Molecules

16 pages, 708 KiB

Open AccessReview

Cymbopogon Species; Ethnopharmacology, Phytochemistry and the Pharmacological Importance

by Opeyemi Avoseh¹, Opeoluwa Oyedeji^1,*, Pamela Rungqu¹, Benedicta Nkeh-Chungag² and Adebola Oyedeji³

¹ Chemistry Department, University of Fort Hare, 5700 Alice, South Africa

² Department of Zoology, Walter Sisulu University, 5099 Mthatha, South Africa

³ Department of Chemistry, Walter Sisulu University, 5099 Mthatha, South Africa

Molecules 2015, 20(5), 7438-7453; https://doi.org/10.3390/molecules20057438 - 23 Apr 2015

Cited by 183 | Viewed by 18592

Abstract

Cymbopogon genus is a member of the family of Gramineae which are herbs known worldwide for their high essential oil content. They are widely distributed across all continents where they are used for various purposes. The commercial and medicinal uses of the various [...] Read more.

Cymbopogon genus is a member of the family of Gramineae which are herbs known worldwide for their high essential oil content. They are widely distributed across all continents where they are used for various purposes. The commercial and medicinal uses of the various species of Cymbopogon are well documented. Ethnopharmacology evidence shows that they possess a wide array of properties that justifies their use for pest control, in cosmetics and as anti-inflammation agents. These plants may also hold promise as potent anti-tumor and chemopreventive drugs. The chemo-types from this genus have been used as biomarkers for their identification and classification. Pharmacological applications of Cymbopogon citratus are well exploited, though studies show that other species may also useful pharmaceutically. Hence this literature review intends to discuss these species and explore their potential economic importance. Full article

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

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20 pages, 3812 KiB

Open AccessArticle

Flavonoids from Sideritis Species: Human Monoamine Oxidase (hMAO) Inhibitory Activities, Molecular Docking Studies and Crystal Structure of Xanthomicrol

by Fatma Pinar Turkmenoglu^1,*

, İpek Baysal², Samiye Ciftci-Yabanoglu², Kemal Yelekci³, Hamdi Temel^4,5, Salih Paşa⁵, Nurten Ezer¹, İhsan Çalış⁶ and Gulberk Ucar²

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

² Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey

³ Department of Bioinformatics and Genetics, Faculty of Engineering and Natural Sciences, Cibali Campus, Kadir Has University, Fatih, Istanbul 34083, Turkey

⁴ Science and Technology Application and Research Center, Faculty of Pharmacy, Dicle University, Diyarbakir 21280, Turkey

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

⁶ Department of Pharmacognosy, Faculty of Pharmacy, Near East University, Lefkoşa, Mersin-10, Turkey

Molecules 2015, 20(5), 7454-7473; https://doi.org/10.3390/molecules20057454 - 23 Apr 2015

Cited by 31 | Viewed by 9166

Abstract

The inhibitory effects of flavonoids on monoamine oxidases (MAOs) have attracted great interest since alterations in monoaminergic transmission are reported to be related to neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases and psychiatric disorders such as depression and anxiety, thus MAOs may [...] Read more.

The inhibitory effects of flavonoids on monoamine oxidases (MAOs) have attracted great interest since alterations in monoaminergic transmission are reported to be related to neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases and psychiatric disorders such as depression and anxiety, thus MAOs may be considered as targets for the treatment of these multi-factorial diseases. In the present study, four Sideritis flavonoids, xanthomicrol (1), isoscutellarein 7-O-[6'''-O-acetyl-β-D-allopyranosyl-(1→2)]-β-D-glucopyranoside (2), isoscutellarein 7-O-[6'''-O-acetyl-β-D-allopyranosyl-(1→2)]-6''-O-acetyl-β-D-glucopyranoside (3) and salvigenin (4) were docked computationally into the active site of the human monoamine oxidase isoforms (hMAO-A and hMAO-B) and were also investigated for their hMAO inhibitory potencies using recombinant hMAO isoenzymes. The flavonoids inhibited hMAO-A selectively and reversibly in a competitive mode. Salvigenin (4) was found to be the most potent hMAO-A inhibitor, while xanthomicrol (1) appeared as the most selective hMAO-A inhibitor. The computationally obtained results were in good agreement with the corresponding experimental values. In addition, the x-ray structure of xanthomicrol (1) has been shown. The current work warrants further preclinical studies to assess the potential of xanthomicrol (1) and salvigenin (4) as new selective and reversible hMAO-A inhibitors for the treatment of depression and anxiety. Full article

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

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21 pages, 3671 KiB

Open AccessArticle

Inhibition of Oncogenic Transcription Factor REL by the Natural Product Derivative Calafianin Monomer 101 Induces Proliferation Arrest and Apoptosis in Human B-Lymphoma Cell Lines

by Alan T. Yeo¹, Spandan Chennamadhavuni^2,3,†, Adrian Whitty^2,3, John A. Porco, Jr.^2,3 and Thomas D. Gilmore^1,3,*

¹ Department of Biology, Boston University, Boston, MA 02215, USA

² Department of Chemistry, Boston University, Boston, MA 02215, USA

³ Center for Molecular Discovery (BU-CMD), Boston University, Boston, MA 02215, USA

^† Current address: Department of Cancer Biology, Dana‐Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

Molecules 2015, 20(5), 7474-7494; https://doi.org/10.3390/molecules20057474 - 23 Apr 2015

Cited by 3 | Viewed by 7187

Abstract

Increased activity of transcription factor NF-κB has been implicated in many B-cell lymphomas. We investigated effects of synthetic compound calafianin monomer (CM101) on biochemical and biological properties of NF-κB. In human 293 cells, CM101 selectively inhibited DNA binding by overexpressed NF-κB subunits REL [...] Read more.

Increased activity of transcription factor NF-κB has been implicated in many B-cell lymphomas. We investigated effects of synthetic compound calafianin monomer (CM101) on biochemical and biological properties of NF-κB. In human 293 cells, CM101 selectively inhibited DNA binding by overexpressed NF-κB subunits REL (human c-Rel) and p65 as compared to NF-κB p50, and inhibition of REL and p65 DNA binding by CM101 required a conserved cysteine residue. CM101 also inhibited DNA binding by REL in human B-lymphoma cell lines, and the sensitivity of several B-lymphoma cell lines to CM101-induced proliferation arrest and apoptosis correlated with levels of cellular and nuclear REL. CM101 treatment induced both phosphorylation and decreased expression of anti-apoptotic protein Bcl-X_L, a REL target gene product, in sensitive B-lymphoma cell lines. Ectopic expression of Bcl-X_L protected SUDHL-2 B-lymphoma cells against CM101-induced apoptosis, and overexpression of a transforming mutant of REL decreased the sensitivity of BJAB B-lymphoma cells to CM101-induced apoptosis. Lipopolysaccharide-induced activation of NF-κB signaling upstream components occurred in RAW264.7 macrophages at CM101 concentrations that blocked NF-κB DNA binding. Direct inhibitors of REL may be useful for treating B-cell lymphomas in which REL is active, and may inhibit B-lymphoma cell growth at doses that do not affect some immune-related responses in normal cells. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 1353 KiB

Open AccessArticle

Synthesis and ¹¹C-Radiolabelling of 2-Carboranyl Benzothiazoles

by Kiran B. Gona¹, Jaya Lakshmi V. N. P. Thota¹, Zuriñe Baz¹, Vanessa Gómez-Vallejo² and Jordi Llop^1,*

¹ Radiochemistry and Nuclear Imaging Group, CIC biomaGUNE, Paseo Miramon 182, Parque Tecnológico de San Sebastián, San Sebastián 20009, Spain

² Radiochemistry Platform, CIC biomaGUNE, Paseo Miramón 182, Parque Tecnológico de San Sebastián, San Sebastián 20009, Spain

Molecules 2015, 20(5), 7495-7508; https://doi.org/10.3390/molecules20057495 - 23 Apr 2015

Cited by 9 | Viewed by 6120

Abstract

Dicarba-closo-dodecaboranes, commonly known as carboranes, possess unique physico-chemical properties and can be used as hydrophobic moieties during the design of new drugs or radiotracers. In this work, we report the synthesis of two analogues of 2-(4-aminophenyl)benzothiazole (a compound that was found [...] Read more.

Dicarba-closo-dodecaboranes, commonly known as carboranes, possess unique physico-chemical properties and can be used as hydrophobic moieties during the design of new drugs or radiotracers. In this work, we report the synthesis of two analogues of 2-(4-aminophenyl)benzothiazole (a compound that was found to elicit pronounced inhibitory effects against certain breast cancer cell lines in vitro) in which the phenyl ring has been substituted by a m-carborane cage. Two different synthetic strategies have been used. For the preparation of 1-(9-amino-1,7-dicarba-closo-dodecaboran-1-yl)-benzo-thiazole, the benzothiazole group was first introduced on one of the cluster carbon atoms of m-carborane and the amine group was further attached in three steps. For the synthesis of 1-(9-amino-1,7-dicarba-closo-dodecaboran-1-yl)-6-hydroxybenzothiazole, iodination was performed before introducing the benzothiazole group, and the amino group was subsequently introduced in six steps. Both compounds were radiolabelled with carbon-11 using [¹¹C]CH₃OTf as the labelling agent. Radiolabelling yields and radiochemical purities achieved should enable subsequent in vitro and in vivo investigations. Full article

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

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19 pages, 892 KiB

Open AccessReview

Significance of β-Galactoside α2,6 Sialyltranferase 1 in Cancers

by Jishun Lu^* and Jianguo Gu^*

Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aobaku, Sendai, Miyagi 981-8558, Japan

Molecules 2015, 20(5), 7509-7527; https://doi.org/10.3390/molecules20057509 - 24 Apr 2015

Cited by 100 | Viewed by 10404

Abstract

Altered glycosylation is a common feature of cancer cells. It takes a variety of forms, which includes loss of expression or excessive expression of some structures, the accumulation of precursors, the appearance of novel structures, etc. Notably, these changes in glycan structure [...] Read more.

Altered glycosylation is a common feature of cancer cells. It takes a variety of forms, which includes loss of expression or excessive expression of some structures, the accumulation of precursors, the appearance of novel structures, etc. Notably, these changes in glycan structure do not occur as a random consequence of disorder biology. Only a limited subset of oligosaccharides is found frequently enriched on the tumor cell surface and implicated in different tumor phenotypes. Among these, altered sialylation has long been associated with metastatic cell behaviors such as invasion and enhanced cell survival and accumulating evidence points to the alteration occurring in the sialic acid linkage to other sugars, which normally exists in three main configurations: α2,3, α2,6, and α2,8, catalyzed by a group of sialyltransferases. The aberrant expression of all three configurations has been described in cancer progression. However, the increased α2,6 sialylation catalyzed by β-galactoside α2,6 sialyltranferase 1 (ST6Gal I) is frequently observed in many types of the cancers. In this review, we describe the findings on the role of ST6Gal I in cancer progression, and highlight in particular the knowledge of how ST6Gal I-mediated α2,6 sialylated glycans or sialylated carrier proteins regulate cell signaling to promote the malignant phenotype of human carcinoma. Full article

(This article belongs to the Section Medicinal Chemistry)

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30 pages, 1191 KiB

Open AccessReview

Recent Developments in the Suzuki-Miyaura Reaction: 2010–2014

by Irene Maluenda and Oscar Navarro^*

Department of Chemistry, University of Sussex, Brighton BN1 9QJ, UK

Molecules 2015, 20(5), 7528-7557; https://doi.org/10.3390/molecules20057528 - 24 Apr 2015

Cited by 316 | Viewed by 21159

Abstract

The Suzuki-Miyaura reaction (SMR), involving the coupling of an organoboron reagent and an organic halide or pseudo-halide in the presence of a palladium or nickel catalyst and a base, has arguably become one of most utilized tools for the construction of a C-C [...] Read more.

The Suzuki-Miyaura reaction (SMR), involving the coupling of an organoboron reagent and an organic halide or pseudo-halide in the presence of a palladium or nickel catalyst and a base, has arguably become one of most utilized tools for the construction of a C-C bond. This review intends to be general account of all types of catalytic systems, new coupling partners and applications, including the literature between September 2010 and December 2014. Full article

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

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16 pages, 1960 KiB

Open AccessArticle

Pi-pi Stacking Mediated Cooperative Mechanism for Human Cytochrome P450 3A4

by Botao Fa¹, Shan Cong² and Jingfang Wang^1,*

¹ Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China

² Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China

Molecules 2015, 20(5), 7558-7573; https://doi.org/10.3390/molecules20057558 - 24 Apr 2015

Cited by 8 | Viewed by 9040

Abstract

Human Cytochrome P450 3A4 (CYP3A4) is an important member of the cytochrome P450 superfamily with responsibility for metabolizing ~50% of clinical drugs. Experimental evidence showed that CYP3A4 can adopt multiple substrates in its active site to form a cooperative binding model, accelerating substrate [...] Read more.

Human Cytochrome P450 3A4 (CYP3A4) is an important member of the cytochrome P450 superfamily with responsibility for metabolizing ~50% of clinical drugs. Experimental evidence showed that CYP3A4 can adopt multiple substrates in its active site to form a cooperative binding model, accelerating substrate metabolism efficiency. In the current study, we constructed both normal and cooperative binding models of human CYP3A4 with antifungal drug ketoconazoles (KLN). Molecular dynamics simulation and free energy calculation were then carried out to study the cooperative binding mechanism. Our simulation showed that the second KLN in the cooperative binding model had a positive impact on the first one binding in the active site by two significant pi-pi stacking interactions. The first one was formed by Phe215, functioning to position the first KLN in a favorable orientation in the active site for further metabolism reactions. The second one was contributed by Phe304. This pi-pi stacking was enhanced in the cooperative binding model by the parallel conformation between the aromatic rings in Phe304 and the dioxolan moiety of the first KLN. These findings can provide an atomic insight into the cooperative binding in CYP3A4, revealing a novel pi-pi stacking mechanism for drug-drug interactions. Full article

(This article belongs to the Special Issue Noncovalent pi-Interactions)

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12 pages, 4846 KiB

Open AccessArticle

Nitric Oxide Plays a Central Role in Water Stress-Induced Tanshinone Production in Salvia miltiorrhiza Hairy Roots

by Xuhong Du^1,†, Chenlu Zhang^2,†, Wanli Guo¹, Weibo Jin¹, Zongsuo Liang^1,*, Xijun Yan³, Zhixin Guo³, Yan Liu⁴ and Dongfeng Yang^1,3,*

¹ College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China

² College of Biological Science & Engineering, Shaanxi University of Technology, Hanzhong 723000, China

³ Tasly R&D Institute, Tasly Holding Group Co. Ltd, Tianjin 300410, China

⁴ Tianjin Tasly Modern TCM Resources Co., Ltd., Tianjin 300402, China

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 7574-7585; https://doi.org/10.3390/molecules20057574 - 24 Apr 2015

Cited by 18 | Viewed by 6217

Abstract

Nitric oxide (NO), a well-known signaling molecule plays an important role in abiotic and biotic stress-induced production of plant secondary metabolites. In this study, roles of NO in water stress-induced tanshinone production in Salvia miltiorrhiza hairy roots were investigated. The results showed that [...] Read more.

Nitric oxide (NO), a well-known signaling molecule plays an important role in abiotic and biotic stress-induced production of plant secondary metabolites. In this study, roles of NO in water stress-induced tanshinone production in Salvia miltiorrhiza hairy roots were investigated. The results showed that accumulations of four tanshinone compounds in S. miltiorrhiza hairy roots were significantly stimulated by sodium nitroprusside (SNP, a NO donor) at 100 μM. Effects of SNP were just partially arrested by the mevalonate (MVA) pathway inhibitor (mevinolin), but were completely inhibited by the 2-C-methyl-d-erythritol-4-phosphate pathway (MEP) inhibitor (fosmidomycin). The increase of tanshinone accumulation and the up-regulation of HMGR and DXR expression by PEG and ABA treatments were partially inhibited by an inhibitor of NO biosynthesis (N^ω-nitro-L-arginine methyl ester (L-NAME)) and a NO scavenger (2-(4-Carboxyphenyl)- 4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO)). Simultaneously, NO generation in the hairy roots was triggered by PEG and ABA, and the effects were also arrested by c-PTIO and L-NAME. These results indicated that NO signaling probably plays a central role in water stress-induced tanshinone production in S. miltiorrhiza hairy roots. SNP mainly stimulated the MEP pathway to increase tanshinone accumulation. Full article

(This article belongs to the Special Issue Nitric Oxide (NO) Release Chemistry)

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16 pages, 10557 KiB

Open AccessArticle

BMP Signaling Regulates Bone Morphogenesis in Zebrafish through Promoting Osteoblast Function as Assessed by Their Nitric Oxide Production

by Thomas Windhausen, Steeve Squifflet, Jörg Renn and Marc Muller^*

Laboratory for Organogenesis and Regeneration, Université de Liège, GIGA-R B34, Sart Tilman, 4000 Liège, Belgium

Molecules 2015, 20(5), 7586-7601; https://doi.org/10.3390/molecules20057586 - 24 Apr 2015

Cited by 23 | Viewed by 9640

Abstract

Bone morphogenetic proteins (BMPs) control many developmental and physiological processes, including skeleton formation and homeostasis. Previous studies in zebrafish revealed the crucial importance of proper BMP signaling before 48 h post-fertilization (hpf) for cartilage formation in the skull. Here, we focus on the [...] Read more.

Bone morphogenetic proteins (BMPs) control many developmental and physiological processes, including skeleton formation and homeostasis. Previous studies in zebrafish revealed the crucial importance of proper BMP signaling before 48 h post-fertilization (hpf) for cartilage formation in the skull. Here, we focus on the involvement of the BMP pathway between 48 and 96 hpf in bone formation after 96 hpf. Using BMP inhibitors and the expression of a dominant-negative BMP receptor, we analyze whether the loss of BMP signaling affects osteoblastogenesis, osteoblast function and bone mineralization. To this end, we used the transgenic zebrafish line Tg(osterix:mCherry), detection of nitric oxide (NO) production, and alizarin red staining, respectively. We observed that inhibition of BMP signaling between 48 and 72 hpf led to a reduction of NO production and bone mineralization. Osteoblast maturation and chondrogenesis, on the other hand, seemed unchanged. Osteoblast function and bone formation were less affected when BMP signaling was inhibited between 72 and 96 hpf. These results suggest that for the onset of bone formation, proper BMP signaling between 48 and 72 hpf is crucial to ensure osteoblast function and ossification. Furthermore, detection of NO in developing zebrafish larvae appears as an early indicator of bone calcification activity. Full article

(This article belongs to the Special Issue Nitric Oxide (NO) Release Chemistry)

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18 pages, 1604 KiB

Open AccessArticle

Modulation of the RNA Interference Activity Using Central Mismatched siRNAs and Acyclic Threoninol Nucleic Acids (aTNA) Units

by Adele Alagia¹, Montserrat Terrazas^1,2 and Ramon Eritja^1,*

¹ Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), CIBER-BBN Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Jordi Girona 18-26, 08034 Barcelona, Spain

² Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona, Spain

Molecules 2015, 20(5), 7602-7619; https://doi.org/10.3390/molecules20057602 - 24 Apr 2015

Cited by 15 | Viewed by 8174

Abstract

The understanding of the mechanisms behind nucleotide recognition by Argonaute 2, core protein of the RNA-induced silencing complex, is a key aspect in the optimization of small interfering RNAs (siRNAs) activity. To date, great efforts have been focused on the modification of certain [...] Read more.

The understanding of the mechanisms behind nucleotide recognition by Argonaute 2, core protein of the RNA-induced silencing complex, is a key aspect in the optimization of small interfering RNAs (siRNAs) activity. To date, great efforts have been focused on the modification of certain regions of siRNA, such as the 3'/5'-termini and the seed region. Only a few reports have described the roles of central positions flanking the cleavage site during the silence process. In this study, we investigate the potential correlations between the thermodynamic and silencing properties of siRNA molecules carrying, at internal positions, an acyclic L-threoninol nucleic acid (aTNA) modification. Depending on position, the silencing is weakened or impaired. Furthermore, we evaluate the contribution of mismatches facing either a natural nucleotide or an aTNA modification to the siRNA potency. The position 11 of the antisense strand is more permissive to mismatches and aTNA modification, in respect to the position 10. Additionally, comparing the ON-/OFF-target silencing of central mismatched siRNAs with 5'-terminal modified siRNA, we concluded: (i) central perturbation of duplex pairing features weights more on potency rather than silencing asymmetry; (ii) complete bias for the ON-target silencing can be achieved with single L-threoninol modification near the 5'-end of the sense strand. Full article

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

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17 pages, 1297 KiB

Open AccessArticle

5-Methoxyquinoline Derivatives as a New Class of EZH2 Inhibitors

by Pu Xiang^1,†, Hui Jie^1,†, Yang Zhou¹, Bo Yang², Hui-Juan Wang¹, Jing Hu¹, Jian Hu³, Sheng-Yong Yang¹ and Ying-Lan Zhao^1,*

¹ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China

² West China School of Pharmacy, Sichuan University, Chengdu 610041, China

³ The Second Division of Hepatobiliary Surgery, Center of PLA, Center of General Surgery of PLA, General Hospital of Chengdu Military Region, Chengdu 610083, China

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 7620-7636; https://doi.org/10.3390/molecules20057620 - 27 Apr 2015

Cited by 11 | Viewed by 7980

Abstract

A series of quinoline derivatives was synthesized and biologically evaluated as Enhancer of Zeste Homologue 2 (EZH2) inhibitors. Structure-activity relationship (SAR) studies led to the discovery of 5-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinolin-4-amine (5k), which displayed an IC₅₀ value of 1.2 μM against [...] Read more.

A series of quinoline derivatives was synthesized and biologically evaluated as Enhancer of Zeste Homologue 2 (EZH2) inhibitors. Structure-activity relationship (SAR) studies led to the discovery of 5-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinolin-4-amine (5k), which displayed an IC₅₀ value of 1.2 μM against EZH2, decreased global H3K27me3 level in cells and also showed good anti-viability activities against two tumor cell lines. Due to the low molecular weight and the fact that no quinoline derivative has been reported as an EZH2 inhibitor, this compound could serve as a lead compound for further optimization. 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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20 pages, 1130 KiB

Open AccessReview

Lectin Engineering, a Molecular Evolutionary Approach to Expanding the Lectin Utilities

by Dan Hu¹, Hiroaki Tateno² and Jun Hirabayashi^2,*

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

² Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Central-2, 1-1-1, Umezono, Tsukuba, Ibaraki 305-8568, Japan

Molecules 2015, 20(5), 7637-7656; https://doi.org/10.3390/molecules20057637 - 27 Apr 2015

Cited by 42 | Viewed by 8387

Abstract

In the post genomic era, glycomics—the systematic study of all glycan structures of a given cell or organism—has emerged as an indispensable technology in various fields of biology and medicine. Lectins are regarded as “decipherers of glycans”, being useful reagents for their structural [...] Read more.

In the post genomic era, glycomics—the systematic study of all glycan structures of a given cell or organism—has emerged as an indispensable technology in various fields of biology and medicine. Lectins are regarded as “decipherers of glycans”, being useful reagents for their structural analysis, and have been widely used in glycomic studies. However, the inconsistent activity and availability associated with the plant-derived lectins that comprise most of the commercially available lectins, and the limit in the range of glycan structures covered, have necessitated the development of innovative tools via engineering of lectins on existing scaffolds. This review will summarize the current state of the art of lectin engineering and highlight recent technological advances in this field. The key issues associated with the strategy of lectin engineering including selection of template lectin, construction of a mutagenesis library, and high-throughput screening methods are discussed. Full article

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

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26 pages, 4304 KiB

Open AccessArticle

Preclinical Validation of the Heparin-Reactive Peptide p5+14 as a Molecular Imaging Agent for Visceral Amyloidosis

by Jonathan S. Wall^1,2,*, Emily B. Martin¹, Tina Richey¹, Alan C. Stuckey², Sallie Macy¹, Craig Wooliver¹, Angela Williams¹, James S. Foster¹, Penney McWilliams-Koeppen², Ed Uberbacher^3,4, Xiaolin Cheng^3,4 and Stephen J. Kennel^1,2

¹ Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USA

² Department of and Radiology, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USA

³ Bioscience Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA

⁴ Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA

Molecules 2015, 20(5), 7657-7682; https://doi.org/10.3390/molecules20057657 - 27 Apr 2015

Cited by 33 | Viewed by 8420

Abstract

Amyloid is a complex pathologic matrix comprised principally of paracrystalline protein fibrils and heparan sulfate proteoglycans. Systemic amyloid diseases are rare, thus, routine diagnosis is often challenging. The glycosaminoglycans ubiquitously present in amyloid deposits are biochemically and electrochemically distinct from those found in [...] Read more.

Amyloid is a complex pathologic matrix comprised principally of paracrystalline protein fibrils and heparan sulfate proteoglycans. Systemic amyloid diseases are rare, thus, routine diagnosis is often challenging. The glycosaminoglycans ubiquitously present in amyloid deposits are biochemically and electrochemically distinct from those found in the healthy tissues due to the high degree of sulfation. We have exploited this unique property and evaluated heparin-reactive peptides, such as p5+14, as novel agents for specifically targeting and imaging amyloid. Herein, we demonstrate that radiolabeled p5+14 effectively bound murine AA amyloid in vivo by using molecular imaging. Biotinylated peptide also reacted with the major forms of human amyloid in tissue sections as evidenced immunohistochemically. Furthermore, we have demonstrated that the peptide also binds synthetic amyloid fibrils that lack glycosaminoglycans implying that the dense anionic motif present on heparin is mimicked by the amyloid protein fibril itself. These biochemical and functional data support the translation of radiolabeled peptide p5+14 for the clinical imaging of amyloid in patients. Full article

(This article belongs to the Special Issue Glycosaminoglycans and Their Mimetics)

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17 pages, 3229 KiB

Open AccessArticle

Special Effect of Ionic Liquids on the Extraction of Flavonoid Glycosides from Chrysanthemum morifolium Ramat by Microwave Assistance

by Ying Zhou¹, Datong Wu², Pengfei Cai², Guifang Cheng¹, Chaobiao Huang^1,3,* and Yuanjiang Pan^2,*

¹ College of Chemistry and Life Science, Zhejiang Normal University, Jinhua 321004, Zhejiang, China

² Department of Chemistry, Zhejiang University, Hangzhou 310027, Zhejiang, China

³ Xingzhi College, Zhejiang Normal University, Jinhua 321004, Zhejiang, China

Molecules 2015, 20(5), 7683-7699; https://doi.org/10.3390/molecules20057683 - 28 Apr 2015

Cited by 34 | Viewed by 8270

Abstract

A microwave-assisted extraction approach based on ionic liquids of different chain lengths was successfully applied to the extraction of ten flavonoid glycosides from the flowering heads of Chrysanthemum morifolium Ramat. The pretreated sample was quantified by HPLC-ESI-MSⁿ. The main components were [...] Read more.

A microwave-assisted extraction approach based on ionic liquids of different chain lengths was successfully applied to the extraction of ten flavonoid glycosides from the flowering heads of Chrysanthemum morifolium Ramat. The pretreated sample was quantified by HPLC-ESI-MSⁿ. The main components were identified as flavonoid glycosides, including three luteolin glycosides, three apigenin glycosides, three kaempferide glycosides, and one acacetin glycoside according to the characteristics of the corresponding CID mass spectrometric patterns. Eight ionic liquids from the imidazolium family with different chain lengths, namely, 1-alkyl-3-methylimidazolium bromide, [C_nmim]Br, (n = 2–16) were studied as extraction medium in water. Results indicated that alkyl chain length had an irregular impact on the extraction efficiency. Moreover, the best extraction efficiency was achieved by 1-dodecyl-3-methylimidazolium bromide aqueous solution ([C₁₂mim]Br). Besides the alkyl chain length of the cations, other factors influencing extraction efficiency were systematically investigated, including concentration of the IL solutions, extraction time, matrix-to-solvent ratio and irradiation power. Full article

(This article belongs to the Special Issue New Technologies for the Recovery of Natural Products)

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19 pages, 1087 KiB

Open AccessReview

Investigation of Carbohydrate Recognition via Computer Simulation

by Quentin R. Johnson¹, Richard J. Lindsay², Loukas Petridis³ and Tongye Shen^2,*

¹ UT-ORNL Graduate School of Genome Science and Technology, Knoxville, TN 37996, USA

² Department of Biochemistry and Cellular & Molecular Biology, University of Tennessee, Knoxville, TN 37996, USA

³ Center for Molecular Biophysics, Oak Ridge National Lab, Oak Ridge, TN 37830, USA

Molecules 2015, 20(5), 7700-7718; https://doi.org/10.3390/molecules20057700 - 28 Apr 2015

Cited by 27 | Viewed by 8536

Abstract

Carbohydrate recognition by proteins, such as lectins and other (bio)molecules, can be essential for many biological functions. Recently, interest has arisen due to potential protein and drug design and future bioengineering applications. A quantitative measurement of carbohydrate-protein interaction is thus important for the [...] Read more.

Carbohydrate recognition by proteins, such as lectins and other (bio)molecules, can be essential for many biological functions. Recently, interest has arisen due to potential protein and drug design and future bioengineering applications. A quantitative measurement of carbohydrate-protein interaction is thus important for the full characterization of sugar recognition. We focus on the aspect of utilizing computer simulations and biophysical models to evaluate the strength and specificity of carbohydrate recognition in this review. With increasing computational resources, better algorithms and refined modeling parameters, using state-of-the-art supercomputers to calculate the strength of the interaction between molecules has become increasingly mainstream. We review the current state of this technique and its successful applications for studying protein-sugar interactions in recent years. Full article

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

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18 pages, 1964 KiB

Open AccessArticle

Pharmacokinetics, Tissue Distribution and Excretion of Isoalantolactone and Alantolactone in Rats after Oral Administration of Radix Inulae Extract

by Renjie Xu, Guisheng Zhou, Ying Peng, Mengyue Wang and Xiaobo Li^*

School of Pharmacy, Shanghai Jiao Tong University, No.800 Dongchuan Road, Minhang District, Shanghai 200240, China

Molecules 2015, 20(5), 7719-7736; https://doi.org/10.3390/molecules20057719 - 28 Apr 2015

Cited by 26 | Viewed by 7535

Abstract

Radix Inulae is endemic to China and has been used in traditional medicine to treat upper body pain, emesis and diarrhoea, and to eliminate parasites. Here, an UPLC-MS/MS method was developed and applied to study the pharmacokinetics, distribution and excretion of isoalantolactone and [...] Read more.

