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Molecules, Volume 20, Issue 3 (March 2015), Pages 3496-5259

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Open AccessArticle Neferine Attenuates the Protein Level and Toxicity of Mutant Huntingtin in PC-12 Cells via Induction of Autophagy
Molecules 2015, 20(3), 3496-3514; doi:10.3390/molecules20033496
Received: 18 December 2014 / Revised: 11 February 2015 / Accepted: 13 February 2015 / Published: 18 February 2015
Cited by 18 | PDF Full-text (1151 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mutant huntingtin aggregation is highly associated with the pathogenesis of Huntington’s disease, an adult-onset autosomal dominant disorder, which leads to a loss of motor control and decline in cognitive function. Recent literature has revealed the protective role of autophagy in neurodegenerative diseases through
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Mutant huntingtin aggregation is highly associated with the pathogenesis of Huntington’s disease, an adult-onset autosomal dominant disorder, which leads to a loss of motor control and decline in cognitive function. Recent literature has revealed the protective role of autophagy in neurodegenerative diseases through degradation of mutant toxic proteins, including huntingtin or a-synuclein. Through the GFP-LC3 autophagy detection platform, we have identified neferine, isolated from the lotus seed embryo of Nelumbo nucifera, which is able to induce autophagy through an AMPK-mTOR-dependent pathway. Furthermore, by overexpressing huntingtin with 74 CAG repeats (EGFP-HTT 74) in PC-12 cells, neferine reduces both the protein level and toxicity of mutant huntingtin through an autophagy-related gene 7 (Atg7)-dependent mechanism. With the variety of novel active compounds present in medicinal herbs, our current study suggests the possible protective mechanism of an autophagy inducer isolated from Chinese herbal medicine, which is crucial for its further development into a potential therapeutic agent for neurodegenerative disorders in the future. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Effect of Diterpenes Isolated of the Marine Alga Canistrocarpus cervicornis against Some Toxic Effects of the Venom of the Bothrops jararaca Snake
Molecules 2015, 20(3), 3515-3526; doi:10.3390/molecules20033515
Received: 17 December 2014 / Revised: 12 February 2015 / Accepted: 13 February 2015 / Published: 18 February 2015
Cited by 6 | PDF Full-text (335 KB) | HTML Full-text | XML Full-text
Abstract
Snake venoms are composed of a complex mixture of active proteins and peptides which induce a wide range of toxic effects. Envenomation by Bothrops jararaca venom results in hemorrhage, edema, pain, tissue necrosis and hemolysis. In this work, the effect of a mixture
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Snake venoms are composed of a complex mixture of active proteins and peptides which induce a wide range of toxic effects. Envenomation by Bothrops jararaca venom results in hemorrhage, edema, pain, tissue necrosis and hemolysis. In this work, the effect of a mixture of two secodolastane diterpenes (linearol/isolinearol), previously isolated from the Brazilian marine brown alga, Canistrocarpus cervicornis, was evaluated against some of the toxic effects induced by B. jararaca venom. The mixture of diterpenes was dissolved in dimethylsulfoxide and incubated with venom for 30 min at room temperature, and then several in vivo (hemorrhage, edema and lethality) and in vitro (hemolysis, plasma clotting and proteolysis) assays were performed. The diterpenes inhibited hemolysis, proteolysis and hemorrhage, but failed to inhibit clotting and edema induced by B. jararaca venom. Moreover, diterpenes partially protected mice from lethality caused by B. jararaca venom. The search for natural inhibitors of B. jararaca venom in C. cervicornis algae is a relevant subject, since seaweeds are a rich and powerful source of active molecules which are as yet but poorly explored. Our results suggest that these diterpenes have the potential to be used against Bothropic envenomation accidents or to improve traditional treatments for snake bites. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Anti-Glycation Activities of Phenolic Constituents from Silybum marianum (Milk Thistle) Flower in Vitro and on Human Explants
Molecules 2015, 20(3), 3549-3564; doi:10.3390/molecules20033549
Received: 25 November 2014 / Revised: 13 February 2015 / Accepted: 15 February 2015 / Published: 19 February 2015
Cited by 4 | PDF Full-text (1309 KB) | HTML Full-text | XML Full-text
Abstract
Glycation is an ageing reaction of naturally occurring sugars with dermal proteins, with clinical signs appearing in vivo around age 30, and increasing steadily/regularly with age. The suppleness of the dermis is affected by the formation of bridges between proteins and sugars (Maillard’s
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Glycation is an ageing reaction of naturally occurring sugars with dermal proteins, with clinical signs appearing in vivo around age 30, and increasing steadily/regularly with age. The suppleness of the dermis is affected by the formation of bridges between proteins and sugars (Maillard’s reaction). The accumulation of advanced glycation end products (AGEs) in skin plays a very important role in skin ageing. Therefore, natural compounds or extracts that possess antiglycation activities may have great anti-ageing potential. In the present study, Silybum marianum flower extract (SMFE) was demonstrated to possess antiglycation activity. We found that SMFE inhibits glycation reaction between BSA and glucose. In addition, antiglycation activity of SMFE was confirmed in a human skin explants model. SMFE reduced Nε-(carboxymethyl) lysine (CML) expression, whereas SMFE stimulated fibrillin-1 expression compared to treatment with methyglyoxal. An active ingredient contributing to the observed activities was identified as silibinin. The antiglycation activity of silibinin was dose-dependent. The beneficial effects of silibinin may be applied to prevention or management of AGE-mediated pathologies, targeting in a pleiotropic and complementary way the biochemical and cellular bases of skin aging. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Divinyl Sulfone Cross-Linked Cyclodextrin-Based Polymeric Materials: Synthesis and Applications as Sorbents and Encapsulating Agents
Molecules 2015, 20(3), 3565-3581; doi:10.3390/molecules20033565
Received: 18 November 2014 / Accepted: 13 February 2015 / Published: 19 February 2015
Cited by 13 | PDF Full-text (3192 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The aim of this study was to evaluate the crosslinking abilities of divinyl sulfone (DVS) for the preparation of novel water-insoluble cyclodextrin-based polymers (CDPs) capable of forming inclusion complexes with different guest molecules. Reaction of DVS with native α-cyclodextrin (α-CD), β-cyclodextrin (β-CD) and/or
[...] Read more.
The aim of this study was to evaluate the crosslinking abilities of divinyl sulfone (DVS) for the preparation of novel water-insoluble cyclodextrin-based polymers (CDPs) capable of forming inclusion complexes with different guest molecules. Reaction of DVS with native α-cyclodextrin (α-CD), β-cyclodextrin (β-CD) and/or starch generates a variety of homo- and hetero-CDPs with different degrees of crosslinking as a function of the reactants’ stoichiometric ratio. The novel materials were characterized by powder X-ray diffraction, electron microscopy and for their sorption of phenol and 4-nitrophenol. They were further evaluated as sorbents with phenolic pollutants (bisphenol A and β-naphthol) and bioactive compounds (the hormone progesterone and curcumin). Data obtained from the inclusion experiments show that the degree of cross-linking has a minor influence on the yield of inclusion complex formation and highlight the important role of the CDs, supporting a sorption process based on the formation of inclusion complexes. In general, the inclusion processes are better described by a Freundlich isotherm although an important number of them can also be fitted to the Langmuir isotherm with R2 ≥ 0.9, suggesting a sorption onto a monolayer of homogeneous sites. Full article
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Open AccessArticle Antibacterial Barbituric Acid Analogues Inspired from Natural 3-Acyltetramic Acids; Synthesis, Tautomerism and Structure and Physicochemical Property-Antibacterial Activity Relationships
Molecules 2015, 20(3), 3582-3627; doi:10.3390/molecules20033582
Received: 7 January 2015 / Revised: 5 February 2015 / Accepted: 12 February 2015 / Published: 20 February 2015
Cited by 7 | PDF Full-text (2392 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The synthesis, tautomerism and antibacterial activity of novel barbiturates is reported. In particular, 3-acyl and 3-carboxamidobarbiturates exhibited antibacterial activity, against susceptible and some resistant Gram-positive strains of particular interest is that these systems possess amenable molecular weight, rotatable bonds and number of proton-donors/acceptors
[...] Read more.
The synthesis, tautomerism and antibacterial activity of novel barbiturates is reported. In particular, 3-acyl and 3-carboxamidobarbiturates exhibited antibacterial activity, against susceptible and some resistant Gram-positive strains of particular interest is that these systems possess amenable molecular weight, rotatable bonds and number of proton-donors/acceptors for drug design as well as less lipophilic character, with physicochemical properties and ionic states that are similar to current antibiotic agents for oral and injectable use. Unfortunately, the reduction of plasma protein affinity by the barbituric core is not sufficient to achieve activity in vivo. Further optimization to reduce plasma protein affinity and/or elevate antibiotic potency is therefore required, but we believe that these systems offer unusual opportunities for antibiotic drug discovery. Full article
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Open AccessArticle Eliminating Aluminum Toxicity in an Acid Sulfate Soil for Rice Cultivation Using Plant Growth Promoting Bacteria
Molecules 2015, 20(3), 3628-3646; doi:10.3390/molecules20033628
Received: 3 November 2014 / Revised: 30 December 2014 / Accepted: 4 January 2015 / Published: 20 February 2015
Cited by 4 | PDF Full-text (870 KB) | HTML Full-text | XML Full-text
Abstract
Aluminum toxicity is widely considered as the most important limiting factor for plants growing in acid sulfate soils. A study was conducted in laboratory and in field to ameliorate Al toxicity using plant growth promoting bacteria (PGPB), ground magnesium limestone (GML) and ground
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Aluminum toxicity is widely considered as the most important limiting factor for plants growing in acid sulfate soils. A study was conducted in laboratory and in field to ameliorate Al toxicity using plant growth promoting bacteria (PGPB), ground magnesium limestone (GML) and ground basalt. Five-day-old rice seedlings were inoculated by Bacillus sp., Stenotrophomonas maltophila, Burkholderia thailandensis and Burkholderia seminalis and grown for 21 days in Hoagland solution (pH 4.0) at various Al concentrations (0, 50 and 100 μM). Toxicity symptoms in root and leaf were studied using scanning electron microscope. In the field, biofertilizer (PGPB), GML and basalt were applied (4 t·ha−1 each). Results showed that Al severely affected the growth of rice. At high concentrations, the root surface was ruptured, leading to cell collapse; however, no damages were observed in the PGPB inoculated seedlings. After 21 days of inoculation, solution pH increased to >6.0, while the control treatment remained same. Field study showed that the highest rice growth and yield were obtained in the bio-fertilizer and GML treatments. This study showed that Al toxicity was reduced by PGPB via production of organic acids that were able to chelate the Al and the production of polysaccharides that increased solution pH. The release of phytohormones further enhanced rice growth that resulted in yield increase. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle An Efficient Agrobacterium-Mediated Transformation of Strawberry cv. Camarosa by a Dual Plasmid System
Molecules 2015, 20(3), 3647-3666; doi:10.3390/molecules20033647
Received: 24 October 2014 / Accepted: 25 November 2014 / Published: 23 February 2015
Cited by 2 | PDF Full-text (3433 KB) | HTML Full-text | XML Full-text
Abstract
An Agrobacterium-mediated transformation method was applied to introduce the luciferase reporter gene under the control of the CaMV35S promoter in the pGreen0049 binary vector into strawberry cv. Camarosa. The in vitro regeneration system of strawberry leaves to be used in the transformation
[...] Read more.
An Agrobacterium-mediated transformation method was applied to introduce the luciferase reporter gene under the control of the CaMV35S promoter in the pGreen0049 binary vector into strawberry cv. Camarosa. The in vitro regeneration system of strawberry leaves to be used in the transformation was optimized using different TDZ concentrations in MS medium. TDZ at 16 µM showed the highest percentage (100%) of shoot formation and the highest mean number of shoots (24) produced per explant. Studies on the effects of different antibiotics, namely timentin, cefotaxime, carbenicillin and ampicillin, on shoot regeneration of strawberry leaf explants showed the best shoot regeneration in the presence of 300 mg/L timentin and 150 mg/L cefotaxime. Assessment of the different factors affecting Agrobacterium mediated-transformation of strawberry with the luciferase gene showed the highest efficiency of putative transformant production (86%) in the treatment with no preculture, bacterial OD600 of 0.6 and the addition of 150 mg/L cefotaxime in the pre-selection and selection media. The presence of the luciferase gene in the plant genome was verified by the luciferase reporter gene assay, nested PCR amplification and dot blot of genomic DNA isolated from the young leaves of each putatively transformed plantlet. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Comparative Study of Two Table Grape Varieties with Contrasting Texture during Cold Storage
Molecules 2015, 20(3), 3667-3680; doi:10.3390/molecules20033667
Received: 27 November 2014 / Accepted: 15 February 2015 / Published: 23 February 2015
Cited by 2 | PDF Full-text (1308 KB) | HTML Full-text | XML Full-text
Abstract
Postharvest softening of grape berries is one of the main problems affecting grape quality during export. Cell wall disassembly, especially of pectin polysaccharides, has been commonly related to fruit softening, but its influence has been poorly studied in grapes during postharvest life. In
[...] Read more.
Postharvest softening of grape berries is one of the main problems affecting grape quality during export. Cell wall disassembly, especially of pectin polysaccharides, has been commonly related to fruit softening, but its influence has been poorly studied in grapes during postharvest life. In order to better understand this process, the Thompson seedless (TS) variety, which has significantly decreased berry texture after prolonged cold storage, was compared to NN107, a new table grape variety with higher berry firmness. Biochemical analysis revealed a greater amount of calcium in the cell wall of the NN107 variety and less reduction of uronic acids than TS during cold storage. In addition, the activity of polygalacturonase was higher in TS than NN107 berries; meanwhile pectin methylesterase activity was similar in both varieties. Polysaccharide analysis using carbohydrate gel electrophoresis (PACE) suggests a differential pectin metabolism during prolonged cold storage. Results revealed lower pectin fragments in TS after 60 days of cold storage and shelf life (SL) compared to 30 days of cold storage and 30 + SL, while NN107 maintained the same fragment profile across all time points evaluated. Our results suggest that these important differences in cell wall metabolism during cold storage could be related to the differential berry firmness observed between these contrasting table grape varieties. Full article
(This article belongs to the collection Wine Chemistry)
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Open AccessArticle Synthesis and Disinfection Effect of the Pyridine-4-aldoxime Based Salts
Molecules 2015, 20(3), 3681-3696; doi:10.3390/molecules20033681
Received: 4 January 2015 / Revised: 6 February 2015 / Accepted: 12 February 2015 / Published: 24 February 2015
Cited by 5 | PDF Full-text (765 KB) | HTML Full-text | XML Full-text
Abstract
A set of new quaternary ammonium compounds based on pyridine-4-aldoxime was synthesized, characterized with analytical data (NMR, EA, HPLC, MS) and tested for in vitro antimicrobial activity (antibacterial, antifungal) and cytotoxicity. Quaternary pyridinium-4-aldoxime salts with length of alkyl side chain from C8 to
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A set of new quaternary ammonium compounds based on pyridine-4-aldoxime was synthesized, characterized with analytical data (NMR, EA, HPLC, MS) and tested for in vitro antimicrobial activity (antibacterial, antifungal) and cytotoxicity. Quaternary pyridinium-4-aldoxime salts with length of alkyl side chain from C8 to C20 and belonging to the group of cationic surfactants were investigated in this work. An HPLC experimental protocol for characterization of mixtures of all homologues has been found. Antimicrobial evaluation found that yeast-type fungi were most sensitive towards C14 and C16 analogues, whereas the C16 analogue was completely ineffective against filamentous fungi. Antibacterial assessment showed versatility of C14 and relatively high efficacy of C16 against G+ strains and C14 against G− strains. Notably, none of the studied compounds exceeded the efficacy and versatility of the benzalkonium C12 analogue, and benzalkonium analogues also exhibited lower cytotoxicity in the cell viability assay. Full article
Open AccessArticle Bioassay-Guided Fractionation of Melastoma malabathricum Linn. Leaf Solid Phase Extraction Fraction and Its Anticoagulant Activity
Molecules 2015, 20(3), 3697-3715; doi:10.3390/molecules20033697
Received: 19 November 2014 / Revised: 17 December 2014 / Accepted: 9 January 2015 / Published: 24 February 2015
PDF Full-text (1023 KB) | HTML Full-text | XML Full-text
Abstract
The aims of this study were to examine the bioactive component(s) responsible for the anticoagulant activity of M. malabathricum Linn. leaf hot water crude extract via bioassay-guided fractionation and to evaluate the effect of bioactive component(s) on the intrinsic blood coagulation pathway. The
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The aims of this study were to examine the bioactive component(s) responsible for the anticoagulant activity of M. malabathricum Linn. leaf hot water crude extract via bioassay-guided fractionation and to evaluate the effect of bioactive component(s) on the intrinsic blood coagulation pathway. The active anticoagulant fraction of F3 was subjected to a series of chromatographic separation and spectroscopic analyses. Furthermore, the effect of the bioactive component(s) on the intrinsic blood coagulation pathway was studied through immediate and time incubation mixing studies. Through Activated Partial Thromboplastin Time (APTT) assay-guided fractionation, Subfraction B was considered the most potent anticoagulant fraction. Characterisation of Subfraction B indicated that anticoagulant activity could partly be due to the presence of cinnamic acid and a cinnamic acid derivative. APTT assays for both the immediate and time incubation mixing were corrected back into normal clotting time range (35.4–56.3 s). In conclusion, cinnamic acid and cinnamic acid derivative from Subfraction B were the first such compounds to be discovered from M. malabathricum Linn. leaf hot water crude extract that possess anticoagulant activity. This active anticoagulant Subfraction B prolonged blood clotting time by causing factor(s) deficiency in the intrinsic blood coagulation pathway. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle In Vitro and in Vivo Evaluation of Novel Cross-Linked Saccharide Based Polymers as Bile Acid Sequestrants
Molecules 2015, 20(3), 3716-3729; doi:10.3390/molecules20033716
Received: 18 November 2014 / Revised: 11 February 2015 / Accepted: 16 February 2015 / Published: 24 February 2015
Cited by 3 | PDF Full-text (2680 KB) | HTML Full-text | XML Full-text
Abstract
Bile acid sequestrants (BAS) represent a therapeutic approach for the management of hypercholesterolemia that relies on the cationic polymeric nature of BAS to selectively bind negatively charged bile acids. We hypothesized that the cross-linking of β-cyclodextrin (β-CD) and saccharides such as starch or
[...] Read more.
Bile acid sequestrants (BAS) represent a therapeutic approach for the management of hypercholesterolemia that relies on the cationic polymeric nature of BAS to selectively bind negatively charged bile acids. We hypothesized that the cross-linking of β-cyclodextrin (β-CD) and saccharides such as starch or dextrin with divinyl sulfone (DVS) yields homo- and hetero-polymeric materials with the ability to trap sterols. Our hypothesis was put to test by synthesizing a library of 22 polymers that were screened to evaluate their capability to sequester both cholesterol (CHOL) and cholic and deoxycholic acids (CA and DCA). Three polymers synthesized in high yield were identified as promising. Two were neutral hetero-polymers of β-CD and starch or dextrin and the third was a weakly cationic homo-polymer of starch, highlighting the importance of the cavity effect. They were tested in hypercholesterolemic male Wistar rats and their ability to regulate hypercholesterolemia was similar to that for the reference BAS cholestyramine, but with two additional advantages: (i) they normalized the TG level and (ii) they did not increase the creatinine level. Neither hepatotoxicity nor kidney injury was detected, further supporting them as therapeutical candidates to manage hypercholesterolemia. Full article
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Open AccessArticle Dose-Dependent Cytotoxic Effects of Boldine in HepG-2 Cells—Telomerase Inhibition and Apoptosis Induction
Molecules 2015, 20(3), 3730-3743; doi:10.3390/molecules20033730
Received: 31 December 2014 / Revised: 11 February 2015 / Accepted: 12 February 2015 / Published: 24 February 2015
Cited by 5 | PDF Full-text (1531 KB) | HTML Full-text | XML Full-text
Abstract
Plant metabolites are valuable sources of novel therapeutic compounds. In an anti-telomerase screening study of plant secondary metabolites, the aporphine alkaloid boldine (1,10-dimethoxy-2,9-dihydroxyaporphine) exhibited a dose and time dependent cytotoxicity against hepatocarcinoma HepG-2 cells. Here we focus on the modes and mechanisms of
[...] Read more.
