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Molecules, Volume 18, Issue 2 (February 2013), Pages 1337-2457

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Editorial

Jump to: Research, Review

Open AccessEditorial Molecules Best Paper Award 2013
Molecules 2013, 18(2), 2081-2083; doi:10.3390/molecules18022081
Received: 25 January 2013 / Revised: 25 January 2013 / Accepted: 4 February 2013 / Published: 5 February 2013
PDF Full-text (116 KB) | Supplementary Files
Abstract
Molecules has started to institute a "Best Paper" award to recognize the most outstanding papers in the area of natural products, medicinal chemistry and molecular diversity published in Molecules. We are pleased to announce the second "Molecules Best Paper Award" [...] Read more.
Molecules has started to institute a "Best Paper" award to recognize the most outstanding papers in the area of natural products, medicinal chemistry and molecular diversity published in Molecules. We are pleased to announce the second "Molecules Best Paper Award" for 2013. Candidates were chosen by the Editor-in-Chief and selected editorial board members from among all the papers published in 2009. [...] Full article
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Research

Jump to: Editorial, Review

Open AccessArticle Profiling and Characterization of Volatile Components from Non-Fumigated and Sulfur-Fumigated Flos Lonicerae Japonicae Using Comprehensive Two-Dimensional Gas Chromatography Time-of-Flight Mass Spectrometry Coupled with Chemical Group Separation
Molecules 2013, 18(2), 1368-1382; doi:10.3390/molecules18021368
Received: 25 October 2012 / Revised: 10 January 2013 / Accepted: 14 January 2013 / Published: 24 January 2013
Cited by 8 | PDF Full-text (977 KB)
Abstract
Flos Lonicerae Japonicae (FLJ) is a popular herb used for many centuries in Traditional Chinese Medicine as a treatment of fever and inflammation. Non-fumigated processing of FLJ has been the traditional approach used in post-harvest preparation of the commodity for commercial use. [...] Read more.
Flos Lonicerae Japonicae (FLJ) is a popular herb used for many centuries in Traditional Chinese Medicine as a treatment of fever and inflammation. Non-fumigated processing of FLJ has been the traditional approach used in post-harvest preparation of the commodity for commercial use. However, in recent years, natural drying processing of FLJ has been replaced by sulfur-fumigation for efficiency and pest control. Sulfur-fumigation can induce changes in the volatile compounds of the herb, altering its medicinal properties. A comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOF/MS) method was established for the resolution and determination of volatile components in non-fumigated and sulfur-fumigated FLJ. In this paper, analysis of the volatile oils in non-fumigated and sulfur-fumigated (including lab-prepared sulfur- fumigated and industrial sulfur-fumigated) FLJ was performed using GC×GC-TOF/MS. Seventy-three representative volatile components were identified, including furans, alkalies, acids, aldehydes, ketones, alcohols, terpenes, esters, and others, as the main components of FLJ volatile oils. The proposed method was successfully applied for rapid and accurate quality evaluation of FLJ and its related medicinal materials and preparations. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synthesis and Structure-Activity Relationships of Novel Amino/Nitro Substituted 3-Arylcoumarins as Antibacterial Agents
Molecules 2013, 18(2), 1394-1404; doi:10.3390/molecules18021394
Received: 24 December 2012 / Revised: 15 January 2013 / Accepted: 17 January 2013 / Published: 24 January 2013
Cited by 14 | PDF Full-text (213 KB)
Abstract
A new series of amino/nitro-substituted 3-arylcoumarins were synthesized and their antibacterial activity against clinical isolates of Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) was evaluated. Some of these molecules exhibited antibacterial activity against S. aureus comparable to the standards used (oxolinic acid [...] Read more.
A new series of amino/nitro-substituted 3-arylcoumarins were synthesized and their antibacterial activity against clinical isolates of Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) was evaluated. Some of these molecules exhibited antibacterial activity against S. aureus comparable to the standards used (oxolinic acid and ampicillin). The preliminary structure-activity relationship (SAR) study showed that the antibacterial activity against S. aureus depends on the position of the 3-arylcoumarin substitution pattern. With the aim of finding the structural features for the antibacterial activity and selectivity, in the present manuscript different positions of nitro, methyl, methoxy, amino and bromo substituents on the 3-arylcoumarin scaffold were reported. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Cytotoxic and Radical Scavenging Nor-Dammarane Triterpenoids from Viburnum mongolicum
Molecules 2013, 18(2), 1405-1417; doi:10.3390/molecules18021405
Received: 11 December 2012 / Revised: 28 December 2012 / Accepted: 5 January 2013 / Published: 24 January 2013
Cited by 3 | PDF Full-text (271 KB)
Abstract
The ethanol extract of the whole plants of Viburnum mongolicum afforded six new nor-dammarane triterpenoids: 3β,12β-dihydroxy-25,26,27-trinordammara-22-en -24,20-olide (1), 3β,12β-dihydroxy-24α-methoxy-25,26,27-trinordammara-20,24-epoxy (2), 3β-O-acetyl-12β-hydroxy-23,24,25,26,27-hexanordammarane-20-one ( [...] Read more.
The ethanol extract of the whole plants of Viburnum mongolicum afforded six new nor-dammarane triterpenoids: 3β,12β-dihydroxy-25,26,27-trinordammara-22-en -24,20-olide (1), 3β,12β-dihydroxy-24α-methoxy-25,26,27-trinordammara-20,24-epoxy (2), 3β-O-acetyl-12β-hydroxy-23,24,25,26,27-hexanordammarane-20-one (3), 12β-O- acetyl-15α-hydroxy-17β-methoxy-3-oxo-20,21,22-23,24,25,26,27-octanordammanrane (4), 12β-O-acetyl-15α,17β-dihydroxy-3-oxo-20,21,22-23,24,25,26,27-octanordammanrane (5), and 12β,15α-dihydroxy-3-oxo-17-en-20,21,22-23,24,25,26,27-octanordammanrane (6), together with two known nor-dammarane triterpenoids, 12β-hydroxy-3-oxo-24α-methoxy- 25,26,27-trinordammara-20,24-epoxy (7) and 3β,12β-dihydroxy-23,24,25,26,27- hexanordammarane-20-one (8). The structures of the isolated compounds were established based on 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated compounds were tested in vitro for cytotoxic potential against seven tumor cell lines and radical scavenging activities. Compounds 46 exhibited significant cytotoxic activities against all tested tumor cell lines and radical scavenging activities against ABTS·+ radicals comparable with the standard drug Trolox. Full article
(This article belongs to the Special Issue Triterpenes and Triterpenoids)
Open AccessArticle Induction of Apoptosis by Costunolide in Bladder Cancer Cells is Mediated through ROS Generation and Mitochondrial Dysfunction
Molecules 2013, 18(2), 1418-1433; doi:10.3390/molecules18021418
Received: 26 November 2012 / Revised: 15 January 2013 / Accepted: 16 January 2013 / Published: 24 January 2013
Cited by 23 | PDF Full-text (1379 KB)
Abstract
Despite the availability of several therapeutic options, a safer and more effective modality is urgently needed for treatment of bladder cancer. Costunolide, a member of sesquiterpene lactone family, possesses potent anticancer properties. In this study, for the first time we investigated the [...] Read more.
Despite the availability of several therapeutic options, a safer and more effective modality is urgently needed for treatment of bladder cancer. Costunolide, a member of sesquiterpene lactone family, possesses potent anticancer properties. In this study, for the first time we investigated the effects of costunolide on the cell viability and apoptosis in human bladder cancer T24 cells. Treatment of T24 cells with costunolide resulted in a dose-dependent inhibition of cell viability and induction of apoptosis which was associated with the generation of ROS and disruption of mitochondrial membrane potential (Δψm). These effects were significantly blocked when the cells were pretreated with N-acetyl- cysteine (NAC), a specific ROS inhibitor. Exposure of T24 cells to costunolide was also associated with increased expression of Bax, down-regulation of Bcl-2, survivin and significant activation of caspase-3, and its downstream target PARP. These findings provide the rationale for further in vivo and clinical investigation of costunolide against human bladder cancer. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Cytotoxicity and Anti-Inflammatory Activity of Methylsulfanyl-triazoloquinazolines
Molecules 2013, 18(2), 1434-1446; doi:10.3390/molecules18021434
Received: 24 December 2012 / Revised: 10 January 2013 / Accepted: 14 January 2013 / Published: 24 January 2013
Cited by 5 | PDF Full-text (239 KB) | Retraction
Abstract
A series of twenty five 2-methylsulfanyl-[1,2,4]triazolo[1,5-a]quinazoline derivatives 125 was previously synthesized. We have now investigated their cytotoxic effects against hepatocellular Hep-G2 and colon HCT-116 carcinoma cells and effect on the macrophage growth, in addition to their influence of [...] Read more.
A series of twenty five 2-methylsulfanyl-[1,2,4]triazolo[1,5-a]quinazoline derivatives 125 was previously synthesized. We have now investigated their cytotoxic effects against hepatocellular Hep-G2 and colon HCT-116 carcinoma cells and effect on the macrophage growth, in addition to their influence of the inflammatory mediators [nitric oxide (NO), tumor necrosis factor-α (TNF-α), prostaglandin E-2 (PGE-2) and in bacterial lipopolysachharide (LPS)-stimulated macrophages]. The findings revealed that compounds 13 and 17 showed the highest cytotoxicity and that 3, 68 and 25 are promising multi-potent anti-inflammatory agents. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Degradation Kinetics of Atorvastatin under Stress Conditions and Chemical Analysis by HPLC
Molecules 2013, 18(2), 1447-1456; doi:10.3390/molecules18021447
Received: 9 January 2013 / Revised: 9 January 2013 / Accepted: 14 January 2013 / Published: 24 January 2013
Cited by 3 | PDF Full-text (298 KB)
Abstract
Atorvastatin is an antilipemic drug belonging to the statins class, whose reference drug is Pfizer’s Lipitor®. It is used to reduce the levels of lipoproteins rich in cholesterol and reduce the risk of coronary artery disease. It is well-known that [...] Read more.
Atorvastatin is an antilipemic drug belonging to the statins class, whose reference drug is Pfizer’s Lipitor®. It is used to reduce the levels of lipoproteins rich in cholesterol and reduce the risk of coronary artery disease. It is well-known that calcium atorvastatin (ATV), C66H68CaF2N4O10•3H2O, presents polymorphism. The drug in question is commonly sought after by pharmaceutical industries that produce generic drugs, due to the fact that the drug has a high value price, it is consumed globally, and its patent expired in late 2010. Many questions concerning this drug’s pharmaceutical scope demonstrate its importance regarding stability studies and the identification of degradation products of drugs and pharmaceutical formulations. ATV has been found to degrade under acid and basic conditions, including a first order kinetic degradation under acid conditions, as compared to a zero order kinetic degradation under basic conditions, which tends to be less stable when studied within acid mediums. The rate constant (k) for degradation in acid medium was 1.88 × 10−2 s−1 (first order), while for basic medium k = 2.35 × 10−4 mol L−1 s−1 (zero order), demonstrating a lower stability of the drug within acid mediums. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Degradation of Methyl Blue Using Fe-Tourmaline as a Novel Photocatalyst
Molecules 2013, 18(2), 1457-1463; doi:10.3390/molecules18021457
Received: 10 December 2012 / Revised: 8 January 2013 / Accepted: 14 January 2013 / Published: 24 January 2013
Cited by 4 | PDF Full-text (234 KB)
Abstract
This study investigated the photocatalytic activity of tourmaline by itself. Under irradiation of a 13 W, 254 nm UV lamp, 50% of methyl blue disappeared in the presence of 130 mg·L−1 tourmaline. The reaction was inhibited by the addition of ethanol, [...] Read more.
This study investigated the photocatalytic activity of tourmaline by itself. Under irradiation of a 13 W, 254 nm UV lamp, 50% of methyl blue disappeared in the presence of 130 mg·L−1 tourmaline. The reaction was inhibited by the addition of ethanol, Cl, SO42− and Cu2+, and promoted a little by addition of 50 mg/L Mg2+, which supports the inference of involvement of OH radicals. This is the first proposal of tourmaline as a single photocatalyst without the need to add any artificial chemical products. Results from this study might contribute to the broadened usage of this mineral to approach the goals of saving energy and eliminate direct or indirect environmental pollution. Full article
Open AccessArticle Crystal Structure, Antibacterial and Cytotoxic Activities of a New Complex of Bismuth(III) with Sulfapyridine
Molecules 2013, 18(2), 1464-1476; doi:10.3390/molecules18021464
Received: 21 December 2012 / Revised: 17 January 2013 / Accepted: 17 January 2013 / Published: 24 January 2013
Cited by 5 | PDF Full-text (272 KB) | Supplementary Files
Abstract
A new complex of Bi(III) and sulfapyridine was synthesized and characterized by elemental analysis, atomic absorption spectrometry, conductivity analysis, electrospray ionization mass spectrometry (ESI-MS), infrared spectroscopy, and single crystal X-ray diffraction methods. The antimicrobial and the cytotoxic activities of the compound were [...] Read more.
A new complex of Bi(III) and sulfapyridine was synthesized and characterized by elemental analysis, atomic absorption spectrometry, conductivity analysis, electrospray ionization mass spectrometry (ESI-MS), infrared spectroscopy, and single crystal X-ray diffraction methods. The antimicrobial and the cytotoxic activities of the compound were investigated. Elemental and conductivity analyses are in accordance to the formulation [BiCl3(C11H11N3O2S)3]. The structure of the complex reveals a distorted octahedral geometry around the bismuth atom, which is bound to three sulfonamidic nitrogens from sulfapyridine, acting as a monodentate ligand, and to three chloride ions. The presence of the compound in solution was confirmed by ESI-MS studies. The complex is 3 times more potent than the ligand against Salmonella typhimurium, 4 times against Staphylococcus aureus, Shigella dysenteriae, and Shigella sonnei and 8 times more potent against Pseudomonas aeruginosa and Escherichia coli. The compound inhibits the growth of chronic myelogenous leukemia cells with an IC50 value of 44 μM whereas the free ligand has no effect up to 100 μM. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Two New Derivatives of 2, 5-Dihydroxyphenylacetic Acid from the Kernel of Entada phaseoloides
Molecules 2013, 18(2), 1477-1482; doi:10.3390/molecules18021477
Received: 14 January 2013 / Revised: 18 January 2013 / Accepted: 18 January 2013 / Published: 25 January 2013
Cited by 3 | PDF Full-text (206 KB)
Abstract
Two new aromatic compounds, butyl 2,5-dihydroxyphenylacetate (1) and butyl 2-O-β-D-glucopyranosyloxy-5-dihydroxyphenylacetate (2), together with three known ones, methyl 2,5-dihydroxyphenylacetate (3), ethyl 2,5-dihydroxyphenylacetate (4) and 2-O-β-D-glucopyranosyloxy-5-hydroxyphenylacetic acid (5), were isolated [...] Read more.
Two new aromatic compounds, butyl 2,5-dihydroxyphenylacetate (1) and butyl 2-O-β-D-glucopyranosyloxy-5-dihydroxyphenylacetate (2), together with three known ones, methyl 2,5-dihydroxyphenylacetate (3), ethyl 2,5-dihydroxyphenylacetate (4) and 2-O-β-D-glucopyranosyloxy-5-hydroxyphenylacetic acid (5), were isolated from the EtOH extract of the kernel of Entada phaseoloides. The structures of the new compounds were elucidated by MS and NMR experiments. Compounds 1, 3 and 4 displayed potent inhibitory activities against HIV-1 replication, with EC50 values of 9.80 μM, 11.70 μM and 9.93 μM, respectively. Full article
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Open AccessArticle Synthesis of Thiophene and NO-Curcuminoids for Antiinflammatory and Anti-Cancer Activities
Molecules 2013, 18(2), 1483-1501; doi:10.3390/molecules18021483
Received: 13 November 2012 / Revised: 7 January 2013 / Accepted: 15 January 2013 / Published: 25 January 2013
Cited by 7 | PDF Full-text (426 KB)
Abstract
In search of better NSAIDs four novel nitric oxide donating derivatives of curcumin (compounds 9ad), and four thiophene curcuminoids (compounds 10ac, 11) have been synthesised. The cytotoxic effects of these compounds along with the lead [...] Read more.
