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Molecules, Volume 24, Issue 13 (July-1 2019)

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Cover Story (view full-size image) Nature has tailored a wide range of metalloenzymes that catalyze some of the most important [...] Read more.
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Open AccessArticle
Signal Enhancement of Cadmium in Lettuce Using Laser-Induced Breakdown Spectroscopy Combined with Pyrolysis Process
Molecules 2019, 24(13), 2517; https://doi.org/10.3390/molecules24132517
Received: 3 June 2019 / Revised: 3 July 2019 / Accepted: 8 July 2019 / Published: 9 July 2019
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Abstract
Fast detection of heavy metals in lettuce is significant for food market regulation and the control of heavy metal pollution. Advanced methods like laser-induced breakdown spectroscopy (LIBS) technology have been tried to determine the cadmium (Cd) content. To retard the negative effect of [...] Read more.
Fast detection of heavy metals in lettuce is significant for food market regulation and the control of heavy metal pollution. Advanced methods like laser-induced breakdown spectroscopy (LIBS) technology have been tried to determine the cadmium (Cd) content. To retard the negative effect of complex matrix composition from samples and improve quantitative performance of LIBS technology, the pyrolysis process combined with LIBS was adopted to determine the cadmium (Cd) content of lettuce. Adaptive iteratively reweighted penalized least squares (airPLS) was used to preprocess the LIBS spectra and solve the baseline drift. For multivariate linear regression based on the three selected Cd emission lines correlation coefficient in the prediction set Rp2 increased from 0.9154 to 0.9969, and the limit of detection (LOD) decreased from 9.1 mg/kg to 0.9 mg/kg after the pyrolysis process. The partial least squares (PLS) regression and support vector regression (SVR) were applied to construct calibration models based on full spectra. In addition, the least absolute shrinkage and selection operator (LASSO) was implemented to choose limited lines to predict the Cd content. The PLS model with the pyrolysis process obtained the best results with Rp2 = 0.9973 and LOD = 0.8 mg/kg. The results indicated that the pyrolysis method could enhance the spectral signal of cadmium and thus significantly improve the analysis results for all the models. It is shown in this experiment that proper sample preprocessing could effectively amplify the Cd signal in LIBS and make LIBS measurement an efficient method to assess Cd contamination in the vegetable industry. Full article
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Open AccessArticle
Molecular Characterization and Heterologous Production of the Bacteriocin Peocin, a DNA Starvation/Stationary Phase Protection Protein, from Paenibacillus ehimensis NPUST1
Molecules 2019, 24(13), 2516; https://doi.org/10.3390/molecules24132516
Received: 13 May 2019 / Revised: 2 July 2019 / Accepted: 8 July 2019 / Published: 9 July 2019
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Abstract
The production of a bacteriocin-like substance with antimicrobial activity, named peocin, by the probiotic Paenibacillus ehimensis NPUST1 was previously reported by our laboratory. The present study aimed to identify peocin and increase the peocin yield by heterologous expression in Escherichia coli BL21(DE3). Peocin [...] Read more.
The production of a bacteriocin-like substance with antimicrobial activity, named peocin, by the probiotic Paenibacillus ehimensis NPUST1 was previously reported by our laboratory. The present study aimed to identify peocin and increase the peocin yield by heterologous expression in Escherichia coli BL21(DE3). Peocin was identified as a DNA starvation/stationary phase protection protein, also called DNA-binding protein from starved cells (Dps), by gel overlay and LC-MS/MS analysis. For mass production of peocin, fed-batch cultivation of E. coli was performed using a pH-stat control system. Purification by simple nickel affinity chromatography and dialysis yielded 45.3 mg of purified peocin from a 20-mL fed-batch culture (49.3% recovery). The biological activity of the purified peocin was confirmed by determination of the MIC and MBC against diverse pathogens. Purified peocin exhibited antimicrobial activity against aquatic, food spoilage, clinical and antibiotic-resistant pathogens. In an in vivo challenge test, zebrafish treated with purified peocin exhibited significantly increased survival rates after A. hydrophila challenge. The present study is the first to show the antimicrobial activity of Dps and provides an efficient strategy for production of bioactive peocin, which will aid the development of peocin as a novel antimicrobial agent with potential applications in diverse industries. Full article
(This article belongs to the Special Issue Biotechnology of Microbial Enzymes)
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Open AccessFeature PaperArticle
Thermal Decomposition of Maya Blue: Extraction of Indigo Thermal Decomposition Steps from a Multistep Heterogeneous Reaction Using a Kinetic Deconvolution Analysis
Molecules 2019, 24(13), 2515; https://doi.org/10.3390/molecules24132515
Received: 2 June 2019 / Revised: 5 July 2019 / Accepted: 6 July 2019 / Published: 9 July 2019
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Abstract
Examining the kinetics of solids’ thermal decomposition with multiple overlapping steps is of growing interest in many fields, including materials science and engineering. Despite the difficulty of describing the kinetics for complex reaction processes constrained by physico-geometrical features, the kinetic deconvolution analysis (KDA) [...] Read more.
Examining the kinetics of solids’ thermal decomposition with multiple overlapping steps is of growing interest in many fields, including materials science and engineering. Despite the difficulty of describing the kinetics for complex reaction processes constrained by physico-geometrical features, the kinetic deconvolution analysis (KDA) based on a cumulative kinetic equation is one practical method of obtaining the fundamental information needed to interpret detailed kinetic features. This article reports the application of KDA to thermal decomposition of clay minerals and indigo–clay mineral hybrid compounds, known as Maya blue, from ancient Mayan civilization. Maya blue samples were prepared by heating solid mixtures of indigo and clay minerals (palygorskite and sepiolite), followed by purification. The multistep thermal decomposition processes of the clay minerals and Maya blue samples were analyzed kinetically in a stepwise manner through preliminary kinetic analyses based on a conventional isoconversional method and mathematical peak deconvolution to finally attain the KDA. By comparing the results of KDA for the thermal decomposition processes of the clay minerals and the Maya blue samples, information about the thermal decomposition steps of the indigo incorporated into the Maya blue samples was extracted. The thermal stability of Maya blue samples was interpreted through the kinetic characterization of the extracted indigo decomposition steps. Full article
(This article belongs to the Special Issue Thermal Analysis Kinetics for Understanding Materials Behavior)
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Open AccessReview
On the Aggregation and Sensing Properties of Zinc(II) Schiff-Base Complexes of Salen-Type Ligands
Molecules 2019, 24(13), 2514; https://doi.org/10.3390/molecules24132514
Received: 27 June 2019 / Revised: 8 July 2019 / Accepted: 9 July 2019 / Published: 9 July 2019
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Abstract
The zinc(II) ion forms stable complexes with a wide variety of ligands, but those related to Schiff-bases are among the most largely investigated. This review deals with the peculiar aggregation characteristics of Zn(II) Schiff-base complexes from tetradentate N2O2 salen-type ligands, [...] Read more.
The zinc(II) ion forms stable complexes with a wide variety of ligands, but those related to Schiff-bases are among the most largely investigated. This review deals with the peculiar aggregation characteristics of Zn(II) Schiff-base complexes from tetradentate N2O2 salen-type ligands, L, derivatives from salicylaldehydes and 1,2-diamines, and is mostly focused on their spectroscopic properties in solution. Thanks to their Lewis acidic character, ZnL complexes show interesting structural, nanostructural, and aggregation/deaggregation properties in relation to the absence/presence of a Lewis base. Deaggregation of these complexes is accompanied by relevant changes of their spectroscopic properties that can appropriately be exploited for sensing Lewis bases. Thus, ZnL complexes have been investigated as chromogenic and fluorogenic chemosensors of charged and neutral Lewis bases, including cell imaging, and have shown to be selective and sensitive to the Lewis basicity of the involved species. From these studies emerges that these popular, Lewis acidic bis(salicylaldiminato)Zn(II) Schiff-base complexes represent classical coordination compounds for modern applications. Full article
(This article belongs to the Special Issue Schiff Base and Its Metal Complexes)
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Open AccessArticle
Effect of Different Proportions of Three Microbial Agents on Ammonia Mitigation during the Composting of Layer Manure
Molecules 2019, 24(13), 2513; https://doi.org/10.3390/molecules24132513
Received: 17 May 2019 / Revised: 18 June 2019 / Accepted: 3 July 2019 / Published: 9 July 2019
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Abstract
Odor emissions represent one of the important issues of aerobic composting. The addition of microbial agents to compost is an important method for solving this problem, but this process is often unstable when a single microbial agent is added to the compost. Therefore, [...] Read more.
