Molecules

3341 KiB

Open AccessArticle

Preparation of Pd-Loaded Hierarchical FAU Membranes and Testing in Acetophenone Hydrogenation

by Raffaele Molinari, Cristina Lavorato, Teresa F. Mastropietro, Pietro Argurio, Enrico Drioli and Teresa Poerio

Molecules 2016, 21(3), 394; https://doi.org/10.3390/molecules21030394 - 22 Mar 2016

Cited by 15 | Viewed by 5920

Abstract

Pd-loaded hierarchical FAU (Pd-FAU) membranes, containing an intrinsic secondary non-zeolitic (meso)porosity, were prepared and tested in the catalytic transfer hydrogenation of acetophenone (AP) to produce phenylethanol (PE), an industrially relevant product. The best operating conditions were preliminarily identified by testing different solvents and [...] Read more.

Pd-loaded hierarchical FAU (Pd-FAU) membranes, containing an intrinsic secondary non-zeolitic (meso)porosity, were prepared and tested in the catalytic transfer hydrogenation of acetophenone (AP) to produce phenylethanol (PE), an industrially relevant product. The best operating conditions were preliminarily identified by testing different solvents and organic hydrogen donors in a batch hydrogenation process where micron-sized FAU seeds were employed as catalyst support. Water as solvent and formic acid as hydrogen source resulted to be the best choice in terms of conversion for the catalytic hydrogenation of AP, providing the basis for the design of a green and sustainable process. The best experimental conditions were selected and applied to the Pd-loaded FAU membrane finding enhanced catalytic performance such as a five-fold higher productivity than with the unsupported Pd-FAU crystals (11.0 vs. 2.2 mg_product g_cat⁻¹·h⁻¹). The catalytic performance of the membrane on the alumina support was also tested in a tangential flow system obtaining a productivity higher than that of the batch system (22.0 vs. 11.0 mg_product g_cat⁻¹·h⁻¹). Full article

(This article belongs to the Special Issue Membrane Catalysis)

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1260 KiB

Open AccessArticle

Development of Wax-Incorporated Emulsion Gel Beads for the Encapsulation and Intragastric Floating Delivery of the Active Antioxidant from Tamarindus indica L.

by Sitthiphong Soradech, Intira Petchtubtim, Jeerayu Thongdon-A and Thanchanok Muangman

Molecules 2016, 21(3), 380; https://doi.org/10.3390/molecules21030380 - 22 Mar 2016

Cited by 9 | Viewed by 7474

Abstract

In this study, tamarind (Tamarindus indica L.) seed extracts with potential antioxidant activity and toxicity to cancer cells were developed as functional foods and nutraceutical ingredients in the form of emulsion gel beads. Three extracts were obtained from ethanol and water: TSCH50, [...] Read more.

In this study, tamarind (Tamarindus indica L.) seed extracts with potential antioxidant activity and toxicity to cancer cells were developed as functional foods and nutraceutical ingredients in the form of emulsion gel beads. Three extracts were obtained from ethanol and water: TSCH50, TSCH95 and TSCH. All extracts exhibited high potential for superoxide anion scavenging activity over the IC₅₀ range < 5–11 µg/mL and had no toxic effects on normal cells, however, the water extract (TSCH) was the most effective due to its free radical scavenging activity and toxicity in mitochondrial membranes of cancer cells. Next a study was designed to develop a new formulation for encapsulation and intragastric floating delivery of tamarind seed extract (TSCH) using wax-incorporated emulsion gel beads, which were prepared using a modified ionotropic gelation technique. Tamarind seed extract at 1% (w/w) was used as the active ingredient in all formulations. The effect of the types and amounts of wax on the encapsulation efficiency and percentage of the active release of alginate gel beads was also investigated. The results demonstrated that the incorporation of both waxes into the gel beads had an effect on the percentage of encapsulation efficiency (%) and the percentage of the active ingredient release. Furthermore, the addition of water insoluble waxes (carnauba and bee wax) significantly retarded the release of the active ingredient. The addition of both waxes had a slight effect on drug release behavior. Nevertheless, the increase in incorporated waxes in all formulations could sustain the percentage of active ingredient release. In conclusion, wax-incorporated emulsion gel beads using a modified ionotropic gelation technique could be applied for the intragastric floating delivery and controlled release of functional food and nutraceutical products for their antioxidant and anticancer capacity. 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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7889 KiB

Open AccessArticle

Trapa japonica Pericarp Extract Reduces LPS-Induced Inflammation in Macrophages and Acute Lung Injury in Mice

by Yon-Suk Kim, Jin-Woo Hwang, Jae-Hyuk Jang, Sangkeun Son, Il-Bok Seo, Jae-Hyun Jeong, Ee-Hwa Kim, Sang-Ho Moon, Byong-Tae Jeon and Pyo-Jam Park

Molecules 2016, 21(3), 392; https://doi.org/10.3390/molecules21030392 - 21 Mar 2016

Cited by 31 | Viewed by 7537

Abstract

In this study, we found that chloroform fraction (CF) from TJP ethanolic extract inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and intracellular ROS in RAW264.7 cells. In addition, expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) genes was reduced, as [...] Read more.

In this study, we found that chloroform fraction (CF) from TJP ethanolic extract inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and intracellular ROS in RAW264.7 cells. In addition, expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) genes was reduced, as evidenced by western blot. Our results indicate that CF exerts anti-inflammatory effects by down-regulating expression of iNOS and COX-2 genes through inhibition of MAPK (ERK, JNK and p38) and NF-κB signaling. Similarly we also evaluated the effects of CF on LPS-induced acute lung injury. Male Balb/c mice were pretreated with dexamethasone or CF 1 h before intranasal instillation of LPS. Eight hours after LPS administration, the inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The results indicated that CF inhibited LPS-induced TNF-α and IL-6 production in a dose dependent manner. It was also observed that CF attenuated LPS-induced lung histopathologic changes. In conclusion, these data demonstrate that the protective effect of CF on LPS-induced acute lung injury (ALI) in mice might relate to the suppression of excessive inflammatory responses in lung tissue. Thus, it can be suggested that CF might be a potential therapeutic agent for ALI. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessCommunication

Quorum Sensing Inhibitory Activity of Giganteone A from Myristica cinnamomea King against Escherichia coli Biosensors

by Yasodha Sivasothy, Thiba Krishnan, Kok-Gan Chan, Siti Mariam Abdul Wahab, Muhamad Aqmal Othman, Marc Litaudon and Khalijah Awang

Molecules 2016, 21(3), 391; https://doi.org/10.3390/molecules21030391 - 21 Mar 2016

Cited by 7 | Viewed by 5140

Abstract

Malabaricones A–C (1–3) and giganteone A (4) were isolated from the bark of Myristica cinnamomea King. Their structures were elucidated and characterized by means of NMR and MS spectral analyses. These isolates were evaluated for their anti-quorum sensing activity using quorum sensing biosensors, [...] Read more.

