; its existence depend on the other excited state process such as much faster vibrational relaxation; the IC and etc. The ground state PES curve (S₀) of the ionic TSPP exhibited two minima at the dihedral angle (C_α-C_m-C_ϕ-C) of about 66° (corresponds to the lowest ground state) and 110° (corresponds to next energetically stable state or the local minima). The energy deference between these two minima is 0.0132 eV (or 106 cm⁻¹) and the highest potential energy barrier when undergoing from the lowest ground state to this local state is only 0.0219 eV (177 cm⁻¹; which is compatible with the thermal energy (kT) at 298 K is 207.2 cm⁻¹. Full article

(This article belongs to the Special Issue Advances of Vibrational Spectroscopic Technologies in Life Sciences)

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12 pages, 727 KiB

Open AccessArticle

Efficient Synthesis and Reaction Kinetics of Readily Water Soluble Esters Containing Sulfonic Groups

by Krzysztof R. Idzik^*, Karsten Nödler, Friedrich Maier and Tobias Licha

Department Applied Geology, Geoscience Centre of the University of Göttingen, Goldschmidtstrasse 3, Göttingen 37077, Germany

Molecules 2014, 19(12), 21022-21033; https://doi.org/10.3390/molecules191221022 - 15 Dec 2014

Cited by 4 | Viewed by 7323

Abstract

A series of various readily water soluble esters were synthesized by a very efficient procedure. These compounds can be useful as thermosensitive tracers for studying the cooling progress in a low enthalpy georeservoir exploitable by double flash geothermal power plant systems. The kinetics [...] Read more.

A series of various readily water soluble esters were synthesized by a very efficient procedure. These compounds can be useful as thermosensitive tracers for studying the cooling progress in a low enthalpy georeservoir exploitable by double flash geothermal power plant systems. The kinetics of their hydrolysis was investigated. Acylation of primary alcohols or phenols was carried out by a method based on a single-phase solvent system consisting of ethyl acetate acting as an organic solvent and triethylamine acting as a catalyst. Products were characterized by ¹H-NMR, and ¹³C-NMR. Full article

(This article belongs to the Section Organic Chemistry)

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10 pages, 885 KiB

Open AccessArticle

Stability of Anthocyanins from Red Grape Skins under Pressurized Liquid Extraction and Ultrasound-Assisted Extraction Conditions

by Ali Liazid¹, Gerardo F. Barbero¹

, Latifa Azaroual², Miguel Palma^1,* and Carmelo G. Barroso¹

¹ Department of Analytical Chemistry, University of Cadiz, Puerto Real 11510, Spain

² Faculty of Sciences, Abdelmalek Essaâdi University, Tetouan 93000, Morocco

Molecules 2014, 19(12), 21034-21043; https://doi.org/10.3390/molecules191221034 - 15 Dec 2014

Cited by 27 | Viewed by 6818

Abstract

The stability of anthocyanins from grape skins after applying different extraction techniques has been determined. The following compounds, previously extracted from real samples, were assessed: delphinidin 3-glucoside, cyanidin 3-glucoside, petunidin 3-glucoside, peonidin 3-glucoside, malvidin 3-glucoside, peonidin 3-acetylglucoside, malvidin 3-acetylglucoside, malvidin 3-caffeoylglucoside, petunidin 3- [...] Read more.

The stability of anthocyanins from grape skins after applying different extraction techniques has been determined. The following compounds, previously extracted from real samples, were assessed: delphinidin 3-glucoside, cyanidin 3-glucoside, petunidin 3-glucoside, peonidin 3-glucoside, malvidin 3-glucoside, peonidin 3-acetylglucoside, malvidin 3-acetylglucoside, malvidin 3-caffeoylglucoside, petunidin 3-p-coumaroylglucoside and malvidin 3-p-coumaroylglucoside (trans). The techniques used were ultrasound-assisted extraction and pressurized liquid extraction. In ultrasound-assisted extraction, temperatures up to 75 °C can be applied without degradation of the aforementioned compounds. In pressurized liquid extraction the anthocyanins were found to be stable up to 100 °C. The relative stabilities of both the glycosidic and acylated forms were evaluated. Acylated derivatives were more stable than non-acylated forms. The differences between the two groups of compounds became more marked on working at higher temperatures and on using extraction techniques with higher levels of oxygen in the extraction media. Full article

(This article belongs to the Special Issue Anthocyanins)

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22 pages, 817 KiB

Open AccessArticle

Antiprotozoal Activity against Entamoeba histolytica of Plants Used in Northeast Mexican Traditional Medicine. Bioactive Compounds from Lippia graveolens and Ruta chalepensis

by Ramiro Quintanilla-Licea^1,*, Benito David Mata-Cárdenas², Javier Vargas-Villarreal³, Aldo Fabio Bazaldúa-Rodríguez¹, Isvar Kavimngeles-Hernández¹, Jesús Norberto Garza-González³ and Magda Elizabeth Hernández-García³

¹ Universidad Autónoma de Nuevo León, UANL, Facultad de Ciencias Biológicas, Av. Universidad S/N, Cd. Universitaria, San Nicolás de los Garza, C.P. 66451 Nuevo León, Mexico

² Universidad Autónoma de Nuevo León, UANL, Facultad de Ciencias Químicas, Av. Universidad S/N, Cd. Universitaria, San Nicolás de los Garza, C.P. 66451 Nuevo León, Mexico

³ Laboratorio de Bioquímica y Biología Celular, Centro de Investigaciones Biomédicas del Noreste (CIBIN), Dos de abril esquina con San Luis Potosí, C.P. 64720 Monterrey, Mexico

Molecules 2014, 19(12), 21044-21065; https://doi.org/10.3390/molecules191221044 - 15 Dec 2014

Cited by 37 | Viewed by 12755

Abstract

Amoebiasis caused by Entamoeba histolytica is associated with high morbidity and mortality is becoming a major public health problem worldwide, especially in developing countries. Because of the side-effects and the resistance that pathogenic protozoa build against the standard antiparasitic drugs, e.g., metronidazole, much [...] Read more.

Amoebiasis caused by Entamoeba histolytica is associated with high morbidity and mortality is becoming a major public health problem worldwide, especially in developing countries. Because of the side-effects and the resistance that pathogenic protozoa build against the standard antiparasitic drugs, e.g., metronidazole, much recent attention has been paid to plants used in traditional medicine around the world in order to find new antiprotozoal agents. We collected 32 plants used in Northeast Mexican traditional medicine and the methanolic extracts of these species were screened for antiprotozoal activity against E. histolytica trophozoites using in vitro tests. Only 18 extracts showed a significant inhibiting activity and among them six plant extracts showed more than 80% growth inhibition against E. histolytica at a concentration of 150 µg/mL and the IC₅₀ values of these extracts were determined. Lippia graveolens Kunth and Ruta chalepensis Pers. showed the more significant antiprotozoal activity (91.54% and 90.50% growth inhibition at a concentration of 150 µg/mL with IC₅₀ values of 59.14 and 60.07 µg/mL, respectively). Bioassay-guided fractionation of the methanolic extracts from these two plants afforded carvacrol (1) and chalepensin (2), respectively, as bioactive compounds with antiprotozoal activity. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

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19 pages, 1585 KiB

Open AccessArticle

Obtaining Ready-to-Eat Blue Corn Expanded Snacks with Anthocyanins Using an Extrusion Process and Response Surface Methodology

by Anayansi Escalante-Aburto¹, Benjamín Ramírez-Wong^1,*, Patricia Isabel Torres-Chávez¹, Jaime López-Cervantes², Juan De Dios Figueroa-Cárdenas³, Jesús Manuel Barrón-Hoyos¹, Ignacio Morales-Rosas¹, Néstor Ponce-García^1,4 and Roberto Gutiérrez-Dorado⁵

¹ Programa de Doctorado en Ciencias de los Alimentos, Universidad de Sonora, Blvd. Luis Encinas y Rosales s/n, Hermosillo, Sonora 83000, Mexico

² Centro de Investigación e Innovación en Biotecnología Agropecuaria, Instituto Tecnológico de Sonora, 5 de Febrero 818 Sur, Col. Centro, Ciudad Obregón, Sonora 8500, Mexico

³ Centro de Investigación y Estudios Avanzados (CINVESTAV—Unidad Querétaro), Libramiento Norponiente#2000, Fraccionamiento Real de Juriquilla, Querétaro, Querétaro 76230, Mexico

⁴ UAEMex Campus Universitario "El Cerrillo". El Cerrillo Piedras Blancas s/n, Toluca, Estado de Mexico 50200, Mexico

⁵ Programa Regional del Noroeste para el Doctorado en Biotecnología, Universidad Autónoma de Sinaloa, Av. de las Américas y Blvd. Universitarios s/n, Culiacán, Sinaloa 80010, Mexico

Molecules 2014, 19(12), 21066-21084; https://doi.org/10.3390/molecules191221066 - 15 Dec 2014

Cited by 17 | Viewed by 6821

Abstract

Extrusion is an alternative technology for the production of nixtamalized products. The aim of this study was to obtain an expanded nixtamalized snack with whole blue corn and using the extrusion process, to preserve the highest possible total anthocyanin content, intense blue/purple coloration [...] Read more.