Plant metabolites are valuable sources of novel therapeutic compounds. In an anti-telomerase screening study of plant secondary metabolites, the aporphine alkaloid boldine (1,10-dimethoxy-2,9-dihydroxyaporphine) exhibited a dose and time dependent cytotoxicity against hepatocarcinoma HepG-2 cells. Here we focus on the modes and mechanisms of the growth-limiting effects of this compound. Telomerase activity and expression level of some related genes were estimated by real-time PCR. Modes of cell death also were examined by microscopic inspection, staining methods and by evaluating the expression level of some critically relevant genes. The growth inhibition was correlated with down-regulation of the catalytic subunit of telomerase (hTERT) gene (p < 0.01) and the corresponding reduction of telomerase activity in sub-cytotoxic concentrations of boldine (p < 0.002). However, various modes of cell death were stimulated, depending on the concentration of boldine. Very low concentrations of boldine over a few passages resulted in an accumulation of senescent cells so that HepG-2 cells lost their immortality. Moreover, boldine induced apoptosis concomitantly with increasing the expression of bax/bcl2 (p < 0.02) and p21 (p < 0.01) genes. Boldine might thus be an interesting candidate as a potential natural compound that suppresses telomerase activity in non-toxic concentrations. Full article
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Open AccessArticle Purification and Immobilization of the Recombinant Brassica oleracea Chlorophyllase 1 (BoCLH1) on DIAION®CR11 as Potential Biocatalyst for the Production of Chlorophyllide and Phytol
Molecules 2015, 20(3), 3744-3757; doi:10.3390/molecules20033744
Received: 4 December 2014 / Revised: 16 February 2015 / Accepted: 17 February 2015 / Published: 24 February 2015
Cited by 5 | PDF Full-text (947 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Recombinant Brassica oleracea chlorophyllase 1 (BoCLH1) with a protein molecular weight of 38.63 kDa was successfully expressed in E. coli and could catalyze chlorophyll (Chl) hydrolysis to chlorophyllide and phytol in vitro. In this study, we used DIAION®CR11, a highly
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Recombinant Brassica oleracea chlorophyllase 1 (BoCLH1) with a protein molecular weight of 38.63 kDa was successfully expressed in E. coli and could catalyze chlorophyll (Chl) hydrolysis to chlorophyllide and phytol in vitro. In this study, we used DIAION®CR11, a highly porous cross-linked polystyrene divinylbenzene-based metal chelator, for purifying and immobilizing the poly (His)-tagged enzyme. The Cu(II) showed the highest protein adsorption (9.2 ± 0.43 mg/g gel) and enzyme activity (46.3 ± 3.14 U/g gel) for the immobilization of the poly (His)-tagged recombinant BoCLH1 compared with other metal chelators. Biochemical analysis of the immobilized enzyme showed higher chlorophyllase activity for Chl a hydrolysis in a weak base environment (pH 8.0), and activity above 70% was in a high-temperature environment, compared with the free enzyme. In addition, compared with free BoCLH1, the enzyme half-life (t1/2) of the immobilized BoCLH1 increased from 25.42 to 54.35 min (approximately two-fold) at 60 °C. The immobilized enzyme retained a residual activity of approximately 60% after 17 cycles in a repeated-batch operation. Therefore, DIAION®CR11Cu(II)-immobilized recombinant BoCLH1 can be repeatedly used to lower the cost and is potentially useful for the industrial production of chlorophyllide and phytol. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Tyrosol Prevents Ischemia/Reperfusion-Induced Cardiac Injury in H9c2 Cells: Involvement of ROS, Hsp70, JNK and ERK, and Apoptosis
Molecules 2015, 20(3), 3758-3775; doi:10.3390/molecules20033758
Received: 20 December 2014 / Revised: 15 January 2015 / Accepted: 4 February 2015 / Published: 25 February 2015
Cited by 21 | PDF Full-text (598 KB) | HTML Full-text | XML Full-text
Abstract
Ischemia-Reperfusion (I/R) injury causes ROS overproduction, creating oxidative stress, and can trigger myocyte death, resulting in heart failure. Tyrosol is an antioxidant abounded in diets and medicine. Our objective was to investigate the protective effect of tyrosol on I/R-caused mortality in H9c2 cardiomyocytes
[...] Read more.
Ischemia-Reperfusion (I/R) injury causes ROS overproduction, creating oxidative stress, and can trigger myocyte death, resulting in heart failure. Tyrosol is an antioxidant abounded in diets and medicine. Our objective was to investigate the protective effect of tyrosol on I/R-caused mortality in H9c2 cardiomyocytes through its influence on ROS, Hsp70, ERK, JNK, Bcl-2, Bax and caspase-8. A simulated I/R model was used, myocytes loss was examined by MTT, and ROS levels were measured using DCFH-DA. Nuclear condensation and caspase-3 activity were assessed by DAPI staining and fluorometric assay. Phosphorylated ERK and JNK were determined by electrochemiluminescent ELISA, and Hsp70, Bcl-2, Bax and caspase-8 were examined by Western blotting. Results show that tyrosol salvaged myocyte loss, inhibited nuclear condensation and caspase-3 activity dose-dependently, indicating its protection against I/R-caused myocyte loss. Furthermore, tyrosol significantly inhibited ROS accumulation and activation of ERK and JNK, augmenting Hsp70 expression. Besides, tyrosol inhibited I/R-induced apoptosis, associated with retained anti-apoptotic Bcl-2 protein, and attenuated pro-apoptotic Bax protein, resulting in a preservation of Bcl-2/Bax ratio. Finally, tyrosol notably decreased cleaved caspase-8 levels. In conclusion, cytoprotection of tyrosol in I/R-caused myocyte mortality was involved with the mitigation of ROS, prohibition of the activation of ERK, JNK and caspase-8, and elevation of Hsp70 and Bcl-2/Bax ratio. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Targeting the Cryptococcus neoformans var. grubii Cell Wall Using Lectins: Study of the Carbohydrate-Binding Domain
Molecules 2015, 20(3), 3776-3782; doi:10.3390/molecules20033776
Received: 15 November 2014 / Revised: 9 January 2015 / Accepted: 16 January 2015 / Published: 25 February 2015
PDF Full-text (806 KB) | HTML Full-text | XML Full-text
Abstract
Cryptococcus neoformans var. grubii is considered to be the major cause of cryptococcosis in immunosuppressed patients. Understanding cell wall glycoproteins using lectins is of medical interest and can contribute to specific therapy. The aim of this study was to evaluate the carbohydrates on
[...] Read more.
Cryptococcus neoformans var. grubii is considered to be the major cause of cryptococcosis in immunosuppressed patients. Understanding cell wall glycoproteins using lectins is of medical interest and can contribute to specific therapy. The aim of this study was to evaluate the carbohydrates on the cell wall of Cryptococcus neoformans var. grubii clinical isolates, using a fluorescein isothiocyanate-lectin binding protocol. Thirty yeast strains stocked in the culture collection were cultivated for 2 days at 30 °C with shaking. Cells were obtained by centrifugation, washed in phosphate-buffered saline, and a suspension of 107 cells/mL was obtained. To determine the binding profile of lectins, concanavalin A (Con A), wheat germ agglutinin (WGA), Ulex europaeus agglutinin I (UEA-I), and peanut agglutinin (PNA) conjugated to fluorescein were used. All the tested clinical isolates of Cryptococcus neoformans var. grubii were intensely stained by WGA, moderately stained by Con A, and weakly stained by PNA and UEA-I. Thus, Cryptococcus can be detected in clinical specimens such as blood and cerebrospinal fluid using the fluorescent lectin WGA, which may be considered as an option for detection in cases of suspected cryptococcosis with low laboratory sensitivity. Future applications may be developed using this basic tool. Full article
(This article belongs to the Special Issue Lectins)
Open AccessArticle Inorganic Mercury Sequestration by a Poly(ethylene imine) Dendrimer in Aqueous Solution
Molecules 2015, 20(3), 3783-3790; doi:10.3390/molecules20033783
Received: 26 January 2015 / Revised: 12 February 2015 / Accepted: 15 February 2015 / Published: 26 February 2015
Cited by 2 | PDF Full-text (911 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The interaction of the G-2 poly(ethylene imine) dendrimer L, derived from ammonia as initiating core, with Hg(II) and HgCl42− was studied in aqueous solution by means of potentiometric (pH-metric) measurements. Speciation of these complex systems showed that L is able to
[...] Read more.
The interaction of the G-2 poly(ethylene imine) dendrimer L, derived from ammonia as initiating core, with Hg(II) and HgCl42− was studied in aqueous solution by means of potentiometric (pH-metric) measurements. Speciation of these complex systems showed that L is able to form a wide variety of complexes including 1:1, 2:1, 3:1 and 3:2 metal-to-ligand species, of different protonation states, as well as the anion complexes [(H7L)HgCl4]5+ and [(H8L)HgCl4]6+. The stability of the metal complexes is very high, making L an excellent sequestering agent for Hg(II), over a large pH range, and a promising ligand for the preparation of functionalized activated carbons to be employed in the remediation and the prevention of environmental problems. Full article
Open AccessArticle An Efficient Synthesis of 3,4-Dihydropyrimidin-2(1H)-Ones and Thiones Catalyzed by a Novel Brønsted Acidic Ionic Liquid under Solvent-Free Conditions
Molecules 2015, 20(3), 3811-3820; doi:10.3390/molecules20033811
Received: 24 November 2014 / Revised: 15 February 2015 / Accepted: 17 February 2015 / Published: 26 February 2015
Cited by 11 | PDF Full-text (412 KB) | HTML Full-text | XML Full-text
Abstract
We report here an efficient and green method for Biginelli condensation reaction of aldehydes, β-ketoesters and urea or thiourea catalyzed by Brønsted acidic ionic liquid [Btto][p-TSA] under solvent-free conditions. Compared to the classical Biginelli reaction conditions, the present method has the
[...] Read more.
We report here an efficient and green method for Biginelli condensation reaction of aldehydes, β-ketoesters and urea or thiourea catalyzed by Brønsted acidic ionic liquid [Btto][p-TSA] under solvent-free conditions. Compared to the classical Biginelli reaction conditions, the present method has the advantages of giving good yields, short reaction times, near room temperature conditions and the avoidance of the use of organic solvents and metal catalyst. Full article
(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)
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Open AccessArticle Synthesis, Central Nervous System Activity and Structure-Activity Relationships of Novel 1-(1-Alkyl-4-aryl-4,5-dihydro-1H-imidazo)-3-substituted Urea Derivatives
Molecules 2015, 20(3), 3821-3840; doi:10.3390/molecules20033821
Received: 27 December 2014 / Revised: 21 January 2015 / Accepted: 9 February 2015 / Published: 26 February 2015
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Abstract
A series of 10 novel urea derivatives has been synthesized and evaluated for their central nervous system activity. Compounds 3a3h were prepared in the reaction between the respective 1-alkyl-4-aryl-4,5-dihydro-1H-imidazol-2-amines 1a and 1b and appropriate benzyl-, phenethyl-isocyanate or ethyl 4-isocyanatobenzoate
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A series of 10 novel urea derivatives has been synthesized and evaluated for their central nervous system activity. Compounds 3a3h were prepared in the reaction between the respective 1-alkyl-4-aryl-4,5-dihydro-1H-imidazol-2-amines 1a and 1b and appropriate benzyl-, phenethyl-isocyanate or ethyl 4-isocyanatobenzoate and ethyl isocyanatoacetate 2 in dichloromethane. Derivatives 4c and 4g resulted from the conversion of 3c and 3g into the respective amides due to action of an aqueous ammonia solution. The results obtained in this study, based on literature data suggest a possible involvement of serotonin system and/or the opioid system in the effects of tested compounds, and especially in the effect of compound 3h. The best activity of compound 3h may be primarily attributed to its favourable ADMET properties, i.e., higher lipophilicity (related to lower polar surface area and greater molecular surface, volume and mass than for other compounds) and good blood-brain permeation. This compound has also the greatest polarizability and ovality. The HOMO and LUMO energies do not seem to be directly related to activity. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Anti-Tumor Activity of a Polysaccharide from Blueberry
Molecules 2015, 20(3), 3841-3853; doi:10.3390/molecules20033841
Received: 20 January 2015 / Revised: 16 February 2015 / Accepted: 16 February 2015 / Published: 27 February 2015
Cited by 7 | PDF Full-text (721 KB) | HTML Full-text | XML Full-text
Abstract
Blueberries (Vaccinium spp.) are rich in bioactive compounds. However, the biological activity of polysaccharides from blueberry has not been reported so far. This study evaluated the anti-tumor and immunological activities of a polysaccharide (BBP3-1) from blueberry in S180-bearing mice. The
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Blueberries (Vaccinium spp.) are rich in bioactive compounds. However, the biological activity of polysaccharides from blueberry has not been reported so far. This study evaluated the anti-tumor and immunological activities of a polysaccharide (BBP3-1) from blueberry in S180-bearing mice. The experimental results indicated that BBP3-1 (100 mg·kg−1·d−1) inhibited the tumor growth rate by 73.4%. Moreover, this group, compared with the model control, had shown an effect of increasing both the spleen and thymus indices (p < 0.05), increasing phagocytosis by macrophages (p < 0.05), boosting the proliferation and transformation of lymphocytes (p < 0.01), promoting the secretion of TNF-α, IFN-γ, and IL-2 (p < 0.05) and improving NK cell activity (p < 0.01). From this study, we could easily conclude that BBP3-1 has the ability to inhibit tumor progression and could act as a good immunomodulator. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis, Larvicidal Activities and Antifungal Activities of Novel Chlorantraniliprole Derivatives and Their Target in the Ryanodine Receptor
Molecules 2015, 20(3), 3854-3867; doi:10.3390/molecules20033854
Received: 21 January 2015 / Revised: 15 February 2015 / Accepted: 24 February 2015 / Published: 2 March 2015
Cited by 4 | PDF Full-text (852 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In order to identify novel chlorantraniliprole derivatives as potential insecticides or fungicides, 25 analogues of chlorantraniliprole were synthesized. The insecticidal activities against oriental armyworm and the antifungal activities against five typical fungi of these derivatives were tested. Compounds 2u, 2x and 2y
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In order to identify novel chlorantraniliprole derivatives as potential insecticides or fungicides, 25 analogues of chlorantraniliprole were synthesized. The insecticidal activities against oriental armyworm and the antifungal activities against five typical fungi of these derivatives were tested. Compounds 2u, 2x and 2y exhibited good activities against oriental armyworm, especially compounds 2u and 2x which showed higher larvicidal activities than indoxacarb. Moreover, all of the tested compounds exhibited activities against five typical fungi. The Ki values of all synthesized compounds were calculated using AutoDock4. The relationship between the Ki values and the results of insecticidal activities against oriental armyworm further indicated that the membrane-spanning domain protein of the ryanodine receptor might contain chlorantraniliprole binding sites. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Exploring the Effects of Pulsed Electric Field Processing Parameters on Polyacetylene Extraction from Carrot Slices
Molecules 2015, 20(3), 3942-3954; doi:10.3390/molecules20033942
Received: 14 January 2015 / Revised: 17 February 2015 / Accepted: 25 February 2015 / Published: 2 March 2015
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Abstract
The effects of various pulsed electric field (PEF) parameters on the extraction of polyacetylenes from carrot slices were investigated. Optimised conditions with regard to electric field strength (1–4 kV/cm), number of pulses (100–1500), pulse frequency (10–200 Hz) and pulse width (10–30 μs) were
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The effects of various pulsed electric field (PEF) parameters on the extraction of polyacetylenes from carrot slices were investigated. Optimised conditions with regard to electric field strength (1–4 kV/cm), number of pulses (100–1500), pulse frequency (10–200 Hz) and pulse width (10–30 μs) were identified using response surface methodology (RSM) to maximise the extraction of falcarinol (FaOH), falcarindiol (FaDOH) and falcarindiol-3-acetate (FaDOAc) from carrot slices. Data obtained from RSM and experiments fitted significantly (p < 0.0001) the proposed second-order response functions with high regression coefficients (R2) ranging from 0.82 to 0.75. Maximal FaOH (188%), FaDOH (164.9%) and FaDOAc (166.8%) levels relative to untreated samples were obtained from carrot slices after applying PEF treatments at 4 kV/cm with 100 number of pulses of 10 μs at 10 Hz. The predicted values from the developed quadratic polynomial equation were in close agreement with the actual experimental values with low average mean deviations (E%) ranging from 0.68% to 3.58%. Full article
(This article belongs to the Special Issue New Technologies for the Recovery of Natural Products)
Open AccessArticle Metabolites Software-Assisted Flavonoid Hunting in Plants Using Ultra-High Performance Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometry
Molecules 2015, 20(3), 3955-3971; doi:10.3390/molecules20033955
Received: 31 January 2015 / Revised: 17 February 2015 / Accepted: 25 February 2015 / Published: 2 March 2015
Cited by 4 | PDF Full-text (1539 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Plant secondary metabolism drives the generation of metabolites used for host plant resistance, as biopesticides and botanicals, even for the discovery of new therapeutics for human diseases. Flavonoids are one of the largest and most studied classes of specialized plant metabolites. To quickly
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Plant secondary metabolism drives the generation of metabolites used for host plant resistance, as biopesticides and botanicals, even for the discovery of new therapeutics for human diseases. Flavonoids are one of the largest and most studied classes of specialized plant metabolites. To quickly identify the potential bioactive flavonoids in herbs, a metabolites software-assisted flavonoid hunting approach was developed, which mainly included three steps: firstly, utilizing commercial metabolite software, a flavonoids database was established based on the biosynthetic pathways; secondly, mass spectral data of components in herbs were acquired by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF-MS); and finally, the acquired LC-MS data were imported into the database and the compounds in the herbs were automatically identified by comparison of their mass spectra with the theoretical values. As a case study, the flavonoids in Smilax glabra were profiled using this approach. As a result, 104 flavonoids including 27 potential new compounds were identified. To our knowledge, this is the first report on profiling the components in the plants utilizing the plant metabolic principles with the assistance of metabolites software. This approach can be extended to the analysis of flavonoids in other plants. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle The Synthetic Antimicrobial Peptide Pexiganan and Its Nanoparticles (PNPs) Exhibit the Anti-Helicobacter pylori Activity in Vitro and in Vivo
Molecules 2015, 20(3), 3972-3985; doi:10.3390/molecules20033972
Received: 3 January 2015 / Revised: 25 February 2015 / Accepted: 26 February 2015 / Published: 2 March 2015
Cited by 7 | PDF Full-text (726 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to probe the potential anti-H. pylori activity of the synthetic antimicrobial peptide pexiganan, which is an analog of the peptide magainin, and its nanoparticles (PNPs) that were prepared in our laboratory. To compare their antibacterial effects
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The aim of this study was to probe the potential anti-H. pylori activity of the synthetic antimicrobial peptide pexiganan, which is an analog of the peptide magainin, and its nanoparticles (PNPs) that were prepared in our laboratory. To compare their antibacterial effects in vitro and in vivo, studies of H. pylori growth inhibition, kinetics and resistance assays were undertaken. The gastric mucoadhesive efficiency and H. pylori clearance efficiency of pexiganan and PNPs were evaluated in rats and mice infected with H. pylori. The eradication of H. pylori was determined using urease tests and a microbial culture method. We observed that PNPs adhered to gastric mucosa more effectively owing to a prolonged stay in the stomach, which resulted in a more effective H. pylori clearance. In addition, PNPs had greater anti-H. pylori effect than pexiganan in infected mice. The amount of pexiganan required to eradicate H. pylori was significantly less using PNPs than the corresponding pexiganan suspension. The results confirmed that PNPs improved peptide stability in the stomach and more effectively eradicated H. pylori from mice stomachs than pexiganan. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Volatile Compounds and Antioxidant Capacity of the Bio-Oil Obtained by Pyrolysis of Japanese Red Pine (Pinus Densiflora Siebold and Zucc.)
