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Molecules, Volume 24, Issue 4 (February-2 2019)

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Cover Story (view full-size image) Cistanche tubulosa aqueous extract (CTE) is already used as a botanical prescription drug for [...] Read more.
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Open AccessReview Synthesis of Phthalides and α,β-butenolides by Transition Metal-Catalyzed Activation of C—H Bonds
Molecules 2019, 24(4), 824; https://doi.org/10.3390/molecules24040824
Received: 31 January 2019 / Revised: 15 February 2019 / Accepted: 17 February 2019 / Published: 25 February 2019
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Abstract
Phthalides and α,β-butenolides are two related classes of oxygenated heterocycles with a wide range of biological activities. An innovative strategy to prepare these compounds is based on C—H bond functionalization reactions, in which two simple, unfunctionalized molecules are coupled together with cleavage of [...] Read more.
Phthalides and α,β-butenolides are two related classes of oxygenated heterocycles with a wide range of biological activities. An innovative strategy to prepare these compounds is based on C—H bond functionalization reactions, in which two simple, unfunctionalized molecules are coupled together with cleavage of a C—H bond and formation of a C—X bond (X=C or heteroatom). This paper reviews the methods for the synthesis of phthalides and α,β-butenolides by C—H bond functionalization from non-halogenated starting materials. Over 30 methods are reported, mostly developed during the past ten years. Full article
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Open AccessArticle New Brush-Type Chiral Stationary Phases for Enantioseparation of Pharmaceutical Drugs
Molecules 2019, 24(4), 823; https://doi.org/10.3390/molecules24040823
Received: 25 January 2019 / Revised: 20 February 2019 / Accepted: 21 February 2019 / Published: 25 February 2019
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Abstract
The importance of chirality in drug development is unquestionable, with chiral liquid chromatography (LC) being the most adequate technique for its analysis. Among the various types of chiral stationary phases (CSPs) for LC, brush-type CSPs provide the base for interaction analysis of CSPs [...] Read more.
The importance of chirality in drug development is unquestionable, with chiral liquid chromatography (LC) being the most adequate technique for its analysis. Among the various types of chiral stationary phases (CSPs) for LC, brush-type CSPs provide the base for interaction analysis of CSPs and enantiomers, which provide valuable results that can be applied to interaction studies of other CSP types. In order to analyze the influence of aromatic interactions in chiral recognition, we designed a set of ten new brush-type CSPs based on (S)-N-(1-aryl-propyl)-3,5-dinitrobenzamides which differ in the aromatic unit directly linked to the chiral center. Thirty diverse racemates, including several nonsteroidal anti-inflammatory drugs and 3-hydroxybenzodiazepine drugs, were used to evaluate the prepared CSPs. Chromatographic analysis showed that the three new CSPs separate enantiomers of a wide range of compounds and their chromatographic behavior is comparable to the most versatile brush-type CSP—Whelk-O1. The critical role of the nonbonding interactions in positioning of the analyte (naproxen) in the cleft of CSP-6, as well as the analysis of interactions that make enantioseparation possible, were elucidated using computational methods. Furthermore, the influence of acetic acid as a mobile phase additive, on this enantiorecognition process was corroborated by calculations. Full article
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Open AccessArticle Single Molecule Fluorescence Spectroscopy of PSI Trimers from Arthrospira platensis: A Computational Approach
Molecules 2019, 24(4), 822; https://doi.org/10.3390/molecules24040822
Received: 11 December 2018 / Revised: 20 February 2019 / Accepted: 21 February 2019 / Published: 25 February 2019
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Abstract
Based on single molecule spectroscopy analysis and our preliminary theoretical studies, the linear and fluorescence spectra of the PSI trimer from Arthrospira platensis with different realizations of the static disorder were modeled at cryogenic temperature. Considering the previously calculated spectral density of chlorophyll, [...] Read more.
Based on single molecule spectroscopy analysis and our preliminary theoretical studies, the linear and fluorescence spectra of the PSI trimer from Arthrospira platensis with different realizations of the static disorder were modeled at cryogenic temperature. Considering the previously calculated spectral density of chlorophyll, an exciton model for the PSI monomer and trimer including the red antenna states was developed taking into account the supposed similarity of PSI antenna structures from Thermosynechococcus e., Synechocystis sp. PCC6803, and Arthrospira platensis. The red Chls in the PSI monomer were assumed to be in the nearest proximity of the reaction center. The PSI trimer model allowed the simulation of experimentally measured zero phonon line distribution of the red states considering a weak electron-phonon coupling for the antenna exciton states. However, the broad absorption and fluorescence spectra of an individual emitter at 760 nm were calculated by adjusting the Huang-Rhys factors of the chlorophyll lower phonon modes assuming strong electron-phonon coupling. Full article
(This article belongs to the Special Issue Single-Molecule Fluorescence Spectroscopy)
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Open AccessArticle Linear Response Functions of Densities and Spin Densities for Systematic Modeling of the QM/MM Approach for Mono- and Poly-Nuclear Transition Metal Systems
Molecules 2019, 24(4), 821; https://doi.org/10.3390/molecules24040821
Received: 30 December 2018 / Revised: 28 January 2019 / Accepted: 15 February 2019 / Published: 25 February 2019
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Abstract
We applied our analysis, based on a linear response function of density and spin density, to two typical transition metal complex systems-the reaction centers of P450, and oxygen evolving center in Photosystem II, both of which contain open-shell transition metal ions. We discuss [...] Read more.
We applied our analysis, based on a linear response function of density and spin density, to two typical transition metal complex systems-the reaction centers of P450, and oxygen evolving center in Photosystem II, both of which contain open-shell transition metal ions. We discuss the relationship between LRF of electron density and spin density and the types of units and interactions of the systems. The computational results are discussed in relation to quantum mechanics (QM) cluster and quantum mechanics/molecular mechanics (QM/MM) modeling that are employed to compute the reaction centers of enzymes. Full article
(This article belongs to the Special Issue Open-Shell Systems for Functional Materials)
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Open AccessArticle Analysis of 27 β-Blockers and Metabolites in Milk Powder by High Performance Liquid Chromatography Coupled to Quadrupole Orbitrap High-Resolution Mass Spectrometry
Molecules 2019, 24(4), 820; https://doi.org/10.3390/molecules24040820
Received: 31 January 2019 / Revised: 19 February 2019 / Accepted: 19 February 2019 / Published: 25 February 2019
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Abstract
This paper presents an application of high performance liquid chromatography coupled with quadrupole orbitrap high-resolution mass spectrometry (HPLC-Q-Orbitrap HRMS) for the analysis of 27 β-blockers and metabolites in milk powder. Homogenized milk power samples were extracted by acetonitrile and purified by using Oasis [...] Read more.