Odor emissions represent one of the important issues of aerobic composting. The addition of microbial agents to compost is an important method for solving this problem, but this process is often unstable when a single microbial agent is added to the compost. Therefore, in this study, five treatments comprising different proportions of Bacillus stearothermophilus, Candida utilis, and Bacillus subtilis were tested to determine the best combination of the three microbial agents for ammonia reduction, as follows: control group (CK), 2:1:1 (A), 1:1:2 (B), 1:2:1 (C), and 1:1:1 (D). Compared with the CK group, the A, B, C, and D groups reduced ammonia emissions by 17.02, 9.68, 53.11, and 46.23%, respectively. The total ammonia emissions were significantly lower in C and D than in CK (p < 0.05). These two treatment groups had significantly increased nitrate nitrogen concentrations and decreased pH values and ammonium nitrogen concentrations (p < 0.05). Throughout the composting process, the total bacterial number was significantly higher in C and D than in CK (p < 0.05). Therefore, it is likely that B. stearothermophilus, C. utilis, and B. subtilis compounded from 1:2:1 (C) to 1:1:1 (D) reduced the ammonia emissions due to (1) a reduction in the pH and (2) the promotion of the growth of ammonia-oxidizing bacteria and the conversion of ammonium nitrogen to nitrate nitrogen. This study provides a theoretical basis and technical support for the odor problem of layer manure compost and promotes the development of composting technology. Full article
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Open AccessReview
Quinoa Secondary Metabolites and Their Biological Activities or Functions
Molecules 2019, 24(13), 2512; https://doi.org/10.3390/molecules24132512
Received: 31 May 2019 / Revised: 3 July 2019 / Accepted: 3 July 2019 / Published: 9 July 2019
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Abstract
Quinoa (Chenopodium quinoa Willd.) was known as the “golden grain” by the native Andean people in South America, and has been a source of valuable food over thousands of years. It can produce a variety of secondary metabolites with broad spectra of [...] Read more.
Quinoa (Chenopodium quinoa Willd.) was known as the “golden grain” by the native Andean people in South America, and has been a source of valuable food over thousands of years. It can produce a variety of secondary metabolites with broad spectra of bioactivities. At least 193 secondary metabolites from quinoa have been identified in the past 40 years. They mainly include phenolic acids, flavonoids, terpenoids, steroids, and nitrogen-containing compounds. These metabolites exhibit many physiological functions, such as insecticidal, molluscicidal and antimicrobial activities, as well as various kinds of biological activities such as antioxidant, cytotoxic, anti-diabetic and anti-inflammatory properties. This review focuses on our knowledge of the structures, biological activities and functions of quinoa secondary metabolites. Biosynthesis, development and utilization of the secondary metabolites especially from quinoa bran were prospected. Full article
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Open AccessArticle
Development of a Novel Series of Anticancer and Antidiabetic: Spirothiazolidines Analogs
Molecules 2019, 24(13), 2511; https://doi.org/10.3390/molecules24132511
Received: 13 June 2019 / Revised: 3 July 2019 / Accepted: 3 July 2019 / Published: 9 July 2019
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Abstract
4-(4-Aminophenyl)-1-thia-4-azaspiro[4.5]decan-3-one 1 was prepared and allowed to react with nitrogen nucleophiles to give the corresponding hydrazones 24. Further, compound 1 underwent diazotization and afforded the parallel hydrazono derivative 5; moreover, compound 1 refluxed with active methylene derivatives yielded the [...] Read more.
4-(4-Aminophenyl)-1-thia-4-azaspiro[4.5]decan-3-one 1 was prepared and allowed to react with nitrogen nucleophiles to give the corresponding hydrazones 24. Further, compound 1 underwent diazotization and afforded the parallel hydrazono derivative 5; moreover, compound 1 refluxed with active methylene derivatives yielded the corresponding aminospirothiazolo pyridine–carbonitrile derivative 6 and spirothiazolopyridinone–carbonitrile derivative 7. Condensation of spirothiazolidine 1 with 4-chlorobenzaldehyde gave the corresponding spiro arylidiene derivative 8, which was utilized as a component of Micheal addition to react with excess of nitrogen nucleophiles to yield novel ring frameworks 4-(3-(4-chlorophenyl)–spiro [cyclohexane-1,5-pyrazolo[3,4-d]thiazol]-6(1′H)-yl)aniline (9) and 4-(3-(4-chlorophenyl)-6′H- spiro[cyclohexane-1,5-thiazolo[5,4-d]isoxazol]-6-yl)aniline (10). Finally, when spirothiazolo pyridinone–carbonitrile derivative 7 sodium salt generated in situ was reacted with different alkyl halides, it produced the corresponding N-derivatives 1216. Three compounds, 6, 14, and 16, showed high significantly anticancer activities compared with Doxorubicin® (positive control) against human breast carcinoma (MCF-7) and human liver carcinoma (HepG-2) cell lines. On the other hand, compounds 6 and 9 showed higher therapeutic indices for both of alpha-amylase inhibitor and alpha-glucosidase inhibitor than the other tested compounds compared with the antidiabetic Acarbose (positive control). Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle
The 3S Enantiomer Drives Enolase Inhibitory Activity in SF2312 and Its Analogues
Molecules 2019, 24(13), 2510; https://doi.org/10.3390/molecules24132510
Received: 9 May 2019 / Revised: 25 June 2019 / Accepted: 4 July 2019 / Published: 9 July 2019
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Abstract
We recently reported that SF2312 ((1,5-dihydroxy-2-oxopyrrolidin-3-yl)phosphonic acid), a phosphonate antibiotic with a previously unknown mode of action, is a potent inhibitor of the glycolytic enzyme, Enolase. SF2312 can only be synthesized as a racemic-diastereomeric mixture. However, co-crystal structures with Enolase 2 (ENO2) have [...] Read more.
We recently reported that SF2312 ((1,5-dihydroxy-2-oxopyrrolidin-3-yl)phosphonic acid), a phosphonate antibiotic with a previously unknown mode of action, is a potent inhibitor of the glycolytic enzyme, Enolase. SF2312 can only be synthesized as a racemic-diastereomeric mixture. However, co-crystal structures with Enolase 2 (ENO2) have consistently shown that only the (3S,5S)-enantiomer binds to the active site. The acidity of the alpha proton at C-3, which deprotonates under mildly alkaline conditions, results in racemization; thus while the separation of four enantiomeric intermediates was achieved via chiral High Performance Liquid Chromatography (HPLC) of the fully protected intermediate, deprotection inevitably nullified enantiopurity. To prevent epimerization of the C-3, we designed and synthesized MethylSF2312, ((1,5-dihydroxy-3-methyl-2-oxopyrrolidin-3-yl)phosphonic acid), which contains a fully-substituted C-3 alpha carbon. As a racemic-diastereomeric mixture, MethylSF2312 is equipotent to SF2312 in enzymatic and cellular systems against Enolase. Chiral HPLC separation of a protected MethylSF2312 precursor resulted in the efficient separation of the four enantiomers. After deprotection and inevitable re-equilibration of the anomeric C-5, (3S)-MethylSF2312 was up to 2000-fold more potent than (3R)-MethylSF2312 in an isolated enzymatic assay. This observation strongly correlates with biological activity in both human cancer cells and bacteria for the 3S enantiomer of SF2312. Novel X-ray structures of human ENO2 with chiral and racemic MethylSF2312 show that only (3S,5S)-enantiomer occupies the active site. Enolase inhibition is thus a direct result of binding by the (3S,5S)-enantiomer of MethylSF2312. Concurrent with these results for MethylSF2312, we contend that the (3S,5S)-SF2312 is the single active enantiomer of inhibitor SF2312. Full article
(This article belongs to the Special Issue Anti-Cancer Drug: Discovery, Development and Combination)
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Open AccessArticle
Hemodynamic Effects on Particle Targeting in the Arterial Bifurcation for Different Magnet Positions
Molecules 2019, 24(13), 2509; https://doi.org/10.3390/molecules24132509
Received: 31 May 2019 / Revised: 5 July 2019 / Accepted: 8 July 2019 / Published: 9 July 2019
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Abstract
The present study investigated the possibilities and feasibility of drug targeting for an arterial bifurcation lesion to influence the host healing response. A micrometer sized iron particle was used only to model the magnetic carrier in the experimental investigation (not intended for clinical [...] Read more.
