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Molecules, Volume 18, Issue 10 (October 2013), Pages 11658-13123

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Open AccessArticle The Clip-Segment of the von Willebrand Domain 1 of the BMP Modulator Protein Crossveinless 2 Is Preformed
Molecules 2013, 18(10), 11658-11682; doi:10.3390/molecules181011658
Received: 2 August 2013 / Revised: 17 September 2013 / Accepted: 17 September 2013 / Published: 25 September 2013
Cited by 3 | PDF Full-text (2817 KB) | HTML Full-text | XML Full-text
Abstract
Bone Morphogenetic Proteins (BMPs) are secreted protein hormones that act as morphogens and exert essential roles during embryonic development of tissues and organs. Signaling by BMPs occurs via hetero-oligomerization of two types of serine/threonine kinase transmembrane receptors. Due to the small number of
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Bone Morphogenetic Proteins (BMPs) are secreted protein hormones that act as morphogens and exert essential roles during embryonic development of tissues and organs. Signaling by BMPs occurs via hetero-oligomerization of two types of serine/threonine kinase transmembrane receptors. Due to the small number of available receptors for a large number of BMP ligands ligand-receptor promiscuity presents an evident problem requiring additional regulatory mechanisms for ligand-specific signaling. Such additional regulation is achieved through a plethora of extracellular antagonists, among them members of the Chordin superfamily, that modulate BMP signaling activity by binding. The key-element in Chordin-related antagonists for interacting with BMPs is the von Willebrand type C (VWC) module, which is a small domain of about 50 to 60 residues occurring in many different proteins. Although a structure of the VWC domain of the Chordin-member Crossveinless 2 (CV2) bound to BMP-2 has been determined by X-ray crystallography, the molecular mechanism by which the VWC domain binds BMPs has remained unclear. Here we present the NMR structure of the Danio rerio CV2 VWC1 domain in its unbound state showing that the key features for high affinity binding to BMP-2 is a pre-oriented peptide loop. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
Open AccessArticle Characterization of Amide Bond Conformers for a Novel Heterocyclic Template of N-acylhydrazone Derivatives
Molecules 2013, 18(10), 11683-11704; doi:10.3390/molecules181011683
Received: 4 August 2013 / Revised: 10 September 2013 / Accepted: 13 September 2013 / Published: 25 September 2013
Cited by 16 | PDF Full-text (970 KB) | HTML Full-text | XML Full-text
Abstract
Herein we describe NMR experiments and structural modifications of 4-methyl-2-phenylpyrimidine-N-acylhydrazone compounds (aryl-NAH) in order to discover if duplication of some signals in their 1H- and 13C-NMR spectra was related to a mixture of imine double bond stereoisomers (E/Z
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Herein we describe NMR experiments and structural modifications of 4-methyl-2-phenylpyrimidine-N-acylhydrazone compounds (aryl-NAH) in order to discover if duplication of some signals in their 1H- and 13C-NMR spectra was related to a mixture of imine double bond stereoisomers (E/Z) or CO-NH bond conformers (syn and anti-periplanar). NMR data from NOEdiff, 2D-NOESY and 1H-NMR spectra at different temperatures, and also the synthesis of isopropylidene hydrazone revealed the nature of duplicated signals of a 4-methyl-2-phenylpyrimidine-N-acylhydrazone derivative as a mixture of two conformers in solution. Further we investigated the stereoelectronic influence of substituents at the ortho position on the pyrimidine ring with respect to the carbonyl group, as well as the electronic effects of pyrimidine by changing it to phenyl. The conformer equilibrium was attributed to the decoplanarization of the aromatic ring and carbonyl group (generated by an ortho-alkyl group) and/or the electron withdrawing character of the pyrimidine ring. Both effects increased the rotational barrier of the C-N amide bond, as verified by the DG values calculated from dynamic NMR. As far as we know, it is the first description of aryl-NAH compounds presenting two CO-NH bond- related conformations. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
Open AccessArticle Modes of Neighbouring Group Participation by the Methyl Selenyl Substituent in β-Methylselenylmethyl-substituted 1-Phenylethyl Carbenium Ions
Molecules 2013, 18(10), 11705-11711; doi:10.3390/molecules181011705
Received: 29 July 2013 / Revised: 7 September 2013 / Accepted: 9 September 2013 / Published: 25 September 2013
Cited by 1 | PDF Full-text (461 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Selenium substituents which are disposed β to an electron deficient centre, such as a carbocation p-orbital, or the π* orbital of an electron deficient p-system, interact in a stabilising way by a combination of C-Se hyperconjugation (σSe-Cπ* interaction),
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Selenium substituents which are disposed β to an electron deficient centre, such as a carbocation p-orbital, or the π* orbital of an electron deficient p-system, interact in a stabilising way by a combination of C-Se hyperconjugation (σSe-Cπ* interaction), and a through-space homoconjugative nSe–π* interaction. The relative importance of these two modes of interaction is dependant on the electron demand of the cation, with hyperconjugation predominating for low electron demand systems, and the nSe–π* interaction predominating for high electron demand cations. Full article
(This article belongs to the Special Issue Selenium and Tellurium Chemistry)
Open AccessArticle A Commonly Used Chinese Herbal Formula, Shu-Jing-Hwo-Shiee-Tang, Potentiates Anticoagulant Activity of Warfarin in a Rabbit Model
Molecules 2013, 18(10), 11712-11723; doi:10.3390/molecules181011712
Received: 13 June 2013 / Revised: 16 September 2013 / Accepted: 16 September 2013 / Published: 25 September 2013
Cited by 5 | PDF Full-text (315 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Background: Drug interactions between traditional Chinese herbal medicines and the anticoagulant warfarin may cause patient harm and are, therefore, important in clinical practice. Our experience in daily practice suggests that prothrombin time (PT) is prolonged when warfarin is used in combination with
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Background: Drug interactions between traditional Chinese herbal medicines and the anticoagulant warfarin may cause patient harm and are, therefore, important in clinical practice. Our experience in daily practice suggests that prothrombin time (PT) is prolonged when warfarin is used in combination with the Chinese herbal formula Shu-Jing-Hwo-Shiee-Tang (SJHST) commonly used by patients with osteoarthritis. Objective: We conducted animal experiments to confirm the effect of SJHST and warfarin on anticoagulant activity. Methods: Forty-eight male New Zealand white rabbits were randomized into eight groups of six rabbits. Group A (Control group) was administered normal saline. Group B (Western Medicine group) was administered warfarin 1.5 mg/kg/day. Groups C, D, and E [Traditional Chinese Medicine (TCM) groups] were administered different doses of SJHST (0.5 mg/kg/day, 1 mg/kg/day, and 2 mg/kg/day, respectively). Groups F, G, and H (Combination Therapy groups) were administered warfarin 1.5 mg/kg/day and different doses of SJHST (0.5 mg/kg/day, 1 mg/kg/day, and 2 mg/kg/day, respectively). The total duration of treatment was 14 days. Blood samples were obtained prior to beginning the experiments (day 0) and on day 7, day 14, and day 17 (3 days after discontinuation of the medications). The activated partial thromboplastin time (APTT), PT, and thrombin time (TT) were calculated and compared among the different groups. Results: No significant changes were noted in APTT, PT or TT between the control and SJHST-only groups. Significant prolongations of APTT and PTT, but not TT, were observed in the combination groups compared to the warfarin-only group. The enhanced anticoagulant effects returned to normal three days after discontinuation of SJHST treatment. Conclusions: We confirmed that the Chinese herb SJHST enhances the anticoagulant effect of warfarin. Although the exact mechanisms of the interaction are unknown, physicians should be aware of the possibility of drug interactions between warfarin and Chinese herbal medicines owing to the increased risk of bleeding. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Impact of Origin and Biological Source on Chemical Composition, Anticholinesterase and Antioxidant Properties of Some St. John’s Wort Species (Hypericum spp., Hypericaceae) from the Central Balkans
Molecules 2013, 18(10), 11733-11750; doi:10.3390/molecules181011733
Received: 9 August 2013 / Revised: 10 September 2013 / Accepted: 12 September 2013 / Published: 25 September 2013
Cited by 11 | PDF Full-text (360 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The study shows the influence of the origin of plant material and biological source on the in vitro antioxidant (neutralization of DPPH and OH radical, nitric oxide, and inhibition of lipid peroxidation) and anticholinesterase activity of chemically characterized and quantified ethanol extracts of
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The study shows the influence of the origin of plant material and biological source on the in vitro antioxidant (neutralization of DPPH and OH radical, nitric oxide, and inhibition of lipid peroxidation) and anticholinesterase activity of chemically characterized and quantified ethanol extracts of ten St. John’s wort samples. The investigated samples were: five Hypericum perforatum species representatives collected at different localities, one commercial sample of Hyperici herba purchased at a local market and four Hypericum species autochtonous to the Balkan Peninsula (H. maculatum subsp. immaculatum, H. olympicum, H. richeri subsp. grisebachii and H. barbatum). All the examined extracts exhibited notable antioxidant potential, but in most of the cases indigenous Hypericum species expressed stronger effects compared to the original source of the drug, H. perforatum. The changes in the content of phenolic compounds, especially flavonoids, hyperforin and hypericin, related to the source of the drug affected the investigated activities. Since all of the investigated species have shown prominent inhibition of acetylcholinesterase in vitro activity, they could be further investigated as potential substances in preventing of Alzheimer’s disease. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle A Highly Sensitive Telomerase Activity Assay that Eliminates False-Negative Results Caused by PCR Inhibitors
Molecules 2013, 18(10), 11751-11767; doi:10.3390/molecules181011751
Received: 9 August 2013 / Revised: 5 September 2013 / Accepted: 11 September 2013 / Published: 25 September 2013
Cited by 3 | PDF Full-text (981 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An assay for telomerase activity based on asymmetric polymerase chain reaction (A-PCR) on magnetic beads (MBs) and subsequent application of cycling probe technology (CPT) is described. In this assay, the telomerase reaction products are immobilized on MBs, which are then washed to remove
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An assay for telomerase activity based on asymmetric polymerase chain reaction (A-PCR) on magnetic beads (MBs) and subsequent application of cycling probe technology (CPT) is described. In this assay, the telomerase reaction products are immobilized on MBs, which are then washed to remove PCR inhibitors that are commonly found in clinical samples. The guanine-rich sequences (5'-(TTAGGG)n-3') of the telomerase reaction products are then preferentially amplified by A-PCR, and the amplified products are subsequently detected via CPT, where a probe RNA with a fluorophore at the 5' end and a quencher at the 3' end is hydrolyzed by RNase H in the presence of the target DNA. The catalyst-mediated cleavage of the probe RNA enhances fluorescence from the 5' end of the probe. The assay allowed us to successfully detect HeLa cells selectively over normal human dermal fibroblast (NHDF) cells. Importantly, this selectivity produced identical results with regard to detection of HeLa cells in the absence and presence of excess NHDF cells; therefore, this assay can be used for practical clinical applications. The lower limit of detection for HeLa cells was 50 cells, which is lower than that achieved with a conventional telomeric repeat amplification protocol assay. Our assay also eliminated false-negative results caused by PCR inhibitors. Furthermore, we show that this assay is appropriate for screening among G-quadruplex ligands to find those that inhibit telomerase activity. Full article
(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)
Open AccessArticle Lipid Classes and Fatty Acid Regiodistribution in Triacylglycerols of Seed Oils of Two Sambucus Species (S. nigra L. and S. ebulus L.)
Molecules 2013, 18(10), 11768-11782; doi:10.3390/molecules181011768
Received: 30 July 2013 / Accepted: 4 September 2013 / Published: 25 September 2013
Cited by 8 | PDF Full-text (258 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The oil content and fatty acid composition of total lipids (TLs) and main lipid classes (NLs- neutral and PLs- polar lipids) in seeds of two wild Sambucus species (S. nigra and S. ebulus) from Transylvania (Romania) were determined by capillary gas chromatography
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The oil content and fatty acid composition of total lipids (TLs) and main lipid classes (NLs- neutral and PLs- polar lipids) in seeds of two wild Sambucus species (S. nigra and S. ebulus) from Transylvania (Romania) were determined by capillary gas chromatography (GC-MS). In addition, the positional distribution of fatty acids in seed triacylglycerols (TAGs) was determined by hydrolysis with pancreatic lipase. The seeds were found to be rich in fat (22.40–24.90 g/100g) with high amounts of polyunsaturated fatty acids (PUFAs) ranging from 68.96% (S. ebulus) to 75.15% (S. nigra). High ratios of PUFAs/SFAs (saturated fatty acids), ranging from 7.06 (S. nigra) to 7.64 (S. ebulus), and low ratios of n-6/n-3, ranging from 0.84 (S. nigra) to 1.51 (S. ebulus), were determined in both oils. The lipid classes/subclasses analyzed (PLs, MAGs—monoacylglycerols, DAGs—diacylglycerols, FFAs—free fatty acids, TAGs and SEs—sterol esters) were separated and identified using thin-layer chromatography. The fatty acid compositions of the TAG fractions were practically identical to the profiles of TLs, with the same dominating fatty acids in both analyzed species. SEs and FFAs, were characterized by high proportions of SFAs. The sn-2 position of TAGs was esterified predominantly with linoleic acid (43.56% for S. nigra and 50.41% for S. ebulus). Full article
Open AccessCommunication Design and Synthesis of a Biotinylated Chemical Probe for Detecting the Molecular Targets of an Inhibitor of the Production of the Pseudomonas aeruginosa Virulence Factor Pyocyanin
Molecules 2013, 18(10), 11783-11796; doi:10.3390/molecules181011783
Received: 5 August 2013 / Revised: 9 September 2013 / Accepted: 17 September 2013 / Published: 25 September 2013
PDF Full-text (279 KB) | HTML Full-text | XML Full-text
Abstract
Pseudomonas aeruginosa is a human pathogen associated with a variety of life-threatening nosocomial infections. This organism produces a range of virulence factors which actively cause damage to host tissues. One such virulence factor is pyocyanin, known to play a crucial role in the
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Pseudomonas aeruginosa is a human pathogen associated with a variety of life-threatening nosocomial infections. This organism produces a range of virulence factors which actively cause damage to host tissues. One such virulence factor is pyocyanin, known to play a crucial role in the pathogenesis of P. aeruginosa infections. Previous studies had identified a novel compound capable of strongly inhibiting the production of pyocyanin. It was postulated that this inhibition results from modulation of an intercellular communication system termed quorum sensing, via direct binding of the compound with the LasR protein receptor. This raised the possibility that the compound could be an antagonist of quorum sensing in P. aeruginosa, which could have important implications as this intercellular signaling mechanism is known to regulate many additional facets of P. aeruginosa pathogenicity. However, there was no direct evidence for the binding of the active compound to LasR (or any other targets). Herein we describe the design and synthesis of a biotin-tagged version of the active compound. This could potentially be used as an affinity-based chemical probe to ascertain, in a direct fashion, the active compound’s macromolecular biological targets, and thus better delineate the mechanism by which it reduces the level of pyocyanin production. Full article
(This article belongs to the Special Issue Reagents and Methods for Protein Target Identification)
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Open AccessArticle Optical Characterization of Oligonucleotide DNA Influenced by Magnetic Fields
Molecules 2013, 18(10), 11797-11808; doi:10.3390/molecules181011797
Received: 2 July 2013 / Revised: 3 September 2013 / Accepted: 12 September 2013 / Published: 25 September 2013
Cited by 4 | PDF Full-text (735 KB) | HTML Full-text | XML Full-text
Abstract
UV-VIS spectroscopic analysis of oligonucleotide DNA exposed to different magnetic fields was performed in order to investigate the relationship between DNA extinction coefficients and optical parameters according to magnetic-field strength. The results with the oligonucleotides adenine-thymine 100 mer (AT-100 DNA) and cytosine-guanine 100
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UV-VIS spectroscopic analysis of oligonucleotide DNA exposed to different magnetic fields was performed in order to investigate the relationship between DNA extinction coefficients and optical parameters according to magnetic-field strength. The results with the oligonucleotides adenine-thymine 100 mer (AT-100 DNA) and cytosine-guanine 100 mer (CG-100 DNA) indicate that the magnetic field influences DNA molar extinction coefficients and refractive indexes. The imaginary parts of the refractive index and molar extinction coefficients of the AT-100 and CG-100 DNA decreased after exposure to a magnetic field of 750 mT due to cleavage of the DNA oligonucleotides into smaller segments. Full article
Open AccessArticle A Comparative Analysis of the Influence of Human Salivary Enzymes on Odorant Concentration in Three Palm Wines
Molecules 2013, 18(10), 11809-11823; doi:10.3390/molecules181011809
Received: 21 July 2013 / Revised: 2 September 2013 / Accepted: 3 September 2013 / Published: 25 September 2013
Cited by 4 | PDF Full-text (278 KB) | HTML Full-text | XML Full-text
Abstract
The influence of human salivary enzymes on palm wines’ odorant concentrations were investigated by the application of aroma extracts dilution analysis (AEDA) and by the calculation of odour activity values (OAVs), respectively. The odorants were quantified by means of stable isotope dilution assays
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The influence of human salivary enzymes on palm wines’ odorant concentrations were investigated by the application of aroma extracts dilution analysis (AEDA) and by the calculation of odour activity values (OAVs), respectively. The odorants were quantified by means of stable isotope dilution assays (SIDA), and the degradation profiles of odorants by human saliva were also studied. Results revealed 46 odour-active compounds in the flavour dilution (FD) factor range of 4-256, and all were subsequently identified. Of the 46 odorants, 41 were identified in the Elaeis guineensis wine, 36 in Raphia hookeri wine and 29 in Borassus flabellifer wine. Among the odorants, the highest FD-factors were obtained from acetoin, 2-acetyl-1-pyrroline and 3-isobutyl-2-methoxypyrazine. Among the 13 potent odorants identified, five aroma compounds are reported here as important contributors to palm wine aroma, namely 3-isobutyl-2-methoxy-pyrazine, acetoin, 2-acetyl-1-pyrroline, 3-methylbutylacetate and ethyl hexanoate. Meanwhile, salivary enzymic degradation of odorants was more pronounced among the aldehydes, esters and thiols. Full article
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Open AccessArticle Improved Quality Control Method for Prescriptions of Polygonum capitatum through Simultaneous Determination of Nine Major Constituents by HPLC Coupled with Triple Quadruple Mass Spectrometry
Molecules 2013, 18(10), 11824-11835; doi:10.3390/molecules181011824
Received: 13 June 2013 / Revised: 28 August 2013 / Accepted: 4 September 2013 / Published: 25 September 2013
Cited by 2 | PDF Full-text (938 KB) | HTML Full-text | XML Full-text
Abstract
As a traditional Miao-nationality medicinal plant, Polygonum capitatum has been used in clinical practice for several thousand years. Its prescriptions, including three dosage forms: granules, capsule and tablet are known by the brand name Relinqing® and have played an indispensable role in
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As a traditional Miao-nationality medicinal plant, Polygonum capitatum has been used in clinical practice for several thousand years. Its prescriptions, including three dosage forms: granules, capsule and tablet are known by the brand name Relinqing® and have played an indispensable role in the treatment of urinary system infection, pyelonephritis and kidney stones. However, no study about the comprehensive quality evaluation of Relinqing® has been reported. In the present paper, a method for the simultaneous determination of nine major compounds in three dosage forms of Relinqing® using HPLC coupled with triple quadrupole mass spectrometry (HPLC-QQQ MS) was established to comprehensively evaluate their quality. The nine compounds, including four phenolic acids, four flavonoids and a lignin, were analyzed with acceptable linear regression relationship (r2, 0.9923–0.9992), precision (RSD, 1.25%–2.78%), repeatability (RSD, 2.05%%–3.47%), stability (RSD, 1.84%–3.72%) and recovery (93.60%–108.54%, RSD ≤ 3.67%). The present study fills the gap in the multivariate quality control of Relinqing® and provides a valuable reference for quality standards and dosage reforming of this traditional Chinese medicine. Full article
Open AccessArticle The Effect of Butanolides from Cinnamomum tenuifolium on Platelet Aggregation
Molecules 2013, 18(10), 11836-11841; doi:10.3390/molecules181011836
Received: 10 July 2013 / Revised: 27 August 2013 / Accepted: 6 September 2013 / Published: 25 September 2013
Cited by 4 | PDF Full-text (196 KB) | HTML Full-text | XML Full-text
Abstract
This study investigated the effects of isotenuifolide and tenuifolide B from the stems of Cinnamomum tenuifolium on adenosine diphosphate (ADP)-induced human platelet aggregation. Treatment of human platelet-rich plasma with isotenuifolide (1 and 2 μg/μL) and tenuifolide B (1, 2 and 4 μg/μL) did
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This study investigated the effects of isotenuifolide and tenuifolide B from the stems of Cinnamomum tenuifolium on adenosine diphosphate (ADP)-induced human platelet aggregation. Treatment of human platelet-rich plasma with isotenuifolide (1 and 2 μg/μL) and tenuifolide B (1, 2 and 4 μg/μL) did not have any significant effect on human platelet aggregation in vitro, however, treatment of human platelet-rich plasma with isotenuifolide (4 μg/μL) resulted in an inhibitory effect on platelet aggregation, suggesting the potential of this compound as an anti-atherosclerogenic agent in humans. Isotenuifolide is a new butanolide compound, whose structure was characterized by spectral analyses. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle In Vitro and in Vivo Studies of the Inhibitory Effects of Emodin Isolated from Polygonum cuspidatum on Coxsakievirus B4
Molecules 2013, 18(10), 11842-11858; doi:10.3390/molecules181011842
Received: 29 July 2013 / Revised: 4 September 2013 / Accepted: 10 September 2013 / Published: 25 September 2013
Cited by 21 | PDF Full-text (2579 KB) | HTML Full-text | XML Full-text
Abstract
The lack of effective therapeutics for Coxsackievirus B4 (CVB4) infection underscores the importance of finding novel antiviral compounds. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is one of the natural anthraquinone derivatives obtained from the root and rhizome of Polygonum cuspidatum. In the present
[...] Read more.
