Molecules

16 pages, 1017 KiB

Open AccessArticle

The Unusual Acid-Accumulating Behavior during Ripening of Cherimoya (Annona cherimola Mill.) is Linked to Changes in Transcription and Enzyme Activity Related to Citric and Malic Acid Metabolism

by Mauricio González-Agüero^1,*

, Luis Tejerina Pardo², María Sofía Zamudio¹, Carolina Contreras¹, Pedro Undurraga³

and Bruno G. Defilippi¹

¹ Instituto de Investigaciones Agropecuarias, INIA La Platina, Santa Rosa 11610, Santiago 8831314, Chile

² Facultad Ciencias Biológicas, Escuela de Ingeniería en Biotecnología, Universidad Andrés Bello, República 217, Santiago 8370146, Chile

³ Facultad de Agronomía, Pontificia Universidad Católica de Valparaíso, Calle San Francisco s/n, Casilla 4-D, Quillota 2260000, Chile

Molecules 2016, 21(5), 398; https://doi.org/10.3390/molecules21050398 - 25 Apr 2016

Cited by 17 | Viewed by 6075

Abstract

Cherimoya (Annona cherimola Mill.) is a subtropical fruit characterized by a significant increase in organic acid levels during ripening, making it an interesting model for studying the relationship between acidity and fruit flavor. In this work, we focused on understanding the balance [...] Read more.

Cherimoya (Annona cherimola Mill.) is a subtropical fruit characterized by a significant increase in organic acid levels during ripening, making it an interesting model for studying the relationship between acidity and fruit flavor. In this work, we focused on understanding the balance between the concentration of organic acids and the gene expression and activity of enzymes involved in the synthesis and degradation of these metabolites during the development and ripening of cherimoya cv. “Concha Lisa”. Our results showed an early accumulation of citric acid and other changes associated with the accumulation of transcripts encoding citrate catabolism enzymes. During ripening, a 2-fold increase in malic acid and a 6-fold increase in citric acid were detected. By comparing the contents of these compounds with gene expression and enzymatic activity levels, we determined that cytoplasmic NAD-dependent malate dehydrogenase (cyNAD-MDH) and mitochondrial citrate synthase (mCS) play important regulatory roles in the malic and citric acid biosynthetic pathways. Full article

(This article belongs to the Section Medicinal Chemistry)

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9 pages, 3774 KiB

Open AccessArticle

Development of an in Vitro System to Simulate the Adsorption of Self-Emulsifying Tea (Camellia oleifera) Seed Oil

by Issara Sramala^*, Wichchunee Pinket, Pawinee Pongwan, Suwatchai Jarussophon and Kittiwut Kasemwong

Nano Agro and Food Innovation Laboratory, National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), 111 Thailand Science Park, Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathumthani 12120, Thailand

Molecules 2016, 21(5), 479; https://doi.org/10.3390/molecules21050479 - 29 Apr 2016

Cited by 11 | Viewed by 6491

Abstract

In this study, tea (Camellia oleifera) seed oil was formulated into self-emulsifying oil formulations (SEOF) to enhance the aqueous dispersibility and intestinal retention to achieve higher bioavailability. Self-emulsifying tea seed oils were developed by using different concentrations of lecithin in combination [...] Read more.

In this study, tea (Camellia oleifera) seed oil was formulated into self-emulsifying oil formulations (SEOF) to enhance the aqueous dispersibility and intestinal retention to achieve higher bioavailability. Self-emulsifying tea seed oils were developed by using different concentrations of lecithin in combination with surfactant blends (Span^®80 and Tween^®80). The lecithin/surfactant systems were able to provide clear and stable liquid formulations. The SEOF were investigated for physicochemical properties including appearance, emulsion droplets size, PDI and zeta potential. The chemical compositions of tea seed oil and SEOF were compared using GC-MS techniques. In addition, the oil adsorption measurement on artificial membranes was performed using a Franz cell apparatus and colorimetric analysis. The microscopic structure of membranes was observed with scanning electron microscopy (SEM). After aqueous dilution with fed-state simulated gastric fluid (FeSSGF), the droplet size of all SEOF was close to 200 nm with low PDI values and the zeta potential was negative. GC-MS chromatograms revealed that the chemical compositions of SEOF were not significantly different from that of the original tea seed oil. The morphological study showed that only the SEOF could form film layers. The oil droplets were extracted both from membrane treated with tea seed oil and the SEOF in order to evaluate the chemical compositions by GC-MS. Full article

(This article belongs to the Special Issue Selected Papers from the 6th International Conference on Natural Products for Health and Beauty (NATPRO 6))

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13 pages, 1404 KiB

Open AccessArticle

Ultrasound- and Molecular Sieves-Assisted Synthesis, Molecular Docking and Antifungal Evaluation of 5-(4-(Benzyloxy)-substituted phenyl)-3-((phenylamino)methyl)-1,3,4-oxadiazole-2(3H)-thiones

by Urja D. Nimbalkar¹, Santosh G. Tupe², Julio A. Seijas Vazquez³

, Firoz A. Kalam Khan⁴, Jaiprakash N. Sangshetti⁴ and Anna Pratima G. Nikalje^4,*

¹ Maulana Azad P. G. and Research Centre, Dr. Rafiq Zakaria Campus, Rauza Baug, Aurangabad 431001, India

² Biochemical Sciences Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pashan, Pune 411008, India

³ Departamento de Química Orgánica, Facultad de Ciencias, Universidad of Santiago De Compostela, Alfonso X el Sabio, Lugo 27002, Spain

⁴ Y. B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Rauza Baug, Aurangabad 431001, India

Molecules 2016, 21(5), 484; https://doi.org/10.3390/molecules21050484 - 10 May 2016

Cited by 29 | Viewed by 6177

Abstract

A novel series of 5-(4-(benzyloxy)substituted phenyl)-3-((phenyl amino)methyl)-1,3,4-oxadiazole-2(3H)-thione Mannich bases 6a–o were synthesized in good yield from the key compound 5-(4-(benzyloxy)phenyl)-1,3,4-oxadiazole-2(3H)-thione by aminomethylation with paraformaldehyde and substituted amines using molecular sieves and sonication as green chemistry tools. The antifungal activity [...] Read more.

A novel series of 5-(4-(benzyloxy)substituted phenyl)-3-((phenyl amino)methyl)-1,3,4-oxadiazole-2(3H)-thione Mannich bases 6a–o were synthesized in good yield from the key compound 5-(4-(benzyloxy)phenyl)-1,3,4-oxadiazole-2(3H)-thione by aminomethylation with paraformaldehyde and substituted amines using molecular sieves and sonication as green chemistry tools. The antifungal activity of the new products was evaluated against seven human pathogenic fungal strains, namely, Candida albicans ATCC 24433, Candida albicans ATCC 10231, Candida glabrata NCYC 388, Cryptococcus neoformans ATCC 34664, Cryptococcus neoformans PRL 518, Aspergillus fumigatus NCIM 902 and Aspergillus niger ATCC 10578. The synthesized compounds 6d, 6f, 6g, 6h and 6j exhibited promising antifungal activity against the tested fungal pathogens. In molecular docking studies, derivatives 6c, 6f and 6i showed good binding at the active site of C. albicans cytochrome P450 enzyme lanosterol 14 α-demethylase. The in vitro antifungal activity results and docking studies indicated that the synthesized compounds have potential antifungal activity and can be further optimized as privileged scaffolds to design and develop potent antifungal drugs. Full article

(This article belongs to the Special Issue ECSOC-19)

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11 pages, 3015 KiB

Open AccessArticle

Forsythoside A Controls Influenza A Virus Infection and Improves the Prognosis by Inhibiting Virus Replication in Mice

by Li Deng^*,†, Peng Pang^†, Ke Zheng, Jiao Nie, Huachong Xu, Sizhi Wu, Jia Chen and Xiaoyin Chen^*

¹ Department of Traditional Chinese Medicine, School of Medicine, Jinan University, Guangzhou 510632, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 524; https://doi.org/10.3390/molecules21050524 - 26 Apr 2016

Cited by 45 | Viewed by 7616

Abstract

Objective: The objective of this study was to observe the effects of forsythoside A on controlling influenza A virus (IAV) infection and improving the prognosis of IAV infection. Methods: Forty-eight SPF C57BL/6j mice were randomly divided into the following four groups: [...] Read more.

Objective: The objective of this study was to observe the effects of forsythoside A on controlling influenza A virus (IAV) infection and improving the prognosis of IAV infection. Methods: Forty-eight SPF C57BL/6j mice were randomly divided into the following four groups: Group A: normal control group (normal con); Group B: IAV control group (V con); Group C: IAV+ oseltamivir treatment group (V oseltamivir; 0.78 mg/mL, 0.2 mL/mouse/day); Group D: IAV+ forsythoside A treatment group (V FTA; 2 μg/mL, 0.2 mL/mouse/day). Real-time fluorescence quantitative PCR (RT-qPCR) was used to measure mRNA expression of the TLR7, MyD88, TRAF6, IRAK4 and NF-κB p65 mRNA in TLR7 signaling pathway and the virus replication level in lung. Western blot was used to measure TLR7, MyD88 and NF-κB p65 protein. Flow cytometry was used to detect the proportion of the T cell subsets Th1/Th2 and Th17/Treg. Results: The body weight began to decrease after IAV infection, while FTA and oseltamivir could reduce the rate of body weight loss. The pathological damages in the FTA and oseltamivir group were less serious. TLR7, MyD88, TRAF6, IRAK4 and NF-κB p65 mRNA were up-regulated after virus infection (p < 0.01) while down-regulated after oseltamivir and FTA treatment (p < 0.01). The results of TLR7, MyD88 and NF-κB p65 protein consisted with correlative mRNA. Flow cytometry showed the Th1/Th2 differentiated towards Th2, and the Th17/Treg cells differentiated towards Treg after FTA treatment. Conclusions: Our study suggests forsythoside A can control influenza A virus infection and improve the prognosis of IAV infection by inhibiting influenza A virus replication. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

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11 pages, 554 KiB

Open AccessArticle

Chemical Constituents of Malaysian U. cordata var. ferruginea and Their in Vitro α-Glucosidase Inhibitory Activities

by Nur Hakimah Abdullah¹, Fatimah Salim^2,3 and Rohaya Ahmad^1,3,*

¹ Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor Darul Ehsan, Malaysia

² Center of Foundation Studies, Universiti Teknologi MARA, Dengkil Campus, 43800 Dengkil, Selangor Darul Ehsan, Malaysia

³ Atta-ur-Rahman Institute for Natural Products Discovery, Universiti Teknologi MARA, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia

Molecules 2016, 21(5), 525; https://doi.org/10.3390/molecules21050525 - 27 Apr 2016

Cited by 40 | Viewed by 9186

Abstract

Continuing our interest in the Uncaria genus, the phytochemistry and the in-vitro α-glucosidase inhibitory activities of Malaysian Uncaria cordata var. ferruginea were investigated. The phytochemical study of this plant, which employed various chromatographic techniques including recycling preparative HPLC, led to the [...] Read more.

Continuing our interest in the Uncaria genus, the phytochemistry and the in-vitro α-glucosidase inhibitory activities of Malaysian Uncaria cordata var. ferruginea were investigated. The phytochemical study of this plant, which employed various chromatographic techniques including recycling preparative HPLC, led to the isolation of ten compounds with diverse structures comprising three phenolic acids, two coumarins, three flavonoids, a terpene and an iridoid glycoside. These constituents were identified as 2-hydroxybenzoic acid or salicylic acid (1), 2,4-dihydroxybenzoic acid (2), 3,4-dihydroxybenzoic acid (3), scopoletin or 7-hydroxy-6-methoxy-coumarin (4), 3,4-dihydroxy-7-methoxycoumarin (5), quercetin (6), kaempferol (7), taxifolin (8), loganin (9) and β-sitosterol (10). Structure elucidation of the compounds was accomplished with the aid of 1D and 2D Nuclear Magnetic Resonance (NMR) spectral data and Ultraviolet-Visible (UV-Vis), Fourier Transform Infrared (FTIR) spectroscopy and mass spectrometry (MS). In the α-glucosidase inhibitory assay, the crude methanolic extract of the stems of the plant and its acetone fraction exhibited strong α-glucosidase inhibition activity of 87.7% and 89.2%, respectively, while its DCM fraction exhibited only moderate inhibition (75.3%) at a concentration of 1 mg/mL. The IC₅₀ values of both fractions were found to be significantly lower than the standard acarbose suggesting the presence of potential α-glucosidase inhibitors. Selected compounds isolated from the active fractions were then subjected to α-glucosidase assay in which 2,4-dihydroxybenzoic acid and quercetin showed strong inhibitory effects against the enzyme with IC₅₀ values of 549 and 556 μg/mL compared to acarbose (IC₅₀ 580 μg/mL) while loganin and scopoletin only showed weak α-glucosidase inhibition of 44.9% and 34.5%, respectively. This is the first report of the isolation of 2-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid and loganin from the genus and the first report of the α-glucosidase inhibitory potential of 2,4-dihydroxybenzoic acid. Full article

(This article belongs to the Special Issue Selected Papers from the 6th International Conference on Natural Products for Health and Beauty (NATPRO 6))

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40 pages, 1600 KiB

Open AccessReview

Nerolidol: A Sesquiterpene Alcohol with Multi-Faceted Pharmacological and Biological Activities

by Weng-Keong Chan^1,2, Loh Teng-Hern Tan^1,2, Kok-Gan Chan³

, Learn-Han Lee^1,2,4,* and Bey-Hing Goh^1,2,4,*

¹ School of Pharmacy, Monash University Malaysia, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia

² Biomedical Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia

³ Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia

⁴ Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, 56000 Phayao, Thailand

Molecules 2016, 21(5), 529; https://doi.org/10.3390/molecules21050529 - 28 Apr 2016

Cited by 349 | Viewed by 34098

Abstract

Nerolidol (3,7,11-trimethyl-1,6,10-dodecatrien-3-ol) is a naturally occurring sesquiterpene alcohol that is present in various plants with a floral odor. It is synthesized as an intermediate in the production of (3E)-4,8-dimethy-1,3,7-nonatriene (DMNT), a herbivore-induced volatile that protects plants from herbivore damage. Chemically, nerolidol [...] Read more.

Nerolidol (3,7,11-trimethyl-1,6,10-dodecatrien-3-ol) is a naturally occurring sesquiterpene alcohol that is present in various plants with a floral odor. It is synthesized as an intermediate in the production of (3E)-4,8-dimethy-1,3,7-nonatriene (DMNT), a herbivore-induced volatile that protects plants from herbivore damage. Chemically, nerolidol exists in two geometric isomers, a trans and a cis form. The usage of nerolidol is widespread across different industries. It has been widely used in cosmetics (e.g., shampoos and perfumes) and in non-cosmetic products (e.g., detergents and cleansers). In fact, U.S. Food and Drug Administration (FDA) has also permitted the use of nerolidol as a food flavoring agent. The fact that nerolidol is a common ingredient in many products has attracted researchers to explore more medicinal properties of nerolidol that may exert beneficial effect on human health. Therefore, the aim of this review is to compile and consolidate the data on the various pharmacological and biological activities displayed by nerolidol. Furthermore, this review also includes pharmacokinetic and toxicological studies of nerolidol. In summary, the various pharmacological and biological activities demonstrated in this review highlight the prospects of nerolidol as a promising chemical or drug candidate in the field of agriculture and medicine. Full article

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

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15 pages, 5375 KiB

Open AccessArticle

Novel N-Substituted 2-(2-(Adamantan-1-yl)-1H-Indol-3-yl)-2-Oxoacetamide Derivatives: Synthesis and Biological Evaluation

by Hong-Yu Hu^†, Xu-Dong Yu^†, Fei Wang, Chun-Rong Lin, Jin-Zhang Zeng, Ying-Kun Qiu

, Mei-Juan Fang^* and Zhen Wu^*

¹ School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, South Xiang-An Road, Xiamen 361102, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 530; https://doi.org/10.3390/molecules21050530 - 5 May 2016

Cited by 5 | Viewed by 6569

Abstract

In this study, a series of novel N-substituted 2-(2-(adamantan-1-yl)-1H-indol-3-yl)-2-oxoacetamide derivatives were synthesized, and evaluated for their cytotoxicity in human cell lines including Hela (cervical cancer), MCF7 (breast cancer ) and HepG2 (liver cancer). Several compounds were found to have potent [...] Read more.

In this study, a series of novel N-substituted 2-(2-(adamantan-1-yl)-1H-indol-3-yl)-2-oxoacetamide derivatives were synthesized, and evaluated for their cytotoxicity in human cell lines including Hela (cervical cancer), MCF7 (breast cancer ) and HepG2 (liver cancer). Several compounds were found to have potent anti-proliferative activity against those human cancer cell lines and compound 5r showed the most potent biological activity against HepG2 cells with an IC₅₀ value of 10.56 ± 1.14 μΜ. In addition, bioassays showed that compound 5r induced time-dependent and dose-dependent cleavage of poly ADP-ribose polymerase (PARP), and also induced a dose-dependent increase in caspase-3 and caspase-8 activity, but had little effect on caspase-9 protease activity in HepG2 cells. These results provide evidence that 5r-induced apoptosis in HepG2 cell is caspase-8-dependent. 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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7 pages, 200 KiB

Open AccessArticle

Characterization of Novel Microsatellite Loci for Primula poissonii (Primulaceae) Using High-Throughput Sequencing Technology

by Yun-Jiao Liu^1,2

, Cai-Yun Zhang², Gang Hao², Xue-Jun Ge¹ and Hai-Fei Yan^1,*

¹ Key Laboratory of Plant Resources Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China

² College of Life Sciences, South China Agricultural University, Guangzhou 510642, China

Molecules 2016, 21(5), 536; https://doi.org/10.3390/molecules21050536 - 9 May 2016

Cited by 1 | Viewed by 4132

Abstract

Primula poissonii (Primulaceae) is a perennial herb, widely distributed in the Hengduan Mountain region of Southwest China. In this study, Roche 454 pyrosequencing was used to isolate microsatellite markers. A total of 4528 unique sequences were identified from 68,070 unique reads. Of these, [...] Read more.

Primula poissonii (Primulaceae) is a perennial herb, widely distributed in the Hengduan Mountain region of Southwest China. In this study, Roche 454 pyrosequencing was used to isolate microsatellite markers. A total of 4528 unique sequences were identified from 68,070 unique reads. Of these, eighty-seven microsatellite loci were screened for utility using two criteria: successful PCR amplification and variation of these loci within three wild P. poissonii populations. Twenty loci were successfully amplified and exhibited polymorphic alleles. The number of observed alleles ranged from 1 to 9 with an average of 3.5. The observed and expected heterozygosities ranged from 0.087 to 1.000 and from 0.124 to 0.828, respectively. Among these SSR loci, only the P69 locus could not be cross-amplified successfully in two closely related species P. wilsonii and P. anisodora. The microsatellite loci developed in this study will be useful for studying genetic diversity and speciation events between P. poissonii and closely related Primula species. Full article

14 pages, 1797 KiB

Open AccessReview

Biodegradable Polymers and Stem Cells for Bioprinting

by Meijuan Lei¹ and Xiaohong Wang^1,2,*

¹ Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China

² Center of 3D printing & Organ Manufacturing, Department of Tissue Engineering, China Medical University (CMU), Shenyang 110122, China

Molecules 2016, 21(5), 539; https://doi.org/10.3390/molecules21050539 - 29 Apr 2016

Cited by 73 | Viewed by 10479

Abstract

It is imperative to develop organ manufacturing technologies based on the high organ failure mortality and serious donor shortage problems. As an emerging and promising technology, bioprinting has attracted more and more attention with its super precision, easy reproduction, fast manipulation and advantages [...] Read more.

It is imperative to develop organ manufacturing technologies based on the high organ failure mortality and serious donor shortage problems. As an emerging and promising technology, bioprinting has attracted more and more attention with its super precision, easy reproduction, fast manipulation and advantages in many hot research areas, such as tissue engineering, organ manufacturing, and drug screening. Basically, bioprinting technology consists of inkjet bioprinting, laser-based bioprinting and extrusion-based bioprinting techniques. Biodegradable polymers and stem cells are common printing inks. In the printed constructs, biodegradable polymers are usually used as support scaffolds, while stem cells can be engaged to differentiate into different cell/tissue types. The integration of biodegradable polymers and stem cells with the bioprinting techniques has provided huge opportunities for modern science and technologies, including tissue repair, organ transplantation and energy metabolism. Full article

(This article belongs to the Special Issue Biomaterials and Bioprinting)

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13 pages, 4862 KiB

Open AccessArticle

Selective Extraction of Gardenia Yellow and Geniposide from Gardenia jasminoides by Mechanochemistry

by Wenhao Xu^1,2

, Jingbo Yu¹

, Wen Feng¹ and Weike Su^1,*

¹ National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China

² Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China

Molecules 2016, 21(5), 540; https://doi.org/10.3390/molecules21050540 - 28 Apr 2016

Cited by 25 | Viewed by 8927

Abstract

A novel method for the selective extraction of gardenia yellow and geniposide from Gardenia Jasminoides, based on a mechanochemical method is described. Without the need of complex separation techniques, gardenia yellow compliant with the national standard could be extracted in a simple [...] Read more.

A novel method for the selective extraction of gardenia yellow and geniposide from Gardenia Jasminoides, based on a mechanochemical method is described. Without the need of complex separation techniques, gardenia yellow compliant with the national standard could be extracted in a simple fashion. The optimal ball-milling conditions determined were as follows: 30% g/g. active carbon milling at 200 rpm in a planetary mill for 5 min. The extraction conditions of the milled mixtures were as follows: the milled mixtures were extracted with water (liquid-solid ratio 10:1) at 20 °C for 5 min with yields 85% of total geniposide, followed by extraction with 80% ethanol solution (liquid-solid ratio 5:1) and 1% g/g. Tween 20 at 75 °C for 5 min to yield 1.45% ± 0.108% g/g of gardenia yellow. The mechanism of this selective extraction was demonstrated to follow a microstructure change of activated carbon, which occurred during milling and lead to alteration of the corresponding desorption capacities. Compared with traditional extraction methods, this novel extraction technique greatly simplifies the separation process, and proves to be advantageous in terms of low organic solvent consumption, easy operation, rapid process and high efficiency. Full article

(This article belongs to the Special Issue Mechanochemistry)

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16 pages, 1801 KiB

Open AccessArticle

Ptaquiloside in Irish Bracken Ferns and Receiving Waters, with Implications for Land Managers

by Connie O’Driscoll^1,2,*, Carmel Ramwell³, Brendan Harhen⁴, Liam Morrison⁵, Frederik Clauson-Kaas⁶, Hans Christian B. Hansen⁶, Graeme Campbell⁷, Jerome Sheahan⁸, Bruce Misstear¹ and Liwen Xiao^1,*

¹ Department of Civil, Structural and Environmental Engineering, Trinity College Dublin, Dublin 2, Ireland

² Department of Civil Engineering, National University of Ireland, Galway H91 HX31, Ireland

³ Centre for Chemical Safety and Stewardship, Fera Science Ltd., Sand Hutton, York YO41 1LZ, UK

⁴ National Centre for Biomedical Engineering Science, National University of Ireland, Galway H91 HX31, Ireland

⁵ Earth and Ocean Sciences, School of Natural Sciences and Ryan Institute, National University of Ireland, Galway H91 HX31, Ireland

⁶ Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg DK-1871, Denmark

⁷ College of Agriculture Food and Rural Enterprise Greenmount Campus, 45 Tirgracy Road, Muckamore, Antrim BT41 4PS, UK

⁸ School of Mathematics, Statistics and Applied Mathematics, National University of Ireland, Galway H91 HX31, Ireland

Molecules 2016, 21(5), 543; https://doi.org/10.3390/molecules21050543 - 26 Apr 2016

Cited by 29 | Viewed by 8530

Abstract

Ptaquiloside, along with other natural phytotoxins, is receiving increased attention from scientists and land use managers. There is an urgent need to increase empirical evidence to understand the scale of phytotoxin mobilisation and potential to enter into the environment. In this study the [...] Read more.

Ptaquiloside, along with other natural phytotoxins, is receiving increased attention from scientists and land use managers. There is an urgent need to increase empirical evidence to understand the scale of phytotoxin mobilisation and potential to enter into the environment. In this study the risk of ptaquiloside to drinking water was assessed by quantifying ptaquiloside in the receiving waters at three drinking water abstraction sites across Ireland and in bracken fronds surrounding the abstraction sites. We also investigated the impact of different management regimes (spraying, cutting and rolling) on ptaquiloside concentrations at plot-scale in six locations in Northern Ireland, UK. Ptaquiloside concentrations were determined using recent advances in the use of LC-MS for the detection and quantification of ptaquiloside. The results indicate that ptaquiloside is present in bracken stands surrounding drinking water abstractions in Ireland, and ptaquiloside concentrations were also observed in the receiving waters. Furthermore, spraying was found to be the most effective bracken management regime observed in terms of reducing ptaquiloside load. Increased awareness is vital on the implications of managing land with extensive bracken stands. Full article

(This article belongs to the Special Issue Natural Toxins)

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9 pages, 2794 KiB

Open AccessArticle

Hydrophilic Modification of Multi-Walled Carbon Nanotube for Building Photonic Crystals with Enhanced Color Visibility and Mechanical Strength

by Feihu Li, Bingtao Tang^*, Jinghai Xiu and Shufen Zhang

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

Molecules 2016, 21(5), 547; https://doi.org/10.3390/molecules21050547 - 28 Apr 2016

Cited by 23 | Viewed by 6400

Abstract

Low color visibility and poor mechanical strength of polystyrene (PS) photonic crystal films have been the main shortcomings for the potential applications in paints or displays. This paper presents a simple method to fabricate PS/MWCNTs (multi-walled carbon nanotubes) composite photonic crystal films with [...] Read more.

Low color visibility and poor mechanical strength of polystyrene (PS) photonic crystal films have been the main shortcomings for the potential applications in paints or displays. This paper presents a simple method to fabricate PS/MWCNTs (multi-walled carbon nanotubes) composite photonic crystal films with enhanced color visibility and mechanical strength. First, MWCNTs was modified through radical addition reaction by aniline 2,5-double sulfonic acid diazonium salt to generate hydrophilic surface and good water dispersity. Then the MWCNTs dispersion was blended with PS emulsion to form homogeneous PS/MWCNTs emulsion mixtures and fabricate composite films through thermal-assisted method. The obtained films exhibit high color visibility under natural light and improved mechanical strength owing to the light-adsorption property and crosslinking effect of MWCNTs. The utilization of MWCNTs in improving the properties of photonic crystals is significant for various applications, such as in paints and displays. Full article

(This article belongs to the Special Issue Carbon Nanotubes: Advances and Applications)

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14 pages, 2722 KiB

Open AccessArticle

Neuroprotective Effects of Biochanin A against β-Amyloid-Induced Neurotoxicity in PC12 Cells via a Mitochondrial-Dependent Apoptosis Pathway

by Ji Wei Tan¹ and Min Kyu Kim^2,*

¹ Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

² Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

Molecules 2016, 21(5), 548; https://doi.org/10.3390/molecules21050548 - 25 Apr 2016

Cited by 65 | Viewed by 8579

Abstract

Alzheimer’s disease is considered one of the major neurodegenerative diseases and is characterized by the production of β-amyloid (Aβ) proteins and progressive loss of neurons. Biochanin A, a phytoestrogen compound found mainly in Trifolium pratense, was used in the present study as [...] Read more.

Alzheimer’s disease is considered one of the major neurodegenerative diseases and is characterized by the production of β-amyloid (Aβ) proteins and progressive loss of neurons. Biochanin A, a phytoestrogen compound found mainly in Trifolium pratense, was used in the present study as a potential alternative to estrogen replacement therapy via the investigation of its neuroprotective effects against Aβ_25–35-induced toxicity, as well as of its potential mechanisms of action in PC12 cells. Exposure of these cells to the Aβ_25–35 protein significantly increased cell viability loss and apoptosis. However, the effects induced by Aβ_25–35 were markedly reversed in the present of biochanin A. Pretreatment with biochanin A attenuated the cytotoxic effect of the Aβ_25–35 protein by decreasing viability loss, LDH release, and caspase activity in cells. Moreover, we found that expression of cytochrome c and Puma were reduced, alongside with the restoration of Bcl-2/Bax and Bcl-xL/Bax ratio in the presence of biochanin A, which led to a decrease in the apoptotic rate. These data demonstrate that mitochondria are involved in the protective effect of biochanin A against Aβ_25–35 and that this drug attenuated Aβ_25–35-induced PC12 cell injury and apoptosis by preventing mitochondrial dysfunction. Thus, biochanin A might raise a possibility as a potential therapeutic agent for Alzheimer’s disease and other related neurodegenerative diseases. Full article

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

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11 pages, 2038 KiB

Open AccessArticle

Neuroprotective and Cytotoxic Phthalides from Angelicae Sinensis Radix

by Wenxia Gong¹, Yuzhi Zhou^1,*, Xiao Li¹, Xiaoxia Gao¹, Junsheng Tian¹, Xuemei Qin^1,* and Guanhua Du^1,2

¹ Modern Research Center for Traditional Chinese Medicine, Shanxi University, No.92, Wucheng Road, Taiyuan 030006, China

² Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

Molecules 2016, 21(5), 549; https://doi.org/10.3390/molecules21050549 - 26 Apr 2016

Cited by 44 | Viewed by 7401 | Correction

Abstract

Seven phthalides, including a new dimeric one named tokinolide C (7), were isolated from Angelicae Sinensis Radix and characterized. The structures of these compounds were elucidated on the basis of comprehensive analysis of spectroscopic data and comparison with literature data. All of the [...] Read more.

Seven phthalides, including a new dimeric one named tokinolide C (7), were isolated from Angelicae Sinensis Radix and characterized. The structures of these compounds were elucidated on the basis of comprehensive analysis of spectroscopic data and comparison with literature data. All of the compounds were evaluated for their cytotoxic activities against the A549, HCT-8, and HepG2 cancer cell lines. Riligustilide (4) showed cytotoxicity against three cancer cell lines, with IC₅₀ values of 13.82, 6.79, and 7.92 μM, respectively. Tokinolide A (6) and tokinolide C (6) exerted low cytotoxicity in these cancer cell lines, while the remaining compounds were inactive. Flow cytometry analysis was employed to evaluate the possible mechanism of cytotoxic action of riligustilide (4). We observed that compound 4 was able to arrest the cell cycle in the G1, S phases and induce apoptosis in a time-dependent manner in HCT-8 cell lines. In addition, these compounds were evaluated for neuroprotective effect against SH-SY5Y cells injured by glutamate. The result showed that ligustilide (1), Z-butylidenephthalide (3) and tokinolide A (6) exhibited significant neuroprotective effects. Full article

(This article belongs to the Collection Bioactive Compounds)

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12 pages, 1295 KiB

Open AccessArticle

Bioconversion of Biomass-Derived Phenols Catalyzed by Myceliophthora thermophila Laccase

by Anastasia Zerva¹

, Nikolaos Manos¹, Stamatina Vouyiouka², Paul Christakopoulos³ and Evangelos Topakas^1,3,*

¹ Biotechnology Laboratory, School of Chemical Engineering, National Technical University of Athens, 5 Iroon Polytechniou Str., Zografou Campus, Athens 15780, Greece

² Laboratory of Polymer Technology, School of Chemical Engineering, National Technical University of Athens, 5 Iroon Polytechniou Str., Zografou Campus, Athens 15780, Greece

³ Biochemical and Chemical Process Engineering, Division of Sustainable Process Engineering, Department of Civil, Environmental and Natural Resources Engineering, Luleå University of Technology, Luleå SE-97187, Sweden

Molecules 2016, 21(5), 550; https://doi.org/10.3390/molecules21050550 - 27 Apr 2016

Cited by 24 | Viewed by 6826

Abstract

Biomass-derived phenols have recently arisen as an attractive alternative for building blocks to be used in synthetic applications, due to their widespread availability as an abundant renewable resource. In the present paper, commercial laccase from the thermophilic fungus Myceliophthora thermophila was used to [...] Read more.

Biomass-derived phenols have recently arisen as an attractive alternative for building blocks to be used in synthetic applications, due to their widespread availability as an abundant renewable resource. In the present paper, commercial laccase from the thermophilic fungus Myceliophthora thermophila was used to bioconvert phenol monomers, namely catechol, pyrogallol and gallic acid in water. The resulting products from catechol and gallic acid were polymers that were partially characterized in respect to their optical and thermal properties, and their average molecular weight was estimated via solution viscosity measurements and GPC. FT-IR and ¹H-NMR data suggest that phenol monomers are connected with ether or C–C bonds depending on the starting monomer, while the achieved molecular weight of polycatechol is found higher than the corresponding poly(gallic acid). On the other hand, under the same condition, pyrogallol was dimerized in a pure red crystalline compound and its structure was confirmed by ¹H-NMR as purpurogallin. The herein studied green synthesis of enzymatically synthesized phenol polymers or biological active compounds could be exploited as an alternative synthetic route targeting a variety of applications. Full article

(This article belongs to the Section Bioorganic Chemistry)

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16 pages, 1058 KiB

Open AccessReview

Polysaccharides from the Marine Environment with Pharmacological, Cosmeceutical and Nutraceutical Potential

by Nadia Ruocco^1,2,3,†, Susan Costantini^4,†, Stefano Guariniello⁵ and Maria Costantini^1,*

¹ Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Napoli, Italy

² Department of Biology, University of Naples Federico II, Complesso Universitario di Monte Sant’Angelo, Via Cinthia, 80126 Napoli, Italy

³ Bio-Organic Chemistry Unit, Institute of Biomolecular Chemistry-CNR, Via Campi Flegrei 34, Pozzuoli, 80078 Naples, Italy

⁴ CROM, Istituto Nazionale Tumori “Fondazione G. Pascale”, IRCCS, 80131 Napoli, Italy

⁵ Dipartimento di Biochimica, Biofisica e Patologia Generale, Seconda Università degli Studi di Napoli, 80131 Napoli, Italy

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 551; https://doi.org/10.3390/molecules21050551 - 27 Apr 2016

Cited by 213 | Viewed by 16930

Abstract

Carbohydrates, also called saccharides, are molecules composed of carbon, hydrogen, and oxygen. They are the most abundant biomolecules and essential components of many natural products and have attracted the attention of researchers because of their numerous human health benefits. Among carbohydrates the polysaccharides [...] Read more.

Carbohydrates, also called saccharides, are molecules composed of carbon, hydrogen, and oxygen. They are the most abundant biomolecules and essential components of many natural products and have attracted the attention of researchers because of their numerous human health benefits. Among carbohydrates the polysaccharides represent some of the most abundant bioactive substances in marine organisms. In fact, many marine macro- and microorganisms are good resources of carbohydrates with diverse applications due to their biofunctional properties. By acting on cell proliferation and cycle, and by modulating different metabolic pathways, marine polysaccharides (including mainly chitin, chitosan, fucoidan, carrageenan and alginate) also have numerous pharmaceutical activities, such as antioxidative, antibacterial, antiviral, immuno-stimulatory, anticoagulant and anticancer effects. Moreover, these polysaccharides have many general beneficial effects for human health, and have therefore been developed into potential cosmeceuticals and nutraceuticals. In this review we describe current advances in the development of marine polysaccharides for nutraceutical, cosmeceutical and pharmacological applications. Research in this field is opening new doors for harnessing the potential of marine natural products. Full article

(This article belongs to the Collection Advances in Glycosciences)

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14 pages, 1757 KiB

Open AccessArticle

Introducing Thermal Wave Transport Analysis (TWTA): A Thermal Technique for Dopamine Detection by Screen-Printed Electrodes Functionalized with Molecularly Imprinted Polymer (MIP) Particles

by Marloes M. Peeters^1,*,†

, Bart Van Grinsven^2,†

, Christopher W. Foster¹, Thomas J. Cleij²

and Craig E. Banks¹

¹ Faculty of Science and Engineering, School of Science and the Environment, Division of Chemistry and Environmental Science, Manchester Metropolitan University, Chester Street, Manchester M1 5GD, UK

² Maastricht Science Programme, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands

^† Authors share first authorship.

Molecules 2016, 21(5), 552; https://doi.org/10.3390/molecules21050552 - 26 Apr 2016

Cited by 31 | Viewed by 7347

Abstract

A novel procedure is developed for producing bulk modified Molecularly Imprinted Polymer (MIP) screen-printed electrodes (SPEs), which involves the direct mixing of the polymer particles within the screen-printed ink. This allowed reduction of the sample preparation time from 45 min to 1 min, [...] Read more.

