Next Issue
Previous Issue

E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Table of Contents

Molecules, Volume 20, Issue 2 (February 2015), Pages 1755-3495

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-97
Export citation of selected articles as:

Editorial

Jump to: Research, Review, Other

Open AccessEditorial Phytoalexins: Current Progress and Future Prospects
Molecules 2015, 20(2), 2770-2774; doi:10.3390/molecules20022770
Received: 2 February 2015 / Accepted: 4 February 2015 / Published: 5 February 2015
Cited by 9 | PDF Full-text (623 KB) | HTML Full-text | XML Full-text
Abstract
Phytoalexins are low molecular weight antimicrobial compounds that are produced by plants as a response to biotic and abiotic stresses. As such they take part in an intricate defense system which enables plants to control invading microorganisms. In the 1950s, research on phytoalexins
[...] Read more.
Phytoalexins are low molecular weight antimicrobial compounds that are produced by plants as a response to biotic and abiotic stresses. As such they take part in an intricate defense system which enables plants to control invading microorganisms. In the 1950s, research on phytoalexins started with progress in their biochemistry and bio-organic chemistry, resulting in the determination of their structure, their biological activity, as well as mechanisms of their synthesis and catabolism by microorganisms. Elucidation of the biosynthesis of numerous phytoalexins also permitted the use of molecular biology tools for the exploration of the genes encoding enzymes of their synthesis pathways and their regulators. This has led to potential applications for increasing plant resistance to diseases. Phytoalexins display an enormous diversity belonging to various chemical families such as for instance, phenolics, terpenoids, furanoacetylenes, steroid glycoalkaloids, sulfur-containing compounds and indoles.[...] Full article
Open AccessEditorial The Games Radicals Play: Special Issue on Free Radicals and Radical Ions
Molecules 2015, 20(2), 2831-2834; doi:10.3390/molecules20022831
Received: 3 February 2015 / Accepted: 5 February 2015 / Published: 9 February 2015
PDF Full-text (625 KB) | HTML Full-text | XML Full-text
Abstract
Chemistry and Physics have aptly been described as “most excellent children of Intellect and Art” [1]. Both these “children” engage with many playthings, and molecules rank as one of their first favorites, especially radicals, which are amongst the most lively and exciting. Checking
[...] Read more.
Chemistry and Physics have aptly been described as “most excellent children of Intellect and Art” [1]. Both these “children” engage with many playthings, and molecules rank as one of their first favorites, especially radicals, which are amongst the most lively and exciting. Checking out radicals dancing to the music of entropy round their potential energy ballrooms is surely both entertaining and enlightening. Radicals’ old favorite convolutions are noteworthy, but the new styles, modes and arrangements appearing on the scene are even more interesting. Some of these are ephemeral and enjoy only a brief appearance, others are retro-types reappearing in new guises, still others are genuinely new and “go viral” in the scientific world. This Special Issue of Molecules contains the observations and reflections of a select group of chemists and physicists fascinated by this spectacle. It contains an eclectic mix reflecting on new modes and advances as well as on permutations and combinations that revive mature themes. [...] Full article
(This article belongs to the Special Issue Free Radicals and Radical Ions)

Research

Jump to: Editorial, Review, Other

Open AccessCommunication Electron Transfer-Induced Coupling of Haloarenes to Styrenes and 1,1-Diphenylethenes Triggered by Diketopiperazines and Potassium tert-Butoxide
Molecules 2015, 20(2), 1755-1774; doi:10.3390/molecules20021755
Received: 22 December 2014 / Accepted: 6 January 2015 / Published: 22 January 2015
Cited by 11 | PDF Full-text (853 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The coupling of haloarenes to styrenes and 1,1-diarylethenes has been achieved with potassium tert-butoxide in the presence of N,N'-dialkyldiketopiperazines. In contrast to previously reported reactions where phenanthroline has been used to mediate the reactions, the use of diketopiperazines can lead
[...] Read more.
The coupling of haloarenes to styrenes and 1,1-diarylethenes has been achieved with potassium tert-butoxide in the presence of N,N'-dialkyldiketopiperazines. In contrast to previously reported reactions where phenanthroline has been used to mediate the reactions, the use of diketopiperazines can lead to either 1,1,2-triarylethenes or 1,1,2-triarylethanes, depending on the conditions used. Full article
(This article belongs to the Special Issue Free Radicals and Radical Ions)
Open AccessArticle A Redox-Controllable Molecular Switch Based on Weak Recognition of BPX26C6 at a Diphenylurea Station
Molecules 2015, 20(2), 1775-1787; doi:10.3390/molecules20021775
Received: 9 December 2014 / Revised: 8 January 2015 / Accepted: 15 January 2015 / Published: 22 January 2015
Cited by 1 | PDF Full-text (1598 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The Na+ ion–assisted recognition of urea derivatives by BPX26C6 has allowed the construction of a redox-controllable [2]rotaxane-type molecular switch based on two originally very weakly interacting host/guest systems. Using NOBF4 to oxidize the triarylamine terminus into a corresponding radical cation attracted
[...] Read more.
The Na+ ion–assisted recognition of urea derivatives by BPX26C6 has allowed the construction of a redox-controllable [2]rotaxane-type molecular switch based on two originally very weakly interacting host/guest systems. Using NOBF4 to oxidize the triarylamine terminus into a corresponding radical cation attracted the macrocyclic component toward its adjacent carbamate station; subsequent addition of Zn powder moved the macrocyclic component back to its urea station. Full article
(This article belongs to the Special Issue Host-Guest Chemistry)
Figures

Open AccessArticle Synthesis, Bioactivity, Molecular Docking and POM Analyses of Novel Substituted Thieno[2,3-b]thiophenes and Related Congeners
Molecules 2015, 20(2), 1824-1841; doi:10.3390/molecules20021824
Received: 17 December 2014 / Revised: 13 January 2015 / Accepted: 14 January 2015 / Published: 23 January 2015
Cited by 10 | PDF Full-text (1841 KB) | HTML Full-text | XML Full-text
Abstract
Several series of novel substituted thienothiophene derivatives were synthesized by reacting the synthone 1 with different reagents. The newly synthesized compounds were characterized by means of different spectroscopic methods such as IR, NMR, mass spectrometry and by elemental analyses. The new compounds displayed
[...] Read more.
Several series of novel substituted thienothiophene derivatives were synthesized by reacting the synthone 1 with different reagents. The newly synthesized compounds were characterized by means of different spectroscopic methods such as IR, NMR, mass spectrometry and by elemental analyses. The new compounds displayed significant activity against both Gram-positive and Gram negative bacteria, in addition to fungi. Molecular docking and POM analyses show the crucial role and impact of substituents on bioactivity and indicate the unfavorable structural parameters in actual drug design: more substitution doesn’t guaranty more efficiency in bioactivity. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Microwave-Assisted Synthesis and Antimicrobial Evaluation of Novel Spiroisoquinoline and Spiropyrido[4,3-d]pyrimidine Derivatives
Molecules 2015, 20(2), 1842-1859; doi:10.3390/molecules20021842
Received: 27 December 2014 / Accepted: 20 January 2015 / Published: 23 January 2015
Cited by 3 | PDF Full-text (775 KB) | HTML Full-text | XML Full-text
Abstract
Bromination of N-substituted homophthalimides and tetrahydropyrido[4,3-d]- pyrimidine-5,7-diones produces 4,4-dibromohomophthalimide and 8,8-dibromo-tetrahydropyrido[4,3-d]pyrimidine-5,7-dione derivatives, respectively, that can be used as precursors for spiro derivatives. The dibromo derivatives react with different binucleophilic reagents to produce several spiroisoquinoline and spirotetrahydropyrido[4,3-d]-
[...] Read more.
Bromination of N-substituted homophthalimides and tetrahydropyrido[4,3-d]- pyrimidine-5,7-diones produces 4,4-dibromohomophthalimide and 8,8-dibromo-tetrahydropyrido[4,3-d]pyrimidine-5,7-dione derivatives, respectively, that can be used as precursors for spiro derivatives. The dibromo derivatives react with different binucleophilic reagents to produce several spiroisoquinoline and spirotetrahydropyrido[4,3-d]- pyrimidine-5,7-dione derivatives, respectively. Reaction of the dibromo derivatives with malononitrile produces dicyanomethylene derivatives which react with different binucleophiles to produce new spiro derivatives. All new compounds are prepared by using the usual chemical conditions and microwave assisted conditions. The latter conditions improved the reaction yields, reduced reaction times and ameliorated the effects on the surrounding environment as the reactions are carried out in closed systems. Structures of the newly synthesized compounds are proved using spectroscopic methods such as IR, MS, 1H-NMR and 13C-NMR and elemental analyses. Some of the newly synthesized compounds were tested for their antimicrobial activities, whereby four of them showed moderate activities and the rest showed low or no activities towards the investigated species. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Antimicrobial and Seasonal Evaluation of the Carvacrol-Chemotype Oil from Lippia origanoides Kunth.
Molecules 2015, 20(2), 1860-1871; doi:10.3390/molecules20021860
Received: 9 December 2014 / Accepted: 14 January 2015 / Published: 23 January 2015
Cited by 9 | PDF Full-text (734 KB) | HTML Full-text | XML Full-text
Abstract
This study evaluated the influence of seasonal variation on the yield and composition of essential oil of Lippia origanoides occurring in the Middle Rio Amazonas, Brazil, and the impact on its antimicrobial potential. The average oil yield was 1.7% ± 0.2% in the
[...] Read more.
This study evaluated the influence of seasonal variation on the yield and composition of essential oil of Lippia origanoides occurring in the Middle Rio Amazonas, Brazil, and the impact on its antimicrobial potential. The average oil yield was 1.7% ± 0.2% in the rainy season and 1.6% ± 0.3% in the dry season. Some correlations with climatic parameters were observed. The major components were carvacrol (rainy, 43.5% ± 1.9%; dry, 41.4% ± 2.04%), thymol (rainy, 10.7% ± 1.1%; dry, 10.6% ± 0.9%), p-cymene (rainy, 9.8% ± 0.7%; dry, 10.0% ± 1.4%) and p-methoxythymol (rainy, 9.6% ± 0.8%; dry, 10.4% ± 1.4%). It was found that the antibacterial activity of L. origanoides against Staphylococcus aureus and Escherichia coli was little influenced by the changes in oil composition due to seasonal variation. Against S. aureus, the oil Minimum Inhibitory Concentration (MIC) value was 1.25 μL/mL over ten months. Against E. coli, the oil MIC values ranged from 0.15 μL/mL to 0.31 μL/mL in different months of the year. The Minimum Bactericidal Concentration (MBC) value was 2.5 μL/mL against S. aureus and 1.25 μL/mL against E. coli. The results suggest that the antimicrobial activity identified in the oil remain unchanged for the full year, allowing its medicinal use without any risk of loss or absence of the active principles of the plant. Full article
(This article belongs to the collection Bioactive Compounds)
Figures

Open AccessArticle Ameliorating the Effect of Astragaloside IV on Learning and Memory Deficit after Chronic Cerebral Hypoperfusion in Rats
Molecules 2015, 20(2), 1904-1921; doi:10.3390/molecules20021904
Received: 28 October 2014 / Accepted: 12 January 2015 / Published: 23 January 2015
Cited by 11 | PDF Full-text (1072 KB) | HTML Full-text | XML Full-text
Abstract
Astragaloside IV (AS-IV) has been reported to have a prominent antioxidant effect and was proposed as a promising agent for the prevention of neurodegenerative disorders accompanied by cognitive impairment. The present study investigated the ameliorating effect of AS-IV on learning and memory deficits
[...] Read more.
Astragaloside IV (AS-IV) has been reported to have a prominent antioxidant effect and was proposed as a promising agent for the prevention of neurodegenerative disorders accompanied by cognitive impairment. The present study investigated the ameliorating effect of AS-IV on learning and memory deficits induced by chronic cerebral hypoperfusion in rats. Rats were treated with two doses of AS-IV (10 and 20 mg/kg, i.p.) daily for 28 days starting from the 5th week after permanent bilateral common carotid artery occlusion. AS-IV treatment (at dose of 20 mg/kg) significantly improved the spatial learning and memory deficits assessed using the Morris water maze test in rats with chronic cerebral hypoperfusion. AS-IV significantly attenuated neuronal apoptosis as well as the levels of superoxide dismutase and lipid peroxidation markers, including malondialdehyde and 4-hydroxy-2-nonenal, in the hippocampus. AS-IV also significantly reduced 8-hydroxy-2’-deoxyguanosine expression, a maker of oxidative DNA damage, while significantly inhibited the astrocyte and microglia activation in the hippocampus. The results indicate that AS-IV has therapeutic potential for the prevention of dementia caused by cerebral hypoperfusion and suggest that the ameliorating effect of AS-IV on learning and memory deficits might be the result of suppressing neuronal apoptosis and oxidative damage in the hippocampus. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
Figures

Open AccessArticle Characterization of Four Popular Sweet Cherry Cultivars Grown in Greece by Volatile Compound and Physicochemical Data Analysis and Sensory Evaluation
Molecules 2015, 20(2), 1922-1940; doi:10.3390/molecules20021922
Received: 20 October 2014 / Accepted: 16 January 2015 / Published: 26 January 2015
Cited by 6 | PDF Full-text (717 KB) | HTML Full-text | XML Full-text
Abstract
Volatile compounds, physicochemical and sensory attributes of four sweet cherry cultivars (Canada giant, Ferrovia, Lapins and Skeena) grown in Northern Greece were determined. Eighteen volatile compounds were identified and semi-quantified in cherries using solid phase micro extraction in combination with gas chromatography/mass spectrometry
[...] Read more.
Volatile compounds, physicochemical and sensory attributes of four sweet cherry cultivars (Canada giant, Ferrovia, Lapins and Skeena) grown in Northern Greece were determined. Eighteen volatile compounds were identified and semi-quantified in cherries using solid phase micro extraction in combination with gas chromatography/mass spectrometry (SPME-GC/MS). Carbonyl compounds were the most abundant in sweet cherry aroma, followed by alcohols, esters and hydrocarbons/terpenes. Cherry cultivars in order of increasing amounts of volatiles were: Lapins < Canada giant < Ferrovia < Skeena. Physicochemical parameters determined included: titratable acidity (TA), pH, total soluble solids (TSS), maturity index (MI) and total phenolic content (TPC). TA ranged between 0.21 and 0.28 g malic acid/100 g fresh weight (FW). The pH ranged between 3.81 and 3.96. TSS ranged between 13.00 and 16.00 °Brix. MI ranged between 51.8 and 75.0. TPC ranged between 95.14 and 170.35 mg gallic acid equivalents (GAE)/100 g FW. Sensory evaluation showed that cherry colour, in order of increasing intensity, was: Canada giant < Ferrovia < Lapins < Skeena. Respective order for cherry firmness was: Canada giant < Lapins ≤ Ferrovia < Skeena and for flavour: Lapins < Canada giant < Skeena ≤ Ferrovia. Correlation of volatiles to physicochemical and sensory attributes showed varying trends. Full article
(This article belongs to the Special Issue Aromas and Volatiles of Fruits)
Open AccessArticle Visible Light Induced Green Transformation of Primary Amines to Imines Using a Silicate Supported Anatase Photocatalyst
Molecules 2015, 20(2), 1941-1954; doi:10.3390/molecules20021941
Received: 30 October 2014 / Accepted: 22 January 2015 / Published: 26 January 2015
Cited by 3 | PDF Full-text (2738 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Catalytic oxidation of amine to imine is of intense present interest since imines are important intermediates for the synthesis of fine chemicals, pharmaceuticals, and agricultural chemicals. However, considerable efforts have been made to develop efficient methods for the oxidation of secondary amines to
[...] Read more.
Catalytic oxidation of amine to imine is of intense present interest since imines are important intermediates for the synthesis of fine chemicals, pharmaceuticals, and agricultural chemicals. However, considerable efforts have been made to develop efficient methods for the oxidation of secondary amines to imines, while little attention has until recently been given to the oxidation of primary amines, presumably owing to the high reactivity of generated imines of primary amines that are easily dehydrogenated to nitriles. Herein, we report the oxidative coupling of a series of primary benzylic amines into corresponding imines with dioxygen as the benign oxidant over composite catalysts of TiO2 (anatase)-silicate under visible light irradiation of λ > 460 nm. Visible light response of this system is believed to be as a result of high population of defects and contacts between silicate and anatase crystals in the composite and the strong interaction between benzylic amine and the catalyst. It is found that tuning the intensity and wavelength of the light irradiation and the reaction temperature can remarkably enhance the reaction activity. Water can also act as a green medium for the reaction with an excellent selectivity. This report contributes to the use of readily synthesized, environmentally benign, TiO2 based composite photocatalyst and solar energy to realize the transformation of primary amines to imine compounds. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
Figures

Open AccessArticle Purification and Characterization of Chitinases from Ridgetail White Prawn Exopalaemon carinicauda
Molecules 2015, 20(2), 1955-1967; doi:10.3390/molecules20021955
Received: 17 December 2014 / Accepted: 19 January 2015 / Published: 26 January 2015
Cited by 5 | PDF Full-text (7722 KB) | HTML Full-text | XML Full-text
Abstract
In this paper, we purified two native chitinases from the hepatopancreas of the ridgetail white prawn Exopalaemon carinicauda by using ion-exchange resin chromatography (IEC) and gel filtration. These two chitinases, named EcChi1 and EcChi2, were identified by chitinolytic activity assay and LC-ESI-MS/MS. Their
[...] Read more.
In this paper, we purified two native chitinases from the hepatopancreas of the ridgetail white prawn Exopalaemon carinicauda by using ion-exchange resin chromatography (IEC) and gel filtration. These two chitinases, named EcChi1 and EcChi2, were identified by chitinolytic activity assay and LC-ESI-MS/MS. Their apparent molecular weights were 44 kDa and 65 kDa as determined by sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The specific activity of EcChi1 and EcChi2 was 1305.97 U·mg−1 and 28.69 U·mg−1. The optimal temperature and pH of EcChi1 were 37 °C and pH 4.0, respectively. Co2+, Fe3+, Zn2+, Cd2+, and Cu2+ had an obvious promoting effect upon chitinase activity of EcChi1. For colloidal chitin, the Km and Vmax values of EcChi1 were 2.09 mg·mL−1 and 31.15 U·mL−1·h−1. Full article
(This article belongs to the collection Advances in Carbohydrate Chemistry)
Open AccessCommunication Synthesis and Biological Evaluation of Novel 6-Hydroxy-benzo[d][1,3]oxathiol-2-one Schiff Bases as Potential Anticancer Agents
Molecules 2015, 20(2), 1968-1983; doi:10.3390/molecules20021968
Received: 29 September 2014 / Revised: 25 December 2014 / Accepted: 31 December 2014 / Published: 27 January 2015
Cited by 7 | PDF Full-text (1158 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
With the aim of discovering new anticancer agents, we have designed and synthesized novel 6-hydroxy-benzo[d][1,3]oxathiol-2-one Schiff bases. The synthesis started with the selective nitration at 5-position of 6-hydroxybenzo[d][1,3]oxathiol-2-one (1) leading to the nitro derivative 2. The
[...] Read more.
With the aim of discovering new anticancer agents, we have designed and synthesized novel 6-hydroxy-benzo[d][1,3]oxathiol-2-one Schiff bases. The synthesis started with the selective nitration at 5-position of 6-hydroxybenzo[d][1,3]oxathiol-2-one (1) leading to the nitro derivative 2. The nitro group of 2 was reduced to give the amino intermediate 3. Schiff bases 4ar were obtained from coupling reactions between 3 and various benzaldehydes and heteroaromatic aldehydes. All the new compounds were fully identified and characterized by NMR (1H and 13C) and specifically for 4q by X-ray crystallography. The in vitro cytotoxicity of the compounds was evaluated against cancer cell lines (ACP-03, SKMEL-19 and HCT-116) by using MTT assay. Schiff bases 4b and 4o exhibited promising cytotoxicity against ACP-03 and SKMEL-19, respectively, with IC50 values lower than 5 μM. This class of compounds can be considered as a good starting point for the development of new lead molecules in the fight against cancer. Full article
Figures