The lack of effective therapeutics for Coxsackievirus B4 (CVB4) infection underscores the importance of finding novel antiviral compounds. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is one of the natural anthraquinone derivatives obtained from the root and rhizome of Polygonum cuspidatum. In the present study, the possibility of using emodin as a potential antiviral to treat CVB4 infection was explored in vitro and in mice. Emodin reduced CVB4 entry and replication on Hep-2 cells in a concentration- and time-dependent manner, with a 50% effective concentration (EC50) of 12.06 μM and selectivity index (SI) of 5.08, respectively. The inhibitory effect of emodin for CVB4 entry and replication was further confirmed by a quantitative real time PCR (qPCR) assay. The results further showed that the mice orally treated with different dosages of emodin displayed a dose dependent increase of survival rate, body weight and prolonged mean time of death (MTD), accompanied by significantly decreased myocardial virus titers and pathologic scores/lesions. Moreover, emodin could inhibit CVB4-induced apoptosis in vitro and in vivo. Our results indicated that emodin could be used as potential antiviral in the post-exposure prophylaxis for CVB4 infection. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Chemical Constituents from the Roots of Ranunculus ternatus and their Inhibitory Effects on Mycobacterium tuberculosis
Molecules 2013, 18(10), 11859-11865; doi:10.3390/molecules181011859
Received: 12 August 2013 / Revised: 14 September 2013 / Accepted: 17 September 2013 / Published: 25 September 2013
PDF Full-text (192 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new benzophenones, methyl (R)-3-[2-(3,4-dihydroxybenzoyl)-4,5-dihydroxyphenyl]-2-hydroxypropanoate (1) and n-butyl (R)-3-[2-(3,4-dihydroxybenzoyl)-4,5-dihydroxyphenyl]-2-hydroxypropanoate (2), were isolated from the roots of Ranunculus ternatus along with the two known compounds vanillic acid (3) and gallic acid (4
[...] Read more.
Two new benzophenones, methyl (R)-3-[2-(3,4-dihydroxybenzoyl)-4,5-dihydroxyphenyl]-2-hydroxypropanoate (1) and n-butyl (R)-3-[2-(3,4-dihydroxybenzoyl)-4,5-dihydroxyphenyl]-2-hydroxypropanoate (2), were isolated from the roots of Ranunculus ternatus along with the two known compounds vanillic acid (3) and gallic acid (4). Their structures were elucidated by physical and spectroscopic analysis. In addition, compound 1 exhibited obvious activity against tuberculosis, while the activity of a 1:1 mixture of compound 1 plus 4 is better than that of 1 alone. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Two New Monoterpenes from the Fruits of Illicium lanceolatum
Molecules 2013, 18(10), 11866-11872; doi:10.3390/molecules181011866
Received: 5 August 2013 / Revised: 1 September 2013 / Accepted: 4 September 2013 / Published: 26 September 2013
PDF Full-text (234 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new monoterpenes, p-mentha-1(7),8-dien-2-O-b-d-glucoside (1) and trans-2,4-dihydroxy-2,4-dimethyl-trans-1-acetic acid g-lactone (2) were isolated from the fruits of Illicium lanceolatum along with trans-2,4-dihydroxy-2,4-dimethyl-cis-1-acetic acid g-lactone (3),
[...] Read more.
Two new monoterpenes, p-mentha-1(7),8-dien-2-O-b-d-glucoside (1) and trans-2,4-dihydroxy-2,4-dimethyl-trans-1-acetic acid g-lactone (2) were isolated from the fruits of Illicium lanceolatum along with trans-2,4-dihydroxy-2,4-dimethyl-cis-1-acetic acid g-lactone (3), (1R,2R,4R)-8-p-menthen-1,2-diol (4), trans-sobrerol (5), (1S,2S,4R)-p-menthane-1,2,8-triol (6) and (1S, 2S, 4R, 8R)-p-menthane-1,2,9-triol (7). The structures of the isolates were confirmed by spectroscopic analysis and they showed no inhibitory effects on the in vitro growth of microbial organisms (Escherichia coli, Staphyloccocus aureus, Bacillus subtilis) at less than 1.0 mg/mL. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Macrocyclic Pyridyl Polyoxazoles: Structure-Activity Studies of the Aminoalkyl Side-Chain on G-Quadruplex Stabilization and Cytotoxic Activity
Molecules 2013, 18(10), 11938-11963; doi:10.3390/molecules181011938
Received: 22 August 2013 / Revised: 10 September 2013 / Accepted: 17 September 2013 / Published: 26 September 2013
Cited by 3 | PDF Full-text (357 KB) | HTML Full-text | XML Full-text
Abstract
Pyridyl polyoxazoles are 24-membered macrocyclic lactams comprised of a pyridine, four oxazoles and a phenyl ring. A derivative having a 2-(dimethylamino)ethyl chain attached to the 5-position of the phenyl ring was recently identified as a selective G-quadruplex stabilizer with excellent cytotoxic activity, and
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Pyridyl polyoxazoles are 24-membered macrocyclic lactams comprised of a pyridine, four oxazoles and a phenyl ring. A derivative having a 2-(dimethylamino)ethyl chain attached to the 5-position of the phenyl ring was recently identified as a selective G-quadruplex stabilizer with excellent cytotoxic activity, and good in vivo anticancer activity against a human breast cancer xenograft in mice. Here we detail the synthesis of eight new dimethylamino-substituted pyridyl polyoxazoles in which the point of attachment to the macrocycle, as well as the distance between the amine and the macrocycle are varied. Each compound was evaluated for selective G-quadruplex stabilization and cytotoxic activity. The more active analogs have the amine either directly attached to, or separated from the phenyl ring by two methylene groups. There is a correlation between those macrocycles that are effective ligands for the stabilization of G-quadruplex DNA (DTtran 15.5–24.6 °C) and cytotoxicity as observed in the human tumor cell lines, RPMI 8402 (IC50 0.06–0.50 μM) and KB3-1 (IC50 0.03–0.07 μM). These are highly selective G-quadruplex stabilizers, which should prove especially useful for evaluating both in vitro and in vivo mechanism(s) of biological activity associated with G-quaqdruplex ligands. Full article
(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)
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Open AccessArticle An Efficient Solvent-Free Synthesis of 2-Hydroxy-2-(trifluoromethyl)-2H-chromenes Using Silica-Immobilized L-Proline
Molecules 2013, 18(10), 11964-11977; doi:10.3390/molecules181011964
Received: 15 July 2013 / Revised: 7 September 2013 / Accepted: 11 September 2013 / Published: 26 September 2013
Cited by 10 | PDF Full-text (465 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An efficient synthesis of 2-hydroxy-2-(trifluoromethyl)-2H-chromene-3-carboxylates was carried out under solvent-free conditions in an oven or microwave oven via the Knoevenagel condensation of salicylaldehydes with ethyl trifluoroacetoacetate followed by intramolecular cyclization in the presence of silica-immobilized L-proline. The structures of the title
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An efficient synthesis of 2-hydroxy-2-(trifluoromethyl)-2H-chromene-3-carboxylates was carried out under solvent-free conditions in an oven or microwave oven via the Knoevenagel condensation of salicylaldehydes with ethyl trifluoroacetoacetate followed by intramolecular cyclization in the presence of silica-immobilized L-proline. The structures of the title compounds were characterized by IR, 1H-NMR, 13C-NMR, HRMS and X-ray single crystal diffraction. The improved method described herein is economical, easily-operated and environmentally friendly. Furthermore, the catalyst can be recovered conveniently and reused without obvious loss of activity. Full article
Open AccessArticle Synthesis and Antibacterial Evaluation of Some Novel Imidazole and Benzimidazole Sulfonamides
Molecules 2013, 18(10), 11978-11995; doi:10.3390/molecules181011978
Received: 6 August 2013 / Revised: 11 September 2013 / Accepted: 12 September 2013 / Published: 26 September 2013
Cited by 14 | PDF Full-text (450 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Several new substituted sulfonamide compounds were synthesized and their structures were confirmed by 1H-NMR, 13C-NMR, FT-IR, and mass spectroscopy. The antibacterial activities of the synthesized compounds were screened against standard strains of six Gram positive and four Gram negative bacteria using
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Several new substituted sulfonamide compounds were synthesized and their structures were confirmed by 1H-NMR, 13C-NMR, FT-IR, and mass spectroscopy. The antibacterial activities of the synthesized compounds were screened against standard strains of six Gram positive and four Gram negative bacteria using the microbroth dilution assay. Most of the compounds studied showed promising activities against both types of bacteria. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Structural Correlation of Some Heterocyclic Chalcone Analogues and Evaluation of Their Antioxidant Potential
Molecules 2013, 18(10), 11996-12011; doi:10.3390/molecules181011996
Received: 12 August 2013 / Revised: 14 September 2013 / Accepted: 23 September 2013 / Published: 26 September 2013
Cited by 17 | PDF Full-text (2367 KB) | HTML Full-text | XML Full-text
Abstract
A series of six novel heterocyclic chalcone analogues 4(af) has been synthesized by condensing 2-acetyl-5-chlorothiophene with benzaldehyde derivatives in methanol at room temperature using a catalytic amount of sodium hydroxide. The newly synthesized compounds are characterized by IR,
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A series of six novel heterocyclic chalcone analogues 4(af) has been synthesized by condensing 2-acetyl-5-chlorothiophene with benzaldehyde derivatives in methanol at room temperature using a catalytic amount of sodium hydroxide. The newly synthesized compounds are characterized by IR, mass spectra, elemental analysis and melting point. Subsequently; the structures of these compounds were determined using single crystal X-ray diffraction. All the synthesized compounds were screened for their antioxidant potential by employing various in vitro models such as DPPH free radical scavenging assay, ABTS radical scavenging assay, ferric reducing antioxidant power and cupric ion reducing antioxidant capacity. Results reflect the structural impact on the antioxidant ability of the compounds. The IC50 values illustrate the mild to good antioxidant activities of the reported compounds. Among them, 4f with a p-methoxy substituent was found to be more potent as antioxidant agent. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Yields, Phenolic Profiles and Antioxidant Activities of Ziziphus jujube Mill. in Response to Different Fertilization Treatments
Molecules 2013, 18(10), 12029-12040; doi:10.3390/molecules181012029
Received: 21 August 2013 / Revised: 10 September 2013 / Accepted: 17 September 2013 / Published: 27 September 2013
PDF Full-text (228 KB) | HTML Full-text | XML Full-text
Abstract
Increasing demand for more jujube (Ziziphus jujube Mill.) production requires understanding the specific fertilization needs of jujube trees. This study was conducted to compare fruit yields, phenolic profiles and antioxidant activity of jujube in response to different fertilizers. Application of organic
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Increasing demand for more jujube (Ziziphus jujube Mill.) production requires understanding the specific fertilization needs of jujube trees. This study was conducted to compare fruit yields, phenolic profiles and antioxidant activity of jujube in response to different fertilizers. Application of organic fertilizer appeared to enhance the phenolics and antioxidant activity accumulation of jujubes, compared to conventional fertilized jujubes. Amongst inorganic fertilizers, supplemental potassium as an individual nutrient improved the accumulation of phenolics in jujubes. Our results demonstrate that phenolics levels and antioxidant activity of jujube can be manipulated through fertilizer management and tracked by following proanthocyanidin concentrations. In a practical production context, the combination of organic fertilizers and inorganic fertilizers such as more supplemental individual potassium, and less supplemental individual nitrogen and phosphorus, might be the best management combination for achieving higher phenolic concentration, stronger antioxidant activity and a good harvest. Full article
Open AccessArticle Conductance Studies on Complex Formation between c-Methylcalix[4]resorcinarene and Titanium (III) in Acetonitrile-H2O Binary Solutions
Molecules 2013, 18(10), 12041-12050; doi:10.3390/molecules181012041
Received: 25 April 2013 / Revised: 8 May 2013 / Accepted: 10 May 2013 / Published: 27 September 2013
Cited by 7 | PDF Full-text (458 KB) | HTML Full-text | XML Full-text
Abstract
Calixresorcinarenes have proved to be unique molecules for molecular recognition via hydrogen bonding, hydrophobic and ionic interactions with suitable substrates such as cations. The study of the interactions involved in the complexation of different cations with calixresorcinarenes in solvent mixtures is important for
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Calixresorcinarenes have proved to be unique molecules for molecular recognition via hydrogen bonding, hydrophobic and ionic interactions with suitable substrates such as cations. The study of the interactions involved in the complexation of different cations with calixresorcinarenes in solvent mixtures is important for a better understanding of the mechanism of biological transport, molecular recognition, and other analytical applications. This article summarizes different aspects of the complexes of the Ti3+ metal cation with c-methylcalix[4]resorcinarene (CMCR) as studied by conductometry in acetonitrile (AN)–water (H2O) binary mixtures at different temperatures. Conductance data show that the metal cation/ligand (ML) stoichiometry of the complexes in solution is 1:1 in all cases. Non-linear behaviour was observed for the variation of logKf of the complexes vs. the composition of the binary solvent mixtures. Selectivity of CMCR for the Ti3+ cation is sensitive to solvent composition; in some cases and at certain compositions of the mixed solvent systems, the selectivity order is changed. Values of thermodynamic parameters (,) for formation of the CMCR–Ti3+ complexes in AN–H2O binary systems were obtained from the temperature dependence of stability constants, and the results show that the thermodynamics of complexation reactions are affected by the nature and composition of the mixed solvents. Full article
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Open AccessArticle Identification of New Natural DNA G-Quadruplex Binders Selected by a Structure-Based Virtual Screening Approach
Molecules 2013, 18(10), 12051-12070; doi:10.3390/molecules181012051
Received: 4 September 2013 / Revised: 18 September 2013 / Accepted: 22 September 2013 / Published: 30 September 2013
Cited by 10 | PDF Full-text (2354 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The G-quadruplex DNA structures are mainly present at the terminal portion of telomeres and can be stabilized by ligands able to recognize them in a specific manner. The recognition process is usually related to the inhibition of the enzyme telomerase indirectly involved and
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The G-quadruplex DNA structures are mainly present at the terminal portion of telomeres and can be stabilized by ligands able to recognize them in a specific manner. The recognition process is usually related to the inhibition of the enzyme telomerase indirectly involved and over-expressed in a high percentage of human tumors. There are several ligands, characterized by different chemical structures, already reported in the literature for their ability to bind and stabilize the G-quadruplex structures. Using the structural and biological information available on these structures; we performed a high throughput in silico screening of commercially natural compounds databases by means of a structure-based approach followed by docking experiments against the human telomeric sequence d[AG3(T2AG3)3]. We identified 12 best hits characterized by different chemical scaffolds and conformational and physicochemical properties. All of them were associated to an improved theoretical binding affinity with respect to that of known selective G-binders. Among these hits there is a chalcone derivative; structurally very similar to the polyphenol butein; known to remarkably inhibit the telomerase activity. Full article
(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)
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Open AccessArticle Anti-Inflammatory Activity of Iridoids and Verbascoside Isolated from Castilleja tenuiflora
Molecules 2013, 18(10), 12109-12118; doi:10.3390/molecules181012109
Received: 23 July 2013 / Revised: 5 September 2013 / Accepted: 23 September 2013 / Published: 30 September 2013
Cited by 14 | PDF Full-text (264 KB) | HTML Full-text | XML Full-text
Abstract
Castilleja tenuiflora (Orobanchaceae) has been used in Mexican traditional medicine as a treatment for cough, dysentery, anxiety, nausea and vomiting as well as hepatic and gastrointestinal diseases. The ethanolic extract of the aerial parts of Castilleja tenuiflora was separated by silica gel column
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Castilleja tenuiflora (Orobanchaceae) has been used in Mexican traditional medicine as a treatment for cough, dysentery, anxiety, nausea and vomiting as well as hepatic and gastrointestinal diseases. The ethanolic extract of the aerial parts of Castilleja tenuiflora was separated by silica gel column chromatography. The fractions were evaluated using the induced edema acetate 12-O-tetradecanoylphorbol (TPA) anti-inflammatory activity model. The most active fraction was subjected to medium-pressure liquid chromatography (MPLC) with UV detection at 206 and 240 nm. The following iridoids were isolated: geniposidic acid, aucubin, bartioside, 8-epi-loganin, mussaenoside, and the phenylpropanoid verbascoside. The most active iridoid was geniposidic acid, which was more active than the control (indomethacin), and the least active iridoid was mussaenoside. 8-epi-Loganin, and mussaenoside have not been previously reported to be anti-inflammatory compounds. The results of these investigations confirm the potential of Mexican plants for the production of bioactive compounds and validate the ethnomedical use of Castilleja tenuiflora-like anti-inflammatory plants. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Syntheses of Precursors and Reference Compounds of the Melanin-Concentrating Hormone Receptor 1 (MCHR1) Tracers [11C]SNAP-7941 and [18F]FE@SNAP for Positron Emission Tomography
Molecules 2013, 18(10), 12119-12143; doi:10.3390/molecules181012119
Received: 12 August 2013 / Revised: 22 September 2013 / Accepted: 22 September 2013 / Published: 30 September 2013
Cited by 1 | PDF Full-text (589 KB) | HTML Full-text | XML Full-text
Abstract