In search of better NSAIDs four novel nitric oxide donating derivatives of curcumin (compounds 9ad), and four thiophene curcuminoids (compounds 10ac, 11) have been synthesised. The cytotoxic effects of these compounds along with the lead compound curcumin (7) and their effect on the production of the reactive oxygen species nitric oxide and pro-inflammatory cytokines IL-1β, TNF-α and chemokine CXCL-8 were evaluated using human monocytic THP-1 and colon adenocarcinoma CACO-2 cell lines. All of the nitric oxide donating curcuminoids 9ad and the thiophene curcuminoids 10ac and 11 were non-cytotoxic to THP-1 cells over a concentration range of 10-100 μM and compared with curcumin compounds 10b and 10c, were more toxic. In CACO-2 cells, 10b and 11 appeared to be non-toxic at 10 to 50 μM, whereas 10a and 10c were non-cytotoxic at 10 μM only. These results clearly indicate that the introduction of a nitroxybutyl moiety to curcumin and replacement of phenyl rings with thiophene units reduces the cytotoxic effect of the parent curcumin, whereas a methyl substituted thiophene increases the cytotoxic effects. In THP-1 cells, drugs 10a and 11 significantly decreased IL-1-β production at their non-cytotoxic concentrations, whereas, they did not decrease TNF-α production in CACO-2 cells. Compound 11 showed a significant decrease in CXCL-8 production. Full article
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Open AccessArticle Synthesis and Characterization of Novel Dendrons Bearing Amino-Nitro-Substituted Azobenzene Units and Oligo(ethylene glycol) Spacers: Thermal, Optical Properties, Langmuir Blodgett Films and Liquid-Crystalline Behaviour
Molecules 2013, 18(2), 1502-1527; doi:10.3390/molecules18021502
Received: 6 December 2012 / Revised: 28 December 2012 / Accepted: 18 January 2013 / Published: 25 January 2013
Cited by 4 | PDF Full-text (685 KB)
Abstract
In this work, we report the synthesis and characterization of a novel series of first and second generation Fréchet type dendrons bearing amino-nitro substituted azobenzene units and tetra(ethylene glycol) spacers. These compounds were fully characterized by FTIR, 1H and 13C-NMR [...] Read more.
In this work, we report the synthesis and characterization of a novel series of first and second generation Fréchet type dendrons bearing amino-nitro substituted azobenzene units and tetra(ethylene glycol) spacers. These compounds were fully characterized by FTIR, 1H and 13C-NMR spectroscopies, and their molecular weights were determined by MALDI-TOF-MS. The thermal properties of the obtained dendrons were studied by TGA and DSC and their optical properties by absorption spectroscopy in solution and cast film. Molecular calculations were performed in order to determine the optimized geometries of these molecules in different environments. Besides, Langmuir and Langmuir Blodgett films were prepared with the first generation dendrons that were shown to be amphiphilic. Finally, some of the dendrons showed a liquid crystalline behaviour, which was studied by light polarized microscopy as a function of the temperature in order to determine the transition temperatures and the structure of the mesophase. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Oxygen Radical Absorbance Capacity of Different Varieties of Strawberry and the Antioxidant Stability in Storage
Molecules 2013, 18(2), 1528-1539; doi:10.3390/molecules18021528
Received: 10 December 2012 / Revised: 18 January 2013 / Accepted: 21 January 2013 / Published: 25 January 2013
Cited by 3 | PDF Full-text (335 KB)
Abstract
Total antioxidant capacity of different varieties of strawberry (Ningfeng, Ningyu, Zijin 4, Toyonoka, Benihope, Sweet Charlie) in different developmental stages (including green unripe stages, half red stages, and red ripe stages) was investigated by oxygen radical absorbance capacity (ORAC) assay. In addition, [...] Read more.
Total antioxidant capacity of different varieties of strawberry (Ningfeng, Ningyu, Zijin 4, Toyonoka, Benihope, Sweet Charlie) in different developmental stages (including green unripe stages, half red stages, and red ripe stages) was investigated by oxygen radical absorbance capacity (ORAC) assay. In addition, effects of the antioxidant properties of strawberry stored at 4 °C or −18 °C for a period of five months were studied. The results showed that antioxidant capacity of strawberry changed based on tested part, developmental stage, variety, and time of collection. Calyces had significantly higher ORAC values compared with fruits. Strawberry fruits had higher ORAC values during the green unripe stages than the half red stages and red ripe stages. Strawberries got higher ORAC values during short-time storage, and then decreased during long-time storage. Samples stored at −18 °C exhibited higher antioxidant capacity than those stored at 4 °C, while vacuum treatment could further increase ORAC values. The results indicated the potential market role of strawberries as a functional food and could provide great value in preventing oxidation reaction in food processing and storage for the dietary industry. Full article
Open AccessCommunication Original TDAE Strategy Using Propargylic Chloride: Rapid Access to 1,4-Diarylbut-3-ynol Derivatives
Molecules 2013, 18(2), 1540-1548; doi:10.3390/molecules18021540
Received: 12 November 2012 / Revised: 16 January 2013 / Accepted: 22 January 2013 / Published: 25 January 2013
Cited by 4 | PDF Full-text (221 KB)
Abstract We report herein the first synthesis of propargylic alcohols using an organic reducing agent. Diarylbutynol derivatives are formed in moderate to good yields under mild conditions from the reaction of 1-(3-chloroprop-1-ynyl)-4-nitrobenzene with various aromatic aldehydes using tetrakis(dimethylamino)ethylene (TDAE) as reductant. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Fruit Coloration and Anthocyanin Biosynthesis after Bag Removal in Non-Red and Red Apples (Malus × domestica Borkh.)
Molecules 2013, 18(2), 1549-1563; doi:10.3390/molecules18021549
Received: 28 November 2012 / Revised: 10 January 2013 / Accepted: 22 January 2013 / Published: 25 January 2013
Cited by 12 | PDF Full-text (714 KB)
Abstract
In the present study, evolution of apple color (L* and a/b), the accumulation of anthocyanins and the activity of the related enzymes, phenylalanine ammonia-lyase (PAL), chalcone isomerase (CHI), dihydroflavonol4-reductase (DFR) and UDP-Glucose: flavonoid-3-O-galactosyl transferase (UFGT), were investigated in bagged non-red [...] Read more.
In the present study, evolution of apple color (L* and a/b), the accumulation of anthocyanins and the activity of the related enzymes, phenylalanine ammonia-lyase (PAL), chalcone isomerase (CHI), dihydroflavonol4-reductase (DFR) and UDP-Glucose: flavonoid-3-O-galactosyl transferase (UFGT), were investigated in bagged non-red apple cultivars (‘Granny Smith’ and ‘Golden Delicious’) and red apple cultivars (‘Starkrimon’ and ‘Pink Lady’). Young fruits were bagged 40–45 days after flowering (DAF), and fruits of ‘Golden Delicious’ and ‘Starkrimon’ were uncovered and exposed to light 120 DAF, while those of ‘Granny Smith’ and ‘Pink Lady’ were exposed for 160 DAF. Results showed that cyanidin 3-galactoside (cy3-gal) was the most abundant anthocyanin in both non-red and red cultivars. Level of anthocyanins was higher in ‘Granny Smith’ than in ‘Golden Delicious’, indicating that red color was easier to develop in green cultivar ‘Granny Smith’ than in yellow cultivar ‘Golden Delicious’ after bag removal. The cy3-gal accumulation of non-red cultivars tested was not significantly correlated with PAL, CHI and DFR activity, but was significantly correlated with UFGT activity. During the reddening of non-red apples, UFGT may be the more important factor in the anthocyanin biosynthesis. Full article
Open AccessArticle Synergism of Antifungal Activity between Mitochondrial Respiration Inhibitors and Kojic Acid
Molecules 2013, 18(2), 1564-1581; doi:10.3390/molecules18021564
Received: 4 January 2013 / Revised: 19 January 2013 / Accepted: 22 January 2013 / Published: 25 January 2013
Cited by 4 | PDF Full-text (559 KB)
Abstract
Co-application of certain types of compounds to conventional antimicrobial drugs can enhance the efficacy of the drugs through a process termed chemosensitization. We show that kojic acid (KA), a natural pyrone, is a potent chemosensitizing agent of complex III inhibitors disrupting the [...] Read more.
Co-application of certain types of compounds to conventional antimicrobial drugs can enhance the efficacy of the drugs through a process termed chemosensitization. We show that kojic acid (KA), a natural pyrone, is a potent chemosensitizing agent of complex III inhibitors disrupting the mitochondrial respiratory chain in fungi. Addition of KA greatly lowered the minimum inhibitory concentrations of complex III inhibitors tested against certain filamentous fungi. Efficacy of KA synergism in decreasing order was pyraclostrobin > kresoxim-methyl > antimycin A. KA was also found to be a chemosensitizer of cells to hydrogen peroxide (H2O2), tested as a mimic of reactive oxygen species involved in host defense during infection, against several human fungal pathogens and Penicillium strains infecting crops. In comparison, KA-mediated chemosensitization to complex III inhibitors/H2O2 was undetectable in other types of fungi, including Aspergillus flavus, A. parasiticus, and P. griseofulvum, among others. Of note, KA was found to function as an antioxidant, but not as an antifungal chemosensitizer in yeasts. In summary, KA could serve as an antifungal chemosensitizer to complex III inhibitors or H2O2 against selected human pathogens or Penicillium species. KA-mediated chemosensitization to H2O2 seemed specific for filamentous fungi. Thus, results indicate strain- and/or drug-specificity exist during KA chemosensitization. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Extraction of Antioxidant Components from Bidens pilosa Flowers and Their Uptake by Human Intestinal Caco-2 Cells
Molecules 2013, 18(2), 1582-1601; doi:10.3390/molecules18021582
Received: 11 December 2012 / Revised: 9 January 2013 / Accepted: 22 January 2013 / Published: 25 January 2013
Cited by 6 | PDF Full-text (579 KB)
Abstract
Bidens pilosa L. var. radiata (BPR, Asteraceae) is a commonly used folk medicine for treating various disorders such as diabetes, inflammation and hypertension. Recent studies to determine its chemical composition have revealed three di-O-caffeoylquinic acids (DiCQAs) and three polyacetylene glucosides [...] Read more.
Bidens pilosa L. var. radiata (BPR, Asteraceae) is a commonly used folk medicine for treating various disorders such as diabetes, inflammation and hypertension. Recent studies to determine its chemical composition have revealed three di-O-caffeoylquinic acids (DiCQAs) and three polyacetylene glucosides (PGAs) to be among the major bioactive markers. To obtain the major compounds of these two chemical classes, the ethyl acetate fraction (EM) obtained using liquid-liquid partition from the methanol extract resulted in a fraction with the highest total phenolic and total flavonoid contents and antioxidant activities in radical scavenging and ferric reducing power assays. To assess the bioavailability of EM, we examined the in vitro uptake using the Caco-2 human colonic cell line. The apparent permeability coefficient (Papp) for each of the compounds within PGAs measured in both apical (AP) to basolateral (BL) and BL to AP was found to preferentially appear BL to AP direction, indicated that a basolateral to apical efflux system was detected in the study. DiCQAs had a lower efflux ratio than those from PGAs (2.32–3.67 vs. 6.03–78.36). Thus, it strongly implies that most of the DiCQAs are better absorbed than the PGAs. Full article
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Open AccessArticle An Efficient Microwave-Assisted Suzuki Reaction using a New Pyridine-Pyrazole/Pd(II) Species as Catalyst in Aqueous Media
Molecules 2013, 18(2), 1602-1612; doi:10.3390/molecules18021602
Received: 27 December 2012 / Revised: 21 January 2013 / Accepted: 22 January 2013 / Published: 25 January 2013
Cited by 4 | PDF Full-text (332 KB) | Supplementary Files
Abstract
A new pyridine-pyrazole N–N ligand has been conveniently synthesized and characterized by 1H-, 13C-NMR, IR spectroscopies, HRMS and X-ray single-crystal crystallography analyses. The ligand adds to palladium(II) under basic conditions to give high yields of an air-stable and water-soluble complex [...] Read more.
A new pyridine-pyrazole N–N ligand has been conveniently synthesized and characterized by 1H-, 13C-NMR, IR spectroscopies, HRMS and X-ray single-crystal crystallography analyses. The ligand adds to palladium(II) under basic conditions to give high yields of an air-stable and water-soluble complex that was fully characterized by NMR and HRMS. The complex was investigated as a catalyst for the Suzuki reaction in aqueous media under microwave irradiation. The compound proved to be an effective catalyst. Full article
Open AccessArticle Microwave-Assisted Improved Synthesis of Pyrrolo[2,3,4-kl]acridine and Dihydropyrrolo[2,3,4-kl]acridine Derivatives Catalyzed by Silica Sulfuric Acid
Molecules 2013, 18(2), 1613-1625; doi:10.3390/molecules18021613
Received: 29 November 2012 / Revised: 21 December 2012 / Accepted: 5 January 2013 / Published: 28 January 2013
Cited by 9 | PDF Full-text (223 KB)
Abstract
An improved synthesis of multifunctionalized pyrrolo[2,3,4-kl]acridine derivatives with different substituted patterns using silica sulfuric acid (SSA) as a heterogeneous catalyst under microwave irradiation conditions was developed. The reaction could be conducted by using readily available and inexpensive substrates within short [...] Read more.
An improved synthesis of multifunctionalized pyrrolo[2,3,4-kl]acridine derivatives with different substituted patterns using silica sulfuric acid (SSA) as a heterogeneous catalyst under microwave irradiation conditions was developed. The reaction could be conducted by using readily available and inexpensive substrates within short periods of 12–15 min. under microwave irradiation. Compared with the conventional methods, the remarkable advantages of this method are milder reaction conditions, operational simplicity, higher yields, short reaction times, and an environmentally friendly procedure. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Diastereoselective [2+2] Photocycloaddition of Chiral Cyclic Enones with Olefins in Aqueous Media Using Surfactants
Molecules 2013, 18(2), 1626-1637; doi:10.3390/molecules18021626
Received: 7 January 2013 / Revised: 15 January 2013 / Accepted: 21 January 2013 / Published: 28 January 2013
Cited by 4 | PDF Full-text (269 KB)
Abstract
We conducted diastereodifferentiating [2+2] photocycloadditions of cyclo-hexenones modified with a chiral 8-(p-methoxy phenyl)menthyl auxiliary with olefins in water. Although the photoreaction didn’t proceed at all in pure water owing to very low solubility, the use of surfactants [sodium dodecyl sulfate [...] Read more.
We conducted diastereodifferentiating [2+2] photocycloadditions of cyclo-hexenones modified with a chiral 8-(p-methoxy phenyl)menthyl auxiliary with olefins in water. Although the photoreaction didn’t proceed at all in pure water owing to very low solubility, the use of surfactants [sodium dodecyl sulfate (SDS) or dodecylamine hydrochloride (DAH)] and additive (organic solvent) enabled the reactions to progress with moderate to high conversions and yields. Furthermore, we synthesized a new menthol derivative substrate containing a (p-octyloxy)phenyl group for enhancing hydrophobicity, and elucidated that this new substrate was found to be a suitable chiral auxiliary in this asymmetric photoreaction in aqueous system. The additive effect of organic molecules on the yield and diastereoselectivity of the photo-adducts is also discussed. Full article
(This article belongs to the Special Issue New Trends in Photochemistry)
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Open AccessArticle Use of Pyrogallol Red and Pyranine as Probes to Evaluate Antioxidant Capacities towards Hypochlorite
Molecules 2013, 18(2), 1638-1652; doi:10.3390/molecules18021638
Received: 13 November 2012 / Revised: 20 December 2012 / Accepted: 14 January 2013 / Published: 28 January 2013
Cited by 5 | PDF Full-text (817 KB)
Abstract
Hypochlorite is a strong oxidant able to induce deleterious effects in biological systems. The goal of this work was to investigate the use of PGR and PYR as probes in assays aimed at evaluating antioxidant activities towards hypochorite and apply it to [...] Read more.