A novel procedure is developed for producing bulk modified Molecularly Imprinted Polymer (MIP) screen-printed electrodes (SPEs), which involves the direct mixing of the polymer particles within the screen-printed ink. This allowed reduction of the sample preparation time from 45 min to 1 min, and resulted in higher reproducibility of the electrodes. The samples are measured with a novel detection method, namely, thermal wave transport analysis (TWTA), relying on the analysis of thermal waves through a functional interface. As a first proof-of-principle, MIPs for dopamine are developed and successfully incorporated within a bulk modified MIP SPE. The detection limits of dopamine within buffer solutions for the MIP SPEs are determined via three independent techniques. With cyclic voltammetry this was determined to be 4.7 × 10⁻⁶ M, whereas by using the heat-transfer method (HTM) 0.35 × 10⁻⁶ M was obtained, and with the novel TWTA concept 0.26 × 10⁻⁶ M is possible. This TWTA technique is measured simultaneously with HTM and has the benefits of reducing measurement time to less than 5 min and increasing effect size by nearly a factor of two. The two thermal methods are able to enhance dopamine detection by one order of magnitude compared to the electrochemical method. In previous research, it was not possible to measure neurotransmitters in complex samples with HTM, but with the improved signal-to-noise of TWTA for the first time, spiked dopamine concentrations were determined in a relevant food sample. In summary, novel concepts are presented for both the sensor functionalization side by employing screen-printing technology, and on the sensing side, the novel TWTA thermal technique is reported. The developed bio-sensing platform is cost-effective and suitable for mass-production due to the nature of screen-printing technology, which makes it very interesting for neurotransmitter detection in clinical diagnostic applications. Full article

(This article belongs to the Special Issue Nanozymes and Beyond)

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11 pages, 4109 KiB

Open AccessArticle

Anti-Cancer Activity of Solanum nigrum (AESN) through Suppression of Mitochondrial Function and Epithelial-Mesenchymal Transition (EMT) in Breast Cancer Cells

by Ying-Jang Lai^1,†, Chen-Jei Tai^2,3,4,†, Chia-Woei Wang^4,5, Chen-Yen Choong⁴, Bao-Hong Lee^2,6, Yeu-Ching Shi^7,* and Cheng-Jeng Tai^6,7,*

¹ Department of Food Science, National Quemoy University, Quemoy 89250, Taiwan

² Department of Chinese Medicine, Taipei University Hospital, Taipei 11042, Taiwan

³ Traditioal Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei 11042, Taiwan

⁴ Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan

⁵ Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei 11042, Taiwan

⁶ Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan

⁷ Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medicine University Hospital, Taipei 11042, Taiwan

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 553; https://doi.org/10.3390/molecules21050553 - 28 Apr 2016

Cited by 62 | Viewed by 9552

Abstract

Chemotherapy is the main approach for treating advanced and recurrent carcinoma, but the clinical performance of chemotherapy is limited by relatively low response rates, drug resistance, and adverse effects that severely affect the quality of life of patients. An association between epithelial-mesenchymal transition [...] Read more.

Chemotherapy is the main approach for treating advanced and recurrent carcinoma, but the clinical performance of chemotherapy is limited by relatively low response rates, drug resistance, and adverse effects that severely affect the quality of life of patients. An association between epithelial-mesenchymal transition (EMT) and chemotherapy resistance has been investigated in recent studies. Our recent studies have found that the aqueous extract of Solanum nigrum (AESN) is a crucial ingredient in some traditional Chinese medicine formulas for treating various types of cancer patients and exhibits antitumor effects. We evaluated the suppression of EMT in MCF-7 breast cancer cells treated with AESN. The mitochondrial morphology was investigated using Mitotracker Deep-Red FM stain. Our results indicated that AESN markedly inhibited cell viability of MCF-7 breast cancer cells through apoptosis induction and cell cycle arrest mediated by activation of caspase-3 and production of reactive oxygen species. Furthermore, mitochondrial fission was observed in MCF-7 breast cancer cells treated with AESN. In addition to elevation of E-cadherin, downregulations of ZEB1, N-cadherin, and vimentin were found in AESN-treated MCF-7 breast cancer cells. These results suggested that AESN could inhibit EMT of MCF-7 breast cancer cells mediated by attenuation of mitochondrial function. AESN could be potentially beneficial in treating breast cancer cells, and may be of interest for future studies in developing integrative cancer therapy against proliferation, metastasis, and migration of breast cancer cells. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 1913 KiB

Open AccessArticle

Inhibitory Effects of Aschantin on Cytochrome P450 and Uridine 5′-diphospho-glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

by Soon-Sang Kwon^1,†, Ju-Hyun Kim^1,†, Hyeon-Uk Jeong¹, Yong Yeon Cho¹, Sei-Ryang Oh² and Hye Suk Lee^1,*

¹ Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Korea

² Natural Medicine Research Center, Korea Research Institute of Biology and Biotechnology, Chungbuk 363-883, Korea

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 554; https://doi.org/10.3390/molecules21050554 - 27 Apr 2016

Cited by 15 | Viewed by 5931

Abstract

Aschantin is a bioactive neolignan found in Magnolia flos with antiplasmodial, Ca²⁺-antagonistic, platelet activating factor-antagonistic, and chemopreventive activities. We investigated its inhibitory effects on the activities of eight major human cytochrome P450 (CYP) and uridine 5′-diphospho-glucuronosyltransferase (UGT) enzymes of human liver [...] Read more.

Aschantin is a bioactive neolignan found in Magnolia flos with antiplasmodial, Ca²⁺-antagonistic, platelet activating factor-antagonistic, and chemopreventive activities. We investigated its inhibitory effects on the activities of eight major human cytochrome P450 (CYP) and uridine 5′-diphospho-glucuronosyltransferase (UGT) enzymes of human liver microsomes to determine if mechanistic aschantin–enzyme interactions were evident. Aschantin potently inhibited CYP2C8-mediated amodiaquine N-de-ethylation, CYP2C9-mediated diclofenac 4′-hydroxylation, CYP2C19-mediated [S]-mephenytoin 4′-hydroxylation, and CYP3A4-mediated midazolam 1′-hydroxylation, with K_i values of 10.2, 3.7, 5.8, and 12.6 µM, respectively. Aschantin at 100 µM negligibly inhibited CYP1A2-mediated phenacetin O-de-ethylation, CYP2A6-mediated coumarin 7-hydroxylation, CYP2B6-mediated bupropion hydroxylation, and CYP2D6-mediated bufuralol 1′-hydroxylation. At 200 µM, it weakly inhibited UGT1A1-catalyzed SN-38 glucuronidation, UGT1A6-catalyzed N-acetylserotonin glucuronidation, and UGT1A9-catalyzed mycophenolic acid glucuronidation, with IC₅₀ values of 131.7, 144.1, and 71.0 µM, respectively, but did not show inhibition against UGT1A3, UGT1A4, or UGT2B7 up to 200 µM. These in vitro results indicate that aschantin should be examined in terms of potential interactions with pharmacokinetic drugs in vivo. It exhibited potent mechanism-based inhibition of CYP2C8, CYP2C9, CYP2C19, and CYP3A4. Full article

(This article belongs to the Section Medicinal Chemistry)

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7 pages, 505 KiB

Open AccessArticle

Five 2-(2-Phenylethyl)chromones from Sodium Chloride-Elicited Aquilaria sinensis Cell Suspension Cultures

by Zhongxiu Zhang^1,2, Xiaohui Wang¹, Wanqing Yang^1,2, Juan Wang^1,2, Cong Su^1,2, Xiao Liu¹, Jun Li¹

, Yunfang Zhao¹, Shepo Shi^1,* and Pengfei Tu^1,*

¹ Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China

² School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China

Molecules 2016, 21(5), 555; https://doi.org/10.3390/molecules21050555 - 27 Apr 2016

Cited by 11 | Viewed by 4950

Abstract

Five 2-(2-phenylethyl)chromones including a new one, (5S,6R,7S,8R)-5,8-dichloro-6,7-dihydroxy-2-phenylethyl-5,6,7,8-tetrahydro-4H-chromen-4-one (1), and four known ones (2–5), were isolated from 150 mM NaCl-elicited Aquilaria sinensis cell suspension cultures. In addition, three feruloyl amides (6–8), six nucleosides (9–14), [...] Read more.

Five 2-(2-phenylethyl)chromones including a new one, (5S,6R,7S,8R)-5,8-dichloro-6,7-dihydroxy-2-phenylethyl-5,6,7,8-tetrahydro-4H-chromen-4-one (1), and four known ones (2–5), were isolated from 150 mM NaCl-elicited Aquilaria sinensis cell suspension cultures. In addition, three feruloyl amides (6–8), six nucleosides (9–14), (+)-syringaresinol (15), indole-3-carboxaldehyde (16), and two glycosides (17–18) were also obtained. The structures were unambiguously identified by analysis of their UV, IR, NMR, and HRESIMS data. The absolute configuration of the new 2-(2-phenylethyl)chromone (1) was established by a dimolybdenum tetraacetate-induced circular dichroism experiment. Compared to un-elicited cell lines, the appearance of 2-(2-phenylethyl)chromones in NaCl-treated cells occurred on the 3rd and 5th days of their treatment. 2-(2-Phenylethyl)chromones, feruloyl amides, nucleosides, and lignins have been reported to be closely related to plant defense; therefore, the identification of these compounds from NaCl-elicited A. sinensis cell suspension cultures would be useful for further exploring the mechanism of agarwood formation. Full article

(This article belongs to the Section Natural Products Chemistry)

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20 pages, 1478 KiB

Open AccessReview

Military Importance of Natural Toxins and Their Analogs

by Vladimír Pitschmann^1,2 and Zdeněk Hon^1,*

¹ Faculty of Biomedical Engineering, Czech Technical University in Prague, Sítná sq. 3105, 272 01 Kladno, Czech Republic

² Oritest spol. s r.o., Staropramenná 17, 156 00 Prague, Czech Republic

Molecules 2016, 21(5), 556; https://doi.org/10.3390/molecules21050556 - 28 Apr 2016

Cited by 37 | Viewed by 11500

Abstract

Toxin weapon research, development, production and the ban on its uses is an integral part of international law, with particular attention paid to the protection against these weapons. In spite of this, hazards associated with toxins cannot be completely excluded. Some of these [...] Read more.

Toxin weapon research, development, production and the ban on its uses is an integral part of international law, with particular attention paid to the protection against these weapons. In spite of this, hazards associated with toxins cannot be completely excluded. Some of these hazards are also pointed out in the present review. The article deals with the characteristics and properties of natural toxins and synthetic analogs potentially constituting the basis of toxin weapons. It briefly describes the history of military research and the use of toxins from distant history up to the present age. With respect to effective disarmament conventions, it mentions certain contemporary concepts of possible toxin applications for military purposes and the protection of public order (suppression of riots); it also briefly refers to the question of terrorism. In addition, it deals with certain traditional as well as modern technologies of the research, synthesis, and use of toxins, which can affect the continuing development of toxin weapons. These are, for example, cases of new toxins from natural sources, their chemical synthesis, production of synthetic analogs, the possibility of using methods of genetic engineering and modern biotechnologies or the possible applications of nanotechnology and certain pharmaceutical methods for the effective transfer of toxins into the organism. The authors evaluate the military importance of toxins based on their comparison with traditional chemical warfare agents. They appeal to the ethics of the scientific work as a principal condition for the prevention of toxin abuse in wars, military conflicts, as well as in non-military attacks. Full article

(This article belongs to the Special Issue Natural Toxins)

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11 pages, 1138 KiB

Open AccessArticle

Changes in the Subpopulations of Porcine Peripheral Blood Lymphocytes Induced by Exposure to Low Doses of Zearalenone (ZEN) and Deoxynivalenol (DON)

by Michał Dąbrowski, Kazimierz Obremski, Magdalena Gajęcka, Maciej Tadeusz Gajęcki and Łukasz Zielonka^*

Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13/29, 10-718 Olsztyn, Poland

Molecules 2016, 21(5), 557; https://doi.org/10.3390/molecules21050557 - 27 Apr 2016

Cited by 34 | Viewed by 4977

Abstract

Zearalenone and deoxynivalenol are secondary metabolites of fungi of the genus Fusarium. The presence of mycotoxins in cereals and the resulting contamination of feeds and foods pose health risks for animals and humans. The dangers associated with high doses of mycotoxins have [...] Read more.

Zearalenone and deoxynivalenol are secondary metabolites of fungi of the genus Fusarium. The presence of mycotoxins in cereals and the resulting contamination of feeds and foods pose health risks for animals and humans. The dangers associated with high doses of mycotoxins have been extensively researched but very little is known about NOAEL (No Observed Adverse Effect Level) doses or exposure to a combination of mycotoxins (mixed mycotoxicoses). The aim of this study was to determine the effects of six-week exposure to NOAEL doses of individual and combined mycotoxins on the subpopulations of CD4⁺8⁻, CD4⁻8⁺ and CD4⁺8⁺ lymphocytes in the peripheral blood of pigs. The experiment was performed on 72 gilts with average body weight of 25 kg, divided into three experimental groups (E1, E2 and E3, administered zearalenone (ZEN), deoxynivalenol (DON) and ZEN + DON, respectively, on a daily basis) and a control group (C) receiving placebo. Changes in lymphocyte subpopulations were evaluated by flow cytometry at weekly intervals (experimental days 7, 14, 21, 28, 35 and 42). A linear increase in the percentage of CD4⁺8⁺ lymphocytes was highly correlated with time (r = 0.682) in group C. The correlations and linear increase in the above subpopulation were disrupted in the remaining groups. In group E3, a statistically significant (p < 0.05) decrease in CD4⁺8⁺ counts was observed in week 5, which could point to a transient depletion of regulatory mechanisms of immune responses. The noted results also suggest that in mixed mycotoxicosis, ZEN and DON exerted stronger immunomodulatory effects. Full article

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12 pages, 4297 KiB

Open AccessArticle

A Novel Photosensitizer 3¹,13¹-phenylhydrazine -Mppa (BPHM) and Its in Vitro Photodynamic Therapy against HeLa Cells

by Wenting Li^†, Guanghui Tan^*, Jianjun Cheng^†, Lishuang Zhao^†, Zhiqiang Wang^*

and Yingxue Jin^*

¹ Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 558; https://doi.org/10.3390/molecules21050558 - 29 Apr 2016

Cited by 13 | Viewed by 6291

Abstract

Photodynamic therapy (PDT) has attracted widespread attention due to its potential in the treatment of various cancers. Porphyrinic pyropheophorbide-a (PPa) has been shown to be a potent photosensitizer in PDT experiments. In this paper, a C-3¹,13¹ bisphenylhydrazone modified methyl pyropheophorbide-a [...] Read more.

Photodynamic therapy (PDT) has attracted widespread attention due to its potential in the treatment of various cancers. Porphyrinic pyropheophorbide-a (PPa) has been shown to be a potent photosensitizer in PDT experiments. In this paper, a C-3¹,13¹ bisphenylhydrazone modified methyl pyropheophorbide-a (BPHM) was designed and synthesized with the consideration that phenylhydrazone structure may extend absorption wavelength of methyl pyro-pheophorbide-a (Mppa), and make the photosensitizer potential in deep tumor treatment. The synthesis, spectral properties and in vitro photodynamic therapy (PDT) against human HeLa cervical cancer cell line was studied. Methyl thiazolyl tetrazolium (MTT) assay showed the title compound could achieve strong inhibition of cervical cancer cell viability under visible light (675 nm, 25 J/cm²). Cell uptake experiments were performed on HeLa cells. Morphological changes were examined and analyzed by fluorescent inverted microscope. In addition, the mechanism of the photochemical processes of PDT was investigated, which showed that the formation of singlet oxygen after treatment with PDT played a moderate important role. Full article

(This article belongs to the Special Issue Photoactive Molecules)

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18 pages, 2929 KiB

Open AccessReview

The Traditional Medicine and Modern Medicine from Natural Products

by Haidan Yuan^1,2, Qianqian Ma¹, Li Ye¹ and Guangchun Piao^1,2,*

¹ College of Pharmacy, Yanbian University, Yanji 133002, China

² Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Yanbian University, Yanji 133002, China

Molecules 2016, 21(5), 559; https://doi.org/10.3390/molecules21050559 - 29 Apr 2016

Cited by 1624 | Viewed by 87070

Abstract

Natural products and traditional medicines are of great importance. Such forms of medicine as traditional Chinese medicine, Ayurveda, Kampo, traditional Korean medicine, and Unani have been practiced in some areas of the world and have blossomed into orderly-regulated systems of medicine. This study [...] Read more.

Natural products and traditional medicines are of great importance. Such forms of medicine as traditional Chinese medicine, Ayurveda, Kampo, traditional Korean medicine, and Unani have been practiced in some areas of the world and have blossomed into orderly-regulated systems of medicine. This study aims to review the literature on the relationship among natural products, traditional medicines, and modern medicine, and to explore the possible concepts and methodologies from natural products and traditional medicines to further develop drug discovery. The unique characteristics of theory, application, current role or status, and modern research of eight kinds of traditional medicine systems are summarized in this study. Although only a tiny fraction of the existing plant species have been scientifically researched for bioactivities since 1805, when the first pharmacologically-active compound morphine was isolated from opium, natural products and traditional medicines have already made fruitful contributions for modern medicine. When used to develop new drugs, natural products and traditional medicines have their incomparable advantages, such as abundant clinical experiences, and their unique diversity of chemical structures and biological activities. Full article

(This article belongs to the Collection Herbal Medicine Research)

16 pages, 2525 KiB

Open AccessArticle

De Novo Sequencing and Transcriptome Analysis of Pleurotus eryngii subsp. tuoliensis (Bailinggu) Mycelia in Response to Cold Stimulation

by Yong-Ping Fu^1,2,†, Yuan Liang^3,†, Yue-Ting Dai¹, Chen-Tao Yang⁴

, Ming-Zheng Duan¹

, Zhuo Zhang¹, Song-Nian Hu^3,*

, Zhi-Wu Zhang^2,* and Yu Li^1,*

¹ Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, College of Agriculture, Jilin Agricultural University, Changchun 130118, China

² Department of Crop and Soil Sciences, Washington State University, Pullman, WA 99163, USA

³ Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China

⁴ China National GeneBank, Environmental Genomics, BGI, Shenzhen 518083, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 560; https://doi.org/10.3390/molecules21050560 - 17 May 2016

Cited by 46 | Viewed by 7901

Abstract

Cold stimulation of Bailinggu’s mycelia is the main factor that triggers primordia initiation for successful production of fruiting bodies under commercial cultivation. Yet, the molecular-level mechanisms involved in mycelia response to cold stimulation are still unclear. Here, we performed comparative transcriptomic analysis using [...] Read more.

Cold stimulation of Bailinggu’s mycelia is the main factor that triggers primordia initiation for successful production of fruiting bodies under commercial cultivation. Yet, the molecular-level mechanisms involved in mycelia response to cold stimulation are still unclear. Here, we performed comparative transcriptomic analysis using RNA-Seq technology to better understand the gene expression regulation during different temporal stages of cold stimulation in Bailinggu. A total of 21,558 Bailinggu mycelia unigenes were de novo assembled and annotated from four libraries (control at 25 °C, plus cold stimulation treatments at −3 °C for a duration of 1–2 days, 5–6 days, and 9–10 days). GO and KEGG pathway analysis indicated that functional groups of differentially expressed unigenes associated with cell wall and membrane stabilization, calcium signaling and mitogen-activated protein kinases (MAPK) pathways, and soluble sugars and protein biosynthesis and metabolism pathways play a vital role in Bailinggu’s response to cold stimulation. Six hundred and seven potential EST-based SSRs loci were identified in these unigenes, and 100 EST-SSR primers were randomly selected for validation. The overall polymorphism rate was 92% by using 10 wild strains of Bailinggu. Therefore, these results can serve as a valuable resource for a better understanding of the molecular mechanisms associated with Bailinggu’s response to cold stimulation. Full article

(This article belongs to the Section Molecular Diversity)

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14 pages, 4057 KiB

Open AccessArticle

Nanocellulose Derivative/Silica Hybrid Core-Shell Chiral Stationary Phase: Preparation and Enantioseparation Performance

by Xiaoli Zhang^1,2, Litao Wang¹, Shuqing Dong¹, Xia Zhang¹, Qi Wu^1,2, Liang Zhao^1,* and Yanping Shi^1,*

¹ Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Science, Lanzhou 730000, China

² University of Chinese Academy of Science, Beijing 100039, China

Molecules 2016, 21(5), 561; https://doi.org/10.3390/molecules21050561 - 4 May 2016

Cited by 11 | Viewed by 8094

Abstract

Core-shell silica microspheres with a nanocellulose derivative in the hybrid shell were successfully prepared as a chiral stationary phase by a layer-by-layer self-assembly method. The hybrid shell assembled on the silica core was formed using a surfactant as template by the copolymerization reaction [...] Read more.

Core-shell silica microspheres with a nanocellulose derivative in the hybrid shell were successfully prepared as a chiral stationary phase by a layer-by-layer self-assembly method. The hybrid shell assembled on the silica core was formed using a surfactant as template by the copolymerization reaction of tetraethyl orthosilicate and the nanocellulose derivative bearing triethoxysilyl and 3,5-dimethylphenyl groups. The resulting nanocellulose hybrid core-shell chiral packing materials (CPMs) were characterized and packed into columns, and their enantioseparation performance was evaluated by high performance liquid chromatography. The results showed that CPMs exhibited uniform surface morphology and core-shell structures. Various types of chiral compounds were efficiently separated under normal and reversed phase mode. Moreover, chloroform and tetrahydrofuran as mobile phase additives could obviously improve the resolution during the chiral separation processes. CPMs still have good chiral separation property when eluted with solvent systems with a high content of tetrahydrofuran and chloroform, which proved the high solvent resistance of this new material. Full article

(This article belongs to the Special Issue Chromatographic Separation of Enantiomers: Commemorative Issue in Honor of Professor Stig Allenmark on the Occasion of His 80th Birthday)

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12 pages, 4801 KiB

Open AccessArticle

Thermal Hazard Evaluation of Cumene Hydroperoxide-Metal Ion Mixture Using DSC, TAM III, and GC/MS

by Mei-Li You

Department of General Education Center, Chienkuo Technology University, 1 Chieh-Shou N. Rd., Changhua 50094, Taiwan

Molecules 2016, 21(5), 562; https://doi.org/10.3390/molecules21050562 - 28 Apr 2016

Cited by 7 | Viewed by 7717

Abstract

Cumene hydroperoxide (CHP) is widely used in chemical processes, mainly as an initiator for the polymerization of acrylonitrile–butadiene–styrene. It is a typical organic peroxide and an explosive substance. It is susceptible to thermal decomposition and is readily affected by contamination; moreover, it has [...] Read more.

Cumene hydroperoxide (CHP) is widely used in chemical processes, mainly as an initiator for the polymerization of acrylonitrile–butadiene–styrene. It is a typical organic peroxide and an explosive substance. It is susceptible to thermal decomposition and is readily affected by contamination; moreover, it has high thermal sensitivity. The reactor tank, transit storage vessel, and pipeline used for manufacturing and transporting this substance are made of metal. Metal containers used in chemical processes can be damaged through aging, wear, erosion, and corrosion; furthermore, the containers might release metal ions. In a metal pipeline, CHP may cause incompatibility reactions because of catalyzed exothermic reactions. This paper discusses and elucidates the potential thermal hazard of a mixture of CHP and an incompatible material’s metal ions. Differential scanning calorimetry (DSC) and thermal activity monitor III (TAM III) were employed to preliminarily explore and narrate the thermal hazard at the constant temperature environment. The substance was diluted and analyzed by using a gas chromatography spectrometer (GC) and gas chromatography/mass spectrometer (GC/MS) to determine the effect of thermal cracking and metal ions of CHP. The thermokinetic parameter values obtained from the experiments are discussed; the results can be used for designing an inherently safer process. As a result, the paper finds that the most hazards are in the reaction of CHP with Fe²⁺. When the metal release is exothermic in advance, the system temperature increases, even leading to uncontrollable levels, and the process may slip out of control. Full article

(This article belongs to the Section Molecular Diversity)

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13 pages, 3430 KiB

Open AccessArticle

Interaction of Di-2-pyridylketone 2-pyridine Carboxylic Acid Hydrazone and Its Copper Complex with BSA: Effect on Antitumor Activity as Revealed by Spectroscopic Studies

by Cuiping Li^1,†, Tengfei Huang^1,†, Yun Fu¹, Youxun Liu¹, Sufeng Zhou¹, Zhangyang Qi¹ and Changzheng Li^1,2,*

¹ Department of Molecular Biology & Biochemistry, Xinxiang Medical University, Xinxiang 453003, Henan, China

² Henan Collaborative Innovation Center of Molecular Diagnostics and Laboratory Medicine, Xinxiang 453003, Henan, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 563; https://doi.org/10.3390/molecules21050563 - 28 Apr 2016

Cited by 16 | Viewed by 5349

Abstract

The drug, di-2-pyridylketone-2-pyridine carboxylic acid hydrazone (DPPCAH) and its copper complex (DPPCAH-Cu) exhibit significant antitumor activity. However, the mechanism of their pharmacological interaction with the biological molecule bovine serum albumin (BSA) remains poorly understood. The present study elucidates the interactions between the drug [...] Read more.

The drug, di-2-pyridylketone-2-pyridine carboxylic acid hydrazone (DPPCAH) and its copper complex (DPPCAH-Cu) exhibit significant antitumor activity. However, the mechanism of their pharmacological interaction with the biological molecule bovine serum albumin (BSA) remains poorly understood. The present study elucidates the interactions between the drug and BSA through MTT assays, spectroscopic methods and molecular docking analysis. Our results indicate that BSA could attenuate effect on the cytotoxicity of DPPCAH, but not DPPCAH-Cu. Data from fluorescence quenching measurements demonstrated that both DPPCAH and DPPCAH-Cu could bind to BSA, with a reversed effect on the environment of tryptophan residues in polarity. CD spectra revealed that the DPPCAH-Cu exerted a slightly stronger effect on the secondary structure of BSA than DPPCAH. The association constant of DPPCAH with BSA was greater than that of DPPCAH-Cu. Docking studies indicated that the binding of DPPCAH to BSA involved a greater number of hydrogen bonds compared to DPPCAH-Cu. The calculated distances between bound ligands and tryptophans in BSA were in agreement with fluorescence resonance energy transfer results. Thus, the binding affinity of the drug (DPPCAH or DPPCAH-Cu) with BSA partially contributes to its antitumor activity; the greater the drug affinity is to BSA, the less is its antitumor activity. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 2464 KiB

Open AccessArticle

Agrimonia eupatoria L. and Cynara cardunculus L. Water Infusions: Comparison of Anti-Diabetic Activities

by Anika Kuczmannová¹, Andrea Balažová², Eva Račanská³, Miroslava Kameníková¹, Silvia Fialová¹, Jaroslav Majerník⁴

, Milan Nagy¹, Peter Gál^1,5,6,*

and Pavel Mučaji^1,*

¹ Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University, Odbojárov 10, Bratislava 83232, Slovakia

² Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, Bratislava 83232, Slovakia

³ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojárov 10, Bratislava 83232, Slovakia

⁴ Department of Medical Informatics, Faculty of Medicine, Pavol Jozef Šafárik University, Trieda SNP 1, Košice 04011, Slovakia

⁵ Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, Trieda SNP 1, Košice 04011, Slovakia

⁶ Department for Biomedical Research, East-Slovak Institute of Cardiovascular Diseases, Inc., Ondavská 8, Košice 04011, Slovakia

Molecules 2016, 21(5), 564; https://doi.org/10.3390/molecules21050564 - 28 Apr 2016

Cited by 33 | Viewed by 7482

Abstract

Diabetes mellitus (DM) is frequently diagnosed at a time when patients already suffer from several cardiovascular complications. Our previously published data (Molecules 201520 (11): 20538-50) on the anti-oxidative properties of Agrimonia eupatoria L. (AE) and Cynara cardunculus L. (CC) prompted us to extend [...] Read more.

Diabetes mellitus (DM) is frequently diagnosed at a time when patients already suffer from several cardiovascular complications. Our previously published data (Molecules 201520 (11): 20538-50) on the anti-oxidative properties of Agrimonia eupatoria L. (AE) and Cynara cardunculus L. (CC) prompted us to extend the available evidence on their possible protective activities on selected DM-related parameters in a streptozotocin-induced DM rat model and in a series of in vitro experiments. Male rats were divided into four groups: control group, untreated diabetic group, AE and CC treated diabetic groups. During a five-week period, changes in blood glucose and body weight were monitored. Then, rats were sacrificed and subjected to the assessment of changes in the reactivity of aortas and measurement of butyrylcholinesterase activity. To complete the panel of experiments, α-glucosidase activity was assessed in vitro. Our results demonstrate that both tested extracts exert similar anti-diabetic activities. However, better anti-oxidant activity of the A. eupatoria extract indicates its higher clinical potential in the prevention and/or adjuvant therapy of developing cardiovascular complications related to DM and diseases associated with oxidative stress. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

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8 pages, 1772 KiB

Open AccessArticle

Ultrasound-Assisted Enantioselective Esterification of Ibuprofen Catalyzed by a Flower-Like Nanobioreactor

by Baiyi An¹, Hailin Fan², Zhuofu Wu^3,4, Lu Zheng⁴, Lei Wang⁴, Zhi Wang^4,* and Guang Chen^3,*

¹ College of Horticulture, Jilin Agricultural University, Changchun 130118, China

² College of Resources and Environment, Jilin Agricultural University, Changchun 130118, China

³ College of Life Science, Jilin Agricultural University, Changchun 130118, China

⁴ Key Laboratory of Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China

Molecules 2016, 21(5), 565; https://doi.org/10.3390/molecules21050565 - 28 Apr 2016

Cited by 12 | Viewed by 5282

Abstract

A flower-like nanobioreactor was prepared for resolution of ibuprofen in organic solvents. Ultrasound irradiation has been used to improve the enzyme performance of APE1547 (a thermophilic esterase from the archaeon Aeropyrum pernix K1) in the enantioselective esterification. Under optimum reaction conditions (ultrasound power, [...] Read more.

A flower-like nanobioreactor was prepared for resolution of ibuprofen in organic solvents. Ultrasound irradiation has been used to improve the enzyme performance of APE1547 (a thermophilic esterase from the archaeon Aeropyrum pernix K1) in the enantioselective esterification. Under optimum reaction conditions (ultrasound power, 225 W; temperature, 45 °C; water activity, 0.21), the immobilized APE1547 showed an excellent catalytic performance (enzyme activity, 13.26 μmol/h/mg; E value, 147.1). After ten repeated reaction batches, the nanobioreactor retained almost 100% of its initial enzyme activity and enantioselectivity. These results indicated that the combination of the immobilization method and ultrasound irradiation can enhance the enzyme performance dramatically. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 234 KiB

Open AccessArticle

Antimicrobial Activity and Chromatographic Analysis of Extracts from Tropaeolum pentaphyllum Lam. Tubers

by Ritiel Corrêa Da Cruz^1,*

, Laura Bedin Denardi²

, Natalia Jank Mossmann¹, Mariana Piana¹, Sydney Hartz Alves²

and Marli Matiko Anraku De Campos³

¹ Departamento de Farmácia Industrial, Universidade Federal de Santa Maria (UFSM), Avenida Roraima 1000, Block 26, Santa Maria 97105-900, Rio Grande do Sul, Brazil

² Departamento de Parasitologia, Microbiologia e Imunologia, Universidade Federal de Santa Maria (UFSM), Avenida Roraima 1000, Block 20, Santa Maria 97105-900, Rio Grande do Sul, Brazil

³ Departamento de Análises Clínicas e Toxicológicas, Universidade Federal de Santa Maria (UFSM), Avenida Roraima 1000, Block 26, Santa Maria 97105-900, Rio Grande do Sul, Brazil

Molecules 2016, 21(5), 566; https://doi.org/10.3390/molecules21050566 - 28 Apr 2016

Cited by 7 | Viewed by 6998

Abstract

Background: Tropaeolum pentaphyllum Lam. tubers (Tropaeolaceae) are known and used as a condiment and for the treatment of skin infections in Southern Brazil. However, its activity and composition has not yet been investigated. Thus, different extracts and the essential oil from the tubers [...] Read more.

Background: Tropaeolum pentaphyllum Lam. tubers (Tropaeolaceae) are known and used as a condiment and for the treatment of skin infections in Southern Brazil. However, its activity and composition has not yet been investigated. Thus, different extracts and the essential oil from the tubers were tested against a range of microorganisms. The most active extracts were submitted to chromatographic analysis. Methods: Hydroalcoholic extract (70%), fractions of it, and the essential oil from the tubers were tested against several bacteria, yeasts and molds, furnishing the corresponding inhibitory, bactericidal and fungicidal minimal concentration values. The most active extracts were submitted to GC-MS investigation. Results: The strongest effects against different strains of microorganisms, such as Gram-positive and negative bacteria, Candida spp. and dermatophytes were observed for the essential oil and the chloroform fraction, with minimal inhibitory concentrations (MICs) well below 200 µg/mL. GC-MS analysis revealed that the major essential oil constituent is benzyl isothiocyanate (BITC), while the chloroform fraction is constituted of BITC, amides, sulfur, fatty acids and its esters, all compounds that may be related to the demonstrated activity. Conclusions: Overall, the results support the popular use of the plant for the treatment of skin infections, and revealed the main active compounds. Full article

(This article belongs to the Collection Bioactive Compounds)

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17 pages, 4164 KiB

Open AccessArticle

Design, Synthesis, Antimicrobial Evaluation and Molecular Modeling Study of 1,2,4-Triazole-Based 4-Thiazolidinones

by Sahar Ahmed^1,2,*, Mohamed F. Zayed^1,3

, Shahenda M. El-Messery^1,4, Mohamed H. Al-Agamy^5,6 and Hamdy M. Abdel-Rahman²

¹ Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al-Madinah, Al-Munawarah 30001, Saudi Arabia

² Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt

³ Pharmaceutical Chemistry, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt

⁴ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt

⁵ Department of Pharmaceutics, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia

⁶ Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo 11884, Egypt

Molecules 2016, 21(5), 568; https://doi.org/10.3390/molecules21050568 - 30 Apr 2016

Cited by 39 | Viewed by 7555

Abstract

A series of 3-(2H-1,2,4-triazol-5-yl)-1,3-thiazolidin-4-one derivatives (7c–l) was designed and synthesized. Their structures have been elucidated based on analytical and spectral data. They were evaluated for their antibacterial and antifungal activities. Compound 7h showed the highest activity against [...] Read more.

A series of 3-(2H-1,2,4-triazol-5-yl)-1,3-thiazolidin-4-one derivatives (7c–l) was designed and synthesized. Their structures have been elucidated based on analytical and spectral data. They were evaluated for their antibacterial and antifungal activities. Compound 7h showed the highest activity against all tested strains, except P. vulgaris, with MIC 8 μg/mL and 4 μg/mL against S. aureus and C. albicans, respectively. Furthermore, Compounds 7c, 7h, and 7j demonstrated moderate anti-mycobacterium activity. The binding mode of the synthesized thiazolidinones to bacterial MurB enzyme was also studied. Good interactions between the docked compounds to the MurB active site were observed primarily with Asn83, Arg310, Arg188 and Ser82 amino acid residues. Full article

(This article belongs to the Section Medicinal Chemistry)

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9 pages, 1204 KiB

Open AccessArticle

Using LC and Hierarchical Cluster Analysis as Tools to Distinguish Timbó Collections into Two Deguelia Species: A Contribution to Chemotaxonomy

by Danielle Da Costa

, Consuelo E Silva, Aline Pinheiro, Débora Frommenwiler, Mara Arruda, Giselle Guilhon, Cláudio Alves, Alberto Arruda and Milton Da Silva^*

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

Molecules 2016, 21(5), 569; https://doi.org/10.3390/molecules21050569 - 30 Apr 2016

Cited by 6 | Viewed by 4953

Abstract

The species Deguelia utilis and Deguelia rufescens var. urucu, popularly known as “timbó,” have been used for many years as rotenone sources in insecticide formulations. In this work, a method was developed and validated using a high-performance liquid chromatography-photodiode array (HPLC-PDA) system, [...] Read more.