The MCH receptor has been revealed as a target of great interest in positron emission tomography imaging. The receptor′s eponymous substrate melanin-concentrating hormone (MCH) is a cyclic peptide hormone, which is located predominantly in the hypothalamus with a major influence on energy and
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The MCH receptor has been revealed as a target of great interest in positron emission tomography imaging. The receptor′s eponymous substrate melanin-concentrating hormone (MCH) is a cyclic peptide hormone, which is located predominantly in the hypothalamus with a major influence on energy and weight regulation as well as water balance and memory. Therefore, it is thought to play an important role in the pathophysiology of adiposity, which is nowadays a big issue worldwide. Based on the selective and high-affinity MCH receptor 1 antagonist SNAP-7941, a series of novel SNAP derivatives has been developed to provide different precursors and reference compounds for the radiosyntheses of the novel PET radiotracers [11C]SNAP-7941 and [18F]FE@SNAP. Positron emission tomography promotes a better understanding of physiologic parameters on a molecular level, thus giving a deeper insight into MCHR1 related processes as adiposity. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Metabolite Analysis of Toosendanin by an Ultra-High Performance Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometry Technique
Molecules 2013, 18(10), 12144-12153; doi:10.3390/molecules181012144
Received: 29 July 2013 / Revised: 25 September 2013 / Accepted: 26 September 2013 / Published: 30 September 2013
Cited by 3 | PDF Full-text (214 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Toosendanin is the major bioactive component of Melia toosendan Sieb. et Zucc., which is traditionally used for treatment of abdominal pain and as an insecticide. Previous studies reported that toosendanin possesses hepatotoxicity, but the mechanism remains unknown. Its bioavailability in rats is low,
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Toosendanin is the major bioactive component of Melia toosendan Sieb. et Zucc., which is traditionally used for treatment of abdominal pain and as an insecticide. Previous studies reported that toosendanin possesses hepatotoxicity, but the mechanism remains unknown. Its bioavailability in rats is low, which indicates the hepatotoxicity might be induced by its metabolites. In this connection, in the current study, we examined the metabolites obtained by incubating toosendanin with human live microsomes, and then six of these metabolites (M1–M6) were identified for the first time by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF/MS). Further analysis on the MS spectra showed M1, M2, and M3 are oxidative products and M6 is a dehydrogenation product, while M4 and M5 are oxidative and dehydrogenation products of toosendanin. Moreover, their possible structures were deduced from the MS/MS spectral features. Quantitative analysis demonstrated that M1-M5 levels rapidly increased and reached a plateau at 30 min, while M6 rapidly reached a maximal level at 20 min and then decreased slowly afterwards. These findings have provided valuable data not only for understanding the metabolic fate of toosendanin in liver microsomes, but also for elucidating the possible molecular mechanism of its hepatotoxicity. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Effect of Black Grape Juice against Heart Damage from Acute Gamma TBI in Rats
Molecules 2013, 18(10), 12154-12167; doi:10.3390/molecules181012154
Received: 1 July 2013 / Revised: 18 September 2013 / Accepted: 18 September 2013 / Published: 30 September 2013
Cited by 5 | PDF Full-text (397 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to evaluate the potential positive effect of black grape juice (BGJ) on lipid peroxidation considering Total Body Irradiation (TBI) in Wistar rats. As a potential feasible means of evaluation in situ, blood serum lactate dehydrogenase (LDH)
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The aim of this study was to evaluate the potential positive effect of black grape juice (BGJ) on lipid peroxidation considering Total Body Irradiation (TBI) in Wistar rats. As a potential feasible means of evaluation in situ, blood serum lactate dehydrogenase (LDH) levels were evaluated as a marker for heart damage from acute radiation syndrome (ARS). Twenty rats were divided into four groups, two of them being irradiated by gamma-rays from a Co-60 source. Animals were treated by gavage with 2 mL per day of BGJ or placebo for one week before and 4 days after 6 Gy whole body gamma-irradiation, when they were euthanasiated. LDH on serum and lipid peroxidation on heart tissue were evaluated. High concentration of metabolites from lipid peroxidation in heart, and high LDH level on serum were found only in gamma-irradiated group given placebo, mainly at the first 24 h after radiation. Phytochemical analysis of BGJ was performed by determining total phenolics, flavonoids, and tannins followed by a high-performance liquid chromatography (HPLC/DAD) analysis, which showed resveratrol as the major constituent. Results suggest that BGJ is a good protective candidate compound against heart damage from ARS and its effects suggest its use as a radiomodifier. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Intracellular Environment-Responsive Stabilization of Polymer Vesicles Formed from Head-Tail Type Polycations Composed of a Polyamidoamine Dendron and Poly(L-lysine)
Molecules 2013, 18(10), 12168-12179; doi:10.3390/molecules181012168
Received: 6 August 2013 / Revised: 18 September 2013 / Accepted: 23 September 2013 / Published: 30 September 2013
Cited by 4 | PDF Full-text (1165 KB) | HTML Full-text | XML Full-text
Abstract
For the development of effective drug carriers, nanocapsules that respond to micro-environmental changes including a decrease in pH and a reductive environment were prepared by the stabilization of polymer vesicles formed from head-tail type polycations, composed of a polyamidoamine dendron head and a
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For the development of effective drug carriers, nanocapsules that respond to micro-environmental changes including a decrease in pH and a reductive environment were prepared by the stabilization of polymer vesicles formed from head-tail type polycations, composed of a polyamidoamine dendron head and a poly(L-lysine) tail (PAMAM dendron-PLL), through the introduction of disulfide bonds between the PLL tails. Disulfide bonds were successfully introduced through the reaction of Lys residues in the PAMAM dendron-PLL polymer vesicles with 2-iminothiolane. The stabilization of PAMAM dendron-PLL polymer vesicles was confirmed by dynamic light scattering measurements. In acid-base titration experiments, nanocapsules cross-linked by disulfide bonds had a buffering effect during the cellular uptake process. The PAMAM dendron-PLL nanocapsules were used to incorporate the fluorescent dyes rhodamine 6G and fluorescein as a drug model. Cationic rhodamine 6G was generally not released from the nanocapsules because of the electrostatic barrier of the PLL membrane. However, the nanocapsules were destabilized at high glutathione concentrations corresponding to intracellular concentrations. Rhodamine 6G was immediately released from the nanocapsules because of destabilization upon the cleavage of disulfide bonds. This release of rhodamine 6G from the nanocapsules was also observed in HeLa cells by laser confocal microscopy. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
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Open AccessArticle Lepidotrichilins A and B, New Protolimonoids with Cytotoxic Activity from Trichilia Lepidota (Meliaceae)
Molecules 2013, 18(10), 12180-12191; doi:10.3390/molecules181012180
Received: 20 August 2013 / Revised: 20 September 2013 / Accepted: 26 September 2013 / Published: 30 September 2013
Cited by 4 | PDF Full-text (300 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two novel protolimonoids, named lepidotrichilins A (1) and B (2), four known protolimonoids, 21,23-epoxy-7α-21α-dihydroxyapotirucalla-14,24-dien-3-one (3), 21,23-epoxy-7α-21β-dihydroxyapotiru-calla-14,24-dien-3-one (4), dysorone D (5), deoxy-flindissone (6), and the two steroids β-sitosterol (7) and
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Two novel protolimonoids, named lepidotrichilins A (1) and B (2), four known protolimonoids, 21,23-epoxy-7α-21α-dihydroxyapotirucalla-14,24-dien-3-one (3), 21,23-epoxy-7α-21β-dihydroxyapotiru-calla-14,24-dien-3-one (4), dysorone D (5), deoxy-flindissone (6), and the two steroids β-sitosterol (7) and stigmasterol (8) were identified in leaves of Trichilia lepidota subsp. schumanniana (Harms) T.D. Pennington. From wood the coumarin scopoletin (9) was isolated. The structures were established by NMR (1D 1H and 13C-NMR and 2D 1H-1H COSY, HMQC and HMBC), mass spectroscopy and infrared (IR) spectral data. The hexane and methanol extracts of the leaves, the protolimonoids lepidotrichilins A (1) and B (2) (IC50 42.7 µg mL−1) and the protolimonoid deoxy-flindissone (6; IC50 9.3 µgmL−1) exhibited significant cytotoxic activity against the MOLT-4 and U937 leukemic cell lines. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Qualitative and Quantitative Analysis of Andrographis paniculata by Rapid Resolution Liquid Chromatography/Time-of-Flight Mass Spectrometry
Molecules 2013, 18(10), 12192-12207; doi:10.3390/molecules181012192
Received: 29 August 2013 / Revised: 18 September 2013 / Accepted: 26 September 2013 / Published: 30 September 2013
Cited by 10 | PDF Full-text (329 KB) | HTML Full-text | XML Full-text
Abstract
A rapid resolution liquid chromatography/time-of-flight tandem mass spectrometry (RRLC-TOF/MS) method was developed for qualitative and quantitative analysis of the major chemical constituents in Andrographis paniculata. Fifteen compounds, including flavonoids and diterpenoid lactones, were unambiguously or tentatively identified in 10 min by comparing
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A rapid resolution liquid chromatography/time-of-flight tandem mass spectrometry (RRLC-TOF/MS) method was developed for qualitative and quantitative analysis of the major chemical constituents in Andrographis paniculata. Fifteen compounds, including flavonoids and diterpenoid lactones, were unambiguously or tentatively identified in 10 min by comparing their retention times and accurate masses with standards or literature data. The characteristic fragmentation patterns of flavonoids and diterpenoid lactones were summarized, and the structures of the unknown compounds were predicted. Andrographolide, dehydroandrographolide and neoandrographolide were further quantified as marker substances. It was found that the calibration curves for all analytes showed good linearity (R2 > 0.9995) within the test ranges. The overall limits of detection (LODs) and limits of quantification (LOQs) were 0.02 μg/mL to 0.06 μg/mL and 0.06 μg/mL to 0.2 μg/mL, respectively. The relative standard deviations (RSDs) for intra- and inter-day precisions were below 3.3% and 4.2%, respectively. The mean recovery rates ranged from 96.7% to 104.5% with the relative standard deviations (RSDs) less than 2.72%. It is concluded that RRLC-TOF/MS is powerful and practical in qualitative and quantitative analysis of complex plant samples due to time savings, sensitivity, precision, accuracy and lowering solvent consumption. Full article
Open AccessArticle In Vitro Anti-Candida Activity of Certain New 3-(1H-Imidazol-1-yl)propan-1-one Oxime Esters
Molecules 2013, 18(10), 12208-12221; doi:10.3390/molecules181012208
Received: 1 September 2013 / Revised: 19 September 2013 / Accepted: 23 September 2013 / Published: 30 September 2013
Cited by 14 | PDF Full-text (250 KB) | HTML Full-text | XML Full-text
Abstract
Anti-Candida activities of certain new oximes 4ad and their respective aromatic esters 5al are reported. The tested compounds 4ad and 5al exhibited better anti-Candida profiles than fluconazole. Compound 5j, namely (E
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Anti-Candida activities of certain new oximes 4ad and their respective aromatic esters 5al are reported. The tested compounds 4ad and 5al exhibited better anti-Candida profiles than fluconazole. Compound 5j, namely (E)-3-(1H-imidazol-1-yl)-1-phenylpropan-1-one O-4-chlorobenzoyl oxime emerged as the most active congener, with a MIC value of 0.0054 µmol/mL being more potent than both fluconazole (MIC > 1.6325 µmol/mL) and miconazole (MIC value = 0.0188 µmol/mL) as a new anti-Candida albicans agent. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Promising Low-Toxicity of Viologen-Phosphorus Dendrimers against Embryonic Mouse Hippocampal Cells
Molecules 2013, 18(10), 12222-12240; doi:10.3390/molecules181012222
Received: 12 August 2013 / Revised: 24 September 2013 / Accepted: 24 September 2013 / Published: 30 September 2013
Cited by 7 | PDF Full-text (604 KB) | HTML Full-text | XML Full-text
Abstract
A new class of viologen-phosphorus dendrimers (VPDs) has been recently shown to possess the ability to inhibit neurodegenerative processes in vitro. Nevertheless, in the Central Nervous Systems domain, there is little information on their impact on cell functions, especially on neuronal cells.
[...] Read more.
A new class of viologen-phosphorus dendrimers (VPDs) has been recently shown to possess the ability to inhibit neurodegenerative processes in vitro. Nevertheless, in the Central Nervous Systems domain, there is little information on their impact on cell functions, especially on neuronal cells. In this work, we examined the influence of two VPD (VPD1 and VPD3) of zero generation (G0) on murine hippocampal cell line (named mHippoE-18). Extended analyses of cell responses to these nanomolecules comprised cytotoxicity test, reactive oxygen species (ROS) generation studies, mitochondrial membrane potential (ΔΨm) assay, cell death detection, cell morphology assessment, cell cycle studies, as well as measurements of catalase (CAT) activity and glutathione (GSH) level. The results indicate that VPD1 is more toxic than VPD3. However, these two tested dendrimers did not cause a strong cellular response, and induced a low level of apoptosis. Interestingly, VPD1 and VPD3 treatment led to a small decline in ROS level compared to untreated cells, which correlated with slightly increased catalase activity. This result indicates that the VPDs can indirectly lower the level of ROS in cells. Summarising, low-cytotoxicity on mHippoE-18 cells together with their ability to quench ROS, make the VPDs very promising nanodevices for future applications in the biomedical field as nanocarriers and/or drugs per se. Full article
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Open AccessArticle Glycosyl-Nucleolipids as New Bioinspired Amphiphiles
Molecules 2013, 18(10), 12241-12263; doi:10.3390/molecules181012241
Received: 28 August 2013 / Revised: 25 September 2013 / Accepted: 25 September 2013 / Published: 30 September 2013
Cited by 4 | PDF Full-text (417 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four new Glycosyl-NucleoLipid (GNL) analogs featuring either a single fluorocarbon or double hydrocarbon chains were synthesized in good yields from azido thymidine as starting material. Physicochemical studies (surface tension measurements, differential scanning calorimetry) indicate that hydroxybutanamide-based GNLs feature endothermic phase transition temperatures like
[...] Read more.
Four new Glycosyl-NucleoLipid (GNL) analogs featuring either a single fluorocarbon or double hydrocarbon chains were synthesized in good yields from azido thymidine as starting material. Physicochemical studies (surface tension measurements, differential scanning calorimetry) indicate that hydroxybutanamide-based GNLs feature endothermic phase transition temperatures like the previously reported double chain glycerol-based GNLs. The second generation of GNFs featuring a free nucleobase reported here presents a better surface activity (lower glim) compared to the first generation of GNFs. Full article
(This article belongs to the Special Issue Synthesis of Nucleosides, Nucleotides and Their Derivatives)
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Open AccessArticle Anti-Plasmodial Activity of Some Zulu Medicinal Plants and of Some Triterpenes Isolated from Them
Molecules 2013, 18(10), 12313-12323; doi:10.3390/molecules181012313
Received: 6 August 2013 / Revised: 16 September 2013 / Accepted: 24 September 2013 / Published: 8 October 2013
Cited by 9 | PDF Full-text (206 KB) | HTML Full-text | XML Full-text
Abstract
Mimusops caffra E. Mey. ex A.DC and Mimusops obtusifolia Lam (both members of the Sapotaceae family), and Hypoxis colchicifolia Bak (family Hypoxidaceae) are used by traditional healers in Zululand to manage malaria. Anti-plasmodial investigation of the crude extracts and some triterpenes isolated
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Mimusops caffra E. Mey. ex A.DC and Mimusops obtusifolia Lam (both members of the Sapotaceae family), and Hypoxis colchicifolia Bak (family Hypoxidaceae) are used by traditional healers in Zululand to manage malaria. Anti-plasmodial investigation of the crude extracts and some triterpenes isolated from the plants showed activity against a chloroquine sensitive (CQS) strain of Plasmodium falciparum (D10). Among the crude extracts the leaves of M. caffra exhibited the highest activity, with an IC50 of 2.14 μg/mL. The pentacyclic tritepenoid ursolic acid (1), isolated from the leaves of M. caffra was the most active compound (IC50 6.8 μg/mL) as compared to taraxerol (2) and sawamilletin (3) isolated from the stem bark of M. obtusifolia (IC50 > 100). Chemical modification of the ursolic acid (1) to 3β-acetylursolic acid (4) greatly enhanced its anti-plasmodial activity. Compound 4 reduced parasitaemia against Plasmodium berghei by 94.01% in in vivo studies in mice. The cytotoxicity of 3β-acetylursolic acid (IC50) to two human cell lines (HEK293 and HepG2) was 366.00 μg/mL and 566.09 μg/mL, respectively. The results validate the use of these plants in folk medicine. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Characterization and Determination of 2-(2-Phenylethyl)chromones in Agarwood by GC-MS
Molecules 2013, 18(10), 12324-12345; doi:10.3390/molecules181012324
Received: 31 July 2013 / Revised: 19 September 2013 / Accepted: 26 September 2013 / Published: 8 October 2013
Cited by 12 | PDF Full-text (776 KB) | HTML Full-text | XML Full-text
Abstract
Agarwood is the fragrant resinous heartwood obtained from certain trees in the genus Aquilaria belonging to the family Thymelaeaceae. 2-(2-Phenylethyl)chromones and characteristic sesquiterpenes are the main classes of aromatic compounds isolated from agarwood. Although there are many sesquiterpenes, relatively few 2-(2-phenylethyl)chromones have been
[...] Read more.