Extrusion is an alternative technology for the production of nixtamalized products. The aim of this study was to obtain an expanded nixtamalized snack with whole blue corn and using the extrusion process, to preserve the highest possible total anthocyanin content, intense blue/purple coloration (color b) and the highest expansion index. A central composite experimental design was used. The extrusion process factors were: feed moisture (FM, 15%–23%), calcium hydroxide concentration (CHC, 0%–0.25%) and final extruder temperature (T, 110–150 °C). The chemical and physical properties evaluated in the extrudates were moisture content (MC, %), total anthocyanins (TA, mg·kg⁻¹), pH, color (L, a, b) and expansion index (EI). ANOVA and surface response methodology were applied to evaluate the effects of the extrusion factors. FM and T significantly affected the response variables. An optimization step was performed by overlaying three contour plots to predict the best combination region. The extrudates were obtained under the following optimum factors: FM (%) = 16.94, CHC (%) = 0.095 and T (°C) = 141.89. The predicted extrusion processing factors were highly accurate, yielding an expanded nixtamalized snack with 158.87 mg·kg⁻¹ TA (estimated: 160 mg·kg⁻¹), an EI of 3.19 (estimated: 2.66), and color parameter b of −0.44 (estimated: 0.10). Full article

(This article belongs to the Special Issue Anthocyanins)

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28 pages, 2830 KiB

Open AccessReview

HIV-1 and Its Resistance to Peptidic Carbohydrate-Binding Agents (CBAs): An Overview

by Geoffrey Férir, Stephanie C. Gordts and Dominique Schols^*

Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10. Leuven B-3000, Belgium

Molecules 2014, 19(12), 21085-21112; https://doi.org/10.3390/molecules191221085 - 15 Dec 2014

Cited by 7 | Viewed by 6817

Abstract

The glycoproteins on the surfaces of enveloped viruses, such as HIV, can be considered as a unique target for antiviral therapy. Different carbohydrate-binding agents (CBAs) target specific glycans present on viral glycoproteins of enveloped viruses. It has been shown that long-term CBA pressure [...] Read more.

The glycoproteins on the surfaces of enveloped viruses, such as HIV, can be considered as a unique target for antiviral therapy. Different carbohydrate-binding agents (CBAs) target specific glycans present on viral glycoproteins of enveloped viruses. It has been shown that long-term CBA pressure in vitro can result in mutant HIV-1 isolates with several N-linked glycan deletions on gp120. These studies demonstrated that mainly high-mannose type glycans are deleted. However, interestingly, N241, N262 and N356 on gp120 have never been found to be affected after prolonged CBA exposure. Here, we review the mutation and (cross)-resistance profiles of eleven specific generated CBA-resistant HIV-1 strains. We observed that the broad-neutralizing anti-carbohydrate binding mAb 2G12 became completely inactive against all the generated CBA-resistant HIV-1 clade B isolates. In addition, all of the CBAs discussed in this review, with the exception of NICTABA, interfered with the binding of 2G12 mAb to gp120 expressed on HIV-1-infected T cells. The cross-resistance profiles of mutant HIV-1 strains are varying from increased susceptibility to very high resistance levels, even among different classes of CBAs with dissimilar sugar specificities or binding moieties [e.g., α(1,3), α(1,2), α(1,6)]. Recent studies demonstrated promising results in non-topical formulations (e.g., intranasally or subcutaneously), highlighting their potential for prevention (microbicides) and antiviral therapy. Full article

(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)

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14 pages, 1669 KiB

Open AccessArticle

Crystallographic Studies Evidencing the High Energy Tolerance to Disrupting the Interface Disulfide Bond of Thioredoxin 1 from White Leg Shrimp Litopenaeus vannamei

by Adam A. Campos-Acevedo and Enrique Rudiño-Piñera^*

Departamento de Medicina molecular y Bioprocesos, Instituto de Biotecnología (IBT), Universidad Nacional Autónoma de México (UNAM), Avenida Universidad 2001, Colonia Chamilpa, Cuernavaca 62210, Mexico

Molecules 2014, 19(12), 21113-21126; https://doi.org/10.3390/molecules191221113 - 15 Dec 2014

Cited by 5 | Viewed by 6999

Abstract

Thioredoxin (Trx) is a small 12-kDa redox protein that catalyzes the reduction of disulfide bonds in proteins from different biological systems. A recent study of the crystal structure of white leg shrimp thioredoxin 1 from Litopenaeus vannamei (LvTrx) revealed a dimeric [...] Read more.

Thioredoxin (Trx) is a small 12-kDa redox protein that catalyzes the reduction of disulfide bonds in proteins from different biological systems. A recent study of the crystal structure of white leg shrimp thioredoxin 1 from Litopenaeus vannamei (LvTrx) revealed a dimeric form of the protein mediated by a covalent link through a disulfide bond between Cys73 from each monomer. In the present study, X-ray-induced damage in the catalytic and the interface disulfide bond of LvTrx was studied at atomic resolution at different transmission energies of 8% and 27%, 12.8 keV at 100 K in the beamline I-24 at Diamond Light Source. We found that at an absorbed dose of 32 MGy, the X-ray induces the cleavage of the disulfide bond of each catalytic site; however, the interface disulfide bond was cleaved at an X-ray adsorbed dose of 85 MGy; despite being the most solvent-exposed disulfide bond in LvTrx (~50 Å²). This result clearly established that the interface disulfide bond is very stable and, therefore, less susceptible to being reduced by X-rays. In fact, these studies open the possibility of the existence in solution of a dimeric LvTrx. Full article

(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)

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27 pages, 1097 KiB

Open AccessReview

Curcumin and Inflammatory Bowel Disease: Potential and Limits of Innovative Treatments

by Liza Vecchi Brumatti^1,*, Annalisa Marcuzzi¹, Paola Maura Tricarico², Valentina Zanin¹, Martina Girardelli¹ and Anna Monica Bianco¹

¹ Institute for Maternal and Child Health—IRCCS "Burlo Garofolo"—via dell'Istria, 65/1, Trieste 34137, Italy

² Department of Medicine and Surgery and Health Sciences, University of Trieste, Piazzale Europa, 1, Trieste 34137, Italy

Molecules 2014, 19(12), 21127-21153; https://doi.org/10.3390/molecules191221127 - 16 Dec 2014

Cited by 119 | Viewed by 30479

Abstract

Curcumin belongs to the family of natural compounds collectively called curcuminoids and it possesses remarkable beneficial anti-oxidant, anti-inflammatory, anti-cancer, and neuroprotective properties. Moreover it is commonly assumed that curcumin has also been suggested as a remedy for digestive diseases such as inflammatory bowel [...] Read more.

Curcumin belongs to the family of natural compounds collectively called curcuminoids and it possesses remarkable beneficial anti-oxidant, anti-inflammatory, anti-cancer, and neuroprotective properties. Moreover it is commonly assumed that curcumin has also been suggested as a remedy for digestive diseases such as inflammatory bowel diseases (IBD), a chronic immune disorder affecting the gastrointestinal tract and that can be divided in two major subgroups: Crohn’s disease (CD) and Ulcerative Colitis (UC), depending mainly on the intestine tract affected by the inflammatory events. The chronic and intermittent nature of IBD imposes, where applicable, long-term treatments conducted in most of the cases combining different types of drugs. In more severe cases and where there has been no good response to the drugs, a surgery therapy is carried out. Currently, IBD-pharmacological treatments are generally not curative and often present serious side effects; for this reason, being known the relationship between nutrition and IBD, it is worthy of interesting the study and the development of new dietary strategy. The curcumin principal mechanism is the suppression of IBD inflammatory compounds (NF-κB) modulating immune response. This review summarizes literature data of curcumin as anti-inflammatory and anti-oxidant in IBD, trying to understand the different effects in CD e UC. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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14 pages, 1087 KiB

Open AccessArticle

In Vitro and in Vivo Evaluation of the Antioxidant and Prooxidant Activity of Phenolic Compounds Obtained from Grape (Vitis vinifera) Pomace

by Milena Cotoras^1,*, Herman Vivanco¹, Ricardo Melo¹, María Aguirre², Evelyn Silva¹ and Leonora Mendoza^1,*

¹ Laboratorio de Micología, Facultad de Química y Biología, Universidad de Santiago de Chile, Alameda 3363, Estación Central, Santiago 916000, Chile

² Laboratorio de Electroquímica, Facultad de Química y Biología, Universidad de Santiago de Chile, Alameda 3363, Estación Central, Santiago 916000, Chile

Molecules 2014, 19(12), 21154-21167; https://doi.org/10.3390/molecules191221154 - 16 Dec 2014

Cited by 89 | Viewed by 8851

Abstract

The antioxidant and/or prooxidant ability of extracts obtained from wine waste were analyzed using in vitro and in vivo assays. Cyclic voltammetry was used as the in vitro assay to determine the antioxidant and/or prooxidant properties and, the in vivo effect on mycelial [...] Read more.

The antioxidant and/or prooxidant ability of extracts obtained from wine waste were analyzed using in vitro and in vivo assays. Cyclic voltammetry was used as the in vitro assay to determine the antioxidant and/or prooxidant properties and, the in vivo effect on mycelial growth of the fungus Botrytis cinerea was evaluated. In addition, the prooxidant activity was evaluated by intracellular oxidation of compound 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) in B. cinerea. The extracts used in this study were obtained from grape pomace of Cabernet Sauvignon, Carménère and Syrah varieties from the Misiones de Rengo Vineyard by simple extraction, using methanol/HCl 1% (v/v), ethanol 70% (v/v), or Soxhlet extraction. According to the results obtained, gallic acid was the most represented phenolic compound independent of grape variety and extraction method. In addition, vanillic acid; protocatechuic acid, syringic acid, quercetin and kaempferol were found in the extracts. From this study it was possible concluded that, depending of the method of extraction of the grape residues and the grape variety (Cabernet Sauvignon, Carménère and Syrah), the extracts showed antioxidant and/or prooxidant activity. However, no correlation can be established between the anodic oxidation potentials of the extracts and their effect on the fungus B. cinerea. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 1801 KiB

Open AccessArticle

Toxicity of Evodiae fructus on Rat Liver Mitochondria: The Role of Oxidative Stress and Mitochondrial Permeability Transition

by Qingyan Cai, Jingjing Wei, Wei Zhao, Si Shi, Yu Zhang, Renrong Wei, Yue Zhang, Weirong Li^* and Qi Wang^*

Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China

Molecules 2014, 19(12), 21168-21182; https://doi.org/10.3390/molecules191221168 - 16 Dec 2014

Cited by 59 | Viewed by 8987

Abstract

Evodiae fructus (EF) has been used in China for thousands of years as an analgesic, antiemetic, anti-inflammatory and antidiarrheal drug. EF is a toxic drug and causes hepatotoxicity in humans. Although recent chronic toxicity studies performed on aqueous extract of EF has revealed [...] Read more.