This paper presents an application of high performance liquid chromatography coupled with quadrupole orbitrap high-resolution mass spectrometry (HPLC-Q-Orbitrap HRMS) for the analysis of 27 β-blockers and metabolites in milk powder. Homogenized milk power samples were extracted by acetonitrile and purified by using Oasis PRiME HLB solid-phase extraction cartridges. The Ascentis® C8 chromatographic column was used to separate the analytes. The quantification was achieved by using matrix-matched standard calibration curves with carazolol-d7 and propranolol-d7 as the internal standards. The results show an exceptional linear relationship with the concentrations of analytes over wide concentration ranges (0.5–500 μg kg−1) as all the fitting coefficients of determination r2 are > 0.995. All the limits of detection (LODs) and quantitation (LOQs) values were within the respective range of 0.2–1.5 μg kg−1 and 0.5–5.0 μg kg−1. Overall average recoveries were able to reach 66.1–100.4% with the intra- and inter-day variability under 10%. This method has been successfully applied to the screening of β-blockers and metabolites in commercial milk powders. At the same time, the corresponding characteristic fragmentation behavior of the 27 compounds was explored. The characteristic product ions were determined and applied to the actual samples screening. Full article
(This article belongs to the Special Issue Advances in Food Analysis)
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Open AccessArticle A Density Functional Theory-Based Scheme to Compute the Redox Potential of a Transition Metal Complex: Applications to Heme Compound
Molecules 2019, 24(4), 819; https://doi.org/10.3390/molecules24040819
Received: 30 December 2018 / Revised: 18 February 2019 / Accepted: 21 February 2019 / Published: 25 February 2019
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Abstract
We estimated the redox potential of a model heme compound by using the combination of our density functionals with a computational scheme, which corrects the solvation energy to the normal solvent model. Among many density functionals, the LC-BOP12 functional gave the smallest mean [...] Read more.
We estimated the redox potential of a model heme compound by using the combination of our density functionals with a computational scheme, which corrects the solvation energy to the normal solvent model. Among many density functionals, the LC-BOP12 functional gave the smallest mean absolute error of 0.16 V in the test molecular sets. The application of these methods revealed that the redox potential of a model heme can be controlled within 200 mV by changing the protonation state and even within 20 mV by the flipping of the ligand histidine. In addition, the redox potential depends on the inverse of the dielectric constant, which controls the surroundings. The computational results also imply that a system with a low dielectric constant avoids the charged molecule by controlling either the redox potential or the protonation system. Full article
(This article belongs to the Special Issue Open-Shell Systems for Functional Materials)
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Open AccessArticle In Vitro Metabolism of 25B-NBF, 2-(4-Bromo-2,5-Dimethoxyphenyl)-N-(2-Fluorobenzyl)ethanamine, in Human Hepatocytes Using Liquid Chromatography–Mass Spectrometry
Molecules 2019, 24(4), 818; https://doi.org/10.3390/molecules24040818
Received: 29 January 2019 / Revised: 17 February 2019 / Accepted: 22 February 2019 / Published: 25 February 2019
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Abstract
25B-NBF, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-fluorobenzyl)ethanamine, is a new psychoactive substance classified as a phenethylamine. It is a potent agonist of the 5-hydroxytryptamine receptor, but little is known about its metabolism and elimination properties since it was discovered. To aid 25B-NBF abuse screening, the metabolic [...] Read more.
25B-NBF, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-fluorobenzyl)ethanamine, is a new psychoactive substance classified as a phenethylamine. It is a potent agonist of the 5-hydroxytryptamine receptor, but little is known about its metabolism and elimination properties since it was discovered. To aid 25B-NBF abuse screening, the metabolic characteristics of 25B-NBF were investigated in human hepatocytes and human cDNA-expressed cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes using liquid chromatography–high resolution mass spectrometry. At a hepatic extraction ratio of 0.80, 25B-NBF was extensively metabolized into 33 metabolites via hydroxylation, O-demethylation, bis-O-demethylation, N-debenzylation, glucuronidation, sulfation, and acetylation after incubation with pooled human hepatocytes. The metabolism of 25B-NBF was catalyzed by CYP1A1, CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2J2, CYP3A4, and UGT2B7 enzymes. Based on these results, it is necessary to develop a bioanalytical method for the determination of not only 25B-NBF but also its metabolites in biological samples for the screening of 25B-NBF abuse. Full article
(This article belongs to the Special Issue Forensic Analytical Chemistry)
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Open AccessArticle Multimerization Increases Tumor Enrichment of Peptide–Photosensitizer Conjugates
Molecules 2019, 24(4), 817; https://doi.org/10.3390/molecules24040817
Received: 22 January 2019 / Revised: 8 February 2019 / Accepted: 19 February 2019 / Published: 25 February 2019
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Abstract
Photodynamic therapy (PDT) is an established therapeutic modality for the management of cancers. Conjugation with tumor-specific small molecule ligands (e.g., short peptides or peptidomimetics) could increase the tumor targeting of PDT agents, which is very important for improving the outcome of PDT. However, [...] Read more.
Photodynamic therapy (PDT) is an established therapeutic modality for the management of cancers. Conjugation with tumor-specific small molecule ligands (e.g., short peptides or peptidomimetics) could increase the tumor targeting of PDT agents, which is very important for improving the outcome of PDT. However, compared with antibody molecules, small molecule ligands have a much weaker affinity to their receptors, which means that their tumor enrichment is not always ideal. In this work, we synthesized multimeric RGD ligand-coupled conjugates of pyropheophorbide-a (Pyro) to increase the affinity through multivalent and cluster effects to improve the tumor enrichment of the conjugates. Thus, the dimeric and trimeric RGD peptide-coupled Pyro conjugates and the monomeric one for comparison were efficiently synthesized via a convergent strategy. A short polyethylene glycol spacer was introduced between two RGD motifs to increase the distance required for multivalence. A subsequent binding affinity assay verified the improvement of the binding towards integrin αvβ3 receptors after the increase in the valence, with an approximately 20-fold improvement in the binding affinity of the trimeric conjugate compared with that of the monomeric conjugate. In vivo experiments performed in tumor-bearing mice also confirmed a significant increase in the distribution of the conjugates in the tumor site via multimerization, in which the trimeric conjugate had the best tumor enrichment compared with the other two conjugates. These results indicated that the multivalence interaction can obviously increase the tumor enrichment of RGD peptide-conjugated Pyro photosensitizers, and the prepared trimeric conjugate can be used as a novel antitumor photodynamic agent with high tumor enrichment. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessReview Antimicrobial Activities of Tea Polyphenol on Phytopathogens: A Review
Molecules 2019, 24(4), 816; https://doi.org/10.3390/molecules24040816
Received: 29 January 2019 / Revised: 22 February 2019 / Accepted: 23 February 2019 / Published: 25 February 2019
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Abstract
The use of natural antimicrobial compounds in crop production has gained much attention from consumers and the agricultural industry. Consequently, interest in more natural, non-synthetic antimicrobials as potential alternatives to conventional chemical pesticides to combat phytopathogens has heightened. Tea polyphenol (TP), a unique [...] Read more.