Malabaricones A–C (1–3) and giganteone A (4) were isolated from the bark of Myristica cinnamomea King. Their structures were elucidated and characterized by means of NMR and MS spectral analyses. These isolates were evaluated for their anti-quorum sensing activity using quorum sensing biosensors, namely Escherichia coli [pSB401] and Escherichia coli [pSB1075], whereby the potential of giganteone A (4) as a suitable anti-quorum sensing agent was demonstrated. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Synthesis and Evaluation of Ester Derivatives of 10-Hydroxycanthin-6-one as Potential Antimicrobial Agents

by Fei Zhao, Jiang-Kun Dai, Dan Liu, Shi-Jun Wang and Jun-Ru Wang

Molecules 2016, 21(3), 390; https://doi.org/10.3390/molecules21030390 - 21 Mar 2016

Cited by 18 | Viewed by 5190

Abstract

As part of our continuing research on canthin-6-one antimicrobial agents, a new series of ester derivatives of 10-hydroxycanthin-6-one were synthesized using a simple and effective synthetic route. The structure of each compound was characterized by NMR, ESI-MS, FT-IR, UV, and elemental analysis. The [...] Read more.

As part of our continuing research on canthin-6-one antimicrobial agents, a new series of ester derivatives of 10-hydroxycanthin-6-one were synthesized using a simple and effective synthetic route. The structure of each compound was characterized by NMR, ESI-MS, FT-IR, UV, and elemental analysis. The antimicrobial activity of these compounds against three phytopathogenic fungi (Alternaria solani, Fusarium graminearum, and Fusarium solani) and four bacteria (Bacillus cereus, Bacillus subtilis, Ralstonia solanacearum, and Pseudomonas syringae) were evaluated using the mycelium linear growth rate method and micro-broth dilution method, respectively. The structure-activity relationship is discussed. Of the tested compounds, 4 and 7s displayed significant antifungal activity against F. graminearum, with inhibition rates of 100% at a concentration of 50 μg/mL. Compounds 5, 7s, and 7t showed the best inhibitory activity against all the tested bacteria, with minimum inhibitory concentrations (MICs) between 3.91 and 31.25 μg/mL. Thus, 7s emerged as a promising lead compound for the development of novel canthine-6-one antimicrobial agents. Full article

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

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3256 KiB

Open AccessArticle

Antibacterial Activity and Action Mechanism of the Essential Oil from Enteromorpha linza L. against Foodborne Pathogenic Bacteria

by Jayanta Kumar Patra and Kwang-Hyun Baek

Molecules 2016, 21(3), 388; https://doi.org/10.3390/molecules21030388 - 21 Mar 2016

Cited by 63 | Viewed by 8268

Abstract

Foodborne illness and disease caused by foodborne pathogenic bacteria is continuing to increase day by day and it has become an important topic of concern among various food industries. Many types of synthetic antibacterial agents have been used in food processing and food [...] Read more.

Foodborne illness and disease caused by foodborne pathogenic bacteria is continuing to increase day by day and it has become an important topic of concern among various food industries. Many types of synthetic antibacterial agents have been used in food processing and food preservation; however, they are not safe and have resulted in various health-related issues. Therefore, in the present study, essential oil from an edible seaweed, Enteromorpha linza (AEO), was evaluated for its antibacterial activity against foodborne pathogens, along with the mechanism of its antibacterial action. AEO at 25 mg/disc was highly active against Bacillus cereus (12.3–12.7 mm inhibition zone) and Staphylococcus aureus (12.7–13.3 mm inhibition zone). The minimum inhibitory concentration and minimum bactericidal concentration values of AEO ranged from 12.5–25 mg/mL. Further investigation of the mechanism of action of AEO revealed its strong impairing effect on the viability of bacterial cells and membrane permeability, as indicated by a significant increase in leakage of 260 nm absorbing materials and K⁺ ions from the cell membrane and loss of high salt tolerance. Taken together, these data suggest that AEO has the potential for use as an effective antibacterial agent that functions by impairing cell membrane permeability via morphological alternations, resulting in cellular lysis and cell death. Full article

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

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Open AccessArticle

Synthesis and Biological Evaluation of an ¹⁸Fluorine-Labeled COX Inhibitor—[¹⁸F]Fluorooctyl Fenbufen Amide—For Imaging of Brain Tumors

by Ying-Cheng Huang, Yu-Chia Chang, Chun-Nan Yeh and Chung-Shan Yu

Molecules 2016, 21(3), 387; https://doi.org/10.3390/molecules21030387 - 21 Mar 2016

Cited by 14 | Viewed by 5631

Abstract

Molecular imaging of brain tumors remains a great challenge, despite the advances made in imaging technology. An anti-inflammatory compound may be a useful tool for this purpose because there is evidence of inflammatory processes in brain tumor micro-environments. Fluorooctylfenbufen amide (FOFA) was prepared [...] Read more.

Molecular imaging of brain tumors remains a great challenge, despite the advances made in imaging technology. An anti-inflammatory compound may be a useful tool for this purpose because there is evidence of inflammatory processes in brain tumor micro-environments. Fluorooctylfenbufen amide (FOFA) was prepared from 8-chlorooctanol via treatment with potassium phthalimide, tosylation with Ts₂O, fluorination with KF under phase transfer catalyzed conditions, deprotection using aqueous hydrazine, and coupling with fenbufen. The corresponding radiofluoro product [¹⁸F]FOFA, had a final radiochemical yield of 2.81 mCi and was prepared from activated [¹⁸F]F⁻ (212 mCi) via HPLC purification and concentration. The radiochemical purity was determined to be 99%, and the specific activity was shown to exceed 22 GBq/μmol (EOS) based on decay-corrected calculations. Ex-vivo analysis of [¹⁸F]FOFA in plasma using HPLC showed that the agent had a half-life of 15 min. PET scanning showed significant accumulation of [¹⁸F]FOFA over tumor loci with reasonable contrast in C6-glioma bearing rats. These results suggest that this molecule is a promising agent for the visualization of brain tumors. Further investigations should focus on tumor micro-environments. Full article

(This article belongs to the Section Bioorganic Chemistry)

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3091 KiB

Open AccessArticle

A Solvent-Free Surface Suspension Melt Technique for Making Biodegradable PCL Membrane Scaffolds for Tissue Engineering Applications

by Ratima Suntornnond, Jia An, Ajay Tijore, Kah Fai Leong, Chee Kai Chua and Lay Poh Tan

Molecules 2016, 21(3), 386; https://doi.org/10.3390/molecules21030386 - 21 Mar 2016

Cited by 4 | Viewed by 6972

Abstract

In tissue engineering, there is limited availability of a simple, fast and solvent-free process for fabricating micro-porous thin membrane scaffolds. This paper presents the first report of a novel surface suspension melt technique to fabricate a micro-porous thin membrane scaffolds without using any [...] Read more.