Agarwood is the fragrant resinous heartwood obtained from certain trees in the genus Aquilaria belonging to the family Thymelaeaceae. 2-(2-Phenylethyl)chromones and characteristic sesquiterpenes are the main classes of aromatic compounds isolated from agarwood. Although there are many sesquiterpenes, relatively few 2-(2-phenylethyl)chromones have been determined in agarwood by GC-MS. After analysis of the MS spectra of eighteen 2-(2-phenylethyl)chromone derivatives isolated from agarwood and identified by NMR spectroscopy, together with the reported MS data and characteristic of structures of 2-(2-phenylethyl)chromones, the MS characterization, fragmentation patterns and characteristic fragment peaks for the compounds were deduced and a table summarizing MS characterization of 2-(2-phenylethyl)chromones in agarwood is presented. All the 2-(2-phenylethyl)chromones previously reported in agarwood are substituted by methoxy or/and hydroxy groups, except for one compound. Due to the fact they all possess the same basic skeleton (molecular weight: 250) and similar substituent groups (methoxy or hydroxy groups), a formula (30m + 16n = MW − 250) is provided to calculate the number of methoxy (m) or hydroxy (n) groups according to molecular ion peak or molecular weight (MW). We deduced that the characteristic fragmentation behaviors of the 2-(2-phenylethyl)chromones are the cleavages of the CH2-CH2 bond between chromone moiety and phenyl moiety. Thus, characteristic fragment ions, such as m/z 91 [C7H7], 107 [C7H6+OH], 121 [C7H6+OCH3], 137 [C7H5+OH+OCH3] are formed by different substituted benzyl moieties, while characteristic fragment ions such as m/z 160 [C10H8O2], 176 [C10H7O2+OH], 190 [C10H7O2+OCH3], 220 [C10H6O2+OCH3×2] are formed by different substituted chromone moieties. Furthermore, rules regarding to the relationship between the positions of hydroxy or methoxy groups and the relative abundances of benzyl and chromone fragment ions have been deduced. Elucidation of how the positions of hydroxy or methoxy groups affect the relative abundances of benzyl and chromone fragment peaks is also provided. Fifteen unidentified compounds of an artificial agarwood sample analyzed by GC-MS, were preliminary determined as 2-(2-phenylethyl)chromones by analysis of their MS characterization and by comparison of their MS spectra with those of 18 standard compounds or 2-(2-phenylethyl)chromones reported in literature according to the above-mentioned methods and rules. This report will be helpful for the analysis and structural elucidation of 2-(2-phenylethyl)chromones in agarwood by GC-MS, and provides fast and reliable characterization of the quality of agarwood. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of Boron-Containing Primary Amines
Molecules 2013, 18(10), 12346-12367; doi:10.3390/molecules181012346
Received: 30 August 2013 / Revised: 27 September 2013 / Accepted: 30 September 2013 / Published: 8 October 2013
Cited by 3 | PDF Full-text (585 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, boron-containing primary amines were synthesized for use as building blocks in the study of peptoids. In the first step, Gabriel synthesis conditions were modified to enable the construction of seven different aminomethylphenyl boronate esters in good to excellent yields. These
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In this study, boron-containing primary amines were synthesized for use as building blocks in the study of peptoids. In the first step, Gabriel synthesis conditions were modified to enable the construction of seven different aminomethylphenyl boronate esters in good to excellent yields. These compounds were further utilized to build peptoid analogs via an Ugi four-component reaction (Ugi-4CR) under microwave irradiation. The prepared Ugi-4CR boronate esters were then successfully converted to the corresponding boronic acids. Finally, the peptoid structures were successfully modified by cross-coupling to aryl/heteroaryl chlorides via a palladium-mediated Suzuki coupling reaction to yield the corresponding derivatives in moderate to good yields. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Mechanical, Rheological and Release Behaviors of a Poloxamer 407/ Poloxamer 188/Carbopol 940 Thermosensitive Composite Hydrogel
Molecules 2013, 18(10), 12415-12425; doi:10.3390/molecules181012415
Received: 22 July 2013 / Revised: 18 September 2013 / Accepted: 26 September 2013 / Published: 8 October 2013
Cited by 10 | PDF Full-text (1799 KB) | HTML Full-text | XML Full-text
Abstract
The aims of this study were to prepare a thermosensitive composite hydrogel (TCH) by mixing 24% (w/v) poloxamer 407 (P407), 16% (w/v) poloxamer 188 (P188) and 0.1% (w/v) carbopol 940 (C940), and to determine the effect of natural borneol/ (2-hydroxypropyl)-β-cyclodextrin (NB/HP-
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The aims of this study were to prepare a thermosensitive composite hydrogel (TCH) by mixing 24% (w/v) poloxamer 407 (P407), 16% (w/v) poloxamer 188 (P188) and 0.1% (w/v) carbopol 940 (C940), and to determine the effect of natural borneol/ (2-hydroxypropyl)-β-cyclodextrin (NB/HP-β-CD) inclusion complex on the phase transition temperature, mechanical, rheological properties, and release behaviors of the TCH using the tube inversion method, a texture analyzer, a rheometer, and in vitro release , respectively. The results showed that as the concentration of NB/HP-β-CD increased, the phase transition temperature of the TCH was increased from 37.26 to 38.34 °C and the mechanical properties of the TCH showed that the hardness, cohesiveness, strength, and adhesiveness were increased from 0.025 to 0.064 kg, 0.022 to 0.064 kg, 0.110 to 0.307 kg and 0.036 to 0.105 kg, respectively, but the rheological properties of the TCH showed that G′, G′′ and η were decreased from 7,760 to 157.50 Pa, 1,274 to 36.28 Pa and 1,252 to 25.37 Pas, respectively. The in vitro release showed that an increasing NB/HP-β-CD concentration decreased the release rate of NB from the TCH, but the amount of NB released was more than 96% at 60 min, which showed the TCH had good release behavior. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Antioxidant and Photoprotective Effects of Blanch Water, a Byproduct of the Almond Processing Industry
Molecules 2013, 18(10), 12426-12440; doi:10.3390/molecules181012426
Received: 28 August 2013 / Revised: 26 September 2013 / Accepted: 27 September 2013 / Published: 9 October 2013
Cited by 2 | PDF Full-text (395 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the present work was to evaluate the antioxidant and photoprotective effect of blanch water (BW), a byproduct of the almond processing industry. The polyphenolic content of a BW extract, the level of proanthocyanidins and the vanillin index determination were determined.
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The aim of the present work was to evaluate the antioxidant and photoprotective effect of blanch water (BW), a byproduct of the almond processing industry. The polyphenolic content of a BW extract, the level of proanthocyanidins and the vanillin index determination were determined. The antioxidant activity and the radical scavenging activity of the BW were evaluated by a range of in vitro tests. The in vivo photoprotective effect was investigated using a formulation containing 2% of the BW extract on skin erythema induced by acute UV-B exposure in twelve volunteers. Results confirmed the presence of added-value antioxidant compounds in the industrial BW extract, and the most representative compounds were naringenin-7-O-glucoside and kaempferol-7-O-rutinoside. The proanthocyanidin content was 71.84 ± 5.21 cyanidin equivalents/g of BW extract. The good antiradical activity of the BW extract was demonstrated in both the DPPH test and in the Reducing Power test. The percentage inhibition of erythema obtained using a formulation of BW was 50.48, value clearly demonstrating an effect against photooxidative damage in vivo. Full article
Open AccessArticle Protein Adsorption on Various Plasma-Treated Polyethylene Terephthalate Substrates
Molecules 2013, 18(10), 12441-12463; doi:10.3390/molecules181012441
Received: 2 August 2013 / Revised: 30 September 2013 / Accepted: 8 October 2013 / Published: 10 October 2013
Cited by 14 | PDF Full-text (2443 KB) | HTML Full-text | XML Full-text
Abstract
Protein adhesion and cell response to plasma-treated polymer surfaces were studied. The polymer polyethylene terephthalate (PET) was treated in either an oxygen plasma to make the surface hydrophilic, or a tetrafluoromethane CF4 plasma to make the surface hydrophobic. The plasma source was
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Protein adhesion and cell response to plasma-treated polymer surfaces were studied. The polymer polyethylene terephthalate (PET) was treated in either an oxygen plasma to make the surface hydrophilic, or a tetrafluoromethane CF4 plasma to make the surface hydrophobic. The plasma source was radiofrequency (RF) discharge. The adsorption of albumin and other proteins from a cell-culture medium onto these surfaces was studied using a quartz crystal microbalance (QCM), X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The cellular response to plasma-treated surfaces was studied as well using an MTT assay and scanning electron microscopy (SEM). The fastest adsorption rate was found on the hydrophilic oxygen plasma-treated sample, and the lowest was found on the pristine untreated sample. Additionally, the amount of adsorbed proteins was higher for the oxygen-plasma-treated surface, and the adsorbed layer was more viscoelastic. In addition, cell adhesion studies support this finding because the best cell adhesion was observed on oxygen-plasma-treated substrates. Full article
Open AccessArticle Four New Glycosides from the Fruit of Xanthium sibiricum Patr.
Molecules 2013, 18(10), 12464-12473; doi:10.3390/molecules181012464
Received: 19 July 2013 / Revised: 26 September 2013 / Accepted: 29 September 2013 / Published: 10 October 2013
Cited by 2 | PDF Full-text (376 KB) | HTML Full-text | XML Full-text
Abstract
Four new glycosides, namely 3β-norpinan-2-one 3-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (1), (6Z)-3-hydroxymethyl-7-methylocta-1,6-dien-3-ol 8-O-β-d-glucopyranoside (2), (6E)-3-hydroxymethyl-7-methylocta-1,6-dien-3-ol 8-O-β-d-gluco-pyranoside (3), and 7-[(β-d-apiofuranosyl-(1→6)-β-d-glucopyranosyl)oxymethy]-8,8-dimethyl-4,8-dihydrobenzo[1,4]thiazine-3,5-dione (4), were isolated from the fruits of Xanthium sibiricum Patr
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Four new glycosides, namely 3β-norpinan-2-one 3-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (1), (6Z)-3-hydroxymethyl-7-methylocta-1,6-dien-3-ol 8-O-β-d-glucopyranoside (2), (6E)-3-hydroxymethyl-7-methylocta-1,6-dien-3-ol 8-O-β-d-gluco-pyranoside (3), and 7-[(β-d-apiofuranosyl-(1→6)-β-d-glucopyranosyl)oxymethy]-8,8-dimethyl-4,8-dihydrobenzo[1,4]thiazine-3,5-dione (4), were isolated from the fruits of Xanthium sibiricum Patr together with three known compounds, xanthiside (5), adenosine (6), and 2,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-propan-1-one (7). The structures of the new compounds were determined on the basis of detailed spectroscopic analyses. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Ultrasound-Assisted Extraction (UAE) and Solvent Extraction of Papaya Seed Oil: Yield, Fatty Acid Composition and Triacylglycerol Profile
Molecules 2013, 18(10), 12474-12487; doi:10.3390/molecules181012474
Received: 1 August 2013 / Revised: 16 September 2013 / Accepted: 29 September 2013 / Published: 10 October 2013
Cited by 12 | PDF Full-text (539 KB) | HTML Full-text | XML Full-text
Abstract
The main objective of the current work was to evaluate the suitability of ultrasound-assisted extraction (UAE) for the recovery of oil from papaya seed as compared to conventional extraction techniques (i.e., Soxhlet extraction (SXE) and solvent extraction (SE)). In the present
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The main objective of the current work was to evaluate the suitability of ultrasound-assisted extraction (UAE) for the recovery of oil from papaya seed as compared to conventional extraction techniques (i.e., Soxhlet extraction (SXE) and solvent extraction (SE)). In the present study, the recovery yield, fatty acid composition and triacylglycerol profile of papaya seed oil obtained from different extraction methods and conditions were compared. Results indicated that both solvent extraction (SE, 12 h/25 °C) and ultrasound-assisted extraction (UAE) methods recovered relatively high yields (79.1% and 76.1% of total oil content, respectively). Analysis of fatty acid composition revealed that the predominant fatty acids in papaya seed oil were oleic (18:1, 70.5%–74.7%), palmitic (16:0, 14.9%–17.9%), stearic (18:0, 4.50%–5.25%), and linoleic acid (18:2, 3.63%–4.6%). Moreover, the most abundant triacylglycerols of papaya seed oil were triolein (OOO), palmitoyl diolein (POO) and stearoyl oleoyl linolein (SOL). In this study, ultrasound-assisted extraction (UAE) significantly (p < 0.05) influenced the triacylglycerol profile of papaya seed oil, but no significant differences were observed in the fatty acid composition of papaya seed oil extracted by different extraction methods (SXE, SE and UAE) and conditions. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Copper-Catalyzed Three- Five- or Seven-Component Coupling Reactions: The Selective Synthesis of Cyanomethylamines, N,N-Bis(Cyanomethyl)Amines and N,N'-Bis(Cyanomethyl)Methylenediamines Based on a Strecker-Type Synthesis
Molecules 2013, 18(10), 12488-12499; doi:10.3390/molecules181012488
Received: 28 August 2013 / Revised: 27 September 2013 / Accepted: 27 September 2013 / Published: 10 October 2013
Cited by 2 | PDF Full-text (292 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We have demonstrated that a cooperative catalytic system comprised of CuCl and Cu(OTf)2 could be used to effectively catalyse the three-, five- and seven-component coupling reactions of aliphatic or aromatic amines, formaldehyde, and trimethylsilyl cyanide (TMSCN), and selectively produce in good yields
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We have demonstrated that a cooperative catalytic system comprised of CuCl and Cu(OTf)2 could be used to effectively catalyse the three-, five- and seven-component coupling reactions of aliphatic or aromatic amines, formaldehyde, and trimethylsilyl cyanide (TMSCN), and selectively produce in good yields the corresponding cyanomethylamines, N,N-bis(cyanomethyl)amines and N,N'-bis(cyanomethyl)methylenediamines. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Volatile Compounds Profile of Sous-Vide Cooked Pork Cheeks as Affected by Cooking Conditions (Vacuum Packaging, Temperature and Time)
Molecules 2013, 18(10), 12538-12547; doi:10.3390/molecules181012538
Received: 23 July 2013 / Revised: 27 September 2013 / Accepted: 7 October 2013 / Published: 10 October 2013
Cited by 6 | PDF Full-text (233 KB) | HTML Full-text | XML Full-text
Abstract
The volatile organic compound (VOC) profile of pork cheeks as affected by the cooking conditions was investigated. Pork cheeks were cooked under different combinations of temperature (60 °C or 80 °C), time (5 or 12 h) and vacuum (vacuum or air-packaged). As a
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The volatile organic compound (VOC) profile of pork cheeks as affected by the cooking conditions was investigated. Pork cheeks were cooked under different combinations of temperature (60 °C or 80 °C), time (5 or 12 h) and vacuum (vacuum or air-packaged). As a general rule, the VOCs originating from lipid degradation were positively affected by the cooking temperature and negatively by the cooking time, reaching the highest amounts in pork cheeks cooked at 80 °C during 5 h and the lowest in samples cooked at 80 °C during 12 h. On the contrary, VOCs originated from amino acids and Maillard reactions were positively affected by both factors. The proportion between lipid degradation and amino acids reactions was estimated by the hexanal/3-methylbutanal ratio, which reached its highest values in samples cooked at 60 °C during 5 h in the presence of air and the lowest values in samples cooked at 80 °C during 12 h, regardless of the vacuum status. Full article
(This article belongs to the Special Issue Flavors and Fragrances)
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Open AccessArticle Hypolipidemic and Antioxidant Properties of Phenolic Compound-Rich Extracts from White Ginseng (Panax ginseng) in Cholesterol-Fed Rabbits
Molecules 2013, 18(10), 12548-12560; doi:10.3390/molecules181012548
Received: 31 July 2013 / Revised: 26 September 2013 / Accepted: 27 September 2013 / Published: 10 October 2013
Cited by 11 | PDF Full-text (310 KB) | HTML Full-text | XML Full-text
Abstract
In this study, the effect of low-molecular weight white ginseng compounds on various biochemical indices, including blood lipid concentrations and antioxidant enzyme activities and morphological changes was investigated in rabbits with high cholesterol diet-induced hypercholesterolemia. The experimental animals were 16-week-old male New Zealand
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In this study, the effect of low-molecular weight white ginseng compounds on various biochemical indices, including blood lipid concentrations and antioxidant enzyme activities and morphological changes was investigated in rabbits with high cholesterol diet-induced hypercholesterolemia. The experimental animals were 16-week-old male New Zealand white rabbits divided into normal control diet, high cholesterol diet, and high cholesterol with 0.05% white ginseng low-molecule compound groups, treated for 4 weeks. Blood lipid concentrations were higher in the high cholesterol groups compared to the normal control group but were not improved by the white ginseng low-molecular weight compound. We note however that antioxidant enzyme activities and morphological changes of the aorta showed that white ginseng small compounds had a positive effect on hypercholesterolemia. Based on such results, low-molecular weight compounds rich in phenolic compounds in white ginseng can be said to be effective in part in improving hyperlipidemia and atherosclerosis induced by a high cholesterol diet among New Zealand white rabbits. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Antifungal Activity of Copaifera langsdorffii Desf Oleoresin against Dermatophytes
Molecules 2013, 18(10), 12561-12570; doi:10.3390/molecules181012561
Received: 2 September 2013 / Revised: 8 October 2013 / Accepted: 9 October 2013 / Published: 11 October 2013
Cited by 7 | PDF Full-text (1847 KB) | HTML Full-text | XML Full-text
Abstract
Dermatophytoses are mycoses that affect keratinized tissues in both humans and animals. The aim of this study was to investigate the antifungal activity of the oleoresin extracted from Copaifera langsdorffii Desf. against the strains Microsporum canis ATCC 32903, Microsporum gypseum ATCC 14683, Trichophyton
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Dermatophytoses are mycoses that affect keratinized tissues in both humans and animals. The aim of this study was to investigate the antifungal activity of the oleoresin extracted from Copaifera langsdorffii Desf. against the strains Microsporum canis ATCC 32903, Microsporum gypseum ATCC 14683, Trichophyton mentagrophytes ATCC 11481 and Trichophyton rubrum CCT 5507. The antimicrobial activity was determined by minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values. Ketoconazole and terbinafine were used as reference drugs. The copaiba oleoresin showed moderate fungicidal activity against T. mentagrophytes ATCC 11481 (MIC and MFC = 170 μg mL−1) and weak fungicidal activity against T. rubrum CCT 5507 (MIC = 1,360 μg mL−1 and MFC = 2,720 μg mL−1). There was no activity against M. canis ATCC 32903 and M. gypseum ATCC 14683. SEM analysis revealed physical damage and morphological alterations such as compression and hyphae clustering in the structure of the fungi exposed to the action of the oleoresin. The results stimulate the achievement of in vivo assays to confirm the benefits of the application of oleoresin extracted from copaiba in the treatment of dermatophytosis, both in humans and in animals. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Enzymatic Synthesis of Highly Fluorescent 8-Azapurine Ribosides Using a Purine Nucleoside Phosphorylase Reverse Reaction: Variable Ribosylation Sites
Molecules 2013, 18(10), 12587-12598; doi:10.3390/molecules181012587
Received: 30 August 2013 / Revised: 25 September 2013 / Accepted: 30 September 2013 / Published: 11 October 2013
Cited by 4 | PDF Full-text (414 KB) | HTML Full-text | XML Full-text
Abstract
Various forms of purine-nucleoside phosphorylase (PNP) were used as catalysts of enzymatic ribosylation of selected fluorescent 8-azapurines. It was found that the recombinant calf PNP catalyzes ribosylation of 2,6-diamino-8-azapurine in a phosphate-free medium, with ribose-1-phosphate as ribose donor, but the ribosylation site is