Radix Inulae is endemic to China and has been used in traditional medicine to treat upper body pain, emesis and diarrhoea, and to eliminate parasites. Here, an UPLC-MS/MS method was developed and applied to study the pharmacokinetics, distribution and excretion of isoalantolactone and alantolactone, which are two main active sesquiterpene lactones in Radix Inulae, in Sprague-Dawley rats following oral administration of total Radix Inulae extract. Isoalantolactone, alantolactone and osthole (internal standard) were prepared using acetonitrile precipitation, and the separation of isoalantolactone and alantolactone was achieved by isocratic elution using water (containing 0.1% formic acid) and acetonitrile as the mobile phase using a ZORBAX Eclipse Plus C₁₈ column. The total run time was 6.4 min. The present study showed poor absorption of isoalantolactone and alantolactone in vivo. The apparent C_max, T_max, T_1/2 and total exposure (AUC_0–12h) in rat plasma were 37.8 ng/mL, 120 min, 351.7 min and 6112.3 ng-min/mL for isoalantolactone and 25.9 ng/mL, 90 min, 321.0 min and 4918.9 ng-min/mL for alantolactone, respectively. It was shown that the highest concentration was achieved in the small intestine and feces clearance was shown to be the dominant elimination pathway of the lactones. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 6803 KiB

Open AccessArticle

Proteomic Analysis of Polysaccharide-Milk Protein Interactions Induced by Chitosan

by Chun-Chi Chen^1,2, Shui-Tein Chen^3,† and Jung-Feng Hsieh^1,2,*,†

¹ Ph.D. Program in Nutrition & Food Science, Fu Jen Catholic University, Taipei 242, Taiwan

² Department of Food Science, Fu Jen Catholic University, Taipei 242, Taiwan

³ Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 7737-7749; https://doi.org/10.3390/molecules20057737 - 28 Apr 2015

Cited by 23 | Viewed by 8526

Abstract

The chitosan-induced coacervation of milk proteins was investigated using a proteomic approach. The addition of 0.8% chitosan to milk caused the milk proteins to coacervate after a 1 h incubation period. Approximately 86% of the milk proteins were present in the milk pellet [...] Read more.

The chitosan-induced coacervation of milk proteins was investigated using a proteomic approach. The addition of 0.8% chitosan to milk caused the milk proteins to coacervate after a 1 h incubation period. Approximately 86% of the milk proteins were present in the milk pellet fraction (MPF), and the protein concentration of the milk supernatant fraction (MSF) decreased from 29.4 ± 0.2 to 4.2 ± 0.6 mg/mL. SDS-PAGE analysis showed that the total intensities of serum albumin (BSA), α_S-casein (α_S-CN), β-casein (β-CN), κ-casein (κ-CN) and β-lactoglobulin (β-LG) in the MSF decreased to 8.5% ± 0.2%, 0.9% ± 0.3%, 0.7% ± 0.3%, 0.5% ± 0.2% and 15.0% ± 0.5%, respectively. Two-dimensional electrophoresis analysis indicated that α_S1-, α_S2-, β- and κ-CN and a fraction of the β-LG and BSA were found in the MSF following incubation with 0.8% chitosan. Isothermal titration calorimetry analysis indicated that binding of chitosan to milk proteins is an exothermic reaction based on binding titration curves of milk proteins dispersions with chitosan, and the enthalpy of binding (ΔH) and binding constant (Ka) were −7.85 × 10⁴ cal/mol and 1.06 × 10⁵/mol, respectively. These results suggested that the addition of 0.8% chitosan causes milk proteins to coacervate due to polysaccharide-protein interactions. Full article

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

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22 pages, 790 KiB

Open AccessReview

Anti-Trypanosomal Activity of Nigerian Plants and Their Constituents

by Ngozi Justina Nwodo^1,*, Akachukwu Ibezim¹, Fidele Ntie-Kang²

, Michael Umale Adikwu³ and Chika John Mbah¹

¹ Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, Nsukka 410001, Nigeria

² Department of Chemistry, Chemical and Bioactivity Information Centre, Faculty of Science, University of Buea, P.O. Box 63, Buea 00237, Cameroon

³ Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Nigeria

Molecules 2015, 20(5), 7750-7771; https://doi.org/10.3390/molecules20057750 - 28 Apr 2015

Cited by 55 | Viewed by 11796

Abstract

African trypanosomiasis is a vector-borne parasitic disease causing serious risks to the lives of about 60 million people and 48 million cattle globally. Nigerian medicinal plants are known to contain a large variety of chemical structures and some of the plant extracts have [...] Read more.

African trypanosomiasis is a vector-borne parasitic disease causing serious risks to the lives of about 60 million people and 48 million cattle globally. Nigerian medicinal plants are known to contain a large variety of chemical structures and some of the plant extracts have been screened for antitrypanosomal activity, in the search for potential new drugs against the illness. We surveyed the literatures on plants and plant-derived products with antitrypanosomal activity from Nigerian flora published from 1990 to 2014. About 90 plants were identified, with 54 compounds as potential active agents and presented by plant families in alphabetical order. This review indicates that the Nigerian flora may be suitable as a starting point in searching for new and more efficient trypanocidal molecules. Full article

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

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3 pages, 609 KiB

Open AccessEditorial

Special Issue: Single Molecule Techniques

by Hans H. Gorris

Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, 93040 Regensburg, Germany

Molecules 2015, 20(5), 7772-7774; https://doi.org/10.3390/molecules20057772 - 28 Apr 2015

Cited by 1 | Viewed by 5372

Abstract

Technological advances in the detection and manipulation of single molecules have enabled new insights into the function, structure and interactions of biomolecules. This Special Issue was launched to account for the rapid progress in the field of “Single Molecule Techniques”. Four original research [...] Read more.

Technological advances in the detection and manipulation of single molecules have enabled new insights into the function, structure and interactions of biomolecules. This Special Issue was launched to account for the rapid progress in the field of “Single Molecule Techniques”. Four original research articles and seven review articles provide an introduction, as well as an in-depth discussion, of technical developments that are indispensable for the characterization of individual biomolecules. Fluorescence microscopy takes center stage in this Special Issue because it is one of the most sensitive and flexible techniques, which has been adapted in many variations to the specific demands of single molecule analysis. Two additional articles are dedicated to single molecule detection based on atomic force microscopy. Full article

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

15 pages, 1028 KiB

Open AccessReview

Riluzole as a Neuroprotective Drug for Spinal Cord Injury: From Bench to Bedside

by Narihito Nagoshi^1,2, Hiroaki Nakashima^1,3 and Michael G. Fehlings^1,4,*

¹ Spinal Program, Krembil Neuroscience Center, Toronto Western Hospital, University Health Network, Toronto, ON M5T 2S8, Canada

² Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan

³ Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan

⁴ Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada

Molecules 2015, 20(5), 7775-7789; https://doi.org/10.3390/molecules20057775 - 29 Apr 2015

Cited by 112 | Viewed by 26528

Abstract

Spinal cord injury (SCI) is a devastating event resulting in permanent loss of neurological function. To date, effective therapies for SCI have not been established. With recent progress in neurobiology, however, there is hope that drug administration could improve outcomes after SCI. Riluzole [...] Read more.

Spinal cord injury (SCI) is a devastating event resulting in permanent loss of neurological function. To date, effective therapies for SCI have not been established. With recent progress in neurobiology, however, there is hope that drug administration could improve outcomes after SCI. Riluzole is a benzothiazole anticonvulsant with neuroprotective effects. It has been approved by the U.S. Food and Drug Administration as a safe and well-tolerated treatment for patients with amyotrophic lateral sclerosis. The mechanism of action of riluzole involves the inhibition of pathologic glutamatergic transmission in synapses of neurons via sodium channel blockade. There is convincing evidence that riluzole diminishes neurological tissue destruction and promotes functional recovery in animal SCI models. Based on these results, a phase I/IIa clinical trial with riluzole was conducted for patients with SCI between 2010 and 2011. This trial demonstrated significant improvement in neurological outcomes and showed it to be a safe drug with no serious adverse effects. Currently, an international, multi-center clinical trial (Riluzole in Acute Spinal Cord Injury Study: RISCIS) in phase II/III is in progress with riluzole for patients with SCI (clinicaltrials.gov, registration number NCT01597518). This article reviews the pharmacology and neuroprotective mechanisms of riluzole, and focuses on existing preclinical evidence, and emerging clinical data in the treatment of SCI. Full article

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

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17 pages, 2168 KiB

Open AccessArticle

Development of a Novel Antimicrobial Screening System Targeting the Pyoverdine-Mediated Iron Acquisition System and Xenobiotic Efflux Pumps

by Kazuki Sato^1,†, Kenichi Ushioda^1,†, Keiji Akiba¹, Yoshimi Matsumoto², Hideaki Maseda³, Tasuke Ando¹, Emiko Isogai¹, Taiji Nakae⁴ and Hiroshi Yoneyama^1,*

¹ Laboratory of Animal Microbiology, Department of Microbial Biotechnology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori, Amamiya-machi, Aoba-ku, Sendai 981-8555, Japan

² Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan

³ Department of Biological Science and Technology, Faculty of Engineering, 2-1 Minamijyousanjima-cho, Tokushima 770-8605, Japan

⁴ Laboratory for Antimicrobial Agents, Kitasato University, 1-15-1 Kitasato, Sagamihara 228-8555, Japan

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 7790-7806; https://doi.org/10.3390/molecules20057790 - 29 Apr 2015

Viewed by 6565

Abstract

The iron acquisition systems in Pseudomonas aeruginosa are inducible in response to low-iron conditions and important for growth of this organism under iron limitation. OprM is the essential outer membrane subunit of the MexAB-OprM xenobiotic efflux pump. We designed and constructed a new [...] Read more.

The iron acquisition systems in Pseudomonas aeruginosa are inducible in response to low-iron conditions and important for growth of this organism under iron limitation. OprM is the essential outer membrane subunit of the MexAB-OprM xenobiotic efflux pump. We designed and constructed a new model antimicrobial screening system targeting both the iron-uptake system and xenobiotic efflux pumps. The oprM gene was placed immediately downstream of the ferri-pyoverdine receptor gene, fpvA, in the host lacking chromosomal oprM and the expression of oprM was monitored by an antibiotic susceptibility test under iron depleted and replete conditions. The recombinant cells showed wild-type susceptibility to pump substrate antibiotics, e.g., aztreonam, under iron limitation and became supersusceptible to them under iron repletion, suggesting that expression of oprM is under control of the iron acquisition system. Upon screening of a chemical library comprising 2952 compounds using this strain, a compound—ethyl 2-(1-acetylpiperidine-4-carboxamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate—was found to enhance the efficacy of aztreonam under iron limitation, suggesting that the compound inhibits either the iron acquisition system or the MexAB-OprM efflux pump. This compound was subsequently found to inhibit the growth of wild-type cells in the presence of sublethal amounts of aztreonam, regardless of the presence or absence of dipyridyl, an iron-chelator. The compound was eventually identified to block the function of the MexAB-OprM efflux pump, showing the validity of this new method. Full article

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

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13 pages, 784 KiB

Open AccessArticle

Gd-Complexes of New Arylpiperazinyl Conjugates of DTPA-Bis(amides): Synthesis, Characterization and Magnetic Relaxation Properties

by Abdullah O. Ba-Salem¹, Nisar Ullah^1,*, M. Nasiruzzaman Shaikh^2,*, Mohamed Faiz³ and Zaheer Ul-Haq⁴

¹ Chemistry Department, King Fahd University of Petroleum and Minerals, Dhahran-31261, Saudi Arabia

² Center of Research Excellence in Nanotechnology, King Fahd University of Petroleum and Minerals, Dhahran-31261, Saudi Arabia

³ Physics Department, King Fahd University of Petroleum and Minerals, Dhahran-31261, Saudi Arabia

⁴ Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan

Molecules 2015, 20(5), 7807-7819; https://doi.org/10.3390/molecules20057807 - 29 Apr 2015

Cited by 4 | Viewed by 5771

Abstract

Two new DTPA-bis(amide) based ligands conjugated with the arylpiperazinyl moiety were synthesized and subsequently transformed into their corresponding Gd(III) complexes 1 and 2 of the type [Gd(L)H₂O]·nH₂O. The relaxivity (R₁) of these complexes was measured, which [...] Read more.

Two new DTPA-bis(amide) based ligands conjugated with the arylpiperazinyl moiety were synthesized and subsequently transformed into their corresponding Gd(III) complexes 1 and 2 of the type [Gd(L)H₂O]·nH₂O. The relaxivity (R₁) of these complexes was measured, which turned out to be comparable with that of Omniscan^®, a commercially available MRI contrast agent. The cytotoxicity studies of these complexes indicated that they are non-toxic, which reveals their potential and physiological suitability as MRI contrast agents. All the synthesized ligands and complexes were characterized with the aid of analytical and spectroscopic methods, including elemental analysis, ¹H-NMR, FT-IR, XPS and fast atom bombardment (FAB) mass spectrometry. Full article

(This article belongs to the Section Medicinal Chemistry)

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25 pages, 1935 KiB

Open AccessArticle

Regulated Deficit Irrigation Alters Anthocyanins, Tannins and Sensory Properties of Cabernet Sauvignon Grapes and Wines

by Luis Federico Casassa^1,2, Markus Keller³ and James F. Harbertson^1,*

¹ School of Food Science, Washington State University, Wine Science Center, 2710 Crimson Way, Richland, WA 99354, USA

² Wine Research Center, Estación Experimental Agropecuaria Mendoza, Instituto Nacional de Tecnología Agropecuaria, Luján de Cuyo, 5507 Mendoza, Argentina

³ Department of Horticulture, Washington State University, Irrigated Agriculture Research and Extension Center, 24106 N. Bunn Rd., Prosser, WA 99350, USA

Molecules 2015, 20(5), 7820-7844; https://doi.org/10.3390/molecules20057820 - 29 Apr 2015

Cited by 91 | Viewed by 10341

Abstract

Four regulated deficit irrigation (RDI) regimes were applied to Cabernet Sauvignon grapes, which were analyzed for phenolics and also made into wine over three consecutive growing seasons. Relative to an industry standard regime (IS), yield was reduced over the three years by 37% [...] Read more.

Four regulated deficit irrigation (RDI) regimes were applied to Cabernet Sauvignon grapes, which were analyzed for phenolics and also made into wine over three consecutive growing seasons. Relative to an industry standard regime (IS), yield was reduced over the three years by 37% in a full-deficit (FD) regime and by 18% in an early deficit (ED) regime, whereas no yield reduction occurred with a late deficit (LD) regime. Relative to IS, skin anthocyanin concentration (fresh weight basis) was 18% and 24% higher in ED and FD, respectively, whereas no effect was seen in LD. Seed tannin concentration was 3% and 8% higher in ED and FD, respectively, relative to the other two RDI regimes, whereas seed tannin content (amount per berry) was higher in IS than in FD. There were no practically relevant effects on the basic chemistry of the wines. The finished wines showed concentrations of tannins and anthocyanins that generally mirrored observed differences in skin and seed phenolic concentrations, although these were amplified in FD wines. Descriptive sensory analysis of the 2008 wines showed that FD wines were the most saturated in color, with higher purple hue, roughness, dryness and harshness, followed by ED wines, whereas IS and LD wines were less saturated in color and with higher brown and red hues. Overall, FD and ED seemed to yield fruit and wine with greater concentrations of phenolics than IS and LD, with the additional advantage of reducing water usage. However, these apparent benefits need to be balanced out with reductions in crop yields and potential long-term effects associated with pre-véraison water deficits. Full article

(This article belongs to the Collection Wine Chemistry)

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29 pages, 902 KiB

Open AccessArticle

Potential Grape-Derived Contributions to Volatile Ester Concentrations in Wine

by Paul K. Boss^1,*, Anthony D. Pearce^2,†, Yanjia Zhao², Emily L. Nicholson¹, Eric G. Dennis^1,‡

and David W. Jeffery²

¹ CSIRO Agriculture Flagship, PMB 2, Glen Osmond, SA 5064, Australia

² School of Agriculture, Food and Wine, Waite Research Institute, The University of Adelaide, PMB 1, Glen Osmond, SA 5064, Australia

^† Present address: South Australian Research and Development Institute, GPO Box 397, Adelaide, SA 5001, Australia

^‡ Present address: Department of Chemistry, The University of British Columbia, Okanagan Campus, 3333 University Way, Kelowna, BC V1V 1V7, Canada

Molecules 2015, 20(5), 7845-7873; https://doi.org/10.3390/molecules20057845 - 29 Apr 2015

Cited by 52 | Viewed by 9114

Abstract

Grape composition affects wine flavour and aroma not only through varietal compounds, but also by influencing the production of volatile compounds by yeast. C₉ and C₁₂ compounds that potentially influence ethyl ester synthesis during fermentation were studied using a model grape [...] Read more.

Grape composition affects wine flavour and aroma not only through varietal compounds, but also by influencing the production of volatile compounds by yeast. C₉ and C₁₂ compounds that potentially influence ethyl ester synthesis during fermentation were studied using a model grape juice medium. It was shown that the addition of free fatty acids, their methyl esters or acyl-carnitine and acyl-amino acid conjugates can increase ethyl ester production in fermentations. The stimulation of ethyl ester production above that of the control was apparent when lower concentrations of the C₉ compounds were added to the model musts compared to the C₁₂ compounds. Four amino acids, which are involved in CoA biosynthesis, were also added to model grape juice medium in the absence of pantothenate to test their ability to influence ethyl and acetate ester production. β-Alanine was the only one shown to increase the production of ethyl esters, free fatty acids and acetate esters. The addition of 1 mg∙L⁻¹ β-alanine was enough to stimulate production of these compounds and addition of up to 100 mg∙L⁻¹ β-alanine had no greater effect. The endogenous concentrations of β-alanine in fifty Cabernet Sauvignon grape samples exceeded the 1 mg∙L⁻¹ required for the stimulatory effect on ethyl and acetate ester production observed in this study. Full article

(This article belongs to the Collection Wine Chemistry)

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16 pages, 1388 KiB

Open AccessArticle

Improving Properties of a Novel β-Galactosidase from Lactobacillus plantarum by Covalent Immobilization

by Rocio Benavente^1,†, Benevides C. Pessela^1,*, Jose Antonio Curiel^2,†, Blanca De las Rivas^2,†, Rosario Muñoz^2,†, Jose Manuel Guisán^3,†

, Jose M. Mancheño^4,†

, Alejandra Cardelle-Cobas^5,†, Ana I. Ruiz-Matute^6,†

and Nieves Corzo^6,*

¹ Departamento de Biotecnología y Microbiología de Alimentos, Instituto de Investigación en Ciencias de la Alimentación CIAL (CSIC-UAM), Campus de la Universidad Autónoma de Madrid, Nicolás Cabrera 9, 28049 Madrid, Spain

² Grupo de Biotecnología Bacteriana, Instituto de Ciencia y Tecnología de Alimentos y Nutrición, (ICTAN-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain

³ Departamento de Biocatálisis, Instituto de Catálisis y Petroleoquímica (ICP-CSIC), Marie Curie 2, Cantoblanco, 28049 Madrid, Spain

⁴ Grupo de Cristalografía y Biología Estructural, Instituto de Química Física Rocasolano (IQFR-CSIC), Serrano 119, 28006 Madrid, Spain

⁵ CBQF—Centro de Biotecnologia e Química Fina, Escola Superior de Biotecnologia, Centro Regional do Porto da Universidade Católica Portuguesa, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal

⁶ Departamento de Bioactividad y Análisis de Alimentos, Instituto de Investigación en Ciencias de la Alimentación CIAL (CSIC-UAM), Campus de la Universidad Autónoma de Madrid, Nicolás Cabrera 9, 28049 Madrid, Spain

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 7874-7889; https://doi.org/10.3390/molecules20057874 - 30 Apr 2015

Cited by 24 | Viewed by 7164

Abstract

A novel β-galactosidase from Lactobacillus plantarum (LPG) was over-expressed in E. coli and purified via a single chromatographic step by using lowly activated IMAC (immobilized metal for affinity chromatography) supports. The pure enzyme exhibited a high hydrolytic activity of 491 IU/mL towards o [...] Read more.

A novel β-galactosidase from Lactobacillus plantarum (LPG) was over-expressed in E. coli and purified via a single chromatographic step by using lowly activated IMAC (immobilized metal for affinity chromatography) supports. The pure enzyme exhibited a high hydrolytic activity of 491 IU/mL towards o-nitrophenyl β-d-galactopyranoside. This value was conserved in the presence of different divalent cations and was quite resistant to the inhibition effects of different carbohydrates. The pure multimeric enzyme was stabilized by multipoint and multisubunit covalent attachment on glyoxyl-agarose. The glyoxyl-LPG immobilized preparation was over 20-fold more stable than the soluble enzyme or the one-point CNBr-LPG immobilized preparation at 50 °C. This β-galactosidase was successfully used in the hydrolysis of lactose and lactulose and formation of different oligosaccharides was detected. High production of galacto-oligosaccharides (35%) and oligosaccharides derived from lactulose (30%) was found and, for the first time, a new oligosaccharide derived from lactulose, tentatively identified as 3'-galactosyl lactulose, has been described. Full article

(This article belongs to the Section Natural Products Chemistry)

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25 pages, 964 KiB

Open AccessArticle

A High-Throughput UHPLC-QqQ-MS Method for Polyphenol Profiling in Rosé Wines

by Marine Lambert¹, Emmanuelle Meudec¹, Arnaud Verbaere¹, Gérard Mazerolles¹, Jérémie Wirth¹, Gilles Masson², Véronique Cheynier¹ and Nicolas Sommerer^1,*

¹ INRA, UMR 1083 Sciences Pour l'Oenologie, Polyphenol Analysis Facility, 2 place Viala, F-34060 Montpellier, France

² Centre de Recherche et d'Expérimentation sur le Vin Rosé, 70 avenue Wilson, F-83550 Vidauban, France

Molecules 2015, 20(5), 7890-7914; https://doi.org/10.3390/molecules20057890 - 30 Apr 2015

Cited by 99 | Viewed by 12285

Abstract

A rapid, sensitive and selective analysis method using Ultra High Performance Liquid Chromatography coupled to triple-quadrupole Mass Spectrometry (UHPLC-QqQ-MS) has been developed for the quantification of polyphenols in rosé wines. The compound detection being based on specific MS transitions in Multiple Reaction Monitoring [...] Read more.

A rapid, sensitive and selective analysis method using Ultra High Performance Liquid Chromatography coupled to triple-quadrupole Mass Spectrometry (UHPLC-QqQ-MS) has been developed for the quantification of polyphenols in rosé wines. The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, the present method allows the selective quantification of up to 152 phenolic and two additional non-phenolic wine compounds in 30 min without sample purification or pre-concentration, even at low concentration levels. This method was repeatably applied to a set of 12 rosé wines and thus proved to be suitable for high-throughput and large-scale metabolomics studies. Full article

(This article belongs to the Collection Wine Chemistry)

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10 pages, 955 KiB

Open AccessArticle

Cytotoxic Lignan from the Non-Transformed Root Culture of Phyllanthus amarus

by Barbara Sparzak¹, Mirosława Krauze-Baranowska^1,*, Anna Kawiak² and Paweł Sowiński³

¹ Department of Pharmacognosy with Medicinal Plants Garden, Medical University of Gdańsk, Gdańsk 80-210, Poland

² Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk 80-822, Poland

³ NMR Laboratory, Faculty of Chemistry, Technical University of Gdańsk, Gdańsk 80-233, Poland

Molecules 2015, 20(5), 7915-7924; https://doi.org/10.3390/molecules20057915 - 30 Apr 2015

Cited by 10 | Viewed by 6166

Abstract

A new lignan from the non-transformed root in vitro cultures of Phyllanthus amarus was isolated. The structure of the compound was established on the basis of one- and two-dimensional NMR, as well as mass spectrometry data, as 7'-oxocubebin dimethylether (1,4-bis(benzo[d][1,3]dioxol-5-yl)-2,3-bis(methoxymethyl)butan-1-on). The [...] Read more.

A new lignan from the non-transformed root in vitro cultures of Phyllanthus amarus was isolated. The structure of the compound was established on the basis of one- and two-dimensional NMR, as well as mass spectrometry data, as 7'-oxocubebin dimethylether (1,4-bis(benzo[d][1,3]dioxol-5-yl)-2,3-bis(methoxymethyl)butan-1-on). The non-transformed root cultures of P. amarus showed to be a selective source of this compound. The lignan revealed strong cytotoxic activity against HeLa cell line with an IC₅₀ value of 3.8 µg/mL. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 2334 KiB

Open AccessArticle

Antinociceptive Activity and Toxicity Evaluation of the Fatty Oil from Plukenetia polyadenia Mull. Arg. (Euphorbiaceae)

by Amanda S. Mota¹, Anderson B. De Lima^1,2, Thayana Lucy F. Albuquerque¹, Tiago S. Silveira², José Luiz M. do Nascimento³, Joyce Kelly R. da Silva^2,*

, Alcy F. Ribeiro⁴, José Guilherme S. Maia^5,6,* and Gilmara N. T. Bastos^1,*

¹ Laboratório de Neuroinflamação, Universidade Federal do Pará (UFPA), 66075-900 Belém, PA, Brazil

² Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Pará (UFPA), 66075-900 Belém, PA, Brazil

³ Laboratório de Neuroquímica Molecular e Celular, Universidade Federal do Pará (UFPA), 66075-900 Belém, PA, Brazil

⁴ Instituto de Ciências Exatas e Naturais, Universidade Federal do Sul e Sudeste do Pará (UNIFESSPA), 68507-590 Marabá, PA, Brazil

⁵ Programa de Pós-Graduação em Química, Universidade Federal do Pará (UFPA), 66075-900 Belém, PA, Brazil

⁶ Programa de Pós-Graduação em Recursos Naturais, Universidade Federal do Oeste do Pará (UFOPA), 68035-110 Santarém, PA, Brazil

Molecules 2015, 20(5), 7925-7939; https://doi.org/10.3390/molecules20057925 - 30 Apr 2015

Cited by 12 | Viewed by 6509

Abstract

Seed oil (Pp-oil) of Plukenetia polyadenia is used by native people of the Brazilian Amazon against arthritis and rheumatism, spreading it on the arms and legs to reduce the pain and inflammation. Pp-oil was obtained by pressing dried seeds at room temperature to [...] Read more.

Seed oil (Pp-oil) of Plukenetia polyadenia is used by native people of the Brazilian Amazon against arthritis and rheumatism, spreading it on the arms and legs to reduce the pain and inflammation. Pp-oil was obtained by pressing dried seeds at room temperature to give a 47.0% yield of oil. It was then subjected to fatty acid composition analysis. The principal fatty acids were linoleic acid (46.5%), α-linolenic acid (34.4%) and oleic acid (13.9%). Then, it was evaluated for its antinociceptive activity in mice, using the acetic acid-induced abdominal writhing, hot plate and formalin test models. Additionally, its toxicity was determined. The Pp-oil proved to have no toxicological effects, showing dose-dependent antinociceptive effect under chemical stimulation. At oral doses of 25–100 mg/kg, Pp-oil significantly reduced the abdominal writhes in the writhing test. A higher oral dose of 200 mg/kg did not induce alterations in the latency time of the hot plate test when compared to the control, suggesting an analgesic activity of peripheral origin. At oral doses of 50 and 100 mg/kg, the Pp-oil significantly reduced the second phase of the algic stimulus in the formalin test. In addition, the antinociception of Pp-oil was reversed by naloxone in the evaluation of its mechanism of action. Therefore, the Pp-oil proved to be safe at very high doses and to show significant analgesic properties. The role of Pp-oil is still being investigated with respect the mechanism of action, but the results suggest that opiod receptors could be involved in the antinociception action observed for the oil of P. polyadenia. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 1077 KiB

Open AccessArticle

Effect of Culture Conditions on Metabolite Production of Xylaria sp.

by Hongqi Zhang¹, Zhangshuang Deng^1,*, Zhiyong Guo¹, Yan Peng², Nianyu Huang¹, Haibo He¹, Xuan Tu¹ and Kun Zou^1,*

¹ Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China

² The First College of Clinical Medical Science, China Three Gorges University, Yichang 443002, China

Molecules 2015, 20(5), 7940-7950; https://doi.org/10.3390/molecules20057940 - 30 Apr 2015

Cited by 16 | Viewed by 5296

Abstract

Seeking a strategy for triggering the cryptic natural product biosynthesis to yield novel compounds in the plant-associated fungus Xylaria sp., the effect of culture conditions on metabolite production was investigated. A shift in the production of five known cytochalasin-type analogues 1–5 [...] Read more.