In tissue engineering, there is limited availability of a simple, fast and solvent-free process for fabricating micro-porous thin membrane scaffolds. This paper presents the first report of a novel surface suspension melt technique to fabricate a micro-porous thin membrane scaffolds without using any organic solvent. Briefly, a layer of polycaprolactone (PCL) particles is directly spread on top of water in the form of a suspension. After that, with the use of heat, the powder layer is transformed into a melted layer, and following cooling, a thin membrane is obtained. Two different sizes of PCL powder particles (100 µm and 500 µm) are used. Results show that membranes made from 100 µm powders have lower thickness, smaller pore size, smoother surface, higher value of stiffness but lower ultimate tensile load compared to membranes made from 500 µm powder. C2C12 cell culture results indicate that the membrane supports cell growth and differentiation. Thus, this novel membrane generation method holds great promise for tissue engineering. Full article

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

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Open AccessArticle

Deoxyelephantopin from Elephantopus scaber Inhibits HCT116 Human Colorectal Carcinoma Cell Growth through Apoptosis and Cell Cycle Arrest

by Chim Kei Chan, Gomathi Chan, Khalijah Awang and Habsah Abdul Kadir

Molecules 2016, 21(3), 385; https://doi.org/10.3390/molecules21030385 - 21 Mar 2016

Cited by 32 | Viewed by 7750

Abstract

Deoxyelephantopin (DET), one of the major sesquiterpene lactones derived from Elephantopus scaber was reported to possess numerous pharmacological functions. This study aimed to assess the apoptosis inducing effects and cell cycle arrest by DET followed by elucidation of the mechanisms underlying cell death [...] Read more.

Deoxyelephantopin (DET), one of the major sesquiterpene lactones derived from Elephantopus scaber was reported to possess numerous pharmacological functions. This study aimed to assess the apoptosis inducing effects and cell cycle arrest by DET followed by elucidation of the mechanisms underlying cell death in HCT116 cells. The anticancer activity of DET was evaluated by a MTT assay. Morphological and biochemical changes were detected by Hoescht 33342/PI and Annexin V/PI staining. The results revealed that DET and isodeoxyelephantopin (isoDET) could be isolated from the ethyl acetate fraction of E. scaber leaves via a bioassay-guided approach. DET induced significant dose- and time-dependent growth inhibition of HCT116 cells. Characteristics of apoptosis including nuclear morphological changes and externalization of phosphatidylserine were observed. DET also significantly resulted in the activation of caspase-3 and PARP cleavage. Additionally, DET induced cell cycle arrest at the S phase along with dose-dependent upregulation of p21 and phosphorylated p53 protein expression. DET dose-dependently downregulated cyclin D1, A2, B1, E2, CDK4 and CDK2 protein expression. In conclusion, our data showed that DET induced apoptosis and cell cycle arrest in HCT116 colorectal carcinoma, suggesting that DET has potential as an anticancer agent for colorectal carcinoma. Full article

(This article belongs to the Section Natural Products Chemistry)

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478 KiB

Open AccessArticle

Screening of Satureja subspicata Vis. Honey by HPLC-DAD, GC-FID/MS and UV/VIS: Prephenate Derivatives as Biomarkers

by Igor Jerković, Marina Kranjac, Zvonimir Marijanović, Marina Zekić, Ani Radonić and Carlo Ignazio Giovanni Tuberoso

Molecules 2016, 21(3), 377; https://doi.org/10.3390/molecules21030377 - 21 Mar 2016

Cited by 11 | Viewed by 6071

Abstract

The samples of Satureja subspicata Vis. honey were confirmed to be unifloral by melissopalynological analysis with the characteristic pollen share from 36% to 71%. Bioprospecting of the samples was performed by HPLC-DAD, GC-FID/MS, and UV/VIS. Prephenate derivatives were shown to be dominant by [...] Read more.

The samples of Satureja subspicata Vis. honey were confirmed to be unifloral by melissopalynological analysis with the characteristic pollen share from 36% to 71%. Bioprospecting of the samples was performed by HPLC-DAD, GC-FID/MS, and UV/VIS. Prephenate derivatives were shown to be dominant by the HPLC-DAD analysis, particularly phenylalanine (167.8 mg/kg) and methyl syringate (MSYR, 114.1 mg/kg), followed by tyrosine and benzoic acid. Higher amounts of MSYR (3–4 times) can be pointed out for distinguishing S. subspicata Vis. honey from other Satureja spp. honey types. GC-FID/MS analysis of ultrasonic solvent extracts of the samples revealed MSYR (46.68%, solvent pentane/Et₂O 1:2 (v/v); 52.98%, solvent CH₂Cl₂) and minor abundance of other volatile prephenate derivatives, as well as higher aliphatic compounds characteristic of the comb environment. Two combined extracts (according to the solvents) of all samples were evaluated for their antioxidant properties by FRAP and DPPH assay; the combined extracts demonstrated higher activity (at lower concentrations) in comparison with the average honey sample. UV/VIS analysis of the samples was applied for determination of CIE Lab colour coordinates, total phenolics (425.38 mg GAE/kg), and antioxidant properties (4.26 mmol Fe²⁺/kg (FRAP assay) and 0.8 mmol TEAC/kg (DDPH assay)). Full article

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

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Open AccessArticle

Isoquercitrin Inhibits Hydrogen Peroxide-Induced Apoptosis of EA.hy926 Cells via the PI3K/Akt/GSK3β Signaling Pathway

by Meixia Zhu, Jiankuan Li, Ke Wang, Xuliang Hao, Rui Ge and Qingshan Li

Molecules 2016, 21(3), 356; https://doi.org/10.3390/molecules21030356 - 21 Mar 2016

Cited by 48 | Viewed by 8369

Abstract

Oxidative stress plays a critical role in endothelial injury and the pathogenesis of diverse cardiovascular diseases, including atherosclerosis. Isoquercitrin (quercetin-3-glucoside), a flavonoid distributed widely in plants, exhibits many biological activities, including anti-allergic, anti-viral, anti-inflammatory, and anti-oxidative effects. In the present study, the inhibitory [...] Read more.

Oxidative stress plays a critical role in endothelial injury and the pathogenesis of diverse cardiovascular diseases, including atherosclerosis. Isoquercitrin (quercetin-3-glucoside), a flavonoid distributed widely in plants, exhibits many biological activities, including anti-allergic, anti-viral, anti-inflammatory, and anti-oxidative effects. In the present study, the inhibitory effect of isoquercitrin on H₂O₂-induced apoptosis of EA.hy926 cells was evaluated. MTT assays showed that isoquercitrin significantly inhibited H₂O₂-induced loss of viability in EA.hy926 cells. Hoechst33342/PI and Annexin V-FITC/PI fluorescent double staining indicated that isoquercitrin inhibited H₂O₂-induced apoptosis of EA.hy926 cells. Western blotting demonstrated that isoquercitrin prevented H₂O₂-induced increases in cleaved caspase-9 and cleaved caspase-3 expression, while increasing expression of anti-apoptotic protein Mcl-1. Additionally, isoquercitrin significantly increased the expression of p-Akt and p-GSK3β in a dose-dependent manner in EA.hy926 cells. LY294002, a PI3K/Akt inhibitor, inhibited isoquercitrin-induced GSK3β phosphorylation and increase of Mcl-1 expression, which indicated that regulation of isoquercitrin on Mcl-1 expression was likely related to the modulation of Akt activation. These results demonstrated that the anti-apoptotic effect of isoquercitrin on H₂O₂-induced EA.hy926 cells was likely associated with the regulation of isoquercitrin on Akt/GSK3β signaling pathway and that isoquercitrin could be used clinically to interfere with the progression of endothelial injury-associated cardiovascular disease. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Synthesis, Characterization, and Antifungal Activity of Phenylpyrrole-Substituted Tetramic Acids Bearing Carbonates

by Wen-Qin Xu, Min Chen, Kun-Yao Wang, Zheng-Jiao Ren, Ai-Min Lu and Chun-Long Yang

Molecules 2016, 21(3), 355; https://doi.org/10.3390/molecules21030355 - 21 Mar 2016

Cited by 12 | Viewed by 5291

Abstract

For the aim of discovering new fungicide, a series of phenylpyrrole-substituted tetramic acid derivatives bearing carbonates 6a–q were designed and synthesized via 4-(2,4-dioxopyrrolidin-3-ylidene)-4-(phenylamino)butanoic acids 4a–k and the cyclized products 1′,3,4,5′-tetrahydro-[2,3′-bipyrrolylidene]-2′,4′,5(1H)-triones 5a–k. The compounds were characterized using IR, ¹H- and ¹³ [...] Read more.

