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Molecules, Volume 25, Issue 11 (June-1 2020) – 256 articles

Cover Story (view full-size image): Honey was extracted with solvent and the lipid fractions purified by HPLC prior to analysis by qTOF LC–MS, resulting in the detection of 20-hydroxy-7-deydrocholesterol, vitamin D3, lumisterol, and species corresponding to 20-hydroxy-7-dehydrocholesterol, 20-hydroxyvitamin D3, 1,20-dihydroxyvitamin D3, 25-hydroxyvitamin D3, and 1,25-dihydroxyvitamin D3. The quantification of one of the major products, 20-hydroxyvitamin D3, revealed a concentration in dietary honey that could potentially display biological activity in humans. The detection of vitamin D metabolites in honey implies that 7-dehydrocholesterol undergoes phototransformation to vitamin D in bees, consistent with previous studies, with prior or subsequent enzymatic hydroxylation at C20, C25, and/or C1α. View this paper.
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49 pages, 13389 KiB  
Review
Hormesis and Ginseng: Ginseng Mixtures and Individual Constituents Commonly Display Hormesis Dose Responses, Especially for Neuroprotective Effects
by Edward J. Calabrese
Molecules 2020, 25(11), 2719; https://doi.org/10.3390/molecules25112719 - 11 Jun 2020
Cited by 21 | Viewed by 4449
Abstract
This paper demonstrates that ginseng mixtures and individual ginseng chemical constituents commonly induce hormetic dose responses in numerous biological models for endpoints of biomedical and clinical relevance, typically providing a mechanistic framework. The principal focus of ginseng hormesis-related research has been directed toward [...] Read more.
This paper demonstrates that ginseng mixtures and individual ginseng chemical constituents commonly induce hormetic dose responses in numerous biological models for endpoints of biomedical and clinical relevance, typically providing a mechanistic framework. The principal focus of ginseng hormesis-related research has been directed toward enhancing neuroprotection against conditions such as Alzheimer’s and Parkinson’s Diseases, stroke damage, as well as enhancing spinal cord and peripheral neuronal damage repair and reducing pain. Ginseng was also shown to reduce symptoms of diabetes, prevent cardiovascular system damage, protect the kidney from toxicities due to immune suppressant drugs, and prevent corneal damage, amongst other examples. These findings complement similar hormetic-based chemoprotective reports for other widely used dietary-type supplements such as curcumin, ginkgo biloba, and green tea. These findings, which provide further support for the generality of the hormetic dose response in the biomedical literature, have potentially important public health and clinical implications. Full article
(This article belongs to the Special Issue Nutraceuticals in Immune Function)
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19 pages, 1395 KiB  
Review
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and Transporters
by Jiapeng Li and Hao-Jie Zhu
Molecules 2020, 25(11), 2718; https://doi.org/10.3390/molecules25112718 - 11 Jun 2020
Cited by 23 | Viewed by 5941
Abstract
Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics is a powerful tool for identifying and quantifying proteins in biological samples, outperforming conventional antibody-based methods in many aspects. LC-MS/MS-based proteomics studies have revealed the protein abundances of many drug-metabolizing enzymes and transporters (DMETs) in tissues relevant [...] Read more.
Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics is a powerful tool for identifying and quantifying proteins in biological samples, outperforming conventional antibody-based methods in many aspects. LC-MS/MS-based proteomics studies have revealed the protein abundances of many drug-metabolizing enzymes and transporters (DMETs) in tissues relevant to drug metabolism and disposition. Previous studies have consistently demonstrated marked interindividual variability in DMET protein expression, suggesting that varied DMET function is an important contributing factor for interindividual variability in pharmacokinetics (PK) and pharmacodynamics (PD) of medications. Moreover, differential DMET expression profiles were observed across different species and in vitro models. Therefore, caution must be exercised when extrapolating animal and in vitro DMET proteomics findings to humans. In recent years, DMET proteomics has been increasingly utilized for the development of physiologically based pharmacokinetic models, and DMET proteins have also been proposed as biomarkers for prediction of the PK and PD of the corresponding substrate drugs. In sum, despite the existence of many challenges in the analytical technology and data analysis methods of LC-MS/MS-based proteomics, DMET proteomics holds great potential to advance our understanding of PK behavior at the individual level and to optimize treatment regimens via the DMET protein biomarker-guided precision pharmacotherapy. Full article
(This article belongs to the Special Issue CZE/LC-MS-based Proteomics)
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16 pages, 3284 KiB  
Article
Valorization of Lignin via Oxidative Depolymerization with Hydrogen Peroxide: Towards Carboxyl-Rich Oligomeric Lignin Fragments
by Ulrike Junghans, Justin J. Bernhardt, Ronja Wollnik, Dominik Triebert, Gerd Unkelbach and Daniela Pufky-Heinrich
Molecules 2020, 25(11), 2717; https://doi.org/10.3390/molecules25112717 - 11 Jun 2020
Cited by 14 | Viewed by 6479
Abstract
The extraction and characterization of defined and carboxyl-rich oligomeric lignin fragments with narrow molecular weight distribution is presented herein. With regard to the well-known pulp bleaching process, oxidative lignin depolymerization was investigated using hydrogen peroxide in an aqueous alkaline solution (i.e., at T [...] Read more.