Open AccessArticle Development and Validation of 697 Novel Polymorphic Genomic and EST-SSR Markers in the American Cranberry (Vaccinium macrocarpon Ait.)
Molecules 2015, 20(2), 2001-2013; doi:10.3390/molecules20022001
Received: 18 December 2014 / Revised: 13 January 2015 / Accepted: 26 January 2015 / Published: 27 January 2015
Cited by 10 | PDF Full-text (1049 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The American cranberry, Vaccinium macrocarpon Ait., is an economically important North American fruit crop that is consumed because of its unique flavor and potential health benefits. However, a lack of abundant, genome-wide molecular markers has limited the adoption of modern molecular assisted selection
[...] Read more.
The American cranberry, Vaccinium macrocarpon Ait., is an economically important North American fruit crop that is consumed because of its unique flavor and potential health benefits. However, a lack of abundant, genome-wide molecular markers has limited the adoption of modern molecular assisted selection approaches in cranberry breeding programs. To increase the number of available markers in the species, this study identified, tested, and validated microsatellite markers from existing nuclear and transcriptome sequencing data. In total, new primers were designed, synthesized, and tested for 979 SSR loci; 697 of the markers amplified allele patterns consistent with single locus segregation in a diploid organism and were considered polymorphic. Of the 697 polymorphic loci, 507 were selected for additional genetic diversity and segregation analyses in 29 cranberry genotypes. More than 95% of the 507 loci did not display segregation distortion at the p < 0.05 level, and contained moderate to high levels of polymorphism with a polymorphic information content >0.25. This comprehensive collection of developed and validated microsatellite loci represents a substantial addition to the molecular tools available for geneticists, genomicists, and breeders in cranberry and Vaccinium. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle The Synthesis and Antitumor Activity of Twelve Galloyl Glucosides
Molecules 2015, 20(2), 2034-2060; doi:10.3390/molecules20022034
Received: 26 December 2014 / Revised: 5 January 2015 / Accepted: 21 January 2015 / Published: 27 January 2015
Cited by 4 | PDF Full-text (934 KB) | HTML Full-text | XML Full-text
Abstract
Twelve galloyl glucosides 112, showing diverse substitution patterns with two or three galloyl groups, were synthesized using commercially available, low-cost D-glucose and gallic acid as starting materials. Among them, three compounds, methyl 3,6-di-O-galloyl-α-D-glucopyranoside (9),
[...] Read more.
Twelve galloyl glucosides 112, showing diverse substitution patterns with two or three galloyl groups, were synthesized using commercially available, low-cost D-glucose and gallic acid as starting materials. Among them, three compounds, methyl 3,6-di-O-galloyl-α-D-glucopyranoside (9), ethyl 2,3-di-O-galloyl-α-D-glucopyranoside (11) and ethyl 2,3-di-O-galloyl-β-D-glucopyranoside (12), are new compounds and other six, 1,6-di-O-galloyl-β-D-glucopyranose (1), 1,4,6-tri-O-galloyl-β-D-glucopyranose (2), 1,2-di-O-galloyl-β-D-glucopyranose (3), 1,3-di-O-galloyl-β-D-glucopyranose (4), 1,2,3-tri-O-galloyl-α-D-glucopyranose (6) and methyl 3,4,6-tri-O-galloyl-α-D-glucopyranoside (10), were synthesized for the first time in the present study. In in vitro MTT assay, 112 inhibited human cancer K562, HL-60 and HeLa cells with inhibition rates ranging from 64.2% to 92.9% at 100 μg/mL, and their IC50 values were determined to be varied in 17.2–124.7 μM on the tested three human cancer cell lines. In addition, compounds 112 inhibited murine sarcoma S180 cells with inhibition rates ranging from 38.7% to 52.8% at 100 μg/mL in the in vitro MTT assay, and in vivo antitumor activity of 1 and 2 was also detected in murine sarcoma S180 tumor-bearing Kunming mice using taxol as positive control. Full article
(This article belongs to the Section Organic Synthesis)
Figures

Open AccessArticle Distinctive Anthocyanin Accumulation Responses to Temperature and Natural UV Radiation of Two Field-Grown Vitis vinifera L. Cultivars
Molecules 2015, 20(2), 2061-2080; doi:10.3390/molecules20022061
Received: 9 September 2014 / Accepted: 20 January 2015 / Published: 27 January 2015
Cited by 10 | PDF Full-text (794 KB) | HTML Full-text | XML Full-text
Abstract
The responses of two red grape varieties, Bovale Grande (syn. Carignan) and Cannonau (syn. Grenache), to temperature and natural UV radiation were studied in a three-years field experiment conducted in Sardinia (Italy), under Mediterranean climate conditions. Vines were covered with plastic films with
[...] Read more.
The responses of two red grape varieties, Bovale Grande (syn. Carignan) and Cannonau (syn. Grenache), to temperature and natural UV radiation were studied in a three-years field experiment conducted in Sardinia (Italy), under Mediterranean climate conditions. Vines were covered with plastic films with different transmittances to UV radiation and compared to uncovered controls. Light intensity and spectral composition at the fruit zone were monitored and berry skin temperature was recorded from veraison. Total skin anthocyanin content (TSA) and composition indicated positive but inconsistent effects of natural UV light. Elevated temperatures induced alterations to a greater extent, decreasing TSA and increasing the degree of derivatives acylation. In Cannonau total soluble solids increases were not followed by increasing TSA as in Bovale Grande, due to both lower phenolic potential and higher sensitivity to permanence of high temperatures. Multi linear regression analysis tested the effects of different ranges of temperature as source of variation on anthocyanin accumulation patterns. To estimate the thermal time for anthocyanin accumulation, the use of normal heat hours model had benefit from the addition of predictor variables that take into account the permanence of high (>35 °C) and low (<15 °C and <17 °C) temperatures during ripening. Full article
(This article belongs to the Special Issue Anthocyanins) Printed Edition available
Figures

Open AccessArticle Evaluation of the Radiolabeled Boronic Acid-Based FAP Inhibitor MIP-1232 for Atherosclerotic Plaque Imaging
Molecules 2015, 20(2), 2081-2099; doi:10.3390/molecules20022081
Received: 4 December 2014 / Revised: 29 December 2014 / Accepted: 20 January 2015 / Published: 27 January 2015
Cited by 1 | PDF Full-text (4619 KB) | HTML Full-text | XML Full-text
Abstract
Research towards the non-invasive imaging of atherosclerotic plaques is of high clinical priority as early recognition of vulnerable plaques may reduce the incidence of cardiovascular events. The fibroblast activation protein alpha (FAP) was recently proposed as inflammation-induced protease involved in the process of
[...] Read more.
Research towards the non-invasive imaging of atherosclerotic plaques is of high clinical priority as early recognition of vulnerable plaques may reduce the incidence of cardiovascular events. The fibroblast activation protein alpha (FAP) was recently proposed as inflammation-induced protease involved in the process of plaque vulnerability. In this study, FAP mRNA and protein levels were investigated by quantitative polymerase chain reaction and immunohistochemistry, respectively, in human endarterectomized carotid plaques. A published boronic-acid based FAP inhibitor, MIP-1232, was synthetized and radiolabeled with iodine-125. The potential of this radiotracer to image plaques was evaluated by in vitro autoradiography with human carotid plaques. Specificity was assessed with a xenograft with high and one with low FAP level, grown in mice. Target expression analyses revealed a moderately higher protein level in atherosclerotic plaques than normal arteries correlating with plaque vulnerability. No difference in expression was determined on mRNA level. The radiotracer was successfully produced and accumulated strongly in the FAP-positive SK-Mel-187 melanoma xenograft in vitro while accumulation was negligible in an NCI-H69 xenograft with low FAP levels. Binding of the tracer to endarterectomized tissue was similar in plaques and normal arteries, hampering its use for atherosclerosis imaging. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle Metabolic Profiling of the Uncaria Hook Alkaloid Geissoschizine Methyl Ether in Rat and Human Liver Microsomes Using High-Performance Liquid Chromatography with Tandem Mass Spectrometry
Molecules 2015, 20(2), 2100-2114; doi:10.3390/molecules20022100
Received: 28 November 2014 / Accepted: 19 January 2015 / Published: 27 January 2015
Cited by 4 | PDF Full-text (809 KB) | HTML Full-text | XML Full-text
Abstract
Geissoschizine methyl ether (GM) is an indole alkaloid found in Uncaria hook, which is a galenical constituent of yokukansan, a traditional Japanese medicine. GM has been identified as the active component responsible for anti-aggressive effects. In this study, the metabolic profiling of
[...] Read more.
Geissoschizine methyl ether (GM) is an indole alkaloid found in Uncaria hook, which is a galenical constituent of yokukansan, a traditional Japanese medicine. GM has been identified as the active component responsible for anti-aggressive effects. In this study, the metabolic profiling of GM in rat and human liver microsomes was investigated. Thirteen metabolites of GM were elucidated and identified using a high-performance liquid chromatography with tandem mass spectrometry method, and their molecular structures were proposed on the basis of the characteristics of their precursor ions, product ions, and chromatographic retention times. There were no differences in the metabolites between the rat and human liver microsomes. Among the 13 identified metabolites, there were two demethylation metabolites, one dehydrogenation metabolite, three methylation metabolites, three oxidation metabolites, two water-adduct metabolites, one di-demethylation metabolite, and one water-adduct metabolite followed by oxidation. The metabolic pathways of GM were proposed on the basis of this study. This study will be helpful in understanding the metabolic routes of GM and related Uncaria hook alkaloids, and provide useful information on the pharmacokinetics and pharmacodynamics. This is the first report that describes the separation and identification of GM metabolites in rat and human liver microsomes. Full article
(This article belongs to the Section Metabolites)
Figures

Open AccessArticle Synthesis, Crystal Structure, Spectroscopic Properties and Potential Biological Activities of Salicylate‒Neocuproine Ternary Copper(II) Complexes
Molecules 2015, 20(2), 2115-2137; doi:10.3390/molecules20022115
Received: 1 December 2014 / Accepted: 22 January 2015 / Published: 27 January 2015
Cited by 18 | PDF Full-text (1757 KB) | HTML Full-text | XML Full-text
Abstract
Mixed ligand copper(II) complexes containing derivatives of salicylic acid and heterocyclic ligands with nitrogen donor atoms have been the subject of various studies and reviews. In this paper, synthesis and characterization of the ternary copper(II) complexes of neocuproine (2,9-dimethyl-1,10-phenanthroline, Neo) and salicylate ligands
[...] Read more.
Mixed ligand copper(II) complexes containing derivatives of salicylic acid and heterocyclic ligands with nitrogen donor atoms have been the subject of various studies and reviews. In this paper, synthesis and characterization of the ternary copper(II) complexes of neocuproine (2,9-dimethyl-1,10-phenanthroline, Neo) and salicylate ligands (Sal) are reported. In addition, the crystal structures of ([Cu(H2O)(5-Cl-Sal)(Neo)] (1), [Cu(μ-Sal)(Neo)]2 (2), Cu2(μ-5-Cl-Sal)(5-Cl-HSal)2(Neo)2]·EtOH (3)) were determined. In order to compare structural and biological properties of the prepared complexes, spectroscopic and biological studies were performed. Results of X-ray diffraction show that prepared complexes form three types of crystal structures in a given system: monomeric, dimeric and dinuclear complex. The preliminary study on the DNA cleavage activity has shown that the complexes under study behave as the chemical nucleases in the presence of added hydrogen peroxide with slight differences in the activity (1 > 2 > 3). The complexes 1 and 2 exhibited nuclease activity itself indicating the interaction of complexes with the DNA. It has been proposed that the enhanced destructive effect of the complexes 1 and 2 on the DNA is a result of two possible mechanisms of action: (i) the conversion of closed circular DNA (form I) to the nicked DNA (form II) caused by the copper complex itself and (ii) damage of DNA by Reactive Oxygen Species (ROS)—products of the interaction of copper with hydrogen peroxide by means of Fenton reaction (hydroxyl radicals). Thus the biological activity of the prepared Cu(II) complexes containing derivatives of salicylic acid and phenanthroline molecules is substantiated by two independent mechanisms. While derivatives of salicylic acids in the coordination sphere of copper complexes are responsible for radical-scavenging activity (predominantly towards superoxide radical anion), the presence of chelating ligand 2,9-dimethyl-1,10-phenanthroline significantly enhances capability of Cu(II) complexes binding to DNA via intercalation. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle New Lignans and Iridoid Glycosides from Dipsacus asper Wall
Molecules 2015, 20(2), 2165-2175; doi:10.3390/molecules20022165
Received: 7 January 2015 / Revised: 20 January 2015 / Accepted: 22 January 2015 / Published: 28 January 2015
Cited by 3 | PDF Full-text (788 KB) | HTML Full-text | XML Full-text
Abstract
Six new compounds, including four new lignans, dipsalignan A (1), B–D (35), and two new bis-iridoid glycoside dimmers, dipsanosides M (7) and N (8), together with two known compounds (2) and
[...] Read more.
Six new compounds, including four new lignans, dipsalignan A (1), B–D (35), and two new bis-iridoid glycoside dimmers, dipsanosides M (7) and N (8), together with two known compounds (2) and (6), have been isolated from the roots of Dipsacus asper Wall. Their structures were established on the basis of spectroscopic data (MS, 1D, 2D NMR, and CD) and chemical methods. All the isolated compounds were tested against human immunodeficiency virus-1 (HIV-1) integrase inhibition activities, and only compounds 1, 2, 7, and 8 displayed weak activities. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle The Content of Phenolic Compounds in Leaf Tissues of Aesculus glabra and Aesculus parviflora Walt.
Molecules 2015, 20(2), 2176-2189; doi:10.3390/molecules20022176
Received: 20 November 2014 / Revised: 15 December 2014 / Accepted: 29 December 2014 / Published: 28 January 2015
Cited by 6 | PDF Full-text (1351 KB) | HTML Full-text | XML Full-text
Abstract
In plants, flavonoids play an important role in biological processes. They are involved in UV-scavenging, fertility and disease resistance. Therefore, in this study, we attempted to quantify and characterize phenolic compounds in Aesculus parviflora Walt. leaves and Aesculus glabra leaves partly suffering from
[...] Read more.
In plants, flavonoids play an important role in biological processes. They are involved in UV-scavenging, fertility and disease resistance. Therefore, in this study, we attempted to quantify and characterize phenolic compounds in Aesculus parviflora Walt. leaves and Aesculus glabra leaves partly suffering from attack by a leaf mining insect (C. ohridella). A total of 28 phenolic compounds belonging to the hydroxycinnamic acid, flavan-3-ols and flavonol groups were identified and quantified in Aesculus parviflora and A. glabra leaf extracts. Significantly decreased concentrations of some phenolic compounds, especially of flavan-3-ols, were observed in infected leaves compared to the non-infected ones. Additionally, a higher content of polymeric procyanidins in leaves of Aesculus parviflora than in Aesculus glabra may explain their greater resistance to C. ohridella insects. Full article
Figures

Open AccessArticle Characterisation of Mediterranean Grape Pomace Seed and Skin Extracts: Polyphenolic Content and Antioxidant Activity
Molecules 2015, 20(2), 2190-2207; doi:10.3390/molecules20022190
Received: 25 November 2014 / Revised: 8 January 2015 / Accepted: 19 January 2015 / Published: 29 January 2015
Cited by 18 | PDF Full-text (724 KB) | HTML Full-text | XML Full-text
Abstract
Grape pomace seeds and skins from different Mediterranean varieties (Grenache [GRE], Syrah [SYR], Carignan [CAR], Mourvèdre [MOU] and Alicante [ALI]) were extracted using water and water/ethanol 70% in order to develop edible extracts (an aqueous extract [EAQ] and a 70% hydro-alcoholic extract [EA70])
[...] Read more.
Grape pomace seeds and skins from different Mediterranean varieties (Grenache [GRE], Syrah [SYR], Carignan [CAR], Mourvèdre [MOU] and Alicante [ALI]) were extracted using water and water/ethanol 70% in order to develop edible extracts (an aqueous extract [EAQ] and a 70% hydro-alcoholic extract [EA70]) for potential use in nutraceutical or cosmetic formulations. In this study, global content (total polyphenols, total anthocyanins and total tannins), flavan-3-ols and anthocyanins were assessed using HPLC-UV-Fluo-MSn. In addition, extract potential was evaluated by four different assays: Oxygen Radical Absorbance Capacity (ORAC), Ferric Reducing Antioxidant Potential assay (FRAP), Trolox equivalent antioxidant capacity (TEAC) or ABTS assay and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. As expected, seed pomace extracts contained higher amounts of polyphenols then skin pomace extracts. Indeed, seeds from Syrah contained a particularly important amount of total polyphenols and tannins in both type of extract (up to 215.84 ± 1.47 mg of gallic acid equivalent [GAE]/g dry weight (DW) and 455.42 ± 1.84 mg/g DW, respectively). These extracts also expressed the highest antioxidant potential with every test. For skins, the maximum total phenolic was found in Alicante EAQ (196.71 ± 0.37 mg GAE/g DW) and in Syrah EA70 (224.92 ± 0.18 mg GAE/g DW). Results obtained in this article constitute a useful tool for the pre-selection of grape pomace seed and skin extracts for nutraceutical purposes. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
Open AccessArticle A Facile Ionic Liquid Promoted Synthesis, Cholinesterase Inhibitory Activity and Molecular Modeling Study of Novel Highly Functionalized Spiropyrrolidines
Molecules 2015, 20(2), 2296-2309; doi:10.3390/molecules20022296
Received: 17 November 2014 / Revised: 8 January 2015 / Accepted: 23 January 2015 / Published: 29 January 2015
Cited by 11 | PDF Full-text (758 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of novel dimethoxyindanone embedded spiropyrrolidines were synthesized in ionic liquid, [bmim]Br and were evaluated for their inhibitory activities towards cholinesterases. Among the spiropyrrolidines, compound 4f exhibited the most potent activity with an IC50 value of 1.57 µM against acethylcholinesterase (AChE).
[...] Read more.
A series of novel dimethoxyindanone embedded spiropyrrolidines were synthesized in ionic liquid, [bmim]Br and were evaluated for their inhibitory activities towards cholinesterases. Among the spiropyrrolidines, compound 4f exhibited the most potent activity with an IC50 value of 1.57 µM against acethylcholinesterase (AChE). Molecular docking simulation for the most active compound was employed with the aim of disclosing its binding mechanism to the active site of AChE receptor. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle Soy Isoflavones in Nutritionally Relevant Amounts Have Varied Nutrigenomic Effects on Adipose Tissue
Molecules 2015, 20(2), 2310-2322; doi:10.3390/molecules20022310
Received: 25 November 2014 / Revised: 11 December 2014 / Accepted: 22 January 2015 / Published: 30 January 2015
Cited by 6 | PDF Full-text (909 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Soy consumption has been suggested to afford protection from cardiovascular disease (CVD). Indeed, accumulated albeit controversial evidence suggests that daily consumption of ≥25 g of soy protein with its associated phytochemicals intact can improve lipid profiles in hypercholesterolemic humans. However, the belief that
[...] Read more.
Soy consumption has been suggested to afford protection from cardiovascular disease (CVD). Indeed, accumulated albeit controversial evidence suggests that daily consumption of ≥25 g of soy protein with its associated phytochemicals intact can improve lipid profiles in hypercholesterolemic humans. However, the belief that soy foods and supplements positively impact human health has become increasingly controversial among the general public because of the reported estrogenic activities of soy isoflavones. In this study, we investigated the nutrigenomic actions of soy isoflavones (in nutritionally-relevant amounts) with a specific focus on the adipose tissue, due to its pivotal role in cardiometabolism. Young C57BL/6 mice were maintained for eight weeks under two different diet regimes: (1) purified control diet; or (2) purified control diet supplemented with 0.45 g% soybean dry purified extract (a genistein/daidzein mix). Soy isoflavones increased plasma total cholesterol concentrations and decreased triglyceride ones. Circulating leptin levels was also increased by soy consumption. Differentially expressed genes in adipose tissue were classified according to their role(s) in cellular or metabolic pathways. Our data show that soy isoflavones, administered in nutritionally-relevant amounts, have diverse nutrigenomic effects on adipose tissue. Taking into account the moderate average exposure to such molecules, their impact on cardiovascular health needs to be further investigated to resolve the issue of whether soy consumption does indeed increase or decrease cardiovascular risk. Full article
Open AccessArticle Preparation of a Titania/X-Zeolite/Porous Glass Composite Photocatalyst Using Hydrothermal and Drop Coating Processes
Molecules 2015, 20(2), 2349-2363; doi:10.3390/molecules20022349
Received: 28 December 2014 / Revised: 15 January 2015 / Accepted: 22 January 2015 / Published: 30 January 2015
Cited by 3 | PDF Full-text (2655 KB) | HTML Full-text | XML Full-text
Abstract
Combinations of TiO2 photocatalysts and various adsorbents have been widely studied for the adsorption and photocatalytic decomposition of gaseous pollutants such as volatile organic compounds (VOCs). Herein, a TiO2-zeolite-porous glass composite was prepared using melt-quenching and partial sintering, hydrothermal treatment,
[...] Read more.
Combinations of TiO2 photocatalysts and various adsorbents have been widely studied for the adsorption and photocatalytic decomposition of gaseous pollutants such as volatile organic compounds (VOCs). Herein, a TiO2-zeolite-porous glass composite was prepared using melt-quenching and partial sintering, hydrothermal treatment, and drop coating for preparation of the porous glass support and X-zeolite and their combination with TiO2, respectively. The obtained composite comprised anatase phase TiO2, X-zeolite, and the porous glass support, which were combined at the micro to nanometer scales. The composite had a relatively high specific surface area of approximately 25 m2/g and exhibited a good adsorption capacity for 2-propanol. These data indicated that utilization of this particular phase-separated glass as the support was appropriate for the formation of the bulk photocatalyst-adsorbent composite. Importantly, the photocatalytic decomposition of adsorbed 2-propanol proceeded under UV light irradiation. The 2-propanol was oxidized to acetone and then trapped by the X-zeolite rather than being released to the atmosphere. Consequently, it was demonstrated that the micrometer-scaled combination of TiO2 and zeolite in the bulk form is very useful for achieving both the removal of gaseous organic pollutants and decreasing the emission of harmful intermediates. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
Open AccessArticle A Sorghum MYB Transcription Factor Induces 3-Deoxyanthocyanidins and Enhances Resistance against Leaf Blights in Maize
Molecules 2015, 20(2), 2388-2404; doi:10.3390/molecules20022388
Received: 14 October 2014 / Accepted: 22 January 2015 / Published: 30 January 2015
Cited by 12 | PDF Full-text (871 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Sorghum responds to the ingress of the fungal pathogen Colletotrichum sublineolum through the biosynthesis of 3-deoxyanthocyanidin phytoalexins at the site of primary infection. Biosynthesis of 3-deoxyanthocyanidins in sorghum requires a MYB transcription factor encoded by yellow seed1 (y1), an orthologue of
[...] Read more.
Sorghum responds to the ingress of the fungal pathogen Colletotrichum sublineolum through the biosynthesis of 3-deoxyanthocyanidin phytoalexins at the site of primary infection. Biosynthesis of 3-deoxyanthocyanidins in sorghum requires a MYB transcription factor encoded by yellow seed1 (y1), an orthologue of the maize gene pericarp color1 (p1). Maize lines with a functional p1 and flavonoid structural genes do not produce foliar 3-deoxyanthocyanidins in response to fungal ingress. To perform a comparative metabolic analysis of sorghum and maize 3-deoxyanthocyanidin biosynthetic pathways, we developed transgenic maize lines expressing the sorghum y1 gene. In maize, the y1 transgene phenocopied p1-regulated pigment accumulation in the pericarp and cob glumes. LC-MS profiling of fungus-challenged Y1-maize leaves showed induction of 3-deoxyanthocyanidins, specifically luteolinidin. Y1-maize plants also induced constitutive and higher levels of flavonoids in leaves. In response to Colletotrichum graminicola, Y1-maize showed a resistance response. Full article
Figures