For the aim of discovering new fungicide, a series of phenylpyrrole-substituted tetramic acid derivatives bearing carbonates 6a–q were designed and synthesized via 4-(2,4-dioxopyrrolidin-3-ylidene)-4-(phenylamino)butanoic acids 4a–k and the cyclized products 1′,3,4,5′-tetrahydro-[2,3′-bipyrrolylidene]-2′,4′,5(1H)-triones 5a–k. The compounds were characterized using IR, ¹H- and ¹³C-NMR spectroscopy, mass spectrometry (EI-MS), and elemental analysis. The structure of 6b was confirmed by X-ray diffraction crystallography. The title compounds 6a–q were bioassayed in vitro against the phytopathogenic fungi Fusarium graminearum, Botrytis cinerea and Rhizoctonia solani at a concentration of 100 μg/mL, respectively. Most compounds displayed good inhibitory activity. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessArticle

Casticin Inhibits A375.S2 Human Melanoma Cell Migration/Invasion through Downregulating NF-κB and Matrix Metalloproteinase-2 and -1

by Zih-Yun Wu, Jin-Cherng Lien, Yi-Ping Huang, Ching-Lung Liao, Jen-Jyh Lin, Ming-Jen Fan, Yang-Ching Ko, Yu-Ping Hsiao, Hsu-Feng Lu and Jing-Gung Chung

Molecules 2016, 21(3), 384; https://doi.org/10.3390/molecules21030384 - 19 Mar 2016

Cited by 26 | Viewed by 8362

Abstract

Casticin is one of the main components from Fructus Viticis, which is widely used as an anti-inflammatory agent. The mechanism of how casticin affects melanoma cell migration and invasion is still not well known. Here we studied the anti-metastasis effects of casticin [...] Read more.

Casticin is one of the main components from Fructus Viticis, which is widely used as an anti-inflammatory agent. The mechanism of how casticin affects melanoma cell migration and invasion is still not well known. Here we studied the anti-metastasis effects of casticin on A375.S2 melanoma cells by using a non-lethal concentration. First; we used an adhesion assay to test the A375.S2 cells’ adhesion ability after treatment with casticin. We next investigated the cell migration ability after casticin treatment by using a wound healing assay to prove that the migration of A375.S2 cells can be inhibited by casticin and double checked the results using the transwell-migration assay. The suppressive effects on matrix metalloproteinase-2; and -9 (MMP-2; and -9) activities were examined by gelatin zymography. Furthermore, western blotting was used to investigate the protein level changes in A375.S2 cells. We found that p-EGFR; Ras and p-ERK1/2 are decreased by casticin, indicating that casticin can down-regulate the migration and invasion ability of A375.S2 cells via the p-EGFR/Ras/p-ERK pathway. The NF-κB p65 and p-ERK levels in nuclear proteins are also decreased by treatment with casticin. An EMSA assay also discovered that the NF-κB p65 and DNA interaction is decreased. NF-κB p65 protein level was examined by immunofluorescence staining and also decreased. Our findings suggest that casticin has anti-metastatic potential by decreasing the invasiveness of A375.S2 cells. We also found that casticin suppressed A375.S2 cell proliferation and cell adhesion ability, but did not affect cell death, as examined using cytometry and a collagen adhesion assay. Based on these observations, casticin could be used as an inhibitor of migration and invasion of human melanoma cells in the future. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

A New Megastigmane Sesquiterpenoid from Zanthoxylum Schinifolium Sieb. et Zucc

by Linzhen Hu, Kongchao Wang, Zhenzhen Wang, Junjun Liu, Kaiping Wang, Jinwen Zhang, Zengwei Luo, Yongbo Xue, Yu Zhang and Yonghui Zhang

Molecules 2016, 21(3), 383; https://doi.org/10.3390/molecules21030383 - 19 Mar 2016

Cited by 5 | Viewed by 5456

Abstract

Zanthoxylum schinifolium Sieb. et Zucc. (Rutaceae), a dioecious shrub with hooked prickly branches, has been used as folk medicine for the treatment of the common cold, stomach ache, diarrhea, and jaundice in China, Korea, and Japan. In our phytochemical investigations on this genus, [...] Read more.

Zanthoxylum schinifolium Sieb. et Zucc. (Rutaceae), a dioecious shrub with hooked prickly branches, has been used as folk medicine for the treatment of the common cold, stomach ache, diarrhea, and jaundice in China, Korea, and Japan. In our phytochemical investigations on this genus, a new megastigmane sesquiterpenoid, which is referred to as schinifolenol A (1), was isolated from Z. schinifolium. The stereochemistry was characterized via the analyses of extensive spectra. The absolute configuration was established by the application of a modified Mosher’s experiment and assisted by a time-dependent density functional theory (TD-DFT) on calculated electronic circular dichroism (ECD). Bioactivity screenings showed that compound 1 exhibited a safe hypotoxicity and a better selectivity on anti-Kaposi’s sarcoma associated herpes virus (KSHV). Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Effects of Astaxanthin from Litopenaeus Vannamei on Carrageenan-Induced Edema and Pain Behavior in Mice

by Zulkiflee Kuedo, Anantita Sangsuriyawong, Wanwimol Klaypradit, Varomyalin Tipmanee and Pennapa Chonpathompikunlert

Molecules 2016, 21(3), 382; https://doi.org/10.3390/molecules21030382 - 19 Mar 2016

Cited by 25 | Viewed by 8207

Abstract

Carrageenan produces both inflammation and pain when injected in mouse paws via enhancement of reactive oxygen species formation. We have investigated an effect of astaxanthin extracted from Litopenaeus vannamei in carrageenan-induced mice paw edema and pain. The current study demonstrates interesting effects from [...] Read more.