Hypochlorite is a strong oxidant able to induce deleterious effects in biological systems. The goal of this work was to investigate the use of PGR and PYR as probes in assays aimed at evaluating antioxidant activities towards hypochorite and apply it to plant extracts employed in Chilean folk medicine. The consumption of PGR and PYR was evaluated from the decrease in the visible absorbance and fluorescence intensity, respectively. Total phenolic content was determined by the Folin Ciocalteau assay. PGR and PYR react with hypochlorite with different kinetics, being considerably faster the consumption of PGR. Different stoichiometric values were also determined: 0.7 molecules of PGR and 0.33 molecules of PYR were bleached per each molecule of added hypochlorite. Both probes were protected by antioxidants, but the rate of PGR bleaching was too fast to perform a kinetic analysis. For PYR, the protection took place without changes in its initial consumption rate, suggesting a competition between the dye and the antioxidant for hypochlorite. Plant extracts protected PYR giving a PYR-HOCl index that follows the order: Fuchsia magellanica » Marrubium vulgare » Tagetes minuta > Chenopodium ambrosoides » Satureja montana > Thymus praecox. Based on both the kinetic data and the protection afforded by pure antioxidants, we selected PYR as the best probe. The proposed methodology allows evaluating an antioxidant capacity index of plant extracts related to the reactivity of the samples towards hypochlorite. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Graphite-Supported Perchloric Acid (HClO4-C): An Efficient and Recyclable Heterogeneous Catalyst for the One-Pot Synthesis of Amidoalkyl Naphthols
Molecules 2013, 18(2), 1653-1659; doi:10.3390/molecules18021653
Received: 14 November 2012 / Revised: 21 January 2013 / Accepted: 22 January 2013 / Published: 28 January 2013
Cited by 8 | PDF Full-text (187 KB)
Abstract
An efficient and direct protocol for the preparation of amidoalkylnaphthols employing a multi-component, one-pot condensation reaction of 2-naphthol, aromatic aldehydes and acetamide or benzamide in the presence of graphite supported perchloric acid under solvent-free conditions is described. The thermal solvent-free procedure offers [...] Read more.
An efficient and direct protocol for the preparation of amidoalkylnaphthols employing a multi-component, one-pot condensation reaction of 2-naphthol, aromatic aldehydes and acetamide or benzamide in the presence of graphite supported perchloric acid under solvent-free conditions is described. The thermal solvent-free procedure offers advantages such as simple work-up, shorter reaction times and higher product yields, and the catalyst exhibited remarkable reactivity and can be recycled. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Production of Polygalacturonases by Aspergillus section Nigri Strains in a Fixed Bed Reactor
Molecules 2013, 18(2), 1660-1671; doi:10.3390/molecules18021660
Received: 26 November 2012 / Revised: 9 January 2013 / Accepted: 11 January 2013 / Published: 28 January 2013
Cited by 5 | PDF Full-text (551 KB)
Abstract
Polygalacturonases (PG) are pectinolytic enzymes that have technological, functional and biological applications in food processing, fruit ripening and plant-fungus interactions, respectively. In the present, a microtitre plate methodology was used for rapid screening of 61 isolates of fungi from Aspergillus section Nigri [...] Read more.
Polygalacturonases (PG) are pectinolytic enzymes that have technological, functional and biological applications in food processing, fruit ripening and plant-fungus interactions, respectively. In the present, a microtitre plate methodology was used for rapid screening of 61 isolates of fungi from Aspergillus section Nigri to assess production of endo- and exo-PG. Studies of scale-up were carried out in a fixed bed reactor operated under different parameters using the best producer strain immobilised in orange peels. Four experiments were conducted under the following conditions: the immobilised cells without aeration; immobilised cells with aeration; immobilised cells with aeration and added pectin; and free cells with aeration. The fermentation was performed for 168 h with removal of sample every 24 h. Aspergillus niger strain URM 5162 showed the highest PG production. The results obtained indicated that the maximum endo- and exo-PG activities (1.18 U·mL−1 and 4.11 U·mL−1, respectively) were obtained when the reactor was operating without aeration. The microtitre plate method is a simple way to screen fungal isolates for PG activity detection. The fixed bed reactor with orange peel support and using A. niger URM 5162 is a promising process for PG production at the industrial level. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle The Passiflora tripartita (Banana Passion) Fruit: A Source of Bioactive Flavonoid C-Glycosides Isolated by HSCCC and Characterized by HPLC–DAD–ESI/MS/MS
Molecules 2013, 18(2), 1672-1692; doi:10.3390/molecules18021672
Received: 12 November 2012 / Revised: 6 January 2013 / Accepted: 10 January 2013 / Published: 28 January 2013
Cited by 31 | PDF Full-text (1050 KB) | Supplementary Files
Abstract
The banana passion fruit (Passiflora tripartita Breiter, Passifloraceae) known as “tumbo” is very appreciated in tropical and subtropical countries of South America. Methanolic extracts from peel and the fruit juice of P. tripartita growing in Chile were analyzed for antioxidant capacity [...] Read more.
The banana passion fruit (Passiflora tripartita Breiter, Passifloraceae) known as “tumbo” is very appreciated in tropical and subtropical countries of South America. Methanolic extracts from peel and the fruit juice of P. tripartita growing in Chile were analyzed for antioxidant capacity as well as for flavonoid and phenolic content. A chromatographic method was developed for the rapid identification of the main phenolics in the samples by HPLC-DAD and HPLC-MS. The fast fingerprint analysis allowed the detection of eighteen flavonoid C-glycosides and four flavonoid O-glycoside derivatives which were characterized by UV spectra and ESI-MS-MS analysis. Several of the C-glycosides detected are structurally related to the orientin derivative 4′-methoxy-luteolin-8-C-(6″acetyl)-b-D-glucopyranoside (31), fully elucidated by spectroscopic methods. The antioxidant derivative 31 along with schaftoside, vicenin II, orientin and vitexin were isolated from the fruit extract by high-speed countercurrent chromatography (HSCCC). A suitable method for the preparative isolation of flavonol C-glycosides from “tumbo” extracts by HSCCC is reported. The pulp of the fruits showed good antioxidant capacity (12.89 ± 0.02 mg/mL in the DPPH assay). The peel presented the highest content of flavonoids (56.03 ± 4.34 mg quercetin/100 g dry weight) which is related to the highest antioxidant power (10.41 ± 0.01 mg/mL in the DPPH assay). Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle The Synthesis and Evaluation of Novel Hydroxyl Substituted Chalcone Analogs with in Vitro Anti-Free Radicals Pharmacological Activity and in Vivo Anti-Oxidation Activity in a Free Radical-Injury Alzheimer’s Model
Molecules 2013, 18(2), 1693-1703; doi:10.3390/molecules18021693
Received: 29 November 2012 / Revised: 20 December 2012 / Accepted: 20 January 2013 / Published: 28 January 2013
Cited by 3 | PDF Full-text (359 KB)
Abstract
Alzheimer’s disease (AD) pathogenesis involves an imbalance between free radical formation and destruction. In order to obtain a novel preclinical anti-AD drug candidate, we synthesized a series of novel hydroxyl chalcone analogs which possessed anti-free radical activity, and screened their effects on [...] Read more.
Alzheimer’s disease (AD) pathogenesis involves an imbalance between free radical formation and destruction. In order to obtain a novel preclinical anti-AD drug candidate, we synthesized a series of novel hydroxyl chalcone analogs which possessed anti-free radical activity, and screened their effects on scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and OH free radicals in vitro. Compound C7, 4,2'-dihydroxy-3,5-dimethoxychalcone was found to have potent activity in these anti-free radical activity tests. Further research revealed that C7 could elevate glutathione peroxidase (GSH-PX) and super oxide dismutase (SOD) levels and lower malonaldehyde (MDA) level in vivo in the Alzheimer’s model. The indication of C7’s effect on AD needs further study. Full article
Open AccessArticle Sinapyl Alcohol Derivatives from the Lipo-soluble Part of Dichrocephala benthamii C. B. Clarke
Molecules 2013, 18(2), 1720-1727; doi:10.3390/molecules18021720
Received: 19 December 2012 / Revised: 18 January 2013 / Accepted: 18 January 2013 / Published: 29 January 2013
Cited by 5 | PDF Full-text (259 KB) | Supplementary Files
Abstract
Four new sinapyl alcohol derivatives dichrocephols A–D (compounds 14) were isolated from the lipo-soluble part of the whole herb of Dichrocephala benthamii C. B. Clarke, together with the known compound syringenin isovalerate (5). Their structures were elucidated [...] Read more.
Four new sinapyl alcohol derivatives dichrocephols A–D (compounds 14) were isolated from the lipo-soluble part of the whole herb of Dichrocephala benthamii C. B. Clarke, together with the known compound syringenin isovalerate (5). Their structures were elucidated on the basis of spectroscopic analysis. Their absolute configurations were established by the method of alkaline hydrohysis. Compounds 13 showed moderate cytotoxity against HeLa cells, with IC50 values of 14.8 μM, 51.6 μM and 81.6 μM, respectively. This is the first time that sinapyl alcohol derivatives were isolated from the genus Dichrocephala. Full article
Open AccessArticle Anti-Mycobacterial Activity of Marine Fungus-Derived 4-Deoxybostrycin and Nigrosporin
Molecules 2013, 18(2), 1728-1740; doi:10.3390/molecules18021728
Received: 28 November 2012 / Revised: 17 December 2012 / Accepted: 15 January 2013 / Published: 29 January 2013
Cited by 9 | PDF Full-text (202 KB)
Abstract
4-Deoxybostrycin is a natural anthraquinone compound isolated from the Mangrove endophytic fungus Nigrospora sp. collected from the South China Sea. Nigrosporin is the deoxy-derivative of 4-deoxybostrycin. They were tested against mycobacteria, especially Mycobacterium tuberculosis. In the Kirby-Bauer disk diffusion susceptibility test, [...] Read more.
4-Deoxybostrycin is a natural anthraquinone compound isolated from the Mangrove endophytic fungus Nigrospora sp. collected from the South China Sea. Nigrosporin is the deoxy-derivative of 4-deoxybostrycin. They were tested against mycobacteria, especially Mycobacterium tuberculosis. In the Kirby-Bauer disk diffusion susceptibility test, they both had inhibition zone sizes of over 25 mm. The results of the absolute concentration susceptibility test suggested that they had inhibitory effects against mycobacteria. Moreover, 4-deoxybostrycin exhibited good inhibition which was even better than that of first line anti-tuberculosis (TB) drugs against some clinical multidrug-resistant (MDR) M. tuberculosis strains. The gene expression profile of M. tuberculosis H37Rv after treatment with 4-deoxybostrycin was compared with untreated bacteria. One hundred and nineteen out of 3,875 genes were significantly different in M. tuberculosis exposed to 4-deoxybostrycin from control. There were 46 functionally known genes which are involved in metabolism, information storage and processing and cellular processes. The differential expressions of six genes were further confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). The present study provides a useful experiment basis for exploitation of correlative new drugs against TB and for finding out new targets of anti-mycobacterial therapy. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Ganoderma tsugae Hepatoprotection against Exhaustive Exercise-Induced Liver Injury in Rats
Molecules 2013, 18(2), 1741-1754; doi:10.3390/molecules18021741
Received: 18 December 2012 / Revised: 24 January 2013 / Accepted: 25 January 2013 / Published: 29 January 2013
Cited by 10 | PDF Full-text (1979 KB)
Abstract
Several studies have been shown that accelerated apoptosis is involved in post-exercise lymphocytopenia and tissue damage after high-intensity exercise. Ganoderma tsugae (GT) is one of the well-known medicinal mushrooms that possess various pharmacological functions. This mushroom has traditionally been used for health [...] Read more.
Several studies have been shown that accelerated apoptosis is involved in post-exercise lymphocytopenia and tissue damage after high-intensity exercise. Ganoderma tsugae (GT) is one of the well-known medicinal mushrooms that possess various pharmacological functions. This mushroom has traditionally been used for health promotion purposes. This study investigates the hepatoprotective effects of GT on exhaustive exercise-induced liver damage. Twenty-four male Sprague-Dawley rats were randomly divided into four groups and designated as exhaustive exercise only (E), exhaustive exercise with low dosage (EL), medium dosage (EM) and high dosage (EH) GT at 0, 0.1875, 0.9375 and 1.875 g/kg/day, respectively. After 30 days all rats were euthanized immediately after an exhaustive running challenge on a motorized treadmill. The rat livers were immediately harvested. Evidence of apoptotic liver cell death was revealed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and caspases mediated cascade events. DNA fragmentation, an apoptosis process, can be examined using TUNEL assay. A few TUNEL-positive hepatocytes, compared to the exercise only group, were observed in the livers from exhaustive animals supplemented with GT. Immunoblot analysis also showed that caspase-6-mediated specific cleavage of lamin A/C was increased significantly in the livers of group E, but was significantly decreased in the EM and EH groups. Our observations demonstrate that GT possesses anti-apoptotic and hepatoprotective potential after exhaustive exercise. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Microwave-Enhanced Cross-Coupling Reactions Involving Alkynyltrifluoroborates with Aryl Bromides
Molecules 2013, 18(2), 1755-1761; doi:10.3390/molecules18021755
Received: 21 December 2012 / Revised: 1 January 2013 / Accepted: 12 January 2013 / Published: 29 January 2013
PDF Full-text (195 KB)
Abstract
Palladium-catalyzed alkynylation has emerged as one of the most reliable methods for the synthesis of alkynes which are often used in natural product syntheses and material science. An efficient method for coupling alkynyltrifluoroborates with various aryl bromides in the presence of a [...] Read more.
Palladium-catalyzed alkynylation has emerged as one of the most reliable methods for the synthesis of alkynes which are often used in natural product syntheses and material science. An efficient method for coupling alkynyltrifluoroborates with various aryl bromides in the presence of a palladium catalyst has been developed using microwave irradiation. The microwave reactions are rapid and efficient. Full article
(This article belongs to the Special Issue Organoboron Chemistry)
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Open AccessArticle Antioxidant Capacity of Two Novel Bioactive Fe(III)-Cyclophane Complexes
Molecules 2013, 18(2), 1762-1774; doi:10.3390/molecules18021762
Received: 13 November 2012 / Revised: 6 January 2013 / Accepted: 7 January 2013 / Published: 29 January 2013
PDF Full-text (919 KB)
Abstract
The cyclophanes 2,9,25,32-tetraoxo-4,7,27,30-tetrakis(carboxymethyl)-1,4,7,10, 24,27,30,33-octaaza-17,40-dioxa[10.1.10.1]paracyclophane (PO) and 2,9,25,32-tetraoxo-4,7,27,30-tetrakis(carboxymethyl)-1,4,7,10,24,27,30,33-octaaza[10.1.10.1]paracyclophane (PC) were coordinated with iron to form cationic binuclear Fe(III) Fe2PO and Fe2PC complexes, respectively. Their antioxidant capacity, superoxide dismutase and peroxidase mimetic activity, as well as [...] Read more.
The cyclophanes 2,9,25,32-tetraoxo-4,7,27,30-tetrakis(carboxymethyl)-1,4,7,10, 24,27,30,33-octaaza-17,40-dioxa[10.1.10.1]paracyclophane (PO) and 2,9,25,32-tetraoxo-4,7,27,30-tetrakis(carboxymethyl)-1,4,7,10,24,27,30,33-octaaza[10.1.10.1]paracyclophane (PC) were coordinated with iron to form cationic binuclear Fe(III) Fe2PO and Fe2PC complexes, respectively. Their antioxidant capacity, superoxide dismutase and peroxidase mimetic activity, as well as their toxicity toward peripheral blood mononuclear cells (PBMCs) were evaluated. Both Fe2PO and Fe2PC are interesting biomimetics with antioxidant capacity similar to that of ascorbic acid that prevent mortality in cultured PBMCs, with the potential to have bioactive and protective functions in disease animal models. Full article
Open AccessArticle Effects of Adenosine Extract from Pholiota adiposa (Fr.) Quel on mRNA Expressions of Superoxide Dismutase and Immunomodulatory Cytokines
Molecules 2013, 18(2), 1775-1782; doi:10.3390/molecules18021775
Received: 18 December 2012 / Revised: 23 January 2013 / Accepted: 24 January 2013 / Published: 29 January 2013
Cited by 4 | PDF Full-text (292 KB)
Abstract
Pholiota adiposa is a kind of edible mushroom which has long been known for its health care applications. To reveal the exact mechanism of its protective functions in humans, in this study we isolated and identified the active compound PB3 of P [...] Read more.