The present study investigated the possibilities and feasibility of drug targeting for an arterial bifurcation lesion to influence the host healing response. A micrometer sized iron particle was used only to model the magnetic carrier in the experimental investigation (not intended for clinical use), to demonstrate the feasibility of the particle targeting at the lesion site and facilitate the new experimental investigations using coated superparamagnetic iron oxide nanoparticles. Magnetic fields were generated by a single permanent external magnet (ferrite magnet). Artery bifurcation exerts severe impacts on drug distribution, both in the main vessel and the branches, practically inducing an uneven drug concentration distribution in the bifurcation lesion area. There are permanently positioned magnets in the vicinity of the bifurcation near the diseased area. The generated magnetic field induced deviation of the injected ferromagnetic particles and were captured onto the vessel wall of the test section. To increase the particle accumulation in the targeted region and consequently avoid the polypharmacology (interaction of the injected drug particles with multiple target sites), it is critical to understand flow hemodynamics and the correlation between flow structure, magnetic field gradient, and spatial position. Full article
(This article belongs to the Special Issue Cardiovascular Nanomedicines and Nanomaterials )
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Open AccessArticle
Sequence-Specific DNA Binding by Noncovalent Peptide–Azocyclodextrin Dimer Complex as a Suitable Model for Conformational Fuzziness
Molecules 2019, 24(13), 2508; https://doi.org/10.3390/molecules24132508
Received: 17 May 2019 / Revised: 3 July 2019 / Accepted: 5 July 2019 / Published: 9 July 2019
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Abstract
Transcription factors are proteins lying at the endpoint of signaling pathways that control the complex process of DNA transcription. Typically, they are structurally disordered in the inactive state, but in response to an external stimulus, like a suitable ligand, they change their conformation, [...] Read more.
Transcription factors are proteins lying at the endpoint of signaling pathways that control the complex process of DNA transcription. Typically, they are structurally disordered in the inactive state, but in response to an external stimulus, like a suitable ligand, they change their conformation, thereby activating DNA transcription in a spatiotemporal fashion. The observed disorder or fuzziness is functionally beneficial because it can add adaptability, versatility, and reversibility to the interaction. In this context, mimetics of the basic region of the GCN4 transcription factor (Tf) and their interaction with dsDNA sequences would be suitable models to explore the concept of conformational fuzziness experimentally. Herein, we present the first example of a system that mimics the DNA sequence-specific recognition by the GCN4 Tf through the formation of a non- covalent tetra-component complex: peptide–azoβ-CyD(dimer)–peptide–DNA. The non-covalent complex is constructed on the one hand by a 30 amino acid peptide corresponding to the basic region of GCN4 and functionalized with an adamantane moiety, and on the other hand an allosteric receptor, the azoCyDdimer, that has an azobenzene linker connecting two β-cyclodextrin units. The azoCyDdimer responds to light stimulus, existing as two photo-states: the first thermodynamically stable with an E:Z isomer ratio of 95:5 and the second obtained after irradiation with ultraviolet light, resulting in a photostationary state with a 60:40 E:Z ratio. Through electrophoretic shift assays and circular dichroism spectroscopy, we demonstrate that the E isomer is responsible for dimerization and recognition. The formation of the non-covalent tetra component complex occurs in the presence of the GCN4 cognate dsDNA sequence (′5-..ATGA cg TCAT..-3′) but not with (′5-..ATGA c TCAT..-3′) that differs in only one spacing nucleotide. Thus, we demonstrated that the tetra-component complex is formed in a specific manner that depends on the geometry of the ligand, the peptide length, and the ds DNA sequence. We hypothesized that the mechanism of interaction is sequential, and it can be described by the polymorphism model of static fuzziness. We argue that chemically modified peptides of the GCN4 Tf are suitable minimalist experimental models to investigate conformational fuzziness in protein–DNA interactions. Full article
(This article belongs to the Special Issue The Fuzziness in Molecular, Supramolecular, and Systems Chemistry)
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Open AccessArticle
Ionic Liquid-Microwave-Based Extraction of Biflavonoids from Selaginella sinensis
Molecules 2019, 24(13), 2507; https://doi.org/10.3390/molecules24132507
Received: 12 June 2019 / Revised: 5 July 2019 / Accepted: 6 July 2019 / Published: 9 July 2019
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Abstract
Selaginella sinensis (Desv.) Spring has been used for many years as traditional Chinese medicine (TCM) for many years. Recently, ionic liquids (ILs) have attracted great attentions in extraction and separation technology of TCM as a new green solvent. In this paper, microwave assisted [...] Read more.
Selaginella sinensis (Desv.) Spring has been used for many years as traditional Chinese medicine (TCM) for many years. Recently, ionic liquids (ILs) have attracted great attentions in extraction and separation technology of TCM as a new green solvent. In this paper, microwave assisted extraction-IL (MAE-IL) that extracted amentoflavone (AME) and hinokiflavone (HIN) from Selaginella sinensis was reported for the first time. The contents of two biflavonoids were simultaneously determined by a high performance liquid chromatography (HPLC) method. After different ionic liquids were compared, it was found [C6mim]BF4 had a high selectivity and efficiency. Moreover, the important extraction conditions, including solid-liquid ratio, IL concentration, extraction time, microwave power and radiation temperature, were also investigated and optimized by response surface methodology (RSM) using AME and HIN yields as index. The results showed that the extraction yields of AME and HIN from S. sinensis were 1.96 mg/g and 0.79 mg/g, respectively, under the optimal process parameters (0.55 mmol/L, 300 W, 40 min, 1:11 g/mL and 48 °C). Compared with the conventional extraction methods, MAE-IL could not only achieve higher yield in shorter time, but also could reduce the consumption of solvent. This effective, rapid and green MAE-IL method was suitable for the extraction of AME and HIN. Full article
(This article belongs to the Section Green Chemistry)
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Open AccessArticle
Variety Identification of Orchids Using Fourier Transform Infrared Spectroscopy Combined with Stacked Sparse Auto-Encoder
Molecules 2019, 24(13), 2506; https://doi.org/10.3390/molecules24132506
Received: 11 June 2019 / Revised: 2 July 2019 / Accepted: 3 July 2019 / Published: 9 July 2019
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Abstract
The feasibility of using the fourier transform infrared (FTIR) spectroscopic technique with a stacked sparse auto-encoder (SSAE) to identify orchid varieties was studied. Spectral data of 13 orchids varieties covering the spectral range of 4000–550 cm−1 were acquired to establish discriminant models [...] Read more.