Evodiae fructus (EF) has been used in China for thousands of years as an analgesic, antiemetic, anti-inflammatory and antidiarrheal drug. EF is a toxic drug and causes hepatotoxicity in humans. Although recent chronic toxicity studies performed on aqueous extract of EF has revealed that it can produce obvious cumulative hepatotoxicity, the mechanism behind this toxicity is still uncertain. In the present study, we investigated the influence of EF on oxidative stress, mitochondrial permeability transition, adenosine triphosphate (ATP), and cytochrome C release of hepatic mitochondria. Rats were divided into four groups and fed distilled water, 6, 12, 24 g/kg of aqueous extract of EF daily for 15 days. Evodiamine, rutaecarpine and evodine were quantified in the aqueous extract by high performance liquid chromatography with ultraviolet detection (HPLC/UV). The results showed that aqueous extract of EF could significantly (p < 0.05) decrease MnSOD levels to 56.50%, 46.77% and 19.67% of control group, GSH level was decreased to 74.24%, 53.97% and 47.91% of control group and MDA level was increased to 131.55%, 134.34% and 150.81% of control group in the 6, 12 and 24 g/kg groups, respectively; extract also induced mitochondria swelling, vacuolation, MPT pore opening and a significant decrease (p < 0.05) in mitochondrial potential, while ATP levels were significant decreased (p < 0.05) to 65.24%, 38.08% and 34.59% of control group in the 6, 12 and 24 g/kg groups, respectively, resulting in ATP depletion and CytC release, finally trigger cell death signaling, which are the partial hepatotoxicity mechanisms of EF. Full article

(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)

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17 pages, 717 KiB

Open AccessReview

Hydrogen Sulfide and Endothelium-Dependent Vasorelaxation

by Jerzy Bełtowski^1,* and Anna Jamroz-Wiśniewska²

¹ Department of Pathophysiology, Medical University, 20-150 Lublin, Poland

² Department of Neurology, Medical University, 20-090 Lublin, Poland

Molecules 2014, 19(12), 21183-21199; https://doi.org/10.3390/molecules191221183 - 16 Dec 2014

Cited by 83 | Viewed by 10259

Abstract

In addition to nitric oxide and carbon monoxide, hydrogen sulfide (H₂S), synthesized enzymatically from l-cysteine or l-homocysteine, is the third gasotransmitter in mammals. Endogenous H₂S is involved in the regulation of many physiological processes, including vascular tone. Although initially [...] Read more.

In addition to nitric oxide and carbon monoxide, hydrogen sulfide (H₂S), synthesized enzymatically from l-cysteine or l-homocysteine, is the third gasotransmitter in mammals. Endogenous H₂S is involved in the regulation of many physiological processes, including vascular tone. Although initially it was suggested that in the vascular wall H₂S is synthesized only by smooth muscle cells and relaxes them by activating ATP-sensitive potassium channels, more recent studies indicate that H₂S is synthesized in endothelial cells as well. Endothelial H₂S production is stimulated by many factors, including acetylcholine, shear stress, adipose tissue hormone leptin, estrogens and plant flavonoids. In some vascular preparations H₂S plays a role of endothelium-derived hyperpolarizing factor by activating small and intermediate-conductance calcium-activated potassium channels. Endothelial H₂S signaling is up-regulated in some pathologies, such as obesity and cerebral ischemia-reperfusion. In addition, H₂S activates endothelial NO synthase and inhibits cGMP degradation by phosphodiesterase 5 thus potentiating the effect of NO-cGMP pathway. Moreover, H₂S-derived polysulfides directly activate protein kinase G. Finally, H₂S interacts with NO to form nitroxyl (HNO)—a potent vasorelaxant. H₂S appears to play an important and multidimensional role in endothelium-dependent vasorelaxation. Full article

(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)

15 pages, 794 KiB

Open AccessCommunication

Design and Synthesis of a Series of Truncated Neplanocin Fleximers

by Sarah C. Zimmermann¹, Elizaveta O'Neill¹, Godwin U. Ebiloma², Lynsey J. M. Wallace², Harry P. De Koning² and Katherine L. Seley-Radtke^1,*

¹ Department of Chemistry & Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA

² Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK

Molecules 2014, 19(12), 21200-21214; https://doi.org/10.3390/molecules191221200 - 16 Dec 2014

Cited by 13 | Viewed by 7562

Abstract

In an effort to study the effects of flexibility on enzyme recognition and activity, we have developed several different series of flexible nucleoside analogues in which the purine base is split into its respective imidazole and pyrimidine components. The focus of this particular [...] Read more.

In an effort to study the effects of flexibility on enzyme recognition and activity, we have developed several different series of flexible nucleoside analogues in which the purine base is split into its respective imidazole and pyrimidine components. The focus of this particular study was to synthesize the truncated neplanocin A fleximers to investigate their potential anti-protozoan activities by inhibition of S-adenosylhomocysteine hydrolase (SAHase). The three fleximers tested displayed poor anti-trypanocidal activities, with EC₅₀ values around 200 μM. Further studies of the corresponding ribose fleximers, most closely related to the natural nucleoside substrates, revealed low affinity for the known T. brucei nucleoside transporters P1 and P2, which may be the reason for the lack of trypanocidal activity observed. Full article

(This article belongs to the Special Issue Nucleoside Modifications)

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11 pages, 750 KiB

Open AccessArticle

Chemical Constituents from Licania cruegeriana and Their Cardiovascular and Antiplatelet Effects

by Omar Estrada¹, Whendy Contreras¹, Giovana Acha¹, Eva Lucena¹, Whitney Venturini¹, Alfonso Cardozo² and Claudia Alvarado-Castillo^1,*

¹ Centro de Biofisica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Altos de Pipe 1020-A, Venezuela

² Facultad de Agronomía, Universidad Central de Venezuela, Maracay 2101, Venezuela

Molecules 2014, 19(12), 21215-21225; https://doi.org/10.3390/molecules191221215 - 17 Dec 2014

Cited by 13 | Viewed by 6960

Abstract

Three new lupane-type triterpenoids: 6β,30-dihydroxybetulinic acid glucopyranosyl ester (4), 6β,30-dihydroxybetulinic acid (5) and 6β-hydroxybetulinic acid (6), were isolated from Licania cruegeriana Urb. along with six known compounds. Their structures were elucidated on the basis of spectroscopic methods, [...] Read more.

Three new lupane-type triterpenoids: 6β,30-dihydroxybetulinic acid glucopyranosyl ester (4), 6β,30-dihydroxybetulinic acid (5) and 6β-hydroxybetulinic acid (6), were isolated from Licania cruegeriana Urb. along with six known compounds. Their structures were elucidated on the basis of spectroscopic methods, including IR, ESIMS, 1D- and 2D-NMR experiments, as well as by comparison of their spectral data with those of related compounds. All compounds were evaluated in vivo for their effects on the mean arterial blood pressure (MABP) and heart rate (HR) of spontaneously hypertensive rats (SHR) and also in vitro for their capacity to inhibit the human platelet aggregation. None of the isolated flavonoids 1–3 showed cardiovascular effects on SHR and among the isolated triterpenoids 4–9 only 5 and 6 produced a significant reduction in MABP (60.1% and 17.2%, respectively) and an elevation in HR (11.0% and 41.2%, respectively). Compounds 3, 4, 5 and 6 were able to inhibit human platelet aggregation induced by ADP, collagen and arachidonic acid with different selectivity profiles. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 704 KiB

Open AccessArticle

Antioxidant Activity of Leaf Extracts from Different Hibiscus sabdariffa Accessions and Simultaneous Determination Five Major Antioxidant Compounds by LC-Q-TOF-MS

by Jin Wang^1,†, Xianshuang Cao^1,†, Hao Jiang¹, Yadong Qi^2,3,*, Kit L. Chin² and Yongde Yue^1,*

¹ SFA Key Laboratory of Bamboo and Rattan Science and Technology, International Centre for Bamboo and Rattan, No. 8 Futong Dongdajie, Wangjing, Chaoyang District, Beijing 100102, China

² Southern University Agricultural Research and Extension Center, Baton Rouge, LA 70813, USA

³ Urban Forestry Program, College of Science and Agriculture, Southern University, Baton Rouge, LA 70813, USA

^† These authors contributed equally to this work.

Molecules 2014, 19(12), 21226-21238; https://doi.org/10.3390/molecules191221226 - 17 Dec 2014

Cited by 52 | Viewed by 9844

Abstract

Hibiscus sabdariffa has gained attention for its antioxidant activity. There are many accessions of H. sabdariffa in the world. However, information on the quantification of antioxidant compounds in different accessions is rather limited. In this paper, a liquid chromatography/quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS) method [...] Read more.