Open AccessArticle Production and Characterization of Cosmetic Nanoemulsions Containing Opuntia ficus-indica (L.) Mill Extract as Moisturizing Agent
Molecules 2015, 20(2), 2492-2509; doi:10.3390/molecules20022492
Received: 20 November 2014 / Revised: 11 December 2014 / Accepted: 6 January 2015 / Published: 2 February 2015
Cited by 12 | PDF Full-text (752 KB) | HTML Full-text | XML Full-text
Abstract
This study aimed to produce and characterize an oil in water (O/W) nanoemulsion containing Opuntia ficus-indica (L.) Mill hydroglycolic extract, as well as evaluate its preliminary and accelerated thermal stability and moisturizing efficacy. The formulations containing 0.5% of xanthan gum (FX) and 0.5%
[...] Read more.
This study aimed to produce and characterize an oil in water (O/W) nanoemulsion containing Opuntia ficus-indica (L.) Mill hydroglycolic extract, as well as evaluate its preliminary and accelerated thermal stability and moisturizing efficacy. The formulations containing 0.5% of xanthan gum (FX) and 0.5% of xanthan gum and 1% of Opuntia ficus-indica Mill extract (FXE) were white, homogeneous and fluid in aspect. Both formulations were stable during preliminary and accelerated stability tests. FX and FXE presented a pH compatible to skin pH (4.5–6.0); droplet size varying from 92.2 to 233.6 nm; a polydispersion index (PDI) around 0.200 and a zeta potential from −26.71 to −47.01 mV. FXE was able to increase the water content of the stratum corneum for 5 h after application on the forearm. The O/W nanoemulsions containing 1% of Opuntia ficus-indica (L.) Mill extract presented suitable stability for at least for 60 days. Besides, this formulation was able to increase the water content of stratum corneum, showing its moisturizing efficacy. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Propane Dehydrogenation Catalyzed by ZSM-5 Zeolites. A Mechanistic Study Based on the Selective Energy Transfer (SET) Theory
Molecules 2015, 20(2), 2529-2535; doi:10.3390/molecules20022529
Received: 18 November 2014 / Revised: 4 January 2015 / Accepted: 27 January 2015 / Published: 2 February 2015
PDF Full-text (759 KB) | HTML Full-text | XML Full-text
Abstract
Experimentally determined activation energies of propane dehydrogenation catalyzed by ZSM-5 zeolites have been used to test the SET theory. The basis of this theory is that the catalyst system transfers vibrational energy via a resonance process to a specific vibration mode of the
[...] Read more.
Experimentally determined activation energies of propane dehydrogenation catalyzed by ZSM-5 zeolites have been used to test the SET theory. The basis of this theory is that the catalyst system transfers vibrational energy via a resonance process to a specific vibration mode of the reacting molecule. Being excited up to a certain number of vibrational quanta the molecule is brought to reaction. By analyzing the above-mentioned activation energies we found the wave number of this “specific mode” to be 1065 cm−1. This is very close to the rocking vibration of propane (1053 cm−1). We suggest that the propane molecule reacts when excited so that the CH3 group has been forced towards a flat structure with a carbon atom hybridization that is more sp2 than sp3. Consequently there is no way for three H-atoms to bind to the carbon and one of them must leave. This is the starting point of the reaction. The isokinetic temperature of the system was found as Tiso = 727 ± 4 K. From the SET formula for Tiso when both energy-donating (ω) and energy-accepting (ν) vibrations have the same frequency, viz., Tiso = Nhcν/2R, we obtain ν = ω = 1011 ± 6 cm−1. This agrees rather well with the CH3 rocking mode (1053 cm−1) and also with asymmetric “TO4” stretching vibrations of the zeolite structure (ω). Full article
(This article belongs to the Special Issue Zeolite Chemistry)
Open AccessArticle Promoting Effect of Foliage Sprayed Zinc Sulfate on Accumulation of Sugar and Phenolics in Berries of Vitis vinifera cv. Merlot Growing on Zinc Deficient Soil
Molecules 2015, 20(2), 2536-2554; doi:10.3390/molecules20022536
Received: 16 December 2014 / Accepted: 26 January 2015 / Published: 2 February 2015
Cited by 8 | PDF Full-text (951 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The effect of foliage sprayed zinc sulfate on berry development of Vitis vinifera cv. Merlot growing on arid zone Zn-deficient soils was investigated over two consecutive seasons, 2013 and 2014. Initial zinc concentration in soil and vines, photosynthesis at three berry developmental stages,
[...] Read more.
The effect of foliage sprayed zinc sulfate on berry development of Vitis vinifera cv. Merlot growing on arid zone Zn-deficient soils was investigated over two consecutive seasons, 2013 and 2014. Initial zinc concentration in soil and vines, photosynthesis at three berry developmental stages, berry weight, content of total soluble solids, titratable acidity, phenolics and expression of phenolics biosynthetic pathway genes throughout the stages were measured. Foliage sprayed zinc sulfate showed promoting effects on photosynthesis and berry development of vines and the promotion mainly occurred from veraison to maturation. Zn treatments enhanced the accumulation of total soluble solids, total phenols, flavonoids, flavanols, tannins and anthocyanins in berry skin, decreasing the concentration of titratable acidity. Furthermore, foliage sprayed zinc sulfate could significantly influence the expression of phenolics biosynthetic pathway genes throughout berry development, and the results of expression analysis supported the promotion of Zn treatments on phenolics accumulation. This research is the first comprehensive and detailed study about the effect of foliage sprayed Zn fertilizer on grape berry development, phenolics accumulation and gene expression in berry skin, providing a basis for improving the quality of grape and wine in Zn-deficient areas. Full article
Open AccessArticle Synthesis and Antioxidant Activity of Polyhydroxylated trans-Restricted 2-Arylcinnamic Acids
Molecules 2015, 20(2), 2555-2575; doi:10.3390/molecules20022555
Received: 30 October 2014 / Accepted: 26 January 2015 / Published: 2 February 2015
Cited by 4 | PDF Full-text (866 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of sixteen polyhydroxylated trans-restricted 2-arylcinnamic acid analogues 3ap were synthesized through a one-pot reaction between homophthalic anhydrides and various aromatic aldehydes, followed by treatment with BBr3. The structure of the newly synthesized compounds was confirmed by
[...] Read more.
A series of sixteen polyhydroxylated trans-restricted 2-arylcinnamic acid analogues 3ap were synthesized through a one-pot reaction between homophthalic anhydrides and various aromatic aldehydes, followed by treatment with BBr3. The structure of the newly synthesized compounds was confirmed by spectroscopic methods and the configuration around the double bond was unequivocally estimated by means of gated decoupling 13C-NMR spectra. It was shown that the trans-cinnamic acid fragment incorporated into the target compounds’ structure ensures the cis-configuration of the stilbene backbone and prevents further isomerization along the carbon–carbon double bond. The antioxidant activity of compounds 3ap was measured against 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (OH) and superoxide (O2) radicals. The results obtained showed that the tested compounds possess higher activities than natural antioxidants such as protocatechuic acid, caffeic acid and gallic acid. Moreover, it was shown that a combination of two different and independently acting fragments of well-known pharmacological profiles into one covalently bonded hybrid molecule evoke a synergistic effect resulting in higher than expected activity. To rationalize the apparent antioxidant activity and to establish the mechanism of action, a SAR analysis and DFT quantum chemical computations were also performed. Full article
(This article belongs to the Special Issue Cinnamic Acids Hybrids with Biological Interest)
Figures

Open AccessArticle Anti-Tuberculous Activity of Treponemycin Produced by a Streptomyces Strain MS-6-6 Isolated from Saudi Arabia
Molecules 2015, 20(2), 2576-2590; doi:10.3390/molecules20022576
Received: 21 December 2014 / Accepted: 27 January 2015 / Published: 2 February 2015
Cited by 4 | PDF Full-text (1108 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A Streptomyces strain MS-6-6 with promising anti-tuberculous activity was isolated from soil samples in Saudi Arabia. The nucleotide sequence of its 16S rRNA gene (1426 bp) evidenced a 100% similarity to Streptomyces mutabilis. Through an anti-tuberculous activity-guided approach, a polyketide macrolide was
[...] Read more.
A Streptomyces strain MS-6-6 with promising anti-tuberculous activity was isolated from soil samples in Saudi Arabia. The nucleotide sequence of its 16S rRNA gene (1426 bp) evidenced a 100% similarity to Streptomyces mutabilis. Through an anti-tuberculous activity-guided approach, a polyketide macrolide was isolated and identified as treponemycin (TP). The structure of the isolated compound was determined by comprehensive analyses of its 1D and 2D NMR as well as HRESI-MS. In addition to the promising anti-tuberculous activity (MIC = 13.3 µg/mL), TP showed broad spectrum of activity against the Gram positive, Gram negative strains, and Candida albicans. Improvement of TP productivity (150%) was achieved through modification in liquid starch nitrate medium by replacing KNO3 with corn steep liquor and yeast extract or tryptone, and removing CaCO3 and K2HPO4. The follow up of TP percentage as well as its metabolites profile for each media was assessed by LC/DAD/MS. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of Novel Triazoles, Tetrazine, Thiadiazoles and Their Biological Activities
Molecules 2015, 20(2), 2591-2610; doi:10.3390/molecules20022591
Received: 1 December 2014 / Revised: 18 December 2014 / Accepted: 23 January 2015 / Published: 2 February 2015
Cited by 9 | PDF Full-text (1257 KB) | HTML Full-text | XML Full-text
Abstract
An expedient synthesis of novel triazoles, tetrazine and thiadiazoles, using conveniently accessible and commercially available starting materials has been achieved. The synthesized compounds were characterized by spectroscopic and elemental analyses, and screened for their antibacterial activities against four different strains, namely E. coli
[...] Read more.
An expedient synthesis of novel triazoles, tetrazine and thiadiazoles, using conveniently accessible and commercially available starting materials has been achieved. The synthesized compounds were characterized by spectroscopic and elemental analyses, and screened for their antibacterial activities against four different strains, namely E. coli, P. aeruginosa, S. aureus and B. megaterium. In particular, the compounds 5, 24 and 26h exhibited excellent antibacterial activities compared to the reference antibiotic. To get further insight about their behavior, these compounds were tested for their antioxidant activities via SOD-like activity, DPPH free radical scavenging activity, ABST and NO, which showed promising results. Furthermore, these compounds effectively promoted the cleavage of genomic DNA as well, in the absence of any external additives. Full article
(This article belongs to the Section Organic Synthesis)
Figures