The feasibility of using the fourier transform infrared (FTIR) spectroscopic technique with a stacked sparse auto-encoder (SSAE) to identify orchid varieties was studied. Spectral data of 13 orchids varieties covering the spectral range of 4000–550 cm−1 were acquired to establish discriminant models and to select optimal spectral variables. K nearest neighbors (KNN), support vector machine (SVM), and SSAE models were built using full spectra. The SSAE model performed better than the KNN and SVM models and obtained a classification accuracy 99.4% in the calibration set and 97.9% in the prediction set. Then, three algorithms, principal component analysis loading (PCA-loading), competitive adaptive reweighted sampling (CARS), and stacked sparse auto-encoder guided backward (SSAE-GB), were used to select 39, 300, and 38 optimal wavenumbers, respectively. The KNN and SVM models were built based on optimal wavenumbers. Most of the optimal wavenumbers-based models performed slightly better than the all wavenumbers-based models. The performance of the SSAE-GB was better than the other two from the perspective of the accuracy of the discriminant models and the number of optimal wavenumbers. The results of this study showed that the FTIR spectroscopic technique combined with the SSAE algorithm could be adopted in the identification of the orchid varieties. Full article
(This article belongs to the Section Analytical Chemistry)
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Open AccessArticle
Similar Safety Profile of the Enantiomeric N-Aminoalkyl Derivatives of Trans-2-Aminocyclohexan-1-ol Demonstrating Anticonvulsant Activity
Molecules 2019, 24(13), 2505; https://doi.org/10.3390/molecules24132505
Received: 25 June 2019 / Revised: 7 July 2019 / Accepted: 9 July 2019 / Published: 9 July 2019
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Abstract
Epilepsy is one of the most common neurological disorder in the world. Many antiepileptic drugs cause multiple adverse effects. Moreover, multidrug resistance is a serious problem in epilepsy treatment. In the present study we evaluated the safety profile of three (1 [...] Read more.
Epilepsy is one of the most common neurological disorder in the world. Many antiepileptic drugs cause multiple adverse effects. Moreover, multidrug resistance is a serious problem in epilepsy treatment. In the present study we evaluated the safety profile of three (13) new chiral N-aminoalkyl derivatives of trans-2-aminocyclohexan-1-ol demonstrating anticonvulsant activity. Our aim was also to determine differences between the enantiomeric compounds with respect to their safety profile. The results of the study indicated that compounds 13 are non-cytotoxic for astrocytes, although they exhibit cytotoxic activity against human glioblastoma cells. Moreover, 13 did not affect the viability of HepG2 cells and did not produce adducts with glutathione. Compounds 13 demonstrated no mutagenic activity either in the Salmonella typhimurium or in Vibrio harveyi tests. Additionally, the compounds displayed a strong or moderate antimutagenic effect. Finally, the P-glycoprotein (P-gp) ATPase assay demonstrated that both enantiomers are potent P-gp inhibitors. To sum up, our results indicate that the newly synthesized derivatives may be considered promising candidates for further research on anticonvulsant drug discovery and development. Our study indicated the similar safety profile of the enantiomeric N-aminoalkyl derivatives of trans-2-aminocyclohexan-1-ol, although in the previous studies both enantiomers differ in their biotransformation pathways and pharmacological activity. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle
Marylosides A-G, Norcycloartane Glycosides from Leaves of Cymbidium Great Flower ‘Marylaurencin’
Molecules 2019, 24(13), 2504; https://doi.org/10.3390/molecules24132504
Received: 2 July 2019 / Revised: 5 July 2019 / Accepted: 6 July 2019 / Published: 9 July 2019
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Abstract
Seven novel norcycloartane glycosides, maryloside A–G (17), were isolated from the leaves of Cymbidium Great Flower ‘Marylaurencin’, along with a known norcycloartane glycoside, cymbidoside (8). These structures were determined on the basis of mainly NMR experiments as [...] Read more.
Seven novel norcycloartane glycosides, maryloside A–G (17), were isolated from the leaves of Cymbidium Great Flower ‘Marylaurencin’, along with a known norcycloartane glycoside, cymbidoside (8). These structures were determined on the basis of mainly NMR experiments as well as chemical degradation and X-ray crystallographic analysis. The isolated compounds (16 and 8) were evaluated for the inhibitory activity on lipopolysaccharide (LPS) and interferon-γ (IFN-γ)-stimulated nitric oxide (NO) production in RAW 264.7 cells. Consequently, 1 and 3 exhibited moderate activity. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle
A Promising Polymer Blend Electrolytes Based on Chitosan: Methyl Cellulose for EDLC Application with High Specific Capacitance and Energy Density
Molecules 2019, 24(13), 2503; https://doi.org/10.3390/molecules24132503
Received: 3 June 2019 / Revised: 4 July 2019 / Accepted: 5 July 2019 / Published: 9 July 2019
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Abstract
In the present work, promising proton conducting solid polymer blend electrolytes (SPBEs) composed of chitosan (CS) and methylcellulose (MC) were prepared for electrochemical double-layer capacitor (EDLC) application with a high specific capacitance and energy density. The change in intensity and the broad nature [...] Read more.
In the present work, promising proton conducting solid polymer blend electrolytes (SPBEs) composed of chitosan (CS) and methylcellulose (MC) were prepared for electrochemical double-layer capacitor (EDLC) application with a high specific capacitance and energy density. The change in intensity and the broad nature of the XRD pattern of doped samples compared to pure CS:MC system evidencedthe amorphous character of the electrolyte samples. The morphology of the samples in FESEM images supported the amorphous behavior of the solid electrolyte films. The results of impedance and Bode plotindicate that the bulk resistance decreasedwith increasing salt concentration. The highest DC conductivity was found to be 2.81 × 10−3 S/cm. The electrical equivalent circuit (EEC) model was conducted for selected samples to explain the complete picture of the electrical properties.The performance of EDLC cells was examined at room temperature by electrochemical techniques, such as impedance spectroscopy, cyclic voltammetry (CV) and constant current charge–discharge techniques. It was found that the studied samples exhibit a very good performance as electrolyte for EDLC applications. Ions were found to be the dominant charge carriers in the polymer electrolyte. The ion transference number (tion) was found to be 0.84 while 0.16 for electron transference number (tel). Through investigation of linear sweep voltammetry (LSV), the CS:MC:NH4SCN system was found to be electrochemically stable up to 1.8 V. The CV plot revealed no redox peak, indicating the occurrence of charge double-layer at the surface of activated carbon electrodes. Specific capacitance (Cspe) for the fabricated EDLC was calculated using CV plot and charge–discharge analyses. It was found to be 66.3 F g−1 and 69.9 F g−1 (at thefirst cycle), respectively. Equivalent series resistance (Resr) of the EDLC was also identified, ranging from 50.0 to 150.0 Ω. Finally, energy density (Ed) was stabilized to anaverage of 8.63 Wh kg−1 from the 10th cycle to the 100th cycle. The first cycle obtained power density (Pd) of 1666.6 W kg−1 and then itdropped to 747.0 W kg−1 at the 50th cycle and continued to drop to 555.5 W kg−1 as the EDLC completed 100 cycles. Full article
(This article belongs to the Special Issue Advances in Electrochemical Energy Storage Devices)
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Open AccessArticle
An Established HPLC-MS/MS Method for Evaluation of the Influence of Salt Processing on Pharmacokinetics of Six Compounds in Cuscutae Semen
Molecules 2019, 24(13), 2502; https://doi.org/10.3390/molecules24132502
Received: 16 May 2019 / Revised: 25 June 2019 / Accepted: 2 July 2019 / Published: 9 July 2019
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Abstract
A sensitive and effective method was developed for clarifying the pharmacokinetic properties of six compounds (including hyperin, chlorogenic acid, neochlorogenic acid, p-coumaric acid, astragalin, and isoquercitrin) in two processed Cuscutae Semen samples by high performance liquid chromatography mass spectrometry (HPLC-MS/MS). The six compounds [...] Read more.