Hibiscus sabdariffa has gained attention for its antioxidant activity. There are many accessions of H. sabdariffa in the world. However, information on the quantification of antioxidant compounds in different accessions is rather limited. In this paper, a liquid chromatography/quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS) method for simultaneous determination of five antioxidant compounds (neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, rutin, and isoquercitrin) in H. sabdariffa leaves was developed. The method was validated for linearity, sensitivity, precision, repeatability and accuracy. The validated method has been successfully applied for determination of the five analytes in eight accessions of H. sabdariffa. The eight accessions of H. sabdariffa were evaluated for their antioxidant activities by DPPH free radical scavenging assay. The investigated accessions of H. sabdariffa were rich in rutin and exhibited strong antioxidant activity. The two accessions showing the highest antioxidant activities were from Cuba (No. 2) and Taiwan (No. 5). The results indicated that H. sabdariffa leaves could be considered as a potential antioxidant source for the food industry. The developed LC-Q-TOF-MS method is helpful for quality control of H. sabdariffa. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 3589 KiB

Open AccessArticle

A Sensitive A₃B Porphyrin Nanomaterial for CO₂ Detection

by Eugenia Fagadar-Cosma^1,*

, Dana Vlascici^1,2, Gheorghe Fagadar-Cosma³, Anca Palade¹, Anca Lascu¹, Ionela Creanga¹, Mihaela Birdeanu^1,4, Rodica Cristescu⁵

and Ileana Cernica⁶

¹ Department of Organic Chemistry, Institute of Chemistry Timisoara of Romanian Academy, M. Viteazul Ave, No. 24, 300223 Timisoara, Romania

² Department of Chemistry, Chemistry-Biology-Geography Faculty, West University of Timisoara, Pestalozzi Street, No. 16, 300115 Timisoara, Romania

³ CAICAM Department, Faculty of Industial Chemistry and Environmental Engineering, Politehnica University, V. Parvan Bv., No. 6, 300223 Timisoara, Romania

⁴ National Institute for Research and Development in Electrochemistry and Condensed Matter, P. Andronescu Street, No. 1, 300224 Timisoara, Romania

⁵ Lasers Department, National Institute for Lasers, Plasma & Radiation Physics, P.O. Box MG-36, Magurele, 077125 Bucharest, Romania

⁶ National R&D Institute for Microtechnology, Erou Iancu Nicolae Street, No. 126 A, Voluntari, 077190 Bucharest, Romania

Molecules 2014, 19(12), 21239-21252; https://doi.org/10.3390/molecules191221239 - 17 Dec 2014

Cited by 20 | Viewed by 9106

Abstract

The present report deals with the tailoring, preparation and characterization of novel nanomaterials sensitive to CO₂ for use in detection of this gas during space habitation missions. A new nanostructured material based on mixed substituted asymmetrical A₃B porphyrin: 5-(4-pyridyl)-10,15,20-tris(3,4-dimethoxyphenyl)-porphyrin (PyTDMeOPP) [...] Read more.

The present report deals with the tailoring, preparation and characterization of novel nanomaterials sensitive to CO₂ for use in detection of this gas during space habitation missions. A new nanostructured material based on mixed substituted asymmetrical A₃B porphyrin: 5-(4-pyridyl)-10,15,20-tris(3,4-dimethoxyphenyl)-porphyrin (PyTDMeOPP) was synthesized and characterized by ¹H-NMR, FT-IR, UV-vis, fluorescence, MS, HPLC and AFM. Introducing one pyridyl substituent in the 5-meso-position of porphyrin macrocycle confers some degree of hydrophilicity, which may cause self-assembly properties and a better response to increased acidity. The influence of pH and nature of the solvent upon H and J aggregates of the porphyrin are discussed. Porphyrin aggregation at the air–THF interface gave a triangular type morphology, randomly distributed but uniformly oriented. When deposition was made by multiple drop-casting operations, a network of triangles of uniform size was created and a porous structure was obtained, being reorganized finally in rings. When the deposition was made from CHCl₃, ring structures ranging in internal diameter from 300 nm to 1 µm, but with the same width of the corona circular of approx. 200 nm were obtained. This porphyrin-based material, capable of generating ring aggregates in both THF and CHCl₃, has been proven to be sensitive to CO₂ detection. The dependence between the intensity of porphyrin UV-vis absorption and the concentration of CO₂ has a good correlation of 98.4%. Full article

(This article belongs to the Section Molecular Diversity)

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23 pages, 928 KiB

Open AccessArticle

Largely Reduced Grid Densities in a Vibrational Self-Consistent Field Treatment Do Not Significantly Impact the ResultingWavenumbers

by Oliver M. D. Lutz^1,*, Bernd M. Rode², Günther K. Bonn¹ and Christian W. Huck¹

¹ Institute of Analytical Chemistry and Radiochemistry, Center for Chemistry and Biomedicine, University of Innsbruck, Innrain 80-82, Innsbruck 6020, Austria

² Institute of General, Inorganic and Theoretical Chemistry, Center for Chemistry and Biomedicine, University of Innsbruck, Innrain 80-82, Innsbruck 6020, Austria

Molecules 2014, 19(12), 21253-21275; https://doi.org/10.3390/molecules191221253 - 17 Dec 2014

Cited by 15 | Viewed by 6957

Abstract

Especially for larger molecules relevant to life sciences, vibrational self-consistent field (VSCF) calculations can become unmanageably demanding even when only first and second order potential coupling terms are considered. This paper investigates to what extent the grid density of the VSCF’s underlying potential [...] Read more.

Especially for larger molecules relevant to life sciences, vibrational self-consistent field (VSCF) calculations can become unmanageably demanding even when only first and second order potential coupling terms are considered. This paper investigates to what extent the grid density of the VSCF’s underlying potential energy surface can be reduced without sacrificing accuracy of the resulting wavenumbers. Including single-mode and pair contributions, a reduction to eight points per mode did not introduce a significant deviation but improved the computational efficiency by a factor of four. A mean unsigned deviation of 1.3% from the experiment could be maintained for the fifteen molecules under investigation and the approach was found to be applicable to rigid, semi-rigid and soft vibrational problems likewise. Deprotonated phosphoserine, stabilized by two intramolecular hydrogen bonds, was investigated as an exemplary application. Full article

(This article belongs to the Special Issue Advances of Vibrational Spectroscopic Technologies in Life Sciences)

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15 pages, 1073 KiB

Open AccessArticle

Insecticidal Activities of Bark, Leaf and Seed Extracts of Zanthoxylum heitzii against the African Malaria Vector Anopheles gambiae

by Hans J. Overgaard^1,2,3, Patcharawan Sirisopa², Bertin Mikolo⁴, Karl E. Malterud^5,*, Helle Wangensteen⁵, Yuan-Feng Zou⁵, Berit S. Paulsen⁵, Daniel Massamba⁴, Stephane Duchon^2,3, Vincent Corbel^2,3 and Fabrice Chandre³

¹ Department of Mathematical Sciences and Technology, Norwegian University of Life Sciences, P.O. Box 5003, Ås 1432, Norway

² Department of Entomology, Faculty of Agriculture, Kasetsart University, 50 Ngam Wong Wan Rd, Ladyaow, Chatuchak, Bangkok 10900, Thailand

³ Institut de Recherche pour le Développement (IRD), Maladies Infectieuses et Vecteurs, Ecologie, Génétique, Evolution et Contrôle (IRD 224-CNRS 5290 UM1-UM2), Montpellier Cedex 5 34394, France

⁴ National Polytechnic High School, Marien Ngouabi University, BP 69, Brazzaville, Congo

⁵ School of Pharmacy, Department of Pharmaceutical Chemistry, Section Pharmacognosy, University of Oslo, P.O. Box 1068 Blindern, Oslo 0316, Norway

Molecules 2014, 19(12), 21276-21290; https://doi.org/10.3390/molecules191221276 - 17 Dec 2014

Cited by 18 | Viewed by 14109

Abstract

The olon tree, Zanthoxylum heitzii (syn. Fagara heitzii) is commonly found in the central-west African forests. In the Republic of Congo (Congo-Brazzaville) its bark is anecdotally reported to provide human protection against fleas. Here we assess the insecticidal activities of Z. heitzii [...] Read more.

The olon tree, Zanthoxylum heitzii (syn. Fagara heitzii) is commonly found in the central-west African forests. In the Republic of Congo (Congo-Brazzaville) its bark is anecdotally reported to provide human protection against fleas. Here we assess the insecticidal activities of Z. heitzii stem bark, seed and leaf extracts against Anopheles gambiae s.s, the main malaria vector in Africa. Extracts were obtained by Accelerated Solvent Extraction (ASE) using solvents of different polarity and by classical Soxhlet extraction using hexane as solvent. The insecticidal effects of the crude extracts were evaluated using topical applications of insecticides on mosquitoes of a susceptible reference strain (Kisumu [Kis]), a strain homozygous for the L1014F kdr mutation (kdrKis), and a strain homozygous for the G119S Ace1R allele (AcerKis). The insecticidal activities were measured using LD₅₀ and LD₉₅ and active extracts were characterized by NMR spectroscopy and HPLC chromatography. Results show that the ASE hexane stem bark extract was the most effective compound against An. gambiae (LD₅₀ = 102 ng/mg female), but was not as effective as common synthetic insecticides. Overall, there was no significant difference between the responses of the three mosquito strains to Z. heitzii extracts, indicating no cross resistance with conventional pesticides. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

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19 pages, 734 KiB

Open AccessReview

Applications of Solid-Phase Microextraction and Gas Chromatography/Mass Spectrometry (SPME-GC/MS) in the Study of Grape and Wine Volatile Compounds

by Annarita Panighel^* and Riccardo Flamini

Consiglio per la Ricerca e la Sperimentazione in Agricoltura-Centro di Ricerca per la Viticoltura (CRA-VIT), Viale XXVIII aprile 26, Conegliano (TV) 31015, Italy

Molecules 2014, 19(12), 21291-21309; https://doi.org/10.3390/molecules191221291 - 18 Dec 2014

Cited by 79 | Viewed by 17183

Abstract

Volatile compounds are responsible for the wine “bouquet”, which is perceived by sniffing the headspace of a glass, and of the aroma component (palate-aroma) of the overall flavor, which is perceived on drinking. Grape aroma compounds are transferred to the wine and undergo [...] Read more.