The extraction and characterization of defined and carboxyl-rich oligomeric lignin fragments with narrow molecular weight distribution is presented herein. With regard to the well-known pulp bleaching process, oxidative lignin depolymerization was investigated using hydrogen peroxide in an aqueous alkaline solution (i.e., at T = 318 K, t = 1 h) and subsequent selective fractionation with a 10/90 (v/v) acetone/water mixture. While the weight average molecular weight (MW) of lignin in comparison to the starting material was reduced by 82% after oxidation (T = 318 K, t = 1 h, clignin = 40 g L−1, cH2O2 = 80 g L−1, cNaOH = 2 mol L−1) and subsequent solvent fractionation (T = 298 K, t = 18 h, ccleavage product = 20 g L−1), the carboxyl group (–COOH) content increased from 1.29 mmol g−1 up to 2.66 mmol g−1. Finally, the successful scale-up of this whole process to 3 L scale led to gram amounts (14% yield) of oligomeric lignin fragments with a MW of 1607 g mol−1, a number average molecular weight (MN) of 646 g mol−1, a narrow polydispersity index of 3.0, and a high –COOH content of 2.96 mmol g−1. Application of these oligomeric lignin fragments in epoxy resins or as adsorbents is conceivable without further functionalization. Full article
(This article belongs to the Special Issue Lignin – A Natural Resource with Huge Potential)
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21 pages, 4547 KiB  
Article
Unsaturated Fatty Acid-Induced Conformational Transitions and Aggregation of the Repeat Domain of Tau
by Carlo Giorgio Barracchia, Roberto Tira, Francesca Parolini, Francesca Munari, Luigi Bubacco, Georgios A. Spyroulias, Mariapina D’Onofrio and Michael Assfalg
Molecules 2020, 25(11), 2716; https://doi.org/10.3390/molecules25112716 - 11 Jun 2020
Cited by 14 | Viewed by 3181
Abstract
Background: The intrinsically disordered, amyloidogenic protein Tau associates with diverse classes of molecules, including proteins, nucleic acids, and lipids. Mounting evidence suggests that fatty acid molecules could play a role in the dysfunction of this protein, however, their interaction with Tau remains poorly [...] Read more.
Background: The intrinsically disordered, amyloidogenic protein Tau associates with diverse classes of molecules, including proteins, nucleic acids, and lipids. Mounting evidence suggests that fatty acid molecules could play a role in the dysfunction of this protein, however, their interaction with Tau remains poorly characterized. Methods: In a bid to elucidate the association of Tau with unsaturated fatty acids at the sub-molecular level, we carried out a variety of solution NMR experiments in combination with circular dichroism and fluorescence measurements. Our study shows that Tau4RD, the highly basic four-repeat domain of Tau, associates strongly with arachidonic and oleic acid assemblies in a high lipid/protein ratio, perturbing their supramolecular states and itself undergoing time-dependent structural adaptation. The structural signatures of Tau4RD/fatty acid aggregates appear similar for arachidonic acid and oleic acid, however, they are distinct from those of another prototypical intrinsically disordered protein, α-synuclein, when bound to these lipids, revealing protein-specific conformational adaptations. Both fatty acid molecules are found to invariably promote the self-aggregation of Tau4RD and of α-synuclein. Conclusions: This study describes the reciprocal influence that Tau4RD and fatty acids exert on their conformational states, contributing to our understanding of fundamental aspects of Tau/lipid co-assembly. Full article
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13 pages, 3940 KiB  
Article
The Role of Structural Representation in the Performance of a Deep Neural Network for X-ray Spectroscopy
by Marwah M.M. Madkhali, Conor D. Rankine and Thomas J. Penfold
Molecules 2020, 25(11), 2715; https://doi.org/10.3390/molecules25112715 - 11 Jun 2020
Cited by 12 | Viewed by 3795
Abstract
An important consideration when developing a deep neural network (DNN) for the prediction of molecular properties is the representation of the chemical space. Herein we explore the effect of the representation on the performance of our DNN engineered to predict Fe K-edge X-ray [...] Read more.