Pholiota adiposa is a kind of edible mushroom which has long been known for its health care applications. To reveal the exact mechanism of its protective functions in humans, in this study we isolated and identified the active compound PB3 of P. adiposa for the first time by a combination of chromatography techniques, including NKA macroporous resin and Sephadex G-15. PB3, with molecular mass of 267.2 Da and molecular formula of C10H13N5O4 discovered by mass spectrum (MS) was identified to be adenosine. Mice were injected intraperitoneally with purified fraction PB3. Seven days after injection, we found a 1.5-fold increase of IL10 at the mRNA level, while a down regulated expression of IL-2, IL-6 and IFN-γ to 49.0%, 56.9% and 73.4%, respectively, was detected in spleen by real-time quantitative PCR. What’s more, SOD expression level was significantly increased by 1.6-fold compared to control. Fraction PB3 displayed anti-inflammatory potency and heightened SOD activity on the transcriptional level, which could be considered of further pharmaceutical or medication value. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Improvement of Ylang-Ylang Essential Oil Characterization by GC×GC-TOFMS
Molecules 2013, 18(2), 1783-1797; doi:10.3390/molecules18021783
Received: 11 December 2012 / Revised: 24 January 2013 / Accepted: 25 January 2013 / Published: 30 January 2013
Cited by 7 | PDF Full-text (689 KB)
Abstract
A single fraction of essential oil can often contain hundreds of compounds. Despite of the technical improvements and the enhanced selectivity currently offered by the state-of-the-art gas chromatography (GC) and mass spectrometry (MS) instruments, the complexity of essential oils is frequently underestimated. [...] Read more.
A single fraction of essential oil can often contain hundreds of compounds. Despite of the technical improvements and the enhanced selectivity currently offered by the state-of-the-art gas chromatography (GC) and mass spectrometry (MS) instruments, the complexity of essential oils is frequently underestimated. Comprehensive two-dimensional GC coupled to time-of-flight MS (GC×GC-TOFMS) was used to improve the chemical characterization of ylang-ylang essential oil fractions recently reported in a previous one-dimensional (1D) GC study. Based on both, the enhanced chromatographic separation and the mass spectral deconvolution, 161 individual compounds were identified and labeled as potentially characteristic analytes found in both low and high boiling fractions issued from distillation of mature ylang-ylang flowers. Compared to the most recent full GC-MS characterization, this represents 75 new compounds, essentially consisting of terpenes, terpenoid esters, and alcohols. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Radical Scavenging Capacity of Methanolic Phillyrea latifolia L. Extract: Anthocyanin and Phenolic Acids Composition of Fruits
Molecules 2013, 18(2), 1798-1810; doi:10.3390/molecules18021798
Received: 29 November 2012 / Revised: 19 January 2013 / Accepted: 23 January 2013 / Published: 30 January 2013
Cited by 4 | PDF Full-text (280 KB)
Abstract
Radical scavenging capacity of a crude methanolic extract from the fruits of Phillyrea latifolia L., commonly known as green olive tree or mock privet, was investigated with reference to anthocyanin standards, as flavonoids, and phenolic acid standards, as phenylpropanoids. Characterization with high [...] Read more.
Radical scavenging capacity of a crude methanolic extract from the fruits of Phillyrea latifolia L., commonly known as green olive tree or mock privet, was investigated with reference to anthocyanin standards, as flavonoids, and phenolic acid standards, as phenylpropanoids. Characterization with high performance liquid chromatography-diode array detection (HPLC-DAD) indicated the presence of keracyanin, kuromanin, cyanidin, ferulic acid, caffeic acid and rosmarinic acid at amounts of 289.1, 90.4, 191.4, 225.2, 221.2 and 190.1 mg/100 g fresh weight (FW) of fruits, respectively. Chlorogenic and p-coumaric acids were found to exist in lower amounts. Trolox equivalent antioxidant capacity (TEAC) and IC50 values of the plant extract were found to be 1.8 mM Trolox equivalents (TE)/g FW of fruits and 69.4 µg/mL, respectively, indicating the close radical scavenging activity of the extract to those of keracyanin and p-coumaric acid. The crude methanolic P. latifolia L. fruit extract was seen to be fairly potent in radical scavenging. Total phenolic content (TPC) of the plant extract was found to be 1652.9 mg gallic acid equivalent (GAE)/100 g FW of fruits. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Study of Total Antioxidant Activity of Human Serum Blood in the Pathology of Alcoholism
Molecules 2013, 18(2), 1811-1818; doi:10.3390/molecules18021811
Received: 28 November 2012 / Revised: 10 January 2013 / Accepted: 15 January 2013 / Published: 30 January 2013
Cited by 3 | PDF Full-text (220 KB)
Abstract
The total antioxidant activity (TAA) of human serum blood of patients suffering from alcoholism was tested by cathode voltammetry with a model process of oxygen electroreduction. A known spectrophotometrical method was used for comparison. As results the total antioxidant activity of serum [...] Read more.
The total antioxidant activity (TAA) of human serum blood of patients suffering from alcoholism was tested by cathode voltammetry with a model process of oxygen electroreduction. A known spectrophotometrical method was used for comparison. As results the total antioxidant activity of serum blood of patients with alcoholism was estimated by voltammetry during therapy in hospital. It was shown the TAA of serum blood of patients in pathology before and after treatment is lower than that one of healthy people. However, during the process of 10 days of alcoholism treatment the TAA coefficient increases. The relationship between the coefficient of total antioxidant activity of human serum blood and the stage of treatment was detected. Full article
(This article belongs to the Special Issue Antioxidants 2012)
Open AccessArticle Two New Koumine-Type Indole Alkaloids from Gelsemium elegans Benth.
Molecules 2013, 18(2), 1819-1825; doi:10.3390/molecules18021819
Received: 27 December 2012 / Revised: 24 January 2013 / Accepted: 25 January 2013 / Published: 31 January 2013
Cited by 5 | PDF Full-text (640 KB)
Abstract
Two new indole alkaloids, 21-oxokoumine (1) and furanokoumine (2), were isolated from the roots of Gelsemium elegans Benth together with three known compounds. The structures of the two novel compounds were elucidated by spectroscopic methods, including NMR, HR-ESI-MS, [...] Read more.
Two new indole alkaloids, 21-oxokoumine (1) and furanokoumine (2), were isolated from the roots of Gelsemium elegans Benth together with three known compounds. The structures of the two novel compounds were elucidated by spectroscopic methods, including NMR, HR-ESI-MS, UV, IR, CD and molecular modeling. Compound 1 is the first instance of a koumine-type alkaloid with a carbonyl at the C-21 position, while compound 2 possesses a tetrahydrofuran ring located on C-20 and C-21. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Development and Molecular Characterization of 55 Novel Polymorphic cDNA-SSR Markers in Faba Bean (Vicia faba L.) Using 454 Pyrosequencing
Molecules 2013, 18(2), 1844-1856; doi:10.3390/molecules18021844
Received: 4 January 2013 / Revised: 17 January 2013 / Accepted: 23 January 2013 / Published: 31 January 2013
Cited by 19 | PDF Full-text (220 KB)
Abstract
Faba bean (Vicia faba L.) is a major food source and fodder legume, popularly known for its high content of seed-protein. Its role is critical in crop rotation, and for fixing nitrogen effectively. Polymorphic simple sequence repeat markers from transcript sequences [...] Read more.
Faba bean (Vicia faba L.) is a major food source and fodder legume, popularly known for its high content of seed-protein. Its role is critical in crop rotation, and for fixing nitrogen effectively. Polymorphic simple sequence repeat markers from transcript sequences (cDNA; simple sequence repeat [SSR]) were developed for faba bean (Vicia faba). We found that 1,729 SSR loci from 81,333 individual sequence reads and 240 primer pairs were designed and synthesized. In total, 55 primer pairs were found to be polymorphic and scorable consistently when screened in 32 accessions. The number of alleles ranged from 2 to 15, frequency of major alleles per locus varied from 0.17 to 0.91, the genotypes number ranged from 2 to 17, observed and expected heterozycosity values ranged from 0.00 to 0.44 and 0.17 to 0.89 and overall PIC values ranged from 0.16 to 0.88 respectively. These markers will be a useful tool for assessing the genetic diversity, understanding the population structure, and breeding patterns of faba bean. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Seasonal Difference in Antioxidant Capacity and Active Compounds Contents of Eucommia ulmoides Oliver Leaf
Molecules 2013, 18(2), 1857-1868; doi:10.3390/molecules18021857
Received: 12 December 2012 / Revised: 28 January 2013 / Accepted: 29 January 2013 / Published: 1 February 2013
Cited by 14 | PDF Full-text (282 KB)
Abstract
Leaf of Eucommia ulmoides Oliver (EU) is a Traditional Chinese Medicine and a functional food in China. Antioxidant contents of EU leaves, which were collected monthly during the period of May–October in three years, were determined. Samples’ antioxidant capacity was characterized by [...] Read more.
Leaf of Eucommia ulmoides Oliver (EU) is a Traditional Chinese Medicine and a functional food in China. Antioxidant contents of EU leaves, which were collected monthly during the period of May–October in three years, were determined. Samples’ antioxidant capacity was characterized by DPPH radical scavenging activity, hydroxyl radical scavenging activity, ferrous chelating ability, and antioxidant capacity in linoleic acid emulsion and in rapeseed oil assays. The results showed that contents of some active compounds and antioxidant activity were related to a certain time of the year. Samples collected in August showed high content of phenolics, and the samples collected in May contained higher amount of flavonoids than other samples. Leaves collected in May or June exhibited high contents of rutin, quercetin, geniposidic acid and aucubin. The August leaves showed stable and high DPPH radical scavenging activity, and ferrous chelating ability. May samples showed strong inhibitory effects on oxidation of rapeseed oil and linoleic acid. The DPPH radical scavenging activity was related to the total phenolics content. Flavonoids played an important role in the inhibitory effects on rapeseed oil and linoleic acid oxidation. Therefore, August and May were indicated as the best months to harvest EU leaves for industry. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Silica-Supported Polyphosphoric Acid in the Synthesis of 4-Substituted Tetrahydroisoquinoline Derivatives
Molecules 2013, 18(2), 1869-1880; doi:10.3390/molecules18021869
Received: 19 December 2012 / Revised: 21 January 2013 / Accepted: 22 January 2013 / Published: 1 February 2013
Cited by 3 | PDF Full-text (200 KB)
Abstract
We report herein an application of an α-amidoalkylation reaction, as an alternative efficient synthesis of 4-aryl- and 4-methyl-1,2,3,4-tetrahydroisoquinoline derivatives. The amides required for this purpose would result from reaction of aminoacetaldehyde dimethylacetal with different substituted benzenes in polyphosphoric acid, followed by acylation [...] Read more.
We report herein an application of an α-amidoalkylation reaction, as an alternative efficient synthesis of 4-aryl- and 4-methyl-1,2,3,4-tetrahydroisoquinoline derivatives. The amides required for this purpose would result from reaction of aminoacetaldehyde dimethylacetal with different substituted benzenes in polyphosphoric acid, followed by acylation of the obtained amines with different acid chlorides or sulfochlorides. We compared the cyclisation step using conventional (milieu of acetic-trifluoracetic acid = 4:1) and solid supported reagents (SiO2/PPA), as recovered, regenerated and reused without loss of its activity catalyst. We found that in comparison to conventional methods, the yields of the reaction are greater and the reaction time is shorter. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Synthesis and Antiproliferative Activity of C-3 Functionalized Isobenzofuran-1(3H)-ones
Molecules 2013, 18(2), 1881-1896; doi:10.3390/molecules18021881
Received: 25 October 2012 / Revised: 20 December 2012 / Accepted: 24 December 2012 / Published: 1 February 2013
Cited by 12 | PDF Full-text (269 KB)
Abstract
A series of thirteen C-3 functionalized isobenzofuran-1(3H)-ones (phtalides) was synthesized via condensation, aromatization, and acetylation reactions. NMR (one and two dimensional experiments), IR, and mass spectrometry analysis allowed confirmation of the identity of the synthesized compounds. The substances were submitted [...] Read more.
A series of thirteen C-3 functionalized isobenzofuran-1(3H)-ones (phtalides) was synthesized via condensation, aromatization, and acetylation reactions. NMR (one and two dimensional experiments), IR, and mass spectrometry analysis allowed confirmation of the identity of the synthesized compounds. The substances were submitted to in vitro bioassays against U937 (lymphoma) and K562 (myeloid leukemia) cancer cell lines using the MTT cytotoxicity assay. Some derivatives inhibited 90% of cell viability at 100 µM. Also, two phtalides presented biological activity superior than that of etoposide (VP16), a commercial drug used as a positive control in the assays. In silico drug properties of the evaluated compounds were calculated and the results are discussed. Full article
Open AccessArticle A Pyrene- and Phosphonate-Containing Fluorescent Probe as Guest Molecule in a Host Polymer Matrix
Molecules 2013, 18(2), 1897-1915; doi:10.3390/molecules18021897
Received: 8 November 2012 / Revised: 23 January 2013 / Accepted: 24 January 2013 / Published: 1 February 2013
Cited by 3 | PDF Full-text (1180 KB) | Supplementary Files
Abstract
New host-guest materials have been prepared by incorporation of a home-made organic probe displaying a pyrene motif and a phosphonate function into a regular amphiphilic copolymer. Using powder X-Ray diffraction, photoluminescence and FT-IR spectroscopy, we have been able to study the non-covalent [...] Read more.
New host-guest materials have been prepared by incorporation of a home-made organic probe displaying a pyrene motif and a phosphonate function into a regular amphiphilic copolymer. Using powder X-Ray diffraction, photoluminescence and FT-IR spectroscopy, we have been able to study the non-covalent interactions between the host matrix and the guest molecule in the solid state. Interestingly, we have shown that the matrix directs the guest spatial localization and alters its properties. Thanks to the comparison of pyrene vs. N-pyrenylmaleimide derivatives, the influence of the chemical nature of the guest molecules on the non-covalent interactions with the host have been studied. In addition, using polyethylene glycol as a reference host, we have been able to evidence a true matrix effect within our new insertion materials. The phosphonated guest molecule appears to be a novel probe targeting the hydrophilic domain of the host copolymer. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Anti-Oxidative and Cholinesterase Inhibitory Effects of Leaf Extracts and Their Isolated Compounds from Two Closely Related Croton Species
Molecules 2013, 18(2), 1916-1932; doi:10.3390/molecules18021916
Received: 5 December 2012 / Revised: 7 January 2013 / Accepted: 15 January 2013 / Published: 1 February 2013
Cited by 12 | PDF Full-text (276 KB)
Abstract
A comparative evaluation of the antioxidant and acetylcholinesterase inhibitory activity of the leaf extracts of Croton gratissimus and Croton zambesicus (subgratissimus) and compounds isolated from the extracts was carried out to determine their potential and suitability or otherwise as a [...] Read more.