Volatile compounds are responsible for the wine “bouquet”, which is perceived by sniffing the headspace of a glass, and of the aroma component (palate-aroma) of the overall flavor, which is perceived on drinking. Grape aroma compounds are transferred to the wine and undergo minimal alteration during fermentation (e.g., monoterpenes and methoxypyrazines); others are precursors of aroma compounds which form in winemaking and during wine aging (e.g., glycosidically-bound volatile compounds and C₁₃-norisoprenoids). Headspace solid phase microextraction (HS-SPME) is a fast and simple technique which was developed for analysis of volatile compounds. This review describes some SPME methods coupled with gas chromatography/mass spectrometry (GC/MS) used to study the grape and wine volatiles. Full article

(This article belongs to the Special Issue Aromas and Volatiles of Fruits)

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14 pages, 1816 KiB

Open AccessArticle

Effects of High Hydrostatic Pressure on Escherichia coli Ultrastructure, Membrane Integrity and Molecular Composition as Assessed by FTIR Spectroscopy and Microscopic Imaging Techniques

by María Prieto-Calvo¹, Miguel Prieto^1,2, Mercedes López² and Avelino Alvarez-Ordóñez^3,*

¹ Institute of Food Science and Technology, University of León, León 24071, Spain

² Department of Food Hygiene and Technology, University of León, León 24071, Spain

³ Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland

Molecules 2014, 19(12), 21310-21323; https://doi.org/10.3390/molecules191221310 - 18 Dec 2014

Cited by 26 | Viewed by 8750

Abstract

High hydrostatic pressure (HHP) is a novel food processing technology that is considered as an attractive alternative to conventional heat treatments for the preservation of foods, due to its lethal effects on pathogenic and spoilage microorganisms, while causing minor effects on food quality [...] Read more.

High hydrostatic pressure (HHP) is a novel food processing technology that is considered as an attractive alternative to conventional heat treatments for the preservation of foods, due to its lethal effects on pathogenic and spoilage microorganisms, while causing minor effects on food quality and sensorial attributes. This study is aimed at investigating how HHP treatments at varying intensities in the range 50–900 MPa affect the viability, membrane integrity, ultrastructure and molecular composition of Escherichia coli. Results of membrane integrity tests (measurement of cellular leakage and monitoring of propidium iodide uptake through fluorescence microscopy) and ultrastructural observations by transmission electron microscopy demonstrated that HHP gave rise to cellular enlargement, membrane damage or detachment, DNA and protein denaturation and loss of intracellular contents. Fourier-transform infrared (FTIR) spectroscopy analyses evidenced minor changes in molecular composition in response to high pressures, which were mostly observed on the spectral region w₄ (1200–900 cm⁻¹), mainly informative of carbohydrates and polysaccharides of the cell wall. These findings suggest that exposure of E. coli cells to HHP causes alterations in their physical integrity while producing minor modifications in biochemical cellular composition. The current study increases the knowledge on the mechanisms of E. coli inactivation by HHP and provides valuable information for the design of more effective food preservation regimes based on the integration of mild HHP in combination with other food preservation strategies into a multi-target hurdle technology approach. Full article

(This article belongs to the Special Issue Advances of Vibrational Spectroscopic Technologies in Life Sciences)

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11 pages, 741 KiB

Open AccessArticle

Synthesis, Characterisation and Reactions of Phosphine-Substituted Alkynylboronates and Alkynyltrifluoroborate Salts

by Jérôme F. Vivat, Sylvestre P. J. T. Bachollet, Harry Adams and Joseph P. A. Harrity^*

Department of Chemistry, University of Sheffield, Sheffield S3 7HF, UK

Molecules 2014, 19(12), 21324-21334; https://doi.org/10.3390/molecules191221324 - 18 Dec 2014

Cited by 1 | Viewed by 6282

Abstract

The synthesis and structural characterisation of phosphine-substituted alkynylboronates is reported. A P(III)-centred alkynylboronate (2) was prepared that showed little evidence for the conjugation of the P-lone pair to the boron via the alkyne π-system, as judged by X-ray crystallography studies of [...] Read more.

The synthesis and structural characterisation of phosphine-substituted alkynylboronates is reported. A P(III)-centred alkynylboronate (2) was prepared that showed little evidence for the conjugation of the P-lone pair to the boron via the alkyne π-system, as judged by X-ray crystallography studies of 2 and a related P(V) compound, 3. In addition, corresponding alkynyltrifluoroborate salts were prepared that showed improved stability by comparison to their boronic ester counterparts. These salts undergo Pd-catalysed cross-coupling reactions with aryl halides. Full article

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

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15 pages, 5382 KiB

Open AccessArticle

Lignin Hydrolysis and Phosphorylation Mechanism during Phosphoric Acid–Acetone Pretreatment: A DFT Study

by Wu Qin^*, Lingnan Wu, Zongming Zheng^*, Changqing Dong and Yongping Yang

National Engineering Laboratory for Biomass Power Generation Equipment, School of Renewable Energy Engineering, North China Electric Power University, Beijing 102206, China

Molecules 2014, 19(12), 21335-21349; https://doi.org/10.3390/molecules191221335 - 18 Dec 2014

Cited by 27 | Viewed by 10292

Abstract

The study focused on the structural sensitivity of lignin during the phosphoric acid–acetone pretreatment process and the resulting hydrolysis and phosphorylation reaction mechanisms using density functional theory calculations. The chemical stabilities of the seven most common linkages (β-O-4, β-β, 4-O- [...] Read more.

The study focused on the structural sensitivity of lignin during the phosphoric acid–acetone pretreatment process and the resulting hydrolysis and phosphorylation reaction mechanisms using density functional theory calculations. The chemical stabilities of the seven most common linkages (β-O-4, β-β, 4-O-5, β-1, 5-5, α-O-4, and β-5) of lignin in H₃PO₄, CH₃COCH₃, and H₂O solutions were detected, which shows that α-O-4 linkage and β-O-4 linkage tend to break during the phosphoric acid–acetone pretreatment process. Then α-O-4 phosphorylation and β-O-4 phosphorylation follow a two-step reaction mechanism in the acid treatment step, respectively. However, since phosphorylation of α-O-4 is more energetically accessible than phosphorylation of β-O-4 in phosphoric acid, the phosphorylation of α-O-4 could be controllably realized under certain operational conditions, which could tune the electron and hole transfer on the right side of β-O-4 in the H₂PO₄⁻ functionalized lignin. The results provide a fundamental understanding for process-controlled modification of lignin and the potential novel applications in lignin-based imprinted polymers, sensors, and molecular devices. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 748 KiB

Open AccessArticle

Is Development of High-Grade Gliomas Sulfur-Dependent?

by Maria Wróbel^1,*

, Jerzy Czubak¹, Patrycja Bronowicka-Adamska¹, Halina Jurkowska¹, Dariusz Adamek² and Bolesław Papla²

¹ Chair of Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7 St., Kraków 31-034, Poland

² Department of Pathomorphology, Jagiellonian University Medical College, Grzegórzecka 16 St., Kraków 31-531, Poland

Molecules 2014, 19(12), 21350-21362; https://doi.org/10.3390/molecules191221350 - 19 Dec 2014

Cited by 44 | Viewed by 8296

Abstract

We characterized γ-cystathionase, rhodanese and 3-mercaptopyruvate sulfurtransferase activities in various regions of human brain (the cortex, thalamus, hypothalamus, hippocampus, cerebellum and subcortical nuclei) and human gliomas with II to IV grade of malignancy (according to the WHO classification). The human brain regions, as [...] Read more.

We characterized γ-cystathionase, rhodanese and 3-mercaptopyruvate sulfurtransferase activities in various regions of human brain (the cortex, thalamus, hypothalamus, hippocampus, cerebellum and subcortical nuclei) and human gliomas with II to IV grade of malignancy (according to the WHO classification). The human brain regions, as compared to human liver, showed low γ-cystathionase activity. The activity of rhodanese was also much lower and it did not vary significantly between the investigated brain regions. The activity of 3-mercaptopyruvate sulfurtransferase was the highest in the thalamus, hypothalamus and subcortical nuclei and essentially the same level of sulfane sulfur was found in all the investigated brain regions. The investigations demonstrated that the level of sulfane sulfur in gliomas with the highest grades was high in comparison to various human brain regions, and was correlated with a decreased activity of γ-cystathionase, 3-mercaptopyruvate sulfurtransferase and rhodanese. This can suggest sulfane sulfur accumulation and points to its importance for malignant cell proliferation and tumor growth. In gliomas with the highest grades of malignancy, despite decreased levels of total free cysteine and total free glutathione, a high ratio of GSH/GSSG was maintained, which is important for the process of malignant cells proliferation. A high level of sulfane sulfur and high GSH/GSSG ratio could result in the elevated hydrogen sulfide levels. Because of the disappearance of γ-cystathionase activity in high-grade gliomas, it seems to be possible that 3-mercaptopyruvate sulfurtransferase could participate in hydrogen sulfide production. The results confirm sulfur dependence of malignant brain tumors. Full article

(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)

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15 pages, 826 KiB

Open AccessArticle

One New and Nine Known Flavonoids from Choerospondias axillaries and Their in Vitro Antitumor, Anti-Hypoxia and Antibacterial Activities

by Chang-Wei Li and Cheng-Bin Cui^*

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China

Molecules 2014, 19(12), 21363-21377; https://doi.org/10.3390/molecules191221363 - 19 Dec 2014

Cited by 19 | Viewed by 6762

Abstract

In the present study, a new flavanoid 1, together with nine known ones 2–10 were isolated from the stem bark of Choerospondias axillaries, the fruit of which was used mainly for treatment of cardiovascular diseases in China. The structure [...] Read more.