An important consideration when developing a deep neural network (DNN) for the prediction of molecular properties is the representation of the chemical space. Herein we explore the effect of the representation on the performance of our DNN engineered to predict Fe K-edge X-ray absorption near-edge structure (XANES) spectra, and address the question: How important is the choice of representation for the local environment around an arbitrary Fe absorption site? Using two popular representations of chemical space—the Coulomb matrix (CM) and pair-distribution/radial distribution curve (RDC)—we investigate the effect that the choice of representation has on the performance of our DNN. While CM and RDC featurisation are demonstrably robust descriptors, it is possible to obtain a smaller mean squared error (MSE) between the target and estimated XANES spectra when using RDC featurisation, and converge to this state a) faster and b) using fewer data samples. This is advantageous for future extension of our DNN to other X-ray absorption edges, and for reoptimisation of our DNN to reproduce results from higher levels of theory. In the latter case, dataset sizes will be limited more strongly by the resource-intensive nature of the underlying theoretical calculations. Full article
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15 pages, 2599 KiB  
Article
Conjugation of Doxorubicin to siRNA Through Disulfide-based Self-immolative Linkers
by Florian Gauthier, Jean-Rémi Bertrand, Jean-Jacques Vasseur, Christelle Dupouy and Françoise Debart
Molecules 2020, 25(11), 2714; https://doi.org/10.3390/molecules25112714 - 11 Jun 2020
Cited by 16 | Viewed by 4612
Abstract
Co-delivery systems of siRNA and chemotherapeutic drugs have been developed as an attractive strategy to optimize the efficacy of chemotherapy towards cancer cells with multidrug resistance. In these typical systems, siRNAs are usually associated to drugs within a carrier but without covalent interactions [...] Read more.
Co-delivery systems of siRNA and chemotherapeutic drugs have been developed as an attractive strategy to optimize the efficacy of chemotherapy towards cancer cells with multidrug resistance. In these typical systems, siRNAs are usually associated to drugs within a carrier but without covalent interactions with the risk of a premature release and degradation of the drugs inside the cells. To address this issue, we propose a covalent approach to co-deliver a siRNA-drug conjugate with a redox-responsive self-immolative linker prone to intracellular glutathione-mediated disulfide cleavage. Herein, we report the use of two disulfide bonds connected by a pentane spacer or a p-xylene spacer as self-immolative linker between the primary amine of the anticancer drug doxorubicin (Dox) and the 2′-position of one or two ribonucleotides in RNA. Five Dox-RNA conjugates were successfully synthesized using two successive thiol-disulfide exchange reactions. The Dox-RNA conjugates were annealed with their complementary strands and the duplexes were shown to form an A-helix sufficiently stable under physiological conditions. The enzymatic stability of Dox-siRNAs in human serum was enhanced compared to the unmodified siRNA, especially when two Dox are attached to siRNA. The release of native Dox and RNA from the bioconjugate was demonstrated under reducing conditions suggesting efficient linker disintegration. These results demonstrate the feasibility of making siRNA-drug conjugates via disulfide-based self-immolative linkers for potential therapeutic applications. Full article
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13 pages, 1294 KiB  
Article
Synthesis and Antibacterial Analysis of Analogues of the Marine Alkaloid Pseudoceratidine
by David Barker, Stephanie Lee, Kyriakos G. Varnava, Kevin Sparrow, Michelle van Rensburg, Rebecca C. Deed, Melissa M. Cadelis, Steven A. Li, Brent R. Copp, