Molecules

Editorial

Jump to: Research, Review, Other

6 pages, 222 KiB

Open AccessEditorial

Introduction to Nanomedicine

by Didier Astruc

Molecules 2016, 21(1), 4; https://doi.org/10.3390/molecules21010004 - 22 Dec 2015

Cited by 34 | Viewed by 8020

Abstract

Although mentions of nanoparticles in relation to biomedicine appeared in the late 1970s and are now the subject of over 10,000 publications per year, the term “Nanomedicine” only appeared at the turn of this century, and less than 30 papers including this term [...] Read more.

Although mentions of nanoparticles in relation to biomedicine appeared in the late 1970s and are now the subject of over 10,000 publications per year, the term “Nanomedicine” only appeared at the turn of this century, and less than 30 papers including this term were published up to 2005. [...] Full article

(This article belongs to the Collection Nanomedicine)

34 pages, 765 KiB

Open AccessEditorial

Acknowledgement to Reviewers of Molecules in 2015

by Molecules Editorial Office

Molecules 2016, 21(1), 131; https://doi.org/10.3390/molecules21010131 - 21 Jan 2016

Viewed by 8356

Abstract

The editors of Molecules would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2015. [...] Full article

Research

Jump to: Editorial, Review, Other

8 pages, 633 KiB

Open AccessArticle

Extended Functional Groups (EFG): An Efficient Set for Chemical Characterization and Structure-Activity Relationship Studies of Chemical Compounds

by Elena S. Salmina, Norbert Haider and Igor V. Tetko

Molecules 2016, 21(1), 1; https://doi.org/10.3390/molecules21010001 - 23 Dec 2015

Cited by 41 | Viewed by 16268

Abstract

The article describes a classification system termed “extended functional groups” (EFG), which are an extension of a set previously used by the CheckMol software, that covers in addition heterocyclic compound classes and periodic table groups. The functional groups are defined as SMARTS patterns [...] Read more.

The article describes a classification system termed “extended functional groups” (EFG), which are an extension of a set previously used by the CheckMol software, that covers in addition heterocyclic compound classes and periodic table groups. The functional groups are defined as SMARTS patterns and are available as part of the ToxAlerts tool (http://ochem.eu/alerts) of the On-line CHEmical database and Modeling (OCHEM) environment platform. The article describes the motivation and the main ideas behind this extension and demonstrates that EFG can be efficiently used to develop and interpret structure-activity relationship models. Full article

(This article belongs to the Special Issue Chemoinformatics)

► Show Figures

Graphical abstract

15 pages, 2378 KiB

Open AccessArticle

Polyphenolic Composition and Evaluation of Antioxidant Activity, Osmotic Fragility and Cytotoxic Effects of Raphiodon echinus (Nees & Mart.) Schauer

by Antonia Eliene Duarte, Emily Pansera Waczuk, Katiane Roversi, Maria Arlene Pessoa Da Silva, Luiz Marivando Barros, Francisco Assis Bezerra Da Cunha, Irwin Rose Alencar De Menezes, José Galberto Martins Da Costa, Aline Augusti Boligon, Adedayo Oluwaseun Ademiluyi, Jean Paul Kamdem, João Batista Teixeira Rocha and Marilise Escobar Burger

Molecules 2016, 21(1), 2; https://doi.org/10.3390/molecules21010002 - 29 Dec 2015

Cited by 23 | Viewed by 6323

Abstract

Raphiodon echinus (R. echinus) is used in Brazilian folk medicine for the treatment of inflammation, coughs, and infectious diseases. However, no information is available on the potential antioxidant, cytotoxicity and genotoxicity of this plant. In this study, the polyphenolic constituents, antioxidant [...] Read more.

Raphiodon echinus (R. echinus) is used in Brazilian folk medicine for the treatment of inflammation, coughs, and infectious diseases. However, no information is available on the potential antioxidant, cytotoxicity and genotoxicity of this plant. In this study, the polyphenolic constituents, antioxidant capacity and potential toxic effects of aqueous and ethanolic extracts of R. echinus on human erythrocytes and leukocytes were investigated for the first time. R. echinus extracts showed the presence of Gallic, chlorogenic, caffeic and ellagic acids, rutin, quercitrin and quercetin. Aqueous and ethanolic extracts of R. echinus exhibited antioxidant activity in DPPH radical scavenging with IC₅₀ = 111.9 μg/mL (EtOH extract) and IC₅₀ = 227.9 μg/mL (aqueous extract). The extracts inhibited Fe²⁺ (10 μM) induced thiobarbituric acid reactive substances (TBARS) formation in rat brain and liver homogenates. The extracts (30–480 μg/mL) did not induce genotoxicity, cytotoxicity or osmotic fragility in human blood cells. The findings of this present study therefore suggest that the therapeutic effect of R. echinus may be, in part, related to its antioxidant potential. Nevertheless, further in vitro and in vivo studies are required to ascertain the safety margin of its use in folk medicine. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

17 pages, 4220 KiB

Open AccessArticle

Synthesis, Characterization and Molecular Docking of Novel Bioactive Thiazolyl-Thiazole Derivatives as Promising Cytotoxic Antitumor Drug

by Sobhi M. Gomha, Taher A. Salaheldin, Huwaida M. E. Hassaneen, Hassan M. Abdel-Aziz and Mohammed A. Khedr

Molecules 2016, 21(1), 3; https://doi.org/10.3390/molecules21010003 - 22 Dec 2015

Cited by 36 | Viewed by 7758

Abstract

Reactions of ethylidenethiocarbohydrazide with hydrazonoyl halides gave 1,3-thiazole or 1,3,4-thiadiazole derivatives according to the type of hydrazonoyl halides. Treatment of ethylidenethiosemicarbazide with hydrazonoyl halides and dimethylacetylene dicarboxylate (DMAD) afforded the corresponding arylazothiazoles and 1,3-thiazolidin-4-one derivatives, respectively. The structures of the synthesized products were [...] Read more.

Reactions of ethylidenethiocarbohydrazide with hydrazonoyl halides gave 1,3-thiazole or 1,3,4-thiadiazole derivatives according to the type of hydrazonoyl halides. Treatment of ethylidenethiosemicarbazide with hydrazonoyl halides and dimethylacetylene dicarboxylate (DMAD) afforded the corresponding arylazothiazoles and 1,3-thiazolidin-4-one derivatives, respectively. The structures of the synthesized products were confirmed by IR, ¹H-NMR, ¹³C-NMR and mass spectral techniques. The cytotoxic activity of the selected products against the Hepatic carcinoma cell line (Hepg-2) was determined by MTT assay indicating a concentration dependent cellular growth inhibitory effect, especially for compounds 14c and 14e. The dose response curves indicated the IC₅₀ (the concentration of test compounds required to kill 50% of cell population) were 0.54 μM and 0.50 μM, respectively. Confocal laser scanning imaging of the treated cells stained by Rhodamin 123 and Acridine orange dyes confirmed that the selected compounds inhibit the mitochondrial lactate dehydrogenase enzymes. The binding mode of the active compounds was interpreted by a molecular docking study. The obtained results revealed promising cytotoxic activity. Full article

► Show Figures

Figure 1

16 pages, 2569 KiB

Open AccessArticle

Microreactors—A Powerful Tool to Synthesize Peroxycarboxylic Esters

by Tobias Illg, Annett Knorr and Lutz Fritzsche

Molecules 2016, 21(1), 5; https://doi.org/10.3390/molecules21010005 - 22 Dec 2015

Cited by 4 | Viewed by 6788

Abstract

The synthesis of peroxycarboxylic esters, as one subgroup of organic peroxides, is characterized by a high thermal hazard potential regarding process safety. In case of failure in the production process, e.g., if the heat of reaction cannot be removed sufficiently fast, decomposition reactions [...] Read more.

The synthesis of peroxycarboxylic esters, as one subgroup of organic peroxides, is characterized by a high thermal hazard potential regarding process safety. In case of failure in the production process, e.g., if the heat of reaction cannot be removed sufficiently fast, decomposition reactions can be triggered, and as a result, remarkable amounts of heat and gas can be released and can cause a high extent of damage. Multifarious technical and organizational measures are necessary to ensure the safe industrial production of peroxides. With the introduction of microreaction technology plenty of possibilities have been opened to carry out highly exothermic reactions in smaller volumes and with more efficient heat removal. In this paper we report the application of three different microstructured reactors, representing different mixing strategies, to synthesize two peroxymonocarboxylic esters, namely tert-butyl peroxypivalate and tert-butyl peroxy-2-ethylhexanoate. The following reactor types were considered: an orifice microreactor, a split and recombine microreactor and a capillary tube reactor in combination with ultrasonication. The efficiency of the two phase liquid/liquid reaction is expressed in comparison of conversion and selectivity. With microreaction technology a remarkable increase in space-time-yield, ranging from 12,500 kg·m⁻³·h⁻¹ to 414,000 kg·m⁻³·h⁻¹, is achieved. Full article

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

► Show Figures

Graphical abstract

26 pages, 6190 KiB

Open AccessArticle

Solubilization Behavior of Polyene Antibiotics in Nanomicellar System: Insights from Molecular Dynamics Simulation of the Amphotericin B and Nystatin Interactions with Polysorbate 80

by Meysam Mobasheri, Hossein Attar, Seyed Mehdi Rezayat Sorkhabadi, Ali Khamesipour and Mahmoud Reza Jaafari

Molecules 2016, 21(1), 6; https://doi.org/10.3390/molecules21010006 - 24 Dec 2015

Cited by 27 | Viewed by 10615

Abstract

Amphotericin B (AmB) and Nystatin (Nys) are the drugs of choice for treatment of systemic and superficial mycotic infections, respectively, with their full clinical potential unrealized due to the lack of high therapeutic index formulations for their solubilized delivery. In the present study, [...] Read more.

Amphotericin B (AmB) and Nystatin (Nys) are the drugs of choice for treatment of systemic and superficial mycotic infections, respectively, with their full clinical potential unrealized due to the lack of high therapeutic index formulations for their solubilized delivery. In the present study, using a coarse-grained (CG) molecular dynamics (MD) simulation approach, we investigated the interaction of AmB and Nys with Polysorbate 80 (P80) to gain insight into the behavior of these polyene antibiotics (PAs) in nanomicellar solution and derive potential implications for their formulation development. While the encapsulation process was predominantly governed by hydrophobic forces, the dynamics, hydration, localization, orientation, and solvation of PAs in the micelle were largely controlled by hydrophilic interactions. Simulation results rationalized the experimentally observed capability of P80 in solubilizing PAs by indicating (i) the dominant kinetics of drugs encapsulation over self-association; (ii) significantly lower hydration of the drugs at encapsulated state compared with aggregated state; (iii) monomeric solubilization of the drugs; (iv) contribution of drug-micelle interactions to the solubilization; (v) suppressed diffusivity of the encapsulated drugs; (vi) high loading capacity of the micelle; and (vii) the structural robustness of the micelle against drug loading. Supported from the experimental data, our simulations determined the preferred location of PAs to be the core-shell interface at the relatively shallow depth of 75% of micelle radius. Deeper penetration of PAs was impeded by the synergistic effects of (i) limited diffusion of water; and (ii) perpendicular orientation of these drug molecules with respect to the micelle radius. PAs were solvated almost exclusively in the aqueous poly-oxyethylene (POE) medium due to the distance-related lack of interaction with the core, explaining the documented insensitivity of Nys solubilization to drug-core compatibility in detergent micelles. Based on the obtained results, the dearth of water at interior sites of micelle and the large lateral occupation space of PAs lead to shallow insertion, broad radial distribution, and lack of core interactions of the amphiphilic drugs. Hence, controlled promotion of micelle permeability and optimization of chain crowding in palisade layer may help to achieve more efficient solubilization of the PAs. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Graphical abstract

11 pages, 1645 KiB

Open AccessArticle

Anti-Diabetic, Anti-Oxidant and Anti-Hyperlipidemic Activities of Flavonoids from Corn Silk on STZ-Induced Diabetic Mice

by Yan Zhang, Liying Wu, Zhongsu Ma, Jia Cheng and Jingbo Liu

Molecules 2016, 21(1), 7; https://doi.org/10.3390/molecules21010007 - 23 Dec 2015

Cited by 67 | Viewed by 12257

Abstract

Corn silk is a well-known ingredient frequently used in traditional Chinese herbal medicines. This study was designed to evaluate the anti-diabetic, anti-oxidant and anti-hyperlipidemic activities of crude flavonoids extracted from corn silk (CSFs) on streptozotocin (STZ)-induced diabetic mice. The results revealed that treatment [...] Read more.

Corn silk is a well-known ingredient frequently used in traditional Chinese herbal medicines. This study was designed to evaluate the anti-diabetic, anti-oxidant and anti-hyperlipidemic activities of crude flavonoids extracted from corn silk (CSFs) on streptozotocin (STZ)-induced diabetic mice. The results revealed that treatment with 300 mg/kg or 500 mg/kg of CSFs significantly reduced the body weight loss, water consumption, and especially the blood glucose (BG) concentration of diabetic mice, which indicated their potential anti-diabetic activities. Serum total superoxide dismutase (SOD) and malondialdehyde (MDA) assays were also performed to evaluate the anti-oxidant effects. Besides, several serum lipid values including total cholesterol (TC), triacylglycerol (TG), low density lipoprotein cholesterol (LDL-C) were reduced and the high density lipoprotein cholesterol level (HDL-C) was increased. The anti-diabetic, anti-oxidant and anti-hyperlipidemic effect of the CSFs suggest a potential therapeutic treatment for diabetic conditions. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

6 pages, 880 KiB

Open AccessArticle

The Synthesis of the Metabolites of 2′,3′,5′-Tri-O-acetyl-N₆-(3-hydroxyphenyl) Adenosine (WS070117)

by Wen-Xuan Zhang, Hong-Na Wu, Bo Li, Hong-Lin Wu, Dong-Mei Wang and Song Wu

Molecules 2016, 21(1), 8; https://doi.org/10.3390/molecules21010008 - 28 Dec 2015

Cited by 4 | Viewed by 5492

Abstract

Seven metabolites of 2′,3′,5′-tri-O-acetyl-N₆-(3-hydroxyphenyl) adenosine (WS070117) were synthesized by deacetylation, hydrolysis, cyclization, sulfonylation and glycosylation reactions, respectively. All these compounds, which could be useful as material standards for metabolic research, were characterized by NMR and HPLC-MS (ESI) analyses. Full article

(This article belongs to the Section Metabolites)

► Show Figures

Graphical abstract

14 pages, 1186 KiB

Open AccessArticle

Isolation of Terpenoids from the Stem of Ficus aurantiaca Griff and their Effects on Reactive Oxygen Species Production and Chemotactic Activity of Neutrophils

by Shukranul Mawa, Ibrahim Jantan and Khairana Husain

Molecules 2016, 21(1), 9; https://doi.org/10.3390/molecules21010009 - 5 Jan 2016

Cited by 19 | Viewed by 6469

Abstract

Three new triterpenoids; namely 28,28,30-trihydroxylupeol (1); 3,21,21,26-tetrahydroxy-lanostanoic acid (2) and dehydroxybetulinic acid (3) and seven known compounds; i.e., taraxerone (4); taraxerol (5); ethyl palmitate (6); herniarin (7); stigmasterol [...] Read more.

Three new triterpenoids; namely 28,28,30-trihydroxylupeol (1); 3,21,21,26-tetrahydroxy-lanostanoic acid (2) and dehydroxybetulinic acid (3) and seven known compounds; i.e., taraxerone (4); taraxerol (5); ethyl palmitate (6); herniarin (7); stigmasterol (8); ursolic acid (9) and acetyl ursolic acid (10) were isolated from the stem of Ficus aurantiaca Griff. The structures of the compounds were established by spectroscopic techniques. The compounds were evaluated for their inhibitory effects on polymorphonuclear leukocyte (PMN) chemotaxis by using the Boyden chamber technique and on human whole blood and neutrophil reactive oxygen species (ROS) production by using a luminol-based chemiluminescence assay. Among the compounds tested, compounds 1–4, 6 and 9 exhibited strong inhibition of PMN migration towards the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP) with IC₅₀ values of 6.8; 2.8; 2.5; 4.1; 3.7 and 3.6 μM, respectively, comparable to that of the positive control ibuprofen (6.7 μM). Compounds 2–4, 6, 7 and 9 exhibited strong inhibition of ROS production of PMNs with IC₅₀ values of 0.9; 0.9; 1.3; 1.1; 0.5 and 0.8 μM, respectively, which were lower than that of aspirin (9.4 μM). The bioactive compounds might be potential lead molecules for the development of new immunomodulatory agents to modulate the innate immune response of phagocytes. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

13 pages, 1124 KiB

Open AccessArticle

Preparative Isolation of Two Prenylated Biflavonoids from the Roots and Rhizomes of Sinopodophyllum emodi by Sephadex LH-20 Column and High-Speed Counter-Current Chromatography

by Yan-Jun Sun, Li-Xin Pei, Kai-Bo Wang, Yin-Shi Sun, Jun-Min Wang, Yan-Li Zhang, Mei-Ling Gao and Bao-Yu Ji

Molecules 2016, 21(1), 10; https://doi.org/10.3390/molecules21010010 - 23 Dec 2015

Cited by 14 | Viewed by 7800

Abstract

Two prenylated biflavonoids, podoverines B–C, were isolated from the dried roots and rhizomes of Sinopodophyllum emodi using a Sephadex LH-20 column (SLHC) and high-speed counter-current chromatography (HSCCC). The 95% ethanol extract was partitioned with ethyl acetate in water. Target compounds from the ethyl [...] Read more.

Two prenylated biflavonoids, podoverines B–C, were isolated from the dried roots and rhizomes of Sinopodophyllum emodi using a Sephadex LH-20 column (SLHC) and high-speed counter-current chromatography (HSCCC). The 95% ethanol extract was partitioned with ethyl acetate in water. Target compounds from the ethyl acetate fraction were further enriched and purified by the combined application of SLHC and HSCCC. n-Hexane–ethyl acetate–methanol–water (3.5:5:3.5:5, v/v) was chosen as the two phase solvent system. The flow rate of mobile phase was optimized at 2.0 mL·min⁻¹. Finally, under optimized conditions, 13.8 mg of podoverine B and 16.2 mg of podoverine C were obtained from 200 mg of the enriched sample. The purities of podoverines B and C were 98.62% and 99.05%, respectively, as determined by HPLC. For the first time, podoverins B and C were found in the genus Sinopodophyllum. Their structures were determined by spectroscopic methods (HR-ESI-MS, ¹H-NMR, ¹³C-NMR, HSQC, HMBC). Their absolute configurations were elucidated by comparison of their experimental and calculated ECD spectra. The cytotoxic activities were evaluated against MCF-7 and HepG2 cell lines. The separation procedures proved to be practical and economical, especially for trace prenylated biflavonoids from traditional Chinese medicine. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

13 pages, 1017 KiB

Open AccessArticle

New Alcamide and Anti-oxidant Activity of Pilosocereus gounellei A. Weber ex K. Schum. Bly. ex Rowl. (Cactaceae)

by Jéssica K. S. Maciel, Otemberg S. Chaves, Severino G. Brito Filho, Yanna C. F. Teles, Marianne G. Fernandes, Temilce S. Assis, Pedro Dantas Fernandes, Alberício Pereira De Andrade, Leonardo P. Felix, Tania M. S. Silva, Nathalia S. M. Ramos, Girliane R. Silva and Maria De Fátima Vanderlei De Souza

Molecules 2016, 21(1), 11; https://doi.org/10.3390/molecules21010011 - 22 Dec 2015

Cited by 30 | Viewed by 7144

Abstract

The Cactaceae family is composed by 124 genera and about 1438 species. Pilosocereus gounellei, popularly known in Brazil as xique-xique, is used in folk medicine to treat prostate inflammation, gastrointestinal and urinary diseases. The pioneering phytochemical study of P. gounellei was performed [...] Read more.

The Cactaceae family is composed by 124 genera and about 1438 species. Pilosocereus gounellei, popularly known in Brazil as xique-xique, is used in folk medicine to treat prostate inflammation, gastrointestinal and urinary diseases. The pioneering phytochemical study of P. gounellei was performed using column chromatography and HPLC, resulting in the isolation of 10 substances: pinostrobin (1), β-sitosterol (2), a mixture of sitosterol 3-O-β-d-glucopyranoside/stigmasterol 3-O-β-d-glucopyranoside (3a/3b), 13²-hydroxyphaeophytin a (4), phaeophytin a (5), a mixture of β-sitosterol and stigmasterol (6a/6b), kaempferol (7), quercetin (8), 7′-ethoxy-trans-feruloyltyramine (mariannein, 9) and trans-feruloyl tyramine (10). Compound 9 is reported for the first time in the literature. The structural characterization of the compounds was performed by analyses of 1-D and 2-D NMR data. In addition, a phenolic and flavonol total content assay was carried out, and the anti-oxidant potential of P. gounellei was demonstrated. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

11 pages, 2638 KiB

Open AccessArticle

Synthesis and Crystal Structures of Benzimidazole-2-thione Derivatives by Alkylation Reactions

by El Sayed H. El Ashry, Yeldez El Kilany, Nariman M. Nahas, Assem Barakat, Nadia Al-Qurashi, Hazem A. Ghabbour and Hoong-Kun Fun

Molecules 2016, 21(1), 12; https://doi.org/10.3390/molecules21010012 - 22 Dec 2015

Cited by 24 | Viewed by 9492

Abstract

Alkylated, benzylated and bromoalkylated benzimidazole-thione that intramolecularly heterocyclized to 3,4-dihydro-2H-[1,3]thiazino[3,2-a]benzimidazole were synthesized. The chemical structure of the synthesized product was characterized by Infra Red, ¹H-NMR, ¹³C-NMR, and Mass spectroscopy. Furthermore, the molecular structures of 8 and 9 [...] Read more.

Alkylated, benzylated and bromoalkylated benzimidazole-thione that intramolecularly heterocyclized to 3,4-dihydro-2H-[1,3]thiazino[3,2-a]benzimidazole were synthesized. The chemical structure of the synthesized product was characterized by Infra Red, ¹H-NMR, ¹³C-NMR, and Mass spectroscopy. Furthermore, the molecular structures of 8 and 9 were confirmed by X-ray single crystallography in different space groups, Pbca and P2₁/c, respectively. Full article

(This article belongs to the Section Organic Chemistry)

► Show Figures

Figure 1

14 pages, 2523 KiB

Open AccessArticle

Cytotoxic and Antifungal Constituents Isolated from the Metabolites of Endophytic Fungus DO14 from Dendrobium officinale

by Ling-Shang Wu, Min Jia, Ling Chen, Bo Zhu, Hong-Xiu Dong, Jin-Ping Si, Wei Peng and Ting Han

Molecules 2016, 21(1), 14; https://doi.org/10.3390/molecules21010014 - 22 Dec 2015

Cited by 45 | Viewed by 7724

Abstract

Two novel cytotoxic and antifungal constituents, (4S,6S)-6-[(1S,2R)-1, 2-dihydroxybutyl]-4-hydroxy-4-methoxytetrahydro-2H-pyran-2-one (1), (6S,2E)-6-hydroxy-3-methoxy-5-oxodec-2-enoic acid (2), together with three known compounds, LL-P880γ (3), LL-P880α (4), [...] Read more.

Two novel cytotoxic and antifungal constituents, (4S,6S)-6-[(1S,2R)-1, 2-dihydroxybutyl]-4-hydroxy-4-methoxytetrahydro-2H-pyran-2-one (1), (6S,2E)-6-hydroxy-3-methoxy-5-oxodec-2-enoic acid (2), together with three known compounds, LL-P880γ (3), LL-P880α (4), and Ergosta-5,7,22-trien-3b-ol (5) were isolated from the metabolites of endophytic fungi from Dendrobium officinale. The chemical structures were determined based on spectroscopic methods. All the isolated compounds 1–5 were evaluated by cytotoxicity and antifungal effects. Our present results indicated that compounds 1–4 showed notable anti-fungal activities (minimal inhibitory concentration (MIC) ≤ 50 μg/mL) for all the tested pathogens including Candida albicans, Cryptococcus neoformans, Trichophyton rubrum, Aspergillus fumigatus. In addition, compounds 1–4 possessed notable cytotoxcities against human cancer cell lines of HL-60 cells with the IC₅₀ values of below 100 μM. Besides, compounds 1, 2, 4 and 5 showed strong cytotoxities on the LOVO cell line with the IC₅₀ values were lower than 100 μM. In conclusion, our study suggested that endophytic fungi of D. officinale are great potential resources to discover novel agents for preventing or treating pathogens and tumors. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

11 pages, 1942 KiB

Open AccessArticle

Flavones Isolated from Scutellariae radix Suppress Propionibacterium Acnes-Induced Cytokine Production In Vitro and In Vivo

by Po-Jung Tsai, Wen-Cheng Huang, Ming-Chi Hsieh, Ping-Jyun Sung, Yueh-Hsiung Kuo and Wen-Huey Wu

Molecules 2016, 21(1), 15; https://doi.org/10.3390/molecules21010015 - 24 Dec 2015

Cited by 40 | Viewed by 7552

Abstract

Scutellariae radix, the root of Scutellaria baicalensis, has long been applied in traditional formulations and modern herbal medications. Propionibacterium acnes (P. acnes) in follicles can trigger inflammation and lead to the symptom of inflammatory acnes vulgaris. This study was [...] Read more.

Scutellariae radix, the root of Scutellaria baicalensis, has long been applied in traditional formulations and modern herbal medications. Propionibacterium acnes (P. acnes) in follicles can trigger inflammation and lead to the symptom of inflammatory acnes vulgaris. This study was aimed at evaluating the effect of Scutellariae radix extract and purified components isolated from it on inflammation induced by P. acnes in vitro and in vivo. The results showed the ethyl acetate (EA) soluble fraction from the partition of crude ethanolic extract from Scutellariae radix inhibited P. acnes-induced interleukin IL-8 and IL-1β production in human monocytic THP-1 cells. Seven flavones were isolated from the EA fraction by repeated chromatographies, and identified as 5,7-dihydroxy-6-methoxyflavone (FL1, oroxylin), 5,7-dihydroxy-8-methoxyflavone (FL2, wogonin), 5-hydroxy-7,8-dimethoxyflavone (FL3, 7-O-methylwogonin), 5,6′-dihydroxy-6,7,8,2′-tetramethoxy flavone (FL4, skullcapflavone II), 5,7,4′-trihydroxy-8-methoxyflavone (FL5), 5,2′,6′-trihydroxy-7,8-dimethoxyflavone (FL6, viscidulin II), and 5,7,2′,5′-tetrahydroxy-8,6′-dimethoxyflavone (FL7, ganhuangenin). They all significantly suppressed P. acnes-induced IL-8 and IL-1β production in THP-1 cells, and FL2 exerted the strongest effect with half maximal inhibition (IC₅₀) values of 8.7 and 4.9 μM, respectively. Concomitant intradermal injection of each of the seven flavones (20 μg) with P. acnes effectively attenuated P. acnes-induced ear swelling, and decreased the production of IL-6 and tumor necrosis factor-α in ear homogenates. Our results suggested that all the seven flavones can be potential therapeutic agents against P. acnes-induced skin inflammation. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

24 pages, 6083 KiB

Open AccessArticle

Synthesis and Properties of Bis-Porphyrin Molecular Tweezers: Effects of Spacer Flexibility on Binding and Supramolecular Chirogenesis

by Magnus Blom, Sara Norrehed, Claes-Henrik Andersson, Hao Huang, Mark E. Light, Jonas Bergquist, Helena Grennberg and Adolf Gogoll

Molecules 2016, 21(1), 16; https://doi.org/10.3390/molecules21010016 - 23 Dec 2015

Cited by 22 | Viewed by 11532

Abstract

Ditopic binding of various dinitrogen compounds to three bisporphyrin molecular tweezers with spacers of varying conformational rigidity, incorporating the planar enediyne (1), the helical stiff stilbene (2), or the semi-rigid glycoluril motif fused to the porphyrins (3), [...] Read more.

Ditopic binding of various dinitrogen compounds to three bisporphyrin molecular tweezers with spacers of varying conformational rigidity, incorporating the planar enediyne (1), the helical stiff stilbene (2), or the semi-rigid glycoluril motif fused to the porphyrins (3), are compared. Binding constants K_a = 10⁴–10⁶ M⁻¹ reveal subtle differences between these tweezers, that are discussed in terms of porphyrin dislocation modes. Exciton coupled circular dichroism (ECCD) of complexes with chiral dinitrogen guests provides experimental evidence for the conformational properties of the tweezers. The results are further supported and rationalized by conformational analysis. Full article

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

► Show Figures

Graphical abstract

11 pages, 1973 KiB

Open AccessArticle

Antioxidant Activity of Flaxseed Extracts in Lipid Systems

by Adriana Slavova-Kazakova, Magdalena Karamać, Vessela Kancheva and Ryszard Amarowicz

Molecules 2016, 21(1), 17; https://doi.org/10.3390/molecules21010017 - 23 Dec 2015

Cited by 33 | Viewed by 7039

Abstract

The aim of this work was to compare the antioxidant activity of the extract of flaxseed and its alkaline hydrolysate in two model systems: lipid autoxidation of triacylglycerols of sunflower oil (TGSO)—in a homogeneous lipid media and during β-carotene-linoleate emulsion system. In addition, [...] Read more.

The aim of this work was to compare the antioxidant activity of the extract of flaxseed and its alkaline hydrolysate in two model systems: lipid autoxidation of triacylglycerols of sunflower oil (TGSO)—in a homogeneous lipid media and during β-carotene-linoleate emulsion system. In addition, pure lignans were tested. The material was defatted with hexane and then phenolic compounds were extracted using dioxane-ethanol (50:50, v/v) mixture. Carbohydrates were removed from the crude extract using an Amberlite XAD-16 column chromatography. The content of total phenolic compounds in the crude extract and after alkaline hydrolysis was determined using a Folin-Ciocalteu’s phenol reagent. Individual phenolic compounds were determined by nordihydroguaiaretic acid (RP-HPLC) method in gradient system. The alkaline hydrolysis increased the content of total phenolics in the extract approximately by 10%. In the extracts of flaxseed, phenolic compounds were present in the form of macromolecular complex. In the alkaline hydrolysate, secoisolariciresinol diglucoside (SDG) was found as the main phenolic compound. Small amounts of p-coumaric and ferulic acids were also determined. SDG and both extracts were not able to inhibit effectively lipid autoxidation. The kinetics of TGSO autoxidation at 80 °C in absence and in presence of the extract before hydrolysis (EBH) and after hydrolysis (EAH) was monitored and compared with known standard antioxidants. Ferulic acid (FA) and butylated hydroxyl toluene (BHT) showed much higher antioxidant efficiency and reactivity than that of both extracts. Secoisolariciresinol (SECO) showed a higher activity in both model systems than SDG. However, the activity of SECO was much lower than that of nordihydroquaiaretic acid (NDGA). Full article

(This article belongs to the Special Issue Selected papers from the 2nd International Conference on Natural Products Utilization: from Plants to Pharmacy Shelf (ICNPU 2015, Plovdiv, Bulgaria))

► Show Figures

Figure 1

12 pages, 1317 KiB

Open AccessArticle

Optimization of Ultrasound-Assisted Extraction of Natural Antioxidants from the Flower of Jatropha integerrima by Response Surface Methodology

by Dong-Ping Xu, Yue Zhou, Jie Zheng, Sha Li, An-Na Li and Hua-Bin Li

Molecules 2016, 21(1), 18; https://doi.org/10.3390/molecules21010018 - 24 Dec 2015

Cited by 63 | Viewed by 7541

Abstract

An ultrasound-assisted extraction (UAE) method was developed for the efficient extraction of natural antioxidants from the flowers of Jatropha integerrima. Four independent variables, including ethanol concentration, solvent/material ratio, ultrasound irradiation time and temperature were studied by single factor experiments. Then, the central [...] Read more.

An ultrasound-assisted extraction (UAE) method was developed for the efficient extraction of natural antioxidants from the flowers of Jatropha integerrima. Four independent variables, including ethanol concentration, solvent/material ratio, ultrasound irradiation time and temperature were studied by single factor experiments. Then, the central composite rotatable design and response surface methodology were employed to investigate the effect of three key parameters (ethanol concentration, solvent/material ratio, and ultrasound irradiation time) on the antioxidant activities of the flower extracts. The optimal extraction conditions were an ethanol concentration of 59.6%, solvent/material ratio of 50:1, ultrasound irradiation time of 7 min, and ultrasound irradiation temperature of 40 °C. Under these conditions, the optimized experimental value was 1103.38 ± 16.11 µmol Trolox/g dry weight (DW), which was in accordance with the predicted value (1105.49 µmol Trolox/g DW). Furthermore, the antioxidant activities of flower extracts obtained by UAE were compared with those produced by the traditional maceration and Soxhlet extraction methods, and UAE resulted in higher antioxidant activities after a shorter time at a lower temperature. The results obtained are helpful for the full utilization of Jatropha integerrima, and also indicate that ultrasound-assisted extraction is an efficient method for the extraction of natural antioxidants from plant materials. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

8 pages, 708 KiB

Open AccessArticle

Synthesis and Anti-Tumor Activities of 4-Anilinoquinoline Derivatives

by Dan Liu, Tian Luan, Jian Kong, Ying Zhang and Hai-Feng Wang

Molecules 2016, 21(1), 21; https://doi.org/10.3390/molecules21010021 - 23 Dec 2015

Cited by 5 | Viewed by 5720

Abstract

Twenty-two 7-fluoro (or 8-methoxy)-4-anilinoquinolines compounds were designed and synthesized as potentially potent and selective antitumor inhibitors. All the prepared compounds were evaluated for their in vitro antiproliferative activities against the HeLa and BGC823 cell lines. Ten compounds (1a–g; 2c [...] Read more.

Twenty-two 7-fluoro (or 8-methoxy)-4-anilinoquinolines compounds were designed and synthesized as potentially potent and selective antitumor inhibitors. All the prepared compounds were evaluated for their in vitro antiproliferative activities against the HeLa and BGC823 cell lines. Ten compounds (1a–g; 2c; 2e and 2i) exhibited excellent antitumor activity superior to that of gefitinib. Among the ten compounds; seven (1a–c; 1e–1g and 2i) displayed excellent selectivity for BGC823 cells. In particular; 1f and 2i exhibited potent cytotoxic activities against HeLa cells and BGC823 cells with better IC₅₀ values than gefitinib. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

13 pages, 1896 KiB

Open AccessArticle

Detecting and Quantifying Biomolecular Interactions of a Dendritic Polyglycerol Sulfate Nanoparticle Using Fluorescence Lifetime Measurements

by Alexander Boreham, Jens Pikkemaat, Pierre Volz, Robert Brodwolf, Christian Kuehne, Kai Licha, Rainer Haag, Jens Dernedde and Ulrike Alexiev

Molecules 2016, 21(1), 22; https://doi.org/10.3390/molecules21010022 - 24 Dec 2015

Cited by 29 | Viewed by 8482

Abstract

Interactions of nanoparticles with biomaterials determine the biological activity that is key for the physiological response. Dendritic polyglycerol sulfates (dPGS) were found recently to act as an inhibitor of inflammation by blocking selectins. Systemic application of dPGS would present this nanoparticle to various [...] Read more.

Interactions of nanoparticles with biomaterials determine the biological activity that is key for the physiological response. Dendritic polyglycerol sulfates (dPGS) were found recently to act as an inhibitor of inflammation by blocking selectins. Systemic application of dPGS would present this nanoparticle to various biological molecules that rapidly adsorb to the nanoparticle surface or lead to adsorption of the nanoparticle to cellular structures such as lipid membranes. In the past, fluorescence lifetime measurements of fluorescently tagged nanoparticles at a molecular and cellular/tissue level have been proven to reveal valuable information on the local nanoparticle environment via characteristic fluorescent lifetime signatures of the nanoparticle bound dye. Here, we established fluorescence lifetime measurements as a tool to determine the binding affinity to fluorescently tagged dPGS (dPGS-ICC; ICC: indocarbocyanine). The binding to a cell adhesion molecule (L-selectin) and a human complement protein (C1q) to dPGS-ICC was evaluated by the concentration dependent change in the unique fluorescence lifetime signature of dPGS-ICC. The apparent binding affinity was found to be in the nanomolar range for both proteins (L-selectin: 87 ± 4 nM and C1q: 42 ± 12 nM). Furthermore, the effect of human serum on the unique fluorescence lifetime signature of dPGS-ICC was measured and found to be different from the interactions with the two proteins and lipid membranes. A comparison between the unique lifetime signatures of dPGS-ICC in different biological environments shows that fluorescence lifetime measurements of unique dPGS-ICC fluorescence lifetime signatures are a versatile tool to probe the microenvironment of dPGS in cells and tissue. Full article

(This article belongs to the Collection Nanomedicine)

► Show Figures

Figure 1

15 pages, 3922 KiB

Open AccessArticle

Benz[c,d]indolium-containing Monomethine Cyanine Dyes: Synthesis and Photophysical Properties

by Eduardo Soriano, Cory Holder, Andrew Levitz and Maged Henary

Molecules 2016, 21(1), 23; https://doi.org/10.3390/molecules21010023 - 24 Dec 2015

Cited by 26 | Viewed by 12283

Abstract

Asymmetric monomethine cyanines have been extensively used as probes for nucleic acids among other biological systems. Herein we report the synthesis of seven monomethine cyanine dyes that have been successfully prepared with various heterocyclic moieties such as quinoline, benzoxazole, benzothiazole, dimethyl indole, and [...] Read more.

Asymmetric monomethine cyanines have been extensively used as probes for nucleic acids among other biological systems. Herein we report the synthesis of seven monomethine cyanine dyes that have been successfully prepared with various heterocyclic moieties such as quinoline, benzoxazole, benzothiazole, dimethyl indole, and benz[e]indole adjoining benz[c,d]indol-1-ium, which was found to directly influence their optical and energy profiles. In this study the optical properties vs. structural changes were investigated using nuclear magnetic resonance and computational approaches. The twisted conformation unique to monomethine cyanines was exploited in DNA binding studies where the newly designed sensor displayed an increase in fluorescence when bound in the DNA grooves compared to the unbound form. Full article

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

► Show Figures

Graphical abstract

11 pages, 983 KiB

Open AccessArticle

Reduced Reactivity of Amines against Nucleophilic Substitution via Reversible Reaction with Carbon Dioxide

by Fiaz S. Mohammed and Christopher L. Kitchens

Molecules 2016, 21(1), 24; https://doi.org/10.3390/molecules21010024 - 23 Dec 2015

Cited by 7 | Viewed by 13237

Abstract

The reversible reaction of carbon dioxide (CO₂) with primary amines to form alkyl-ammonium carbamates is demonstrated in this work to reduce amine reactivity against nucleophilic substitution reactions with benzophenone and phenyl isocyanate. The reversible formation of carbamates has been recently exploited [...] Read more.

The reversible reaction of carbon dioxide (CO₂) with primary amines to form alkyl-ammonium carbamates is demonstrated in this work to reduce amine reactivity against nucleophilic substitution reactions with benzophenone and phenyl isocyanate. The reversible formation of carbamates has been recently exploited for a number of unique applications including the formation of reversible ionic liquids and surfactants. For these applications, reduced reactivity of the carbamate is imperative, particularly for applications in reactions and separations. In this work, carbamate formation resulted in a 67% reduction in yield for urea synthesis and 55% reduction for imine synthesis. Furthermore, the amine reactivity can be recovered upon reversal of the carbamate reaction, demonstrating reversibility. The strong nucleophilic properties of amines often require protection/de-protection schemes during bi-functional coupling reactions. This typically requires three separate reaction steps to achieve a single transformation, which is the motivation behind Green Chemistry Principle #8: Reduce Derivatives. Based upon the reduced reactivity, there is potential to employ the reversible carbamate reaction as an alternative method for amine protection in the presence of competing reactions. For the context of this work, CO₂ is envisioned as a green protecting agent to suppress formation of n-phenyl benzophenoneimine and various n-phenyl–n-alky ureas. Full article

(This article belongs to the Special Issue Ionic Liquids in Organic Synthesis)

► Show Figures

Graphical abstract

15 pages, 1286 KiB

Open AccessArticle

Heterocycles 36. Single-Walled Carbon Nanotubes-Bound N,N-Diethyl Ethanolamine as Mild and Efficient Racemisation Agent in the Enzymatic DKR of 2-Arylthiazol-4-yl-alanines

by Denisa Leonte, László Csaba Bencze, Csaba Paizs, Monica Ioana Toşa, Valentin Zaharia and Florin Dan Irimie

Molecules 2016, 21(1), 25; https://doi.org/10.3390/molecules21010025 - 25 Dec 2015

Cited by 3 | Viewed by 5021

Abstract

In this paper we describe the chemoenzymatic synthesis of enantiopure l-2-arylthiazol-4-yl alanines starting from their racemic N-acetyl derivatives; by combining the lipase-catalysed dynamic kinetic resolution of oxazol-5(4H)-ones with a chemical and an enzymatic enantioselective hydrolytic step affording the desired [...] Read more.

In this paper we describe the chemoenzymatic synthesis of enantiopure l-2-arylthiazol-4-yl alanines starting from their racemic N-acetyl derivatives; by combining the lipase-catalysed dynamic kinetic resolution of oxazol-5(4H)-ones with a chemical and an enzymatic enantioselective hydrolytic step affording the desired products in good yields (74%–78%) and high enantiopurities (ee > 99%). The developed procedure exploits the utility of the single-walled carbon nanotubes-bound diethylaminoethanol as mild and efficient racemisation agent for the dynamic kinetic resolution of the corresponding oxazolones. Full article

(This article belongs to the Section Organic Chemistry)

► Show Figures

Graphical abstract

17 pages, 3647 KiB

Open AccessArticle

Strong and Nonspecific Synergistic Antibacterial Efficiency of Antibiotics Combined with Silver Nanoparticles at Very Low Concentrations Showing No Cytotoxic Effect

by Aleš Panáček, Monika Smékalová, Martina Kilianová, Robert Prucek, Kateřina Bogdanová, Renata Večeřová, Milan Kolář, Markéta Havrdová, Grażyna Anna Płaza, Joanna Chojniak, Radek Zbořil and Libor Kvítek

Molecules 2016, 21(1), 26; https://doi.org/10.3390/molecules21010026 - 28 Dec 2015

Cited by 149 | Viewed by 15802

Abstract

The resistance of bacteria towards traditional antibiotics currently constitutes one of the most important health care issues with serious negative impacts in practice. Overcoming this issue can be achieved by using antibacterial agents with multimode antibacterial action. Silver nano-particles (AgNPs) are one of [...] Read more.

The resistance of bacteria towards traditional antibiotics currently constitutes one of the most important health care issues with serious negative impacts in practice. Overcoming this issue can be achieved by using antibacterial agents with multimode antibacterial action. Silver nano-particles (AgNPs) are one of the well-known antibacterial substances showing such multimode antibacterial action. Therefore, AgNPs are suitable candidates for use in combinations with traditional antibiotics in order to improve their antibacterial action. In this work, a systematic study quantifying the synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus was performed. Employing the microdilution method as more suitable and reliable than the disc diffusion method, strong synergistic effects were shown for all tested antibiotics combined with AgNPs at very low concentrations of both antibiotics and AgNPs. No trends were observed for synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs, indicating non-specific synergistic effects. Moreover, a very low amount of silver is needed for effective antibacterial action of the antibiotics, which represents an important finding for potential medical applications due to the negligible cytotoxic effect of AgNPs towards human cells at these concentration levels. Full article

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

► Show Figures

Graphical abstract

9 pages, 1704 KiB

Open AccessArticle

Comparison of Fluorescent Microspheres and Colloidal Gold as Labels in Lateral Flow Immunochromatographic Assays for the Detection of T-2 Toxin

by Xiya Zhang, Chao Wu, Kai Wen, Haiyang Jiang, Jianzhong Shen, Suxia Zhang and Zhanhui Wang

Molecules 2016, 21(1), 27; https://doi.org/10.3390/molecules21010027 - 28 Dec 2015

Cited by 31 | Viewed by 8298

Abstract

A new highly specific and sensitive monoclonal antibody (MAb) to T-2 toxin (T-2) was produced, providing an IC₅₀ value of 1.02 ng/mL and negligible cross-reactivity (CR) to other related mycotoxins. Based on the new MAb, a lateral-flow immunochromatographic assay (LFIA) using colloidal [...] Read more.

A new highly specific and sensitive monoclonal antibody (MAb) to T-2 toxin (T-2) was produced, providing an IC₅₀ value of 1.02 ng/mL and negligible cross-reactivity (CR) to other related mycotoxins. Based on the new MAb, a lateral-flow immunochromatographic assay (LFIA) using colloidal gold (CG) and fluorescent microspheres (FMs) as labels was proposed for T-2. Under the optimized conditions, in rapid qualitative assay, the cut-off values of the CG-LFIA were 400 μg/kg in rice and 50 μg/L in fresh milk, and the cut-off values of the FMs-LFIA were 100 μg/kg in both rice and chicken feed. For the quantitative assay with the FMs-LFIA, the limit of detection (LOD) were 0.23 μg/kg and 0.41 μg/kg in rice and chicken feed, respectively, and the average recoveries ranged from 80.2% to 100.8% with the coefficient of variation (CV) below 10.8%. In addition, we found that the CG-LFIA could tolerate the matrix effect of fresh milk better than the FMs-LFIA, while the FMs-LFIA could tolerate the matrix effect of chicken feed better than CG-LFIA under the same experimental conditions. These results provide a certain reference for the selection of appropriate labels to establish a rapid LFIA in various biological samples. Full article

(This article belongs to the Special Issue Natural Toxins)

► Show Figures

Graphical abstract

15 pages, 2340 KiB

Open AccessArticle

Synthesis, Biological Evaluation and Molecular Docking Studies of 6-Aryl-2-Styrylquinazolin-4(3H)-Ones

by Emmanuel Ndubuisi Agbo, Tshepiso Jan Makhafola, Yee Siew Choong, Malose Jack Mphahlele and Ponnadurai Ramasami

Molecules 2016, 21(1), 28; https://doi.org/10.3390/molecules21010028 - 25 Dec 2015

Cited by 11 | Viewed by 5859

Abstract

Suzuki-Miyaura cross-coupling of 6-bromo-2-styrylquinazolin-4(3H)-ones with arylboronic acids afforded a series of novel 6-aryl-2-styrylquinazolin-4(3H)-ones. These compounds were evaluated for potential anticancer properties against the human renal (TK-10), melanoma (UACC-62) and breast cancer (MCF-7) cell lines. Their antimicrobial properties were also [...] Read more.

Suzuki-Miyaura cross-coupling of 6-bromo-2-styrylquinazolin-4(3H)-ones with arylboronic acids afforded a series of novel 6-aryl-2-styrylquinazolin-4(3H)-ones. These compounds were evaluated for potential anticancer properties against the human renal (TK-10), melanoma (UACC-62) and breast cancer (MCF-7) cell lines. Their antimicrobial properties were also evaluated against six Gram-positive and four Gram-negative bacteria, as well as two strains of fungi. Molecular docking studies (in silico) were conducted on compounds 5a, b, d and 6a, b, d–f to recognize the hypothetical binding motif of the title compounds within the active site of the dihydrofolate reductase and thymidylate synthase enzymes. Full article

(This article belongs to the Section Bioorganic Chemistry)

► Show Figures

Graphical abstract

15 pages, 1068 KiB

Open AccessArticle

Synthesis and Cytotoxic Effect of Some Novel 1,2-Dihydropyridin-3-carbonitrile and Nicotinonitrile Derivatives

by Eman M. Flefel, Hebat-Allah S. Abbas, Randa E. Abdel Mageid and Wafaa A. Zaghary

Molecules 2016, 21(1), 30; https://doi.org/10.3390/molecules21010030 - 31 Dec 2015

Cited by 14 | Viewed by 6989

Abstract

1-(2,4-Dichlorophenyl)-3-(4-fluorophenyl)propen-1-one (1) was prepared and reacted with an active methylene compound (ethyl cyanoacetate) in the presence of ammonium acetate to give the corresponding cyanopyridone 2. Compound 2 reacted with hydrazine hydrate, malononitrile, ethyl bromoacetate and phosphorous oxychloride to afford compounds [...] Read more.

1-(2,4-Dichlorophenyl)-3-(4-fluorophenyl)propen-1-one (1) was prepared and reacted with an active methylene compound (ethyl cyanoacetate) in the presence of ammonium acetate to give the corresponding cyanopyridone 2. Compound 2 reacted with hydrazine hydrate, malononitrile, ethyl bromoacetate and phosphorous oxychloride to afford compounds 4 and 7–11, respectively. The 2-chloropyridine derivative 11 reacted with different primary amines, namely benzyl amine, piperonyl amine, 1-phenylethyl amine, and/or the secondary amines 2-methyl-pipridine and morpholine to give the corresponding derivatives 12–15. Hydrazinolysis of chloropyridine derivative 11 with hydrazine hydrate afforded the corresponding hydrazino derivative 17. Condensation of compound 17 with ethyl acetoacetate, acetylacetone, isatin and different aldehydes gave the corresponding derivatives 18–21. Some of newly synthesized compounds were screened for cytotoxic activity against three tumor cell lines. The results indicated that compounds 8 and 16 showed the best results, exhibiting the highest inhibitory effects towards the three tumor cell lines, which were higher than that of the reference doxorubicin and these compounds were non-cytotoxic towards normal cells (IC₅₀ values > 100 μg/mL). Full article

(This article belongs to the Section Bioorganic Chemistry)

► Show Figures

Figure 1

6 pages, 739 KiB

Open AccessArticle

Terpenoids from the Marine-Derived Fungus Aspergillus fumigatus YK-7

by Yu Wang, Da-Hong Li, Zhan-Lin Li, Yan-Jun Sun, Hui-Ming Hua, Tao Liu and Jiao Bai

Molecules 2016, 21(1), 31; https://doi.org/10.3390/molecules21010031 - 28 Dec 2015

Cited by 27 | Viewed by 6693

Abstract

Two new β-bergamotane sesquiterpenoids, E-β-trans-5,8,11-trihydroxybergamot-9-ene (1) and β-trans-2β,5,15-trihydroxybergamot-10-ene (2), were isolated from the marine-derived fungus Aspergillus fumigatus YK-7, along with three known terpenoids 3–5. Their structures were determined by spectroscopic methods [...] Read more.

Two new β-bergamotane sesquiterpenoids, E-β-trans-5,8,11-trihydroxybergamot-9-ene (1) and β-trans-2β,5,15-trihydroxybergamot-10-ene (2), were isolated from the marine-derived fungus Aspergillus fumigatus YK-7, along with three known terpenoids 3–5. Their structures were determined by spectroscopic methods (1D and 2D NMR, HR-ESI-MS). Antiproliferative effects on human leukemic monocyte lymphoma U937 and human prostate cancer PC-3 cell lines were measured in vitro. Compound 4 exhibited potent activity against the U937 cell line with an IC₅₀ value of 4.2 μM. Full article

(This article belongs to the Collection Bioactive Compounds)

► Show Figures

Figure 1

15 pages, 1120 KiB

Open AccessArticle

Bioactive Compound Content and Cytotoxic Effect on Human Cancer Cells of Fresh and Processed Yellow Tomatoes

by Assunta Raiola, Rita Del Giudice, Daria Maria Monti, Gian Carlo Tenore, Amalia Barone and Maria Manuela Rigano

Molecules 2016, 21(1), 33; https://doi.org/10.3390/molecules21010033 - 25 Dec 2015

Cited by 23 | Viewed by 6931

Abstract

Tomato, as a fresh or processed product, has a high nutritional value due to its content of bioactive components such as phenolic compounds. Few studies describe the effect of processing on antioxidant content and the cancer cell growth inhibition activity. In this study [...] Read more.

Tomato, as a fresh or processed product, has a high nutritional value due to its content of bioactive components such as phenolic compounds. Few studies describe the effect of processing on antioxidant content and the cancer cell growth inhibition activity. In this study we determined the phenolic and ascorbic acid content of three yellow tomato varieties, before and after thermal processing. Moreover, we determined the antioxidative power and tested the effects of tomato extracts on three human cancer cell lines. We found that the amount of phenolic acids (chlorogenic acid and caffeic acid) decreased in all the samples after processing, whereas the flavonoid content increased after the heat treatment in two samples. A cytotoxic effect of tomato extracts was observed only after processing. This result well correlates with the flavonoid content after processing and clearly indicates that processed yellow tomatoes have a high content of bioactive compounds endowed with cytotoxicity towards cancer cells, thus opening the way to obtain tomato-based functional foods. Full article

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

► Show Figures

Figure 1

10 pages, 1615 KiB

Open AccessArticle

Asteltoxins with Antiviral Activities from the Marine Sponge-Derived Fungus Aspergillus sp. SCSIO XWS02F40

by Yong-Qi Tian, Xiu-Ping Lin, Zhen Wang, Xue-Feng Zhou, Xiao-Chu Qin, Kumaravel Kaliyaperumal, Tian-Yu Zhang, Zheng-Chao Tu and Yonghong Liu

Molecules 2016, 21(1), 34; https://doi.org/10.3390/molecules21010034 - 26 Dec 2015

Cited by 54 | Viewed by 8774

Abstract

Two new asteltoxins named asteltoxin E (2) and F (3), and a new chromone (4), together with four known compounds were isolated from a marine sponge–derived fungus, Aspergillus sp. SCSIO XWS02F40. The structures of the compounds ( [...] Read more.

Two new asteltoxins named asteltoxin E (2) and F (3), and a new chromone (4), together with four known compounds were isolated from a marine sponge–derived fungus, Aspergillus sp. SCSIO XWS02F40. The structures of the compounds (1–7) were determined by the extensive 1D- and 2D-NMR spectra, and HRESIMS spectrometry. All the compounds were tested for their antiviral (H1N1 and H3N2) activity. Compounds 2 and 3 showed significant activity against H3N2 with the prominent IC₅₀ values of 6.2 ± 0.08 and 8.9 ± 0.3 μM, respectively. In addition, compound 2 also exhibited inhibitory activity against H1N1 with an IC₅₀ value of 3.5 ± 1.3 μM. Full article

(This article belongs to the Collection Bioactive Compounds)

► Show Figures

Graphical abstract

13 pages, 1984 KiB

Open AccessArticle

A Herbal Formula, Atofreellage, Ameliorates Atopic Dermatitis-Like Skin Lesions in an NC/Nga Mouse Model

by Won-Yong Kim, Hyeong-Geug Kim, Hye-Won Lee, Jin-Seok Lee, Hwi-Jin Im, Hyo-Seon Kim, Sung-Bae Lee and Chang-Gue Son

Molecules 2016, 21(1), 35; https://doi.org/10.3390/molecules21010035 - 25 Dec 2015

Cited by 9 | Viewed by 7858

Abstract

We evaluated the anti-atopic dermatitis (AD) effect of Atofreellage (AF), a herbal formula composed of 10 medicinal plants. AD was induced on the dorsal skin areas of NC/Nga mice (male, seven weeks old) by daily application of 2,4-dinitrochlorobenzene (DNCB) for five weeks. After [...] Read more.

We evaluated the anti-atopic dermatitis (AD) effect of Atofreellage (AF), a herbal formula composed of 10 medicinal plants. AD was induced on the dorsal skin areas of NC/Nga mice (male, seven weeks old) by daily application of 2,4-dinitrochlorobenzene (DNCB) for five weeks. After three weeks of DNCB application, 200 μL of AF (0, 25, 50 or 100 mg/mL) was applied to the skin lesions. Histological findings, blood cell populations, serum levels of immunoglobulin E (IgE), histamine, pro-inflammatory cytokines, and inflammatory signaling in the skin tissue, and T-helper cell type 2 (Th₂)-related cytokines in splenocytes were analyzed. Histopathological findings showed AF treatment notably attenuated the thickness of dorsal skin, and eosinophil infiltration. AF treatment (especially 100 mg/mL) also demonstrably ameliorated the blood cell population abnormalities, as the notable elevation of serum concentrations of IgE, histamine, TNF-α, IL-6 and IL-1β were remarkably normalized by AF treatment. Western blot analysis evidenced the apparent normalization of inflammatory signals (ERK, p38 MAP kinase, JNK, and NF-κB) in the skin tissue. Additionally, AF treatment notably attenuated the activation of Th₂-dominant cytokines (IL-13, IL-4, and IL-5) in Con A-treated splenocytes in an ex vivo assay. In conclusion, this study provides experimental evidence for the clinical relevance of Atofreellage. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

10 pages, 4485 KiB

Open AccessArticle

Mechanism of NO Photocatalytic Oxidation on g-C₃N₄ Was Changed by Pd-QDs Modification

by Yuhan Li, Liping Yang, Guohui Dong and Wingkei Ho

Molecules 2016, 21(1), 36; https://doi.org/10.3390/molecules21010036 - 26 Dec 2015

Cited by 26 | Viewed by 8774

Abstract

Quantum dot (QD) sensitization can increase the light absorption and electronic transmission of photocatalysts. However, limited studies have been conducted on the photocatalytic activity of photocatalysts after modification by noble metal QDs. In this study, we developed a simple method for fabricating Pd-QD-modified [...] Read more.

Quantum dot (QD) sensitization can increase the light absorption and electronic transmission of photocatalysts. However, limited studies have been conducted on the photocatalytic activity of photocatalysts after modification by noble metal QDs. In this study, we developed a simple method for fabricating Pd-QD-modified g-C₃N₄. Results showed that the modification of Pd-QDs can improve the NO photocatalytic oxidation activity of g-C₃N₄. Moreover, Pd-QD modification changed the NO oxidation mechanism from the synergistic action of h⁺ and O₂⁻ to the single action of ·OH. We found that the main reason for the mechanism change was that Pd-QD modification changed the molecular oxygen activation pathway from single-electron reduction to two-electron reduction. This study can not only develop a novel strategy for modifying Pd-QDs on the surface of photocatalysts, but also provides insight into the relationship between Pd-QD modification and the NO photocatalytic oxidation activity of semiconductor photocatalysts. Full article

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

► Show Figures

Figure 1

14 pages, 1953 KiB

Open AccessArticle

Peptide KSL-W-Loaded Mucoadhesive Liquid Crystalline Vehicle as an Alternative Treatment for Multispecies Oral Biofilm

by Jéssica Bernegossi, Giovana Maria Fioramonti Calixto, Paulo Ricardo da Silva Sanches, Carla Raquel Fontana, Eduardo Maffud Cilli, Saulo Santesso Garrido and Marlus Chorilli

Molecules 2016, 21(1), 37; https://doi.org/10.3390/molecules21010037 - 25 Dec 2015

Cited by 43 | Viewed by 7237

Abstract

Decapeptide KSL-W shows antibacterial activities and can be used in the oral cavity, however, it is easily degraded in aqueous solution and eliminated. Therefore, we aimed to develop liquid crystalline systems (F1 and F2) for KSL-W buccal administration to treat multispecies oral biofilms. [...] Read more.

Decapeptide KSL-W shows antibacterial activities and can be used in the oral cavity, however, it is easily degraded in aqueous solution and eliminated. Therefore, we aimed to develop liquid crystalline systems (F1 and F2) for KSL-W buccal administration to treat multispecies oral biofilms. The systems were prepared with oleic acid, polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol (PPG-5-CETETH-20), and a 1% poloxamer 407 dispersion as the oil phase (OP), surfactant (S), and aqueous phase (AP), respectively. We characterized them using polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheology, and in vitro bioadhesion, and performed in vitro biological analysis. PLM showed isotropy (F1) or anisotropy with lamellar mesophases (F2), confirmed by peak ratio quantification using SAXS. Rheological tests demonstrated that F1 exhibited Newtonian behavior but not F2, which showed a structured AP concentration-dependent system. Bioadhesion studies revealed an AP concentration-dependent increase in the system’s bioadhesiveness (F2 = 15.50 ± 1.00 mN·s) to bovine teeth blocks. Antimicrobial testing revealed 100% inhibition of multispecies oral biofilm growth after KSL-W administration, which was incorporated in the F2 aqueous phase at a concentration of 1 mg/mL. Our results suggest that this system could serve as a potential vehicle for buccal administration of antibiofilm peptides. Full article

(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)

► Show Figures

Figure 1

12 pages, 2702 KiB

Open AccessArticle

Synthesis and Herbicidal Activity of 5-Heterocycloxy-3-methyl-1-substituted-1H-pyrazoles

by Jing Kang, Xia Li Yue, Chang Shui Chen, Jian Hong Li and Hong Ju Ma

Molecules 2016, 21(1), 39; https://doi.org/10.3390/molecules21010039 - 25 Dec 2015

Cited by 9 | Viewed by 5979

Abstract

With the objective of finding valuable herbicidal candidates, a series of new 5-heterocycloxy-3-methyl-1-substituted-1H-pyrazoles were synthesized and their herbicidal activities were evaluated. The bioassay results showed that some compounds exhibited excellent herbicidal activities at the concentration of 100 mg/L, and compound 5-chloro-2-((3-methyl-1-(2,2,2-trifluoroethyl)-1 [...] Read more.

With the objective of finding valuable herbicidal candidates, a series of new 5-heterocycloxy-3-methyl-1-substituted-1H-pyrazoles were synthesized and their herbicidal activities were evaluated. The bioassay results showed that some compounds exhibited excellent herbicidal activities at the concentration of 100 mg/L, and compound 5-chloro-2-((3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)oxy)pyrimidine showed bleaching activity to green weeds. In greenhouse conditions, this compound also showed excellent post-emergence herbicidal effect against Digitaria sanguinalis L. at the dosage of 750 g a. i. ha⁻¹. Full article

(This article belongs to the Section Organic Chemistry)

► Show Figures

Figure 1

14 pages, 1210 KiB

Open AccessArticle

Application of Ultra-High-Performance Liquid Chromatography Coupled with LTQ-Orbitrap Mass Spectrometry for the Qualitative and Quantitative Analysis of Polygonum multiflorum Thumb. and Its Processed Products

by Teng-Hua Wang, Jing Zhang, Xiao-Hui Qiu, Jun-Qi Bai, You-Heng Gao and Wen Xu

Molecules 2016, 21(1), 40; https://doi.org/10.3390/molecules21010040 - 26 Dec 2015

Cited by 41 | Viewed by 7251

Abstract

In order to quickly and simultaneously obtain the chemical profiles and control the quality of the root of Polygonum multiflorum Thumb. and its processed form, a rapid qualitative and quantitative method, using ultra-high-performance liquid chromatography coupled with electrospray ionization-linear ion trap-Orbitrap hybrid mass [...] Read more.

In order to quickly and simultaneously obtain the chemical profiles and control the quality of the root of Polygonum multiflorum Thumb. and its processed form, a rapid qualitative and quantitative method, using ultra-high-performance liquid chromatography coupled with electrospray ionization-linear ion trap-Orbitrap hybrid mass spectrometry (UHPLC-LTQ-Orbitrap MSⁿ) has been developed. The analysis was performed within 10 min on an AcQuity UPLC™ BEH C₁₈ column with a gradient elution of 0.1% formic acid-acetonitrile at flow rate of 400 μL/min. According to the fragmentation mechanism and high resolution MSⁿ data, a diagnostic ion searching strategy was used for rapid and tentative identification of main phenolic components and 23 compounds were simultaneously identified or tentatively characterized. The difference in chemical profiles between P. multiflorum and its processed preparation were observed by comparing the ions abundances of main constituents in the MS spectra and significant changes of eight metabolite biomarkers were detected in the P. multiflorum samples and their preparations. In addition, four of the representative phenols, namely gallic acid, trans-2,3,5,4′-tetra-hydroxystilbene-2-O-β-d-glucopyranoside, emodin and emodin-8-O-β-d-glucopyranoside were quantified by the validated UHPLC-MS/MS method. These phenols are considered to be major bioactive constituents in P. multiflorum, and are generally regarded as the index for quality assessment of this herb. The method was successfully used to quantify 10 batches of P. multiflorum and 10 batches of processed P. multiflorum. The results demonstrated that the method is simple, rapid, and suitable for the discrimination and quality control of this traditional Chinese herb. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

16 pages, 1677 KiB

Open AccessArticle

Synthesis of Novel Pyrido[4,3-e][1,2,4]triazino[3,2-c][1,2,4]thiadiazine 6,6-dioxide Derivatives with Potential Anticancer Activity

by Jarosław Sławiński, Aleksandra Grzonek, Beata Żołnowska and Anna Kawiak

Molecules 2016, 21(1), 41; https://doi.org/10.3390/molecules21010041 - 29 Dec 2015

Cited by 7 | Viewed by 6317

Abstract

A series of novel 3-/2,3-substituted pyrido[4,3-e][1,2,4]triazino[3,2-c][1,2,4]thiadiazine 6,6-dioxides 4–28 have been synthesized by the reaction of 3-amino-2-(4-thioxo-1,4-dihydropyridin-3-yl-sulfonyl)guanidine with either 2-oxoalkanoic acids and its esters, or phenylglyoxylic hydrates in glacial acetic acid. Some of them exhibited reasonable or moderate [...] Read more.

A series of novel 3-/2,3-substituted pyrido[4,3-e][1,2,4]triazino[3,2-c][1,2,4]thiadiazine 6,6-dioxides 4–28 have been synthesized by the reaction of 3-amino-2-(4-thioxo-1,4-dihydropyridin-3-yl-sulfonyl)guanidine with either 2-oxoalkanoic acids and its esters, or phenylglyoxylic hydrates in glacial acetic acid. Some of them exhibited reasonable or moderate anticancer activity toward human cancer cell lines, HCT-116, MCF-7 and HeLa. The structure of this novel heterocyclic ring system was confirmed by ¹D-NMR and ²D-NMR spectroscopic data including COSY, ROESY and HMBC, elemental analyses and MS spectrometry. Full article

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

► Show Figures

Graphical abstract

14 pages, 2240 KiB

Open AccessArticle

Turkish Scorzonera Species Extracts Attenuate Cytokine Secretion via Inhibition of NF-κB Activation, Showing Anti-Inflammatory Effect in Vitro

by Özlem Bahadır Acikara, Jan Hošek, Petr Babula, Josef Cvačka, Miloš Budešínský, Martin Dračinský, Gülçin Saltan İşcan, Daniela Kadlecová, Ludmila Ballová and Karel Šmejkal

Molecules 2016, 21(1), 43; https://doi.org/10.3390/molecules21010043 - 30 Dec 2015

Cited by 23 | Viewed by 6557

Abstract

Scorzonera species are used in different folk medicines to combat many diseases, including the illnesses connected with inflammation. Previous experiments showed anti-inflammatory activity of Scorzonera extracts in vivo. S. latifolia, S. cana var. jacquiniana, S. tomentosa, S. mollis ssp. [...] Read more.

Scorzonera species are used in different folk medicines to combat many diseases, including the illnesses connected with inflammation. Previous experiments showed anti-inflammatory activity of Scorzonera extracts in vivo. S. latifolia, S. cana var. jacquiniana, S. tomentosa, S. mollis ssp. szowitsii, S. eriophora, S. incisa, S. cinerea, and S. parviflora extracts were, therefore, evaluated for their inhibitory activities of TNF-α and IL-1β production, and NF-κB nuclear translocation in THP-1 macrophages. The HPLC analysis was carried out to elucidate and to compare the composition of these extracts. Major compounds of the tested extracts have been isolated using different chromatographic techniques and further tested for their inhibitory activities on TNF-α and IL-1β production. Several extracts showed promising anti-inflammatory activity in these in vitro tests. Results of HPLC analysis revealed chlorogenic acid as a compound present in all tested extracts. Hyperoside, quercetin-3-O-β-d-glucoside and rutin were also present in varying amount in some Scorzonera species analyzed. Furthermore, eight phenolics which were identified as quercetin-3-O-β-d-glucoside (1), hyperoside (2), hydrangenol-8-O-glucoside (3), swertisin (4), 7-methylisoorientin (5), 4,5-O-dicaffeoyl-quinic acid (6), 3,5-di-O-caffeoyl-quinic acid (7), and chlorogenic acid (8) have been isolated as major phenolic compounds of the tested extracts and, together with eight terpenoids (9–16) previously obtained from different Scorzonera species, have been tested for the inhibition of TNF-α production, unfortunately with no activity comparable with standard. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

10 pages, 870 KiB

Open AccessArticle

Site-Selective Ribosylation of Fluorescent Nucleobase Analogs Using Purine-Nucleoside Phosphorylase as a Catalyst: Effects of Point Mutations

by Alicja Stachelska-Wierzchowska, Jacek Wierzchowski, Agnieszka Bzowska and Beata Wielgus-Kutrowska

Molecules 2016, 21(1), 44; https://doi.org/10.3390/molecules21010044 - 28 Dec 2015

Cited by 13 | Viewed by 5400

Abstract

Enzymatic ribosylation of fluorescent 8-azapurine derivatives, like 8-azaguanine and 2,6-diamino-8-azapurine, with purine-nucleoside phosphorylase (PNP) as a catalyst, leads to N9, N8, and N7-ribosides. The final proportion of the products may be modulated by point mutations in the enzyme active site. As an example, [...] Read more.

Enzymatic ribosylation of fluorescent 8-azapurine derivatives, like 8-azaguanine and 2,6-diamino-8-azapurine, with purine-nucleoside phosphorylase (PNP) as a catalyst, leads to N9, N8, and N7-ribosides. The final proportion of the products may be modulated by point mutations in the enzyme active site. As an example, ribosylation of the latter substrate by wild-type calf PNP gives N7- and N8-ribosides, while the N243D mutant directs the ribosyl substitution at N9- and N7-positions. The same mutant allows synthesis of the fluorescent N7-β-d-ribosyl-8-azaguanine. The mutated form of the E. coli PNP, D204N, can be utilized to obtain non-typical ribosides of 8-azaadenine and 2,6-diamino-8-azapurine as well. The N7- and N8-ribosides of the 8-azapurines can be analytically useful, as illustrated by N7-β-d-ribosyl-2,6-diamino-8-azapurine, which is a good fluorogenic substrate for mammalian forms of PNP, including human blood PNP, while the N8-riboside is selective to the E. coli enzyme. Full article

(This article belongs to the Special Issue Nucleoside Modifications)

► Show Figures

Figure 1

14 pages, 16507 KiB

Open AccessArticle

Improved Schmidt Conversion of Aldehydes to Nitriles Using Azidotrimethylsilane in 1,1,1,3,3,3-Hexafluoro-2-propanol

by Hashim F. Motiwala, Qin Yin and Jeffrey Aubé

Molecules 2016, 21(1), 45; https://doi.org/10.3390/molecules21010045 - 29 Dec 2015

Cited by 11 | Viewed by 9064

Abstract

The Schmidt reaction of aromatic aldehydes using a substoichiometric amount (40 mol %) of triflic acid is described. Low catalyst loading was enabled by a strong hydrogen-bond-donating solvent hexafluoro-2-propanol (HFIP). This improved protocol tolerates a broad scope of aldehydes with diverse functional groups [...] Read more.

The Schmidt reaction of aromatic aldehydes using a substoichiometric amount (40 mol %) of triflic acid is described. Low catalyst loading was enabled by a strong hydrogen-bond-donating solvent hexafluoro-2-propanol (HFIP). This improved protocol tolerates a broad scope of aldehydes with diverse functional groups and the corresponding nitriles were obtained in good to high yields without the need for aqueous work up. Full article

(This article belongs to the Special Issue Organic Azides)

► Show Figures

Figure 1

13 pages, 1048 KiB

Open AccessArticle

The Alterations in the Expression and Function of P-Glycoprotein in Vitamin A-Deficient Rats as well as the Effect of Drug Disposition in Vivo

by Yubang Wang, Heng Qin, Chengxiang Zhang, Fei Huan, Ting Yan and Lulu Zhang

Molecules 2016, 21(1), 46; https://doi.org/10.3390/molecules21010046 - 29 Dec 2015

Cited by 6 | Viewed by 4990

Abstract

This study was aimed to investigate whether vitamin A deficiency could alter P-GP expression and function in tissues of rats and whether such effects affected the drug distribution in vivo of vitamin A-deficient rats. We induced vitamin A-deficient rats by giving them a [...] Read more.

This study was aimed to investigate whether vitamin A deficiency could alter P-GP expression and function in tissues of rats and whether such effects affected the drug distribution in vivo of vitamin A-deficient rats. We induced vitamin A-deficient rats by giving them a vitamin A-free diet for 12 weeks. Then, Abcb1/P-GP expression was evaluated by qRT-PCR and Western blot. qRT-PCR analysis revealed that Abcb1a mRNA levels were increased in hippocampus and liver. In kidney, it only showed an upward trend. Abcb1b mRNA levels were increased in hippocampus, but decreased in cerebral cortex, liver and kidney. Western blot results were in good accordance with the alterations of Abcb1b mRNA levels. P-GP function was investigated through tissue distribution and body fluid excretion of rhodamine 123 (Rho123), and the results proclaimed that P-GP activities were also in good accordance with P-GP expression in cerebral cortex, liver and kidney. The change of drug distribution was also investigated through the tissue distribution of vincristine, and the results showed a significantly upward trend in all indicated tissues of vitamin A-deficient rats. In conclusion, vitamin A deficiency may alter Abcb1/P-GP expression and function in rat tissues, and the alterations may increase drug activity/toxicity through the increase of tissue accumulation. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

25 pages, 1273 KiB

Open AccessArticle

Synthesis of Bioconjugate Sesterterpenoids with Phospholipids and Polyunsaturated Fatty Acids

by Ana Gil-Mesón, Alejandro M. Roncero, Ignacio E. Tobal, Pilar Basabe, David Díez, Faustino Mollinedo and Isidro S. Marcos

Molecules 2016, 21(1), 47; https://doi.org/10.3390/molecules21010047 - 30 Dec 2015

Cited by 8 | Viewed by 6972

Abstract

A series of sesterterpenoid bioconjugates with phospholipids and polyunsaturated fatty acids (PUFAs) have been synthesized for biological activity testing as antiproliferative agents in several cancer cell lines. Different substitution analogues of the original lipidic ether edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) [...] Read more.

A series of sesterterpenoid bioconjugates with phospholipids and polyunsaturated fatty acids (PUFAs) have been synthesized for biological activity testing as antiproliferative agents in several cancer cell lines. Different substitution analogues of the original lipidic ether edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) are obtained varying the sesterterpenoid in position 1 or 2 of the glycerol or a phosphocholine or PUFA unit in position 3. Simple bioconjugates of sesterterpenoids and eicosapentaenoic acid (EPA) have been obtained too. All synthetic derivatives were tested against the human tumour cell lines HeLa (cervix) and MCF-7 (breast). Some compounds showed good IC₅₀ (0.3 and 0.2 μM) values against these cell lines. Full article

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

► Show Figures

Graphical abstract

14 pages, 890 KiB

Open AccessArticle

Design, Synthesis and Antimycobacterial Activity of Novel Imidazo[1,2-a]pyridine Amide-Cinnamamide Hybrids

by Linhu Li, Zhuorong Li, Mingliang Liu, Weiyi Shen, Bin Wang, Huiyuan Guo and Yu Lu

Molecules 2016, 21(1), 49; https://doi.org/10.3390/molecules21010049 - 30 Dec 2015

Cited by 20 | Viewed by 7074

Abstract

We report herein the design and synthesis of a series of novel imidazo[1,2-a]pyridine amide-cinnamamide hybrids linked via an alkyl carbon chain. All 38 new hybrids were evaluated for their antimycobacterial activity against M. tuberculosis (MTB) H37Rv ATCC 27294 using the microplate [...] Read more.

We report herein the design and synthesis of a series of novel imidazo[1,2-a]pyridine amide-cinnamamide hybrids linked via an alkyl carbon chain. All 38 new hybrids were evaluated for their antimycobacterial activity against M. tuberculosis (MTB) H37Rv ATCC 27294 using the microplate Alamar Blue assay (MABA). Although the hybrids are less active than the two reference compounds, the promising activity (MICs: 4 μg/mL) of 2,6-dimethylimidazo[1,2-a]pyridine amide-cinnamamide hybrids 11e and 11k could be a good starting point to further find new lead compounds against multi-drug-resistant tuberculosis. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Graphical abstract

9 pages, 207 KiB

Open AccessArticle

The Activity of Cotinus coggygria Scop. Leaves on Staphylococcus aureus Strains in Planktonic and Biofilm Growth Forms

by Katarína Rendeková, Silvia Fialová, Lucia Jánošová, Pavel Mučaji and Lívia Slobodníková

Molecules 2016, 21(1), 50; https://doi.org/10.3390/molecules21010050 - 30 Dec 2015

Cited by 19 | Viewed by 6467

Abstract

The purpose of this study was to detect the effectiveness of Cotinus coggygria Scop. leaves methanol extract against planktonic and biofilm growth forms of Staphylococcus aureus. The antimicrobial activity was determined by the broth microdilution test. Minimal inhibitory concentrations and minimal bactericidal [...] Read more.

The purpose of this study was to detect the effectiveness of Cotinus coggygria Scop. leaves methanol extract against planktonic and biofilm growth forms of Staphylococcus aureus. The antimicrobial activity was determined by the broth microdilution test. Minimal inhibitory concentrations and minimal bactericidal concentrations were detected against two collection and ten clinical S. aureus strains. Anti-biofilm activity of the tested extract was detected using 24 h bacterial biofilm on the surface of microtiter plate wells. The biofilm inhibitory activity was evaluated visually after 24 h interaction of extract with biofilm, and the eradicating activity by a regrowth method. The tested extract showed bactericidal activity against all S. aureus strains (methicillin susceptible or methicillin resistant) in concentrations ranging from 0.313 to 0.625 mg·mL⁻¹. Biofilm inhibitory concentrations were 10-times higher and biofilm eradicating concentrations 100-times higher (8 and 32 mg·mL⁻¹, respectively). The phytochemical analysis of C. coggygria leaves 60% methanol extract performed by LC-DAD-MS/MS revealed quercetin rhamnoside, methyl gallate, and methyl trigallate as main constituents. Results of our study indicate that C. coggygria, rich in tannins and flavonoids, seems to be a prospective topical antibacterial agent with anti-biofilm activity. Full article

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

19 pages, 3907 KiB

Open AccessArticle

Synthesis, Spectroscopic, Structural and Quantum Chemical Studies of a New Imine Oxime and Its Palladium(II) Complex: Hydrolysis Mechanism

by Yunus Kaya, Veysel T. Yilmaz and Orhan Buyukgungor

Molecules 2016, 21(1), 52; https://doi.org/10.3390/molecules21010052 - 21 Jan 2016

Cited by 13 | Viewed by 8621

Abstract

In this work, we report synthesis, crystallographic, spectroscopic and quantum chemical studies of a new imine oxime, namely (4-nitro-phenyl)-(1-phenyl-ethylimino)-acetaldehyde oxime (nppeieoH). Spectroscopic and X-ray diffraction studies showed that nppeieoH is hydrolyzed in aqueous solution, forming nitroisonitrosoacetophenone (ninap) and the hydrolysis product binds to [...] Read more.

In this work, we report synthesis, crystallographic, spectroscopic and quantum chemical studies of a new imine oxime, namely (4-nitro-phenyl)-(1-phenyl-ethylimino)-acetaldehyde oxime (nppeieoH). Spectroscopic and X-ray diffraction studies showed that nppeieoH is hydrolyzed in aqueous solution, forming nitroisonitrosoacetophenone (ninap) and the hydrolysis product binds to Pd(II) to yield [Pd(nppeieo)(ninap)]. The mechanism of the hydrolysis reaction has been theoretically investigated in detail, using density functional theory (DFT) with the B3LYP method. The vibrational and the electronic spectra of nppeieoH and its Pd(II) complex, the HOMO and LUMO analysis, Mulliken atomic charges and molecular electrostatic potential were also performed. The predicted nonlinear optical properties of both compounds are higher than those of urea. Full article

(This article belongs to the Section Molecular Diversity)

► Show Figures

Graphical abstract

11 pages, 1353 KiB

Open AccessArticle

Effect of Donepezil, Tacrine, Galantamine and Rivastigmine on Acetylcholinesterase Inhibition in Dugesia tigrina

by Cristiane Bezerra da Silva, Arnildo Pott, Selene Elifio-Esposito, Luciane Dalarmi, Kátia Fialho do Nascimento, Ligia Moura Burci, Maislian De Oliveira, Josiane De Fátima Gaspari Dias, Sandra Maria Warumby Zanin, Obdulio Gomes Miguel and Marilis Dallarmi Miguel

Molecules 2016, 21(1), 53; https://doi.org/10.3390/molecules21010053 - 11 Jan 2016

Cited by 20 | Viewed by 9016

Abstract

Dugesia tigrina is a non-parasitic platyhelminth, which has been recently utilized in pharmacological models, regarding the nervous system, as it presents a wide sensitivity to drugs. Our trials aimed to propose a model for an in vivo screening of substances with inhibitory activity [...] Read more.

Dugesia tigrina is a non-parasitic platyhelminth, which has been recently utilized in pharmacological models, regarding the nervous system, as it presents a wide sensitivity to drugs. Our trials aimed to propose a model for an in vivo screening of substances with inhibitory activity of the enzyme acetylcholinesterase. Trials were performed with four drugs commercialized in Brazil: donepezil, tacrine, galantamine and rivastigmine, utilized in the control of Alzheimer’s disease, to inhibit the activity of acetylcholinesterase. We tested five concentrations of the drugs, with an exposure of 24 h, and the mortality and the inhibition of acetylcholinesterase planarian seizure-like activity (pSLA) and planarian locomotor velocity (pLMV) were measured. Galantamine showed high anticholinesterasic activity when compared to the other drugs, with a reduction of 0.05 μmol·min⁻¹ and 63% of convulsant activity, presenting screw-like movement and hypokinesia, with pLMV of 65 crossed lines during 5 min. Our results showed for the first time the anticholinesterasic and convulsant effect, in addition to the decrease in locomotion induced by those drugs in a model of invertebrates. The experimental model proposed is simple and low cost and could be utilized in the screening of substances with anticholinesterasic action. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

14 pages, 3970 KiB

Open AccessArticle

DNA Binding, Photonuclease Activity and Human Serum Albumin Interaction of a Water-Soluble Freebase Carboxyl Corrole

by Ning Na, Da-Qiang Zhao, Heng Li, Nan Jiang, Jin-Yan Wen and Hai-Yang Liu

Molecules 2016, 21(1), 54; https://doi.org/10.3390/molecules21010054 - 31 Dec 2015

Cited by 33 | Viewed by 7373

Abstract

The DNA binding property of 5,10,15-Tris(4-carboxyphenyl) corrole (TCPC) was studied by UV-Visible, fluorescence and circular dichroism (CD) spectroscopic methods. TCPC can bind to ct-DNA via an outside binding mode with the binding constant of K_b = 1.05 × 10⁵ M⁻¹ [...] Read more.

The DNA binding property of 5,10,15-Tris(4-carboxyphenyl) corrole (TCPC) was studied by UV-Visible, fluorescence and circular dichroism (CD) spectroscopic methods. TCPC can bind to ct-DNA via an outside binding mode with the binding constant of K_b = 1.05 × 10⁵ M⁻¹. TCPC also displayed good photonuclease activity, which involves singlet oxygen species (¹O₂). The binding constant between TCPC and human serum albumin (HSA) is K_A = 2.24 × 10⁵ M⁻¹ with a simulated binding distance of 2.06 nm. The fluorescence quenching of HSA by TCPC followed a static quenching process. Site marker competitive displacement experiments indicated that warfarin site I is the main binding site. The secondary structure of HSA was changed upon interaction with TCPC, which was confirmed by UV-Visible and CD spectroscopy. Full article

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

► Show Figures

Figure 1

8 pages, 1066 KiB

Open AccessArticle

Silymarin Constituents Enhance ABCA1 Expression in THP-1 Macrophages

by Limei Wang, Susanne Rotter, Angela Ladurner, Elke H. Heiss, Nicholas H. Oberlies, Verena M. Dirsch and Atanas G. Atanasov

Molecules 2016, 21(1), 55; https://doi.org/10.3390/molecules21010055 - 31 Dec 2015

Cited by 28 | Viewed by 6759

Abstract

Silymarin is a hepatoprotective mixture of flavonolignans and flavonoids extracted from the seeds of milk thistle (Silybum marianum L. Gaertn). This study investigates the effect of major bioactive constituents from silymarin, silybin A, silybin B, isosilybin A, isosilybin B, silydianin, silychristin, isosilychristin, [...] Read more.

Silymarin is a hepatoprotective mixture of flavonolignans and flavonoids extracted from the seeds of milk thistle (Silybum marianum L. Gaertn). This study investigates the effect of major bioactive constituents from silymarin, silybin A, silybin B, isosilybin A, isosilybin B, silydianin, silychristin, isosilychristin, and taxifolin, on the expression of ABCA1, an important cholesterol efflux transporter, in THP-1-derived macrophages. Four of the studied compounds, isosilybin A, silybin B, silychristin and isosilychristin, were found to significantly induce ABCA1 protein expression without affecting cell viability. Moreover, isosilybin A, a partial PPARγ agonist, was found to promote cholesterol efflux from THP-1 macrophages in a concentration-dependent manner. These findings first show ABCA1 protein up-regulating activity of active constituents of silymarin and provide new avenues for their further study in the context of cardiovascular disease. Full article

(This article belongs to the Special Issue Selected papers from the 2nd International Conference on Natural Products Utilization: from Plants to Pharmacy Shelf (ICNPU 2015, Plovdiv, Bulgaria))

► Show Figures

Graphical abstract

9 pages, 2598 KiB

Open AccessArticle

Evaluation of the Nano-TiO₂ as a Novel Deswelling Material

by Ming Chu, Yue-Long Hou, Lan Xu, Zheng-Yun Chu, Ming-Bo Zhang and Yue-Dan Wang

Molecules 2016, 21(1), 57; https://doi.org/10.3390/molecules21010057 - 4 Jan 2016

Cited by 5 | Viewed by 6014

Abstract

Nano-TiO₂ is widely applied in the automobile exhaust hose reels as a catalyst to reduce oxynitride emissions, including nitric oxide (NO). In the biomedicine field, NO plays an important role in vasodilation and edema formation in human bodies. However, the deswelling activity [...] Read more.

Nano-TiO₂ is widely applied in the automobile exhaust hose reels as a catalyst to reduce oxynitride emissions, including nitric oxide (NO). In the biomedicine field, NO plays an important role in vasodilation and edema formation in human bodies. However, the deswelling activity of nano-TiO₂ has not been reported. Here, we demonstrated that nano-TiO₂ can significantly degrade the production of NO in LPS-induced RAW264.7 mouse macrophages. Further study indicated that nano-TiO₂ exhibited an effect on vascular permeability inhibition, and prevented carrageenan-induced footpad edema. Therefore, we prepared a nano-TiO₂ ointment and observed similar deswelling effects. In conclusion, nano-TiO₂ might act as a novel deswelling agent related with its degradation of NO, which will aid in our ability to design effective interventions for edema involved diseases. Full article

(This article belongs to the Collection Nanomedicine)

► Show Figures

Figure 1

12 pages, 747 KiB

Open AccessArticle

New Phragmalin-Type Limonoids from Chukrasia tabularis and Their α-Glucosidase Inhibitory Activity

by Jun-Lin Peng, Jun Wang, Fan-Dong Kong, Zi-Qi Liu, Pei Wang, Cui-Juan Gai, Bei Jiang, Wen-Li Mei and Hao-Fu Dai

Molecules 2016, 21(1), 58; https://doi.org/10.3390/molecules21010058 - 5 Jan 2016

Cited by 9 | Viewed by 4778

Abstract

Phytochemical investigation on the stems of C. tabularis led to the isolation of five new phragmalin-type limonoids and six known ones. The structures of the new compounds 1–5, named chukbularisins A–E, were elucidated by spectroscopic techniques (IR, HRESIMS, 1D and [...] Read more.

Phytochemical investigation on the stems of C. tabularis led to the isolation of five new phragmalin-type limonoids and six known ones. The structures of the new compounds 1–5, named chukbularisins A–E, were elucidated by spectroscopic techniques (IR, HRESIMS, 1D and 2D NMR) and comparisons with published data. All the compounds were evaluated for in vitro α-glucosidase inhibitory activity. Compounds 2, 3, 4, 5, and 8 exhibited inhibitory activity against α-glucosidase with IC₅₀ values of 0.06 ± 0.008, 0.04 ± 0.002, 0.52 ± 0.039, 1.09 ± 0.040, and 0.20 ± 0.057 mM, respectively (using acarbose as positive control, IC₅₀ 0.95 ± 0.092 mM). Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

8 pages, 874 KiB

Open AccessArticle

Isolation and Biosynthetic Analysis of Haliamide, a New PKS-NRPS Hybrid Metabolite from the Marine Myxobacterium Haliangium ochraceum

by Yuwei Sun, Tomohiko Tomura, Junichi Sato, Takashi Iizuka, Ryosuke Fudou and Makoto Ojika

Molecules 2016, 21(1), 59; https://doi.org/10.3390/molecules21010059 - 6 Jan 2016

Cited by 44 | Viewed by 9817

Abstract

Myxobacteria of marine origin are rare and hard-to-culture microorganisms, but they genetically harbor high potential to produce novel antibiotics. An extensive investigation on the secondary metabolome of the unique marine myxobacterium Haliangium ochraceum SMP-2 led to the isolation of a new polyketide-nonribosomal peptide [...] Read more.

Myxobacteria of marine origin are rare and hard-to-culture microorganisms, but they genetically harbor high potential to produce novel antibiotics. An extensive investigation on the secondary metabolome of the unique marine myxobacterium Haliangium ochraceum SMP-2 led to the isolation of a new polyketide-nonribosomal peptide hybrid product, haliamide (1). Its structure was elucidated by spectroscopic analyses including NMR and HR-MS. Haliamide (1) showed cytotoxicity against HeLa-S3 cells with IC₅₀ of 12 μM. Feeding experiments were performed to identify the biosynthetic building blocks of 1, revealing one benzoate, one alanine, two propionates, one acetate and one acetate-derived terminal methylene. The biosynthetic gene cluster of haliamide (hla, 21.7 kbp) was characterized through the genome mining of the producer, allowing us to establish a model for the haliamide biosynthesis. The sulfotransferase (ST)-thioesterase (TE) domains encoded in hlaB appears to be responsible for the terminal alkene formation via decarboxylation. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

8 pages, 1023 KiB

Open AccessArticle

Unimolecular Solvolyses in Ionic Liquid: Alcohol Dual Solvent Systems

by Elizabeth D. Kochly, Nicole Jean Lemon and Anne Marie Deh-Lee

Molecules 2016, 21(1), 60; https://doi.org/10.3390/molecules21010060 - 6 Jan 2016

Cited by 8 | Viewed by 4914

Abstract

A study was undertaken of the solvolysis of pivaloyl triflate in a variety of ionic liquid:alcohol solvent mixtures. The solvolysis is a k_Δ process (i.e., a process in which ionization occurs with rearrangement), and the resulting rearranged carbocation intermediate reacts [...] Read more.

A study was undertaken of the solvolysis of pivaloyl triflate in a variety of ionic liquid:alcohol solvent mixtures. The solvolysis is a k_Δ process (i.e., a process in which ionization occurs with rearrangement), and the resulting rearranged carbocation intermediate reacts with the alcohol cosolvent via two competing pathways: nucleophilic attack or elimination of a proton. Five different ionic liquids and three different alcohol cosolvents were investigated to give a total of fifteen dual solvent systems. ¹H-NMR analysis was used to determine relative amounts of elimination and substitution products. It was found, not surprisingly, that increasing the bulkiness of alcohol cosolvent led to increased elimination product. The change in the amount of elimination product with increasing ionic liquid concentration, however, varied greatly between ionic liquids. These differences correlate strongly, though not completely, to the Kamlet–Taft solvatochromic parameters of the hydrogen bond donating and accepting ability of the solvent systems. An additional factor playing into these differences is the bulkiness of the ionic liquid anion. Full article

(This article belongs to the Special Issue Ionic Liquids in Organic Synthesis)

► Show Figures

Graphical abstract

6 pages, 443 KiB

Open AccessCommunication

Synthesis of Chlorinated Tetracyclic Compounds and Testing for Their Potential Antidepressant Effect in Mice

by Usama Karama, Mujeeb A. Sultan, Abdulrahman I. Almansour and Kamal Eldin El-Taher

Molecules 2016, 21(1), 61; https://doi.org/10.3390/molecules21010061 - 5 Jan 2016

Cited by 10 | Viewed by 5356

Abstract

The synthesis of the tetracyclic compounds 1-(4,5-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl)-N-methylmethanamine (5) and 1-(1,8-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl)-N-methylmethanamine (6) as a homologue of the anxiolytic and antidepressant drugs benzoctamine and maprotiline were described. The key intermediate aldehydes (3) and (4 [...] Read more.

The synthesis of the tetracyclic compounds 1-(4,5-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl)-N-methylmethanamine (5) and 1-(1,8-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl)-N-methylmethanamine (6) as a homologue of the anxiolytic and antidepressant drugs benzoctamine and maprotiline were described. The key intermediate aldehydes (3) and (4) were successfully synthesized via a [4 + 2] cycloaddition between acrolein and 1,8-dichloroanthracene. The synthesized compounds were investigated for antidepressant activity using the forced swimming test. Compounds (5), (6) and (3) showed significant reduction in the mice immobility indicating significant antidepressant effects. These compounds significantly reduced the immobility times at a dose 80 mg/kg by 84.0%, 86.7% and 71.1% respectively. Full article

(This article belongs to the Section Organic Chemistry)

► Show Figures

Figure 1

14 pages, 2636 KiB

Open AccessArticle

Antibacterial Properties of Tebipenem Pivoxil Tablet, a New Oral Carbapenem Preparation against a Variety of Pathogenic Bacteria in Vitro and in Vivo

by Qi Yao, Jingkun Wang, Tao Cui, Zhi Yang, Mei Su, Peiyue Zhao, Hong Yan, Yi Zhan and Hongbo Yang

Molecules 2016, 21(1), 62; https://doi.org/10.3390/molecules21010062 - 6 Jan 2016

Cited by 21 | Viewed by 10301

Abstract

Aims: To systemically investigate the in vitro and in vivo antibacterial properties of tebipenem pivoxil tablet. In addition, acute toxicity of this preparation was also studied. Methods: In vitro, minimum inhibitory concentration (MIC) or minimal inhibitory concentration (MBC) were determined by using [...] Read more.

Aims: To systemically investigate the in vitro and in vivo antibacterial properties of tebipenem pivoxil tablet. In addition, acute toxicity of this preparation was also studied. Methods: In vitro, minimum inhibitory concentration (MIC) or minimal inhibitory concentration (MBC) were determined by using the serial 2-fold broth or agar dilution methods. Further, cumulative MIC inhibition curves were then made to assess the antibacterial effects of the drug at various concentrations. In vivo, minimum lethal dose (MLD) in combination with maximum tolerance dose (MTD) was used to measure the acute toxicity of the tebipenem pivoxil tablet in mice. After that, sepsis mouse models challenged with Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, respectively, were established to evaluate the anti-infective effect of this preparation. Results: The MIC₉₀ values of tebipenem pivoxil against Gram-positive bacteria such as methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus epidermidis (MSSE), methicillin-resistant Staphylococcus epidermidis (MRSE), Pyogenic streptococcus, and Enterococcus faecalis were ≤0.125, 16, 0.5, 8, ≤0.125, and 32 μg/mL, respectively. Correspondingly, the MIC₉₀ values of tebipenem pivoxil against Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Haemophilus influenzae, Pseudomonas aeruginosa, and Acinetobacter baumannii were 1, 0.5, ≤0.125, 0.25, 64, 64 μg/mL, respectively. The MBC values of tebipenem pivoxil against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae were 0.016–2, 0.063–32, 0.031–32 μg/mL, respectively. The acute toxicity study showed that the MLD of the tebipenem pivoxil tablet was 4.00 g/kg and the MTD was 3.40 g/kg in mice. In all the sepsis mouse models, the simultaneous administration of the tebipenem pivoxil tablets significantly reduced mortality of the sepsis-model mice as compared with the control. Furthermore, the survival rate in the tebipenem pivoxil tablet group was remarkably higher than that in the meropenem group in all the sepsis mouse models tested. In the sepsis model challenged with Staphylococcus aureus ATCC29213, Escherichia coli ATCC25922, Pseudomonas aeruginosa ATCC27853, and Pseudomonas aeruginosa clinical strain, respectively, tebipenem pivoxil tablet (100 mg/kg) displayed a better protective effect than tebipenem pivoxil granules (100 mg/kg). Conclusions: In summary, tebipenem pivoxil displays an excellent antibacterial activity against a variety of pathogenic bacteria in vitro. Importantly, tebipenem pivoxil tablet significantly protects the sepsis mice challenged with various pathogenic bacteria, which may provide a potential approach to treating bacterial sepsis in clinic. Full article

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

► Show Figures

Figure 1

14 pages, 217 KiB

Open AccessArticle

Nutrition Composition and Single, 14-Day and 13-Week Repeated Oral Dose Toxicity Studies of the Leaves and Stems of Rubus coreanus Miquel

by Ae-Son Om, Yu-Na Song, GeonMin Noh, HaengRan Kim and JeongSook Choe

Molecules 2016, 21(1), 65; https://doi.org/10.3390/molecules21010065 - 8 Jan 2016

Cited by 5 | Viewed by 5170

Abstract

The leaves and stems of the plant Rubus coreanus Miquel (RCMLS) are rich in vitamins, minerals and phytochemicals which have antioxidant, anti-hemolytic, anti-inflammatory, anti-fatigue and anti-cancer effects. However, RCMLS is not included in the Korean Food Standards Codex due to the lack of [...] Read more.

The leaves and stems of the plant Rubus coreanus Miquel (RCMLS) are rich in vitamins, minerals and phytochemicals which have antioxidant, anti-hemolytic, anti-inflammatory, anti-fatigue and anti-cancer effects. However, RCMLS is not included in the Korean Food Standards Codex due to the lack of safety assurance concerning RCMLS. We evaluated single and repeated oral dose toxicity of RCMLS in Sprague-Dawley rats. RCMLS did not induce any significant toxicological changes in both male and female rats at a single doses of 2500 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects in clinical signs, body weight, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology at doses of 625, 1250, and 2500 mg/kg/day. The LD₅₀ and LOAEL of RCMLS might be over 2500 mg/kg body weight/day and no target organs were identified. Therefore, this study revealed that single and repeated oral doses of RCMLS are safe. Full article

(This article belongs to the Section Medicinal Chemistry)

13 pages, 1085 KiB

Open AccessArticle

Genetic Diversity and Association of EST-SSR and SCoT Markers with Rust Traits in Orchardgrass (Dactylis glomerata L.)

by Haidong Yan, Yu Zhang, Bing Zeng, Guohua Yin, Xinquan Zhang, Yang Ji, Linkai Huang, Xiaomei Jiang, Xinchun Liu, Yan Peng, Xiao Ma and Yanhong Yan

Molecules 2016, 21(1), 66; https://doi.org/10.3390/molecules21010066 - 8 Jan 2016

Cited by 38 | Viewed by 6011

Abstract

Orchardgrass (Dactylis glomerata L.), is a well-known perennial forage species; however, rust diseases have caused a noticeable reduction in the quality and production of orchardgrass. In this study, genetic diversity was assessed and the marker-trait associations for rust were examined using 18 [...] Read more.

Orchardgrass (Dactylis glomerata L.), is a well-known perennial forage species; however, rust diseases have caused a noticeable reduction in the quality and production of orchardgrass. In this study, genetic diversity was assessed and the marker-trait associations for rust were examined using 18 EST-SSR and 21 SCoT markers in 75 orchardgrass accessions. A high level of genetic diversity was detected in orchardgrass with an average genetic diversity index of 0.369. For the EST-SSR and SCoT markers, 164 and 289 total bands were obtained, of which 148 (90.24%) and 272 (94.12%) were polymorphic, respectively. Results from an AMOVA analysis showed that more genetic variance existed within populations (87.57%) than among populations (12.43%). Using a parameter marker index, the efficiencies of the EST-SSR and SCoT markers were compared to show that SCoTs have higher marker efficiency (8.07) than EST-SSRs (4.82). The results of a UPGMA cluster analysis and a STRUCTURE analysis were both correlated with the geographic distribution of the orchardgrass accessions. Linkage disequilibrium analysis revealed an average r² of 0.1627 across all band pairs, indicating a high extent of linkage disequilibrium in the material. An association analysis between the rust trait and 410 bands from the EST-SSR and SCoT markers using TASSEL software revealed 20 band panels were associated with the rust trait in both 2011 and 2012. The 20 bands obtained from association analysis could be used in breeding programs for lineage selection to prevent great losses of orchardgrass caused by rust, and provide valuable information for further association mapping using this collection of orchardgrass. Full article

(This article belongs to the Section Molecular Diversity)

► Show Figures

Figure 1

11 pages, 1688 KiB

Open AccessArticle

Cross-Species, Amplifiable EST-SSR Markers for Amentotaxus Species Obtained by Next-Generation Sequencing

by Chiuan-Yu Li, Tzen-Yuh Chiang, Yu-Chung Chiang, Hsin-Mei Hsu, Xue-Jun Ge, Chi-Chun Huang, Chaur-Tzuhn Chen and Kuo-Hsiang Hung

Molecules 2016, 21(1), 67; https://doi.org/10.3390/molecules21010067 - 7 Jan 2016

Cited by 21 | Viewed by 6351

Abstract

Amentotaxus, a genus of Taxaceae, is an ancient lineage with six relic and endangered species. Four Amentotaxus species, namely A. argotaenia, A. formosana, A. yunnanensis, and A. poilanei, are considered a species complex because of their morphological similarities. [...] Read more.

Amentotaxus, a genus of Taxaceae, is an ancient lineage with six relic and endangered species. Four Amentotaxus species, namely A. argotaenia, A. formosana, A. yunnanensis, and A. poilanei, are considered a species complex because of their morphological similarities. Small populations of these species are allopatrically distributed in Asian forests. However, only a few codominant markers have been developed and applied to study population genetic structure of these endangered species. In this study, we developed and characterized polymorphic expressed sequence tag-simple sequence repeats (EST-SSRs) from the transcriptome of A. formosana. We identified 4955 putative EST-SSRs from 68,281 unigenes as potential molecular markers. Twenty-six EST-SSRs were selected for estimating polymorphism and transferability among Amentotaxus species, of which 23 EST-SSRs were polymorphic within Amentotaxus species. Among these, the number of alleles ranged from 1–4, the polymorphism information content ranged from 0.000–0.692, and the observed and expected heterozygosity were 0.000–1.000 and 0.080–0.740, respectively. Population genetic structure analyses confirmed that A. argotaenia and A. formosana were separate species and A. yunnanensis and A. poilanei were the same species. These novel EST-SSRs can facilitate further population genetic structure research of Amentotaxus species. Full article

(This article belongs to the Section Molecular Diversity)

► Show Figures

Figure 1

11 pages, 1365 KiB

Open AccessArticle

Design, Synthesis, DFT Study and Antifungal Activity of Pyrazolecarboxamide Derivatives

by Jin-Xia Mu, Yan-Xia Shi, Ming-Yan Yang, Zhao-Hui Sun, Xing-Hai Liu, Bao-Ju Li and Na-Bo Sun

Molecules 2016, 21(1), 68; https://doi.org/10.3390/molecules21010068 - 8 Jan 2016

Cited by 67 | Viewed by 9379

Abstract

A series of novel pyrazole amide derivatives were designed and synthesized by multi-step reactions from phenylhydrazine and ethyl 3-oxobutanoate as starting materials, and their structures were characterized by NMR, MS and elemental analysis. The antifungal activity of the title compounds was determined. The [...] Read more.

A series of novel pyrazole amide derivatives were designed and synthesized by multi-step reactions from phenylhydrazine and ethyl 3-oxobutanoate as starting materials, and their structures were characterized by NMR, MS and elemental analysis. The antifungal activity of the title compounds was determined. The results indicated that some of title compounds exhibited moderate antifungal activity. Furthermore, DFT calculations were used to study the structure-activity relationships (SAR). Full article

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

► Show Figures

Figure 1

14 pages, 1287 KiB

Open AccessArticle

Biochanin A Ameliorates Arsenic-Induced Hepato- and Hematotoxicity in Rats

by Abdulkadhar Mohamed Jalaludeen, Woo Tae Ha, Ran Lee, Jin Hoi Kim, Jeong Tae Do, Chankyu Park, Young Tae Heo, Won Young Lee and Hyuk Song

Molecules 2016, 21(1), 69; https://doi.org/10.3390/molecules21010069 - 9 Jan 2016

Cited by 53 | Viewed by 7148

Abstract

Biochanin A (BCA) is a natural organic compound of the phytoestrogenic isoflavone class that has antioxidant and metal chelator properties in the presence of transition metal ions, however, its efficacy in animal models is still obscure. Therefore, the objective of this study was [...] Read more.

Biochanin A (BCA) is a natural organic compound of the phytoestrogenic isoflavone class that has antioxidant and metal chelator properties in the presence of transition metal ions, however, its efficacy in animal models is still obscure. Therefore, the objective of this study was to investigate the protective effects of BCA against arsenic-induced hepatic injury and hematotoxicity in rats. The results suggest that arsenic intoxicated rats showed significantly higher levels of plasma hepatic markers than normal control rats. Furthermore, an increase in lipid peroxidation with depletion of reduced glutathione (GSH) and activities of superoxide dismutase (SOD) and catalase (CAT) occurred in the livers of rats exposed to arsenic. Administration of BCA (20 mg/kg·bw/day) and selenium (3 mg/kg·bw/day) resulted in a significant reversal of hepatic and oxidative stress markers in arsenic-intoxicated rats. A low dose of BCA (10 mg/kg·bw/day) did not show any preventive effect, while a high dose of BCA (40 mg/kg·bw/day) partially prevented all hepatotoxicity events. These biochemical perturbations were supported by histopathological observations of the liver. Our results suggest that administration of BCA (20 mg/kg·bw/day) attenuated the arsenic hepatotoxicity, a property that could contribute to the therapeutic approaches for chronic liver diseases. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

13 pages, 2104 KiB

Open AccessArticle

Garlic Supplementation Ameliorates UV-Induced Photoaging in Hairless Mice by Regulating Antioxidative Activity and MMPs Expression

by Hye Kyung Kim

Molecules 2016, 21(1), 70; https://doi.org/10.3390/molecules21010070 - 8 Jan 2016

Cited by 40 | Viewed by 9331

Abstract

UV exposure is associated with oxidative stress and is the primary factor in skin photoaging. UV-induced reactive oxygen species (ROS) cause the up-regulation of metalloproteinase (MMPs) and the degradation of dermal collagen and elastic fibers. Garlic and its components have been reported to [...] Read more.

UV exposure is associated with oxidative stress and is the primary factor in skin photoaging. UV-induced reactive oxygen species (ROS) cause the up-regulation of metalloproteinase (MMPs) and the degradation of dermal collagen and elastic fibers. Garlic and its components have been reported to exert antioxidative effects. The present study investigated the protective effect of garlic on UV-induced photoaging and MMPs regulation in hairless mice. Garlic was supplemented in the diet, and Skh-1 hairless mice were exposed to UV irradiation five days/week for eight weeks. Mice were divided into four groups; Non-UV, UV-irradiated control, UV+1% garlic powder diet group, and UV+2% garlic powder diet group. Chronic UV irradiation induced rough wrinkling of the skin with hyperkeratosis, and administration of garlic diminished the coarse wrinkle formation. UV-induced dorsal skin and epidermal thickness were also ameliorated by garlic supplementation. ROS generation, skin and serum malondialdehyde levels were significantly increased by UV exposure and were ameliorated by garlic administration although the effects were not dose-dependent. Antioxidant enzymes such as superoxide dismutase and catalase activities in skin tissues were markedly reduced by UV irradiation and garlic treatment increased these enzyme activities. UV-induced MMP-1 and MMP-2 protein levels were suppressed by garlic administration. Furthermore, garlic supplementation prevented the UV-induced increase of MMP-1 mRNA expression and the UV-induced decrease of procollagen mRNA expression. These results suggest that garlic may be effective for preventing skin photoaging accelerated by UV irradiation through the antioxidative system and MMP regulation. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

14 pages, 1862 KiB

Open AccessArticle

High Milk-Clotting Activity Expressed by the Newly Isolated Paenibacillus spp. Strain BD3526

by Feng Hang, Peiyi Liu, Qinbo Wang, Jin Han, Zhengjun Wu, Caixia Gao, Zhenmin Liu, Hao Zhang and Wei Chen

Molecules 2016, 21(1), 73; https://doi.org/10.3390/molecules21010073 - 12 Jan 2016

Cited by 30 | Viewed by 9000

Abstract

Paenibacillus spp. BD3526, a bacterium exhibiting a protein hydrolysis circle surrounded with an obvious precipitation zone on skim milk agar, was isolated from raw yak (Bos grunniens) milk collected in Tibet, China. Phylogenetic analysis based on 16S rRNA and whole genome [...] Read more.

Paenibacillus spp. BD3526, a bacterium exhibiting a protein hydrolysis circle surrounded with an obvious precipitation zone on skim milk agar, was isolated from raw yak (Bos grunniens) milk collected in Tibet, China. Phylogenetic analysis based on 16S rRNA and whole genome sequence comparison indicated the isolate belong to the genus Paenibacillus. The strain BD3526 demonstrated strong ability to produce protease with milk clotting activity (MCA) in wheat bran broth. The protease with MCA was predominantly accumulated during the late-exponential phase of growth. The proteolytic activity (PA) of the BD3526 protease was 1.33-fold higher than that of the commercial R. miehei coagulant. A maximum MCA (6470 ± 281 SU mL⁻¹) of the strain BD3526 was reached under optimal cultivation conditions. The protease with MCA was precipitated from the cultivated supernatant of wheat bran broth with ammonium sulfate and purified by anion-exchange chromatography. The molecular weight of the protease with MCA was determined as 35 kDa by sodium dodecyl sulfate-polyacrylamide gels electrophoresis (SDS-PAGE) and gelatin zymography. The cleavage site of the BD3526 protease with MCA in κ-casein was located at the Met₁₀₆–Ala₁₀₇ bond, as determined by mass spectrometry analysis. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

11 pages, 4250 KiB

Open AccessArticle

The Protective Effects of Alisol A 24-Acetate from Alisma canaliculatum on Ovariectomy Induced Bone Loss in Vivo

by Yun-Ho Hwang, Kyung-Yun Kang, Sung-Ju Lee, Sang-Jip Nam, Young-Jin Son and Sung-Tae Yee

Molecules 2016, 21(1), 74; https://doi.org/10.3390/molecules21010074 - 9 Jan 2016

Cited by 25 | Viewed by 8362

Abstract

Alisma canaliculatum is a herb commonly used in traditional Korean medicine, and has been shown in scientific studies to have antitumor, diuretic hepatoprotective, and antibacterial effects. Recently, the anti-osteoclastogenesis of alisol A 24-acetate from Alisma canaliculatum was investigated in vitro. However, the [...] Read more.

Alisma canaliculatum is a herb commonly used in traditional Korean medicine, and has been shown in scientific studies to have antitumor, diuretic hepatoprotective, and antibacterial effects. Recently, the anti-osteoclastogenesis of alisol A 24-acetate from Alisma canaliculatum was investigated in vitro. However, the influence of alisol A 24-acetate on osteoporosis in animals has not been investigated. The present study was undertaken to investigate the anti-osteoporotic effect of alisol A 24-acetate on bone mass in ovariectomized (OVX) mice and to identify the mechanism responsible for its effects. OVX mice were treated daily with 0.5 or 2 μg/g of alisol A 24-acetate for a period of six weeks. It was found that these administrations significantly suppressed osteoporosis in OVX mice and improved bone morphometric parameters. The serum estradiol, bone alkaline phosphatase levels, regulatory T/Th17 cell numbers were significantly increased by alisol A 24-acetate as compared with untreated OVX mice. In addition, TRAP activity was inhibited by alisol A 24-acetate in OVX mice. These results suggest alisol A 24-acetate effectively prevents bone loss in OVX mice, and that it can be considered a potential therapeutic for the treatment of postmenopausal osteoporosis. Full article

(This article belongs to the Collection Herbal Medicine Research)

► Show Figures

Figure 1

18 pages, 3062 KiB

Open AccessArticle

Chemical Structure-Related Drug-Like Criteria of Global Approved Drugs

by Fei Mao, Wei Ni, Xiang Xu, Hui Wang, Jing Wang, Min Ji and Jian Li

Molecules 2016, 21(1), 75; https://doi.org/10.3390/molecules21010075 - 12 Jan 2016

Cited by 88 | Viewed by 12482

Abstract

The chemical structure of a drug determines its physicochemical properties, further determines its ADME/Tox properties, and ultimately affects its pharmacological activity. Medicinal chemists can regulate the pharmacological activity of drug molecules by modifying their structure. Ring systems and functional groups are important components [...] Read more.

The chemical structure of a drug determines its physicochemical properties, further determines its ADME/Tox properties, and ultimately affects its pharmacological activity. Medicinal chemists can regulate the pharmacological activity of drug molecules by modifying their structure. Ring systems and functional groups are important components of a drug. The proportion of non-hydrocarbon atoms among non-hydrogen atoms reflects the heavy atoms proportion of a drug. The three factors have considerable potential for the assessment of the drug-like properties of organic molecules. However, to the best of our knowledge, there have been no studies to systematically analyze the simultaneous effects of the number of aromatic and non-aromatic rings, the number of some special functional groups and the proportion of heavy atoms on the drug-like properties of an organic molecule. To this end, the numbers of aromatic and non-aromatic rings, the numbers of some special functional groups and the heavy atoms proportion of 6891 global approved small drugs have been comprehensively analyzed. We first uncovered three important structure-related criteria closely related to drug-likeness, namely: (1) the best numbers of aromatic and non-aromatic rings are 2 and 1, respectively; (2) the best functional groups of candidate drugs are usually -OH, -COOR and -COOH in turn, but not -CONHOH, -SH, -CHO and -SO₃H. In addition, the -F functional group is beneficial to CNS drugs, and -NH₂ functional group is beneficial to anti-infective drugs and anti-cancer drugs; (3) the best R value intervals of candidate drugs are in the range of 0.05–0.50 (preferably 0.10–0.35), and R value of the candidate CNS drugs should be as small as possible in this interval. We envision that the three chemical structure-related criteria may be applicable in a prospective manner for the identification of novel candidate drugs and will provide a theoretical foundation for designing new chemical entities with good drug-like properties. Full article

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

► Show Figures

Figure 1

10 pages, 568 KiB

Open AccessArticle

Antibacterial Activity of Alkaloid Fractions from Berberis microphylla G. Forst and Study of Synergism with Ampicillin and Cephalothin

by Loreto Manosalva, Ana Mutis, Alejandro Urzúa, Victor Fajardo and Andrés Quiroz

Molecules 2016, 21(1), 76; https://doi.org/10.3390/molecules21010076 - 11 Jan 2016

Cited by 28 | Viewed by 7989

Abstract

Berberis microphylla is a native plant that grows in Patagonia and is commonly used by aboriginal ethnic groups in traditional medicine as an antiseptic for different diseases. The present study evaluated the antibacterial and synergistic activity of alkaloid extracts of B. microphylla leaves, [...] Read more.

Berberis microphylla is a native plant that grows in Patagonia and is commonly used by aboriginal ethnic groups in traditional medicine as an antiseptic for different diseases. The present study evaluated the antibacterial and synergistic activity of alkaloid extracts of B. microphylla leaves, stems and roots used either individually or in combination with antibiotics against Gram-positive and Gram-negative bacteria. The in vitro antibacterial activities of leaf, stem and root alkaloid extracts had significant activity only against Gram-positive bacteria. Disc diffusion tests demonstrated that the root extract showed similar activity against B. cereus and S. epidermidis compared to commercial antibiotics, namely ampicillin and cephalothin, and pure berberine, the principal component of the alkaloid extracts, was found to be active only against S. aureus and S. epidermidis with similar activity to that of the root extract. The minimum inhibitory concentrations (MICs) of the alkaloid extracts ranged from 333 to 83 μg/mL, whereas minimum bactericidal concentrations (MBCs) varied from 717 to 167 μg/mL. In addition, synergistic or indifferent effects between the alkaloid extracts and antibiotics against bacterial strains were confirmed. Full article

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

► Show Figures

Figure 1

11 pages, 2109 KiB

Open AccessArticle

The Protective Effects of HJB-1, a Derivative of 17-Hydroxy-Jolkinolide B, on LPS-Induced Acute Distress Respiratory Syndrome Mice

by Xiaohan Xu, Ning Liu, Yu-Xin Zhang, Jinjin Cao, Donglin Wu, Qisheng Peng, Hong-Bing Wang and Wan-Chun Sun

Molecules 2016, 21(1), 77; https://doi.org/10.3390/molecules21010077 - 11 Jan 2016

Cited by 17 | Viewed by 6824

Abstract

Acute respiratory distress syndrome (ARDS),which is inflammatory disorder of the lung, which is caused by pneumonia, aspiration of gastric contents, trauma and sepsis, results in widespread lung inflammation and increased pulmonary vascular permeability. Its pathogenesis is complicated and the mortality is high. Thus, [...] Read more.

Acute respiratory distress syndrome (ARDS),which is inflammatory disorder of the lung, which is caused by pneumonia, aspiration of gastric contents, trauma and sepsis, results in widespread lung inflammation and increased pulmonary vascular permeability. Its pathogenesis is complicated and the mortality is high. Thus, there is a tremendous need for new therapies. We have reported that HJB-1, a 17-hydroxy-jolkinolide B derivative, exhibited strong anti-inflammatory effects in vitro. In this study, we investigated its impacts on LPS-induced ARDS mice. We found that HJB-1 significantly alleviated LPS-induced pulmonary histological alterations, inflammatory cells infiltration, lung edema, as well as the generation of inflammatory cytokines TNF-α, IL-1β and IL-6 in BALF. In addition, HJB-1 markedly suppressed LPS-induced IκB-α degradation, nuclear accumulation of NF-κB p65 subunit and MAPK phosphorylation. These results suggested that HJB-1 improved LPS-induced ARDS by suppressing LPS-induced NF-κB and MAPK activation. Full article

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

► Show Figures

Figure 1

16 pages, 1341 KiB

Open AccessArticle

Role of Nitric Oxide and Hydrogen Sulfide in the Vasodilator Effect of Ursolic Acid and Uvaol from Black Cherry Prunus serotina Fruits

by Francisco J. Luna-Vázquez, César Ibarra-Alvarado, Alejandra Rojas-Molina, Antonio Romo-Mancillas, Fabián H. López-Vallejo, Mariana Solís-Gutiérrez, Juana I. Rojas-Molina and Fausto Rivero-Cruz

Molecules 2016, 21(1), 78; https://doi.org/10.3390/molecules21010078 - 12 Jan 2016

Cited by 32 | Viewed by 7687

Abstract

The present research aimed to isolate the non-polar secondary metabolites that produce the vasodilator effects induced by the dichloromethane extract of Prunus serotina (P. serotina) fruits and to determine whether the NO/cGMP and the H₂S/K_ATP channel pathways are [...] Read more.

The present research aimed to isolate the non-polar secondary metabolites that produce the vasodilator effects induced by the dichloromethane extract of Prunus serotina (P. serotina) fruits and to determine whether the NO/cGMP and the H₂S/K_ATP channel pathways are involved in their mechanism of action. A bioactivity-directed fractionation of the dichloromethane extract of P. serotina fruits led to the isolation of ursolic acid and uvaol as the main non-polar vasodilator compounds. These compounds showed significant relaxant effect on rat aortic rings in an endothelium- and concentration-dependent manner, which was inhibited by NG-nitro-l-arginine methyl ester (l-NAME), dl-propargylglycine (PAG) and glibenclamide (Gli). Additionally, both triterpenes increased NO and H₂S production in aortic tissue. Molecular docking studies showed that ursolic acid and uvaol are able to bind to endothelial NOS and CSE with high affinity for residues that form the oligomeric interface of both enzymes. These results suggest that the vasodilator effect produced by ursolic acid and uvaol contained in P. serotina fruits, involves activation of the NO/cGMP and H₂S/K_ATP channel pathways, possibly through direct activation of NOS and CSE. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

9 pages, 579 KiB

Open AccessArticle

Antibacterial Activity and Antibiotic-Enhancing Effects of Honeybee Venom against Methicillin-Resistant Staphylococcus aureus

by Sang Mi Han, Joung Min Kim, In Pyo Hong, Soon Ok Woo, Se Gun Kim, He Rye Jang and Sok Cheon Pak

Molecules 2016, 21(1), 79; https://doi.org/10.3390/molecules21010079 - 12 Jan 2016

Cited by 45 | Viewed by 8969

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA), along with other antibiotic resistant bacteria, has become a significant social and clinical problem. There is thus an urgent need to develop naturally bioactive compounds as alternatives to the few antibiotics that remain effective. Here we assessed the in [...] Read more.

Methicillin-resistant Staphylococcus aureus (MRSA), along with other antibiotic resistant bacteria, has become a significant social and clinical problem. There is thus an urgent need to develop naturally bioactive compounds as alternatives to the few antibiotics that remain effective. Here we assessed the in vitro activities of bee venom (BV), alone or in combination with ampicillin, penicillin, gentamicin or vancomycin, on growth of MRSA strains. The antimicrobial activity of BV against MRSA strains was investigated using minimum inhibitory concentrations (MIC), minimum bactericidal concentrations (MBC) and a time-kill assay. Expression of atl which encodes murein hydrolase, a peptidoglycan-degrading enzyme involved in cell separation, was measured by reverse transcription-polymerase chain reaction. The MICs of BV were 0.085 µg/mL and 0.11 µg/mL against MRSA CCARM 3366 and MRSA CCARM 3708, respectively. The MBC of BV against MRSA 3366 was 0.106 µg/mL and that against MRSA 3708 was 0.14 µg/mL. The bactericidal activity of BV corresponded to a decrease of at least 3 log CFU/g cells. The combination of BV with ampicillin or penicillin yielded an inhibitory concentration index ranging from 0.631 to 1.002, indicating a partial and indifferent synergistic effect. Compared to ampicillin or penicillin, both MRSA strains were more susceptible to the combination of BV with gentamicin or vancomycin. The expression of atl gene was increased in MRSA 3366 treated with BV. These results suggest that BV exhibited antibacterial activity and antibiotic-enhancing effects against MRSA strains. The atl gene was increased in MRSA exposed to BV, suggesting that cell division was interrupted. BV warrants further investigation as a natural antimicrobial agent and synergist of antibiotic activity. Full article

(This article belongs to the Special Issue Natural Toxins)

► Show Figures

Graphical abstract

16 pages, 2896 KiB

Open AccessArticle

Identification of Selective ERRγ Inverse Agonists

by Jina Kim, Chun Young Im, Eun Kyung Yoo, Min Jung Ma, Sang-Bum Kim, Eunmi Hong, Jungwook Chin, Hayoung Hwang, Sungwoo Lee, Nam Doo Kim, Jae-Han Jeon, In-Kyu Lee, Yong Hyun Jeon, Hueng-Sik Choi, Seong Heon Kim and Sung Jin Cho

Molecules 2016, 21(1), 80; https://doi.org/10.3390/molecules21010080 - 12 Jan 2016

Cited by 15 | Viewed by 6710

Abstract

GSK5182 (4) is currently one of the lead compounds for the development of estrogen-related receptor gamma (ERRγ) inverse agonists. Here, we report the design, synthesis, pharmacological and in vitro absorption, distribution, metabolism, excretion, toxicity (ADMET) properties of a series of compounds [...] Read more.

GSK5182 (4) is currently one of the lead compounds for the development of estrogen-related receptor gamma (ERRγ) inverse agonists. Here, we report the design, synthesis, pharmacological and in vitro absorption, distribution, metabolism, excretion, toxicity (ADMET) properties of a series of compounds related to 4. Starting from 4, a series of analogs were structurally modified and their ERRγ inverse agonist activity was measured. A key pharmacophore feature of this novel class of ligands is the introduction of a heterocyclic group for A-ring substitution in the core scaffold. Among the tested compounds, several of them are potent ERRγ inverse agonists as determined by binding and functional assays. The most promising compound, 15g, had excellent binding selectivity over related subtypes (IC₅₀ = 0.44, >10, >10, and 10 μM at the ERRγ, ERRα, ERRβ, and ERα subtypes, respectively). Compound 15g also resulted in 95% transcriptional repression at a concentration of 10 μM, while still maintaining an acceptable in vitro ADMET profile. This novel class of ERRγ inverse agonists shows promise in the development of drugs targeting ERRγ-related diseases. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Graphical abstract

15 pages, 8700 KiB

Open AccessFeature PaperArticle

Screening a Small Library of Xanthones for Antitumor Activity and Identification of a Hit Compound which Induces Apoptosis

by João Barbosa, Raquel T. Lima, Diana Sousa, Ana Sara Gomes, Andreia Palmeira, Hugo Seca, Kantima Choosang, Pannee Pakkong, Hassan Bousbaa, Madalena M. Pinto, Emília Sousa, M. Helena Vasconcelos and Madalena Pedro

Molecules 2016, 21(1), 81; https://doi.org/10.3390/molecules21010081 - 13 Jan 2016

Cited by 26 | Viewed by 5744

Abstract

Our previous work has described a library of thioxanthones designed to have dual activity as P-glycoprotein modulators and antitumor agents. Some of these compounds had shown a significant cell growth inhibitory activity towards leukemia cell lines, without affecting the growth of non-tumor human [...] Read more.

Our previous work has described a library of thioxanthones designed to have dual activity as P-glycoprotein modulators and antitumor agents. Some of these compounds had shown a significant cell growth inhibitory activity towards leukemia cell lines, without affecting the growth of non-tumor human fibroblasts. However, their effect in cell lines derived from solid tumors has not been previously studied. The present work aimed at: (i) screening this small series of compounds from an in-house library, for their in vitro cell growth inhibitory activity in human tumor cell lines derived from solid tumors; and (ii) initiate a study of the effect of the most potent compound on apoptosis. The tumor cell growth inhibitory effect of 27 compounds was first analysed in different human tumor cell lines, allowing the identification of a hit compound, TXA1. Its hydrochloride salt TXA1·HCl was then synthesized, to improve solubility and bioavailability. Both TXA1 and TXA1·HCl inhibited the growth of MCF-7, NCI-H460, A375-C5, HeLa, 786-O, Caki-2 and AGS cell lines. The effect of TXA1·HCl in MCF-7 cells was found to be irreversible and was associated, at least in part, with an increase in cellular apoptosis. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

9 pages, 2855 KiB

Open AccessArticle

A New Bioactive Metabolite Isolated from the Red Sea Marine Sponge Hyrtios erectus

by Sameh S. Elhady, Ali M. El-Halawany, Abdulrahman M. Alahdal, Hashim A. Hassanean and Safwat A. Ahmed

Molecules 2016, 21(1), 82; https://doi.org/10.3390/molecules21010082 - 15 Jan 2016

Cited by 30 | Viewed by 7935

Abstract

Chemical investigation of the lipophilic fraction of Hyrtios erectus, a Red Sea sponge, yielded a new pentacyclic nitrogen-containing scalarane; 24-methoxypetrosaspongia C (1), together with the previously reported scalaranes sesterstatin 3 (2), 12-deacetyl-12-epi-scalaradial (3) and [...] Read more.

Chemical investigation of the lipophilic fraction of Hyrtios erectus, a Red Sea sponge, yielded a new pentacyclic nitrogen-containing scalarane; 24-methoxypetrosaspongia C (1), together with the previously reported scalaranes sesterstatin 3 (2), 12-deacetyl-12-epi-scalaradial (3) and 12-deacetyl-12,18-di-epi-scalaradial (4). The compounds were identified using HRESIMS, 1D and 2D NMR experiments. The isolated compounds showed growth inhibitory activity against hepatocellular carcinoma (HepG2), colorectal carcinoma (HCT-116) and breast adenocarcinoma cells (MCF-7). Full article

(This article belongs to the Collection Bioactive Compounds)

► Show Figures

Graphical abstract

10 pages, 1263 KiB

Open AccessArticle

Quantitative Analysis of Differential Proteome Expression in Epithelial-to-Mesenchymal Transition of Bladder Epithelial Cells Using SILAC Method

by Ganglong Yang, Wei Lu, Di Yu, Chengwen Sun, Jia Guo, Zheng Li and Feng Guan

Molecules 2016, 21(1), 84; https://doi.org/10.3390/molecules21010084 - 15 Jan 2016

Cited by 11 | Viewed by 6135

Abstract

Epithelial-to-mesenchymal transition (EMT) is an essential biological process involved in embryonic development, cancer progression, and metastatic diseases. EMT has often been used as a model for elucidating the mechanisms that underlie bladder cancer progression. However, no study to date has addressed the quantitative [...] Read more.

Epithelial-to-mesenchymal transition (EMT) is an essential biological process involved in embryonic development, cancer progression, and metastatic diseases. EMT has often been used as a model for elucidating the mechanisms that underlie bladder cancer progression. However, no study to date has addressed the quantitative global variation of proteins in EMT using normal and non-malignant bladder cells. We treated normal bladder epithelial HCV29 cells and low grade nonmuscle invasive bladder cancer KK47 cells with transforming growth factor-beta (TGF-β) to establish an EMT model, and studied non-treated and treated HCV29 and KK47 cells by the stable isotope labeling amino acids in cell culture (SILAC) method. Labeled proteins were analyzed by 2D ultrahigh-resolution liquid chromatography/LTQ Orbitrap mass spectrometry. Among a total of 2994 unique identified and annotated proteins in HCV29 and KK47 cells undergoing EMT, 48 and 56 proteins, respectively, were significantly upregulated, and 106 and 24 proteins were significantly downregulated. Gene ontology (GO) term analysis and pathways analysis indicated that the differentially regulated proteins were involved mainly in enhancement of DNA maintenance and inhibition of cell-cell adhesion. Proteomes were compared for bladder cell EMT vs. bladder cancer cells, revealing 16 proteins that displayed similar changes in the two situations. Studies are in progress to further characterize these 16 proteins and their biological functions in EMT. Full article

(This article belongs to the Section Molecular Diversity)

► Show Figures

Figure 1

12 pages, 1127 KiB

Open AccessArticle

Low Temperature Soda-Oxygen Pulping of Bagasse

by Fengxia Yue, Ke-Li Chen and Fachuang Lu

Molecules 2016, 21(1), 85; https://doi.org/10.3390/molecules21010085 - 13 Jan 2016

Cited by 28 | Viewed by 6586

Abstract

Wood shortages, environmental pollution and high energy consumption remain major obstacles hindering the development of today’s pulp and paper industry. Energy-saving and environmental friendly pulping processes are still needed, especially for non-woody materials. In this study, soda-oxygen pulping of bagasse was investigated and [...] Read more.

Wood shortages, environmental pollution and high energy consumption remain major obstacles hindering the development of today’s pulp and paper industry. Energy-saving and environmental friendly pulping processes are still needed, especially for non-woody materials. In this study, soda-oxygen pulping of bagasse was investigated and a successful soda-oxygen pulping process for bagasse at 100 °C was established. The pulping parameters of choice were under active alkali charge of 23%, maximum cooking temperature 100 °C, time hold at maximum temperature 180 min, initial pressure of oxygen 0.6 MPa, MgSO₄ charge 0.5%, and de-pithed bagasse consistency 12%. Properties of the resultant pulp were screened yield 60.9%, Kappa number 14, viscosity 766 dm³/kg, and brightness 63.7% ISO. Similar pulps were also obtained at 110 °C or 105 °C with a cooking time of 90 min. Compared with pulps obtained at higher temperatures (115–125 °C), this pulp had higher screened yield, brightness, and acceptable viscosity, while the delignification degree was moderate. These results indicated that soda-oxygen pulping at 100 °C, the lowest cooking temperature reported so far for soda-oxygen pulping, is a suitable process for making chemical pulp from bagasse. Pulping at lower temperature and using oxygen make it an environmental friendly and energy-saving pulping process. Full article

(This article belongs to the Special Issue Enabling Technologies and Green Processes for Biorefinery Strategies and Biomass Valorization)

► Show Figures

Figure 1

6 pages, 564 KiB

Open AccessCommunication

Bioactive Diterpenoids from Clerodendrum kiangsiense

by Mingfeng Xu, Shengjia Wang, Ouya Jia, Qin Zhu and Lu’e Shi

Molecules 2016, 21(1), 86; https://doi.org/10.3390/molecules21010086 - 15 Jan 2016

Cited by 10 | Viewed by 5091

Abstract

A new abeo-abietane diterpenoid, 12-methoxy-6,11,14,16-tetrahydroxy-17(15→16)-abeo-5,8,11,13-abietatetraen-3,7-dione (8), was isolated from the hydroalcoholic extract of the herb of Clerodendrum kiangsiense along with seven known diterpenoids (1–7). Their structures were identified on the basis of spectroscopic analyses including two-dimensional NMR [...] Read more.

A new abeo-abietane diterpenoid, 12-methoxy-6,11,14,16-tetrahydroxy-17(15→16)-abeo-5,8,11,13-abietatetraen-3,7-dione (8), was isolated from the hydroalcoholic extract of the herb of Clerodendrum kiangsiense along with seven known diterpenoids (1–7). Their structures were identified on the basis of spectroscopic analyses including two-dimensional NMR and comparison with literature data. All of these compounds were evaluated for their cytotoxic activities against the growth of human cancer cells lines HL-60, SMMC-7721, A-549 and MCF-7 by the MTT assay. The results showed that cryptojaponol (4), fortunin E (6) and 8 exhibited significant cytotoxicity against four human cancer cell lines. Full article

► Show Figures

Graphical abstract

8 pages, 2087 KiB

Open AccessFeature PaperArticle

Selective and Efficient Generation of ortho-Brominated para-Substituted Phenols in ACS-Grade Methanol

by David Georgiev, Bartholomeus W. H. Saes, Heather J. Johnston, Sarah K. Boys, Alan Healy and Alison N. Hulme

Molecules 2016, 21(1), 88; https://doi.org/10.3390/molecules21010088 - 13 Jan 2016

Cited by 11 | Viewed by 9145

Abstract

The mono ortho-bromination of phenolic building blocks by NBS has been achieved in short reaction times (15–20 min) using ACS-grade methanol as a solvent. The reactions can be conducted on phenol, naphthol and biphenol substrates, giving yields of >86% on gram scale. [...] Read more.

The mono ortho-bromination of phenolic building blocks by NBS has been achieved in short reaction times (15–20 min) using ACS-grade methanol as a solvent. The reactions can be conducted on phenol, naphthol and biphenol substrates, giving yields of >86% on gram scale. Excellent selectivity for the desired mono ortho-brominated products is achieved in the presence of 10 mol % para-TsOH, and the reaction is shown to be tolerant of a range of substituents, including CH₃, F, and NHBoc. Full article

(This article belongs to the Section Organic Chemistry)

► Show Figures

Graphical abstract

8 pages, 663 KiB

Open AccessArticle

Synthesis of Isotopically Labeled ¹³C₃-Simazine and Development of a Simultaneous UPLC-MS/MS Method for the Analysis of Simazine in Soil

by Yan Song, Yangzhen Guo, Xia Zhang, Yue Yang, Shuo Chen, Gaimei She and Dongmei She

Molecules 2016, 21(1), 89; https://doi.org/10.3390/molecules21010089 - 14 Jan 2016

Cited by 9 | Viewed by 6685

Abstract

The isotope dilution mass spectrometry (IDMS) is a highly efficient method for tackling the ion suppression in complex matrix by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), but a lack of commercial internal standards is a limiting factor for these analyses. Herein, an economical [...] Read more.

The isotope dilution mass spectrometry (IDMS) is a highly efficient method for tackling the ion suppression in complex matrix by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), but a lack of commercial internal standards is a limiting factor for these analyses. Herein, an economical and efficient strategy for the synthesis of ¹³C₃-simazine via a three-step procedure was developed. The isotope-labeled internal standard was used for determination of simazine residue in soil samples. The quantitation method has a limit of detection of 0.015 μg/kg and quantitation of 0.08 μg/kg. The inter-day and intra-day precision of the method were below 4.6%. Recovery values were ranged between 92.9% and 99.2%. All the samples obtained from six provinces in China contained from 1 to 62 μg/kg of simazine. Full article

(This article belongs to the Section Organic Chemistry)

► Show Figures

Figure 1

9 pages, 643 KiB

Open AccessArticle

The Stimulatory Effect of Strontium Ions on Phytoestrogens Content in Glycine max (L.) Merr

by Magdalena Wójciak-Kosior, Ireneusz Sowa, Tomasz Blicharski, Maciej Strzemski, Sławomir Dresler, Grażyna Szymczak, Artur Wnorowski, Ryszard Kocjan and Ryszard Świeboda

Molecules 2016, 21(1), 90; https://doi.org/10.3390/molecules21010090 - 14 Jan 2016

Cited by 25 | Viewed by 6315

Abstract

The amount of secondary metabolites in plants can be enhanced or reduced by various external factors. In this study, the effect of strontium ions on the production of phytoestrogens in soybeans was investigated. The plants were treated with Hoagland’s solution, modified with Sr [...] Read more.

The amount of secondary metabolites in plants can be enhanced or reduced by various external factors. In this study, the effect of strontium ions on the production of phytoestrogens in soybeans was investigated. The plants were treated with Hoagland’s solution, modified with Sr²⁺ with concentrations ranging from 0.5 to 3.0 mM, and were grown for 14 days in hydroponic cultivation. After harvest, soybean plants were separated into roots and shoots, dried, and pulverized. The plant material was extracted with methanol and hydrolyzed. Phytoestrogens were quantified by HPLC. The significant increase in the concentration of the compounds of interest was observed for all tested concentrations of strontium ions when compared to control. Sr²⁺ at a concentration of 2 mM was the strongest elicitor, and the amount of phytoestrogens in plant increased ca. 2.70, 1.92, 3.77 and 2.88-fold, for daidzein, coumestrol, genistein and formononetin, respectively. Moreover, no cytotoxic effects were observed in HepG2 liver cell models after treatment with extracts from 2 mM Sr²⁺-stressed soybean plants when compared to extracts from non-stressed plants. Our results indicate that the addition of strontium ions to the culture media may be used to functionalize soybean plants with enhanced phytoestrogen content. Full article

(This article belongs to the Special Issue Selected papers from the 2nd International Conference on Natural Products Utilization: from Plants to Pharmacy Shelf (ICNPU 2015, Plovdiv, Bulgaria))

► Show Figures

Graphical abstract

9 pages, 1875 KiB

Open AccessArticle

Evidence for the Formation of Benzacridine Derivatives in Alkaline-Treated Sunflower Meal and Model Solutions

by Verena Bongartz, Lisa Brandt, Mai Linh Gehrmann, Benno F. Zimmermann, Nadine Schulze-Kaysers and Andreas Schieber

Molecules 2016, 21(1), 91; https://doi.org/10.3390/molecules21010091 - 14 Jan 2016

Cited by 52 | Viewed by 8163

Abstract

Sunflower extraction meal (SEM) is an economically interesting protein source. During alkaline extraction of proteins, the presence of chlorogenic acid (CQA) in the meal gives rise to the formation of o-quinones. Reactions with nucleophiles present in proteins can lead to green discoloration. [...] Read more.

Sunflower extraction meal (SEM) is an economically interesting protein source. During alkaline extraction of proteins, the presence of chlorogenic acid (CQA) in the meal gives rise to the formation of o-quinones. Reactions with nucleophiles present in proteins can lead to green discoloration. Although such reactions have been known for a long time, there is a lack of information on the chemical nature of the reaction products. SEM and model systems consisting of amino acids and CQA were subjected to alkaline treatment and, for comparison, to oxidation of CQA by polyphenoloxidase (PPO). Several green trihydroxy benzacridine (TBA) derivatives were tentatively identified in all samples by UHPLC-DAD-MS/MS. Surprisingly, in alkaline-treated samples of particular amino acids as well as in SEM, the same six TBA isomers were detected. In contrast, the enzymatically oxidized samples resulted in only three TBA derivatives. Contrary to previous findings, neither peptide nor amino acid residues were attached to the resultant benzacridine core. The results indicate that the formation of TBA derivatives is caused by the reaction between CQA quinones and free NH₂ groups. Further research is necessary to elucidate the structure of the addition products for a comprehensive evaluation of food and feed safety aspects. Full article

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

► Show Figures

Figure 1

14 pages, 3138 KiB

Open AccessArticle

Fast Detection of Phenolic Compounds in Extracts of Easter Pears (Pyrus communis) from the Atacama Desert by Ultrahigh-Performance Liquid Chromatography and Mass Spectrometry (UHPLC–Q/Orbitrap/MS/MS)

by Mario J. Simirgiotis, Cristina Quispe, Jorge Bórquez, Carlos Areche and Beatriz Sepúlveda

Molecules 2016, 21(1), 92; https://doi.org/10.3390/molecules21010092 - 15 Jan 2016

Cited by 52 | Viewed by 8313

Abstract

A small Chilean variety of pears growing in the town of Toconao, an oasis located at the northeastern edge of the Salar de Atacama, northern Chile, was studied by means of modern PDA and high resolution mass spectral data (UHPLC-PDA-HESI-orbitrap-MS/MS). In addition, the [...] Read more.

A small Chilean variety of pears growing in the town of Toconao, an oasis located at the northeastern edge of the Salar de Atacama, northern Chile, was studied by means of modern PDA and high resolution mass spectral data (UHPLC-PDA-HESI-orbitrap-MS/MS). In addition, the antioxidant features of the fruits were compared with the varieties Packhman’s Triumph and Abate Fetel and correlated with the presence of phenolic compounds. The non-pigmented phenolics were fingerprinted and related to the antioxidant capacities measured by the bleaching of the DPPH radical, the ferric reducing antioxidant power (FRAP), the superoxide anion scavenging activity assay (SA), and total content of phenolics and flavonoids measured by spectroscopic methods. The machine allowed a fast separation of 15 min employing a flow rate of 1 mL per minute and could accurately identify 25 compounds, including several isorhamnetin derivatives and phenolic acids, present in the peel and pulps of this Chilean variety for the first time. The compounds were monitored using a wavelength range of 210–800 nm. The native small Chilean pear showed the highest antioxidant activity measured as the bleaching of the DPPH radical, the ferric reducing antioxidant power and superoxide anion scavenging activity (8.61 ± 0.65 μg/mL, 712.63 ± 12.12 micromols trolox equivalents (μmol/TE)/100 g FW, and 82.89% ± 2.52% at 100 μg/mL, respectively). Full article

► Show Figures

Graphical abstract

13 pages, 737 KiB

Open AccessArticle

HPLC Analysis, Optimization of Extraction Conditions and Biological Evaluation of Corylopsis coreana Uyeki Flos

by Ji-Hye Seo, Jung-Eun Kim, Jung-Hyun Shim, Goo Yoon, Mi-Ae Bang, Chun-Sik Bae, Kyung-Jin Lee, Dae-Hun Park and Seung-Sik Cho

Molecules 2016, 21(1), 94; https://doi.org/10.3390/molecules21010094 - 15 Jan 2016

Cited by 42 | Viewed by 7968

Abstract

A method for the separation and quantification of three flavonoids and one isocoumarin by reverse-phase high performance liquid chromatography (HPLC) has been developed and validated. Four constituents present in a crude ethanolic extract of the flowers of Coryloposis coreana Uyeki, were analyzed. Bergenin, [...] Read more.

A method for the separation and quantification of three flavonoids and one isocoumarin by reverse-phase high performance liquid chromatography (HPLC) has been developed and validated. Four constituents present in a crude ethanolic extract of the flowers of Coryloposis coreana Uyeki, were analyzed. Bergenin, quercetin, quercitrin and isosalipurposide were used as calibration standards. In the present study, an excellent linearity was obtained with an r² higher than 0.999. The chromatographic peaks showed good resolution. In combination with other validation data, including precision, specificity, and accuracy, this method demonstrated good reliability and sensitivity, and can be conveniently used for the quantification of bergenin, quercetin, quercitrin and isosalipurposide in the crude ethanolic extract of C. coreana Uyeki flos. Furthermore, the plant extracts were analyzed with HPLC to determine the four constituents and compositional differences in the extracts obtained under different extraction conditions. Several extracts of them which was dependent on the ethanol percentage of solvent were also analyzed for their antimicrobial and antioxidant activities. One hundred % ethanolic extract from C. coreana Uyeki flos showed the best antimicrobial activity against the methicillin-resistant Staphylococcus aureus (MRSA) strain. Eighty % ethanolic extract showed the best antioxidant activity and phenolic content. Taken of all, these results suggest that the flower of C. coreana Uyeki flos may be a useful source for the cure and/or prevention of septic arthritis, and the validated method was useful for the quality control of C. coreana Uyeki. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

19 pages, 1679 KiB

Open AccessArticle

iPPBS-Opt: A Sequence-Based Ensemble Classifier for Identifying Protein-Protein Binding Sites by Optimizing Imbalanced Training Datasets

by Jianhua Jia, Zi Liu, Xuan Xiao, Bingxiang Liu and Kuo-Chen Chou

Molecules 2016, 21(1), 95; https://doi.org/10.3390/molecules21010095 - 19 Jan 2016

Cited by 153 | Viewed by 8955

Abstract

Knowledge of protein-protein interactions and their binding sites is indispensable for in-depth understanding of the networks in living cells. With the avalanche of protein sequences generated in the postgenomic age, it is critical to develop computational methods for identifying in a timely fashion [...] Read more.

Knowledge of protein-protein interactions and their binding sites is indispensable for in-depth understanding of the networks in living cells. With the avalanche of protein sequences generated in the postgenomic age, it is critical to develop computational methods for identifying in a timely fashion the protein-protein binding sites (PPBSs) based on the sequence information alone because the information obtained by this way can be used for both biomedical research and drug development. To address such a challenge, we have proposed a new predictor, called iPPBS-Opt, in which we have used: (1) the K-Nearest Neighbors Cleaning (KNNC) and Inserting Hypothetical Training Samples (IHTS) treatments to optimize the training dataset; (2) the ensemble voting approach to select the most relevant features; and (3) the stationary wavelet transform to formulate the statistical samples. Cross-validation tests by targeting the experiment-confirmed results have demonstrated that the new predictor is very promising, implying that the aforementioned practices are indeed very effective. Particularly, the approach of using the wavelets to express protein/peptide sequences might be the key in grasping the problem’s essence, fully consistent with the findings that many important biological functions of proteins can be elucidated with their low-frequency internal motions. To maximize the convenience of most experimental scientists, we have provided a step-by-step guide on how to use the predictor’s web server (http://www.jci-bioinfo.cn/iPPBS-Opt) to get the desired results without the need to go through the complicated mathematical equations involved. Full article

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

► Show Figures

Figure 1

16 pages, 1159 KiB

Open AccessArticle

Efficient Synthesis and Antibacterial Evaluation of (±)-Yanglingmycin and Its Analogues

by Wenjia Dan, Huiling Geng, Jianwen Qiao, Rui Guo, Shaopeng Wei, Longbo Li, Wenjun Wu and Jiwen Zhang

Molecules 2016, 21(1), 96; https://doi.org/10.3390/molecules21010096 - 15 Jan 2016

Cited by 8 | Viewed by 5025

Abstract

An efficient synthetic route was developed for the large-scale preparation of (±)-Yanglingmycin and its analogues. Three series of derivatives of (±)-Yanglingmycin were synthesized and the structures of all compounds were elucidated by analyses of NMR and ESI-MS spectra data. Moreover, their antibacterial activities [...] Read more.

An efficient synthetic route was developed for the large-scale preparation of (±)-Yanglingmycin and its analogues. Three series of derivatives of (±)-Yanglingmycin were synthesized and the structures of all compounds were elucidated by analyses of NMR and ESI-MS spectra data. Moreover, their antibacterial activities against seven species of bacteria were systematically evaluated by the micro-broth dilution method, most of which displayed considerable activity. It was worth noting that compounds 5b, 5c, 5d, 6g, and 7 were found to be the most promising leading candidates, with peak MIC values of 0.98 μg·mL⁻¹ for Bacillus subtilis, which is superior to positive controls (MIC = 3.91 μg·mL⁻¹). The above results might lay the firm foundation for the design and synthesis of novel antibacterial drugs based on (±)-Yanglingmycin. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

11 pages, 3001 KiB

Open AccessArticle

Analysis on the Physicochemical Properties of Ginkgo biloba Leaves after Enzymolysis Based Ultrasound Extraction and Soxhlet Extraction

by Chang-Wei Zhang, Cheng-Zhang Wang and Ran Tao

Molecules 2016, 21(1), 97; https://doi.org/10.3390/molecules21010097 - 15 Jan 2016

Cited by 21 | Viewed by 6117

Abstract

In this study, high performance liquid chromatography (HPLC), ultraviolet (UV), thermagravimetric analyzer (TGA), pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS), and scanning electron microscope (SEM) were used as measurement techniques, contents of chemical composition, pyrolytic products, thermal stability, morphological characterization of Ginkgo biloba leaves (GBL) acted [...] Read more.

In this study, high performance liquid chromatography (HPLC), ultraviolet (UV), thermagravimetric analyzer (TGA), pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS), and scanning electron microscope (SEM) were used as measurement techniques, contents of chemical composition, pyrolytic products, thermal stability, morphological characterization of Ginkgo biloba leaves (GBL) acted as the index, and physicochemical properties of GBL after enzymolysis based ultrasound extraction (EBUE) and Soxhlet extraction were studied. The detection results of chemical composition revealed that contents of general flavone, soluble protein, soluble total sugar and protein in the GBL declined significantly after EBUE, and contents of polyprenols and crude fat obviously reduced as well after Soxhlet extraction. Py-GC-MS results indicated that total GC contents of micromolecules with carbon less than 12 from 54.0% before EBUE decline to 8.34% after EBUE. Total GC contents of long-chain fatty acids with carbon less than 20 from 43.0% before EBUE reduced to 27.0% after Soxhlet extraction. Thermal stability results showed that GBL after Soxhlet extraction was easier to decompose than GBL before EBUE. SEM results illustrated that surface structure of GBL was damaged severely after EBUE, compared with GBL before EBUE, while organic solvent extraction had little influence on the morphological characterization of GBL after Soxhlet extraction compared with GBL after EBUE. Full article

(This article belongs to the Section Molecular Diversity)

► Show Figures

Figure 1

10 pages, 206 KiB

Open AccessArticle

Nutritional and Biochemical Profiling of Leucopaxillus candidus (Bres.) Singer Wild Mushroom

by Vanessa Vieira, Lillian Barros, Anabela Martins and Isabel C. F. R. Ferreira

Molecules 2016, 21(1), 99; https://doi.org/10.3390/molecules21010099 - 15 Jan 2016

Cited by 8 | Viewed by 6131

Abstract

The wild mushroom Leucopaxillus candidus (Bres.) Singer was studied for the first time to obtain information about its chemical composition, nutritional value and bioactivity. Free sugars, fatty acids, tocopherols, organic and phenolic acids were analysed by chromatographic techniques coupled to different detectors. L. [...] Read more.

The wild mushroom Leucopaxillus candidus (Bres.) Singer was studied for the first time to obtain information about its chemical composition, nutritional value and bioactivity. Free sugars, fatty acids, tocopherols, organic and phenolic acids were analysed by chromatographic techniques coupled to different detectors. L. candidus methanolic extract was tested regarding antioxidant potential (reducing power, radical scavenging activity and lipid peroxidation inhibition). L. candidus was shown to be an interesting species in terms of nutritional value, with high content in proteins and carbohydrates, but low fat levels, with the prevalence of polyunsaturated fatty acids. Mannitol was the most abundant free sugar and β-tocopherol was the main tocopherol isoform. Other compounds detected were oxalic and fumaric acids, p-hydroxybenzoic and cinnamic acids. The methanolic extract revealed antioxidant activity and did not show hepatoxicity in porcine liver primary cells. The present study provides new information about L. candidus. Full article

(This article belongs to the Collection Bioactive Compounds)

► Show Figures

Graphical abstract

12 pages, 1254 KiB

Open AccessArticle

Synthesis of Canthardin Sulfanilamides and Their Acid Anhydride Analogues via a Ring-Opening Reaction of Activated Aziridines and Their Associated Pharmacological Effects

by Ling-Ling Chiang, Ing-Jy Tseng, Pen-Yuan Lin, Shiow-Yunn Sheu, Ching-Tung Lin, Yun-Han Hsieh, Yi-Jing Lin, Hsiao-Ling Chen and Mei-Hsiang Lin

Molecules 2016, 21(1), 100; https://doi.org/10.3390/molecules21010100 - 16 Jan 2016

Cited by 7 | Viewed by 6752

Abstract

The cantharidinimide derivatives, 5a–h, including sulfanilamides containing pyrimidyl, pyrazinyl, hydrogen, thiazolyl, and oxazolyl groups were synthesized. Modification of cantharidinimide by means of the reaction of activated aziridine ring opening led to the discovery of a novel class of antitumor compounds. [...] Read more.

The cantharidinimide derivatives, 5a–h, including sulfanilamides containing pyrimidyl, pyrazinyl, hydrogen, thiazolyl, and oxazolyl groups were synthesized. Modification of cantharidinimide by means of the reaction of activated aziridine ring opening led to the discovery of a novel class of antitumor compounds. The analogues 10i–k, 11l–n, 12o–p, and 16q–s were obtained from treating cantharidinimide 6 and analogues (7, 8, and 13) with activated aziridines, which produced a series of ring-opened products including normal and abnormal types. Some of these compounds showed cytotoxic effects in vitro against HL-60, Hep3B, MCF7, and MDA-MB-231 cancer cells. The most potent cytostatic compound, N-cantharidinimido-sulfamethazine (5a), exhibited anti-HL-60 and anti-Hep3B cell activities. Two compounds 5g and 5h displayed slight effects on the Hep3B cell line, while the other compounds produced no response in these four cell lines. Full article

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

► Show Figures

Graphical abstract

12 pages, 596 KiB

Open AccessArticle

A New Indirect Spectrofluorimetric Method for Determination of Ascorbic Acid with 2,4,6-Tripyridyl-S-Triazine in Pharmaceutical Samples

by Lejla Klepo, Amira Copra-Janicijevic and Lea Kukoc-Modun

Molecules 2016, 21(1), 101; https://doi.org/10.3390/molecules21010101 - 19 Jan 2016

Cited by 10 | Viewed by 6351

Abstract

Ascorbic acid (AA) is a water-soluble vitamin which shows no fluorescence. However, in reaction with iron(III), AA is oxidised to dehydroascorbic acid and iron(III) is reduced to iron(II) which forms a complex with 2,4,6-tripyridyl-S-triazine (TPTZ) in buffered medium. The relative fluorescence [...] Read more.

Ascorbic acid (AA) is a water-soluble vitamin which shows no fluorescence. However, in reaction with iron(III), AA is oxidised to dehydroascorbic acid and iron(III) is reduced to iron(II) which forms a complex with 2,4,6-tripyridyl-S-triazine (TPTZ) in buffered medium. The relative fluorescence intensity of the resulting Fe(TPTZ)₂²⁺ complex can be measured at excitation and emission wavelengths of 393 and 790 nm, respectively. Based on this data, a new indirect spectrofluorimetric method for the determination of AA in pharmaceutical samples was proposed. Influence of the reaction conditions, such as acidity of acetic buffer, concentration of TPTZ and iron(III), reaction time and instrumental parameters were investigated in detail. The linear range was from 5.4 × 10⁻⁴ to 5.4 × 10⁻⁶ mol·L⁻¹ (R = 0.9971). The LOD was 7.7 × 10⁻⁷ mol·L⁻¹ and LOQ was 2.3 × 10⁻⁴ mol·L⁻¹. Fourteen pharmaceutical samples containing various amounts of AA were analysed. Influences of potential interfering substances were also examined. Analysis of commercial pharmaceutical formulations showed good correlation with the nominal values given by the manufacturers and with the results obtained by a titration method. The proposed method can be applied in routine quality control in the pharmaceutical industry due to its sensitivity, simplicity, selectivity and low cost. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Graphical abstract

15 pages, 3726 KiB

Open AccessArticle

Phenylethanol Glycosides from Cistanche tubulosa Suppress Hepatic Stellate Cell Activation and Block the Conduction of Signaling Pathways in TGF-β₁/smad as Potential Anti-Hepatic Fibrosis Agents

by Shu-Ping You, Long Ma, Jun Zhao, Shi-Lei Zhang and Tao Liu

Molecules 2016, 21(1), 102; https://doi.org/10.3390/molecules21010102 - 18 Jan 2016

Cited by 46 | Viewed by 7627

Abstract

Cistanche tubulosa is a traditional Chinese herbal medicine widely used for regulating immunity and phenylethanol glycosides (CPhGs) are among the primary components responsible for this activity. Previous studies have indicated the preventive and therapeutic effects of CPhGs on bovine serum albumin (BSA)-induced hepatic [...] Read more.

Cistanche tubulosa is a traditional Chinese herbal medicine widely used for regulating immunity and phenylethanol glycosides (CPhGs) are among the primary components responsible for this activity. Previous studies have indicated the preventive and therapeutic effects of CPhGs on bovine serum albumin (BSA)-induced hepatic fibrosis in rats. The aim of the study was to evaluate the anti-hepatic fibrosis effect of CPhGs and the monomers echinacoside and acteoside by inhibiting hepatic stellate cell (HSC) activation, blocking the conduction of signaling pathways in transforming growth factor-β₁ (TGF-β₁)/smad, and determine their in vitro hepatoprotective activity. HSC proliferation was obviously inhibited after treatment with CPhGs (100, 50 μg/mL)/echinacoside (500, 250, 125 μg/mL)/acteoside (6, 3 μg/mL), with IC₅₀ values of 119.125, 520.345 and 6.999 μg/mL, respectively, in the MTT assay. Different concentrations of CPhGs/echinacoside/acteoside did not affect the cellular toxicity on HSC according to lactate dehydrogenase (LDH) measurements. Different concentrations of CPhGs/echinacoside/acteoside increased the mRNA level and protein expression of smad7, and decreased the mRNA levels of smad2, smad3 and the protein expression of smad2, phospho-smad2 (p-smad2), smad3, phospho-smad3 (p-smad3) in HSC. In summary, these results demonstrate that CPhGs/echinacoside/acteoside can block the conduction of the signaling pathways in TGF-β₁/smad, and inhibit the activation of HSC, suggesting that C. tubulosa may thus be a potential herbal medicine for the treatment of liver fibrosis. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

10 pages, 1244 KiB

Open AccessArticle

Antibacterial Peptide CecropinB2 Production via Various Host and Construct Systems

by Wei-Shiang Lai, Shu-Chen Kan, Chia-Chi Lin, Chwen-Jen Shieh and Yung-Chuan Liu

Molecules 2016, 21(1), 103; https://doi.org/10.3390/molecules21010103 - 16 Jan 2016

Cited by 9 | Viewed by 5747

Abstract

Cecropin is a cationic antibacterial peptide composed of 35–39 residues. This peptide has been identified as possessing strong antibacterial activity and low toxicity against eukaryotic cells, and it has been claimed that some types of the cecropin family of peptides are capable of [...] Read more.

Cecropin is a cationic antibacterial peptide composed of 35–39 residues. This peptide has been identified as possessing strong antibacterial activity and low toxicity against eukaryotic cells, and it has been claimed that some types of the cecropin family of peptides are capable of killing cancer cells. In this study, the host effect of cloning antibacterial peptide cecropinB2 was investigated. Three different host expression systems were chosen, i.e., Escherichia coli, Bacillus subtilis and Pichia pastoris. Two gene constructs, cecropinB2 (cecB2) and intein-cecropinB2 (INT-cecB2), were applied. Signal peptide and propeptide from Armigeres subalbatus were also attached to the gene construct. The results showed that the best host for cloning cecropinB2 was P. pastoris SMD1168 harboring the gene of pGAPzαC-prepro-cecB2 via Western blot confirmation. The cecropinB2 that was purified using immobilized-metal affinity chromatography resin showed strong antibacterial activity against the Gram-negative strains, including the multi-drug-resistant bacteria Acinetobacter baumannii. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

14 pages, 3501 KiB

Open AccessArticle

Exploration of Scaffolds from Natural Products with Antiplasmodial Activities, Currently Registered Antimalarial Drugs and Public Malarial Screen Data

by Samuel Egieyeh, James Syce, Alan Christoffels and Sarel F. Malan

Molecules 2016, 21(1), 104; https://doi.org/10.3390/molecules21010104 - 16 Jan 2016

Cited by 8 | Viewed by 7440

Abstract

In light of current resistance to antimalarial drugs, there is a need to discover new classes of antimalarial agents with unique mechanisms of action. Identification of unique scaffolds from natural products with in vitro antiplasmodial activities may be the starting point for such [...] Read more.

In light of current resistance to antimalarial drugs, there is a need to discover new classes of antimalarial agents with unique mechanisms of action. Identification of unique scaffolds from natural products with in vitro antiplasmodial activities may be the starting point for such new classes of antimalarial agents. We therefore conducted scaffold diversity and comparison analysis of natural products with in vitro antiplasmodial activities (NAA), currently registered antimalarial drugs (CRAD) and malaria screen data from Medicine for Malaria Ventures (MMV). The scaffold diversity analyses on the three datasets were performed using scaffold counts and cumulative scaffold frequency plots. Scaffolds from the NAA were compared to those from CRAD and MMV. A Scaffold Tree was also generated for each of the datasets and the scaffold diversity of NAA was found to be higher than that of MMV. Among the NAA compounds, we identified unique scaffolds that were not contained in any of the other compound datasets. These scaffolds from NAA also possess desirable drug-like properties making them ideal starting points for antimalarial drug design considerations. The Scaffold Tree showed the preponderance of ring systems in NAA and identified virtual scaffolds, which may be potential bioactive compounds. Full article

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

► Show Figures

Graphical abstract

11 pages, 2487 KiB

Open AccessArticle

An Unusual Stress Metabolite from a Hydrothermal Vent Fungus Aspergillus sp. WU 243 Induced by Cobalt

by Chihong Ding, Xiaodan Wu, Bibi Nazia Auckloo, Chen-Tung Arthur Chen, Ying Ye, Kuiwu Wang and Bin Wu

Molecules 2016, 21(1), 105; https://doi.org/10.3390/molecules21010105 - 16 Jan 2016

Cited by 30 | Viewed by 7484

Abstract

A novel hybrid polyketide-terpenoid, aspergstressin (1), possessing a unique fused polycyclic structure, was induced from culture broth of strain Aspergillus sp. WU 243 by cobalt ion stimulation. The strain was isolated from the digestive gland of Xenograpsus testudinatus, a unique [...] Read more.

A novel hybrid polyketide-terpenoid, aspergstressin (1), possessing a unique fused polycyclic structure, was induced from culture broth of strain Aspergillus sp. WU 243 by cobalt ion stimulation. The strain was isolated from the digestive gland of Xenograpsus testudinatus, a unique type of crab which dwells in the Kueishantao hydrothermal vents off Taiwan. The chemical structure and relative configuration of the stress metabolite were established by spectroscopic means. Aspergillus sp. WU 243 produced aspergstressin (1) only under cobalt stressed culture conditions. The results show that stress-driven discovery of new natural products from hydrothermal vent fungi is an effective strategy to unveil the untapped reservoir of small molecules from species found in the hydrothermal vent environment. Full article

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

► Show Figures

Figure 1

10 pages, 1061 KiB

Open AccessArticle

Assessment of Egg Yolk Oil Extraction Methods of for ShiZhenKang Oil by Pharmacodynamic Index Evaluation

by Ping Wu, Yu Pan, Jianye Yan, Dan Huang and Shunxiang Li

Molecules 2016, 21(1), 106; https://doi.org/10.3390/molecules21010106 - 18 Jan 2016

Cited by 14 | Viewed by 21919

Abstract

To assess the extraction methods of egg yolk oil in ShiZhenKang (SZK) oil, which is used to treat eczema, a mice model of eczema was established by using 2,4-dinitrochlorobenzene (DNCB). The therapeutic effects of egg yolk oil extracted by different methods from SZK [...] Read more.

To assess the extraction methods of egg yolk oil in ShiZhenKang (SZK) oil, which is used to treat eczema, a mice model of eczema was established by using 2,4-dinitrochlorobenzene (DNCB). The therapeutic effects of egg yolk oil extracted by different methods from SZK oil on the model of acute eczema in mice were evaluated. The oil yield rate of ethanol extraction is 42.06%. Its egg yolk oil is orange and has a rich, sweet, egg smell. Moreover, the SZK oil prepared from it has a very good therapeutic effect on the model of acute eczema in mice. The alcohol extraction method is the preferable method according to a comprehensive evaluation of each index of seven kinds of methods to extract the egg yolk oil. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

10 pages, 2423 KiB

Open AccessArticle

An Amidochlorin-Based Colorimetric Fluorescent Probe for Selective Cu²⁺ Detection

by Wenting Li, Guohua Zhu, Jinghua Li, Zhiqiang Wang and Yingxue Jin

Molecules 2016, 21(1), 107; https://doi.org/10.3390/molecules21010107 - 18 Jan 2016

Cited by 27 | Viewed by 7682

Abstract

The design and synthesis of selective and sensitive chemosensors for the quantification of environmentally and biologically important ionic species has attracted widespread attention. Amidochlorin p6 (ACP); an effective colorimetric and fluorescent probe for copper ions (Cu²⁺) in aqueous solution [...] Read more.