The species Deguelia utilis and Deguelia rufescens var. urucu, popularly known as “timbó,” have been used for many years as rotenone sources in insecticide formulations. In this work, a method was developed and validated using a high-performance liquid chromatography-photodiode array (HPLC-PDA) system, and results were analyzed using hierarchical cluster analysis (HCA). By quantifying the major rotenoids of these species, it was possible to establish a linear relation between them. The ratio between the concentrations of rotenone and deguelin for D. utilis is approximately 1:0.8, respectively, while for D. rufescens var. urucu it is 2:1. These results may help to distinguish these species contributing to their taxonomic identification. Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 3580 KiB

Open AccessArticle

Photoactivatable Caged Prodrugs of VEGFR-2 Kinase Inhibitors

by Boris Pinchuk, Rebecca Horbert, Alexander Döbber, Lydia Kuhl and Christian Peifer^*

Institute of Pharmacy, University of Kiel, Gutenbergstr. 76, D-24118 Kiel, Germany

Molecules 2016, 21(5), 570; https://doi.org/10.3390/molecules21050570 - 29 Apr 2016

Cited by 18 | Viewed by 8288

Abstract

In this study, we report on the design, synthesis, photokinetic properties and in vitro evaluation of photoactivatable caged prodrugs for the receptor tyrosine kinase VEGFR-2. Highly potent VEGFR-2 inhibitors 1 and 3 were caged by introduction of a photoremovable protecting group (PPG) to [...] Read more.

In this study, we report on the design, synthesis, photokinetic properties and in vitro evaluation of photoactivatable caged prodrugs for the receptor tyrosine kinase VEGFR-2. Highly potent VEGFR-2 inhibitors 1 and 3 were caged by introduction of a photoremovable protecting group (PPG) to yield the caged prodrugs 4 and 5. As expected, enzymatic and cellular proliferation assays showed dramatically diminished efficacy of caged prodrugs in vitro. Upon ultraviolet (UV) irradiation of the prodrugs original inhibitory activity was completely restored and even distinctly reinforced, as was the case for the prodrug 4. The presented results are a further evidence for caging technique being an interesting approach in the protein kinase field. It could enable spatial and temporal control for the inhibition of VEGFR-2. The described photoactivatable prodrugs might be highly useful as biological probes for studying the VEGFR-2 signal transduction. Full article

(This article belongs to the Special Issue Photoresponsive Drugs)

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6 pages, 974 KiB

Open AccessArticle

Two New Cinnamyl Isovalerate Derivatives from Sabina gaussenii

by Zhang-Hua Sun^1,2, Ning-Hua Tan³, Guang-Zhi Zeng³ and Yu-Mei Zhang^1,3,*

¹ Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming 650223, China

² State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou 510070, China

³ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China

Molecules 2016, 21(5), 571; https://doi.org/10.3390/molecules21050571 - 29 Apr 2016

Cited by 6 | Viewed by 5310

Abstract

Chemical investigation of the 90% acetone extract of the branches and leaves of Sabina gaussenii led to the isolation of two new cinnamyl isovalerate derivatives (1–2) and eighteen known compounds (3–20). Their structures were determined mainly by means of MS, 1D- and 2D-NMR [...] Read more.

Chemical investigation of the 90% acetone extract of the branches and leaves of Sabina gaussenii led to the isolation of two new cinnamyl isovalerate derivatives (1–2) and eighteen known compounds (3–20). Their structures were determined mainly by means of MS, 1D- and 2D-NMR data, and this is the first time these compounds have been reported from this plant. The biological activity test results indicated that the 90% acetone extract showed cytotoxicity against the human lung adenocarcinoma (A549) cell line (IC₅₀ = 0.98 ± 0.1 μg/mL), compound 6 showed cytotoxicities against human cervical carcinoma (HeLa) (IC₅₀ = 0.4 ± 0.1 μM ) and human gastric carcinoma (BGC-823) (IC₅₀ = 0.9 ± 0.2 μM) cancer cell lines, and compound 19 showed cytotoxicities against HeLa (IC₅₀ = 1.5 ± 0.4 μM), BGC-823 (IC₅₀ = 7.0 ± 0.8 μM ), and A549 (IC₅₀ = 10.6 ± 1.5 μM ) cancer cell lines. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 4164 KiB

Open AccessArticle

An Electrostatically Self-Assembled Ternary Nanocomplex as a Non-Viral Vector for the Delivery of Plasmid DNA into Human Adipose-Derived Stem Cells

by Sun-Hee Cho^†, Young-Woock Noh^†, Mi Young Cho and Yong Taik Lim^*

¹ SKKU Advanced Institute of Nanotechnology (SAINT), School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Korea

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 572; https://doi.org/10.3390/molecules21050572 - 29 Apr 2016

Cited by 7 | Viewed by 7555

Abstract

In this study, we developed electrostatically self-assembled ternary nanocomplexes as a safe and effective non-viral vector for the delivery of plasmid DNA (pDNA) into human adipose-derived stem cells (hASCs). Although polyethylenimine (PEI) polymers initially showed excellent performance as gene delivery carriers, their broad [...] Read more.

In this study, we developed electrostatically self-assembled ternary nanocomplexes as a safe and effective non-viral vector for the delivery of plasmid DNA (pDNA) into human adipose-derived stem cells (hASCs). Although polyethylenimine (PEI) polymers initially showed excellent performance as gene delivery carriers, their broad use has been limited by cytotoxicity resulting from their strong positive charge. To reduce the cytotoxicity, we utilized anionic hyaluronic acid (HA) as a corona layer material for pDNA/PEI binary nanocomplexes. HA was also introduced to increase the targeting efficiency of pDNA/PEI nanocomplexes because HA has can bind CD44 that is highly expressed on the surface of hASCs. We confirmed that the addition of HA changed the surface charge of pDNA/PEI nanocomplexes from positive to negative. The pDNA/PEI/HA ternary nanocomplexes showed high transfection efficiency and low cytotoxicity compared with commercially available products. When hASCs were pretreated with HA to passivate CD44, the transfection efficiency of pDNA/PEI/HA nanocomplexes was significantly reduced. These results suggest that HA that can act as a targeting ligand to CD44 contributed to the improved transfection of pDNA into hASCs. Our novel pDNA/PEI/HA nanocomplexes may be used as an effective non-viral pDNA delivery system for hASCs. Full article

(This article belongs to the Collection Nanomedicine)

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17 pages, 636 KiB

Open AccessReview

Role of Plant Growth Promoting Rhizobacteria in Agricultural Sustainability—A Review

by Pravin Vejan¹

, Rosazlin Abdullah^1,2,*, Tumirah Khadiran³, Salmah Ismail¹ and Amru Nasrulhaq Boyce^1,2

¹ Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia

² Centre for Research in Biotechnology for Agriculture (CEBAR), Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia

³ Forest Product Divisions, Forest Research Institute Malaysia, 52109 Kepong, Selangor, Malaysia

Molecules 2016, 21(5), 573; https://doi.org/10.3390/molecules21050573 - 29 Apr 2016

Cited by 1004 | Viewed by 47713

Abstract

Plant growth promoting rhizobacteria (PGPR) shows an important role in the sustainable agriculture industry. The increasing demand for crop production with a significant reduction of synthetic chemical fertilizers and pesticides use is a big challenge nowadays. The use of PGPR has been proven [...] Read more.

Plant growth promoting rhizobacteria (PGPR) shows an important role in the sustainable agriculture industry. The increasing demand for crop production with a significant reduction of synthetic chemical fertilizers and pesticides use is a big challenge nowadays. The use of PGPR has been proven to be an environmentally sound way of increasing crop yields by facilitating plant growth through either a direct or indirect mechanism. The mechanisms of PGPR include regulating hormonal and nutritional balance, inducing resistance against plant pathogens, and solubilizing nutrients for easy uptake by plants. In addition, PGPR show synergistic and antagonistic interactions with microorganisms within the rhizosphere and beyond in bulk soil, which indirectly boosts plant growth rate. There are many bacteria species that act as PGPR, described in the literature as successful for improving plant growth. However, there is a gap between the mode of action (mechanism) of the PGPR for plant growth and the role of the PGPR as biofertilizer—thus the importance of nano-encapsulation technology in improving the efficacy of PGPR. Hence, this review bridges the gap mentioned and summarizes the mechanism of PGPR as a biofertilizer for agricultural sustainability. Full article

(This article belongs to the Section Molecular Diversity)

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11 pages, 1792 KiB

Open AccessArticle

Celastrol Induces Cell Apoptosis and Inhibits the Expression of the AML1-ETO/C-KIT Oncoprotein in t(8;21) Leukemia

by Xianjun Yu^1,2,3,*, Xuzhi Ruan¹, Jingxuan Zhang¹ and Qun Zhao^2,*

¹ School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, China

² Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China

³ Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, China

Molecules 2016, 21(5), 574; https://doi.org/10.3390/molecules21050574 - 30 Apr 2016

Cited by 25 | Viewed by 6460

Abstract

Resistance to chemotherapy is a major challenge to improving overall survival in Acute Myeloid Leukemia (AML). Therefore, the development of innovative therapies and the identification of more novel agents for AML are urgently needed. Celastrol, a compound extracted from the Chinese herb Tripterygium [...] Read more.

Resistance to chemotherapy is a major challenge to improving overall survival in Acute Myeloid Leukemia (AML). Therefore, the development of innovative therapies and the identification of more novel agents for AML are urgently needed. Celastrol, a compound extracted from the Chinese herb Tripterygium wilfordii Hook, exerts anticancer activity. We investigated the effect of celastrol in the t(8;21) AML cell lines Kasumi-1 and SKNO-1. We demonstrated that inhibition of cell proliferation activated caspases and disrupted mitochondrial function. In addition, we found that celastrol downregulated the AML1-ETO fusion protein, therefore downregulating C-KIT kinases and inhibiting AKT, STAT3 and Erk1/2. These findings provide clear evidence that celastrol might provide clinical benefits to patients with t(8;21) leukemia. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 2091 KiB

Open AccessArticle

Antitumor and Antibacterial Derivatives of Oridonin: A Main Composition of Dong-Ling-Cao

by Dahong Li^1,2,3,4, Tong Han¹, Shengtao Xu², Tingting Zhou¹, Kangtao Tian¹, Xu Hu¹, Keguang Cheng^4,*, Zhanlin Li¹, Huiming Hua^1,* and Jinyi Xu^2,*

¹ Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China

² State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China

³ State Key Laboratory of New-Tech for Chinese Medicine Pharmaceutical Processes, National Post-Doctoral Research Workstation, Jiangsu Kanion Pharmaceutical Co. Ltd., Lianyungang 222001, China

⁴ State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, Guilin 541004, China

Molecules 2016, 21(5), 575; https://doi.org/10.3390/molecules21050575 - 30 Apr 2016

Cited by 45 | Viewed by 7035

Abstract

Isodon rubescens has been used as a traditional green tea for more than 1000 years and many medicinal functions of I. rubescens are also very useful, such as its well-known antitumor and antibacterial activities. Oridonin, a bioactive ent-kaurane diterpenoid, is the major [...] Read more.

Isodon rubescens has been used as a traditional green tea for more than 1000 years and many medicinal functions of I. rubescens are also very useful, such as its well-known antitumor and antibacterial activities. Oridonin, a bioactive ent-kaurane diterpenoid, is the major ingredient of this medicinal tea. Herein, 22 novel oridonin derivatives were designed and synthesized. The antibacterial activity was evaluated for the first time. Compound 12 was the most promising one with MIC of 2.0 μg/mL against B. subtilis, which was nearly 3-fold stronger than positive control chloromycetin. The antiproliferative property was also assayed and compound 19 showed stronger activity than taxol. The apoptosis-inducing ability, cell cycle arrest effect at S phase and influence of mitochondrial membrane potential by 19 in CaEs-17 cancer cells were first disclosed. Based on the above results, the cell apoptosis induced by compound 19 in CaEs-17 cells was most probably involved in the intrinsic apoptotic pathway. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 1185 KiB

Open AccessArticle

Synthesis of a Cytokinin Linked by a Spacer to Dexamethasone and Biotin: Conjugates to Detect Cytokinin-Binding Proteins

by You Wang¹, David S. Letham²

, Peter C. L. John² and Ren Zhang^1,*

¹ School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia

² Research School of Biology, Australian National University, Canberra, ACT 0200, Australia

Molecules 2016, 21(5), 576; https://doi.org/10.3390/molecules21050576 - 30 Apr 2016

Cited by 7 | Viewed by 6851

Abstract

Yeast cells expressing cDNA libraries have provided two new approaches to facilitate further identification of cytokinin-binding proteins and receptors. These are the yeast three hybrid (Y3H) system and fluorescence activated cell sorting (FACS). The Y3H system requires a synthetic hybrid ligand comprising an [...] Read more.

Yeast cells expressing cDNA libraries have provided two new approaches to facilitate further identification of cytokinin-binding proteins and receptors. These are the yeast three hybrid (Y3H) system and fluorescence activated cell sorting (FACS). The Y3H system requires a synthetic hybrid ligand comprising an “anchor” moiety (e.g., dexamethasone) linked to a cytokinin via a spacer. In the yeast nucleus, this ligand by binding connects two fusion proteins leading to a reporter gene activation and detection and characterisation of cytokinin binding proteins. Herein is reported the first synthesis of dexamethasone-cytokinin ligands with a spacer linkage. This was attached to the purine ring of 6-benzylaminopurine (BAP) at positions 2, 8 or 9. To achieve this, dexamethasone was modified by periodate oxidation yielding a carboxylic group used for conjugation to the spacer by amide formation. Biotinyl derivatives of cytokinins for FACS included those synthesised by reaction of an activated ester of biotin with 8-(10-amino-decylamino) derivatives of BAP and BAP 9-riboside. Properties of the conjugates and some biological situations where they could be applicable are discussed briefly. Full article

(This article belongs to the Section Organic Chemistry)

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11 pages, 1780 KiB

Open AccessArticle

New Aspects in the Formulation of Drugs Based on Three Case Studies

by Patrick Frohberg^*, Thi Nhat Phuong Nguyen and Joachim Ulrich

Thermische Verfahrenstechnik, Zentrum für Ingenieurwissenschaften, Martin-Luther-Universität Halle-Wittenberg, Zentrum für Ingenieurwissenschaften, Halle 06099, Germany

Molecules 2016, 21(5), 577; https://doi.org/10.3390/molecules21050577 - 30 Apr 2016

Cited by 4 | Viewed by 5212

Abstract

The improvement of pharmaceutical dosage forms, such as tablets, towards drug delivery control and cost efficiency is of great importance in formulation technologies. Here, three examples: in situ coating, freeze casting and protein-based biocomposites are presented that address the above mentioned issues and [...] Read more.

The improvement of pharmaceutical dosage forms, such as tablets, towards drug delivery control and cost efficiency is of great importance in formulation technologies. Here, three examples: in situ coating, freeze casting and protein-based biocomposites are presented that address the above mentioned issues and contribute to further developments in formulation technologies. The in situ coating increases the economic efficiency by saving process steps in comparison to a conventional tableting process and provides a crystalline coating for a tailorable drug delivery rate. The freeze casting allows the control over the surface area of a drug delivery system (DDS) by providing different numbers and sizes of pores, which in conjunction with adequate additives offer an efficient instrument for drug delivery control, especially by accelerating the dissolution effect. Protein-based biocomposites are attractive materials for biomedical and pharmaceutical applications that can be applied as a polymeric DDS. They inherently combine degradability in vivo and in vitro, show a good biocompatibility, offer sites of adhesion for cells and may additionally be used to release embedded bioactive molecules. Here, a new approach regarding the incorporation of crystalline active pharmaceutical ingredients (API) into a protein matrix in one process step is presented. All three presented techniques mark decisive progress towards tailor-made drug delivery systems with respect to function, economic efficiency and the generation of additional values. Full article

(This article belongs to the Special Issue Crystallization of Pharmaceuticals)

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19 pages, 4561 KiB

Open AccessArticle

Synthesis of Thiazolo[5,4-f]quinazolin-9(8H)-ones as Multi-Target Directed Ligands of Ser/Thr Kinases

by Damien Hédou¹

, Julien Godeau¹, Nadège Loaëc^2,3, Laurent Meijer³

, Corinne Fruit¹

and Thierry Besson^1,*

¹ Normandie Univ; Uni Rouen; INSA; CNRS, COBRA, UMR 6014, 76000 Rouen, France

² Protein Phosphorylation & Human Disease group, Station Biologique, 29680 Roscoff, France

³ Manros Therapeutics, Centre de Perharidy, 29680 Roscoff, France

Molecules 2016, 21(5), 578; https://doi.org/10.3390/molecules21050578 - 30 Apr 2016

Cited by 19 | Viewed by 5917

Abstract

A library of thirty novel thiazolo[5,4-f]quinazolin-9(8H)-one derivatives belonging to four series designated as 12, 13, 14 and 15 was efficiently prepared, helped by microwave-assisted technology when required. The efficient multistep synthesis of methyl 6-amino-2-cyano- benzo[d]thiazole-7-carboxylate [...] Read more.

A library of thirty novel thiazolo[5,4-f]quinazolin-9(8H)-one derivatives belonging to four series designated as 12, 13, 14 and 15 was efficiently prepared, helped by microwave-assisted technology when required. The efficient multistep synthesis of methyl 6-amino-2-cyano- benzo[d]thiazole-7-carboxylate (1) has been reinvestigated and performed on a multigram scale. The inhibitory potency of the final products against five kinases involved in Alzheimer’s disease was evaluated. This study demonstrates that some molecules of the 12 and 13 series described in this paper are particularly promising for the development of new multi-target inhibitors of kinases. Full article

(This article belongs to the Special Issue Sulfur-Nitrogen Heteroaromatics)

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9 pages, 347 KiB

Open AccessArticle

Design, Synthesis and Evaluation of Antiproliferative Activity of New Benzimidazolehydrazones

by Valentina Onnis^1,*

, Monica Demurtas¹

, Alessandro Deplano¹

, Gianfranco Balboni¹

, Anna Baldisserotto²

, Stefano Manfredini²

, Salvatore Pacifico³

, Sandra Liekens⁴ and Jan Balzarini⁴

¹ Dipartimento di Scienze della Vita e dell’Ambiente, Sezione di Scienze Farmaceutiche, Farmacologiche e Nutraceutiche, Università degli Studi di Cagliari, Via Ospedale 72, Cagliari I-09124, Italy

² Dipartimento di Scienze della Vita e Biotecnologie, Università degli Studi di Ferrara, Via Fossato di Mortara 17-19, Ferrara I-44121, Italy

³ Dipartmento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Ferrara, Via Fossato di Mortara 17-19, Ferrara I-44121, Italy

⁴ KU Leuven—University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven B-3000, Belgium

Molecules 2016, 21(5), 579; https://doi.org/10.3390/molecules21050579 - 30 Apr 2016

Cited by 38 | Viewed by 5993

Abstract

The synthesis and antiproliferative activity of new benzimidazole derivatives bearing an hydrazone mojety at the 2-position is described. The new N′-(4-arylidene)-1H-benzo[d]imidazole-2-carbohydrazides were evaluated for their cytostatic activity toward the murine leukemia (L1210), human T-cell leukemia (CEM), human cervix [...] Read more.

The synthesis and antiproliferative activity of new benzimidazole derivatives bearing an hydrazone mojety at the 2-position is described. The new N′-(4-arylidene)-1H-benzo[d]imidazole-2-carbohydrazides were evaluated for their cytostatic activity toward the murine leukemia (L1210), human T-cell leukemia (CEM), human cervix carcinoma (HeLa) and human pancreas carcinoma cells (Mia Paca-2). A preliminary structure-activity relationship could be defined. Some of the compounds possess encouraging and consistent antiproliferative activity, having IC₅₀ values in the low micromolar range. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 3869 KiB

Open AccessReview

MRI Reporter Genes for Noninvasive Molecular Imaging

by Caixia Yang^†, Rui Tian^†, Ting Liu and Gang Liu^*

¹ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 580; https://doi.org/10.3390/molecules21050580 - 18 May 2016

Cited by 37 | Viewed by 9704

Abstract

Magnetic resonance imaging (MRI) is one of the most important imaging technologies used in clinical diagnosis. Reporter genes for MRI can be applied to accurately track the delivery of cell in cell therapy, evaluate the therapy effect of gene delivery, and monitor tissue/cell-specific [...] Read more.

Magnetic resonance imaging (MRI) is one of the most important imaging technologies used in clinical diagnosis. Reporter genes for MRI can be applied to accurately track the delivery of cell in cell therapy, evaluate the therapy effect of gene delivery, and monitor tissue/cell-specific microenvironments. Commonly used reporter genes for MRI usually include genes encoding the enzyme (e.g., tyrosinase and β-galactosidase), the receptor on the cells (e.g., transferrin receptor), and endogenous reporter genes (e.g., ferritin reporter gene). However, low sensitivity limits the application of MRI and reporter gene-based multimodal imaging strategies are common including optical imaging and radionuclide imaging. These can significantly improve diagnostic efficiency and accelerate the development of new therapies. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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13 pages, 2739 KiB

Open AccessArticle

Supported Pd-Au Membrane Reactor for Hydrogen Production: Membrane Preparation, Characterization and Testing

by Adolfo Iulianelli^1,*, Marjan Alavi^1,2, Giuseppe Bagnato¹

, Simona Liguori³, Jennifer Wilcox³, Mohammad Reza Rahimpour², Reza Eslamlouyan², Bryce Anzelmo³ and Angelo Basile^1,*

¹ Institute on Membrane Technology of the Italian National Research Council (TM-CNR), Cubo 17/C, University of Calabria, Rende 87036, Italy

² Department of Chemical Engineering, School of Chemical and Petroleum Engineering, Shiraz University, Shiraz 71345, Iran

³ Department of Energy Resources Engineering, Stanford University, Stanford 94305, CA, USA

Molecules 2016, 21(5), 581; https://doi.org/10.3390/molecules21050581 - 9 May 2016

Cited by 32 | Viewed by 6962

Abstract

A supported Pd-Au (Au 7wt%) membrane was produced by electroless plating deposition. Permeation tests were performed with pure gas (H₂, H₂, N₂, CO₂, CH₄) for long time operation. After around 400 h under [...] Read more.

A supported Pd-Au (Au 7wt%) membrane was produced by electroless plating deposition. Permeation tests were performed with pure gas (H₂, H₂, N₂, CO₂, CH₄) for long time operation. After around 400 h under testing, the composite Pd-Au membrane achieved steady state condition, with an H₂/N₂ ideal selectivity of around 500 at 420 °C and 50 kPa as transmembrane pressure, remaining stable up to 1100 h under operation. Afterwards, the membrane was allocated in a membrane reactor module for methane steam reforming reaction tests. As a preliminary application, at 420 °C, 300 kPa of reaction pressure, space velocity of 4100 h⁻¹, 40% methane conversion and 35% hydrogen recovery were reached using a commercial Ni/Al₂O₃ catalyst. Unfortunately, a severe coke deposition affected irreversibly the composite membrane, determining the loss of the hydrogen permeation characteristics of the supported Pd-Au membrane. Full article

(This article belongs to the Special Issue Membrane Catalysis)

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16 pages, 2761 KiB

Open AccessCommunication

Synthesis and Pharmacological Evaluation of Novel 1-(1,4-Alkylaryldisubstituted-4,5-dihydro-1H-imidazo)-3-substituted Urea Derivatives

by Elżbieta Szacoń^1,*, Marzena Rządkowska¹, Agnieszka A. Kaczor^1,2, Ewa Kędzierska³, Jolanta Orzelska-Górka³, Sylwia Fidecka³ and Dariusz Matosiuk^1,*

¹ Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4a Chodźki St., Lublin PL-20093, Poland

² School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, Kuopio FI-70211, Finland

³ Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodźki St., Lublin PL-20093, Poland

Molecules 2016, 21(5), 582; https://doi.org/10.3390/molecules21050582 - 30 Apr 2016

Cited by 4 | Viewed by 4834

Abstract

Novel 1-(1,4-alkylaryldisubstituted-4,5-dihydro-1H-imidazo)-3-substituted urea derivatives have been synthesized and evaluated for their central nervous system activity. Compounds 3a–m were prepared in the reaction between the respective 1-alkyl-4-aryl-4,5-dihydro-1H-imidazol-2-amines 1a–c and appropriate isocyanates 2 in dichloromethane. The compounds [...] Read more.

Novel 1-(1,4-alkylaryldisubstituted-4,5-dihydro-1H-imidazo)-3-substituted urea derivatives have been synthesized and evaluated for their central nervous system activity. Compounds 3a–m were prepared in the reaction between the respective 1-alkyl-4-aryl-4,5-dihydro-1H-imidazol-2-amines 1a–c and appropriate isocyanates 2 in dichloromethane. The compounds were subjected to in silico ADMET studies in order to select best candidates for in vivo experiments. The effects of the compounds on the spontaneous locomotor activity and amphetamine-evoked hyperactivity were estimated. Analgesic activity, without or in the presence of naloxone, was assessed in the writhing test. The tendency to change the HTR, evoked by l-5-HTP and the involvement in alteration in body temperature in mice was studied. Additionally, to check possible occurrence of drug-induced changes in the muscle relaxant activity of mice, which may have contributed to their behaviour in other tests, the rota-rod and chimney tests were performed. The new urea derivatives exerted significant activities in the performed pharmacological tests, although the presented results show a preliminary estimation, and thus, need to be extended for identification and understanding the complete pharmacological profile of the examined compounds. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 1621 KiB

Open AccessArticle

Development of Chromatographic Fingerprints of Eurycoma longifolia (Tongkat Ali) Roots Using Online Solid Phase Extraction-Liquid Chromatography (SPE-LC)

by Nor Nasriah Zaini¹, Rozita Osman¹, Hafizan Juahir² and Norashikin Saim^1,*

¹ Faculty of Applied Sciences, Universiti Teknologi MARA, Shah Alam 40450, Selangor, Malaysia

² East Coast Environmental Research Institute, Universiti Sultan Zainal Abidin, Kuala Terengganu 21300, Malaysia

Molecules 2016, 21(5), 583; https://doi.org/10.3390/molecules21050583 - 30 Apr 2016

Cited by 13 | Viewed by 7123

Abstract

E. longifolia is attracting interest due to its pharmacological properties and pro-vitality effects. In this study, an online SPE-LC approach using polystyrene divinyl benzene (PSDVB) and C18 columns was developed in obtaining chromatographic fingerprints of E. longifolia. E. longifolia root samples were [...] Read more.

E. longifolia is attracting interest due to its pharmacological properties and pro-vitality effects. In this study, an online SPE-LC approach using polystyrene divinyl benzene (PSDVB) and C18 columns was developed in obtaining chromatographic fingerprints of E. longifolia. E. longifolia root samples were extracted using pressurized liquid extraction (PLE) technique prior to online SPE-LC. The effects of mobile phase compositions and column switching time on the chromatographic fingerprint were optimized. Validation of the developed method was studied based on eurycomanone. Linearity was in the range of 5 to 50 µg∙mL⁻¹ (r² = 0.997) with 3.2% relative standard deviation of peak area. The developed method was used to analyze 14 E. longifolia root samples and 10 products (capsules). Selected chemometric techniques: cluster analysis (CA), discriminant analysis (DA), and principal component analysis (PCA) were applied to the fingerprint datasets of 37 selected peaks to evaluate the ability of the chromatographic fingerprint in classifying quality of E. longifolia. Three groups were obtained using CA. DA yielded 100% correlation coefficient with 19 discriminant compounds. Using PCA, E. longifolia root samples were clearly discriminated from the products. This study showed that the developed online SPE-LC method was able to provide comprehensive evaluation of E. longifolia samples for quality control purposes. Full article

(This article belongs to the Special Issue Selected Papers from the 6th International Conference on Natural Products for Health and Beauty (NATPRO 6))

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16 pages, 967 KiB

Open AccessFeature PaperArticle

Encapsulation of Beetroot Pomace Extract: RSM Optimization, Storage and Gastrointestinal Stability

by Vesna Tumbas Šaponjac^*, Jasna Čanadanović-Brunet, Gordana Ćetković, Mirjana Jakišić, Sonja Djilas, Jelena Vulić and Slađana Stajčić

Faculty of Technology, University of Novi Sad, Bulevar cara Lazara 1, Novi Sad 21000, Serbia

Molecules 2016, 21(5), 584; https://doi.org/10.3390/molecules21050584 - 30 Apr 2016

Cited by 93 | Viewed by 10674

Abstract

One of the great problems in food production are surplus by-products, usually utilized for feeding animals and for preparation of dietary fibre or biofuel. These products represent potential sources of bioactive antioxidants and colour-giving compounds which could be used in the pharmaceutical industry [...] Read more.

One of the great problems in food production are surplus by-products, usually utilized for feeding animals and for preparation of dietary fibre or biofuel. These products represent potential sources of bioactive antioxidants and colour-giving compounds which could be used in the pharmaceutical industry and as food additives. In the present study beetroot pomace extract was encapsulated in soy protein by a freeze drying method. Process parameters (core: wall ratio, extract concentration and mixing time) were optimized using response surface methodology (RSM) in order to obtain the optimum encapsulate (OE) with the highest polyphenol encapsulation efficiency (EE) and radical scavenging activity on DPPH radicals (SA). Using the calculated optimum conditions, the EE (86.14%) and SA (1668.37 μmol Trolox equivalents/100 g) of OE did not differ significantly (p < 0.05) from the predicted ones. The contents of total polyphenols (326.51 mg GAE/100 g), flavonoids (10.23 mg RE/100 g), and betalains (60.52 mg betanin/100 g and 61.33 mg vulgaxanthin-I/100 g), individual content of phenolic compounds and betalains by HPLC, and the ability to reduce Fe³⁺ ions, i.e., reducing power (394.95 μmol Trolox equivalents/100 g) of OE were determined as well. During three months of storage at room temperature, polyphenol retention was much higher (76.67%) than for betalain pigments, betacyanins (17.77%) and betaxanthins (17.72%). In vitro digestion and release of phenolics from OE showed higher release rate in simulated intestinal fluid than in gastric fluid. These results suggest encapsulation as a contemporary method for valorisation of sensitive bioactive compounds from food industry by-products. Full article

(This article belongs to the Special Issue New Frontiers on the Metabolism, Bioavailability and Health Effects of Phenolic Compounds)

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16 pages, 1112 KiB

Open AccessArticle

New Trends on Antineoplastic Therapy Research: Bullfrog (Rana catesbeiana Shaw) Oil Nanostructured Systems

by Lucas Amaral-Machado^1,2,3, Francisco H. Xavier-Júnior¹, Renata Rutckeviski¹, Andreza R. V. Morais¹, Éverton N. Alencar¹

, Teresa R. F. Dantas¹, Ana K. M. Cruz⁴, Julieta Genre¹, Arnóbio A. Da Silva-Junior⁵

, Matheus F. F. Pedrosa⁵, Hugo A. O. Rocha⁴ and Eryvaldo S. T. Egito^1,2,3,*

¹ Disperse Systems Laboratory (LaSiD), Pharmacy Department, Federal University of Rio Grande do Norte (UFRN), Av. General Gustavo de Cordeiro-SN-Petropolis, Natal 59012-570, Brazil

² Graduated Program in Pharmaceutical Sciences, LaSiD, UFRN, Av. General Gustavo de Cordeiro-SN-Petrópolis, Natal 59012-570, Brazil

³ Graduated Program in Health Sciences, LaSiD, UFRN, Av. General Gustavo de Cordeiro-SN-Petrópolis, Natal 59012-570, Brazil

⁴ Laboratory of Biotechnology of Natural Polymers (BIOPOL), Biochemistry Department, Federal University of Rio Grande do Norte, Av. Senador Salgado Filho-3000-Lagoa Nova, Natal 59064-741, Brazil

⁵ Pharmaceutical Technology & Biotechnology Laboratory (TecBioFar), Pharmacy Department, Federal University of Rio Grande do Norte, Av. General Gustavo de Cordeiro-SN-Petrópolis, Natal–RN 59012-570, Brazil

Molecules 2016, 21(5), 585; https://doi.org/10.3390/molecules21050585 - 30 Apr 2016

Cited by 20 | Viewed by 6968

Abstract

Bullfrog oil is a natural product extracted from the Rana catesbeiana Shaw adipose tissue and used in folk medicine for the treatment of several diseases. The aim of this study was to evaluate the extraction process of bullfrog oil, to develop a suitable [...] Read more.

Bullfrog oil is a natural product extracted from the Rana catesbeiana Shaw adipose tissue and used in folk medicine for the treatment of several diseases. The aim of this study was to evaluate the extraction process of bullfrog oil, to develop a suitable topical nanoemulsion and to evaluate its efficacy against melanoma cells. The oil samples were obtained by hot and organic solvent extraction processes and were characterized by titration techniques and gas chromatography mass spectrometry (GC-MS). The required hydrophile-lipophile balance and the pseudo-ternary phase diagram (PTPD) were assessed to determine the emulsification ability of the bullfrog oil. The anti-tumoral activity of the samples was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for normal fibroblast (3T3) and melanoma (B16F10) cell lines. Both extraction methods produced yielded around 60% and the oil was mainly composed of unsaturated compounds (around 60%). The bullfrog oil nanoemulsion obtained from PTPD presented a droplet size of about 390 nm and polydispersity = 0.05 and a zeta potential of about −25 mV. Both the bullfrog oil itself and its topical nanoemulsion did not show cytotoxicity in 3T3 linage. However, these systems showed growth inhibition in B16F10 cells. Finally, the bullfrog oil presented itself as a candidate for the development of pharmaceutical products free from cytotoxicity and effective for antineoplastic therapy. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 3781 KiB

Open AccessArticle

Soy Isoflavones Regulate Lipid Metabolism through an AKT/mTORC1 Pathway in Diet-Induced Obesity (DIO) Male Rats

by Chao Huang^1,2,†, Dejiang Pang^3,†, Qihui Luo^1,2, Xiaolin Chen^1,2, Qi Gao^1,2, Liangqin Shi^1,2, Wentao Liu^1,2, Yuanfeng Zou⁴

, Lixia Li⁴ and Zhengli Chen^1,2,*

¹ Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China

² Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China

³ Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China

⁴ Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 586; https://doi.org/10.3390/molecules21050586 - 3 May 2016

Cited by 38 | Viewed by 8019

Abstract

The pandemic tendency of obesity and its strong association with serious co-morbidities have elicited interest in the underlying mechanisms of these pathologies. Lipid homeostasis, closely involved in obesity, has been reported to be regulated by multiple pathways. mTORC1 is emerging as a critical [...] Read more.

The pandemic tendency of obesity and its strong association with serious co-morbidities have elicited interest in the underlying mechanisms of these pathologies. Lipid homeostasis, closely involved in obesity, has been reported to be regulated by multiple pathways. mTORC1 is emerging as a critical regulator of lipid metabolism. Here, we describe that the consumption of soy isoflavones, with a structural similarity to that of estradiol, could mitigate obesity through an AKT/mTORC1 pathway. Fed with soy isoflavones, the diet-induced obesity (DIO) male rats exhibited decreased body weight, accompanied with suppressed lipogenesis and adipogenesis, as well as enhanced lipolysis and β‑oxidation. The phosphorylation of AKT and S6 were decreased after soy isoflavone treatment in vivo and in vitro, suggesting an inhibition effect of soy isoflavones on mTORC1 activity. Our study reveals a potential mechanism of soy isoflavones regulating lipid homeostasis, which will be important for obesity treatment. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

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7 pages, 698 KiB

Open AccessArticle

New Cembrane-Type Diterpenoids from the South China Sea Soft Coral Sarcophyton ehrenbergi

by Gui-Hua Tang¹, Zhang-Hua Sun^1,2, Yi-Hong Zou¹ and Sheng Yin^1,*

¹ School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China

² State Key Laboratory of Applied Microbiology Southern China, Guangdong Institute of Microbiology, Guangzhou 510070, China

Molecules 2016, 21(5), 587; https://doi.org/10.3390/molecules21050587 - 4 May 2016

Cited by 11 | Viewed by 5518

Abstract

Chemical investigation on the soft coral Sarcophyton ehrenbergi collected from the Xisha Islands of the South China Sea have led to the isolation of eight cembranoids including five new ones, sarcophytonoxides A–E (1–5). The structures of new cembranoids (1–5) were determined by spectroscopic [...] Read more.