Molecules 2015, 20(3), 3986-4006; doi:10.3390/molecules20033986
Received: 16 January 2015 / Revised: 13 February 2015 / Accepted: 25 February 2015 / Published: 2 March 2015
Cited by 9 | PDF Full-text (1758 KB) | HTML Full-text | XML Full-text
Abstract
In the present study, sawdust bio-oil (SBO) manufactured by fast pyrolysis of Japanese red pine (Pinus densiflora Siebold and Zucc.) sawdust was analyzed for its volatile chemical compound composition and evaluated for its free radical scavenging potential, inhibition of lipid peroxidation and
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In the present study, sawdust bio-oil (SBO) manufactured by fast pyrolysis of Japanese red pine (Pinus densiflora Siebold and Zucc.) sawdust was analyzed for its volatile chemical compound composition and evaluated for its free radical scavenging potential, inhibition of lipid peroxidation and reducing power. Gas chromatography and mass spectroscopy revealed 29 volatile compounds, comprising 97.6% of the total volatile compounds in SBO. The antioxidant potential of SBO in terms of IC50 values was 48.44 µg/mL for hydroxyl radical scavenging, 89.52 µg/mL for 1,1-diphenyl-2-picrylhydraxyl radical scavenging, 94.23 µg/mL for 2,2'-azino-bis[3-ethylbenzothiazoline-6-sulphonic acid] radical scavenging, and 136.06 µg/mL for superoxide radical scavenging activity. The total phenol content in SBO was 5.7% gallic acid equivalent. Based on the composition of its volatile compounds, high free radical scavenging potential and antioxidant properties, SBO could be used as a source of antioxidant compounds, flavoring agents and nutraceuticals in the food, pharmaceutical, and cosmetic industries. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Image Monitoring of Pharmaceutical Blending Processes and the Determination of an End Point by Using a Portable Near-Infrared Imaging Device Based on a Polychromator-Type Near-Infrared Spectrometer with a High-speed and High-Resolution Photo Diode Array Detector
Molecules 2015, 20(3), 4007-4019; doi:10.3390/molecules20034007
Received: 15 January 2015 / Revised: 17 February 2015 / Accepted: 26 February 2015 / Published: 3 March 2015
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Abstract
In the present study we have developed a new version (ND-NIRs) of a polychromator-type near-infrared (NIR) spectrometer with a high-resolution photo diode array detector, which we built before (D-NIRs). The new version has four 5 W halogen lamps compared with the three lamps
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In the present study we have developed a new version (ND-NIRs) of a polychromator-type near-infrared (NIR) spectrometer with a high-resolution photo diode array detector, which we built before (D-NIRs). The new version has four 5 W halogen lamps compared with the three lamps for the older version. The new version also has a condenser lens with a shorter focal point length. The increase in the number of the lamps and the shortening of the focal point of the condenser lens realize high signal-to-noise ratio and high-speed NIR imaging measurement. By using the ND-NIRs we carried out the in-line monitoring of pharmaceutical blending and determined an end point of the blending process. Moreover, to determinate a more accurate end point, a NIR image of the blending sample was acquired by means of a portable NIR imaging device based on ND-NIRs. The imaging result has demonstrated that the mixing time of 8 min is enough for homogeneous mixing. In this way the present study has demonstrated that ND-NIRs and the imaging system based on a ND-NIRs hold considerable promise for process analysis. Full article
(This article belongs to the Special Issue Advances of Vibrational Spectroscopic Technologies in Life Sciences)
Open AccessArticle Hybridisation Potential of 1',3'-Di-O-methylaltropyranoside Nucleic Acids
Molecules 2015, 20(3), 4020-4041; doi:10.3390/molecules20034020
Received: 22 January 2015 / Revised: 16 February 2015 / Accepted: 24 February 2015 / Published: 3 March 2015
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Abstract
In further study of our series of six-membered ring-containing nucleic acids, different 1',3'-di-O-methyl altropyranoside nucleoside analogs (DMANA) were synthesized comprising all four base moieties, adenine, cytosine, uracil and guanine. Following assembly into oligonucleotides (ONs), their affinity for natural oligonucleotides was evaluated
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In further study of our series of six-membered ring-containing nucleic acids, different 1',3'-di-O-methyl altropyranoside nucleoside analogs (DMANA) were synthesized comprising all four base moieties, adenine, cytosine, uracil and guanine. Following assembly into oligonucleotides (ONs), their affinity for natural oligonucleotides was evaluated by thermal denaturation of the respective duplexes. Data were compared with results obtained previously for both anhydrohexitol (HNAs) and 3'-O-methylated altrohexitol modified ONs (MANAs). We hereby demonstrate that ONs modified with DMANA monomers, unlike some of our previously described analogues with constrained 6-membered hexitol rings, did not improve thermodynamic stability of dsRNA complexes, most probably in view of an energetic penalty when forced in the required 1C4 pairing conformation. Overall, a single incorporation was more or less tolerated or even positive for the adenine congener, but incorporation of a second modification afforded a slight destabilization (except for A), while a fully modified sequence displayed a thermal stability of −0.3 °C per modification. The selectivity of pairing remained very high, and the new modification upon incorporation into a DNA strand, strongly destabilized the corresponding DNA duplexes. Unfortunately, this new modification does not bring any advantage to be further evaluated for antisense or siRNA applications. Full article
(This article belongs to the Special Issue Nucleoside Modifications) Printed Edition available
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Open AccessArticle Theoretical and Experimental Electrostatic Potential around the m-Nitrophenol Molecule
Molecules 2015, 20(3), 4042-4054; doi:10.3390/molecules20034042
Received: 22 December 2014 / Revised: 25 February 2015 / Accepted: 25 February 2015 / Published: 3 March 2015
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Abstract
This work concerns a comparison of experimental and theoretical results of the electron charge density distribution and the electrostatic potential around the m-nitrophenol molecule (m-NPH) known for its interesting physical characteristics. The molecular experimental results have been obtained from a high-resolution X-ray
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This work concerns a comparison of experimental and theoretical results of the electron charge density distribution and the electrostatic potential around the m-nitrophenol molecule (m-NPH) known for its interesting physical characteristics. The molecular experimental results have been obtained from a high-resolution X-ray diffraction study. Theoretical investigations were performed using the Density Functional Theory at B3LYP level of theory at 6-31G* in the Gaussian program. The multipolar model of Hansen and Coppens was used for the experimental electron charge density distribution around the molecule, while we used the DFT methods for the theoretical calculations. The electron charge density obtained in both methods allowed us to find out different molecular properties such us the electrostatic potential and the dipole moment, which were finally subject to a comparison leading to a good match obtained between both methods. The intramolecular charge transfer has also been confirmed by an HOMO-LUMO analysis. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle In Situ EPR Studies of Reaction Pathways in Titania Photocatalyst-Promoted Alkylation of Alkenes
Molecules 2015, 20(3), 4055-4070; doi:10.3390/molecules20034055
Received: 15 January 2015 / Revised: 17 February 2015 / Accepted: 26 February 2015 / Published: 3 March 2015
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Abstract
In situ EPR spectroscopy at cryogenic temperatures has been used to observe and identify paramagnetic species produced when titania is irradiated in the presence of reactants used in the photocatalytic alkylation of maleimide with t-butyl carboxylic acid or phenoxyacetic acid. It is shown
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In situ EPR spectroscopy at cryogenic temperatures has been used to observe and identify paramagnetic species produced when titania is irradiated in the presence of reactants used in the photocatalytic alkylation of maleimide with t-butyl carboxylic acid or phenoxyacetic acid. It is shown that maleimide acts as an acceptor of conduction band electrons. Valence band holes oxidise t-butyl carboxylic acid to the t-butyl radical and phenoxyacetic acid to the phenoxyacetic acid radical cation. In the presence of maleimide, the phenoxymethyl radical is formed from phenoxyacetic acid. The relevance of these observations to the mechanisms of titania photocatalyst-promoted alkylation of alkenes is discussed. Full article
(This article belongs to the Special Issue Free Radicals and Radical Ions)
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Open AccessArticle Synthesis, Antifungal Activity and QSAR of Some Novel Carboxylic Acid Amides
Molecules 2015, 20(3), 4071-4087; doi:10.3390/molecules20034071
Received: 31 December 2014 / Revised: 28 February 2015 / Accepted: 2 March 2015 / Published: 4 March 2015
Cited by 3 | PDF Full-text (2825 KB) | HTML Full-text | XML Full-text
Abstract
A series of novel aromatic carboxylic acid amides were synthesized and tested for their activities against six phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to good activity. Among them N-(2-(1H-indazol-1-yl)phenyl)-2-(trifluoromethyl)benzamide (3c
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A series of novel aromatic carboxylic acid amides were synthesized and tested for their activities against six phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to good activity. Among them N-(2-(1H-indazol-1-yl)phenyl)-2-(trifluoromethyl)benzamide (3c) exhibited the highest antifungal activity against Pythium aphanidermatum (EC50 = 16.75 µg/mL) and Rhizoctonia solani (EC50 = 19.19 µg/mL), compared to the reference compound boscalid with EC50 values of 10.68 and 14.47 µg/mL, respectively. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were employed to develop a three-dimensional quantitative structure-activity relationship model for the activity of the compounds. In the molecular docking, a fluorine atom and the carbonyl oxygen atom of 3c formed hydrogen bonds toward the hydroxyl hydrogens of TYR58 and TRP173. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Nitric Oxide Released from Luminal S-Nitroso-N-Acetylcysteine Increases Gastric Mucosal Blood Flow
Molecules 2015, 20(3), 4109-4123; doi:10.3390/molecules20034109
Received: 22 December 2014 / Revised: 18 February 2015 / Accepted: 26 February 2015 / Published: 4 March 2015
Cited by 4 | PDF Full-text (1216 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nitric oxide (NO)-mediated vasodilation plays a key role in gastric mucosal defense, and NO-donor drugs may protect against diseases associated with gastric mucosal blood flow (GMBF) deficiencies. In this study, we used the ex vivo gastric chamber method and Laser Doppler Flowmetry to
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Nitric oxide (NO)-mediated vasodilation plays a key role in gastric mucosal defense, and NO-donor drugs may protect against diseases associated with gastric mucosal blood flow (GMBF) deficiencies. In this study, we used the ex vivo gastric chamber method and Laser Doppler Flowmetry to characterize the effects of luminal aqueous NO-donor drug S-nitroso-N-acetylcysteine (SNAC) solution administration compared to aqueous NaNO2 and NaNO3 solutions (pH 7.4) on GMBF in Sprague-Dawley rats. SNAC solutions (600 μM and 12 mM) led to a rapid threefold increase in GMBF, which was maintained during the incubation of the solutions with the gastric mucosa, while NaNO2 or NaNO3 solutions (12 mM) did not affect GMBF. SNAC solutions (600 μM and 12 mM) spontaneously released NO at 37 °C at a constant rate of 0.3 or 14 nmol·mL−1·min−1, respectively, while NaNO2 (12 mM) released NO at a rate of 0.06 nmol·mL−1·min−1 and NaNO3 (12 mM) did not release NO. These results suggest that the SNAC-induced GMBF increase is due to their higher rates of spontaneous NO release compared to equimolar NaNO2 solutions. Taken together, our data indicate that oral SNAC administration is a potential approach for gastric acid-peptic disorder prevention and treatment. Full article
(This article belongs to the Special Issue Nitric Oxide (NO) Release Chemistry)
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Open AccessArticle Carbopol-Incorporated Thermoreversible Gel for Intranasal Drug Delivery
Molecules 2015, 20(3), 4124-4135; doi:10.3390/molecules20034124
Received: 21 January 2015 / Revised: 27 February 2015 / Accepted: 2 March 2015 / Published: 4 March 2015
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Abstract
The present study describes the preparation and evaluation of a poloxamer 407 (P407)-based thermoreversible gel using Carbopol 934P (C934P) as a mucoadhesive polymer and hydroxypropyl-β-cyclodextrin (HP-β-CD) for enhancing the aqueous solubility and intranasal absorption of fexofenadine hydrochloride (FXD HCl). The prepared gels were
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The present study describes the preparation and evaluation of a poloxamer 407 (P407)-based thermoreversible gel using Carbopol 934P (C934P) as a mucoadhesive polymer and hydroxypropyl-β-cyclodextrin (HP-β-CD) for enhancing the aqueous solubility and intranasal absorption of fexofenadine hydrochloride (FXD HCl). The prepared gels were characterized by gelation temperature, viscoelasticity, and drug release profile. Thermoreversibility of P407/C934P gel was demonstrated by rheological studies. The incorporation of carbopol into P407 gel also reduced the amounts of drug released from the gel formulations (p < 0.05). In vivo pharmacokinetic results of the prepared gel formulations in rabbits (at 0.5 mg/kg dose) showed that the relative bioavailability of drug from P407/C934P gel was 11.3 and 2.7-fold higher than those of drug solution and P407 gel group, respectively. These findings suggested that developed thermoreversible gels could be used as promising dosage forms to improve intranasal drug absorption. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle DNA-Catalyzed Henry Reaction in Pure Water and the Striking Influence of Organic Buffer Systems
Molecules 2015, 20(3), 4136-4147; doi:10.3390/molecules20034136
Received: 5 February 2015 / Revised: 18 February 2015 / Accepted: 27 February 2015 / Published: 4 March 2015
Cited by 2 | PDF Full-text (1375 KB) | HTML Full-text | XML Full-text
Abstract
In this manuscript we report a critical evaluation of the ability of natural DNA to mediate the nitroaldol (Henry) reaction at physiological temperature in pure water. Under these conditions, no background reaction took place (i.e., control experiment without DNA). Both heteroaromatic
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In this manuscript we report a critical evaluation of the ability of natural DNA to mediate the nitroaldol (Henry) reaction at physiological temperature in pure water. Under these conditions, no background reaction took place (i.e., control experiment without DNA). Both heteroaromatic aldehydes (e.g., 2-pyridinecarboxaldehyde) and aromatic aldehydes bearing strong or moderate electron-withdrawing groups reacted satisfactorily with nitromethane obeying first order kinetics and affording the corresponding β-nitroalcohols in good yields within 24 h. In contrast, aliphatic aldehydes and aromatic aldehydes having electron-donating groups either did not react or were poorly converted. Moreover, we discovered that a number of metal-free organic buffers efficiently promote the Henry reaction when they were used as reaction media without adding external catalysts. This constitutes an important observation because the influence of organic buffers in chemical processes has been traditionally underestimated. Full article
(This article belongs to the collection Recent Advances in Organocatalysis)
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Open AccessArticle Tethering in RNA: An RNA-Binding Fragment Discovery Tool
Molecules 2015, 20(3), 4148-4161; doi:10.3390/molecules20034148
Received: 5 December 2014 / Revised: 20 January 2015 / Accepted: 17 February 2015 / Published: 4 March 2015
PDF Full-text (3613 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Tethering has been extensively used to study small molecule interactions with proteins through reversible disulfide bond forming reactions to cysteine residues. We describe the adaptation of Tethering to the study of small molecule binding to RNA using a thiol-containing adenosine analog (ASH
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Tethering has been extensively used to study small molecule interactions with proteins through reversible disulfide bond forming reactions to cysteine residues. We describe the adaptation of Tethering to the study of small molecule binding to RNA using a thiol-containing adenosine analog (ASH). Among 30 disulfide-containing small molecules screened for efficient Tethering to ASH-bearing RNAs derived from pre-miR21, a benzotriazole-containing compound showed prominent adduct formation and selectivity for one of the RNAs tested. The results of this screen demonstrate the viability of using thiol-modified nucleic acids to discover molecules with binding affinity and specificity for the purpose of therapeutic compound lead discovery. Full article
(This article belongs to the Special Issue Nucleoside Modifications) Printed Edition available
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Open AccessArticle Chemical Constituents and Structural Characterization of Polysaccharides from Four Typical Bamboo Species Leaves
Molecules 2015, 20(3), 4162-4179; doi:10.3390/molecules20034162
Received: 1 December 2014 / Revised: 14 January 2015 / Accepted: 12 February 2015 / Published: 5 March 2015
Cited by 4 | PDF Full-text (815 KB) | HTML Full-text | XML Full-text
Abstract
In order to find bamboo leaves with high contents of bioactive polysaccharides, 32 samples were chosen to analyze their polysaccharide content by GC and sulfuric acid-anthrone colorimetric assays. Purified polysaccharides (BLPS) were separated from the four varieties P. nigra (Lodd.) Munro (PN), P.
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In order to find bamboo leaves with high contents of bioactive polysaccharides, 32 samples were chosen to analyze their polysaccharide content by GC and sulfuric acid-anthrone colorimetric assays. Purified polysaccharides (BLPS) were separated from the four varieties P. nigra (Lodd.) Munro (PN), P. vivax McClure (PV), Chimonobambusa quadrangularis (Fenzi) Makino (CQ), and P. bambussoides cv. Tanakae (PB) by ultrasound extraction, solution precipitation, ion exchange resin, DEAE-52 and Sephadex G-100 chromatography. BLPS structural characterization was accomplished by HPLC-GPC, Fourier transform infra-red spectroscopy (FTIR) and NaIO4-HIO4 oxidation reactions. The results showed that the total polysaccharides of the bamboo leaves in samples 1–32 ranged between 1.4% and 5.4%, Samples No. 29–No. 32 (PN, PV, CQ, and PB) contained 2–3 fold more polysaccharides than No. 1~No. 28 among the 32 different species, particularly the content of galactose was in a range of 21.5%–34.1% for these four typical bamboo species leaves, which was also more than 2–3 fold higher than in No. 1–No. 28. Sugar analysis indicated that PN-PBLPS-1, PV-PBLPS-1, CQ-PBLPS-1 and PB-PBLPS-1 from the four varieties were homogeneous polysaccharides with molecular weights of 2.04 × 104, 1.15 × 104, 8.75 × 104 and 1.48 × 104 Da, respectively. PB-PBLPS-1 was a mixture of α-galactopyranose and β-d-glucopyranose linkages with α-(1→6) or β-(1→6)glycosidic bonds, while PN-PBLPS-1, PV-PBLPS-1, and CQ-PBLPS-1 had α galactopyranose linkages with α-(1→6) glycosidic bonds. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Assessing Chemical Constituents of Mimosa caesalpiniifolia Stem Bark: Possible Bioactive Components Accountable for the Cytotoxic Effect of M. caesalpiniifolia on Human Tumour Cell Lines
Molecules 2015, 20(3), 4204-4224; doi:10.3390/molecules20034204
Received: 21 November 2014 / Revised: 4 January 2015 / Accepted: 26 January 2015 / Published: 5 March 2015
Cited by 6 | PDF Full-text (783 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mimosa caesalpiniifolia is a native plant of the Brazilian northeast, and few studies have investigated its chemical composition and biological significance. This work describes the identification of the first chemical constituents in the ethanolic extract and fractions of M. caesalpiniifolia stem bark based
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Mimosa caesalpiniifolia is a native plant of the Brazilian northeast, and few studies have investigated its chemical composition and biological significance. This work describes the identification of the first chemical constituents in the ethanolic extract and fractions of M. caesalpiniifolia stem bark based on NMR, GC-qMS and HRMS analyses, as well as an assessment of their cytotoxic activity. GC-qMS analysis showed fatty acid derivatives, triterpenes and steroid substances and confirmed the identity of the chemical compounds isolated from the hexane fraction. Metabolite biodiversity in M. caesalpiniifolia stem bark revealed the differentiated accumulation of pentacyclic triterpenic acids, with a high content of betulinic acid and minor amounts of 3-oxo and 3β-acetoxy derivatives. Bioactive analysis based on total phenolic and flavonoid content showed a high amount of these compounds in the ethanolic extract, and ESI-(−)-LTQ-Orbitrap-MS identified caffeoyl hexose at high intensity, as well as the presence of phenolic acids and flavonoids. Furthermore, the evaluation of the ethanolic extract and fractions, including betulinic acid, against colon (HCT-116), ovarian (OVCAR-8) and glioblastoma (SF-295) tumour cell lines showed that the crude extract, hexane and dichloromethane fractions possessed moderate to high inhibitory activity, which may be related to the abundance of betulinic acid. The phytochemical and biological study of M. caesalpiniifolia stem bark thus revealed a new alternative source of antitumour compounds, possibly made effective by the presence of betulinic acid and by chemical co-synergism with other compounds. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Pharmacokinetics and Tissue Distribution Study of Caudatin in Normal and Diethylnitrosamine-Induced Hepatocellular Carcinoma Model Rats
Molecules 2015, 20(3), 4225-4237; doi:10.3390/molecules20034225
Received: 17 November 2014 / Revised: 15 February 2015 / Accepted: 26 February 2015 / Published: 5 March 2015
Cited by 3 | PDF Full-text (1572 KB) | HTML Full-text | XML Full-text
Abstract
Caudatin is a potential antitumor agent isolated from the traditional Chinese medicine “baishouwu”, which was the root tuber of Cynanchum auriculatum Royle ex Wight. In our previous studies, caudatin showed selectivity on human hepatoma cell line SMMC7721 among several different tumor
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Caudatin is a potential antitumor agent isolated from the traditional Chinese medicine “baishouwu”, which was the root tuber of Cynanchum auriculatum Royle ex Wight. In our previous studies, caudatin showed selectivity on human hepatoma cell line SMMC7721 among several different tumor cell lines, and further in vivo tests validated the inhibitory action of caudatin against hepatic cancer using an H22 solid tumor model in mice, but to our knowledge, the biopharmaceutical properties of caudatin are largely unknown. In this study, a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of caudatin in rat plasma and tissues, which kept the run time to detect one sample within 4 min, was developed and validated. Pharmacokinetics and tissue distribution studies of caudatin in conventional rats and hepatocellular carcinoma (HCC) model rats were then conducted for the first time. Statistically significant differences were observed between conventional rats and diethylnitrosamine (DEN)-induced HCC rats with respect to pharmacokinetic parameters, including maximum concentration (Cmax), time to reach Cmax (Tmax), half-life (t1/2), area under the concentration-time curve (AUC0-t, AUC0-∞), mean residence time (MRT0-t and MRT0-∞), and oral clearance (CL/F). Increased exposures of caudatin were found in the plasma and livers of HCC model rats, which would be helpful for a better understanding of pharmacological effect of caudatin in treating HCC disease. Full article
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Open AccessArticle A Novel and Effective Chromatographic Approach to the Separation of Isoflavone Derivatives from Pueraria lobata
Molecules 2015, 20(3), 4238-4253; doi:10.3390/molecules20034238
Received: 24 November 2014 / Revised: 13 February 2015 / Accepted: 16 February 2015 / Published: 5 March 2015
Cited by 1 | PDF Full-text (2043 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A novel and effective chromatographic approach to the separation and purification of isoflavone compounds from Pueraria lobata is described. The method is based on flash chromatography (FC), coupled to preparative high performance liquid chromatography (prep-HPLC) via a six-way valve. The FC step comprised
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A novel and effective chromatographic approach to the separation and purification of isoflavone compounds from Pueraria lobata is described. The method is based on flash chromatography (FC), coupled to preparative high performance liquid chromatography (prep-HPLC) via a six-way valve. The FC step comprised tandem reversed phase columns, pre-packed with MCI gel (Mitsubishi Chemical Corp., Tokyo, Japan) and C18 (Fuji Silysia Chemical Ltd, Osaka, Japan) resin, respectively, and was designed to separate a crude Pueraria lobata extract into several preliminary fractions. Fractions containing the target compounds were then directly injected via the six-way valve into prep-HPLC columns, without further treatment, for final isolation and purification. Nine isoflavonoids were successfully isolated, three through an online mode and the other six through an offline mode. The purities of all compounds exceeded 95.0%, as determined by HPLC with an UV-vis photodiode array detector. The convenience, low solvent consumption, and time-saving advantages of this method offer an attractive and promising approach to the isolation of natural products. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Screening Antitumor Bioactive Fraction from Sauromatum giganteum (Engl.) Cusimano & Hett and Sensitive Cell Lines with the Serum Pharmacology Method and Identification by UPLC-TOF-MS
Molecules 2015, 20(3), 4290-4306; doi:10.3390/molecules20034290
Received: 21 November 2014 / Revised: 9 December 2014 / Accepted: 12 February 2015 / Published: 6 March 2015
Cited by 4 | PDF Full-text (745 KB) | HTML Full-text | XML Full-text
Abstract
Sauromatum giganteum (Engl.) Cusimano & Hett Tuber are used in Chinese folklore medicine for treatment of neoplasms. However, the claim has not been scientifically validated. The aim of the study is to screen the antitumor bioactive fraction of Sauromatum giganteum (Engl.) Cusimano &