The use of natural antimicrobial compounds in crop production has gained much attention from consumers and the agricultural industry. Consequently, interest in more natural, non-synthetic antimicrobials as potential alternatives to conventional chemical pesticides to combat phytopathogens has heightened. Tea polyphenol (TP), a unique and highly important functional component of tea plants, has been reported to possess antimicrobial properties against a wide spectrum of plant pathogens. The aim of this review is to discuss the emerging findings on the mechanisms of antimicrobial action, and the antimicrobial properties of TP, including their major components, effectiveness, and synergistic effects. More studies, particularly field studies, are still necessary to establish conclusive evidence for the effectiveness of TP against phytopathogens. However, the basic conclusion from existing studies suggests that TP is a potential antimicrobial agent for pesticide reduction in agricultural systems. Full article
(This article belongs to the Special Issue EGCG, Green Tea and Polyphenols)
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Open AccessArticle Microwave-Assisted Extraction of Multiple Trace Levels of Intermediate Metabolites for Camptothecin Biosynthesis in Camptotheca acuminata and Their Simultaneous Determination by HPLC-LTQ-Orbitrap-MS/MS and HPLC-TSQ-MS
Molecules 2019, 24(4), 815; https://doi.org/10.3390/molecules24040815
Received: 6 January 2019 / Revised: 10 February 2019 / Accepted: 16 February 2019 / Published: 25 February 2019
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Abstract
Camptothecin (CPT) has strong antitumor activity and is used as an anticancer therapeutic agent. To better understand and decipher the pathway of CPT biosynthesis in Camptotheca acuminata, the main purpose here was focused on creating an effective extraction strategy for a rich [...] Read more.
Camptothecin (CPT) has strong antitumor activity and is used as an anticancer therapeutic agent. To better understand and decipher the pathway of CPT biosynthesis in Camptotheca acuminata, the main purpose here was focused on creating an effective extraction strategy for a rich intermediate metabolite profile. In the present study, a 70% aqueous acetonitrile was verified as an optimal extraction solvent for microwave-assisted extraction (MAE) of metabolites by spiking experiments. Based on multi-objective optimization, the best extraction conditions of a solid-liquid ratio of 1:20, microwave power of 230 W, and a time of 4 min were achieved using a full factorial 34 experimental design. Crude extracts obtained from the shoot apex of C. acuminata using MAE have been qualitatively profiled by high-performance liquid chromatography coupled with linear ion trap quadrupole-orbitrap mass spectrometry (HPLC-LTQ-Orbitrap-MS/MS) and a HPLC triple quadrupole-MS (HPLC-TSQ-MS) analysis was conducted for their metabolite content in different tissues. CPT, and ten related metabolites and their isomers, including tryptamine, loganic acid, secologanic acid, strictosidinic acid, strictosamide, strictosamide epoxide, strictosamide diol, strictosamide ketolactam, pumiloside, and deoxypumiloside, were detected and tentatively identified. Scanning electron microscopy (SEM) imaging of the shoot apex demonstrated that severe cell disruption was evident after intensified extraction processes. The study showed the difference of metabolite profiles and the enhancement of metabolite content after microwave-pretreated techniques, and the established MAE procedure is an effective methodology to preserve valuable metabolite compounds for analysis. Full article
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Open AccessArticle Engineering of Antimicrobial Surfaces by Using Temporin Analogs to Tune the Biocidal/antiadhesive Effect
Molecules 2019, 24(4), 814; https://doi.org/10.3390/molecules24040814
Received: 14 January 2019 / Revised: 19 February 2019 / Accepted: 20 February 2019 / Published: 24 February 2019
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Abstract
Proliferation of resistant bacteria on biomaterials is a major problem leading to nosocomial infections. Due to their broad-spectrum activity and their ability to disrupt bacterial membranes through a rapid membranolytic mechanism, antimicrobial peptides (AMPs) are less susceptible to the development of bacterial resistance [...] Read more.
Proliferation of resistant bacteria on biomaterials is a major problem leading to nosocomial infections. Due to their broad-spectrum activity and their ability to disrupt bacterial membranes through a rapid membranolytic mechanism, antimicrobial peptides (AMPs) are less susceptible to the development of bacterial resistance and therefore represent good candidates for surface coating strategies to prevent biofilm formation. In this study, we report on the covalent immobilization of temporin-SHa, a small hydrophobic and low cationic antimicrobial peptide exhibiting broad-spectrum activity, and (SHa) analogs on modified gold surfaces. Several analogs derived from SHa with either a carboxamidated ([K3]SHa, d-[K3]SHa) or a carboxylated C-terminus ([K3]SHa-COOH) were used to achieve peptide grafting on gold surfaces modified by a thiolated self-assembled monolayer (SAM). Surface functionalization was characterized by polarization modulation infrared reflection absorption spectroscopy (PM-RAIRS) and X-ray photoemission spectroscopy (XPS). The antibacterial properties of the temporin-functionalized surfaces were tested against the Gram-positive Listeria ivanovii. Direct visualization of the peptide effects on the bacterial membrane was investigated by scanning electron microscopy equipped with a field emission gun (SEM-FEG). All active temporin analogs were successfully grafted and display significant antibacterial activity (from 80 to 90% killing efficiency) in addition to a 2-fold decrease of bacterial adhesion when all d-SHa analogs were used. Full article
(This article belongs to the Special Issue Recent Advances in Antimicrobial Biomaterials)
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Open AccessArticle The Proanthocyanidin-Rich Fraction Obtained from Red Rice Germ and Bran Extract Induces HepG2 Hepatocellular Carcinoma Cell Apoptosis
Molecules 2019, 24(4), 813; https://doi.org/10.3390/molecules24040813
Received: 5 February 2019 / Revised: 20 February 2019 / Accepted: 20 February 2019 / Published: 23 February 2019
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Abstract
This study aims to determine the anti-carcinogenic effects of the proanthocyanidin-rich fraction (PRFR) obtained from red rice germ and bran extract on HepG2 cells. The PRFR obtained from red rice germ and bran extract could reduce the cell viability of HepG2 cells as [...] Read more.