Seeking a strategy for triggering the cryptic natural product biosynthesis to yield novel compounds in the plant-associated fungus Xylaria sp., the effect of culture conditions on metabolite production was investigated. A shift in the production of five known cytochalasin-type analogues 1–5 to six new α-pyrone derivatives, xylapyrones A–F (compounds 6–11), from a solid to a liquid medium was observed. These compounds were identified by analysis of 1D and 2D NMR and HRMS data. Compounds 1–3 showed moderate cytotoxicity against HepG2 and Caski cancer cell lines with IC₅₀ values ranging from 25 to 63 μM and compounds 4–11 were found to be inactive, with IC₅₀ values >100 μM. Full article

(This article belongs to the Section Natural Products Chemistry)

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6 pages, 645 KiB

Open AccessEditorial

Special Issue: Practical Applications of Metal Complexes

by Iztok Turel

Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia

Molecules 2015, 20(5), 7951-7956; https://doi.org/10.3390/molecules20057951 - 30 Apr 2015

Cited by 24 | Viewed by 8430

Abstract

In 1913 Alfred Werner received the Nobel Prize in Chemistry for his work that was of great importance for the development of coordination chemistry. In the years that followed numerous complexes consisting of metal ions and organic ligands were isolated, thus building a [...] Read more.

In 1913 Alfred Werner received the Nobel Prize in Chemistry for his work that was of great importance for the development of coordination chemistry. In the years that followed numerous complexes consisting of metal ions and organic ligands were isolated, thus building a strong connection between inorganic and organic chemistry. Coordination compounds have many interesting properties which find diverse applications in numerous aspects of human life. Fourteeen contributions were received for this Special Issue covering very different aspects of metal complexes and their practical applications. The highest number of manuscripts deals with the biological activity of complexes which might potentially be used in the clinical practice. Authors have tested their cytotoxicity, antibacterial activity and enzyme inhibition. Their optical properties were studied in view of their potential use in photodynamic therapy. Moreover, optical properties could also be used for bioanalysis. It is also known that metal complexes are useful catalysts and a few such examples are also described herein. Many other interesting properties and facts about the isolated and described complexes are also reported (radioactivity, design of metal-organic frameworks, etc.). Full article

(This article belongs to the Special Issue Practical Applications of Metal Complexes)

17 pages, 1151 KiB

Open AccessArticle

Effective Immobilization of Agrobacterium sp. IFO 13140 Cells in Loofa Sponge for Curdlan Biosynthesis

by Camila Ortiz Martinez¹, Suelen Pereira Ruiz¹, Marcela Tiemi Nogueira², Evandro Bona³, Márcia Portilho² and Graciette Matioli^1,2,*

¹ Postgraduate Program in Food Science, State University of Maringá (UEM), Av. Colombo, 5790, Maringá-PR 87020-900, Brazil

² Pharmacy Department, State University of Maringá (UEM), Av. Colombo, 5790, Maringá-PR 87020-900, Brazil

³ Food Engineering Department, Federal Technological University of Paraná (UTFPR), Via Rosalina Maria dos Santos, 1233, Campo Mourão-PR 87301-899, Brazil

Molecules 2015, 20(5), 7957-7973; https://doi.org/10.3390/molecules20057957 - 4 May 2015

Cited by 13 | Viewed by 5295

Abstract

Curdlan production by Agrobacterium sp. IFO13140 immobilized on loofa sponge, alginate and loofa sponge with alginate was investigated. There was no statistically-significant difference in curdlan production when the microorganism was immobilized in different matrices. The loofa sponge was chosen because of its practical [...] Read more.

Curdlan production by Agrobacterium sp. IFO13140 immobilized on loofa sponge, alginate and loofa sponge with alginate was investigated. There was no statistically-significant difference in curdlan production when the microorganism was immobilized in different matrices. The loofa sponge was chosen because of its practical application and economy and because it provides a high stability through its continued use. The best conditions for immobilization on loofa sponge were 50 mg of cell, 200 rpm and 72 h of incubation, which provided a curdlan production 1.50-times higher than that obtained by free cells. The higher volumetric productivity was achieved by immobilized cells (0.09 g/L/h) at 150 rpm. The operating stability was evaluated, and until the fourth cycle, immobilized cells retained 87.40% of the production of the first cycle. The immobilized cells remained active after 300 days of storage at 4 °C. The results of this study demonstrate success in immobilizing cells for curdlan biosynthesis, making the process potentially suitable for industrial scale-up. Additional studies may show a possible contribution to the reduction of operating costs. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 1228 KiB

Open AccessArticle

Investigating the Effect of Cold Soak Duration on Phenolic Extraction during Cabernet Sauvignon Fermentation

by Siriwan Panprivech^1,2, Larry A. Lerno², Charles A. Brenneman², David E. Block² and Anita Oberholster^2,*

¹ Faculty of Biotechnology, Assumption University, Bangkok 10240, Thailand

² Department of Viticulture and Enology, University of California, Davis, CA 95616-8749, USA

Molecules 2015, 20(5), 7974-7989; https://doi.org/10.3390/molecules20057974 - 4 May 2015

Cited by 31 | Viewed by 7264

Abstract

The impact of increasing cold soak (CS) duration (0, 1, 4, 7, and 10 days at 10 °C) on the extraction of phenolic compounds during the CS period and primary fermentation as well as the final composition of Cabernet Sauvignon wine was investigated. [...] Read more.

The impact of increasing cold soak (CS) duration (0, 1, 4, 7, and 10 days at 10 °C) on the extraction of phenolic compounds during the CS period and primary fermentation as well as the final composition of Cabernet Sauvignon wine was investigated. The results showed that CS duration had no effect on hydroxycinnamate and flavonol extractions. Greater amounts of gallic acid, (+)-catechin, (−)-epicatechin, and total tannins were extracted with increasing CS duration, with differences maintained during bottle aging. Anthocyanin extraction and color density increased with longer periods of CS; however, by the end of primary fermentation, as well as three months’ bottle aging, there were no significant differences due to CS duration. The wines made with seven and 10 days of CS had higher seed tannin contributions and total tannin compared to the non-CS wine, which could potentially result in increased astringency. Full article

(This article belongs to the Collection Wine Chemistry)

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10 pages, 862 KiB

Open AccessArticle

Chemical Composition and Insecticidal Activity of Essential Oils from Zanthoxylum dissitum Leaves and Roots against Three Species of Storage Pests

by Cheng-Fang Wang^1,2, Kai Yang¹, Chun-Xue You¹

, Wen-Juan Zhang¹

, Shan-Shan Guo¹, Zhu-Feng Geng¹, Shu-Shan Du^1,* and Yong-Yan Wang¹

¹ Beijing Key Laboratory of Traditional Chinese Medicine Protection and Utilization, Beijing Normal University, No.19, Xinjiekouwai Street, Beijing 100875, China

² 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

Molecules 2015, 20(5), 7990-7999; https://doi.org/10.3390/molecules20057990 - 4 May 2015

Cited by 38 | Viewed by 6643

Abstract

This work aimed to investigate chemical composition of essential oils obtained from Zanthoxylum dissitum leaves and roots and their insecticidal activities against several stored product pests, namely the cigarette beetle (Lasioderma serricorne), red flour beetle (Tribolium castaneum) and black [...] Read more.

This work aimed to investigate chemical composition of essential oils obtained from Zanthoxylum dissitum leaves and roots and their insecticidal activities against several stored product pests, namely the cigarette beetle (Lasioderma serricorne), red flour beetle (Tribolium castaneum) and black carpet beetle (Attagenus piceus). The analysis by GC-MS of the essential oils allowed the identification of 28 and 22 components, respectively. It was found that sesquiterpenoids comprised a fairly high portion of the two essential oils, with percentages of 74.0% and 80.9% in the leaves and roots, respectively. The main constituents identified in the essential oil of Z. dissitum leaves were δ-cadinol (12.8%), caryophyllene (12.7%), β-cubebene (7.9%), 4-terpineol (7.5%) and germacrene D-4-ol (5.7%), while humulene epoxide II (29.4%), caryophyllene oxide (24.0%), diepicedrene-1-oxide (10.7%) and Z,Z,Z-1,5,9,9-tetramethyl-1,4,7-cycloundecatriene (8.7%) were the major components in the essential oil of Z. dissitum roots. The insecticidal activity results indicated that the essential oil of Z. dissitum roots exhibited moderate contact toxicity against three species of storage pests, L. serricorne,T. castaneum and A. piceus, with LD₅₀ values of 13.8, 43.7 and 96.8 µg/adult, respectively. Full article

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20 pages, 1070 KiB

Open AccessArticle

NBM-T-BBX-OS01, Semisynthesized from Osthole, Induced G1 Growth Arrest through HDAC6 Inhibition in Lung Cancer Cells

by Jih-Tung Pai¹, Chia-Yun Hsu², Kuo-Tai Hua³, Sheng-Yung Yu², Chung-Yang Huang⁴, Chia-Nan Chen⁴, Chiung-Ho Liao⁵ and Meng-Shih Weng^2,*

¹ Division of Hematology and Oncology, Tao-Yuan General Hospital, Ministry of Health and Welfare, Taoyuan City 33004, Taiwan

² Department of Nutritional Science, Fu Jen Catholic University, New Taipei City 24205, Taiwan

³ Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan

⁴ NatureWise Biotech and Medicals Corporation, Taipei 11559, Taiwan

⁵ Division of Drug and New Technology Product, Food and Drug Administration, Ministry of Health and Welfare, Executive Yuan, Taipei 11516, Taiwan

Molecules 2015, 20(5), 8000-8019; https://doi.org/10.3390/molecules20058000 - 4 May 2015

Cited by 18 | Viewed by 7197

Abstract

Disrupting lung tumor growth via histone deacetylases (HDACs) inhibition is a strategy for cancer therapy or prevention. Targeting HDAC6 may disturb the maturation of heat shock protein 90 (Hsp90) mediated cell cycle regulation. In this study, we demonstrated the effects of semisynthesized NBM-T-BBX-OS01 [...] Read more.

Disrupting lung tumor growth via histone deacetylases (HDACs) inhibition is a strategy for cancer therapy or prevention. Targeting HDAC6 may disturb the maturation of heat shock protein 90 (Hsp90) mediated cell cycle regulation. In this study, we demonstrated the effects of semisynthesized NBM-T-BBX-OS01 (TBBX) from osthole on HDAC6-mediated growth arrest in lung cancer cells. The results exhibited that the anti-proliferative activity of TBBX in numerous lung cancer cells was more potent than suberoylanilide hydroxamic acid (SAHA), a clinically approved pan-HDAC inhibitor, and the growth inhibitory effect has been mediated through G1 growth arrest. Furthermore, the protein levels of cyclin D1, CDK2 and CDK4 were reduced while cyclin E and CDK inhibitor, p21^Waf1/Cip1, were up-regulated in TBBX-treated H1299 cells. The results also displayed that TBBX inhibited HDAC6 activity via down-regulation HDAC6 protein expression. TBBX induced Hsp90 hyper-acetylation and led to the disruption of cyclin D1/Hsp90 and CDK4/Hsp90 association following the degradation of cyclin D1 and CDK4 proteins through proteasome. Ectopic expression of HDAC6 rescued TBBX-induced G1 arrest in H1299 cells. Conclusively, the data suggested that TBBX induced G1 growth arrest may mediate HDAC6-caused Hsp90 hyper-acetylation and consequently increased the degradation of cyclin D1 and CDK4. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 1817 KiB

Open AccessArticle

Silver(I) 2,2'-(1,2-Phenylenedisulfanediyl)diacetic Acid as a Molecular Building Block for a Silver(I)-Cadmium(II) Coordination Polymer

by Ioana Georgeta Grosu^1,2,†, Christiane Berghof^1,†, Peter Lönnecke¹

, Luminita Silaghi-Dumitrescu² and Evamarie Hey-Hawkins^1,*

¹ Institut für Anorganische Chemie, Universität Leipzig, Johannisallee 29, D-04103 Leipzig, Germany

² Department of Chemistry, Babeş-Bolyai University, Kogalniceanu 1, RO-400084 Cluj-Napoca, Romania

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 8020-8032; https://doi.org/10.3390/molecules20058020 - 4 May 2015

Cited by 1 | Viewed by 5557

Abstract

Starting from heterotopic multidentate ligand 2,2'-(1,2-phenylenedisulfanediyl)diacetic acid, (R_S,R_S,R_S,R_S/S_S,S_S,S_S,S_S)-[Ag{1,2-C₆H₄(SCH₂COOH)₂-κ²S,S'}₂]BF₄ (1) was prepared and further used as a building block for the synthesis of heterobimetallic Ag-Cd coordination polymer [Ag₂Cd₂{1,2-(OOCCH₂S)₂C₆H₄}₃(H₂O)₃·5H₂O]_n (2). Both complexes were characterized by X-ray structure analysis and conventional spectroscopic techniques. Full article

(This article belongs to the Special Issue Metal-Organic Frameworks: Chemistry and Applications)

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15 pages, 715 KiB

Open AccessArticle

Chemical Characterization and Anti-Oomycete Activity of Laureliopsis philippianna Essential Oils against Saprolegnia parasitica and S. australis

by Alejandro Madrid^1,*, Patricio Godoy², Sebastián González², Luis Zaror³, Alejandra Moller⁴, Enrique Werner⁵, Mauricio Cuellar⁶, Joan Villena⁴ and Iván Montenegro^7,*

¹ Departamento de Química, Facultad de Ciencias Naturales y Exactas, Universidad de Playa Ancha, Avda. Leopoldo Carvallo 270, Playa Ancha, Valparaíso 2340000, Chile

² Instituto de Microbiología Clínica, Facultad de Medicina, Universidad Austral de Chile, Los Laureles s/n, Isla Teja, Valdivia 5090000, Chile

³ Escuela de Tecnología Médica, Facultad de Medicina, Universidad Mayor, Av. Alemania 0281, Temuco 4780000, Chile

⁴ Centro de Investigaciones Biomédicas (CIB), Escuela de Medicina, Universidad de Valparaíso, Av. Hontaneda N° 2664, Valparaíso 2340000, Chile

⁵ Departamento de Ciencias Básicas, Campus Fernando May, Universidad del Bío-Bío, Avda. Andrés Bello s/n casilla 447, Chillán 3780000, Chile

⁶ Facultad de Farmacia, Escuela de Química y Farmacia, Universidad de Valparaíso, Av. Gran Bretaña N° 1093, Valparaíso 2340000, Chile

⁷ Escuela de Obstetricia y Puericultura, Facultad de Medicina, Universidad de Valparaíso, Blanco N° 1911, Valparaíso 2340000, Chile

Molecules 2015, 20(5), 8033-8047; https://doi.org/10.3390/molecules20058033 - 5 May 2015

Cited by 31 | Viewed by 6873

Abstract

Laureliopsis philippiana (Looser) R. Schodde (Monimiaceae) is a native tree widespread in the forest areas in the south of Chile and Argentina, known for its medicinal properties and excellent wood. The aim of this study was to evaluate the chemical composition of L. [...] Read more.

Laureliopsis philippiana (Looser) R. Schodde (Monimiaceae) is a native tree widespread in the forest areas in the south of Chile and Argentina, known for its medicinal properties and excellent wood. The aim of this study was to evaluate the chemical composition of L. philippiana leaf and bark essential oils (EOs) using gas chromatography-mass spectrometry (GC-MS), and to quantify its anti-oomycete activity, specifically against Saprolegnia parasitica and S. australis. Only six components were identified in leaf EO, 96.92% of which are phenylpropanoids and 3.08% are terpenes. As for bark EO, 29 components were identified, representing 67.61% for phenylpropanoids and 32.39% for terpenes. Leaf EO was characterized mainly by safrole (96.92%) and β-phellandrene (1.80%). Bark EO was characterized mainly by isosafrole (30.07%), safrole (24.41%), eucalyptol (13.89%), methyleugenol (7.12%), and eugenol (6.01%). Bark EO has the most promising anti-Saprolegnia activity, with a minimum inhibition concentration (MIC) value of 30.0 µg/mL against mycelia growth and a minimum fungicidal concentration (MFC) value of 50.0 μg/mL against spores; for leaf EO, the MIC and MFC values are 100 and 125 µg/mL, respectively. These findings demonstrate that bark EO has potential to be developed as a remedy for the control of Saprolegnia spp. in aquaculture. Full article

(This article belongs to the Section Natural Products Chemistry)

12 pages, 704 KiB

Open AccessArticle

Composition of the Essential Oil of Salvia ballotiflora (Lamiaceae) and Its Insecticidal Activity

by Norma Cecilia Cárdenas-Ortega¹, Marco Martín González-Chávez¹, Rodolfo Figueroa-Brito², Antonio Flores-Macías³, Diana Romo-Asunción⁴, Diana Elizabeth Martínez-González⁴, Víctor Pérez-Moreno⁵ and Miguel Angel Ramos-López^5,*

¹ Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, Zona Universitaria, C.P. 78290 San Luis Potosí, S.L.P., Mexico

² Centro de Desarrollo de Productos Bióticos, Instituto Politécnico Nacional, Carretera Yautepec-Jojutla, km 6, Calle Ceprobi No. 6, Col. San Isidro, C.P. 62731 Yautepec, Morelos, Mexico

³ Departamento de Producción Agrícola y Animal, Universidad Autónoma Metropolitana Unidad Xochimilco, Calzada del Hueso 1100, Col. Villa Quietud, C.P. 04960 Deleg. Coyoacán, D.F., Mexico

⁴ Estudiante de la Maestría en Ciencias Agropecuarias, Universidad Autónoma Metropolitana Unidad Xochimilco, Calzada del Hueso 1100, Col. Villa Quietud, C.P. 04960 Deleg. Coyoacán, D.F., Mexico

⁵ Facultad de Química, Universidad Autónoma de Querétaro, Cerro de las Campanas s/n, Col. Las Campanas, C.P. 76010 Santiago de Querétaro, Querétaro, Mexico

Molecules 2015, 20(5), 8048-8059; https://doi.org/10.3390/molecules20058048 - 5 May 2015

Cited by 44 | Viewed by 7792

Abstract

Essential oils can be used as an alternative to using synthetic insecticides for pest management. Therefore, the insectistatic and insecticidal activities of the essential oil of aerial parts of Salvia ballotiflora (Lamiaceae) were tested against the fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae). The [...] Read more.

Essential oils can be used as an alternative to using synthetic insecticides for pest management. Therefore, the insectistatic and insecticidal activities of the essential oil of aerial parts of Salvia ballotiflora (Lamiaceae) were tested against the fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae). The results demonstrated insecticidal and insectistatical activities against this insect pest with concentrations at 80 µg·mL⁻¹ resulting in 20% larval viability and 10% pupal viability. The larval viability fifty (LV₅₀) corresponded to a concentration of 128.8 µg·mL⁻¹. This oil also increased the duration of the larval phase by 5.5 days and reduced the pupal weight by 29.2% withrespect to the control. The GC-MS analysis of the essential oil of S. ballotiflora showed its main components to be caryophyllene oxide (15.97%), and β-caryophyllene (12.74%), which showed insecticidal and insectistatical activities against S. frugiperda. The insecticidal activity of β-caryophyllene began at 80 µg·mL⁻¹, giving a larval viability of 25% and viability pupal of 20%. The insectistatic activity also started at 80 µg·mL⁻¹ reducing the pupal weight by 22.1% with respect to control. Caryophyllene oxide showed insecticidal activity at 80 µg·mL⁻¹ giving a larval viability of 35% and viability pupal of 20%.The insectistatic activity started at 400 µg·mL⁻¹ and increased the larval phase by 8.8% days with respect to control. The LV₅₀ values for these compounds were 153.1 and 146.5 µg·mL⁻¹, respectively. Full article

(This article belongs to the Collection Bioactive Compounds)

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12 pages, 1664 KiB

Open AccessArticle

Interference of Phenylethanoid Glycosides from Cistanche tubulosa with the MTT Assay

by Yu-Jie Wang^1,*, Si-Min Zhou², Gang Xu² and Yu-Qi Gao²

¹ College of Ethnomedicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China

² College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China

Molecules 2015, 20(5), 8060-8071; https://doi.org/10.3390/molecules20058060 - 5 May 2015

Cited by 24 | Viewed by 14594

Abstract

The MTT assay, as a screening method, has been widely used to measure the viability and proliferation of cells. However, it should be noted that MTT assay may not accurately reflect the effect of Cistanche tubulosa ethanolic extract on EA.hy926 cells viability. To [...] Read more.

The MTT assay, as a screening method, has been widely used to measure the viability and proliferation of cells. However, it should be noted that MTT assay may not accurately reflect the effect of Cistanche tubulosa ethanolic extract on EA.hy926 cells viability. To investigate and identity the components responsible for the contradictory observations of the MTT assay, echinacoside and acteoside, two main phenylethanoid glycosides, from C. tubulosa ethanolic extract were isolated. The data derived from CCK-8, Hoechst 33342 and annexin V-FITC/PI assays suggest that the caffeyl group present in both isolated compounds was responsible for the conflicting results of the MTT assay. These data emphasize the need of using a variety of different methods to determine the effect of medicinal agents on cell viability to avoid generating misleading results. Full article

(This article belongs to the Section Natural Products Chemistry)

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22 pages, 2145 KiB

Open AccessArticle

Antimycobacterial and Anti-Inflammatory Activities of Substituted Chalcones Focusing on an Anti-Tuberculosis Dual Treatment Approach

by Thatiana Lopes Biá Ventura^1,2, Sanderson Dias Calixto¹, Bárbara De Azevedo Abrahim-Vieira³, Alessandra Mendonça Teles de Souza³, Marcos Vinícius Palmeira Mello⁴, Carlos Rangel Rodrigues³, Leandro Soter de Mariz e Miranda⁵, Rodrigo Octavio Mendonça Alves De Souza⁵, Ivana Correa Ramos Leal³

, Elena B. Lasunskaia^1,*,† and Michelle Frazão Muzitano^2,*,†

¹ Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes 28013-602, RJ, Brazil

² Laboratório de Produtos Bioativos, Curso de Farmácia, Universidade Federal do Rio de Janeiro, Campus Macaé, Pólo Novo Cavaleiro—IMMT, Macaé 27933-378, RJ, Brazil

³ Faculdade de Farmácia, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro 21941-901, RJ, Brazil

⁴ Instituto de Química, Universidade Federal Fluminense, Niterói, Rio de Janeiro 24020141, RJ, Brazil

⁵ Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, RJ, Brazil

^† E.B.L. and M.F.M. authors are joint senior authors on this work.

Molecules 2015, 20(5), 8072-8093; https://doi.org/10.3390/molecules20058072 - 5 May 2015

Cited by 46 | Viewed by 8108

Abstract

Tuberculosis (TB) remains a serious public health problem aggravated by the emergence of M. tuberculosis (Mtb) strains resistant to multiple drugs (MDR). Delay in TB treatment, common in the MDR-TB cases, can lead to deleterious life-threatening inflammation in susceptible hyper-reactive individuals, encouraging the [...] Read more.

Tuberculosis (TB) remains a serious public health problem aggravated by the emergence of M. tuberculosis (Mtb) strains resistant to multiple drugs (MDR). Delay in TB treatment, common in the MDR-TB cases, can lead to deleterious life-threatening inflammation in susceptible hyper-reactive individuals, encouraging the discovery of new anti-Mtb drugs and the use of adjunctive therapy based on anti-inflammatory interventions. In this study, a series of forty synthetic chalcones was evaluated in vitro for their anti-inflammatory and antimycobacterial properties and in silico for pharmacokinetic parameters. Seven compounds strongly inhibited NO and PGE₂ production by LPS-stimulated macrophages through the specific inhibition of iNOS and COX-2 expression, respectively, with compounds 4 and 5 standing out in this respect. Four of the seven most active compounds were able to inhibit production of TNF-α and IL-1β. Chalcones that were not toxic to cultured macrophages were tested for antimycobacterial activity. Eight compounds were able to inhibit growth of the M. bovis BCG and Mtb H37Rv strains in bacterial cultures and in infected macrophages. Four of them, including compounds 4 and 5, were active against a hypervirulent clinical Mtb isolate as well. In silico analysis of ADMET properties showed that the evaluated chalcones displayed satisfactory pharmacokinetic parameters. In conclusion, the obtained data demonstrate that at least two of the studied chalcones, compounds 4 and 5, are promising antimycobacterial and anti-inflammatory agents, especially focusing on an anti-tuberculosis dual treatment approach. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 1473 KiB

Open AccessArticle

Effect of Chum Salmon Egg Lectin on Tight Junctions in Caco-2 Cell Monolayers

by Ryo Nemoto¹, Shintaro Yamamoto¹, Tomohisa Ogawa¹, Ryno Naude² and Koji Muramoto^1,*

¹ Graduate School of Life Sciences, Tohoku University, Katahira 2-1-1, Aoba-ku, Sendai 980-8577, Japan

² Department of Biochemistry and Microbiology, Nelson Mandel Metropolitan University, Port Elizabeth 6031, South Africa

Molecules 2015, 20(5), 8094-8106; https://doi.org/10.3390/molecules20058094 - 5 May 2015

Cited by 10 | Viewed by 6150

Abstract

The effect of a chum salmon egg lectin (CSL3) on tight junction (TJ) of Caco-2 cell monolayers was investigated. The lectin opened TJ as indicated by the decrease of the transepithelial electrical resistance (TER) value and the increase of the permeation of lucifer [...] Read more.

The effect of a chum salmon egg lectin (CSL3) on tight junction (TJ) of Caco-2 cell monolayers was investigated. The lectin opened TJ as indicated by the decrease of the transepithelial electrical resistance (TER) value and the increase of the permeation of lucifer yellow, which is transported via the TJ-mediated paracellular pathway. The effects of CSL3 were inhibited by the addition of 10 mM L-rhamnose or D-galactose which were specific sugars for CSL3. The lectin increased the intracellular Ca²⁺ of Caco-2 cell monolayers, that could be inhibited by the addition of L-rhamnose. The fluorescence immunostaining of β-actin in Caco-2 cell monolayers revealed that the cytoskeleton was changed by the CSL3 treatment, suggesting that CSL3 depolymerized β-actin to cause reversible TJ structural and functional disruption. Although Japanese jack bean lectin and wheat germ lectin showed similar effects in the decrease of the TER values and the increase of the intracellular Ca²⁺, they could not be inhibited by the same concentrations of simple sugars, such as D-glucose and N-acetyl-D-glucosamine. Full article

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

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18 pages, 873 KiB

Open AccessArticle

Qualitative and Quantitative Analysis of Lignan Constituents in Caulis Trachelospermi by HPLC-QTOF-MS and HPLC-UV

by Xiao-Ting Liu^1,2, Xu-Guang Wang¹, Rui Xu¹, Fan-Hua Meng¹, Neng-Jiang Yu^1,* and Yi-Min Zhao^1,*

¹ Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China

² School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China

Molecules 2015, 20(5), 8107-8124; https://doi.org/10.3390/molecules20058107 - 5 May 2015

Cited by 14 | Viewed by 7518

Abstract

A high-performance liquid chromatography coupled with quadrupole tandem time-of-flight mass (HPLC-QTOF-MS) and ultraviolet spectrometry (HPLC-UV) was established for simultaneous qualitative and quantitative analysis of the major chemical constituents in Caulis Trachelospermi, respectively. The analysis was performed on an Agilent Zorbax Eclipse Plus C18 [...] Read more.

A high-performance liquid chromatography coupled with quadrupole tandem time-of-flight mass (HPLC-QTOF-MS) and ultraviolet spectrometry (HPLC-UV) was established for simultaneous qualitative and quantitative analysis of the major chemical constituents in Caulis Trachelospermi, respectively. The analysis was performed on an Agilent Zorbax Eclipse Plus C18 column (4.6 mm × 150 mm, 5 μm) using a binary gradient system of water and methanol, with ultraviolet absorption at 230 nm. Based on high-resolution ESI-MS/MS fragmentation behaviors of the reference standards, the characteristic cleavage patterns of lignano-9, 9'-lactones and lignano-8'-hydroxy-9, 9'-lactones were obtained. The results demonstrated that the characteristic fragmentation patterns are valuable for identifying and differentiating lignano-9,9'-lactones and lignano-8'-hydroxy-9,9'-lactones. As such, a total of 25 compounds in Caulis Trachelospermi were unambiguously or tentatively identified via comparisons with reference standards or literature. In addition, 14 dibenzylbutyrolatone lignans were simultaneously quantified in Caulis Trachelospermi by HPLC-UV method. The method is suitable for the qualitative and quantitative analyses of dibenzylbutyrolatone lignans in Caulis Trachelospermi. Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 754 KiB

Open AccessArticle

Synthesis, Antimicrobial and Hypoglycemic Activities of Novel N-(1-Adamantyl)carbothioamide Derivatives

by Ebtehal S. Al-Abdullah¹, Hanaa M. Al-Tuwaijri¹, Hanan M. Hassan², Monirah A. Al-Alshaikh³, Elsayed E. Habib^4,5 and Ali A. El-Emam^1,*

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

² Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia

³ Department of Chemistry, College of Sciences, King Saud University, Riyadh 11451, Saudi Arabia

⁴ Department of Microbiology, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt

⁵ Department of Pharmaceutics and Pharmaceutical Technology (Microbiology), College of Pharmacy, Taibah University, Almadinah Almunawwarah 11344, Saudi Arabia

Molecules 2015, 20(5), 8125-8143; https://doi.org/10.3390/molecules20058125 - 6 May 2015

Cited by 29 | Viewed by 6555

Abstract

The reaction of 1-adamantyl isothiocyanate 4 with the various cyclic secondary amines yielded the corresponding N-(1-adamantyl)carbothioamides 5a–e, 6, 7, 8a–c and 9. Similarly, the reaction of 4 with piperazine and trans-2,5-dimethylpiperazine in 2:1 [...] Read more.