A sensitive and effective method was developed for clarifying the pharmacokinetic properties of six compounds (including hyperin, chlorogenic acid, neochlorogenic acid, p-coumaric acid, astragalin, and isoquercitrin) in two processed Cuscutae Semen samples by high performance liquid chromatography mass spectrometry (HPLC-MS/MS). The six compounds were separated by acetonitrile and 0.1% formic acid-water on an Agilent Eclipse plus C18 column (4.6 mm × 100 mm, 1.8 μm). All compounds were analyzed with negative ion mode in multiple reaction monitoring (MRM). The lower limits of quantification (LLOQ) of hyperin, astragalin, neochlorogenic acid, chlorogenic acid, isoquercitrin, and p-coumaric acid were 1, 0.1, 4, 0.1, 2, and 4 ng·mL−1, respectively. The validated approach was effectively used for the pharmacokinetics of six compounds of two processed Cuscutae Semen samples after oral administration to rat. The results indicated that salt processing could improve the adsorption and bioavailability of astragalin in Cuscutae Semen. Full article
(This article belongs to the Section Analytical Chemistry)
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Open AccessArticle
Hybrid Solid-Phase Extraction for Selective Determination of Methamphetamine and Amphetamine in Dyed Hair by Using Gas Chromatography–Mass Spectrometry
Molecules 2019, 24(13), 2501; https://doi.org/10.3390/molecules24132501
Received: 3 June 2019 / Revised: 2 July 2019 / Accepted: 8 July 2019 / Published: 9 July 2019
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Abstract
Sample preparation is an important step in the isolation of target compounds from complex matrices to perform their reliable and accurate analysis. Hair samples are commonly pulverized or processed as fine cut, depending on preference, before extraction by techniques such as solid-phase extraction [...] Read more.
Sample preparation is an important step in the isolation of target compounds from complex matrices to perform their reliable and accurate analysis. Hair samples are commonly pulverized or processed as fine cut, depending on preference, before extraction by techniques such as solid-phase extraction (SPE), liquid–liquid extraction, and other methods. In this study, a method based on hybrid solid-phase extraction (hybridSPE) and gas chromatography–mass spectrometry (GC–MS) was developed and validated for the determination of methamphetamine (MA) and amphetamine (AP) in hair. The hair samples were mechanically pulverized after washing with de-ionized water and acetone. The samples were then sonicated in methanol at 50 °C for 1 h and centrifuged at 50,000× g for 3 min. The supernatants were transferred onto the hybridSPE cartridge and extracted using 1 mL of 0.05 M methanolic hydrogen chloride. The combined solutions were evaporated to dryness, derivatized using pentafluoropropionic anhydride, and analyzed by GC–MS. Excellent linearity (R2 > 0.9998) was achieved in the ranges of 0.05–5.0 ng/mg for AP and 0.1–10.0 ng/mg for MA. The recovery was 83.4–96.8%. The intra- and inter-day accuracies were −9.4% to 5.5% and −5.1% to 3.1%, while the intra- and inter-day precisions were within 8.3% and 6.7%, respectively. The limits of detections were 0.016 ng/mg for AP and 0.031 ng/mg for MA. The validated hybridSPE method was applied to dyed hair for MA and AP extraction and compared to a methanol extraction method currently being used in our laboratory. The results showed that an additional hybridSPE step improved the recovery by 5.7% for low-concentration quality control (QC) samples and by 24.1% for high-concentration QC samples. Additionally, the hybridSPE method was compared to polymeric reversed-phase SPE methods, and the absolute recoveries for hybridSPE were 50% and 20% greater for AP (1.5 ng/mg) and MA (3.0 ng/mg), respectively. In short, the hybridSPE technique was shown to minimize the matrix effects, improving GC–MS analysis of hair. Based on the results, the proposed method proved to be effective for the selective determination of MA and AP in hair samples. Full article
(This article belongs to the Special Issue Forensic Analytical Chemistry)
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Open AccessArticle
Anti-Multiple Myeloma Potential of Secondary Metabolites from Hibiscus sabdariffa
Molecules 2019, 24(13), 2500; https://doi.org/10.3390/molecules24132500
Received: 9 May 2019 / Revised: 4 July 2019 / Accepted: 6 July 2019 / Published: 9 July 2019
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Abstract
Multiple myeloma (MM) belongs to hematological cancers and its incidence is increasing worldwide. Despite recent advances in its therapy, MM still causes many deaths every year. In fact, current therapies sometimes fail and are associated with severe adverse effects, including neurotoxicity. As a [...] Read more.
Multiple myeloma (MM) belongs to hematological cancers and its incidence is increasing worldwide. Despite recent advances in its therapy, MM still causes many deaths every year. In fact, current therapies sometimes fail and are associated with severe adverse effects, including neurotoxicity. As a part of our ongoing efforts to discover new potential therapies against MM, we prepared Hibiscus sabdariffa extracts obtained by a microwave-assisted solvent extraction and investigate their activity by in vitro assays on the RPMI-8226 cell line. The bioguided fractionation of the crude ethanolic extract allowed the identification of HsFC as the most effective extract. We assessed cell viability (MTT and Tripan blue test), cell migration (Boyden chamber assay), and neurotoxicity (DRG neurotoxicity assay). The promising results prompted us to further fractionate HsFC and we obtained two molecules effective against RPMI-8226 cells without neurotoxic effects at their active concentrations. Moreover, both compounds are able to significantly reduce cell migration. Full article
(This article belongs to the Special Issue Recent Advances in Anticancer Drugs)
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Open AccessArticle
Ketogenic Diet-Induced Weight Loss is Associated with an Increase in Vitamin D Levels in Obese Adults
Molecules 2019, 24(13), 2499; https://doi.org/10.3390/molecules24132499
Received: 11 June 2019 / Revised: 26 June 2019 / Accepted: 5 July 2019 / Published: 9 July 2019
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Abstract
Vitamin D is an important micronutrient involved in several processes. Evidence has shown a strong association between hypovitaminosis D and cardio-metabolic diseases, including obesity. A ketogenic diet has proven to be very effective for weight loss, especially in reducing fat mass while preserving [...] Read more.
Vitamin D is an important micronutrient involved in several processes. Evidence has shown a strong association between hypovitaminosis D and cardio-metabolic diseases, including obesity. A ketogenic diet has proven to be very effective for weight loss, especially in reducing fat mass while preserving fat-free mass. The aim of this study was to investigate the effect of a ketogenic diet-induced weight loss on vitamin D status in a population of obese adults. We enrolled 56 obese outpatients, prescribed with either traditional standard hypocaloric Mediterranean diet (SHMD) or very low-calorie ketogenic diet (VLCKD). Serum 25(OH)D concentrations were measured by chemiluminescence. The mean value of serum 25-hydroxyvitamin D (25(OH)D) concentrations in the whole population at baseline was 17.8 ± 5.6 ng/mL, without differences between groups. After 12 months of dietetic treatment, in VLCKD patients serum 25(OH)D concentrations increased from 18.4 ± 5.9 to 29.3 ± 6.8 ng/mL (p < 0.0001), vs 17.5 ± 6.1 to 21.3 ± 7.6 ng/mL (p = 0.067) in the SHMD group (for each kilogram of weight loss, 25(OH)D concentration increased 0.39 and 0.13 ng/mL in the VLCKD and in the SHMD groups, respectively). In the VLCKD group, the increase in serum 25(OH)D concentrations was strongly associated with body mass index, waist circumference, and fatty mass variation. In a multiple regression analysis, fatty mass was the strongest independent predictor of serum 25(OH)D concentration, explaining 15.6%, 3.3%, and 9.4% of its variation in the whole population, in SHMD, and VLCKD groups, respectively. We also observed a greater reduction of inflammation (evaluated by high-sensitivity C reactive protein (hsCRP) values) and a greater improvement in glucose homeostasis, confirmed by a reduction of HOMA values, in the VLCKD versus the SHMD group. Taken together, all these data suggest that a dietetic regimen, which implies a great reduction of fat mass, can improve vitamin D status in the obese. Full article
(This article belongs to the Special Issue Natural Bioactives in Anti-Obesity Therapy)
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Open AccessArticle
Preparation of Chitosan–Hexaconazole Nanoparticles as Fungicide Nanodelivery System for Combating Ganoderma Disease in Oil Palm
Molecules 2019, 24(13), 2498; https://doi.org/10.3390/molecules24132498
Received: 29 May 2019 / Revised: 5 July 2019 / Accepted: 5 July 2019 / Published: 8 July 2019
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Abstract
Fungicide is used to control fungal disease by destroying and inhibiting the fungus or fungal spores that cause the disease. However, failure to deliver fungicide to the disease region leads to ineffectiveness in the disease control. Hence, in the present study, nanotechnology has [...] Read more.
Fungicide is used to control fungal disease by destroying and inhibiting the fungus or fungal spores that cause the disease. However, failure to deliver fungicide to the disease region leads to ineffectiveness in the disease control. Hence, in the present study, nanotechnology has enabled the fungicide active agents (hexaconazole) to be encapsulated into chitosan nanoparticles with the aim of developing a fungicide nanodelivery system that can transport them more effectively to the target cells (Ganoderma fungus). A pathogenic fungus, Ganoderma boninense (G. boninense), is destructive to oil palm whereby it can cause significant loss to oil palm plantations located in the Southeast Asian countries, especially Malaysia and Indonesia. In regard to this matter, a series of chitosan nanoparticles loaded with the fungicide, hexaconazole, was prepared using various concentrations of crosslinking agent sodium tripolyphosphate (TPP). The resulting particle size revealed that the increase of the TPP concentration produced smaller particles. In addition, the in vitro fungicide released at pH 5.5 demonstrated that the fungicide from the nanoparticles was released in a sustainable manner with a prolonged release time up to 86 h. On another note, the in vitro antifungal studies established that smaller particle size leads to lower half maximum effective concentration (EC50) value, which indicates higher antifungal activity against G. boninense. Full article
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Open AccessArticle
Antispasmodic Activity of Prenylated Phenolic Compounds from the Root Bark of Morus nigra
Molecules 2019, 24(13), 2497; https://doi.org/10.3390/molecules24132497
Received: 27 May 2019 / Revised: 29 June 2019 / Accepted: 3 July 2019 / Published: 8 July 2019
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Abstract
Black mulberry is a widely acknowledged ancient traditional medicine. Its extract and constituents have been reported to exert various bioactivities including antimicrobial, hypotensive, analgesic etc. effects. While black mulberry preparations are also used as antispasmodic agents in folk medicine, no related studies are [...] Read more.
Black mulberry is a widely acknowledged ancient traditional medicine. Its extract and constituents have been reported to exert various bioactivities including antimicrobial, hypotensive, analgesic etc. effects. While black mulberry preparations are also used as antispasmodic agents in folk medicine, no related studies are available on its isolated constituents. Through an extensive chromatographic purification, seven phenolic compounds were isolated from the methanol extract of Morus nigra root bark, including morusin (1), kuwanon U (2), kuwanon E (3), moracin P (4), moracin O (5), albanol A (6), and albanol B (7). A complete NMR signal assignment of moracin P and O was achieved, and related literature errors confusing the identity of moracin derivatives are hereby clarified. Compounds 2, 5 and 7 were identified as strong antispasmodic agents on isolated rat ileum and tracheal smooth muscles, while compound 3, a methoxy derivative of 2, was inactive. Moracin O (5) inhibited the ileal and tracheal smooth muscle contractions with Emax values of 85% and 302 mg, respectively. Those actions were superior as compared with papaverine. Our findings demonstrate that prenylated arylbenzofurans, geranylated flavonoids and Diels-Alder adducts from Morus nigra are valuable antispasmodic agents. Compounds 2, 5 and 7 are suggested as marker compounds for quality control of antispasmodic mulberry preparations. Moracin O (5) is a new lead compound for related drug development initiatives. Full article
(This article belongs to the Special Issue Discovery of Active Ingredients from Natural Products)
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Open AccessArticle
Preclinical Evaluation of Radiolabeled Peptides for PET Imaging of Glioblastoma Multiforme
Molecules 2019, 24(13), 2496; https://doi.org/10.3390/molecules24132496
Received: 7 June 2019 / Revised: 2 July 2019 / Accepted: 7 July 2019 / Published: 8 July 2019
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Abstract
In this study, we have compared four 68Ga-labeled peptides (three Arg-Gly-Asp (RGD) peptides and substance-P) with two 18F-tracers clinically approved for tumor imaging. We have studied in vitro and in vivo characteristics of selected radiolabeled tracers in a glioblastoma multiforme tumor [...] Read more.
In this study, we have compared four 68Ga-labeled peptides (three Arg-Gly-Asp (RGD) peptides and substance-P) with two 18F-tracers clinically approved for tumor imaging. We have studied in vitro and in vivo characteristics of selected radiolabeled tracers in a glioblastoma multiforme tumor model. The in vitro part of the study was mainly focused on the evaluation of radiotracers stability under various conditions. We have also determined in vivo stability of studied 68Ga-radiotracers by analysis of murine urine collected at various time points after injection. The in vivo behavior of tested 68Ga-peptides was evaluated through ex vivo biodistribution studies and PET/CT imaging. The obtained data were compared with clinically used 18F-tracers. 68Ga-RGD peptides showed better imaging properties compared to 18F-tracers, i.e., higher tumor/background ratios and no accumulation in non-target organs except for excretory organs. Full article
(This article belongs to the Special Issue Analytical Chemistry in Clinical Studies and PET Developments)
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Open AccessArticle
Alpinia zerumbet (Pers.): Food and Medicinal Plant with Potential In Vitro and In Vivo Anti-Cancer Activities
Molecules 2019, 24(13), 2495; https://doi.org/10.3390/molecules24132495
Received: 2 June 2019 / Revised: 30 June 2019 / Accepted: 5 July 2019 / Published: 8 July 2019
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Abstract
Background/Aim: Plants play an important role in anti-cancer drug discovery, therefore, the current study aimed to evaluate the biological activity of Alpinia zerumbet (A. zerumbet) flowers. Methods: The phytochemical and biological criteria of A. zerumbet were in vitro investigated as well [...] Read more.
Background/Aim: Plants play an important role in anti-cancer drug discovery, therefore, the current study aimed to evaluate the biological activity of Alpinia zerumbet (A. zerumbet) flowers. Methods: The phytochemical and biological criteria of A. zerumbet were in vitro investigated as well as in mouse xenograft model. Results: A. zerumbet extracts, specially CH2Cl2 and MeOH extracts, exhibited the highest potent anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells. The most active CH2Cl2 extract was subjected to bioassay-guided fractionation leading to isolatation of the naturally occurring 5,6-dehydrokawain (DK) which was characterized by IR, MS, 1H-NMR and 13C-NMR. A. zerumbet extracts, specially MeOH and CH2Cl2 extracts, exhibited significant inhibitory activity towards tumor volume (TV). Furthermore, A. zerumbet extracts declined the high level of malonaldehyde (MDA) as well as elevated the levels of superoxide dismutase (SOD) and catalase (CAT) in liver tissue homogenate. Moreover, DK showed anti-proliferative action on different human cancer cell lines. The recorded IC50 values against breast carcinoma (MCF-7), liver carcinoma (Hep-G2) and larynx carcinoma cells (HEP-2) were 3.08, 6.8, and 8.7 µg/mL, respectively. Conclusion: Taken together, these findings open the door for further investigations in order to explore the potential medicinal properties of A. zerumbet. Full article
(This article belongs to the Special Issue Phytochemicals in Medicine and Food)
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Open AccessFeature PaperArticle
Experimental Insight into the Structural and Functional Roles of the ‘Black’ and ‘Gray’ Clusters in Recoverin, a Calcium Binding Protein with Four EF-Hand Motifs
Molecules 2019, 24(13), 2494; https://doi.org/10.3390/molecules24132494
Received: 17 June 2019 / Revised: 3 July 2019 / Accepted: 7 July 2019 / Published: 8 July 2019
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Abstract
Recently, we have found that calcium binding proteins of the EF-hand superfamily (i.e., a large family of proteins containing helix-loop-helix calcium binding motif or EF-hand) contain two types of conserved clusters called cluster I (‘black’ cluster) and cluster II (‘grey’ cluster), which provide [...] Read more.