This study aims to determine the anti-carcinogenic effects of the proanthocyanidin-rich fraction (PRFR) obtained from red rice germ and bran extract on HepG2 cells. The PRFR obtained from red rice germ and bran extract could reduce the cell viability of HepG2 cells as shown by the IC50 value at 20 µg/mL. Notably, PRFR concentrations at 20 and 40 µg/mL significantly increased the number of cells in the G2/M phase from 25.7% ± 1.4%in the control group to 36.2% ± 3.4% (p < 0.01) and 48.9% ± 2.6% (p < 0.0001), respectively, suggesting that the cells were arrested in this phase, which was confirmed by the reduction of survival proteins, including cyclin B1 and cdc25. Moreover, the PRFR at 20 and 40 µg/mL could induce cell death via the apoptosis cascade, indicated by the percentage of total apoptotic cells from 9.9% ± 3.1% in the control group to 41.1 ± 3.9 (p < 0.0001) and 82.2% ± 5.8% (p < 0.0001), respectively. This was clarified by increasing apoptotic proteins (such as cleaved PARP-1, cleaved caspase-8 and cleaved caspase-3) and decreasing anti-apoptotic protein survivin without p53 alterations. These results demonstrated that the PRFR obtained from red rice germ and bran extract could inhibit cell proliferation and induce cell apoptosis in HepG2 cells via survivin, which could potentially serve as a new target for cancer therapeutics making it an excellent “lead candidate” molecule for in vivo proof-of concept studies. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle Relationship between Cocoa Intake and Healthy Status: A Pilot Study in University Students
Molecules 2019, 24(4), 812; https://doi.org/10.3390/molecules24040812
Received: 2 January 2019 / Revised: 12 February 2019 / Accepted: 22 February 2019 / Published: 23 February 2019
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Abstract
Due to its polyphenol content, cocoa’s potential health effects are attracting much attention, showing, among other things, cardioprotective, anti-inflammatory, anti-obesity, and neuroprotective actions. However, there is very limited information regarding the effect of cocoa on human immunity. This study aimed to establish the [...] Read more.
Due to its polyphenol content, cocoa’s potential health effects are attracting much attention, showing, among other things, cardioprotective, anti-inflammatory, anti-obesity, and neuroprotective actions. However, there is very limited information regarding the effect of cocoa on human immunity. This study aimed to establish the relationship between cocoa consumption and health status, focusing on physical activity habits and allergy prevalence in young people. For this, a sample of 270 university students was recruited to complete a food frequency questionnaire, the International Physical Activity Questionnaire (IPAQ), and a lifestyle and health status questionnaire. The results were analysed by classifying the participants into tertiles defined according to their cocoa consumption: low (LC), moderate (MC), and high (HC) consumers. The consumption of cocoa inversely correlated with physical activity and the MC group had significantly less chronic disease frequency than the LC group. The percentage of allergic people in the MC and HC groups was lower than that in the LC group and, moreover, the cocoa intake, especially moderate consumption, was also associated with a lower presence of allergic symptoms. Thus, from these results a positive effect of cocoa intake on allergy can be suggested in the young population. Full article
(This article belongs to the Special Issue Natural Polyphenols and Health)
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Open AccessArticle Identification of Novel Benzoxa-[2,1,3]-diazole Substituted Amino Acid Hydrazides as Potential Anti-Tubercular Agents
Molecules 2019, 24(4), 811; https://doi.org/10.3390/molecules24040811
Received: 29 January 2019 / Revised: 18 February 2019 / Accepted: 20 February 2019 / Published: 23 February 2019
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Abstract
Discovery and development of new therapeutic options for the treatment of Mycobacterium tuberculosis (Mtb) infection are desperately needed to tackle the continuing global burden of this disease and the efficacy and cost limitations associated with current medicines. Herein, we report the [...] Read more.
Discovery and development of new therapeutic options for the treatment of Mycobacterium tuberculosis (Mtb) infection are desperately needed to tackle the continuing global burden of this disease and the efficacy and cost limitations associated with current medicines. Herein, we report the synthesis of a series of novel benzoxa-[2,1,3]-diazole substituted amino acid hydrazides in a two-step synthesis and evaluate their inhibitory activity against Mtb and selected bacterial strains of clinical importance utilising an end point-determined REMA assay. Alongside this, their potential for undesired cytotoxicity against mammalian cells was assessed employing standard MTT assay methodologies. It has been demonstrated using modification at three sites (the hydrazine, amino acid, and the benzodiazole) it is possible to change both the antibacterial activity and cytotoxicity of these molecules whilst not affecting their microbial selectivity, making them attractive architectures for further exploitation as novel antibacterial agents. Full article
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Open AccessArticle Selective Inhibition of Human Monoamine Oxidase B by Acacetin 7-Methyl Ether Isolated from Turnera diffusa (Damiana)
Molecules 2019, 24(4), 810; https://doi.org/10.3390/molecules24040810
Received: 29 December 2018 / Revised: 18 February 2019 / Accepted: 19 February 2019 / Published: 23 February 2019
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Abstract
The investigation of the constituents that were isolated from Turnera diffusa (damiana) for their inhibitory activities against recombinant human monoamine oxidases (MAO-A and MAO-B) in vitro identified acacetin 7-methyl ether as a potent selective inhibitor of MAO-B (IC50 = 198 nM). Acacetin [...] Read more.
The investigation of the constituents that were isolated from Turnera diffusa (damiana) for their inhibitory activities against recombinant human monoamine oxidases (MAO-A and MAO-B) in vitro identified acacetin 7-methyl ether as a potent selective inhibitor of MAO-B (IC50 = 198 nM). Acacetin 7-methyl ether (also known as 5-hydroxy-4′, 7-dimethoxyflavone) is a naturally occurring flavone that is present in many plants and vegetables. Acacetin 7-methyl ether was four-fold less potent as an inhibitor of MAO-B when compared to acacetin (IC50 = 50 nM). However, acacetin 7-methyl ether was >500-fold selective against MAO-B over MAO-A as compared to only two-fold selectivity shown by acacetin. Even though the IC50 for inhibition of MAO-B by acacetin 7-methyl ether was ~four-fold higher than that of the standard drug deprenyl (i.e., SelegilineTM or ZelaparTM, a selective MAO-B inhibitor), acacetin 7-methyl ether’s selectivity for MAO-B over MAO-A inhibition was greater than that of deprenyl (>500- vs. 450-fold). The binding of acacetin 7-methyl ether to MAO-B was reversible and time-independent, as revealed by enzyme-inhibitor complex equilibrium dialysis assays. The investigation on the enzyme inhibition-kinetics analysis with varying concentrations of acacetin 7-methyl ether and the substrate (kynuramine) suggested a competitive mechanism of inhibition of MAO-B by acacetin 7-methyl ether with Ki value of 45 nM. The docking scores and binding-free energies of acacetin 7-methyl ether to the X-ray crystal structures of MAO-A and MAO-B confirmed the selectivity of binding of this molecule to MAO-B over MAO-A. In addition, molecular dynamics results also revealed that acacetin 7-methyl ether formed a stable and strong complex with MAO-B. The selective inhibition of MAO-B suggests further investigations on acacetin 7-methyl as a potential new drug lead for the treatment of neurodegenerative disorders, including Parkinson’s disease. Full article
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Open AccessFeature PaperReview The Pharmaceutical Industry in 2018. An Analysis of FDA Drug Approvals from the Perspective of Molecules
Molecules 2019, 24(4), 809; https://doi.org/10.3390/molecules24040809
Received: 29 January 2019 / Revised: 21 February 2019 / Accepted: 21 February 2019 / Published: 23 February 2019
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Abstract
The Food and Drug Administration approved 59 new drugs (42 New Chemical Entities and 17 Biologics) during 2018. This number breaks the previous record of 53 approved by the same organization in 1996. The 17 new biologics approved in 2018 also represent an [...] Read more.