Chemical investigation on the soft coral Sarcophyton ehrenbergi collected from the Xisha Islands of the South China Sea have led to the isolation of eight cembranoids including five new ones, sarcophytonoxides A–E (1–5). The structures of new cembranoids (1–5) were determined by spectroscopic analysis and comparison of the NMR data with those of related analogues. The cytotoxicities of compounds 1–8 against human ovarian cancer cell line A2780 were also evaluated. Full article

(This article belongs to the Section Natural Products Chemistry)

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18 pages, 14859 KiB

Open AccessArticle

In Silico Investigation of Traditional Chinese Medicine for Potential Lead Compounds as SPG7 Inhibitors against Coronary Artery Disease

by Kuen-Bao Chen^1,2,3,†, Kuan-Chung Chen^4,†

, Ya-Lin Chang^1,†, Kun-Lung Chang^1,5, Pei-Chun Chang¹, Tung-Ti Chang^6,7,* and Yu-Chian Chen^1,8,9,10,*

¹ Department of Bioinformatics and Medical Engineering, Asia University, Taichung 41354, Taiwan

² School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan

³ Department of Anesthesiology, China Medical University Hospital, Taichung 40447, Taiwan

⁴ School of Pharmacy, China Medical University, Taichung 40402, Taiwan

⁵ Department of Pharmacy, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan

⁶ School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan

⁷ Department of Chinese Pediatrics, China Medical University Hospital, Taichung 40402, Taiwan

⁸ Research Center for Chinese Medicine and Acupuncture, China Medical University, Taichung 40402, Taiwan

⁹ Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan

¹⁰ Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

^† These authors contributed equally to this work.

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Molecules 2016, 21(5), 588; https://doi.org/10.3390/molecules21050588 - 5 May 2016

Cited by 7 | Viewed by 6433

Abstract

Coronary artery disease (CAD) is the most common cause of heart attack and the leading cause of mortality in the world. It is associated with mitochondrial dysfunction and increased level of reactive oxygen species production. According to the Ottawa Heart Genomics Study genome-wide [...] Read more.

Coronary artery disease (CAD) is the most common cause of heart attack and the leading cause of mortality in the world. It is associated with mitochondrial dysfunction and increased level of reactive oxygen species production. According to the Ottawa Heart Genomics Study genome-wide association study, a recent research identified that Q688 spastic paraplegia 7 (SPG7) variant is associated with CAD as it bypasses the regulation of tyrosine phosphorylation of AFG3L2 and enhances the processing and maturation of SPG7 protein. This study aims to identify potential compounds isolated from Traditional Chinese Medicines (TCMs) as potential lead compounds for paraplegin (SPG7) inhibitors. For the crystallographic structure of paraplegin, the disordered disposition of key amino acids in the binding site was predicted using the PONDR-Fit protocol before virtual screening. The TCM compounds saussureamine C and 3-(2-carboxyphenyl)-4(3H)-quinazolinone, have potential binding affinities with stable H-bonds and hydrophobic contacts with key residues of paraplegin. A molecular dynamics simulation was performed to validate the stability of the interactions between each candidate and paraplegin under dynamic conditions. Hence, we propose these compounds as potential candidates as lead drug from the compounds isolated from TCM for further study in drug development process with paraplegin protein for coronary artery disease. Full article

(This article belongs to the Special Issue Computational Design: A New Approach to Drug and Molecular Discovery)

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14 pages, 2290 KiB

Open AccessArticle

Arginase Flavonoid Anti-Leishmanial in Silico Inhibitors Flagged against Anti-Targets

by Sanja Glisic¹, Milan Sencanski¹, Vladimir Perovic¹, Strahinja Stevanovic¹ and Alfonso T. García-Sosa^2,*

¹ Center for Multidisciplinary Research, Institute of Nuclear Sciences VINCA, University of Belgrade, P.O. Box 522, 11001 Belgrade, Serbia

² Institute of Chemistry, University of Tartu, Ravila 14a, Tartu 50411, Estonia

Molecules 2016, 21(5), 589; https://doi.org/10.3390/molecules21050589 - 5 May 2016

Cited by 28 | Viewed by 7814

Abstract

Arginase, a drug target for the treatment of leishmaniasis, is involved in the biosynthesis of polyamines. Flavonoids are interesting natural compounds found in many foods and some of them may inhibit this enzyme. The MetIDB database containing 5667 compounds was screened using an [...] Read more.

Arginase, a drug target for the treatment of leishmaniasis, is involved in the biosynthesis of polyamines. Flavonoids are interesting natural compounds found in many foods and some of them may inhibit this enzyme. The MetIDB database containing 5667 compounds was screened using an EIIP/AQVN filter and 3D QSAR to find the most promising candidate compounds. In addition, these top hits were screened in silico versus human arginase and an anti-target battery consisting of cytochromes P450 2a6, 2c9, 3a4, sulfotransferase, and the pregnane-X-receptor in order to flag their possible interactions with these proteins involved in the metabolism of substances. The resulting compounds may have promise to be further developed for the treatment of leishmaniasis. Full article

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

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25 pages, 6274 KiB

Open AccessReview

The Application of Ultrasound in 3D Bio-Printing

by Yufeng Zhou

Singapore Centre for 3D Printing (SC3DP), School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798, Singapore

Molecules 2016, 21(5), 590; https://doi.org/10.3390/molecules21050590 - 5 May 2016

Cited by 35 | Viewed by 12104

Abstract

Three-dimensional (3D) bioprinting is an emerging and promising technology in tissue engineering to construct tissues and organs for implantation. Alignment of self-assembly cell spheroids that are used as bioink could be very accurate after droplet ejection from bioprinter. Complex and heterogeneous tissue structures [...] Read more.

Three-dimensional (3D) bioprinting is an emerging and promising technology in tissue engineering to construct tissues and organs for implantation. Alignment of self-assembly cell spheroids that are used as bioink could be very accurate after droplet ejection from bioprinter. Complex and heterogeneous tissue structures could be built using rapid additive manufacture technology and multiple cell lines. Effective vascularization in the engineered tissue samples is critical in any clinical application. In this review paper, the current technologies and processing steps (such as printing, preparation of bioink, cross-linking, tissue fusion and maturation) in 3D bio-printing are introduced, and their specifications are compared with each other. In addition, the application of ultrasound in this novel field is also introduced. Cells experience acoustic radiation force in ultrasound standing wave field (USWF) and then accumulate at the pressure node at low acoustic pressure. Formation of cell spheroids by this method is within minutes with uniform size and homogeneous cell distribution. Neovessel formation from USWF-induced endothelial cell spheroids is significant. Low-intensity ultrasound could enhance the proliferation and differentiation of stem cells. Its use is at low cost and compatible with current bioreactor. In summary, ultrasound application in 3D bio-printing may solve some challenges and enhance the outcomes. Full article

(This article belongs to the Special Issue Biomaterials and Bioprinting)

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15 pages, 11480 KiB

Open AccessArticle

In Silico Exploration of 1,7-Diazacarbazole Analogs as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and Molecular Dynamics Simulations

by Xiaodong Gao

, Liping Han and Yujie Ren^*

School of Chemistry and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China

Molecules 2016, 21(5), 591; https://doi.org/10.3390/molecules21050591 - 5 May 2016

Cited by 10 | Viewed by 5687

Abstract

Checkpoint kinase 1 (Chk1) is an important serine/threonine kinase with a self-protection function. The combination of Chk1 inhibitors and anti-cancer drugs can enhance the selectivity of tumor therapy. In this work, a set of 1,7-diazacarbazole analogs were identified as potent Chk1 inhibitors through [...] Read more.

Checkpoint kinase 1 (Chk1) is an important serine/threonine kinase with a self-protection function. The combination of Chk1 inhibitors and anti-cancer drugs can enhance the selectivity of tumor therapy. In this work, a set of 1,7-diazacarbazole analogs were identified as potent Chk1 inhibitors through a series of computer-aided drug design processes, including three-dimensional quantitative structure–activity relationship (3D-QSAR) modeling, molecular docking, and molecular dynamics simulations. The optimal QSAR models showed significant cross-validated correlation q² values (0.531, 0.726), fitted correlation r² coefficients (higher than 0.90), and standard error of prediction (less than 0.250). These results suggested that the developed models possess good predictive ability. Moreover, molecular docking and molecular dynamics simulations were applied to highlight the important interactions between the ligand and the Chk1 receptor protein. This study shows that hydrogen bonding and electrostatic forces are key interactions that confer bioactivity. Full article

(This article belongs to the Section Medicinal Chemistry)

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20 pages, 1163 KiB

Open AccessArticle

Developing an Absorption–Based Quality Control Method for Hu–Gan–Kang–Yuan Capsules by UFLC–QTOF–MS/MS Screening and HPLC–DAD Quantitative Determination

by Fenghuan Wei^*, Minting Chen, Chaohua Luo, Feilong Chen, Qun Shen and Zhixian Mo

College of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China

Molecules 2016, 21(5), 592; https://doi.org/10.3390/molecules21050592 - 18 May 2016

Cited by 14 | Viewed by 6433

Abstract

Traditional Chinese Medicine Preparations (TCMPs) contain massive numbers of ingredients responsible for their multiple efficacies. An absorption–based quality control method for complicated TCMPs using Hu–gan–kang–yuan Capsule (HGKYC) as an example was developed. To select proper chemical markers for quality control of HGKYC, an [...] Read more.

Traditional Chinese Medicine Preparations (TCMPs) contain massive numbers of ingredients responsible for their multiple efficacies. An absorption–based quality control method for complicated TCMPs using Hu–gan–kang–yuan Capsule (HGKYC) as an example was developed. To select proper chemical markers for quality control of HGKYC, an ultra–fast liquid chromatography (UFLC) coupled with electrospray ionization quadrupole time–off light mass spectrometry (UFLC–QTOF–MS/MS) method was used for the rapid separation and structural identification of the constituents in the HGKYC extract and the rat serum after oral administration of HGKYC. As a result, one hundred and seven prototype constituents including flavonoids, organic acid, phenylpropanoids, anthraquinones, saponins, alkaloids, terpenes, phenols and amino acids in HGKYC extract, and 43 compounds found in rat serum after oral administration of HGKYC were unambiguously identified or tentatively characterized by comparing retention times and MS information with those of authentic standards or available literature references. Finally, a simple, low–cost and effective method of simultaneous determination for baicalein, wogonin, paeonol and emodin in HGKYC was developed using high performance liquid chromatography coupled with a diode array detector. In conclusion, an absorption–based quality control pattern was developed and successfully used for evaluating HGKYC. Full article

(This article belongs to the Section Natural Products Chemistry)

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18 pages, 7146 KiB

Open AccessArticle

Predicting the Solubility of Pharmaceutical Cocrystals in Solvent/Anti-Solvent Mixtures

by Linda Lange, Stefan Heisel and Gabriele Sadowski^*

Department of Chemical and Biochemical Engineering, Laboratory of Thermodynamics, TU Dortmund University, Emil-Figge-Str. 70, D-44227 Dortmund, Germany

Molecules 2016, 21(5), 593; https://doi.org/10.3390/molecules21050593 - 7 May 2016

Cited by 35 | Viewed by 8791

Abstract

In this work, the solubilities of pharmaceutical cocrystals in solvent/anti-solvent systems were predicted using PC-SAFT in order to increase the efficiency of cocrystal formation processes. Modeling results and experimental data were compared for the cocrystal system nicotinamide/succinic acid (2:1) in the solvent/anti-solvent mixtures [...] Read more.

In this work, the solubilities of pharmaceutical cocrystals in solvent/anti-solvent systems were predicted using PC-SAFT in order to increase the efficiency of cocrystal formation processes. Modeling results and experimental data were compared for the cocrystal system nicotinamide/succinic acid (2:1) in the solvent/anti-solvent mixtures ethanol/water, ethanol/acetonitrile and ethanol/ethyl acetate at 298.15 K and in the ethanol/ethyl acetate mixture also at 310.15 K. The solubility of the investigated cocrystal slightly increased when adding small amounts of anti-solvent to the solvent, but drastically decreased for high anti-solvent amounts. Furthermore, the solubilities of nicotinamide, succinic acid and the cocrystal in the considered solvent/anti-solvent mixtures showed strong deviations from ideal-solution behavior. However, by accounting for the thermodynamic non-ideality of the components, PC-SAFT is able to predict the solubilities in all above-mentioned solvent/anti-solvent systems in good agreement with the experimental data. Full article

(This article belongs to the Special Issue Crystallization of Pharmaceuticals)

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0 pages, 1942 KiB

Open AccessArticle

RETRACTED: The Aminopyridinol Derivative BJ-1201 Protects Murine Hippocampal Cells against Glutamate-Induced Neurotoxicity via Heme Oxygenase-1

by Dong-Sung Lee¹, Tae-Gyu Nam², Byeong-Seon Jeong^3,* and Gil-Saeng Jeong^4,*

¹ College of Pharmacy, Chosun University, Dong-gu, Gwangju 61452, Korea

² Department of Pharmacy, Hanyang University, Ansan 15588, Korea

³ College of Pharmacy, Yeungnam University, Gyeongsan 38541, Korea

⁴ College of Pharmacy, Keimyung University, Daegu 42601, Korea

Molecules 2016, 21(5), 594; https://doi.org/10.3390/molecules21050594 - 5 May 2016

Cited by 2 | Viewed by 6253 | Retraction

Abstract

Glutamate is the major excitatory neurotransmitter in the brain. It can cause neuronal cell damage in the context of oxidative stress. BJ-1201 is a derivative of the compound aminopyridinol, which is known for its antioxidant activity. In this study, we examined the effect [...] Read more.

Glutamate is the major excitatory neurotransmitter in the brain. It can cause neuronal cell damage in the context of oxidative stress. BJ-1201 is a derivative of the compound aminopyridinol, which is known for its antioxidant activity. In this study, we examined the effect of BJ-1201, a 6-(diphenylamino)-2,4,5-trimethylpyridin-3-ol compound, on neuroprotection in HT22 cells. Our data showed that BJ-1201 can protect HT22 cells against glutamate-induced cell cytotoxicity. In addition, BJ-1201 upregulated heme oxygenase-1 (HO-1) to levels comparable to those of the CoPP-treated group. BJ-1201 treatment induced phosphorylation of JNK, but not p38-MAPK or ERK. It also increased the signal in the reporter assay based on β-galactosidase activity driven by the nuclear transcription factor erythroid-2 related factor 2 (Nrf2) promoter harboring antioxidant response elements (AREs) and induced the translocation of Nrf2. These results demonstrate that BJ-1201 may be a good therapeutic platform against neurodegenerative diseases induced by oxidative stress. Full article

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

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8 pages, 661 KiB

Open AccessArticle

An Aqueous Extract of Tuberaria lignosa Inhibits Cell Growth, Alters the Cell Cycle Profile, and Induces Apoptosis of NCI-H460 Tumor Cells

by Joana M. Pereira¹, Vanessa Lopes-Rodrigues^2,3,4, Cristina P. R. Xavier^2,3

, M. João Lima¹, Raquel T. Lima^2,3,5, Isabel C. F. R. Ferreira^6,*

and M. Helena Vasconcelos^1,2,3,*

¹ Department of Biological Sciences, FFUP—Faculty of Pharmacy of the University of Porto, Rua de Jorge Viterbo Ferreira 228, Porto 4050-313, Portugal

² i3S—Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal

³ Cancer Drug Resistance Group, IPATIMUP—Institute of Molecular Pathology and Immunology of the University of Porto, Porto 4200-135, Portugal

⁴ ICBAS-UP—Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto 4050-313, Portugal

⁵ Department of Pathology and Oncology, FMUP—Faculty of Medicine of the University of Porto, Alameda Prof. Hernâni Monteiro, Porto 4200-319, Portugal

⁶ Mountain Research Centre (CIMO), Polytechnic Institute of Bragança, Apartado 1172, Bragança 5301-855, Portugal

Molecules 2016, 21(5), 595; https://doi.org/10.3390/molecules21050595 - 6 May 2016

Cited by 11 | Viewed by 6024

Abstract

Tuberaria lignosa (Sweet) Samp. is found in European regions, and has antioxidant properties due to its composition in ascorbic acid and phenolic compounds. Given its traditional use and antioxidant properties, the tumor cell growth inhibitory potential of aqueous extracts from T. lignosa (prepared [...] Read more.

Tuberaria lignosa (Sweet) Samp. is found in European regions, and has antioxidant properties due to its composition in ascorbic acid and phenolic compounds. Given its traditional use and antioxidant properties, the tumor cell growth inhibitory potential of aqueous extracts from T. lignosa (prepared by infusion and decoction) was investigated in three human tumor cell lines: MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), and HCT-15 (human colorectal adenocarcinoma). Both extracts inhibited the growth of these cell lines; the most potent one being the T. lignosa extract obtained by infusion in the NCI-H460 cells (GI₅₀ of approximately 50 μg/mL). Further assays were carried out with this extract in NCI-H460 cells. At 100 μg/mL or 150 μg/mL it caused an increase in the percentage of cells in the G0/G1 phase and a decrease of cells in S phase of the cell cycle. Additionally, these concentrations caused an increase in the percentage of apoptotic cells. In agreement, a decrease in total poly (ADP-ribose) polymerase (PARP) and pro-caspase 3 levels was found. In conclusion, the T. lignosa extract obtained by infusion was more potent in NCI-H460 cells, altering the cell cycle progression and inducing apoptosis. This work highlights the importance of T. lignosa as a source of bioactive compounds with tumor cell growth inhibitory potential. Full article

(This article belongs to the Collection Bioactive Compounds)

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10 pages, 2307 KiB

Open AccessArticle

Fused 1,2,3-Dithiazoles: Convenient Synthesis, Structural Characterization, and Electrochemical Properties

by Lidia S. Konstantinova^1,2, Ilia V. Baranovsky¹, Irina G. Irtegova³, Irina Y. Bagryanskaya^3,4, Leonid A. Shundrin^3,4, Andrey V. Zibarev^3,5 and Oleg A. Rakitin^1,2,*

¹ N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russia

² Nanotechnology Education and Research Center, South Ural State University, 454080 Chelyabinsk, Russia

³ N. N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, 630090 Novosibirsk, Russia

⁴ Department of Natural Sciences, National Research University–Novosibirsk State University, 630090 Novosibirsk, Russia

⁵ Department of Chemistry, National Research University–Tomsk State University, 634050 Tomsk, Russia

Molecules 2016, 21(5), 596; https://doi.org/10.3390/molecules21050596 - 6 May 2016

Cited by 18 | Viewed by 5753

Abstract

A new general protocol for synthesis of fused 1,2,3-dithiazoles by the reaction of cyclic oximes with S₂Cl₂ and pyridine in acetonitrile has been developed. The target 1,2,3-dithiazoles fused with various carbocycles, such as indene, naphthalenone, cyclohexadienone, cyclopentadiene, and benzoannulene, were [...] Read more.

A new general protocol for synthesis of fused 1,2,3-dithiazoles by the reaction of cyclic oximes with S₂Cl₂ and pyridine in acetonitrile has been developed. The target 1,2,3-dithiazoles fused with various carbocycles, such as indene, naphthalenone, cyclohexadienone, cyclopentadiene, and benzoannulene, were selectively obtained in low to high yields. In most cases, the hetero ring-closure was accompanied by chlorination of the carbocyclic moieties. With naphthalenone derivatives, a novel dithiazole rearrangement (15→13) featuring unexpected movement of the dithiazole ring from α- to β-position, with respect to keto group, was discovered. Molecular structure of 4-chloro-5H-naphtho[1,2-d][1,2,3]dithiazol-5-one 13 was confirmed by single-crystal X-ray diffraction. Electrochemical properties of 13 were studied by cyclic voltammetry and a complex behavior was observed, most likely including hydrodechlorination at a low potential. Full article

(This article belongs to the Special Issue Sulfur-Nitrogen Heteroaromatics)

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9 pages, 1521 KiB

Open AccessArticle

In Vitro Effects of Concomitant Use of Herbal Preparations on Cytochrome P450s Involved in Clozapine Metabolism

by Wei Wang, Dan-Dan Tian and Zhang-Jin Zhang^*

School of Chinese Medicine, LKS Faculty of Medicine, the University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China

Molecules 2016, 21(5), 597; https://doi.org/10.3390/molecules21050597 - 6 May 2016

Cited by 2 | Viewed by 5229

Abstract

Herbal supplements are increasingly used in psychiatric practice. Our epidemiological study has identified several herbal preparations associated with adverse outcomes of antipsychotic therapy. In this study, we evaluated the in vitro effects of four herbal preparations—Radix Rehmanniae (RR), Fructus Schisandrae (FS), Radix [...] Read more.

Herbal supplements are increasingly used in psychiatric practice. Our epidemiological study has identified several herbal preparations associated with adverse outcomes of antipsychotic therapy. In this study, we evaluated the in vitro effects of four herbal preparations—Radix Rehmanniae (RR), Fructus Schisandrae (FS), Radix Bupleuri (RB) and Fructus Gardeniae (FG)—on cytochrome P450s (CYPs) involved in the metabolism of clozapine in human liver microsomes (HLMs) and recombinant human cytochrome P450 enzymes (rCYPs). N-desmethylclozapine and clozapine N-oxide, two major metabolites of clozapine, were measured using high-performance liquid chromatography (HPLC). FG, RR and RB showed negligible inhibitory effects in both in vitro systems, with estimated half-maximal inhibitory concentrations (IC₅₀) and apparent inhibitory constant values (K_i) greater than 1 mg/mL (raw material), suggesting that minimal metabolic interaction occurs when these preparations are used concomitantly with clozapine. The FS extract affected CYP activity with varying potency; its effect on CYP 3A4-catalyzed clozapine oxidation was relatively strong (K_i: 0.11 mg/mL). Overall, the weak-to-moderate inhibitory effect of FS on in vitro clozapine metabolism indicated its potential role in herb-drug interaction in practice. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 1897 KiB

Open AccessArticle

The Role of fadD19 and echA19 in Sterol Side Chain Degradation by Mycobacterium smegmatis

by Natalia Wrońska¹, Anna Brzostek²

, Rafał Szewczyk¹

, Adrian Soboń¹, Jarosław Dziadek^2,*

and Katarzyna Lisowska^1,*

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

² Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa Street, 93-232 Lodz, Poland

Molecules 2016, 21(5), 598; https://doi.org/10.3390/molecules21050598 - 6 May 2016

Cited by 13 | Viewed by 5683

Abstract

Mycobacteria are able to degrade natural sterols and use them as a source of carbon and energy. Several genes which play an important role in cholesterol ring degradation have been described in Mycobacterium smegmatis. However, there are limited data describing the molecular [...] Read more.

Mycobacteria are able to degrade natural sterols and use them as a source of carbon and energy. Several genes which play an important role in cholesterol ring degradation have been described in Mycobacterium smegmatis. However, there are limited data describing the molecular mechanism of the aliphatic side chain degradation by Mycobacterium spp. In this paper, we analyzed the role of the echA19 and fadD19 genes in the degradation process of the side chain of cholesterol and β-sitosterol. We demonstrated that the M. smegmatis fadD19 and echA19 genes are not essential for viability. FadD19 is required in the initial step of the biodegradation of C-24 branched sterol side chains in Mycobacterium smegmatis mc²155, but not those carrying a straight chain like cholesterol. Additionally, we have shown that echA19 is not essential in the degradation of either substrate. This is the first report, to our knowledge, on the molecular characterization of the genes playing an essential role in C-24 branched side chain sterol degradation in M. smegmatis mc²155. Full article

(This article belongs to the Section Molecular Diversity)

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9 pages, 1177 KiB

Open AccessArticle

Thermoregulated Coacervation, Metal-Encapsulation and Nanoparticle Synthesis in Novel Triazine Dendrimers

by Fermín Ramírez-Crescencio¹, Alan E. Enciso², Mirza Hasan², Viviana C. P. Da Costa², Onofrio Annunziata², Rocío Redón¹, Jeffery L. Coffer² and Eric E. Simanek^2,*

¹ Centro de Ciencias Aplicadas y Desarrollo Tecnológico, Universidad Nacional Autónoma de México, Cd. Universitaria, A.P. 70–186, C.P., Cd. Mx. 04510, Mexico

² Department of Chemistry & Biochemistry, Texas Christian University, Fort Worth, TX 76129, USA

Molecules 2016, 21(5), 599; https://doi.org/10.3390/molecules21050599 - 11 May 2016

Cited by 10 | Viewed by 6709

Abstract

The synthesis and solubility behaviors of four generation five (G5) triazine dendrimers are studied. While the underivatized cationic dendrimer is soluble in water, the acetylated and propanoylated derivatives undergo coacervation in water upon increasing temperature. Occurring around room temperature, this behavior is related [...] Read more.

The synthesis and solubility behaviors of four generation five (G5) triazine dendrimers are studied. While the underivatized cationic dendrimer is soluble in water, the acetylated and propanoylated derivatives undergo coacervation in water upon increasing temperature. Occurring around room temperature, this behavior is related to a liquid-liquid phase transition with a lower critical solution temperature (LCST) and is explained by differences in composition, notably, the hydrophobic nature of the terminal groups. Interestingly, the water solubility of the acetylated dendrimer is affected by the addition of selected metal ions. Titrating solutions of acetylated dendrimer at temperatures below the LCST with gold or palladium ions promoted precipitation, but platinum, iridium, and copper did not. Gold nanoparticles having diameters of 2.5 ± 0.8 nm can be obtained from solutions of the acetylated dendrimer at concentrations of gold less than that required to induce precipitation by treating the solution with sodium borohydride. Full article

(This article belongs to the Special Issue Functional Dendrimers)

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11 pages, 832 KiB

Open AccessArticle

Total Synthesis and Antifungal Activity of Palmarumycin CP₁₇ and Its Methoxy Analogues

by Ruina Wang¹, Guoyue Liu¹, Mingyan Yang¹, Mingan Wang^1,*

and Ligang Zhou^2,*

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

² Department of Plant Pathology, China Agricultural University, Beijing 100193, China

Molecules 2016, 21(5), 600; https://doi.org/10.3390/molecules21050600 - 7 May 2016

Cited by 15 | Viewed by 5968

Abstract

Total synthesis of naturally occurring spirobisnaphthalene palmarumycin CP₁₇ and its methoxy analogues was first achieved through Friedel-Crafts acylation, Wolff-Kishner reduction, intramolecular cyclization, ketalization, benzylic oxidation, and demethylation using the inexpensive and readily available methoxybenzene, 1,2-dimethoxybenzene and 1,4-dimethoxybenzene and 1,8-dihydroxynaphthalene as raw materials. [...] Read more.

Total synthesis of naturally occurring spirobisnaphthalene palmarumycin CP₁₇ and its methoxy analogues was first achieved through Friedel-Crafts acylation, Wolff-Kishner reduction, intramolecular cyclization, ketalization, benzylic oxidation, and demethylation using the inexpensive and readily available methoxybenzene, 1,2-dimethoxybenzene and 1,4-dimethoxybenzene and 1,8-dihydroxynaphthalene as raw materials. Demethylation with (CH₃)₃SiI at ambient temperature resulted in ring A aromatization and acetal cleavage to give rise to binaphthyl ethers. The antifungal activities of these spirobisnaphthalene derivatives were evaluated, and the results revealed that 5 and 9b exhibit EC₅₀ values of 9.34 µg/mL and 12.35 µg/mL, respectively, against P. piricola. Full article

(This article belongs to the Section Organic Chemistry)

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11 pages, 1340 KiB

Open AccessArticle

Anticancer Activity of γ-Bisabolene in Human Neuroblastoma Cells via Induction of p53-Mediated Mitochondrial Apoptosis

by Yu-Jen Jou^1,†, Chun-Hung Hua^2,†, Chen-Sheng Lin^3,†, Ching-Ying Wang¹, Lei Wan⁴

, Ying-Ju Lin⁴, Su-Hua Huang^5,* and Cheng-Wen Lin^1,5,*

¹ Department of Medical Laboratory Science and Biotechnology, China Medical University, No. 91, Hsueh-Shih Road, Taichung 404, Taiwan

² Department of Otolaryngology, China Medical University Hospital, Taichung 404, Taiwan

³ Division of Gastroenterology, Kuang Tien General Hospital, Taichung 433, Taiwan

⁴ Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung 404, Taiwan

⁵ Department of Biotechnology, College of Health Science, Asia University, Wufeng, Taichung 413, Taiwan

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 601; https://doi.org/10.3390/molecules21050601 - 7 May 2016

Cited by 22 | Viewed by 6753

Abstract

γ-Bisabolene has demonstrated antiproliferative activities against several human cancer cell lines. This study first discloses the antiproliferative and apoptosis induction activities of γ-bisabolene to human neuroblastoma TE671 cells. A CC₅₀ value of γ-bisabolene was 8.2 μM to TE671 cells. Cell cycle analysis [...] Read more.

γ-Bisabolene has demonstrated antiproliferative activities against several human cancer cell lines. This study first discloses the antiproliferative and apoptosis induction activities of γ-bisabolene to human neuroblastoma TE671 cells. A CC₅₀ value of γ-bisabolene was 8.2 μM to TE671 cells. Cell cycle analysis with PI staining showed γ-bisabolene elevating the sub-G1 fractions in a time-dependent manner. In addition, annexin V-FITC/PI staining showed γ-bisabolene significantly triggering early (annexin-V positive/PI negative) and late (annexin-V positive/PI positive) apoptosis in dose-dependent manners. γ-Bisabolene induced caspase 3/8/9 activation, intracellular ROS increase, and mitochondrial membrane potential decrease in apoptosis of human neuro-blastoma cells. Moreover, γ-bisabolene increased p53 phosphorylation and up-regulated p53-mediated apoptotic genes Bim and PUMA, as well as decreased the mRNA and protein levels of CK2α. Notably, the results indicated the involvement of CK2α-p53 pathways in mitochondria-mediated apoptosis of human neuroblastoma cells treated with γ-bisabolene. This study elucidated the apoptosis induction pathways of γ-bisabolene-treated neuroblastoma cells, in which could be useful for developing anti-neuroblastoma drugs. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 956 KiB

Open AccessArticle

Identification of New Epididymal Luminal Fluid Proteins Involved in Sperm Maturation in Infertile Rats Treated by Dutasteride Using iTRAQ

by Shu-Wu Xie^1,†, Guo-Ting Li^1,†, Li-Juan Qu^2,*, Yang Cao³, Qian Wang⁴, Jie-Yun Zhou¹, Rui-Hua Zhong¹, Xiang-Jie Guo¹ and Yan Zhu^1,*

¹ Department of Reproductive Pharmacology, Key Lab of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai 200032, China

² Department of Laboratory Medicine, Shanghai Eighth People’s Hospital, Shanghai 200233, China

³ Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200437, China

⁴ Ming Qi Natural Healthcare Center, New York, NY 10016, USA

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 602; https://doi.org/10.3390/molecules21050602 - 11 May 2016

Cited by 15 | Viewed by 6576

Abstract

Background: Spermatozoa become mature and acquire fertilizing capacity during their passage through the epididymal lumen. In this study, we identified new epididymal luminal fluid proteins involved in sperm maturation in infertile rats by dutasteride, a dual 5α-reductase inhibitor, in order to provide [...] Read more.

Background: Spermatozoa become mature and acquire fertilizing capacity during their passage through the epididymal lumen. In this study, we identified new epididymal luminal fluid proteins involved in sperm maturation in infertile rats by dutasteride, a dual 5α-reductase inhibitor, in order to provide potential epididymal targets for new contraceptives and infertility treatment. Methods: Male rats were treated with dutasteride for 28 consecutive days. We observed the protein expression profiles in the epididymal luminal fluids in infertile and normal rats using isobaric tags for relative and absolute quantitation (iTRAQ) technique. The confidence of proteome data was validated by enzyme-linked immunosorbent assays. Results: 1045 proteins were tested, and 23 of them presented different expression profiling in the infertile and normal rats. The seven proteins were down-regulated, and 16 proteins were up-regulated. Among the seven proteins which were significantly down-regulated by dutasteride in the epididymal luminal fluids, there were three β-defensins (Defb2, Defb18 and Defb39), which maybe the key proteins involved in epididymal sperm maturation and male fertility. Conclusions: We report for the first time that dutasteride influences the protein expression profiling in the epididymal luminal fluids of rats, and this result provides some new epididymal targets for male contraception and infertility therapy. Full article

(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)

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14 pages, 2704 KiB

Open AccessArticle

High-Performance Liquid Chromatography with Diode Array Detector and Electrospray Ionization Ion Trap Time-of-Flight Tandem Mass Spectrometry to Evaluate Ginseng Roots and Rhizomes from Different Regions

by Hong-Ping Wang¹, You-Bo Zhang¹, Xiu-Wei Yang^1,*, Xin-Bao Yang¹, Wei Xu¹, Feng Xu¹, Shao-Qing Cai¹, Ying-Ping Wang², Yong-Hua Xu³ and Lian-Xue Zhang³

¹ State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing 100191, China

² Institute of Special Wild Economic Animals and Plants Science, Chinese Academy of Agricultural Sciences, Changchun 130112, China

³ College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China

Molecules 2016, 21(5), 603; https://doi.org/10.3390/molecules21050603 - 9 May 2016

Cited by 29 | Viewed by 7804

Abstract

Ginseng, Panax ginseng C. A. Meyer, is an industrial crop in China and Korea. The functional components in ginseng roots and rhizomes are characteristic ginsenosides. This work developed a new high-performance liquid chromatography coupled with electrospray ionization ion trap time-of-flight multistage mass spectrometry [...] Read more.

Ginseng, Panax ginseng C. A. Meyer, is an industrial crop in China and Korea. The functional components in ginseng roots and rhizomes are characteristic ginsenosides. This work developed a new high-performance liquid chromatography coupled with electrospray ionization ion trap time-of-flight multistage mass spectrometry (LC–ESI-IT-TOF-MSⁿ) method to identify the triterpenoids. Sixty compounds (1–60) including 58 triterpenoids were identified from the ginseng cultivated in China. Substances 1, 2, 7, 15–20, 35, 39, 45–47, 49, 55–57, 59, and 60 were identified for the first time. To evaluate the quality of ginseng cultivated in Northeast China, this paper developed a practical liquid chromatography–diode array detection (LC–DAD) method to simultaneously quantify 14 interesting ginsenosides in ginseng collected from 66 different producing areas for the first time. The results showed the quality of ginseng roots and rhizomes from different sources was different due to growing environment, cultivation technology, and so on. The developed LC–ESI-IT-TOF-MSⁿ method can be used to identify many more ginsenosides and the LC–DAD method can be used not only to assess the quality of ginseng, but also to optimize the cultivation conditions for the production of ginsenosides. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

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13 pages, 4657 KiB

Open AccessArticle

Protective Effects of Dihydromyricetin against •OH-Induced Mesenchymal Stem Cells Damage and Mechanistic Chemistry

by Xican Li^1,*

, Jingjing Liu¹, Jian Lin², Tingting Wang¹, Jieyuan Huang¹, Yongqiang Lin¹ and Dongfeng Chen^2,*

¹ School of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

² School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

Molecules 2016, 21(5), 604; https://doi.org/10.3390/molecules21050604 - 9 May 2016

Cited by 37 | Viewed by 7386

Abstract

As a natural flavonoid in Ampelopsis grossedentata, dihydromyricetin (DHM, 2R,3R-3,5,7,3′,4′,5′-hexahydroxy-2,3-dihydroflavonol) was observed to increase the viability of •OH-treated mesenchymal stem cells using a MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl] assay and flow cytometry analysis. This protective effect indicates DHM may be a beneficial agent for [...] Read more.