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Various forms of purine-nucleoside phosphorylase (PNP) were used as catalysts of enzymatic ribosylation of selected fluorescent 8-azapurines. It was found that the recombinant calf PNP catalyzes ribosylation of 2,6-diamino-8-azapurine in a phosphate-free medium, with ribose-1-phosphate as ribose donor, but the ribosylation site is predominantly N7 and N8, with the proportion of N8/N7 ribosylated products markedly dependent on the reaction conditions. Both products are fluorescent. Application of the E. coli PNP gave a mixture of N8 and N9-substituted ribosides. Fluorescence of the ribosylated 2,6-diamino-8-azapurine has been briefly characterized. The highest quantum yield, ~0.9, was obtained for N9-β-d-riboside (λmax 365 nm), while for N8-β-d-riboside, emitting at ~430 nm, the fluorescence quantum yield was found to be close to 0.4. Ribosylation of 8-azaguanine with calf PNP as a catalyst goes exclusively to N9. By contrast, the E. coli PNP ribosylates 8-azaGua predominantly at N9, with minor, but highly fluorescent products ribosylated at N8/N7. Full article
(This article belongs to the Special Issue Synthesis of Nucleosides, Nucleotides and Their Derivatives)
Open AccessCommunication Comparative Analysis of Click Chemistry Mediated Activity-Based Protein Profiling in Cell Lysates
Molecules 2013, 18(10), 12599-12608; doi:10.3390/molecules181012599
Received: 26 June 2013 / Revised: 7 August 2013 / Accepted: 26 September 2013 / Published: 11 October 2013
Cited by 7 | PDF Full-text (426 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Activity-based protein profiling uses chemical probes that covalently attach to active enzyme targets. Probes with conventional tags have disadvantages, such as limited cell permeability or steric hindrance around the reactive group. A tandem labeling strategy with click chemistry is now widely used to
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Activity-based protein profiling uses chemical probes that covalently attach to active enzyme targets. Probes with conventional tags have disadvantages, such as limited cell permeability or steric hindrance around the reactive group. A tandem labeling strategy with click chemistry is now widely used to study enzyme targets in situ and in vivo. Herein, the probes are reacted in live cells, whereas the ensuing detection by click chemistry takes place in cell lysates. We here make a comparison of the efficiency of the activity-based tandem labeling strategy by using Cu(I)-catalyzed and strain-promoted click chemistry, different ligands and different lysis conditions. Full article
(This article belongs to the Special Issue Advances in Click Chemistry)
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Open AccessArticle Size Effect of Gold Nanoparticles in Catalytic Reduction of p-Nitrophenol with NaBH4
Molecules 2013, 18(10), 12609-12620; doi:10.3390/molecules181012609
Received: 2 September 2013 / Revised: 1 October 2013 / Accepted: 6 October 2013 / Published: 11 October 2013
Cited by 39 | PDF Full-text (1404 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Gold nanoparticles (Au NPs) were prepared by reducing HAuCl4 with NaBH4. Their average particle sizes could be tuned in the range of 1.7 and 8.2 nm, by adjusting the amount of NaBH4 used during synthesis. The obtained Au NPs
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Gold nanoparticles (Au NPs) were prepared by reducing HAuCl4 with NaBH4. Their average particle sizes could be tuned in the range of 1.7 and 8.2 nm, by adjusting the amount of NaBH4 used during synthesis. The obtained Au NPs (colloids) were then loaded onto a commercial Al2O3 support to prepare Au/Al2O3 catalysts with tunable Au particle sizes. An optimal pH value (5.9) of the Au colloid solution was found to be essential for loading Au NPs onto Al2O3 while avoiding the growth of Au NPs. Au NPs and Au/Al2O3 catalysts were tested in the reduction of p-nitrophenol with NaBH4. Interestingly, the catalytic activity depended on the size of Au NPs, being the highest when the average size was 3.4 nm. Relevant characterization by UV-Vis, TEM, and XRD was conducted. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Assessment of the Anti-Protozoal Activity of Crude Carica papaya Seed Extract against Trypanosoma cruzi
Molecules 2013, 18(10), 12621-12632; doi:10.3390/molecules181012621
Received: 27 August 2013 / Revised: 20 September 2013 / Accepted: 23 September 2013 / Published: 11 October 2013
Cited by 3 | PDF Full-text (617 KB) | HTML Full-text | XML Full-text
Abstract
In order to determine the in vivo activity against the protozoan Trypanosoma cruzi, two doses (50 and 75 mg/kg) of a chloroform extract of Carica papaya seeds were evaluated compared with a control group of allopurinol. The activity of a mixture of
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In order to determine the in vivo activity against the protozoan Trypanosoma cruzi, two doses (50 and 75 mg/kg) of a chloroform extract of Carica papaya seeds were evaluated compared with a control group of allopurinol. The activity of a mixture of the three main compounds (oleic, palmitic and stearic acids in a proportion of 45.9% of oleic acid, 24.1% of palmitic and 8.52% of stearic acid previously identified in the crude extract of C. papaya was evaluated at doses of 100, 200 and 300 mg/kg. Both doses of the extracts were orally administered for 28 days. A significant reduction (p < 0.05) in the number of blood trypomastigotes was observed in animals treated with the evaluated doses of the C. papaya extract in comparison with the positive control group (allopurinol 8.5 mg/kg). Parasitemia in animals treated with the fatty acids mixture was also significantly reduced (p < 0.05), compared to negative control animals. These results demonstrate that the fatty acids identified in the seed extracts of C. papaya (from ripe fruit) are able to reduce the number of parasites from both parasite stages, blood trypomastigote and amastigote (intracellular stage). Full article
(This article belongs to the Special Issue Plant Natural Products against Human Parasites)
Open AccessArticle Antimicrobial and Selected In Vitro Enzyme Inhibitory Effects of Leaf Extracts, Flavonols and Indole Alkaloids Isolated from Croton menyharthii
Molecules 2013, 18(10), 12633-12644; doi:10.3390/molecules181012633
Received: 12 July 2013 / Revised: 9 September 2013 / Accepted: 17 September 2013 / Published: 11 October 2013
Cited by 10 | PDF Full-text (246 KB) | HTML Full-text | XML Full-text
Abstract
Croton species are used in folk medicine in the management of infections, inflammation and oxidative stress-related diseases. In order to isolate, characterize and evaluate the bioactive constituents of Croton menyharthii Pax leaf extracts, repeated column fractionation of the ethyl acetate fraction from a
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Croton species are used in folk medicine in the management of infections, inflammation and oxidative stress-related diseases. In order to isolate, characterize and evaluate the bioactive constituents of Croton menyharthii Pax leaf extracts, repeated column fractionation of the ethyl acetate fraction from a 20% aqueous methanol crude extract afforded three flavonols identified by NMR (1D and 2D) spectroscopic methods as myricetrin-3-O-rhamnoside (myricetrin, 1), quercetin-3-O-rhamnoside (2) and quercetin (3) along with an indole alkaloid, (E)-N-(4-hydroxycinnamoyl)-5-hydroxytryptamine, [trans-N-(p-coumaroyl) serotonin, 4]. All the compounds are reported from the leaf extract of this plant for the first time. The crude extracts, four solvent fractions (hexane, DCM, ethyl acetate and butanol) and isolated compounds obtained from the leaves were evaluated for their inhibitory effects on selected bacteria, a fungus (Candida albicans), cyclooxygenase (COX-2), α-glucosidase and acetylcholinesterase (AChE). Amongst the compounds, quercetin (3) was the most active against Bacillus subtilis and Candida albicans while myricetrin-3-O-rhamnoside (1) and trans-N-(p-coumaroyl) serotonin (4) were the most active compounds against Escherichia coli, Klebsiella pneumonia and Staphylococcus aureus. The inhibitory activity of myricetrin-3-O-rhamnoside (1) against COX-2 was insignificant while that of the other three compounds 24 was low. The AChE inhibitory activity of the alkaloid, trans-N-(p-coumaroyl) serotonin was high, with a percentage inhibitory activity of 72.6% and an IC50 value of 15.0 µg/mL. The rest of the compounds only had moderate activity. Croton menyharthii leaf extracts and isolated compounds inhibit α-glucosidase at very low IC50 values compared to the synthetic drug acarbose. Structure activity relationship of the isolated flavonols 13 is briefly outlined. Compounds 14 and the leaf extracts exhibited a broad spectrum of activities. This validates the ethnomedicinal use of the plant in folk medicine. Full article
(This article belongs to the Special Issue Structure-Activity Relationship of Flavonoids)
Open AccessArticle Structural Studies and Investigation on the Activity of Imidazole-Derived Thiosemicarbazones and Hydrazones against Crop-Related Fungi
Molecules 2013, 18(10), 12645-12662; doi:10.3390/molecules181012645
Received: 14 August 2013 / Revised: 25 September 2013 / Accepted: 26 September 2013 / Published: 14 October 2013
Cited by 8 | PDF Full-text (952 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
New imidazole derived thiosemicarbazones and hydrazones were prepared by condensation of 4(5)-imidazole carboxaldehyde, 4-(1H-imidazole-1-yl)benzaldehyde and 4-(1H-imidazole-1-yl)acetophenone with a thiosemicarbazide or hydrazide. All compounds were characterized by quantitative elemental analysis, IR and NMR techniques. Eight structures were determined by single
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New imidazole derived thiosemicarbazones and hydrazones were prepared by condensation of 4(5)-imidazole carboxaldehyde, 4-(1H-imidazole-1-yl)benzaldehyde and 4-(1H-imidazole-1-yl)acetophenone with a thiosemicarbazide or hydrazide. All compounds were characterized by quantitative elemental analysis, IR and NMR techniques. Eight structures were determined by single crystal X-ray diffraction. The antifungal activities of the compounds were evaluated. None of the compounds exhibited significant activity against Aspergillus flavus and Candida albicans, while 4(5)-imidazolecarboxaldehyde thiosemicarbazone (ImT) and 4-(1H-imidazole-1-yl)benzaldehyde thiosemicabazone (4ImBzT) were highly and selectively active against Cladosporium cladosporioides. 4(5)-Imidazolecarboxaldehyde benzoyl hydrazone (4(5)ImPh), 4(5)-imidazolecarboxaldehyde-para-chlorobenzoyl hydrazone (4(5)ImpClPh), 4(5)-imidazolecarboxaldehyde-para-nitrobenzoyl hydrazone (4(5)ImpNO2Ph), 4-(imidazole-1-yl)acetophenone-para-chloro-benzoyl hydrazone (4ImAcpClPh) and 4-(imidazole-1-yl)acetophenone-para-nitro-benzoylhydrazone (4ImAcpNO2Ph) were highly active against Candida glabrata. 4(5)ImpClPh and 4(5)ImpNO2Ph were very effective against C. cladosporioides. In many cases, activity was superior to that of the reference compound nystatin. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Understanding the Molecular Aspects of Tetrahydrocannabinol and Cannabidiol as Antioxidants
Molecules 2013, 18(10), 12663-12674; doi:10.3390/molecules181012663
Received: 4 October 2013 / Revised: 4 October 2013 / Accepted: 10 October 2013 / Published: 14 October 2013
Cited by 2 | PDF Full-text (2614 KB) | HTML Full-text | XML Full-text
Abstract
An antioxidant mechanism of tetrahydrocannabinol (THC) and cannabidiol (CBD) were compared with a simplified model of α-tocopherol, butylhydroxytoluene and hydroxytoluene in order to understand the antioxidant nature of THC and CBD molecules using DFT. The following electronic properties were evaluated: frontier orbitals nature,
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An antioxidant mechanism of tetrahydrocannabinol (THC) and cannabidiol (CBD) were compared with a simplified model of α-tocopherol, butylhydroxytoluene and hydroxytoluene in order to understand the antioxidant nature of THC and CBD molecules using DFT. The following electronic properties were evaluated: frontier orbitals nature, ionization potential, O-H bond dissociation energy (BDEOH), stabilization energy, and spin density distribution. An important factor that shows an influence in the antioxidant property of THC is the electron abstraction at the phenol position. Our data indicate that the decrease of the HOMO values and the highest ionization potential values are related to phenol, ether, and alkyl moieties. On the other hand, BDEOH in molecules with the cyclohexenyl group at ortho position of phenol are formed from lower energies than the molecules with an ether group at the meta position. In the light of our results, the properties calculated here predict that THC has a sightly higher antioxidant potential than CBD. Full article
Open AccessArticle Electrochemical Enzyme-Linked Immunosorbent Assay (ELISA) for α-Fetoprotein Based on Glucose Detection with Multienzyme-Nanoparticle Amplification
Molecules 2013, 18(10), 12675-12686; doi:10.3390/molecules181012675
Received: 2 August 2013 / Revised: 7 October 2013 / Accepted: 10 October 2013 / Published: 14 October 2013
Cited by 16 | PDF Full-text (963 KB) | HTML Full-text | XML Full-text
Abstract
Since glucose biosensors are one of the most popular and widely used point-of-care testing devices, a novel electrochemical enzyme-linked immunosorbent assay (ELISA) for protein biomarkers has been developed based on a glucose detection strategy. In this study, α-fetoprotein (AFP) was used as the
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Since glucose biosensors are one of the most popular and widely used point-of-care testing devices, a novel electrochemical enzyme-linked immunosorbent assay (ELISA) for protein biomarkers has been developed based on a glucose detection strategy. In this study, α-fetoprotein (AFP) was used as the target protein. An electrochemical ELISA system was constructed using anti-AFP antibodies immobilized on microwell plates as the capture antibody (Ab1) and multi-label bioconjugates as signal tracer. The bioconjugates were synthesized by attaching glucoamylase and the secondary anti-AFP antibodies (Ab2) to gold nanoparticles (AuNPs). After formation of the sandwich complex, the Ab2-glucoamylase-AuNPs conjugates converted starch into glucose in the presence of AFP. The concentration of AFP can be calculated based on the linear relation between AFP and glucose, the concentration of which can be detected by the glucose biosensor. When the AFP concentration ranged from 0.05 to 100 ng/mL, a linear calibration plot (i (µA) = 13.62033 − 2.86252 logCAFP (ng/mL), r = 0.99886) with a detection limit of 0.02 ng/mL was obtained under optimal conditions. The electrochemical ELISA developed in this work shows acceptable stability and reproducibility, and the assay for AFP spiked in human serum also shows good recovery (97.0%–104%). This new method could be applied for detecting any protein biomarker with the corresponding antibodies. Full article
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Open AccessArticle Orbital Interaction and Electron Density Transfer in PdII([9]aneB2A)L2 Complexes: Theoretical Approaches
Molecules 2013, 18(10), 12687-12706; doi:10.3390/molecules181012687
Received: 29 July 2013 / Revised: 13 September 2013 / Accepted: 29 September 2013 / Published: 14 October 2013
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Abstract
The geometric structures of Pd-complexes {Pd([9]aneB2A)L2 and Pd([9]aneBAB)L2 where A = P, S; B = N; L = PH3, P(CH3)3, Cl}, their selective orbital interaction
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The geometric structures of Pd-complexes {Pd([9]aneB2A)L2 and Pd([9]aneBAB)L2 where A = P, S; B = N; L = PH3, P(CH3)3, Cl}, their selective orbital interaction towards equatorial or axial (soft A…Pd) coordination of macrocyclic [9]aneB2A tridentate to PdL2, and electron density transfer from the electron-rich trans L-ligand to the low-lying unfilled a1g(5s)-orbital of PdL2 were investigated using B3P86/lanl2DZ for Pd and 6-311+G** for other atoms. The pentacoordinate endo-[Pd([9]aneB2A)(L-donor)2]2+ complex with an axial (soft A--Pd) quasi-bond was optimized for stability. The fifth (soft A--Pd) quasi-bond between the σ-donor of soft A and the partially unfilled a1g(5s)-orbital of PdL2 was formed. The pentacoordinate endo-Pd([9]aneB2A)(L-donor)2]2+ complex has been found to be more stable than the corresponding tetracoordinate endo-Pd complexes. Except for the endo-Pd pentacoordinates, the tetracoordinate Pd([9]aneBAB)L2 complex with one equatorial (soft A-Pd) bond is found to be more stable than the Pd([9]aneB2A)L2 isomer without the equatorial (A-Pd) bond. In particular, the geometric configuration of endo-[Pd([9]anePNP)(L-donor)2]2+ could not be optimized. Full article
(This article belongs to the Special Issue Macrocyclic Chemistry)
Open AccessArticle Heteroaryl Chalcones: Design, Synthesis, X-ray Crystal Structures and Biological Evaluation
Molecules 2013, 18(10), 12707-12724; doi:10.3390/molecules181012707
Received: 11 September 2013 / Revised: 1 October 2013 / Accepted: 9 October 2013 / Published: 15 October 2013
Cited by 18 | PDF Full-text (1626 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chalcone derivatives have attracted increasing attention due to their numerous pharmacological activities. Changes in their structures have displayed high degree of diversity that has proven to result in a broad spectrum of biological activities. The present study highlights the synthesis of some halogen
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Chalcone derivatives have attracted increasing attention due to their numerous pharmacological activities. Changes in their structures have displayed high degree of diversity that has proven to result in a broad spectrum of biological activities. The present study highlights the synthesis of some halogen substituted chalcones 3(ai) containing the 5-chlorothiophene moiety, their X-ray crystal structures and the evaluation of possible biological activities such as antibacterial, antifungal and reducing power abilities. The results indicate the tested compounds show a varied range of inhibition values against all the tested microbial strains. Compound 3c with a p-fluoro substituent on the phenyl ring exhibits elevated antimicrobial activity, whereas the compounds 3e and 3f displayed the least antimicrobial activities. The compounds 3d, 3e, 3f and 3i showed good ferric and cupric reducing abilities, and the compounds 3b and 3c showed the weakest reducing power in the series. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Microwave Assisted Synthesis, Antifungal Activity and DFT Theoretical Study of Some Novel 1,2,4-Triazole Derivatives Containing the 1,2,3-Thiadiazole Moiety
Molecules 2013, 18(10), 12725-12739; doi:10.3390/molecules181012725
Received: 3 September 2013 / Revised: 11 October 2013 / Accepted: 11 October 2013 / Published: 15 October 2013
Cited by 38 | PDF Full-text (525 KB) | HTML Full-text | XML Full-text
Abstract
In order to investigate the biological activity of 1,2,4-triazole compounds, seventeen novel 1,2,4-triazole derivatives containing 1,2,3-thiadiazole moieties were synthesized by multi-step reactions under microwave assisted conditions. The structures were characterized by 1H-NMR, 13C-NMR, MS and elemental analyses. The target compounds
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In order to investigate the biological activity of 1,2,4-triazole compounds, seventeen novel 1,2,4-triazole derivatives containing 1,2,3-thiadiazole moieties were synthesized by multi-step reactions under microwave assisted conditions. The structures were characterized by 1H-NMR, 13C-NMR, MS and elemental analyses. The target compounds were evaluated for their in vivo fungicidal activities against Corynespora cassiicola, Pseudomonas syringae pv. Lachrymans, and Pseudoperonospora cubensis, and the results indicated that some of the title compounds displayed good fungicidal activities. Theoretical calculations on the title compounds were carried out at the B3LYP/6-31G (d,p). level. The full geometry optimization was carried out using the 6-31G(d,p) basis set, and the frontier orbital energy, atomic net charges were discussed, and the structure-activity relationships were also studied. Full article
Open AccessArticle An Efficient and Facile Methodology for Bromination of Pyrimidine and Purine Nucleosides with Sodium Monobromoisocyanurate (SMBI)
Molecules 2013, 18(10), 12740-12750; doi:10.3390/molecules181012740
Received: 2 September 2013 / Revised: 2 October 2013 / Accepted: 9 October 2013 / Published: 15 October 2013
Cited by 1 | PDF Full-text (199 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An efficient and facile strategy has been developed for bromination of nucleosides using sodium monobromoisocyanurate (SMBI). Our methodology demonstrates bromination at the C-5 position of pyrimidine nucleosides and the C-8 position of purine nucleosides. Unprotected and also several protected nucleosides were brominated in
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An efficient and facile strategy has been developed for bromination of nucleosides using sodium monobromoisocyanurate (SMBI). Our methodology demonstrates bromination at the C-5 position of pyrimidine nucleosides and the C-8 position of purine nucleosides. Unprotected and also several protected nucleosides were brominated in moderate to high yields following this procedure. Full article
(This article belongs to the Special Issue Synthesis of Nucleosides, Nucleotides and Their Derivatives)