The Food and Drug Administration approved 59 new drugs (42 New Chemical Entities and 17 Biologics) during 2018. This number breaks the previous record of 53 approved by the same organization in 1996. The 17 new biologics approved in 2018 also represent an important milestone for this kind of drug and they clearly exceed the 12 approved in 2015 and 2017. Herein, the 59 new drugs of the class of 2018 are analyzed from a strictly chemical perspective. The classification has been carried out on the basis of the chemical structure and includes the following: Biologics (antibodies and enzymes); TIDES (peptides and oligonucleotides) and natural products; drug combinations; and small molecules. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle The Effect of the Chemical Character of Ionic Liquids on Biomass Pre-Treatment and Posterior Enzymatic Hydrolysis
Molecules 2019, 24(4), 808; https://doi.org/10.3390/molecules24040808
Received: 3 February 2019 / Revised: 15 February 2019 / Accepted: 20 February 2019 / Published: 23 February 2019
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Abstract
Ionic liquids have been recognised as interesting solvents applicable in efficient lignocellulosic biomass valorisation, especially in biomass fractionation into individual polymeric components or direct hydrolysis of some biomass fractions. Considering the chemical character of ionic liquids, two different approaches paved the way for [...] Read more.
Ionic liquids have been recognised as interesting solvents applicable in efficient lignocellulosic biomass valorisation, especially in biomass fractionation into individual polymeric components or direct hydrolysis of some biomass fractions. Considering the chemical character of ionic liquids, two different approaches paved the way for the fractionation of biomass. The first strategy integrated a pre-treatment, hydrolysis and conversion of biomass through the employment of hydrogen-bond acidic 1-ethyl-3-methyimidazolim hydrogen sulphate ionic liquid. The second strategy relied on the use of a three-step fractionation process with hydrogen-bond basic 1-ethyl-3-methylimidazolium acetate to produce high purity cellulose, hemicellulose and lignin fractions. The proposed approaches were scrutinised for wheat straw and eucalyptus residues. These different biomasses enabled an understanding that enzymatic hydrolysis yields are dependent on the crystallinity of the pre-treated biomass. The use of acetate based ionic liquid allowed crystalline cellulose I to change to cellulose II and consequently enhanced the glucan to glucose yield to 93.1 ± 4.1 mol% and 82.9 ± 1.2 mol% for wheat straw and eucalyptus, respectively. However, for hydrogen sulphate ionic liquid, the same enzymatic hydrolysis yields were 61.6 ± 0.2 mol% for wheat straw and only 7.9 ± 0.3 mol% for eucalyptus residues. These results demonstrate the importance of both ionic liquid character and biomass type for efficient biomass processing. Full article
(This article belongs to the Special Issue Efficient Technology for the Pretreatment of Biomass II)
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Open AccessArticle Site-Specific Cleavage of RNAs Derived from the PIM1 3′-UTR by a Metal-Free Artificial Ribonuclease
Molecules 2019, 24(4), 807; https://doi.org/10.3390/molecules24040807
Received: 6 February 2019 / Accepted: 19 February 2019 / Published: 23 February 2019
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Abstract
Oligonucleotide conjugates of tris(2-aminobenzimidazole) have been reported previously to cleave complementary RNA strands with high levels of sequence and site specificity. The RNA substrates used in these studies were oligonucleotides not longer than 29-mers. Here we show that ~150–400-mer model transcripts derived from [...] Read more.
Oligonucleotide conjugates of tris(2-aminobenzimidazole) have been reported previously to cleave complementary RNA strands with high levels of sequence and site specificity. The RNA substrates used in these studies were oligonucleotides not longer than 29-mers. Here we show that ~150–400-mer model transcripts derived from the 3′-untranslated region of the PIM1 mRNA reacted with rates and specificities comparable to those of short oligonucleotide substrates. The replacement of DNA by DNA/LNA mixmers further increased the cleavage rate. Tris(2-aminobenzimidazoles) were designed to interact with phosphates and phosphate esters. A cell, however, contains large amounts of phosphorylated species that may cause competitive inhibition of RNA cleavage. It is thus important to note that no loss in reaction rates was observed in phosphate buffer. This opens the way to in-cell applications for this type of artificial nuclease. Furthermore, we disclose a new synthetic method giving access to tris(2-aminobenzimidazoles) in multigram amounts. Full article
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Open AccessArticle A Comprehensive Study on the Dye Adsorption Behavior of Polyoxometalate-Complex Nano-Hybrids Containing Classic β-Octamolybdate and Biimidazole Units
Molecules 2019, 24(4), 806; https://doi.org/10.3390/molecules24040806
Received: 25 December 2018 / Revised: 8 February 2019 / Accepted: 11 February 2019 / Published: 22 February 2019
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Abstract
Six new hybrids based on β-[Mo8O26]4− polyoxometalates, [Ni(H2biim)3]2[β-Mo8O26]•8DMF(1); (DMA)2[M(H2biim)2(H2O)2][β-Mo8O26]•4DMF (M = Ni [...] Read more.
Six new hybrids based on β-[Mo8O26]4− polyoxometalates, [Ni(H2biim)3]2[β-Mo8O26]•8DMF(1); (DMA)2[M(H2biim)2(H2O)2][β-Mo8O26]•4DMF (M = Ni (2), Co (3)), DMA = dimethyl-ammonium, H2biim=2,2′-biimidazole); [M(H2biim)(DMF)3]2[β-Mo8O26]•2DMF (M = Zn (4), Cu (5)); [(DMA)2[Cu(DMF)4][β-Mo8O26]•2DMF]n (6), have been successfully synthesized and characterized. Compounds 2–5 show favorable capacity to adsorb methylene blue (MB) at room temperature, and they can selectively capture MB molecules from binary-mixture solutions of MB/MO (MO = Methyl Orange), or MB/RhB (RhB = Rhodamine B). Compound 3 can uptake up to 521.7 mg g−1 MB cationic dyes rapidly, which perform the maximum adsorption in an hour among the reported materials as far as we know. The compounds are stable and still work very efficiently after three cycles. For compound 3, the preliminary adsorption mechanism studies indicated that the adsorption is an ion exchange process and the adsorption behavior of polyoxometalate-complex can be benefited from additional exchangeable protons in the complex cations. Full article
(This article belongs to the Special Issue Polyoxometalates and Polyoxometalate-Based Systems)
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Open AccessArticle Novel Substituted Thiophenes and Sulf-Polyacetylene Ester from Echinops ritro L.