In the present study, a new flavanoid 1, together with nine known ones 2–10 were isolated from the stem bark of Choerospondias axillaries, the fruit of which was used mainly for treatment of cardiovascular diseases in China. The structure of 1 was established on the basis of its extensive spectral data, and the absolute structures of 1 and 10 were determined by their CD data. The absolute structure of 10 was established for the first time. Among the obtained compounds, 5–8 inhibited the proliferation of K562 cells with inhibition rates of 26.6%, 65.7%, 40.4% and 45.6% at 100 µg/mL; 1 and 4–10 showed significant protective effects on anoxia-induced injury in cultured ECV304 or PC12 cells at 50 µg/mL; 8 and 9 showed antibacterial effects on Staphylococcus aureus ATCC6538 at the tested concentration of 150 µg/8 mm paper disc. Compounds 2 and 4–10 were isolated for the first time from this genus. The proliferation inhibiting activities of 7 and 8, the anti-hypoxia activities of 1 and 4–10, and the antibacterial effect of 8 and 9 on Staphylococcus aureus ATCC6538 are reported here for the first time. Full article

(This article belongs to the Section Natural Products Chemistry)

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8 pages, 774 KiB

Open AccessArticle

New and Cytotoxic Components from Antrodia camphorata

by Tzong-Huei Lee¹, Chien-Chih Chen^2,3, Jih-Jung Chen⁴, Hui-Fen Liao^5,†, Hsun-Shuo Chang^6,7

, Ping-Jyun Sung^8,9,10

, Mei-Hwei Tseng¹¹, Sheng-Yang Wang¹², Horng-Huey Ko^13,† and Yueh-Hsiung Kuo^14,15,*

¹ Institute of Fisheries Science, National Taiwan University, Taipei 106, Taiwan

² Department of Nursing, Hungkuang University, Taichung 443, Taiwan

³ Department of Biotechnology, Hungkuang University, Taichung 443, Taiwan

⁴ Department of Pharmacy, Tajen University, Pingtung 907, Taiwan

⁵ Department of Biochemical Science and Technology, National Chiayi University, Chiayi 600, Taiwan

⁶ School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan

⁷ Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan

⁸ Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung 944, Taiwan

⁹ Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Pingtung 944, Taiwan

¹⁰ National Museum of Marine Biology and Aquarium, Pingtung 944, Taiwan

¹¹ Department of Applied Physics and Chemistry, Taipei Municipal University of Education, Taipei 100, Taiwan

¹² Department of Forestry, National Chung-Hsing University, Taichung 402, Taiwan

¹³ Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan

¹⁴ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan

¹⁵ Department of Biotechnology, Asia University, Taichung 413, Taiwan

^† These authors contributed equally to this work.

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Molecules 2014, 19(12), 21378-21385; https://doi.org/10.3390/molecules191221378 - 19 Dec 2014

Cited by 17 | Viewed by 7362

Abstract

The solid-state cultured products of Antrodia camphorata as health foods has been blooming for the past few decades in Taiwan. In continuing our studies on the chemical constituents of the solid-state cultured products of this fungus, 6-methoxy-4-methyl-2,3-(methylenedioxy)phenol (1) and 4,4'-(ethane-1,2-diyl)bis(2,3,6-trimethoxyphenol)(2 [...] Read more.

The solid-state cultured products of Antrodia camphorata as health foods has been blooming for the past few decades in Taiwan. In continuing our studies on the chemical constituents of the solid-state cultured products of this fungus, 6-methoxy-4-methyl-2,3-(methylenedioxy)phenol (1) and 4,4'-(ethane-1,2-diyl)bis(2,3,6-trimethoxyphenol)(2) together with 2,3,6-trimethoxy-4-methylphenol (3), 1(10→6)abeo-ergosta-5,7,9,22-tetraen-3α-ol (4), citreoanthrasteroid B (5) and dankasterones A (6) and B (7) were purified by a series of column chromatography. Their structures were elucidated by spectral data analysis. For bioactivity assay, compounds 4–7 showed significant cytotoxicity toward murine colorectal CT26 and human leukemia K562 cancer cell lines with IC₅₀ values ranging from 6.7 to 15.3 µM and from 12.5 to 23.1 µM, respectively. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 782 KiB

Open AccessArticle

Liquid Chromatographic Resolution of Fendiline and Its Analogues on a Chiral Stationary Phase Based on (+)-(18-Crown-6)-2,3,11,12-tetracarboxylic Acid

by Ga Ram Lee and Myung Ho Hyun^*

Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 690-735, Korea

Molecules 2014, 19(12), 21386-21397; https://doi.org/10.3390/molecules191221386 - 19 Dec 2014

Cited by 9 | Viewed by 7179

Abstract

Fendiline, an effective anti-anginal drug for the treatment of coronary heart diseases, and its sixteen analogues were resolved on a CSP based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid. Fendiline was resolved quite well with the separation factor (α) of 1.25 and resolution (R_S) of [...] Read more.

Fendiline, an effective anti-anginal drug for the treatment of coronary heart diseases, and its sixteen analogues were resolved on a CSP based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid. Fendiline was resolved quite well with the separation factor (α) of 1.25 and resolution (R_S) of 1.55 when a mobile phase consisting of methanol–acetonitrile–trifluoroacetic acid–triethylamine at a ratio of 80/20/0.1/0.5 (v/v/v/v) was used. The comparison of the chromatographic behaviors for the resolution of fendiline and its analogues indicated that the 3,3-diphenylpropyl group bonded to the secondary amino group of fendiline is important in the chiral recognition and the difference in the steric bulkiness between the phenyl group and the methyl group at the chiral center of fendiline is also important in the chiral recognition. Full article

(This article belongs to the Special Issue Dynamic Stereochemistry)

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13 pages, 1140 KiB

Open AccessArticle

A New Solid Phase Extraction for the Determination of Anthocyanins in Grapes

by Marta Ferreiro-González^1,2

, Ceferino Carrera³, Ana Ruiz-Rodríguez^1,3, Gerardo F. Barbero^1,3, Jesús Ayuso²

, Miguel Palma^1,3,* and Carmelo G. Barroso^1,3

¹ Department of Analytical Chemistry, University of Cadiz, Puerto Real 11510, Spain

² Department of Physical Chemistry, University of Cadiz, Puerto Real 11510, Spain

³ Andalusian Center for Wine Research, University of Cadiz, Puerto Real 11510, Spain

Molecules 2014, 19(12), 21398-21410; https://doi.org/10.3390/molecules191221398 - 19 Dec 2014

Cited by 24 | Viewed by 8068

Abstract

A method for the concentration and cleaning of red grape extracts prior to the determination of anthocyanins by UPLC-DAD has been developed. This method is of special interest in the determination of phenolic maturity as it allows the analysis of the anthocyanins present [...] Read more.

A method for the concentration and cleaning of red grape extracts prior to the determination of anthocyanins by UPLC-DAD has been developed. This method is of special interest in the determination of phenolic maturity as it allows the analysis of the anthocyanins present in grapes. Several different SPE cartridges were assessed, including both C-18- and vinylbenzene-based cartridges. C-18-based cartridges presented a very low retention for the glucosylated anthocyanidins while vinylbenzene-based cartridges showed excellent retention for these compounds. The optimized method involves the initial conditioning of the cartridge using 10 mL of methanol and 10 mL of water, followed by loading of up to 100 mL of red grape extract. Ten mL of water was used in the washing step and anthocyanins were subsequently eluted using 1.5 mL of acidified methanol at pH 2. This method simplifies the determination of individual anthocyanins as, on the one hand, it cleans the sample of interference and, on the other hand, it increases the concentration to up to 25:1.5. The developed method has been validated with a range of different grapes and it has also been tested as a means of determining the different anthocyanins in grapes with different levels of maturity. Full article

(This article belongs to the Special Issue Anthocyanins)

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13 pages, 1705 KiB

Open AccessArticle

Effects of Platycodin D on Proliferation, Apoptosis and PI3K/Akt Signal Pathway of Human Glioma U251 Cells

by Chong Xu¹, Guibo Sun¹, Guangxin Yuan², Rui Wang³ and Xiaobo Sun^1,*

¹ Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China

² Pharmaceutical College, Beihua University, Jilin 132013, China

³ School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China

Molecules 2014, 19(12), 21411-21423; https://doi.org/10.3390/molecules191221411 - 19 Dec 2014

Cited by 44 | Viewed by 7554

Abstract

Effects of platycodin D (PD) on the proliferation, apoptosis and PI3K/Akt signaling pathway of human glioma U251 cells were investigated. Glioma U251 cells were treated with PD at final concentrations of 0, 16.3, 40.8, 81.6, 163.2 μM, and inhibition rate, early and late [...] Read more.