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Open AccessArticle The Effect of Molecular Crowding on the Stability of Human c-MYC Promoter Sequence I-Motif at Neutral pH
Molecules 2013, 18(10), 12751-12767; doi:10.3390/molecules181012751
Received: 16 August 2013 / Revised: 26 September 2013 / Accepted: 10 October 2013 / Published: 15 October 2013
Cited by 18 | PDF Full-text (423 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We have previously shown that c-MYC promoter sequences can form stable i-motifs in acidic solution (pH 4.5–5.5). In terms of drug targeting, the question is whether c-MYC promoter sequence i-motifs will exist in the nucleus at neutral pH. In this work, we have
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We have previously shown that c-MYC promoter sequences can form stable i-motifs in acidic solution (pH 4.5–5.5). In terms of drug targeting, the question is whether c-MYC promoter sequence i-motifs will exist in the nucleus at neutral pH. In this work, we have investigated the stability of a mutant c-MYC i-motif in solutions containing a molecular crowding agent. The crowded nuclear environment was modeled by the addition of up to 40% w/w polyethylene glycols having molecular weights up to 12,000 g/mol. CD and DSC were used to establish the presence and stability of c-MYC i-motifs in buffer solutions over the pH range 4 to 7. We have shown that the c-MYC i-motif can exist as a stable structure at pH values as high as 6.7 in crowded solutions. Generic dielectric constant effects, e.g., a shift in the pKa of cytosine by more than 2 units (e.g., 4.8 to 7.0), or the formation of non-specific PEG/DNA complexes appear to contribute insignificantly to i-motif stabilization. Molecular crowding, largely an excluded volume effect of added PEG, having a molecular weight in excess of 1,000 g/mol, appears to be responsible for stabilizing the more compact i-motif over the random coil at higher pH values. Full article
(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)
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Open AccessArticle Ring-Opening Polymerization of l-Lactic Acid O-Carboxyanhydrides Initiated by Alkoxy Rare Earth Compounds
Molecules 2013, 18(10), 12768-12776; doi:10.3390/molecules181012768
Received: 20 August 2013 / Revised: 28 September 2013 / Accepted: 30 September 2013 / Published: 15 October 2013
Cited by 3 | PDF Full-text (308 KB) | HTML Full-text | XML Full-text
Abstract
The ring-opening polymerization of l-lactic acid O-carboxyanhydrides was initiated by triisopropoxyneodymium in toluene-THF mixtures. Typically, high yields and relatively high molecular weight PLAs were obtained within 4 h at 25 °C. The reaction was highly controllable and easy to conduct, and the
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The ring-opening polymerization of l-lactic acid O-carboxyanhydrides was initiated by triisopropoxyneodymium in toluene-THF mixtures. Typically, high yields and relatively high molecular weight PLAs were obtained within 4 h at 25 °C. The reaction was highly controllable and easy to conduct, and the molecular weight distribution of the PLAs was rather narrow (Mw/Mn = 1.10–1.36). NMR analysis showed that one end of the PLA chain consisted of an isopropoxy group, while the other end of the chain contained a hydroxyl group. Due to their availability and high polymerizability, Lac-OCAs are promising monomers for the preparation of tailored architectures derived from well-defined PLAs. Full article
Open AccessArticle Ginsenoside Rb1 Attenuates Oxygen-Glucose Deprivation-Induced Apoptosis in SH-SY5Y Cells via Protection of Mitochondria and Inhibition of AIF and Cytochrome c Release
Molecules 2013, 18(10), 12777-12792; doi:10.3390/molecules181012777
Received: 29 July 2013 / Revised: 22 September 2013 / Accepted: 14 October 2013 / Published: 16 October 2013
Cited by 16 | PDF Full-text (948 KB) | HTML Full-text | XML Full-text
Abstract
To investigate the role of mitochondria in the protective effects of ginsenoside Rb1 on cellular apoptosis caused by oxygen-glucose deprivation, in this study, MTT assay, TUNEL staining, flow cytometry, immunocytochemistry and western blotting were used to examine the cellular viability, apoptosis, ROS level,
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To investigate the role of mitochondria in the protective effects of ginsenoside Rb1 on cellular apoptosis caused by oxygen-glucose deprivation, in this study, MTT assay, TUNEL staining, flow cytometry, immunocytochemistry and western blotting were used to examine the cellular viability, apoptosis, ROS level, mitochondrial membrane potential, and the distribution of apoptosis inducing factor, cytochrome c, Bax and Bcl-2 in nucleus, mitochondria and cytoplasm. We found that pretreatment with GRb1 improved the cellular viability damaged by OGD. Moreover, GRb1 inhibited apoptosis in SH-SY5Y cells induced by OGD. Further studies showed that the elevation of cellular reactive oxygen species levels and the reduction of mitochondrial membrane potential caused by OGD were both counteracted by GRb1. Additionally, GRb1 not only suppressed the translocation of apoptosis inducing factor into nucleus and cytochrome c into cytoplasm, but also inhibited the increase of Bax within mitochondria and alleviated the decrease of mitochondrial Bcl-2. Our study indicates that the protection of GRb1 on OGD-induced apoptosis in SH-SY5Y cells is associated with its protection on mitochondrial function and inhibition of release of AIF and cytochrome c. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Apoptosis Sensitization by Euphorbia Factor L1 in ABCB1-Mediated Multidrug Resistant K562/ADR Cells
Molecules 2013, 18(10), 12793-12808; doi:10.3390/molecules181012793
Received: 9 September 2013 / Revised: 11 October 2013 / Accepted: 11 October 2013 / Published: 16 October 2013
Cited by 7 | PDF Full-text (2917 KB) | HTML Full-text | XML Full-text
Abstract
In this article, reversal activities of Euphorbia factor L1 (EFL1) against ABCB1-mediated multidrug resistance (MDR) and apoptosis sensitization in K562/ADR cells are reported. EFL1 decreased the IC50 values of anticancer agents in K562/ADR cells over-expressing ABCB1. However, EFL1 did not affect the
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In this article, reversal activities of Euphorbia factor L1 (EFL1) against ABCB1-mediated multidrug resistance (MDR) and apoptosis sensitization in K562/ADR cells are reported. EFL1 decreased the IC50 values of anticancer agents in K562/ADR cells over-expressing ABCB1. However, EFL1 did not affect the IC50 values of anticancer agents in sensitive K562 cells. Additionally, EFL1 increased the intracellular accumulation of rhodamine 123 and doxorubicin in K562/ADR cells without affecting their accumulation in K562 cells. Furthermore, EFL1 sensitized the apoptosis triggered by vincristine in K562/ADR cells via mitochondrial pathway, as confirmed by Annexin V-FITC/PI detection and western blot. At the same time, EFL1 did not influence the apoptosis induced by vincristine in K562 cells. Western blot results showed that EFL1 did not affect the phosphorylation level of AKT and ERK in K562 and K562/ADR cells. Finally, EFL1 did not down-regulate protein expression of ABCB1. Full article
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Open AccessArticle Astragaloside IV Stimulates Angiogenesis and Increases Nitric Oxide Accumulation via JAK2/STAT3 and ERK1/2 Pathway
Molecules 2013, 18(10), 12809-12819; doi:10.3390/molecules181012809
Received: 23 August 2013 / Revised: 30 September 2013 / Accepted: 10 October 2013 / Published: 16 October 2013
Cited by 14 | PDF Full-text (1454 KB) | HTML Full-text | XML Full-text
Abstract
Astragaloside IV (AS-IV), one of the major active constituents of Astragalus membranaceus in Traditional Chinese Medicine, has been widely used to treat ischemic diseases. However, the potential mechanism is this action is unclear. In this study, we tested the hypothesis that AS-IV might
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Astragaloside IV (AS-IV), one of the major active constituents of Astragalus membranaceus in Traditional Chinese Medicine, has been widely used to treat ischemic diseases. However, the potential mechanism is this action is unclear. In this study, we tested the hypothesis that AS-IV might promote angiogenesis through multiple signaling pathways. Our data indicate that AS-IV treatment promotes umbilical vein endothelial cells (HUVEC) proliferation, migration, and tube formation. AS-IV treatment also activates JAK2/STAT3 and ERK1/2 signaling pathways, and up-regulates endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) production. AS-IV-induced angiogenesis in HUVECs is significantly blocked by specific kinase inhibitors. Our study indicated that AS-IV is a key regulator of NO and angiogenesis through the JAK2/STAT3 and ERK1/2 pathways, which provides a mechanistic basis for the potential use of this compound in the treatment of clinical ischemic diseases. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of Cycloveratrylene Macrocycles and Benzyl Oligomers Catalysed by Bentonite under Microwave/Infrared and Solvent-Free Conditions
Molecules 2013, 18(10), 12820-12844; doi:10.3390/molecules181012820
Received: 25 August 2013 / Revised: 11 October 2013 / Accepted: 11 October 2013 / Published: 16 October 2013
Cited by 1 | PDF Full-text (916 KB) | HTML Full-text | XML Full-text
Abstract
Tonsil Actisil FF, which is a commercial bentonitic clay, promotes the formation of cycloveratrylene macrocycles and benzyl oligomers from the corresponding benzyl alcohols in good yields under microwave heating and infrared irradiation in the absence of solvent in both cases. The catalytic reaction
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Tonsil Actisil FF, which is a commercial bentonitic clay, promotes the formation of cycloveratrylene macrocycles and benzyl oligomers from the corresponding benzyl alcohols in good yields under microwave heating and infrared irradiation in the absence of solvent in both cases. The catalytic reaction is sensitive to the type of substituent on the aromatic ring. Thus, when benzyl alcohol was substituted with a methylenedioxy, two methoxy or three methoxy groups, a cyclooligomerisation process was induced. Unsubstituted, methyl and methoxy benzyl alcohols yielded linear oligomers. In addition, computational chemistry calculations were performed to establish a validated mechanistic pathway to explain the growth of the obtained linear oligomers. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Cs+ Removal from Aqueous Solutions through Adsorption onto Florisil® Impregnated with Trihexyl(tetradecyl)phosphonium Chloride
Molecules 2013, 18(10), 12845-12856; doi:10.3390/molecules181012845
Received: 1 August 2013 / Revised: 9 October 2013 / Accepted: 10 October 2013 / Published: 16 October 2013
Cited by 10 | PDF Full-text (195 KB) | HTML Full-text | XML Full-text
Abstract
This research determined the adsorption performance of Florisil® impregnated with trihexyl(tetradecyl)phosphonium chloride (Cyphos IL-101) in the process of Cs+ removal from aqueous solutions. The obtained Florisil® impregnated with the studied ionic liquid was characterized through energy dispersive X-ray analysis and
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This research determined the adsorption performance of Florisil® impregnated with trihexyl(tetradecyl)phosphonium chloride (Cyphos IL-101) in the process of Cs+ removal from aqueous solutions. The obtained Florisil® impregnated with the studied ionic liquid was characterized through energy dispersive X-ray analysis and Fourier transform infrared spectroscopy in order to verify that the impregnation with the ionic liquid had occurred. The adsorption process has been investigated as a function of pH, solid:liquid ratio, adsorbate concentration, contact time and temperature. The isotherm data was well described by a Langmuir isotherm model. The maximum adsorption capacities of the Florisil® impregnated with the studied ionic liquid was found to be 3.086 mg Cs+/g of adsorbent. The results indicated that the adsorption fitted well with the pseudo-second order kinetic model. Full article
(This article belongs to the Special Issue Organophosphorus Chemistry)
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Open AccessArticle Chemometric Evaluation of Urinary Steroid Hormone Levels as Potential Biomarkers of Neuroendocrine Tumors
Molecules 2013, 18(10), 12857-12876; doi:10.3390/molecules181012857
Received: 7 August 2013 / Revised: 25 September 2013 / Accepted: 10 October 2013 / Published: 16 October 2013
Cited by 2 | PDF Full-text (674 KB) | HTML Full-text | XML Full-text
Abstract
Neuroendocrine tumors (NETs) are uncommon tumors which can secrete specific hormone products such as peptides, biogenic amines and hormones. So far, the diagnosis of NETs has been difficult because most NET markers are not specific for a given tumor and none of the
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Neuroendocrine tumors (NETs) are uncommon tumors which can secrete specific hormone products such as peptides, biogenic amines and hormones. So far, the diagnosis of NETs has been difficult because most NET markers are not specific for a given tumor and none of the NET markers can be used to fulfil the criteria of high specificity and high sensitivity for the screening procedure. However, by combining the measurements of different NET markers, they become highly sensitive and specific diagnostic tests. The aim of the work was to identify whether urinary steroid hormones can be identified as potential new biomarkers of NETs, which could be used as prognostic and clinical course monitoring factors. Thus, a rapid and sensitive reversed-phase high-performance liquid chromatographic method (RP-HPLC) with UV detection has been developed for the determination of cortisol, cortisone, corticosterone, testosterone, epitestosterone and progesterone in human urine. The method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The limits of detection and quantification were 0.5 and 1 ng mL−1 for each steroid hormone, respectively. Linearity was confirmed within a range of 1–300 ng mL−1 with a correlation coefficient greater than 0.9995 for all analytes. The described method was successfully applied for the quantification of six endogenous steroid levels in human urine. Studies were performed on 20 healthy volunteers and 19 patients with NETs. Next, for better understanding of tumor biology in NETs and for checking whether steroid hormones can be used as potential biomarkers of NETs, a chemometric analysis of urinary steroid hormone levels in both data sets was performed. Full article
(This article belongs to the Special Issue Steroids)
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Open AccessArticle Elicitation of Induced Resistance against Pectobacterium carotovorum and Pseudomonas syringae by Specific Individual Compounds Derived from Native Korean Plant Species
Molecules 2013, 18(10), 12877-12895; doi:10.3390/molecules181012877
Received: 27 August 2013 / Revised: 30 September 2013 / Accepted: 9 October 2013 / Published: 16 October 2013
Cited by 4 | PDF Full-text (1148 KB) | HTML Full-text | XML Full-text
Abstract
Plants have developed general and specific defense mechanisms for protection against various enemies. Among the general defenses, induced resistance has distinct characteristics, such as broad-spectrum resistance and long-lasting effectiveness. This study evaluated over 500 specific chemical compounds derived from native Korean plant species
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Plants have developed general and specific defense mechanisms for protection against various enemies. Among the general defenses, induced resistance has distinct characteristics, such as broad-spectrum resistance and long-lasting effectiveness. This study evaluated over 500 specific chemical compounds derived from native Korean plant species to determine whether they triggered induced resistance against Pectobacterium carotovorum supsp. carotovorum (Pcc) in tobacco (Nicotiana tabacum) and Pseudomonas syringae pv. tomato (Pst) in Arabidopsis thaliana. To select target compound(s) with direct and indirect (volatile) effects, a new Petri-dish-based in vitro disease assay system with four compartments was developed. The screening assay showed that capsaicin, fisetin hydrate, jaceosidin, and farnesiferol A reduced the disease severity significantly in tobacco. Of these four compounds, capsaicin and jaceosidin induced resistance against Pcc and Pst, which depended on both salicylic acid (SA) and jasmonic acid (JA) signaling, using Arabidopsis transgenic and mutant lines, including npr1 and NahG for SA signaling and jar1 for JA signaling. The upregulation of the PR2 and PDF1.2 genes after Pst challenge with capsaicin pre-treatment indicated that SA and JA signaling were primed. These results demonstrate that capsaicin and jaceosidin can be effective triggers of strong induced resistance against both necrotrophic and biotrophic plant pathogens. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Preparative Separation of Spirobisnaphthalenes from Endophytic Fungus Berkleasmium sp. Dzf12 by High-Speed Counter-Current Chromatography
Molecules 2013, 18(10), 12896-12908; doi:10.3390/molecules181012896
Received: 8 July 2013 / Revised: 29 September 2013 / Accepted: 12 October 2013 / Published: 16 October 2013
Cited by 7 | PDF Full-text (280 KB) | HTML Full-text | XML Full-text
Abstract
High-speed counter-current chromatography (HSCCC) was applied for the first time for the preparative separation of spirobisnaphthalenes from a crude extract of the endophytic fungus Berkleasmium sp. Dzf12, associated with the medicinal plant Dioscorea zingiberensis. Six spirobisnaphthalenes were successfully separated by HSCCC with
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High-speed counter-current chromatography (HSCCC) was applied for the first time for the preparative separation of spirobisnaphthalenes from a crude extract of the endophytic fungus Berkleasmium sp. Dzf12, associated with the medicinal plant Dioscorea zingiberensis. Six spirobisnaphthalenes were successfully separated by HSCCC with a two-phase solvent system composed of n-hexane-chloroform-methanol-water (1.5:3.0:2.5:2.0, v/v). About 18.0 mg of diepoxin k (1), 245.7 mg of palmarumycin C13 (2), 42.4 mg of palmarumycin C16 (3), 42.2 mg of palmarumycin C15 (4), 32.6 mg of diepoxin δ (5), and 22.3 mg of diepoxin γ (6) with purities of 56.82, 71.39, 76.57, 75.86, 91.01 and 82.48%, respectively, as determined by high-performance liquid chromatography (HPLC), were obtained from 500 mg of the crude extract in a one-step elution within 7 h of separation procedure by HSCCC. The purified spirobisnaphthalenes were further structurally characterized by means of physicochemical and spectrometric analysis. Full article
Open AccessArticle Direct Light-up of cAMP Derivatives in Living Cells by Click Reactions
Molecules 2013, 18(10), 12909-12915; doi:10.3390/molecules181012909
Received: 1 August 2013 / Revised: 10 October 2013 / Accepted: 13 October 2013 / Published: 17 October 2013
Cited by 4 | PDF Full-text (668 KB) | HTML Full-text | XML Full-text
Abstract
8-Azidoadenosine 3′,5′-cyclic monophosphate (8-azido cAMP) was directly detected in living cells, by applying Cu-free azide-alkyne cycloaddition to probe cAMP derivatives by fluorescence light-up. Fluorescence emission was generated by two non-fluorescent molecules, 8-azido cAMP as a model target and difluorinated cyclooctyne (DIFO) reagent as
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8-Azidoadenosine 3′,5′-cyclic monophosphate (8-azido cAMP) was directly detected in living cells, by applying Cu-free azide-alkyne cycloaddition to probe cAMP derivatives by fluorescence light-up. Fluorescence emission was generated by two non-fluorescent molecules, 8-azido cAMP as a model target and difluorinated cyclooctyne (DIFO) reagent as a probe. The azide-alkyne cycloaddition reaction between 8-azido cAMP and DIFO induces fluorescence in 8-azido cAMP. The fluorescence emission serves as a way to probe 8-azido cAMP in cells. Full article
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Open AccessArticle The Anti-Lung Cancer Activities of Steroidal Saponins of P. polyphylla Smith var. chinensis (Franch.) Hara through Enhanced Immunostimulation in Experimental Lewis Tumor-Bearing C57BL/6 Mice and Induction of Apoptosis in the A549 Cell Line
Molecules 2013, 18(10), 12916-12936; doi:10.3390/molecules181012916
Received: 15 August 2013 / Revised: 8 October 2013 / Accepted: 9 October 2013 / Published: 17 October 2013
Cited by 16 | PDF Full-text (3446 KB) | HTML Full-text | XML Full-text
Abstract
P. polyphylla Smith var. chinensis (Franch.) Hara (PPSCFH) has been used as medicinal Paris for the prevention and treatment of cancers in China for thousands of years. Its main components, steroidal saponins (PRS), have been confirmed to inhibit tumor growth. In the present