Recently, we have found that calcium binding proteins of the EF-hand superfamily (i.e., a large family of proteins containing helix-loop-helix calcium binding motif or EF-hand) contain two types of conserved clusters called cluster I (‘black’ cluster) and cluster II (‘grey’ cluster), which provide a supporting scaffold for the Ca2+ binding loops and contribute to the hydrophobic core of the EF-hand domains. Cluster I is more conservative and mostly incorporates aromatic amino acids, whereas cluster II includes a mix of aromatic, hydrophobic, and polar amino acids of different sizes. Recoverin is EF-hand Ca2+-binding protein containing two ‘black’ clusters comprised of F35, F83, Y86 (N-terminal domain) and F106, E169, F172 (C-terminal domain) as well as two ‘gray’ clusters comprised of F70, Q46, F49 (N-terminal domain) and W156, K119, V122 (C-terminal domain). To understand a role of these residues in structure and function of human recoverin, we sequentially substituted them for alanine and studied the resulting mutants by a set of biophysical methods. Under metal-free conditions, the ‘black’ clusters mutants (except for F35A and E169A) were characterized by an increase in the α-helical content, whereas the ‘gray’ cluster mutants (except for K119A) exhibited the opposite behavior. By contrast, in Ca2+-loaded mutants the α-helical content was always elevated. In the absence of calcium, the substitutions only slightly affected multimerization of recoverin regardless of their localization (except for K119A). Meanwhile, in the presence of calcium mutations in N-terminal domain of the protein significantly suppressed this process, indicating that surface properties of Ca2+-bound recoverin are highly affected by N-terminal cluster residues. The substitutions in C-terminal clusters generally reduced thermal stability of recoverin with F172A (‘black’ cluster) as well as W156A and K119A (‘gray’ cluster) being the most efficacious in this respect. In contrast, the mutations in the N-terminal clusters caused less pronounced differently directed changes in thermal stability of the protein. The substitutions of F172, W156, and K119 in C-terminal domain of recoverin together with substitution of Q46 in its N-terminal domain provoked significant but diverse changes in free energy associated with Ca2+ binding to the protein: the mutant K119A demonstrated significantly improved calcium binding, whereas F172A and W156A showed decrease in the calcium affinity and Q46A exhibited no ion coordination in one of the Ca2+-binding sites. The most of the N-terminal clusters mutations suppressed membrane binding of recoverin and its inhibitory activity towards rhodopsin kinase (GRK1). Surprisingly, the mutant W156A aberrantly activated rhodopsin phosphorylation regardless of the presence of calcium. Taken together, these data confirm the scaffolding function of several cluster-forming residues and point to their critical role in supporting physiological activity of recoverin. Full article
(This article belongs to the Special Issue Metalloproteins)
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Open AccessArticle
Interactome Analysis and Docking Sites of MutS Homologs Reveal New Physiological Roles in Arabidopsis thaliana
Molecules 2019, 24(13), 2493; https://doi.org/10.3390/molecules24132493
Received: 10 May 2019 / Revised: 25 June 2019 / Accepted: 26 June 2019 / Published: 8 July 2019
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Abstract
Due to their sedentary lifestyle, plants are constantly exposed to different stress stimuli. Stress comes in variety of forms where factors like radiation, free radicals, “replication errors, polymerase slippage”, and chemical mutagens result in genotoxic or cytotoxic damage. In order to face “the [...] Read more.
Due to their sedentary lifestyle, plants are constantly exposed to different stress stimuli. Stress comes in variety of forms where factors like radiation, free radicals, “replication errors, polymerase slippage”, and chemical mutagens result in genotoxic or cytotoxic damage. In order to face “the base oxidation or DNA replication stress”, plants have developed many sophisticated mechanisms. One of them is the DNA mismatch repair (MMR) pathway. The main part of the MMR is the MutS homologue (MSH) protein family. The genome of Arabidopsis thaliana encodes at least seven homologues of the MSH family: AtMSH1, AtMSH2, AtMSH3, AtMSH4, AtMSH5, AtMSH6, and AtMSH7. Despite their importance, the functions of AtMSH homologs have not been investigated. In this work, bioinformatics tools were used to obtain a better understanding of MSH-mediated DNA repair mechanisms in Arabidopsis thaliana and to understand the additional biological roles of AtMSH family members. In silico analysis, including phylogeny tracking, prediction of 3D structure, interactome analysis, and docking site prediction, suggested interactions with proteins were important for physiological development of A. thaliana. The MSH homologs extensively interacted with both TIL1 and TIL2 (DNA polymerase epsilon catalytic subunit), proteins involved in cell fate determination during plant embryogenesis and involved in flowering time repression. Additionally, interactions with the RECQ protein family (helicase enzymes) and proteins of nucleotide excision repair pathway were detected. Taken together, the results presented here confirm the important role of AtMSH proteins in mismatch repair and suggest important new physiological roles. Full article
(This article belongs to the collection Molecular Docking)
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Open AccessArticle
Study on the Synthetic Characteristics of Biomass-Derived Isosorbide-Based Poly(arylene ether ketone)s for Sustainable Super Engineering Plastic
Molecules 2019, 24(13), 2492; https://doi.org/10.3390/molecules24132492
Received: 13 June 2019 / Revised: 2 July 2019 / Accepted: 7 July 2019 / Published: 8 July 2019
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Abstract
Demand for the development of novel polymers derived from biomass that can replace petroleum resources has been increasing. In this study, biomass-derived isosorbide was used as a monomer in the polymerization of poly(arylene ether ketone)s, and its synthetic characteristics were investigated. As a [...] Read more.
Demand for the development of novel polymers derived from biomass that can replace petroleum resources has been increasing. In this study, biomass-derived isosorbide was used as a monomer in the polymerization of poly(arylene ether ketone)s, and its synthetic characteristics were investigated. As a phase-transfer catalyst, crown ether has increased the weight-average molecular weight of polymers over 100 kg/mol by improving the reaction efficiency of isosorbide and minimizing the effect of moisture. By controlling the experimental parameters such as halogen monomer, polymerization solvent, time, and temperature, the optimal conditions were found to be fluorine-type monomer, dimethyl sulfoxide, 24 h, and 155 °C, respectively. Biomass contents from isosorbide-based polymers were determined by nuclear magnetic resonance and accelerator mass spectroscopy. The synthesized polymer resulted in a high molecular weight that enabled the preparation of transparent polymer films by the solution casting method despite its weak thermal degradation stability compared to aromatic polysulfone. The melt injection molding process was enabled by the addition of plasticizer. The tensile properties were comparable or superior to those of commercial petrochemical specimens of similar molecular weight. Interestingly, the prepared specimens exhibited a significantly lower coefficient of thermal expansion at high temperatures over 150 °C compared to polysulfone. Full article
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Open AccessArticle
Conformational and Tautomeric Control by Supramolecular Approach in Ureido-N-iso-propyl,N’-4-(3-pyridin-2-one)pyrimidine
Molecules 2019, 24(13), 2491; https://doi.org/10.3390/molecules24132491
Received: 7 June 2019 / Revised: 29 June 2019 / Accepted: 5 July 2019 / Published: 8 July 2019
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Abstract
Ureido-N-iso-propyl,N’-4-(3-pyridin-2-one)pyrimidine (1) and its 2-methoxy pyridine derivative (1Me) has been designed and prepared. The conformational equilibrium in urea moiety and tautomerism in the pyrimidine part have been investigated by variable temperature and 1H NMR [...] Read more.