Carrageenan produces both inflammation and pain when injected in mouse paws via enhancement of reactive oxygen species formation. We have investigated an effect of astaxanthin extracted from Litopenaeus vannamei in carrageenan-induced mice paw edema and pain. The current study demonstrates interesting effects from astaxanthin treatment in mice: an inhibition of paw edema induced in hind paw, an increase in mechanical paw withdrawal threshold and thermal paw withdrawal latency, and a reduction in the amount of myeloperoxidase enzyme and lipid peroxidation products in the paw. Furthermore the effect was comparable to indomethacin, a standard treatment for inflammation symptoms. Due to adverse effects of indomethacin on cardiovascular and gastrointestinal systems, our study suggests promising prospect of astaxanthin extract as an anti-inflammatory alternative against carrageenan-induced paw edema and pain behavior. 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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Open AccessFeature PaperArticle

Clean Transformation of Ethanol to Useful Chemicals. The Behavior of a Gold-Modified Silicalite Catalyst

by Ermelinda Falletta, Michele Rossi, Joaquim Henrique Teles and Cristina Della Pina

Molecules 2016, 21(3), 379; https://doi.org/10.3390/molecules21030379 - 19 Mar 2016

Cited by 4 | Viewed by 7049

Abstract

Upon addition of gold to silicalite-1 pellets (a MFI-type zeolite), the vapor phase oxidation of ethanol could be addressed to acetaldehyde or acetic acid formation. By optimizing the catalyst composition and reaction conditions, the conversion of ethanol could be tuned to acetaldehyde with [...] Read more.

Upon addition of gold to silicalite-1 pellets (a MFI-type zeolite), the vapor phase oxidation of ethanol could be addressed to acetaldehyde or acetic acid formation. By optimizing the catalyst composition and reaction conditions, the conversion of ethanol could be tuned to acetaldehyde with 97% selectivity at 71% conversion or to acetic acid with 78% selectivity at total conversion. Considering that unloaded silicalite-1 was found to catalyze the dehydration of ethanol to diethylether or ethene, a green approach for the integrated production of four important chemicals is herein presented. This is based on renewable ethanol as a reagent and a modular catalytic process. Full article

(This article belongs to the Special Issue Coinage Metal (Copper, Silver, and Gold) Catalysis)

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Open AccessArticle

Fluidized Bed Membrane Reactors for Ultra Pure H₂ Production—A Step forward towards Commercialization

by Arash Helmi, Ekain Fernandez, Jon Melendez, David Alfredo Pacheco Tanaka, Fausto Gallucci and Martin Van Sint Annaland

Molecules 2016, 21(3), 376; https://doi.org/10.3390/molecules21030376 - 19 Mar 2016

Cited by 49 | Viewed by 8065

Abstract

In this research the performance of a fluidized bed membrane reactor for high temperature water gas shift and its long term stability was investigated to provide a proof-of-concept of the new system at lab scale. A demonstration unit with a capacity of 1 [...] Read more.

In this research the performance of a fluidized bed membrane reactor for high temperature water gas shift and its long term stability was investigated to provide a proof-of-concept of the new system at lab scale. A demonstration unit with a capacity of 1 Nm³/h of ultra-pure H₂ was designed, built and operated over 900 h of continuous work. Firstly, the performance of the membranes were investigated at different inlet gas compositions and at different temperatures and H₂ partial pressure differences. The membranes showed very high H₂ fluxes (3.89 × 10⁻⁶ mol·m⁻²·Pa⁻¹·s⁻¹ at 400 °C and 1 atm pressure difference) with a H₂/N₂ ideal perm-selectivity (up to 21,000 when integrating five membranes in the module) beyond the DOE 2015 targets. Monitoring the performance of the membranes and the reactor confirmed a very stable performance of the unit for continuous high temperature water gas shift under bubbling fluidization conditions. Several experiments were carried out at different temperatures, pressures and various inlet compositions to determine the optimum operating window for the reactor. The obtained results showed high hydrogen recovery factors, and very low CO concentrations at the permeate side (in average <10 ppm), so that the produced hydrogen can be directly fed to a low temperature PEM fuel cell. Full article

(This article belongs to the Special Issue Membrane Catalysis)

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Open AccessArticle

Functionalization of Calcium Sulfate/Bioglass Scaffolds with Zinc Oxide Whisker

by Cijun Shuai, Jianhua Zhou, Dan Gao, Chengde Gao, Pei Feng and Shuping Peng

Molecules 2016, 21(3), 378; https://doi.org/10.3390/molecules21030378 - 18 Mar 2016

Cited by 21 | Viewed by 5708

Abstract

There are urgent demands for satisfactory antibacterial activity and mechanical properties of bone scaffolds. In this study, zinc oxide whisker (ZnOw) was introduced into calcium sulfate/bioglass scaffolds. Antimicrobial behavior was analyzed using Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). [...] Read more.

There are urgent demands for satisfactory antibacterial activity and mechanical properties of bone scaffolds. In this study, zinc oxide whisker (ZnOw) was introduced into calcium sulfate/bioglass scaffolds. Antimicrobial behavior was analyzed using Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The results showed that the scaffolds presented a strong antibacterial activity after introducing ZnOw, due to the antibacterial factors released from the degradation of ZnO. Moreover, ZnOw was also found to have a distinct reinforcing effect on mechanical properties. This was ascribed to whisker pull-out, crack bridging, crack deflection, crack branching and other toughening mechanisms. In addition, the cell culture experiments showed that the scaffolds with ZnOw had a good biocompatibility. Full article

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Open AccessArticle

A Novel Biomolecule-Mediated Reduction of Graphene Oxide: A Multifunctional Anti-Cancer Agent

by Yun-Jung Choi, Eunsu Kim, JaeWoong Han, Jin-Hoi Kim and Sangiliyandi Gurunathan

Molecules 2016, 21(3), 375; https://doi.org/10.3390/molecules21030375 - 18 Mar 2016

Cited by 63 | Viewed by 9172

Abstract

Graphene oxide (GO) is a monolayer of carbon atoms that form a dense honeycomb structure, consisting of hydroxyl and epoxide functional groups on the two accessible sides and carboxylic groups at the edges. In contrast, graphene is a two-dimensional sheet of sp2-hybridized carbon [...] Read more.

Graphene oxide (GO) is a monolayer of carbon atoms that form a dense honeycomb structure, consisting of hydroxyl and epoxide functional groups on the two accessible sides and carboxylic groups at the edges. In contrast, graphene is a two-dimensional sheet of sp2-hybridized carbon atoms packed into a honeycomb lattice. Graphene has great potential for use in biomedical applications due to its excellent physical and chemical properties. In this study, we report a facile and environmentally friendly approach for the synthesis of reduced graphene oxide (rGO) using uric acid (UA). The synthesized uric acid-reduced graphene oxide (UA-rGO) was fully characterized by ultraviolet-visible (UV-Vis) absorption spectra, X-ray diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), and Raman spectroscopy. GO and UA-rGO induced a dose-dependent decrease in cell viability and induced cytotoxicity in human ovarian cancer cells. The results from this study suggest that UA-rGO could cause apoptosis in mammalian cells. The toxicity of UA-rGO is significantly higher than GO. Based on our findings, UA-rGO shows cytotoxic effects against human ovarian cancer cells, and its synthesis is environmentally friendly. UA-rGO significantly inhibits cell viability by increasing lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) generation, activation of caspase-3, and DNA fragmentation. This is the first report to describe the comprehensive effects of UA-rGO in ovarian cancer cells. We believe that the functional aspects of newly synthesized UA-rGO will provide advances towards various biomedical applications in the near future. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Compound Library Screening Identified Cardiac Glycoside Digitoxin as an Effective Growth Inhibitor of Gefitinib-Resistant Non-Small Cell Lung Cancer via Downregulation of α-Tubulin and Inhibition of Microtubule Formation

by Yi-Ze Zhang, Xi Chen, Xing-Xing Fan, Jian-Xing He, Jun Huang, Da-Kai Xiao, Yan-Ling Zhou, Sen-You Zheng, Jia-Hui Xu, Xiao-Jun Yao, Liang Liu and Elaine Lai-Han Leung

Molecules 2016, 21(3), 374; https://doi.org/10.3390/molecules21030374 - 18 Mar 2016

Cited by 26 | Viewed by 8100

Abstract

Non-small-cell lung cancer (NSCLC) dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI) for EGFR downstream signaling is initially [...] Read more.