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Sauromatum giganteum (Engl.) Cusimano & Hett Tuber are used in Chinese folklore medicine for treatment of neoplasms. However, the claim has not been scientifically validated. The aim of the study is to screen the antitumor bioactive fraction of Sauromatum giganteum (Engl.) Cusimano & Hett Tuber and sensitive tumor cell lines using a cytotoxicity assay in vitro and tumor transplantation method in vivo, to support its use in folk medicine. The petroleum ether fraction, chloroform fraction, ethyl acetate fraction, n-butanol fraction and water fraction were successively extracted by turn by the maceration under reflux assay. Screening of antitumor bioactive fraction and sensitive cell lines were measured by MTT assay and the serum pharmacology method, and in vivo the antitumor activities of the active fraction was evaluated by using S180 or H22 tumor-bearing mice model and Kunming mice. The active constituents of ethyl acetate fraction of Sauromatum giganteum (Engl.) Cusimano & Hett were characterized by UPLC-TOF-MS. Compared with control groups, mice serum containing ethyl acetate fraction had a inhibition effect on SMMC-7721 cell, SGC-7901 cell, MCF-7 cell, HeLa cell, A549 cell, HT-29, and MDA-MB-231, respectively, but mice serum containing other four fractions had no different with that of control group. The inhibition capabilities of mice serum containing ethyl acetate fraction on the seven cell lines in descending order is SGC-7901 > SMMC-7721 > MCF-7 > HT-29 > A549 > HeLa > MDA-MB-231. In vivo the inhibition rate of 106, 318, 954 mg/kg·d ethyl acetate fraction dry extract to sarcoma S180 is 15.22%, 26.15% and 40.24%, respectively, and life prolonging rate to hepatoma H22 is 33.61%, 40.16% and 55.74%. A total of 14 compounds were identified in the ethyl acetate fraction of Sauromatum giganteum (Engl.) Cusimano & Hett. The results of the experimental studies proved the antitumor activity of Sauromatum giganteum (Engl.) Cusimano & Hett and supported the traditional use of this plant. These data indicate the potential for the use of ethyl acetate fraction of Sauromatum giganteum (Engl.) Cusimano & Hett Tuber in tumor therapy, anti-tumor activity on cancer cell line in descending order is SGC-7901 > SMMC-7721 > MCF-7 > HT-29 > A549 > HeLa > MDA-MB-231. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication New Synthesis Method for Sultone Derivatives: Synthesis, Crystal Structure and Biological Evaluation of S-CA
Molecules 2015, 20(3), 4307-4318; doi:10.3390/molecules20034307
Received: 25 January 2015 / Revised: 26 February 2015 / Accepted: 27 February 2015 / Published: 6 March 2015
Cited by 4 | PDF Full-text (1525 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
There has been no remarkable progress in the synthesis of sultones in recent years. To facilitate more detailed studies of this functional group, we found a new method to synthesize the sulfonic acid lactone derivatives and finish its ring-closing reaction. A new sultone
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There has been no remarkable progress in the synthesis of sultones in recent years. To facilitate more detailed studies of this functional group, we found a new method to synthesize the sulfonic acid lactone derivatives and finish its ring-closing reaction. A new sultone derivative, (E)-ethyl 4-oxo-6-styryl-3,4-dihydro-1,2-oxathiine-5-carboxylate 2,2-dioxide (S-CA), was synthesized and structurally identified by 1H-NMR, 13C-NMR, HMQC and X-ray single crystal diffraction analysis. The new rapid synthesis extended the method of ring-closing reaction of sulfonic acid lactone derivatives. The angiogenesis activities of S-CA were evaluated by the chick chorioallantoic membrane (CAM) model. It could selectively suppress small angiogenesis in CAM, without influencing either middle and large angiogenesis. In addition, anticancer efficacy of S-CA was evaluated in vivo using a murine sarcoma S180 model. Reduction of the tumor weight and tumor HE staining regions demonstrated that S-CA (10 mg/kg, intraperitoneal injection) had potent inhibition effects and a 44.71% inhibitory rate in S180 mice. Moreover, an acute toxicity test showed that the LD50 value of S-CA via intraperitoneal injection was 25.624 mg/kg. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle LC-ESI-MS/MS Analysis and Pharmacokinetics of GP205, an Innovative Potent Macrocyclic Inhibitor of Hepatitis C Virus NS3/4A Protease in Rats
Molecules 2015, 20(3), 4319-4336; doi:10.3390/molecules20034319
Received: 7 December 2014 / Revised: 12 February 2015 / Accepted: 25 February 2015 / Published: 6 March 2015
Cited by 2 | PDF Full-text (1142 KB) | HTML Full-text | XML Full-text
Abstract
A high-throughput, sensitive and specific LC-ESI-MS/MS method was established for the quantitative determination of GP205, a potent inhibitor of hepatitis C virus NS3/4A protease, in rat. The analyte was isolated from 25 μL plasma sample by 96-well LLE. Good linearity was achieved within
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A high-throughput, sensitive and specific LC-ESI-MS/MS method was established for the quantitative determination of GP205, a potent inhibitor of hepatitis C virus NS3/4A protease, in rat. The analyte was isolated from 25 μL plasma sample by 96-well LLE. Good linearity was achieved within the concentration range of 2–5000 ng/mL (r2 > 0.996). The intra- and inter-day precision was less than 10%. The accuracy ranged from 0.8% to 5.5% for GP205 in quality control samples at three levels. GP205 was stable during the analysis and the storage period. The method was successfully applied to pharmacokinetic studies of GP205 in Sprague-Dawley rats. The pharmacokinetic profiles of GP205 at three dose levels with oral administration and one dose level with intravenous administration were successfully studied for the first time in SD rats, respectively. After single oral administration of GP205 at the doses of 2.5, 5, 10 mg/kg, respectively, Cmax and AUC0-τ were proportional to the doses given. The absolute bioavailability was estimated as 34% based on the AUCs of oral administration at the dose of 5 mg/kg and intravenous administration at the dose of 1 mg/kg. The data presented in this study provides useful information for further study for GP205. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Bioavailability Enhancement of Paclitaxel via a Novel Oral Drug Delivery System: Paclitaxel-Loaded Glycyrrhizic Acid Micelles
Molecules 2015, 20(3), 4337-4356; doi:10.3390/molecules20034337
Received: 7 November 2014 / Revised: 19 February 2015 / Accepted: 25 February 2015 / Published: 6 March 2015
Cited by 11 | PDF Full-text (2009 KB) | HTML Full-text | XML Full-text
Abstract
Paclitaxel (PTX, taxol), a classical antitumor drug against a wide range of tumors, shows poor oral bioavailability. In order to improve the oral bioavailability of PTX, glycyrrhizic acid (GA) was used as the carrier in this study. This was the first report on
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Paclitaxel (PTX, taxol), a classical antitumor drug against a wide range of tumors, shows poor oral bioavailability. In order to improve the oral bioavailability of PTX, glycyrrhizic acid (GA) was used as the carrier in this study. This was the first report on the preparation, characterization and the pharmacokinetic study in rats of PTX-loaded GA micelles The PTX-loaded micelles, prepared with ultrasonic dispersion method, displayed small particle sizes and spherical shapes. Differential scanning calorimeter (DSC) thermograms indicated that PTX was entrapped in the GA micelles and existed as an amorphous state. The encapsulation efficiency was about 90%, and the drug loading rate could reach up to 7.90%. PTX-loaded GA micelles displayed a delayed drug release compared to Taxol in the in vitro release experiment. In pharmacokinetic study via oral administration, the area under the plasma concentration-time curve (AUC0→24 h) of PTX-loaded GA micelles was about six times higher than that of Taxol (p < 0.05). The significant oral absorption enhancement of PTX from PTX-loaded GA micelles could be largely due to the increased absorption in jejunum and colon intestine. All these results suggested that GA would be a promising carrier for the oral delivery of PTX. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle “In-plant” NMR: Analysis of the Intact Plant Vesicularia dubyana by High Resolution NMR Spectroscopy
Molecules 2015, 20(3), 4359-4368; doi:10.3390/molecules20034359
Received: 22 January 2015 / Revised: 20 February 2015 / Accepted: 3 March 2015 / Published: 9 March 2015
Cited by 1 | PDF Full-text (1403 KB) | HTML Full-text | XML Full-text
Abstract
We present here the concept of “in-plant” NMR and show that high-resolution NMR spectroscopy is suitable for the analysis of intact plants and can be used to follow the changes in the intraorganismal molecular composition over long time periods. The NMR-based analysis of
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We present here the concept of “in-plant” NMR and show that high-resolution NMR spectroscopy is suitable for the analysis of intact plants and can be used to follow the changes in the intraorganismal molecular composition over long time periods. The NMR-based analysis of the effect of different concentrations of heavy water on the aquatic plant Vesicularia dubyana revealed that due to the presence of specific adaptive mechanisms this plant can sustain the presence of up to 85% of D2O. However, it dies in 100% heavy water. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Self-Assembled Polyelectrolyte Nanoparticles as Fluorophore-Free Contrast Agents for Multicolor Optical Imaging
Molecules 2015, 20(3), 4369-4382; doi:10.3390/molecules20034369
Received: 17 February 2015 / Revised: 2 March 2015 / Accepted: 3 March 2015 / Published: 9 March 2015
Cited by 3 | PDF Full-text (2241 KB) | HTML Full-text | XML Full-text
Abstract
In this work, we describe the fabrication of self-assembled polyelectrolyte nanoparticles that provide a multicolor optical imaging modality. Poly(γ-glutamic acid)(γ-PGA) formed self-assembled nanoparticles through electrostatic interactions with two different cationic polymers: poly(L-lysine)(PLL) and chitosan. The self-assembled γ-PGA/PLL and γ-PGA/chitosan nanoparticles were crosslinked by
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In this work, we describe the fabrication of self-assembled polyelectrolyte nanoparticles that provide a multicolor optical imaging modality. Poly(γ-glutamic acid)(γ-PGA) formed self-assembled nanoparticles through electrostatic interactions with two different cationic polymers: poly(L-lysine)(PLL) and chitosan. The self-assembled γ-PGA/PLL and γ-PGA/chitosan nanoparticles were crosslinked by glutaraldehyde. Crosslinking of the ionic self-assembled nanoparticles with glutaraldehyde not only stabilized the nanoparticles but also generated a strong autofluorescence signal. Fluorescent Schiff base bonds (C=N) and double bonds (C=C) were generated simultaneously by crosslinking of the amine moiety of the cationic polyelectrolytes with monomeric glutaraldehyde or with polymeric glutaraldehyde. The unique optical properties of the nanoparticles that resulted from the crosslinking by glutaraldehyde were analyzed using UV/Vis and fluorescence spectroscopy. We observed that the fluorescence intensity of the nanoparticles could be regulated by adjusting the crosslinker concentration and the reaction time. The nanoparticles also exhibited high performance in the labeling and monitoring of therapeutic immune cells (macrophages and dendritic cells). These self-assembled nanoparticles are expected to be a promising multicolor optical imaging contrast agent for the labeling, detection, and monitoring of cells. Full article
(This article belongs to the collection Nanomedicine)
Open AccessArticle Synthesis and Antifungal Activity of the Derivatives of Novel Pyrazole Carboxamide and Isoxazolol Pyrazole Carboxylate
Molecules 2015, 20(3), 4383-4394; doi:10.3390/molecules20034383
Received: 13 January 2015 / Revised: 17 February 2015 / Accepted: 4 March 2015 / Published: 9 March 2015
Cited by 6 | PDF Full-text (768 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of pyrazole carboxamide and isoxazolol pyrazole carboxylate derivatives were designed and synthesized in this study. The structures of the compounds were elucidated based on spectral data (infrared, proton nuclear magnetic resonance and mass spectroscopy). Then, all of the compounds were bioassayed
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A series of pyrazole carboxamide and isoxazolol pyrazole carboxylate derivatives were designed and synthesized in this study. The structures of the compounds were elucidated based on spectral data (infrared, proton nuclear magnetic resonance and mass spectroscopy). Then, all of the compounds were bioassayed in vitro against four types of phytopathogenic fungi (Alternaria porri, Marssonina coronaria, Cercospora petroselini and Rhizoctonia solani) using the mycelium growth inhibition method. The results showed that some of the synthesized pyrazole carboxamides displayed notable antifungal activity. The isoxazole pyrazole carboxylate 7ai exhibited significant antifungal activity against R. solani, with an EC50 value of 0.37 μg/mL. Nonetheless, this value was lower than that of the commercial fungicide, carbendazol. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Phytochemicals and Other Characteristics of Croatian Monovarietal Extra Virgin Olive Oils from Oblica, Lastovka and Levantinka Varieties
Molecules 2015, 20(3), 4395-4409; doi:10.3390/molecules20034395
Received: 23 January 2015 / Revised: 26 February 2015 / Accepted: 4 March 2015 / Published: 9 March 2015
Cited by 7 | PDF Full-text (742 KB) | HTML Full-text | XML Full-text
Abstract
Virgin olive oils from the fruits of Croatian autochthonous varieties Oblica, Lastovka and Levantinka were characterized for the first time. Headspace volatiles were analyzed by HS-SPME/GC-FID/MS. The main volatiles were C6 compounds. The most abundant was (E)-hex-2-enal (62.60%–69.20%). (Z
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Virgin olive oils from the fruits of Croatian autochthonous varieties Oblica, Lastovka and Levantinka were characterized for the first time. Headspace volatiles were analyzed by HS-SPME/GC-FID/MS. The main volatiles were C6 compounds. The most abundant was (E)-hex-2-enal (62.60%–69.20%). (Z)-Hex-3-enal was not found in Lastovka oil, while Levantinka oil did not contain hexanal. Tocopherols, chlorophylls and carotenoids were determined by HPLC-FL. Levantinka oil was characterized by the highest α-tocopherol level (222.00 mg/kg). Total phenolic contents (TPs), as well as antioxidant activity (DPPH assay) of the oils hydrophilic fractions (HFs) were assessed by spectroscopic methods. The antioxidant activity of Oblica oil HF was the most pronounced (0.91 mmol TEAC/kg) and the HF contained the highest TPs amount (212.21 mg/kg). HFs phenolic composition was determined by HPLC-DAD. The main identified phenols were secoiridoids dominated in Oblica oil: decarboxymethyl ligstroside aglycone (p-HPEA-EDA up to 158.5 mg/kg), oleuropein aglycone (3,4-HPEA-EA up to 96.4 mg/kg) and decarboxymethyl oleuropein aglycon (3,4-DHPEA-EDA up to 93.5 mg/kg). Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Phaleria macrocarpa Boerl. (Thymelaeaceae) Leaves Increase SR-BI Expression and Reduce Cholesterol Levels in Rats Fed a High Cholesterol Diet
Molecules 2015, 20(3), 4410-4429; doi:10.3390/molecules20034410
Received: 29 October 2014 / Revised: 23 December 2014 / Accepted: 13 January 2015 / Published: 9 March 2015
Cited by 1 | PDF Full-text (1872 KB) | HTML Full-text | XML Full-text
Abstract
In vitro and in vivo studies of the activity of Phaleria macrocarpa Boerl (Thymelaeaceae) leaves against the therapeutic target for hypercholesterolemia were done using the HDL receptor (SR-BI) and hypercholesterolemia-induced Sprague Dawley rats. The in vitro study showed that the active
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In vitro and in vivo studies of the activity of Phaleria macrocarpa Boerl (Thymelaeaceae) leaves against the therapeutic target for hypercholesterolemia were done using the HDL receptor (SR-BI) and hypercholesterolemia-induced Sprague Dawley rats. The in vitro study showed that the active fraction (CF6) obtained from the ethyl acetate extract (EMD) and its component 2',6',4-trihydroxy-4'-methoxybenzophenone increased the SR-BI expression by 95% and 60%, respectively. The in vivo study has proven the effect of EMD at 0.5 g/kgbw dosage in reducing the total cholesterol level by 224.9% and increasing the HDL cholesterol level by 157% compared to the cholesterol group. In the toxicity study, serum glutamate oxalate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) activity were observed to be at normal levels. The liver histology also proved no toxicity and abnormalities in any of the treatment groups, so it can be categorized as non-toxic to the rat liver. The findings taken together show that P. macrocarpa leaves are safe and suitable as an alternative control and prevention treatment for hypercholesterolemia in Sprague Dawley rats. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessCommunication New Sesquiterpenoids from Ambrosia artemisiifolia L.
Molecules 2015, 20(3), 4450-4459; doi:10.3390/molecules20034450
Received: 19 January 2015 / Revised: 28 January 2015 / Accepted: 4 March 2015 / Published: 10 March 2015
Cited by 3 | PDF Full-text (737 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new pseudoguaianolide 1 and two new guaiane-type sesquiterpene glucosides 2 and 3, were isolated from the aerial parts of Ambrosia artemisiifolia L together with two known sesquiterpene dilactones 4 and 5. The new compounds were determined on the basis of
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A new pseudoguaianolide 1 and two new guaiane-type sesquiterpene glucosides 2 and 3, were isolated from the aerial parts of Ambrosia artemisiifolia L together with two known sesquiterpene dilactones 4 and 5. The new compounds were determined on the basis of spectroscopic and chemical methods to be 3β-acetoxy-4β-hydroxy-1α,7α, 10β,11αH-pseudoguaia-12,8β-olide (1), 1β,7β,9β,10β,13αH-guaia-4(5)-en-12,6β-olide 9-O-β-d-glucoside (2) and 4β-hydroxy-1α,5α,7α,9αH-guaia-10(14),11(13)-dien-12-acid 9-O-β-d-glucoside (3). The isolated compounds were evaluated for cytotoxicity against human promyelocytic leukemia HL-60 cell lines in vitro, but were all inactive. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle The Effect of Number and Position of P=O/P=S Bridging Units on Cavitand Selectivity toward Methyl Ammonium Salts
Molecules 2015, 20(3), 4460-4472; doi:10.3390/molecules20034460
Received: 12 February 2015 / Revised: 2 March 2015 / Accepted: 5 March 2015 / Published: 10 March 2015
PDF Full-text (1027 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The present work reports the synthesis and complexation properties of five mixed bridge P=O/P=S cavitands toward N,N-methyl butyl ammonium chloride (1) as prototype guest. The influence of number and position of P=O and P=S groups on the affinity of phosphonate
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The present work reports the synthesis and complexation properties of five mixed bridge P=O/P=S cavitands toward N,N-methyl butyl ammonium chloride (1) as prototype guest. The influence of number and position of P=O and P=S groups on the affinity of phosphonate cavitands toward 1 is assessed via ITC titrations in DCE as solvent. Comparison of the resulting Kass values, the enthalpic and entropic contributions to the overall binding with those of the parent tetraphosphonate Tiiii and tetrathiophosphonate TSiiii cavitands allows one to single out the simultaneous dual H-bond between the cavitand and the salt as the major player in complexation. Full article
(This article belongs to the Special Issue Host-Guest Chemistry)
Open AccessArticle Inhibitory Effect of Duabanga grandiflora on MRSA Biofilm Formation via Prevention of Cell-Surface Attachment and PBP2a Production
Molecules 2015, 20(3), 4473-4482; doi:10.3390/molecules20034473
Received: 28 October 2014 / Revised: 10 December 2014 / Accepted: 12 February 2015 / Published: 10 March 2015
Cited by 8 | PDF Full-text (655 KB) | HTML Full-text | XML Full-text
Abstract
Formation of biofilms is a major factor for nosocomial infections associated with methicillin-resistance Staphylococcus aureus (MRSA). This study was carried out to determine the ability of a fraction, F-10, derived from the plant Duabanga grandiflora to inhibit MRSA biofilm formation. Inhibition of biofilm
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Formation of biofilms is a major factor for nosocomial infections associated with methicillin-resistance Staphylococcus aureus (MRSA). This study was carried out to determine the ability of a fraction, F-10, derived from the plant Duabanga grandiflora to inhibit MRSA biofilm formation. Inhibition of biofilm production and microtiter attachment assays were employed to study the anti-biofilm activity of F-10, while latex agglutination test was performed to study the influence of F-10 on penicillin-binding protein 2a (PBP2a) level in MRSA biofilm. PBP2a is a protein that confers resistance to beta-lactam antibiotics. The results showed that, F-10 at minimum inhibitory concentration (MIC, 0.75 mg/mL) inhibited biofilm production by 66.10%; inhibited cell-surface attachment by more than 95%; and a reduced PBP2a level in the MRSA biofilm was observed. Although ampicilin was more effective in inhibiting biofilm production (MIC of 0.05 mg/mL, 84.49%) compared to F-10, the antibiotic was less effective in preventing cell-surface attachment. A higher level of PBP2a was detected in ampicillin-treated MRSA showing the development of further resistance in these colonies. This study has shown that F-10 possesses anti-biofilm activity, which can be attributed to its ability to reduce cell-surface attachment and attenuate the level of PBP2a that we postulated to play a crucial role in mediating biofilm formation. Full article
Open AccessArticle Two New Phenolic Glucosides from Lagerstroemia speciosa
Molecules 2015, 20(3), 4483-4491; doi:10.3390/molecules20034483
Received: 6 February 2015 / Revised: 4 March 2015 / Accepted: 5 March 2015 / Published: 10 March 2015
Cited by 1 | PDF Full-text (718 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new phenolic glucosides, 1-O-benzyl-6-O-E-caffeoyl-β-d-glucopyranoside and 1-O-(7S,8R)-guaiacylglycerol-(6-O-E-caffeoyl)-β-d-glucopyranoside, were isolated from the aerial parts of Lagerstroemia speciosa, along with ten known compounds. The structures of the isolated
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Two new phenolic glucosides, 1-O-benzyl-6-O-E-caffeoyl-β-d-glucopyranoside and 1-O-(7S,8R)-guaiacylglycerol-(6-O-E-caffeoyl)-β-d-glucopyranoside, were isolated from the aerial parts of Lagerstroemia speciosa, along with ten known compounds. The structures of the isolated compounds were determined based on 1D- and 2D-NMR, Q-TOF MS and optical rotation spectroscopic data. All of the compounds showed moderate inhibitory activities against nitric oxide production in lipopolysaccharide-treated RAW264.7 cells, with IC50 values of 69.5–83.3 μM. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Multigram Synthesis and in Vivo Efficacy Studies of a Novel Multitarget Anti-Alzheimer’s Compound
Molecules 2015, 20(3), 4492-4515; doi:10.3390/molecules20034492
Received: 22 January 2015 / Revised: 25 February 2015 / Accepted: 3 March 2015 / Published: 10 March 2015
Cited by 3 | PDF Full-text (1264 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We describe the multigram synthesis and in vivo efficacy studies of a donepezil‒huprine hybrid that has been found to display a promising in vitro multitarget profile of interest for the treatment of Alzheimer’s disease (AD). Its synthesis features as the key step a
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We describe the multigram synthesis and in vivo efficacy studies of a donepezil‒huprine hybrid that has been found to display a promising in vitro multitarget profile of interest for the treatment of Alzheimer’s disease (AD). Its synthesis features as the key step a novel multigram preparative chromatographic resolution of intermediate racemic huprine Y by chiral HPLC. Administration of this compound to transgenic CL4176 and CL2006 Caenorhabditis elegans strains expressing human Aβ42, here used as simplified animal models of AD, led to a significant protection from the toxicity induced by Aβ42. However, this protective effect was not accompanied, in CL2006 worms, by a reduction of amyloid deposits. Oral administration for 3 months to transgenic APPSL mice, a well-established animal model of AD, improved short-term memory, but did not alter brain levels of Aβ peptides nor cortical and hippocampal amyloid plaque load. Despite the clear protective and cognitive effects of AVCRI104P4, the lack of Aβ lowering effect in vivo might be related to its lower in vitro potency toward Aβ aggregation and formation as compared with its higher anticholinesterase activities. Further lead optimization in this series should thus focus on improving the anti-amyloid/anticholinesterase activity ratio. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle N-Hydroxycinnamide Derivatives of Osthole Ameliorate Hyperglycemia through Activation of AMPK and p38 MAPK
Molecules 2015, 20(3), 4516-4529; doi:10.3390/molecules20034516
Received: 20 January 2015 / Revised: 4 March 2015 / Accepted: 5 March 2015 / Published: 11 March 2015
Cited by 5 | PDF Full-text (5106 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and
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Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and the p38 MAPK inhibitor, SB203580, significantly reversed activation of AMPK and p38 MAPK, respectively, in OHC-4p- and OHC-2m-treated cells. Compound C and SB203580 also inhibited glucose uptake induced by OHC-4p and OHC-2m. Next, we found that OHC-4p and OHC-2m significantly increased glucose transporter 4 (GLUT4) translocation to plasma membranes and counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that activation of AMPK and p38 MAPK by OHC-4p and OHC-2m is associated with increased glucose uptake and GLUT4 translocation and subsequently led to amelioration of hyperglycemia. Therefore, OHC-4p and OHC-2m might have potential as antidiabetic agents for treating type 2 diabetes. Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and the p38 MAPK inhibitor, SB203580, significantly reversed activation of AMPK and p38 MAPK, respectively, in OHC-4p- and OHC-2m-treated cells. Compound C and SB203580 also inhibited glucose uptake induced by OHC-4p and OHC-2m. Next, we found that OHC-4p and OHC-2m significantly increased glucose transporter 4 (GLUT4) translocation to plasma membranes and counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that activation of AMPK and p38 MAPK by OHC-4p and OHC-2m is associated with increased glucose uptake and GLUT4 translocation and subsequently led to amelioration of hyperglycemia. Therefore, OHC-4p and OHC-2m might have potential as antidiabetic agents for treating type 2 diabetes. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessCommunication σ- versus π-Activation of Alkynyl Benzoates Using B(C6F5)3
Molecules 2015, 20(3), 4530-4547; doi:10.3390/molecules20034530
Received: 8 February 2015 / Revised: 17 February 2015 / Accepted: 28 February 2015 / Published: 12 March 2015
Cited by 5 | PDF Full-text (1515 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We have prepared a range of alkynyl benzoates in high yields and have investigated their reactivities with the strong Lewis acid B(C6F5)3. In such molecules both σ-activation of the carbonyl and π-activation of the alkyne are possible.