A comparative evaluation of the antioxidant and acetylcholinesterase inhibitory activity of the leaf extracts of Croton gratissimus and Croton zambesicus (subgratissimus) and compounds isolated from the extracts was carried out to determine their potential and suitability or otherwise as a substitute for each other in the management of oxidative and neurodegenerative conditions. Different antioxidant assays (DPPH, FRAP, β-carotene-linoleic and the lipid peroxidation models) and the microplate assay for acetylcholinesterase (AChE) inhibition were carried out separately to study the activities of the crude leaf extracts and four solvent fractions from each of the two Croton species. Bioassay guided fractionation was used to target antioxidant constituents of the crude extracts and ethyl acetate fractions of 20% aqueous methanol extract of C. gratissimus on silica gel and Sephadex LH-20 columns resulted in the isolation of kaempferol-3-O-β-6''(p-coumaroyl) glucopyranoside (tiliroside, 2), apigenin-6-C-glucoside (isovitexin, 3) and kampferol (4). The extract of C. zambesicus yielded quercetin-3-O-β-6''(p-coumaroyl) glucopyranoside-3'-methyl ether (helichrysoside- 3'-methyl ether, 1), kaempferol-3-O-β-6''(p-coumaroyl) glucopyranoside (tiliroside, 2) and apigenin-6-C-glucoside (isovitexin, 3). Three of the isolated compounds and their different combinations were also included in the bioassays. In all the assays performed, the antioxidant capacity and AChE inhibitory effects of C. zambesicus extracts were weaker than those of C. gratissimus. This suggests that C. gratissimus may not be substituted by C. zambesicus, despite the similarity in some of their constituents. Generally, the combinations made from the isolated compounds showed better activities in most of the assays compared to the individual isolated compounds. This suggests mechanisms such as synergism and/or additive effects to be taking place. This study established low, moderate and high antioxidant activities as well as AChE inhibitory effects by the crude extracts, fractions, compounds and compound combinations. This means some of the extracts, isolated compounds and compound combinations could be useful in the management of neurodegenerative conditions and serve as sources of natural neurodegenerative agents. Full article
Open AccessArticle Design, Synthesis and Hepatoprotective Activity of Analogs of the Natural Product Goodyeroside A
Molecules 2013, 18(2), 1933-1948; doi:10.3390/molecules18021933
Received: 21 December 2012 / Revised: 29 January 2013 / Accepted: 30 January 2013 / Published: 1 February 2013
PDF Full-text (302 KB) | Supplementary Files
Abstract
Goodyeroside A, a natural product isolated from the Goodyera species, possesses significant hepatoprotective activity and has a novel skeleton not previously observed in other synthetic drugs used for the treatment of hepatitis. Herein, we report a highly stereoselective synthesis of goodyeroside A [...] Read more.
Goodyeroside A, a natural product isolated from the Goodyera species, possesses significant hepatoprotective activity and has a novel skeleton not previously observed in other synthetic drugs used for the treatment of hepatitis. Herein, we report a highly stereoselective synthesis of goodyeroside A and related analogs with varying substituents at the α position of the carbonyl group to explore the structure-activity relationships of goodyeroside A. The absolute configuration of analog 5d was confirmed by single crystal X-ray analysis. The results from in vitro and in vivo studies indicate that 5a, the fully acetylated compound of goodyeroside A, is worthy of further investigation as a lead to identify novel hepatoprotective agents. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Euphorbia formosana Root Extract Induces Apoptosis by Caspase-Dependent Cell Death via Fas and Mitochondrial Pathway in THP-1 Human Leukemic Cells
Molecules 2013, 18(2), 1949-1962; doi:10.3390/molecules18021949
Received: 31 December 2012 / Revised: 28 January 2013 / Accepted: 29 January 2013 / Published: 1 February 2013
Cited by 5 | PDF Full-text (1553 KB)
Abstract
Acute myeloid leukemia (AML), a very rare type of cancer, generally affects patients over 50 years old. While clinical drugs to treat advanced stages of AML exist, the disease becomes increasingly resistant to therapies. Euphorbia formosana Hayata (EF) is a native Taiwanese [...] Read more.
Acute myeloid leukemia (AML), a very rare type of cancer, generally affects patients over 50 years old. While clinical drugs to treat advanced stages of AML exist, the disease becomes increasingly resistant to therapies. Euphorbia formosana Hayata (EF) is a native Taiwanese medicinal plant used to treat rheumatism, liver cirrhosis, herpes zoster, scabies, and photoaging, along with tumor suppression. However, the mechanisms by which it suppresses tumors have not been explored. Here, we provide molecular evidence that a hot-water extract of Euphorbia formosana (EFW) selectively inhibited the growth of human leukemic cancer cells more than other solid human cancer cell lines. Most importantly, the plant extract had limited toxicity toward healthy peripheral blood mononuclear cells (PBMCs). After THP-1 leukemic cells were treated with 50–100 µg/mL EFW for one day, the S phase DNA content of the cells increased, while treatment with 200–400 µg/mL caused the cells to accumulate in the G0/G1 phase. Notably, EFW did not affect A-549 lung cancer cells. The effectiveness of EFW against THP-1 cells may be through caspase-dependent apoptosis in leukemic cells, which is mediated through the Fas and mitochondrial pathways. The potent antileukemic activity of EFW in vitro warrants further investigation of this plant to treat leukemias and other malignancies. Full article
Open AccessArticle Biohybrid -Se-S- Coupling Reactions of an Amino Acid Derived Seleninate
Molecules 2013, 18(2), 1963-1972; doi:10.3390/molecules18021963
Received: 9 January 2013 / Revised: 28 January 2013 / Accepted: 30 January 2013 / Published: 4 February 2013
PDF Full-text (232 KB) | Supplementary Files
Abstract
We describe the synthesis of the N-(2-seleninatoethyl) amide of N-Boc-phenylalanine, serving here as a peptide model, and its reductive coupling reactions under mild conditions with unprotected thiouridine and glutathione. Selenosulfide products such as these comprise reversibly conjugated bio-components, and can [...] Read more.
We describe the synthesis of the N-(2-seleninatoethyl) amide of N-Boc-phenylalanine, serving here as a peptide model, and its reductive coupling reactions under mild conditions with unprotected thiouridine and glutathione. Selenosulfide products such as these comprise reversibly conjugated bio-components, and can potentially find uses as probes of biological function, such as enzyme inhibitors, delivery systems, or structural mimics. Full article
(This article belongs to the Special Issue Disulfide and Diselenide Chemistry)
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Open AccessArticle Synthesis and Characterization of Novel Unsymmetrical and Symmetrical 3-Halo- or 3-Methoxy-substituted 2-Dibenzoylamino-1,4-naphthoquinone Derivatives
Molecules 2013, 18(2), 1973-1984; doi:10.3390/molecules18021973
Received: 31 December 2012 / Revised: 30 January 2013 / Accepted: 30 January 2013 / Published: 4 February 2013
Cited by 4 | PDF Full-text (248 KB)
Abstract Symmetrical and unsymmetrical 3-halo- or 3-methoxy- substituted 2-dibenzoylamino- 1,4-naphthoquinone analogs were synthesized with an average yield of 45% via sodium hydride promoted bis-acylation of 2-amino-3-chloro-1,4-naphthoquinone, 2-amino-3-bromo-1,4-naphthoquinone and 2-amino-3-methoxy-1,4-naphthoquinone. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Cytotoxicity and Structure-Activity Relationships of Xanthone Derivatives from Mesua beccariana, Mesua ferrea and Mesua congestiflora towards Nine Human Cancer Cell Lines
Molecules 2013, 18(2), 1985-1994; doi:10.3390/molecules18021985
Received: 17 December 2012 / Revised: 16 January 2013 / Accepted: 22 January 2013 / Published: 4 February 2013
Cited by 7 | PDF Full-text (300 KB)
Abstract
The cytotoxic structure-activity relationships among a series of xanthone derivatives from Mesua beccariana, Mesua ferrea and Mesua congestiflora were studied. Eleven xanthone derivatives identified as mesuarianone (1), mesuasinone (2), mesuaferrin A (3), mesuaferrin B ( [...] Read more.
The cytotoxic structure-activity relationships among a series of xanthone derivatives from Mesua beccariana, Mesua ferrea and Mesua congestiflora were studied. Eleven xanthone derivatives identified as mesuarianone (1), mesuasinone (2), mesuaferrin A (3), mesuaferrin B (4), mesuaferrin C (5), 6-deoxyjacareubin (6), caloxanthone C (7), macluraxanthone (8), 1,5-dihydroxyxanthone (9), tovopyrifolin C (10) and α-mangostin (11) were isolated from the three Mesua species. The human cancer cell lines tested were Raji, SNU-1, K562, LS-174T, SK-MEL-28, IMR-32, HeLa, Hep G2 and NCI-H23. Mesuaferrin A (3), macluraxanthone (8) and α-mangostin (11) showed strong cytotoxicities as they possess significant inhibitory effects against all the cell lines. The structure-activity relationship (SAR) study revealed that the diprenyl, dipyrano and prenylated pyrano substituent groups of the xanthone derivatives contributed towards the cytotoxicities. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle The Reaction Mechanism of Claisen Rearrangement Obtained by Transition State Spectroscopy and Single Direct-Dynamics Trajectory
Molecules 2013, 18(2), 1995-2004; doi:10.3390/molecules18021995
Received: 9 January 2013 / Revised: 14 January 2013 / Accepted: 28 January 2013 / Published: 4 February 2013
Cited by 5 | PDF Full-text (558 KB)
Abstract
Chemical bond breaking and formation during chemical reactions can be observed using “transition state spectroscopy”. Comparing the measurement result of the transition state spectroscopy with the simulation result of single direct-dynamics trajectory, we have elucidated the reaction dynamics of Claisen rearrangement of [...] Read more.
Chemical bond breaking and formation during chemical reactions can be observed using “transition state spectroscopy”. Comparing the measurement result of the transition state spectroscopy with the simulation result of single direct-dynamics trajectory, we have elucidated the reaction dynamics of Claisen rearrangement of allyl vinyl ether. Observed the reaction of the neat sample liquid, we have estimated the time constants of transformation from straight-chain structure to aromatic-like six-membered ring structure forming the C1-C6 bond. The result clarifies that the reaction proceeds via three steps taking longer time than expected from the gas phase calculation. This finding provides new hypothesis and discussions, helping the development of the field of reaction mechanism analysis. Full article
Open AccessArticle Antioxidant Activity of the Extracts of Some Cowpea (Vigna unguiculata (L) Walp.) Cultivars Commonly Consumed in Pakistan
Molecules 2013, 18(2), 2005-2017; doi:10.3390/molecules18022005
Received: 23 November 2012 / Revised: 28 January 2013 / Accepted: 31 January 2013 / Published: 5 February 2013
Cited by 16 | PDF Full-text (277 KB)
Abstract
The present investigation has been carried out to determine the antioxidant activity of the methanolic extracts obtained from four cultivars of cowpea (Vigna unguiculata (L) Walp.) seeds. Phenolic compounds present in the extracts showed the antioxidant and antiradical properties when investigated [...] Read more.
The present investigation has been carried out to determine the antioxidant activity of the methanolic extracts obtained from four cultivars of cowpea (Vigna unguiculata (L) Walp.) seeds. Phenolic compounds present in the extracts showed the antioxidant and antiradical properties when investigated using a linoleic acid peroxidation model, FRAP, ORAC and TRAP assays, as well as DPPH, hydroxyl, nitric oxide and superoxide radical scavenging activity. The HPLC analysis of the cowpea extracts showed the presence of neochlorogenic acid, chlorogenic acid and caffeic acids. The results indicated that methanolic extract of the cowpea resembled in the aforementioned activities those from other leguminous seeds and pulses. Phenolic constituents contained in cowpea may have a future role as ingredients in the development of functional foods. Full article
(This article belongs to the Special Issue Antioxidants 2012)
Open AccessArticle The Degradation Mechanism of Toxic Atractyloside in Herbal Medicines by Decoction
Molecules 2013, 18(2), 2018-2028; doi:10.3390/molecules18022018
Received: 12 December 2012 / Revised: 31 January 2013 / Accepted: 1 February 2013 / Published: 5 February 2013
Cited by 4 | PDF Full-text (1465 KB)
Abstract
Atractyloside (ATR) is found in many Asteraceae plants that are commonly used as medicinal herbs in China and other eastern Asian countries. ATR binds specifically to the adenine nucleotide translocator in the inner mitochondrial membrane and competitively inhibits ADP and ATP transport. [...] Read more.
Atractyloside (ATR) is found in many Asteraceae plants that are commonly used as medicinal herbs in China and other eastern Asian countries. ATR binds specifically to the adenine nucleotide translocator in the inner mitochondrial membrane and competitively inhibits ADP and ATP transport. The toxicity of ATR in medical herbs can be reduced by hydrothermal processing, but the mechanisms of ATR degradation are not well understood. In this study, GC-MS coupled with SPE and TMS derivatisation was used to detect ATR levels in traditional Chinese medicinal herbs. Our results suggest that ATR molecules were disrupted by decomposition, hydrolysis and saponification after heating with water (decoction) for a long period of time. Hydrothermal processing could decompose the endogenous toxic compounds and also facilitate the detoxification of raw materials used in the Chinese medicine industry. Full article
Open AccessArticle Structural Requirements for the Antifungal Activities of Natural Drimane Sesquiterpenes and Analogues, Supported by Conformational and Electronic Studies
Molecules 2013, 18(2), 2029-2051; doi:10.3390/molecules18022029
Received: 18 December 2012 / Revised: 22 January 2013 / Accepted: 31 January 2013 / Published: 5 February 2013
Cited by 4 | PDF Full-text (1073 KB)
Abstract
Seventeen drimanes including polygodial (1), isopolygodial (2), drimenol (3) and confertifolin (4) obtained from natural sources and the semi-synthetic derivatives 5–17 obtained from 1–3, were evaluated in vitro for antifungal properties against a [...] Read more.
Seventeen drimanes including polygodial (1), isopolygodial (2), drimenol (3) and confertifolin (4) obtained from natural sources and the semi-synthetic derivatives 5–17 obtained from 1–3, were evaluated in vitro for antifungal properties against a unique panel of fungi with standardized procedures by using two end-points, MIC100 and MIC50. A SAR analysis of the whole series, supported by conformational and electronic studies, allowed us to show that the Δ7,8 -double bond would be one of the key structural features related to the antifungal activity. The MEPs obtained for active compounds exhibit a clear negative minimum value (deep red zone) in the vicinity of the Δ7,8 -double bond, which is not present in the inactive ones. Apart of this negative zone, a positive region (deep blue) appears in 1, which is not observed either in its epimer 2 nor in the rest of the active compounds. The LogP of active compounds varies between 2.33 and 3.84, but differences in MICs are not correlated with concomitant variations in LogP values. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Evaluation of the Anti-Inflammatory Effect of Chalcone and Chalcone Analogues in a Zebrafish Model
Molecules 2013, 18(2), 2052-2060; doi:10.3390/molecules18022052
Received: 18 December 2012 / Revised: 29 January 2013 / Accepted: 29 January 2013 / Published: 5 February 2013
Cited by 7 | PDF Full-text (537 KB)
Abstract
The aim of this study was to investigate novel chalcones with potent anti-inflammatory activities in vivo. Chalcone and two chalcone analogues (compound 5 and 9) were evaluated using a caudal fin-wounded transgenic zebrafish line “Tg(mpx:gfp)” to [...] Read more.
The aim of this study was to investigate novel chalcones with potent anti-inflammatory activities in vivo. Chalcone and two chalcone analogues (compound 5 and 9) were evaluated using a caudal fin-wounded transgenic zebrafish line “Tg(mpx:gfp)” to visualize the effect of neutrophil recruitment dynamically. Results showed that treatment with compound 9 not only affected wound-induced neutrophil recruitment, but also affected Mpx enzymatic activity. Moreover, protein expression levels of pro-inflammatory factors (Mpx, NFκB, and TNFα) were also regulated by compound 9. Taken together, our results provide in vivo evidence of the anti-inflammatory effects of synthesized chalcone analogues on wound-induced inflammation. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Antioxidant Capacity and HPLC-DAD-MS Profiling of Chilean Peumo (Cryptocarya alba) Fruits and Comparison with German Peumo (Crataegus monogyna) from Southern Chile
Molecules 2013, 18(2), 2061-2080; doi:10.3390/molecules18022061
Received: 27 November 2012 / Revised: 21 January 2013 / Accepted: 31 January 2013 / Published: 5 February 2013
Cited by 28 | PDF Full-text (1499 KB)
Abstract
Liquid chromatography (LC) coupled with UV detection and electrospray ionization (ESI) tandem mass spectrometry (MS/MS) was used for the generation of chemical fingerprints and the identification of phenolic compounds in peumo fruits and aerial parts from southern Chile. Thirty three compounds (19 [...] Read more.
Liquid chromatography (LC) coupled with UV detection and electrospray ionization (ESI) tandem mass spectrometry (MS/MS) was used for the generation of chemical fingerprints and the identification of phenolic compounds in peumo fruits and aerial parts from southern Chile. Thirty three compounds (19 of these detected in C. alba and 23 in C. monogyna) were identified, mainly flavonoid glycosides, phenolic acids, anthocyanins and flavonoid aglycons. Total phenolic content and total flavonoid content was measured for both species, and were higher in the extracts from C. monogyna fruits and aerial parts than extracts from C. alba. The fruits of Cryptocarya alba (Chilean peumo) presented high antioxidant capacity (9.12 ± 0.01 mg/mL in the DPPH assay), but was three times lower to that of Crataegus monogyna (German peumo) (3.61 ± 0.01 mg/mL in the DPPH assay). Full article
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Open AccessArticle The Reaction of Ethyl 2-oxo-2H-chromene-3-carboxylate with Hydrazine Hydrate
Molecules 2013, 18(2), 2084-2095; doi:10.3390/molecules18022084
Received: 12 January 2013 / Revised: 29 January 2013 / Accepted: 30 January 2013 / Published: 6 February 2013
Cited by 5 | PDF Full-text (223 KB)
Abstract
Although salicylaldehyde azine (3) was reported in 1985 as the single product of the reaction of ethyl 2-oxo-2H-chromene-3-carboxylate (1) with hydrazine hydrate, we identified another main reaction product, besides 3, which was identified as malono-hydrazide [...] Read more.
Although salicylaldehyde azine (3) was reported in 1985 as the single product of the reaction of ethyl 2-oxo-2H-chromene-3-carboxylate (1) with hydrazine hydrate, we identified another main reaction product, besides 3, which was identified as malono-hydrazide (4). In the last two decades, however, some articles have claimed that this reaction afforded exclusively hydrazide 2 and they have reported the use of this hydrazide 2 as a precursor in the syntheses of several heterocyclic compounds and hydrazones 6. We reported herein a study of the formation of 2 and a facile route for the synthesis of the target compounds N'-arylidene-2-oxo-2H-chromene-3-carbohydrazides 6af. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Palladium-Catalyzed Amination of Dichloroquinolines with Adamantane-Containing Amines
Molecules 2013, 18(2), 2096-2109; doi:10.3390/molecules18022096
Received: 31 December 2012 / Revised: 24 January 2013 / Accepted: 1 February 2013 / Published: 6 February 2013
Cited by 4 | PDF Full-text (324 KB)
Abstract
Pd-catalyzed amination of isomeric 2,6-, 2,8-, 4,8- and 4,7-dichloroquinolines was studied using adamantane-containing amines in which substituents at the nitrogen atom differ in bulkiness. The selectivity of the amination of 2,6-dichloroquinoline was very low, substantially better results were obtained with 2,8-dichloroquinoline, and [...] Read more.
Pd-catalyzed amination of isomeric 2,6-, 2,8-, 4,8- and 4,7-dichloroquinolines was studied using adamantane-containing amines in which substituents at the nitrogen atom differ in bulkiness. The selectivity of the amination of 2,6-dichloroquinoline was very low, substantially better results were obtained with 2,8-dichloroquinoline, and 4,8- and 4,7-dichloroquinolines provided the best yields of the amination products. Diamination of 4,8- and 4,7-dichloroquinolines was carried out with two amines which differ strongly in the bulkiness of the alkyl group. In the majority of cases BINAP ligand was successfully applied, however, it had to be replaced with DavePhos in certain reactions when using the most sterically hindered amine as well as for the diamination reactions. Full article
(This article belongs to the Special Issue Advances in Heteroaromatic Chemistry)
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Open AccessArticle Simultaneous Determination of Multiple Sesquiterpenes in Curcuma wenyujin Herbal Medicines and Related Products with One Single Reference Standard
Molecules 2013, 18(2), 2110-2121; doi:10.3390/molecules18022110
Received: 31 December 2012 / Revised: 25 January 2013 / Accepted: 1 February 2013 / Published: 6 February 2013
Cited by 4 | PDF Full-text (317 KB)
Abstract
Some Curcuma species are widely used as herbal medicines. Sesquiterpenes are their important bioactive compounds and their quantitative analysis is generally accomplished by gas chromatography (GC) or high performance liquid chromatography (HPLC), but the instability and high cost of some sesquiterpene reference [...] Read more.
Some Curcuma species are widely used as herbal medicines. Sesquiterpenes are their important bioactive compounds and their quantitative analysis is generally accomplished by gas chromatography (GC) or high performance liquid chromatography (HPLC), but the instability and high cost of some sesquiterpene reference standards have limited their application. It is necessary to find a practicable means to control the quality of herbal medicines. Using one stable component contained in Curcuma species to determine multiple analogues should be a practical option. In this study, a simple HPLC method for determination of sesquiterpenes using relative response factors (RRFs) has been developed. The easily available and stable active component curdione was selected as the reference compound for calculating the RRFs of the other eight sesquiterpenes, including zedoarondiol (Zedo), isozedoarondiol (Isoz), aerugidiol (Aeru), (4S,5S)-(+)-germacrone-4,5-epoxide (Epox), curcumenone (Curc), neocurdione (Neoc), germacrone (Germ) and furanodiene (Fura). Their RRFs against curdione were between 0.131–1.301, with a good reproducibility. By using the RRFs, the quantification of sesquiterpenes in Curcuma wenyujin herbal medicines and related products was carried out. The method is especially useful for the determination of (4S,5S)-(+)-germacrone-4,5-epoxide, curcumenone, germacrone and furanodiene, which often are regarded as the principle components in Curcuma species, but unstable when were purified. It is an ideal means to analyze the components for which reference standards are not readily available. Full article
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Open AccessArticle PF2401-SF, Standardized Fraction of Salvia miltiorrhiza, Induces Apoptosis of Activated Hepatic Stellate Cells in Vitro and in Vivo
Molecules 2013, 18(2), 2122-2134; doi:10.3390/molecules18022122
Received: 28 December 2012 / Revised: 25 January 2013 / Accepted: 4 February 2013 / Published: 6 February 2013
Cited by 8 | PDF Full-text (503 KB)
Abstract
During the course of our attempts to develop a potential herbal medicine, we had previously prepared PF2401-SF, a standardized fraction of S. miltiorrhiza, and reported its hepatoprotective activity in vitro as well as in vivo. Since apoptosis of activated hepatic [...] Read more.
During the course of our attempts to develop a potential herbal medicine, we had previously prepared PF2401-SF, a standardized fraction of S. miltiorrhiza, and reported its hepatoprotective activity in vitro as well as in vivo. Since apoptosis of activated hepatic stellate cells (HSCs) is a well-accepted anti-fibrotic strategy, in this study, we investigated the direct effect of PF2401-SF on t-HSC/Cl-6 cells in vitro and on CCl4-induced liver injury in vivo. We evaluated the activation and cleavage of hallmarkers of apoptosis, namely, caspase 3, 8, 9 and PARP. Upregulation of the pro-apoptotic Bax protein and downregulation of the anti-apoptotic Bcl2 protein were also analyzed. Furthermore, in the PF2401-SF treated rats, apoptosis induction of activated HSCs was demonstrated by reduced distribution of α-SMA-positive cells and the presence of high number of TUNEL-positive cells in vivo. Our data suggest that PF2401-SF can mediate HSCs apoptosis induction, and may be a potential herbal medicine for the treatment of liver fibrosis. Full article
Open AccessArticle Anti-Helicobacter pylori and Urease Inhibition Activities of Some Traditional Medicinal Plants
Molecules 2013, 18(2), 2135-2149; doi:10.3390/molecules18022135
Received: 31 December 2012 / Revised: 22 January 2013 / Accepted: 23 January 2013 / Published: 7 February 2013
Cited by 13 | PDF Full-text (249 KB)
Abstract
Different parts of Acacia nilotica (L.) Delile, Calotropis procera (Aiton) W.T. Aiton, Adhatoda vasica Nees, Fagoniaar abica L. and Casuarina equisetifolia L. are traditionally used in folk medicine for the treatment of a variety of common ailments like nausea, cold, [...] Read more.
Different parts of Acacia nilotica (L.) Delile, Calotropis procera (Aiton) W.T. Aiton, Adhatoda vasica Nees, Fagoniaar abica L. and Casuarina equisetifolia L. are traditionally used in folk medicine for the treatment of a variety of common ailments like nausea, cold, cough, asthma, fevers, diarrhea, sore throat, swelling, etc. The present study was aimed to evaluate the anti-Helicobacter pylori and urease inhibition activities of extracts produced from the above selected medicinal plants native to Soon Valley (home to an old civilization) in the Punjab province of Pakistan. Methanol, acetone and water extracts of the plants were evaluated for anti-bacterial activity against thirty four clinical isolates and two reference strains of H. pylori. Minimum inhibitory concentrations (MICs) of the extracts were determined using the agar dilution method and compared with some standard antibiotics like amoxicillin (AMX), clarithromycin (CLA), tetracycline (TET) and metronidazole (MNZ), used in the triple therapy for H. pylori eradication. H. pylori urease inhibition activity of the extracts was assessed by the phenol red method, wherein, Lineweaver-Burk plots were used to determine Michaelis-Menten constants for elucidating the mechanism of inhibition. Methanol and acetone extracts from Acacia nilotica and Calotropis procera exhibited stronger anti-H. pylori activity than MNZ, almost comparable activity with TET, but were found to be less potent than AMX and CLT. The rest of the extracts exhibited lower activity than the standard antibiotics used in this study. In the H. pylori urease inhibitory assay, methanol and acetone extracts of Acacia nilotica and Calotropis procera showed significant inhibition. Lineweaver-Burk plots indicated a competitive mechanism for extract of Acacia nilotica, whereas extract of Calotropis procera exhibited a mixed type of inhibition. Full article
Open AccessArticle Volatiles and Water- and Fat-Soluble Precursors of Saanen Goat and Cross Suffolk Lamb Flavour
Molecules 2013, 18(2), 2150-2165; doi:10.3390/molecules18022150
Received: 11 December 2012 / Revised: 28 January 2013 / Accepted: 29 January 2013 / Published: 7 February 2013
Cited by 5 | PDF Full-text (231 KB)
Abstract
This paper evaluates the concentrations of water- and fat-soluble precursors of meat flavour, with the aim of characterising the effect of species on the volatile profile of grilled goat and lamb meat. Compared to goat, lamb meat had higher levels of saturated [...] Read more.
This paper evaluates the concentrations of water- and fat-soluble precursors of meat flavour, with the aim of characterising the effect of species on the volatile profile of grilled goat and lamb meat. Compared to goat, lamb meat had higher levels of saturated fatty acids—SFA, monounsaturated fatty acids—MUFA and polyunsaturated fatty acids—PUFA and similar levels of sugars and free amino acids, except for lysine and glycine, which were higher in goat. Major differences were detected in lipid-derived volatiles; only pyrazine, thiazole, and some Strecker aldehydes were at different concentrations in these species. Volatile compounds derived from the oxidation of linoleic acid were at higher levels in meat from lamb due to the higher concentration of the latter, while compounds formed from α-linolenic acid were at higher levels in goat. It can be concluded that lamb meat has a stronger flavour profile compared to goat meat because it has the highest concentrations of lipid-derived volatile compounds, primarily straight saturated alkanals, pyrazines and thiazole. Full article
Open AccessArticle Antibacterial/Antifungal Activity and Synergistic Interactions between Polyprenols and Other Lipids Isolated from Ginkgo Biloba L. Leaves
Molecules 2013, 18(2), 2166-2182; doi:10.3390/molecules18022166
Received: 28 November 2012 / Revised: 21 January 2013 / Accepted: 31 January 2013 / Published: 7 February 2013
Cited by 17 | PDF Full-text (491 KB)
Abstract
Polyprenols separated from lipids are promising new components from Ginkgo biloba L. leaves (GBL). In this paper, ginkgo lipids were isolated by extraction with petroleum ether, saponification, and molecular distillation. Eight known compounds: isophytol (1), nerolidol (2), linalool [...] Read more.
Polyprenols separated from lipids are promising new components from Ginkgo biloba L. leaves (GBL). In this paper, ginkgo lipids were isolated by extraction with petroleum ether, saponification, and molecular distillation. Eight known compounds: isophytol (1), nerolidol (2), linalool (3), β-sitosterol acetate (4), β-sitosterol (5), stigmasterol (6), ergosterol (7), β-sitosterol-3-O-β-D-glucopyranoside (8) and Ginkgo biloba polyprenols (GBP) were separated from GBL by chromatography and identified mainly by NMR. The separated and identified compounds 1, 2 and 3 are reported here for the first time in GBL. The 3D-DAD-HPLC-chromatogram (190–232 nm) of GBP was recorded. This study provides new evidence as there are no previous reports on antibacterial/antifungal activities and synergistic interactions between GBP and the compounds separated from GBL lipids against Salmonella enterica, Staphylocococus aureus and Aspergillus niger. Nerolidol (2) showed the highest activity among all the tested samples and of all mixture groups tested the GBP with isophytol (1) mixture had the strongest synergistic effect against Salmonella enterica among the three tested strains. A proportion of isophytol and GBP of 38.19%:61.81% (wt/wt) was determined by mixture design as the optimal proportion for the synergistic effect of GBP with isophytol against Salmonella enterica. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Anti-Escherichia coli O157:H7 Properties of Purple Prairie Clover and Sainfoin Condensed Tannins
Molecules 2013, 18(2), 2183-2199; doi:10.3390/molecules18022183
Received: 21 December 2012 / Revised: 31 January 2013 / Accepted: 31 January 2013 / Published: 8 February 2013
Cited by 9 | PDF Full-text (834 KB)
Abstract
Condensed tannins (CT) from purple prairie clover (PPC; Dalea purpurea Vent.) and sainfoin (SF; Onobrychis viciifolia) were assessed for anti-Escherichia coli activity by comparing their ability to react with proteins and liposome, cause cell aggregation, and alter outer membrane (OM) [...] Read more.
Condensed tannins (CT) from purple prairie clover (PPC; Dalea purpurea Vent.) and sainfoin (SF; Onobrychis viciifolia) were assessed for anti-Escherichia coli activity by comparing their ability to react with proteins and liposome, cause cell aggregation, and alter outer membrane (OM) morphology and permeability. The PPC CT had greater (P < 0.01) protein-precipitating capacity than SF CT using either bovine serum albumin or ribulose 1,5-disphosphate carboxylase as model proteins. Minimum inhibitory concentration of PPC CT for two strains of E. coli and five strains of E. coli O157:H7 was four to six times lower than that of SF CT. E. coli exposed to 10 µg/mL of both CT had higher (P < 0.05) OM permeability than controls and was greater (P < 0.05) for PPC than for SF CT. Addition of both CT at 50 and 200 µg/mL caused cell aggregation which was more evident (P < 0.05) for PPC than for SF CT. Transmission electron microscopy showed electron dense material on the cell surface when cells were exposed to 50 µg/mL of PPC CT. The greater anti-E. coli activity of PPC than SF CT was due to its enhanced ability to precipitate protein that increased OM permeability and promoted cell aggregation. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Gelam Honey Protects against Gamma-Irradiation Damage to Antioxidant Enzymes in Human Diploid Fibroblasts
Molecules 2013, 18(2), 2200-2211; doi:10.3390/molecules18022200
Received: 10 December 2012 / Revised: 18 January 2013 / Accepted: 22 January 2013 / Published: 11 February 2013
Cited by 2 | PDF Full-text (269 KB)
Abstract
The present study was designed to determine the radioprotective effects of Malaysian Gelam honey on gene expression and enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) of human diploid fibroblasts (HDFs) subjected to gamma-irradiation. Six groups of HDFs [...] Read more.