Open AccessArticle A Study on the Application of Near Infrared Hyperspectral Chemical Imaging for Monitoring Moisture Content and Water Activity in Low Moisture Systems
Molecules 2015, 20(2), 2611-2621; doi:10.3390/molecules20022611
Received: 8 December 2014 / Revised: 20 January 2015 / Accepted: 22 January 2015 / Published: 3 February 2015
Cited by 4 | PDF Full-text (1057 KB) | HTML Full-text | XML Full-text
Abstract
Moisture content and water activity are key parameters in predicting the stability of low moisture content products. However, conventional methods for moisture content and water activity determination (e.g., loss on drying method, ‎Karl Fischer titration, dew point method) are time consuming, demand specialized
[...] Read more.
Moisture content and water activity are key parameters in predicting the stability of low moisture content products. However, conventional methods for moisture content and water activity determination (e.g., loss on drying method, ‎Karl Fischer titration, dew point method) are time consuming, demand specialized equipment and are not amenable to online processing. For this reason they are typically applied at-line on a limited number of samples. Near infrared hyperspectral chemical imaging is an emerging technique for spatially characterising the spectral properties of samples. Due to the fast acquisition of chemical images, many samples can be evaluated simultaneously, thus providing the potential for online evaluation of samples during processing. In this study, the potential of NIR chemical imaging for predicting the moisture content and water activity of a selection of low moisture content food systems is evaluated. Full article
(This article belongs to the Special Issue Advances of Vibrational Spectroscopic Technologies in Life Sciences)
Open AccessArticle Selective Reduction of Cr(VI) in Chromium, Copper and Arsenic (CCA) Mixed Waste Streams Using UV/TiO2 Photocatalysis
Molecules 2015, 20(2), 2622-2635; doi:10.3390/molecules20022622
Received: 15 December 2014 / Revised: 8 January 2015 / Accepted: 22 January 2015 / Published: 3 February 2015
Cited by 12 | PDF Full-text (1476 KB) | HTML Full-text | XML Full-text
Abstract
The highly toxic Cr(VI) is a critical component in the Chromated Copper Arsenate (CCA) formulations extensively employed as wood preservatives. Remediation of CCA mixed waste and discarded treated wood products is a significant challenge. We demonstrate that UV/TiO2 photocatalysis effectively reduces Cr(VI)
[...] Read more.
The highly toxic Cr(VI) is a critical component in the Chromated Copper Arsenate (CCA) formulations extensively employed as wood preservatives. Remediation of CCA mixed waste and discarded treated wood products is a significant challenge. We demonstrate that UV/TiO2 photocatalysis effectively reduces Cr(VI) to less toxic Cr(III) in the presence of arsenate, As(V), and copper, Cu(II). The rapid conversion of Cr(VI) to Cr(III) during UV/TiO2 photocatalysis occurs over a range of concentrations, solution pH and at different Cr:As:Cu ratios. The reduction follows pseudo-first order kinetics and increases with decreasing solution pH. Saturation of the reaction solution with argon during UV/TiO2 photocatalysis had no significant effect on the Cr(VI) reduction demonstrating the reduction of Cr(VI) is independent of dissolved oxygen. Reduction of Cu(II) and As(V) does not occur under the photocatalytic conditions employed herein and the presence of these two in the tertiary mixtures had a minimal effect on Cr(VI) reduction. The Cr(VI) reduction was however, significantly enhanced by the addition of formic acid, which can act as a hole scavenger and enhance the reduction processes initiated by the conduction band electron. Our results demonstrate UV/TiO2 photocatalysis effectively reduces Cr(VI) in mixed waste streams under a variety of conditions. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
Open AccessArticle Effect of Gedunin on Acute Articular Inflammation and Hypernociception in Mice
Molecules 2015, 20(2), 2636-2657; doi:10.3390/molecules20022636
Received: 19 December 2014 / Revised: 15 January 2015 / Accepted: 24 January 2015 / Published: 3 February 2015
Cited by 3 | PDF Full-text (2335 KB) | HTML Full-text | XML Full-text
Abstract
Gedunin, a natural limonoid from Meliaceae species, has been previously described as an antiinflammatory compound in experimental models of allergic inflammation. Here, we report the antiinflammatory and antinociceptive effects of gedunin in an acute model of articular inflammation induced by zymosan (500 μg/cavity;
[...] Read more.
Gedunin, a natural limonoid from Meliaceae species, has been previously described as an antiinflammatory compound in experimental models of allergic inflammation. Here, we report the antiinflammatory and antinociceptive effects of gedunin in an acute model of articular inflammation induced by zymosan (500 μg/cavity; intra-articular) in C57BL/6 mice. Intraperitoneal (i.p.) pretreatment with gedunin (0.005–5 mg/kg) impaired zymosan-induced edema formation, neutrophil accumulation and hypernociception in mouse knee joints, due to decreased expression of preproET-1 mRNA and production of LTB4, PGE2, TNF-α and IL-6. Mouse post-treatment with gedunin (0.05 mg/kg; i.p.) 1 and 6 h after stimulation also impaired articular inflammation, by reverting edema formation, neutrophil accumulation and the production of lipid mediators, cytokines and endothelin. In addition, gedunin directly modulated the functions of neutrophils and macrophages in vitro. The pre-incubation of neutrophil with gedunin (100 µM) impaired shape change, adhesion to endothelial cells, chemotaxis and lipid body formation triggered by different stimuli. Macrophage pretreatment with gedunin impaired intracellular calcium mobilization, nitric oxide production, inducible nitric oxide synthase expression and induced the expression of the antiinflammatory chaperone heat shock protein 70. Our results demonstrate that gedunin presents remarkable antiinflammatory and anti-nociceptive effects on zymosan-induced inflamed knee joints, modulating different cell populations. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle A Study of the Geo-Herbalism of Evodiae Fructus Based on a Flow-Injection Mass Spectrometric Fingerprinting Method Combined with Chemometrics
Molecules 2015, 20(2), 2658-2667; doi:10.3390/molecules20022658
Received: 21 November 2014 / Revised: 6 January 2015 / Accepted: 29 January 2015 / Published: 3 February 2015
Cited by 1 | PDF Full-text (690 KB) | HTML Full-text | XML Full-text
Abstract
A flow-injection mass spectrometric (FIMS) fingerprinting method in combination with principal component analysis (PCA) was used to study the geo-herbalism of Evodiae Fructus (EF) samples. Twenty four EF samples from different regions in China were collected and analyzed. The PCA scores plot showed
[...] Read more.
A flow-injection mass spectrometric (FIMS) fingerprinting method in combination with principal component analysis (PCA) was used to study the geo-herbalism of Evodiae Fructus (EF) samples. Twenty four EF samples from different regions in China were collected and analyzed. The PCA scores plot showed that the samples from Guizhou Province were scattered in different groups, however, most of the samples from other provinces were basically scattered in the same group. Nine characteristic compounds responsible for the classification of the samples were tentatively characterized. These nine compounds might help differentiating EF samples from different regions. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Synthesis and Evaluation of New 1,5-Diaryl-3-[4-(methyl-sulfonyl)phenyl]-4,5-dihydro-1H-pyrazole Derivatives as Potential Antidepressant Agents
Molecules 2015, 20(2), 2668-2684; doi:10.3390/molecules20022668
Received: 5 January 2015 / Revised: 28 January 2015 / Accepted: 30 January 2015 / Published: 4 February 2015
Cited by 11 | PDF Full-text (819 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In an effort to develop potent antidepressant agents, new pyrazoline derivatives 2as were synthesized and evaluated for their antidepressant-like activity by tail suspension test (TST) and modified forced swimming test (MFST). The effects of the compounds on spontaneous locomotor activity were
[...] Read more.
In an effort to develop potent antidepressant agents, new pyrazoline derivatives 2as were synthesized and evaluated for their antidepressant-like activity by tail suspension test (TST) and modified forced swimming test (MFST). The effects of the compounds on spontaneous locomotor activity were also investigated using an activity cage apparatus. Among these derivatives, compounds 2b, 2d, 2f, 2o, and 2r decreased both horizontal and vertical activity number of the mice. On the other hand, compounds 2a, 2h, 2j, 2k, 2l, 2m, and 2n, which did not induce any significant change in the locomotor activity, significantly shortened the immobility time of mice in TST and MFST, representing the presence of the antidepressant-like effect. Additionally, the same compounds increased the swimming time of mice in MFST without any change in climbing duration, similar to the reference drug fluoxetine (10 mg/kg). In the light of previous papers examining the effects of pyrazolines on central nervous system, this study, once more, pointed out remarkable antidepressant activity potential of pyrazoline derivatives. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle Development and Characterization of Polymorphic Microsatellite Markers (SSRs) for an Endemic Plant, Pseudolarix amabilis (Nelson) Rehd. (Pinaceae)
Molecules 2015, 20(2), 2685-2692; doi:10.3390/molecules20022685
Received: 14 January 2015 / Revised: 21 January 2015 / Accepted: 29 January 2015 / Published: 4 February 2015
Cited by 3 | PDF Full-text (664 KB) | HTML Full-text | XML Full-text
Abstract
Pseudolarix (Pinaceae) is a vulnerable (sensu IUCN) monotypic genus restricted to southeastern China. To better understand levels of genetic diversity, population structure and gene flow among populations of P. amabilis, we developed five compound SSR markers and ten novel polymorphic expressed sequence
[...] Read more.
Pseudolarix (Pinaceae) is a vulnerable (sensu IUCN) monotypic genus restricted to southeastern China. To better understand levels of genetic diversity, population structure and gene flow among populations of P. amabilis, we developed five compound SSR markers and ten novel polymorphic expressed sequence tags (EST) derived microsatellites. The results showed that all 15 loci were polymorphic with the number of alleles per locus ranging from two to seven. The expected and observed heterozygosities varied from 0.169 to 0.752, and 0.000 to 1.000, respectively. The inbreeding coefficient ranged from −0.833 to 1.000. These markers will contribute to research on genetic diversity and population genetic structure of P. amabilis, which in turn will contribute to the species conservation. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Silver Nanoparticles Biosynthesized Using Achillea biebersteinii Flower Extract: Apoptosis Induction in MCF-7 Cells via Caspase Activation and Regulation of Bax and Bcl-2 Gene Expression
Molecules 2015, 20(2), 2693-2706; doi:10.3390/molecules20022693
Received: 18 October 2014 / Revised: 17 November 2014 / Accepted: 5 December 2014 / Published: 5 February 2015
Cited by 23 | PDF Full-text (996 KB) | HTML Full-text | XML Full-text
Abstract
Silver nanoparticles (Ag-NPs), the most popular nanoparticles, possess unique properties. Achillea biebersteinii is a plant of the Asteraceae family rich in active antitumor components. The aim of this research was the characterization and investigation of the cytotoxic properties of Ag-NPs synthesized using A.
[...] Read more.
Silver nanoparticles (Ag-NPs), the most popular nanoparticles, possess unique properties. Achillea biebersteinii is a plant of the Asteraceae family rich in active antitumor components. The aim of this research was the characterization and investigation of the cytotoxic properties of Ag-NPs synthesized using A. biebersteinii flower extract, on a human breast cancer cell line. The Ag-NPs were synthesized after approximately 180 min of reaction at 40 °C, then they were characterized by UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The anti-apoptosis effect of Ag-NPs on the MCF-7 cell line was investigated by MTT assay, DAPI and acridine orange staining and caspase activity. The transcriptional expression of bax, bcl-2, caspase-3, -8 and -9 were also evaluated by RT-PCR. The TEM images revealed that the Ag-NPs morphology had a different shape. The DLS indicated that the average hydrodynamic diameter of the biosynthesized Ag-NPs was around 12 nm. By UV-visible spectroscopy the strongest absorbance peak was observed at 460 nm. The FTIR results also showed interaction between the plant extract and Ag-NPs due to the similarity in the peak patterns. The EDS results showed that Ag-NPs display an absorption peak at 3 keV, indicating the presence of the element silver. The Ag-NPs caused a dose-dependent decrease in cell viability, fragmentation in nucleic acid, inhibited the proliferation and induction of apoptosis on MCF-7 by suppressing specific cell cycle genes, and simulation programmed cell dead genes. Further investigation is required to establish the potential of this novel and promising approach in cancer therapy. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle The Role of Phosphoglycans in the Susceptibility of Leishmania mexicana to the Temporin Family of Anti-Microbial Peptides
Molecules 2015, 20(2), 2775-2785; doi:10.3390/molecules20022775
Received: 11 December 2014 / Accepted: 28 January 2015 / Published: 6 February 2015
Cited by 12 | PDF Full-text (2936 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Natural product antimicrobial peptides (AMPs) have been proposed as promising agents against the Leishmania species, insect vector borne protozoan parasites causing the neglected tropical disease leishmaniasis. However, recent studies have shown that the mammalian pathogenic amastigote form of L. mexicana, a causative
[...] Read more.
Natural product antimicrobial peptides (AMPs) have been proposed as promising agents against the Leishmania species, insect vector borne protozoan parasites causing the neglected tropical disease leishmaniasis. However, recent studies have shown that the mammalian pathogenic amastigote form of L. mexicana, a causative agent of cutaneous leishmaniasis, is resistant to the amphibian-derived temporin family of AMPs when compared to the insect stage promastigote form. The mode of resistance is unknown, however the insect and mammalian stages of Leishmania possess radically different cell surface coats, with amastigotes displaying low (or zero) quantities of lipophosphoglycan (LPG) and proteophosphoglycan (PPG), macromolecules which form thick a glycocalyx in promastigotes. It has been predicted that negatively charged LPG and PPG influence the sensitivity/resistance of promastigote forms to cationic temporins. Using LPG and PPG mutant L. mexicana, and an extended range of temporins, in this study we demonstrated that whilst LPG has little role, PPG is a major factor in promastigote sensitivity to the temporin family of AMPs, possibly due to the conferred anionic charge. Therefore, the lack of PPG seen on the surface of pathogenic amastigote L. mexicana may be implicated in their resistance to these peptides. Full article
Open AccessArticle Scopoletin Protects against Methylglyoxal-Induced Hyperglycemia and Insulin Resistance Mediated by Suppression of Advanced Glycation Endproducts (AGEs) Generation and Anti-Glycation
Molecules 2015, 20(2), 2786-2801; doi:10.3390/molecules20022786
Received: 28 October 2014 / Accepted: 3 February 2015 / Published: 9 February 2015
Cited by 8 | PDF Full-text (3574 KB) | HTML Full-text | XML Full-text
Abstract
Recently, several types of foods and drinks, including coffee, cream, and cake, have been found to result in high methylglyoxal (MG) levels in the plasma, thus causing both nutritional and health concerns. MG can be metabolized by phase-II enzymes in liver through the
[...] Read more.
Recently, several types of foods and drinks, including coffee, cream, and cake, have been found to result in high methylglyoxal (MG) levels in the plasma, thus causing both nutritional and health concerns. MG can be metabolized by phase-II enzymes in liver through the positive regulation of nuclear factor-erythroid 2-related factor 2 (Nrf2). In this study, we investigated the ability of scopoletin (SP) to protect against MG-induced hyperglycemia and insulin resistance. Recently, SP was shown to be a peroxisome proliferator-activated receptor-γ activator to elevate insulin sensitivity. We investigated the effects of oral administration of SP on the metabolic, biochemical, and molecular abnormalities characteristic of type 2 diabetes in MG-treated Wistar rats to understand the potential mechanism of scopoletin for diabetes protection. Our results suggested that SP activated Nrf2 by Ser40 phosphorylation, resulting in the metabolism of MG into d-lactic acid and the inhibition of AGEs generation, which reduced the accumulation of AGEs in the livers of MG-induced rats. In this manner, SP improved the results of the oral glucose tolerance test and dyslipidemia. Moreover, SP also increased the plasma translocation of glucose transporter-2 and promoted Akt phosphorylation caused by insulin treatment in MG-treated FL83B hepatocytes. In contrast, SP effectively suppressed protein tyrosine phosphatase 1B (PTP1B) expression, thereby alleviating insulin resistance. These findings suggest that SP acts as an anti-glycation and anti-diabetic agent, and thus has therapeutic potential for the prevention of diabetes. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessCommunication Novel Zinc-Catalytic Systems for Ring-Opening Polymerization of ε-Caprolactone
Molecules 2015, 20(2), 2816-2827; doi:10.3390/molecules20022816
Received: 17 December 2014 / Accepted: 3 January 2015 / Published: 9 February 2015
Cited by 7 | PDF Full-text (995 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Polycaprolactone (PCL) is a biodegradable synthetic polymer that is currently widely used in many pharmaceutical and medical applications. In this paper we describe the coordination ring-opening polymerization of ε-caprolactone in the presence of two newly synthesized catalytic systems: diethylzinc/gallic acid and diethylzinc/propyl gallate.
[...] Read more.
Polycaprolactone (PCL) is a biodegradable synthetic polymer that is currently widely used in many pharmaceutical and medical applications. In this paper we describe the coordination ring-opening polymerization of ε-caprolactone in the presence of two newly synthesized catalytic systems: diethylzinc/gallic acid and diethylzinc/propyl gallate. The chemical structures of the obtained PCLs were characterized by 1H- or 13C-NMR, FTIR spectroscopy and MALDI TOF mass spectrometry. The average molecular weight of the resulting polyesters was analysed by gel permeation chromatography and a viscosity method. The effects of temperature, reaction time and type of catalytic system on the polymerization process were examined. Linear PCLs with defined average molecular weight were successfully obtained. Importantly, in some cases the presence of macrocyclic products was not observed during the polymerization process. This study provides an effective method for the synthesis of biodegradable polyesters for medical and pharmaceutical applications due to the fact that gallic acid/propyl gallate are commonly used in the pharmaceutical industry. Full article
(This article belongs to the Special Issue Ring-Opening Polymerization)
Open AccessArticle Solvent-Free Copper-Catalyzed Azide-Alkyne Cycloaddition under Mechanochemical Activation
Molecules 2015, 20(2), 2837-2849; doi:10.3390/molecules20022837
Received: 6 January 2015 / Accepted: 2 February 2015 / Published: 9 February 2015
Cited by 11 | PDF Full-text (2682 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The ball-mill-based mechanochemical activation of metallic copper powder facilitates solvent-free alkyne-azide click reactions (CuAAC). All parameters that affect reaction rate (i.e., milling time, revolutions/min, size and milling ball number) have been optimized. This new, efficient, facile and eco-friendly procedure has been
[...] Read more.
The ball-mill-based mechanochemical activation of metallic copper powder facilitates solvent-free alkyne-azide click reactions (CuAAC). All parameters that affect reaction rate (i.e., milling time, revolutions/min, size and milling ball number) have been optimized. This new, efficient, facile and eco-friendly procedure has been tested on a number of different substrates and in all cases afforded the corresponding 1,4-disubstituted 1,2,3-triazole derivatives in high yields and purities. The final compounds were isolated in almost quantitative overall yields after simple filtration, making this procedure facile and rapid. The optimized CuAAC protocol was efficiently applied even with bulky functionalized β-cyclodextrins (β-CD) and scaled-up to 10 g of isolated product. Full article
(This article belongs to the Special Issue Advances in Click Chemistry)
Figures

Open AccessCommunication New Cytotoxic Sesquiterpenoids from Siegesbeckia glabrescens
Molecules 2015, 20(2), 2850-2856; doi:10.3390/molecules20022850
Received: 6 January 2015 / Accepted: 2 February 2015 / Published: 10 February 2015
PDF Full-text (679 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new sesquiterpenoids, siegenolides A (1) and B (2), and two known sesquiterpenes 3 and 4 were isolated from Siegesbeckia glabrescens. Their structures were elucidated by spectroscopic analyses, and they were further evaluated for their cytotoxic activities against
[...] Read more.
Two new sesquiterpenoids, siegenolides A (1) and B (2), and two known sesquiterpenes 3 and 4 were isolated from Siegesbeckia glabrescens. Their structures were elucidated by spectroscopic analyses, and they were further evaluated for their cytotoxic activities against human cancer cells (MCF-7, AsPC-1, SW480, HCT 116, HepG2, HeLa). Compounds 14 showed differential cytotoxic effects on the target cancer cells with IC50 values in the range of 0.9–33.3 μM. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Ring-Opening Polymerization of ε-Caprolactone Initiated by Ganciclovir (GCV) for the Preparation of GCV-Tagged Polymeric Micelles
Molecules 2015, 20(2), 2857-2867; doi:10.3390/molecules20022857
Received: 13 December 2014 / Accepted: 3 February 2015 / Published: 10 February 2015
Cited by 3 | PDF Full-text (1151 KB) | HTML Full-text | XML Full-text
Abstract
Ganciclovir (GCV) is a nucleoside analogue with antiviral activity against herpes viral infections, and the most widely used antiviral to treat cytomegalovirus infections. However, the low bioavailability and short half-life of GCV necessitate the development of a carrier for sustained delivery. In this
[...] Read more.
Ganciclovir (GCV) is a nucleoside analogue with antiviral activity against herpes viral infections, and the most widely used antiviral to treat cytomegalovirus infections. However, the low bioavailability and short half-life of GCV necessitate the development of a carrier for sustained delivery. In this study, guanosine-based GCV was used as the initiator directly in ring-opening polymerization of ε-caprolactone (ε-CL) to form hydrophobic GCV-poly(caprolactone) (GCV-PCL) which was then grafted with hydrophilic chitosan to form amphiphilic copolymers for the preparation of stable micellar nanoparticles. Successful synthesis of GCV-PCL and GCV-PCL-chitosan were verified by 1H-NMR analysis. Self-assembled micellar nanoparticles were characterized by dynamic light scattering and zetasizer with an average size of 117 nm and a positive charge of 24.2 mV. The drug release kinetics of GCV was investigated and cytotoxicity assay demonstrated that GCV-tagged polymeric micelles were non-toxic. Our results showed that GCV could be used directly in the initiation of ring-opening polymerization of ε-CL and non-toxic polymeric micelles for GCV delivery can be formed. Full article
(This article belongs to the Special Issue Ring-Opening Polymerization)
Open AccessArticle Distribution and Evolution of the Lectin Family in Soybean (Glycine max)
Molecules 2015, 20(2), 2868-2891; doi:10.3390/molecules20022868
Received: 28 November 2014 / Accepted: 6 February 2015 / Published: 11 February 2015
Cited by 11 | PDF Full-text (1170 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Lectins are a diverse group of proteins that bind specific carbohydrates and are found throughout all kingdoms. In plants, lectins are involved in a range of important processes such as plant defense and stress signaling. Although the genome sequence of Glycine max (soybean)
[...] Read more.
Lectins are a diverse group of proteins that bind specific carbohydrates and are found throughout all kingdoms. In plants, lectins are involved in a range of important processes such as plant defense and stress signaling. Although the genome sequence of Glycine max (soybean) has been published, little is known about the abundance and expansion patterns of lectin genes in soybean. Using BLAST and hidden Markov models, a total of 359 putative lectin genes have been identified. Furthermore, these sequences could be classified in nine of the twelve plant lectin families identified today. Analysis of the domain organization demonstrated that most of the identified lectin genes encode chimerolectins, consisting of one or multiple lectin domains combined with other known protein domains. Both tandem and segmental duplication events have contributed to the expansion of the lectin gene family. These data provide a detailed understanding of the domain architecture and molecular evolution of the lectin gene family in soybean. Full article
(This article belongs to the Special Issue Lectins)
Open AccessArticle Synthesis and Molecular Structure of the 5-Methoxycarbonylpentyl α-Glycoside of the Upstream, Terminal Moiety of the O-Specific Polysaccharide of Vibrio cholerae O1, Serotype Inaba
Molecules 2015, 20(2), 2892-2902; doi:10.3390/molecules20022892
Received: 14 January 2015 / Accepted: 5 February 2015 / Published: 11 February 2015
Cited by 1 | PDF Full-text (1919 KB) | HTML Full-text | XML Full-text
Abstract
The trimethylsilyl trifluoromethanesulfonate (TMSOTf)-catalyzed reaction of methyl 6-hydroxyhexanoate with 3-O-benzyl-4-(2,4-di-O-acetyl-3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-2-O-levulinoyl-α-d-mannopyranosyl trichloroacetimidate followed by a two-step deprotection (hydrogenolysis over Pd/C catalyst and Zemplén deacylation, to simultaneously remove the acetyl and levulinoyl groups) gave 5-(methoxycarbonyl)pentyl 4-(3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-α-D-mannopyranoside. The
[...] Read more.
The trimethylsilyl trifluoromethanesulfonate (TMSOTf)-catalyzed reaction of methyl 6-hydroxyhexanoate with 3-O-benzyl-4-(2,4-di-O-acetyl-3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-2-O-levulinoyl-α-d-mannopyranosyl trichloroacetimidate followed by a two-step deprotection (hydrogenolysis over Pd/C catalyst and Zemplén deacylation, to simultaneously remove the acetyl and levulinoyl groups) gave 5-(methoxycarbonyl)pentyl 4-(3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-α-D-mannopyranoside. The structure of the latter, for which crystals were obtained in the analytically pure state for the first time, followed from its NMR and high-resolution mass spectra and was confirmed by X-ray crystallography. The molecule has two approximately linear components; a line through the aglycon intersects a line through the mannosyl and tetronylamido groups at 120°. The crystal packing separates the aglycon groups from the tetronylamido and mannosyl groups, with only C-H…O hydrogen bonding among the aglycon groups and N-H…O, O-H…O and C-H…O links among the tetronylamido and mannosyl groups. A carbonyl oxygen atom accepts the strongest O-H…O hydrogen bond and two strong C-H…O hydrogen bonds. The geometric properties were compared with those of related molecules. Full article
(This article belongs to the Special Issue Oligosaccharides and Glyco-Conjugates)
Open AccessArticle Enzymatic Hydrolysis of Oleuropein from Olea europea (Olive) Leaf Extract and Antioxidant Activities
Molecules 2015, 20(2), 2903-2921; doi:10.3390/molecules20022903
Received: 9 December 2014 / Accepted: 30 January 2015 / Published: 11 February 2015
Cited by 14 | PDF Full-text (2917 KB) | HTML Full-text | XML Full-text
Abstract
Oleuropein (OE), the main polyphenol in olive leaf extract, is likely to decompose into hydroxytyrosol (HT) and elenolic acid under the action of light, acid, base, high temperature. In the enzymatic process, the content of OE in olive leaf extract and enzyme are
[...] Read more.
Oleuropein (OE), the main polyphenol in olive leaf extract, is likely to decompose into hydroxytyrosol (HT) and elenolic acid under the action of light, acid, base, high temperature. In the enzymatic process, the content of OE in olive leaf extract and enzyme are key factors that affect the yield of HT. A selective enzyme was screened from among 10 enzymes with a high OE degradation rate. A single factor (pH, temperature, time, enzyme quantity) optimization process and a Box-Behnken design were studied for the enzymatic hydrolysis of 81.04% OE olive leaf extract. Additionally, enzymatic hydrolysis results with different substrates (38.6% and 81.04% OE) were compared and the DPPH antioxidant properties were also evaluated. The result showed that the performance of hydrolysis treatments was best using hemicellulase as a bio-catalyst, and the high purity of OE in olive extract was beneficial to biotransform OE into HT. The optimal enzymatic conditions for achieving a maximal yield of HT content obtained by the regression were as follows: pH 5, temperature 55 °C and enzyme quantity 55 mg. The experimental result was 11.31% ± 0.15%, and the degradation rate of OE was 98.54%. From the present investigation of the antioxidant activity determined by the DPPH method, the phenol content and radical scavenging effect were both decreased after enzymatic hydrolysis by hemicellulase. However, a high antioxidant activity of the ethyl acetate extract enzymatic hydrolysate (IC50 = 41.82 μg/mL) was demonstated. The results presented in this work suggested that hemicellulase has promising and attractive properties for industrial production of HT, and indicated that HT might be a valuable biological component for use in pharmaceutical products and functional foods. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Facile Access to Unnatural Dipeptide-Alcohols Based on cis-2,5-Disubstituted Pyrrolidines
Molecules 2015, 20(2), 2922-2930; doi:10.3390/molecules20022922
Received: 11 December 2014 / Accepted: 30 January 2015 / Published: 11 February 2015
PDF Full-text (714 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Well-defined unnatural dipeptide-alcohols based on a cis-2,5-disubstitued pyrrolidine backbone were synthesized from commercially available starting materials meso-diethyl-2,5-dibromoadipate, (S)-(−)-1-phenylethylamine, and phenylalaninol. The structures of these unnatural dipeptide-alcohols are supported by HRMS, 1H- and 13C-NMR spectroscopy. These unnatural dipeptide-alcohols
[...] Read more.
Well-defined unnatural dipeptide-alcohols based on a cis-2,5-disubstitued pyrrolidine backbone were synthesized from commercially available starting materials meso-diethyl-2,5-dibromoadipate, (S)-(−)-1-phenylethylamine, and phenylalaninol. The structures of these unnatural dipeptide-alcohols are supported by HRMS, 1H- and 13C-NMR spectroscopy. These unnatural dipeptide-alcohols can act as building blocks for peptidomimetics. Full article
Figures