The reaction of 1-adamantyl isothiocyanate 4 with the various cyclic secondary amines yielded the corresponding N-(1-adamantyl)carbothioamides 5a–e, 6, 7, 8a–c and 9. Similarly, the reaction of 4 with piperazine and trans-2,5-dimethylpiperazine in 2:1 molar ratio yielded the corresponding N,N'-bis(1-adamantyl)piperazine-1,4-dicarbothioamides 10a and 10b, respectively. The reaction of N-(1-adamantyl)-4-ethoxycarbonylpiperidine-1-carbothioamide 8c with excess hydrazine hydrate yielded the target carbohydrazide 11, in addition to 4-(1-adamantyl)thiosemicarbazide 12 as a minor product. The reaction of the carbohydrazide 11 with methyl or phenyl isothiocyanate followed by heating in aqueous sodium hydroxide yielded the 1,2,4-triazole analogues 14a and 14b. The reaction of the carbohydrazide 11 with various aromatic aldehydes yielded the corresponding N'-arylideneamino derivatives 15a–g. The compounds 5a–e, 6, 7, 8a–c, 9, 10a, 10b, 14a, 14b and 15a–g were tested for in vitro antimicrobial activity against certain strains of pathogenic Gram-positive and Gram-negative bacteria and the yeast-like fungus Candida albicans. The compounds 5c, 5d, 5e, 6, 7, 10a, 10b, 15a, 15f and 15g showed potent antibacterial activity against one or more of the tested microorganisms. The oral hypoglycemic activity of compounds 5c, 6, 8b, 9, 14a and 15b was determined in streptozotocin (STZ)-induced diabetic rats. Compound 5c produced significant reduction of serum glucose levels, compared to gliclazide. Full article

(This article belongs to the Section Medicinal Chemistry)

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24 pages, 1049 KiB

Open AccessReview

Hitting the Sweet Spot: Glycans as Targets of Fungal Defense Effector Proteins

by Markus Künzler

Institute of Microbiology, Department of Biology, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland

Molecules 2015, 20(5), 8144-8167; https://doi.org/10.3390/molecules20058144 - 6 May 2015

Cited by 34 | Viewed by 7339

Abstract

Organisms which rely solely on innate defense systems must combat a large number of antagonists with a comparatively low number of defense effector molecules. As one solution of this problem, these organisms have evolved effector molecules targeting epitopes that are conserved between different [...] Read more.

Organisms which rely solely on innate defense systems must combat a large number of antagonists with a comparatively low number of defense effector molecules. As one solution of this problem, these organisms have evolved effector molecules targeting epitopes that are conserved between different antagonists of a specific taxon or, if possible, even of different taxa. In order to restrict the activity of the defense effector molecules to physiologically relevant taxa, these target epitopes should, on the other hand, be taxon-specific and easily accessible. Glycans fulfill all these requirements and are therefore a preferred target of defense effector molecules, in particular defense proteins. Here, we review this defense strategy using the example of the defense system of multicellular (filamentous) fungi against microbial competitors and animal predators. Full article

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

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13 pages, 607 KiB

Open AccessArticle

Antitrypanosomal Acetylene Fatty Acid Derivatives from the Seeds of Porcelia macrocarpa (Annonaceae)

by Luciana De Á. Santos^1,*, Alberto J. Cavalheiro¹, Andre G. Tempone², Daniela S. Correa², Tatiana R. Alexandre², Natalia F. Quintiliano³, André F. Rodrigues-Oliveira³, Diogo Oliveira-Silva³, Roberto Carlos C. Martins⁴ and João Henrique G. Lago³

¹ Bioensaios, Biossíntese e Ecofisiologia de Produtos Naturais—NuBBE, Instituto de Química, Universidade Estadual Paulista, 14800-060 Araraquara, SP, Brazil

² Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, 01246-902 São Paulo, SP, Brazil

³ Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, 09972-270 Diadema, SP, Brazil

⁴ Instituto de Pesquisa em Produtos Naturais, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, RJ, Brazil

Molecules 2015, 20(5), 8168-8180; https://doi.org/10.3390/molecules20058168 - 7 May 2015

Cited by 9 | Viewed by 6804

Abstract

Chagas’ disease is caused by a parasitic protozoan and affects the poorest population in the world, causing high mortality and morbidity. As a result of the toxicity and long duration of current treatments, the discovery of novel and more efficacious drugs is crucial. [...] Read more.

Chagas’ disease is caused by a parasitic protozoan and affects the poorest population in the world, causing high mortality and morbidity. As a result of the toxicity and long duration of current treatments, the discovery of novel and more efficacious drugs is crucial. In this work, the hexane extract from seeds of Porcelia macrocarpa R.E. Fries (Annonaceae) displayed in vitro antitrypanosomal activity against trypomastigote forms of T. cruzi by the colorimetric MTT assay (IC₅₀ of 65.44 μg/mL). Using chromatographic fractionation over SiO₂, this extract afforded a fraction composed by one active compound (IC₅₀ of 10.70 µg/mL), which was chemically characterized as 12,14-octadecadiynoic acid (macrocarpic acid). Additionally, two new inactive acetylene compounds (α,α'-dimacro-carpoyl-β-oleylglycerol and α-macrocarpoyl-α'-oleylglycerol) were also isolated from the hexane extract. The complete characterization of the isolated compounds was performed by analysis of NMR and MS data as well as preparation of derivatives. Full article

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

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17 pages, 3436 KiB

Open AccessArticle

Novel All Trans-Retinoic Acid Derivatives: Cytotoxicity, Inhibition of Cell Cycle Progression and Induction of Apoptosis in Human Cancer Cell Lines

by Ebtesam Saad Al-Sheddi¹, Mai Mohammad Al-Oqail¹, Quaiser Saquib^2,3, Maqsood Ahmed Siddiqui^2,3, Javed Musarrat^2,3, Abdulaziz Ali Al-Khedhairy² and Nida Nayyar Farshori^1,*

¹ Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia

² Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia

³ Al-Jeraisy Chair for DNA Research, College of Science, King Saud University, Riyadh 11451, Saudi Arabia

Molecules 2015, 20(5), 8181-8197; https://doi.org/10.3390/molecules20058181 - 7 May 2015

Cited by 23 | Viewed by 8136

Abstract

Owing to the pharmacological potential of ATRA (all trans-retinoic acid), a series of retinamides and a 1-(retinoyl)-1,3-dicyclohexylurea compound were prepared by reacting ATRA with long chain alkyl or alkenyl fatty amines by using a 4-demethylaminopyridine (DMAP)-catalyzed N,N¢-dicyclohexylcarbodiimide (DCC) coupling. The successful synthesis [...] Read more.

Owing to the pharmacological potential of ATRA (all trans-retinoic acid), a series of retinamides and a 1-(retinoyl)-1,3-dicyclohexylurea compound were prepared by reacting ATRA with long chain alkyl or alkenyl fatty amines by using a 4-demethylaminopyridine (DMAP)-catalyzed N,N¢-dicyclohexylcarbodiimide (DCC) coupling. The successful synthesis of the target compounds was demonstrated using a range of spectroscopic techniques. The cytotoxicity of the compounds was measured along with their ability to induce cell cycle arrest and apoptosis in human cancer cell lines MCF-7 (breast cancer) and HepG2 (liver cancer) and normal human cell line HEK293 (embryonic kidney). The results of cytotoxicity and flow cytometry data showed that the compounds had a moderate to strong effect against MCF-7 and HepG2 cells and were less toxic to HEK293 cells. N-oleyl-retinamide was found to be the most potent anticancer agent and was more effective against MCF-7 cells than HepG2 cells. Full article

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

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15 pages, 4335 KiB

Open AccessArticle

Antiproliferative Activity of Hinokitiol, a Tropolone Derivative, Is Mediated via the Inductions of p-JNK and p-PLCγ1 Signaling in PDGF-BB-Stimulated Vascular Smooth Muscle Cells

by Po-Sheng Yang^1,2,3,†, Meng-Jiy Wang^4,5,†, Thanasekaran Jayakumar⁴, Duen-Suey Chou⁴, Ching-Ya Ko⁴, Ming-Jen Hsu^4,* and Cheng-Ying Hsieh^4,*

¹ Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, No. 92, Sec. 2, Zhongshan N. Rd., Taipei City 10449, Taiwan

² Mackay Junior College of Medicine, Nursing, and Management, No. 92, Shengjing Rd., Beitou District, Taipei 112, Taiwan

³ School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, Taiwan

⁴ Department of Pharmacology, School of Medicine, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, Taiwan

⁵ Department of Chemical Engineering, National Taiwan University of Science and Technology, No. 43, Sec. 4, Keelung Rd., Da’an District, Taipei City 10607, Taiwan

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 8198-8212; https://doi.org/10.3390/molecules20058198 - 7 May 2015

Cited by 18 | Viewed by 7094

Abstract

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is important in the pathogenesis of vascular disorders such as atherosclerosis and restenosis. Hinokitiol, a tropolone derivative found in Chamacyparis taiwanensis, has been found to exhibit anticancer activity in a variety of cancers through [...] Read more.

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is important in the pathogenesis of vascular disorders such as atherosclerosis and restenosis. Hinokitiol, a tropolone derivative found in Chamacyparis taiwanensis, has been found to exhibit anticancer activity in a variety of cancers through inhibition of cell proliferation. In the present study, the possible anti-proliferative effect of hinokitiol was investigated on VSMCs. Our results showed that hinokitiol significantly attenuated the PDGF-BB-stimulated proliferation of VSMCs without cytotoxicity. Hinokitiol suppressed the expression of proliferating cell nuclear antigen (PCNA), a maker for cell cycle arrest, and caused G0/G1 phase arrest in cell cycle progression. To investigate the mechanism underlying the anti-proliferative effect of hinokitiol, we examined the effects of hinokitiol on phosphorylations of Akt, ERK1/2, p38 and JNK1/2. Phospholipase C (PLC)-γ1 phosphorylation, its phosphorylated substrates and p27^kip1 expression was also analyzed. Pre-treatment of VSMCs with hinikitiol was found to significantly inhibit the PDGF-BB-induced phosphorylations of JNK1/2 and PLC-γ1, however no effects on Akt, ERK1/2, and p38. The up-regulation of p27^kip1 was also observed in hinokitiol-treated VSMCs. Taken together, our results suggest that hinokitiol inhibits PDGF-BB-induced proliferation of VSMCs by inducing cell cycle arrest, suppressing JNK1/2 phosphorylation and PLC-γ1, and stimulating p27^kip1 expression. These findings suggest that hinokitiol may be beneficial for the treatment of vascular-related disorders and diseases. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 720 KiB

Open AccessArticle

A Facile and Mild Synthesis of Trisubstituted Allylic Sulfones from Morita-Baylis-Hillman Carbonates

by Lin Jiang^1,2,*, Yong-Gen Li¹, Jiang-Feng Zhou¹, Yong-Ming Chuan^1,2, Hong-Li Li^1,2 and Ming-Long Yuan^1,2,*

¹ Engineering Research Center of Biopolymer Functional Materials of Yunnan, School of Chemistry and Biotechnology, Yunnan Minzu University, Kunming 650500, China

² Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, School of Chemistry and Biotechnology, Yunnan Minzu University, Kunming 650500, China

Molecules 2015, 20(5), 8213-8222; https://doi.org/10.3390/molecules20058213 - 7 May 2015

Cited by 16 | Viewed by 5812

Abstract

An efficient and catalyst-free synthesis of trisubstituted allylic sulfones through an allylic sulfonylation reaction of Morita-Baylis-Hillman (MBH) carbonates with sodium sulfinates has been developed. Under the optimized reaction conditions, a series of trisubstituted allylic sulfones were rapidly prepared in good to excellent yields [...] Read more.

An efficient and catalyst-free synthesis of trisubstituted allylic sulfones through an allylic sulfonylation reaction of Morita-Baylis-Hillman (MBH) carbonates with sodium sulfinates has been developed. Under the optimized reaction conditions, a series of trisubstituted allylic sulfones were rapidly prepared in good to excellent yields (71%–99%) with good to high selectivity (Z/E from 79:21 to >99:1). Compared with known synthetic methods, the current protocol features mild reaction temperature, high efficiency and easily available reagents. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Conjugated and Non Conjugated Small Molecules)

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19 pages, 2614 KiB

Open AccessArticle

Synthesis, Molecular Structure and Spectroscopic Investigations of Novel Fluorinated Spiro Heterocycles

by Mohammad Shahidul Islam^1,*,†

, Abdullah Mohammed Al-Majid^1,†, Assem Barakat^1,2,*,†

, Saied M. Soliman^2,3,†

, Hazem A. Ghabbour^4,†

, Ching Kheng Quah^5,† and Hoong-Kun Fun^4,5,†

¹ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

² Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt

³ Department of Chemistry, Rabigh College of Science and Art, King Abdulaziz University, P.O. Box 344, Rabigh 21911, Saudi Arabia

⁴ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

⁵ X-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, Penang 11800, Malaysia

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 8223-8241; https://doi.org/10.3390/molecules20058223 - 7 May 2015

Cited by 9 | Viewed by 7236

Abstract

This paper describes an efficient and regioselective method for the synthesis of novel fluorinated spiro-heterocycles in excellent yield by cascade [5+1] double Michael addition reactions. The compounds 7,11-bis(4-fluorophenyl)-2,4-dimethyl- 2,4-diazaspiro[5.5] undecane-1,3,5,9-tetraone (3a) and 2,4-dimethyl-7,11-bis (4-(trifluoromethyl)phenyl)-2,4-diazaspiro[5.5]undecane-1,3,5,9-tetraone (3b) were characterized [...] Read more.

This paper describes an efficient and regioselective method for the synthesis of novel fluorinated spiro-heterocycles in excellent yield by cascade [5+1] double Michael addition reactions. The compounds 7,11-bis(4-fluorophenyl)-2,4-dimethyl- 2,4-diazaspiro[5.5] undecane-1,3,5,9-tetraone (3a) and 2,4-dimethyl-7,11-bis (4-(trifluoromethyl)phenyl)-2,4-diazaspiro[5.5]undecane-1,3,5,9-tetraone (3b) were characterized by single-crystal X-ray diffraction, FT-IR and NMR techniques. The optimized geometrical parameters, infrared vibrational frequencies and NMR chemical shifts of the studied compounds have also been calculated using the density functional theory (DFT) method, using Becke-3-Lee-Yang-Parr functional and the 6-311G(d,p) basis set. There is good agreement between the experimentally determined structural parameters, vibrational frequencies and NMR chemical shifts of the studied compounds and those predicted theoretically. The calculated natural atomic charges using NBO method showed higher polarity of 3a compared to 3b.The calculated electronic spectra are also discussed based on the TD-DFT calculations. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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28 pages, 2547 KiB

Open AccessArticle

Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells

by Mohamad Hafizi Abu Bakar^1,*, Kian-Kai Cheng^1,2, Mohamad Roji Sarmidi^2,3,*, Harisun Yaakob³ and Hasniza Zaman Huri^4,5

¹ Department of Bioprocess Engineering, Faculty of Chemical Engineering, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor, Malaysia

² Innovation Centre in Agritechnology for Advanced Bioprocessing (ICA), Universiti Teknologi Malaysia, 81310 Skudai, Johor, Malaysia

³ Institute of Bioproduct Development, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor, Malaysia

⁴ Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia

⁵ Clinical Investigation Centre, 13th Floor Main Tower, University Malaya Medical Centre, 59100 Lembah Pantai, Kuala Lumpur, Malaysia

Molecules 2015, 20(5), 8242-8269; https://doi.org/10.3390/molecules20058242 - 7 May 2015

Cited by 37 | Viewed by 8937

Abstract

Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A [...] Read more.

Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA) in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells. Full article

(This article belongs to the Section Medicinal Chemistry)

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17 pages, 738 KiB

Open AccessArticle

Prediction of Placental Barrier Permeability: A Model Based on Partial Least Squares Variable Selection Procedure

by Yong-Hong Zhang^1,*, Zhi-Ning Xia², Li Yan³ and Shu-Shen Liu^4,*

¹ Medicine Engineering Research Center, School of Pharmacy, Chongqing Medical University, Chongqing 400016, China

² College of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400030, China

³ Department of Chinese Traditional Medicine, Chongqing Medical University, Chongqing 400016, China

⁴ State Key Laboratory of Pollution Control and Resources Reuse, Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China

Molecules 2015, 20(5), 8270-8286; https://doi.org/10.3390/molecules20058270 - 7 May 2015

Cited by 27 | Viewed by 7516

Abstract

Assessing the human placental barrier permeability of drugs is very important to guarantee drug safety during pregnancy. Quantitative structure–activity relationship (QSAR) method was used as an effective assessing tool for the placental transfer study of drugs, while in vitro human placental perfusion is [...] Read more.

Assessing the human placental barrier permeability of drugs is very important to guarantee drug safety during pregnancy. Quantitative structure–activity relationship (QSAR) method was used as an effective assessing tool for the placental transfer study of drugs, while in vitro human placental perfusion is the most widely used method. In this study, the partial least squares (PLS) variable selection and modeling procedure was used to pick out optimal descriptors from a pool of 620 descriptors of 65 compounds and to simultaneously develop a QSAR model between the descriptors and the placental barrier permeability expressed by the clearance indices (CI). The model was subjected to internal validation by cross-validation and y-randomization and to external validation by predicting CI values of 19 compounds. It was shown that the model developed is robust and has a good predictive potential (r² = 0.9064, RMSE = 0.09, q² = 0.7323, r_p² = 0.7656, RMSP = 0.14). The mechanistic interpretation of the final model was given by the high variable importance in projection values of descriptors. Using PLS procedure, we can rapidly and effectively select optimal descriptors and thus construct a model with good stability and predictability. This analysis can provide an effective tool for the high-throughput screening of the placental barrier permeability of drugs. Full article

(This article belongs to the Section Molecular Diversity)

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16 pages, 876 KiB

Open AccessArticle

Variety and Harvesting Season Effects on Antioxidant Activity and Vitamins Content of Citrus sinensis Macfad.

by Vanessa Cardeñosa¹, João C. M. Barreira², Lillian Barros², Francisco J. Arenas-Arenas³, José M. Moreno-Rojas¹ and Isabel C. F. R. Ferreira^2,*

¹ Postharvest Technology and Agrifood Industry Area, Andalusian Institute of Agricultural and Fishering Research and Training (IFAPA) Alameda del Obispo, 14004 Córdoba, Spain

² Mountain Research Center (CIMO), ESA, Polytechnic Institute of Bragança, Apartado 1172, 5301-855 Bragança, Portugal

³ Centro IFAPA "Las Torres-Tomejil", Instituto de Investigación y Formación Agraria y Pesquera, Ctra Sevilla—Cazalla Km. 12,2, 41200 Alcalá del Río (Sevilla), Spain

Molecules 2015, 20(5), 8287-8302; https://doi.org/10.3390/molecules20058287 - 7 May 2015

Cited by 19 | Viewed by 6513

Abstract

Five sweet orange (Citrus sinensis Osbeck) varieties cultivated in Huelva (Spain) and picked at two seasons during two consecutive years, were characterized for their antioxidant activity (free radicals scavenging activity, reducing power and lipid peroxidation inhibition) and vitamin content (vitamin E and [...] Read more.

Five sweet orange (Citrus sinensis Osbeck) varieties cultivated in Huelva (Spain) and picked at two seasons during two consecutive years, were characterized for their antioxidant activity (free radicals scavenging activity, reducing power and lipid peroxidation inhibition) and vitamin content (vitamin E and vitamin C). The effects induced by sweet orange variety and stage of maturity were comprehensively compared by applying 2-way ANOVA and linear discriminant analysis. The results indicated higher differences in antioxidant activity and vitamin contents in response to the effect of the harvesting season, when compared to the effect of sweet orange variety. Nevertheless, the results observed in 2012 showed less marked differences among the assayed sweet orange varieties. Either way, it might be concluded that oranges sampled in January show the highest antioxidant activity and vitamin contents. Furthermore, concerning the properties evaluated in this work, all sweet orange varieties represent good alternatives, except for Rhode Summer, which would not be the preferable choice as a target to enhance sweet orange overall characteristics. Full article

(This article belongs to the Collection Bioactive Compounds)

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1 pages, 591 KiB

Open AccessCorrection

Correction: Chigrinova, M., et al. Kinugasa Reactions in Water: From Green Chemistry to Bioorthogonal Labelling. Molecules 2015, 20, 6959-6969

by Mariya Chigrinova^1,†, Douglas A. MacKenzie^1,2,†, Allison R. Sherratt¹, Lawrence L. W. Cheung^1,2 and John Paul Pezacki^1,2,*

¹ Life Sciences Division, National Research Council of Canada, Ottawa, ON K1A 0R6, Canada

² Department of Chemistry, University of Ottawa, Ottawa, ON K1N 6N5, Canada

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 8303; https://doi.org/10.3390/molecules20058303 - 7 May 2015

Cited by 24 | Viewed by 4111

Abstract

The authors wish to make the following correction to this paper [1]: The author name “Paul Pezacki” should be “John Paul Pezacki”. [...] Full article

(This article belongs to the Special Issue Recent Developments of the Kinugasa Reaction)

12 pages, 775 KiB

Open AccessArticle

Culture Conditions Affect Expression of DUX4 in FSHD Myoblasts

by Sachchida Nand Pandey¹, Hunain Khawaja¹ and Yi-Wen Chen^1,2,*

¹ Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, USA

² Department of Integrative Systems Biology and Department of Pediatrics, George Washington University, Washington, DC 20037, USA

Molecules 2015, 20(5), 8304-8315; https://doi.org/10.3390/molecules20058304 - 8 May 2015

Cited by 17 | Viewed by 6965

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is believed to be caused by aberrant expression of double homeobox 4 (DUX4) due to epigenetic changes of the D4Z4 region at chromosome 4q35. Detecting DUX4 is challenging due to its stochastic expression pattern and low transcription level. In [...] Read more.

Facioscapulohumeral muscular dystrophy (FSHD) is believed to be caused by aberrant expression of double homeobox 4 (DUX4) due to epigenetic changes of the D4Z4 region at chromosome 4q35. Detecting DUX4 is challenging due to its stochastic expression pattern and low transcription level. In this study, we examined different cDNA synthesis strategies and the sensitivity for DUX4 detection. In addition, we investigated the effects of dexamethasone and knockout serum replacement (KOSR) on DUX4 expression in culture. Our data showed that DUX4 was consistently detected in cDNA samples synthesized using Superscript III. The sensitivity of DUX4 detection was higher in the samples synthesized using oligo(dT) primers compared to random hexamers. Adding dexamethasone to the culture media significantly suppressed DUX4 expression in immortalized (1.3 fold, p < 0.01) and primary (4.7 fold, p < 0.01) FSHD myoblasts, respectively. Culture medium with KOSR increased DUX4 expression and the response is concentration dependent. The findings suggest that detection strategies and culture conditions should be carefully considered when studying DUX4 in cultured cells. Full article

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

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25 pages, 3125 KiB

Open AccessArticle

Structure Based Modeling of Small Molecules Binding to the TLR7 by Atomistic Level Simulations

by Francesco Gentile¹

, Marco A. Deriu^2,†

, Ginevra Licandro^2,†, Alessio Prunotto², Andrea Danani² and Jack A. Tuszynski^1,3,*

¹ Department of Physics, University of Alberta, Edmonton, AB T6G 2E1, Canada

² Institute of Computer Integrated Manufacturing for Sustainable Innovation, Department of Innovative Technologies, University of Applied Sciences and Arts of Southern Switzerland (SUPSI), Manno CH-6928, Switzerland

³ Cross Cancer Institute, Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 8316-8340; https://doi.org/10.3390/molecules20058316 - 8 May 2015

Cited by 26 | Viewed by 9571

Abstract

Toll-Like Receptors (TLR) are a large family of proteins involved in the immune system response. Both the activation and the inhibition of these receptors can have positive effects on several diseases, including viral pathologies and cancer, therefore prompting the development of new compounds. [...] Read more.

Toll-Like Receptors (TLR) are a large family of proteins involved in the immune system response. Both the activation and the inhibition of these receptors can have positive effects on several diseases, including viral pathologies and cancer, therefore prompting the development of new compounds. In order to provide new indications for the design of Toll-Like Receptor 7 (TLR7)-targeting drugs, the mechanism of interaction between the TLR7 and two important classes of agonists (imidazoquinoline and adenine derivatives) was investigated through docking and Molecular Dynamics simulations. To perform the computational analysis, a new model for the dimeric form of the receptors was necessary and therefore created. Qualitative and quantitative differences between agonists and inactive compounds were determined. The in silico results were compared with previous experimental observations and employed to define the ligand binding mechanism of TLR7. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 1428 KiB

Open AccessArticle

Classification of Sparkling Wine Style and Quality by MIR Spectroscopy

by Julie Culbert^†, Daniel Cozzolino^†, Renata Ristic^† and Kerry Wilkinson^*,†

School of Agriculture, Food and Wine, University of Adelaide, PMB 1, Glen Osmond, SA 5064, Australia

Molecules 2015, 20(5), 8341-8356; https://doi.org/10.3390/molecules20058341 - 8 May 2015

Cited by 39 | Viewed by 9101

Abstract

In this study, the suitability of attenuated total reflection (ATR) mid-infrared (MIR) spectroscopy, combined with principal component analysis (PCA) and partial least squares (PLS) regression, was evaluated as a rapid analytical technique for the classification of sparkling wine style and quality. Australian sparkling [...] Read more.

In this study, the suitability of attenuated total reflection (ATR) mid-infrared (MIR) spectroscopy, combined with principal component analysis (PCA) and partial least squares (PLS) regression, was evaluated as a rapid analytical technique for the classification of sparkling wine style and quality. Australian sparkling wines (n = 139) comprising a range of styles (i.e., white, rosé, red, Prosecco and Moscato) were analyzed by ATR-MIR spectroscopy combined with multivariate data analysis. The MIR spectra of 50 sparkling white wines, produced according to four different production methods (i.e., Carbonation, Charmat, Transfer and Methodé Traditionelle) were also evaluated against: (i) quality ratings determined by an expert panel; and (ii) sensory attributes rated by a trained sensory panel. Wine pH, titratable acidity (TA), residual sugar (RS), alcohol and total phenolic content were also determined. The sparkling wine styles were separated on the PCA score plot based on their MIR spectral data; while the sparkling white wines showed separation based on production method, which strongly influenced the style and sensory properties of wine (i.e., the intensity of fruit versus yeast-derived characters). PLS calibrations of 0.73, 0.77, 0.82 and 0.86 were obtained for sweetness, tropical fruit, confectionary and toasty characters (on the palate), respectively. Full article

(This article belongs to the Collection Wine Chemistry)

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38 pages, 993 KiB

Open AccessReview

A Survey of Recent Synthetic Applications of 2,3-Dideoxy-Hex-2-enopyranosides

by Ana M. Gomez^*

, Fernando Lobo, Silvia Miranda and J. Cristobal Lopez^*

Instituto de Química Orgánica General (IQOG-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain

Molecules 2015, 20(5), 8357-8394; https://doi.org/10.3390/molecules20058357 - 8 May 2015

Cited by 21 | Viewed by 10219

Abstract

Unsaturated carbohydrate derivatives are useful intermediates in synthetic transformations leading to a variety of compounds. The aim of this review is to highlight the rich chemistry of ∆-2,3 unsaturated pyranosides, emphasizing the variety of transformations that have been carried out in these substrates [...] Read more.

Unsaturated carbohydrate derivatives are useful intermediates in synthetic transformations leading to a variety of compounds. The aim of this review is to highlight the rich chemistry of ∆-2,3 unsaturated pyranosides, emphasizing the variety of transformations that have been carried out in these substrates during the last decade. Full article

(This article belongs to the Collection Advances in Glycosciences)

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14 pages, 937 KiB

Open AccessArticle

Synthesis, Antifungal Activity and Structure-Activity Relationships of Novel 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic Acid Amides

by Shijie Du¹, Zaimin Tian², Dongyan Yang¹, Xiuyun Li¹, Hong Li¹, Changqing Jia¹, Chuanliang Che¹, Mian Wang¹ and Zhaohai Qin^1,*

¹ Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China

² College of Agricultural and Forestry Science and Technology, Hebei North University, Zhangjiakou 075131, Hebei, China

Molecules 2015, 20(5), 8395-8408; https://doi.org/10.3390/molecules20058395 - 8 May 2015

Cited by 61 | Viewed by 9177

Abstract

A series of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-yl)phenyl)-3-(difluoro-methyl)-1-methyl-1H-pyrazole-4-carboxamide [...] Read more.

A series of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-yl)phenyl)-3-(difluoro-methyl)-1-methyl-1H-pyrazole-4-carboxamide (9m) exhibited higher antifungal activity against the seven phytopathogenic fungi than boscalid. Topomer CoMFA was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds. In molecular docking, the carbonyl oxygen atom of 9m could form hydrogen bonds towards the hydroxyl of TYR58 and TRP173 on SDH. Full article

(This article belongs to the Section Medicinal Chemistry)

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20 pages, 1880 KiB

Open AccessArticle

Effects of Two Different Rhodiola rosea Extracts on Primary Human Visceral Adipocytes

by Elena Pomari, Bruno Stefanon and Monica Colitti^*

Department of Agricultural and Environmental Sciences, University of Udine, via delle Scienze, 206, 33100 Udine, Italy

Molecules 2015, 20(5), 8409-8428; https://doi.org/10.3390/molecules20058409 - 11 May 2015

Cited by 26 | Viewed by 10744

Abstract

Rhodiola rosea (Rro) has been reported to have various pharmacological properties, including anti-fatigue, anti-stress and anti-inflammatory activity. It is also known to improve glucose and lipid metabolism, but the effects of Rhodiola rosea on adipocyte differentiation and metabolism are not still [...] Read more.