The present study was designed to determine the radioprotective effects of Malaysian Gelam honey on gene expression and enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) of human diploid fibroblasts (HDFs) subjected to gamma-irradiation. Six groups of HDFs were studied: untreated control, irradiated HDFs, Gelam honey-treated HDFs and HDF treated with Gelam honey pre-, during- and post-irradiation. HDFs were treated with 6 mg/mL of sterilized Gelam honey (w/v) for 24 h and exposed to 1 Gray (Gy) of gamma rays at the dose rate of 0.25 Gy/min. Gamma-irradiation was shown to down-regulate SOD1, SOD2, CAT and GPx1 gene expressions (p < 0.05). Conversely, HDFs treated with Gelam honey alone showed up-regulation of all genes studied. Similarly, SOD, CAT and GPx enzyme activities in HDFs decreased with gamma-irradiation and increased when cells were treated with Gelam honey (p < 0.05). Furthermore, of the three different stages of study treatment, pre-treatment with Gelam honey caused up-regulation of SOD1, SOD2 and CAT genes expression and increased the activity of SOD and CAT. As a conclusion, Gelam honey modulates the expression of antioxidant enzymes at gene and protein levels in irradiated HDFs indicating its potential as a radioprotectant agent. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle An Efficient Chemoselective Reduction of Furan Series Unsaturated Dinitriles
Molecules 2013, 18(2), 2212-2221; doi:10.3390/molecules18022212
Received: 14 December 2012 / Revised: 28 January 2013 / Accepted: 30 January 2013 / Published: 11 February 2013
Cited by 3 | PDF Full-text (193 KB)
Abstract
An efficient reduction of double bonds conjugated with nitrile groups and acid or base sensitive furan rings with 2-phenylbenzimidazoline generated in situ has been successfully accomplished with high yields and excellent selectivity. The employed reducing agent was prepared in one step from [...] Read more.
An efficient reduction of double bonds conjugated with nitrile groups and acid or base sensitive furan rings with 2-phenylbenzimidazoline generated in situ has been successfully accomplished with high yields and excellent selectivity. The employed reducing agent was prepared in one step from ordinary chemicals. The other advantages of the presented method include mild and convenient reaction conditions, a benign and cost effective reagent, simple work-up and separation of the products. As this process does neither affect cyano and nitro groups nor furan rings, it is a valuable alternative when metal-catalyzed hydrogenations or borohydride reductions have failed. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Preparation of an Immunoaffinity Column with Amino-Silica Gel Microparticles and Its Application in Sample Cleanup for Aflatoxin Detection in Agri-Products
Molecules 2013, 18(2), 2222-2235; doi:10.3390/molecules18022222
Received: 13 December 2012 / Revised: 24 January 2013 / Accepted: 28 January 2013 / Published: 11 February 2013
Cited by 11 | PDF Full-text (451 KB)
Abstract
This study established an immunoaffinity column for selective extraction of aflatoxins in agri-products. Specifically, the immunoaffinity column was developed by covalently coupling monoclonal antibody 1C11 against aflatoxins to amino-silica gel microparticles and then packing these into a cartridge. The extraction conditions were [...] Read more.
This study established an immunoaffinity column for selective extraction of aflatoxins in agri-products. Specifically, the immunoaffinity column was developed by covalently coupling monoclonal antibody 1C11 against aflatoxins to amino-silica gel microparticles and then packing these into a cartridge. The extraction conditions were thoroughly optimized in terms of loading, washing and eluting solutions. Under the optimal conditions, the immunoaffinity column had a capacity of 200 ng of aflatoxins. The detection limits (S/N = 3) for aflatoxin G1, B1, G2 and B2 were 0.03, 0.07, 0.05 and 0.09 μg·kg−1, and the corresponding quantification limits (S/N = 10) were 0.10, 0.25, 0.18 and 0.30 μg·kg−1, respectively. The recoveries of aflatoxins in samples were 90.1%–104.4% and RSDs were <4.4%. The developed method was further applied to the determination of aflatoxins in peanut, vegetable oil and tea samples, and the results indicated that peanut (26.9%), vegetable oils (28.0%) and tea (5.3%) samples were contaminated with aflatoxins, with levels ranging from 0.49 to 20.79 μg·kg−1. Full article
Open AccessArticle New Spiral γ-Lactone Enantiomers from the Plant Endophytic Fungus Pestalotiopsis foedan
Molecules 2013, 18(2), 2236-2242; doi:10.3390/molecules18022236
Received: 27 December 2012 / Revised: 20 January 2013 / Accepted: 22 January 2013 / Published: 11 February 2013
Cited by 4 | PDF Full-text (285 KB) | Supplementary Files
Abstract
(−)-(4S, 8S)-Foedanolide (1a) and (+)-(4R, 8R)-foedanolide (1b), a pair of new spiro-γ-lactone enantiomers, were isolated from the fermentation broth of the plant endophytic fungus Pestalotiopsis foedan by HPLC using a [...] Read more.
(−)-(4S, 8S)-Foedanolide (1a) and (+)-(4R, 8R)-foedanolide (1b), a pair of new spiro-γ-lactone enantiomers, were isolated from the fermentation broth of the plant endophytic fungus Pestalotiopsis foedan by HPLC using a chiral column, achieving over 7% ee. Their structures and absolute configurations were determined on the basis of extensive analysis of NMR spectra combined with computational methods via calculation of the electronic circular dichroism (ECD) and optical rotation (OR). Compounds 1a and 1b showed moderate activities against HeLa, A-549, U-251, HepG2 and MCF-7 tumor cell lines. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Growth of Fullerene Fragments Using the Diels-Alder Cycloaddition Reaction: First Step towards a C60 Synthesis by Dimerization
Molecules 2013, 18(2), 2243-2254; doi:10.3390/molecules18022243
Received: 25 December 2012 / Revised: 20 January 2013 / Accepted: 5 February 2013 / Published: 13 February 2013
Cited by 3 | PDF Full-text (576 KB)
Abstract
Density Functional Theory has been used to model the Diels-Alder reactions of the fullerene fragments triindenetriphenilene and pentacyclopentacorannulene with ethylene and 1,3-butadiene. The purpose is to prove the feasibility of using Diels-Alder cycloaddition reactions to grow fullerene fragments step by step, and [...] Read more.
Density Functional Theory has been used to model the Diels-Alder reactions of the fullerene fragments triindenetriphenilene and pentacyclopentacorannulene with ethylene and 1,3-butadiene. The purpose is to prove the feasibility of using Diels-Alder cycloaddition reactions to grow fullerene fragments step by step, and to dimerize fullerene fragments, as a way to obtain C60. The dienophile character of the fullerene fragments is dominant, and the reaction of butadiene with pentacyclopentacorannulene is favored. Full article
(This article belongs to the Special Issue Diels-Alder Reaction)
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Open AccessArticle Characterization of Proanthocyanidins in Stems of Polygonum multiflorum Thunb as Strong Starch Hydrolase Inhibitors
Molecules 2013, 18(2), 2255-2265; doi:10.3390/molecules18022255
Received: 10 December 2012 / Revised: 5 February 2013 / Accepted: 5 February 2013 / Published: 18 February 2013
Cited by 7 | PDF Full-text (385 KB) | HTML Full-text | XML Full-text
Abstract
Characterzation of polyphenolic compounds in the stems of P. multiflorum was conducted using HPLC, high resolution LC-MS and LC-MSn. Proanthocyanidins in particular were isolated in 4.8% yield using solvent extraction followed by Sephadex LH-20 fractionation. HPLC analysis using a diol [...] Read more.
Characterzation of polyphenolic compounds in the stems of P. multiflorum was conducted using HPLC, high resolution LC-MS and LC-MSn. Proanthocyanidins in particular were isolated in 4.8% yield using solvent extraction followed by Sephadex LH-20 fractionation. HPLC analysis using a diol column revealed oligomers (from dimer to nonamer) as minor components, with (epi)catechin monomeric units predominating, and oligomers with higher degree of polymerization being dominant. Thiolysis treatment of the proanthocyanidins using mercaptoacetic acid produced thioether derivatives of (epi)catechin as the major product and a mean value of the degree of polymerization of 32.6 was estimated from the ratio of terminal and extension units of the (epi)catechin. The isolated proanthocyanidins were shown to strongly inhibit α-amylase with an acarbose equivalence (AE) value of 1,954.7 µmol AE/g and inhibit α-glucosidase with an AE value of 211.1 µmol AE/g. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Quenching of Tryptophan Fluorescence in the Presence of 2,4-DNP, 2,6-DNP, 2,4-DNA and DNOC and Their Mechanism of Toxicity
Molecules 2013, 18(2), 2266-2280; doi:10.3390/molecules18022266
Received: 4 January 2013 / Revised: 6 February 2013 / Accepted: 13 February 2013 / Published: 18 February 2013
Cited by 4 | PDF Full-text (493 KB) | HTML Full-text | XML Full-text
Abstract
Although they are widely used as insecticides, acaricides and fungicides in the agriculture or as raw materials in the dye industry, dinitrophenols (DNPs) are extremely noxious, death cases having been registered. These compounds produce cataracts, lower leucocyte levels, disturb the general metabolism [...] Read more.
Although they are widely used as insecticides, acaricides and fungicides in the agriculture or as raw materials in the dye industry, dinitrophenols (DNPs) are extremely noxious, death cases having been registered. These compounds produce cataracts, lower leucocyte levels, disturb the general metabolism and can cause cancer. It is also assumed that DNPs hinder the proton translocation through the mitochondrial inner membrane and therefore inhibit oxidative phosphorylation. Their fluorescence quenching properties can help understand and explain their toxicity. Fluorescence quenching of tryptophan was tested using different dinitrophenols such as 2,4-dinitrophenol (2,4-DNP), 4,6-dinitro-orthocresol (DNOC), 2-[(2,4-dinitrophenyl)amino]acetic acid (GlyDNP), 2-(1-methyl-heptyl)-4.6-dinitrophenyl crotonate (Karathan), 2-amino-5-[(1-((carboxymethyl)amino)-3-((2,4-dinitrophenyl)thio)-1-oxopropan-2-yl)amino]-5-oxopentanoic acid (SDN GSH), 2,4-dinitroanisole (2,4-DNA) and 2,4-dinitrobenzoic acid (2,4-DNB). 2,4-DNP and DNOC showed the highest tryptophan fluorescence quenching constant values, these being also the most toxic compounds. The electronic chemical potential value of the most stable complex of 2,4-DNP-with tryptophan is higher than the values of the electronic chemical potentials of complexes corresponding to the derivatives. Full article
Open AccessArticle Enthalpy/Entropy Contributions to Conformational KIEs: Theoretical Predictions and Comparison with Experiment
Molecules 2013, 18(2), 2281-2296; doi:10.3390/molecules18022281
Received: 4 December 2012 / Revised: 22 January 2013 / Accepted: 1 February 2013 / Published: 18 February 2013
Cited by 1 | PDF Full-text (530 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Previous theoretical studies of Mislow’s doubly-bridged biphenyl ketone 1 and dihydrodimethylphenanthrene 2 have determined significant entropic contributions to their normal (1) and inverse (2) conformational kinetic isotope effects (CKIEs). To broaden our investigation, we have used density functional [...] Read more.
Previous theoretical studies of Mislow’s doubly-bridged biphenyl ketone 1 and dihydrodimethylphenanthrene 2 have determined significant entropic contributions to their normal (1) and inverse (2) conformational kinetic isotope effects (CKIEs). To broaden our investigation, we have used density functional methods to characterize the potential energy surfaces and vibrational frequencies for ground and transition structures of additional systems with measured CKIEs, including [2.2]-metaparacyclophane-d (3), 1,1'-binaphthyl (4), 2,2'-dibromo-[1,1'-biphenyl]-4,4'-dicarboxylic acid (5), and the 2-(N,N,N-trimethyl)-2'-(N,N-dimethyl)-diaminobiphenyl cation (6). We have also computed CKIEs in a number of systems whose experimental CKIEs are unknown. These include analogs of 1 in which the C=O groups have been replaced with CH2 (7), O (8), and S (9) atoms and ring-expanded variants of 2 containing CH2 (10), O (11), S (12), or C=O (13) groups. Vibrational entropy contributes to the CKIEs in all of these systems with the exception of cyclophane 3, whose isotope effect is predicted to be purely enthalpic in origin and whose Bigeleisen-Mayer ZPE term is equivalent to ΔΔ H. There is variable correspondence between these terms in the other molecules studied, thus identifying additional examples of systems in which the Bigeleisen-Mayer formalism does not correlate with ΔHS dissections. Full article
(This article belongs to the Special Issue Isotope Effects)
Open AccessArticle Neglschisandrins E–F: Two New Lignans and Related Cytotoxic Lignans from Schisandra neglecta
Molecules 2013, 18(2), 2297-2306; doi:10.3390/molecules18022297
Received: 13 December 2012 / Revised: 30 January 2013 / Accepted: 31 January 2013 / Published: 19 February 2013
Cited by 5 | PDF Full-text (364 KB) | HTML Full-text | XML Full-text
Abstract
Phytochemical investigation of an ethanolic extract of stems of Schisandra neglecta led to the isolation and identification of two new dibenzocyclooctadiene lignans, designated neglschisandrins E (1) and F (2), and thirteen known lignans. All structures and stereochemistries were [...] Read more.
Phytochemical investigation of an ethanolic extract of stems of Schisandra neglecta led to the isolation and identification of two new dibenzocyclooctadiene lignans, designated neglschisandrins E (1) and F (2), and thirteen known lignans. All structures and stereochemistries were determined by spectroscopic methods, including 2D-NMR techniques. The isolates were evaluated for in vitro cytotoxic activity. Among them, compounds 26 exhibited moderate to weak cytotoxicity against the human colorectal carcinoma HCT-8 cell line with EC50 values of 7.33~19.8 μg/mL. In addition, compounds 24 also exhibited marginal cytotoxicity against the human lung carcinoma A549 cell line with EC50 values of 11.8~15.0 μg/mL. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Free Radical Scavenging Activity of Kielmeyera variabilis (Clusiaceae)
Molecules 2013, 18(2), 2376-2385; doi:10.3390/molecules18022376
Received: 7 January 2013 / Revised: 1 February 2013 / Accepted: 1 February 2013 / Published: 19 February 2013
Cited by 5 | PDF Full-text (237 KB) | HTML Full-text | XML Full-text
Abstract
As part of our ongoing research on antioxidant agents from Brazilian flora, we screened the free radical scavenging activity of two extracts and eight fractions of Kielmeyera variabilis (Clusiaceae) using DPPH· (2,2-diphenyl-1-picrylhydrazyl-hydrate) and ABTS·+ [2,2'-azinobis(3-ethylenebenzothiazoline-6-sulfonic acid)] colorimetric assays. The [...] Read more.
As part of our ongoing research on antioxidant agents from Brazilian flora, we screened the free radical scavenging activity of two extracts and eight fractions of Kielmeyera variabilis (Clusiaceae) using DPPH· (2,2-diphenyl-1-picrylhydrazyl-hydrate) and ABTS·+ [2,2'-azinobis(3-ethylenebenzothiazoline-6-sulfonic acid)] colorimetric assays. The ethyl acetate and n-butanol fractions of the leaves of K. variabilis displayed the strongest activity (IC50 of 3.5 ± 0.3 and 4.4 ± 0.2 μg mL−1 for DPPH· and 6.6 ± 0.4 and 3.1 ± 0.1 μg mL−1 for ABTS·+, respectively). Chromatographic fractionation of the most potent fractions led to identification of three flavonols with previously described antioxidant activity, quercitrin (1), quercetin-3-O-b-glucoside (3), and quercetin-3-O-b-galactoside (4), and of one biflavone, podocarpusflavone A (2). This is the first time that the presence of these flavonoids in Kielmeyera variabilis has been reported. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Crystal Structures of N-Substituted Pyrazolines
Molecules 2013, 18(2), 2386-2396; doi:10.3390/molecules18022386
Received: 12 December 2012 / Revised: 2 February 2013 / Accepted: 7 February 2013 / Published: 20 February 2013
Cited by 1 | PDF Full-text (821 KB) | HTML Full-text | XML Full-text
Abstract
Four pyrazole compounds, 3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde (1), 5-(4-bromophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehyde (2), 1-[5-(4-chlorophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl]ethanone (3) and 1-[3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl]propan-1-one (4), have been prepared by condensing chalcones with hydrazine hydrate in the presence of aliphatic [...] Read more.