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P. polyphylla Smith var. chinensis (Franch.) Hara (PPSCFH) has been used as medicinal Paris for the prevention and treatment of cancers in China for thousands of years. Its main components, steroidal saponins (PRS), have been confirmed to inhibit tumor growth. In the present study, the immunostimulation of PRS was investigated in Lewis bearing-C57BL/6 mice while the induction of apoptosis in A549 cells was also studied. The treatment with PRS (2.5, 5.0 and 7.5 mg/kg) significantly inhibited tumor, volume, and weight in the C57BL/6 mice. The rates of inhibition of PRS (at 2.5, 5.0 and 7.5 mg/kg) were 26.49 ± 17.30%, 40.32 ± 18.91% and 54.94 ± 16.48%, respectively. The spleen and thymus indexes were increased remarkably, while the levels of inflammatory cytokines including TNF-α, IL-8 and IL-10 in serum were decreased according to ELISA assays. For A549 cells, Hoechst 33342 staining and annexin V/PI by flow cytometry showed that PRS (0.25, 0.50 and 0.75 mg/mL) induced nuclear changes of A549 cells with DNA condensation and fragmentations of chromatin, as well as inducing apoptosis. Furthermore, PRS could also attenuate the over-generation of intracellular ROS. Western blotting analysis showed a significant decrease on the expressions of proinflammatory cytokines MCP-1, IL-6 and TGF-β1, as well as cell adhesion molecule ICAM-1, by treatment with PRS. Our results demonstrated that the inhibition of PRS on tumor growth might be associated with the amelioration of inflammation responses, induction of apoptosis, as well as the decrease of ROS. These results suggested that PRS implied a potential therapeutic effect in the lung cancer treatment. Full article
Open AccessArticle Antioxidant Activity and Anti-Adipogenic Effects of Wild Herbs Mainly Cultivated in Korea
Molecules 2013, 18(10), 12937-12950; doi:10.3390/molecules181012937
Received: 13 September 2013 / Accepted: 9 October 2013 / Published: 17 October 2013
Cited by 17 | PDF Full-text (1695 KB) | HTML Full-text | XML Full-text
Abstract
Wild herbs, which are edible plants that grow in mountainous areas, have diverse biological effects such as anti-obesity and anti-cancer activities. The aim of this study was to evaluate the total phenolic and flavonoid contents as well as the antioxidant activity of methanol
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Wild herbs, which are edible plants that grow in mountainous areas, have diverse biological effects such as anti-obesity and anti-cancer activities. The aim of this study was to evaluate the total phenolic and flavonoid contents as well as the antioxidant activity of methanol extracts of Aster scaber, Ligularia fischeri, Kalopanax pictus, Codonopsis lanceolata, and Cirsium setidens and to assess their effects on lipid accumulation and reactive oxygen species (ROS) production during adipogenesis of 3T3-L1 cells. The results revealed that among the five studied wild herb extracts, Ligularia fischeri showed the highest total phenolic contents (215.8 ± 14.2 mg GAE/g) and Aster scaber showed the highest total flavonoid content (103.9 ± 3.4 mg RE/g). Furthermore, Aster scaber and Ligularia fischeri extracts showed higher antioxidant activity than the other wild herbs. Regarding anti-adipogenic activity, the Cirsium setidens extract significantly inhibited lipid accumulation (~80%) and ROS production (~50%) during adipogenesis of 3T3-L1 cells compared with control cells. These results suggest that wild herbs could be used for the development of functional foods as well as health promoting and pharmaceutical agents. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of Bistetrahydroquinolines as Potential Anticholinesterasic Agents by Double Diels-Alder Reactions
Molecules 2013, 18(10), 12951-12965; doi:10.3390/molecules181012951
Received: 2 September 2013 / Revised: 27 September 2013 / Accepted: 8 October 2013 / Published: 17 October 2013
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Abstract
The tetrahydroquinoline ring system is a unit found in many biologically active natural products and pharmacologically relevant therapeutic agents. A new series of bistetrahydroquinolines (bis-THQs) was synthesized using imino Diels-Alder reactions between dialdehydes, anilines and N-vinyl-2-pyrrolidone (NVP). The notable features
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The tetrahydroquinoline ring system is a unit found in many biologically active natural products and pharmacologically relevant therapeutic agents. A new series of bistetrahydroquinolines (bis-THQs) was synthesized using imino Diels-Alder reactions between dialdehydes, anilines and N-vinyl-2-pyrrolidone (NVP). The notable features of this procedure are mild reaction conditions, greater selectivity and good yields of products. In addition, the inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) of some selected derivatives is reported. The feasible binding modes of these active compounds, within AChE and BuChE binding sites, were predicted by molecular docking experiments and their binding affinity was estimated by means of free energy calculations through the MM-GBSA approximation. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessCommunication Oligonucleotide Labelling Using a Fluorogenic “Click” Reaction with a Hemicarboxonium Salt
Molecules 2013, 18(10), 12966-12976; doi:10.3390/molecules181012966
Received: 28 August 2013 / Revised: 30 September 2013 / Accepted: 9 October 2013 / Published: 17 October 2013
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Abstract Two fluorescent streptocyanine labelled oligonucleotides have been synthesized by a simple “click” reaction between a non-fluorescent hemicarboxonium salt and aminoalkyl functionalized thymidines within the oligonucleotide and their spectrophotometric properties have been studied. Full article
(This article belongs to the Special Issue Synthesis of Nucleosides, Nucleotides and Their Derivatives)
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Open AccessArticle Endogenous Protection Derived from Activin A/Smads Transduction Loop Stimulated via Ischemic Injury in PC12 Cells
Molecules 2013, 18(10), 12977-12986; doi:10.3390/molecules181012977
Received: 12 July 2013 / Revised: 10 October 2013 / Accepted: 11 October 2013 / Published: 17 October 2013
Cited by 9 | PDF Full-text (868 KB) | HTML Full-text | XML Full-text
Abstract
Activin A (ActA), a member of transforming growth factor-beta (TGF-b) super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD) injury have already been reported by us, the endogenous role of ActA remains
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Activin A (ActA), a member of transforming growth factor-beta (TGF-b) super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD) injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate ischemic injury on neurons in vitro. Cells were pre-treated by monoclonal antibody against activin receptor type IIA (ActRII-Ab). We found that ActRII-Ab augments ischemic injury in PC12 cells. Further, the extracellular secretion of ActA as well as phosphorylation of smad3 in PC12 cells was also up-regulated by OGD, but suppressed by ActRII-Ab. Taken together, our results show that ActRII-Ab may augment ischemic injury via blocking of transmembrane signal transduction of ActA, which confirmed the existence of endogenous neuroprotective effects derived from the ActA/Smads pathway. ActRIIA plays an important role in transferring neuronal protective signals inside. It is highly possible that ActA transmembrance signaling is a part of the positive feed-back loop for extracellular ActA secretion. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle SOCS3-Mediated Blockade Reveals Major Contribution of JAK2/STAT5 Signaling Pathway to Lactation and Proliferation of Dairy Cow Mammary Epithelial Cells in Vitro
Molecules 2013, 18(10), 12987-13002; doi:10.3390/molecules181012987
Received: 12 August 2013 / Revised: 21 September 2013 / Accepted: 30 September 2013 / Published: 17 October 2013
Cited by 19 | PDF Full-text (3483 KB) | HTML Full-text | XML Full-text
Abstract
Suppressor of cytokine signaling 3 (SOCS3) is a cytokine-induced negative feedback-loop regulator of cytokine signaling. More and more evidence has proved it to be an inhibitor of signal transducers and activators of transcription 5 (STAT5). Here, we used dairy cow mammary epithelial cells
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Suppressor of cytokine signaling 3 (SOCS3) is a cytokine-induced negative feedback-loop regulator of cytokine signaling. More and more evidence has proved it to be an inhibitor of signal transducers and activators of transcription 5 (STAT5). Here, we used dairy cow mammary epithelial cells (DCMECs) to analyze the function of SOCS3 and the interaction between SOCS3 and STAT5a. The expression of SOCS3 was found in cytoplasm and nucleus of DCMECs by fluorescent immunostaining. Overexpression and inhibition of SOCS3 brought a remarkable milk protein synthesis change through the regulation of JAK2/STAT5a pathway activity, and SOCS3 expression also decreased SREBP-1c expression and fatty acid synthesis. Inhibited STAT5a activation correlated with reduced SOCS3 expression, which indicated that SOCS3 gene might be one of the targets of STAT5a activation, DCMECs treated with L-methionine (Met) resulted in a decrease of SOCS3 expression. SOCS3 could also decrease cell proliferation and viability by CASY-TT detection. Together, our findings indicate that SOCS3 acts as an inhibitor of JAK2/STAT5a pathway and disturbs fatty acid synthesis by decreasing SREBP-1c expression, which validates its involvement in both milk protein synthesis and fat synthesis. In aggregate, these results reveal that low SOCS3 expression is required for milk synthesis and proliferation of DCMECs in vitro. Full article
Open AccessArticle Biological Activity of Oleanane Triterpene Derivatives Obtained by Chemical Derivatization
Molecules 2013, 18(10), 13003-13019; doi:10.3390/molecules181013003
Received: 5 September 2013 / Revised: 11 October 2013 / Accepted: 14 October 2013 / Published: 18 October 2013
Cited by 3 | PDF Full-text (785 KB) | HTML Full-text | XML Full-text
Abstract
Nine new derivatives of oleanane triterpenoids isolated from Fatsia polycarpa Hayata were synthesized through chemical transformations. Acetylation was effected by reaction with acetic anhydride in pyridine to afford compounds 15, while compound 6 was obtained using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) in
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Nine new derivatives of oleanane triterpenoids isolated from Fatsia polycarpa Hayata were synthesized through chemical transformations. Acetylation was effected by reaction with acetic anhydride in pyridine to afford compounds 15, while compound 6 was obtained using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) in CH2Cl2. The others derivatives 79 were obtained in reactions of the corresponding triterpenoids with EDC·HCl, 4-N,N-dimethylaminopyridine hydrochloride and 4-N,N-dimethylaminopyridine in CH2Cl2. The structures of 19 were elucidated from extensive spectroscopic and HRESIMS data, while the structure of 9 was further confirmed by X-ray diffraction analysis. The cytotoxic, anti-hepatitis B virus (HBV), antibacterial, hypoglycaemic and Wnt signaling activities of these derivatives were evaluated in vitro. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Selection of a Mimotope Peptide of S-adenosyl-l-homocysteine and Its Application in Immunoassays
Molecules 2013, 18(10), 13020-13026; doi:10.3390/molecules181013020
Received: 15 August 2013 / Revised: 9 October 2013 / Accepted: 11 October 2013 / Published: 18 October 2013
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Abstract
A competitive immunoassay for S-adenosyl-l-homocysteine (SAH) has been used in the clinical test for homocysteine via an enzymatic conversion reaction. Since S-adenosyl-l-homocysteine is a relatively unstable compound, we have used peptide library phage display to select a new mimotope peptide that
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A competitive immunoassay for S-adenosyl-l-homocysteine (SAH) has been used in the clinical test for homocysteine via an enzymatic conversion reaction. Since S-adenosyl-l-homocysteine is a relatively unstable compound, we have used peptide library phage display to select a new mimotope peptide that interacts with the anti-SAH antibody. By immobilizing the synthetic peptide on solid phase as a competitive surrogate for SAH, we demonstrate its utility in a competitive ELISA assay. The linear range of the assay for SAH was 0.4–6.4 µM, in good correlation to the conventional assay using an SAH-conjugated plate. Our results show that the mimotope peptide has potential to substitute for SAH in immunoassays. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Synthesis and Protective Effect of New Ligustrazine-Benzoic Acid Derivatives against CoCl2-Induced Neurotoxicity in Differentiated PC12 Cells
Molecules 2013, 18(10), 13027-13042; doi:10.3390/molecules181013027
Received: 10 September 2013 / Revised: 30 September 2013 / Accepted: 9 October 2013 / Published: 18 October 2013
Cited by 12 | PDF Full-text (1356 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of novel ligustrazine-benzoic acid derivatives were synthesized and evaluated for their protective effect against cobalt chloride-induced neurotoxicity in differentiated PC12 cells. Combining hematoxylin and eosin staining, we found compound that (3,5,6-trimethylpyrazin-2-yl)methyl 3-methoxy-4-[(3,5,6-trimethylpyrazin-2-yl)methoxy]benzoate (4a) displayed promising protective effect on the
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A series of novel ligustrazine-benzoic acid derivatives were synthesized and evaluated for their protective effect against cobalt chloride-induced neurotoxicity in differentiated PC12 cells. Combining hematoxylin and eosin staining, we found compound that (3,5,6-trimethylpyrazin-2-yl)methyl 3-methoxy-4-[(3,5,6-trimethylpyrazin-2-yl)methoxy]benzoate (4a) displayed promising protective effect on the proliferation of the injured PC12 cells (EC50 = 4.249 µM). Structure-activity relationships are briefly discussed. Full article
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Open AccessArticle Synthesis and Structure-Activity Relationships of Amino Acid Conjugates of Cholanic Acid as Antagonists of the EphA2 Receptor
Molecules 2013, 18(10), 13043-13060; doi:10.3390/molecules181013043
Received: 29 August 2013 / Revised: 11 October 2013 / Accepted: 12 October 2013 / Published: 21 October 2013
Cited by 7 | PDF Full-text (4285 KB) | HTML Full-text | XML Full-text
Abstract
The Eph–ephrin system plays a critical role in tumor growth and vascular functions during carcinogenesis. We had previously identified cholanic acid as a competitive and reversible EphA2 antagonist able to disrupt EphA2-ephrinA1 interaction and to inhibit EphA2 activation in prostate cancer cells. Herein,
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The Eph–ephrin system plays a critical role in tumor growth and vascular functions during carcinogenesis. We had previously identified cholanic acid as a competitive and reversible EphA2 antagonist able to disrupt EphA2-ephrinA1 interaction and to inhibit EphA2 activation in prostate cancer cells. Herein, we report the synthesis and biological evaluation of a set of cholanic acid derivatives obtained by conjugation of its carboxyl group with a panel of naturally occurring amino acids with the aim to improve EphA2 receptor inhibition. Structure-activity relationships indicate that conjugation of cholanic acid with linear amino acids of small size leads to effective EphA2 antagonists whereas the introduction of aromatic amino acids reduces the potency in displacement studies. The b-alanine derivative 4 was able to disrupt EphA2-ephrinA1 interaction in the micromolar range and to dose-dependently inhibit EphA2 activation on PC3 cells. These findings may help the design of novel EphA2 antagonists active on cancer cell lines. Full article
(This article belongs to the Special Issue Steroids)
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Open AccessArticle Sesquiterpene Lactones and Their Derivatives Inhibit High Glucose-Induced NF-κB Activation and MCP-1 and TGF-β1 Expression in Rat Mesangial Cells
Molecules 2013, 18(10), 13061-13077; doi:10.3390/molecules181013061
Received: 12 September 2013 / Revised: 12 September 2013 / Accepted: 14 October 2013 / Published: 21 October 2013
Cited by 11 | PDF Full-text (896 KB) | HTML Full-text | XML Full-text
Abstract
Diabetic nephropathy (DN) is one of the most common and serious chronic complications of diabetes mellitus, however, no efficient clinical drugs exist for the treatment of DN. We selected and synthesized several sesquiterpene lactones (SLs), and then used the MTT assay to detect
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Diabetic nephropathy (DN) is one of the most common and serious chronic complications of diabetes mellitus, however, no efficient clinical drugs exist for the treatment of DN. We selected and synthesized several sesquiterpene lactones (SLs), and then used the MTT assay to detect rat mesangial cells (MCs) proliferation, ELISA to measure the expression level of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta (TGF-β1) and fibronectin(FN), real-time fluorescent quantitative PCR analysis to measure the MCP-1 and TGF-β1 gene expression, western blot to detect the level of IκBα protein and EMSA to measure the activation of nuclear factor kappa B (NF-κB). We discovered that SLs, including parthenolide (PTL), micheliolide (MCL), arglabin, and isoalantolactone (IAL), as well as several synthetic analogs of these molecules, could effectively attenuate the high glucose-stimulated activation of NF-κB, the degradation of IκBα, and the expression of MCP-1, TGF-β1 and FN in rat mesangial cells (MCs). These findings suggest that SLs and their derivatives have potential as candidate drugs for the treatment of DN. Full article
Open AccessArticle Synthesis of Laboratory Ultrasound Contrast Agents
Molecules 2013, 18(10), 13078-13095; doi:10.3390/molecules181013078
Received: 4 June 2013 / Revised: 10 October 2013 / Accepted: 11 October 2013 / Published: 21 October 2013
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Abstract
Ultrasound Contrast Agents (UCAs) were developed to maximize reflection contrast so that organs can be seen clearly in ultrasound imaging. UCAs increase the signal to noise ratio (SNR) by linear and non-linear mechanisms and thus help more accurately visualize the internal organs and
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Ultrasound Contrast Agents (UCAs) were developed to maximize reflection contrast so that organs can be seen clearly in ultrasound imaging. UCAs increase the signal to noise ratio (SNR) by linear and non-linear mechanisms and thus help more accurately visualize the internal organs and blood vessels. However, the UCAs on the market are not only expensive, but are also not optimized for use in various therapeutic research applications such as ultrasound-aided drug delivery. The UCAs fabricated in this study utilize conventional lipid and albumin for shell formation and perfluorobutane as the internal gas. The shape and density of the UCA bubbles were verified by optical microscopy and Cryo SEM, and compared to those of the commercially available UCAs, Definity® and Sonovue®. The size distribution and characteristics of the reflected signal were also analyzed using a particle size analyzer and ultrasound imaging equipment. Our experiments indicate that UCAs composed of spherical microbubbles, the majority of which were smaller than 1 um, were successfully synthesized. Microbubbles 10 um or larger were also identified when different shell characteristics and filters were used. These laboratory UCAs can be used for research in both diagnoses and therapies. Full article
Open AccessArticle Non-Classical Transformation of Benzendiazonium Hydrogen Sulfates. Access to 1,3-Dimethylisochromeno[4,3-c]pyrazol-5(1H)-one, a Potential Benzodiazepine Receptor Ligand
Molecules 2013, 18(10), 13096-13110; doi:10.3390/molecules181013096
Received: 13 September 2013 / Revised: 12 October 2013 / Accepted: 15 October 2013 / Published: 22 October 2013
Cited by 2 | PDF Full-text (253 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The compound 2-((1,3-dimethyl-1H-pyrazol-5-yl)(methyl)carbamoyl)benzene-diazonium hydrogen sulfate (10) was reacted with copper sulfate and sodium chloride, in the presence of ascorbic acid as reducing agent, to afford a mixture of the chlorinated epimers 4′-chloro-2,2′,5′-trimethyl-2′,4′-dihydrospiro[isoindoline-1,3′-pyrazol]-3-one (18) and (19),
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The compound 2-((1,3-dimethyl-1H-pyrazol-5-yl)(methyl)carbamoyl)benzene-diazonium hydrogen sulfate (10) was reacted with copper sulfate and sodium chloride, in the presence of ascorbic acid as reducing agent, to afford a mixture of the chlorinated epimers 4′-chloro-2,2′,5′-trimethyl-2′,4′-dihydrospiro[isoindoline-1,3′-pyrazol]-3-one (18) and (19), the epimers 4′-hydroxy-2,2′,5′-trimethyl-2′,4′-dihydrospiro[isoindoline-1,3′-pyrazol]-3-one (20) and (21), and N-(1,3-dimethyl-1H-pyrazol-5-yl)benzamide (22). Under the foregoing conditions, diazonium salt 10 affords neither the 2-chloro-N-(1,3-dimethyl-1H-pyrazol-5-yl)-N-methylbenzamide (23) nor the tricyclic derivative 24, the classical products of the Sandmeyer and Pschorr reactions, respectively. Finally, by heating 20 at 210 °C the compound 1,3-dimethylisochromeno[4,3-c]pyrazol-5(1H)-one (24) was obtained. The transformation under the above conditions of 2-((4-chloro-3-methyl-1-phenyl- 1H-pyrazol-5-yl)(methyl)carbamoyl)benzendiazonium hydrogen sulphate (11) afforded 4′,4′-dichloro-2,5′-dimethyl-2′-phenyl-2′,4′-dihydrospiro[isoindoline-1,3′-pyrazol]-3-one (29) as the sole reaction product. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Synthesis and Structural Characterization of Fluorinated Thiosemicarbazones