Molecules 2019, 24(4), 805; https://doi.org/10.3390/molecules24040805
Received: 17 November 2018 / Revised: 13 February 2019 / Accepted: 13 February 2019 / Published: 22 February 2019
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Abstract
Three new substituted bithiophenes (13), and one new sulf-polyacetylene ester, ritroyne A (16) were isolated from the whole plant of Echinops ritro together with twelve known substituted thiophenes. The structures were elucidated on the basis of extensive [...] Read more.
Three new substituted bithiophenes (13), and one new sulf-polyacetylene ester, ritroyne A (16) were isolated from the whole plant of Echinops ritro together with twelve known substituted thiophenes. The structures were elucidated on the basis of extensive spectroscopic analysis including 1D and 2D NMR as well as MS. Furthermore, the absolute configuration of ritroyne A (16) was established by computational methods. In bioscreening experiments, four compounds (2, 4, 12, 14) showed similar antibacterial activity against Staphylococcus aureus ATCC 2592 with levofloxacin (8 µg/mL). Five compounds (2, 4, 9, 12, 14) exhibited antibacterial activities against Escherichia coli ATCC 25922, with minimum inhibitory concentration (MIC) values of 32–64 µg/mL. Three compounds (2, 4, 12) exhibited antifungal activities against Candida albicans ATCC 2002 with MIC values of 32–64 µg/mL. However, compound 16 did not exhibit antimicrobial activities against three microorganisms. Full article
(This article belongs to the Special Issue Natural Product Isolation, Identification and Biological Activity)
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Open AccessCommunication Chemical Composition and Antimicrobial Activity of Laurus nobilis L. Essential Oils from Bulgaria
Molecules 2019, 24(4), 804; https://doi.org/10.3390/molecules24040804
Received: 25 January 2019 / Revised: 13 February 2019 / Accepted: 16 February 2019 / Published: 22 February 2019
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Abstract
Laurel, Laurus nobilis L. is an evergreen plant belonging to the Lauraceae family, native to Southern Europe and the Mediterranean area. This is the first report on the composition and bioactivity of laurel essential oil (EO) from Bulgaria. The oil yield was 0.78%, [...] Read more.
Laurel, Laurus nobilis L. is an evergreen plant belonging to the Lauraceae family, native to Southern Europe and the Mediterranean area. This is the first report on the composition and bioactivity of laurel essential oil (EO) from Bulgaria. The oil yield was 0.78%, 0.80%, and 3.25% in the fruits, twigs, and leaves, respectively. The main constituents in the fruit EO were 1,8-cineole (33.3%), α-terpinyl acetate (10.3%), α-pinene (11.0%), β-elemene (7.5%), sabinene (6.3%), β-phellandrene (5.2%), bornyl acetate (4.4%), and camphene (4.3%); those in the twig EO were 1,8-cineole (48.5%), α-terpinyl acetate (13.1%), methyl eugenol (6.6%), β-linalool (3.8%), β-pinene (3.4%), sabinene (3.3%) and terpinene-4-ol (3.3%); and the ones in the leaf EO were 1,8-cineole (41.0%), α-terpinyl acetate (14.4%), sabinene (8.8%), methyl eugenole (6.0%), β-linalool (4.9%), and α-terpineol (3.1%). The antibacterial and antifungal properties of laurel EOs were examined according to the agar well diffusion method. The leaf EO showed antibacterial and antifungal activities against almost all strains of the microorganisms tested, whereas the twig EO was only able to inhibit Staphylococcus aureus. Pseudomonas aeruginosa ATCC 9027 and Escherichia coli ATCC 8739 were the bacterial strains that showed the highest resistance to the laurel EO. The results can benefit the EO industry and biopesticide development. Full article
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Open AccessArticle The Morphology and Performance of Poly(Vinyl Chloride) Containing Melamine Schiff Bases against Ultraviolet Light
Molecules 2019, 24(4), 803; https://doi.org/10.3390/molecules24040803
Received: 10 February 2019 / Revised: 20 February 2019 / Accepted: 21 February 2019 / Published: 22 February 2019
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Abstract
Five Schiff bases derived from melamine have been used as efficient additives to reduce the process of photodegradation of poly(vinyl chloride) films. The performance of Schiff bases has been investigated using various techniques. Poly(vinyl chloride) films containing Schiff bases were irradiated with ultraviolet [...] Read more.
Five Schiff bases derived from melamine have been used as efficient additives to reduce the process of photodegradation of poly(vinyl chloride) films. The performance of Schiff bases has been investigated using various techniques. Poly(vinyl chloride) films containing Schiff bases were irradiated with ultraviolet light and any changes in their infrared spectra, weight, and the viscosity of their average molecular weight were investigated. In addition, the surface morphology of the films was inspected using a light microscope, atomic force microscopy, and a scanning electron micrograph. The additives enhanced the films resistance against irradiation and the polymeric surface was much smoother in the presence of the Schiff bases compared with the blank film. Schiff bases containing an ortho-hydroxyl group on the aryl rings showed the greatest photostabilization effect, which may possibly have been due to the direct absorption of ultraviolet light. This phenomenon seems to involve the transfer of a proton as well as several intersystem crossing processes. Full article
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Open AccessArticle Simultaneous Quantification of L-Arginine and Monosaccharides during Fermentation: An Advanced Chromatography Approach
Molecules 2019, 24(4), 802; https://doi.org/10.3390/molecules24040802
Received: 6 February 2019 / Revised: 15 February 2019 / Accepted: 17 February 2019 / Published: 22 February 2019
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Abstract
Increasing demand for L-arginine by the food and pharmaceutical industries has sparked the search for sustainable ways of producing it. Microbial fermentation offers a suitable alternative; however, monitoring of arginine production and carbon source uptake during fermentation, requires simple and reliable quantitative methods [...] Read more.