As a natural flavonoid in Ampelopsis grossedentata, dihydromyricetin (DHM, 2R,3R-3,5,7,3′,4′,5′-hexahydroxy-2,3-dihydroflavonol) was observed to increase the viability of •OH-treated mesenchymal stem cells using a MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl] assay and flow cytometry analysis. This protective effect indicates DHM may be a beneficial agent for cell transplantation therapy. Mechanistic chemistry studies indicated that compared with myricetin, DHM was less effective at ABTS⁺• (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radical) scavenging and reducing Cu²⁺, and had higher •O₂⁻ and DPPH• (1,1-diphenyl-2-picrylhydrazyl radical) scavenging activities. Additionally, DHM could also chelate Fe²⁺ to give an absorption maximum at 589 nm. Hence, such protective effect of DHM may arise from its antioxidant activities which are thought to occur via direct radical-scavenging and Fe²⁺-chelation. Direct radical-scavenging involves an electron transfer (ET) pathway. The hydrogenation of the 2,3-double bond is hypothesized to reduce the ET process by blocking the formation of a larger π-π conjugative system. The glycosidation of the 3–OH in myricitrin is assumed to sterically hinder atom transfer in the •O₂⁻ and DPPH• radical-scavenging processes. In DHM, the Fe²⁺-chelating effect can actually be attributed to the 5,3′,4′,5′–OH and 4–C=O groups, and the 3–OH group itself can neither scavenge radicals nor chelate metal. Full article

(This article belongs to the Collection Bioactive Compounds)

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30 pages, 7058 KiB

Open AccessReview

Self-resistance in Streptomyces, with Special Reference to β-Lactam Antibiotics

by Hiroshi Ogawara^1,2

¹ HO Bio Institute, 33-9, Yushima-2, Bunkyo-ku, Tokyo 113-0034, Japan

² Department of Biochemistry, Meiji Pharmaceutical University, 522-1, Noshio-2, Kiyose, Tokyo 204-8588, Japan

Molecules 2016, 21(5), 605; https://doi.org/10.3390/molecules21050605 - 10 May 2016

Cited by 36 | Viewed by 8636

Abstract

Antibiotic resistance is one of the most serious public health problems. Among bacterial resistance, β-lactam antibiotic resistance is the most prevailing and threatening area. Antibiotic resistance is thought to originate in antibiotic-producing bacteria such as Streptomyces. In this review, β-lactamases and penicillin-binding [...] Read more.

Antibiotic resistance is one of the most serious public health problems. Among bacterial resistance, β-lactam antibiotic resistance is the most prevailing and threatening area. Antibiotic resistance is thought to originate in antibiotic-producing bacteria such as Streptomyces. In this review, β-lactamases and penicillin-binding proteins (PBPs) in Streptomyces are explored mainly by phylogenetic analyses from the viewpoint of self-resistance. Although PBPs are more important than β-lactamases in self-resistance, phylogenetically diverse β-lactamases exist in Streptomyces. While class A β-lactamases are mostly detected in their enzyme activity, over two to five times more classes B and C β-lactamase genes are identified at the whole genomic level. These genes can subsequently be transferred to pathogenic bacteria. As for PBPs, two pairs of low affinity PBPs protect Streptomyces from the attack of self-producing and other environmental β-lactam antibiotics. PBPs with PASTA domains are detectable only in class A PBPs in Actinobacteria with the exception of Streptomyces. None of the Streptomyces has PBPs with PASTA domains. However, one of class B PBPs without PASTA domain and a serine/threonine protein kinase with four PASTA domains are located in adjacent positions in most Streptomyces. These class B type PBPs are involved in the spore wall synthesizing complex and probably in self-resistance. Lastly, this paper emphasizes that the resistance mechanisms in Streptomyces are very hard to deal with, despite great efforts in finding new antibiotics. Full article

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

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7 pages, 4013 KiB

Open AccessCommunication

The Homocoupling Reaction of Aromatic Terminal Alkynes by a Highly Active Palladium(II)/AgNO₃ Cocatalyst in Aqueous Media Under Aerobic Conditions

by Mengping Guo^1,2,*

, Bo Chen^1,2, Meiyun Lv¹, Xiuling Zhou¹, Yongju Wen¹ and Xiuli Shen¹

¹ Institue of Coordination Catalysis, College of Chemistry and Bio-Engineering, Yichun University, Yichun 336000, China

² Engineering Center of Jiangxi University for Lithium Energy, Yichun University, Yichun 336000, China

Molecules 2016, 21(5), 606; https://doi.org/10.3390/molecules21050606 - 10 May 2016

Cited by 14 | Viewed by 4952

Abstract

A new and efficient Pd(II)/AgNO₃-cocatalyzed homocoupling of aromatic terminal alkynes is described. Various symmetrical 1,4-disubstituted-1,3-diynes are obtained in good to excellent yields. This protocol employs a loading with relatively low palladium(II) in aqueous media under aerobic conditions. Full article

(This article belongs to the Special Issue Palladium Catalysts 2016)

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8 pages, 618 KiB

Open AccessArticle

Lignan Glucosides from the Stem Barks of Illicium difengpi

by Zheng-Hong Pan^1,*,†, De-Sheng Ning^1,†, Si-Si Huang¹, Ling Cheng^1,2, Meng-Wen Xia^1,2, Li-Yan Peng³ and Dian-Peng Li^1,*

¹ Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, Guangxi Institute of Botany, Chinese Academy of Sciences, Guilin 541006, China

² Faculty of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming 650500, China

³ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 607; https://doi.org/10.3390/molecules21050607 - 10 May 2016

Cited by 14 | Viewed by 5067

Abstract

In this study, four new lignan glucosides, named difengpiosides A–D (1–4), were isolated from the stem barks of Illicium difengpi, together with seven known compounds 5–11. Their structures were identified on the basis of spectroscopic analyses (1D and 2D NMR, HRESIMS, CD) [...] Read more.

In this study, four new lignan glucosides, named difengpiosides A–D (1–4), were isolated from the stem barks of Illicium difengpi, together with seven known compounds 5–11. Their structures were identified on the basis of spectroscopic analyses (1D and 2D NMR, HRESIMS, CD) and a comparison with literature data. All the compounds were evaluated for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 746 KiB

Open AccessArticle

Antimicrobial Activity of Xanthohumol and Its Selected Structural Analogues

by Monika Stompor^1,2,*

and Barbara Żarowska³

¹ Department of Chemistry, University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland

² Centre for Innovative Research in Medical and Natural Sciences, Faculty of Medicine, University of Rzeszów, Warzywna 1a, 35-310 Rzeszów, Poland

³ Department of Biotechnology and Food Microbiology, University of Environmental and Life Sciences, Chełmońskiego 37/41, 51-630 Wrocław, Poland

Molecules 2016, 21(5), 608; https://doi.org/10.3390/molecules21050608 - 11 May 2016

Cited by 58 | Viewed by 8786

Abstract

The objective of this study was to evaluate the antimicrobial activity of structural analogues of xanthohumol 1, a flavonoid compound found in hops (Humulus lupulus). The agar-diffusion method using filter paper disks was applied. Biological tests performed for selected strains of [...] Read more.

The objective of this study was to evaluate the antimicrobial activity of structural analogues of xanthohumol 1, a flavonoid compound found in hops (Humulus lupulus). The agar-diffusion method using filter paper disks was applied. Biological tests performed for selected strains of Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, fungi (Alternaria sp.), and yeasts (Rhodotorula rubra, Candida albicans) revealed that compounds with at least one hydroxyl group—all of them have it at the C-4 position—demonstrated good activity. Our research showed that the strain S. aureus was more sensitive to chalcones than to the isomers in which the heterocyclic ring C is closed (flavanones). The strain R. rubra was moderately sensitive to only one compound: 4-hydroxy-4’-methoxychalcone 8. Loss of the hydroxyl group in the B-ring of 4’-methoxychalcones or its replacement by a halogen atom (−Cl, −Br), nitro group (−NO₂), ethoxy group (−OCH₂CH₃), or aliphatic substituent (−CH₃, −CH₂CH₃) resulted in the loss of antimicrobial activity towards both R. rubra yeast and S. aureus bacteria. Xanthohumol 1, naringenin 5, and chalconaringenin 7 inhibited growth of S. aureus, whereas 4-hydroxy-4′-methoxychalcone 8 was active towards two strains: S. aureus and R. rubra. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

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16 pages, 1551 KiB

Open AccessReview

Current Knowledge on the Importance of Selenium in Food for Living Organisms: A Review

by Marek Kieliszek^*

and Stanisław Błażejak

Faculty of Food Sciences, Department of Biotechnology, Microbiology and Food Evaluation, Warsaw University of Life Sciences—SGGW, Nowoursynowska 159 C, 02-776 Warsaw, Poland

Molecules 2016, 21(5), 609; https://doi.org/10.3390/molecules21050609 - 10 May 2016

Cited by 376 | Viewed by 20384

Abstract

Selenium is one of the elements classified within the group of micronutrients which are necessary in trace amounts for the proper functioning of organisms. Selenium participates in the protection of cells against excess H₂O₂, in heavy metal detoxification, and [...] Read more.

Selenium is one of the elements classified within the group of micronutrients which are necessary in trace amounts for the proper functioning of organisms. Selenium participates in the protection of cells against excess H₂O₂, in heavy metal detoxification, and regulation of the immune and reproductive systems as well. It also ensures the proper functioning of the thyroid gland. Selenium induces the occurrence of the selenoprotein synthesis process involved in the antioxidant defense mechanism of the organism. Recent years have brought much success in the studies on selenium. Anticarcinogenic properties of selenium against some cancers have been reported. Supplementation is increasingly becoming a solution to this problem. A large number of different supplementation methods are promoting studies in this area. Slight differences in the selenium content can result in excess or deficiency, therefore supplementation has to be done carefully and cautiously. Full article

(This article belongs to the Special Issue Celebrating Two Centuries of Research in Selenium Chemistry: State of the Art and New Prospectives)

15 pages, 1418 KiB

Open AccessArticle

Effect of the Algaecide Palmitoleic Acid on the Immune Function of the Bay Scallop Argopecten irradians

by Cheng Chi

, Sib Sankar Giri, Jin Woo Jun, Hyoun Joong Kim, Sang Guen Kim, Saekil Yun and Se Chang Park^*

Laboratory of Aquatic Biomedicine, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul-151742, Korea

Molecules 2016, 21(5), 610; https://doi.org/10.3390/molecules21050610 - 10 May 2016

Cited by 15 | Viewed by 5070

Abstract

Palmitoleic acid (PA), an algicidal compound, is used against the toxin producing dinofagelate Alexandrium tamarense, however, its impact on the edible bay scallop (Argopecten irradians) is still unclear. Therefore, we investigated the impacts of effective algicidal concentrations (20, 40, and [...] Read more.

Palmitoleic acid (PA), an algicidal compound, is used against the toxin producing dinofagelate Alexandrium tamarense, however, its impact on the edible bay scallop (Argopecten irradians) is still unclear. Therefore, we investigated the impacts of effective algicidal concentrations (20, 40, and 80 mg/L) of PA on immune responses in A. irradians. Various immune parameters including acid phosphatase (ACP) activity, superoxide dismutase (SOD), lysozyme, phagocytic activity, total protein, malondialdehyde (MDA) level, and reactive oxygen species (ROS) production and the expression of immune-related genes (PrxV, CLT-6, MT, and BD) were measured at 3, 6, 12, 24, and 48 h post-exposure (hpe) to PA. Lysozyme activity was lower in scallops at 12–48 hpe to 80 mg/L. SOD, ACP activity, ROS production, the total protein, and MDA level was higher at 12 to 48 hpe with different concentrations of PA. Phagocytic activity increased at 6–12 hpe to 40–80 mg/L of PA, but decreased at 24–48 hpe. The expressions of genes PrxV, CLT-6, MT and BD down-regulated at 3 hpe were observed, while differential expressions from 6–48 hpe with different concentrations of PA. The present study demonstrated that immersing A. irradians in PA at effective concentrations could result in differential effects on non-specific immune responses and expressions of immune-related genes. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 583 KiB

Open AccessArticle

Synthesis and in Vitro Antiproliferative Evaluation of C-13 Epimers of Triazolyl-d-Secoestrone Alcohols: The First Potent 13α-d-Secoestrone Derivative

by Johanna Szabó¹

, Nóra Jerkovics¹, Gyula Schneider¹, János Wölfling¹, Noémi Bózsity², Renáta Minorics², István Zupkó²

and Erzsébet Mernyák^1,*

¹ Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged H-6720, Hungary

² Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, Szeged H-6720, Hungary

Molecules 2016, 21(5), 611; https://doi.org/10.3390/molecules21050611 - 12 May 2016

Cited by 29 | Viewed by 5583

Abstract

The syntheses of C-13 epimeric 3-[(1-benzyl-1,2,3-triazol-4-yl)methoxy]-d-secoestrones are reported. Triazoles were prepared from 3-(prop-2-inyloxy)-d-secoalcohols and p-substituted benzyl azides via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The antiproliferative activities of the products and their precursors were determined in vitro against a panel [...] Read more.

The syntheses of C-13 epimeric 3-[(1-benzyl-1,2,3-triazol-4-yl)methoxy]-d-secoestrones are reported. Triazoles were prepared from 3-(prop-2-inyloxy)-d-secoalcohols and p-substituted benzyl azides via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The antiproliferative activities of the products and their precursors were determined in vitro against a panel of human adherent cervical (HeLa, SiHa and C33A), breast (MCF-7, MDA-MB-231, MDA-MB-361 and T47D) and ovarian (A2780) cell lines by means of MTT assays. The orientation of the angular methyl group and the substitution pattern of the benzyl group of the azide greatly influenced the cell growth-inhibitory potential of the compounds. The 13β derivatives generally proved to be more potent than their 13α counterparts. Introduction of a benzyltriazolylmethyl group onto the 3-OH position seemed to be advantageous. One 13α compound containing an unsubstituted benzyltriazolyl function displayed outstanding antiproliferative activities against three cell lines. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 5865 KiB

Open AccessArticle

Discovery of Potent c-MET Inhibitors with New Scaffold Having Different Quinazoline, Pyridine and Tetrahydro-Pyridothienopyrimidine Headgroups

by Yingnan Jiang, Ke Zhang, Suyu Gao, Guihua Wang, Jian Huang, Jinhui Wang^* and Lixia Chen^*

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

Molecules 2016, 21(5), 612; https://doi.org/10.3390/molecules21050612 - 11 May 2016

Cited by 9 | Viewed by 6910

Abstract

Cellular mesenchymal-epithelial transition factor (c-MET) is closely linked to human malignancies, which makes it an important target for treatment of cancer. In this study, a series of 3-methoxy-N-phenylbenzamide derivatives, N-(3-(tert-butyl)-1-phenyl-1H-pyrazol-5-yl) benzamide derivatives and N¹-(3-fluoro-4-methoxyphenyl)- [...] Read more.

Cellular mesenchymal-epithelial transition factor (c-MET) is closely linked to human malignancies, which makes it an important target for treatment of cancer. In this study, a series of 3-methoxy-N-phenylbenzamide derivatives, N-(3-(tert-butyl)-1-phenyl-1H-pyrazol-5-yl) benzamide derivatives and N¹-(3-fluoro-4-methoxyphenyl)-N³-(4-fluorophenyl) malonamide derivatives were designed and synthesized, some of them were identified as c-MET inhibitors. Among these compounds with new scaffolds having different quinazoline, pyridine and tetrahydro-pyridothienopyrimidine head groups, compound 11c, 11i, 13b, 13h exhibited both potent inhibitory activities against c-MET and high anticancer activity against tested cancer cell lines in vitro. In addition, kinase selectivity assay further demonstrated that both 13b and 13h are potent and selective c-MET inhibitors. Molecular docking supported that they bound well to c-MET and VEGFR2, which demonstrates that they are potential c-MET RTK inhibitors for cancer therapy. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 3559 KiB

Open AccessArticle

The Effect of Phenazine-1-Carboxylic Acid on the Morphological, Physiological, and Molecular Characteristics of Phellinus noxius

by Huazhi Huang^1,2, Longhua Sun², Keke Bi², Guohua Zhong¹ and Meiying Hu^1,*

¹ Key Laboratory of Natural Pesticide and Chemical Biology, College of Agriculture, South China Agricultural University, Guangzhou 510642, China

² Guangzhou Insitute of Forestry and Landscape Architecture, Guangzhou 510405, China

Molecules 2016, 21(5), 613; https://doi.org/10.3390/molecules21050613 - 11 May 2016

Cited by 30 | Viewed by 6499

Abstract

In this study, the effect of phenazine-1-carboxylic acid (PCA) on morphological, physiological, and molecular characteristics of Phellinus noxius has been investigated, and the potential antifungal mechanism of PCA against P. noxius was also explored. The results revealed that PCA showed in vitro antifungal [...] Read more.

In this study, the effect of phenazine-1-carboxylic acid (PCA) on morphological, physiological, and molecular characteristics of Phellinus noxius has been investigated, and the potential antifungal mechanism of PCA against P. noxius was also explored. The results revealed that PCA showed in vitro antifungal potential against P. noxius and completely inhibited P. noxius hyphae at concentrations >40 μg/mL. PCA inhibited both mycelial growth and the loss of mycelial biomass in vitro in a dose-dependent manner. Morphological changes in PCA-treated P. noxius hyphae, such as irregularly swollen mycelia as well as short hyphae with increased septation and less branching, were observed by optical microscopy. The intracellular reactive oxygen species (ROS) levels were significantly increased in PCA-treated P. noxius cells as compared to control groups. Induced hyperpolarization of the mitochondrial membrane potential (MMP), repressed superoxide dismutase (SOD) activity and up-regulated gene expression of seven tested genes were also found in PCA-treated P. noxius groups. Thus, the present results suggested that the mechanism of action of PCA against P. noxius might be attributed to direct damage of mycelium and high intracellular ROS production, and indirect induction of genes involved in cell detoxification, oxidation-reduction process, and electron transport of the respiratory chain. Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 4488 KiB

Open AccessArticle

Efficient Synthesis of the Lewis A Tandem Repeat

by Daisuke Kobayashi¹, Akiharu Ueki^1,2,3,*, Tomoya Yamaji¹, Kazuya Nagao¹, Akihiro Imamura¹, Hiromune Ando^1,2

, Makoto Kiso^1,2 and Hideharu Ishida^1,*

¹ Department of Applied Bioorganic Chemistry, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan

² Institute for Integrated Cell-Material Sciences (WPI Program), Kyoto University, Yoshida-ushinomiya-cho, Sakyo-ku, Kyoto-shi, Kyoto 606-8302, Japan

³ Faculty of Pharmaceutical Sciences, Aomori University, 2-3-1 Kobata, Aomori-shi, Aomori 030-0943, Japan

Molecules 2016, 21(5), 614; https://doi.org/10.3390/molecules21050614 - 11 May 2016

Cited by 5 | Viewed by 6011

Abstract

The convergent synthesis of the Lewis A (Le^a) tandem repeat is described. The Le^a tandem repeat is a carbohydrate ligand for a mannose binding protein that shows potent inhibitory activity against carcinoma growth. The Le^a unit, {β-d-Gal-(1→3)-[α- [...] Read more.

The convergent synthesis of the Lewis A (Le^a) tandem repeat is described. The Le^a tandem repeat is a carbohydrate ligand for a mannose binding protein that shows potent inhibitory activity against carcinoma growth. The Le^a unit, {β-d-Gal-(1→3)-[α-l-Fuc-(1→4)]-β-d-GlcNAc}, was synthesized by stereoselective nitrile-assisted β-galactosylation with the phenyl 3-O-allyl-2,4,6-tri-O-benzyl-1-thio-β-galactoside, and ether-assisted α-fucosylation with fucosyl (N-phenyl)trifluoroacetimidate. This common Le^a unit was easily converted to an acceptor and donor in high yields, and the stereoselective assembly of the hexasaccharide and dodecasaccharide as the Le^a tandem repeat framework was achieved by 2-trichloroacetamido-assisted β-glycosylation and the (N-phenyl)trifluoroacetimidate method. Full article

(This article belongs to the Collection Advances in Glycosciences)

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32 pages, 6867 KiB

Open AccessReview

Inhibitors of the Hydrolytic Enzyme Dimethylarginine Dimethylaminohydrolase (DDAH): Discovery, Synthesis and Development

by Rhys B. Murphy^†

, Sara Tommasi^†, Benjamin C. Lewis and Arduino A. Mangoni^*

¹ Department of Clinical Pharmacology, School of Medicine, Flinders University, Bedford Park, Adelaide 5042, Australia

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 615; https://doi.org/10.3390/molecules21050615 - 11 May 2016

Cited by 28 | Viewed by 13049

Abstract

Dimethylarginine dimethylaminohydrolase (DDAH) is a highly conserved hydrolytic enzyme found in numerous species, including bacteria, rodents, and humans. In humans, the DDAH-1 isoform is known to metabolize endogenous asymmetric dimethylarginine (ADMA) and monomethyl arginine (l-NMMA), with ADMA proposed to be a [...] Read more.

Dimethylarginine dimethylaminohydrolase (DDAH) is a highly conserved hydrolytic enzyme found in numerous species, including bacteria, rodents, and humans. In humans, the DDAH-1 isoform is known to metabolize endogenous asymmetric dimethylarginine (ADMA) and monomethyl arginine (l-NMMA), with ADMA proposed to be a putative marker of cardiovascular disease. Current literature reports identify the DDAH family of enzymes as a potential therapeutic target in the regulation of nitric oxide (NO) production, mediated via its biochemical interaction with the nitric oxide synthase (NOS) family of enzymes. Increased DDAH expression and NO production have been linked to multiple pathological conditions, specifically, cancer, neurodegenerative disorders, and septic shock. As such, the discovery, chemical synthesis, and development of DDAH inhibitors as potential drug candidates represent a growing field of interest. This review article summarizes the current knowledge on DDAH inhibition and the derived pharmacokinetic parameters of the main DDAH inhibitors reported in the literature. Furthermore, current methods of development and chemical synthetic pathways are discussed. Full article

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

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10 pages, 511 KiB

Open AccessReview

Anti-Inflammatory Applications of Melittin, a Major Component of Bee Venom: Detailed Mechanism of Action and Adverse Effects

by Gihyun Lee

and Hyunsu Bae^*

Department of Physiology, College of Korean Medicine, Kyung Hee University, 1 Hoeki-Dong, Dongdaemoon-gu, Seoul 130-701, Korea

Molecules 2016, 21(5), 616; https://doi.org/10.3390/molecules21050616 - 11 May 2016

Cited by 186 | Viewed by 23413

Abstract

Inflammation is a pervasive phenomenon triggered by the innate and adaptive immune systems to maintain homeostasis. The phenomenon normally leads to recovery from infection and healing, but when not properly phased, inflammation may cause immune disorders. Bee venom is a toxin that bees [...] Read more.

Inflammation is a pervasive phenomenon triggered by the innate and adaptive immune systems to maintain homeostasis. The phenomenon normally leads to recovery from infection and healing, but when not properly phased, inflammation may cause immune disorders. Bee venom is a toxin that bees use for their protection from enemies. However, for centuries it has been used in the Orient as an anti-inflammatory medicine for the treatment of chronic inflammatory diseases. Bee venom and its major component, melittin, are potential means of reducing excessive immune responses and provide new alternatives for the control of inflammatory diseases. Recent experimental studies show that the biological functions of melittin could be applied for therapeutic use in vitro and in vivo. Reports verifying the therapeutic effects of melittin are accumulating in the literature, but the cellular mechanism(s) of the anti-inflammatory effects of melittin are not fully elucidated. In the present study, we review the current knowledge on the therapeutic effects of melittin and its detailed mechanisms of action against several inflammatory diseases including skin inflammation, neuroinflammation, atherosclerosis, arthritis and liver inflammation, its adverse effects as well as future prospects regarding the use of melittin. Full article

(This article belongs to the Special Issue Natural Toxins)

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10 pages, 3986 KiB

Open AccessArticle

Imidazolium Ionic Liquid Functionalized Carbon Nanotubes for Improved Interfacial Charge Transfer and Simultaneous Determination of Dihydroxybenzene Isomers

by Huan Wei^1,2, Xiao-Shuai Wu^1,2, Guo-Yun Wen^1,2 and Yan Qiao^1,2,*

¹ Chongqing Key Laboratory for Advanced Materials & Technologies of Clean Energies, Southwest University, Chongqing 400715, China

² Faculty of Materials & Energy, Southwest University, Chongqing 400715, China

Molecules 2016, 21(5), 617; https://doi.org/10.3390/molecules21050617 - 14 May 2016

Cited by 22 | Viewed by 5685

Abstract

In this paper; an imidazolium ionic liquid (IL) is used to functionalize multi-walled carbon nanotubes (MWNTs) by covalent bonding on the MWNT surface. The functionalization not only provides a hydrophilic surface for ion accessibility but also prevents the aggregation of MWNTs. The IL-functionalized [...] Read more.

In this paper; an imidazolium ionic liquid (IL) is used to functionalize multi-walled carbon nanotubes (MWNTs) by covalent bonding on the MWNT surface. The functionalization not only provides a hydrophilic surface for ion accessibility but also prevents the aggregation of MWNTs. The IL-functionalized MWNTs were then applied for the electrochemical determination of the dihydroxybenzene isomers hydroquinone (HQ); catechol (CC); and resorcinol (RC), exhibiting excellent recognition ability towards the three compounds. The linear calibration ranges for HQ; CC and RC are 0.9–150 μM; 0.9–150 μM and 1.9–145 μM and the detection limits are found to be 0.15 μM for HQ; 0.10 μM for CC and 0.38 μM for RC based on S/N of 3. The proposed electrochemical sensor was also found to be useful for the determination of the dihydroxybenzene isomers in Yellow River water with reliable recovery. Full article

(This article belongs to the Special Issue Carbon Nanotubes: Advances and Applications)

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11 pages, 5055 KiB

Open AccessArticle

Preparation of Pd/Bacterial Cellulose Hybrid Nanofibers for Dopamine Detection

by Dawei Li, Kelong Ao, Qingqing Wang, Pengfei Lv and Qufu Wei^*

Key Laboratory of Eco–Textiles, Ministry of Education, Jiangnan University, Wuxi 214122, Jiang Su, China

Molecules 2016, 21(5), 618; https://doi.org/10.3390/molecules21050618 - 11 May 2016

Cited by 46 | Viewed by 7187

Abstract

Palladium nanoparticle-bacterial cellulose (PdBC) hybrid nanofibers were synthesized by in-situ chemical reduction method. The obtained PdBC nanofibers were characterized by a series of analytical techniques. The results revealed that Pd nanoparticles were evenly dispersed on the surfaces of BC nanofibers. Then, the as-prepared [...] Read more.

Palladium nanoparticle-bacterial cellulose (PdBC) hybrid nanofibers were synthesized by in-situ chemical reduction method. The obtained PdBC nanofibers were characterized by a series of analytical techniques. The results revealed that Pd nanoparticles were evenly dispersed on the surfaces of BC nanofibers. Then, the as-prepared PdBC nanofibers were mixed with laccase (Lac) and Nafion to obtain mixture suspension, which was further modified on electrode surface to construct novel biosensing platform. Finally, the prepared electrochemical biosensor was employed to detect dopamine. The analysis result was satisfactory, the sensor showed excellent electrocatalysis towards dopamine with high sensitivity (38.4 µA·mM⁻¹), low detection limit (1.26 µM), and wide linear range (5–167 µM). Moreover, the biosensor also showed good repeatability, reproducibility, selectivity and stability and was successfully used in the detection of dopamine in human urine, thus providing a promising method for dopamine analysis in clinical application. Full article

(This article belongs to the Section Bioorganic Chemistry)

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9 pages, 1008 KiB

Open AccessArticle

Identification and Synthesis of (Z,Z)-8,11-Heptadecadienyl Formate and (Z)-8-Heptadecenyl Formate: Unsaturated Aliphatic Formates Found in the Unidentified Astigmatid Mite, Sancassania sp. Sasagawa (Acari: Acaridae)

by Nobuhiro Shimizu^1,*, Daisuke Sakata¹, Honami Miyazaki¹, Yasuhiro Shimura² and Yasumasa Kuwahara^3,4

¹ Faculty of Bioenvironmental Science, Kyoto Gakuen University, 1-1 Nanjo, Sogabe, Kameoka 621-8555, Japan

² Institute of Applied Biochemistry, The University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan

³ Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan

⁴ Asano Active Enzyme Molecule Project, JST, ERATO, Imizu, Toyama 939-0398, Japan

Molecules 2016, 21(5), 619; https://doi.org/10.3390/molecules21050619 - 11 May 2016

Cited by 3 | Viewed by 4895

Abstract

We identified two aliphatic formates, (Z,Z)-8,11-heptadecadienyl formate and (Z)-8-heptadecenyl formate in the opisthonotal gland secretions of an unidentified acarid species, namely Sancassania sp. Sasagawa. Both compounds were isolated using silica gel column chromatography and the structures were [...] Read more.

We identified two aliphatic formates, (Z,Z)-8,11-heptadecadienyl formate and (Z)-8-heptadecenyl formate in the opisthonotal gland secretions of an unidentified acarid species, namely Sancassania sp. Sasagawa. Both compounds were isolated using silica gel column chromatography and the structures were elucidated by ¹H-NMR and GC/FT-IR. Further information on the double bond positions was obtained by GC-MS analysis of the corresponding dimethyl disulfide derivatives. Based on the estimated structures of the two formates and using linoleic and oleic acids as the respective starting materials, a simple four-step synthesis was achieved via Barton decarboxylation as the key step. The aliphatic formates identified in acarids thus far are neryl formate ((Z)-3,7-dimethylocta-2,6-dienyl formate) and lardolure (1,3,5,7-tetramethyldecyl formate), and both have been reported to have pheromone functions. The biological function of the two formates isolated in this study is currently being investigated. Although we can speculate that the two compounds were biosynthesized from linoleic and oleic acid, there is a possibility that the synthetic processes featured a novel chain shortening and formic acid esterification mechanism. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 1410 KiB

Open AccessArticle

Synthesis and Biological Testing of Novel Glucosylated Epigallocatechin Gallate (EGCG) Derivatives

by Xin Zhang^1,2,3, Jing Wang^1,2, Jiang-Miao Hu⁴, Ye-Wei Huang^1,2, Xiao-Yun Wu^1,2,3, Cheng-Ting Zi^1,2,3,*, Xuan-Jun Wang^1,2,3,5,* and Jun Sheng^1,2,5,*

¹ Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China

² Tea Research Center of Yunnan, Kunming 650201, China

³ Pu-er Tea Academy, Yunnan Agricultural University, Kunming 650201, China

⁴ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China

⁵ State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Kunming 650201, China

Molecules 2016, 21(5), 620; https://doi.org/10.3390/molecules21050620 - 11 May 2016

Cited by 45 | Viewed by 10177

Abstract

Epigallocatechin gallate (EGCG) is the most abundant component of green tea catechins and has strong physiological activities. In this study, two novel EGCG glycosides (EGCG-G1 and EGCG-G2) were chemoselectively synthesized by a chemical modification strategy. Each of these EGCG glycosides underwent structure identification, [...] Read more.

Epigallocatechin gallate (EGCG) is the most abundant component of green tea catechins and has strong physiological activities. In this study, two novel EGCG glycosides (EGCG-G1 and EGCG-G2) were chemoselectively synthesized by a chemical modification strategy. Each of these EGCG glycosides underwent structure identification, and the structures were assigned as follows: epigallocatechin gallate-4′′-O-β-d-glucopyranoside (EGCG-G1, 2) and epigallocatechin gallate-4′,4′′-O-β-d-gluco-pyranoside (EGCG-G2, 3). The EGCG glycosides were evaluated for their anticancer activity in vitro against two human breast cell lines (MCF-7 and MDA-MB-231) using MTT assays. The inhibition rate of EGCG glycosides (EGCG-G1 and EGCG-G2) is not obvious. The EGCG glycosides are more stable than EGCG in aqueous solutions, but exhibited decreasing antioxidant activity in the DPPH radical-scavenging assay (EGCG > EGCG-G2 > EGCG-G1). Additionally, the EGCG glycosides exhibited increased water solubility: EGCG-G2 and EGCG-G1 were 15 and 31 times as soluble EGCG, respectively. The EGCG glycosides appear to be useful, and further studies regarding their biological activity are in progress. Full article

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

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11 pages, 1476 KiB

Open AccessArticle

Antifungal Activity of Eucalyptus Oil against Rice Blast Fungi and the Possible Mechanism of Gene Expression Pattern

by Li-Jun Zhou^1,2, Fu-Rong Li¹, Li-Jie Huang¹, Zhi-Rong Yang¹, Shu Yuan^2,*

and Lin-Han Bai^1,*

¹ Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, College of Life Sciences, Sichuan University, Chengdu 610064, China

² College of Life Sciences and College of Resources, Sichuan Agricultural University, Ya’an 625000, China

Molecules 2016, 21(5), 621; https://doi.org/10.3390/molecules21050621 - 12 May 2016

Cited by 35 | Viewed by 8179

Abstract

Eucalyptus oil possesses a wide spectrum of biological activity, including anti-microbial, fungicidal, herbicidal, acaricidal and nematicidal properties. We studied anti-fungal activities of the leaf oil extracted from Eucalyptus. grandis × E. urophylla. Eleven plant pathogenic fungi were tested based on the mycelium [...] Read more.

Eucalyptus oil possesses a wide spectrum of biological activity, including anti-microbial, fungicidal, herbicidal, acaricidal and nematicidal properties. We studied anti-fungal activities of the leaf oil extracted from Eucalyptus. grandis × E. urophylla. Eleven plant pathogenic fungi were tested based on the mycelium growth rates with negative control. The results showed that Eucalyptus oil has broad-spectrum inhibitory effects toward these fungi. Remarkable morphological and structural alterations of hypha have been observed for Magnaporthe grisea after the treatment. The mRNA genome array of M. grisea was used to detect genes that were differentially expressed in the test strains treated by the Eucalyptus oil than the normal strains. The results showed 1919 genes were significantly affected, among which 1109 were down-regulated and 810 were up-regulated (p < 0.05, absolute fold change >2). According to gene ontology annotation analysis, these differentially expressed genes may cause abnormal structures and physiological function disorders, which may reduce the fungus growth. These results show the oil has potential for use in the biological control of plant disease as a green biopesticide. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 2900 KiB

Open AccessArticle

What Characteristics Confer Proteins the Ability to Induce Allergic Responses? IgE Epitope Mapping and Comparison of the Structure of Soybean 2S Albumins and Ara h 2

by Youngshin Han^1,2,*, Jing Lin¹, Ludmilla Bardina¹, Galina A. Grishina¹, Chaeyoon Lee³, Won Hee Seo^4,* and Hugh A. Sampson¹

¹ Division of Pediatric Allergy and Immunology and the Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA

² Department of Medical Science, Sungkyunkwan University School of Medicine, Seoul 06351, Korea

³ Department of Food Science and Engineering, Ewha Woman’s University, Seoul 03760, Korea

⁴ Department of Pediatrics, Korea University College of Medicine, Seoul 02841, Korea

Molecules 2016, 21(5), 622; https://doi.org/10.3390/molecules21050622 - 12 May 2016

Cited by 21 | Viewed by 8139

Abstract

Ara h 2, a peanut 2S albumin, is associated with severe allergic reactions, but a homologous protein, soybean 2S albumin, is not recognized as an important allergen. Structural difference between these proteins might explain this clinical discrepancy. Therefore, we mapped sequential epitopes and [...] Read more.

Ara h 2, a peanut 2S albumin, is associated with severe allergic reactions, but a homologous protein, soybean 2S albumin, is not recognized as an important allergen. Structural difference between these proteins might explain this clinical discrepancy. Therefore, we mapped sequential epitopes and compared the structure of Ara h 2, Soy Al 1, and Soy Al 3 (Gly m 8) to confirm whether structural differences account for the discrepancy in clinical responses to these two proteins. Commercially synthesized peptides covering the full length of Ara h 2 and two soybean 2S albumins were analyzed by peptide microarray. Sera from 10 patients with peanut and soybean allergies and seven non-atopic controls were examined. The majority of epitopes in Ara h 2 identified by microarray are consistent with those identified previously. Several regions in the 2S albumins are weakly recognized by individual sera from different patients. A comparison of allergenic epitopes on peanut and soybean proteins suggests that loop-helix type secondary structures and some amino acids with a large side chain including lone electron pair, such as arginine, glutamine, and tyrosine, makes the peptides highly recognizable by the immune system. By utilizing the peptide microarray assay, we mapped IgE epitopes of Ara h 2 and two soybean 2S albumins. The use of peptide microarray mapping and analysis of the epitope characteristics may provide critical information to access the allergenicity of food proteins. Full article

(This article belongs to the Special Issue Molecules Mediating Allergic and Autoimmune Inflammation: Commemorative Issue in Honor of Professor Christopher W. K. Lam’s Research Achievements on the Occasion of His 70th Birthday)

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15 pages, 393 KiB

Open AccessReview

Quercetin and Its Anti-Allergic Immune Response

by Jiri Mlcek^1,*, Tunde Jurikova²

, Sona Skrovankova¹ and Jiri Sochor³

¹ Department of Food Analysis and Chemistry, Faculty of Technology, Tomas Bata University in Zlín, Vavreckova 275, CZ-760 01 Zlín, Czech Republic

² Institute for Teacher Training, Faculty of Central European Studies, Constantine the Philosopher University in Nitra, Drazovska 4, SK-949 74 Nitra, Slovakia

³ Department of Viticulture and Enology, Faculty of Horticulture, Mendel University in Brno, Valticka 337, CZ-691 44 Lednice, Czech Republic

Molecules 2016, 21(5), 623; https://doi.org/10.3390/molecules21050623 - 12 May 2016

Cited by 346 | Viewed by 56824

Abstract

Quercetin is the great representative of polyphenols, flavonoids subgroup, flavonols. Its main natural sources in foods are vegetables such as onions, the most studied quercetin containing foods, and broccoli; fruits (apples, berry crops, and grapes); some herbs; tea; and wine. Quercetin is known [...] Read more.