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We have prepared a range of alkynyl benzoates in high yields and have investigated their reactivities with the strong Lewis acid B(C6F5)3. In such molecules both σ-activation of the carbonyl and π-activation of the alkyne are possible. In contrast to the reactivity of propargyl esters with B(C6F5)3 which proceed via 1,2-addition of the ester and B(C6F5)3 across the alkyne, the inclusion of an additional CH2 spacer switches off the intramolecular cyclization and selective σ-activation of the carbonyl group is observed through adduct formation. This change in reactivity appears due to the instability of the species which would be formed through B(C6F5)3 activation of the alkyne. Full article
(This article belongs to the Special Issue Recent Advances in Boron Chemistry)
Open AccessArticle Anti-Ageing Effects of Sonchus oleraceus L. (pūhā) Leaf Extracts on H2O2-Induced Cell Senescence
Molecules 2015, 20(3), 4548-4564; doi:10.3390/molecules20034548
Received: 21 January 2015 / Revised: 3 March 2015 / Accepted: 3 March 2015 / Published: 12 March 2015
Cited by 5 | PDF Full-text (868 KB) | HTML Full-text | XML Full-text
Abstract
Antioxidants protect against damage from free radicals and are believed to slow the ageing process. Previously, we have reported the high antioxidant activity of 70% methanolic Sonchus oleraceus L. (Asteraceae) leaf extracts. We hypothesize that S. oleraceus extracts protect cells against H2
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Antioxidants protect against damage from free radicals and are believed to slow the ageing process. Previously, we have reported the high antioxidant activity of 70% methanolic Sonchus oleraceus L. (Asteraceae) leaf extracts. We hypothesize that S. oleraceus extracts protect cells against H2O2-induced senescence by mediating oxidative stress. Premature senescence of young WI-38 cells was induced by application of H2O2. Cells were treated with S. oleraceus extracts before or after H2O2 stress. The senescence- associated β-galactosidase (SA-β-gal) activity was used to indicate cell senescence. S. oleraceus extracts showed higher cellular antioxidant activity than chlorogenic acid in WI-38 cells. S. oleraceus extracts suppressed H2O2 stress-induced premature senescence in a concentration-dependent manner. At 5 and 20 mg/mL, S. oleraceus extracts showed better or equivalent effects of reducing stress-induced premature senescence than the corresponding ascorbic acid treatments. These findings indicate the potential of S. oleraceus extracts to be formulated as an anti-ageing agent. Full article
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Open AccessArticle Multifaceted Strategy for the Synthesis of Diverse 2,2'-Bithiophene Derivatives
Molecules 2015, 20(3), 4565-4593; doi:10.3390/molecules20034565
Received: 13 January 2015 / Revised: 22 February 2015 / Accepted: 26 February 2015 / Published: 12 March 2015
Cited by 2 | PDF Full-text (858 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
New catalytically or high pressure activated reactions and routes, including coupling, double bond migration in allylic systems, and various types of cycloaddition and dihydroamination have been used for the synthesis of novel bithiophene derivatives. Thanks to the abovementioned reactions and routes combined with
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New catalytically or high pressure activated reactions and routes, including coupling, double bond migration in allylic systems, and various types of cycloaddition and dihydroamination have been used for the synthesis of novel bithiophene derivatives. Thanks to the abovementioned reactions and routes combined with non-catalytic ones, new acetylene, butadiyne, isoxazole, 1,2,3-triazole, pyrrole, benzene, and fluoranthene derivatives with one, two or six bithiophenyl moieties have been obtained. Basic sources of crucial substrates which include bithiophene motif for catalytic reactions were 2,2'-bithiophene, gaseous acetylene and 1,3-butadiyne. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Ni-SiO2 Catalysts for the Carbon Dioxide Reforming of Methane: Varying Support Properties by Flame Spray Pyrolysis
Molecules 2015, 20(3), 4594-4609; doi:10.3390/molecules20034594
Received: 16 December 2014 / Revised: 27 February 2015 / Accepted: 2 March 2015 / Published: 12 March 2015
Cited by 11 | PDF Full-text (994 KB) | HTML Full-text | XML Full-text
Abstract
Silica particles were prepared by flame spray pyrolysis (FSP) as a support for nickel catalysts. The impact of precursor feed rate (3, 5 and 7 mL/min) during FSP on the silica characteristics and the ensuing effect on catalytic performance for the carbon dioxide,
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Silica particles were prepared by flame spray pyrolysis (FSP) as a support for nickel catalysts. The impact of precursor feed rate (3, 5 and 7 mL/min) during FSP on the silica characteristics and the ensuing effect on catalytic performance for the carbon dioxide, or dry, reforming of methane (DRM) was probed. Increasing the precursor feed rate: (i) progressively lowered the silica surface area from ≈340 m2/g to ≈240 m2/g; (ii) altered the silanol groups on the silica surface; and (iii) introduced residual carbon-based surface species to the sample at the highest feed rate. The variations in silica properties altered the (5 wt %) nickel deposit characteristics which in turn impacted on the DRM reaction. As the silica surface area increased, the nickel dispersion increased which improved catalyst performance. The residual carbon-based species also appeared to improve nickel dispersion, and in turn catalyst activity, although not to the same extent as the change in silica surface area. The findings illustrate both the importance of silica support characteristics on the catalytic performance of nickel for the DRM reaction and the capacity for using FSP to control these characteristics. Full article
(This article belongs to the Special Issue Methane Reforming)
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Open AccessArticle Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins
Molecules 2015, 20(3), 4610-4622; doi:10.3390/molecules20034610
Received: 20 January 2015 / Revised: 26 February 2015 / Accepted: 9 March 2015 / Published: 12 March 2015
PDF Full-text (3624 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for
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Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA), for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV), and human cytomegalovirus (HCMV). In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man9GlcNAc2Asn (Man9)-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn). These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation. Full article
(This article belongs to the collection Advances in Carbohydrate Chemistry)
Open AccessArticle Construction of an Isonucleoside on a 2,6-Dioxobicyclo[3.2.0]-heptane Skeleton
Molecules 2015, 20(3), 4623-4634; doi:10.3390/molecules20034623
Received: 2 February 2015 / Revised: 3 March 2015 / Accepted: 4 March 2015 / Published: 12 March 2015
Cited by 1 | PDF Full-text (655 KB) | HTML Full-text | XML Full-text
Abstract
We have built a new isonucleoside derivative on a 2,6-dioxobicyclo[3.2.0]heptane skeleton as a potential anti-HIV agent. To synthesize the target compound, an acetal-protected dihydroxyacetone was first converted to a 2,3-epoxy-tetrahydrofuran derivative. Introduction of an azide group, followed by the formation of an oxetane
[...] Read more.
We have built a new isonucleoside derivative on a 2,6-dioxobicyclo[3.2.0]heptane skeleton as a potential anti-HIV agent. To synthesize the target compound, an acetal-protected dihydroxyacetone was first converted to a 2,3-epoxy-tetrahydrofuran derivative. Introduction of an azide group, followed by the formation of an oxetane ring, gave a pseudosugar derivative with a 2,6-dioxobicyclo[3.2.0]heptane skeleton. The desired isonucleoside was obtained by constructing a purine base moiety on the scaffold, followed by amination. Full article
(This article belongs to the Special Issue Nucleoside Modifications) Printed Edition available
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Open AccessArticle Synthesis and Photoluminescent Properties of Geometrically Hindered cis-Tris(diphenylaminofluorene) as Precursors to Light-Emitting Devices
Molecules 2015, 20(3), 4635-4654; doi:10.3390/molecules20034635
Received: 12 January 2015 / Revised: 4 March 2015 / Accepted: 4 March 2015 / Published: 13 March 2015
PDF Full-text (3111 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A novel highly luminescent tris-fluorenyl ring-interconnected chromophore tris(DPAF-C9) was synthesized using a C3 symmetrical triaminobenzene core as the synthon. This structure bears three light-harvesting 2-diphenylamino-9,9-dialkylfluorenyl (DPAF) ring moieties with each attached by two branched 3',5',5'-trimethylhexyl (C9) arms. A
[...] Read more.
A novel highly luminescent tris-fluorenyl ring-interconnected chromophore tris(DPAF-C9) was synthesized using a C3 symmetrical triaminobenzene core as the synthon. This structure bears three light-harvesting 2-diphenylamino-9,9-dialkylfluorenyl (DPAF) ring moieties with each attached by two branched 3',5',5'-trimethylhexyl (C9) arms. A major stereoisomer was chromatographically isolated and characterized to possess a 3D structural configuration of cis-conformer in a cup-form. Molecular calculation at B3LYP/6-31G* level revealed the unexpected stability of this cis-cup-conformer of tris(DPAF-C9) better than that of the stereoisomer in a propeller-form and the trans-conformer. The structural geometry is proposed to be capable of minimizing the aggregation related self-quenching effect in the condensed phase. Fluorescence emission wavelength of tris(DPAF-C9) was found to be in a close range to that of PVK that led to its potential uses as the secondary blue hole-transporting material for enhancing the device property toward the modulation of PLED performance. Full article
(This article belongs to the Special Issue Light-Harvesting Complexes)
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Open AccessArticle Simultaneous Determination of Ferulic Acid and Phthalides of Angelica Sinensis Based on UPLC-Q-TOF/MS
Molecules 2015, 20(3), 4681-4694; doi:10.3390/molecules20034681
Received: 4 January 2015 / Revised: 17 February 2015 / Accepted: 25 February 2015 / Published: 13 March 2015
Cited by 4 | PDF Full-text (2135 KB) | HTML Full-text | XML Full-text
Abstract
The radix of Angelica sinensis (AS) is one of the most commonly used as a herbal medicine. To investigate the geoherbalism and quality evaluation of AS, an ultra performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF/MS) method was
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The radix of Angelica sinensis (AS) is one of the most commonly used as a herbal medicine. To investigate the geoherbalism and quality evaluation of AS, an ultra performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF/MS) method was established to analyze and identify ferulic acid and phthalides in AS. The results showed that among samples collected in four regions, the relative contents of ferulic acid and phthalides were highest in samples collected in Gansu, and the samples from the four different regions were apparently classified into four groups. Meanwhile, the relative content in non-fumigated root was higher than after sulfur-fumigation and the sulfur-fumigated and non-fumigated samples were obviously divided into two groups by PCA. The paper establishes a systematic and objective evaluation system to provide a scientific basis for evaluating the quality of AS. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Synthesis of Peptide Nucleic Acids Containing a Crosslinking Agent and Evaluation of Their Reactivities
Molecules 2015, 20(3), 4708-4719; doi:10.3390/molecules20034708
Received: 26 January 2015 / Revised: 3 March 2015 / Accepted: 9 March 2015 / Published: 13 March 2015
Cited by 4 | PDF Full-text (1197 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Peptide nucleic acids (PNAs) are structural mimics of nucleic acids that form stable hybrids with DNA and RNA. In addition, PNAs can invade double-stranded DNA. Due to these characteristics, PNAs are widely used as biochemical tools, for example, in antisense/antigene therapy. Interstrand crosslink
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Peptide nucleic acids (PNAs) are structural mimics of nucleic acids that form stable hybrids with DNA and RNA. In addition, PNAs can invade double-stranded DNA. Due to these characteristics, PNAs are widely used as biochemical tools, for example, in antisense/antigene therapy. Interstrand crosslink formation in nucleic acids is one of the strategies for preparing a stable duplex by covalent bond formation. In this study, we have synthesized PNAs incorporating 4-amino-6-oxo-2-vinylpyrimidine (AOVP) as a crosslinking agent and evaluated their reactivities for targeting DNA and RNA. Full article
(This article belongs to the Special Issue Nucleoside Modifications) Printed Edition available
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Open AccessArticle Antimicrobial and Antioxidant Activities and Phenolic Profile of Eucalyptus globulus Labill. and Corymbia ficifolia (F. Muell.) K.D. Hill & L.A.S. Johnson Leaves
Molecules 2015, 20(3), 4720-4734; doi:10.3390/molecules20034720
Received: 23 January 2015 / Revised: 22 February 2015 / Accepted: 9 March 2015 / Published: 16 March 2015
Cited by 16 | PDF Full-text (735 KB) | HTML Full-text | XML Full-text
Abstract
This study was performed to evaluate the in vitro antimicrobial and antioxidant activities and the phenolic profile of Eucalytus globulus Labill. and Corymbia ficifolia (F. Muell.) K.D. Hill & L.A.S. Johnson leaves. Both leave extracts contain significant amounts of phenolic compounds, mainly flavonoids.
[...] Read more.
This study was performed to evaluate the in vitro antimicrobial and antioxidant activities and the phenolic profile of Eucalytus globulus Labill. and Corymbia ficifolia (F. Muell.) K.D. Hill & L.A.S. Johnson leaves. Both leave extracts contain significant amounts of phenolic compounds, mainly flavonoids. Qualitative and quantitative analyses of the phenolic compounds were performed using a HPLC/MS method. The main flavonoid was hyperoside and its highest amount was found in E. globulus (666.42 ± 5.02 μg/g dw plant material). Regarding the flavonol profile, myricetin was the dominant compound and its highest amount was found in C. ficifolia leaves (124.46 ± 0.24 μg/g dw plant material). The antioxidant activity was evaluated by DPPH, TEAC, hemoglobin ascorbate peroxidase activity inhibition (HAPX) and inhibition of lipid peroxidation catalyzed by cytochrome c assays, revealing an important antioxidant potential for both species. In the antimicrobial assays, C. ficifolia extract was found to be more active than E. globulus against both Gram-positive and Gram-negative bacterial strains with the exception of Bacillus subtilis. The results of the present study provide new valuable data regarding the bioactivities of these medicinal species. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Chemical Composition and Biological Activities of the Essential Oil of Skimmia laureola Leaves
Molecules 2015, 20(3), 4735-4745; doi:10.3390/molecules20034735
Received: 22 January 2015 / Revised: 10 March 2015 / Accepted: 12 March 2015 / Published: 16 March 2015
Cited by 4 | PDF Full-text (768 KB) | HTML Full-text | XML Full-text
Abstract
The composition of the essential oil from leaves of Skimmia laureola was determined by GC and GC-MS. Twenty-eight components were identified, accounting for 93.9% of the total oil. The oil is mainly composed of monoterpenes (93.5%), of which monoterpene hydrocarbons and oxygenated monoterpenes
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The composition of the essential oil from leaves of Skimmia laureola was determined by GC and GC-MS. Twenty-eight components were identified, accounting for 93.9% of the total oil. The oil is mainly composed of monoterpenes (93.5%), of which monoterpene hydrocarbons and oxygenated monoterpenes represent 11.0% and 82.5%, respectively. Sesquiterpenes constitute only 0.3% of the total oil. Linalyl acetate is the main component (50.5%), with linalool (13.1%), geranyl acetate (8.5%) and cis-p-menth-2-en-1-ol (6.2%) as other principal constituents. The essential oil showed a significant antispasmodic activity, in a dose range of 0.03–10 mg/mL. The essential oil also possesses antibacterial and antifungal activities against some pathogenic strains. The phytotoxic and cytotoxic activities were also assessed. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
Open AccessArticle Protective Effects of Labisia pumila var. alata on Biochemical and Histopathological Alterations of Cardiac Muscle Cells in Isoproterenol-Induced Myocardial Infarction Rats
Molecules 2015, 20(3), 4746-4763; doi:10.3390/molecules20034746
Received: 31 January 2015 / Revised: 20 February 2015 / Accepted: 4 March 2015 / Published: 16 March 2015
Cited by 6 | PDF Full-text (1655 KB) | HTML Full-text | XML Full-text
Abstract
The study was designed to evaluate the cardioprotective effects of the standardized aqueous and 80% ethanol extracts of Labisia pumila var. alata (LPva) in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. The extracts were administered to Wistar rats orally for 28 days with
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The study was designed to evaluate the cardioprotective effects of the standardized aqueous and 80% ethanol extracts of Labisia pumila var. alata (LPva) in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. The extracts were administered to Wistar rats orally for 28 days with three doses (100, 200 and 400 mg/kg of body weight) prior to ISO (85 mg/kg)-induced MI in two doses on day 29 and 30. The sera and hearts were collected for biochemical and histopathological analysis after the rats were sacrificed 48 h after the first induction. The main components of the extracts, gallic acid, alkylresorcinols and flavonoids were identified and quantitatively analyzed in the extracts by using a validated reversed phase HPLC method. The extracts showed significant protective effects as pretreated rats showed a significant dose-dependent decrease (p < 0.05) in cardiac enzyme activities, i.e., cardiac troponin I (cTnI), creatine kinase MB isoenzyme (CK-MB), lactate dehydrogenase (LDH), alanine transaminase (ALT) and aspartate transaminase (AST), when compared with ISO-control rats. There were significant rises (p < 0.05) in the activity of oxidase enzymes, i.e., glutathione peroxide (GPx), catalase (CAT) and superoxide dismutase (SOD) of the pretreated rats, when compared with ISO-control group. Histopathological examination showed an improvement in membrane cell integrity in pre-treated rats compared to untreated rats. The major components of LPva extracts can be used as their biomarkers and contributed to the cardioprotective effects against ISO-induced MI rats. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Cyclic Comonomers for the Synthesis of Carboxylic Acid and Amine Functionalized Poly(l-Lactic Acid)
Molecules 2015, 20(3), 4764-4779; doi:10.3390/molecules20034764
Received: 15 January 2015 / Revised: 23 February 2015 / Accepted: 2 March 2015 / Published: 16 March 2015
Cited by 4 | PDF Full-text (694 KB) | HTML Full-text | XML Full-text
Abstract
Degradable aliphatic polyesters such as poly(lactic acid) are widely used in biomedical applications, however, they lack functional moieties along the polymer backbone that are amenable for functionalization reactions or could be the basis for interactions with biological systems. Here we present a straightforward
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Degradable aliphatic polyesters such as poly(lactic acid) are widely used in biomedical applications, however, they lack functional moieties along the polymer backbone that are amenable for functionalization reactions or could be the basis for interactions with biological systems. Here we present a straightforward route for the synthesis of functional α-ω epoxyesters as comonomers for lactide polymerization. Salient features of these highly functionalized epoxides are versatility in functionality and a short synthetic route of less than four steps. The α-ω epoxyesters presented serve as a means to introduce carboxylic acid and amine functional groups into poly(lactic acid) polymers via ring-opening copolymerization. Full article
(This article belongs to the Special Issue Ring-Opening Polymerization)
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Open AccessArticle In Vitro Neuroprotective Activities of Compounds from Angelica shikokiana Makino
Molecules 2015, 20(3), 4813-4832; doi:10.3390/molecules20034813
Received: 5 February 2015 / Revised: 3 March 2015 / Accepted: 9 March 2015 / Published: 16 March 2015
Cited by 7 | PDF Full-text (2012 KB) | HTML Full-text | XML Full-text
Abstract
Angelica shikokiana is widely marketed in Japan as a dietary food supplement. With a focus on neurodegenerative conditions such as Alzheimer’s disease, the aerial part was extracted and through bio-guided fractionation, fifteen compounds [α-glutinol, β-amyrin, kaempferol, luteolin, quercetin, kaempferol-3-O-glucoside, kaempferol-3-O
[...] Read more.