Effects of platycodin D (PD) on the proliferation, apoptosis and PI3K/Akt signaling pathway of human glioma U251 cells were investigated. Glioma U251 cells were treated with PD at final concentrations of 0, 16.3, 40.8, 81.6, 163.2 μM, and inhibition rate, early and late apoptotic rate, apoptotic index, expression of apoptosis-related proteins and phosphorylation of the PI3K/Akt signaling pathway were evaluated. The results showed that compared with the control group, PD could increase the proliferation inhibition rate of U251 cells in a dose- and time -dependent manner; PD could also elevate the early and late apoptotic rate, apoptotic index and the level of pro-apoptotic proteins of glioma U251 cells, such as Bax and cleaved caspase-3, but lower the level of apoptosis inhibitory protein, such as Bcl-2; PD could increase the ratio of G₀/G₁ phase U251 cells, and lower the proportion of Sphase U251 cells and the ratio of G₂/M phase U251 cells; PD could reduce the ratio of p-Akt/Akt. The results indicate that PD can inhibit the proliferation, induce the apoptosis and cause the cell cycle arrest in human glioma U251 cells, which may be related to the inhibition of PD on the activation of PI3K/Akt signaling pathway. Full article

(This article belongs to the Section Medicinal Chemistry)

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18 pages, 3500 KiB

Open AccessArticle

Photocatalytic Oxidation of Diethyl Sulfide Vapor over TiO₂-Based Composite Photocatalysts

by Dmitry Selishchev^1,2,3,*

and Denis Kozlov^1,2,3

¹ Boreskov Institute of Catalysis, pr. Ak. Lavrentieva 5, Novosibirsk 630090, Russia

² Novosibirsk State University, st. Pirogova 2, Novosibirsk 630090, Russia

³ Research and Educational Centre for Energoefficient Catalysis (NSU), st. Pirogova 2, Novosibirsk 630090, Russia

Molecules 2014, 19(12), 21424-21441; https://doi.org/10.3390/molecules191221424 - 19 Dec 2014

Cited by 22 | Viewed by 6998

Abstract

Composite TiO₂/activated carbon (TiO₂/AC) and TiO₂/SiO₂ photocatalysts with TiO₂ contents in the 10 to 80 wt. % range were synthesized by the TiOSO₄ thermal hydrolysis method and characterized by AES, BET, X-ray diffraction and [...] Read more.

Composite TiO₂/activated carbon (TiO₂/AC) and TiO₂/SiO₂ photocatalysts with TiO₂ contents in the 10 to 80 wt. % range were synthesized by the TiOSO₄ thermal hydrolysis method and characterized by AES, BET, X-ray diffraction and FT-IR ATR methods. All TiO₂samples were in the anatase form, with a primary crystallite size of about 11 nm. The photocatalytic activities of the TiO₂/AC and TiO₂/SiO₂ samples were tested in the gas-phase photocatalytic oxidation (PCO) reaction of diethyl sulfide (DES) vapor in a static reactor by the FT-IR in situ method. Acetaldehyde, formic acid, ethylene and SO₂ were registered as the intermediate products which finally were completely oxidized to the final oxidation products – H₂O, CO₂, CO and SO₄²⁻ ions. The influence of the support on the kinetics of DES PCO and on the TiO₂/AC and TiO₂/SiO₂ samples’ stability during three long-term DES PCO cycles was investigated. The highest PCO rate was observed for TiO₂/SiO₂ photocatalysts. To evaluate the activity of photocatalysts the turnover frequency values (TOF) were calculated for three photocatalysts (TiO₂, TiO₂/AC and TiO₂/SiO₂) for the same amount of mineralized DES. It was demonstrated that the TOF value for composite TiO₂/SiO₂ photocatalysts was 3.5 times higher than for pure TiO₂. Full article

(This article belongs to the Special Issue Photocatalysis)

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20 pages, 829 KiB

Open AccessArticle

Anti-Depressant-Like Effect of Kaempferitrin Isolated from Justicia spicigera Schltdl (Acanthaceae) in Two Behavior Models in Mice: Evidence for the Involvement of the Serotonergic System

by Julia Cassani¹, Ana María Dorantes-Barrón², Lilian Mayagoitia Novales³, Guadalupe Alva Real⁴ and Rosa Estrada-Reyes^2,*

¹ Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana Unidad Xochimilco, Mexico D.F. 04960, Mexico

² Laboratorio de Fitofarmacología, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico D.F 14370, Mexico

³ Departamento de Etología, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico D.F, 14370, Mexico

⁴ Subdirección de Investigaciones Clínicas del Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada Mexico-Xochimilco 101, Col. San Lorenzo Huipulco, Delegación Tlalpan, Mexico D.F 14370, Mexico

Molecules 2014, 19(12), 21442-21461; https://doi.org/10.3390/molecules191221442 - 19 Dec 2014

Cited by 52 | Viewed by 9538

Abstract

We evaluated the antidepressant-like effect of kaempferitrin (Km) isolated from the plant Justicia spicigera (Asteraceae), which is used in traditional medicine for relieving emotional disorders, such as “la tristeza” (sadness or dysthymia) and “el humor” (mood changes). The actions of Km were evaluated [...] Read more.

We evaluated the antidepressant-like effect of kaempferitrin (Km) isolated from the plant Justicia spicigera (Asteraceae), which is used in traditional medicine for relieving emotional disorders, such as “la tristeza” (sadness or dysthymia) and “el humor” (mood changes). The actions of Km were evaluated in a forced swimming test (FST) and a suspension tail test (TST) in mice. We explored the involvement of the serotonergic system and the hypothalamic-hypophysis-adrenal axis (HPA) in the antidepressant-like effect of Km. To evaluate nonspecific effects of Km on general activity, the open field test (OFT) was performed. Km at 5, 10, and 20 mg/kg induced an antidepressant-like effect. Sub-effective dose of Km (1 mg/kg) produced a synergistic effect with imipramine (6.25 mg/kg) and fluoxetine (10 mg/kg) but not with desipramine (3.12 mg/kg). Pretreatment with p-chlorophenylalanine methyl ester (PCPA), a serotonin synthesis inhibitor, N-{2-(4-(2-methoxyphenyl)-1-piperazinyl}-N-(2-pyridinyl)cyclohexecarboxamide (WAY-100635), a selective 5-HT_1A receptor antagonist, and 8OH-DPAT, a selective 5-HT_1A agonist, but not pindolol (10 mg/kg) blocked the anti- immobility effect induced by Km. Taken together, these results indicate that the antidepressant-like effect of Km is related to the serotonergic system, principally 5-HT_1A. This effect was not related to changes in locomotor activity. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 1720 KiB

Open AccessReview

1-[2-(2-Methoxyphenylamino)ethylamino]-3-(naphthalene-1- yloxy)propan-2-ol May Be a Promising Anticancer Drug

by Tomoyuki Nishizaki^1,*, Takeshi Kanno¹, Ayako Tsuchiya¹, Yoshiko Kaku¹, Tadashi Shimizu² and Akito Tanaka²

¹ Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan

² Laboratory of Chemical Biology, Advanced Medicinal Research Center, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe 650-8530, Japan

Molecules 2014, 19(12), 21462-21472; https://doi.org/10.3390/molecules191221462 - 19 Dec 2014

Cited by 11 | Viewed by 8874

Abstract

We have originally synthesized the naftopidil analogue 1-[2-(2-methoxyphenylamino)ethylamino]-3-(naphthalene-1-yloxy)propan-2-ol (HUHS 1015) as a new anticancer drug. HUHS1015 induces cell death in a wide variety of human cancer cell lines originated from malignant pleural mesothelioma, lung cancer, hepatoma, gastric cancer, colorectal cancer, bladder cancer, prostate [...] Read more.

We have originally synthesized the naftopidil analogue 1-[2-(2-methoxyphenylamino)ethylamino]-3-(naphthalene-1-yloxy)propan-2-ol (HUHS 1015) as a new anticancer drug. HUHS1015 induces cell death in a wide variety of human cancer cell lines originated from malignant pleural mesothelioma, lung cancer, hepatoma, gastric cancer, colorectal cancer, bladder cancer, prostate cancer, and renal cancer. HUHS1015-induced cell death includes necrosis (necroptosis) and apoptosis, and the underlying mechanism differs depending upon cancer cell types. HUHS1015 effectively suppresses tumor growth in mice inoculated with NCI-H2052, MKN45, or CW2 cells, with a potential similar to or higher than that of currently used anticancer drugs. Here we show how HUHS1015 might offer brilliant hope for cancer therapy. 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, 1661 KiB

Open AccessArticle

Design and Synthesis of Chalcone Derivatives as Inhibitors of the Ferredoxin — Ferredoxin-NADP⁺ Reductase Interaction of Plasmodium falciparum: Pursuing New Antimalarial Agents

by Hery Suwito^1,2,*, Jumina¹, Mustofa³, Pratiwi Pudjiastuti², Much Zaenal Fanani⁴, Yoko Kimata-Ariga⁵, Ritsuko Katahira⁵, Toru Kawakami⁵, Toshimichi Fujiwara⁵, Toshiharu Hase⁵, Hasnah Mohd Sirat⁶ and Ni Nyoman Tri Puspaningsih^2,4

¹ Department of Chemistry, Faculty of Science and Mathematics, University of Gajah Mada, Jogjakarta 55281, Indonesia

² Department of Chemistry, Faculty of Science and Technology, Airlangga University, Surabaya 60115, Indonesia

³ Department of Pharmacology and Therapy, Faculty of Medicine, University of Gajah Mada, Jogjakarta 55281, Indonesia

⁴ Institute of Tropical Disease, Airlangga University, Surabaya 60115, Indonesia

⁵ Institute of Protein Research, Osaka University, 3-2 Yamadoaka, Suita-Shi, Osaka 656-0871 Japan

⁶ Department of Chemistry, Faculty of Science, University Technology Malaya, Johor Bahru 81310, Malaysia

Molecules 2014, 19(12), 21473-21488; https://doi.org/10.3390/molecules191221473 - 19 Dec 2014

Cited by 49 | Viewed by 9711

Abstract

Some chalcones have been designed and synthesized using Claisen-Schmidt reactions as inhibitors of the ferredoxin and ferredoxin-NADP⁺ reductase interaction to pursue a new selective antimalaria agent. The synthesized compounds exhibited inhibition interactions between PfFd-PfFNR in the range of 10.94%–50%. [...] Read more.