Quercetin is the great representative of polyphenols, flavonoids subgroup, flavonols. Its main natural sources in foods are vegetables such as onions, the most studied quercetin containing foods, and broccoli; fruits (apples, berry crops, and grapes); some herbs; tea; and wine. Quercetin is known for its antioxidant activity in radical scavenging and anti-allergic properties characterized by stimulation of immune system, antiviral activity, inhibition of histamine release, decrease in pro-inflammatory cytokines, leukotrienes creation, and suppresses interleukin IL-4 production. It can improve the Th1/Th2 balance, and restrain antigen-specific IgE antibody formation. It is also effective in the inhibition of enzymes such as lipoxygenase, eosinophil and peroxidase and the suppression of inflammatory mediators. All mentioned mechanisms of action contribute to the anti-inflammatory and immunomodulating properties of quercetin that can be effectively utilized in treatment of late-phase, and late-late-phase bronchial asthma responses, allergic rhinitis and restricted peanut-induced anaphylactic reactions. Plant extract of quercetin is the main ingredient of many potential anti-allergic drugs, supplements and enriched products, which is more competent in inhibiting of IL-8 than cromolyn (anti-allergic drug disodium cromoglycate) and suppresses IL-6 and cytosolic calcium level increase. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

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13 pages, 1587 KiB

Open AccessArticle

The Mechanism by Which Amentoflavone Improves Insulin Resistance in HepG2 Cells

by Xiaoke Zheng¹, Yingying Ke¹, Aozi Feng², Peipei Yuan¹, Jing Zhou¹, Yang Yu¹, Xiaolan Wang¹ and Weisheng Feng^1,3,*

¹ School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China

² Center for Artery Atheroscerosis Research, Havana University of Medical Sciences, Havana 999075, Cuba

³ Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China

Molecules 2016, 21(5), 624; https://doi.org/10.3390/molecules21050624 - 13 May 2016

Cited by 40 | Viewed by 8309

Abstract

Background: The aim of this study was to explore the mechanism by which amentoflavone (AME) improves insulin resistance in a human hepatocellular liver carcinoma cell line (HepG2). Methods: A model of insulin resistant cells was established in HepG2 by treatment with [...] Read more.

Background: The aim of this study was to explore the mechanism by which amentoflavone (AME) improves insulin resistance in a human hepatocellular liver carcinoma cell line (HepG2). Methods: A model of insulin resistant cells was established in HepG2 by treatment with high glucose and insulin. The glucose oxidase method was used to detect the glucose consumption in each group. To determine the mechanism by which AME improves insulin resistance in HepG2 cells, enzyme-linked immunosorbent assay (ELISA) and western blotting were used to detect the expression of phosphatidyl inositol 3-kinase (PI3K), Akt, and pAkt; the activity of the enzymes involved in glucose metabolism; and the levels of inflammatory cytokines. Results: Insulin resistance was successfully induced in HepG2 cells. After treatment with AME, the glucose consumption increased significantly in HepG2 cells compared with the model group (MG). The expression of PI3K, Akt, and pAkt and the activity of 6-phosphofructokinas (PFK-1), glucokinase (GCK), and pyruvate kinase (PK) increased, while the activity of glycogen synthase kinase-3 (GSK-3), phosphoenolpyruvate carboxylase kinase (PEPCK), and glucose-6-phosphatase (G-6-Pase) as well as the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and C reactive protein (CRP) decreased. Conclusions: The mechanism by which treatment with AME improves insulin resistance in HepG2 cells may involve the PI3K-Akt signaling pathway, the processes of glucose oxygenolysis, glycogen synthesis, gluconeogenesis and inflammatory cytokine expression. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 3100 KiB

Open AccessArticle

In Vivo Anti-Cancer Mechanism of Low-Molecular-Weight Fucosylated Chondroitin Sulfate (LFCS) from Sea Cucumber Cucumaria frondosa

by Xiaoxiao Liu^1,2

, Yong Liu^1,2, Jiejie Hao^1,2, Xiaoliang Zhao^1,2, Yinzhi Lang^1,2, Fei Fan^1,2, Chao Cai^1,2, Guoyun Li^1,2, Lijuan Zhang^1,2 and Guangli Yu^1,2,*

¹ Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China

² Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, Ocean University of China, Qingdao 266003, China

Molecules 2016, 21(5), 625; https://doi.org/10.3390/molecules21050625 - 12 May 2016

Cited by 62 | Viewed by 8450

Abstract

The low-molecular-weight fucosylated chondroitin sulfate (LFCS) was prepared from native fucosylated chondroitin sulfate (FCS), which was extracted and isolated from sea cucumber Cucumaria frondosa, and the anti-cancer mechanism of LFCS on mouse Lewis lung carcinoma (LLC) was investigated. The results showed that [...] Read more.

The low-molecular-weight fucosylated chondroitin sulfate (LFCS) was prepared from native fucosylated chondroitin sulfate (FCS), which was extracted and isolated from sea cucumber Cucumaria frondosa, and the anti-cancer mechanism of LFCS on mouse Lewis lung carcinoma (LLC) was investigated. The results showed that LFCS remarkably inhibited LLC growth and metastasis in a dose-dependent manner. LFCS induced cell cycle arrest by increasing p53/p21 expression and apoptosis through activation of caspase-3 activity in LLC cells. Meanwhile, LFCS suppressed the expression of vascular endothelial growth factor (VEGF), increased the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and downregulated the matrix metalloproteinases (MMPs) level. Furthermore, LFCS significantly suppressed the activation of ERK1/2/p38 MAPK/NF-κB pathway, which played a prime role in expression of MMPs. All of these data indicate LFCS may be used as anti-cancer drug candidates and deserve further study. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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28 pages, 1166 KiB

Open AccessReview

Effects of Brassicaceae Isothiocyanates on Prostate Cancer

by Silvia Novío^1,*

, María Elena Cartea²

, Pilar Soengas², Manuel Freire-Garabal¹ and María Jesús Núñez-Iglesias¹

¹ Lennart Levi Stress and Neuroimmunology Laboratory, School of Medicine and Dentistry, University of Santiago de Compostela, c/San Francisco, s/n, 15782 Santiago de Compostela, A Coruña, Spain

² Group of Genetics, Breeding and Biochemistry of Brassicas, Misión Biológica de Galicia (CSIC) Aptdo. 28, 36080 Pontevedra, Spain

Molecules 2016, 21(5), 626; https://doi.org/10.3390/molecules21050626 - 12 May 2016

Cited by 36 | Viewed by 8089

Abstract

Despite the major progress made in the field of cancer biology, cancer is still one of the leading causes of mortality, and prostate cancer (PCa) is one of the most encountered malignancies among men. The effective management of this disease requires developing better [...] Read more.

Despite the major progress made in the field of cancer biology, cancer is still one of the leading causes of mortality, and prostate cancer (PCa) is one of the most encountered malignancies among men. The effective management of this disease requires developing better anticancer agents with greater efficacy and fewer side effects. Nature is a large source for the development of chemotherapeutic agents, with more than 50% of current anticancer drugs being of natural origin. Isothiocyanates (ITCs) are degradation products from glucosinolates that are present in members of the family Brassicaceae. Although they are known for a variety of therapeutic effects, including antioxidant, immunostimulatory, anti-inflammatory, antiviral and antibacterial properties, nowadays, cell line and animal studies have additionally indicated the chemopreventive action without causing toxic side effects of ITCs. In this way, they can induce cell cycle arrest, activate apoptosis pathways, increase the sensitivity of resistant PCa to available chemodrugs, modulate epigenetic changes and downregulate activated signaling pathways, resulting in the inhibition of cell proliferation, progression and invasion-metastasis. The present review summarizes the chemopreventive role of ITCs with a particular emphasis on specific molecular targets and epigenetic alterations in in vitro and in vivo cancer animal models. Full article

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

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35 pages, 633 KiB

Open AccessReview

Fusarium Toxins in Cereals: Occurrence, Legislation, Factors Promoting the Appearance and Their Management

by Davide Ferrigo^†

, Alessandro Raiola^†

and Roberto Causin^*

¹ Department of Land, Environment, Agriculture and Forestry, University of Padua, Campus of Agripolis, Viale Università 16, 35020 Legnaro, Padua, Italy

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 627; https://doi.org/10.3390/molecules21050627 - 13 May 2016

Cited by 274 | Viewed by 15438

Abstract

Fusarium diseases of small grain cereals and maize cause significant yield losses worldwide. Fusarium infections result in reduced grain yield and contamination with mycotoxins, some of which have a notable impact on human and animal health. Regulations on maximum limits have been established [...] Read more.

Fusarium diseases of small grain cereals and maize cause significant yield losses worldwide. Fusarium infections result in reduced grain yield and contamination with mycotoxins, some of which have a notable impact on human and animal health. Regulations on maximum limits have been established in various countries to protect consumers from the harmful effects of these mycotoxins. Several factors are involved in Fusarium disease and mycotoxin occurrence and among them environmental factors and the agronomic practices have been shown to deeply affect mycotoxin contamination in the field. In the present review particular emphasis will be placed on how environmental conditions and stress factors for the crops can affect Fusarium infection and mycotoxin production, with the aim to provide useful knowledge to develop strategies to prevent mycotoxin accumulation in cereals. Full article

(This article belongs to the Special Issue Natural Toxins)

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11 pages, 206 KiB

Open AccessReview

Adsorption of Emerging Ionizable Contaminants on Carbon Nanotubes: Advancements and Challenges

by Xingmao Ma^*

and Sarang Agarwal

Zachry Department of Civil Engineering, Texas A & M University, College Station, TX 77843, USA

Molecules 2016, 21(5), 628; https://doi.org/10.3390/molecules21050628 - 12 May 2016

Cited by 19 | Viewed by 5571

Abstract

The superior adsorption capacity of carbon nanotubes has been well recognized and there is a wealth of information in the literature concerning the adsorption of unionized organic pollutants on carbon nanotubes. Recently, the adsorption of emerging environmental pollutants, most of which are ionizable, [...] Read more.

The superior adsorption capacity of carbon nanotubes has been well recognized and there is a wealth of information in the literature concerning the adsorption of unionized organic pollutants on carbon nanotubes. Recently, the adsorption of emerging environmental pollutants, most of which are ionizable, has attracted increasing attention due to the heightened concerns about the accumulation of these emerging contaminants in the environment. These recent studies suggest that the adsorption of emerging ionizable contaminants on carbon nanotubes exhibit different characteristics than unionized ones. For example, a new charge-assisted intermolecular force has been proposed for ionizable compounds because some adsorption phenomenon cannot be easily explained by the conventional force theory. The adsorption of ionizable compounds also displayed much stronger dependence on solution pH and ionic strength than unionized compounds. This article aims to present a brief review on the current understanding of the adsorption of emerging ionizable contaminants to carbon nanotubes and discuss further research needs required to advance the mechanistic understanding of the interactions between ionizable contaminants and carbon nanotubes. Full article

(This article belongs to the Special Issue Carbon Nanotubes: Advances and Applications)

36 pages, 11736 KiB

Open AccessReview

Multivalent Carbohydrate-Lectin Interactions: How Synthetic Chemistry Enables Insights into Nanometric Recognition

by René Roy^1,*, Paul V. Murphy²

and Hans-Joachim Gabius³

¹ Pharmaqam and Nanoqam, Department of Chemistry, University du Québec à Montréal, P. O. Box 8888, Succ. Centre-Ville, Montréal, QC H3C 3P8, Canada

² School of Chemistry, National University of Ireland Galway, University Road, Galway, Ireland

³ Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Veterinärstr. 13, München 80539, Germany

Molecules 2016, 21(5), 629; https://doi.org/10.3390/molecules21050629 - 13 May 2016

Cited by 62 | Viewed by 12102

Abstract

Glycan recognition by sugar receptors (lectins) is intimately involved in many aspects of cell physiology. However, the factors explaining the exquisite selectivity of their functional pairing are not yet fully understood. Studies toward this aim will also help appraise the potential for lectin-directed [...] Read more.

Glycan recognition by sugar receptors (lectins) is intimately involved in many aspects of cell physiology. However, the factors explaining the exquisite selectivity of their functional pairing are not yet fully understood. Studies toward this aim will also help appraise the potential for lectin-directed drug design. With the network of adhesion/growth-regulatory galectins as therapeutic targets, the strategy to recruit synthetic chemistry to systematically elucidate structure-activity relationships is outlined, from monovalent compounds to glyco-clusters and glycodendrimers to biomimetic surfaces. The versatility of the synthetic procedures enables to take examining structural and spatial parameters, alone and in combination, to its limits, for example with the aim to produce inhibitors for distinct galectin(s) that exhibit minimal reactivity to other members of this group. Shaping spatial architectures similar to glycoconjugate aggregates, microdomains or vesicles provides attractive tools to disclose the often still hidden significance of nanometric aspects of the different modes of lectin design (sequence divergence at the lectin site, differences of spatial type of lectin-site presentation). Of note, testing the effectors alone or in combination simulating (patho)physiological conditions, is sure to bring about new insights into the cooperation between lectins and the regulation of their activity. Full article

(This article belongs to the Collection Advances in Glycosciences)

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13 pages, 1169 KiB

Open AccessArticle

Research on the Composition and Distribution of Organic Sulfur in Coal

by Lanjun Zhang^1,2, Zenghua Li^1,2,*, Yongliang Yang^1,2, Yinbo Zhou^1,2, Jinhu Li^1,2, Leilei Si^1,2 and Biao Kong^1,2

¹ Key Laboratory of Coal Methane and Fire Control, Ministry of Education, China University of Mining and Technology, Xuzhou 221008, China

² School of Safety Engineering, China University of Mining and Technology, Xuzhou 221116, China

Molecules 2016, 21(5), 630; https://doi.org/10.3390/molecules21050630 - 13 May 2016

Cited by 56 | Viewed by 5933

Abstract

The structure and distribution of organic sulfur in coals of different rank and different sulfur content were studied by combining mild organic solvent extraction with XPS technology. The XPS results have shown that the distribution of organic sulfur in coal is related to [...] Read more.

The structure and distribution of organic sulfur in coals of different rank and different sulfur content were studied by combining mild organic solvent extraction with XPS technology. The XPS results have shown that the distribution of organic sulfur in coal is related to the degree of metamorphism of coal. Namely, thiophenic sulfur content is reduced with decreasing metamorphic degree; sulfonic acid content rises with decreasing metamorphic degree; the contents of sulfate sulfur, sulfoxide and sulfone are rarely related with metamorphic degree. The solvent extraction and GC/MS test results have also shown that the composition and structure of free and soluble organic sulfur small molecules in coal is closely related to the metamorphic degree of coal. The free organic sulfur small molecules in coal of low metamorphic degree are mainly composed of aliphatic sulfides, while those in coal of medium and high metamorphic degree are mainly composed of thiophenes. Besides, the degree of aromatization of organic sulfur small molecules rises with increasing degree of coalification. Full article

(This article belongs to the Section Molecular Diversity)

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13 pages, 2019 KiB

Open AccessArticle

Characterization of the Principal Constituents of Danning Tablets, a Chinese Formula Consisting of Seven Herbs, by an UPLC-DAD-MS/MS Approach

by Changsen Zhan^1,2,3,4, Aizhen Xiong¹, Danping Shen^2,4, Li Yang^1,* and Zhengtao Wang^1,4,*

¹ The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

² Shanghai Hutchison Pharmaceuticals Co., Ltd., Shanghai 200331, China

³ Shanghai Engineering Research Center for Innovation of Solid Preparation of Traditional Chinese Medicine, Shanghai 200331, China

⁴ Shanghai R & D Center for Standardization of Traditional Chinese Medicines, Shanghai 201203, China

Molecules 2016, 21(5), 631; https://doi.org/10.3390/molecules21050631 - 14 May 2016

Cited by 22 | Viewed by 8156

Abstract

Danning Tablets are a traditional Chinese formula showing broad clinical applications in hepatobiliary diseases and containing a diversity of bioactive chemicals. However, the chemical profiling of the formula, which serves as the material foundation of its efficacy, is really a big challenge as [...] Read more.

Danning Tablets are a traditional Chinese formula showing broad clinical applications in hepatobiliary diseases and containing a diversity of bioactive chemicals. However, the chemical profiling of the formula, which serves as the material foundation of its efficacy, is really a big challenge as Danning Tablets consist of seven herbs from different origins. An ultra-performance liquid chromatography coupled to diode array detection and electrospray ionization mass spectrometry (UPLC-DAD-ESI-MS/MS) approach was developed to characterize the principal polyphenol constituents in the formula. As a result, a total of 32 constituents, including 14 anthraquinones and their glucosides, four anthrones, two naphthalene glycosides, two stilbenes and 10 flavonoids were identified based on their retention time, UV absorption and MS/MS fragmentation patterns. The sources of these compounds were also illustrated. Most of the bioactive anthraquinone derivatives were found in Rhei Radix et Rhizoma or Polygoni Cuspidati Rhizoma et Radix, which are the Emperor drugs in the formula for its clinic usage. These findings indicate the merit of using this integrated UPLC-DAD-ESI-MS/MS approach to rapidly illustrate the chemical foundation of complex formulas. The present study will facilitate the quality control of Danning Tablet formulas as well as the individual herbs. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 3454 KiB

Open AccessArticle

Antitumor Effect of the Mannich Base(1,3-bis-((3-Hydroxynaphthalen-2-yl)phenylmethyl)urea) on Hepatocellular Carcinoma

by Vadanasundari Vedarethinam¹, Karthik Dhanaraj¹, Soundharrajan Ilavenil², Mariadhas Valan Arasu³, Ki Choon Choi², Naif Abdullah Al-Dhabi³, Srigopalram Srisesharam², Kyung Dong Lee⁴, Da Hye Kim⁵, Tamilvenvendan Dhanapal⁶, Ravikumar Sivanesan^1,*, Han Sung Choi^7,* and Young Ock Kim^8,*

¹ Department of Biotechnology, PRIST University, Thanjavur, Tamilnadu 613-403, India

² Grassland and Forage Division, National Institute of Animal Science, Chungnam 330-808, Korea

³ Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, College of Science, King Saud University, Riyadh 11451, Saudi Arabia

⁴ Department of Oriental Medicine Materials, Dongshin University, Naju 520-714, Korea

⁵ United Graduate School of Agricultural Sciences, Tottori University, Tottori 680-8550, Japan

⁶ Department of Chemistry, National Institute of Technology, Tiruchirappalli 620-015, India

⁷ Department of Emergency Medicine, College of Medicine, Kyung Hee University, Seoul 02447, Korea

⁸ Development of Ginseng and Medical Plants Research Institute, Rural Administration, Eumseong 369-873, Korea

Molecules 2016, 21(5), 632; https://doi.org/10.3390/molecules21050632 - 14 May 2016

Cited by 10 | Viewed by 5763

Abstract

The present study was designed to evaluate the antitumor effects of the synthetic Mannich base 1,3-bis-((3-hydroxynaphthalen-2-yl)phenylmethyl)urea (1,3-BPMU) against HEP-G2 hepatoma cells and diethylnitrosamine (DEN)-induced hepatocarcinoma (HCC) in albino rats. In vitro analysis results revealed that 1,3-BPMU showed significant cytotoxicity and cell [...] Read more.

The present study was designed to evaluate the antitumor effects of the synthetic Mannich base 1,3-bis-((3-hydroxynaphthalen-2-yl)phenylmethyl)urea (1,3-BPMU) against HEP-G2 hepatoma cells and diethylnitrosamine (DEN)-induced hepatocarcinoma (HCC) in albino rats. In vitro analysis results revealed that 1,3-BPMU showed significant cytotoxicity and cell growth inhibition in HEP-G2 hepatoma cells in a concentration-dependent manner. Furthermore, flow cytometry results indicated that 1,3-BPMU enhanced early and late apoptosis. The maximum apoptosis was exhibited at a concentration of 100 μg/mL of 1,3-BPMU. In in vivo analysis, DEN treatment increased the content of nucleic acids, LPO and the activities of AST, ALT, ALP, LDH, γGT and 5’NT with decreased antioxidant activity as compared to control rats. However, 1,3-BPMU treatment to DEN-induced rats decreased the content of nucleic acids, LPO and the activities of AST, ALT, ALP, LDH, γGT and 5’NT and increased the activities of SOD, CAT, GPx, GST and GR (p < 0.05). Furthermore, 1,3-BPMU enhanced the apoptosis via upregulation of caspase-3 and caspase-9 and the downregulation of Bcl-2 and Bcl-XL mRNA expression as compared to DEN-induced rats. Histological and ultrastructural investigation showed that 1,3-BPMU treatment renovated the internal architecture of the liver in DEN-induced rats. In this study, the molecular and pre-clinical results obtained by treatment of DEN-induced rats with 1,3-BPMU suggested that 1,3-BPMU might be considered as an antitumor compound in the future. Full article

(This article belongs to the Special Issue New Approaches to Counteract Drug Resistance in Cancer)

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21 pages, 1631 KiB

Open AccessReview

Recent Developments in Solid-Phase Extraction for Near and Attenuated Total Reflection Infrared Spectroscopic Analysis

by Christian W. Huck

Institute of Analytical Chemistry and Radiochemistry, CCB-Center for Chemistry and Biomedicine, Leopold-Franzens University, Innrain 80/82, 6020 Innsbruck, Austria

Molecules 2016, 21(5), 633; https://doi.org/10.3390/molecules21050633 - 14 May 2016

Cited by 13 | Viewed by 7119

Abstract

A review with more than 100 references on the principles and recent developments in the solid-phase extraction (SPE) prior and for in situ near and attenuated total reflection (ATR) infrared spectroscopic analysis is presented. New materials, chromatographic modalities, experimental setups and configurations are [...] Read more.

A review with more than 100 references on the principles and recent developments in the solid-phase extraction (SPE) prior and for in situ near and attenuated total reflection (ATR) infrared spectroscopic analysis is presented. New materials, chromatographic modalities, experimental setups and configurations are described. Their advantages for fast sample preparation for distinct classes of compounds containing different functional groups in order to enhance selectivity and sensitivity are discussed and compared. This is the first review highlighting both the fundamentals of SPE, near and ATR spectroscopy with a view to real sample applicability and routine analysis. Most of real sample analyses examples are found in environmental research, followed by food- and bioanalysis. In this contribution a comprehensive overview of the most potent SPE-NIR and SPE-ATR approaches is summarized and provided. Full article

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

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15 pages, 1417 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Benzochromenopyrimidinones as Cholinesterase Inhibitors and Potent Antioxidant, Non-Hepatotoxic Agents for Alzheimer’s Disease

by Youssef Dgachi¹, Oscar M. Bautista-Aguilera², Mohamed Benchekroun^2,†, Hélène Martin³

, Alexandre Bonet³, Damijan Knez⁴

, Justyna Godyń⁵, Barbara Malawska⁵, Stanislav Gobec⁴, Mourad Chioua⁶, Jana Janockova⁷, Ondrej Soukup⁷, Fakher Chabchoub^1,*, José Marco-Contelles^6,* and Lhassane Ismaili^2,*

¹ Laboratory of Applied Chemistry, Heterocycles, Lipids and Polymers, Faculty of Sciences of Sfax, University of Sfax, B.P. 802, Sfax 3000, Tunisia

² Laboratoire de Chimie Organique et Thérapeutique, Neurosciences Intégratives et Cliniques, EA 481, UFR SMP, Univ. Franche-Comté, Univ. Bourgogne Franche-Comté, 19, rue Ambroise Paré, Besançon F-25000, France

³ Laboratory of Cell Toxicology, EA 4267, University of Bourgogne Franche-Comté, 19 rue Ambroise Paré, Besançon Cedex 25030, France

⁴ Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, Ljubljana 1000, Slovenia

⁵ Department of Physicochemical Drug Analysis, Jagiellonian University Medical College, Medyczna 9 Street, Krakow 30-688, Poland

⁶ Laboratory of Medicinal Chemistry (IQOG, CSIC) C/Juan de la Cierva 3, Madrid 28006, Spain

⁷ Biomedical Research Center, University Hospital Hradec Kralove, 500 05 Hradec Králove, Czech Republic

^† Present Address: Centre de Recherche de Gif-sur-Yvette, Institut de Chimie des Substances Naturelles, UPR 2301, CNRS, Avenue de la Terrasse, Gif-sur-Yvette 91198, France.

Molecules 2016, 21(5), 634; https://doi.org/10.3390/molecules21050634 - 14 May 2016

Cited by 31 | Viewed by 6983

Abstract

We report herein the straightforward two-step synthesis and biological assessment of novel racemic benzochromenopyrimidinones as non-hepatotoxic, acetylcholinesterase inhibitors with antioxidative properties. Among them, compound 3Bb displayed a mixed-type inhibition of human acetylcholinesterase (IC₅₀ = 1.28 ± 0.03 μM), good antioxidant activity, and [...] Read more.

We report herein the straightforward two-step synthesis and biological assessment of novel racemic benzochromenopyrimidinones as non-hepatotoxic, acetylcholinesterase inhibitors with antioxidative properties. Among them, compound 3Bb displayed a mixed-type inhibition of human acetylcholinesterase (IC₅₀ = 1.28 ± 0.03 μM), good antioxidant activity, and also proved to be non-hepatotoxic on human HepG2 cell line. Full article

(This article belongs to the Special Issue Molecules against Alzheimer)

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16 pages, 1246 KiB

Open AccessArticle

Mechanism of the Zn(II)Phthalocyanines’ Photochemical Reactions Depending on the Number of Substituents and Geometry

by Leandro Henrique Zucolotto Cocca¹

, Mehmet Menaf Ayhan², Ayşe Gül Gürek², Vefa Ahsen², Yann Bretonnière³, Jonathas De Paula Siqueira¹

, Fernando Gotardo¹, Cleber Renato Mendonça¹, Catherine Hirel^2,*

and Leonardo De Boni^1,*

¹ Instituto de Física de São Carlos, Universidade de São Paulo, CP 369, 13560-970 São Carlos-SP, Brazil

² Department of Chemistry, Faculty of Science, Gebze Technical University, P. O. Box 141, Gebze, 41400 Kocaeli, Turkey

³ Laboratoire de Chimie de l’ENS de Lyon, CNRS UMR 5182, Université Lyon I, ENS de Lyon, 46 allée d’Italie, 69364 Lyon cedex 07, France

Molecules 2016, 21(5), 635; https://doi.org/10.3390/molecules21050635 - 14 May 2016

Cited by 17 | Viewed by 5584

Abstract

In this work, the synthesis and the nonlinear absorption and population dynamics investigation of a series of zinc phthalocyanines (ZnPcs) dissolved in chloroform are reported. In order to determine the relevant spectroscopic parameters, such as absorption cross-sections of singlet and triplet excited states, [...] Read more.

In this work, the synthesis and the nonlinear absorption and population dynamics investigation of a series of zinc phthalocyanines (ZnPcs) dissolved in chloroform are reported. In order to determine the relevant spectroscopic parameters, such as absorption cross-sections of singlet and triplet excited states, fluorescence relaxation times, intersystem crossing, radiative decay and internal conversion, different optical and spectroscopic techniques were used. By single pulse and pulse train Z-scan techniques, respectively, singlet and triplet excited states‘ absorption cross-section were determined at 532 nm. Furthermore, the intersystem crossing time was obtained by using both techniques combined with the fluorescence lifetime determined by time-resolved fluorescence. The radiative and internal conversion rates were determined from the fluorescence quantum yield of the samples. Such spectroscopy parameters are fundamental for selecting photosensitizers used in photodynamic therapy, as well as for many other applications. Full article

(This article belongs to the Special Issue Tetrapyrrolic Macrocycles: Synthesis, Functionalization and Applications)

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7 pages, 1948 KiB

Open AccessArticle

The Suppression of Columnar π-Stacking in 3-Adamantyl-1-phenyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl

by Christos P. Constantinides^1,*, Andrey A. Berezin¹, Georgia A. Zissimou¹, Maria Manoli¹, Gregory M. Leitus² and Panayiotis A. Koutentis^1,*

¹ Department of Chemistry, University of Cyprus, P. O. Box 20537, Nicosia 1678, Cyprus

² Department of Chemical Research Support, Weizmann Institute of Science, Rehovot 76100, Israel

Molecules 2016, 21(5), 636; https://doi.org/10.3390/molecules21050636 - 14 May 2016

Cited by 18 | Viewed by 5593

Abstract

3-Adamantyl-1-phenyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl (4) crystallizes as chains of radicals where the spin bearing benzotriazinyl moieties are isolated from each other. Magnetic susceptibility studies in the 5–300 K temperature region indicate that radical 4 demonstrates typical paramagnetic behavior stemming from non-interacting S = ½ spins. Full article

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

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12 pages, 1127 KiB

Open AccessArticle

A Convenient Synthesis of 3,7′-Bisindole Derivatives

by Teng Liu¹, Hong-You Zhu², Da-Yun Luo¹, Sheng-Jiao Yan^1,* and Jun Lin^1,*

¹ Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China

² Guangdong Goodscend Pharm. Sci &Tech. Co., Ltd., Shantou 650091, China

Molecules 2016, 21(5), 638; https://doi.org/10.3390/molecules21050638 - 17 May 2016

Cited by 8 | Viewed by 5695

Abstract

An efficient and convenient method to synthesize highly functionalized 3,7′-bisindole derivatives has been developed via a Michael addition and cyclic condensation reaction of heterocyclic ketene aminals (HKAs) with 2-(1H-indol-3-yl)cyclohexa-2,5-diene-1,4-dione derivatives in ethanol-based solvents at room temperature. This strategy provides an efficient, [...] Read more.

An efficient and convenient method to synthesize highly functionalized 3,7′-bisindole derivatives has been developed via a Michael addition and cyclic condensation reaction of heterocyclic ketene aminals (HKAs) with 2-(1H-indol-3-yl)cyclohexa-2,5-diene-1,4-dione derivatives in ethanol-based solvents at room temperature. This strategy provides an efficient, environmentally friendly approach for easy access to various novel 3,7′-bisindole derivatives in moderate to good yields. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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20 pages, 3995 KiB

Open AccessArticle

In Vitro Antioxidant, Anti-Diabetes, Anti-Dementia, and Inflammation Inhibitory Effect of Trametes pubescens Fruiting Body Extracts

by Kyung Hoan Im, Trung Kien Nguyen, Jaehyuk Choi and Tae Soo Lee^*

Division of Life Sciences, Incheon National University, (Songdo-dong) 119 Academy-ro, Yeonsu-gu, Incheon 406-772, Korea

Molecules 2016, 21(5), 639; https://doi.org/10.3390/molecules21050639 - 16 May 2016

Cited by 31 | Viewed by 8260

Abstract

Trametes pubescens, white rot fungus, has been used for folk medicine in Asian countries to treat ailments such as cancer and gastrointestinal diseases. This study was initiated to evaluate the in vitro antioxidant, anti-diabetes, anti-dementia, and anti-inflammatory activities of T. pubescens [...] Read more.

Trametes pubescens, white rot fungus, has been used for folk medicine in Asian countries to treat ailments such as cancer and gastrointestinal diseases. This study was initiated to evaluate the in vitro antioxidant, anti-diabetes, anti-dementia, and anti-inflammatory activities of T. pubescens fruiting bodies. The 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging activities of T. pubescens methanol (ME) and hot water (HWE) extracts (2.0 mg/mL) were comparable to butylated hydroxytoluene (BHT), the positive control. However, the chelating effects of ME and HWE were significantly higher than that of BHT. The HWE (6 mg/mL) also showed comparable reducing power to BHT. Eleven phenol compounds were detected by high performance liquid chromatography (HPLC) analysis. The α-amylase and α-glucosidase inhibitory activities of the ME and HWE of the mushroom were lower than Acarbose, the standard reference; however, the inhibitory effects of the mushroom extracts at 2.0 mg/mL were moderate. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory effects of ME and HWE were moderate and comparable with galanthamine, the standard drug to treat early stages of Alzheimer’s disease (AD). The ME had a neuroprotective effect against glutamate-induced PC-12 cell cytotoxicity at the concentration range of 2–40 μg/mL. The mushroom extracts also showed inflammation inhibitory activities such as production of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-induced murine macrophage-like cell lines (RAW 264.7) and significantly suppressed the carrageenan-induced rat paw-edema. Therefore, fruiting body extracts of T. pubescens demonstrated antioxidant related anti-diabetes, anti-dementia and anti-inflammatory activities. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 3518 KiB

Open AccessArticle

Simultaneous Qualitative and Quantitative Analysis of Multiple Chemical Constituents in YiQiFuMai Injection by Ultra-Fast Liquid Chromatography Coupled with Ion Trap Time-of-Flight Mass Spectrometry

by Chunhua Liu^1,†

, Aichun Ju^2,†, Dazheng Zhou², Dekun Li², Junping Kou¹, Boyang Yu^1,3,*

and Jin Qi^1,*

¹ Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 211198, China

² Department of Technology Development, TianJin Tasly Pride Pharmaceutical Co., Ltd., Tianjin 300410, China

³ State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 640; https://doi.org/10.3390/molecules21050640 - 18 May 2016

Cited by 28 | Viewed by 6849

Abstract

YiQiFuMai injection (YQFM) is a modern lyophilized powder preparation derived from the traditional Chinese medicine Sheng-mai san (SMS) used for treating cardiovascular diseases, such as chronic heart failure. However, its chemical composition has not been fully elucidated, particularly for the preparation derived from [...] Read more.

YiQiFuMai injection (YQFM) is a modern lyophilized powder preparation derived from the traditional Chinese medicine Sheng-mai san (SMS) used for treating cardiovascular diseases, such as chronic heart failure. However, its chemical composition has not been fully elucidated, particularly for the preparation derived from Ophiopogon japonicus. This study aimed to establish a systematic and reliable method to quickly and simultaneously analyze the chemical constituents in YQFM by ultra-fast liquid chromatography coupled with ion trap time-of-flight mass spectrometry (UFLC-IT-TOF/MS). Sixty-five compounds in YQFM were tentatively identified by comparison with reference substances or literature data. Furthermore, twenty-one compounds, including three ophiopogonins, fifteen ginsenosides and three lignans were quantified by UFLC-IT-TOF/MS. Notably, this is the first determination of steroidal saponins from O. japonicus in YQFM. The relative standard deviations (RSDs) of intra- and inter-day precision, reproducibility and stability were <4.9% and all analytes showed good linearity (R² ≥ 0.9952) and acceptable recovery of 91.8%–104.2% (RSD ≤ 5.4%), indicating that the methods were reliable. These methods were successfully applied to quantitative analysis of ten batches of YQFM. The developed approach can provide useful and comprehensive information for quality control, further mechanistic studies in vivo and clinical application of YQFM. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 9340 KiB

Open AccessCommunication

Regioselective Benzoylation of Diols and Carbohydrates by Catalytic Amounts of Organobase

by Yuchao Lu¹, Chenxi Hou¹, Jingli Ren¹, Xiaoting Xin¹, Hengfu Xu¹, Yuxin Pei¹

, Hai Dong^2,* and Zhichao Pei^1,*

¹ Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A & F University, Yangling 712100, China

² School of Chemistry & Chemical Engineering, Huazhong University of Science & Technology, Luoyu Road 1037, Wuhan 430074, China

Molecules 2016, 21(5), 641; https://doi.org/10.3390/molecules21050641 - 17 May 2016

Cited by 16 | Viewed by 8137

Abstract

A novel metal-free organobase-catalyzed regioselective benzoylation of diols and carbohydrates has been developed. Treatment of diol and carbohydrate substrates with 1.1 equiv. of 1-benzoylimidazole and 0.2 equiv. of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in MeCN under mild conditions resulted in highly regioselective benzoylation for the primary [...] Read more.