Angelica shikokiana is widely marketed in Japan as a dietary food supplement. With a focus on neurodegenerative conditions such as Alzheimer’s disease, the aerial part was extracted and through bio-guided fractionation, fifteen compounds [α-glutinol, β-amyrin, kaempferol, luteolin, quercetin, kaempferol-3-O-glucoside, kaempferol-3-O-rutinoside, methyl chlorogenate, chlorogenic acid, hyuganin E, 5-(hydroxymethyl)-2-furaldehyde, β-sitosterol-3-O-glucoside, adenosine (isolated for the first time from A. shikokiana), isoepoxypteryxin and isopteryxin] were isolated. Isolated compounds were evaluated for in vitro neuroprotection using acetylcholine esterase inhibitory, protection against hydrogen peroxide and amyloid β peptide (Aβ25-35)-induced neurotoxicity in neuro-2A cells, scavenging of hydroxyl radicals and intracellular reactive oxygen species and thioflavin T assays. Quercetin showed the strongest AChE inhibition (IC50 value = 35.5 µM) through binding to His-440 and Tyr-70 residues at the catalytic and anionic sites of acetylcholine esterase, respectively. Chlorogenic acid, its methyl ester, quercetin and luteolin could significantly protect neuro-2A cells against H2O2-induced neurotoxicity and scavenge hydroxyl radical and intracellular reactive oxygen species. Kaempferol-3-O-rutinoiside, hyuganin E and isoepoxypteryxin significantly decreased Aβ25-35-induced neurotoxicity and Th-T fluorescence. To the best of our knowledge, this is the first report about neuroprotection of hyuganin E and isoepoxypteryxin against Aβ25-35-induced neurotoxicity. Full article
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Open AccessArticle Identification of the Valid Reference Genes for Quantitative RT-PCR in Annual Ryegrass (Lolium multiflorum) under Salt Stress
Molecules 2015, 20(3), 4833-4847; doi:10.3390/molecules20034833
Received: 5 January 2015 / Revised: 6 March 2015 / Accepted: 10 March 2015 / Published: 16 March 2015
Cited by 4 | PDF Full-text (2822 KB) | HTML Full-text | XML Full-text
Abstract
Annual ryegrass (Lolium multiflorum) is a cool-season annual grass cultivated worldwide for its high yield and quality. With the areas of saline soil increasing, investigation of the molecular mechanisms of annual ryegrass tolerance under salt stress has become a significant topic.
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Annual ryegrass (Lolium multiflorum) is a cool-season annual grass cultivated worldwide for its high yield and quality. With the areas of saline soil increasing, investigation of the molecular mechanisms of annual ryegrass tolerance under salt stress has become a significant topic. qRT-PCR has been a predominant assay for determination of the gene expression, in which selecting a valid internal reference gene is a crucial step. The objective of present study was to evaluate and identify suitable reference genes for qRT-PCR in annual ryegrass under salt stress. The results calculated by RefFinder indicated that eEF1A(s) was the most stable reference gene in leaves, whereas EF1-a was the least stable; meanwhile, TBP-1 was the most optimal in roots and in all samples, and the eIF-5A shouldn’t be utilized for normalization of the gene expression. eEF1A(s) is more suitable than TBP-1 as reference gene in leaves when verified with P5CS1 and Cyt-Cu/Zn SOD genes. We should choose optimal reference genes in specific tissues instead of the most stable one selected from different conditions and tissues. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle QSAR-Assisted Virtual Screening of Lead-Like Molecules from Marine and Microbial Natural Sources for Antitumor and Antibiotic Drug Discovery
Molecules 2015, 20(3), 4848-4873; doi:10.3390/molecules20034848
Received: 29 January 2015 / Revised: 27 February 2015 / Accepted: 4 March 2015 / Published: 17 March 2015
Cited by 2 | PDF Full-text (909 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A Quantitative Structure-Activity Relationship (QSAR) approach for classification was used for the prediction of compounds as active/inactive relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1746 compounds from PubChem with empirical CDK descriptors and semi-empirical quantum-chemical descriptors.
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A Quantitative Structure-Activity Relationship (QSAR) approach for classification was used for the prediction of compounds as active/inactive relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1746 compounds from PubChem with empirical CDK descriptors and semi-empirical quantum-chemical descriptors. A data set of 183 active pharmaceutical ingredients was additionally used for the external validation of the best models. The best classification models for antibiotic and antitumor activities were used to screen a data set of marine and microbial natural products from the AntiMarin database—25 and four lead compounds for antibiotic and antitumor drug design were proposed, respectively. The present work enables the presentation of a new set of possible lead like bioactive compounds and corroborates the results of our previous investigations. By other side it is shown the usefulness of quantum-chemical descriptors in the discrimination of biologically active and inactive compounds. None of the compounds suggested by our approach have assigned non-antibiotic and non-antitumor activities in the AntiMarin database and almost all were lately reported as being active in the literature. Full article
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Open AccessArticle Preliminary Biological Evaluation of 18F-FBEM-Cys-Annexin V a Novel Apoptosis Imaging Agent
Molecules 2015, 20(3), 4902-4914; doi:10.3390/molecules20034902
Received: 22 December 2014 / Revised: 24 February 2015 / Accepted: 6 March 2015 / Published: 17 March 2015
Cited by 6 | PDF Full-text (1737 KB) | HTML Full-text | XML Full-text
Abstract
A novel annexin V derivative (Cys-Annexin V) with a single cysteine residue at its C-terminal has been developed and successfully labeled site-specifically with 18F-FBEM. 18F-FBEM was synthesized by coupling 18F-fluorobenzoic acid (18F-FBA) with N-(2-aminoethyl)maleimide using optimized reaction conditions.
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A novel annexin V derivative (Cys-Annexin V) with a single cysteine residue at its C-terminal has been developed and successfully labeled site-specifically with 18F-FBEM. 18F-FBEM was synthesized by coupling 18F-fluorobenzoic acid (18F-FBA) with N-(2-aminoethyl)maleimide using optimized reaction conditions. The yield of 18F-FBEM-Cys-Annexin V was 71.5% ± 2.0% (n = 4, based on the starting 18F-FBEM, non-decay corrected). The radiochemical purity of 18F-FBEM-Cys-Annexin V was >95%. The specific radioactivities of 18F-FBEM and 18F-FBEM-Cys-Annexin V were >150 and 3.17 GBq/µmol, respectively. Like the 1st generation 18F-SFB-Annexin V, the novel 18F-FBEM-Cys-Annexin V mainly shows renal and to a lesser extent, hepatobiliary excretion in normal mice. In rat hepatic apoptosis models a 3.88 ± 0.05 (n = 4, 1 h) and 10.35 ± 0.08 (n = 4, 2 h) increase in hepatic uptake of 18F-FBEM-Cys-Annexin V compared to normal rats was observed after injection via the tail vein. The liver uptake ratio (treated/control) at 2 h p.i. as measured via microPET correlated with the ratio of apoptotic nuclei in liver observed using TUNEL histochemistry, indicating that the novel 18F-FBEM-Cys-Annexin V is a potential apoptosis imaging agent. Full article
(This article belongs to the Special Issue Preparation of Radiopharmaceuticals and Their Use in Drug Development)
Open AccessArticle Understanding the Physicochemical Properties of Mitragynine, a Principal Alkaloid of Mitragyna speciosa, for Preclinical Evaluation
Molecules 2015, 20(3), 4915-4927; doi:10.3390/molecules20034915
Received: 12 January 2015 / Accepted: 27 February 2015 / Published: 18 March 2015
Cited by 5 | PDF Full-text (720 KB) | HTML Full-text | XML Full-text
Abstract
Varied pharmacological responses have been reported for mitragynine in the literature, but no supportive scientific explanations have been given for this. These studies have been undertaken without a sufficient understanding of the physicochemical properties of mitragynine. In this work a UV spectrophotometer approach
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Varied pharmacological responses have been reported for mitragynine in the literature, but no supportive scientific explanations have been given for this. These studies have been undertaken without a sufficient understanding of the physicochemical properties of mitragynine. In this work a UV spectrophotometer approach and HPLC-UV method were employed to ascertain the physicochemical properties of mitragynine. The pKa of mitragynine measured by conventional UV (8.11 ± 0.11) was in agreement with the microplate reader determination (8.08 ± 0.04). Mitragynine is a lipophilic alkaloid, as indicated by a logP value of 1.73. Mitragynine had poor solubility in water and basic media, and conversely in acidic environments, but it is acid labile. In an in vitro dissolution the total drug release was higher for the simulated gastric fluid but was prolonged and incomplete for the simulated intestinal fluid. The hydrophobicity, poor water solubility, high variability of drug release in simulated biological fluids and acid degradable characteristics of mitragynine probably explain the large variability of its pharmacological responses reported in the literature. The determined physicochemical properties of mitragynine will provide a basis for developing a suitable formulation to further improve its solubility, stability and oral absorption for better assessment of this compound in preclinical studies. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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Open AccessArticle Cysteine Specific Targeting of the Functionally Distinct Peroxiredoxin and Glutaredoxin Proteins by the Investigational Disulfide BNP7787
Molecules 2015, 20(3), 4928-4950; doi:10.3390/molecules20034928
Received: 10 November 2014 / Accepted: 5 March 2015 / Published: 18 March 2015
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Abstract
Glutaredoxin (Grx), peroxiredoxin (Prx), and thioredoxin (Trx) are redoxin family proteins that catalyze different types of chemical reactions that impact cell growth and survival through functionally distinct intracellular pathways. Much research is focused on understanding the roles of these redoxin proteins in the
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Glutaredoxin (Grx), peroxiredoxin (Prx), and thioredoxin (Trx) are redoxin family proteins that catalyze different types of chemical reactions that impact cell growth and survival through functionally distinct intracellular pathways. Much research is focused on understanding the roles of these redoxin proteins in the development and/or progression of human diseases. Grx and Prx are overexpressed in human cancers, including human lung cancers. BNP7787 is a novel investigational agent that has been evaluated in previous clinical studies, including non-small cell lung cancer (NSCLC) studies. Herein, data from activity assays, mass spectrometry analyses, and X-ray crystallographic studies indicate that BNP7787 forms mixed disulfides with select cysteine residues on Grx and Prx and modulates their function. Studies of interactions between BNP7787 and Trx have been conducted and reported separately. Despite the fact that Trx, Grx, and Prx are functionally distinct proteins that impact oxidative stress, cell proliferation and disease processes through different intracellular pathways, BNP7787 can modify each protein and appears to modulate function through mechanisms that are unique to each target protein. Tumor cells are often genomically heterogeneous containing subpopulations of cancer cells that often express different tumor-promoting proteins or that have multiple dysregulated signaling pathways modulating cell proliferation and drug resistance. A multi-targeted agent that simultaneously modulates activity of proteins important in mediating cell proliferation by functionally distinct intracellular pathways could have many potentially useful therapeutic applications. Full article
(This article belongs to the Special Issue Thioredoxin and Glutathione Systems)
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Open AccessArticle Determination of Phenolic Compounds and Antioxidant Activity in Leaves from Wild Rubus L. Species
Molecules 2015, 20(3), 4951-4966; doi:10.3390/molecules20034951
Received: 1 December 2014 / Accepted: 10 March 2015 / Published: 18 March 2015
Cited by 5 | PDF Full-text (791 KB) | HTML Full-text | XML Full-text
Abstract
Twenty-six different wild blackberry leaf samples were harvested from various localities throughout southeastern Poland. Leaf samples were assessed regarding their phenolic compound profiles and contents by LC/MS QTOF, and their antioxidant activity by ABTS and FRAP. Thirty-three phenolic compounds were detected (15 flavonols,
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Twenty-six different wild blackberry leaf samples were harvested from various localities throughout southeastern Poland. Leaf samples were assessed regarding their phenolic compound profiles and contents by LC/MS QTOF, and their antioxidant activity by ABTS and FRAP. Thirty-three phenolic compounds were detected (15 flavonols, 13 hydroxycinnamic acids, three ellagic acid derivatives and two flavones). Ellagic acid derivatives were the predominant compounds in the analyzed leaves, especially sanguiin H-6, ellagitannins, lambertianin C, and casuarinin. The content of phenolic compounds was significantly correlated with the antioxidant activity of the analyzed samples. The highest level of phenolic compounds was measured for R. perrobustus, R. wimmerianus, R. pedemontanus and R. grabowskii. The study showed that wild blackberry leaves can be considered a good source of antioxidant compounds. There is clear potential for the utilization of blackberry leaves as a food additive, medicinal source or herbal tea. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Auto-Thermal Reforming Using Mixed Ion-Electronic Conducting Ceramic Membranes for a Small-Scale H2 Production Plant
Molecules 2015, 20(3), 4998-5023; doi:10.3390/molecules20034998
Received: 19 January 2015 / Accepted: 11 March 2015 / Published: 18 March 2015
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Abstract
The integration of mixed ionic electronic conducting (MIEC) membranes for air separation in a small-to-medium scale unit for H2 production (in the range of 650–850 Nm3/h) via auto-thermal reforming of methane has been investigated in the present study. Membranes based
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The integration of mixed ionic electronic conducting (MIEC) membranes for air separation in a small-to-medium scale unit for H2 production (in the range of 650–850 Nm3/h) via auto-thermal reforming of methane has been investigated in the present study. Membranes based on mixed ionic electronic conducting oxides such as Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF) give sufficiently high oxygen fluxes at temperatures above 800 °C with high purity (higher than 99%). Experimental results of membrane permeation tests are presented and used for the reactor design with a detailed reactor model. The assessment of the H2 plant has been carried out for different operating conditions and reactor geometry and an energy analysis has been carried out with the flowsheeting software Aspen Plus, including also the turbomachines required for a proper thermal integration. A micro-gas turbine is integrated in the system in order to supply part of the electricity required in the system. The analysis of the system shows that the reforming efficiency is in the range of 62%–70% in the case where the temperature at the auto-thermal reforming membrane reactor (ATR-MR) is equal to 900 °C. When the electric consumption and the thermal export are included the efficiency of the plant approaches 74%–78%. The design of the reactor has been carried out using a reactor model linked to the Aspen flowsheet and the results show that with a larger reactor volume the performance of the system can be improved, especially because of the reduced electric consumption. From this analysis it has been found that for a production of about 790 Nm3/h pure H2, a reactor with a diameter of 1 m and length of 1.8 m with about 1500 membranes of 2 cm diameter is required. Full article
(This article belongs to the Special Issue Methane Reforming)
Open AccessArticle Secondary Metabolite Localization by Autofluorescence in Living Plant Cells
Molecules 2015, 20(3), 5024-5037; doi:10.3390/molecules20035024
Received: 3 June 2014 / Revised: 9 February 2015 / Accepted: 25 February 2015 / Published: 19 March 2015
Cited by 11 | PDF Full-text (3125 KB) | HTML Full-text | XML Full-text
Abstract
Autofluorescent molecules are abundant in plant cells and spectral images offer means for analyzing their spectra, yielding information on their accumulation and function. Based on their fluorescence characteristics, an imaging approach using multiphoton microscopy was designed to assess localization of the endogenous fluorophores
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Autofluorescent molecules are abundant in plant cells and spectral images offer means for analyzing their spectra, yielding information on their accumulation and function. Based on their fluorescence characteristics, an imaging approach using multiphoton microscopy was designed to assess localization of the endogenous fluorophores in living plant cells. This method, which requires no previous treatment, provides an effective experimental tool for discriminating between multiple naturally-occurring fluorophores in living-tissues. Combined with advanced Linear Unmixing, the spectral analysis extends the possibilities and enables the simultaneous detection of fluorescent molecules reliably separating overlapping emission spectra. However, as with any technology, the possibility for artifactual results does exist. This methodological article presents an overview of the applications of tissular and intra-cellular localization of these intrinsic fluorophores in leaves and fruits (here for coffee and vanilla). This method will provide new opportunities for studying cellular environments and the behavior of endogenous fluorophores in the intracellular environment. Full article
(This article belongs to the Special Issue Fluorescent Probes)
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Open AccessCommunication (−)-Tarchonanthuslactone Exerts a Blood Glucose-Increasing Effect in Experimental Type 2 Diabetes Mellitus
Molecules 2015, 20(3), 5038-5049; doi:10.3390/molecules20035038
Received: 8 December 2014 / Revised: 5 March 2015 / Accepted: 6 March 2015 / Published: 19 March 2015
Cited by 2 | PDF Full-text (995 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A number of studies have proposed an anti-diabetic effect for tarchonanthuslactone based on its structural similarity with caffeic acid, a compound known for its blood glucose-reducing properties. However, the actual effect of tarchonanthuslactone on blood glucose level has never been tested. Here, we
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A number of studies have proposed an anti-diabetic effect for tarchonanthuslactone based on its structural similarity with caffeic acid, a compound known for its blood glucose-reducing properties. However, the actual effect of tarchonanthuslactone on blood glucose level has never been tested. Here, we report that, in opposition to the common sense, tarchonanthuslactone has a glucose-increasing effect in a mouse model of obesity and type 2 diabetes mellitus. The effect is acute and non-cumulative and is present only in diabetic mice. In lean, glucose-tolerant mice, despite a slight increase in blood glucose levels, the effect was not significant. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Design, Synthesis and Insecticidal Activity of Novel Phenylurea Derivatives
Molecules 2015, 20(3), 5050-5061; doi:10.3390/molecules20035050
Received: 28 February 2015 / Revised: 14 March 2015 / Accepted: 17 March 2015 / Published: 19 March 2015
Cited by 1 | PDF Full-text (692 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of novel phenylurea derivatives were designed and synthesized according to the method of active groups linkage and the principle of aromatic groups bioisosterism in this study. The structures of the novel phenylurea derivatives were confirmed based on ESI-MS, IR and 1
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A series of novel phenylurea derivatives were designed and synthesized according to the method of active groups linkage and the principle of aromatic groups bioisosterism in this study. The structures of the novel phenylurea derivatives were confirmed based on ESI-MS, IR and 1H-NMR spectral data. All of the compounds were evaluated for the insecticidal activity against the third instars larvae of Spodoptera exigua Hiibner, Plutella xyllostella Linnaeus, Helicoverpa armigera Hubner and Pieris rapae Linne respectively, at the concentration of 10 mg/L. The results showed that all of the derivatives displayed strong insecticidal activity. Most of the compounds presented higher insecticidal activity against S. exigua than the reference compounds tebufenozide, chlorbenzuron and metaflumizone. Among the synthesized compounds, 3b, 3d, 3f, 4b and 4g displayed broad spectrum insecticidal activity. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Comparison of Two Species of Notopterygium by GC-MS and HPLC
Molecules 2015, 20(3), 5062-5073; doi:10.3390/molecules20035062
Received: 19 January 2015 / Revised: 2 March 2015 / Accepted: 4 March 2015 / Published: 19 March 2015
Cited by 5 | PDF Full-text (1579 KB) | HTML Full-text | XML Full-text
Abstract
Notopterygii Rhizoma et Radix (Qianghuo), including Notopterygium incisum Ting ex H. T. Chang (NI) and Notopterygium franchetii H. de Boiss (NF), is an important traditional Chinese medicine. Of these two plants, NI, is more commonly used and has a much higher price in
[...] Read more.