Ureido-N-iso-propyl,N’-4-(3-pyridin-2-one)pyrimidine (1) and its 2-methoxy pyridine derivative (1Me) has been designed and prepared. The conformational equilibrium in urea moiety and tautomerism in the pyrimidine part have been investigated by variable temperature and 1H NMR titrations as well as DFT quantum chemical calculations. The studied compounds readily associate by triple hydrogen bonding with 2-aminonaphthyridine (A) and/or 2,6-bis(acetylamino)pyridine (B). In 1, the proton is forced to 1,3-tautomeric shift upon stimuli and keeps it position, even when one of the partners in the complex was replaced by another molecule. The observed tautomerism controlled by conformational state (kinetic trapping effect) opens new possibilities in molecular sensing that are based on the fact that reverse reaction is not preferred. Full article
(This article belongs to the Special Issue Noncovalent Interactions and Supramolecular Complex Formation)
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Open AccessArticle
Sonochemically-Promoted Preparation of Silica-Anchored Cyclodextrin Derivatives for Efficient Copper Catalysis
Molecules 2019, 24(13), 2490; https://doi.org/10.3390/molecules24132490
Received: 8 June 2019 / Revised: 1 July 2019 / Accepted: 2 July 2019 / Published: 7 July 2019
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Abstract
Silica-supported metallic species have emerged as valuable green-chemistry catalysts because their high efficiency enables a wide range of applications, even at industrial scales. As a consequence, the preparation of these systems needs to be finely controlled in order to achieve the desired activity. [...] Read more.
Silica-supported metallic species have emerged as valuable green-chemistry catalysts because their high efficiency enables a wide range of applications, even at industrial scales. As a consequence, the preparation of these systems needs to be finely controlled in order to achieve the desired activity. The present work presents a detailed investigation of an ultrasound-promoted synthetic protocol for the grafting of β-cyclodextrin (β-CD) onto silica. Truly, ultrasound irradiation has emerged as a fast technique for promoting efficient derivatization of a silica surface with organic moieties at low temperature. Three different β-CD silica-grafted derivatives have been obtained, and the ability of β-CD to direct and bind Cu when CD is bonded to silica has been studied. A detailed characterization has been performed using TGA, phenolphthalein titration, FT-IR, diffuse reflectance (DR), DR UV-Vis, as well as the inductively-coupled plasma (ICP) of the β-CD silica-grafted systems and the relative Cu-supported catalysts. Spectroscopic characterization monitored the different steps of the reaction, highlighting qualitative differences in the properties of amino-derivatized precursors and final products. In order to ensure that the Cu-β-CD silica catalyst is efficient and robust, its applicability in Cu(II)-catalyzed alkyne azide reactions in the absence of a reducing agent has been explored. The presence of β-CD and an amino spacer has been shown to be crucial for the reactivity of Cu(II), when supported. Full article
(This article belongs to the Special Issue Sonochemistry and Green Chemistry Applications II)
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Open AccessArticle
Development of Novel antimiRzymes for Targeted Inhibition of miR-21 Expression in Solid Cancer Cells
Molecules 2019, 24(13), 2489; https://doi.org/10.3390/molecules24132489
Received: 12 June 2019 / Revised: 5 July 2019 / Accepted: 5 July 2019 / Published: 7 July 2019
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Abstract
MicroRNAs (miRNAs) are short non-coding RNAs that are involved in the regulation of gene expression. Previous reports showed an over-expression of miRNA-21 (miR-21) in various cancer cells, and its up-regulation is closely related to cancer initiation, proliferation and metastasis. In this work, we [...] Read more.
MicroRNAs (miRNAs) are short non-coding RNAs that are involved in the regulation of gene expression. Previous reports showed an over-expression of miRNA-21 (miR-21) in various cancer cells, and its up-regulation is closely related to cancer initiation, proliferation and metastasis. In this work, we envisioned the development of novel antimiRzymes (anti-miRNA-DNAzyme) that are capable of selectively targeting and cleaving miR-21 and inhibit its expression in cancer cells using the DNAzyme technique. For this purpose, we have designed different antimiRzyme candidates by systematically targeting different regions of miR-21. Our results demonstrated that RNV541, a potential arm-loop-arm type antimiRzyme, was very efficient (90%) to suppress miR-21 expression in U87MG malignant glioblastoma cell line at 200 nM concentration. In addition, RNV541 also inhibited miR-21 expression (50%) in MDA-MB-231 breast cancer cell line. For targeted delivery, we conjugated RNV541 with a transferrin receptor (TfR) targeting aptamer for TfR-mediated cancer cell delivery. As expected, the developed chimeric structure efficiently delivered the antimiRzyme RNV541 into TfR positive glioblastoma cells. TfR aptamer-RNV541 chimeric construct showed 52% inhibition of miR-21 expression in U87MG glioblastoma cells at 2000 nM concentration, without using any transfection reagents, making it a highly desirable strategy to tackle miR-21 over-expressed malignant cancers. Although these are in vitro based observations, based on our results, we firmly believe that our findings could be beneficial towards the development of targeted cancer therapeutics where conventional therapies face several challenges. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessArticle
Evaluation of Glycosyl-Hydrolases, Phosphatases, Esterases and Proteases as Potential Biomarker for NaCl-Stress Tolerance in Solanum lycopersicum L. Varieties
Molecules 2019, 24(13), 2488; https://doi.org/10.3390/molecules24132488
Received: 27 May 2019 / Revised: 30 June 2019 / Accepted: 5 July 2019 / Published: 7 July 2019
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Abstract
Salinity stress limited the production in over 30% of irrigated crops and 7% of dryland agriculture worldwide. The objective was to evaluate the effects of NaCl-stress on the enzymatic activity in tomato. Two experiments were carried out in germination and early vegetative growth [...] Read more.
Salinity stress limited the production in over 30% of irrigated crops and 7% of dryland agriculture worldwide. The objective was to evaluate the effects of NaCl-stress on the enzymatic activity in tomato. Two experiments were carried out in germination and early vegetative growth stages. The activity of proline and peroxidase of eight varieties (Missouri, Yaqui, Vita, Feroz, Rio Grande, Tropic, Ace, and Floradade) submitted to NaCl concentrations (0, 50, 100, 150 and 200 mM de NaCl) and the semi-quantitative activity of 19 enzymes APY ZYM® were measured under a completely randomized design with four replications. Data were analyzed using univariate-multivariate analysis of variance, Tukey’s HSD (p = 0.05), canonical discriminant and cluster analysis. The results showed significant differences between varieties and NaCl in proline content. Proline increased as the NaCl concentration increased. Peroxidase did no show significant differences. Eight enzymes were included within the model to properly classify the varieties and NaCl. In shoots, varieties and NaCl showed that enzymatic activity was higher in the order of alkaline-phosphatase > leucine arylamidase > acid phosphatase > naphthol-AS-BI-phosphohydrolase > n-acetyl-β-glucosaminidase > β-galactosidase, while in roots was higher in the order of alkaline-phosphatase > naphthol-AS-BI-phosphohydrolase > acid phosphatase > n-acetyl-β-glucosaminidase. Acid and alkali phosphatase, lipase, esterase, β-galactosidase, and trypsin can be a potential biomarker for NaCl-stress tolerance in tomato. Full article
(This article belongs to the Section Chemical Biology)
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