Four pyrazole compounds, 3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde (1), 5-(4-bromophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehyde (2), 1-[5-(4-chlorophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl]ethanone (3) and 1-[3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl]propan-1-one (4), have been prepared by condensing chalcones with hydrazine hydrate in the presence of aliphatic acids, namely formic acid, acetic acid and propionic acid. The structures were characterized by X-ray single crystal structure determination. The dihedral angles formed between the pyrazole and the fluoro-substituted rings are 4.64(7)° in 1, 5.3(4)° in 2 and 4.89(6)° in 3. In 4, the corresponding angles for molecules A and molecules B are 10.53(10)° and 9.78(10)°, respectively. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle 7-Methoxytacrine-Adamantylamine Heterodimers as Cholinesterase Inhibitors in Alzheimer’s Disease Treatment — Synthesis, Biological Evaluation and Molecular Modeling Studies
Molecules 2013, 18(2), 2397-2418; doi:10.3390/molecules18022397
Received: 14 January 2013 / Revised: 24 January 2013 / Accepted: 4 February 2013 / Published: 20 February 2013
Cited by 16 | PDF Full-text (510 KB) | HTML Full-text | XML Full-text
Abstract
A structural series of 7-MEOTA-adamantylamine thioureas was designed, synthesized and evaluated as inhibitors of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE). The compounds were prepared based on the multi-target-directed ligand strategy with different linker lengths (n = 2–8) joining the well-known NMDA [...] Read more.
A structural series of 7-MEOTA-adamantylamine thioureas was designed, synthesized and evaluated as inhibitors of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE). The compounds were prepared based on the multi-target-directed ligand strategy with different linker lengths (n = 2–8) joining the well-known NMDA antagonist adamantine and the hAChE inhibitor 7-methoxytacrine (7-MEOTA). Based on in silico studies, these inhibitors proved dual binding site character capable of simultaneous interaction with the peripheral anionic site (PAS) of hAChE and the catalytic active site (CAS). Clearly, these structural derivatives exhibited very good inhibitory activity towards hBChE resulting in more selective inhibitors of this enzyme. The most potent cholinesterase inhibitor was found to be thiourea analogue 14 (with an IC50 value of 0.47 µM for hAChE and an IC50 value of 0.11 µM for hBChE, respectively). Molecule 14 is a suitable novel lead compound for further evaluation proving that the strategy of dual binding site inhibitors might be a promising direction for development of novel AD drugs. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Sonolytic and Silent Polymerization of Methacrlyic Acid Butyl Ester Catalyzed by a New Onium Salt with bis-Active Sites in a Biphasic System — A Comparative Investigation
Molecules 2013, 18(2), 2419-2437; doi:10.3390/molecules18022419
Received: 22 November 2012 / Revised: 9 January 2013 / Accepted: 28 January 2013 / Published: 21 February 2013
Cited by 4 | PDF Full-text (256 KB) | HTML Full-text | XML Full-text
Abstract
Currently, ingenious new analytical and process experimental techniques which are environmentally benign techniques, viz., ultrasound irradiation, have become immensely popular in promoting various reactions. In this work, a novel soluble multi-site phase transfer catalyst (PTC) viz., 1,4-bis-(propylmethyleneammounium chloride)benzene (BPMACB) was [...] Read more.
Currently, ingenious new analytical and process experimental techniques which are environmentally benign techniques, viz., ultrasound irradiation, have become immensely popular in promoting various reactions. In this work, a novel soluble multi-site phase transfer catalyst (PTC) viz., 1,4-bis-(propylmethyleneammounium chloride)benzene (BPMACB) was synthesized and its catalytic efficiency was assessed by observing the kinetics of sonolytic polymerization of methacrylic acid butyl ester (MABE) using potassium persulphate (PPS) as an initiator. The ultrasound–multi-site phase transfer catalysis (US-MPTC)-assisted polymerization reaction was compared with the silent (non-ultrasonic) polymerization reaction. The effects of the catalyst and various reaction parameters on the catalytic performance were in detail investigated by following the kinetics of polymerization of MABE in an ethyl acetate-water biphasic system. From the detailed kinetic investigation we propose a plausible mechanism. Further the kinetic results demonstrate clearly that ultrasound-assisted phase-transfer catalysis significantly increased the reaction rate when compared to silent reactions. Notably, this environmentally benign and cost-effective process has great potential to be applied in various polymer industries. Full article
(This article belongs to the Special Issue Phase Transfer Catalysis)
Open AccessArticle The Tandem Ring Opening/Ring Closing Metathesis Route to Oxaspirocycles: An Approach to Phelligridin G
Molecules 2013, 18(2), 2438-2448; doi:10.3390/molecules18022438
Received: 4 December 2012 / Revised: 31 January 2013 / Accepted: 7 February 2013 / Published: 21 February 2013
Cited by 8 | PDF Full-text (310 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phelligridin G is an unusual natural product that contains an embedded spiro-fused furanone core. We have investigated two furan-based synthetic approaches towards the spirocyclic core structure of this natural product from readily available 2-phenylfurans. Although initial studies involving an oxidative cyclization were [...] Read more.
Phelligridin G is an unusual natural product that contains an embedded spiro-fused furanone core. We have investigated two furan-based synthetic approaches towards the spirocyclic core structure of this natural product from readily available 2-phenylfurans. Although initial studies involving an oxidative cyclization were unsuccessful, we were ultimately able to access this key system through a sequential intermolecular furan Diels-Alder reaction followed by a metathesis-based reorganization. A related approach led to an expanded C ring to form spiro-fused pyran spirocycles. Full article
(This article belongs to the Special Issue Spiro Compounds)
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Open AccessCommunication Brazilin Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells
Molecules 2013, 18(2), 2449-2457; doi:10.3390/molecules18022449
Received: 26 November 2012 / Revised: 31 January 2013 / Accepted: 6 February 2013 / Published: 21 February 2013
Cited by 13 | PDF Full-text (276 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Brazilin, isolated from the methanol extract of the heart wood of Caesalpinia sappan, sensitizes cancer cells to apoptosis. Glioblastoma multiforme (GBM), which accounts for most cases of central nervous system malignancy, has a very poor prognosis and lacks effective therapeutic interventions. [...] Read more.
Brazilin, isolated from the methanol extract of the heart wood of Caesalpinia sappan, sensitizes cancer cells to apoptosis. Glioblastoma multiforme (GBM), which accounts for most cases of central nervous system malignancy, has a very poor prognosis and lacks effective therapeutic interventions. We, therefore, investigated the effects of different concentrations of and different periods of exposure to brazilin on cell proliferation and apoptosis in the glioma U87 cell line. Cell proliferation was investigated by MTT assays and growth curve analysis, apoptosis was assessed by FACS analysis and western blot studies. Brazilin showed dose-dependent inhibition of cell proliferation and induction of apoptosis in glioma cells. It also increased the ratio of cleaved poly-(ADP)-ribose polymerase and decreased the expression of caspase-3 and caspase-7. Full article
(This article belongs to the Section Medicinal Chemistry)

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Open AccessReview Case Studies of the Synthesis of Bioactive Cyclodepsipeptide Natural Products
Molecules 2013, 18(2), 1337-1367; doi:10.3390/molecules18021337
Received: 3 December 2012 / Revised: 14 January 2013 / Accepted: 16 January 2013 / Published: 24 January 2013
Cited by 16 | PDF Full-text (757 KB)
Abstract
Cyclodepsipeptide natural products often display intriguing biological activities that along with their complex molecular scaffolds, makes them interesting targets for chemical synthesis. Although cyclodepsipeptides feature highly diverse chemical structures, their synthesis is often associated with similar synthetic challenges such as the establishment [...] Read more.
Cyclodepsipeptide natural products often display intriguing biological activities that along with their complex molecular scaffolds, makes them interesting targets for chemical synthesis. Although cyclodepsipeptides feature highly diverse chemical structures, their synthesis is often associated with similar synthetic challenges such as the establishment of a suitable macrocyclization methodology. This review therefore compiles case studies of synthetic approaches to different bioactive cyclodepsipeptide natural products, thereby illustrating obstacles of cyclodepsipeptide synthesis as well as their overcomings. Full article
(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)
Open AccessReview Antioxidants Improve the Phenotypes of Dilated Cardiomyopathy and Muscle Fatigue in Mitochondrial Superoxide Dismutase-Deficient Mice
Molecules 2013, 18(2), 1383-1393; doi:10.3390/molecules18021383
Received: 10 December 2012 / Revised: 14 January 2013 / Accepted: 16 January 2013 / Published: 24 January 2013
Cited by 11 | PDF Full-text (640 KB)
Abstract
Redox imbalance elevates the reactive oxygen species (ROS) level in cells and promotes age-related diseases. Superoxide dismutases (SODs) are antioxidative enzymes that catalyze the degradation of ROS. There are three SOD isoforms: SOD1/CuZn-SOD, SOD2/Mn-SOD, and SOD3/EC-SOD. SOD2, which is localized in the [...] Read more.
Redox imbalance elevates the reactive oxygen species (ROS) level in cells and promotes age-related diseases. Superoxide dismutases (SODs) are antioxidative enzymes that catalyze the degradation of ROS. There are three SOD isoforms: SOD1/CuZn-SOD, SOD2/Mn-SOD, and SOD3/EC-SOD. SOD2, which is localized in the mitochondria, is an essential enzyme required for mouse survival, and systemic knockout causes neonatal lethality in mice. To investigate the physiological function of SOD2 in adult mice, we generated a conditional Sod2 knockout mouse using a Cre-loxP system. When Sod2 was specifically deleted in the heart and muscle, all mice exhibited dilated cardiomyopathy (DCM) and died by six months of age. On the other hand, when Sod2 was specifically deleted in the skeletal muscle, mice showed severe exercise disturbance without morphological abnormalities. These provide useful model of DCM and muscle fatigue. In this review, we summarize the impact of antioxidants, which were able to regulate mitochondrial superoxide generation and improve the phenotypes of the DCM and the muscle fatigue in mice. Full article
Open AccessReview Chemical Genetics of Acetyl-CoA Carboxylases
Molecules 2013, 18(2), 1704-1719; doi:10.3390/molecules18021704
Received: 3 August 2012 / Revised: 3 January 2013 / Accepted: 11 January 2013 / Published: 28 January 2013
Cited by 10 | PDF Full-text (199 KB)
Abstract
Chemical genetic studies on acetyl-CoA carboxylases (ACCs), rate-limiting enzymes in long chain fatty acid biosynthesis, have greatly advanced the understanding of their biochemistry and molecular biology and promoted the use of ACCs as targets for herbicides in agriculture and for development of [...] Read more.
Chemical genetic studies on acetyl-CoA carboxylases (ACCs), rate-limiting enzymes in long chain fatty acid biosynthesis, have greatly advanced the understanding of their biochemistry and molecular biology and promoted the use of ACCs as targets for herbicides in agriculture and for development of drugs for diabetes, obesity and cancers. In mammals, ACCs have both biotin carboxylase (BC) and carboxyltransferase (CT) activity, catalyzing carboxylation of acetyl-CoA to malonyl-CoA. Several classes of small chemicals modulate ACC activity, including cellular metabolites, natural compounds, and chemically synthesized products. This article reviews chemical genetic studies of ACCs and the use of ACCs for targeted therapy of cancers. Full article
Open AccessReview Pharmacological Actions of Multi-Target-Directed Evodiamine
Molecules 2013, 18(2), 1826-1843; doi:10.3390/molecules18021826
Received: 14 December 2012 / Revised: 28 January 2013 / Accepted: 29 January 2013 / Published: 31 January 2013
Cited by 32 | PDF Full-text (427 KB)
Abstract
Evodiamine, a naturally occurring indole alkaloid, is one of the main bioactive ingredients of Evodiae fructus. With respect to the pharmacological actions of evodiamine, more attention has been paid to beneficial effects in insults involving cancer, obesity, nociception, inflammation, cardiovascular diseases, [...] Read more.
Evodiamine, a naturally occurring indole alkaloid, is one of the main bioactive ingredients of Evodiae fructus. With respect to the pharmacological actions of evodiamine, more attention has been paid to beneficial effects in insults involving cancer, obesity, nociception, inflammation, cardiovascular diseases, Alzheimer's disease, infectious diseases and themoregulative effects. Evodiamine has evolved a superior ability to bind various proteins, so we also argue that it is good starting point for multi-target drugs. This review is primarily addressed to the description of the recent advances in the biological activity studies of evodiamine, with a focus on pharmacological mechanism. The present review also includes the pharmacokinetics and the detailed exploration of target-binding properties of evodiamine in an attempt to provide a direction for further multi-target drug design. Full article
(This article belongs to the Section Natural Products)
Open AccessReview 3-Substituted Prolines: From Synthesis to Structural Applications, from Peptides to Foldamers
Molecules 2013, 18(2), 2307-2327; doi:10.3390/molecules18022307
Received: 1 February 2013 / Revised: 5 February 2013 / Accepted: 6 February 2013 / Published: 19 February 2013
Cited by 16 | PDF Full-text (1038 KB) | HTML Full-text | XML Full-text
Abstract
Among the twenty natural proteinogenic amino acids, proline is unique as its secondary amine forms a tertiary amide when incorporated into biopolymers, thus preventing hydrogen bond formation. Despite the lack of hydrogen bonds and thanks to conformational restriction of flexibility linked to [...] Read more.
Among the twenty natural proteinogenic amino acids, proline is unique as its secondary amine forms a tertiary amide when incorporated into biopolymers, thus preventing hydrogen bond formation. Despite the lack of hydrogen bonds and thanks to conformational restriction of flexibility linked to the pyrrolidine ring, proline is able to stabilize peptide secondary structures such as b-turns or polyproline helices. These unique conformational properties have aroused a great interest in the development of proline analogues. Among them, proline chimeras are tools combining the proline restriction of flexibility together with the information brought by natural amino acids side chains. This review will focus on the chemical syntheses of 3-substituted proline chimeras of potential use for peptide syntheses and as potential use as tools for SAR studies of biologically active peptides and the development of secondary structure mimetics. Their influence on peptide structure will be briefly described. Full article
(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)
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Open AccessReview Techniques for Analysis of Plant Phenolic Compounds
Molecules 2013, 18(2), 2328-2375; doi:10.3390/molecules18022328
Received: 25 October 2012 / Revised: 10 January 2013 / Accepted: 31 January 2013 / Published: 19 February 2013
Cited by 100 | PDF Full-text (600 KB) | HTML Full-text | XML Full-text
Abstract
Phenolic compounds are well-known phytochemicals found in all plants. They consist of simple phenols, benzoic and cinnamic acid, coumarins, tannins, lignins, lignans and flavonoids. Substantial developments in research focused on the extraction, identification and quantification of phenolic compounds as medicinal and/or dietary [...] Read more.
Phenolic compounds are well-known phytochemicals found in all plants. They consist of simple phenols, benzoic and cinnamic acid, coumarins, tannins, lignins, lignans and flavonoids. Substantial developments in research focused on the extraction, identification and quantification of phenolic compounds as medicinal and/or dietary molecules have occurred over the last 25 years. Organic solvent extraction is the main method used to extract phenolics. Chemical procedures are used to detect the presence of total phenolics, while spectrophotometric and chromatographic techniques are utilized to identify and quantify individual phenolic compounds. This review addresses the application of different methodologies utilized in the analysis of phenolic compounds in plant-based products, including recent technical developments in the quantification of phenolics. Full article
(This article belongs to the Special Issue Methods in Polyphenol Analysis)

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