Notopterygii Rhizoma et Radix (Qianghuo), including Notopterygium incisum Ting ex H. T. Chang (NI) and Notopterygium franchetii H. de Boiss (NF), is an important traditional Chinese medicine. Of these two plants, NI, is more commonly used and has a much higher price in the marketplace. To compare these two plants, a combination of gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) was carried out, thus obtaining an overall characterization for both volatile and none-volatile compounds. Combined with hierarchical cluster analysis (HCA) and principal component analysis, GC-MS was successfully applied to distinguish NF and NI. The chemical constitutes of volatile oil in NI and NF were firstly compared in detail, and 1R-alpha-pinene, beta-pinene and 4-isopropyl-1-methyl-1,4-cyclohexadiene had great contribution to the discrimination. Fingerprints of 14 batches of Qinghuo samples were also established based on HPLC, and an obvious difference was found between the two species. The chromatographic fingerprints were further analyzed by similarity analysis and HCA. The present study is the first reported evaluation of two origins of Notopterygii Rhizoma et Radix by GC-MS and HPLC, which will facilitate quality control and its clinical application. Full article
Open AccessArticle Synthesis of Novel Dihydropyridothienopyrimidin-4,9-dione Derivatives
Molecules 2015, 20(3), 5074-5084; doi:10.3390/molecules20035074
Received: 27 January 2015 / Revised: 12 March 2015 / Accepted: 13 March 2015 / Published: 19 March 2015
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Abstract
A novel molecular scaffold, dihydropyridothienopyrimidin-4,9-dione, was synthesized from benzylamine or p-methoxybenzylamine in six steps involving successive ring closure to form a fused ring system composed of dihydropyridone, thiophene and pyrimidone. The pharmacological versatility of the dihydropyridothenopyrimidin-4,9-dione scaffold was demonstrated by inhibitory activity
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A novel molecular scaffold, dihydropyridothienopyrimidin-4,9-dione, was synthesized from benzylamine or p-methoxybenzylamine in six steps involving successive ring closure to form a fused ring system composed of dihydropyridone, thiophene and pyrimidone. The pharmacological versatility of the dihydropyridothenopyrimidin-4,9-dione scaffold was demonstrated by inhibitory activity against metabotropic glutamate receptor subtype 1 (mGluR1), which shows that the title compounds can serve as an interesting scaffold for the discovery of potential bioactive molecules for the treatment of human diseases. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Determination of the Molecular Weight of Low-Molecular-Weight Heparins by Using High-Pressure Size Exclusion Chromatography on Line with a Triple Detector Array and Conventional Methods
Molecules 2015, 20(3), 5085-5098; doi:10.3390/molecules20035085
Received: 30 January 2015 / Revised: 6 March 2015 / Accepted: 12 March 2015 / Published: 19 March 2015
Cited by 5 | PDF Full-text (919 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The evaluation of weight average molecular weight (Mw) and molecular weight distribution represents one of the most controversial aspects concerning the characterization of low molecular weight heparins (LMWHs). As the most commonly used method for the measurement of such parameters is high performance
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The evaluation of weight average molecular weight (Mw) and molecular weight distribution represents one of the most controversial aspects concerning the characterization of low molecular weight heparins (LMWHs). As the most commonly used method for the measurement of such parameters is high performance size exclusion chromatography (HP-SEC), the soundness of results mainly depends on the appropriate calibration of the chromatographic columns used. With the aim of meeting the requirement of proper Mw standards for LMWHs, in the present work the determination of molecular weight parameters (Mw and Mn) by HP-SEC combined with a triple detector array (TDA) was performed. The HP-SEC/TDA technique permits the evaluation of polymeric samples by exploiting the combined and simultaneous action of three on-line detectors: light scattering detectors (LALLS/RALLS); refractometer and viscometer. Three commercial LMWH samples, enoxaparin, tinzaparin and dalteparin, a γ-ray depolymerized heparin (γ-Hep) and its chromatographic fractions, and a synthetic pentasaccharide were analysed by HP-SEC/TDA. The same samples were analysed also with a conventional HP-SEC method employing refractive index (RI) and UV detectors and two different chromatographic column set, silica gel and polymeric gel columns. In both chromatographic systems, two different calibration curves were built up by using (i) γ-Hep chromatographic fractions and the corresponding Mw parameters obtained via HP-SEC/TDA; (ii) the whole γ-Hep preparation with broad Mw dispersion and the corresponding cumulative distribution function calculated via HP-SEC/TDA. In addition, also a chromatographic column calibration according to European Pharmacopoeia indication was built up. By comparing all the obtained results, some important differences among Mw and size distribution values of the three LMWHs were found with the five different calibration methods and with HP-SEC/TDA method. In particular, the detection of the lower molecular weight components turned out to be the most critical aspect. Whereas HP-SEC/TDA may underestimate species under 2 KDa when present in low concentration, other methods appeared to emphasize their content. Full article
(This article belongs to the Special Issue Glycosaminoglycans and Their Mimetics)
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Open AccessArticle Docking and Antiherpetic Activity of 2-Aminobenzo[de]-isoquinoline-1,3-diones
Molecules 2015, 20(3), 5099-5111; doi:10.3390/molecules20035099
Received: 27 January 2015 / Accepted: 9 March 2015 / Published: 19 March 2015
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Abstract
As part of our search for new compounds having antiviral effects, the prepared 2-aminonaphthalimide series was examined for its activity against the herpes simplex viruses HSV-1 and HSV-2. This represents the first study of the antiviral effects of this class of compounds. The
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As part of our search for new compounds having antiviral effects, the prepared 2-aminonaphthalimide series was examined for its activity against the herpes simplex viruses HSV-1 and HSV-2. This represents the first study of the antiviral effects of this class of compounds. The new series of 2-amino-1H-benzo[de]isoquinoline-1,3-diones was examined against HSV-1 and HSV-2 using a cytopathic effect inhibition assay. In terms of effective concentration (EC50), furaldehyde, thiophene aldehyde and allyl isothiocyanide derivatives 1416 showed potent activity against HSV-1 (EC50 = 19.6, 16.2 and 17.8 μg/mL), compared to acyclovir as a reference drug (EC50 = 1.8 μg/mL). Moreover, 14 and 15 were found to exhibit valuable activity against HSV-2. Many of the tested compounds demonstrated weak to moderate EC50 values relative to their inactive parent compound (2-amino-1H-benzo[de]isoquinoline-1,3-dione), while compounds 7, 9, 13, 14, 15, 16, 21 and 22 were the most active set of antiviral compounds throughout this study. The cytotoxicity (CC50), EC50, and the selectivity index (SI) values were determined. In a molecular docking study, the ligand-receptor interactions of compounds 124 and their parent with the HSV-1 thymidine kinase active site were investigated using the Molegro Virtual Docker (MVD) software. Based on the potent anti-HSV properties of the previous naphthalimide condensate products, further exploration of this series of 2-amino-1H-benzo[de]isoquinoline-1,3-diones is warranted. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Functional Characterization of Individual- and Mixed-Burgundian Saccharomyces cerevisiae Isolates for Fermentation of Pinot Noir
Molecules 2015, 20(3), 5112-5136; doi:10.3390/molecules20035112
Received: 8 January 2015 / Revised: 25 February 2015 / Accepted: 9 March 2015 / Published: 19 March 2015
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Abstract
Pinot noir has traditionally been fermented by native flora of multiple yeasts producing a complex combination of aromas and flavors. With the use of industrial dry yeasts, winemakers gained enological reliability and consistency in their wines, but lost diversity and complexity. This research
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Pinot noir has traditionally been fermented by native flora of multiple yeasts producing a complex combination of aromas and flavors. With the use of industrial dry yeasts, winemakers gained enological reliability and consistency in their wines, but lost diversity and complexity. This research evaluated the use of co-culturing yeasts to fulfill this dual role. Fermentations of Burgundian Saccharomyces cerevisiae isolates and their mixtures were evaluated for their enological characteristics and production of volatile compounds, at 22 °C and 27 °C. The novel isolates were genetically unique and enologically equivalent to the industrial strains. Analysis of variance and principal component analysis of 25 headspace volatiles revealed differences among the yeasts and between the fermentation temperatures. Wines from the mixed-Burgundian isolates were most similar to one another and could be differentiated from the industrial strains at both 22 °C and 27 °C. Mixed-Burgundian wines at both temperatures had higher concentrations of ethyl esters and acetate esters, compared to the industrial strains which had higher concentrations of higher alcohols at 27 °C and higher concentration of other ethyl esters at 22 °C. Given the unique profiles of the co-cultured wines, this research offers winemakers a strategy for producing wines with unique and more complex characters without the risk of spontaneous fermentations. Full article
(This article belongs to the collection Wine Chemistry)
Open AccessArticle Antiviral Activity of a Nanoemulsion of Polyprenols from Ginkgo Leaves against Influenza A H3N2 and Hepatitis B Virus in Vitro
Molecules 2015, 20(3), 5137-5151; doi:10.3390/molecules20035137
Received: 4 December 2014 / Revised: 2 March 2015 / Accepted: 10 March 2015 / Published: 19 March 2015
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Abstract
In order to improve the bioavailability levels of polyprenols (derived from ginkgo leaves (GBP)) in the human body, a GBP nanoemulsion was prepared, and its antiviral activity was evaluated against influenza A H3N2 and hepatitis B virus in vitro. Methods: A GBP
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In order to improve the bioavailability levels of polyprenols (derived from ginkgo leaves (GBP)) in the human body, a GBP nanoemulsion was prepared, and its antiviral activity was evaluated against influenza A H3N2 and hepatitis B virus in vitro. Methods: A GBP nanoemulsion was prepared by inversed-phase emulsification (IPE). Next, we investigated the antiviral activity of the GBP nanoemulsion on influenza A H3N2 and hepatitis B virus in vitro by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenlytetrezolium bromide) method. ELISA and the fluorescent quantitative PCR method were used to measure the content of HBsAg, HBeAg and DNA virus in human samples. Results: The GBP nanoemulsion exhibited uniformity at an average particle size 97 nm with a hydrophilic-lipophilic balance (HLB) of 9.5. GBP is non-toxic to normal cells, hepatitis B virus DNA, hepatitis B virus antigen and HepG2215. Furthermore, GBP could reach a 70% virucidal activity and a 74.9% protection rate (*** p < 0.001) on MDCK cells infected with H3N2 virus at a high concentration of 100 μg/mL. GBP had a good inhibition rate on HBsAg (52.11%, ** p < 0.01) at 50 μg/mL and Day 9 of incubation, and a 67.32% inhibition effect on HBeAg at a high concentration of 100 μg/mL and Day 9. GBP had good inhibition on HBV DNA with CT 18.6 and lower copies (** p < 0.01) at a middle concentration of 12.5 to 25 μg/mL. Conclusions: The GBP nanoemulsion was very stable and non-toxic and had very strong antiviral activity against influenza A H3N2 and hepatitis B virus in vitro. The inhibitory effects and reactive mechanisms were similar to the drug, 3TC; by lengthening the incubation time and increasing the drug concentration, GBP has promising potential as an antiviral drug. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Reduction of False Positives in Structure-Based Virtual Screening When Receptor Plasticity Is Considered
Molecules 2015, 20(3), 5152-5164; doi:10.3390/molecules20035152
Received: 5 February 2015 / Revised: 9 March 2015 / Accepted: 16 March 2015 / Published: 19 March 2015
Cited by 4 | PDF Full-text (2414 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Structure-based virtual screening for selecting potential drug candidates is usually challenged by how numerous false positives in a molecule library are excluded when receptor plasticity is considered. In this study, based on the binding energy landscape theory, a hypothesis that a true inhibitor
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Structure-based virtual screening for selecting potential drug candidates is usually challenged by how numerous false positives in a molecule library are excluded when receptor plasticity is considered. In this study, based on the binding energy landscape theory, a hypothesis that a true inhibitor can bind to different conformations of the binding site favorably was put forth, and related strategies to defeat this challenge were devised; reducing false positives when receptor plasticity is considered. The receptor in the study is the influenza A nucleoprotein, whose oligomerization is a requirement for RNA binding. The structural flexibility of influenza A nucleoprotein was explored by molecular dynamics simulations. The resultant distinctive structures and the crystal structure were used as receptor models in docking exercises in which two binding sites, the tail-loop binding pocket and the RNA binding site, were targeted with the Otava PrimScreen1 diversity-molecule library using the GOLD software. The intersection ligands that were listed in the top-ranked molecules from all receptor models were selected. Such selection strategy successfully distinguished high-affinity and low-affinity control molecules added to the molecule library. This work provides an applicable approach for reducing false positives and selecting true ligands from molecule libraries. Full article
(This article belongs to the Special Issue Molecular Docking in Drug Design)
Open AccessArticle Influence of Pea Protein Aggregates on the Structure and Stability of Pea Protein/Soybean Polysaccharide Complex Emulsions
Molecules 2015, 20(3), 5165-5183; doi:10.3390/molecules20035165
Received: 28 November 2014 / Revised: 14 March 2015 / Accepted: 16 March 2015 / Published: 20 March 2015
Cited by 6 | PDF Full-text (2473 KB) | HTML Full-text | XML Full-text
Abstract
The applications of plant proteins in the food and beverage industry have been hampered by their precipitation in acidic solution. In this study, pea protein isolate (PPI) with poor dispersibility in acidic solution was used to form complexes with soybean soluble polysaccharide (SSPS),
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The applications of plant proteins in the food and beverage industry have been hampered by their precipitation in acidic solution. In this study, pea protein isolate (PPI) with poor dispersibility in acidic solution was used to form complexes with soybean soluble polysaccharide (SSPS), and the effects of PPI aggregates on the structure and stability of PPI/SSPS complex emulsions were investigated. Under acidic conditions, high pressure homogenization disrupts the PPI aggregates and the electrostatic attraction between PPI and SSPS facilitates the formation of dispersible PPI/SSPS complexes. The PPI/SSPS complex emulsions prepared from the PPI containing aggregates prove to possess similar droplet structure and similar stability compared with the PPI/SSPS emulsions produced from the PPI in which the aggregates have been previously removed by centrifugation. The oil droplets are protected by PPI/SSPS complex interfacial films and SSPS surfaces. The emulsions show long-term stability against pH and NaCl concentration changes. This study demonstrates that PPI aggregates can also be used to produce stable complex emulsions, which may promote the applications of plant proteins in the food and beverage industry. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Syntheses of Nickel (II) Complexes from Novel Semicarbazone Ligands with Chloroformylarylhydrazine, Benzimidazole and Salicylaldehyde Moieties
Molecules 2015, 20(3), 5184-5201; doi:10.3390/molecules20035184
Received: 30 January 2015 / Revised: 11 March 2015 / Accepted: 13 March 2015 / Published: 20 March 2015
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Abstract
This study addressed the design and syntheses of diverse ligands, which were then successfully treated with Ni (II) ion to afford a series of nickel complexes. α-Chloroformylarylhydrazine hydrochlorides 6 contain two different functional groups. One is a strong nucleophile, and the other is
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This study addressed the design and syntheses of diverse ligands, which were then successfully treated with Ni (II) ion to afford a series of nickel complexes. α-Chloroformylarylhydrazine hydrochlorides 6 contain two different functional groups. One is a strong nucleophile, and the other is a good electrophile. Therefore, it can be designed to react with several reagents to obtain diverse derivatives which can be used as ligands for metal complexes. Furthermore, benzimidazole and salicylaldehyde can provide electron donor sites, N and O electron donors, separately. Hence, the starting materials α-chloroformylarylhydrazine hydrochlorides 6 were first treated with 2-(aminomethyl)-benzimidazole (7) to give the corresponding semicarbazides 8. Then, the semicarbazides 8 reacted with various substituted salicylaldehydes 911 to afford the desired substituted-salicylaldehyde 2-aryl-4-substituted semicarbazones 1214, which could coordinate with nickel (II) ion to give the corresponding nickel complexes 1517. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Selective C-Arylation of 2,5-Dibromo-3-hexylthiophene via Suzuki Cross Coupling Reaction and Their Pharmacological Aspects
Molecules 2015, 20(3), 5202-5214; doi:10.3390/molecules20035202
Received: 4 December 2014 / Revised: 6 February 2015 / Accepted: 16 February 2015 / Published: 23 March 2015
Cited by 4 | PDF Full-text (865 KB) | HTML Full-text | XML Full-text
Abstract
The present study reports the synthesis of various new derivatives based on 5-aryl-2-bromo-3-hexylthiophene with moderate-to-good yields via a palladium-catalyzed Suzuki cross-coupling reaction. This coupling method involved the reaction of 2,5-dibromo-3-hexylthiophene with several arylboronic acids in order to synthesize corresponding thiophene derivatives under controlled
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The present study reports the synthesis of various new derivatives based on 5-aryl-2-bromo-3-hexylthiophene with moderate-to-good yields via a palladium-catalyzed Suzuki cross-coupling reaction. This coupling method involved the reaction of 2,5-dibromo-3-hexylthiophene with several arylboronic acids in order to synthesize corresponding thiophene derivatives under controlled and optimal reaction conditions. The different substituents (CH3, OCH3, Cl, F etc.) present on arylboronic acids are found to have significant electronic effects on the overall properties of new products. The synthesized thiophene molecules were studied for their haemolytic, biofilm inhibition and anti-thrombolytic activities, and almost all products showed potentially good properties. The compound 2-bromo-5-(3-chloro-4-fluorophenyl)-3-hexylthiophenein particular exhibited the highest values for haemolytic and bio-film inhibition activities among all newly synthesized derivatives. In addition, the compound 2-bromo-3-hexyl-5-(4-iodophenyl)thiophene also showed high anti-thrombolytic activity, suggesting the potential medicinal applications of these newly synthesized compounds. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle iso-Petromyroxols: Novel Dihydroxylated Tetrahydrofuran Enantiomers from Sea Lamprey (Petromyzon marinus)
Molecules 2015, 20(3), 5215-5222; doi:10.3390/molecules20035215
Received: 17 February 2015 / Revised: 17 March 2015 / Accepted: 18 March 2015 / Published: 23 March 2015
Cited by 1 | PDF Full-text (959 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An enantiomeric pair of new fatty acid-derived hydroxylated tetrahydrofurans, here named iso-petromyroxols, were isolated from sea lamprey larvae-conditioned water. The relative configuration of iso-petromyroxol was elucidated with 1D and 2D NMR spectroscopic analyses. The ratio of enantiomers (er) in
[...] Read more.
An enantiomeric pair of new fatty acid-derived hydroxylated tetrahydrofurans, here named iso-petromyroxols, were isolated from sea lamprey larvae-conditioned water. The relative configuration of iso-petromyroxol was elucidated with 1D and 2D NMR spectroscopic analyses. The ratio of enantiomers (er) in the natural sample was measured by chiral-HPLC-MS/MS to be ca. 3:1 of (–)- to (+)-antipodes. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Effect of Pulsed Electric Fields on the Flavour Profile of Red-Fleshed Sweet Cherries (Prunus avium var. Stella)
Molecules 2015, 20(3), 5223-5238; doi:10.3390/molecules20035223
Received: 25 November 2014 / Revised: 25 February 2015 / Accepted: 10 March 2015 / Published: 23 March 2015
Cited by 4 | PDF Full-text (1000 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this research was to study the effect of pulsed electric fields (PEF) on the flavour profile of red-fleshed sweet cherries (Prunus avium variety Stella). The cherry samples were treated at a constant pulse frequency of 100 Hz, a constant
[...] Read more.
The aim of this research was to study the effect of pulsed electric fields (PEF) on the flavour profile of red-fleshed sweet cherries (Prunus avium variety Stella). The cherry samples were treated at a constant pulse frequency of 100 Hz, a constant pulse width of 20 μs, different electric field strengths between 0.3 and 2.5 kV/cm and specific energy ranging from 31 to 55 kJ/kg. Volatile compounds of samples were analysed using an automated headspace solid phase microextraction (HS–SPME) method coupled with gas chromatography-mass spectrometry (GC–MS). A total of 33 volatile compounds were identified with benzaldehyde, hexanal, (E)-2-hexenal, (Z)-2-hexen-1-ol, and benzyl alcohol being the predominant volatiles in different PEF-treated samples. Aldehydes namely butanal, octanal, 2-octenal, and nonanal, and (Z)-2-hexen-1-ol increased significantly 24 h after PEF treatment at electric field strengths of more than 1.0 kV/cm. Samples incubated for 24 h after PEF treatment (S3) generated higher concentrations of volatiles than samples immediately after PEF treatments (S2). Quantitative results revealed that more flavour volatiles were released and associated with S3 samples after 24 h storage and S2 samples immediately after PEF both with the highest electric field intensities. Interestingly, this study found that the PEF treatments at the applied electric field strength and energy did not result in releasing/producing undesirable flavour compounds. Full article
(This article belongs to the Special Issue Aromas and Volatiles of Fruits)
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Open AccessArticle Bacillus toyonensis Strain AEMREG6, a Bacterium Isolated from South African Marine Environment Sediment Samples Produces a Glycoprotein Bioflocculant
Molecules 2015, 20(3), 5239-5259; doi:10.3390/molecules20035239
Received: 26 February 2015 / Revised: 15 March 2015 / Accepted: 17 March 2015 / Published: 23 March 2015
Cited by 12 | PDF Full-text (1720 KB) | HTML Full-text | XML Full-text
Abstract
A bioflocculant-producing bacteria, isolated from sediment samples of a marine environment in the Eastern Cape Province of South Africa demonstrated a flocculating activity above 60% for kaolin clay suspension. Analysis of the 16S ribosomal deoxyribonucleic acid (rDNA) nucleotide sequence of the isolate in
[...] Read more.