Increasing demand for L-arginine by the food and pharmaceutical industries has sparked the search for sustainable ways of producing it. Microbial fermentation offers a suitable alternative; however, monitoring of arginine production and carbon source uptake during fermentation, requires simple and reliable quantitative methods compatible with the fermentation medium. Two methods for the simultaneous quantification of arginine and glucose or xylose are described here: high-performance anion-exchange chromatography coupled to integrated pulsed amperometric detection (HPAEC-IPAD) and reversed-phase ultra-high-performance liquid chromatography combined with charged aerosol detection (RP-UHPLC-CAD). Both were thoroughly validated in a lysogeny broth, a minimal medium, and a complex medium containing corn steep liquor. HPAEC-IPAD displayed an excellent specificity, accuracy, and precision for arginine, glucose, and xylose in minimal medium and lysogeny broth, whereas specificity and accuracy for arginine were somewhat lower in medium containing corn steep liquor. RP-UHPLC-CAD exhibited high accuracy and precision, and enabled successful monitoring of arginine and glucose or xylose in all media. The present study describes the first successful application of the above chromatographic methods for the determination and monitoring of L-arginine amounts during its fermentative production by a genetically modified Escherichia coli strain cultivated in various growth media. Full article
(This article belongs to the Special Issue Molecules for Biotechnologies)
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Open AccessArticle Phenethyl Isothiocyanate and Cisplatin Co-Encapsulated in a Liposomal Nanoparticle for Treatment of Non-Small Cell Lung Cancer
Molecules 2019, 24(4), 801; https://doi.org/10.3390/molecules24040801
Received: 3 January 2019 / Revised: 14 February 2019 / Accepted: 19 February 2019 / Published: 22 February 2019
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Abstract
Lung cancer is the leading cause of cancer-related death in the Unites States, and approximately 85% of all lung cancers are classified as non-small cell lung cancer (NSCLC), which is extremely difficult to treat and its survival rate is low. After decades of [...] Read more.
Lung cancer is the leading cause of cancer-related death in the Unites States, and approximately 85% of all lung cancers are classified as non-small cell lung cancer (NSCLC), which is extremely difficult to treat and its survival rate is low. After decades of clinical trials, the most effective treatments are still those that implement the first-generation platinum anticancer agent cisplatin (CDDP) in combination with other drugs. We previously demonstrated that the naturally-occurring compound phenethyl isothiocyanate (PEITC) can be used to sensitize NSCLC cells to CDDP. Furthermore, co-encapsulation of PEITC and CDDP in liposomes enhances their toxicity toward NSCLC cells. We here optimize liposomal-PEITC-CDDP, demonstrate the release of PEITC and CDDP from the nanoparticle, and show that liposomal-PEITC-CDDP is much more toxic toward both A549 and H596 human NSCLC cell lines than toward WI-38 and BEAS-2B human normal lung cell lines. Thus, we have prepared an efficacious therapy that has significantly higher toxicity toward cancer cell lines than normal cell lines. Full article
(This article belongs to the Section Nanochemistry)
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Open AccessArticle White Light-Emitting Devices Based on Inorganic Perovskite and Organic Materials
Molecules 2019, 24(4), 800; https://doi.org/10.3390/molecules24040800
Received: 18 January 2019 / Revised: 17 February 2019 / Accepted: 19 February 2019 / Published: 22 February 2019
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Abstract
Perovskite-based materials have attracted considerable attention in photoelectric devices. In this paper, we report the one-step fabrication of spin-coated CsPbBr2.5I0.5 perovskite films doped with PAN (polyacrylonitrile) polymer. A red perovskite LED (PeLED) composite film was fabricated which featured a maximum [...] Read more.
Perovskite-based materials have attracted considerable attention in photoelectric devices. In this paper, we report the one-step fabrication of spin-coated CsPbBr2.5I0.5 perovskite films doped with PAN (polyacrylonitrile) polymer. A red perovskite LED (PeLED) composite film was fabricated which featured a maximum luminance value of 657 cd/m2 at 8 V. We fabricated white PeLEDs by combining hole transporting layer material emission, perovskite–polymer composite material PAN:CsPbBr2.5I0.5, and pure inorganic perovskite CsPbBr3 as a luminescent layer. The maximum luminance of the device was 360 cd/m2 at 7 V, and the color coordinate was (0.31, 0.36). We obtained an ideal white light-emitting device that paves the way for further development of white PeLEDs. Full article
(This article belongs to the Special Issue Organic Light Emitting Diodes II)
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Open AccessArticle A GC-MS Protocol for Separating Endangered and Non-endangered Pterocarpus Wood Species
Molecules 2019, 24(4), 799; https://doi.org/10.3390/molecules24040799
Received: 9 February 2019 / Revised: 19 February 2019 / Accepted: 20 February 2019 / Published: 22 February 2019
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Abstract
Pterocarpus santalinus and Pterocarpus tincorius are commonly used traded timber species of the genus Pterocarpus. P. santalinus has been listed in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). As a non-CITES species, [...] Read more.
Pterocarpus santalinus and Pterocarpus tincorius are commonly used traded timber species of the genus Pterocarpus. P. santalinus has been listed in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). As a non-CITES species, P. tincorius is also indiscriminately labeled as P. santalinus due to the similar macroscopic and microscopic features with P. santalinus. In order to understand the molecular discrimination between these easily confused species, xylarium heartwoods of these two species were extracted by three different kinds of solvents and analyzed using gas chromatography–mass spectrometry (GC-MS). Multivariate analyses were also applied for the selection of marker compounds that are distinctive between P. santalinus and P. tincorius. A total of twenty volatile compounds were detected and tentatively identified in three kinds of extracts, and these compounds included alcohols, stilbenoids, esters, aromatic hydrocarbons, ketones, miscellaneous, phenols, and flavonoids. GC-MS analyses also revealed that extraction solvents including ethanol and water (EW), ethyl acetate (EA), and benzene–ethanol (BE) gave the best chemotaxonomical discrimination in the chemical components and relative contents of the two Pterocarpus species. After chemometric analyses, EW displayed higher predictive accuracy (100%) than those of EA extract (83.33%) and BE extract (83.33%). Furthermore, spathulenol (17.58 min) and pterostilbene (23.65 min) were elucidated as the critical compounds for the separation of the EW extracts of P. santalinus and P. tinctorius. Thus, a protocol of GC-MS and multivariate analyses was developed to use for successfully distinguishing P. santalinus from P. tinctorius. Full article
(This article belongs to the Section Analytical Chemistry)
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Open AccessArticle Design, Synthesis, and Use of Novel Photoaffinity Probes in Measuring the Serum Concentration of Glycogen Phosphorylase
Molecules 2019, 24(4), 798; https://doi.org/10.3390/molecules24040798
Received: 30 December 2018 / Revised: 18 February 2019 / Accepted: 20 February 2019 / Published: 22 February 2019
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Abstract
A procedure to measure the serum concentration of glycogen phosphorylase during acute myocardial infarction is presented. This method was based on the synthesis of photoaffinity probes, and used the semiquantitative protein electrophoretic mobility shift technique. Three novel photoaffinity probes bearing different secondary tags [...] Read more.