Some chalcones have been designed and synthesized using Claisen-Schmidt reactions as inhibitors of the ferredoxin and ferredoxin-NADP⁺ reductase interaction to pursue a new selective antimalaria agent. The synthesized compounds exhibited inhibition interactions between PfFd-PfFNR in the range of 10.94%–50%. The three strongest inhibition activities were shown by (E)-1-(4-aminophenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (50%), (E)-1-(4-aminophenyl)-3-(2,4-dimethoxyphenyl)prop-2-en-1-one (38.16%), and (E)-1-(4-aminophenyl)-3-(2,3-dimethoxyphenyl)prop-2-en-1-one (31.58%). From the docking experiments we established that the amino group of the methoxyamino chlacone derivatives plays an important role in the inhibition activity by electrostatic interaction through salt bridges and that it forms more stable and better affinity complexes with FNR than with Fd. Full article

(This article belongs to the Section Medicinal Chemistry)

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17 pages, 1103 KiB

Open AccessArticle

Transfer Hydrogenation in Open-Shell Nucleotides — A Theoretical Survey

by Florian Achrainer and Hendrik Zipse^*

Department of Chemistry, Ludwig-Maximilians-Universität Munich, Butenandtstr. 5–13, Munich 81377, Germany

Molecules 2014, 19(12), 21489-21505; https://doi.org/10.3390/molecules191221489 - 22 Dec 2014

Cited by 2 | Viewed by 7003

Abstract

The potential of a larger number of sugar models to act as dihydrogen donors in transfer hydrogenation reactions has been quantified through the calculation of hydrogenation energies of the respective oxidized products. Comparison of the calculated energies to hydrogenation energies of nucleobases shows [...] Read more.

The potential of a larger number of sugar models to act as dihydrogen donors in transfer hydrogenation reactions has been quantified through the calculation of hydrogenation energies of the respective oxidized products. Comparison of the calculated energies to hydrogenation energies of nucleobases shows that many sugar fragment radicals can reduce pyrimidine bases such as uracil in a strongly exothermic fashion. The most potent reducing agent is the C3' ribosyl radical. The energetics of intramolecular transfer hydrogenation processes has also been calculated for a number of uridinyl radicals. The largest driving force for such a process is found for the uridin-C3'-yl radical, whose rearrangement to the C2'-oxidized derivative carrying a dihydrouracil is predicted to be exothermic by 61.1 kJ/mol in the gas phase. Full article

(This article belongs to the Special Issue Free Radicals and Radical Ions)

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23 pages, 1841 KiB

Open AccessReview

Bio and Nanomaterials Based on Fe₃O₄

by Jia-Kun Xu^1,*, Fang-Fang Zhang^1,2, Jing-Jing Sun¹, Jun Sheng¹, Fang Wang¹ and Mi Sun^1,*

¹ Key Laboratory of Sustainable Development of Marine Fisheries, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China

² College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China

Molecules 2014, 19(12), 21506-21528; https://doi.org/10.3390/molecules191221506 - 22 Dec 2014

Cited by 169 | Viewed by 17189

Abstract

During the past few years, nanoparticles have been used for various applications including, but not limited to, protein immobilization, bioseparation, environmental treatment, biomedical and bioengineering usage, and food analysis. Among all types of nanoparticles, superparamagnetic iron oxide nanoparticles, especially Fe₃O₄ [...] Read more.

During the past few years, nanoparticles have been used for various applications including, but not limited to, protein immobilization, bioseparation, environmental treatment, biomedical and bioengineering usage, and food analysis. Among all types of nanoparticles, superparamagnetic iron oxide nanoparticles, especially Fe₃O₄, have attracted a great deal of attention due to their unique magnetic properties and the ability of being easily chemical modified for improved biocompatibility, dispersibility. This review covers recent advances in the fabrication of functional materials based on Fe₃O₄ nanoparticles together with their possibilities and limitations for application in different fields. Full article

(This article belongs to the Special Issue Bio and Nanomaterials Based on Fe3O4)

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12 pages, 906 KiB

Open AccessArticle

Design and Optimisation of Bioactive Cyclic Peptides: Generation of a Down-Regulator of TNF Secretion

by Roger New^1,2,*, Gurpal S. Bansal¹, Malgorzata Dryjska¹, Michal Bogus¹, Patricia Green³, Marc Feldmann³ and Fionula Brennan^3,†

¹ Proxima Concepts Limited, c/o London Bioscience Innovation Centre, 2 Royal College Street, London NW1 0NH, UK

² Bone Medical Limited, 16 Ord Street, West Perth, WA 6005, Australia

³ Kennedy Institute of Rheumatology, Roosevelt Drive, University of Oxford, Headington OX3 7FY, UK

^† Deceased June 2012.

Molecules 2014, 19(12), 21529-21540; https://doi.org/10.3390/molecules191221529 - 22 Dec 2014

Cited by 6 | Viewed by 5747

Abstract

Although strong binding interactions between protein receptor and ligand do not require the participation of a large number of amino acids in either site, short peptide chains are generally poor at recreating the types of protein-protein interactions which take place during cell recognition [...] Read more.

Although strong binding interactions between protein receptor and ligand do not require the participation of a large number of amino acids in either site, short peptide chains are generally poor at recreating the types of protein-protein interactions which take place during cell recognition and signalling process, probably because their flexible backbones prevent the side chains from forming sufficiently rigid and stable epitopes, which can take part in binding with the desired strength and specificity. In a recently-reported study, it was shown that a proto-epitope containing F, R and S amino acids has the ability to down-regulate TNF secretion by macrophages. This paper extends these findings, putting those amino acids into a short cyclic peptide scaffold, and determining the optimal configuration required to overcome the problems of conformational instability, and give rise to molecules which have potential as therapeutic agents in human disease, such as rheumatoid arthritis. Full article

(This article belongs to the Section Medicinal Chemistry)

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19 pages, 3997 KiB

Open AccessArticle

Molecular Insights into the Genetic Diversity of Hemarthria compressa Germplasm Collections Native to Southwest China

by Zhi-Hui Guo¹

, Kai-Xin Fu¹, Xin-Quan Zhang¹, Shi-Qie Bai^1,2, Yan Fan³, Yan Peng¹, Lin-Kai Huang¹

, Yan-Hong Yan¹, Wei Liu¹ and Xiao Ma^1,*

¹ Department of Grassland Science, Animal Science and Technology College, Sichuan Agricultural University, Ya'an 625014, China

² Sichuan Academy of Grassland Science, Chengdu 611731, China

³ Chongqing Municipal Institute of Animal Husbandry, Chongqing 400039, China

Molecules 2014, 19(12), 21541-21559; https://doi.org/10.3390/molecules191221541 - 22 Dec 2014

Cited by 25 | Viewed by 7238

Abstract

Start codon targeted polymorphism (SCoT) analysis was employed to distinguish 37 whipgrass (Hemarthria compressa L.) clones and assess the genetic diversity and population structure among these genotypes. The informativeness of markers was also estimated using various parameters. Using 25 highly reproducible primer [...] Read more.

Start codon targeted polymorphism (SCoT) analysis was employed to distinguish 37 whipgrass (Hemarthria compressa L.) clones and assess the genetic diversity and population structure among these genotypes. The informativeness of markers was also estimated using various parameters. Using 25 highly reproducible primer sets, 368 discernible fragments were generated. Of these, 282 (77.21%) were polymorphic. The number of alleles per locus ranged from five to 21, and the genetic variation indices varied. The polymorphism information content (PIC) was 0.358, the Shannon diversity index (H) was 0.534, the marker index (MI) was 4.040, the resolving power (RP) was 6.108, and the genotype index (GI) was 0.782. Genetic similarity coefficients (GS) between the accessions ranged from 0.563 to 0.872, with a mean of 0.685. Their patterns observed in a dendrogram constructed using the unweighted pair group method with arithmetic mean analysis (UPGMA) based on GS largely confirmed the results of principal coordinate analysis (PCoA). PCoA was further confirmed by Bayesian model-based STRUCTURE analysis, which revealed no direct association between genetic relationship and geographical origins as validated by Mantel’s test (r = 0.2268, p = 0.9999). In addition, high-level genetic variation within geographical groups was significantly greater than that between groups, as determined by Shannon diversity analysis, analysis of molecular variance (AMOVA) and Bayesian analysis. Overall, SCoT analysis is a simple, effective and reliable technique for characterizing and maintaining germplasm collections of whipgrass and related species. Full article

(This article belongs to the Section Molecular Diversity)

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Molecules, Volume 19, Issue 12 (December 2014) – 135 articles , Pages 19253-21578

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