Open AccessArticle Inhibitory Effects of Neochamaejasmin B on P-Glycoprotein in MDCK-hMDR1 Cells and Molecular Docking of NCB Binding in P-Glycoprotein
Molecules 2015, 20(2), 2931-2948; doi:10.3390/molecules20022931
Received: 1 December 2014 / Accepted: 4 February 2015 / Published: 11 February 2015
Cited by 5 | PDF Full-text (3358 KB) | HTML Full-text | XML Full-text
Abstract
Stellera chamaejasme L. (Thymelaeaceae) is widely distributed in Mongolia, Tibet and the northern parts of China. Its roots are commonly used as “Langdu”, which is embodied in the Pharmacopoeia of the P.R. China (2010) as a toxic Traditional Chinese Medicine. It is claimed
[...] Read more.
Stellera chamaejasme L. (Thymelaeaceae) is widely distributed in Mongolia, Tibet and the northern parts of China. Its roots are commonly used as “Langdu”, which is embodied in the Pharmacopoeia of the P.R. China (2010) as a toxic Traditional Chinese Medicine. It is claimed to have antivirus, antitumor and antibacterial properties in China and other Asian countries. Studies were carried out to characterize the inhibition of neochamaejasmin B (NCB) on P-glycoprotein (P-gp, ABCB1, MDR1). Rhodamine-123 (R-123) transport and accumulation studies were performed in MDCK-hMDR1 cells. ABCB1 (MDR1) mRNA gene expression and P-gp protein expression were analyzed. Binding selectivity studies based on molecular docking were explored. R-123 transport and accumulation studies in MDCK-hMDR1 cells indicated that NCB inhibited the P-gp-mediated efflux in a concentration-dependent manner. RT-PCR and Western blot demonstrated that the P-gp expression was suppressed by NCB. To investigate the inhibition type of NCB on P-gp, Ki and Ki values were determined by double-reciprocal plots in R-123 accumulation studies. Since Ki was greater than Ki, the inhibition of NCB on P-gp was likely a mixed type of competitive and non-competitive inhibition. The results were confirmed by molecular docking in our current work. The docking data indicated that NCB had higher affinity to P-gp than to Lig1 ((S)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one). Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Acid Catalyzed Alcoholysis of Sulfinamides: Unusual Stereochemistry, Kinetics and a Question of Mechanism Involving Sulfurane Intermediates and Their Pseudorotation
Molecules 2015, 20(2), 2949-2972; doi:10.3390/molecules20022949
Received: 19 December 2014 / Accepted: 3 February 2015 / Published: 11 February 2015
Cited by 4 | PDF Full-text (1169 KB) | HTML Full-text | XML Full-text
Abstract
The synthesis of optically active sulfinic acid esters has been accomplished by the acid catalyzed alcoholysis of optically active sulfinamides. Sulfinates are formed in this reaction with a full or predominant inversion of configuration at chiral sulfur or with predominant retention of configuration.
[...] Read more.
The synthesis of optically active sulfinic acid esters has been accomplished by the acid catalyzed alcoholysis of optically active sulfinamides. Sulfinates are formed in this reaction with a full or predominant inversion of configuration at chiral sulfur or with predominant retention of configuration. The steric course of the reaction depends mainly on the size of the dialkylamido group in the sulfinamides and of the alcohols used as nucleophilic reagents. It has been found that bulky reaction components preferentially form sulfinates with retention of configuration. It has been demonstrated that the stereochemical outcome of the reaction can be changed from inversion to retention and vice versa by adding inorganic salts to the acidic reaction medium. The unusual stereochemistry of this typical bimolecular nucleophilic substitution reaction, as confirmed by kinetic measurements, has been rationalized in terms of the addition-elimination mechanism, A-E, involving sulfuranes as intermediates which undergo pseudorotations. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Figures

Open AccessArticle Structural Analysis of Metabolites of Asiatic Acid and Its Analogue Madecassic Acid in Zebrafish Using LC/IT-MSn
Molecules 2015, 20(2), 3001-3019; doi:10.3390/molecules20023001
Received: 1 December 2014 / Revised: 26 January 2015 / Accepted: 4 February 2015 / Published: 12 February 2015
Cited by 8 | PDF Full-text (1075 KB) | HTML Full-text | XML Full-text
Abstract
Although zebrafish has become a significant animal model for drug discovery and screening, drug metabolism in zebrafish remains largely unknown. Asiatic acid (AA) and madecassic acid (MA), two natural pentacyclic triterpenoids mainly obtained from Centella asiatica (L.) Urban, have been found to possess
[...] Read more.
Although zebrafish has become a significant animal model for drug discovery and screening, drug metabolism in zebrafish remains largely unknown. Asiatic acid (AA) and madecassic acid (MA), two natural pentacyclic triterpenoids mainly obtained from Centella asiatica (L.) Urban, have been found to possess many pharmacological effects. This study is to probe the metabolic capability of zebrafish via investigation of the drug metabolism of AA and MA in zebrafish, using a sensitive LC/IT-MSn method. In addition, the main fragmentation pathways of AA and MA were reported for the first time. Nineteen metabolites of AA and MA were firstly identified after zebrafish was exposed to the drug, which all were the phase I metabolites and mainly formed from hydroxylation, dehydrogenation, hydroxylation and dehydrogenation, dihydroxylation and dehydrogenation, and dehydroxylation reaction. The results indicated that zebrafish possessed strong metabolic capacity, and the metabolites of AA and MA were formed via similar metabolic pathways and well matched with the known metabolic rules in vivo and in vitro, which supports the widely use of this system in drug metabolism research. This investigation would also contribute to the novel information on the structural elucidation, in vivo metabolites and metabolic mechanism of pentacyclic triterpenoids. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle New Pregnane Glycosides from Gymnema sylvestre
Molecules 2015, 20(2), 3050-3066; doi:10.3390/molecules20023050
Received: 31 December 2014 / Accepted: 5 February 2015 / Published: 12 February 2015
Cited by 2 | PDF Full-text (859 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four new pregnane glycosides 14 were isolated from the ethanol extract of the stem of Gymnema sylvestre and named gymsylvestrosides A–D. Hydrolysis of compound 1 under the catalysis of Aspergilus niger β-glucosidase afforded compound 5 (gymsylvestroside E). Their structures were determined
[...] Read more.
Four new pregnane glycosides 14 were isolated from the ethanol extract of the stem of Gymnema sylvestre and named gymsylvestrosides A–D. Hydrolysis of compound 1 under the catalysis of Aspergilus niger β-glucosidase afforded compound 5 (gymsylvestroside E). Their structures were determined by spectroscopic methods such as HRESIMS, 1D and 2D NMR, as well as HMQC-TOCSY experiment. Compounds 14 were screened for Saccharomyces cerevisiae α-glucosidase inhibitory activity. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Novel Orally Active Analgesic and Anti-Inflammatory Cyclohexyl-N-Acylhydrazone Derivatives
Molecules 2015, 20(2), 3067-3088; doi:10.3390/molecules20023067
Received: 19 December 2014 / Accepted: 3 February 2015 / Published: 12 February 2015
Cited by 9 | PDF Full-text (1404 KB) | HTML Full-text | XML Full-text
Abstract
The N-acylhydrazone (NAH) moiety is considered a privileged structure, being present in many compounds with diverse pharmacological activities. Among the activities attributed to NAH derivatives anti-inflammatory and analgesic ones are recurrent. As part of a research program aiming at the design of
[...] Read more.
The N-acylhydrazone (NAH) moiety is considered a privileged structure, being present in many compounds with diverse pharmacological activities. Among the activities attributed to NAH derivatives anti-inflammatory and analgesic ones are recurrent. As part of a research program aiming at the design of new analgesic and anti-inflammatory lead-candidates, a series of cyclohexyl-N-acylhydrazones 1026 were structurally designed from molecular modification on the prototype LASSBio-294, representing a new class of cycloalkyl analogues. Compounds 1026 and their conformationally restricted analogue 9 were synthetized and evaluated as analgesic and anti-inflammatory agents in classical pharmacologic protocols. The cyclohexyl-N-acylhydrazones 1026 and the cyclohexenyl analogue 9 showed great anti-inflammatory and/or analgesic activities, but compound 13 stood out as a new prototype to treat acute and chronic painful states due to its important analgesic activity in a neuropathic pain model. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle Selective C–C Coupling Reaction of Dimethylphenol to Tetramethyldiphenoquinone Using Molecular Oxygen Catalyzed by Cu Complexes Immobilized in Nanospaces of Structurally-Ordered Materials
Molecules 2015, 20(2), 3089-3106; doi:10.3390/molecules20023089
Received: 15 December 2014 / Accepted: 5 February 2015 / Published: 12 February 2015
Cited by 3 | PDF Full-text (1466 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two high-performance Cu catalysts were successfully developed by immobilization of Cu ions in the nanospaces of poly(propylene imine) (PPI) dendrimer and magadiite for the selective C–C coupling of 2,6-dimethylphenol (DMP) to 3,3',5,5'-tetramethyldiphenoquinone (DPQ) with O2 as a green oxidant. The PPI dendrimer
[...] Read more.
Two high-performance Cu catalysts were successfully developed by immobilization of Cu ions in the nanospaces of poly(propylene imine) (PPI) dendrimer and magadiite for the selective C–C coupling of 2,6-dimethylphenol (DMP) to 3,3',5,5'-tetramethyldiphenoquinone (DPQ) with O2 as a green oxidant. The PPI dendrimer encapsulated Cu ions in the internal nanovoids to form adjacent Cu species, which exhibited significantly high catalytic activity for the regioselective coupling reaction of DMP compared to previously reported enzyme and metal complex catalysts. The magadiite-immobilized Cu complex acted as a selective heterogeneous catalyst for the oxidative C–C coupling of DMP to DPQ. This heterogeneous catalyst was recoverable from the reaction mixture by simple filtration, reusable without loss of efficiency, and applicable to a continuous flow reactor system. Detailed characterization using ultraviolet-visible (UV-vis), Fourier transform infrared (FTIR), electronic spin resonance (ESR), and X-ray absorption fine structure (XAFS) spectroscopies and the reaction mechanism investigation revealed that the high catalytic performances of these Cu catalysts were ascribed to the adjacent Cu species generated within the nanospaces of the PPI dendrimer and magadiite. Full article
(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)
Figures

Open AccessArticle Urine and Serum Metabolite Profiling of Rats Fed a High-Fat Diet and the Anti-Obesity Effects of Caffeine Consumption
Molecules 2015, 20(2), 3107-3128; doi:10.3390/molecules20023107
Received: 31 December 2014 / Revised: 9 February 2015 / Accepted: 9 February 2015 / Published: 13 February 2015
Cited by 13 | PDF Full-text (830 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, we investigated the clinical changes induced by a high fat diet (HFD) and caffeine consumption in a rat model. The mean body weight of the HFD with caffeine (HFDC)-fed rat was decreased compared to that of the HFD-fed rat without
[...] Read more.
In this study, we investigated the clinical changes induced by a high fat diet (HFD) and caffeine consumption in a rat model. The mean body weight of the HFD with caffeine (HFDC)-fed rat was decreased compared to that of the HFD-fed rat without caffeine. The levels of cholesterol, triglycerides (TGs), and free fatty acid, as well as the size of adipose tissue altered by HFD, were improved by caffeine consumption. To investigate the metabolites that affected the change of the clinical factors, the urine and serum of rats fed a normal diet (ND), HFD, and HFDC were analyzed using ultra performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS), gas chromatography (GC-TOF-MS), and linear trap quadruple mass spectrometry (LTQ-XL-MS) combined with multivariate analysis. A total of 68 and 52 metabolites were found to be different in urine and serum, respectively. After being fed caffeine, some glucuronide-conjugated compounds, lysoPCs, CEs, DGs, TGs, taurine, and hippuric acid were altered compared to the HFD group. In this study, caffeine might potentially inhibit HFD-induced obesity and we suggest possible biomarker candidates using MS-based metabolite profiling. Full article
Figures

Open AccessArticle Potential Quality Evaluation Method for Radix Astragali Based on Sweetness Indicators
Molecules 2015, 20(2), 3129-3145; doi:10.3390/molecules20023129
Received: 6 December 2014 / Accepted: 28 January 2015 / Published: 13 February 2015
Cited by 2 | PDF Full-text (3316 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Sweetness is a traditional sensory indicator used to evaluate the quality of the popular Chinese herb Radix Astragali (RA). RA roots with strong sweetness are considered to be of good quality. However, neither a thorough analysis of the component(s) contributing to RA sweetness,
[...] Read more.
Sweetness is a traditional sensory indicator used to evaluate the quality of the popular Chinese herb Radix Astragali (RA). RA roots with strong sweetness are considered to be of good quality. However, neither a thorough analysis of the component(s) contributing to RA sweetness, nor a scientific investigation of the reliability of this indicator has been conducted to date. In this study, seven kinds of sweetness components were identified in RA and a quality evaluation method based on these components was established and used to characterize the quality of 48 RA samples. The sweetness evaluation method of RA was first built based on the sweetness components, and a comprehensive evaluation index commonly used in quality control of RA was also derived, which was based on the contents of four indicators (astragaloside IV, calycosin glucoside, polysaccharides and extracts). After evaluating the correlation of these indexes the results showed that the level of sweetness exhibited a strong positive correlation with the proposed comprehensive index. Our results indicate that sweetness is one of the most important quality attributes of RA and thus provide a scientific basis for the utility of the sweetness indicator in quality assessment of this Chinese herb. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Spectroscopic (FT-IR, FT-Raman, 1H- and 13C-NMR), Theoretical and Microbiological Study of trans o-Coumaric Acid and Alkali Metal o-Coumarates
Molecules 2015, 20(2), 3146-3169; doi:10.3390/molecules20023146
Received: 20 October 2014 / Revised: 29 December 2014 / Accepted: 19 January 2015 / Published: 13 February 2015
Cited by 13 | PDF Full-text (2646 KB) | HTML Full-text | XML Full-text
Abstract
This work is a continuation of research on a correlation between the molecular structure and electronic charge distribution of phenolic compounds and their biological activity. The influence of lithium, sodium, potassium, rubidium and cesium cations on the electronic system of trans o-coumaric
[...] Read more.
This work is a continuation of research on a correlation between the molecular structure and electronic charge distribution of phenolic compounds and their biological activity. The influence of lithium, sodium, potassium, rubidium and cesium cations on the electronic system of trans o-coumaric (2-hydroxy-cinnamic) acid was studied. We investigated the relationship between the molecular structure of the tested compounds and their antimicrobial activity. Complementary molecular spectroscopic techniques such as infrared (FT-IR), Raman (FT-Raman), ultraviolet-visible (UV-VIS) and nuclear magnetic resonance (1H- and 13C-NMR) were applied. Structures of the molecules were optimized and their structural characteristics were calculated by the density functional theory (DFT) using the B3LYP method with 6-311++G** as a basis set. Geometric and magnetic aromaticity indices, atomic charges, dipole moments and energies were also calculated. Theoretical parameters were compared to the experimental characteristics of investigated compounds. Correlations between certain vibrational bands and some metal parameters, such as electronegativity, ionization energy, atomic and ionic radius, were found. The microbial activity of studied compounds was tested against Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus, Proteus vulgaris and Candida albicans. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Synthesis and Antimicrobial Activity of N-Substituted-β-amino Acid Derivatives Containing 2-Hydroxyphenyl, Benzo[b]phenoxazine and Quinoxaline Moieties
Molecules 2015, 20(2), 3170-3189; doi:10.3390/molecules20023170
Received: 8 January 2015 / Revised: 4 February 2015 / Accepted: 4 February 2015 / Published: 13 February 2015
Cited by 7 | PDF Full-text (680 KB) | HTML Full-text | XML Full-text
Abstract
3-[(2-Hydroxyphenyl)amino]butanoic and 3-[(2-hydroxy-5-methyl(chloro)phenyl)amino]butanoic acids were converted to a series of derivatives containing hydrazide, pyrrole and chloroquinoxaline moieties. The corresponding benzo[b]phenoxazine derivatives were synthesized by the reaction of the obtained compounds with 2,3-dichloro-1,4-naphthoquinone. Five of the synthesized compounds exhibited good antimicrobial activity
[...] Read more.
3-[(2-Hydroxyphenyl)amino]butanoic and 3-[(2-hydroxy-5-methyl(chloro)phenyl)amino]butanoic acids were converted to a series of derivatives containing hydrazide, pyrrole and chloroquinoxaline moieties. The corresponding benzo[b]phenoxazine derivatives were synthesized by the reaction of the obtained compounds with 2,3-dichloro-1,4-naphthoquinone. Five of the synthesized compounds exhibited good antimicrobial activity against Staphylococcus aureus and Mycobacterium luteum, whereas three compounds showed significant antifungal activity against Candida tenuis and Aspergillus niger. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Inhibitory Effect of Triterpenoids from Dillenia serrata (Dilleniaceae) on Prostaglandin E2 Production and Quantitative HPLC Analysis of Its Koetjapic Acid and Betulinic Acid Contents
Molecules 2015, 20(2), 3206-3220; doi:10.3390/molecules20023206
Received: 13 November 2014 / Accepted: 30 January 2015 / Published: 16 February 2015
Cited by 4 | PDF Full-text (1667 KB) | HTML Full-text | XML Full-text
Abstract
The crude methanol extracts and fractions of the root and stem barks of Dillenia serrata Thunb. showed 64% to 73% inhibition on the production of prostaglandin E2 (PGE2) in lipopolysaccharide-induced human whole blood using a radioimmunoassay technique. Three triterpenoids isolated
[...] Read more.
The crude methanol extracts and fractions of the root and stem barks of Dillenia serrata Thunb. showed 64% to 73% inhibition on the production of prostaglandin E2 (PGE2) in lipopolysaccharide-induced human whole blood using a radioimmunoassay technique. Three triterpenoids isolated from the root bark of the plant, koetjapic (1), 3-oxoolean-12-en-30-oic (2), and betulinic (3) acids, exhibited significant concentration-dependent inhibitory effects on PGE2 production with IC50 values of 1.05, 1.54, and 2.59 μM, respectively, as compared with the positive control, indomethacin (IC50 = 0.45 μM). Quantification of compounds 1 and 3 in the methanol extracts and fractions were carried out by using a validated reversed-phase high performance liquid chromatography (RP-HPLC) method. The ethyl acetate fraction of the stem bark showed the highest content of both compound 1 (15.1%) and compound 3 (52.8%). The strong inhibition of the extracts and fractions on cyclooxygenase-2 (COX-2) enzymatic activity was due to the presence of their major constituents, especially koetjapic and betulinic acids. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Isolation and Characterisation of in Vitro and Cellular Free Radical Scavenging Peptides from Corn Peptide Fractions
Molecules 2015, 20(2), 3221-3237; doi:10.3390/molecules20023221
Received: 14 October 2014 / Revised: 3 February 2015 / Accepted: 9 February 2015 / Published: 16 February 2015
Cited by 6 | PDF Full-text (768 KB) | HTML Full-text | XML Full-text
Abstract
Corn gluten meal, a corn processing industry by-product, is a good source for the preparation of bioactive peptides due to its special amino acid composition. In the present study, the in vitro and cellular free radical scavenging activities of corn peptide fractions (CPFs)
[...] Read more.
Corn gluten meal, a corn processing industry by-product, is a good source for the preparation of bioactive peptides due to its special amino acid composition. In the present study, the in vitro and cellular free radical scavenging activities of corn peptide fractions (CPFs) were investigated. Results indicated that CPF1 (molecular weight less than 1 kDa) and CPF2 (molecular weight between 1 and 3 kDa) exhibited good hydroxyl radical, superoxide anion radical and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonicacid) diammonium salt (ABTS) radical scavenging activity and oxygen radical absorbance capacity (ORAC). Meanwhile, the in vitro radical scavenging activity of CPF1 was slightly higher than that of CPF2. Both CPF1 and CPF2 also exhibited significant cytoprotective effects and intracellular reactive oxygen species scavenging activity in Caco-2 cells exposed to hydrogen peroxide (H2O2). The amino acid composition analysis revealed that the CPF were rich in hydrophobic amino acids, which comprised of more than 45% of total amino acids. An antioxidant peptide sequence of Tyr-Phe-Cys-Leu-Thr (YFCLT) was identified from CPF1 using matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI TOF/TOF MS). The YFCLT exhibited excellent ABTS radical scavenging activity with a 50% effective concentration (EC50) value of 37.63 µM, which was much lower than that of Trolox. In conclusion, corn gluten meal might be a good source to prepare antioxidant peptides. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
Figures