Non-small-cell lung cancer (NSCLC) dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI) for EGFR downstream signaling is initially effective. However, drug resistance frequently happens due to additional mutation on EGFR, such as substitution from threonine to methionine at amino acid position 790 (T790M). In this study, we screened a traditional Chinese medicine (TCM) compound library consisting of 800 single compounds in TKI-resistance NSCLC H1975 cells, which contains substitutions from leucine to arginine at amino acid 858 (L858R) and T790M mutation on EGFR. Attractively, among these compounds there are 24 compounds CC₅₀ of which was less than 2.5 μM were identified. We have further investigated the mechanism of the most effective one, Digitoxin. It showed a significantly cytotoxic effect in H1975 cells by causing G2 phase arrest, also remarkably activated 5′ adenosine monophosphate-activated protein kinase (AMPK). Moreover, we first proved that Digitoxin suppressed microtubule formation through decreasing α-tubulin. Therefore, it confirmed that Digitoxin effectively depressed the growth of TKI-resistance NSCLC H1975 cells by inhibiting microtubule polymerization and inducing cell cycle arrest. Full article

(This article belongs to the Collection Herbal Medicine Research)

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Open AccessReview

Coenzyme Q and Its Role in the Dietary Therapy against Aging

by Alfonso Varela-López, Francesca Giampieri, Maurizio Battino and José L. Quiles

Molecules 2016, 21(3), 373; https://doi.org/10.3390/molecules21030373 - 18 Mar 2016

Cited by 69 | Viewed by 12578

Abstract

Coenzyme Q (CoQ) is a naturally occurring molecule located in the hydrophobic domain of the phospholipid bilayer of all biological membranes. Shortly after being discovered, it was recognized as an essential electron transport chain component in mitochondria where it is particularly abundant. Since [...] Read more.

Coenzyme Q (CoQ) is a naturally occurring molecule located in the hydrophobic domain of the phospholipid bilayer of all biological membranes. Shortly after being discovered, it was recognized as an essential electron transport chain component in mitochondria where it is particularly abundant. Since then, more additional roles in cell physiology have been reported, including antioxidant, signaling, death prevention, and others. It is known that all cells are able to synthesize functionally sufficient amounts of CoQ under normal physiological conditions. However, CoQ is a molecule found in different dietary sources, which can be taken up and incorporated into biological membranes. It is known that mitochondria have a close relationship with the aging process. Additionally, delaying the aging process through diet has aroused the interest of scientists for many years. These observations have stimulated investigation of the anti-aging potential of CoQ and its possible use in dietary therapies to alleviate the effects of aging. In this context, the present review focus on the current knowledge and evidence the roles of CoQ cells, its relationship with aging, and possible implications of dietary CoQ in relation to aging, lifespan or age-related diseases. Full article

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

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Open AccessArticle

Production of Fusaric Acid by Fusarium spp. in Pure Culture and in Solid Medium Co-Cultures

by Nadine Bohni, Valérie Hofstetter, Katia Gindro, Bart Buyck, Olivier Schumpp, Samuel Bertrand, Michel Monod and Jean-Luc Wolfender

Molecules 2016, 21(3), 370; https://doi.org/10.3390/molecules21030370 - 18 Mar 2016

Cited by 25 | Viewed by 10049

Abstract

The ability of fungi isolated from nails of patients suffering from onychomycosis to induce de novo production of bioactive compounds in co-culture was examined. Comparison between the metabolite profiles produced by Sarocladium strictum, by Fusarium oxysporum, and by these two species [...] Read more.

The ability of fungi isolated from nails of patients suffering from onychomycosis to induce de novo production of bioactive compounds in co-culture was examined. Comparison between the metabolite profiles produced by Sarocladium strictum, by Fusarium oxysporum, and by these two species in co-culture revealed de novo induction of fusaric acid based on HRMS. Structure confirmation of this toxin, using sensitive microflow NMR, required only three 9-cm Petri dishes of fungal culture. A targeted metabolomics study based on UHPLC-HRMS confirmed that the production of fusaric acid was strain-dependent. Furthermore, the detected toxin levels suggested that onychomycosis-associated fungal strains of the F. oxysporum and F. fujikuroi species complexes are much more frequently producing fusaric acid, and in higher amount, than strains of the F. solani species complex. Fusarium strains producing no significant amounts of this compound in pure culture, were shown to de novo produce that compound when grown in co-culture. The role of fusaric acid in fungal virulence and defense is discussed. Full article

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

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Open AccessArticle

Binding Mode and Selectivity of Steroids towards Glucose-6-phosphate Dehydrogenase from the Pathogen Trypanosoma cruzi

by Cecilia Ortiz, Francesca Moraca, Andrea Medeiros, Maurizio Botta, Niall Hamilton and Marcelo A. Comini

Molecules 2016, 21(3), 368; https://doi.org/10.3390/molecules21030368 - 17 Mar 2016

Cited by 20 | Viewed by 7051

Abstract

Glucose-6-phosphate dehydrogenase (G6PDH) plays a housekeeping role in cell metabolism by generating reducing power (NADPH) and fueling the production of nucleotide precursors (ribose-5-phosphate). Based on its indispensability for pathogenic parasites from the genus Trypanosoma, G6PDH is considered a drug target candidate. Several [...] Read more.

Glucose-6-phosphate dehydrogenase (G6PDH) plays a housekeeping role in cell metabolism by generating reducing power (NADPH) and fueling the production of nucleotide precursors (ribose-5-phosphate). Based on its indispensability for pathogenic parasites from the genus Trypanosoma, G6PDH is considered a drug target candidate. Several steroid-like scaffolds were previously reported to target the activity of G6PDH. Epiandrosterone (EA) is an uncompetitive inhibitor of trypanosomal G6PDH for which its binding site to the enzyme remains unknown. Molecular simulation studies with the structure of Trypanosoma cruzi G6PDH revealed that EA binds in a pocket close to the G6P binding-site and protrudes into the active site blocking the interaction between substrates and hence catalysis. Site directed mutagenesis revealed the important steroid-stabilizing effect of residues (L80, K83 and K84) located on helix α-1 of T. cruzi G6PDH. The higher affinity and potency of 16α-Br EA by T. cruzi G6PDH is explained by the formation of a halogen bond with the hydrogen from the terminal amide of the NADP+-nicotinamide. At variance with the human enzyme, the inclusion of a 21-hydroxypregnane-20-one moiety to a 3β-substituted steroid is detrimental for T. cruzi G6PDH inhibition. The species-specificity of certain steroid derivatives towards the parasite G6PDH and the corresponding biochemically validated binding models disclosed in this work may prove valuable for the development of selective inhibitors against the pathogen’s enzyme. 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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Pharmacokinetics of Maleic Acid as a Food Adulterant Determined by Microdialysis in Rat Blood and Kidney Cortex

by Mei-Ling Hou, Chia-Ming Lu, Chi-Hung Lin, Lie-Chwen Lin and Tung-Hu Tsai

Molecules 2016, 21(3), 367; https://doi.org/10.3390/molecules21030367 - 17 Mar 2016

Cited by 7 | Viewed by 5848

Abstract

Maleic acid has been shown to be used as a food adulterant in the production of modified starch by the Taiwan Food and Drug Administration. Due to the potential toxicity of maleic acid to the kidneys, this study aimed to develop an analytical [...] Read more.