A procedure to measure the serum concentration of glycogen phosphorylase during acute myocardial infarction is presented. This method was based on the synthesis of photoaffinity probes, and used the semiquantitative protein electrophoretic mobility shift technique. Three novel photoaffinity probes bearing different secondary tags were synthesized. Their potency was evaluated in an enzyme inhibition assay against rabbit muscle glycogen phosphorylase a (RMGPa). The inhibitory activity of probe 1 was only 100-fold less potent than the mother compound CP-320626. The photoaffinity labeling experiments were also performed, and a protein with molecular weight (MW) of about 90–100 kDa, which was consistent with the MW of GP, was clearly labeled by probe 1. A semiquantitative evaluation of the GP level in serum with probe 1 was also performed. The results showed that the protein band with a MW of about 90–100 kDa was tagged, and the concentration of the protein in serum was found to be between 25 and 50 ng/mL. Mass spectrometric analysis revealed that alpha-1,4 glucan phosphorylase (GPMM) was well-preserved in the bands. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessFeature PaperArticle Influence of Temperature, Solvent and pH on the Selective Extraction of Phenolic Compounds from Tiger Nuts by-Products: Triple-TOF-LC-MS-MS Characterization
Molecules 2019, 24(4), 797; https://doi.org/10.3390/molecules24040797
Received: 26 January 2019 / Revised: 13 February 2019 / Accepted: 18 February 2019 / Published: 22 February 2019
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Abstract
The aim of this study was to assess the effect of temperature, solvent (hydroethanolic mixtures) and pH on the recovery of individual phenolic compounds from “horchata” by-products. These parameters were optimized by response surface methodology and triple-TOF-LC-MS-MS was selected as the analytical tool [...] Read more.
The aim of this study was to assess the effect of temperature, solvent (hydroethanolic mixtures) and pH on the recovery of individual phenolic compounds from “horchata” by-products. These parameters were optimized by response surface methodology and triple-TOF-LC-MS-MS was selected as the analytical tool to identify and quantify the individual compounds. The optimum extraction conditions were 50% ethanol, 35 °C and pH 2.5, which resulted in values of 222.6 mg gallic acid equivalents (GAE)/100 g dry matter and 1948.1 µM trolox equivalent (TE)/g of dry matter for total phenolic content (TPC) and trolox equivalent antioxidant capacity (TEAC), respectively. The extraction of phenolic compounds by the conventional solvent method with agitation was influenced by temperature (p = 0.0073), and more strongly, by the content of ethanol in the extraction solution (p = 0.0007) while the pH did not show a great impact (p = 0.7961). On the other hand, the extraction of phenolic acids was affected by temperature (p = 0.0003) and by ethanol amount (p < 0.0001) but not by the pH values (p = 0.53). In addition, the percentage of ethanol influenced notably the extraction of both 4-vinylphenol (p = 0.0002) and the hydroxycinnamic acids (p = 0.0039). Finally, the main individual phenolic extracted with hydroethanolic mixtures was 4-vinylphenol (303.3 μg/kg DW) followed by spinacetin3-O-glucosyl-(1→6)-glucoside (86.2 μg/kg DW) and sinensetin (77.8 μg/kg DW). Full article
(This article belongs to the Special Issue Natural Additives in Food)
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Open AccessReview Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production
Molecules 2019, 24(4), 796; https://doi.org/10.3390/molecules24040796
Received: 15 January 2019 / Revised: 15 February 2019 / Accepted: 18 February 2019 / Published: 22 February 2019
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Abstract
Tropane alkaloids (TA) are valuable secondary plant metabolites which are mostly found in high concentrations in the Solanaceae and Erythroxylaceae families. The TAs, which are characterized by their unique bicyclic tropane ring system, can be divided into three major groups: hyoscyamine and scopolamine, [...] Read more.
Tropane alkaloids (TA) are valuable secondary plant metabolites which are mostly found in high concentrations in the Solanaceae and Erythroxylaceae families. The TAs, which are characterized by their unique bicyclic tropane ring system, can be divided into three major groups: hyoscyamine and scopolamine, cocaine and calystegines. Although all TAs have the same basic structure, they differ immensely in their biological, chemical and pharmacological properties. Scopolamine, also known as hyoscine, has the largest legitimate market as a pharmacological agent due to its treatment of nausea, vomiting, motion sickness, as well as smooth muscle spasms while cocaine is the 2nd most frequently consumed illicit drug globally. This review provides a comprehensive overview of TAs, highlighting their structural diversity, use in pharmaceutical therapy from both historical and modern perspectives, natural biosynthesis in planta and emerging production possibilities using tissue culture and microbial biosynthesis of these compounds. Full article
(This article belongs to the Special Issue Advances in Plant Alkaloid Research)
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Open AccessArticle A Spectroscopic Study of Tautomeric Equilibrium of Salicylideneaniline in ZSM-5 Zeolites
Molecules 2019, 24(4), 795; https://doi.org/10.3390/molecules24040795
Received: 31 January 2019 / Revised: 18 February 2019 / Accepted: 19 February 2019 / Published: 22 February 2019
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Abstract
Salicylideneaniline (SA) sorbed in cation-exchanged M-ZSM-5 (M = H+, Li+, Na+, K+, Rb+, Cs+ and Zn2+) zeolites was studied by spectroscopic techniques assisted by quantum-chemical calculations. The nature of extra-framework [...] Read more.
Salicylideneaniline (SA) sorbed in cation-exchanged M-ZSM-5 (M = H+, Li+, Na+, K+, Rb+, Cs+ and Zn2+) zeolites was studied by spectroscopic techniques assisted by quantum-chemical calculations. The nature of extra-framework cations present in the zeolite void was found to affect the spectral signature of the sorbed SA molecule that points to the shift of tautomeric equilibrium between the enol and keto forms. Small size cations, such as H+ and Li+, stabilize a cis-keto SA tautomer along with a enol one in the zeolite structure. The calculations indicate that the sorbed cis-keto tautomer may have the dipole large enough to be considered as a zwitterion. New features appearing in the spectra with the increase of the cation size were attributed to the presence of trans-keto SA tautomer, which up to now has been observed only in time-resolved spectroscopic experiments. A strong interaction of the molecule with cations in Zn-ZSM-5 zeolite results in the chelation of enol SA with the divalent Zn2+ ions. The results of the study suggest that the tautomeric equilibrium of molecules belonging to the Schiff base family can be tuned by the confinement in the nanoporous materials via a choice of topology of zeolite framework and the nature of extra-framework cations. Full article
(This article belongs to the Special Issue Microporous/Mesoporous Inorganic Materials)
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