Open AccessCommunication Toxicity of Amorphigenin from the Seeds of Amorpha fruticosa against the Larvae of Culex pipiens pallens (Diptera: Culicidae)
Molecules 2015, 20(2), 3238-3254; doi:10.3390/molecules20023238
Received: 16 December 2014 / Revised: 5 February 2015 / Accepted: 10 February 2015 / Published: 16 February 2015
Cited by 7 | PDF Full-text (1208 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The larvicidal activity of the crude petroleum ether, ethyl acetate, acetone, chloroform and ethanol extracts of Amorpha fruticosa seeds was individually assayed for toxicity against the early fourth-instar larva of the mosquito, Culex pipiens pallens after 24 h exposure. Of the tested extracts,
[...] Read more.
The larvicidal activity of the crude petroleum ether, ethyl acetate, acetone, chloroform and ethanol extracts of Amorpha fruticosa seeds was individually assayed for toxicity against the early fourth-instar larva of the mosquito, Culex pipiens pallens after 24 h exposure. Of the tested extracts, the ethanol one exhibited the highest larvicidal activity (LC50 = 22.69 mg/L). Amorphigenin (8'-hydroxyrotenone), a rotenoid compound which exhibits a strong larvicidal activity with LC50 and LC90 values of 4.29 and 11.27 mg/L, respectively, was isolated from the ethanol extract by column chromatograpy. Its structure was elucidated by 1H-NMR, UV and IR spectral data. Furthermore, investigation of amorphigenin’s effects on mitochondrial complex I activity and protein synthesis in C. pipiens pallens larvae reveals that amorphigenin decreases mitochondrial complex I activities to 65.73% at 10.45 μmol/L, compared to the control, when NADH were used as the substrate. Meanwhile, amorphigenin at 10.45 μmol/L also caused a 1.98-fold decrease in protein content, compared to the control larvae treated with acetone only. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Design, Synthesis, and Cytotoxicity of Perbutyrylated Glycosides of 4β-Triazolopodophyllotoxin Derivatives
Molecules 2015, 20(2), 3255-3280; doi:10.3390/molecules20023255
Received: 11 January 2015 / Accepted: 4 February 2015 / Published: 16 February 2015
Cited by 3 | PDF Full-text (911 KB) | HTML Full-text | XML Full-text
Abstract
A series of novel perbutyrylated glycosides of 4β-triazolopodophyllotoxin derivatives were synthesized by utilizing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Evaluation of cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using the MTT assay shows that some
[...] Read more.
A series of novel perbutyrylated glycosides of 4β-triazolopodophyllotoxin derivatives were synthesized by utilizing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Evaluation of cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using the MTT assay shows that some of these glycosylated derivatives have good anticancer activity. Among the synthesized compounds, compound 21a shows the highest activity, with IC50 values ranging from 0.49 to 6.70 μM, which is more potent than the control drugs etoposide and cisplatin. Compound 21a is characterized by a perbutyrylated α-D(+)-galactosyl residue, the absence of an additional linking spacer between the sugar residue and the triazole ring, as well as a 4'-OH group on the E ring of the podophyllotoxin scaffold. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle Three New Lanostanoids from the Mushroom Ganoderma tropicum
Molecules 2015, 20(2), 3281-3289; doi:10.3390/molecules20023281
Received: 19 December 2014 / Accepted: 5 February 2015 / Published: 16 February 2015
Cited by 3 | PDF Full-text (754 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three new lanostanoid triterpenes—ganotropic acid (1), 3β,7β,15α,24-tetra- hydroxy-11,23-dioxo-lanost-8-en-26-oic acid (2) and 3β,7β,15α,28-tetrahydroxy-11,23- dioxo-lanost-8,16-dien-26-oic acid (3)—were isolated from the n-BuOH extract of the fruiting bodies of the mushroom Ganoderma tropicum. Their structures were elucidated by 1D
[...] Read more.
Three new lanostanoid triterpenes—ganotropic acid (1), 3β,7β,15α,24-tetra- hydroxy-11,23-dioxo-lanost-8-en-26-oic acid (2) and 3β,7β,15α,28-tetrahydroxy-11,23- dioxo-lanost-8,16-dien-26-oic acid (3)—were isolated from the n-BuOH extract of the fruiting bodies of the mushroom Ganoderma tropicum. Their structures were elucidated by 1D and 2D NMR spectroscopy, as well as HR-EI-MS data. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Study of Coumarin-Resveratrol Hybrids as Potent Antioxidant Compounds
Molecules 2015, 20(2), 3290-3308; doi:10.3390/molecules20023290
Received: 13 January 2015 / Revised: 11 February 2015 / Accepted: 12 February 2015 / Published: 16 February 2015
Cited by 8 | PDF Full-text (977 KB) | HTML Full-text | XML Full-text
Abstract
In the present work we synthesized a selected series of hydroxylated 3-phenylcoumarins 58, with the aim of evaluating in detail their antioxidant properties. From an in depth study of the antioxidant capacity data (ORAC-FL, ESR, CV and ROS inhibition) it
[...] Read more.
In the present work we synthesized a selected series of hydroxylated 3-phenylcoumarins 58, with the aim of evaluating in detail their antioxidant properties. From an in depth study of the antioxidant capacity data (ORAC-FL, ESR, CV and ROS inhibition) it was concluded that these derivatives are very good antioxidants, with very interesting profiles in all the performed assays. The study of the effect of the number and position of the hydroxyl groups on the antioxidant activity was the principal aim of this study. In particular, 7-hydroxy-3-(3'-hydroxy)phenylcoumarin (8) proved to be the most active and effective antioxidant of the selected series in four of the performed assays (ORAC-FL = 11.8, capacity of scavenging hydroxyl radicals = 54%, Trolox index = 2.33 and AI30 index = 0.18). However, the presence of two hydroxyl groups on this molecule did not increase greatly the activity profile. Theoretical evaluation of ADME properties of all the derivatives was also carried out. All the compounds can act as potential candidates for preventing or minimizing the free radical overproduction in oxidative-stress related diseases. These preliminary findings encourage us to perform a future structural optimization of this family of compounds. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle Lactones with Methylcyclohexane Systems Obtained by Chemical and Microbiological Methods and Their Antimicrobial Activity
Molecules 2015, 20(2), 3335-3353; doi:10.3390/molecules20023335
Received: 18 December 2014 / Revised: 9 February 2015 / Accepted: 13 February 2015 / Published: 16 February 2015
Cited by 5 | PDF Full-text (1047 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Eight new lactones (δ-chloro-, δ-bromo- and δ-iodo-γ-lactones), each with a methylcyclohexane ring, were obtained by chemical means from (4-methylcyclohex-2-en-1-yl) acetic acid or (6-methylcyclohex-2-en-1-yl) acetic acid. Whole cells of ten fungal strains (Fusarium species, Syncephalastrum racemosum and Botrytis cinerea) were tested on
[...] Read more.
Eight new lactones (δ-chloro-, δ-bromo- and δ-iodo-γ-lactones), each with a methylcyclohexane ring, were obtained by chemical means from (4-methylcyclohex-2-en-1-yl) acetic acid or (6-methylcyclohex-2-en-1-yl) acetic acid. Whole cells of ten fungal strains (Fusarium species, Syncephalastrum racemosum and Botrytis cinerea) were tested on their ability to convert these lactones into other products. Some of the tested fungal strains transformed chloro-, bromo- and iodolactone with a methyl group at C-5 into 2-hydroxy-5-methyl-9-oxabicyclo[4.3.0]nonan-8-one during hydrolytic dehalogenation. When the same lactones had the methyl group at C-3, no structural modifications of halolactones were observed. In most cases, the optical purity of the product was low or medium, with the highest rate for chlorolactone (45.4%) and iodolactone (45.2% and 47.6%). All of the obtained compounds were tested with reference to their smell. Seven halolactones and the hydroxylactone obtained via biotransformation of halolactones with 5-methylcyclohexane ring were examined for their antimicrobial activity. These compounds were capable of inhibiting growth of some bacteria, yeasts and fungi. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle Investigation of Structural Mimetics of Natural Phosphate Ion Binding Motifs
Molecules 2015, 20(2), 3354-3370; doi:10.3390/molecules20023354
Received: 27 December 2014 / Revised: 19 January 2015 / Accepted: 12 February 2015 / Published: 16 February 2015
Cited by 3 | PDF Full-text (2646 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phosphates are ubiquitous in biology and nearly half of all proteins interact with their partners by means of recognition of phosphate residues. Therefore, a better understanding of the phosphate ion binding by peptidic structures is highly desirable. Two new receptors have been designed
[...] Read more.
Phosphates are ubiquitous in biology and nearly half of all proteins interact with their partners by means of recognition of phosphate residues. Therefore, a better understanding of the phosphate ion binding by peptidic structures is highly desirable. Two new receptors have been designed and synthesized and their anion binding properties in an acetonitrile solution have been determined. The structure of hosts mimics a part of the kinase active site that is responsible for the recognition of the phosphate residue. New hosts contain additional free amino groups with the aim to facilitate coordination of protonated anions, such as dihydrogen phosphate. According to spectrophotometric measurements, stepwise 1:1 and 1:2 binding modes have been observed for both receptors in the presence of acetate, hydrogen sulfate and dihydrogen phosphate. Compared with the acyclic receptor, the macrocyclic receptor has demonstrated a remarkably enhanced selectivity for dihydrogen phosphate over other anions. Fluorometric measurements have revealed different responses of the acyclic and macrocyclic receptors towards anions. However, in both cases, a 5–8 nm hypsochromic shift of fluorescence maximum has been observed upon interaction of acetate and dihydrogen phosphate with receptors. Full article
(This article belongs to the Special Issue Host-Guest Chemistry)
Figures

Open AccessArticle A Density Functional Tight Binding Study of Acetic Acid Adsorption on Crystalline and Amorphous Surfaces of Titania
Molecules 2015, 20(2), 3371-3388; doi:10.3390/molecules20023371
Received: 4 January 2015 / Revised: 12 February 2015 / Accepted: 13 February 2015 / Published: 17 February 2015
Cited by 17 | PDF Full-text (3775 KB) | HTML Full-text | XML Full-text
Abstract
We present a comparative density functional tight binding study of an organic molecule attachment to TiO2 via a carboxylic group, with the example of acetic acid. For the first time, binding to low-energy surfaces of crystalline anatase (101), rutile (110) and (B)-TiO
[...] Read more.
We present a comparative density functional tight binding study of an organic molecule attachment to TiO2 via a carboxylic group, with the example of acetic acid. For the first time, binding to low-energy surfaces of crystalline anatase (101), rutile (110) and (B)-TiO2 (001), as well as to the surface of amorphous (a-) TiO2 is compared with the same computational setup. On all surfaces, bidentate configurations are identified as providing the strongest adsorption energy, Eads = −1.93, −2.49 and −1.09 eV for anatase, rutile and (B)-TiO2, respectively. For monodentate configurations, the strongest Eads = −1.06, −1.11 and −0.86 eV for anatase, rutile and (B)-TiO2, respectively. Multiple monodentate and bidentate configurations are identified on a-TiO2 with a distribution of adsorption energies and with the lowest energy configuration having stronger bonding than that of the crystalline counterparts, with Eads up to −4.92 eV for bidentate and −1.83 eV for monodentate adsorption. Amorphous TiO2 can therefore be used to achieve strong anchoring of organic molecules, such as dyes, that bind via a -COOH group. While the presence of the surface leads to a contraction of the band gap vs. the bulk, molecular adsorption caused no appreciable effect on the band structure around the gap in any of the systems. Full article
(This article belongs to the Special Issue Molecular Engineering for Electrochemical Power Sources)
Figures

Open AccessArticle Investigation of Chemomarkers of Astragali Radix of Different Ages and Geographical Origin by NMR Profiling
Molecules 2015, 20(2), 3389-3405; doi:10.3390/molecules20023389
Received: 1 December 2014 / Revised: 24 December 2014 / Accepted: 11 February 2015 / Published: 17 February 2015
Cited by 1 | PDF Full-text (1837 KB) | HTML Full-text | XML Full-text
Abstract
Astragalus roots from Astragalus membranaceus Bunge or Astragalus membranaceus var. mongholicus (Bunge) Hsiao are among the most popular traditional medicinal plants due to their diverse therapeutic uses based on their tonic, antinephritic, immunostimulant, hepatoprotectant, diuretic, antidiabetic, analgesic, expectorant and sedative properties. Currently, the
[...] Read more.
Astragalus roots from Astragalus membranaceus Bunge or Astragalus membranaceus var. mongholicus (Bunge) Hsiao are among the most popular traditional medicinal plants due to their diverse therapeutic uses based on their tonic, antinephritic, immunostimulant, hepatoprotectant, diuretic, antidiabetic, analgesic, expectorant and sedative properties. Currently, the herb is produced or cultivated in various sites, including 10 different locations in China with very diverse environmental conditions. These differences affect their metabolic pools and consequently their medicinal properties. The comparative metabolic profiling of plants of different geographical origins or ages could contribute to detect biomarkers for their quality control and thus guarantee the efficacy of the herbal medicines produced with this drug. In this paper nuclear magnetic resonance spectroscopy (NMR)-based metabolomics was applied for to plants of different origins and age for this purpose. The results of this study show that in the set of samples evaluated, age is more discriminating than geographical location. The quantity of individual flavonoids and some primary metabolites contributed most to this age differentiation. On the other hand, based on the analysis of orthogonal partial least square (OPLS) modeling, the marker metabolites for the geographical origin were saponins and isoflavonoids. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Anti-Proliferative Effect and Induction of Apoptosis in Androgen-Independent Human Prostate Cancer Cells by 1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one
Molecules 2015, 20(2), 3406-3430; doi:10.3390/molecules20023406
Received: 12 December 2014 / Revised: 9 January 2015 / Accepted: 19 January 2015 / Published: 17 February 2015
Cited by 2 | PDF Full-text (3405 KB) | HTML Full-text | XML Full-text
Abstract
Curcumin has poor in vivo absorption and bioavailability, highlighting a need for new curcumin analogues with better characteristics in these aspects. The aim of this study is to determine the anti-cancer properties of four selected curcumin analogues, on the cytotoxicity, proliferative and apoptotic
[...] Read more.
Curcumin has poor in vivo absorption and bioavailability, highlighting a need for new curcumin analogues with better characteristics in these aspects. The aim of this study is to determine the anti-cancer properties of four selected curcumin analogues, on the cytotoxicity, proliferative and apoptotic effects on androgen-independent human prostate cancer cells (PC-3 and DU 145). Initial cytotoxicity screening showed MS17 has the highest cell inhibitory effect, with EC50 values of 4.4 ± 0.3 and 4.1 ± 0.8 µM, followed by MS13 (7.5 ± 0.1 and 7.4 ± 2.6 µM), MS49 (14.5 ± 1.2 and 12.3 ± 2.3 µM) and MS40E (28.0 ± 7.8 and 30.3 ± 1.9 µM) for PC-3 and DU 145 cells, respectively. Time-dependent analysis also revealed that MS13 and MS17 displayed a greater anti-proliferative effect than the other compounds. MS17 was chosen based on the high selectivity index value for further analysis on the morphological and biochemical hallmarks of apoptosis. Fluorescence microscopy analysis revealed apoptotic changes in both treated prostate cancer cells. Relative caspase-3 activity increased significantly at 48 h in PC-3 and 12 h in DU 145 cells. Highest enrichment of free nucleosomes was noted at 48 h after treatment with MS17. In conclusion, MS17 demonstrated anti-proliferative effect and induces apoptosis in a time and dose-dependent manner suggesting its potential for development as an anti-cancer agent for androgen-independent prostate cancer. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Nutritional Value and Volatile Compounds of Black Cherry (Prunus serotina) Seeds
Molecules 2015, 20(2), 3479-3495; doi:10.3390/molecules20023479
Received: 4 January 2015 / Revised: 10 February 2015 / Accepted: 11 February 2015 / Published: 17 February 2015
Cited by 3 | PDF Full-text (733 KB) | HTML Full-text | XML Full-text
Abstract
Prunus serotina (black cherry), commonly known in Mexico as capulín, is used in Mexican traditional medicine for the treatment of cardiovascular, respiratory, and gastrointestinal diseases. Particularly, P. serotina seeds, consumed in Mexico as snacks, are used for treating cough. In the present study,
[...] Read more.
Prunus serotina (black cherry), commonly known in Mexico as capulín, is used in Mexican traditional medicine for the treatment of cardiovascular, respiratory, and gastrointestinal diseases. Particularly, P. serotina seeds, consumed in Mexico as snacks, are used for treating cough. In the present study, nutritional and volatile analyses of black cherry seeds were carried out to determine their nutraceutical potential. Proximate analysis indicated that P. serotina raw and toasted seeds contain mostly fat, followed by protein, fiber, carbohydrates, and ash. The potassium content in black cherry raw and toasted seeds is high, and their protein digestibility-corrected amino acid scores suggest that they might represent a complementary source of proteins. Solid phase microextraction and gas chromatography/flame ionization detection/mass spectrometry analysis allowed identification of 59 and 99 volatile compounds in the raw and toasted seeds, respectively. The major volatile compounds identified in raw and toasted seeds were 2,3-butanediol and benzaldehyde, which contribute to the flavor and odor of the toasted seeds. Moreover, it has been previously demonstrated that benzaldehyde possesses a significant vasodilator effect, therefore, the presence of this compound along with oleic, linoleic, and α-eleostearic fatty acids indicate that black cherry seeds consumption might have beneficial effects on the cardiovascular system. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)