A bioflocculant-producing bacteria, isolated from sediment samples of a marine environment in the Eastern Cape Province of South Africa demonstrated a flocculating activity above 60% for kaolin clay suspension. Analysis of the 16S ribosomal deoxyribonucleic acid (rDNA) nucleotide sequence of the isolate in the GenBank database showed 99% similarity to Bacillus toyonensis strain BCT-7112 and it was deposited in the GenBank as Bacillus toyonensis strain AEMREG6 with accession number KP406731. The bacteria produced a bioflocculant (REG-6) optimally in the presence of glucose and NH4NO3 as the sole carbon and nitrogen source, respectively, initial medium pH of 5 and Ca2+ as the cation of choice. Chemical analysis showed that purified REG-6 was a glycoprotein mainly composed of polysaccharide (77.8%) and protein (11.5%). It was thermally stable and had strong flocculating activity against kaolin suspension over a wide range of pH values (3–11) with a relatively low dosage requirement of 0.1 mg/mL in the presence of Mn2+. Fourier transform infrared spectroscopy (FTIR) revealed the presence of hydroxyl, carboxyl and amide groups preferred for flocculation. Scanning electron microscopy (SEM) revealed that bridging was the main flocculation mechanism of REG-6. The outstanding flocculating performance of REG-6 holds great potential to replace the hazardous chemical flocculants currently used in water treatment. Full article
(This article belongs to the Section Natural Products)

Review

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Open AccessReview Glycosaminoglycans and Glycomimetics in the Central Nervous System
Molecules 2015, 20(3), 3527-3548; doi:10.3390/molecules20033527
Received: 22 January 2015 / Revised: 9 February 2015 / Accepted: 13 February 2015 / Published: 19 February 2015
Cited by 8 | PDF Full-text (425 KB) | HTML Full-text | XML Full-text
Abstract
With recent advances in the construction of synthetic glycans, selective targeting of the extracellular matrix (ECM) as a potential treatment for a wide range of diseases has become increasingly popular. The use of compounds that mimic the structure or bioactive function of carbohydrate
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With recent advances in the construction of synthetic glycans, selective targeting of the extracellular matrix (ECM) as a potential treatment for a wide range of diseases has become increasingly popular. The use of compounds that mimic the structure or bioactive function of carbohydrate structures has been termed glycomimetics. These compounds are mostly synthetic glycans or glycan-binding constructs which manipulate cellular interactions. Glycosaminoglycans (GAGs) are major components of the ECM and exist as a diverse array of differentially sulphated disaccharide units. In the central nervous system (CNS), they are expressed by both neurons and glia and are crucial for brain development and brain homeostasis. The inherent diversity of GAGs make them an essential biological tool for regulating a complex range of cellular processes such as plasticity, cell interactions and inflammation. They are also involved in the pathologies of various neurological disorders, such as glial scar formation and psychiatric illnesses. It is this diversity of functions and potential for selective interventions which makes GAGs a tempting target. In this review, we shall describe the molecular make-up of GAGs and their incorporation into the ECM of the CNS. We shall highlight the different glycomimetic strategies that are currently being used in the nervous system. Finally, we shall discuss some possible targets in neurological disorders that may be addressed using glycomimetics. Full article
(This article belongs to the Special Issue Glycosaminoglycans and Their Mimetics)
Open AccessReview Lectins with Potential for Anti-Cancer Therapy
Molecules 2015, 20(3), 3791-3810; doi:10.3390/molecules20033791
Received: 2 December 2014 / Revised: 13 February 2015 / Accepted: 15 February 2015 / Published: 26 February 2015
Cited by 38 | PDF Full-text (929 KB) | HTML Full-text | XML Full-text
Abstract
This article reviews lectins of animal and plant origin that induce apoptosis and autophagy of cancer cells and hence possess the potential of being developed into anticancer drugs. Apoptosis-inducing lectins encompass galectins, C-type lectins, annexins, Haliotis discus discus lectin, Polygonatum odoratum lectin, mistletoe
[...] Read more.
This article reviews lectins of animal and plant origin that induce apoptosis and autophagy of cancer cells and hence possess the potential of being developed into anticancer drugs. Apoptosis-inducing lectins encompass galectins, C-type lectins, annexins, Haliotis discus discus lectin, Polygonatum odoratum lectin, mistletoe lectin, and concanavalin A, fucose-binding Dicentrarchus labrax lectin, and Strongylocentrotus purpuratus lectin, Polygonatum odoratum lectin, and mistletoe lectin, Polygonatum odoratum lectin, autophagy inducing lectins include annexins and Polygonatum odoratum lectin. Full article
(This article belongs to the Special Issue Lectins)
Open AccessReview Rational Drug Design and Synthesis of Molecules Targeting the Angiotensin II Type 1 and Type 2 Receptors
Molecules 2015, 20(3), 3868-3897; doi:10.3390/molecules20033868
Received: 18 December 2014 / Revised: 6 February 2015 / Accepted: 15 February 2015 / Published: 2 March 2015
Cited by 12 | PDF Full-text (6408 KB) | HTML Full-text | XML Full-text
Abstract
The angiotensin II (Ang II) type 1 and type 2 receptors (AT1R and AT2R) orchestrate an array of biological processes that regulate human health. Aberrant function of these receptors triggers pathophysiological responses that can ultimately lead to death. Therefore,
[...] Read more.
The angiotensin II (Ang II) type 1 and type 2 receptors (AT1R and AT2R) orchestrate an array of biological processes that regulate human health. Aberrant function of these receptors triggers pathophysiological responses that can ultimately lead to death. Therefore, it is important to design and synthesize compounds that affect beneficially these two receptors. Cardiovascular disease, which is attributed to the overactivation of the vasoactive peptide hormone Αng II, can now be treated with commercial AT1R antagonists. Herein, recent achievements in rational drug design and synthesis of molecules acting on the two AT receptors are reviewed. Quantitative structure activity relationships (QSAR) and molecular modeling on the two receptors aim to assist the search for new active compounds. As AT1R and AT2R are GPCRs and drug action is localized in the transmembrane region the role of membrane bilayers is exploited. The future perspectives in this field are outlined. Tremendous progress in the field is expected if the two receptors are crystallized, as this will assist the structure based screening of the chemical space and lead to new potent therapeutic agents in cardiovascular and other diseases. Full article
Open AccessReview Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents
Molecules 2015, 20(3), 3898-3941; doi:10.3390/molecules20033898
Received: 26 December 2014 / Revised: 13 February 2015 / Accepted: 15 February 2015 / Published: 2 March 2015
Cited by 146 | PDF Full-text (1114 KB) | HTML Full-text | XML Full-text
Abstract
Histone dacetylases (HDACs) are a group of enzymes that remove acetyl groups from histones and regulate expression of tumor suppressor genes. They are implicated in many human diseases, especially cancer, making them a promising therapeutic target for treatment of the latter by developing
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Histone dacetylases (HDACs) are a group of enzymes that remove acetyl groups from histones and regulate expression of tumor suppressor genes. They are implicated in many human diseases, especially cancer, making them a promising therapeutic target for treatment of the latter by developing a wide variety of inhibitors. HDAC inhibitors interfere with HDAC activity and regulate biological events, such as cell cycle, differentiation and apoptosis in cancer cells. As a result, HDAC inhibitor-based therapies have gained much attention for cancer treatment. To date, the FDA has approved three HDAC inhibitors for cutaneous/peripheral T-cell lymphoma and many more HDAC inhibitors are in different stages of clinical development for the treatment of hematological malignancies as well as solid tumors. In the intensifying efforts to discover new, hopefully more therapeutically efficacious HDAC inhibitors, molecular modeling-based rational drug design has played an important role in identifying potential inhibitors that vary in molecular structures and properties. In this review, we summarize four major structural classes of HDAC inhibitors that are in clinical trials and different computer modeling tools available for their structural modifications as a guide to discover additional HDAC inhibitors with greater therapeutic utility. Full article
Open AccessReview Untargeted NMR-Based Methodology in the Study of Fruit Metabolites
Molecules 2015, 20(3), 4088-4108; doi:10.3390/molecules20034088
Received: 23 December 2014 / Revised: 17 February 2015 / Accepted: 26 February 2015 / Published: 4 March 2015
Cited by 12 | PDF Full-text (1106 KB) | HTML Full-text | XML Full-text
Abstract
In this review, fundamental aspects of the untargeted NMR-based methodology applied to fruit characterization are described. The strategy to perform the structure elucidation of fruit metabolites is discussed with some examples of spectral assignments by 2D experiments. Primary ubiquitous metabolites as well as
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In this review, fundamental aspects of the untargeted NMR-based methodology applied to fruit characterization are described. The strategy to perform the structure elucidation of fruit metabolites is discussed with some examples of spectral assignments by 2D experiments. Primary ubiquitous metabolites as well as secondary species-specific metabolites, identified in different fruits using an untargeted 1H-NMR approach, are summarized in a comprehensive way. Crucial aspects regarding the quantitative elaboration of spectral data are also discussed. The usefulness of the NMR-based metabolic profiling was highlighted using some results regarding quality, adulteration, varieties and geographical origin of fruits and fruit-derived products such as juices. Full article
(This article belongs to the Section Metabolites)
Open AccessReview Natural Products for the Treatment of Trachoma and Chlamydia trachomatis
Molecules 2015, 20(3), 4180-4203; doi:10.3390/molecules20034180
Received: 15 December 2014 / Revised: 11 February 2015 / Accepted: 24 February 2015 / Published: 5 March 2015
Cited by 6 | PDF Full-text (7225 KB) | HTML Full-text | XML Full-text
Abstract
The neglected tropical disease (NTD) trachoma is currently the leading cause of eye disease in the world, and the pathogenic bacteria causing this condition, Chlamydia trachomatis, is also the most common sexually transmitted pathogenic bacterium. Although the serovars of this bacterial species typically
[...] Read more.
The neglected tropical disease (NTD) trachoma is currently the leading cause of eye disease in the world, and the pathogenic bacteria causing this condition, Chlamydia trachomatis, is also the most common sexually transmitted pathogenic bacterium. Although the serovars of this bacterial species typically vary between ocular and genital infections there is a clear connection between genital C. trachomatis infections and the development of trachoma in infants, such that the solutions to these infections are closely related. It is the unique life cycle of the C. trachomatis bacteria which primarily leads to chronic infections and challenges in treatment using conventional antibiotics. This life cycle involves stages of infective elementary bodies (EBs) and reproductive reticulate bodies (RBs). Most antibiotics only target the reproductive RBs and this often leads to the need for prolonged therapy which facilitates the development of drug resistant pathogens. It is through combining several compounds to obtain multiple antimicrobial mechanisms that we are most likely to develop a reliable means to address all these issues. Traditional and ethnobotanical medicine provides valuable resources for the development of novel formulations and treatment regimes based on synergistic and multi-compound therapy. In this review we intend to summarize the existing literature on the application of natural compounds for controlling trachoma and inhibiting chlamydial bacteria and explore the potential for the development of new treatment modalities. Full article
Open AccessReview Can We Produce Heparin/Heparan Sulfate Biomimetics Using “Mother-Nature” as the Gold Standard?
Molecules 2015, 20(3), 4254-4276; doi:10.3390/molecules20034254
Received: 16 January 2015 / Revised: 13 February 2015 / Accepted: 26 February 2015 / Published: 5 March 2015
Cited by 10 | PDF Full-text (866 KB) | HTML Full-text | XML Full-text
Abstract
Heparan sulfate (HS) and heparin are glycosaminoglycans (GAGs) that are heterogeneous in nature, not only due to differing disaccharide combinations, but also their sulfate modifications. HS is well known for its interactions with various growth factors and cytokines; and heparin for its clinical
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Heparan sulfate (HS) and heparin are glycosaminoglycans (GAGs) that are heterogeneous in nature, not only due to differing disaccharide combinations, but also their sulfate modifications. HS is well known for its interactions with various growth factors and cytokines; and heparin for its clinical use as an anticoagulant. Due to their potential use in tissue regeneration; and the recent adverse events due to contamination of heparin; there is an increased surge to produce these GAGs on a commercial scale. The production of HS from natural sources is limited so strategies are being explored to be biomimetically produced via chemical; chemoenzymatic synthesis methods and through the recombinant expression of proteoglycans. This review details the most recent advances in the field of HS/heparin synthesis for the production of low molecular weight heparin (LMWH) and as a tool further our understanding of the interactions that occur between GAGs and growth factors and cytokines involved in tissue development and repair. Full article
(This article belongs to the Special Issue Glycosaminoglycans and Their Mimetics)
Open AccessReview Discrepancies in Composition and Biological Effects of Different Formulations of Chondroitin Sulfate
Molecules 2015, 20(3), 4277-4289; doi:10.3390/molecules20034277
Received: 14 January 2015 / Revised: 25 February 2015 / Accepted: 26 February 2015 / Published: 6 March 2015
Cited by 14 | PDF Full-text (685 KB) | HTML Full-text | XML Full-text
Abstract
Osteoarthritis is a common, progressive joint disease, and treatments generally aim for symptomatic improvement. However, SYmptomatic Slow-Acting Drugs in Osteoarthritis (SYSADOAs) not only reduce joint pain, but slow structural disease progression. One such agent is chondroitin sulfate—a complex, heterogeneous polysaccharide. It is extracted
[...] Read more.
Osteoarthritis is a common, progressive joint disease, and treatments generally aim for symptomatic improvement. However, SYmptomatic Slow-Acting Drugs in Osteoarthritis (SYSADOAs) not only reduce joint pain, but slow structural disease progression. One such agent is chondroitin sulfate—a complex, heterogeneous polysaccharide. It is extracted from various animal cartilages, thus has a wide range of molecular weights and different amounts and patterns of sulfation. Chondroitin sulfate has an excellent safety profile, and although various meta-analyses have concluded that it has a beneficial effect on symptoms and structure, others have concluded little or no benefit. This may be due, at least partly, to variations in the quality of the chondroitin sulfate used for a particular study. Chondroitin sulfate is available as pharmaceutical- and nutraceutical-grade products, and the latter have great variations in preparation, composition, purity and effects. Moreover, some products contain a negligible amount of chondroitin sulfate and among samples with reasonable amounts, in vitro testing showed widely varying effects. Of importance, although some showed anti-inflammatory effects, others demonstrated weak effects, and some instances were even pro-inflammatory. This could be related to contaminants, which depend on the origin, production and purification process. It is therefore vitally important that only pharmaceutical-grade chondroitin sulfate be used for treating osteoarthritis patients. Full article
(This article belongs to the Special Issue Glycosaminoglycans and Their Mimetics)
Open AccessReview Development of Advanced Macrosphelides: Potent Anticancer Agents
Molecules 2015, 20(3), 4430-4449; doi:10.3390/molecules20034430
Received: 4 February 2015 / Revised: 1 March 2015 / Accepted: 6 March 2015 / Published: 10 March 2015
Cited by 2 | PDF Full-text (2526 KB) | HTML Full-text | XML Full-text
Abstract
Synthetic approaches to macrosphelide derivatives, based on medicinal chemistry, are summarized. This review contains conventional medicinal chemistry approaches, combinatorial chemistry, fluorous tagging techniques and affinity chromatography preparation. In addition, advances in their apoptosis-inducing activities are also included. Full article
Open AccessReview Potential Role of Olive Oil Phenolic Compounds in the Prevention of Neurodegenerative Diseases
Molecules 2015, 20(3), 4655-4680; doi:10.3390/molecules20034655
Received: 23 January 2015 / Revised: 3 March 2015 / Accepted: 5 March 2015 / Published: 13 March 2015
Cited by 31 | PDF Full-text (562 KB) | HTML Full-text | XML Full-text
Abstract
Adherence to the Mediterranean Diet (MD) has been associated with a reduced incidence of neurodegenerative diseases and better cognitive performance. Virgin olive oil, the main source of lipids in the MD, is rich in minor phenolic components, particularly hydroxytyrosol (HT). HT potent antioxidant
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Adherence to the Mediterranean Diet (MD) has been associated with a reduced incidence of neurodegenerative diseases and better cognitive performance. Virgin olive oil, the main source of lipids in the MD, is rich in minor phenolic components, particularly hydroxytyrosol (HT). HT potent antioxidant and anti-inflammatory actions have attracted researchers’ attention and may contribute to neuroprotective effects credited to MD. In this review HT bioavailability and pharmacokinetics are presented prior to discussing health beneficial effects. In vitro and in vivo neuroprotective effects together with its multiple mechanisms of action are reviewed. Other microconstituents of olive oil are also considered due to their potential neuroprotective effects (oleocanthal, triterpenic acids). Finally, we discuss the potential role of HT as a therapeutic tool in the prevention of neurodegenerative diseases. Full article
Open AccessReview Anti-Allergic Properties of Curine, a Bisbenzylisoquinoline Alkaloid
Molecules 2015, 20(3), 4695-4707; doi:10.3390/molecules20034695
Received: 31 October 2014 / Revised: 13 February 2015 / Accepted: 16 February 2015 / Published: 13 March 2015
Cited by 2 | PDF Full-text (1123 KB) | HTML Full-text | XML Full-text
Abstract
Curine is a bisbenzylisoquinoline alkaloid isolated from Chondrodendron platyphyllum (Menispermaceae). Recent findings have shed light on the actions of curine in different models of allergy and inflammation. Here we review the properties and mechanisms of action of curine focusing on its anti-allergic effects.
[...] Read more.
Curine is a bisbenzylisoquinoline alkaloid isolated from Chondrodendron platyphyllum (Menispermaceae). Recent findings have shed light on the actions of curine in different models of allergy and inflammation. Here we review the properties and mechanisms of action of curine focusing on its anti-allergic effects. Curine pre-treatment significantly inhibited the scratching behavior, paw edema and systemic anaphylaxis induced by either ovalbumin (OVA) in sensitized animals or compound 48/80, through mechanisms of mast cell stabilization and inhibition of mast cell activation to generate lipid mediators. In addition, oral administration of curine significantly inhibited eosinophil recruitment and activation, as well as, OVA-induced airway hyper-responsiveness in a mouse model of asthma, through inhibition of the production of IL-13 and eotaxin, and of Ca2+ influx. In conclusion, curine exhibit anti-allergic effects in models of lung, skin and systemic allergy in the absence of significant toxicity, and as such has the potential for anti-allergic drug development. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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Open AccessReview QM/MM Calculations with deMon2k
Molecules 2015, 20(3), 4780-4812; doi:10.3390/molecules20034780
Received: 19 September 2014 / Revised: 25 February 2015 / Accepted: 2 March 2015 / Published: 16 March 2015
Cited by 5 | PDF Full-text (2130 KB) | HTML Full-text | XML Full-text
Abstract
The density functional code deMon2k employs a fitted density throughout (Auxiliary Density Functional Theory), which offers a great speed advantage without sacrificing necessary accuracy. Powerful Quantum Mechanical/Molecular Mechanical (QM/MM) approaches are reviewed. Following an overview of the basic features of deMon2k that make
[...] Read more.
The density functional code deMon2k employs a fitted density throughout (Auxiliary Density Functional Theory), which offers a great speed advantage without sacrificing necessary accuracy. Powerful Quantum Mechanical/Molecular Mechanical (QM/MM) approaches are reviewed. Following an overview of the basic features of deMon2k that make it efficient while retaining accuracy, three QM/MM implementations are compared and contrasted. In the first, deMon2k is interfaced with the CHARMM MM code (CHARMM-deMon2k); in the second MM is coded directly within the deMon2k software; and in the third the Chemistry in Ruby (Cuby) wrapper is used to drive the calculations. Cuby is also used in the context of constrained-DFT/MM calculations. Each of these implementations is described briefly; pros and cons are discussed and a few recent applications are described briefly. Applications include solvated ions and biomolecules, polyglutamine peptides important in polyQ neurodegenerative diseases, copper monooxygenases and ultra-rapid electron transfer in cryptochromes. Full article
Open AccessReview Modification of Purine and Pyrimidine Nucleosides by Direct C-H Bond Activation
Molecules 2015, 20(3), 4874-4901; doi:10.3390/molecules20034874
Received: 15 February 2015 / Revised: 11 March 2015 / Accepted: 13 March 2015 / Published: 17 March 2015
Cited by 15 | PDF Full-text (1785 KB) | HTML Full-text | XML Full-text
Abstract
Transition metal-catalyzed modifications of the activated heterocyclic bases of nucleosides as well as DNA or RNA fragments employing traditional cross-coupling methods have been well-established in nucleic acid chemistry. This review covers advances in the area of cross-coupling reactions in which nucleosides are functionalized
[...] Read more.
Transition metal-catalyzed modifications of the activated heterocyclic bases of nucleosides as well as DNA or RNA fragments employing traditional cross-coupling methods have been well-established in nucleic acid chemistry. This review covers advances in the area of cross-coupling reactions in which nucleosides are functionalized via direct activation of the C8-H bond in purine and the C5-H or C6-H bond in uracil bases. The review focuses on Pd/Cu-catalyzed couplings between unactivated nucleoside bases with aryl halides. It also discusses cross-dehydrogenative arylations and alkenylations as well as other reactions used for modification of nucleoside bases that avoid the use of organometallic precursors and involve direct C-H bond activation in at least one substrate. The scope and efficiency of these coupling reactions along with some mechanistic considerations are discussed. Full article
(This article belongs to the Special Issue Nucleoside Modifications) Printed Edition available
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Open AccessReview Synthesis of C-Arylnucleoside Analogues
Molecules 2015, 20(3), 4967-4997; doi:10.3390/molecules20034967
Received: 24 January 2015 / Accepted: 10 March 2015 / Published: 18 March 2015
Cited by 2 | PDF Full-text (1086 KB) | HTML Full-text | XML Full-text
Abstract
Modified nucleoside analogues are of great biological importance as antiviral and antitumoral agents. There is special interest in the preparation of C-aryl nucleosides with an aromatic ring in different positions of the glycone for their biological activity. Different chemical synthesis strategies for
[...] Read more.
Modified nucleoside analogues are of great biological importance as antiviral and antitumoral agents. There is special interest in the preparation of C-aryl nucleosides with an aromatic ring in different positions of the glycone for their biological activity. Different chemical synthesis strategies for these targets are described in this review. Full article
(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Organic Chemistry)
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Open AccessCorrection Correction: Chapman, E.; et al. Inhibitors of the AAA+ Chaperone p97. Molecules 2015, 20, 3027-3049
Molecules 2015, 20(3), 4357-4358; doi:10.3390/molecules20034357
Received: 2 March 2015 / Accepted: 4 March 2015 / Published: 9 March 2015
Cited by 1 | PDF Full-text (1451 KB) | HTML Full-text | XML Full-text
Abstract
The authors wish to make the following correction to paper [1], doi:10.3390/molecules20023027, website: http://www.mdpi.com/1420-3049/20/2/3027/. [...] Full article
(This article belongs to the Section Medicinal Chemistry)

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