Maleic acid has been shown to be used as a food adulterant in the production of modified starch by the Taiwan Food and Drug Administration. Due to the potential toxicity of maleic acid to the kidneys, this study aimed to develop an analytical method to investigate the pharmacokinetics of maleic acid in rat blood and kidney cortex. Multiple microdialysis probes were simultaneously inserted into the jugular vein and the kidney cortex for sampling after maleic acid administration (10 or 30 mg/kg, i.v., respectively). The pharmacokinetic results demonstrated that maleic acid produced a linear pharmacokinetic phenomenon within the doses of 10 and 30 mg/kg. The area under concentration versus time curve (AUC) of the maleic acid in kidney cortex was 5-fold higher than that in the blood after maleic acid administration (10 and 30 mg/kg, i.v., respectively), indicating that greater accumulation of maleic acid occurred in the rat kidney. Full article

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

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Open AccessArticle

Fluoride-Promoted Esterification (FPE) Chemistry: A Robust Route to Bis-MPA Dendrons and Their Postfunctionalization

by Patrik Stenström, Oliver C. J. Andrén and Michael Malkoch

Molecules 2016, 21(3), 366; https://doi.org/10.3390/molecules21030366 - 17 Mar 2016

Cited by 18 | Viewed by 6575

Abstract

Bifunctional dendrons based on 2,2-bis(methylol)propionic acid (bis-MPA) are highly desirable scaffolds for biomedical applications. This is due to their flawless nature and large and exact number of functional groups as well as being biodegradable and biocompatible. Herein, we describe a facile divergent growth [...] Read more.

Bifunctional dendrons based on 2,2-bis(methylol)propionic acid (bis-MPA) are highly desirable scaffolds for biomedical applications. This is due to their flawless nature and large and exact number of functional groups as well as being biodegradable and biocompatible. Herein, we describe a facile divergent growth approach to their synthesis from monobenzylated tetraethylene glycol and post functionalization utilizing fluoride-promoted esterification (FPE) chemistry protocols. The scaffolds, presenting selectively deprotectable hydroxyls in the periphery and at the focal point, were isolated on a multigram scale with excellent purity up to the fourth generation dendron with a molecular weight of 2346 Da in seven reactions with a total yield of 50%. The third generation dendron was used as a model compound to demonstrate its functionalizability. Selective deprotection of the dendron’s focal point was achieved with an outstanding yield of 94%, and biotin as well as azido functionalities were introduced to its focal point and periphery, respectively, through FPE chemistry. Bulky disperse red dyes were clicked through CuAAC to the dendron’s azido groups, giving a biotinylated dendron with multivalent dyes with a molecular weight of 6252 Da in a total yield of 37% in five reactions with an average yield of 82% starting from the third generation focally and peripherally protected dendron. FPE chemistry proved to be a superb improvement over previous protocols towards bis-MPA dendrons as high purity and yields were obtained with less toxic solvents and greatly improved monomer utilization. Full article

(This article belongs to the Special Issue Functional Dendrimers)

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Silver Nanoparticles Exhibit the Dose-Dependent Anti-Proliferative Effect against Human Squamous Carcinoma Cells Attenuated in the Presence of Berberine

by Arkadiusz Dziedzic, Robert Kubina, Rafał J. Bułdak, Magda Skonieczna and Krzysztof Cholewa

Molecules 2016, 21(3), 365; https://doi.org/10.3390/molecules21030365 - 17 Mar 2016

Cited by 61 | Viewed by 9797

Abstract

The biological activity of nanosize silver particles towards oral epithelium-derived carcinoma seems to be still underinvestigated. We evaluated the influence of low doses of nanosize scale silver particles on the proliferation and viability of malignant oral epithelial keratinocytes in vitro, alone and [...] Read more.

The biological activity of nanosize silver particles towards oral epithelium-derived carcinoma seems to be still underinvestigated. We evaluated the influence of low doses of nanosize scale silver particles on the proliferation and viability of malignant oral epithelial keratinocytes in vitro, alone and in conjunction with the plant alkaloid berberine. Cells of human tongue squamous carcinoma SCC-25 (ATCC CRL-1628), cultivated with the mixture of Dulbecco's modified Eagle’s medium, were exposed to silver nanoparticles alone (AgNPs, concentrations from 0.31 to 10 μg/mL) and to a combination of AgNPs with berberine chloride (BER, 1/2 IC₅₀ concentration) during 24 h and 48 h. The cytotoxic activity of AgNPs with diameters of 10 nm ± 4 nm was measured by 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Cell cycle analysis was performed by treating cells with propidium iodide followed by flow-activated cell sorting. RT-QPCR reaction was used to assess expression of anti-apoptotic proteins Bcl-2 and pro-apoptotic protein Bcl-2-associated X protein Bax genes expression. Monodisperse silver nanoparticles at a concentration of 10 μg/mL arrested SCC-25 cells cycle after 48 h at the G0/G1 phase in a dose- and time-dependent manner through disruption G0/G1 checkpoint, with increase of Bax/Bcl-2 ratio gene expression. AgNPs exhibit cytotoxic effects on SCC-25 malignant oral epithelial keratinocytes, which is diminished when combined with BER. The AgNPs concentration required to inhibit the growth of carcinoma cells by 50% (IC₅₀) after 48 h was estimated at 5.19 μg/mL. AgNPs combined with BER increased the expression of Bcl-2 while decreasing the ratio of Bax/Bcl-2 in SCC-25 cells. Silver particles at low doses therefore reduce the proliferation and viability of oral squamous cell carcinoma cells. SCC-25 cells are susceptible to damage from AgNPs-induced stress, which can be regulated by the natural alkaloid berberine, suggesting that nanoparticles may be potentially used in a chemoprevention/chemotherapy by augmentation of action of standard anti-cancer drugs. Full article

(This article belongs to the Section Metabolites)

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Comparison of the Profile and Composition of Volatiles in Coniferous Needles According to Extraction Methods

by Yonjin Jun, Sang Mi Lee, Hyun Kyoung Ju, Hong Jin Lee, Hyung-Kyoon Choi, Gyeong Suk Jo and Young-Suk Kim

Molecules 2016, 21(3), 363; https://doi.org/10.3390/molecules21030363 - 17 Mar 2016

Cited by 9 | Viewed by 5684

Abstract

The enantiomeric distribution and profile of volatiles in plants, which affect the biological and organoleptic properties, can be varied depending on extraction methods as well as their cultivars. The secondary volatile components of the needles of three conifer cultivars (Chamaecyparispisifera, Chamaecyparisobtusa [...] Read more.