Review

Jump to: Editorial, Research, Other

Open AccessReview Lectins: Getting Familiar with Translators of the Sugar Code
Molecules 2015, 20(2), 1788-1823; doi:10.3390/molecules20021788
Received: 2 December 2014 / Revised: 23 December 2014 / Accepted: 8 January 2015 / Published: 22 January 2015
Cited by 36 | PDF Full-text (27563 KB) | HTML Full-text | XML Full-text
Abstract
The view on the significance of the presence of glycans in glycoconjugates is undergoing a paradigmatic change. Initially mostly considered to be rather inert and passive, the concept of the sugar code identifies glycans as highly versatile platform to store information. Their chemical
[...] Read more.
The view on the significance of the presence of glycans in glycoconjugates is undergoing a paradigmatic change. Initially mostly considered to be rather inert and passive, the concept of the sugar code identifies glycans as highly versatile platform to store information. Their chemical properties endow carbohydrates to form oligomers with unsurpassed structural variability. Owing to their capacity to engage in hydrogen (and coordination) bonding and C-H/π-interactions these “code words” can be “read” (in Latin, legere) by specific receptors. A distinct class of carbohydrate-binding proteins are the lectins. More than a dozen protein folds have developed carbohydrate-binding capacity in vertebrates. Taking galectins as an example, distinct expression patterns are traced. The availability of labeled endogenous lectins facilitates monitoring of tissue reactivity, extending the scope of lectin histochemistry beyond that which traditionally involved plant lectins. Presentation of glycan and its cognate lectin can be orchestrated, making a glycan-based effector pathway in growth control of tumor and activated T cells possible. In order to unravel the structural basis of lectin specificity for particular glycoconjugates mimetics of branched glycans and programmable models of cell surfaces are being developed by strategic combination of lectin research with synthetic and supramolecular chemistry. Full article
(This article belongs to the Special Issue Lectins)
Open AccessReview Natural Products as Leads in Schistosome Drug Discovery
Molecules 2015, 20(2), 1872-1903; doi:10.3390/molecules20021872
Received: 12 December 2014 / Revised: 31 December 2014 / Accepted: 14 January 2015 / Published: 23 January 2015
Cited by 19 | PDF Full-text (4756 KB) | HTML Full-text | XML Full-text
Abstract
Schistosomiasis is a neglected parasitic tropical disease that claims around 200,000 human lives every year. Praziquantel (PZQ), the only drug recommended by the World Health Organization for the treatment and control of human schistosomiasis, is now facing the threat of drug resistance, indicating
[...] Read more.
Schistosomiasis is a neglected parasitic tropical disease that claims around 200,000 human lives every year. Praziquantel (PZQ), the only drug recommended by the World Health Organization for the treatment and control of human schistosomiasis, is now facing the threat of drug resistance, indicating the urgent need for new effective compounds to treat this disease. Therefore, globally, there is renewed interest in natural products (NPs) as a starting point for drug discovery and development for schistosomiasis. Recent advances in genomics, proteomics, bioinformatics, and cheminformatics have brought about unprecedented opportunities for the rapid and more cost-effective discovery of new bioactive compounds against neglected tropical diseases. This review highlights the main contributions that NP drug discovery and development have made in the treatment of schistosomiasis and it discusses how integration with virtual screening (VS) strategies may contribute to accelerating the development of new schistosomidal leads, especially through the identification of unexplored, biologically active chemical scaffolds and structural optimization of NPs with previously established activity. Full article
Open AccessReview Theory and Applications of Covalent Docking in Drug Discovery: Merits and Pitfalls
Molecules 2015, 20(2), 1984-2000; doi:10.3390/molecules20021984
Received: 12 November 2014 / Revised: 19 December 2014 / Accepted: 12 January 2015 / Published: 27 January 2015
Cited by 29 | PDF Full-text (1935 KB) | HTML Full-text | XML Full-text
Abstract
he present art of drug discovery and design of new drugs is based on suicidal irreversible inhibitors. Covalent inhibition is the strategy that is used to achieve irreversible inhibition. Irreversible inhibitors interact with their targets in a time-dependent fashion, and the reaction proceeds
[...] Read more.
he present art of drug discovery and design of new drugs is based on suicidal irreversible inhibitors. Covalent inhibition is the strategy that is used to achieve irreversible inhibition. Irreversible inhibitors interact with their targets in a time-dependent fashion, and the reaction proceeds to completion rather than to equilibrium. Covalent inhibitors possessed some significant advantages over non-covalent inhibitors such as covalent warheads can target rare, non-conserved residue of a particular target protein and thus led to development of highly selective inhibitors, covalent inhibitors can be effective in targeting proteins with shallow binding cleavage which will led to development of novel inhibitors with increased potency than non-covalent inhibitors. Several computational approaches have been developed to simulate covalent interactions; however, this is still a challenging area to explore. Covalent molecular docking has been recently implemented in the computer-aided drug design workflows to describe covalent interactions between inhibitors and biological targets. In this review we highlight: (i) covalent interactions in biomolecular systems; (ii) the mathematical framework of covalent molecular docking; (iii) implementation of covalent docking protocol in drug design workflows; (iv) applications covalent docking: case studies and (v) shortcomings and future perspectives of covalent docking. To the best of our knowledge; this review is the first account that highlights different aspects of covalent docking with its merits and pitfalls. We believe that the method and applications highlighted in this study will help future efforts towards the design of irreversible inhibitors. Full article
(This article belongs to the Special Issue Molecular Docking in Drug Design)
Figures

Open AccessReview Insecticidal Activity of Plant Lectins and Potential Application in Crop Protection
Molecules 2015, 20(2), 2014-2033; doi:10.3390/molecules20022014
Received: 8 November 2014 / Revised: 15 January 2015 / Accepted: 19 January 2015 / Published: 27 January 2015
Cited by 20 | PDF Full-text (876 KB) | HTML Full-text | XML Full-text
Abstract
Lectins constitute a complex group of proteins found in different organisms. These proteins constitute an important field for research, as their structural diversity and affinity for several carbohydrates makes them suitable for numerous biological applications. This review addresses the classification and insecticidal activities
[...] Read more.
Lectins constitute a complex group of proteins found in different organisms. These proteins constitute an important field for research, as their structural diversity and affinity for several carbohydrates makes them suitable for numerous biological applications. This review addresses the classification and insecticidal activities of plant lectins, providing an overview of the applicability of these proteins in crop protection. The likely target sites in insect tissues, the mode of action of these proteins, as well as the use of lectins as biotechnological tools for pest control are also described. The use of initial bioassays employing artificial diets has led to the most recent advances in this field, such as plant breeding and the construction of fusion proteins, using lectins for targeting the delivery of toxins and to potentiate expected insecticide effects. Based on the data presented, we emphasize the contribution that plant lectins may make as tools for the development of integrated insect pest control strategies. Full article
(This article belongs to the Special Issue Lectins)
Open AccessReview Tyrosine Sulfation as a Protein Post-Translational Modification
Molecules 2015, 20(2), 2138-2164; doi:10.3390/molecules20022138
Received: 6 November 2014 / Revised: 6 January 2015 / Accepted: 14 January 2015 / Published: 28 January 2015
Cited by 15 | PDF Full-text (1539 KB) | HTML Full-text | XML Full-text
Abstract
Integration of inorganic sulfate into biological molecules plays an important role in biological systems and is directly involved in the instigation of diseases. Protein tyrosine sulfation (PTS) is a common post-translational modification that was first reported in the literature fifty years ago. However,
[...] Read more.
Integration of inorganic sulfate into biological molecules plays an important role in biological systems and is directly involved in the instigation of diseases. Protein tyrosine sulfation (PTS) is a common post-translational modification that was first reported in the literature fifty years ago. However, the significance of PTS under physiological conditions and its link to diseases have just begun to be appreciated in recent years. PTS is catalyzed by tyrosylprotein sulfotransferase (TPST) through transfer of an activated sulfate from 3'-phosphoadenosine-5'-phosphosulfate to tyrosine in a variety of proteins and peptides. Currently, only a small fraction of sulfated proteins is known and the understanding of the biological sulfation mechanisms is still in progress. In this review, we give an introductory and selective brief review of PTS and then summarize the basic biochemical information including the activity and the preparation of TPST, methods for the determination of PTS, and kinetics and reaction mechanism of TPST. This information is fundamental for the further exploration of the function of PTS that induces protein-protein interactions and the subsequent biochemical and physiological reactions. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)
Open AccessReview The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation
Molecules 2015, 20(2), 2208-2228; doi:10.3390/molecules20022208
Received: 24 October 2014 / Revised: 11 November 2014 / Accepted: 26 November 2014 / Published: 29 January 2015
Cited by 10 | PDF Full-text (2025 KB) | HTML Full-text | XML Full-text
Abstract
The plant indole alkaloid ibogaine has shown promising anti-addictive properties in animal studies. Ibogaine is also anti-addictive in humans as the drug alleviates drug craving and impedes relapse of drug use. Although not licensed as therapeutic drug and despite safety concerns, ibogaine is
[...] Read more.
The plant indole alkaloid ibogaine has shown promising anti-addictive properties in animal studies. Ibogaine is also anti-addictive in humans as the drug alleviates drug craving and impedes relapse of drug use. Although not licensed as therapeutic drug and despite safety concerns, ibogaine is currently used as an anti-addiction medication in alternative medicine in dozens of clinics worldwide. In recent years, alarming reports of life-threatening complications and sudden death cases, temporally associated with the administration of ibogaine, have been accumulating. These adverse reactions were hypothesised to be associated with ibogaine’s propensity to induce cardiac arrhythmias. The aim of this review is to recapitulate the current knowledge about ibogaine’s effects on the heart and the cardiovascular system, and to assess the cardiac risks associated with the use of this drug in anti- addiction therapy. The actions of 18-methoxycoronaridine (18-MC), a less toxic ibogaine congener with anti-addictive properties, are also considered. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessReview Human Lectins and Their Roles in Viral Infections
Molecules 2015, 20(2), 2229-2271; doi:10.3390/molecules20022229
Received: 17 November 2014 / Revised: 21 January 2015 / Accepted: 23 January 2015 / Published: 29 January 2015
Cited by 19 | PDF Full-text (2601 KB) | HTML Full-text | XML Full-text
Abstract
Innate recognition of virus proteins is an important component of the immune response to viral pathogens. A component of this immune recognition is the family of lectins; pattern recognition receptors (PRRs) that recognise viral pathogen-associated molecular patterns (PAMPs) including viral glycoproteins. In this
[...] Read more.
Innate recognition of virus proteins is an important component of the immune response to viral pathogens. A component of this immune recognition is the family of lectins; pattern recognition receptors (PRRs) that recognise viral pathogen-associated molecular patterns (PAMPs) including viral glycoproteins. In this review we discuss the contribution of soluble and membrane-associated PRRs to immunity against virus pathogens, and the potential role of these molecules in facilitating virus replication. These processes are illustrated with examples of viruses including human immunodeficiency virus (HIV), hepatitis C virus (HCV) and Ebola virus (EBOV). We focus on the structure, function and genetics of the well-characterised C-type lectin mannose-binding lectin, the ficolins, and the membrane-bound CD209 proteins expressed on dendritic cells. The potential for lectin-based antiviral therapies is also discussed. Full article
(This article belongs to the Special Issue Lectins)
Open AccessReview The Roles of Direct Recognition by Animal Lectins in Antiviral Immunity and Viral Pathogenesis
Molecules 2015, 20(2), 2272-2295; doi:10.3390/molecules20022272
Received: 28 August 2014 / Accepted: 21 January 2015 / Published: 29 January 2015
Cited by 10 | PDF Full-text (3659 KB) | HTML Full-text | XML Full-text
Abstract
Lectins are a group of proteins with carbohydrate recognition activity. Lectins are categorized into many families based on their different cellular locations as well as their specificities for a variety of carbohydrate structures due to the features of their carbohydrate recognition domain (CRD)
[...] Read more.
Lectins are a group of proteins with carbohydrate recognition activity. Lectins are categorized into many families based on their different cellular locations as well as their specificities for a variety of carbohydrate structures due to the features of their carbohydrate recognition domain (CRD) modules. Many studies have indicated that the direct recognition of particular oligosaccharides on viral components by lectins is important for interactions between hosts and viruses. Herein, we aim to globally review the roles of this recognition by animal lectins in antiviral immune responses and viral pathogenesis. The different classes of mammalian lectins can either recognize carbohydrates to activate host immunity for viral elimination or can exploit those carbohydrates as susceptibility factors to facilitate viral entry, replication or assembly. Additionally, some arthropod C-type lectins were recently identified as key susceptibility factors that directly interact with multiple viruses and then facilitate infection. Summarization of the pleiotropic roles of direct viral recognition by animal lectins will benefit our understanding of host-virus interactions and could provide insight into the role of lectins in antiviral drug and vaccine development. Full article
(This article belongs to the Special Issue Lectins)
Open AccessReview Targeting Carbonic Anhydrase IX Activity and Expression
Molecules 2015, 20(2), 2323-2348; doi:10.3390/molecules20022323
Received: 18 August 2014 / Accepted: 25 December 2014 / Published: 30 January 2015
Cited by 22 | PDF Full-text (2689 KB) | HTML Full-text | XML Full-text
Abstract
Metastatic tumors are often hypoxic exhibiting a decrease in extracellular pH (~6.5) due to a metabolic transition described by the Warburg Effect. This shift in tumor cell metabolism alters the tumor milieu inducing tumor cell proliferation, angiogenesis, cell motility, invasiveness, and often resistance
[...] Read more.
Metastatic tumors are often hypoxic exhibiting a decrease in extracellular pH (~6.5) due to a metabolic transition described by the Warburg Effect. This shift in tumor cell metabolism alters the tumor milieu inducing tumor cell proliferation, angiogenesis, cell motility, invasiveness, and often resistance to common anti-cancer treatments; hence hindering treatment of aggressive cancers. As a result, tumors exhibiting this phenotype are directly associated with poor prognosis and decreased survival rates in cancer patients. A key component to this tumor microenvironment is carbonic anhydrase IX (CA IX). Knockdown of CA IX expression or inhibition of its activity has been shown to reduce primary tumor growth, tumor proliferation, and also decrease tumor resistance to conventional anti-cancer therapies. As such several approaches have been taken to target CA IX in tumors via small-molecule, anti-body, and RNAi delivery systems. Here we will review recent developments that have exploited these approaches and provide our thoughts for future directions of CA IX targeting for the treatment of cancer. Full article
Figures

Open AccessReview Elderberries: A Source of Ribosome-Inactivating Proteins with Lectin Activity
Molecules 2015, 20(2), 2364-2387; doi:10.3390/molecules20022364
Received: 17 November 2014 / Revised: 20 January 2015 / Accepted: 22 January 2015 / Published: 30 January 2015
Cited by 11 | PDF Full-text (2152 KB) | HTML Full-text | XML Full-text
Abstract
Sambucus (Adoxaceae) species have been used for both food and medicine purposes. Among these, Sambucus nigra L. (black elder), Sambucus ebulus L. (dwarf elder), and Sambucus sieboldiana L. are the most relevant species studied. Their use has been somewhat restricted due
[...] Read more.
Sambucus (Adoxaceae) species have been used for both food and medicine purposes. Among these, Sambucus nigra L. (black elder), Sambucus ebulus L. (dwarf elder), and Sambucus sieboldiana L. are the most relevant species studied. Their use has been somewhat restricted due to the presence of bioactive proteins or/and low molecular weight compounds whose ingestion could trigger deleterious effects. Over the last few years, the chemical and pharmacological characteristics of Sambucus species have been investigated. Among the proteins present in Sambucus species both type 1, and type 2 ribosome-inactivating proteins (RIPs), and hololectins have been reported. The biological role played by these proteins remains unknown, although they are conjectured to be involved in defending plants against insect predators and viruses. These proteins might have an important impact on the nutritional characteristics and food safety of elderberries. Type 2 RIPs are able to interact with gut cells of insects and mammals triggering a number of specific and mostly unknown cell signals in the gut mucosa that could significantly affect animal physiology. In this paper, we describe all known RIPs that have been isolated to date from Sambucus species, and comment on their antiviral and entomotoxic effects, as well as their potential uses. Full article
(This article belongs to the Special Issue Lectins)
Open AccessReview Isotope Effects on Chemical Shifts in the Study of Intramolecular Hydrogen Bonds
Molecules 2015, 20(2), 2405-2424; doi:10.3390/molecules20022405
Received: 4 December 2014 / Revised: 17 December 2014 / Accepted: 5 January 2015 / Published: 30 January 2015
Cited by 8 | PDF Full-text (1360 KB) | HTML Full-text | XML Full-text
Abstract
The paper deals with the use of isotope effects on chemical shifts in characterizing intramolecular hydrogen bonds. Both so-called resonance-assisted (RAHB) and non-RAHB systems are treated. The importance of RAHB will be discussed. Another very important issue is the borderline between “static” and
[...] Read more.
The paper deals with the use of isotope effects on chemical shifts in characterizing intramolecular hydrogen bonds. Both so-called resonance-assisted (RAHB) and non-RAHB systems are treated. The importance of RAHB will be discussed. Another very important issue is the borderline between “static” and tautomeric systems. Isotope effects on chemical shifts are particularly useful in such studies. All kinds of intramolecular hydrogen bonded systems will be treated, typical hydrogen bond donors: OH, NH, SH and NH+, typical acceptors C=O, C=N, C=S C=N. The paper will be deal with both secondary and primary isotope effects on chemical shifts. These two types of isotope effects monitor the same hydrogen bond, but from different angles. Full article
(This article belongs to the Special Issue Intramolecular Hydrogen Bonding)
Figures

Open AccessReview A Review of Odd-Chain Fatty Acid Metabolism and the Role of Pentadecanoic Acid (C15:0) and Heptadecanoic Acid (C17:0) in Health and Disease
Molecules 2015, 20(2), 2425-2444; doi:10.3390/molecules20022425
Received: 11 December 2014 / Revised: 7 January 2015 / Accepted: 23 January 2015 / Published: 30 January 2015
Cited by 57 | PDF Full-text (875 KB) | HTML Full-text | XML Full-text
Abstract
The role of C17:0 and C15:0 in human health has recently been reinforced following a number of important biological and nutritional observations. Historically, odd chain saturated fatty acids (OCS-FAs) were used as internal standards in GC-MS methods of total fatty acids and LC-MS
[...] Read more.
The role of C17:0 and C15:0 in human health has recently been reinforced following a number of important biological and nutritional observations. Historically, odd chain saturated fatty acids (OCS-FAs) were used as internal standards in GC-MS methods of total fatty acids and LC-MS methods of intact lipids, as it was thought their concentrations were insignificant in humans. However, it has been thought that increased consumption of dairy products has an association with an increase in blood plasma OCS-FAs. However, there is currently no direct evidence but rather a casual association through epidemiology studies. Furthermore, a number of studies on cardiometabolic diseases have shown that plasma concentrations of OCS-FAs are associated with lower disease risk, although the mechanism responsible for this is debated. One possible mechanism for the endogenous production of OCS-FAs is α-oxidation, involving the activation, then hydroxylation of the α-carbon, followed by the removal of the terminal carboxyl group. Differentiation human adipocytes showed a distinct increase in the concentration of OCS-FAs, which was possibly caused through α-oxidation. Further evidence for an endogenous pathway, is in human plasma, where the ratio of C15:0 to C17:0 is approximately 1:2 which is contradictory to the expected levels of C15:0 to C17:0 roughly 2:1 as detected in dairy fat. We review the literature on the dietary consumption of OCS-FAs and their potential endogenous metabolism. Full article
(This article belongs to the Section Metabolites)
Figures

Open AccessReview Volatile Compounds of Raspberry Fruit: From Analytical Methods to Biological Role and Sensory Impact
Molecules 2015, 20(2), 2445-2474; doi:10.3390/molecules20022445
Received: 3 November 2014 / Revised: 8 January 2015 / Accepted: 22 January 2015 / Published: 30 January 2015
Cited by 11 | PDF Full-text (1282 KB) | HTML Full-text | XML Full-text
Abstract
Volatile compounds play a key role in the formation of the well-recognized and widely appreciated raspberry aroma. Studies on the isolation and identification of volatile compounds in raspberry fruit (Rubus idaeus L.) are reviewed with a focus on aroma-related compounds. A table
[...] Read more.
Volatile compounds play a key role in the formation of the well-recognized and widely appreciated raspberry aroma. Studies on the isolation and identification of volatile compounds in raspberry fruit (Rubus idaeus L.) are reviewed with a focus on aroma-related compounds. A table is drawn up containing a comprehensive list of the volatile compounds identified so far in raspberry along with main references and quantitative data where available. Two additional tables report the glycosidic bond and enantiomeric distributions of the volatile compounds investigated up to now in raspberry fruit. Studies on the development and evolution of volatile compounds during fruit formation, ripening and senescence, and genetic and environmental influences are also reviewed. Recent investigations showing the potential role of raspberry volatile compounds in cultivar differentiation and fruit resistance to mold disease are reported as well. Finally a summary of research done so far and our vision for future research lines are reported. Full article
(This article belongs to the Special Issue Aromas and Volatiles of Fruits)
Figures