A novel metal-free organobase-catalyzed regioselective benzoylation of diols and carbohydrates has been developed. Treatment of diol and carbohydrate substrates with 1.1 equiv. of 1-benzoylimidazole and 0.2 equiv. of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in MeCN under mild conditions resulted in highly regioselective benzoylation for the primary hydroxyl group. Importantly, compared to most commonly used protecting bulky groups for primary hydroxyl groups, the benzoyl protective group offers a new protection strategy. Full article

(This article belongs to the Section Bioorganic Chemistry)

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10 pages, 963 KiB

Open AccessArticle

A New Canthinone-Type Alkaloid Isolated from Ailanthus altissima Swingle

by Hye Mi Kim¹, Jin Su Lee², Jurdas Sezirahiga¹, Jaeyoung Kwon³, Miran Jeong², Dongho Lee³, Jung-Hye Choi^1,2 and Dae Sik Jang^1,2,*

¹ College of Pharmacy, Kyung Hee University, Seoul 130-701, Korea

² Department of Life & Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Korea

³ Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Korea

Molecules 2016, 21(5), 642; https://doi.org/10.3390/molecules21050642 - 16 May 2016

Cited by 43 | Viewed by 7662

Abstract

The present investigation of the chemical constituents of the stem barks of Ailanthus altissima has resulted in the isolation of six canthinone-type alkaloids, including a new compound, (R)-5-(1-hydroxyethyl)-canthine-6-one (1), and five known compounds (2–6). Moreover, [...] Read more.

The present investigation of the chemical constituents of the stem barks of Ailanthus altissima has resulted in the isolation of six canthinone-type alkaloids, including a new compound, (R)-5-(1-hydroxyethyl)-canthine-6-one (1), and five known compounds (2–6). Moreover, four phenyl propanoids (7–10), two lignans (11 and 12), two triterpenoids (13 and 14) and a fatty acid (15) having previously known chemical structures were isolated during the same course of this study. The structure of the new compound was elucidated by physical (m.p., [α]_D) and spectroscopic data (¹H-NMR, ¹³C-NMR, 2D NMR, and HR-DART-MS) interpretation and its absolute configuration was determined by electronic circular dichroism (ECD) data and quantum chemical calculations. The inflammatory activities of the isolates were screened on lipopolysaccharide (LPS)-induced nitric oxide (NO), a proinflammatory mediator, in RAW 264.7 cells. Among these isolated compounds, six compounds exhibited significant inhibition of NO production, with IC₅₀ values in the range of 5.92 ± 0.9 to 15.09 ± 1.8 μM. Full article

(This article belongs to the Collection Bioactive Compounds)

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16 pages, 2084 KiB

Open AccessArticle

Naturally Inspired Molecules as Multifunctional Agents for Alzheimer’s Disease Treatment

by Angela Rampa^1,*

, Andrea Tarozzi²

, Francesca Mancini¹, Letizia Pruccoli², Rita Maria Concetta Di Martino¹, Silvia Gobbi¹

, Alessandra Bisi¹

, Angela De Simone², Francesco Palomba³, Nelsi Zaccheroni³ and Federica Belluti^1,*

¹ Department of Pharmacy and Biotechnology, Alma Mater Studiorum—University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy

² Department for Life Quality Studies, Alma Mater Studiorum—University of Bologna, Corso D’Augusto 237, 47921 Rimini, Italy

³ Department of Chemistry ‘‘G. Ciamician’’, Alma Mater Studiorum—University of Bologna, Via Selmi 2, 40126 Bologna, Italy

Molecules 2016, 21(5), 643; https://doi.org/10.3390/molecules21050643 - 16 May 2016

Cited by 17 | Viewed by 6770

Abstract

Alzheimer’s disease (AD) has been defined as a multi-factorial disorder resulting from a complex array of networked cellular and molecular mechanisms. In particular, elevated levels of Aβ protein and its aggregation products in the presence of metal ions proved to be highly neurotoxic [...] Read more.

Alzheimer’s disease (AD) has been defined as a multi-factorial disorder resulting from a complex array of networked cellular and molecular mechanisms. In particular, elevated levels of Aβ protein and its aggregation products in the presence of metal ions proved to be highly neurotoxic and therapeutic strategies aimed at preventing Aβ generation and oxidative stress may represent an effective approach for AD treatment. A recent paradigm for the treatment of complex diseases such as AD suggests the employment of multifunctional compounds, single chemical entities capable of simultaneously modulating different targets involved in the pathology. In this paper, the “pharmacophores combination” strategy was applied, connecting the main scaffold of the BACE-1 ligand 1 to that of the chalcone 2, as metal chelating pharmacophore, to obtain a small library of compounds. Conjugate 5 emerged as the most interesting derivative, proving to inhibit BACE-1 with low-micromolar potency, and showing neuroprotective effects. In particular, 5 proved to be able to protect from metal-associated oxidative stress by hampering intracellular Cu²⁺-induced ROS formation without any direct neurotoxic effect. Full article

(This article belongs to the Special Issue Molecules against Alzheimer)

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20 pages, 6715 KiB

Open AccessArticle

Ethyl Acetate Abatement on Copper Catalysts Supported on Ceria Doped with Rare Earth Oxides

by Sónia Alexandra Correia Carabineiro^1,*

, Michalis Konsolakis²

, George Emmanouil-Nontas Marnellos^3,4, Muhammad Faizan Asad¹, Olívia Salomé Gonçalves Pinto Soares¹

, Pedro Bandeira Tavares⁵, Manuel Fernando Ribeiro Pereira¹

, José Joaquim de Melo Órfão¹ and José Luís Figueiredo¹

¹ Laboratório de Catálise e Materiais (LCM), Laboratório Associado LSRE-LCM, Faculdade de Engenharia, Universidade do Porto, 4200-465 Porto, Portugal

² School of Production Engineering and Management, Technical University of Crete, 73100 Chania, Greece

³ Department of Mechanical Engineering, University of Western Macedonia, GR-50100 Kozani, Greece

⁴ Chemical Process & Energy Resources Institute, Centre for Research & Technology Hellas, GR-57001 Thessaloniki, Greece

⁵ CQVR—Centro de Química–Vila Real, Departamento de Química, Universidade de Trás-os-Montes e Alto Douro, 5001-911 Vila Real, Portugal

Molecules 2016, 21(5), 644; https://doi.org/10.3390/molecules21050644 - 17 May 2016

Cited by 36 | Viewed by 7990

Abstract

Different lanthanide (Ln)-doped cerium oxides (Ce_0.5Ln_0.5O_1.75, where Ln: Gd, La, Pr, Nd, Sm) were loaded with Cu (20 wt. %) and used as catalysts for the oxidation of ethyl acetate (EtOAc), a common volatile organic compound (VOC). [...] Read more.

Different lanthanide (Ln)-doped cerium oxides (Ce_0.5Ln_0.5O_1.75, where Ln: Gd, La, Pr, Nd, Sm) were loaded with Cu (20 wt. %) and used as catalysts for the oxidation of ethyl acetate (EtOAc), a common volatile organic compound (VOC). For comparison, both Cu-free (Ce-Ln) and supported Cu (Cu/Ce-Ln) samples were characterized by N₂ adsorption at −196 °C, scanning/transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy and temperature programmed reduction in H₂. The following activity sequence, in terms of EtOAc conversion, was found for bare supports: CeO₂ ≈ Ce_0.5Pr_0.5O_1.75 > Ce_0.5Sm_0.5O_1.75 > Ce_0.5Gd_0.5O_1.75 > Ce_0.5Nd_0.5O_1.75 > Ce_0.5La_0.5O_1.75. Cu addition improved the catalytic performance, without affecting the activity order. The best catalytic performance was obtained for Cu/CeO₂ and Cu/Ce_0.5Pr_0.5O_1.75 samples, both achieving complete EtOAc conversion below ca. 290 °C. A strong correlation was revealed between the catalytic performance and the redox properties of the samples, in terms of reducibility and lattice oxygen availability. Νo particular correlation between the VOC oxidation performance and textural characteristics was found. The obtained results can be explained in terms of a Mars-van Krevelen type redox mechanism involving the participation of weakly bound (easily reduced) lattice oxygen and its consequent replenishment by gas phase oxygen. Full article

(This article belongs to the Special Issue Coinage Metal (Copper, Silver, and Gold) Catalysis)

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11 pages, 609 KiB

Open AccessReview

Finding and Producing Probiotic Glycosylases for the Biocatalysis of Ginsenosides: A Mini Review

by Seockmo Ku

Laboratory of Renewable Resources Engineering, Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907-2022, USA

Molecules 2016, 21(5), 645; https://doi.org/10.3390/molecules21050645 - 16 May 2016

Cited by 33 | Viewed by 7865

Abstract

Various microorganisms have been widely applied in nutraceutical industries for the processing of phytochemical conversion. Specifically, in the Asian food industry and academia, notable attention is paid to the biocatalytic process of ginsenosides (ginseng saponins) using probiotic bacteria that produce high levels of [...] Read more.

Various microorganisms have been widely applied in nutraceutical industries for the processing of phytochemical conversion. Specifically, in the Asian food industry and academia, notable attention is paid to the biocatalytic process of ginsenosides (ginseng saponins) using probiotic bacteria that produce high levels of glycosyl-hydrolases. Multiple groups have conducted experiments in order to determine the best conditions to produce more active and stable enzymes, which can be applicable to produce diverse types of ginsenosides for commercial applications. In this sense, there are various reviews that cover the biofunctional effects of multiple types of ginsenosides and the pathways of ginsenoside deglycosylation. However, little work has been published on the production methods of probiotic enzymes, which is a critical component of ginsenoside processing. This review aims to investigate current preparation methods, results on the discovery of new glycosylases, the application potential of probiotic enzymes and their use for biocatalysis of ginsenosides in the nutraceutical industry. Full article

(This article belongs to the Section Bioorganic Chemistry)

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18 pages, 4510 KiB

Open AccessArticle

Reversible Immobilization of Lipases on Heterofunctional Octyl-Amino Agarose Beads Prevents Enzyme Desorption

by Nazzoly Rueda^1,2,†, Tiago L. Albuquerque^1,3,†, Rocio Bartolome-Cabrero¹, Laura Fernandez-Lopez¹, Rodrigo Torres^2,‡, Claudia Ortiz⁴, Jose C. S. Dos Santos^1,3, Oveimar Barbosa⁵ and Roberto Fernandez-Lafuente^1,*

¹ Departamento de Biocatalisis, Instituto de Catálisis-CSIC; C/ Marie Curie 2, Campus UAM-CSIC, Madrid 28049, Spain

² Escuela de Química, Grupo de investigación en Bioquímica y Microbiología (GIBIM), Edificio Camilo Torres 210, Universidad Industrial de Santander, Bucaramanga 680002, Colombia

³ Departamento de Engenharia Química, Universidade Federal Do Ceará, Campus Do Pici, CEP 60455-760 Fortaleza, Brazil

⁴ Escuela de Microbiología, Universidad Industrial de Santander, Bucaramanga 680002, Colombia

⁵ Departamento de Química, Facultad de Ciencias, Universidad del Tolima, Ibagué 546, Colombia

^† These authors contributed equally to this work.

^‡ Current address: Laboratorio de Biotecnología, Instituto Colombiano del Petróleo-Ecopetrol, Piedecuesta, Bucaramanga 680012, Colombia

Molecules 2016, 21(5), 646; https://doi.org/10.3390/molecules21050646 - 16 May 2016

Cited by 69 | Viewed by 8126

Abstract

Two different heterofunctional octyl-amino supports have been prepared using ethylenediamine and hexylendiamine (OCEDA and OCHDA) and utilized to immobilize five lipases (lipases A (CALA) and B (CALB) from Candida antarctica, lipases from Thermomyces lanuginosus (TLL), from Rhizomucor miehei (RML) and from Candida [...] Read more.

Two different heterofunctional octyl-amino supports have been prepared using ethylenediamine and hexylendiamine (OCEDA and OCHDA) and utilized to immobilize five lipases (lipases A (CALA) and B (CALB) from Candida antarctica, lipases from Thermomyces lanuginosus (TLL), from Rhizomucor miehei (RML) and from Candida rugosa (CRL) and the phospholipase Lecitase Ultra (LU). Using pH 5 and 50 mM sodium acetate, the immobilizations proceeded via interfacial activation on the octyl layer, after some ionic bridges were established. These supports did not release enzyme when incubated at Triton X-100 concentrations that released all enzyme molecules from the octyl support. The octyl support produced significant enzyme hyperactivation, except for CALB. However, the activities of the immobilized enzymes were usually slightly higher using the new supports than the octyl ones. Thermal and solvent stabilities of LU and TLL were significantly improved compared to the OC counterparts, while in the other enzymes the stability decreased in most cases (depending on the pH value). As a general rule, OCEDA had lower negative effects on the stability of the immobilized enzymes than OCHDA and while in solvent inactivation the enzyme molecules remained attached to the support using the new supports and were released using monofunctional octyl supports, in thermal inactivations this only occurred in certain cases. Full article

(This article belongs to the Special Issue Enzyme Immobilization 2016)

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13 pages, 3176 KiB

Open AccessArticle

Broadband Two-Photon Absorption Characteristics of Highly Photostable Fluorenyl-Dicyanoethylenylated [60]Fullerene Dyads

by Seaho Jeon¹, Min Wang¹, Wei Ji^2,*, Loon-Seng Tan³, Thomas Cooper³ and Long Y. Chiang^1,*

¹ Department of Chemistry, Institute of Nanoscience and Engineering Technology, University of Massachusetts Lowell, Lowell, MA 01854, USA

² Department of Physics, National University of Singapore, Singapore 117542, Singapore

³ Functional Materials Division, AFRL/RXA, Air Force Research Laboratory, Wright-Patterson Air Force Base, Dayton, OH 45433, USA

Molecules 2016, 21(5), 647; https://doi.org/10.3390/molecules21050647 - 14 May 2016

Cited by 3 | Viewed by 4955

Abstract

We synthesized four C₆₀-(light-harvesting antenna) dyads C₆₀ (>CPAF-C_n) (n = 4, 9, 12, or 18) 1-C_n for the investigation of their broadband nonlinear absorption effect. Since we have previously demonstrated their high function as two-photon [...] Read more.

We synthesized four C₆₀-(light-harvesting antenna) dyads C₆₀ (>CPAF-C_n) (n = 4, 9, 12, or 18) 1-C_n for the investigation of their broadband nonlinear absorption effect. Since we have previously demonstrated their high function as two-photon absorption (2PA) materials at 1000 nm, a different 2PA wavelength of 780 nm was applied in the study. The combined data taken at two different wavelength ranges substantiated the broadband characteristics of 1-C_n. We proposed that the observed broadband absorptions may be attributed by a partial π-conjugation between the C₆₀ > cage and CPAF-C_n moieties, via endinitrile tautomeric resonance, giving a resonance state with enhanced molecular conjugation. This transient state could increase its 2PA and excited-state absorption at 800 nm. In addition, a trend of concentration-dependent 2PA cross-section (σ₂ ) and excited-state absorption magnitude was detected showing a higher σ value at a lower concentration that was correlated to increasing molecular separation with less aggregation for dyads C₆₀(>CPAF-C₁₈) and C₆₀(>CPAF-C₉), as better 2PA and excited-state absorbers. Full article

(This article belongs to the Special Issue Fullerene and the Related Curved-pi Materials Chemistry)

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9 pages, 1942 KiB

Open AccessArticle

Regioselective Palmitoylation of 9-(2,3-Dihydroxy- propyl)adenine Catalyzed by a Glycopolymer-enzyme Conjugate

by Jana Brabcová¹, Jiří Blažek¹, Marcela Krečmerová¹

, Jiří Vondrášek¹, Jose M. Palomo^2,*

and Marie Zarevúcka^1,*

¹ Institute of Organic Chemistry and Biochemistry, AS CR, Flemingovo nám. 2, Prague 6, Czech Republic

² Departamento de Biocatálisis, Instituto de Catálisis (CSIC) Campus UAM Cantoblanco, Madrid 28049, Spain

Molecules 2016, 21(5), 648; https://doi.org/10.3390/molecules21050648 - 16 May 2016

Cited by 3 | Viewed by 5660

Abstract

The enzymatic regioselective monopalmitoylation of racemic 9-(2,3-dihydroxypropyl)- adenine (DHPA), an approved antiviral agent, has been performed by an immobilized form of Candida antarctica B lipase (CAL-B) using a 4:1 DMF/hexane mixture as the reaction medium. To improve the chemical yield of the desired [...] Read more.

The enzymatic regioselective monopalmitoylation of racemic 9-(2,3-dihydroxypropyl)- adenine (DHPA), an approved antiviral agent, has been performed by an immobilized form of Candida antarctica B lipase (CAL-B) using a 4:1 DMF/hexane mixture as the reaction medium. To improve the chemical yield of the desired monopalmitoylation reaction, solid-phase chemical modifications of the lipase were evaluated. The reaction yield was successfully increased obtaining 100% product after a second treatment of the product solution with fresh immobilised chemically glycosylated-CAL-B. Full article

(This article belongs to the Special Issue Biomolecules Modification)

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15 pages, 1802 KiB

Open AccessArticle

MASM, a Matrine Derivative, Offers Radioprotection by Modulating Lethal Total-Body Irradiation-Induced Multiple Signaling Pathways in Wistar Rats

by Jianzhong Li^1,*, Jing Xu^1,2, Yiming Lu¹, Lei Qiu¹, Weiheng Xu¹, Bin Lu¹, Zhenlin Hu¹, Zhiyong Chu³, Yifeng Chai¹ and Junping Zhang^1,*

¹ School of Pharmacy, Second Military Medical University, Shanghai 200433, China

² Department of Pharmacy, East Hospital, Dongji University, Shanghai 200085, China

³ The Naval Medical Research Institute, Shanghai 200433, China

Molecules 2016, 21(5), 649; https://doi.org/10.3390/molecules21050649 - 17 May 2016

Cited by 17 | Viewed by 6302

Abstract

Matrine is an alkaloid extracted from Sophora flavescens Ait and has many biological activities, such as anti-inflammatory, antitumor, anti-fibrosis, and immunosuppressive properties. In our previous studies, the matrine derivative MASM was synthesized and exhibited potent inhibitory activity against liver fibrosis. In this study, [...] Read more.

Matrine is an alkaloid extracted from Sophora flavescens Ait and has many biological activities, such as anti-inflammatory, antitumor, anti-fibrosis, and immunosuppressive properties. In our previous studies, the matrine derivative MASM was synthesized and exhibited potent inhibitory activity against liver fibrosis. In this study, we mainly investigated its protection against lethal total-body irradiation (TBI) in rats. Administration of MASM reduced the radiation sickness characteristics and increased the 30-day survival of rats before or after lethal TBI. Ultrastructural observation illustrated that pretreatment of rats with MASM significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed that pretreatment with MASM had a dramatic effect on gene expression changes caused by TBI. Pretreatment with MASM prevented differential expression of 53% (765 genes) of 1445 differentially expressed genes induced by TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 21 pathways, such as metabolic pathways, pathways in cancer, and mitogen-activated protein kinase (MAPK) pathways. Our data indicated that pretreatment of rats with MASM modulated these pathways induced by TBI, suggesting that the pretreatment with MASM might provide the protective effects on lethal TBI mainly or partially through the modulation of these pathways, such as multiple MAPK pathways. Therefore, MASM has the potential to be used as an effective therapeutic or radioprotective agent to minimize irradiation damages and in combination with radiotherapy to improve the efficacy of cancer therapy. Full article

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36 pages, 4347 KiB

Open AccessReview

Novel Radioligands for Cyclic Nucleotide Phosphodiesterase Imaging with Positron Emission Tomography: An Update on Developments Since 2012

by Susann Schröder

, Barbara Wenzel, Winnie Deuther-Conrad

, Matthias Scheunemann and Peter Brust^*

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

Molecules 2016, 21(5), 650; https://doi.org/10.3390/molecules21050650 - 19 May 2016

Cited by 21 | Viewed by 6953

Abstract

Cyclic nucleotide phosphodiesterases (PDEs) are a class of intracellular enzymes that inactivate the secondary messenger molecules, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Thus, PDEs regulate the signaling cascades mediated by these cyclic nucleotides and affect fundamental intracellular processes. Pharmacological inhibition [...] Read more.

Cyclic nucleotide phosphodiesterases (PDEs) are a class of intracellular enzymes that inactivate the secondary messenger molecules, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Thus, PDEs regulate the signaling cascades mediated by these cyclic nucleotides and affect fundamental intracellular processes. Pharmacological inhibition of PDE activity is a promising strategy for treatment of several diseases. However, the role of the different PDEs in related pathologies is not completely clarified yet. PDE-specific radioligands enable non-invasive visualization and quantification of these enzymes by positron emission tomography (PET) in vivo and provide an important translational tool for elucidation of the relationship between altered expression of PDEs and pathophysiological effects as well as (pre-)clinical evaluation of novel PDE inhibitors developed as therapeutics. Herein we present an overview of novel PDE radioligands for PET published since 2012. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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10 pages, 1382 KiB

Open AccessReview

Taxanes in the Treatment of Advanced Gastric Cancer

by Byung Woog Kang¹, Oh-Kyoung Kwon², Ho Young Chung², Wansik Yu² and Jong Gwang Kim^1,*

¹ Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Kyungpook National University Cancer Research Institute, 807 Hogukno, buk-gu, Daegu 41404, Korea

² Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu 41494, Korea

Molecules 2016, 21(5), 651; https://doi.org/10.3390/molecules21050651 - 17 May 2016

Cited by 18 | Viewed by 6407

Abstract

Although rapid advances in treatment options have improved the prognosis of advanced gastric cancer (AGC), it remains a major public health problem and the second leading cause of cancer-related deaths in the world. Taxanes (paclitaxel and docetaxel) are microtubule stabilizing agents that inhibit [...] Read more.

Although rapid advances in treatment options have improved the prognosis of advanced gastric cancer (AGC), it remains a major public health problem and the second leading cause of cancer-related deaths in the world. Taxanes (paclitaxel and docetaxel) are microtubule stabilizing agents that inhibit the process of cell division, and have shown antitumor activity in the treatment of AGC as a single or combination chemotherapy. Accordingly, this review focuses on the efficacy and tolerability of taxanes in the first- or second-line chemotherapy setting for AGC. Full article

(This article belongs to the Special Issue New Generation of Microtubule-Interacting Anticancer Agents)

13 pages, 2442 KiB

Open AccessArticle

Design, Synthesis and Structure-Activity Relationships of Novel Chalcone-1,2,3-triazole-azole Derivates as Antiproliferative Agents

by Sai-Yang Zhang^1,†, Dong-Jun Fu^1,†, Xiao-Xin Yue², Ying-Chao Liu¹, Jian Song¹, Hui-Hui Sun¹, Hong-Min Liu^1,* and Yan-Bing Zhang^1,*

¹ Collaborative Innovation Center of New Drug Research and Safety Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China

² Henan Medical College, Zhengzhou 451191, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 653; https://doi.org/10.3390/molecules21050653 - 19 May 2016

Cited by 58 | Viewed by 8913

Abstract

A series of novel chalcone-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (SK-N-SH, EC-109 and MGC-803). Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, [...] Read more.

A series of novel chalcone-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (SK-N-SH, EC-109 and MGC-803). Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, compound I-21 showed the most excellent antiproliferative activity with an IC₅₀ value of 1.52 μM against SK-N-SH cancer cells. Further mechanism studies revealed that compound I-21 induced morphological changes of SK-N-SH cancer cells possibly by inducing apoptosis. Novel chalcone-1,2,3-triazole-azole derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating neuroblastoma. 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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10 pages, 2246 KiB

Open AccessReview

Flavin-Dependent Thymidylate Synthase as a New Antibiotic Target

by Michael Choi, Kalani Karunaratne and Amnon Kohen^*

Department of Chemistry, The University of Iowa, Iowa City, IA 52242-1727, USA

Molecules 2016, 21(5), 654; https://doi.org/10.3390/molecules21050654 - 20 May 2016

Cited by 23 | Viewed by 9739

Abstract

In humans de novo synthesis of 2′-deoxythymidine-5′-monophosphate (dTMP), an essential building block of DNA, utilizes an enzymatic pathway requiring thymidylate synthase (TSase) and dihydrofolate reductase (DHFR). The enzyme flavin-dependent thymidylate synthase (FDTS) represents an alternative enzymatic pathway to synthesize dTMP, which is not [...] Read more.

In humans de novo synthesis of 2′-deoxythymidine-5′-monophosphate (dTMP), an essential building block of DNA, utilizes an enzymatic pathway requiring thymidylate synthase (TSase) and dihydrofolate reductase (DHFR). The enzyme flavin-dependent thymidylate synthase (FDTS) represents an alternative enzymatic pathway to synthesize dTMP, which is not present in human cells. A number of pathogenic bacteria, however, depend on this enzyme in lieu of or in conjunction with the analogous human pathway. Thus, inhibitors of this enzyme may serve as antibiotics. Here, we review the similarities and differences of FDTS vs. TSase including aspects of their structure and chemical mechanism. In addition, we review current progress in the search for inhibitors of flavin dependent thymidylate synthase as potential novel therapeutics. Full article

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

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13 pages, 2301 KiB

Open AccessArticle

Low-Molecular Weight Polyethylenimine Modified with Pluronic 123 and RGD- or Chimeric RGD-NLS Peptide: Characteristics and Transfection Efficacy of Their Complexes with Plasmid DNA

by Jing Hu

, Wenfang Zhao, Kehai Liu^*, Qian Yu, Yuan Mao, Zeyu Lu, Yaguang Zhang and Manman Zhu

Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China

Molecules 2016, 21(5), 655; https://doi.org/10.3390/molecules21050655 - 18 May 2016

Cited by 16 | Viewed by 6741

Abstract

To solve the problem of transfection efficiency vs. cytotoxicity and tumor-targeting ability when polyethylenimine (PEI) was used as a nonviral gene delivery vector, new degradable PEI polymers were synthesized via cross-linking low-molecular-weight PEI with Pluronic P123 and then further coupled with a targeting [...] Read more.

To solve the problem of transfection efficiency vs. cytotoxicity and tumor-targeting ability when polyethylenimine (PEI) was used as a nonviral gene delivery vector, new degradable PEI polymers were synthesized via cross-linking low-molecular-weight PEI with Pluronic P123 and then further coupled with a targeting peptide R4 (RGD) and a bifunctional R11 (RGD-NLS), which were termed as P123-PEI-R4 and P123-PEI-R11, respectively. Agarose gel electrophoresis showed that both P123-PEI-R4 and P123-PEI-R11 efficaciously condense plasmid DNA at a polymer-to-pDNA w/w ratio of 3.0 and 0.4, respectively. The polyplexes were stable in the presence of serum and could protect plasmid DNA against DNaseI. They had uniform spherical nanoparticles with appropriate sizes around 100–280 nm and zeta-potentials about +40 mV. Furthermore, in vitro experiments showed that these polyplexes had lower cytotoxicity at any concentration compared with PEI 25 kDa, thus giving promise to high transfection efficiency as compared with another P123-PEI derivate conjugated with trifunctional peptide RGD-TAT-NLS (P123-PEI-R18). More importantly, compared with the other polymers, P123-PEI-R11 showed the highest transfection efficiency with relatively lower cytotoxicity at any concentration, indicating that the new synthetic polymer P123-PEI-R11 could be used as a safe and efficient gene deliver vector. Full article

(This article belongs to the Special Issue Biomolecules Modification)

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12 pages, 791 KiB

Open AccessArticle

Synthesis and Antioxidant Activity of Alkyl Nitroderivatives of Hydroxytyrosol

by Elena Gallardo^1,2, Rocío Palma-Valdés¹, Beatriz Sarriá², Irene Gallardo¹, José P. De la Cruz³, Laura Bravo², Raquel Mateos^2,* and José L. Espartero^1,*

¹ Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain

² Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN), Spanish National Research Council (CSIC), 28040 Madrid, Spain

³ Department of Pharmacology, Faculty of Medicine, University of Malaga, 29071 Malaga, Spain

Molecules 2016, 21(5), 656; https://doi.org/10.3390/molecules21050656 - 18 May 2016

Cited by 25 | Viewed by 6213

Abstract

A series of alkyl nitrohydroxytyrosyl ether derivatives has been synthesized from free hydroxytyrosol (HT), the natural olive oil phenol, in order to increase the assortment of compounds with potential neuroprotective activity in Parkinson’s disease. In this work, the antioxidant activity of these novel [...] Read more.

A series of alkyl nitrohydroxytyrosyl ether derivatives has been synthesized from free hydroxytyrosol (HT), the natural olive oil phenol, in order to increase the assortment of compounds with potential neuroprotective activity in Parkinson’s disease. In this work, the antioxidant activity of these novel compounds has been evaluated using Ferric Reducing Antioxidant Power (FRAP), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), and Oxygen Radical Scavenging Capacity (ORAC) assays compared to that of nitrohydroxytyrosol (NO₂HT) and free HT. New compounds showed variable antioxidant activity depending on the alkyl side chain length; compounds with short chains (2–4 carbon atoms) maintained or even improved the antioxidant activity compared to NO₂HT and/or HT, whereas those with longer side chains (6–8 carbon atoms) showed lower activity than NO₂HT but higher than HT. Full article

(This article belongs to the Section Medicinal Chemistry)

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19 pages, 1984 KiB

Open AccessArticle

Towards a Rational Design of a Continuous-Flow Method for the Acetalization of Crude Glycerol: Scope and Limitations of Commercial Amberlyst 36 and AlF₃·3H₂O as Model Catalysts

by Sandro Guidi, Marco Noè

, Pietro Riello, Alvise Perosa and Maurizio Selva^*

Department of Molecular Sciences and Nanosystems, Centre for Sustainable Technologies, Ca’ Foscari University of Venice, Via Torino 155, 30175 Venezia Mestre, Italy

Molecules 2016, 21(5), 657; https://doi.org/10.3390/molecules21050657 - 18 May 2016

Cited by 28 | Viewed by 8919

Abstract

The acetalization of six different types of glycerol including pure, wet, and crude-like grade compounds of compositions simulating those of crude glycerols produced by the biodiesel manufacture, was carried out with two model ketones such as acetone and 2-butanone. The reaction was investigated [...] Read more.

The acetalization of six different types of glycerol including pure, wet, and crude-like grade compounds of compositions simulating those of crude glycerols produced by the biodiesel manufacture, was carried out with two model ketones such as acetone and 2-butanone. The reaction was investigated under continuous-flow (CF) conditions through a comparative analysis of an already known acetalization catalyst such as Amberlyst 36 (A36), and aluminum fluoride three hydrate (AlF₃·3H₂O, AF) whose use was never previously reported for the synthesis of acetals. At 10 bar and 25 °C, A36 was a highly active catalyst allowing good-to-excellent conversion (85%–97%) and selectivity (99%) when either pure or wet glycerol was used as a reagent. This catalyst however, proved unsuitable for the CF acetalization of crude-like glycerol (CG) since it severely and irreversibly deactivated in a few hours by the presence of low amounts of NaCl (2.5 wt %) which is a typical inorganic impurity of raw glycerol from the biorefinery. Higher temperature and pressure (up to 100 °C and 30 bar) were not successful to improve the outcome. By contrast, at 10 bar and 100 °C, AF catalyzed the acetalization of CG with both acetone and 2-butanone, yielding stable conversion and productivity up to 78% and 5.6 h⁻¹, respectively. A XRD analysis of fresh and used catalysts proved that the active phase was a solid solution (SS) of formula Al₂[F_1-x(OH)_x]₆(H₂O)_y present as a component of the investigated commercial AF sample. A hypothesis to explain the role of such SS phase was then formulated based on the Brønsted acidity of OH groups of the solid framework. Overall, the AF catalyst allowed not only a straightforward upgrading of CG to acetals, but also a more cost-efficient protocol avoiding the expensive refining of raw glycerol itself. Full article

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

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5 pages, 786 KiB

Open AccessCommunication

Cytotoxicity of Different Excipients on RPMI 2650 Human Nasal Epithelial Cells

by Tamás Horváth^1,2, Csilla Bartos¹, Alexandra Bocsik^1,3, Lóránd Kiss^1,3

, Szilvia Veszelka³, Mária A. Deli³, Gabriella Újhelyi¹, Piroska Szabó-Révész¹ and Rita Ambrus^1,*

¹ Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, Szeged H-6720, Hungary

² Goodwill Pharma Ltd., Cserzy Mihály u. 32, Szeged H-6724, Hungary

³ Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári körút 62, Szeged H-6726, Hungary

Molecules 2016, 21(5), 658; https://doi.org/10.3390/molecules21050658 - 18 May 2016

Cited by 17 | Viewed by 6819

Abstract

The nasal route receives a great deal of attention as a non-invasive method for the systemic administration of drugs. For nasal delivery, specific formulations containing excipients are used. Because of the sensitive respiratory mucosa, not only the active ingredients, but also additives need [...] Read more.

The nasal route receives a great deal of attention as a non-invasive method for the systemic administration of drugs. For nasal delivery, specific formulations containing excipients are used. Because of the sensitive respiratory mucosa, not only the active ingredients, but also additives need to be tested in appropriate models for toxicity. The aim of the study was to measure the cytotoxicity of six pharmaceutical excipients, which could help to reach larger residence time, better permeability, and increased solubility dissolution rate. The following excipients were investigated on RPMI 2650 human nasal septum tumor epithelial cells: β-d-mannitol, sodium hyaluronate, α and β-cyclodextrin, polyvinyl alcohol and methylcellulose. 3-(4,5-dimethyltiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye conversion assay and real-time impedance analysis were used to investigate cytotoxicity. No excipient showed toxicity at 0.3% (w/v) concentration or below while 1% concentration a significantly reduced metabolic activity was measured by MTT assay for methylcellulose and cyclodextrins. Using impedance measurements, only β-cyclodextrin (1%) was toxic to cells. Mannitol at 1% concentration had a barrier opening effect on epithelial cells, but caused no cellular damage. Based on the results, all additives at 0.3%, sodium hyaluronate and polyvinyl alcohol at 1% concentrations can be safely used for nasal formulations. Full article

(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)

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13 pages, 851 KiB

Open AccessArticle

Synthesis of Novel Symmetrical 1,4-Disubstituted 1,2,3-Bistriazole Derivatives via ‘Click Chemistry’ and Their Biological Evaluation

by Esra Düğdü^1,*, Dilek Ünlüer¹, Fatih Çelik¹, Kemal Sancak¹, Şengül Alpay Karaoğlu²

and Arzu Özel³

¹ Department of Chemistry, Karadeniz Technical University, Trabzon 61080, Turkey

² Department of Biology, Recep Tayyip Erdoğan University, Rize 53100, Turkey

³ Faculty of Pharmacy, Karadeniz Technical University, Trabzon 61080, Turkey

Molecules 2016, 21(5), 659; https://doi.org/10.3390/molecules21050659 - 19 May 2016

Cited by 13 | Viewed by 5435

Abstract

A series of symmetric bis-1,2,3-triazole compounds 2–5(a–f) were synthesized as potential antioxidant agents via click chemistry. Their structures were confirmed by ¹H-NMR and ¹³C-NMR. All of the synthesized compounds were subjected to antioxidant and antimicrobial assays. The antioxidant activity of these [...] Read more.

A series of symmetric bis-1,2,3-triazole compounds 2–5(a–f) were synthesized as potential antioxidant agents via click chemistry. Their structures were confirmed by ¹H-NMR and ¹³C-NMR. All of the synthesized compounds were subjected to antioxidant and antimicrobial assays. The antioxidant activity of these compounds (AChE inhibition, DPPH and SOD activities) was evaluated. Compound 2f was found to show the highest AChE inhibition activity of all compounds, while compound 3b showed a strong inhibitory effect on DPPH radical and compound 2a was the most effective of all compounds for SOD activity. All synthesized compounds were found to possess moderate antibacterial activity against the bacteria E. coli and Y.pseudotuberculosis. Full article

(This article belongs to the Section Organic Chemistry)

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25 pages, 3768 KiB

Open AccessReview

Synthetic Strategies for 5- and 6-Membered Ring Azaheterocycles Facilitated by Iminyl Radicals

by John C. Walton

University of St. Andrews, EaStCHEM School of Chemistry, St. Andrews, Fife KY16 9ST, UK

Molecules 2016, 21(5), 660; https://doi.org/10.3390/molecules21050660 - 18 May 2016

Cited by 56 | Viewed by 10468

Abstract

The totality of chemical space is so immense that only a small fraction can ever be explored. Computational searching has indicated that bioactivity is associated with a comparatively small number of ring-containing structures. Pyrrole, indole, pyridine, quinoline, quinazoline and related 6-membered ring-containing aza-arenes [...] Read more.