The enantiomeric distribution and profile of volatiles in plants, which affect the biological and organoleptic properties, can be varied depending on extraction methods as well as their cultivars. The secondary volatile components of the needles of three conifer cultivars (Chamaecyparispisifera, Chamaecyparisobtusa, and Thujaorientalis) were compared. Furthermore, the effects of three different extraction methods—solid-phase microextraction (SPME), steam distillation (SD), and solvent extraction (SE)—on the composition and enantiomeric distribution of those volatiles were elucidated. Monoterpene hydrocarbons predominated in all samples, and the compositions of sesquiterpenes and diterpenes differed according to the cultivar. In particular, the yields of oxygenated monoterpenes and sesquiterpenes were greatest for SD, whereas those of sesquiterpenes and diterpenes were highest for SE. On the other hand, more monoterpenes with higher volatility could be obtained with SPME and SD than when using SE. In addition, the enantiomeric composition of nine chiral compounds found in three cultivars differed according to their chemotype. There were also some differences in the yielded oxygenated monoterpenes and sesquiterpene hydrocarbons, but not monoterpene hydrocarbons, according to the extraction method. These results demonstrate that the extraction methods used as well as the cultivars influence the measured volatile profiles and enantiomeric distribution of coniferous needle extracts. Full article

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

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Open AccessArticle

Searching for Multi-Targeting Neurotherapeutics against Alzheimer’s: Discovery of Potent AChE-MAO B Inhibitors through the Decoration of the 2H-Chromen-2-one Structural Motif

by Leonardo Pisani, Roberta Farina, Ramon Soto-Otero, Nunzio Denora, Giuseppe Felice Mangiatordi, Orazio Nicolotti, Estefania Mendez-Alvarez, Cosimo Damiano Altomare, Marco Catto and Angelo Carotti

Molecules 2016, 21(3), 362; https://doi.org/10.3390/molecules21030362 - 17 Mar 2016

Cited by 48 | Viewed by 7434

Abstract

The need for developing real disease-modifying drugs against neurodegenerative syndromes, particularly Alzheimer’s disease (AD), shifted research towards reliable drug discovery strategies to unveil clinical candidates with higher therapeutic efficacy than single-targeting drugs. By following the multi-target approach, we designed and synthesized a novel [...] Read more.

The need for developing real disease-modifying drugs against neurodegenerative syndromes, particularly Alzheimer’s disease (AD), shifted research towards reliable drug discovery strategies to unveil clinical candidates with higher therapeutic efficacy than single-targeting drugs. By following the multi-target approach, we designed and synthesized a novel class of dual acetylcholinesterase (AChE)-monoamine oxidase B (MAO-B) inhibitors through the decoration of the 2H-chromen-2-one skeleton. Compounds bearing a propargylamine moiety at position 3 displayed the highest in vitro inhibitory activities against MAO-B. Within this series, derivative 3h emerged as the most interesting hit compound, being a moderate AChE inhibitor (IC₅₀ = 8.99 µM) and a potent and selective MAO-B inhibitor (IC₅₀ = 2.8 nM). Preliminary studies in human neuroblastoma SH-SY5Y cell lines demonstrated its low cytotoxicity and disclosed a promising neuroprotective effect at low doses (0.1 µM) under oxidative stress conditions promoted by two mitochondrial toxins (oligomycin-A and rotenone). In a Madin-Darby canine kidney (MDCK)II-MDR1 cell-based transport study, Compound 3h was able to permeate the BBB-mimicking monolayer and did not result in a glycoprotein-p (P-gp) substrate, showing an efflux ratio = 0.96, close to that of diazepam. Full article

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

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Flavonoids, Antioxidant Potential, and Acetylcholinesterase Inhibition Activity of the Extracts from the Gametophyte and Archegoniophore of Marchantia polymorpha L.

by Xin Wang, Jianguo Cao, Yuhuan Wu, Quanxi Wang and Jianbo Xiao

Molecules 2016, 21(3), 360; https://doi.org/10.3390/molecules21030360 - 17 Mar 2016

Cited by 40 | Viewed by 8171

Abstract

Marchantia polymorpha L. is a representative bryophyte used as a traditional Chinese medicinal herb for scald and pneumonia. The phytochemicals in M. polymorpha L. are terpenoids and flavonoids, among which especially the flavonoids show significant human health benefits. Many researches on the gametophyte [...] Read more.

Marchantia polymorpha L. is a representative bryophyte used as a traditional Chinese medicinal herb for scald and pneumonia. The phytochemicals in M. polymorpha L. are terpenoids and flavonoids, among which especially the flavonoids show significant human health benefits. Many researches on the gametophyte of M. polymorpha L. have been reported. However, as the reproductive organ of M. polymorpha L., the bioactivity and flavonoids profile of the archegoniophore have not been reported, so in this work the flavonoid profiles, antioxidant and acetylcholinesterase inhibition activities of the extracts from the archegoniophore and gametophyte of M. polymorpha L. were compared by radical scavenging assay methods (DPPH, ABTS, O²⁻), reducing power assay, acetylcholinesterase inhibition assay and LC-MS analysis. The results showed that the total flavonoids content in the archegoniophore was about 10-time higher than that of the gametophyte. Differences between the archegoniophore and gametophyte of M. polymorpha L. were observed by LC-MS analysis. The archegoniophore extracts showed stronger bio-activities than those of the gametophyte. The archegoniophore extract showed a significant acetylcholinesterase inhibition, while the gametophyte extract hardly inhibited it. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessReview

New Potential Pharmacological Functions of Chinese Herbal Medicines via Regulation of Autophagy

by Betty Yuen Kwan Law, Simon Wing Fai Mok, An Guo Wu, Christopher Wai Kei Lam, Margaret Xin Yi Yu and Vincent Kam Wai Wong

Molecules 2016, 21(3), 359; https://doi.org/10.3390/molecules21030359 - 17 Mar 2016

Cited by 55 | Viewed by 13276

Abstract

Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as misfolded proteins or damaged organelles. Defects in autophagy are implicated [...] Read more.

Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as misfolded proteins or damaged organelles. Defects in autophagy are implicated in the pathogenesis of diseases including cancers, myopathy, neurodegenerations, infections and cardiovascular diseases. In the recent decade, traditional drugs with new clinical applications are not only commonly found in Western medicines, but also highlighted in Chinese herbal medicines (CHM). For instance, pharmacological studies have revealed that active components or fractions from Chaihu (Radix bupleuri), Hu Zhang (Rhizoma polygoni cuspidati), Donglingcao (Rabdosia rubesens), Hou po (Cortex magnoliae officinalis) and Chuan xiong (Rhizoma chuanxiong) modulate cancers, neurodegeneration and cardiovascular disease via autophagy. These findings shed light on the potential new applications and formulation of CHM decoctions via regulation of autophagy. This article reviews the roles of autophagy in the pharmacological actions of CHM and discusses their new potential clinical applications in various human diseases. Full article

(This article belongs to the Collection Herbal Medicine Research)

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