Open AccessReview Emerging Structural Insights into Glycoprotein Quality Control Coupled with N-Glycan Processing in the Endoplasmic Reticulum
Molecules 2015, 20(2), 2475-2491; doi:10.3390/molecules20022475
Received: 8 December 2014 / Revised: 4 January 2015 / Accepted: 22 January 2015 / Published: 30 January 2015
Cited by 13 | PDF Full-text (3221 KB) | HTML Full-text | XML Full-text
Abstract
In the endoplasmic reticulum (ER), the sugar chain is initially introduced onto newly synthesized proteins as a triantennary tetradecasaccharide (Glc3Man9GlcNAc2). The attached oligosaccharide chain is subjected to stepwise trimming by the actions of specific glucosidases and mannosidases.
[...] Read more.
In the endoplasmic reticulum (ER), the sugar chain is initially introduced onto newly synthesized proteins as a triantennary tetradecasaccharide (Glc3Man9GlcNAc2). The attached oligosaccharide chain is subjected to stepwise trimming by the actions of specific glucosidases and mannosidases. In these processes, the transiently expressed N-glycans, as processing intermediates, function as signals for the determination of glycoprotein fates, i.e., folding, transport, or degradation through interactions of a series of intracellular lectins. The monoglucosylated glycoforms are hallmarks of incompletely folded states of glycoproteins in this system, whereas the outer mannose trimming leads to ER-associated glycoprotein degradation. This review outlines the recently emerging evidence regarding the molecular and structural basis of this glycoprotein quality control system, which is regulated through dynamic interplay among intracellular lectins, glycosidases, and glycosyltransferase. Structural snapshots of carbohydrate-lectin interactions have been provided at the atomic level using X-ray crystallographic analyses. Conformational ensembles of uncomplexed triantennary high-mannose-type oligosaccharides have been characterized in a quantitative manner using molecular dynamics simulation in conjunction with nuclear magnetic resonance spectroscopy. These complementary views provide new insights into glycoprotein recognition in quality control coupled with N-glycan processing. Full article
(This article belongs to the Special Issue Lectins)
Open AccessReview The Effect of Glycosaminoglycans (GAGs) on Amyloid Aggregation and Toxicity
Molecules 2015, 20(2), 2510-2528; doi:10.3390/molecules20022510
Received: 27 November 2014 / Accepted: 29 January 2015 / Published: 2 February 2015
Cited by 27 | PDF Full-text (1128 KB) | HTML Full-text | XML Full-text
Abstract
Amyloidosis is a protein folding disorder in which normally soluble proteins are deposited extracellularly as insoluble fibrils, impairing tissue structure and function. Charged polyelectrolytes such as glycosaminoglycans (GAGs) are frequently found associated with the proteinaceous deposits in tissues of patients affected by amyloid
[...] Read more.
Amyloidosis is a protein folding disorder in which normally soluble proteins are deposited extracellularly as insoluble fibrils, impairing tissue structure and function. Charged polyelectrolytes such as glycosaminoglycans (GAGs) are frequently found associated with the proteinaceous deposits in tissues of patients affected by amyloid diseases. Experimental evidence indicate that they can play an active role in favoring amyloid fibril formation and stabilization. Binding of GAGs to amyloid fibrils occurs mainly through electrostatic interactions involving the negative polyelectrolyte charges and positively charged side chains residues of aggregating protein. Similarly to catalyst for reactions, GAGs favor aggregation, nucleation and amyloid fibril formation functioning as a structural templates for the self-assembly of highly cytotoxic oligomeric precursors, rich in β-sheets, into harmless amyloid fibrils. Moreover, the GAGs amyloid promoting activity can be facilitated through specific interactions via consensus binding sites between amyloid polypeptide and GAGs molecules. We review the effect of GAGs on amyloid deposition as well as proteins not strictly related to diseases. In addition, we consider the potential of the GAGs therapy in amyloidosis. Full article
(This article belongs to the Special Issue Glycosaminoglycans and Their Mimetics)
Open AccessReview Diversity of Heparan Sulfate and HSV Entry: Basic Understanding and Treatment Strategies
Molecules 2015, 20(2), 2707-2727; doi:10.3390/molecules20022707
Received: 22 December 2014 / Accepted: 2 February 2015 / Published: 5 February 2015
Cited by 20 | PDF Full-text (797 KB) | HTML Full-text | XML Full-text
Abstract
A modified form of heparan sulfate (HS) known as 3-O-sulfated heparan sulfate (3-OS HS) generates fusion receptor for herpes simplex virus (HSV) entry and spread. Primary cultures of corneal fibroblasts derived from human eye donors have shown the clinical
[...] Read more.
A modified form of heparan sulfate (HS) known as 3-O-sulfated heparan sulfate (3-OS HS) generates fusion receptor for herpes simplex virus (HSV) entry and spread. Primary cultures of corneal fibroblasts derived from human eye donors have shown the clinical significance of this receptor during HSV corneal infection. 3-OS HS- is a product of a rare enzymatic modification at C3 position of glucosamine residue which is catalyzed by 3-O-sulfotransferases (3-OSTs) enzymes. From humans to zebrafish, the 3-OST enzymes are highly conserved and widely expressed in cells and tissues. There are multiple forms of 3-OSTs each producing unique subset of sulfated HS making it chemically diverse and heterogeneous. HSV infection of cells or zebrafish can be used as a unique tool to understand the structural-functional activities of HS and 3-OS HS and likewise, the infection can be used as a functional assay to screen phage display libraries for identifying HS and 3-OS HS binding peptides or small molecule inhibitors. Using this approach over 200 unique 12-mer HS and 3-OS HS recognizing peptides were isolated and characterized against HSV corneal infection where 3-OS HS is known to be a key receptor. In this review we discuss emerging role of 3-OS HS based therapeutic strategies in preventing viral infection and tissue damage. Full article
(This article belongs to the Special Issue Glycosaminoglycans and Their Mimetics)
Open AccessReview The Multifaceted Role of Curcumin in Cancer Prevention and Treatment
Molecules 2015, 20(2), 2728-2769; doi:10.3390/molecules20022728
Received: 10 November 2014 / Accepted: 30 January 2015 / Published: 5 February 2015
Cited by 97 | PDF Full-text (3236 KB) | HTML Full-text | XML Full-text
Abstract
Despite significant advances in treatment modalities over the last decade, neither the incidence of the disease nor the mortality due to cancer has altered in the last thirty years. Available anti-cancer drugs exhibit limited efficacy, associated with severe side effects, and are also
[...] Read more.
Despite significant advances in treatment modalities over the last decade, neither the incidence of the disease nor the mortality due to cancer has altered in the last thirty years. Available anti-cancer drugs exhibit limited efficacy, associated with severe side effects, and are also expensive. Thus identification of pharmacological agents that do not have these disadvantages is required. Curcumin, a polyphenolic compound derived from turmeric (Curcumin longa), is one such agent that has been extensively studied over the last three to four decades for its potential anti-inflammatory and/or anti-cancer effects. Curcumin has been found to suppress initiation, progression, and metastasis of a variety of tumors. These anti-cancer effects are predominantly mediated through its negative regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other oncogenic molecules. It also abrogates proliferation of cancer cells by arresting them at different phases of the cell cycle and/or by inducing their apoptosis. The current review focuses on the diverse molecular targets modulated by curcumin that contribute to its efficacy against various human cancers. Full article
(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)
Open AccessReview Entamoeba histolytica: Adhesins and Lectins in the Trophozoite Surface
Molecules 2015, 20(2), 2802-2815; doi:10.3390/molecules20022802
Received: 16 November 2014 / Accepted: 13 January 2015 / Published: 9 February 2015
Cited by 8 | PDF Full-text (685 KB) | HTML Full-text | XML Full-text
Abstract
Entamoeba histolytica is the causative agent of amebiasis in humans and is responsible for 100,000 deaths annually, making it the third leading cause of death due to a protozoan parasite. Pathogenesis appears to result from the potent cytotoxic activity of the parasite, which
[...] Read more.
Entamoeba histolytica is the causative agent of amebiasis in humans and is responsible for 100,000 deaths annually, making it the third leading cause of death due to a protozoan parasite. Pathogenesis appears to result from the potent cytotoxic activity of the parasite, which kills host cells within minutes. Although the mechanism is unknown, it is well established to be contact-dependent. The life cycle of the parasite alternates with two forms: the resistant cyst and the invasive trophozoite. The adhesive interactions between the parasite and surface glycoconjugates of host cells, as well as those lining the epithelia, are determinants for invasion of human tissues, for its cytotoxic activity, and finally for the outcome of the disease. In this review we present an overview of the information available on the amebic lectins and adhesins that are responsible of those adhesive interactions and we also refer to their effect on the host immune response. Finally, we present some concluding remarks and perspectives in the field. Full article
(This article belongs to the Special Issue Lectins)
Open AccessReview Indole Alkaloids from Catharanthus roseus: Bioproduction and Their Effect on Human Health
Molecules 2015, 20(2), 2973-3000; doi:10.3390/molecules20022973
Received: 30 October 2014 / Revised: 20 January 2015 / Accepted: 4 February 2015 / Published: 12 February 2015
Cited by 30 | PDF Full-text (811 KB) | HTML Full-text | XML Full-text
Abstract
Catharanthus roseus is a medicinal plant belonging to the family Apocynaceae which produces terpenoid indole alkaloids (TIAs) of high medicinal importance. Indeed, a number of activities like antidiabetic, bactericide and antihypertensive are linked to C. roseus. Nevertheless, the high added value of
[...] Read more.
Catharanthus roseus is a medicinal plant belonging to the family Apocynaceae which produces terpenoid indole alkaloids (TIAs) of high medicinal importance. Indeed, a number of activities like antidiabetic, bactericide and antihypertensive are linked to C. roseus. Nevertheless, the high added value of this plant is based on its enormous pharmaceutical interest, producing more than 130 TIAs, some of which exhibit strong pharmacological activities. The most striking biological activity investigated has been the antitumour effect of dimeric alkaloids such as anhydrovinblastine, vinblastine and vincristine which are already in pre-, clinical or in use. The great pharmacological importance of these indole alkaloids, contrasts with the small amounts of them found in this plant, making their extraction a very expensive process. To overcome this problem, researches have looked for alternative sources and strategies to produce them in higher amounts. In this sense, intensive research on the biosynthesis of TIAs and the regulation of their pathways has been developed with the aim to increase by biotechnological approaches, the production of these high added value compounds. This review is focused on the different strategies which improve TIA production, and in the analysis of the beneficial effects that these compounds exert on human health. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessReview Curcumin and Omega-3 Fatty Acids Enhance NK Cell-Induced Apoptosis of Pancreatic Cancer Cells but Curcumin Inhibits Interferon-γ Production: Benefits of Omega-3 with Curcumin against Cancer
Molecules 2015, 20(2), 3020-3026; doi:10.3390/molecules20023020
Received: 12 November 2014 / Revised: 15 January 2015 / Accepted: 27 January 2015 / Published: 12 February 2015
Cited by 16 | PDF Full-text (681 KB) | HTML Full-text | XML Full-text
Abstract
STAT-3 and STAT-1 signaling have opposite effects in oncogenesis with STAT-3 acting as an oncogene and STAT-1 exerting anti-oncogenic activities through interferon-γ and interferon-α. The cytokine IL-6 promotes oncogenesis by stimulation of NFκB and STAT-3 signaling. Curcuminoids have bi-functional effects by blocking NFκB
[...] Read more.
STAT-3 and STAT-1 signaling have opposite effects in oncogenesis with STAT-3 acting as an oncogene and STAT-1 exerting anti-oncogenic activities through interferon-γ and interferon-α. The cytokine IL-6 promotes oncogenesis by stimulation of NFκB and STAT-3 signaling. Curcuminoids have bi-functional effects by blocking NFκB anti-apoptotic signaling but also blocking anti-oncogenic STAT-1 signaling and interferon-γ production. In our recent study (unpublished work [1]) in pancreatic cancer cell cultures, curcuminoids enhanced cancer cell apoptosis both directly and by potentiating natural killer (NK) cell cytotoxic function. The cytotoxic effects of curcuminoids were increased by incubation of cancer cells and NK cells in an emulsion with omega-3 fatty acids and antioxidants (Smartfish), which enhanced cancer cell apoptosis and protected NK cells against degradation. However, as also shown by others, curcuminoids blocked interferon-γ production by NK cells. The combined use of curcuminoids and omega-3 in cancer immunotherapy will require deeper understanding of their in vivo interactions with the immune system. Full article
(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)
Open AccessReview Inhibitors of the AAA+ Chaperone p97
Molecules 2015, 20(2), 3027-3049; doi:10.3390/molecules20023027
Received: 8 December 2014 / Accepted: 3 February 2015 / Published: 12 February 2015
Cited by 24 | PDF Full-text (4198 KB) | HTML Full-text | XML Full-text | Correction
Abstract
It is remarkable that a pathway as ubiquitous as protein quality control can be targeted to treat cancer. Bortezomib, an inhibitor of the proteasome, was first approved by the US Food and Drug Administration (FDA) more than 10 years ago to treat refractory
[...] Read more.
It is remarkable that a pathway as ubiquitous as protein quality control can be targeted to treat cancer. Bortezomib, an inhibitor of the proteasome, was first approved by the US Food and Drug Administration (FDA) more than 10 years ago to treat refractory myeloma and later extended to lymphoma. Its use has increased the survival rate of myeloma patients by as much as three years. This success was followed with the recent accelerated approval of the natural product derived proteasome inhibitor carfilzomib (Kyprolis®), which is used to treat patients with bortezomib-resistant multiple myeloma. The success of these two drugs has validated protein quality control as a viable target to fight select cancers, but begs the question why are proteasome inhibitors limited to lymphoma and myeloma? More recently, these limitations have encouraged the search for additional targets within the protein quality control system that might offer heightened cancer cell specificity, enhanced clinical utility, a lower rate of resistance, reduced toxicity, and mitigated side effects. One promising target is p97, an ATPase associated with various cellular activities (AAA+) chaperone. p97 figures prominently in protein quality control as well as serving a variety of other cellular functions associated with cancer. More than a decade ago, it was determined that up-regulation of p97 in many forms of cancer correlates with a poor clinical outcome. Since these initial discoveries, a mechanistic explanation for this observation has been partially illuminated, but details are lacking. Understandably, given this clinical correlation, myriad roles within the cell, and its importance in protein quality control, p97 has emerged as a potential therapeutic target. This review provides an overview of efforts towards the discovery of small molecule inhibitors of p97, offering a synopsis of efforts that parallel the excellent reviews that currently exist on p97 structure, function, and physiology. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessReview Development of Bioorthogonal Reactions and Their Applications in Bioconjugation
Molecules 2015, 20(2), 3190-3205; doi:10.3390/molecules20023190
Received: 5 January 2015 / Revised: 19 January 2015 / Accepted: 2 February 2015 / Published: 16 February 2015
Cited by 18 | PDF Full-text (1053 KB) | HTML Full-text | XML Full-text
Abstract
Biomolecule labeling using chemical probes with specific biological activities has played important roles for the elucidation of complicated biological processes. Selective bioconjugation strategies are highly-demanded in the construction of various small-molecule probes to explore complex biological systems. Bioorthogonal reactions that undergo fast and
[...] Read more.
Biomolecule labeling using chemical probes with specific biological activities has played important roles for the elucidation of complicated biological processes. Selective bioconjugation strategies are highly-demanded in the construction of various small-molecule probes to explore complex biological systems. Bioorthogonal reactions that undergo fast and selective ligation under bio-compatible conditions have found diverse applications in the development of new bioconjugation strategies. The development of new bioorthogonal reactions in the past decade has been summarized with comments on their potentials as bioconjugation method in the construction of various biological probes for investigating their target biomolecules. For the applications of bioorthogonal reactions in the site-selective biomolecule conjugation, examples have been presented on the bioconjugation of protein, glycan, nucleic acids and lipids. Full article
(This article belongs to the Special Issue Bioconjugations)
Open AccessReview Prevention of Protein Glycation by Natural Compounds
Molecules 2015, 20(2), 3309-3334; doi:10.3390/molecules20023309
Received: 17 December 2014 / Revised: 10 February 2015 / Accepted: 11 February 2015 / Published: 16 February 2015
Cited by 23 | PDF Full-text (731 KB) | HTML Full-text | XML Full-text
Abstract
Non-enzymatic protein glycosylation (glycation) contributes to many diseases and aging of organisms. It can be expected that inhibition of glycation may prolong the lifespan. The search for inhibitors of glycation, mainly using in vitro models, has identified natural compounds able to prevent glycation,
[...] Read more.
Non-enzymatic protein glycosylation (glycation) contributes to many diseases and aging of organisms. It can be expected that inhibition of glycation may prolong the lifespan. The search for inhibitors of glycation, mainly using in vitro models, has identified natural compounds able to prevent glycation, especially polyphenols and other natural antioxidants. Extrapolation of results of in vitro studies on the in vivo situation is not straightforward due to differences in the conditions and mechanism of glycation, and bioavailability problems. Nevertheless, available data allow to postulate that enrichment of diet in natural anti-glycating agents may attenuate glycation and, in consequence, ageing. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
Open AccessReview Analysis of Phenolic and Cyclic Compounds in Plants Using Derivatization Techniques in Combination with GC-MS-Based Metabolite Profiling
Molecules 2015, 20(2), 3431-3462; doi:10.3390/molecules20023431
Received: 18 December 2014 / Revised: 6 January 2015 / Accepted: 10 February 2015 / Published: 17 February 2015
Cited by 6 | PDF Full-text (4126 KB) | HTML Full-text | XML Full-text
Abstract
Metabolite profiling has been established as a modern technology platform for the description of complex chemical matrices and compound identification in biological samples. Gas chromatography coupled with mass spectrometry (GC-MS) in particular is a fast and accurate method widely applied in diagnostics, functional
[...] Read more.
Metabolite profiling has been established as a modern technology platform for the description of complex chemical matrices and compound identification in biological samples. Gas chromatography coupled with mass spectrometry (GC-MS) in particular is a fast and accurate method widely applied in diagnostics, functional genomics and for screening purposes. Following solvent extraction and derivatization, hundreds of metabolites from different chemical groups can be characterized in one analytical run. Besides sugars, acids, and polyols, diverse phenolic and other cyclic metabolites can be efficiently detected by metabolite profiling. The review describes own results from plant research to exemplify the applicability of GC-MS profiling and concurrent detection and identification of phenolics and other cyclic structures. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessReview Nkrp1 Family, from Lectins to Protein Interacting Molecules
Molecules 2015, 20(2), 3463-3478; doi:10.3390/molecules20023463
Received: 15 November 2014 / Revised: 6 February 2015 / Accepted: 11 February 2015 / Published: 17 February 2015
Cited by 1 | PDF Full-text (1044 KB) | HTML Full-text | XML Full-text
Abstract
The C-type lectin-like receptors include the Nkrp1 protein family that regulates the activity of natural killer (NK) cells. Rat Nkrp1a was reported to bind monosaccharide moieties in a Ca2+-dependent manner in preference order of GalNac > GlcNAc >> Fuc >> Gal
[...] Read more.
The C-type lectin-like receptors include the Nkrp1 protein family that regulates the activity of natural killer (NK) cells. Rat Nkrp1a was reported to bind monosaccharide moieties in a Ca2+-dependent manner in preference order of GalNac > GlcNAc >> Fuc >> Gal > Man. These findings established for rat Nkrp1a have been extrapolated to all additional Nkrp1 receptors and have been supported by numerous studies over the past two decades. However, since 1996 there has been controversy and another article showed lack of interactions with saccharides in 1999. Nevertheless, several high affinity saccharide ligands were synthesized in order to utilize their potential in antitumor therapy. Subsequently, protein ligands were introduced as specific binders for Nkrp1 proteins and three dimensional models of receptor/protein ligand interaction were derived from crystallographic data. Finally, for at least some members of the NK cell C-type lectin-like proteins, the “sweet story” was impaired by two reports in recent years. It has been shown that the rat Nkrp1a and CD69 do not bind saccharide ligands such as GlcNAc, GalNAc, chitotetraose and saccharide derivatives (GlcNAc-PAMAM) do not directly and specifically influence cytotoxic activity of NK cells as it was previously described. Full article
(This article belongs to the Special Issue Lectins)

Other

Jump to: Editorial, Research, Review

Open AccessCorrection Correction: Calderon, C.P. Data-Driven Techniques for Detecting Dynamical State Changes in Noisily Measured 3D Single-Molecule Trajectories. Molecules 19, 18381-18398
Molecules 2015, 20(2), 2828-2830; doi:10.3390/molecules20022828
Received: 20 January 2015 / Accepted: 4 February 2015 / Published: 9 February 2015
PDF Full-text (768 KB) | HTML Full-text | XML Full-text
Abstract
The author wishes to make the following corrections to paper [1] (doi:10.3390/molecules191118381, website: http://www.mdpi.com/1420-3049/19/11/18381): Full article
(This article belongs to the Special Issue Single Molecule Techniques)
Figures

Figure 1

Open AccessCorrection Correction: El Azab, I.H., et al. Microwave-Assisted Synthesis of Novel 2H-Chromene Derivatives Bearing Phenylthiazolidinones and Their Biological Activity Assessment. Molecules 2014, 19, 19648-19664
Molecules 2015, 20(2), 2835-2836; doi:10.3390/molecules20022835
Received: 14 January 2015 / Accepted: 30 January 2015 / Published: 9 February 2015
PDF Full-text (592 KB) | HTML Full-text | XML Full-text
Abstract
The authors wish to revise the Author Affiliation section of the title paper, published in Molecules [1], (doi:10.3390/molecules191219648, website: http://www.mdpi.com/1420-3049/19/12/19648). To recognize the fact that the research described was performed in part at the facilities of Taif University and to acknowledge that institution’s
[...] Read more.
The authors wish to revise the Author Affiliation section of the title paper, published in Molecules [1], (doi:10.3390/molecules191219648, website: http://www.mdpi.com/1420-3049/19/12/19648). To recognize the fact that the research described was performed in part at the facilities of Taif University and to acknowledge that institution’s generous financial support[...] Full article
(This article belongs to the Section Organic Synthesis)
Back to Top