The totality of chemical space is so immense that only a small fraction can ever be explored. Computational searching has indicated that bioactivity is associated with a comparatively small number of ring-containing structures. Pyrrole, indole, pyridine, quinoline, quinazoline and related 6-membered ring-containing aza-arenes figure prominently. This review focuses on the search for fast, efficient and environmentally friendly preparative methods for these rings with specific emphasis on iminyl radical-mediated procedures. Oxime derivatives, particularly oxime esters and oxime ethers, are attractive precursors for these radicals. Their use is described in conventional thermolytic, microwave-assisted and UV-vis based preparative procedures. Photoredox-catalyzed protocols involving designer oxime ethers are also covered. Choice can be made amongst these synthetic strategies for a wide variety of 5- and 6-membered ring heterocycles including phenanthridine and related aza-arenes. Applications to selected natural products and bioactive molecules, including trispheridine, vasconine, luotonin A and rutaecarpine, are included. Full article

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

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12 pages, 2816 KiB

Open AccessArticle

Effects of Resveratrol Supplementation and Exercise Training on Exercise Performance in Middle-Aged Mice

by Nai-Wen Kan¹, Chin-Shan Ho², Yen-Shuo Chiu^2,3,4, Wen-Ching Huang², Pei-Yu Chen², Yu-Tang Tung^2,* and Chi-Chang Huang^2,*

¹ Center for Liberal Arts, Taipei Medical University, Taipei 11031, Taiwan

² Graduate Institute of Sports Science, National Taiwan Sport University, 250 Wenhua 1st Rd., Guishan Township, Taoyuan County 33301, Taiwan

³ Department of Orthopedic Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan

⁴ School of Nutrition and Health Sciences, Taipei Medical University, Taipei City 11031, Taiwan

Molecules 2016, 21(5), 661; https://doi.org/10.3390/molecules21050661 - 18 May 2016

Cited by 53 | Viewed by 8856

Abstract

Resveratrol (RES) has antioxidative, anti-inflammatory, anticancer, antidiabetic, antiasthmatic, antalgic, and anti-fatigue activities. Exercise training (ET) improves frailty resulting from aging. This study evaluated the effects of a combination of RES supplementation and ET on the exercise performance of aged mice. C57BL/6J mice (16 [...] Read more.

Resveratrol (RES) has antioxidative, anti-inflammatory, anticancer, antidiabetic, antiasthmatic, antalgic, and anti-fatigue activities. Exercise training (ET) improves frailty resulting from aging. This study evaluated the effects of a combination of RES supplementation and ET on the exercise performance of aged mice. C57BL/6J mice (16 months old) were randomly divided into four groups: an older control group (OC group), supplementation with RES group (RES group), ET group (ET group), and a combination of ET and RES supplementation group (ET+RES group). Other 10-week-old mice were used as a young control group (Y-Ctrl group). In this study, exercise performance was evaluated using forelimb grip strength and exhaustive swimming time, as well as levels of plasma lactate, ammonia, glucose, and creatine kinase after an acute swimming exercise. Our results showed that the forelimb grip strength of mice in the ET+RES group was significantly higher than those in the OC, RES, and ET groups (by 1.3-, 1.2-, and 1.1-fold, respectively, p < 0.05), and exhibited no difference with the Y-Ctrl group. The endurance swimming test showed that swimming times of the ET and ET+RES groups were significantly longer than those of the OC and RES groups. Moreover, plasma lactate and ammonia levels of the ET + RES group after acute swimming exercise were significantly lower compared to the OC group (p < 0.05). Thus, it was suggested that by combining RES supplementation with ET for 4 weeks, the muscle strength and endurance performance of aged mice were significantly improved compared to the single intervention with either RES or ET alone. This combination might help shorten the extent of deterioration accompanying the aging process. Full article

(This article belongs to the Special Issue Improvements for Resveratrol Efficacy)

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11 pages, 2656 KiB

Open AccessArticle

Adsorption and Gas Separation of Molecules by Carbon Nanohorns

by Silvina M. Gatica^1,*, Anton Nekhai^2,† and Adam Scrivener^3,‡

¹ Department of Physics and Astronomy, Howard University, 2355 Sixth Street NW, Washington, DC 20059, USA

² Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, NY 12180, USA

³ Department of Computer Science, University of Rochester, 500 Joseph C. Wilson Boulevard, Rochester, NY 14627, USA

^† Participant in the summer Research Experiences for Undergraduates (REU), National Science Foundation (NSF) summer program, at Howard University (2015)

^‡ Participant in the summer Research Experiences for Undergraduates (REU), National Science Foundation (NSF) summer program, at Howard University (2014)

Molecules 2016, 21(5), 662; https://doi.org/10.3390/molecules21050662 - 19 May 2016

Cited by 10 | Viewed by 5173

Abstract

In this paper, we report the results of Monte Carlo simulations of the adsorption of neon, argon, methane and carbon dioxide in carbon nanohorns. We model the nanohorns as an array of carbon cones and obtained adsorption isotherms and isosteric heats. The main [...] Read more.

In this paper, we report the results of Monte Carlo simulations of the adsorption of neon, argon, methane and carbon dioxide in carbon nanohorns. We model the nanohorns as an array of carbon cones and obtained adsorption isotherms and isosteric heats. The main sites of adsorption are inside the cones and in the interstices between three cones. We also calculated the selectivity of carbon dioxide/methane, finding that nanohorns are a suitable substrate for gas separation. Our simulations are compared to available experimental data. Full article

(This article belongs to the Special Issue Carbon Nanotubes: Advances and Applications)

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18 pages, 1704 KiB

Open AccessReview

Antiproliferative Fate of the Tetraploid Formed after Mitotic Slippage and Its Promotion; A Novel Target for Cancer Therapy Based on Microtubule Poisons

by Yuji Nakayama¹ and Toshiaki Inoue^2,3,*

¹ Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan

² Division of Human Genome Science, Department of Molecular and Cellular Biology, School of Life Sciences, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan

³ Chromosome Engineering Research Center, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan

Molecules 2016, 21(5), 663; https://doi.org/10.3390/molecules21050663 - 19 May 2016

Cited by 28 | Viewed by 8604

Abstract

Microtubule poisons inhibit spindle function, leading to activation of spindle assembly checkpoint (SAC) and mitotic arrest. Cell death occurring in prolonged mitosis is the first target of microtubule poisons in cancer therapies. However, even in the presence of microtubule poisons, SAC and mitotic [...] Read more.

Microtubule poisons inhibit spindle function, leading to activation of spindle assembly checkpoint (SAC) and mitotic arrest. Cell death occurring in prolonged mitosis is the first target of microtubule poisons in cancer therapies. However, even in the presence of microtubule poisons, SAC and mitotic arrest are not permanent, and the surviving cells exit the mitosis without cytokinesis (mitotic slippage), becoming tetraploid. Another target of microtubule poisons-based cancer therapy is antiproliferative fate after mitotic slippage. The ultimate goal of both the microtubule poisons-based cancer therapies involves the induction of a mechanism defined as mitotic catastrophe, which is a bona fide intrinsic oncosuppressive mechanism that senses mitotic failure and responds by driving a cell to an irreversible antiproliferative fate of death or senescence. This mechanism of antiproliferative fate after mitotic slippage is not as well understood. We provide an overview of mitotic catastrophe, and explain new insights underscoring a causal association between basal autophagy levels and antiproliferative fate after mitotic slippage, and propose possible improved strategies. Additionally, we discuss nuclear alterations characterizing the mitotic catastrophe (micronuclei, multinuclei) after mitotic slippage, and a possible new type of nuclear alteration (clustered micronuclei). Full article

(This article belongs to the Special Issue New Generation of Microtubule-Interacting Anticancer Agents)

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14 pages, 2066 KiB

Open AccessCommunication

Comprehensive Qualitative Ingredient Profiling of Chinese Herbal Formula Wu-Zhu-Yu Decoction via a Mass Defect and Fragment Filtering Approach Using High Resolution Mass Spectrometry

by Huarong Xu¹, Huibin Niu¹, Bosai He¹, Chang Cui², Qing Li¹ and Kaishun Bi^1,*

¹ National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China

² Liaoning Institute of Analytical Science, 103 Wanliutang Rd., Shenyang 110015, China

Molecules 2016, 21(5), 664; https://doi.org/10.3390/molecules21050664 - 19 May 2016

Cited by 24 | Viewed by 6716

Abstract

The Wu-Zhu-Yu decoction is a traditional Chinese medicine formula for the treatment of headache. To reveal its material basis, a rapid and reliable liquid chromatography-high resolution mass spectrometry method was established for comprehensive profiling of the chemical ingredients in the Wu-Zhu-Yu decoction. The [...] Read more.

The Wu-Zhu-Yu decoction is a traditional Chinese medicine formula for the treatment of headache. To reveal its material basis, a rapid and reliable liquid chromatography-high resolution mass spectrometry method was established for comprehensive profiling of the chemical ingredients in the Wu-Zhu-Yu decoction. The method was used on a quadrupole time-of-flight mass spectrometer along with an advanced data processing procedure consisting of mass accuracy screening, mass defect filtering and fragment filtering. After eliminating interference with a filtering approach, the MS data profiling was made more distinct and accurate. With the optimized conditions of only 35 min LC separation and single sample injection of each positive or negative ion mode, a total of 168 compounds were characterized, including 23 evodiamine and its analogous alkaloids, 12 limonoids, 17 gingerols, 38 ginsenosides, 15 flavonoids, 16 organic acids, 14 alkaloids, 5 saponins, 3 2,2-dimethylchromenes and 25 other compounds. The fragmentation patterns of representative compounds were illustrated as well. Integrative qualitative analysis of the Wu-Zhu-Yu decoction by high resolution mass spectrometry was accomplished and reported for the first time. The study demonstrated that the established method was a powerful and reliable strategy for comprehensive detection and would be widely applicable for identification of complicated components from herbal prescriptions, and may provide a basis for chemical analysis of other complex mixtures. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 2027 KiB

Open AccessArticle

Novel Cage-Like Hexanuclear Nickel(II) Silsesquioxane. Synthesis, Structure, and Catalytic Activity in Oxidations with Peroxides

by Alexey N. Bilyachenko^1,2,*

, Alexey I. Yalymov¹, Lidia S. Shul’pina¹

, Dalmo Mandelli³, Alexander A. Korlyukov^1,4

, Anna V. Vologzhanina¹

, Marina A. Es’kova¹, Elena S. Shubina¹

, Mikhail M. Levitsky¹ and Georgiy B. Shul’pin^5,6,*

¹ Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov Str. 28, 119991 Moscow, Russia

² Inorganic Chemistry Department, People’s Friendship University of Russia, Miklukho-Maklay Str. 6, 117198 Moscow, Russia

³ Center of Natural and Human Sciences, Federal University of ABC (UFABC), Santa Adélia Street, 166, Bangu, Santo André, SP 09210-170, Brazil

⁴ Chemistry Department, Russian National Research Medical University, Ostrovitianov str. 1, 117997 Moscow, Russia

⁵ Semenov Institute of Chemical Physics, Russian Academy of Sciences, ul. Kosygina, dom 4, 119991 Moscow, Russia

⁶ Chair of Chemistry and Physics, Plekhanov Russian University of Economics, Stremyannyi pereulok, dom 36, 117997 Moscow, Russia

Molecules 2016, 21(5), 665; https://doi.org/10.3390/molecules21050665 - 19 May 2016

Cited by 33 | Viewed by 7450

Abstract

New hexanuclear nickel(II) silsesquioxane [(PhSiO_1.5)₁₂(NiO)₆(NaCl)] (1) was synthesized as its dioxane-benzonitrile-water complex (PhSiO_1,5)₁₂(NiO)₆(NaCl)(C₄H₈O₂)₁₃(PhCN)₂(H₂O)₂ and studied by X-ray and [...] Read more.

New hexanuclear nickel(II) silsesquioxane [(PhSiO_1.5)₁₂(NiO)₆(NaCl)] (1) was synthesized as its dioxane-benzonitrile-water complex (PhSiO_1,5)₁₂(NiO)₆(NaCl)(C₄H₈O₂)₁₃(PhCN)₂(H₂O)₂ and studied by X-ray and topological analysis. The compound exhibits cylinder-like type of molecular architecture and represents very rare case of polyhedral complexation of metallasilsesquioxane with benzonitrile. Complex 1 exhibited catalytic activity in activation of such small molecules as light alkanes and alcohols. Namely, oxidation of alcohols with tert-butylhydroperoxide and alkanes with meta-chloroperoxybenzoic acid. The oxidation of methylcyclohexane gave rise to the isomeric ketones and unusual distribution of alcohol isomers. Full article

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

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12 pages, 2327 KiB

Open AccessArticle

BiOBr/BiOI Photocatalyst Based on Fly Ash Cenospheres with Improved Photocatalytic Performance

by Li Lin^1,2,*, Manhong Huang² and Donghui Chen^2,3,*

¹ School of Chemical and Environmental Engineering, Hunan City University, Yiyang 413000, China

² School of Environmental Science and Engineering, Donghua University, Shanghai 201620, China

³ Shanghai Institute of Technology, Shanghai 200235, China

Molecules 2016, 21(5), 666; https://doi.org/10.3390/molecules21050666 - 19 May 2016

Cited by 18 | Viewed by 6566

Abstract

A series of BiOBr/BiOI photocatalysts supported on fly-ash cenospheres (FACs) were successfully prepared via a facile one-pot alcoholysis method. The as-prepared samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectrometer (XPS) and UV-visible diffuse reflectance spectroscopy (DRS). The [...] Read more.

A series of BiOBr/BiOI photocatalysts supported on fly-ash cenospheres (FACs) were successfully prepared via a facile one-pot alcoholysis method. The as-prepared samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectrometer (XPS) and UV-visible diffuse reflectance spectroscopy (DRS). The results indicate that pH value plays a critical role in BiOBr/BiOI loading. Based on the photodegradation tests under visible light irradiation (blue LED irradiation), the photocatalytic property of BiOBr/BiOI/FACs photocatalysts obtained under alkaline conditions is superior to that prepared under neutral or acidic conditions, and higher than those of BiOB/FACs and BiOI//FACs. The improved photocatalytic performance of BiOBr/BiOI/FACs can be attributed to more BiOBr/BiOI loaded on the surface of FACs and the efficient photogenerated electron-hole separation. Full article

(This article belongs to the Section Photochemistry)

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12 pages, 3889 KiB

Open AccessArticle

Gold Incorporated Mesoporous Silica Thin Film Model Surface as a Robust SERS and Catalytically Active Substrate

by Anandakumari Chandrasekharan Sunil Sekhar^1,2,* and Chathakudath Prabhakaran Vinod^1,2,3,*

¹ Catalysis Division, CSIR-National Chemical Laboratory, Dr Homi Bhabha Road, Pune 411 008, India

² Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2, Rafi Marg, New Delhi 110 001, India

³ Center of Excellence on Surface Science, CSIR-National Chemical Laboratory, Dr Homi Bhabha Road, Pune 411 008, India

Molecules 2016, 21(5), 667; https://doi.org/10.3390/molecules21050667 - 20 May 2016

Cited by 7 | Viewed by 6760

Abstract

Ultra-small gold nanoparticles incorporated in mesoporous silica thin films with accessible pore channels perpendicular to the substrate are prepared by a modified sol-gel method. The simple and easy spin coating technique is applied here to make homogeneous thin films. The surface characterization using [...] Read more.

Ultra-small gold nanoparticles incorporated in mesoporous silica thin films with accessible pore channels perpendicular to the substrate are prepared by a modified sol-gel method. The simple and easy spin coating technique is applied here to make homogeneous thin films. The surface characterization using FESEM shows crack-free films with a perpendicular pore arrangement. The applicability of these thin films as catalysts as well as a robust SERS active substrate for model catalysis study is tested. Compared to bare silica film our gold incorporated silica, GSM-23F gave an enhancement factor of 10³ for RhB with a laser source 633 nm. The reduction reaction of p-nitrophenol with sodium borohydride from our thin films shows a decrease in peak intensity corresponding to –NO₂ group as time proceeds, confirming the catalytic activity. Such model surfaces can potentially bridge the material gap between a real catalytic system and surface science studies. Full article

(This article belongs to the Special Issue Coinage Metal (Copper, Silver, and Gold) Catalysis)

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9 pages, 941 KiB

Open AccessArticle

Anti-Inflammatory Oleanolic Triterpenes from Chinese Acorns

by Jie Huang¹, Yihai Wang¹, Chuan Li¹, Xinluan Wang² and Xiangjiu He^1,*

¹ School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China

² Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China

Molecules 2016, 21(5), 669; https://doi.org/10.3390/molecules21050669 - 20 May 2016

Cited by 23 | Viewed by 6815

Abstract

Acorns play an important role in human history and are a source of food and recipes for many cultures around the world. In this study, eleven oleanolic triterpenes, one of which was novel, were isolated from Chinese acorns (Quercus serrata var. brevipetiolata). [...] Read more.

Acorns play an important role in human history and are a source of food and recipes for many cultures around the world. In this study, eleven oleanolic triterpenes, one of which was novel, were isolated from Chinese acorns (Quercus serrata var. brevipetiolata). The chemical structure of the novel triterpene, which was identified as 2α,3β,19α-trihydroxy-24-oxo-olean-12-en-28-oic acid (1), was established based on the interpretation of chemical and spectroscopic analyses, including IR, HR-ESI-MS, and NMR experiments (¹H, ¹³C NMR, DEPT, ¹H-¹H COSY, HSQC, HMBC, and NOESY). All isolated compounds were tested for their inhibitory effects on LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages. Compared with the positive control drug indomethacin (IC₅₀ = 47.4 μM), compounds 1, 3, 6 and 8 exhibited remarkable anti-inflammatory activities with IC₅₀ values of 5.4, 7.8, 4.0 and 8.9 μM, respectively. Besides, compounds 2, 4, 7 and 9 also showed moderate anti-inflammatory activities with IC₅₀ values of 10.1, 13.0, 20.1 and 17.2 μM, respectively. Furthermore, Compound 1 could inhibit TNF-α-induced IL-6 and IL-8 production in MH7A cells. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

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11 pages, 2353 KiB

Open AccessArticle

Thermal Conductivity of Epoxy Resin Composites Filled with Combustion Synthesized h-BN Particles

by Shyan-Lung Chung^1,2,* and Jeng-Shung Lin²

¹ Advanced Optoelectronic Technology Center, National Cheng Kung University, Tainan 70101, Taiwan

² Department of Chemical Engineering, National Cheng Kung University, Tainan 70101, Taiwan

Molecules 2016, 21(5), 670; https://doi.org/10.3390/molecules21050670 - 20 May 2016

Cited by 99 | Viewed by 11941

Abstract

The thermal conductivity of epoxy resin composites filled with combustion-synthesized hexagonal boron nitride (h-BN) particles was investigated. The mixing of the composite constituents was carried out by either a dry method (involving no use of solvent) for low filler loadings or a solvent [...] Read more.

The thermal conductivity of epoxy resin composites filled with combustion-synthesized hexagonal boron nitride (h-BN) particles was investigated. The mixing of the composite constituents was carried out by either a dry method (involving no use of solvent) for low filler loadings or a solvent method (using acetone as solvent) for higher filler loadings. It was found that surface treatment of the h-BN particles using the silane 3-glycidoxypropyltrimethoxysilane (GPTMS) increases the thermal conductivity of the resultant composites in a lesser amount compared to the values reported by other studies. This was explained by the fact that the combustion synthesized h-BN particles contain less –OH or active sites on the surface, thus adsorbing less amounts of GPTMS. However, the thermal conductivity of the composites filled with the combustion synthesized h-BN was found to be comparable to that with commercially available h-BN reported in other studies. The thermal conductivity of the composites was found to be higher when larger h-BN particles were used. The thermal conductivity was also found to increase with increasing filler content to a maximum and then begin to decrease with further increases in this content. In addition to the effect of higher porosity at higher filler contents, more horizontally oriented h-BN particles formed at higher filler loadings (perhaps due to pressing during formation of the composites) were suggested to be a factor causing this decrease of the thermal conductivity. The measured thermal conductivities were compared to theoretical predictions based on the Nielsen and Lewis theory. The theoretical predictions were found to be lower than the experimental values at low filler contents (< 60 vol %) and became increasing higher than the experimental values at high filler contents (> 60 vol %). Full article

(This article belongs to the Special Issue Boron Nitride: Synthesis and Application)

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12 pages, 2328 KiB

Open AccessArticle

Positively Charged Nanostructured Lipid Carriers and Their Effect on the Dissolution of Poorly Soluble Drugs

by Kyeong-Ok Choi, Jaehyeog Choe, Seokjin Suh and Sanghoon Ko^*

Department of Food Science and Technology, Sejong University, 261 Neungdong-ro, Gwangjin-gu, Seoul 143-747, Korea

Molecules 2016, 21(5), 672; https://doi.org/10.3390/molecules21050672 - 20 May 2016

Cited by 34 | Viewed by 7321

Abstract

The objective of this study is to develop suitable formulations to improve the dissolution rate of poorly water soluble drugs. We selected lipid-based formulation as a drug carrier and modified the surface using positively charged chitosan derivative (HTCC) to increase its water solubility [...] Read more.

The objective of this study is to develop suitable formulations to improve the dissolution rate of poorly water soluble drugs. We selected lipid-based formulation as a drug carrier and modified the surface using positively charged chitosan derivative (HTCC) to increase its water solubility and bioavailability. Chitosan and HTCC-coated lipid particles had higher zeta-potential values than uncoated one over the whole pH ranges and improved encapsulation efficiency. In vitro drug release showed that all NLC formulations showed higher in vitro release efficiency than drug particle at pH 7.4. Furthermore, NLC formulation prepared with chitosan or HTCC represented good sustained release property. The results indicate that chitosan and HTCC can be excellent formulating excipients of lipid-based delivery carrier for improving poorly water soluble drug delivery. Full article

(This article belongs to the Collection Poorly Soluble Drugs)

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1 pages, 144 KiB

Open AccessCorrection

Correction: Xiang, S., et al. Schisandrin B Induces Apoptosis and Cell Cycle Arrest of Gallbladder Cancer Cells. Molecules 2014, 19, 13235–13250

by Shan-Shan Xiang^1,2,3,†, Xu-An Wang^1,2,3,†, Huai-Feng Li^1,2,3,†, Yi-Jun Shu^1,2,3, Run-Fa Bao^1,2,3, Fei Zhang^1,2,3, Yang Cao^1,2,3, Yuan-Yuan Ye^1,2,3, Hao Weng^1,2,3, Wen-Guang Wu^1,2,3, Jia-Sheng Mu^1,2,3, Xiang-Song Wu^1,2,3, Mao-Lan Li^1,2,3, Yun-Ping Hu^1,2,3, Lin Jiang^1,2,3, Zhu-Jun Tan^1,2,3, Wei Lu^1,2,3, Feng Liu^4,* and Ying-Bin Liu^1,2,3,*

¹ Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China

² Laboratory of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China

³ Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, No. 227 South Chongqing Road, Shanghai 200025, China

⁴ The First Affiliated Hospital Nanchang University Emergency Unit, No. 17 Yongwai Road, Nanchang 330006, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 673; https://doi.org/10.3390/molecules21050673 - 20 May 2016

Cited by 1 | Viewed by 4400

Abstract

We would like to change the Affiliation addresses on Page 13235 of paper [1], [...] Full article

(This article belongs to the Section Natural Products Chemistry)

18 pages, 1471 KiB

Open AccessArticle

Synthesis and Characterization of Novel Cu(II), Pd(II) and Pt(II) Complexes with 8-Ethyl-2-hydroxytricyclo(7.3.1.0^2,7)tridecan-13-one-thiosemicarbazone: Antimicrobial and in Vitro Antiproliferative Activity

by Elena Pahonțu^1,*, Codruța Paraschivescu^2,*, Diana-Carolina Ilieș³, Donald Poirier⁴

, Camelia Oprean⁵, Virgil Păunescu⁶, Aurelian Gulea⁷

, Tudor Roșu⁸ and Ovidiu Bratu⁹

¹ Inorganic Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy ”Carol Davila”, 6 Traian Vuia Street, Bucharest 020956, Romania

² Organic Chemistry Department, Faculty of Chemistry, University of Bucharest, 90-92 Panduri Street, Bucharest 050663, Romania

³ Organic Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy ”Carol Davila”, 6 Traian Vuia Street, Bucharest 020956, Romania

⁴ Oncology and Molecular Endocrinology Research Center CHUL, Research Center and Universite Laval, CHUQ-CHUL, 2705 Boulevard Laurier, Quebec City, QC G1V 4G2, Canada

⁵ Pharmaceutical Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Romania

⁶ Functional Sciences Department, Faculty of Medicine, University of Medicine and Pharmacy “Victor Babeş”, 2 Eftimie Murgu Square, Timişoara 300041, Romania

⁷ Coordination Chemistry Department, Moldova State University, 60 Mateevici Street, Chisinau 2009, Moldova

⁸ Inorganic Chemistry Department, Faculty of Chemistry, University of Bucharest, 23 Dumbrava Rosie Street, Bucharest 020462, Romania

⁹ Clinic of Urology, Universitary Emergency Central Military Hospital, Clinical Departament 3, University of Medicine and Pharmacy “Carol Davila”, 6 Traian Vuia Street, Bucharest 020956, Romania

Molecules 2016, 21(5), 674; https://doi.org/10.3390/molecules21050674 - 21 May 2016

Cited by 53 | Viewed by 7429

Abstract

New Cu(II), Pd(II) and Pt(II) complexes, (Cu(L)(H₂O)₂(OAc)) (1), (Cu(HL)(H₂O)₂(SO₄)) (2), (Cu(L)(H₂O)₂(NO₃)) (3), (Cu(L)(H₂O)₂(ClO₄)) (4 [...] Read more.

New Cu(II), Pd(II) and Pt(II) complexes, (Cu(L)(H₂O)₂(OAc)) (1), (Cu(HL)(H₂O)₂(SO₄)) (2), (Cu(L)(H₂O)₂(NO₃)) (3), (Cu(L)(H₂O)₂(ClO₄)) (4), (Cu(L)₂(H₂O)₂) (5), (Pd(L)(OAc))H₂O (6), and (Pt(L)₂) (7) were synthesized from 8-ethyl-2-hydroxytricyclo(7.3.1.0^2,7)tridecan-13-one thiosemicarbazone (HL). The ligand and its metal complexes were characterized by IR, ¹H-NMR, ¹³C-NMR, UV-Vis, FAB, EPR, mass spectroscopy, elemental and thermal analysis, magnetic susceptibility measurements and molar electric conductivity. The free ligand and the metal complexes have been tested for their antimicrobial activity against E. coli, S. enteritidis, S. aureus, E. faecalis, C. albicans and cytotoxicity against the NCI-H1573 lung adenocarcinoma, SKBR-3 human breast, MCF-7 human breast, A375 human melanoma and HL-60 human promyelocytic leukemia cell lines. Copper complex 2 exhibited the best antiproliferative activities against MCF-7 human breast cancer cells. A significant inhibition of malignant HL-60 cell growth was observed for copper complex 2, palladium complex 6 and platinum complex 7, with IC₅₀ values of 1.6 µM, 6.5 µM and 6.4 µM, respectively. Full article

(This article belongs to the Special Issue ECSOC-19)

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15 pages, 2354 KiB

Open AccessArticle

Astragalin, a Flavonoid from Morus alba (Mulberry) Increases Endogenous Estrogen and Progesterone by Inhibiting Ovarian Granulosa Cell Apoptosis in an Aged Rat Model of Menopause

by Min Wei^1,†, Gail B. Mahady^2,†, Daniel Liu^3,*, Zhi S. Zheng¹ and Ye Lu¹

¹ Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210041, China

² Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA

³ Beijing Clinical Services Center, No. 103 Chaoyang North Road, Beijing 100123, China

^† These authors have contributed equally to this work.

Molecules 2016, 21(5), 675; https://doi.org/10.3390/molecules21050675 - 21 May 2016

Cited by 30 | Viewed by 9271

Abstract

Background: To determine the mechanism by which the flavonoid glycoside astragalin (AST) reduces ovarian failure in an aged rat model of menopause. Methods: The in vivo effect of AST on granulosa cell (GC) apoptosis in aged female rats was determined using [...] Read more.

Background: To determine the mechanism by which the flavonoid glycoside astragalin (AST) reduces ovarian failure in an aged rat model of menopause. Methods: The in vivo effect of AST on granulosa cell (GC) apoptosis in aged female rats was determined using flow cytometry. In vitro, the effects of AST on cultured GCs were investigated using the MTT proliferation assay and western blot assays. Results: Aged rats had significantly higher GC apoptosis as compared with young female rats. Treatment of aged rats with AST (all three doses; p < 0.01) or Progynova (p < 0.01) significantly reduced GC apoptosis as compared with the aged controls. The proportions of total apoptotic GCs was 25.70%, 86.65%, 47.04%, 27.02%, 42.09% and 56.42% in the normal, aged, 17β-estradiol (E₂), high dose AST, medium dose AST, and low dose AST-treated groups, respectively. Significant increases of serum E₂ and P₄ levels, as well as altered levels of serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. In cultured rat GCs, AST stimulated GC proliferation, E₂ and progesterone (P₄) secretion, reduced apoptosis, reduced the level of the pro-apoptotic protein Bcl-2 (p < 0.01), but had no effect on BAX. Conclusions: AST enhanced ovarian function in aged female rats by increasing E₂ and P₄ levels, and reducing ovarian GC apoptosis via a mechanism involving Bcl-2. These data demonstrate a new pharmacological activity for AST, as well as a novel mechanism of action, and further suggest that AST may be a new therapeutic agent for the management of menopausal symptoms. Full article

(This article belongs to the Section Natural Products Chemistry)

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21 pages, 1130 KiB

Open AccessArticle

Synthesis and in Vitro and in Vivo Anticoagulant and Antiplatelet Activities of Amidino- and Non-Amidinobenzamides

by Soo Hyun Lee^1,†, Wonhwa Lee^2,3,†, Jong-Sup Bae^2,* and Eunsook Ma^1,*

¹ College of Pharmacy, Catholic University of Daegu, Hayang-ro 13-13, Hayang-eup, Gyeongsan-si, Gyeongbuk 712-702, Korea

² College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, Korea

³ Department of Biochemistry and Cell Biology, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 700-422, Korea

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 676; https://doi.org/10.3390/molecules21050676 - 21 May 2016

Cited by 8 | Viewed by 6442

Abstract

Three amidino- and ten non-amidinobenzamides were synthesized as 3-aminobenzoic acid scaffold-based anticoagulant and antiplatelet compounds. The anticoagulant activities of thirteen synthesized compounds 1–13, and 2b and 3b as prodrugs were preliminary evaluated by screening the prolongation of activated partial thromboplastin [...] Read more.

Three amidino- and ten non-amidinobenzamides were synthesized as 3-aminobenzoic acid scaffold-based anticoagulant and antiplatelet compounds. The anticoagulant activities of thirteen synthesized compounds 1–13, and 2b and 3b as prodrugs were preliminary evaluated by screening the prolongation of activated partial thromboplastin time (aPTT) and prothrombin time (PT) in vitro. From the aPTT results obtained, two amidinobenzamides, N-(3′-amidinophenyl)-3-(thiophen-2′′-ylcarbonylamino) benzamide (1, 33.2 ± 0.7 s) and N-(4′-amidinophenyl)-3-(thiophen-2′′-ylcarbonylamino) benzamide (2, 43.5 ± 0.6 s) were selected to investigate the further anticoagulant and antiplatelet activities. The aPTT results of 1 (33.2 ± 0.7 s) and 2 (43.5 ± 0.6 s) were compared with heparin (62.5 ± 0.8 s) in vitro at 30 μM. We investigated the effect of 1 and 2 on blood anticoagulant activity (ex vivo) and on tail bleeding time (in vivo) on mice. A tail cutting/bleeding time assay revealed that both 1 and 2 prolonged bleeding time in mice at a dose of 24.1 g/mouse and above. Compounds 1 and 2 dose-dependently inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In addition, 1 and 2 were evaluated on the inhibitory activities of thrombin and FXa as well as the generation of thrombin and FXa in human umbilical vein endothelial cells (HUVECs). Collectively, 1 and 2 possess some antiplatelet and anticoagulant activities and offer a basis for development of a novel antithrombotic product. Full article

(This article belongs to the Section Bioorganic Chemistry)

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27 pages, 1858 KiB

Open AccessArticle

Synthesis and p38 Inhibitory Activity of Some Novel Substituted N,N′-Diarylurea Derivatives

by Dianxi Zhu^1,2, Qifeng Xing², Ruiyuan Cao², Dongmei Zhao^1,* and Wu Zhong^2,*

¹ Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China

² Laboratory of Computer-Aided Drug Design and Discovery, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Rd., Beijing 100850, China

Molecules 2016, 21(5), 677; https://doi.org/10.3390/molecules21050677 - 23 May 2016

Cited by 9 | Viewed by 6412

Abstract

We have identified a novel series of substituted N,N′-diarylurea p38α inhibitors. The inhibitory activity of the target compounds against the enzyme p38α, MAPKAPK2 in BHK cells, TNF-α release in LPS-stimulated THP-1 cells and p38α binding experiments were [...] Read more.

We have identified a novel series of substituted N,N′-diarylurea p38α inhibitors. The inhibitory activity of the target compounds against the enzyme p38α, MAPKAPK2 in BHK cells, TNF-α release in LPS-stimulated THP-1 cells and p38α binding experiments were tested. Among these compounds, 25a inhibited the p38α enzyme with an IC₅₀ value of 0.47 nM and a KD value of 1.54 × 10⁻⁸ and appears to be the most promising one in the series. Full article

(This article belongs to the Special Issue Kinase Inhibitor Chemistry)

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Open AccessArticle

Structure Identification and Anti-Cancer Pharmacological Prediction of Triterpenes from Ganoderma lucidum

by Yanyan Shao^1,†, Liansheng Qiao^2,†, Lingfang Wu^1,†, Xuefei Sun¹, Dan Zhu¹, Guanghui Yang¹, Xiaoxue Zhang¹, Xin Mao¹, Wenjing Chen¹, Wenyi Liang¹, Yanling Zhang^2,* and Lanzhen Zhang^1,*

¹ School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China

² Beijing Key Laboratory of TCM Foundation and New Drug Research, School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 678; https://doi.org/10.3390/molecules21050678 - 21 May 2016

Cited by 30 | Viewed by 8645

Abstract

Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, which is a popularly used traditional Chinese medicine for complementary cancer therapy. In the present study, systematic isolation, and in silico pharmacological prediction are implemented to discover potential anti-cancer active GTs [...] Read more.

Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, which is a popularly used traditional Chinese medicine for complementary cancer therapy. In the present study, systematic isolation, and in silico pharmacological prediction are implemented to discover potential anti-cancer active GTs from G. lucidum. Nineteen GTs, three steroids, one cerebroside, and one thymidine were isolated from G. lucidum. Six GTs were first isolated from the fruiting bodies of G. lucidum, including 3β,7β,15β-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid methyl ester (1), 3β,7β,15β-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid (2), 3β,7β,15α,28-tetrahydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid (3), ganotropic acid (4), 26-nor-11,23-dioxo-5α-lanost-8-en-3β,7β,15α,25-tetrol (5) and (3β,7α)-dihydroxy-lanosta-8,24-dien- 11-one (6). (4E,8E)-N-d-2′-hydroxypalmitoyl-l-O-β-d-glucopyranosyl-9-methyl-4,8-spingodienine (7), and stigmasta-7,22-dien-3β,5α,6α-triol (8) were first reported from the genus Ganodema. By using reverse pharmacophoric profiling of the six GTs, thirty potential anti-cancer therapeutic targets were identified and utilized to construct their ingredient-target interaction network. Then nineteen high frequency targets of GTs were selected from thirty potential targets to construct a protein interaction network (PIN). In order to cluster the pharmacological activity of GTs, twelve function modules were identified by molecular complex detection (MCODE) and gene ontology (GO) enrichment analysis. The results indicated that anti-cancer effect of GTs might be related to histone acetylation and interphase of mitotic cell cycle by regulating general control non-derepressible 5 (GCN5) and cyclin-dependent kinase-2 (CDK2), respectively. This research mode of extraction, isolation, pharmacological prediction, and PIN analysis might be beneficial to rapidly predict and discover pharmacological activities of novel compounds. Full article

(This article belongs to the Section Natural Products Chemistry)

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Molecules, Volume 21, Issue 5 (May 2016) – 139 articles

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