Molecules 2013, 18(10), 13111-13123; doi:10.3390/molecules181013111
Received: 10 September 2013 / Revised: 10 October 2013 / Accepted: 11 October 2013 / Published: 22 October 2013
Cited by 2 | PDF Full-text (2408 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Six new fluorinated thiosemicarbazones R‑C(R′)=N-NH-C(S)NH2 (R = 2,4-C6H3F2, R′ = H (1); R = 2,5-C6H3F2, R′ = H (2); R = 2,6-C6H3F
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Six new fluorinated thiosemicarbazones R‑C(R′)=N-NH-C(S)NH2 (R = 2,4-C6H3F2, R′ = H (1); R = 2,5-C6H3F2, R′ = H (2); R = 2,6-C6H3F2, R′ = H (3); R = 3,4-C6H3F2, R′ = H (4); R = 3,5-C6H3F2, R′ = H (5) and R = 4-C6H4F, R′ = C6H5, (6)) have been prepared. The molecular structures of compounds 1 to 6 have been determined. Full article
(This article belongs to the Section Organic Synthesis)

Review

Jump to: Research

Open AccessReview Metabolomics and Fetal-Neonatal Nutrition: Between “Not Enough” and “Too Much”
Molecules 2013, 18(10), 11724-11732; doi:10.3390/molecules181011724
Received: 5 August 2013 / Revised: 13 September 2013 / Accepted: 16 September 2013 / Published: 25 September 2013
Cited by 14 | PDF Full-text (337 KB) | HTML Full-text | XML Full-text
Abstract
Metabolomics is a new analytical technique defined as the study of the complex system of metabolites that is capable of describing the biochemical phenotype of a biological system. In recent years the literature has shown an increasing interest in paediatric obesity and the
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Metabolomics is a new analytical technique defined as the study of the complex system of metabolites that is capable of describing the biochemical phenotype of a biological system. In recent years the literature has shown an increasing interest in paediatric obesity and the onset of diabetes and the metabolic syndrome in adulthood. Some studies show that fetal malnutrition, both excessive and insufficient, may permanently alter the metabolic processes of the fetus and increase the risk of future chronic pathologies. At present then, attention is being focused mainly on the formulation of new hypotheses, by means of metabolomics, concerning the biological mechanisms to departure from fetal-neonatal life that may predispose to the development of these diseases. Full article
Open AccessReview Nuclear Magnetic Resonance Approaches in the Study of 2-Oxo Acid Dehydrogenase Multienzyme Complexes—A Literature Review
Molecules 2013, 18(10), 11873-11903; doi:10.3390/molecules181011873
Received: 30 July 2013 / Revised: 14 September 2013 / Accepted: 16 September 2013 / Published: 26 September 2013
Cited by 1 | PDF Full-text (1081 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The 2-oxoacid dehydrogenase complexes (ODHc) consist of multiple copies of three enzyme components: E1, a 2-oxoacid decarboxylase; E2, dihydrolipoyl acyl-transferase; and E3, dihydrolipoyl dehydrogenase, that together catalyze the oxidative decarboxylation of 2-oxoacids, in the presence of thiamin diphosphate (ThDP), coenzyme A (CoA), Mg
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The 2-oxoacid dehydrogenase complexes (ODHc) consist of multiple copies of three enzyme components: E1, a 2-oxoacid decarboxylase; E2, dihydrolipoyl acyl-transferase; and E3, dihydrolipoyl dehydrogenase, that together catalyze the oxidative decarboxylation of 2-oxoacids, in the presence of thiamin diphosphate (ThDP), coenzyme A (CoA), Mg2+ and NAD+, to generate CO2, NADH and the corresponding acyl-CoA. The structural scaffold of the complex is provided by E2, with E1 and E3 bound around the periphery. The three principal members of the family are pyruvate dehydrogenase (PDHc), 2-oxoglutarate dehydrogenase (OGDHc) and branched-chain 2-oxo acid dehydrogenase (BCKDHc). In this review, we report application of NMR-based approaches to both mechanistic and structural issues concerning these complexes. These studies revealed the nature and reactivity of transient intermediates on the enzymatic pathway and provided site-specific information on the architecture and binding specificity of the domain interfaces using solubilized truncated domain constructs of the multi-domain E2 component in its interactions with the E1 and E3 components. Where studied, NMR has also provided information about mobile loops and the possible relationship of mobility and catalysis. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
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Open AccessReview Measuring Dynamic and Kinetic Information in the Previously Inaccessible Supra-tc Window of Nanoseconds to Microseconds by Solution NMR Spectroscopy
Molecules 2013, 18(10), 11904-11937; doi:10.3390/molecules181011904
Received: 16 July 2013 / Revised: 28 August 2013 / Accepted: 17 September 2013 / Published: 26 September 2013
Cited by 14 | PDF Full-text (665 KB) | HTML Full-text | XML Full-text
Abstract
Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful tool that has enabled experimentalists to characterize molecular dynamics and kinetics spanning a wide range of time-scales from picoseconds to days. This review focuses on addressing the previously inaccessible supra-τc window (defined as τ
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Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful tool that has enabled experimentalists to characterize molecular dynamics and kinetics spanning a wide range of time-scales from picoseconds to days. This review focuses on addressing the previously inaccessible supra-τc window (defined as τc < supra-τc < 40 μs; in which τc is the overall tumbling time of a molecule) from the perspective of local inter-nuclear vector dynamics extracted from residual dipolar couplings (RDCs) and from the perspective of conformational exchange captured by relaxation dispersion measurements (RD). The goal of the first section is to present a detailed analysis of how to extract protein dynamics encoded in RDCs and how to relate this information to protein functionality within the previously inaccessible supra-τc window. In the second section, the current state of the art for RD is analyzed, as well as the considerable progress toward pushing the sensitivity of RD further into the supra-τc scale by up to a factor of two (motion up to 25 ms). From the data obtained with these techniques and methodology, the importance of the supra-τ c scale for protein function and molecular recognition is becoming increasingly clearer as the connection between motion on the supra-τc scale and protein functionality from the experimental side is further strengthened with results from molecular dynamics simulations. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
Open AccessReview Pregnenolone Sulfate: From Steroid Metabolite to TRP Channel Ligand
Molecules 2013, 18(10), 12012-12028; doi:10.3390/molecules181012012
Received: 2 September 2013 / Revised: 20 September 2013 / Accepted: 21 September 2013 / Published: 27 September 2013
Cited by 13 | PDF Full-text (952 KB) | HTML Full-text | XML Full-text
Abstract
Pregnenolone sulfate is a steroid metabolite with a plethora of actions and functions. As a neurosteroid, pregnenolone sulfate modulates a variety of ion channels, transporters, and enzymes. Interestingly, as a sulfated steroid, pregnenolone sulfate is not the final- or waste-product of pregnenolone being
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Pregnenolone sulfate is a steroid metabolite with a plethora of actions and functions. As a neurosteroid, pregnenolone sulfate modulates a variety of ion channels, transporters, and enzymes. Interestingly, as a sulfated steroid, pregnenolone sulfate is not the final- or waste-product of pregnenolone being sulfated via a phase II metabolism reaction and renally excreted, as one would presume from the pharmacology textbook knowledge. Pregnenolone sulfate is also the source and thereby the starting point for subsequent steroid synthesis pathways. Most recently, pregnenolone sulfate has been functionally “upgraded” from modulator of ion channels to an activating ion channel ligand. This review will focus on molecular aspects of the neurosteroid, pregnenolone sulfate, its metabolism, concentrations in serum and tissues and last not least will summarize the functional data. Full article
(This article belongs to the Special Issue Steroids)
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Open AccessReview Gaultheria: Phytochemical and Pharmacological Characteristics
Molecules 2013, 18(10), 12071-12108; doi:10.3390/molecules181012071
Received: 26 August 2013 / Revised: 22 September 2013 / Accepted: 24 September 2013 / Published: 30 September 2013
Cited by 15 | PDF Full-text (353 KB) | HTML Full-text | XML Full-text
Abstract
The genus Gaultheria, comprised of approximately 134 species, is mostly used in ethnic drugs to cure rheumatism and relieve pain. Phytochemical investigations of the genus Gaultheria have revealed the presence of methyl salicylate derivatives, C6-C3 constituents, organic acids, terpenoids,
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The genus Gaultheria, comprised of approximately 134 species, is mostly used in ethnic drugs to cure rheumatism and relieve pain. Phytochemical investigations of the genus Gaultheria have revealed the presence of methyl salicylate derivatives, C6-C3 constituents, organic acids, terpenoids, steroids, and other compounds. Methyl salicylate glycoside is considered as a characteristic ingredient in this genus, whose anti-rheumatic effects may have a new mechanism of action. In this review, comprehensive information on the phytochemistry, volatile components and the pharmacology of the genus Gaultheria is provided to explore its potential and advance research. Full article
(This article belongs to the Section Natural Products)
Open AccessReview Schiff Bases: A Short Survey on an Evergreen Chemistry Tool
Molecules 2013, 18(10), 12264-12289; doi:10.3390/molecules181012264
Received: 10 August 2013 / Revised: 18 September 2013 / Accepted: 23 September 2013 / Published: 8 October 2013
Cited by 36 | PDF Full-text (996 KB) | HTML Full-text | XML Full-text
Abstract
The review reports a short biography of the Italian naturalized chemist Hugo Schiff and an outline on the synthesis and use of his most popular discovery: the imines, very well known and popular as Schiff Bases. Recent developments on their “metallo-imines” variants have
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The review reports a short biography of the Italian naturalized chemist Hugo Schiff and an outline on the synthesis and use of his most popular discovery: the imines, very well known and popular as Schiff Bases. Recent developments on their “metallo-imines” variants have been described. The applications of Schiff bases in organic synthesis as partner in Staudinger and hetero Diels-Alder reactions, as “privileged” ligands in the organometallic complexes and as biological active Schiff intermediates/targets have been reported as well. Full article
(This article belongs to the Special Issue Named Organic Reactions based on Italian Chemists)
Open AccessReview The Piancatelli Rearrangement: New Applications for an Intriguing Reaction
Molecules 2013, 18(10), 12290-12312; doi:10.3390/molecules181012290
Received: 24 July 2013 / Revised: 18 September 2013 / Accepted: 23 September 2013 / Published: 8 October 2013
Cited by 20 | PDF Full-text (315 KB) | HTML Full-text | XML Full-text
Abstract
Nearly forty years ago, at the University of Rome, Giovanni Piancatelli and co-workers discovered the acid-catalyzed water-mediated rearrangement of 2-furylcarbinols into 4-hydroxycyclopentenones. These motifs are core components of several pharmacologically active compounds and precursors of many natural products. The main features of this
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Nearly forty years ago, at the University of Rome, Giovanni Piancatelli and co-workers discovered the acid-catalyzed water-mediated rearrangement of 2-furylcarbinols into 4-hydroxycyclopentenones. These motifs are core components of several pharmacologically active compounds and precursors of many natural products. The main features of this reaction are the simple experimental conditions, the stereochemical outcome and the generality of the procedure. Consequently, a re-emergence of this reaction has been seen recently, including developments of the Piancatelli rearrangement with some interesting inter- and intramolecular variants. This review will mainly focus on the general aspects of the reaction along with its more recent applications. Full article
(This article belongs to the Special Issue Named Organic Reactions based on Italian Chemists)
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Open AccessReview G-Quadruplex Structures in the Human Genome as Novel Therapeutic Targets
Molecules 2013, 18(10), 12368-12395; doi:10.3390/molecules181012368
Received: 14 August 2013 / Revised: 24 September 2013 / Accepted: 27 September 2013 / Published: 8 October 2013
Cited by 53 | PDF Full-text (1219 KB) | HTML Full-text | XML Full-text
Abstract
G-quadruplexes are secondary structures that may form within guanine-rich nucleic acid sequences. Telomeres have received much attention in this regard since they can fold into several distinct intramolecular G-quadruplexes, leading to the rational design and development of G-quadruplex‑stabilizing molecules. These ligands were shown
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G-quadruplexes are secondary structures that may form within guanine-rich nucleic acid sequences. Telomeres have received much attention in this regard since they can fold into several distinct intramolecular G-quadruplexes, leading to the rational design and development of G-quadruplex‑stabilizing molecules. These ligands were shown to selectively exert an antiproliferative and chemosensitizing activity in in vitro and in vivo tumor models, without appreciably affecting normal cells. Such findings point to them as possible drug candidates for clinical applications. Other than in telomeres, G-quadruplexes may form at additional locations in the human genome, including gene promoters and untranslated regions. For instance, stabilization of G-quadruplex structures within the promoter of MYC, KIT, or KRAS resulted in the down-regulation of the corresponding oncogene either in gene reporter assays or in selected experimental models. In addition, the alternative splicing of a number of genes may be affected for a therapeutic benefit through the stabilization of G-quadruplexes located within pre-mRNAs. It is now emerging that G-quadruplex structures may act as key regulators of several biological processes. Consequently, they are considered as attractive targets for broad-spectrum anticancer therapies, and much effort is being made to develop a variety of ligands with improved G-quadruplex recognition properties. Quarfloxin, a fluoroquinolone derivative designed to target a G-quadruplex within ribosomal DNA and disrupt protein-DNA interactions, has entered clinical trials for different malignancies. This review will provide some hints on the role of G-quadruplex structures in biological processes and will evaluate their implications as novel therapeutic targets. Full article
(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)
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Open AccessReview The Involvement of Amino Acid Side Chains in Shielding the Nickel Coordination Site: An NMR Study
Molecules 2013, 18(10), 12396-12414; doi:10.3390/molecules181012396
Received: 6 August 2013 / Revised: 26 September 2013 / Accepted: 29 September 2013 / Published: 8 October 2013
Cited by 6 | PDF Full-text (751 KB) | HTML Full-text | XML Full-text
Abstract
Coordination of proteins and peptides to metal ions is known to affect their properties, often by a change in their structural organization. Side chains of the residues directly involved in metal binding or very close to the coordination centre may arrange themselves around
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Coordination of proteins and peptides to metal ions is known to affect their properties, often by a change in their structural organization. Side chains of the residues directly involved in metal binding or very close to the coordination centre may arrange themselves around it, in such a way that they can, for instance, disrupt the protein functions or stabilize a metal complex by shielding it from the attack of water or other small molecules. The conformation of these side chains may be crucial to different biological or toxic processes. In our research we have encountered such behaviour in several cases, leading to interesting results for our purposes. Here we give an overview on the structural changes involving peptide side chains induced by Ni(II) coordination. In this paper we deal with a number of peptides, deriving from proteins containing one or more metal coordinating sites, which have been studied through a series of NMR experiments in their structural changes caused by Ni(II) complexation. Several peptides have been included in the study: short sequences from serum albumin (HSA), Des-Angiotensinogen, the 30-amino acid tail of histone H4, some fragments from histone H2A and H2B, the initial fragment of human protamine HP2 and selected fragments from prion and Cap43 proteins. NMR was the election technique for gathering structural information. Experiments performed for this purpose included 1D 1H and 13C, and 2D HSQC, COSY, TOCSY, NOESY and ROESY acquisitions, which allowed the calculation of the Ni(II) complexes structural models. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
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Open AccessReview G-Quadruplexes as Potential Therapeutic Targets for Embryonal Tumors
Molecules 2013, 18(10), 12500-12537; doi:10.3390/molecules181012500
Received: 30 August 2013 / Revised: 18 September 2013 / Accepted: 25 September 2013 / Published: 10 October 2013
Cited by 17 | PDF Full-text (292 KB) | HTML Full-text | XML Full-text
Abstract
Embryonal tumors include a heterogeneous group of highly malignant neoplasms that primarily affect infants and children and are characterized by a high rate of mortality and treatment-related morbidity, hence improved therapies are clearly needed. G-quadruplexes are special secondary structures adopted in guanine (G)-rich
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Embryonal tumors include a heterogeneous group of highly malignant neoplasms that primarily affect infants and children and are characterized by a high rate of mortality and treatment-related morbidity, hence improved therapies are clearly needed. G-quadruplexes are special secondary structures adopted in guanine (G)-rich DNA sequences that are often present in biologically important regions, e.g. at the end of telomeres and in the regulatory regions of oncogenes such as MYC. Owing to the significant roles that both telomeres and MYC play in cancer cell biology, G-quadruplexes have been viewed as emerging therapeutic targets in oncology and as tools for novel anticancer drug design. Several compounds that target these structures have shown promising anticancer activity in tumor xenograft models and some of them have entered Phase II clinical trials. In this review we examine approaches to DNA targeted cancer therapy, summarize the recent developments of G-quadruplex ligands as anticancer drugs and speculate on the future direction of such structures as a potential novel therapeutic strategy for embryonal tumors of the nervous system. Full article
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Open AccessReview Flavonoid Profile of Saskatoon Berries (Amelanchier alnifolia Nutt.) and Their Health Promoting Effects
Molecules 2013, 18(10), 12571-12586; doi:10.3390/molecules181012571
Received: 26 August 2013 / Revised: 30 September 2013 / Accepted: 9 October 2013 / Published: 11 October 2013
Cited by 6 | PDF Full-text (219 KB) | HTML Full-text | XML Full-text
Abstract
Flavonoids are a significant group of secondary metabolites in plants. Many of these compounds are potent antioxidants, being an important part in food products derived from the plants. The current status of research on flavonoid compounds in the fruit of Saskatoon berries (
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Flavonoids are a significant group of secondary metabolites in plants. Many of these compounds are potent antioxidants, being an important part in food products derived from the plants. The current status of research on flavonoid compounds in the fruit of Saskatoon berries (Amelanchier alnifolia Nutt.) and their health promoting effects, including recommended utilization, are reviewed. The major classes of flavonoids in the fruit are flavonols (quercetin and rutin), flavanes (proanthocyanidin compounds ranging from dimers through to heptamers and even higher polymers) and finally anthocyanins. The flavonoids represented the group of polyphenols that mostly contributed to the antioxidant activity of Saskatoon berries. High content of the flavoinoids antioxidants in the fruit is responsible for the observed anti-inflammatory, antidiadiabetic and chemo-protective effects. Full article
(This article belongs to the Section Natural Products)

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