The design and synthesis of selective and sensitive chemosensors for the quantification of environmentally and biologically important ionic species has attracted widespread attention. Amidochlorin p6 (ACP); an effective colorimetric and fluorescent probe for copper ions (Cu²⁺) in aqueous solution derived from methyl pheophorbide-a (MPa) was designed and synthesized. A remarkable color change from pale yellow to blue was easily observed by the naked eye upon addition of Cu²⁺; and a fluorescence quenching was also determined. The research of fluorescent quenching of ACP-Cu²⁺ complexation showed the detection limit was 7.5 × 10⁻⁸ mol/L; which suggested that ACP can act as a high sensitive probe for Cu²⁺ and can be used to quantitatively detect low levels of Cu²⁺ in aqueous solution. In aqueous solution the probe exhibits excellent selectivity and sensitivity toward Cu²⁺ ions over other metal ions (M = Zn²⁺; Ni²⁺; Ba²⁺; Ag⁺; Co²⁺; Na⁺; K⁺; Mg²⁺; Cd²⁺; Pb²⁺; Mn²⁺; Fe³⁺; and Ca²⁺). The obvious change from pale yellow to blue upon the addition of Cu²⁺ could make it a suitable “naked eye” indicator for Cu²⁺. Full article

(This article belongs to the Special Issue Photoactive Molecules)

► Show Figures

Graphical abstract

15 pages, 2771 KiB

Open AccessArticle

Sorption of Cu(II) Ions on Chitosan-Zeolite X Composites: Impact of Gelling and Drying Conditions

by Amal Djelad, Amine Morsli, Mike Robitzer, Abdelkader Bengueddach, Francesco Di Renzo and Françoise Quignard

Molecules 2016, 21(1), 109; https://doi.org/10.3390/molecules21010109 - 19 Jan 2016

Cited by 34 | Viewed by 7920

Abstract

Chitosan-zeolite Na-X composite beads with open porosity and different zeolite contents were prepared by an encapsulation method. Preparation conditions had to be optimised in order to stabilize the zeolite network during the polysaccharide gelling process. Composites and pure reference components were characterized using [...] Read more.

Chitosan-zeolite Na-X composite beads with open porosity and different zeolite contents were prepared by an encapsulation method. Preparation conditions had to be optimised in order to stabilize the zeolite network during the polysaccharide gelling process. Composites and pure reference components were characterized using X-ray diffraction (XRD); scanning electron microscopy (SEM); N₂ adsorption–desorption; and thermogravimetric analysis (TG). Cu(II) sorption was investigated at pH 6. The choice of drying method used for the storage of the adsorbent severely affects the textural properties of the composite and the copper sorption effectiveness. The copper sorption capacity of chitosan hydrogel is about 190 mg·g⁻¹. More than 70% of this capacity is retained when the polysaccharide is stored as an aerogel after supercrititcal CO₂ drying, but nearly 90% of the capacity is lost after evaporative drying to a xerogel. Textural data and Cu(II) sorption data indicate that the properties of the zeolite-polysaccharide composites are not just the sum of the properties of the individual components. Whereas a chitosan coating impairs the accessibility of the microporosity of the zeolite; the presence of the zeolite improves the stability of the dispersion of chitosan upon supercritical drying and increases the affinity of the composites for Cu(II) cations. Chitosan-zeolite aerogels present Cu(II) sorption properties. Full article

(This article belongs to the Special Issue Chitin, Chitosan and Related Enzymes)

► Show Figures

Graphical abstract

10 pages, 2054 KiB

Open AccessArticle

An Integrated Experimental/Theoretical Study of Structurally Related Poly-Thiophenes Used in Photovoltaic Systems

by Davide Vanossi, Luigi Cigarini, Andrea Giaccherini, Enrico Da Como and Claudio Fontanesi

Molecules 2016, 21(1), 110; https://doi.org/10.3390/molecules21010110 - 19 Jan 2016

Cited by 12 | Viewed by 5966

Abstract

In this work, a series of eight thiophene-based polymers (exploited as “donors” in bulk heterojunction photovoltaics cells), whose structures were designed to be suitably tuned with the electronic characteristics of the [6,6]-Phenyl C61 butyric acid methyl ester (PCBM), is considered,. The electronic properties [...] Read more.

In this work, a series of eight thiophene-based polymers (exploited as “donors” in bulk heterojunction photovoltaics cells), whose structures were designed to be suitably tuned with the electronic characteristics of the [6,6]-Phenyl C61 butyric acid methyl ester (PCBM), is considered,. The electronic properties of the mono-, di-, trimeric oligomers are reckoned (at the Hartree-Fock and DFT level of the theory) and compared to experimental spectroscopic and electrochemical results. Indeed, electrochemical and spectroscopic results show a systematic difference whose physical nature is assessed and related to the exciton (electron-hole) binding energy ( J e , h ). The critical comparison of the experimental and theoretical band gaps, i.e., the HOMO-LUMO energy difference, suggests that electrochemical and DFT values are the most suited to being used in the design of a polythiophene-based p-n junction for photovoltaics. Full article

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

► Show Figures

Figure 1

16 pages, 6031 KiB

Open AccessArticle

Rapid and Sensitive Detection of Vibrio parahaemolyticus and Vibrio vulnificus by Multiple Endonuclease Restriction Real-Time Loop-Mediated Isothermal Amplification Technique

by Yi Wang, Dongxun Li, Yan Wang, Kewei Li and Changyun Ye

Molecules 2016, 21(1), 111; https://doi.org/10.3390/molecules21010111 - 19 Jan 2016

Cited by 38 | Viewed by 7894

Abstract

Vibrio parahaemolyticus and Vibrio vulnificus are two marine seafood-borne pathogens causing severe illnesses in humans and aquatic animals. In this study, a recently developed novel multiple endonuclease restriction real-time loop-mediated isothermal amplification technology (MERT-LAMP) were successfully developed and evaluated for simultaneous detection of [...] Read more.

Vibrio parahaemolyticus and Vibrio vulnificus are two marine seafood-borne pathogens causing severe illnesses in humans and aquatic animals. In this study, a recently developed novel multiple endonuclease restriction real-time loop-mediated isothermal amplification technology (MERT-LAMP) were successfully developed and evaluated for simultaneous detection of V. parahaemolyticus and V. vulnificus strains in only a single reaction. Two MERT-LAMP primer sets were designed to specifically target toxR gene of V. parahaemolyticus and rpoS gene of V. vulnificus. The MERT-LAMP reactions were conducted at 62 °C, and the positive results were produced in as short as 19 min with the genomic DNA templates extracted from the V. parahaemolyticus and V. vulnificus strains. The two target pathogens present in the same sample could be simultaneously detected and correctly differentiated based on distinct fluorescence curves in a real-time format. The sensitivity of MERT-LAMP assay was 250 fg and 125 fg DNA per reaction with genomic templates of V. parahaemolyticus and V. vulnificus strains, which was in conformity with conventional LAMP detection. Compared with PCR-based techniques, the MERT-LAMP technology was 100- and 10-fold more sensitive than that of PCR and qPCR methods. Moreover, the limit of detection of MERT-LAMP approach for V. parahaemolyticus isolates and V. vulnificus isolates detection in artificially-contaminated oyster samples was 92 CFU and 83 CFU per reaction. In conclusion, the MERT-LAMP assay presented here was a rapid, specific, and sensitive tool for the detection of V. parahaemolyticus and V. vulnificus, and could be adopted for simultaneous screening of V. parahaemolyticus and V. vulnificus in a wide variety of samples. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

12 pages, 2425 KiB

Open AccessArticle

Total Synthesis of Chiral Falcarindiol Analogues Using BINOL-Promoted Alkyne Addition to Aldehydes

by Li Wang, Ping-Ping Shou, Si-Ping Wei, Chun Zhang, Shuang-Xun Li, Ping-Xian Liu, Xi Du and Qin Wang

Molecules 2016, 21(1), 112; https://doi.org/10.3390/molecules21010112 - 19 Jan 2016

Cited by 7 | Viewed by 6567

Abstract

An enantioselective total synthesis of chiral falcarindiol analogues from buta-1,3-diyn-1-yltriisopropylsilane is reported. The key step in this synthesis is BINOL-promoted asymmetric diacetylene addition to aldehydes. The two chiral centers of the falcarindiol analogues can be produced by using the same kind of catalyst [...] Read more.

An enantioselective total synthesis of chiral falcarindiol analogues from buta-1,3-diyn-1-yltriisopropylsilane is reported. The key step in this synthesis is BINOL-promoted asymmetric diacetylene addition to aldehydes. The two chiral centers of the falcarindiol analogues can be produced by using the same kind of catalyst with high selectivity, and the final product can be obtained in only six steps. Full article

(This article belongs to the Section Organic Chemistry)

► Show Figures

Figure 1

16 pages, 1733 KiB

Open AccessArticle

Comparative Study of Essential Oils Extracted from Egyptian Basil Leaves (Ocimum basilicum L.) Using Hydro-Distillation and Solvent-Free Microwave Extraction

by Mohammed Chenni, Douniazad El Abed, Njara Rakotomanomana, Xavier Fernandez and Farid Chemat

Molecules 2016, 21(1), 113; https://doi.org/10.3390/molecules21010113 - 19 Jan 2016

Cited by 117 | Viewed by 15165

Abstract

Solvent-free microwave extraction (SFME) and conventional hydro-distillation (HD) were used for the extraction of essential oils (EOs) from Egyptian sweet basil (Ocimum basilicum L.) leaves. The two resulting EOs were compared with regards to their chemical composition, antioxidant, and antimicrobial activities. The [...] Read more.

Solvent-free microwave extraction (SFME) and conventional hydro-distillation (HD) were used for the extraction of essential oils (EOs) from Egyptian sweet basil (Ocimum basilicum L.) leaves. The two resulting EOs were compared with regards to their chemical composition, antioxidant, and antimicrobial activities. The EO analyzed by GC and GC-MS, presented 65 compounds constituting 99.3% and 99.0% of the total oils obtained by SFME and HD, respectively. The main components of both oils were linalool (43.5% SFME; 48.4% HD), followed by methyl chavicol (13.3% SFME; 14.3% HD) and 1,8-cineole (6.8% SFME; 7.3% HD). Their antioxidant activity were studied with the 2,2-diphenyl-1-picrylhydrazyl (DPPH^•) radical scavenging method. The heating conditions effect was evaluated by the determination of the Total Polar Materials (TPM) content. The antimicrobial activity was investigated against five microorganisms: two Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, two Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, and one yeast, Candida albicans. Both EOs showed high antimicrobial, but weak antioxidant, activities. The results indicated that the SFME method may be a better alternative for the extraction of EO from O. basilicum since it could be considered as providing a richer source of natural antioxidants, as well as strong antimicrobial agents for food preservation. Full article

(This article belongs to the Special Issue Enabling Technologies and Green Processes for Biorefinery Strategies and Biomass Valorization)

► Show Figures

Figure 1

16 pages, 2260 KiB

Open AccessArticle

Synthesis, Biological Evaluation and Molecular Docking of Certain Sulfones as Potential Nonazole Antifungal Agents

by Mohamed Fares, Mohamed A. Said, Muhammad A. Alsherbiny, Radwa A. Eladwy, Hadia Almahli, Marwa M. Abdel-Aziz, Hazem A. Ghabbour, Wagdy M. Eldehna and Hatem A. Abdel-Aziz

Molecules 2016, 21(1), 114; https://doi.org/10.3390/molecules21010114 - 20 Jan 2016

Cited by 17 | Viewed by 6305

Abstract

We reported herein the synthesis, antifungal activity, docking and in silico ADME prediction studies of four novel series of sulfones 6a–f, 8a–c, 10a–f and 12a–c. All the newly synthesized sulfones were tested [...] Read more.

We reported herein the synthesis, antifungal activity, docking and in silico ADME prediction studies of four novel series of sulfones 6a–f, 8a–c, 10a–f and 12a–c. All the newly synthesized sulfones were tested against four strains of Candida (including fluconazole-resistant Candida), two strains of Aspergillus, two dermatophytic fungi (Trichophytons mentagrophyte and Microsporum canis) and Syncephalastrum sp. with fluconazole as a reference drug. In general, compounds 8a and 10b showed selective and potent anticandidal activity (MIC: 0.19–0.81 µM) relative to fluconazole (MIC = 1.00 µM). Furthermore, 10e and 12a elicited a remarkable and selective antifungal activity against Aspergillus sp. and the dermatophytic fungi (MIC: 0.16–0.79 µM) relative to fluconazole (MIC: 2–2.6 µM). Moreover, the docking results of the sulfones 6a, 8a, 10a and 10b at the active site of CYT P450 14α-sterol demethylase showed a comparable binding interaction (interaction Energy = −34.87 to −42.43 kcal/mol) with that of fluconazole (IE = −40.37 kcal/mol). Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Graphical abstract

13 pages, 6193 KiB

Open AccessArticle

Biocompatible 3D Matrix with Antimicrobial Properties

by Alberto Ion, Ecaterina Andronescu, Dragoș Rădulescu, Marius Rădulescu, Florin Iordache, Bogdan Ștefan Vasile, Adrian Vasile Surdu, Madalina Georgiana Albu, Horia Maniu, Mariana Carmen Chifiriuc, Alexandru Mihai Grumezescu and Alina Maria Holban

Molecules 2016, 21(1), 115; https://doi.org/10.3390/molecules21010115 - 20 Jan 2016

Cited by 7 | Viewed by 6749

Abstract

The aim of this study was to develop, characterize and assess the biological activity of a new regenerative 3D matrix with antimicrobial properties, based on collagen (COLL), hydroxyapatite (HAp), β-cyclodextrin (β-CD) and usnic acid (UA). The prepared 3D matrix was characterized by Scanning [...] Read more.

The aim of this study was to develop, characterize and assess the biological activity of a new regenerative 3D matrix with antimicrobial properties, based on collagen (COLL), hydroxyapatite (HAp), β-cyclodextrin (β-CD) and usnic acid (UA). The prepared 3D matrix was characterized by Scanning Electron Microscopy (SEM), Fourier Transform Infrared Microscopy (FT-IRM), Transmission Electron Microscopy (TEM), and X-ray Diffraction (XRD). In vitro qualitative and quantitative analyses performed on cultured diploid cells demonstrated that the 3D matrix is biocompatible, allowing the normal development and growth of MG-63 osteoblast-like cells and exhibited an antimicrobial effect, especially on the Staphylococcus aureus strain, explained by the particular higher inhibitory activity of usnic acid (UA) against Gram positive bacterial strains. Our data strongly recommend the obtained 3D matrix to be used as a successful alternative for the fabrication of three dimensional (3D) anti-infective regeneration matrix for bone tissue engineering. Full article

(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)

► Show Figures

Graphical abstract

14 pages, 4515 KiB

Open AccessArticle

Skin Delivery and in Vitro Biological Evaluation of Trans-Resveratrol-Loaded Solid Lipid Nanoparticles for Skin Disorder Therapies

by Roberta B. Rigon, Naiara Fachinetti, Patrícia Severino, Maria H. A. Santana and Marlus Chorilli

Molecules 2016, 21(1), 116; https://doi.org/10.3390/molecules21010116 - 20 Jan 2016

Cited by 89 | Viewed by 9505

Abstract

The aim of this study was to evaluate the skin delivery and in vitro biological activity of trans-resveratrol (RES)-loaded solid lipid nanoparticles (SLNs). The SLNs were composed of stearic acid, poloxamer 407, soy phosphatidylcholine (SPC), an aqueous phase and 0.1% RES. The [...] Read more.

The aim of this study was to evaluate the skin delivery and in vitro biological activity of trans-resveratrol (RES)-loaded solid lipid nanoparticles (SLNs). The SLNs were composed of stearic acid, poloxamer 407, soy phosphatidylcholine (SPC), an aqueous phase and 0.1% RES. The particle size, polydispersity index (PdI) and zeta potential were analyzed by dynamic light scattering (DLS). The SLNs were analyzed by scanning electron microscopy (SEM-FEG) and differential scanning calorimetry (DSC). In vitro RES-SLN skin permeation/retention assays were conducted, and their tyrosinase inhibitory activity was evaluated. An MTT reduction assay was performed on HaCat keratinocytes to determine in vitro cytotoxicity. The formulations had average diameter lower than 200 nm, the addition of SPC promoted increases in PdI in the RES-SLNs, but decreases PdI in the RES-free SLNs and the formulations exhibited zeta potentials smaller than −3 mV. The DSC analysis of the SLNs showed no endothermic peak attributable to RES. Microscopic analysis suggests that the materials formed had nanometric size distribution. Up to 45% of the RES permeated through the skin after 24 h. The RES-loaded SLNs were more effective than kojic acid at inhibiting tyrosinase and proved to be non-toxic in HaCat keratinocytes. The results suggest that the investigated RES-loaded SLNs have potential use in skin disorder therapies. Full article

(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)

► Show Figures

Figure 1

14 pages, 2233 KiB

Open AccessArticle

A Rapid Screening Analysis of Antioxidant Compounds in Native Australian Food Plants Using Multiplexed Detection with Active Flow Technology Columns

by Emmanuel Janaka Rochana Rupesinghe, Andrew Jones, Ross Andrew Shalliker and Sercan Pravadali-Cekic

Molecules 2016, 21(1), 118; https://doi.org/10.3390/molecules21010118 - 20 Jan 2016

Cited by 15 | Viewed by 5717

Abstract

Conventional techniques for identifying antioxidant and phenolic compounds in native Australian food plants are laborious and time-consuming. Here, we present a multiplexed detection technique that reduces analysis time without compromising separation performance. This technique is achieved using Active Flow Technology-Parallel Segmented Flow (AFT-PSF) [...] Read more.

Conventional techniques for identifying antioxidant and phenolic compounds in native Australian food plants are laborious and time-consuming. Here, we present a multiplexed detection technique that reduces analysis time without compromising separation performance. This technique is achieved using Active Flow Technology-Parallel Segmented Flow (AFT-PSF) columns. Extracts from cinnamon myrtle (Backhousia myrtifolia) and lemon myrtle (Backhousia citriodora) leaves were analysed via multiplexed detection using an AFT-PSF column with underivatised UV-VIS, mass spectroscopy (MS), and the 2,2-diphenyl-1-picrylhydrazyl (DPPH^•) derivatisation for antioxidants as detection methods. A number of antioxidant compounds were detected in the extracts of each leaf extract. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

17 pages, 1365 KiB

Open AccessArticle

Antiproliferative and Antioxidant Activities and Mycosporine-Like Amino Acid Profiles of Wild-Harvested and Cultivated Edible Canadian Marine Red Macroalgae

by Yasantha Athukorala, Susan Trang, Carmen Kwok and Yvonne V. Yuan

Molecules 2016, 21(1), 119; https://doi.org/10.3390/molecules21010119 - 21 Jan 2016

Cited by 59 | Viewed by 9542

Abstract

Antiproliferative and antioxidant activities and mycosporine-like amino acid (MAA) profiles of methanol extracts from edible wild-harvested (Chondrus crispus, Mastocarpus stellatus, Palmaria palmata) and cultivated (C. crispus) marine red macroalgae were studied herein. Palythine, asterina-330, shinorine, palythinol, porphyra-334 [...] Read more.

Antiproliferative and antioxidant activities and mycosporine-like amino acid (MAA) profiles of methanol extracts from edible wild-harvested (Chondrus crispus, Mastocarpus stellatus, Palmaria palmata) and cultivated (C. crispus) marine red macroalgae were studied herein. Palythine, asterina-330, shinorine, palythinol, porphyra-334 and usujirene MAAs were identified in the macroalgal extracts by LC/MS/MS. Extract reducing activity rankings were (p < 0.001): wild P. palmata > cultivated C. crispus = wild M. stellatus > wild low-UV C. crispus > wild high-UV C. crispus; whereas oxygen radical absorbance capacities were (p < 0.001): wild M. stellatus > wild P. palmata > cultivated C. crispus > wild low-UV C. crispus > wild high-UV C. crispus. Extracts were antiproliferative against HeLa and U-937 cells (p < 0.001) from 0.125–4 mg/mL, 24 h. Wild P. palmata and cultivated C. crispus extracts increased (p < 0.001) HeLa caspase-3/7 activities and the proportion of cells arrested at Sub G₁ (apoptotic) compared to wild-harvested C. crispus and M. stellatus extracts. HeLa cells incubated with wild P. palmata and cultivated C. crispus extracts also exhibited morphological changes characteristic of apoptosis (shrinkage, rounding). Thus, extracts rich in low-polarity usujirene and polar palythine and asterina-330 MAAs were antiproliferative as inducers of apoptosis in HeLa cells. Full article

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

► Show Figures

Figure 1

13 pages, 3892 KiB

Open AccessArticle

Cytotoxic Compounds from Juglans sinensis Dode Display Anti-Proliferative Activity by Inducing Apoptosis in Human Cancer Cells

by Yoo Jin Lee, Jun Cui, Jun Lee, Ah-Reum Han, Eun Byul Lee, Ho Hee Jang and Eun Kyoung Seo

Molecules 2016, 21(1), 120; https://doi.org/10.3390/molecules21010120 - 21 Jan 2016

Cited by 16 | Viewed by 8569

Abstract

Phytochemical investigation of the bark of Juglans sinensis Dode (Juglandaceae) led to the isolation of two active compounds, 8-hydroxy-2-methoxy-1,4-naphthoquinone (1) and 5-hydroxy-2-methoxy-1,4-naphthoquinone (2), together with 15 known compounds 3–17. All compounds were isolated from this plant [...] Read more.

Phytochemical investigation of the bark of Juglans sinensis Dode (Juglandaceae) led to the isolation of two active compounds, 8-hydroxy-2-methoxy-1,4-naphthoquinone (1) and 5-hydroxy-2-methoxy-1,4-naphthoquinone (2), together with 15 known compounds 3–17. All compounds were isolated from this plant for the first time. The structures of 1 and 2 were elucidated by spectroscopic data analysis, including 1D and 2D NMR experiments. Compounds 1–17 were tested for their cytotoxicity against the A549 human lung cancer cell line; compounds 1 and 2 exhibited significant cytotoxicity and additionally had potent cytotoxicity against six human cancer cell lines, MCF7 (breast cancer), SNU423 (liver cancer), SH-SY5Y (neuroblastoma), HeLa (cervical cancer), HCT116 (colorectal cancer), and A549 (lung cancer). In particular, breast, colon, and lung cancer cells were more sensitive to the treatment using compound 1. In addition, compounds 1 and 2 showed strong cytotoxic activity towards human breast cancer cells MCF7, HS578T, and T47D, but not towards MCF10A normal-like breast cells. They also inhibited the colony formation of MCF7, A549, and HCT116 cells in a dose-dependent manner. Flow cytometry analysis revealed that the percentage of apoptotic cells significantly increased in MCF7 cells upon the treatment with compounds 1 and 2. The mechanism of cell death caused by compounds 1 and 2 may be attributed to the upregulation of Bax and downregulation of Bcl2. These findings suggest that compounds 1 and 2 may be regarded as potential therapeutic agents against cancer. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

10 pages, 1004 KiB

Open AccessArticle

On-Line Organic Solvent Field Enhanced Sample Injection in Capillary Zone Electrophoresis for Analysis of Quetiapine in Beagle Dog Plasma

by Yuqing Cao, Jun Wen, Tingting Zhou and Guorong Fan

Molecules 2016, 21(1), 121; https://doi.org/10.3390/molecules21010121 - 21 Jan 2016

Cited by 9 | Viewed by 7702

Abstract

A rapid and sensitive capillary zone electrophoresis (CZE) method with field enhanced sample injection (FESI) was developed and validated for the determination of quetiapine fumarate in beagle dog plasma, with a sample pretreatment by LLE in 96-well deep format plate. The optimum separation [...] Read more.

A rapid and sensitive capillary zone electrophoresis (CZE) method with field enhanced sample injection (FESI) was developed and validated for the determination of quetiapine fumarate in beagle dog plasma, with a sample pretreatment by LLE in 96-well deep format plate. The optimum separation was carried out in an uncoated 31.2 cm × 75 μm fused-silica capillary with an applied voltage of 13 kV. The electrophoretic analysis was performed by 50 mM phosphate at pH 2.5. The detection wavelength was 210 nm. Under these optimized conditions, FESI with acetonitrile enhanced the sensitivity of quetiapine about 40–50 folds in total. The method was suitably validated with respect to stability, specificity, linearity, lower limit of quantitation, accuracy, precision and extraction recovery. Using mirtazapine as an internal standard (100 ng/mL), the response of quetiapine was linear over the range of 1–1000 ng/mL. The lower limit of quantification was 1 ng/mL. The intra- and inter-day precisions for the assay were within 4.8% and 12.7%, respectively. The method represents the first application of FESI-CZE to the analysis of quetiapine fumarate in beagle dog plasma after oral administration. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

10 pages, 1430 KiB

Open AccessArticle

Synthesis of Some Novel 2-Amino-5-arylazothiazole Disperse Dyes for Dyeing Polyester Fabrics and Their Antimicrobial Activity

by Hatem E. Gaffer, Moustafa M. G. Fouda and Mohamed E. Khalifa

Molecules 2016, 21(1), 122; https://doi.org/10.3390/molecules21010122 - 21 Jan 2016

Cited by 40 | Viewed by 6094

Abstract

The present work describes the synthesis of a series of four novel biologically active 2-amino-5-arylazothiazole disperse dyes containing the sulfa drug nucleus. The structures of the synthesized thiazole derivatives are confirmed using UV-spectrophotometry, infrared and nuclear magnetic resonance techniques and elemental analysis. The [...] Read more.

The present work describes the synthesis of a series of four novel biologically active 2-amino-5-arylazothiazole disperse dyes containing the sulfa drug nucleus. The structures of the synthesized thiazole derivatives are confirmed using UV-spectrophotometry, infrared and nuclear magnetic resonance techniques and elemental analysis. The synthesized dyes are applied to polyester fabrics as disperse dyes and their fastness properties to washing, perspiration, rubbing, sublimation, and light are evaluated. The synthesized compounds exhibit promising biological efficiency against selected Gram-positive and Gram-negative pathogenic bacteria as well as fungi. Full article

(This article belongs to the Collection Heterocyclic Compounds)

► Show Figures

Figure 1

12 pages, 1610 KiB

Open AccessArticle

Serum Metabolomic Characterization of Liver Fibrosis in Rats and Anti-Fibrotic Effects of Yin-Chen-Hao-Tang

by Hongyang Zhang, Xiaoning Wang, Ping Hu, Wenjun Zhou, Min Zhang, Jia Liu, Yuerong Wang, Ping Liu and Guoan Luo

Molecules 2016, 21(1), 126; https://doi.org/10.3390/molecules21010126 - 21 Jan 2016

Cited by 27 | Viewed by 7426

Abstract

Yin-Chen-Hao-Tang (YCHT) is a famous Chinese medicine formula which has long been used in clinical practice for treating various liver diseases, such as liver fibrosis. However, to date, the mechanism for its anti-fibrotic effects remains unclear. In this paper, an ultra-performance liquid chromatography-time-of-flight [...] Read more.

Yin-Chen-Hao-Tang (YCHT) is a famous Chinese medicine formula which has long been used in clinical practice for treating various liver diseases, such as liver fibrosis. However, to date, the mechanism for its anti-fibrotic effects remains unclear. In this paper, an ultra-performance liquid chromatography-time-of-flight mass spectrometry (UPLC-TOF-MS)-based metabolomic study was performed to characterize dimethylnitrosamine (DMN)-induced liver fibrosis in rats and evaluate the therapeutic effects of YCHT. Partial least squares-discriminant analysis (PLS-DA) showed that the model group was well separated from the control group, whereas the YCHT-treated group exhibited a tendency to restore to the controls. Seven significantly changed fibrosis-related metabolites, including unsaturated fatty acids and lysophosphatidylcholines (Lyso-PCs), were identified. Moreover, statistical analysis demonstrated that YCHT treatment could reverse the levels of most metabolites close to the normal levels. These results, along with histological and biochemical examinations, indicate that YCHT has anti-fibrotic effects, which may be due to the suppression of oxidative stress and resulting lipid peroxidation involved in hepatic fibrogenesis. This study offers new opportunities to improve our understanding of liver fibrosis and the anti-fibrotic mechanisms of YCHT. Full article

(This article belongs to the Section Metabolites)

► Show Figures

Graphical abstract

13 pages, 874 KiB

Open AccessCommunication

The Scavenging of DPPH, Galvinoxyl and ABTS Radicals by Imine Analogs of Resveratrol

by Peter Kotora, František Šeršeň, Juraj Filo, Dušan Loos, Juraj Gregáň and Fridrich Gregáň

Molecules 2016, 21(1), 127; https://doi.org/10.3390/molecules21010127 - 21 Jan 2016

Cited by 55 | Viewed by 8190

Abstract

Resveratrol (3,5,4′-trihydroxystilbene) is a phytoalexin produced by plants. Resveratrol is known for its anti-cancer, antiviral and antioxidant properties. We prepared imine analogs of resveratrol ((hydroxyphenyliminomethyl)phenols) and tested their antioxidant activity. All prepared resveratrol analogs were able to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), galvinoxyl radical (GOR) [...] Read more.