Rhodiola rosea (Rro) has been reported to have various pharmacological properties, including anti-fatigue, anti-stress and anti-inflammatory activity. It is also known to improve glucose and lipid metabolism, but the effects of Rhodiola rosea on adipocyte differentiation and metabolism are not still elucidated. In this study the anti-adipogenic and lipolytic activity of two extracts of Rhodiola rosea, containing 3% salidroside (RS) or 1% salidroside and 3% rosavines (RR) on primary human visceral adipocytes was investigated. Pre-adipocytes were analyzed after 10 and 20 days of treatment during differentiation and after 7 days of treatment when they reached mature shape. The RS extract significantly induced higher apoptosis and lipolysis in comparison to control cells and to RR extract. In contrast, RR extract significantly reduced triglyceride incorporation during maturation. Differentiation of pre-adipocytes in the presence of RS and RR extracts showed a significant decrease in expression of genes involved in adipocyte function such as SLC2A4 and the adipogenic factor FGF2 and significant increase in expression of genes involved in inhibition of adipogenesis, such as GATA3, WNT3A, WNT10B. Furthermore RR extract, in contrast to RS, significantly down-regulates PPARG, the master regulator of adipogenesis and FABP4. These data support the lipolytic and anti-adipogenetic activity of two different commercial extracts of Rhodiola rosea in primary human visceral pre-adipocytes during differentiation. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 732 KiB

Open AccessCommunication

A Mild Catalytic Oxidation System: FePcOTf/H₂O₂ Applied for Cyclohexene Dihydroxylation

by Baocheng Zhou^1,2 and Wenxing Chen^2,*

¹ Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018, China

² Key Laboratory of Advanced Textile Materials and Manufacturing Technology, Ministry of Education of China, Zhejiang Sci-Tech University, Hangzhou 310018, China

Molecules 2015, 20(5), 8429-8439; https://doi.org/10.3390/molecules20058429 - 11 May 2015

Cited by 7 | Viewed by 7245

Abstract

Iron (III) phthalocyanine complexes were employed for the first time as a mild and efficient Lewis acid catalyst in the selective oxidation of cyclohexene to cyclohexane-1,2-diol. It was found that the catalyst FePcOTf shown excellent conversion and moderate selectivity relative to other iron [...] Read more.

Iron (III) phthalocyanine complexes were employed for the first time as a mild and efficient Lewis acid catalyst in the selective oxidation of cyclohexene to cyclohexane-1,2-diol. It was found that the catalyst FePcOTf shown excellent conversion and moderate selectivity relative to other iron (III) phthalocyanine complexes. The optimum conditions of the oxidation reaction catalyzed by FePcOTf/H₂O₂ have been researched in this paper. Iron (III) phthalocyanine triflate (1 mol %) as catalyst, hydrogen peroxide as oxidant, methanol as solvent, and a mole ratio of substrate and oxidant (H₂O₂) of 1:1 were used for achieving moderate yields of 1,2-diols under reflux conditions after eight hours. Full article

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

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13 pages, 733 KiB

Open AccessArticle

Assessing the Chemical Composition and Antimicrobial Activity of Essential Oils from Brazilian Plants—Eremanthus erythropappus (Asteraceae), Plectrantuns barbatus, and P. amboinicus (Lamiaceae)

by Nara O. dos Santos¹, Bruna Mariane¹, João Henrique G. Lago¹, Patricia Sartorelli¹, Welton Rosa², Marisi G. Soares², Adalberto M. Da Silva³, Harri Lorenzi⁴, Marcelo A. Vallim¹ and Renata C. Pascon^1,*

¹ Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, 09972-270 Diadema, SP, Brazil

² Instituto de Química, Universidade Federal de Alfenas, 37130-000 Alfenas, MG, Brazil

³ Departamento de Química, Universidade Federal de Viçosa, 36570-000 Viçosa, MG, Brazil

⁴ Instituto Plantarum de Estudos da Flora. Av. Brasil, 2000, 13460-000 Nova Odessa, SP, Brazil

Molecules 2015, 20(5), 8440-8452; https://doi.org/10.3390/molecules20058440 - 11 May 2015

Cited by 33 | Viewed by 8540

Abstract

The chemical composition and antimicrobial activity of essential oils obtained from three Brazilian plant species—leaves and branches of Eremanthus erythropappus (Asteraceae), leaves of Plectranthus barbatus, and leaves of P. amboinicus (Lamiaceae)—were determined. Analysis by GC/MS and determination of Kovats indexes both indicated [...] Read more.

The chemical composition and antimicrobial activity of essential oils obtained from three Brazilian plant species—leaves and branches of Eremanthus erythropappus (Asteraceae), leaves of Plectranthus barbatus, and leaves of P. amboinicus (Lamiaceae)—were determined. Analysis by GC/MS and determination of Kovats indexes both indicated δ-elemene (leaves—42.61% and branches—23.41%) as well as (−)-α-bisabolol (leaves—24.80% and stem bark—66.16%) as major constituents of E. erythropappus essential oils. The main components of leaves of P. barbatus were identified as (Z)-caryophyllene (17.98%), germacrene D (17.35%), and viridiflorol (14.13%); whereas those of leaves of P. amboinicus were characterized as p-cymene (12.01%), γ-terpinene (14.74%), carvacrol (37.70%), and (Z)-caryophyllene (14.07%). The antimicrobial activity against yeasts and bacteria was assessed in broth microdilution assays to determine the minimum inhibitory concentration (MIC) necessary to inhibit microbial growth. In addition, the crude oil of branches of E. erythropappus was subjected to chromatographic separation procedures to afford purified (−)-α-bisabolol. This compound displayed biological activity against pathogenic yeasts, thus suggesting that the antimicrobial effect observed with crude oils of E. erythropappus leaves and branches may be related to the occurrence of (−)-α-bisabolol as their main component. Our results showed that crude oils of Brazilian plants, specifically E. erythropappus, P. barbatus, and P. amboinicus and its components, could be used as a tool for the developing novel and more efficacious antimicrobial agents. Full article

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

31 pages, 871 KiB

Open AccessArticle

Correlating Wine Quality Indicators to Chemical and Sensory Measurements

by Helene Hopfer^1,2,†, Jenny Nelson^1,2,3, Susan E. Ebeler^1,2

and Hildegarde Heymann^1,*

¹ Department of Viticulture & Enology, University of California-Davis, One Shields Ave., Davis, CA 95616, USA

² Food Safety & Measurement Facility, University of California-Davis, One Shields Ave., Davis, CA 95616, USA

³ Agilent Technologies, Inc., 5301 Stevens Creek Blvd., Santa Clara, CA, 95051, USA

^† Present address: HM.Clause, Inc., 9241 Mace Blvd., Davis, CA 95618, USA.

Molecules 2015, 20(5), 8453-8483; https://doi.org/10.3390/molecules20058453 - 12 May 2015

Cited by 42 | Viewed by 13284

Abstract

Twenty-seven commercial Californian Cabernet Sauvignon wines of different quality categories were analyzed with sensory and chemical methods. Correlations between five quality proxies—points awarded during a wine competition, wine expert scores, retail price, vintage, and wine region—were correlated to sensory attributes, volatile compounds, and [...] Read more.

Twenty-seven commercial Californian Cabernet Sauvignon wines of different quality categories were analyzed with sensory and chemical methods. Correlations between five quality proxies—points awarded during a wine competition, wine expert scores, retail price, vintage, and wine region—were correlated to sensory attributes, volatile compounds, and elemental composition. Wine quality is a multi-faceted construct, incorporating many different layers. Depending on the quality proxy studied, significant correlations between quality and attributes, volatiles and elements were found, some of them previously reported in the literature. Full article

(This article belongs to the Collection Wine Chemistry)

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15 pages, 758 KiB

Open AccessCommunication

Isoindolinones as Michael Donors under Phase Transfer Catalysis: Enantioselective Synthesis of Phthalimidines Containing a Tetrasubstituted Carbon Stereocenter

by Francesco Scorzelli, Antonia Di Mola, Laura Palombi

and Antonio Massa^*

Dipartimento di Chimica e Biologia, Università di Salerno, Via Giovanni Paolo II, 132, 84084-Fisciano, SA, Italy

Molecules 2015, 20(5), 8484-8498; https://doi.org/10.3390/molecules20058484 - 12 May 2015

Cited by 19 | Viewed by 6567

Abstract

Readily available chiral ammonium salts derived from cinchona alkaloids have proven to be effective phase transfer catalysts in the asymmetric Michael reaction of 3-substituted isoindolinones. This protocol provides a convenient method for the construction of valuable asymmetric 3,3-disubstituted isoindolinones in high yields and [...] Read more.

Readily available chiral ammonium salts derived from cinchona alkaloids have proven to be effective phase transfer catalysts in the asymmetric Michael reaction of 3-substituted isoindolinones. This protocol provides a convenient method for the construction of valuable asymmetric 3,3-disubstituted isoindolinones in high yields and moderate to good enantioselectivity. Diastereoselectivity was also investigated in the construction of contiguous tertiary and quaternary stereocenters. The use of acrolein as Michael acceptor led to an interesting tricyclic derivative, a pyrroloisoindolinone analogue, via a tandem conjugated addition/cyclization reaction. Full article

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

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22 pages, 822 KiB

Open AccessArticle

Microwave-Assisted Synthesis of Novel Pyrazolo[3,4-g][1,8]naphthyridin-5-amine with Potential Antifungal and Antitumor Activity

by Paola Acosta¹, Estefanía Butassi², Braulio Insuasty¹, Alejandro Ortiz¹, Rodrigo Abonia¹, Susana A. Zacchino²

and Jairo Quiroga^1,*

¹ Heterocyclic Compounds Research Group, Department of Chemistry, Universidad del Valle, A.A. 25360 Cali, Colombia

² Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, CP 2000 Rosario, Argentina

Molecules 2015, 20(5), 8499-8520; https://doi.org/10.3390/molecules20058499 - 12 May 2015

Cited by 19 | Viewed by 5681

Abstract

The microwave assisted reaction between heterocyclic o-aminonitriles 1 and cyclic ketones 2 catalyzed by zinc chloride led to new series of pyrazolo[3,4-b] [1,8]naphthyridin-5-amines 3 in good yields. This procedure provides several advantages such as being environmentally friendly, high yields, simple [...] Read more.

The microwave assisted reaction between heterocyclic o-aminonitriles 1 and cyclic ketones 2 catalyzed by zinc chloride led to new series of pyrazolo[3,4-b] [1,8]naphthyridin-5-amines 3 in good yields. This procedure provides several advantages such as being environmentally friendly, high yields, simple work-up procedure, broad scope of applicability and the protocol provides an alternative for the synthesis of pyrazolonaphthyridines. The whole series showed antifungal activities against Candida albicans and Cryptococcus neoformans standardized strains, being compounds with a 4-p-tolyl substituent of the naphthyridin scheleton (3a, 3d and 3g), the most active ones mainly against C. albicans, which appear to be related to their comparative hydrophobicity. Among them, 3d, containing a cyclohexyl fused ring, showed the best activity. The anti-Candida activity was corroborated by testing the three most active compounds against clinical isolates of albicans and non-albicans Candida strains. These compounds were also screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines. Compounds 3a and 3e showed remarkable antitumor activity against cancer cell lines, with the most important GI₅₀ values ranging from 0.62 to 2.18 μM Full article

(This article belongs to the Section Medicinal Chemistry)

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27 pages, 1447 KiB

Open AccessReview

A Comprehensive Review on the Phytochemical Constituents and Pharmacological Activities of Pogostemon cablin Benth.: An Aromatic Medicinal Plant of Industrial Importance

by Mallappa Kumara Swamy^†

and Uma Rani Sinniah^*,†

¹ Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, Serdang, Selangor, Darul Ehsan 43400, Malaysia

^† These authors contributed equally to this work

Molecules 2015, 20(5), 8521-8547; https://doi.org/10.3390/molecules20058521 - 12 May 2015

Cited by 311 | Viewed by 31199

Abstract

Pogostemon cablin Benth. (patchouli) is an important herb which possesses many therapeutic properties and is widely used in the fragrance industries. In traditional medicinal practices, it is used to treat colds, headaches, fever, nausea, vomiting, diarrhea, abdominal pain, insect and snake bites. In [...] Read more.

Pogostemon cablin Benth. (patchouli) is an important herb which possesses many therapeutic properties and is widely used in the fragrance industries. In traditional medicinal practices, it is used to treat colds, headaches, fever, nausea, vomiting, diarrhea, abdominal pain, insect and snake bites. In aromatherapy, patchouli oil is used to relieve depression, stress, calm nerves, control appetite and to improve sexual interest. Till now more than 140 compounds, including terpenoids, phytosterols, flavonoids, organic acids, lignins, alkaloids, glycosides, alcohols, aldehydes have been isolated and identified from patchouli. The main phytochemical compounds are patchouli alcohol, α-patchoulene, β-patchoulene, α-bulnesene, seychellene, norpatchoulenol, pogostone, eugenol and pogostol. Modern studies have revealed several biological activities such as antioxidant, analgesic, anti-inflammatory, antiplatelet, antithrombotic, aphrodisiac, antidepressant, antimutagenic, antiemetic, fibrinolytic and cytotoxic activities. However, some of the traditional uses need to be verified and may require standardizing and authenticating the bioactivity of purified compounds through scientific methods. The aim of the present review is to provide comprehensive knowledge on the phytochemistry and pharmacological activities of essential oil and different plant extracts of patchouli based on the available scientific literature. This information will provide a potential guide in exploring the use of main active compounds of patchouli in various medical fields. Full article

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

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12 pages, 1488 KiB

Open AccessArticle

High Fluorescent Porphyrin-PAMAM-Fluorene Dendrimers

by Karla I. Garfias-Gonzalez^†, Ulises Organista-Mateos^†, Andrés Borja-Miranda^†, Virginia Gomez-Vidales^†, Simon Hernandez-Ortega^†, Sandra Cortez-Maya^† and Marcos Martínez-García^*,†

¹ Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior, Coyoacán, México D.F. C.P. 04510, Mexico

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 8548-8559; https://doi.org/10.3390/molecules20058548 - 13 May 2015

Cited by 6 | Viewed by 7639

Abstract

Two new classes of dendrimers bearing 8 and 32 fluorene donor groups have been synthesized. The first and second generations of these porphyrin-PAMAM-fluorene dendrimers were characterized by ¹H-NMR, ¹³C-NMR, FTIR, UV-vis spectroscopy, elemental analyses and MALDI-TOF mass spectrometry. The UV-vis spectra [...] Read more.

Two new classes of dendrimers bearing 8 and 32 fluorene donor groups have been synthesized. The first and second generations of these porphyrin-PAMAM-fluorene dendrimers were characterized by ¹H-NMR, ¹³C-NMR, FTIR, UV-vis spectroscopy, elemental analyses and MALDI-TOF mass spectrometry. The UV-vis spectra showed that the individual properties of donor and acceptor moieties were preserved, indicating that the new dendrimers could be used as photosynthetic antennae. Furthermore, for fluorescent spectroscopy, these dendrimers showed good energy transfer. Full article

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

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14 pages, 3326 KiB

Open AccessArticle

Recovery of Steroidal Alkaloids from Potato Peels Using Pressurized Liquid Extraction

by Mohammad B. Hossain¹, Ashish Rawson^1,2, Ingrid Aguiló-Aguayo^1,3, Nigel P. Brunton^4,* and Dilip K. Rai^1,*

¹ Department of Food Biosciences, Teagasc Food Research Centre, Ashtown, Dublin D15, Ireland

² Indian Institute of Crop Processing Technology, Thanjavur 613005, TN, India

³ IRTA, XaRTA-Postharvest, Edifici Fruitcentre, Parc Científic i Tecnològic Agroalimentari de Lleida, Lleida 25003, Catalonia, Spain

⁴ School of Agriculture and Food Science, University College Dublin, Dublin D4, Ireland

Molecules 2015, 20(5), 8560-8573; https://doi.org/10.3390/molecules20058560 - 13 May 2015

Cited by 42 | Viewed by 9621

Abstract

A higher yield of glycoalkaloids was recovered from potato peels using pressurized liquid extraction (1.92 mg/g dried potato peels) compared to conventional solid–liquid extraction (0.981 mg/g dried potato peels). Response surface methodology deduced the optimal temperature and extracting solvent (methanol) for the pressurized [...] Read more.

A higher yield of glycoalkaloids was recovered from potato peels using pressurized liquid extraction (1.92 mg/g dried potato peels) compared to conventional solid–liquid extraction (0.981 mg/g dried potato peels). Response surface methodology deduced the optimal temperature and extracting solvent (methanol) for the pressurized liquid extraction (PLE) of glycoalkaloids as 80 °C in 89% methanol. Using these two optimum PLE conditions, levels of individual steroidal alkaloids obtained were of 597, 873, 374 and 75 µg/g dried potato peel for α-solanine, α-chaconine, solanidine and demissidine respectively. Corresponding values for solid liquid extraction were 59%, 46%, 40% and 52% lower for α-solanine, α-chaconine, solanidine and demissidine respectively. Full article

(This article belongs to the Special Issue New Technologies for the Recovery of Natural Products)

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9 pages, 857 KiB

Open AccessCommunication

Highly Diastereoselective Synthesis of Spiropyrazolones

by Victor Ceban^1,†, Temitope O. Olomola^1,2,†, Marta Meazza^1,† and Ramon Rios^1,*

¹ Faculty of Natural & Environmental Sciences, University of Southampton Highfield Campus, Southampton SO17 1BJ, UK

² Department of Chemistry, Obafemi Awolowo University, Ile-Ife 220005, Nigeria

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 8574-8582; https://doi.org/10.3390/molecules20058574 - 13 May 2015

Cited by 16 | Viewed by 6771

Abstract

We report a highly diastereoselective synthesis of spiropyrazolones catalyzed by secondary amines. The reported Michael-Aldol cascade reaction affords the desired spiropyrazolones bearing four chiral centers as a single diastereomer in excellent yields. Full article

(This article belongs to the Collection Recent Advances in Organocatalysis)

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12 pages, 1182 KiB

Open AccessArticle

Studies on Transition Metal-Quercetin Complexes Using Electrospray Ionization Tandem Mass Spectrometry

by Yuanzhen Liu¹ and Mingquan Guo^1,2,*

¹ Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden of Chinese Academy of Sciences, Wuhan 430074, China

² The Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA

Molecules 2015, 20(5), 8583-8594; https://doi.org/10.3390/molecules20058583 - 13 May 2015

Cited by 98 | Viewed by 9270

Abstract

To systematically study the effects of the number of d electrons of the first transition metal ions (Fe, Co, Ni, Cu and Zn) on the formation and stability of metal flavonoid complexes, we took the quercetin/M²⁺ complex as a model system to [...] Read more.

To systematically study the effects of the number of d electrons of the first transition metal ions (Fe, Co, Ni, Cu and Zn) on the formation and stability of metal flavonoid complexes, we took the quercetin/M²⁺ complex as a model system to investigate the structures and properties of these complexes. Based on considerable structural information obtained through ESI-MSⁿ, all of the first transition metal ions (Fe²⁺, Co²⁺, Ni²⁺, Cu²⁺ and Zn²⁺) were found to form different complexes with quercetin, while with the number of chelating flavonoids decreasing along with the reduction of the metal ionic radius. Quercetin forms different complexes with the above metal divalent ions through its 5-OH and 4-carbonyl groups; the complex stability is highly dependent on both the metallic ion and the flavonoid chelator itself. As for the central ion (M²⁺), when chelated with quercetin to form the complex, the stability of the complex decreased in the following order: Cu²⁺ > Ni²⁺ > Co²⁺ > Fe²⁺ > Zn²⁺. With flavonoid: metal stoichiometries at 2:1, the complexes formed between quercetin and metal ions (Fe²⁺, Ni²⁺, Co²⁺ and Zn²⁺) have the similar fragmentation mechanism, while Cu²⁺ displayed different fragmentation mechanism due to the concurrent oxidation. Full article

(This article belongs to the Section Molecular Diversity)

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10 pages, 977 KiB

Open AccessArticle

Biological Activity and Photostability of Biflorin Micellar Nanostructures

by Edson R. B. Santana¹, João P. Ferreira-Neto¹, Ricardo Yara², Kêsia X. F. R. Sena³, Adriana Fontes¹ and Cláudia S. A. Lima^1,*

¹ Departamento de Biofísica e Radiobiologia, Universidade Federal de Pernambuco, Recife, PE 50670-901, Brazil

² Departamento de Engenharia Biomédica, Universidade Federal de Pernambuco, Recife, PE 50670-901, Brazil

³ Departamento de Antibióticos, Universidade Federal de Pernambuco, Recife, PE 50670-901, Brazil

Molecules 2015, 20(5), 8595-8604; https://doi.org/10.3390/molecules20058595 - 13 May 2015

Cited by 4 | Viewed by 5145

Abstract

Capraria biflora L. is a shrub from the Scrophulariaceae family which produces in its roots a compound named biflorin, an o-naphthoquinone that shows activity against Gram-positive bacteria and fungi and also presents antitumor and antimetastatic activities. However, biflorin is hydrophobic and photosensitive. [...] Read more.

Capraria biflora L. is a shrub from the Scrophulariaceae family which produces in its roots a compound named biflorin, an o-naphthoquinone that shows activity against Gram-positive bacteria and fungi and also presents antitumor and antimetastatic activities. However, biflorin is hydrophobic and photosensitive. These properties make its application difficult. In this work we prepared biflorin micellar nanostructures looking for a more effective vehiculation and better preservation of the biological activity. Biflorin was obtained, purified and characterized by UV-Vis, infrared (IR) and ¹H- and ¹³C-NMR. Micellar nanostructures of biflorin were then assembled with Tween 80^®, Tween 20^® and saline (0.9%) and characterized by UV-Vis spectroscopy and dynamic light scattering (DLS). The results showed that the micellar nanostructures were stable and presented an average size of 8.3 nm. Biflorin micellar nanostructures’ photodegradation was evaluated in comparison with biflorin in ethanol. Results showed that the biflorin in micellar nanostructures was better protected from light than biflorin dissolved in ethanol, and also indicated that biflorin in micelles were efficient against Gram-positive bacteria and yeast species. In conclusion, the results showed that the micellar nanostructures could ensure the maintenance of the biological activity of biflorin, conferring photoprotection. Moreover, biflorin vehiculation in aqueous media was improved, favoring its applicability in biological systems. Full article

(This article belongs to the Section Natural Products Chemistry)

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29 pages, 1148 KiB

Open AccessReview

Mentha suaveolens Ehrh. (Lamiaceae) Essential Oil and Its Main Constituent Piperitenone Oxide: Biological Activities and Chemistry

by Mijat Božović

, Adele Pirolli and Rino Ragno^*

Rome Center for Molecular Design, Department of Drug Chemistry and Technology, Sapienza University, P.le Aldo Moro 5, 00185 Rome, Italy

Molecules 2015, 20(5), 8605-8633; https://doi.org/10.3390/molecules20058605 - 13 May 2015

Cited by 92 | Viewed by 15562

Abstract

Since herbal medicines play an important role in the treatment of a wide range of diseases, there is a growing need for their quality control and standardization. Mentha suaveolens Ehrh. (MS) is an aromatic herb with fruit and a spearmint flavor, used in [...] Read more.

Since herbal medicines play an important role in the treatment of a wide range of diseases, there is a growing need for their quality control and standardization. Mentha suaveolens Ehrh. (MS) is an aromatic herb with fruit and a spearmint flavor, used in the Mediterranean areas as a traditional medicine. It has an extensive range of biological activities, including cytotoxic, antimicrobial, antioxidant, anti-inflammatory, hypotensive and insecticidal properties, among others. This study aims to review the scientific findings and research reported to date on MS that prove many of the remarkable various biological actions, effects and some uses of this species as a source of bioactive natural compounds. On the other hand, piperitenone oxide (PO), the major chemical constituent of the carvone pathway MS essential oil, has been reported to exhibit numerous bioactivities in cells and animals. Thus, this integrated overview also surveys and interprets the present knowledge of chemistry and analysis of this oxygenated monoterpene, as well as its beneﬁcial bioactivities. Areas for future research are suggested. Full article

(This article belongs to the Section Natural Products Chemistry)

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20 pages, 910 KiB

Open AccessArticle

Synthesis, Biological Activities, and Quantitative Structure–Activity Relationship (QSAR) Study of Novel Camptothecin Analogues

by Dan Wu^1,2,†, Shao-Yong Zhang^1,†, Ying-Qian Liu^1,2,*, Xiao-Bing Wu^1,2, Gao-Xiang Zhu², Yan Zhang², Wei Wei², Huan-Xiang Liu^2,* and An-Liang Chen^1,*

¹ Local and National Joint Engineering Laboratory of Biopesticide High-Efficient Preparation Technology, Zhejiang A&F University, Lin'an 311300, China

² School of Pharmacy, Lanzhou University, Lanzhou 730000, China

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 8634-8653; https://doi.org/10.3390/molecules20058634 - 13 May 2015

Cited by 13 | Viewed by 7093

Abstract

In continuation of our program aimed at the development of natural product-based pesticidal agents, three series of novel camptothecin derivatives were designed, synthesized, and evaluated for their biological activities against T. Cinnabarinus, B. brassicae, and B. xylophilus. All of the [...] Read more.

In continuation of our program aimed at the development of natural product-based pesticidal agents, three series of novel camptothecin derivatives were designed, synthesized, and evaluated for their biological activities against T. Cinnabarinus, B. brassicae, and B. xylophilus. All of the derivatives showed good-to-excellent activity against three insect species tested, with LC₅₀ values ranging from 0.00761 to 0.35496 mmol/L. Remarkably, all of the compounds were more potent than CPT against T. Cinnabarinus, and compounds 4d and 4c displayed superior activity (LC₅₀ 0.00761 mmol/L and 0.00942 mmol/L, respectively) compared with CPT (LC₅₀ 0.19719 mmol/L) against T. Cinnabarinus. Based on the observed bioactivities, preliminary structure–activity relationship (SAR) correlations were also discussed. Furthermore, a three-dimensional quantitative structure–activity relationship (3D-QSAR) model using comparative molecular field analysis (CoMFA) was built. The model gave statistically significant results with the cross-validated q² values of 0.580 and correlation coefficient r² of 0.991 and of 0.993. The QSAR analysis indicated that the size of the substituents play an important in the activity of 7-modified camptothecin derivatives. These findings will pave the way for further design, structural optimization, and development of camptothecin-derived compounds as pesticidal agents. Full article

(This article belongs to the Special Issue Natural Product Synthesis: A Platform for Discovery)

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12 pages, 756 KiB

Open AccessArticle

Synthesis of a Functionalized Benzofuran as a Synthon for Salvianolic Acid C Analogues as Potential LDL Antioxidants

by Gabriela López-Frías, Alejandro A. Camacho-Dávila^*, David Chávez-Flores, Gerardo Zaragoza-Galán and Víctor H. Ramos-Sánchez

Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Circuito Universitario, Campus Universitario #2, Apartado Postal 669, Chihuahua, Chih. 31125, Mexico

Molecules 2015, 20(5), 8654-8665; https://doi.org/10.3390/molecules20058654 - 14 May 2015

Cited by 7 | Viewed by 7670

Abstract

A palladium mediated synthesis of a common synthon for the syntheses of antioxidant analogues of naturally occurring salvianolic acids is presented. The synthetic route may be used to obtain analogues with a balanced lipophilicity/hydrophilicity which may result in potentially interesting LDL antioxidants for [...] Read more.

A palladium mediated synthesis of a common synthon for the syntheses of antioxidant analogues of naturally occurring salvianolic acids is presented. The synthetic route may be used to obtain analogues with a balanced lipophilicity/hydrophilicity which may result in potentially interesting LDL antioxidants for the prevention of cardiovascular diseases. Full article

(This article belongs to the Section Organic Chemistry)

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21 pages, 774 KiB

Open AccessArticle

Synthesis, Antiproliferative and Antifungal Activities of 1,2,3-Triazole-Substituted Carnosic Acid and Carnosol Derivatives

by Mariano Walter Pertino^1,*, Cristina Theoduloz², Estefania Butassi³, Susana Zacchino³

and Guillermo Schmeda-Hirschmann¹

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

² Facultad de Ciencias de la Salud, Universidad de Talca, Casilla 747, Talca, Chile

³ Facultad de Ciencias Bioquímicas y Farmacéuticas, Farmacognosia, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina

Molecules 2015, 20(5), 8666-8686; https://doi.org/10.3390/molecules20058666 - 14 May 2015

Cited by 37 | Viewed by 6856

Abstract

Abietane diterpenes exhibit an array of interesting biological activities, which have generated significant interest among the pharmacological community. Starting from the abietane diterpenes carnosic acid and carnosol, twenty four new triazole derivatives were synthesized using click chemistry. The compounds differ in the length [...] Read more.

Abietane diterpenes exhibit an array of interesting biological activities, which have generated significant interest among the pharmacological community. Starting from the abietane diterpenes carnosic acid and carnosol, twenty four new triazole derivatives were synthesized using click chemistry. The compounds differ in the length of the linker and the substituent on the triazole moiety. The compounds were assessed as antiproliferative and antifungal agents. The antiproliferative activity was determined on normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), lung cancer (SK-MES-1) and bladder carcinoma (J82) cells while the antifungal activity was assessed against Candida albicans ATCC 10231 and Cryptococcus neoformans ATCC 32264. The carnosic acid γ-lactone derivatives 1–3 were the most active antiproliferative compounds of the series, with IC₅₀ values in the range of 43.4–46.9 μM and 39.2–48.9 μM for MRC-5 and AGS cells, respectively. Regarding antifungal activity, C. neoformans was the most sensitive fungus, with nine compounds inhibiting more than 50% of its fungal growth at concentrations ≤250 µg∙mL⁻¹. Compound 22, possessing a p-Br-benzyl substituent on the triazole ring, showed the best activity (91% growth inhibition) at 250 µg∙mL⁻¹ In turn, six compounds inhibited 50% C. albicans growth at concentrations lower than 250 µg∙mL⁻¹. Full article

(This article belongs to the Section Natural Products Chemistry)

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25 pages, 1774 KiB

Open AccessArticle

Synthesis and Biological Evaluation of N-Alkyl-3-(alkylamino)-pyrazine-2-carboxamides

by Lucia Semelkova^1,*, Klara Konecna¹

, Pavla Paterova¹, Vladimir Kubicek¹, Jiri Kunes¹, Lucie Novakova¹

, Jan Marek¹, Lieve Naesens², Matus Pesko³, Katarina Kralova⁴, Martin Dolezal¹

and Jan Zitko^1,*

¹ Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic

² Laboratory of Virology and Chemotherapy, Rega Institute KU Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium

³ Department of Environmental Ecology, Faculty of Natural Sciences, Comenius University, Mlynska Dolina CH-2, Bratislava 84215, Slovakia

⁴ Institute of Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska Dolina CH-2, Bratislava 84215, Slovakia

Molecules 2015, 20(5), 8687-8711; https://doi.org/10.3390/molecules20058687 - 14 May 2015

Cited by 13 | Viewed by 6564

Abstract

A series of N-alkyl-3-(alkylamino)pyrazine-2-carboxamides and their N-alkyl-3-chloropyrazine-2-carboxamide precursors were prepared. All compounds were characterized by analytical methods and tested for antimicrobial and antiviral activity. The antimycobacterial MIC values against Mycobacterium tuberculosis H37Rv of the most effective compounds, 3-(hexylamino)-, 3-(heptylamino)- and 3-(octylamino)- [...] Read more.

A series of N-alkyl-3-(alkylamino)pyrazine-2-carboxamides and their N-alkyl-3-chloropyrazine-2-carboxamide precursors were prepared. All compounds were characterized by analytical methods and tested for antimicrobial and antiviral activity. The antimycobacterial MIC values against Mycobacterium tuberculosis H37Rv of the most effective compounds, 3-(hexylamino)-, 3-(heptylamino)- and 3-(octylamino)-N-methyl-pyrazine-2-carboxamides 14‒16, was 25 μg/mL. The compounds inhibited photosystem 2 photosynthetic electron transport (PET) in spinach chloroplasts. This activity was strongly connected with the lipophilicity of the compounds. For effective PET inhibition longer alkyl chains in the 3-(alkylamino) substituent in the N-alkyl-3-(alkylamino)pyrazine-2-carboxamide molecule were more favourable than two shorter alkyl chains. Full article

(This article belongs to the Section Medicinal Chemistry)

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18 pages, 1867 KiB

Open AccessArticle

Synthesis, In-Vitro Antibacterial, Antifungal, and Molecular Modeling of Potent Anti-Microbial Agents with a Combined Pyrazole and Thiophene Pharmacophore

by Yahia Nasser Mabkhot^1,*,†

, Nahed Ahmed Kaal^1,†, Seham Alterary^1,†, Salim S. Al-Showiman^1,†, Assem Barakat^1,2,*,†

, Hazem A. Ghabbour^3,†

and Wolfgang Frey^4,†

¹ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

² Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia-21321 Alexandria, Egypt

³ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

⁴ Institut für Organische Chemie, Universitat Stuttgart, Pfaffenwaldring 55, Stuttgart 70569, Germany

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 8712-8729; https://doi.org/10.3390/molecules20058712 - 14 May 2015

Cited by 29 | Viewed by 6902

Abstract

Ethyl 5-acetyl-4-methyl-2-(phenylamino)thiophene-3-carboxylate (2) and there derivatives 3a–c, 4, 6a–c and 9a–f were synthesized. The structure of compound 2 was deduced by ¹H-NMR, ¹³C-NMR, FT-IR, MS, microanalysis, and single-crystal X-ray crystallography. The [...] Read more.

Ethyl 5-acetyl-4-methyl-2-(phenylamino)thiophene-3-carboxylate (2) and there derivatives 3a–c, 4, 6a–c and 9a–f were synthesized. The structure of compound 2 was deduced by ¹H-NMR, ¹³C-NMR, FT-IR, MS, microanalysis, and single-crystal X-ray crystallography. The compound crystallized in the monoclinic system, with space group P2₁/c and cell coordinates a = 8.5752(16) Å, b = 21.046(4) Å, c = 8.2941(12) Å, β = 101.131(6)°, V = 1468.7(4) Å³, and Z = 4. Compounds 2, 3a–c, 4, 5a–c and 9a–f were subjected into in vitro antimicrobial activity tests. Compounds 3a and 3c were more potent than standard drug amphotericin B, showing MIC values of 23.8 ± 0.42 and 24.3 ± 0.68, respectively, against Aspergillus fumigatus while the standard drug MIC was 23.7 ± 0.1. Compound 3c was also more potent (MIC 24.8 ± 0.64) than the standard drug amphotericin B (MIC 19.7 ± 0.2) against Syncephalastrum racemosum. Compounds 4 and 9f also showed promising anti-microbial activity. Molecular modeling was performed for the most active compounds. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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12 pages, 976 KiB

Open AccessArticle

Characterization of Melanogenesis Inhibitory Constituents of Morus alba Leaves and Optimization of Extraction Conditions Using Response Surface Methodology

by Ji Yeon Jeong, Qing Liu, Seon Beom Kim, Yang Hee Jo, Eun Jin Mo, Hyo Hee Yang, Dae Hye Song, Bang Yeon Hwang and Mi Kyeong Lee^*

College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 362-763, Korea

Molecules 2015, 20(5), 8730-8741; https://doi.org/10.3390/molecules20058730 - 14 May 2015

Cited by 27 | Viewed by 6885

Abstract

Melanin is a natural pigment that plays an important role in the protection of skin, however, hyperpigmentation cause by excessive levels of melatonin is associated with several problems. Therefore, melanogenesis inhibitory natural products have been developed by the cosmetic industry as skin medications. [...] Read more.

Melanin is a natural pigment that plays an important role in the protection of skin, however, hyperpigmentation cause by excessive levels of melatonin is associated with several problems. Therefore, melanogenesis inhibitory natural products have been developed by the cosmetic industry as skin medications. The leaves of Morus alba (Moraceae) have been reported to inhibit melanogenesis, therefore, characterization of the melanogenesis inhibitory constituents of M. alba leaves was attempted in this study. Twenty compounds including eight benzofurans, 10 flavonoids, one stilbenoid and one chalcone were isolated from M. alba leaves and these phenolic constituents were shown to significantly inhibit tyrosinase activity and melanin content in B6F10 melanoma cells. To maximize the melanogenesis inhibitory activity and active phenolic contents, optimized M. alba leave extraction conditions were predicted using response surface methodology as a methanol concentration of 85.2%; an extraction temperature of 53.2 °C and an extraction time of 2 h. The tyrosinase inhibition and total phenolic content under optimal conditions were found to be 74.8% inhibition and 24.8 μg GAE/mg extract, which were well-matched with the predicted values of 75.0% inhibition and 23.8 μg GAE/mg extract. These results shall provide useful information about melanogenesis inhibitory constituents and optimized extracts from M. alba leaves as cosmetic therapeutics to reduce skin hyperpigmentation. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 1366 KiB

Open AccessReview

Glutathione in Cellular Redox Homeostasis: Association with the Excitatory Amino Acid Carrier 1 (EAAC1)

by Koji Aoyama and Toshio Nakaki^*

Department of Pharmacology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan

Molecules 2015, 20(5), 8742-8758; https://doi.org/10.3390/molecules20058742 - 14 May 2015

Cited by 132 | Viewed by 13323

Abstract

Reactive oxygen species (ROS) are by-products of the cellular metabolism of oxygen consumption, produced mainly in the mitochondria. ROS are known to be highly reactive ions or free radicals containing oxygen that impair redox homeostasis and cellular functions, leading to cell death. Under [...] Read more.

Reactive oxygen species (ROS) are by-products of the cellular metabolism of oxygen consumption, produced mainly in the mitochondria. ROS are known to be highly reactive ions or free radicals containing oxygen that impair redox homeostasis and cellular functions, leading to cell death. Under physiological conditions, a variety of antioxidant systems scavenge ROS to maintain the intracellular redox homeostasis and normal cellular functions. This review focuses on the antioxidant system’s roles in maintaining redox homeostasis. Especially, glutathione (GSH) is the most important thiol-containing molecule, as it functions as a redox buffer, antioxidant, and enzyme cofactor against oxidative stress. In the brain, dysfunction of GSH synthesis leading to GSH depletion exacerbates oxidative stress, which is linked to a pathogenesis of aging-related neurodegenerative diseases. Excitatory amino acid carrier 1 (EAAC1) plays a pivotal role in neuronal GSH synthesis. The regulatory mechanism of EAAC1 is also discussed. Full article

(This article belongs to the Special Issue Thioredoxin and Glutathione Systems)

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13 pages, 2125 KiB

Open AccessArticle

Development and Characterization of Transcription Factor Gene-Derived Microsatellite (TFGM) Markers in Medicago truncatula and Their Transferability in Leguminous and Non-Leguminous Species

by Wenxian Liu^†, Xitao Jia^†, Zhimin Liu, Zhengshe Zhang, Yanrong Wang^*, Zhipeng Liu and Wengang Xie

¹ State Key Laboratory of Grassland Agro-ecosystems, College of Pastoral Agricultural Science and Technology, Lanzhou University, Lanzhou 730020, China

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 8759-8771; https://doi.org/10.3390/molecules20058759 - 15 May 2015

Cited by 25 | Viewed by 5142

Abstract

Transcription factors (TFs) are critical adaptor molecules that regulate many plant processes by controlling gene expression. The recent increase in the availability of TF data has made TFs a valuable resource for genic functional microsatellite marker development. In the present study, we developed [...] Read more.

Transcription factors (TFs) are critical adaptor molecules that regulate many plant processes by controlling gene expression. The recent increase in the availability of TF data has made TFs a valuable resource for genic functional microsatellite marker development. In the present study, we developed TF gene-derived microsatellite (TFGM) markers for Medicago truncatula and assessed their cross-species transferability. A total of 203 SSRs were identified from 1467 M. truncatula TF coding sequences, 87.68% of which were trinucleotide repeats, followed by mono- (4.93%) and hexanucleotide repeats (1.48%). Further, 142 TFGM markers showed a high level of transferability to the leguminous (55.63%–85.21%) and non-leguminous (28.17%–50.00%) species. Polymorphisms of 27 TFGM markers were evaluated in 44 alfalfa accessions. The allele number per marker ranged from two to eight with an average of 4.41, and the PIC values ranged from 0.08 to 0.84 with an average of 0.60. Considering the high polymorphism, these TFGM markers developed in our study will be valuable for genetic relationship assessments, marker-assisted selection and comparative genomic studies in leguminous and non-leguminous species. Full article

(This article belongs to the Section Molecular Diversity)

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19 pages, 1402 KiB

Open AccessArticle

Development and Validation of a Docking-Based Virtual Screening Platform for the Identification of New Lactate Dehydrogenase Inhibitors

by Carlotta Granchi, Alice Capecchi, Gianluca Del Frate, Adriano Martinelli, Marco Macchia, Filippo Minutolo and Tiziano Tuccinardi^*

Department of Pharmacy, University of Pisa, 56126 Pisa, Italy

Molecules 2015, 20(5), 8772-8790; https://doi.org/10.3390/molecules20058772 - 15 May 2015

Cited by 25 | Viewed by 8305

Abstract

The human muscle isoform of lactate dehydrogenase (hLDH5) is one of the key enzymes of the glycolytic process. It is overexpressed in metastatic cancer cells and is linked to the vitality of tumors in hypoxic conditions. With the aim of identifying [...] Read more.

The human muscle isoform of lactate dehydrogenase (hLDH5) is one of the key enzymes of the glycolytic process. It is overexpressed in metastatic cancer cells and is linked to the vitality of tumors in hypoxic conditions. With the aim of identifying new hLDH5 inhibitors, a fully automated docking-based virtual screening platform was developed by considering different protein conformations and the consensus docking strategy. In order to verify the reliability of the reported platform, a small database of about 10,000 compounds was filtered by using this method, and the top-ranked compounds were tested for their hLDH5 inhibition activity. Enzymatic assays revealed that, among the ten selected compounds, two proved to efficiently inhibit enzyme activity with IC₅₀ values in the micromolar range. These results demonstrate the validity of the methodologies we followed, encouraging the application of larger virtual screening studies and further refinements of the platform. Furthermore, the two active compounds herein described may be considered as interesting leads for the development of new and more efficient LDH inhibitors. Full article

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

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9 pages, 303 KiB

Open AccessCommunication

A Structural Hierarchy Matching Approach for Molecular Similarity/Substructure Searching

by Shu-Shen Ji¹, Hong-Ju Dong², Xin-Xin Zhou³, Ya-Min Liu⁴, Feng-Xue Zhang¹, Qi Wang^5,* and Xin-An Huang^1,6,*

¹ Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou 510405, China

² School of Life Sciences, Jilin University, Changchun 130012, China

³ School of Chinese Pharmacy, Guangzhou University of Chinese Medicine, Guangzhou 510405, China

⁴ The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, China

⁵ Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China

⁶ South China Chinese Medicine Collaborative Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China

Molecules 2015, 20(5), 8791-8799; https://doi.org/10.3390/molecules20058791 - 15 May 2015

Viewed by 5321

Abstract

An approach for molecular similarity/substructure searching based on structural hierarchy matching is proposed. In this approach, small molecules are divided into two categories, acyclic and cyclic forms. The latter are further divided into three structural hierarchies, namely, framework, complicated-, and mono-rings. During searching, [...] Read more.

An approach for molecular similarity/substructure searching based on structural hierarchy matching is proposed. In this approach, small molecules are divided into two categories, acyclic and cyclic forms. The latter are further divided into three structural hierarchies, namely, framework, complicated-, and mono-rings. During searching, the similarity coefficients of a structural query and each retrieved molecule are calculated using the hierarchy of the query as the reference. A total of 13,911 chemicals were involved in this work, from which the minimal cyclic and acyclic substructures are extracted, and further processed into fuzzy structural fingerprints. Subsequently, the fingerprints are used as the searching indices for molecular similarity or substructure searching. The tests show that this approach can give user options to choose between one-substructure and multi-substructure searching with sorted results. Moreover, this algorithm has the potential to be developed for molecular similarity searching and substructure analysis. Full article

(This article belongs to the Section Molecular Diversity)

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16 pages, 1105 KiB

Open AccessArticle

Design, Synthesis and Antitubercular Activity of Certain Nicotinic Acid Hydrazides

by Wagdy M. Eldehna^1,*

, Mohamed Fares¹, Marwa M. Abdel-Aziz² and Hatem A. Abdel-Aziz^3,4,*

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt

² The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo 11759, Egypt

³ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

⁴ Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo 12622, Egypt

Molecules 2015, 20(5), 8800-8815; https://doi.org/10.3390/molecules20058800 - 15 May 2015

Cited by 88 | Viewed by 11299

Abstract

Three series of 6-aryl-2-methylnicotinohydrazides 4a–i, N′-arylidene-6-(4-bromophenyl)-2-methylnicotino hydrazides 7a–f, and N′-(un/substituted 2-oxoindolin-3-ylidene)-6-(4-fluorophenyl)-2-methylnicotinohydrazides 8a–c were synthesized and evaluated for their potential in vitro antimycobacterial activity against M. tuberculosis. The results showed that isatin hydrazides [...] Read more.

Three series of 6-aryl-2-methylnicotinohydrazides 4a–i, N′-arylidene-6-(4-bromophenyl)-2-methylnicotino hydrazides 7a–f, and N′-(un/substituted 2-oxoindolin-3-ylidene)-6-(4-fluorophenyl)-2-methylnicotinohydrazides 8a–c were synthesized and evaluated for their potential in vitro antimycobacterial activity against M. tuberculosis. The results showed that isatin hydrazides 8a–c are remarkably more active than the parent hydrazide 4c. Hydrazides 8b and 8c exhibited the highest activity among all the tested compounds (MIC = 12.5 and 6.25 µg/mL, respectively). Compounds 8b and 8c were also devoid of apparent cytotoxicity to HT-29, PC-3, A549, HepG2 and MCF-7 cancer cell lines. Besides, 8b and 8c showed good drug-likeness scores of 0.62 and 0.41, respectively. Those two isatin hydrazides could offer an excellent framework for future development to obtain more potent antitubercular agents. The SAR study suggested that lipophilicity of the synthesized derivatives is a crucial element that accounts for their antimycobacterial activity. Finally, a theoretical kinetic study was established to predict the ADME of the active derivatives. Full article

(This article belongs to the Section Medicinal Chemistry)

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7 pages, 692 KiB

Open AccessArticle

Almond Skin Inhibits HSV-2 Replication in Peripheral Blood Mononuclear Cells by Modulating the Cytokine Network

by Adriana Arena¹, Carlo Bisignano², Giovanna Stassi¹, Angela Filocamo³ and Giuseppina Mandalari^3,*

¹ Department of Human Pathology, Policlinico Universitario, Via C. Valeria, Messina 98125, Italy

² Department of Biological and Environmental Science, University of Messina, Sal. Sperone 31, Messina 98100, Italy

³ Department of Drug Science and Products for Health, Vill. SS. Annunziata, Messina 98100, Italy

Molecules 2015, 20(5), 8816-8822; https://doi.org/10.3390/molecules20058816 - 15 May 2015

Cited by 8 | Viewed by 5865

Abstract

We have investigated the effect of almond skin extracts on the production of pro-inflammatory and anti-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs). PBMCs were either infected or not by herpes simplex virus type 2 (HSV-2), with and without prior treatment with [...] Read more.

We have investigated the effect of almond skin extracts on the production of pro-inflammatory and anti-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs). PBMCs were either infected or not by herpes simplex virus type 2 (HSV-2), with and without prior treatment with almond skin extracts. Production of IL-17 induced by HSV-2 was inhibited by natural skins (NS) treatment. NS triggered PBMC in releasing IFN-α, IFN-γ and IL-4 in cellular supernatants. These results may explain the antiviral potential of almond skins. Full article

(This article belongs to the Section Medicinal Chemistry)

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33 pages, 1326 KiB

Open AccessReview

Current Understanding of Molecular Pathology and Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy

by Tirsa L. E. Van Westering, Corinne A. Betts and Matthew J. A. Wood^*

Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK

Molecules 2015, 20(5), 8823-8855; https://doi.org/10.3390/molecules20058823 - 15 May 2015

Cited by 78 | Viewed by 17264

Abstract

Duchenne muscular dystrophy (DMD) is a genetic muscle disorder caused by mutations in the Dmd gene resulting in the loss of the protein dystrophin. Patients do not only experience skeletal muscle degeneration, but also develop severe cardiomyopathy by their second decade, one of [...] Read more.

Duchenne muscular dystrophy (DMD) is a genetic muscle disorder caused by mutations in the Dmd gene resulting in the loss of the protein dystrophin. Patients do not only experience skeletal muscle degeneration, but also develop severe cardiomyopathy by their second decade, one of the main causes of death. The absence of dystrophin in the heart renders cardiomyocytes more sensitive to stretch-induced damage. Moreover, it pathologically alters intracellular calcium (Ca²⁺) concentration, neuronal nitric oxide synthase (nNOS) localization and mitochondrial function and leads to inflammation and necrosis, all contributing to the development of cardiomyopathy. Current therapies only treat symptoms and therefore the need for targeting the genetic defect is immense. Several preclinical therapies are undergoing development, including utrophin up-regulation, stop codon read-through therapy, viral gene therapy, cell-based therapy and exon skipping. Some of these therapies are undergoing clinical trials, but these have predominantly focused on skeletal muscle correction. However, improving skeletal muscle function without addressing cardiac aspects of the disease may aggravate cardiomyopathy and therefore it is essential that preclinical and clinical focus include improving heart function. This review consolidates what is known regarding molecular pathology of the DMD heart, specifically focusing on intracellular Ca²⁺, nNOS and mitochondrial dysregulation. It briefly discusses the current treatment options and then elaborates on the preclinical therapeutic approaches currently under development to restore dystrophin thereby improving pathology, with a focus on the heart. Full article

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

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19 pages, 1811 KiB

Open AccessReview

Silver Nanoparticles as Potential Antibacterial Agents

by Gianluigi Franci¹, Annarita Falanga^2,3

, Stefania Galdiero^2,3,4

, Luciana Palomba⁵, Mahendra Rai⁶, Giancarlo Morelli^2,3,4 and Massimiliano Galdiero^4,5,*

¹ Dipartimento di Biochimica, Biofisica e Patologia Generale, Seconda Università degli Studi di Napoli, Vico L. De Crecchio 7, 80138 Napoli, Italy

² Department of Pharmacy, University of Naples Federico II, 80100 Naples, Italy

³ Istituto di Biostrutture e Bioimmagini, CNR, 80100 Napoli, Italy

⁴ CIRPEB, and DFM, University of Naples Federico II, 80100 Naples, Italy

⁵ Department of Experimental Medicine, II University of Naples, 80138 Naples, Italy

⁶ Department of Biotechnology, Sant Gadge Baba Amravati University, Amravati, Maharashtra 444602, India

Molecules 2015, 20(5), 8856-8874; https://doi.org/10.3390/molecules20058856 - 18 May 2015

Cited by 1359 | Viewed by 48113

Abstract

Multi-drug resistance is a growing problem in the treatment of infectious diseases and the widespread use of broad-spectrum antibiotics has produced antibiotic resistance for many human bacterial pathogens. Advances in nanotechnology have opened new horizons in nanomedicine, allowing the synthesis of nanoparticles that [...] Read more.

Multi-drug resistance is a growing problem in the treatment of infectious diseases and the widespread use of broad-spectrum antibiotics has produced antibiotic resistance for many human bacterial pathogens. Advances in nanotechnology have opened new horizons in nanomedicine, allowing the synthesis of nanoparticles that can be assembled into complex architectures. Novel studies and technologies are devoted to understanding the mechanisms of disease for the design of new drugs, but unfortunately infectious diseases continue to be a major health burden worldwide. Since ancient times, silver was known for its anti-bacterial effects and for centuries it has been used for prevention and control of disparate infections. Currently nanotechnology and nanomaterials are fully integrated in common applications and objects that we use every day. In addition, the silver nanoparticles are attracting much interest because of their potent antibacterial activity. Many studies have also shown an important activity of silver nanoparticles against bacterial biofilms. This review aims to summarize the emerging efforts to address current challenges and solutions in the treatment of infectious diseases, particularly the use of nanosilver antimicrobials. Full article

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

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18 pages, 1490 KiB

Open AccessArticle

Effect of Extrusion Cooking on Bioactive Compounds in Encapsulated Red Cactus Pear Powder

by Martha G. Ruiz-Gutiérrez¹, Carlos A. Amaya-Guerra², Armando Quintero-Ramos^1,*

, Esther Pérez-Carrillo³

, Teresita De J. Ruiz-Anchondo⁴, Juan G. Báez-González²

and Carmen O. Meléndez-Pizarro¹

¹ Departamento de Investigación y Posgrado, Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Circuito Universitario s/n Campus Universitario 2, Chihuahua 31125, Mexico

² Departamento de Investigación y Posgrado, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, Ciudad Universitaria, San Nicolás de los Garza 66450, Mexico

³ Centro de Biotecnología-FEMSA, Escuela de Ingenería y Ciencias, Tecnológico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, Monterrey 64849, Mexico

⁴ Facultad de Ciencias Agrotecnológicas, Universidad Autónoma de Chihuahua, Circuito Universitario s/n Campus Universitario 1, Chihuahua 31310, Mexico

Molecules 2015, 20(5), 8875-8892; https://doi.org/10.3390/molecules20058875 - 18 May 2015

Cited by 35 | Viewed by 7965

Abstract

Red cactus pear has significant antioxidant activity and potential as a colorant in food, due to the presence of betalains. However, the betalains are highly thermolabile, and their application in thermal process, as extrusion cooking, should be evaluated. The aim of this study [...] Read more.

Red cactus pear has significant antioxidant activity and potential as a colorant in food, due to the presence of betalains. However, the betalains are highly thermolabile, and their application in thermal process, as extrusion cooking, should be evaluated. The aim of this study was to evaluate the effect of extrusion conditions on the chemical components of red cactus pear encapsulated powder. Cornstarch and encapsulated powder (2.5% w/w) were mixed and processed by extrusion at different barrel temperatures (80, 100, 120, 140 °C) and screw speeds (225, 275, 325 rpm) using a twin-screw extruder. Mean residence time (tr_m), color (L*, a*, b*), antioxidant activity, total polyphenol, betacyanin, and betaxanthin contents were determined on extrudates, and pigment degradation reaction rate constants (k) and activation energies (E_a) were calculated. Increases in barrel temperature and screw speed decreased the tr_m, and this was associated with better retentions of antioxidant activity, total polyphenol, betalain contents. The betacyanins k values ranged the −0.0188 to −0.0206/s and for betaxanthins ranged of −0.0122 to −0.0167/s, while E_a values were 1.5888 to 6.1815 kJ/mol, respectively. The bioactive compounds retention suggests that encapsulated powder can be used as pigments and to provide antioxidant properties to extruded products. Full article

(This article belongs to the Collection Bioactive Compounds)

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20 pages, 1612 KiB

Open AccessArticle

Comparative Study on the Efficiency of the Photodynamic Inactivation of Candida albicans Using CdTe Quantum Dots, Zn(II) Porphyrin and Their Conjugates as Photosensitizers

by Osnir S. Viana¹, Martha S. Ribeiro²

, Andréa C. D. Rodas², Júlio S. Rebouças³, Adriana Fontes⁴ and Beate S. Santos^1,*

¹ Pharmaceutical Sciences Department, Pernambuco Federal University, Recife 50670-901, Brazil

² Center for Lasers and Applications, IPEN-CNEN-SP, São Paulo 05508-000, Brazil

³ Chemistry Department, CCEN Universidade Federal da Paraiba, João Pessoa 58051-900, Brazil

⁴ Biophysics and Radiobiology Department, Pernambuco Federal University, Recife 50670-901, Brazil

Molecules 2015, 20(5), 8893-8912; https://doi.org/10.3390/molecules20058893 - 18 May 2015

Cited by 36 | Viewed by 7657

Abstract

The application of fluorescent II-VI semiconductor quantum dots (QDs) as active photosensitizers in photodymanic inactivation (PDI) is still being evaluated. In the present study, we prepared 3 nm size CdTe QDs coated with mercaptosuccinic acid and conjugated them electrostatically with Zn(II) meso-tetrakis [...] Read more.

The application of fluorescent II-VI semiconductor quantum dots (QDs) as active photosensitizers in photodymanic inactivation (PDI) is still being evaluated. In the present study, we prepared 3 nm size CdTe QDs coated with mercaptosuccinic acid and conjugated them electrostatically with Zn(II) meso-tetrakis (N-ethyl-2-pyridinium-2-yl) porphyrin (ZnTE-2-PyP or ZnP), thus producing QDs-ZnP conjugates. We evaluated the capability of the systems, bare QDs and conjugates, to produce reactive oxygen species (ROS) and applied them in photodynamic inactivation in cultures of Candida albicans by irradiating the QDs and testing the hypothesis of a possible combined contribution of the PDI action. Tests of in vitro cytotoxicity and phototoxicity in fibroblasts were also performed in the presence and absence of light irradiation. The overall results showed an efficient ROS production for all tested systems and a low cytotoxicity (cell viability >90%) in the absence of radiation. Fibroblasts incubated with the QDs-ZnP and subjected to irradiation showed a higher cytotoxicity (cell viability <90%) depending on QD concentration compared to the bare groups. The PDI effects of bare CdTe QD on Candida albicans demonstrated a lower reduction of the cell viability (~1 log10) compared to bare ZnP which showed a high microbicidal activity (~3 log10) when photoactivated. The QD-ZnP conjugates also showed reduced photodynamic activity against C. albicans compared to bare ZnP and we suggest that the conjugation with QDs prevents the transmembrane cellular uptake of the ZnP molecules, reducing their photoactivity. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 757 KiB

Open AccessArticle

Influence of Fruit Maturity at Harvest on the Intensity of Smoke Taint in Wine

by Renata Ristic^1,†, Paul K. Boss^2,† and Kerry L. Wilkinson^1,*,†

¹ School of Agriculture, Food and Wine, University of Adelaide, PMB 1, Glen Osmond, SA 5064, Australia

² CSIRO Agriculture, PMB 2, Glen Osmond, SA 5064, Australia

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 8913-8927; https://doi.org/10.3390/molecules20058913 - 18 May 2015

Cited by 30 | Viewed by 7586

Abstract

Bushfire smoke can affect the composition and sensory properties of grapes and wines, in some cases leading to wines which exhibit undesirable “smoky”, “ashy” and “medicinal” characters. This study investigated the extent to which fruit maturity (i.e., ripeness) influences the perception [...] Read more.

Bushfire smoke can affect the composition and sensory properties of grapes and wines, in some cases leading to wines which exhibit undesirable “smoky”, “ashy” and “medicinal” characters. This study investigated the extent to which fruit maturity (i.e., ripeness) influences the perception of smoke taint in wine. Two white grape varieties (Chardonnay and Sauvignon Blanc) and two red grape varieties (Merlot and Shiraz) were exposed to smoke under experimental conditions, at approximately seven days post-veraison. Fruit was then harvested at two levels of maturity: Harvest A, when total soluble solids were 16–20 °Brix, i.e., the berry ripeness typically required for production of sparkling or light-bodied wines; and Harvest B, when total soluble solids were 22–25 °Brix, i.e., the berry ripeness typically required for production of full-bodied wines. The intensity of smoke taint in resulting wines was found to be influenced by fruit maturity, but differed between grape varieties. Smoke-related sensory attributes were apparent in Sauvignon Blanc wine made from early-harvested fruit and in Chardonnay wine made from late-harvested fruit, only; whereas Merlot and Shiraz wines exhibited smoke taint irrespective of fruit maturity. Smoke-derived volatile phenols, and various alcohols, esters and acids, were also quantified to determine the impact of smoke exposure and fruit maturity respectively, on wine composition. Full article

(This article belongs to the Collection Wine Chemistry)

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13 pages, 856 KiB

Open AccessArticle

Absorption and Metabolism Characteristics of Triptolide as Determined by a Sensitive and Reliable LC-MS/MS Method

by Xiaomei Gong^1,*,†, Yan Chen^2,† and Yi Wu^3,*

¹ Department of Radiatin Oncology, Shanghai Pulmonary Hospital, Tongji University, 507 Zhengmin Road, Shanghai 200433, China

² Department of Gastroenterology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China

³ Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, 1# Weigang, Nanjing 210095, Jiangsu, China

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 8928-8940; https://doi.org/10.3390/molecules20058928 - 18 May 2015

Cited by 34 | Viewed by 6583

Abstract

In this research, a sensitive and reliable LC-MS/MS method was developed and applied to determine the concentration of triptolide in rat plasma, microsomes, and cell incubation media. The absolute oral bioavailability of triptolide is 63.9% at a dose of 1 mg·kg⁻¹. [...] Read more.

In this research, a sensitive and reliable LC-MS/MS method was developed and applied to determine the concentration of triptolide in rat plasma, microsomes, and cell incubation media. The absolute oral bioavailability of triptolide is 63.9% at a dose of 1 mg·kg⁻¹. In vitro, the bidirectional transport of triptolide across Caco-2 cells was studied. A markedly higher transport of triptolide across Caco-2 cells was observed in the basolateral-to-apical direction and was abrogated in the presence of the P-gp inhibitor, verapamil. The result indicated that P-gp might be involved in the absorption of triptolide in intestinal. The metabolic stability was also investigated using human liver microsome incubation systems in vitro. In HLMs, incubations with an initial triptolide concentration of 1 μM resulted in an 82.4% loss of substrate over 60 min, and the t_1/2 was 38 min, which indicated that triptolide was easily metabolized in human liver microsomes. In conclusion, the absolute oral bioavailability of triptolide in plasma, transport across Caco-2 cell monolayers, and metabolic stability in human liver microsomes were systematically investigated by using a sensitive and reliable LC-MS/MS method. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 1746 KiB

Open AccessArticle

Structural Characteristics and Non-Linear Optical Behaviour of a 2-Hydroxynicotinate-Containing Zinc-Based Metal-Organic Framework

by Shruti Mendiratta¹, Cheng-Hua Lee¹, Sih-Ying Lee^1,2, Ya-Chuan Kao¹, Bor-Chen Chang³, Yih-Hsing Lo² and Kuang-Lieh Lu^1,*

¹ Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan

² Department of Applied Physics and Chemistry, University of Taipei, Taipei 106, Taiwan

³ Department of Chemistry, National Central University, Taoyuan 320, Taiwan

Molecules 2015, 20(5), 8941-8951; https://doi.org/10.3390/molecules20058941 - 18 May 2015

Cited by 19 | Viewed by 6586

Abstract

Materials with non-linear optical (NLO) properties play an important role in the construction of electronic devices for optical communications, optical data processing and data storage. With this aim in mind, a Zn(II)-based metal-organic framework {[Zn₂(nica)₂(bpy)_1.5(H₂O)]×0.5(bpy)×3H [...] Read more.

Materials with non-linear optical (NLO) properties play an important role in the construction of electronic devices for optical communications, optical data processing and data storage. With this aim in mind, a Zn(II)-based metal-organic framework {[Zn₂(nica)₂(bpy)_1.5(H₂O)]×0.5(bpy)×3H₂O}_n (1), was synthesized using 4,4ʹ-bipyridine (bpy) and a potentially bidentate ligand, 2-hydroxynicotinic acid (H₂nica) with a salicylate binding moiety. A single-crystal X-ray diffraction analysis revealed that compound 1 crystallized in the orthorhombic space group Fdd2 and was composed of a three dimensional porous framework. Since Fdd2 belonged to a class of non-centrosymmetric space groups, we therefore investigated the non-linear optical behaviour of compound 1. Photoluminescence studies revealed that compound 1 exhibited a blue light emission with a maxima at 457 nm. Full article

(This article belongs to the Special Issue Metal-Organic Frameworks: Chemistry and Applications)

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36 pages, 842 KiB

Open AccessReview

Chemistry and Biological Activity of Ramalina Lichenized Fungi

by Antônio Sérgio Nascimento Moreira^1,2,*, Raimundo Braz-Filho^1,†, Vicente Mussi-Dias^3,† and Ivo José Curcino Vieira¹

¹ Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro, UENF, Avenida Alberto Lamego 2000, Campos dos Goytacazes, 28013-602 Rio de Janeiro, Brazil

² Instituto Federal Fluminense, IFF, Avenida Souza Mota 350, Parque Fundão, Campos dos Goytacazes, 28060-010 Rio de Janeiro, Brazil

³ Laboratório de Entomologia e Fitopatologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, UENF, Avenida Alberto Lamego 2000, Campos dos Goytacazes, 28013-602 Rio de Janeiro, Brazil

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 8952-8987; https://doi.org/10.3390/molecules20058952 - 19 May 2015

Cited by 47 | Viewed by 10452

Abstract

Lichens are a form of symbiont between a fungus and an alga or cyanobacterium, which contains a wide variety of organic compounds with certain secondary metabolite classes typical of these organisms. The Ramalina genus has approximately 246 species distributed around the World, of [...] Read more.

Lichens are a form of symbiont between a fungus and an alga or cyanobacterium, which contains a wide variety of organic compounds with certain secondary metabolite classes typical of these organisms. The Ramalina genus has approximately 246 species distributed around the World, of which in this review approximately 118 species with published chemical or biological activity studies of extracts or isolated compounds were cited. From the 153 mentioned compounds, only 27 passed were tested for biological activity, being usnic acid the most studied compound and the one showing the best results in almost all in vitro tests performed, although other compounds also presented excellent results as antimicrobial, antitumor and anti-inflammatory agents, among others. Extracts of several species also presented significant results in performed biological tests, demonstrating the potential that these organisms have, in particular, the gender Ramalina, to produce bioactive molecules that can be used as a model for the production of pharmaceuticals. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 1074 KiB

Open AccessCommunication

Inhibitory Effects of Verrucarin A on Tunicamycin-Induced ER Stress in FaO Rat Liver Cells

by Eun Young Bae¹, Seung Woong Lee², Sin Seong³, Wonjun Cho⁴, Jong Seog Ahn^5,* and Hyun-Sug Cho^6,*

¹ LINC Project Group, Daejeon University, Daejeon 300-716, Korea

² Department of Chemistry, Mokwon University, Daejeon 302-729, Korea

³ Soram Korean Medicine Hospital, M-Tower, Gangnam-Gu, Seoul 135-879, Korea

⁴ Soram Bio-Medicine Research Institute (SBRI), Soram Korean Medicine Hospital, M-Tower, Gangnam-Gu, Seoul 135-879, Korea

⁵ Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yeongudanjiro, Ochang, Cheongwon, Chungbuk 363-883, Korea

⁶ Hyehwa-Liberal Arts College, Daejeon University, Daejeon 300-716, Korea

Molecules 2015, 20(5), 8988-8996; https://doi.org/10.3390/molecules20058988 - 19 May 2015

Cited by 5 | Viewed by 7595

Abstract

Endoplasmic reticulum (ER) stress is linked with development and maintenance of cancer, and serves as a therapeutic target for treatment of cancer. Verrucarin A, isolated from the broth of Fusarium sp. F060190, showed potential inhibitory activity on tunicamycin-induced ER stress in FaO rat [...] Read more.

Endoplasmic reticulum (ER) stress is linked with development and maintenance of cancer, and serves as a therapeutic target for treatment of cancer. Verrucarin A, isolated from the broth of Fusarium sp. F060190, showed potential inhibitory activity on tunicamycin-induced ER stress in FaO rat liver cells. In addition, the compound decreased tunicamycin-induced GRP78 promoter activity in a dose dependent manner without inducing significant inhibition of luciferase activity and cell growth for 6 and 12 h. Moreover, the compound decreased the expression of GRP78, CHOP, XBP-1, and suppressed XBP-1, and reduced phosphorylation of IRE1α in FaO rat liver cells. This evidence suggests for the first time that verrucarin A inhibited tunicamycin-induced ER stress in FaO rat liver cells. Full article

(This article belongs to the Collection Bioactive Compounds)

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32 pages, 3643 KiB

Open AccessArticle

S4MPLE—Sampler for Multiple Protein-Ligand Entities: Methodology and Rigid-Site Docking Benchmarking

by Laurent Hoffer^1,2, Camelia Chira³, Gilles Marcou¹, Alexandre Varnek¹ and Dragos Horvath^1,*

¹ Laboratoire de Chemoinformatique; UMR 7141, Université de Strasbourg, 1 rue B. Pascal, Strasbourg 67000, France

² Novalix, BioParc, bld Sébastien Brant, BP 30170, Illkirch 67405 Cedex, France

³ Department of Computer Science, Technical University, Cluj-Napoca 400027, Romania

Molecules 2015, 20(5), 8997-9028; https://doi.org/10.3390/molecules20058997 - 19 May 2015

Cited by 27 | Viewed by 8833

Abstract

This paper describes the development of the unified conformational sampling and docking tool called Sampler for Multiple Protein-Ligand Entities (S4MPLE). The main novelty in S4MPLE is the unified dealing with intra- and intermolecular degrees of freedom (DoF). While classically programs are either designed [...] Read more.

This paper describes the development of the unified conformational sampling and docking tool called Sampler for Multiple Protein-Ligand Entities (S4MPLE). The main novelty in S4MPLE is the unified dealing with intra- and intermolecular degrees of freedom (DoF). While classically programs are either designed for folding or docking, S4MPLE transcends this artificial specialization. It supports folding, docking of a flexible ligand into a flexible site and simultaneous docking of several ligands. The trick behind it is the formal assimilation of inter-molecular to intra-molecular DoF associated to putative inter-molecular contact axes. This is implemented within the genetic operators powering a Lamarckian Genetic Algorithm (GA). Further novelty includes differentiable interaction fingerprints to control population diversity, and fitting a simple continuum solvent model and favorable contact bonus terms to the AMBER/GAFF force field. Novel applications—docking of fragment-like compounds, simultaneous docking of multiple ligands, including free crystallographic waters—were published elsewhere. This paper discusses: (a) methodology, (b) set-up of the force field energy functions and (c) their validation in classical redocking tests. More than 80% success in redocking was achieved (RMSD of top-ranked pose < 2.0 Å). Full article

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

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25 pages, 2985 KiB

Open AccessReview

Protein-Carbohydrate Interactions as Part of Plant Defense and Animal Immunity

by Kristof De Schutter

and Els J. M. Van Damme^*

Lab Biochemistry and Glycobiology, Department of Molecular Biotechnology, Ghent University, Coupure links 653, B-9000 Ghent, Belgium

Molecules 2015, 20(5), 9029-9053; https://doi.org/10.3390/molecules20059029 - 19 May 2015

Cited by 88 | Viewed by 14439

Abstract

The immune system consists of a complex network of cells and molecules that interact with each other to initiate the host defense system. Many of these interactions involve specific carbohydrate structures and proteins that specifically recognize and bind them, in particular lectins. It [...] Read more.

The immune system consists of a complex network of cells and molecules that interact with each other to initiate the host defense system. Many of these interactions involve specific carbohydrate structures and proteins that specifically recognize and bind them, in particular lectins. It is well established that lectin-carbohydrate interactions play a major role in the immune system, in that they mediate and regulate several interactions that are part of the immune response. Despite obvious differences between the immune system in animals and plants, there are also striking similarities. In both cases, lectins can play a role as pattern recognition receptors, recognizing the pathogens and initiating the stress response. Although plants do not possess an adaptive immune system, they are able to imprint a stress memory, a mechanism in which lectins can be involved. This review will focus on the role of lectins in the immune system of animals and plants. Full article

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

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17 pages, 774 KiB

Open AccessArticle

Effects of Dietary Brazilian Palm Oil (Mauritia flexuosa L.) on Cholesterol Profile and Vitamin A and E Status of Rats

by Jailane De Souza Aquino^1,*, Juliana Késsia Barbosa Soares², Marciane Magnani³, Thayza Christina Montenegro Stamford⁴, Robson De Jesus Mascarenhas⁵, Renata Leite Tavares¹ and Tânia Lúcia Montenegro Stamford⁶

¹ Departamento de Nutrição/CCS, Universidade Federal da Paraíba, Campus I, s/n. Castelo Branco, 58051-900 João Pessoa-PB, Brasil

² Departamento de Nutrição/CES, Universidade Federal de Campina Grande, Olho d'agua da Bica, s/n, 58175-000 Cuité-PB, Brasil

³ Departamento de Engenharia de Alimentos, Universidade Federal da Paraíba, Campus I, s/n. Castelo Branco, 58051-970 João Pessoa-PB, Brasil

⁴ Departamento de Medicina Tropical/CCS, Universidade Federal de Pernambuco, Campus Recife, s/n, Cidade Universitária, 50670-901 Recife-PE, Brasil

⁵ Instituto Federal de Educação, Ciência e Tecnologia do Sertão Pernambucano, Campus Petrolina, BR 407, km 08, Jd. São Paulo, 56314-520 Petrolina-PE, Brasil

⁶ Departamento de Nutrição/ CCS, Universidade Federal de Pernambuco, Campus Recife, s/n, Cidade Universitária, 50670-901 Recife-PE, Brasil

Molecules 2015, 20(5), 9054-9070; https://doi.org/10.3390/molecules20059054 - 19 May 2015

Cited by 23 | Viewed by 7695

Abstract

In vitro studies have been carried out to establish the nutritional differences between crude and refined vegetable oils; however, the impact of the consumption of these foods on metabolism, in particular the effect of buriti oil, needs to be further evaluated. The aim [...] Read more.

In vitro studies have been carried out to establish the nutritional differences between crude and refined vegetable oils; however, the impact of the consumption of these foods on metabolism, in particular the effect of buriti oil, needs to be further evaluated. The aim of this study was to evaluate the biochemical and murine parameters and the vitamin A and E status in young rats fed with diets supplemented with crude or refined buriti oil. The animals (n = 30) were randomized into three groups receiving diet added of soybean oil (control), crude buriti oil (CBO) and refined buriti oil (RBO) for 28 days. Rats fed with diet added of refined buriti oil (RBO) showed reduced total cholesterol (up to 60.27%), LDL (64.75%), triglycerides (55.47%) and enzyme aspartate transaminase (21.57%) compared to those fed with diet added of crude oil. Serum and hepatic retinol and tocopherol were higher by two to three times in CBO and RBO groups compared to the control group, but no differences were observed for murine parameters. The results indicate that buriti oil is an important source of the antioxidant vitamins A and E, and refined buriti oil is suggested as alternative to improve the lipid profile of healthy rats. Full article

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

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13 pages, 780 KiB

Open AccessArticle

Four New Triterpenoids from Callicarpa kwangtungensis

by Guo-Ping Zhou¹, Yan Yu^1,3, Ming-Ming Yuan^1,3, Tengfei Ji^2,*, Hui-Zheng Fu¹ and Rui-Jian Zhong^1,*

¹ Jiangxi Provincial Institute for Drug and Food Control, Nanchang 330029, China

² State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

³ Pharmaceutical Department of Nanchang University, Nanchang 330006, China

Molecules 2015, 20(5), 9071-9083; https://doi.org/10.3390/molecules20059071 - 19 May 2015

Cited by 22 | Viewed by 5408

Abstract

Four new triterpenoids which were identifed as 2α,3β,6β,19α-tetrahydroxy- oleanolic acid 28-O-β-D-glucopyranoside (1), 2-O-β-D-glucopyranosyloxy-3α,19α-di-hydroxyoleanolic acid (2), 2-O-β-D-glucopyranosyloxy-3α,19α-dihydroxyursolic acid (3), 2α,3α,6β,19α-tetrahydroxyursolic acid 28-O-β-D-glucopyranoside (4), were isolated from the aerial [...] Read more.

Four new triterpenoids which were identifed as 2α,3β,6β,19α-tetrahydroxy- oleanolic acid 28-O-β-D-glucopyranoside (1), 2-O-β-D-glucopyranosyloxy-3α,19α-di-hydroxyoleanolic acid (2), 2-O-β-D-glucopyranosyloxy-3α,19α-dihydroxyursolic acid (3), 2α,3α,6β,19α-tetrahydroxyursolic acid 28-O-β-D-glucopyranoside (4), were isolated from the aerial parts of Callicarpa kwangtungensis together with three known triterpenoids identified as 2α,3β,21β-trihydroxyursolic acid 28-O-β-D-glucopyranoside (5), 2α,3α,19α,23-tetrahydroxyoleanolic acid 28-O-β-D-glucopyranoside (6), 2α,3α,19α,23-tetrahydroxyursolic acid 28-O-β-D-glucopyranoside (7). Their structures were elucidated by the combination of mass spectrometry (MS), one and two-dimensional NMR experiments. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 726 KiB

Open AccessArticle

LC-MS/MS Determination and Pharmacokinetic Study of Pedunculoside in Rat Plasma after Oral Administration of Pedunculoside and Ilex rotunda Extract

by Waiou Zhao¹, Li Pang², Dahai Xu² and Nan Zhang^2,*

¹ Cardiovascular Medicine, the First Hospital of Jilin University, Changchun 130021, China

² Emergency Department, the First Hospital of Jilin University, Changchun 130021, China

Molecules 2015, 20(5), 9084-9098; https://doi.org/10.3390/molecules20059084 - 19 May 2015

Cited by 15 | Viewed by 6712

Abstract

Ilex rotunda is widely used to treat many disorders as a traditional Chinese medicine (TCM) containing 4%–5% pedunculoside (PDC). A rapid, selective, and sensitive liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was developed and validated to determine PDC in rat plasma by using 3β,19α-dihydroxyurs-12-en-28-oic [...] Read more.

Ilex rotunda is widely used to treat many disorders as a traditional Chinese medicine (TCM) containing 4%–5% pedunculoside (PDC). A rapid, selective, and sensitive liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was developed and validated to determine PDC in rat plasma by using 3β,19α-dihydroxyurs-12-en-28-oic acid 28-β-D-glucopyranosyl ester (DEOG) as an internal standard. The analytes were extracted by protein precipitation and eluted on a C₁₈ chromatography column using a mobile phase of methanol–H₂O (70:30, v/v) delivered at a flow rate of 0.6 mL/min. Detection was performed using positive ion electrospray ionization in multiple reaction monitoring modes. The assay was linear over the concentration range of 0.60 ng/mL to 200 ng/mL, with a quantification limit of 0.60 ng/mL. Intra-day and inter-day precisions (%RSD) ranged from 2.12 to 9.51 for PDC, whereas the accuracy was within −7.83%~9.40%. The validated method was successfully applied to the pharmacokinetic study of PDC in rat plasma after oral administration of pure PDC and Ilex rotunda extract (IRE). Pharmacokinetic parameters of PDC in IRE, such as C_max, AUC_0–t, AUC_0–∞, t_1/2z_, and CL_z/F, statistically differed from those of the pure monomer (p < 0.01). However, T_max and MRT showed no significant differences between the two groups. Results suggested that other coexisting components in IRE may decrease the absorption of PDC. Compound-compound interactions between PDC and other herbal extract components can alter the pharmacokinetic behavior of PDC. The study will be helpful in providing references for understanding the action mechanism and clinical application of Ilex rotunda. Full article

(This article belongs to the Section Medicinal Chemistry)

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25 pages, 2201 KiB

Open AccessReview

Gaseous Mediators Nitric Oxide and Hydrogen Sulfide in the Mechanism of Gastrointestinal Integrity, Protection and Ulcer Healing

by Marcin Magierowski

, Katarzyna Magierowska, Slawomir Kwiecien and Tomasz Brzozowski^*

Department of Physiology, Jagiellonian University Medical College, Cracow 31-531, Poland

Molecules 2015, 20(5), 9099-9123; https://doi.org/10.3390/molecules20059099 - 19 May 2015

Cited by 101 | Viewed by 13349

Abstract

Nitric oxide (NO) and hydrogen sulfide (H₂S) are known as biological messengers; they play an important role in human organism and contribute to many physiological and pathophysiological processes. NO is produced from l-arginine by constitutive NO synthase (NOS) and inducible NOS [...] Read more.

Nitric oxide (NO) and hydrogen sulfide (H₂S) are known as biological messengers; they play an important role in human organism and contribute to many physiological and pathophysiological processes. NO is produced from l-arginine by constitutive NO synthase (NOS) and inducible NOS enzymatic pathways. This gaseous mediator inhibits platelet aggregation, leukocyte adhesion and contributes to the vessel homeostasis. NO is known as a vasodilatory molecule involved in control of the gastric blood flow (GBF) and the maintenance of gastric mucosal barrier integrity in either healthy gastric mucosa or that damaged by strong irritants. Biosynthesis of H₂S in mammals depends upon two enzymes cystathionine-β-synthase and cystathionine γ-lyase. This gaseous mediator, similarly to NO and carbon monoxide, is involved in neuromodulation, vascular contractility and anti-inflammatory activities. For decades, H₂S has been known to inhibit cytochrome c oxidase and reduce cell energy production. Nowadays it is generally considered to act through vascular smooth muscle ATP-dependent K⁺ channels, interacting with intracellular transcription factors and promote sulfhydration of protein cysteine moieties within the cell, but the mechanism of potential gastroprotective and ulcer healing properties of H₂S has not been fully explained. The aim of this review is to compare current results of the studies concerning the role of H₂S and NO in gastric mucosa protection and outline areas that may pose new opportunities for further development of novel therapeutic targets. Full article

(This article belongs to the Special Issue Nitric Oxide (NO) Release Chemistry)

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15 pages, 2455 KiB

Open AccessArticle

1,3-Diphenylethenylcarbazolyl-Based Monomer for Cross-Linked Hole Transporting Layers

by Maryte Daskeviciene¹, Giedre Bubniene¹, Tadas Malinauskas¹, Vygintas Jankauskas², Valentas Gaidelis², Valdas Paulauskas³ and Vytautas Getautis^1,*

¹ Department of Organic Chemistry, Kaunas University of Technology, Radvilenu pl. 19, 50254 Kaunas, Lithuania

² Department of Solid State Electronics, Vilnius University, Sauletekio 9, 10222 Vilnius, Lithuania

³ Institute of Environment and Ecology, Aleksandras Stulginskis University, Studentu 11, Kaunas Dist., 53361 Akademija, Lithuania

Molecules 2015, 20(5), 9124-9138; https://doi.org/10.3390/molecules20059124 - 19 May 2015

Cited by 1 | Viewed by 5179

Abstract

A new cross-linkable monomer containing 1,3-diphenylethenylcarbazolyl-based hole-transporting moieties and four reactive epoxy groups, was prepared by a multistep synthesis route from 1,3-bis(2,2-diphenylethenyl)-9H-carbazol-2-ol and its application for the in situ formation of cross-linked hole transporting layers was investigated. A high concentration of [...] Read more.

A new cross-linkable monomer containing 1,3-diphenylethenylcarbazolyl-based hole-transporting moieties and four reactive epoxy groups, was prepared by a multistep synthesis route from 1,3-bis(2,2-diphenylethenyl)-9H-carbazol-2-ol and its application for the in situ formation of cross-linked hole transporting layers was investigated. A high concentration of flexible aliphatic epoxy chains ensures good solubility and makes this compound an attractive cross-linking agent. The synthesized compounds were characterized by various techniques, including differential scanning calorimetry, xerographic time of flight, and electron photoemission in air methods. Full article

(This article belongs to the Section Organic Chemistry)

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16 pages, 1634 KiB

Open AccessReview

Nanofibers of Cellulose and Its Derivatives Fabricated Using Direct Electrospinning

by Kousaku Ohkawa

Division of Biological and Medical Fibers and Institute for Fiber Engineering (IFES), Interdisciplinary Cluster for Cutting Edge Research (ICCER), Shinshu University, Tokida 3-15-1, Ueda 386-8567, Nagano Prefecture, Japan

Molecules 2015, 20(5), 9139-9154; https://doi.org/10.3390/molecules20059139 - 19 May 2015

Cited by 70 | Viewed by 9813

Abstract

A short review with 49 references describes the electrospinninng (ES) process for polysaccharides, cellulose and chitosan, and their derivatives, including cellulose acetate and hydroxypropyl cellulose. A majority of applied studies adopted a two step-process, in which the cellulose acetate was used for the [...] Read more.

A short review with 49 references describes the electrospinninng (ES) process for polysaccharides, cellulose and chitosan, and their derivatives, including cellulose acetate and hydroxypropyl cellulose. A majority of applied studies adopted a two step-process, in which the cellulose acetate was used for the first ES process, followed by acetyl group removal to regenerate cellulose thin fibers. The electrospun nonwoven fabrics (ESNW) of regenerated cellulose can be modified by introduction of aldehyde groups by oxidative cleavage of vicinal diols using periodates, and these aldehyde groups serve as acceptors of foreign substances, with various chemical/biological functions, to be immobilized on the fiber surfaces in the ESNW matrices. Direct electrospinning of cellulose from trifluroacetic acid solution was also developed and the applied studies were summarized to conclude the current trends of interests in the ES and related technologies. Full article

(This article belongs to the Special Issue New Trends in Cellulose and Chitin Chemistry)

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15 pages, 1869 KiB

Open AccessArticle

Characterization of Anthocyanins in Perilla frutescens var. acuta Extract by Advanced UPLC-ESI-IT-TOF-MSⁿ Method and Their Anticancer Bioactivity

by Yan-Kang He, You-Yuan Yao and Ya-Ning Chang^*

Department of Applied Biology, College of Bioengineering, East China University of Science and Technology, Shanghai 200237, China

Molecules 2015, 20(5), 9155-9169; https://doi.org/10.3390/molecules20059155 - 19 May 2015

Cited by 46 | Viewed by 8945

Abstract

The anthocyanin extract from a domestic Perilla cultivar (Perilla frutescens var. acuta) were isolated and characterized with high mass accuracy and multi-dimensional fragmentation by means of ultra-performance liquid chromatography (UPLC) and electrospray ionization-ion trap-time of flight mass spectrometry analysis (ESI-IT-TOF-MSⁿ [...] Read more.

The anthocyanin extract from a domestic Perilla cultivar (Perilla frutescens var. acuta) were isolated and characterized with high mass accuracy and multi-dimensional fragmentation by means of ultra-performance liquid chromatography (UPLC) and electrospray ionization-ion trap-time of flight mass spectrometry analysis (ESI-IT-TOF-MSⁿ). The new developed and applied LC-MS method focused on in-depth screening of anthocyanin compounds with similar structures which also provided a new approach of anthocyanin characterization without the use of external standards. Selective detection of interested anthocyanins was achieved utilizing extracted ion chromatogram (EIC) analysis, while MSⁿ spectra were recorded to allow identification of the anthocyanin based on characteristic fragmentation patterns. Seven anthocyanins including one feruloyl (Cyanidin 3-O-feruloylglucoside-5-O-glucoside), two caffeoyl (Cyanidin 3-O-caffeoylglucoside-5-O-glucoside, Cyanidin 3-O-caffeoylglucoside-5-O-malonylglucoside) and four coumaroyl substituted anthocyanins (Cis-shisonin, Malonyl-cis-shisonin, Shisonin, and Malonyl-shisonin) were identified. Annexin-V FITC/PI flow cytometric assay was performed to analyze the influence of anthocyanin extract of P. frutescens var. acuta on cell apoptosis. The results suggested that Perilla anthocyanins can induce Hela cell apoptosis by a dose dependent manner. Full article

(This article belongs to the Special Issue New Technologies for the Recovery of Natural Products)

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13 pages, 1523 KiB

Open AccessArticle

Predicting the Composition of Red Wine Blends Using an Array of Multicomponent Peptide-Based Sensors

by Eman Ghanem¹, Helene Hopfer²

, Andrea Navarro^3,†, Maxwell S. Ritzer^3,†, Lina Mahmood^3,†, Morgan Fredell^3,†, Ashley Cubley^3,†, Jessica Bolen^3,†, Rabia Fattah^3,†, Katherine Teasdale³, Linh Lieu³, Tedmund Chua³, Federico Marini^4,*

, Hildegarde Heymann^2,* and Eric V. Anslyn^1,*

¹ Department of Chemistry, The University of Texas at Austin; 105 E 24th St. Mail Stop A5300, Austin, TX 78712-1224, USA

² Department of Viticulture and Enology, University of California; One Shields Ave., Davis, CA 95616-5270, USA

³ Freshman Research Initiative, The University of Texas at Austin, 1 University Station, Mail Stop G2550, Austin, TX 78712, USA

⁴ Department of Chemistry, University of Rome "La Sapienza", P.le Aldo Moro 5, Rome I-00185, Italy

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 9170-9182; https://doi.org/10.3390/molecules20059170 - 20 May 2015

Cited by 27 | Viewed by 12932

Abstract

Differential sensing using synthetic receptors as mimics of the mammalian senses of taste and smell is a powerful approach for the analysis of complex mixtures. Herein, we report on the effectiveness of a cross-reactive, supramolecular, peptide-based sensing array in differentiating and predicting the [...] Read more.

Differential sensing using synthetic receptors as mimics of the mammalian senses of taste and smell is a powerful approach for the analysis of complex mixtures. Herein, we report on the effectiveness of a cross-reactive, supramolecular, peptide-based sensing array in differentiating and predicting the composition of red wine blends. Fifteen blends of Cabernet Sauvignon, Merlot and Cabernet Franc, in addition to the mono varietals, were used in this investigation. Linear Discriminant Analysis (LDA) showed a clear differentiation of blends based on tannin concentration and composition where certain mono varietals like Cabernet Sauvignon seemed to contribute less to the overall characteristics of the blend. Partial Least Squares (PLS) Regression and cross validation were used to build a predictive model for the responses of the receptors to eleven binary blends and the three mono varietals. The optimized model was later used to predict the percentage of each mono varietal in an independent test set composted of four tri-blends with a 15% average error. A partial least square regression model using the mouth-feel and taste descriptive sensory attributes of the wine blends revealed a strong correlation of the receptors to perceived astringency, which is indicative of selective binding to polyphenols in wine. Full article

(This article belongs to the Collection Wine Chemistry)

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31 pages, 1120 KiB

Open AccessReview

Curcumin, Inflammation, and Chronic Diseases: How Are They Linked?

by Yan He^1,†, Yuan Yue^1,†, Xi Zheng^1,2, Kun Zhang¹, Shaohua Chen³ and Zhiyun Du^1,*

¹ Institute of Natural Medicine & Green Chemistry, School of Chemical Engineering and Light Industry, Guandong University of Technology, 232 Wai Huan West Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, China

² Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA

³ Department of Otorhinolaryngology, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510030, China

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 9183-9213; https://doi.org/10.3390/molecules20059183 - 20 May 2015

Cited by 465 | Viewed by 70603

Abstract

It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, [...] Read more.

It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases. Full article

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

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15 pages, 1715 KiB

Open AccessArticle

Aromatic Amino Acids-Guanidinium Complexes through Cation-π Interactions

by Cristina Trujillo¹, Ana A. Rodriguez-Sanz² and Isabel Rozas^1,*

¹ Trinity Biomedical Sciences Institute, School of Chemistry, Trinity College Dublin, 152-160 Pearse Street, Dublin 2, Ireland

² Departamento de Química Física, Facultade de Ciencias, Universidade de Santiago de Compostela, Campus de Lugo, Avda. Alfonso X El Sabio s/n, 27002 Lugo, Spain

Molecules 2015, 20(5), 9214-9228; https://doi.org/10.3390/molecules20059214 - 20 May 2015

Cited by 12 | Viewed by 9858

Abstract

Continuing with our interest in the guanidinium group and the different interactions than can establish, we have carried out a theoretical study of the complexes formed by this cation and the aromatic amino acids (phenylalanine, histidine, tryptophan and tyrosine) using DFT methods and [...] Read more.

Continuing with our interest in the guanidinium group and the different interactions than can establish, we have carried out a theoretical study of the complexes formed by this cation and the aromatic amino acids (phenylalanine, histidine, tryptophan and tyrosine) using DFT methods and PCM-water solvation. Both hydrogen bonds and cation-π interactions have been found upon complexation. These interactions have been characterized by means of the analysis of the molecular electron density using the Atoms-in-Molecules approach as well as the orbital interactions using the Natural Bond Orbital methodology. Finally, the effect that the cation-π and hydrogen bond interactions exert on the aromaticity of the corresponding amino acids has been evaluated by calculating the theoretical NICS values, finding that the aromatic character was not heavily modified upon complexation. Full article

(This article belongs to the Special Issue Noncovalent pi-Interactions)

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13 pages, 1030 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Hydrazone Derivatives as Antifungal Agents

by Bruna B. Casanova^1,*, Mauro N. Muniz¹, Thayse De Oliveira², Luís Flavio De Oliveira³, Michel M. Machado³, Alexandre M. Fuentefria², Grace Gosmann¹ and Simone C. B. Gnoatto^1,*

¹ Laboratório de Fitoquímica e Síntese Orgânica (LAFIS), Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90610-000, RS, Brazil

² Laboratório de Micologia Aplicada, Departamento de Analises, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90610-000, RS, Brazil

³ Departamento de Farmácia, Universidade Federal do Pampa, Km 592, Uruguaiana 97500-970, RS, Brazil

Molecules 2015, 20(5), 9229-9241; https://doi.org/10.3390/molecules20059229 - 20 May 2015

Cited by 27 | Viewed by 8250

Abstract

Emerging yeasts are among the most prevalent causes of systemic infections with high mortality rates and there is an urgent need to develop specific, effective and non-toxic antifungal agents to respond to this issue. In this study 35 aldehydes, hydrazones and hydrazines were [...] Read more.

Emerging yeasts are among the most prevalent causes of systemic infections with high mortality rates and there is an urgent need to develop specific, effective and non-toxic antifungal agents to respond to this issue. In this study 35 aldehydes, hydrazones and hydrazines were obtained and their antifungal activity was evaluated against Candida species (C. parapsilosis, C. tropicalis, C. krusei, C. albicans, C. glabrata and C. lusitaneae) and Trichosporon asahii, in an in vitro screening. The minimum inhibitory concentrations (MICs) of the active compounds in the screening was determined against 10 clinical isolates of C. parapsilosis and 10 of T. asahii. The compounds 4-pyridin-2-ylbenzaldehyde] (13a) and tert-butyl-(2Z)-2-(3,4,5-trihydroxybenzylidine)hydrazine carboxylate (7b) showed the most promising MIC values in the range of 16–32 μg/mL and 8–16 μg/mL, respectively. The compounds’ action on the stability of the cell membrane and cell wall was evaluated, which suggested the action of the compounds on the fungal cell membrane. Cell viability of leukocytes and an alkaline comet assay were performed to evaluate the cytotoxicity. Compound 13a was not cytotoxic at the active concentrations. These results support the discovery of promising candidates for the development of new antifungal agents. Full article

(This article belongs to the Section Medicinal Chemistry)

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21 pages, 1989 KiB

Open AccessArticle

Caffeic Acid Phenethyl Ester and Ethanol Extract of Propolis Induce the Complementary Cytotoxic Effect on Triple-Negative Breast Cancer Cell Lines

by Anna Rzepecka-Stojko¹, Agata Kabała-Dzik²

, Aleksandra Moździerz³, Robert Kubina²

, Robert D. Wojtyczka⁴

, Rafał Stojko⁵, Arkadiusz Dziedzic⁶

, Żaneta Jastrzębska-Stojko⁷, Magdalena Jurzak⁸, Ewa Buszman¹ and Jerzy Stojko^3,*

¹ Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland

² Department of Pathology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Ostrogórska 30, 41-200 Sosnowiec, Poland

³ Department of Hygiene, Bioanalysis and Environmental Studies, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Ostrogórska 30, 41-200 Sosnowiec, Poland

⁴ Department and Institute of Microbiology and Virology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland

⁵ Department of Women Health, School of Health Sciences, Medical University of Silesia in Katowice, Medyków 12, 40-752 Katowice, Poland

⁶ Department of Conservative Dentistry with Endodontics, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Pl. Akademicki 17, 41-902 Bytom, Poland

⁷ Department of Anesthesiology and Intensive Care, School of Medicine, Medical University of Silesia in Katowice, Medyków 14, 40-752 Katowice, Poland

⁸ Department of Cosmetology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Kasztanowa 3, 41-200 Sosnowiec, Poland

Molecules 2015, 20(5), 9242-9262; https://doi.org/10.3390/molecules20059242 - 20 May 2015

Cited by 63 | Viewed by 10722

Abstract

Chemotherapy of breast cancer could be improved by bioactive natural substances, which may potentially sensitize the carcinoma cells’ susceptibility to drugs. Numerous phytochemicals, including propolis, have been reported to interfere with the viability of carcinoma cells. We evaluated the in vitro cytotoxic activity [...] Read more.

Chemotherapy of breast cancer could be improved by bioactive natural substances, which may potentially sensitize the carcinoma cells’ susceptibility to drugs. Numerous phytochemicals, including propolis, have been reported to interfere with the viability of carcinoma cells. We evaluated the in vitro cytotoxic activity of ethanol extract of propolis (EEP) and its derivative caffeic acid phenethyl ester (CAPE) towards two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and Hs578T, by implementation of the MTT and lactate dehydrogenase (LDH) assays. The morphological changes of breast carcinoma cells were observed following exposure to EEP and CAPE. The IC₅₀ of EEP was 48.35 µg∙mL⁻¹ for MDA-MB-23 cells and 33.68 µg∙mL⁻¹ for Hs578T cells, whereas the CAPE IC₅₀ was 14.08 µM and 8.01 µM for the MDA-MB-231 and Hs578T cell line, respectively. Here, we report that propolis and CAPE inhibited the growth of the MDA-MB-231 and Hs578T lines in a dose-dependent and exposure time-dependent manner. EEP showed less cytotoxic activity against both types of TNBC cells. EEP and, particularly, CAPE may markedly affect the viability of breast cancer cells, suggesting the potential role of bioactive compounds in chemoprevention/chemotherapy by potentiating the action of standard anti-cancer drugs. Full article

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

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32 pages, 1497 KiB

Open AccessReview

Recent Advances in Click Chemistry Applied to Dendrimer Synthesis

by Mathieu Arseneault^†, Caroline Wafer^† and Jean-François Morin^*

¹ Chimie, Université Laval, 1045 avenue de la Médecine, Pavillon Alexandre-Vachon, QC G1V 0A6, Canada

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 9263-9294; https://doi.org/10.3390/molecules20059263 - 20 May 2015

Cited by 136 | Viewed by 20091

Abstract

Dendrimers are monodisperse polymers grown in a fractal manner from a central point. They are poised to become the cornerstone of nanoscale devices in several fields, ranging from biomedicine to light-harvesting. Technical difficulties in obtaining these molecules has slowed their transfer from academia [...] Read more.

Dendrimers are monodisperse polymers grown in a fractal manner from a central point. They are poised to become the cornerstone of nanoscale devices in several fields, ranging from biomedicine to light-harvesting. Technical difficulties in obtaining these molecules has slowed their transfer from academia to industry. In 2001, the arrival of the “click chemistry” concept gave the field a major boost. The flagship reaction, a modified Hüisgen cycloaddition, allowed researchers greater freedom in designing and building dendrimers. In the last five years, advances in click chemistry saw a wider use of other click reactions and a notable increase in the complexity of the reported structures. This review covers key developments in the click chemistry field applied to dendrimer synthesis from 2010 to 2015. Even though this is an expert review, basic notions and references have been included to help newcomers to the field. Full article

(This article belongs to the Collection Advances in Click Chemistry)

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14 pages, 2501 KiB

Open AccessArticle

Comparisons of the Pharmacokinetic Profile of Four Bioactive Components after Oral Administration of Gan-Sui-Ban-Xia Decoction Plus-Minus Gansui and Gancao Drug Combination in Normal Rats

by Yang Zhang¹, Dawei Qian^1,*, Ying Pan¹, Zhenghua Zhu¹, Jing Huang¹, Junzuan Xi¹, Jianming Guo¹, Xueping Zhou², Gansheng Zhong³ and Jinao Duan^1,*

¹ Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China

² The No.1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China

³ Basic Medical College, Beijing University of Chinese Medicine, Beijing 100092, China

Molecules 2015, 20(5), 9295-9308; https://doi.org/10.3390/molecules20059295 - 20 May 2015

Cited by 13 | Viewed by 6814

Abstract

Gan-Sui-Ban-Xia Decoction (GSBXD) was first presented by Zhang Zhongjing in the book Synopsis of Golden Chamber during the Han Dynasty period. The formula was then used for the treatment of persistent fluid retention with floating pulse in Traditional Chinese Medicine (TCM), which in [...] Read more.

Gan-Sui-Ban-Xia Decoction (GSBXD) was first presented by Zhang Zhongjing in the book Synopsis of Golden Chamber during the Han Dynasty period. The formula was then used for the treatment of persistent fluid retention with floating pulse in Traditional Chinese Medicine (TCM), which in modern medicine is known as malignant ascites. Here, a rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the determination of glycyrrhizinic acid, liquiritin, paeoniflorin, albiflorin after oral administration of GSBXD plus-minus Gansui and Gancao anti-drug combination to investigate the possible pharmacokinetic profile differences of different prescriptions with GSBXD in normal rats. The differences of pharmacokinetic parameters among groups were tested by the Student’s t-test with p < 0.05 as the level of significance. Significant differences were found between the Gansui and Gancao anti-drug combination and other herbs in GSBXD on pharmacokinetic profile of glycyrrhizinic acid, liquiritin, paeoniflorin and albiflorin. The obtained knowledge might contribute to the rationality of the clinic use of GSBXD and also reveal the compatibility conditions of the Gansui and Gancao anti-drug combination. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 807 KiB

Open AccessArticle

Synthesis, Structural Characterization and Biological Activity of Novel Cyclohexane-1,3-dione Ligands and Their Metal Complexes

by Nevin Turan^1,*, Hanifi Körkoca², Ragıp Adigüzel³, Naki Çolak⁴ and Kenan Buldurun¹

¹ Department of Chemistry, Faculty of Arts and Sciences, Muş Alparslan University, 49250 Muş, Turkey

² Nursing Department, School of Health, Muş Alparslan University, 49250 Muş, Turkey

³ Department of Chemical Engineering, Faculty of Engineering, Tunceli University, 62000 Tunceli, Turkey

⁴ Department of Chemistry, Faculty of Arts and Sciences, Hitit University, 19100 Çorum, Turkey

Molecules 2015, 20(5), 9309-9325; https://doi.org/10.3390/molecules20059309 - 21 May 2015

Cited by 17 | Viewed by 6635

Abstract

Some new Zn(II) and Cu(II) complexes [Cu(L¹)(OAc)₂]∙H₂O, [Cu(L¹)(NO₃)H₂O]∙NO₃∙3.5H₂O, [Zn(L¹)(NO₃)₂]∙4.5H₂O, [Zn(L¹)(OAc)₂(H₂O)₂]∙3H₂ [...] Read more.

Some new Zn(II) and Cu(II) complexes [Cu(L¹)(OAc)₂]∙H₂O, [Cu(L¹)(NO₃)H₂O]∙NO₃∙3.5H₂O, [Zn(L¹)(NO₃)₂]∙4.5H₂O, [Zn(L¹)(OAc)₂(H₂O)₂]∙3H₂O, [Cu₂(L²)(OAc)₄]∙2H₂O∙2DMF, [Cu(L²)₂]∙2NO₃∙1.5DMF∙H₂O, [Zn(L²)₂(NO₃)₂]∙DMF and [Zn₂(L²)(OAc)₄(H₂O)₄]∙5H₂O; L¹ = 2-[2-(2-methoxyphenyl)hydrazono]cyclohexane-1,3-dione and L² = 2-[2-(3-nitrophenyl)hydrazono]cyclohexane-1,3-dione were synthesized and characterized by IR, ¹H-NMR,¹³C-NMR and ultraviolet (UV-Vis.) spectroscopy, elemental analysis, magnetic susceptibility, mass spectrometry and thermogravimetry-differential thermal analysis (TGA-DTA). The synthesized ligands and their complexes were tested for antibacterial activity against Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 25923, and Salmonella typhimurium CCM 583. Some of complexes showed medium-level antibacterial activity against the test bacteria compared with ampicillin. Full article

(This article belongs to the Section Organic Chemistry)

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18 pages, 1261 KiB

Open AccessReview

Complex Interplay of Hormonal Signals during Grape Berry Ripening

by Ana Margarida Fortes^1,2,*, Rita Teresa Teixeira¹ and Patricia Agudelo-Romero¹

¹ BioISI, Faculdade de Ciências de Lisboa, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal

² Instituto de Tecnologia de Química Biológica (ITQB), Biotecnologia de Células Vegetais, Av. da República, 2781-157 Oeiras, Portugal

Molecules 2015, 20(5), 9326-9343; https://doi.org/10.3390/molecules20059326 - 21 May 2015

Cited by 125 | Viewed by 13705

Abstract

Grape and wine production and quality is extremely dependent on the fruit ripening process. Sensory and nutritional characteristics are important aspects for consumers and their development during fruit ripening involves complex hormonal control. In this review, we explored data already published on grape [...] Read more.

Grape and wine production and quality is extremely dependent on the fruit ripening process. Sensory and nutritional characteristics are important aspects for consumers and their development during fruit ripening involves complex hormonal control. In this review, we explored data already published on grape ripening and compared it with the hormonal regulation of ripening of other climacteric and non-climacteric fruits. The roles of abscisic acid, ethylene, and brassinosteroids as promoters of ripening are discussed, as well as the role of auxins, cytokinins, gibberellins, jasmonates, and polyamines as inhibitors of ripening. In particular, the recently described role of polyamine catabolism in grape ripening is discussed, together with its putative interaction with other hormones. Furthermore, other recent examples of cross-talk among the different hormones are presented, revealing a complex interplay of signals during grape development and ripening. Full article

(This article belongs to the Collection Wine Chemistry)

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14 pages, 2345 KiB

Open AccessArticle

Essential Oil from Berries of Lebanese Juniperus excelsa M. Bieb Displays Similar Antibacterial Activity to Chlorhexidine but Higher Cytocompatibility with Human Oral Primary Cells

by Barbara Azzimonti^1,2, Andrea Cochis^2,3

, Marc El Beyrouthy⁴, Marcello Iriti^5,*

, Francesca Uberti^2,6, Rita Sorrentino¹, Manuela Miriam Landini¹, Lia Rimondini^2,3

and Elena Maria Varoni^7,*

¹ Laboratory of Applied Microbiology, Department of Health Sciences, University of Piemonte Orientale, via Solaroli 17, Novara 28100, Italy

² Consorzio Interuniversitario per la Scienza e Tecnologia dei Materiali (INSTM), via Giusti 9, Florence 50121, Italy

³ Laboratory of Biomedical and Dental Materials, Department of Health Sciences, University of Piemonte Orientale, via Solaroli 17, Novara 28100, Italy

⁴ Department of Agricultural Sciences, Holy Spirit University of Kaslik, Kaslik B. P. 446, Jounieh, Lebanon

⁵ Department of Agricultural and Environmental Sciences, Milan State University, via Celoria, Milan 20133, Italy

⁶ Laboratory of Cellular Physiology, Department of Translational Medicine, University of Piemonte Orientale, via Solaroli 17, Novara 28100, Italy

⁷ Department of Biomedical, Surgical and Dental Sciences, Milan State University, via Beldiletto 1, Milan 20142, Italy

Molecules 2015, 20(5), 9344-9357; https://doi.org/10.3390/molecules20059344 - 21 May 2015

Cited by 57 | Viewed by 8932

Abstract

Chlorhexidine (CHX), one of the most effective drugs administered for periodontal treatment, presents collateral effects including toxicity when used for prolonged periods; here, we have evaluated the bactericidal potency and the cytocompatibility of Juniperus excelsa M. Bieb essential oil (EO) in comparison with [...] Read more.

Chlorhexidine (CHX), one of the most effective drugs administered for periodontal treatment, presents collateral effects including toxicity when used for prolonged periods; here, we have evaluated the bactericidal potency and the cytocompatibility of Juniperus excelsa M. Bieb essential oil (EO) in comparison with 0.05% CHX. The EO was extracted from berries by hydrodistillation and components identified by gas chromatography and mass spectrometry. Bacterial inhibition halo analysis, quantitative cell viability 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenyl amino) carbonyl]-2H-tetrazolium hydroxide assay (XTT), and colony forming unit (CFU) count were evaluated against the two biofilm formers Aggregatibacter actinomycetemcomitans and Streptococcus mutans. Finally, cytocompatibility was assessed with human primary gingival fibroblasts (HGF) and mucosal keratinocytes (HK). The resulting EO was mainly composed of monoterpene hydrocarbons and oxygenated monoterpenes. An inhibition halo test demonstrated that both bacteria were sensitive to the EO; XTT analysis and CFU counts confirmed that 10-fold-diluted EO determined a statistically significant (p < 0.05) reduction in bacteria count and viability towards both biofilm and planktonic forms in a comparable manner to those obtained with CHX. Moreover, EO displayed higher cytocompatibility than CHX (p < 0.05). In conclusion, EO exhibited bactericidal activity similar to CHX, but a superior cytocompatibility, making it a promising antiseptic alternative to CHX. Full article

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

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22 pages, 2577 KiB

Open AccessReview

Green Polymer Chemistry: Enzyme Catalysis for Polymer Functionalization

by Sanghamitra Sen and Judit E. Puskas^*

Department of Chemical and Biomolecular Engineering, The University of Akron, Akron, OH 44325, USA

Molecules 2015, 20(5), 9358-9379; https://doi.org/10.3390/molecules20059358 - 21 May 2015

Cited by 65 | Viewed by 12403

Abstract

Enzyme catalyzed reactions are green alternative approaches to functionalize polymers compared to conventional methods. This technique is especially advantageous due to the high selectivity, high efficiency, milder reaction conditions, and recyclability of enzymes. Selected reactions can be conducted under solventless conditions without the [...] Read more.

Enzyme catalyzed reactions are green alternative approaches to functionalize polymers compared to conventional methods. This technique is especially advantageous due to the high selectivity, high efficiency, milder reaction conditions, and recyclability of enzymes. Selected reactions can be conducted under solventless conditions without the application of metal catalysts. Hence this process is becoming more recognized in the arena of biomedical applications, as the toxicity created by solvents and metal catalyst residues can be completely avoided. In this review we will discuss fundamental aspects of chemical reactions biocatalyzed by Candida antarctica lipase B, and their application to create new functionalized polymers, including the regio- and chemoselectivity of the reactions. Full article

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

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13 pages, 716 KiB

Open AccessArticle

Chemical Composition and Antioxidant Activity of Essential Oil of Six Pinus Taxa Native to China

by Qing Xie, Zhihong Liu and Zhouqi Li^*

College of Forestry, Northwest A & F University, Yangling 712100, China

Molecules 2015, 20(5), 9380-9392; https://doi.org/10.3390/molecules20059380 - 21 May 2015

Cited by 47 | Viewed by 8297

Abstract

The essential oils obtained by steam distillation from needles of six China endemic Pinus taxa (P. tabulaeformis, P. tabulaeformis f. shekanensis, P. tabulaeformis var. mukdensis, P. tabulaeformis var. umbraculifera, P. henryi and P [...] Read more.

The essential oils obtained by steam distillation from needles of six China endemic Pinus taxa (P. tabulaeformis, P. tabulaeformis f. shekanensis, P. tabulaeformis var. mukdensis, P. tabulaeformis var. umbraculifera, P. henryi and P. massoniana) were analysed by GC/MS. A total of 72 components were separated and identified by GC/MS from the six taxa. The major constituents of the essential oils were: α-pinene (6.78%–20.55%), bornyl acetale (3.32%–12.71%), β-caryophellene (18.26%–26.31%), α-guaiene (1.23%–8.19%), and germacrene D (1.26%–9.93%). Moreover, the essential oils were evaluated for antioxidant potential by three assays (DPPH, FRAP and ABTS) and tested for their total phenolic content. The results showed that all essential oils exhibited acceptable antioxidant activities and these strongly suggest that these pine needles may serve as a potential source of natural antioxidants for food and medical purposes. Full article

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

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12 pages, 795 KiB

Open AccessCommunication

Synthesis and Biological Evaluation of Novel Water-Soluble Poly-(ethylene glycol)-10-hydroxycamptothecin Conjugates

by Na Guo, Du Jiang, Luyao Wang, Xing You, Yu-Ou Teng and Peng Yu^*

Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, No.29, 13th Avenue, TEDA, Tianjin 300457, China

Molecules 2015, 20(5), 9393-9404; https://doi.org/10.3390/molecules20059393 - 21 May 2015

Cited by 5 | Viewed by 9115

Abstract

In order to improve the antitumor activity and water solubility of 10-hydroxycamptothecin (HCPT), a series of novel HCPT conjugates were designed and synthesized by conjugating polyethylene glycol (PEG) to the 10-hydroxyl group of HCPT via a valine spacer. The in vitro stability of [...] Read more.

In order to improve the antitumor activity and water solubility of 10-hydroxycamptothecin (HCPT), a series of novel HCPT conjugates were designed and synthesized by conjugating polyethylene glycol (PEG) to the 10-hydroxyl group of HCPT via a valine spacer. The in vitro stability of these synthesized compounds was determined in pH 7.4 buffer at 37 °C, and the results showed that they released HCPT at different rates. All the compounds demonstrated significant antitumor activity in vitro against K562, HepG2 and HT-29 cells. Among them, compounds, 4a, 4d, 4e and 4f, exhibited 2–5 times higher potency than HCPT. The stability and antitumor activity of these conjugates were found to be closely related to the length of PEG and the linker type, conjugates with a relatively short PEG chain and carbamate linkages (compounds 4a and 4f) exhibited controlled release of HCPT and excellent antitumor in vitro activity. 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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14 pages, 2199 KiB

Open AccessArticle

Cellular Structural Changes in Candida albicans Caused by the Hydroalcoholic Extract from Sapindus saponaria L.

by Cristiane S. Shinobu-Mesquita¹, Patricia S. Bonfim-Mendonça¹, Amanda L. Moreira², Izabel C. P. Ferreira², Lucelia Donatti³, Adriana Fiorini⁴ and Terezinha I. E. Svidzinski^1,*

¹ Departamento Análises Clínicas e Biomedicina, Universidade Estadual de Maringá, Av. Colombo 5790, bloco T20, Maringá 87020-900, Brazil

² Departamento de Farmácia, Universidade Estadual de Maringá, Av. Colombo 5790, bloco K80, Maringá 87020-900, Brazil

³ Departamento de Biologia Celular, Universidade Federal do Paraná, Curitiba 85131-990, Brazil

⁴ Campus Palotina, Universidade Federal do Paraná, Palotina 85950-000, Brazil

Molecules 2015, 20(5), 9405-9418; https://doi.org/10.3390/molecules20059405 - 22 May 2015

Cited by 19 | Viewed by 8730

Abstract

Vulvovaginal candidiasis (VVC) is a disease caused by the abnormal growth of yeast-like fungi in the mucosa of the female genital tract. Candida albicans is the principal etiological agent involved in VVC, but reports have shown an increase in the prevalence of Candida [...] Read more.

Vulvovaginal candidiasis (VVC) is a disease caused by the abnormal growth of yeast-like fungi in the mucosa of the female genital tract. Candida albicans is the principal etiological agent involved in VVC, but reports have shown an increase in the prevalence of Candida non-C. albicans (CNCA) cases, which complicates VVC treatment because CNCA does not respond well to antifungal therapy. Our group has reported the in vitro antifungal activity of extracts from Sapindus saponaria L. The present study used scanning electron microscopy and transmission electron microscopy to further evaluate the antifungal activity of hydroalcoholic extract from S. saponaria (HE) against yeast obtained from VVC and structural changes induced by HE. We observed the antifungal activity of HE against 125 vaginal yeasts that belonged to four different species of the Candida genus and S. cerevisae. The results suggest that saponins that are present in HE act on the cell wall or membrane of yeast at the first moments after contact, causing damage to these structures and cell lysis. Full article

(This article belongs to the Section Natural Products Chemistry)

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36 pages, 1539 KiB

Open AccessReview

Palladium-Catalyzed Modification of Unprotected Nucleosides, Nucleotides, and Oligonucleotides

by Kevin H. Shaughnessy

Department of Chemistry, The University of Alabama, Box 870336, Tuscaloosa, AL 35487-0336, USA

Molecules 2015, 20(5), 9419-9454; https://doi.org/10.3390/molecules20059419 - 22 May 2015

Cited by 80 | Viewed by 11710

Abstract

Synthetic modification of nucleoside structures provides access to molecules of interest as pharmaceuticals, biochemical probes, and models to study diseases. Covalent modification of the purine and pyrimidine bases is an important strategy for the synthesis of these adducts. Palladium-catalyzed cross-coupling is a powerful [...] Read more.

Synthetic modification of nucleoside structures provides access to molecules of interest as pharmaceuticals, biochemical probes, and models to study diseases. Covalent modification of the purine and pyrimidine bases is an important strategy for the synthesis of these adducts. Palladium-catalyzed cross-coupling is a powerful method to attach groups to the base heterocycles through the formation of new carbon-carbon and carbon-heteroatom bonds. In this review, approaches to palladium-catalyzed modification of unprotected nucleosides, nucleotides, and oligonucleotides are reviewed. Polar reaction media, such as water or polar aprotic solvents, allow reactions to be performed directly on the hydrophilic nucleosides and nucleotides without the need to use protecting groups. Homogeneous aqueous-phase coupling reactions catalyzed by palladium complexes of water-soluble ligands provide a general approach to the synthesis of modified nucleosides, nucleotides, and oligonucleotides. Full article

(This article belongs to the Special Issue Nucleoside Modifications)

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13 pages, 1008 KiB

Open AccessArticle

Relationship between High-Performance Liquid Chromatography Fingerprints and Uric Acid-Lowering Activities of Cichorium intybus L.

by Chun-Sheng Zhu, Bing Zhang^*, Zhi-Jian Lin^*, Xue-Jie Wang, Yue Zhou, Xiao-Xia Sun and Ming-Liang Xiao

School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China

Molecules 2015, 20(5), 9455-9467; https://doi.org/10.3390/molecules20059455 - 22 May 2015

Cited by 30 | Viewed by 7163

Abstract

This study aimed to explore the spectrum-effect relationships between high-performance liquid chromatography fingerprints and the uric acid-lowering activities of chicory. Chemical fingerprints of chicory samples from ten different sources were determined by high-performance liquid chromatography, and then investigated by similarity analysis and hierarchical [...] Read more.

This study aimed to explore the spectrum-effect relationships between high-performance liquid chromatography fingerprints and the uric acid-lowering activities of chicory. Chemical fingerprints of chicory samples from ten different sources were determined by high-performance liquid chromatography, and then investigated by similarity analysis and hierarchical clustering analysis. Pharmacodynamics experiments were conducted in animals to obtain the uric acid-lowering activity information of each chicory sample. The spectrum-effect relationships between chemical fingerprints and the uric acid-lowering activities of chicory were established by canonical correlation analysis. The structures of potential effective peaks were identified by liquid chromatography with tandem mass spectrometry. The results showed that a close correlation existed between the spectrum and effect of chicory. Aesculin, chlorogenic acid, chicoric acid, isochlorogenic acid A/B/C and 13,14-seco-stigma5(6),14(15)-diene-3α-ol might be the main effective constituents. This work provides a general model of the combination of high-performance liquid chromatography and uric acid-lowering activities to study the spectrum-effect relationships of chicory, which can be used to discover the principle components responsible for the bioactivity. Full article

(This article belongs to the Section Natural Products Chemistry)

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