Resveratrol (3,5,4′-trihydroxystilbene) is a phytoalexin produced by plants. Resveratrol is known for its anti-cancer, antiviral and antioxidant properties. We prepared imine analogs of resveratrol ((hydroxyphenyliminomethyl)phenols) and tested their antioxidant activity. All prepared resveratrol analogs were able to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), galvinoxyl radical (GOR) and 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulphonic acid (ABTS) radicals. The antioxidant activity efficiency correlated with the number and position of hydroxyl groups. The most effective antioxidants were resveratrol analogs containing three hydroxyl groups in the benzylidene part of their molecules. These results provide new insights into the relationship between the chemical structure and biological activity of resveratrol analogs. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

9 pages, 2135 KiB

Open AccessArticle

Pharmacokinetics of Tyrosol Metabolites in Rats

by Da-Hye Lee, Yang-Ji Kim, Min Jung Kim, Jiyun Ahn, Tae-Youl Ha, Sang Hee Lee, Young Jin Jang and Chang Hwa Jung

Molecules 2016, 21(1), 128; https://doi.org/10.3390/molecules21010128 - 21 Jan 2016

Cited by 24 | Viewed by 7321

Abstract

Tyrosol is considered a potential antioxidant; however, little is known regarding the pharmacokinetics of its metabolites. To study the pharmacokinetics of tyrosol-derived metabolites after oral administration of a single dose of tyrosol, we attempted to identify tyrosol metabolites in rat plasma by using [...] Read more.

Tyrosol is considered a potential antioxidant; however, little is known regarding the pharmacokinetics of its metabolites. To study the pharmacokinetics of tyrosol-derived metabolites after oral administration of a single dose of tyrosol, we attempted to identify tyrosol metabolites in rat plasma by using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Two tyrosol metabolites (M1 and M2) were detected in the plasma. M1 was identified as tyrosol-4-sulfate (T4S) with an [M − H]⁻ ion at m/z 217. While M2 showed an [M − H]⁻ ion at m/z 151.0, its metabolite was not identified. Pharmacokinetic analysis of T4S and M2 showed rapid uptake after oral administration of tyrosol within 1 h. The metabolites were rapidly distributed in most organs and tissues and eliminated within 4 h. The greatest T4S deposition by tissue weight was observed in the liver, followed by the kidney and spleen, while M2 was most concentrated in the kidney followed by the liver and spleen. These findings indicate that T4S and M2 were distributed mainly in tissues with an abundant blood supply and were rapidly excreted in urine. Full article

(This article belongs to the Section Metabolites)

► Show Figures

Graphical abstract

Review

Jump to: Editorial, Research, Other

17 pages, 1371 KiB

Open AccessReview

Soy Isoflavones and Breast Cancer Cell Lines: Molecular Mechanisms and Future Perspectives

by Alina Uifălean, Stefanie Schneider, Corina Ionescu, Michael Lalk and Cristina Adela Iuga

Molecules 2016, 21(1), 13; https://doi.org/10.3390/molecules21010013 - 22 Dec 2015

Cited by 81 | Viewed by 16448

Abstract

The potential benefit of soy isoflavones in breast cancer chemoprevention, as suggested by epidemiological studies, has aroused the interest of numerous scientists for over twenty years. Although intensive work has been done in this field, the preclinical results continue to be controversial and [...] Read more.

The potential benefit of soy isoflavones in breast cancer chemoprevention, as suggested by epidemiological studies, has aroused the interest of numerous scientists for over twenty years. Although intensive work has been done in this field, the preclinical results continue to be controversial and the molecular mechanisms are far from being fully understood. The antiproliferative effect of soy isoflavones has been commonly linked to the estrogen receptor interaction, but there is growing evidence that other pathways are influenced as well. Among these, the regulation of apoptosis, cell proliferation and survival, inhibition of angiogenesis and metastasis or antioxidant properties have been recently explored using various isoflavone doses and various breast cancer cells. In this review, we offer a comprehensive perspective on the molecular mechanisms of isoflavones observed in in vitro studies, emphasizing each time the dose-effect relationship and estrogen receptor status of the cells. Furthermore, we present future research directions in this field which could provide a better understanding of the inner molecular mechanisms of soy isoflavones in breast cancer. Full article

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

► Show Figures

Figure 1

22 pages, 5910 KiB

Open AccessReview

Isocyanide-Based Multicomponent Reactions for the Synthesis of Heterocycles

by András Váradi, Travis C. Palmer, Rebecca Notis Dardashti and Susruta Majumdar

Molecules 2016, 21(1), 19; https://doi.org/10.3390/molecules21010019 - 23 Dec 2015

Cited by 129 | Viewed by 18036

Abstract

Multicomponent reactions (MCRs) are extremely popular owing to their facile execution, high atom-efficiency and the high diversity of products. MCRs can be used to access various heterocycles and highly functionalized scaffolds, and thus have been invaluable tools in total synthesis, drug discovery and [...] Read more.

Multicomponent reactions (MCRs) are extremely popular owing to their facile execution, high atom-efficiency and the high diversity of products. MCRs can be used to access various heterocycles and highly functionalized scaffolds, and thus have been invaluable tools in total synthesis, drug discovery and bioconjugation. Traditional isocyanide-based MCRs utilize an external nucleophile attacking the reactive nitrilium ion, the key intermediate formed in the reaction of the imine and the isocyanide. However, when reactants with multiple nucleophilic groups (bisfunctional reactants) are used in the MCR, the nitrilium intermediate can be trapped by an intramolecular nucleophilic attack to form various heterocycles. The implications of nitrilium trapping along with widely applied conventional isocyanide-based MCRs in drug design are discussed in this review. Full article

(This article belongs to the Special Issue MCRs and Related One-Pot Organic Synthesis)

► Show Figures

Graphical abstract

29 pages, 299 KiB

Open AccessReview

Analgesic Potential of Essential Oils

by José Ferreira Sarmento-Neto, Lázaro Gomes Do Nascimento, Cícero Francisco Bezerra Felipe and Damião Pergentino De Sousa

Molecules 2016, 21(1), 20; https://doi.org/10.3390/molecules21010020 - 23 Dec 2015

Cited by 61 | Viewed by 22709

Abstract

Pain is an unpleasant sensation associated with a wide range of injuries and diseases, and affects approximately 20% of adults in the world. The discovery of new and more effective drugs that can relieve pain is an important research goal in both the [...] Read more.

Pain is an unpleasant sensation associated with a wide range of injuries and diseases, and affects approximately 20% of adults in the world. The discovery of new and more effective drugs that can relieve pain is an important research goal in both the pharmaceutical industry and academia. This review describes studies involving antinociceptive activity of essential oils from 31 plant species. Botanical aspects of aromatic plants, mechanisms of action in pain models and chemical composition profiles of the essential oils are discussed. The data obtained in these studies demonstrate the analgesic potential of this group of natural products for therapeutic purposes. Full article

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

26 pages, 8352 KiB

Open AccessFeature PaperReview

Mini Review of Phytochemicals and Plant Taxa with Activity as Microbial Biofilm and Quorum Sensing Inhibitors

by Chieu Anh Kim Ta and John Thor Arnason

Molecules 2016, 21(1), 29; https://doi.org/10.3390/molecules21010029 - 26 Dec 2015

Cited by 99 | Viewed by 12882

Abstract

Microbial biofilms readily form on many surfaces in nature including plant surfaces. In order to coordinate the formation of these biofilms, microorganisms use a cell-to-cell communication system called quorum sensing (QS). As formation of biofilms on vascular plants may not be advantageous to [...] Read more.

Microbial biofilms readily form on many surfaces in nature including plant surfaces. In order to coordinate the formation of these biofilms, microorganisms use a cell-to-cell communication system called quorum sensing (QS). As formation of biofilms on vascular plants may not be advantageous to the hosts, plants have developed inhibitors to interfere with these processes. In this mini review, research papers published on plant-derived molecules that have microbial biofilm or quorum sensing inhibition are reviewed with the objectives of determining the biosynthetic classes of active compounds, their biological activity in assays, and their families of occurrence and range. The main findings are the identification of plant phenolics, including benzoates, phenyl propanoids, stilbenes, flavonoids, gallotannins, proanthocyanidins and coumarins as important inhibitors with both activities. Some terpenes including monoterpenes, sesquiterpenes, diterpenes and triterpenes also have anti-QS and anti-biofilm activities. Relatively few alkaloids were reported. Quinones and organosulfur compounds, especially from garlic, were also active. A common feature is the polar nature of these compounds. Phytochemicals with these activities are widespread in Angiosperms in temperate and tropical regions, but gymnosperms, bryophytes and pteridophytes were not represented. Full article

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

12 pages, 750 KiB

Open AccessReview

Is Stevia rebaudiana Bertoni a Non Cariogenic Sweetener? A Review

by Gianmaria Fabrizio Ferrazzano, Tiziana Cantile, Brunella Alcidi, Marco Coda, Aniello Ingenito, Armando Zarrelli, Giovanni Di Fabio and Antonino Pollio

Molecules 2016, 21(1), 38; https://doi.org/10.3390/molecules21010038 - 26 Dec 2015

Cited by 86 | Viewed by 22787

Abstract

Stevia rebaudiana Bertoni is a small perennial shrub of the Asteraceae (Compositae) family that is native to South America, particularly Brazil and Paraguay, where it is known as “stevia” or “honey leaf” for its powerful sweetness. Several studies have suggested that in addition [...] Read more.

Stevia rebaudiana Bertoni is a small perennial shrub of the Asteraceae (Compositae) family that is native to South America, particularly Brazil and Paraguay, where it is known as “stevia” or “honey leaf” for its powerful sweetness. Several studies have suggested that in addition to their sweetness, steviosides and their related compounds, including rebaudioside A and isosteviol, may offer additional therapeutic benefits. These benefits include anti-hyperglycaemic, anti-hypertensive, anti-inflammatory, anti-tumor, anti-diarrheal, diuretic, and immunomodulatory actions. Additionally, critical analysis of the literature supports the anti-bacterial role of steviosides on oral bacteria flora. The aim of this review is to show the emerging results regarding the anti-cariogenic properties of S. rebaudiana Bertoni. Data shown in the present paper provide evidence that stevioside extracts from S. rebaudiana are not cariogenic. Future research should be focused on in vivo studies to evaluate the effects on dental caries of regular consumption of S. rebaudiana extract-based products. Full article

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

► Show Figures

Figure 1

31 pages, 10816 KiB

Open AccessReview

The Prodrug Approach: A Successful Tool for Improving Drug Solubility

by Daniela Hartmann Jornada, Guilherme Felipe Dos Santos Fernandes, Diego Eidy Chiba, Thais Regina Ferreira De Melo, Jean Leandro Dos Santos and Man Chin Chung

Molecules 2016, 21(1), 42; https://doi.org/10.3390/molecules21010042 - 29 Dec 2015

Cited by 209 | Viewed by 31901

Abstract

Prodrug design is a widely known molecular modification strategy that aims to optimize the physicochemical and pharmacological properties of drugs to improve their solubility and pharmacokinetic features and decrease their toxicity. A lack of solubility is one of the main obstacles to drug [...] Read more.

Prodrug design is a widely known molecular modification strategy that aims to optimize the physicochemical and pharmacological properties of drugs to improve their solubility and pharmacokinetic features and decrease their toxicity. A lack of solubility is one of the main obstacles to drug development. This review aims to describe recent advances in the improvement of solubility via the prodrug approach. The main chemical carriers and examples of successful strategies will be discussed, highlighting the advances of this field in the last ten years. Full article

(This article belongs to the Collection Poorly Soluble Drugs)

► Show Figures

Graphical abstract

11 pages, 3166 KiB

Open AccessReview

Sustainable Biomaterials: Current Trends, Challenges and Applications

by Girish Kumar Gupta, Sudipta De, Ana Franco, Alina Mariana Balu and Rafael Luque

Molecules 2016, 21(1), 48; https://doi.org/10.3390/molecules21010048 - 30 Dec 2015

Cited by 34 | Viewed by 10302

Abstract

Biomaterials and sustainable resources are two complementary terms supporting the development of new sustainable emerging processes. In this context, many interdisciplinary approaches including biomass waste valorization and proper usage of green technologies, etc., were brought forward to tackle future challenges pertaining to [...] Read more.

Biomaterials and sustainable resources are two complementary terms supporting the development of new sustainable emerging processes. In this context, many interdisciplinary approaches including biomass waste valorization and proper usage of green technologies, etc., were brought forward to tackle future challenges pertaining to declining fossil resources, energy conservation, and related environmental issues. The implementation of these approaches impels its potential effect on the economy of particular countries and also reduces unnecessary overburden on the environment. This contribution aims to provide an overview of some of the most recent trends, challenges, and applications in the field of biomaterials derived from sustainable resources. Full article

(This article belongs to the Special Issue Enabling Technologies and Green Processes for Biorefinery Strategies and Biomass Valorization)

► Show Figures

Figure 1

28 pages, 3833 KiB

Open AccessReview

Chemical Analysis of the Herbal Medicine Salviae miltiorrhizae Radix et Rhizoma (Danshen)

by Hanqing Pang, Liang Wu, Yuping Tang, Guisheng Zhou, Cheng Qu and Jin-ao Duan

Molecules 2016, 21(1), 51; https://doi.org/10.3390/molecules21010051 - 5 Jan 2016

Cited by 112 | Viewed by 13656

Abstract

Radix Salviae miltiorrhizae et Rhizoma, known as Danshen in China, is one of the most popular traditional Chinese medicines. Recently, there has been increasing scientific attention on Danshen for its remarkable bioactivities, such as promoting blood circulation, removing blood stasis, and clearing away [...] Read more.

Radix Salviae miltiorrhizae et Rhizoma, known as Danshen in China, is one of the most popular traditional Chinese medicines. Recently, there has been increasing scientific attention on Danshen for its remarkable bioactivities, such as promoting blood circulation, removing blood stasis, and clearing away heat. This review summarized the advances in chemical analysis of Danshen and its preparations since 2009. Representative established methods were reviewed, including spectroscopy, thin layer chromatography, gas chromatography, liquid chromatography (LC), liquid chromatography-mass spectrometry (LC-MS), capillary electrophoresis, electrochemistry, and bioanalysis. Especially the analysis of polysaccharides in Danshen was discussed for the first time. Some proposals were also put forward to benefit quality control of Danshen. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

20 pages, 438 KiB

Open AccessReview

Removal of Indoor Volatile Organic Compounds via Photocatalytic Oxidation: A Short Review and Prospect

by Yu Huang, Steven Sai Hang Ho, Yanfeng Lu, Ruiyuan Niu, Lifeng Xu, Junji Cao and Shuncheng Lee

Molecules 2016, 21(1), 56; https://doi.org/10.3390/molecules21010056 - 4 Jan 2016

Cited by 290 | Viewed by 24978

Abstract

Volatile organic compounds (VOCs) are ubiquitous in indoor environments. Inhalation of VOCs can cause irritation, difficulty breathing, and nausea, and damage the central nervous system as well as other organs. Formaldehyde is a particularly important VOC as it is even a carcinogen. Removal [...] Read more.

Volatile organic compounds (VOCs) are ubiquitous in indoor environments. Inhalation of VOCs can cause irritation, difficulty breathing, and nausea, and damage the central nervous system as well as other organs. Formaldehyde is a particularly important VOC as it is even a carcinogen. Removal of VOCs is thus critical to control indoor air quality (IAQ). Photocatalytic oxidation has demonstrated feasibility to remove toxic VOCs and formaldehyde from indoor environments. The technique is highly-chemical stable, inexpensive, non-toxic, and capable of removing a wide variety of organics under light irradiation. In this paper, we review and summarize the traditional air cleaning methods and current photocatalytic oxidation approaches in both of VOCs and formaldehyde degradation in indoor environments. Influencing factors such as temperature, relative humidity, deactivation and reactivations of the photocatalyst are discussed. Aspects of the application of the photocatalytic technique to improve the IAQ are suggested. Full article

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

► Show Figures

Figure 1

23 pages, 5290 KiB

Open AccessReview

Functionalised Oximes: Emergent Precursors for Carbon-, Nitrogen- and Oxygen-Centred Radicals

by John C. Walton

Molecules 2016, 21(1), 63; https://doi.org/10.3390/molecules21010063 - 7 Jan 2016

Cited by 85 | Viewed by 16629

Abstract

Oxime derivatives are easily made, are non-hazardous and have long shelf lives. They contain weak N–O bonds that undergo homolytic scission, on appropriate thermal or photochemical stimulus, to initially release a pair of N- and O-centred radicals. This article reviews the [...] Read more.

Oxime derivatives are easily made, are non-hazardous and have long shelf lives. They contain weak N–O bonds that undergo homolytic scission, on appropriate thermal or photochemical stimulus, to initially release a pair of N- and O-centred radicals. This article reviews the use of these precursors for studying the structures, reactions and kinetics of the released radicals. Two classes have been exploited for radical generation; one comprises carbonyl oximes, principally oxime esters and amides, and the second comprises oxime ethers. Both classes release an iminyl radical together with an equal amount of a second oxygen-centred radical. The O-centred radicals derived from carbonyl oximes decarboxylate giving access to a variety of carbon-centred and nitrogen-centred species. Methods developed for homolytically dissociating the oxime derivatives include UV irradiation, conventional thermal and microwave heating. Photoredox catalytic methods succeed well with specially functionalised oximes and this aspect is also reviewed. Attention is also drawn to the key contributions made by EPR spectroscopy, aided by DFT computations, in elucidating the structures and dynamics of the transient intermediates. Full article

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

► Show Figures

Graphical abstract

21 pages, 804 KiB

Open AccessReview

Natural Products for the Prevention and Treatment of Hangover and Alcohol Use Disorder

by Fang Wang, Ya Li, Yu-Jie Zhang, Yue Zhou, Sha Li and Hua-Bin Li

Molecules 2016, 21(1), 64; https://doi.org/10.3390/molecules21010064 - 7 Jan 2016

Cited by 83 | Viewed by 45966

Abstract

Alcoholic beverages such as beer, wine and spirits are widely consumed around the world. However, alcohol and its metabolite acetaldehyde are toxic and harmful to human beings. Chronic alcohol use disorder or occasional binge drinking can cause a wide range of health problems, [...] Read more.

Alcoholic beverages such as beer, wine and spirits are widely consumed around the world. However, alcohol and its metabolite acetaldehyde are toxic and harmful to human beings. Chronic alcohol use disorder or occasional binge drinking can cause a wide range of health problems, such as hangover, liver damage and cancer. Some natural products such as traditional herbs, fruits, and vegetables might be potential dietary supplements or medicinal products for the prevention and treatment of the problems caused by excessive alcohol consumption. The aim of this review is to provide an overview of effective natural products for the prevention and treatment of hangover and alcohol use disorder, and special emphasis is paid to the possible functional component(s) and related mechanism(s) of action. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

14 pages, 756 KiB

Open AccessReview

The Structure-Activity Relationship of the Antioxidant Peptides from Natural Proteins

by Tang-Bin Zou, Tai-Ping He, Hua-Bin Li, Huan-Wen Tang and En-Qin Xia

Molecules 2016, 21(1), 72; https://doi.org/10.3390/molecules21010072 - 12 Jan 2016

Cited by 720 | Viewed by 20818

Abstract

Peptides derived from dietary proteins, have been reported to display significant antioxidant activity, which may exert notably beneficial effects in promoting human health and in food processing. Recently, much research has focused on the generation, separation, purification and identification of novel peptides from [...] Read more.

Peptides derived from dietary proteins, have been reported to display significant antioxidant activity, which may exert notably beneficial effects in promoting human health and in food processing. Recently, much research has focused on the generation, separation, purification and identification of novel peptides from various protein sources. Some researchers have tried to discover the structural characteristics of antioxidant peptides in order to lessen or avoid the tedious and aimless work involving the ongoing generated peptide preparation schemes. This review aims to summarize the current knowledge on the relationship between the structural features of peptides and their antioxidant activities. The relationship between the structure of the precursor proteins and their abilities to release antioxidant fragments will also be summarized and inferred. The preparation methods and antioxidant capacity evaluation assays of peptides and a prediction scheme of quantitative structure–activity relationship (QSAR) will also be pointed out and discussed. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

23 pages, 2116 KiB

Open AccessReview

Application of Bioactive Quercetin in Oncotherapy: From Nutrition to Nanomedicine

by Ju-Suk Nam, Ashish Ranjan Sharma, Lich Thi Nguyen, Chiranjib Chakraborty, Garima Sharma and Sang-Soo Lee

Molecules 2016, 21(1), 108; https://doi.org/10.3390/molecules21010108 - 19 Jan 2016

Cited by 159 | Viewed by 15523

Abstract

Phytochemicals as dietary constituents are being explored for their cancer preventive properties. Quercetin is a major constituent of various dietary products and recently its anti-cancer potential has been extensively explored, revealing its anti-proliferative effect on different cancer cell lines, both in vitro and [...] Read more.

Phytochemicals as dietary constituents are being explored for their cancer preventive properties. Quercetin is a major constituent of various dietary products and recently its anti-cancer potential has been extensively explored, revealing its anti-proliferative effect on different cancer cell lines, both in vitro and in vivo. Quercetin is known to have modulatory effects on cell apoptosis, migration and growth via various signaling pathways. Though, quercetin possesses great medicinal value, its applications as a therapeutic drug are limited. Problems like low oral bioavailability and poor aqueous solubility make quercetin an unreliable candidate for therapeutic purposes. Additionally, the rapid gastrointestinal digestion of quercetin is also a major barrier for its clinical translation. Hence, to overcome these disadvantages quercetin-based nanoformulations are being considered in recent times. Nanoformulations of quercetin have shown promising results in its uptake by the epithelial system as well as enhanced delivery to the target site. Herein we have tried to summarize various methods utilized for nanofabrication of quercetin formulations and for stable and sustained delivery of quercetin. We have also highlighted the various desirable measures for its use as a promising onco-therapeutic agent. Full article

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

► Show Figures

Figure 1

20 pages, 5973 KiB

Open AccessReview

NHC Backbone Configuration in Ruthenium-Catalyzed Olefin Metathesis

by Veronica Paradiso, Chiara Costabile and Fabia Grisi

Molecules 2016, 21(1), 117; https://doi.org/10.3390/molecules21010117 - 20 Jan 2016

Cited by 30 | Viewed by 7537

Abstract

The catalytic properties of olefin metathesis ruthenium complexes bearing N-heterocyclic carbene ligands with stereogenic centers on the backbone are described. Differences in catalytic behavior depending on the backbone configurations of symmetrical and unsymmetrical NHCs are discussed. In addition, an overview on asymmetric [...] Read more.

The catalytic properties of olefin metathesis ruthenium complexes bearing N-heterocyclic carbene ligands with stereogenic centers on the backbone are described. Differences in catalytic behavior depending on the backbone configurations of symmetrical and unsymmetrical NHCs are discussed. In addition, an overview on asymmetric olefin metathesis promoted by chiral catalysts bearing C₂-symmetric and C₁-symmetric NHCs is provided. Full article

(This article belongs to the Special Issue Olefin Metathesis)

► Show Figures

Figure 1

Other

Jump to: Editorial, Research, Review

4 pages, 167 KiB

Open AccessComment

The Role of Inclusion Binding Contributions for β-Cyclodextrin Polymers Cross-Linked with Divinyl Sulfone?—A Comment on Morales-Sanfrutos et al. Entitled “Divinyl Sulfone Cross-Linked Cyclodextrin-Based Polymeric Materials: Synthesis and Applications as Sorbents and Encapsulating Agents”, Molecules, 2015, 20, 3565–3581.

by Lee D. Wilson, Mohamed H. Mohamed and Dena W. McMartin

Molecules 2016, 21(1), 93; https://doi.org/10.3390/molecules21010093 - 14 Jan 2016

Cited by 6 | Viewed by 3967

Abstract

This commentary reports on a recent scientific study reported in this journal (cf. Molecules 2015, 20(3), 3565–3581). Some key scientific issues that require further explanation and clarification in the former article are as follows: (i) the relationship between the [...] Read more.

This commentary reports on a recent scientific study reported in this journal (cf. Molecules 2015, 20(3), 3565–3581). Some key scientific issues that require further explanation and clarification in the former article are as follows: (i) the relationship between the inclusion site accessibility and the level of cross-linking employed are brought into question for the case of α-CD and β-CD cross-linked adsorbent materials; (ii) the binding affinity of the CD/guest complexes were not related to the isotherm parameters for the CD-polymer/guest systems; (iii) the limited molecular level structural characterization of the cross-linked polymer materials; and (iv) the interpretation of the adsorption isotherm results by the authors. Full article

(This article belongs to the Section Organic Chemistry)

4 pages, 372 KiB

Open AccessReply

Response to Wilson et al. Comments on Lopez-Jaramillo et al. DivinylSulfone Cross-Linked Cyclodextrin-Based Polymeric Materials: Synthesis and Applications as Sorbents and Encapsulating Agents. Molecules, 2015, 20, 3565–3581.

by Francisco Javier Lopez-Jaramillo, Fernando Hernández-Mateo and Francisco Santoyo-Gonzalez

Molecules 2016, 21(1), 98; https://doi.org/10.3390/molecules21010098 - 15 Jan 2016

Viewed by 3744

Abstract

Wilson et al. raisea number of issues that, according to their opinion, require explanation. [...] Full article

► Show Figures

Figure 1

1 pages, 308 KiB

Open AccessCorrection

Correction: Yan, R.Y., et al. HPLC-DPPH Screening Method for Evaluation of Antioxidant Compounds Extracted from Semen Oroxyli. Molecules 2014, 19, 4409–4417

by Renyi Yan, Yangyang Cao and Bin Yang

Molecules 2016, 21(1), 125; https://doi.org/10.3390/molecules21010125 - 21 Jan 2016

Viewed by 3912

Abstract

The authors wish to inform readers that there is an error in the chemical structures shown in Figure 4 of this paper [1]. [...] Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 4

2 pages, 153 KiB

Open AccessCorrection

Correction: Hasan, I., et al. A Galactose-Binding Lectin Isolated from Aplysia kurodai (Sea Hare) Eggs Inhibits Streptolysin-Induced Hemolysis. Molecules 2014, 19, 13990–14003

by Imtiaj Hasan, Miharu Watanabe, Naoto Ishizaki, Yoshiko Sugita-Konishi, Yasushi Kawakami, Jun Suzuki, Chikaku Dogasaki, Sultana Rajia, Sarkar M. A. Kawsar, Yasuhiro Koide, Robert A. Kanaly, Shigeki Sugawara, Masahiro Hosono, Yukiko Ogawa, Yuki Fujii, Hideyuki Iriko, Jiharu Hamako, Taei Matsui and Yasuhiro Ozeki

Molecules 2016, 21(1), 129; https://doi.org/10.3390/molecules21010129 - 21 Jan 2016

Viewed by 4859

Abstract

The authors wish to make the following correction to their paper [1]. [...] Full article

(This article belongs to the Special Issue Lectins)

Journal Menu

Journal Browser

Molecules, Volume 21, Issue 1 (January 2016) – 124 articles

Editorial

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI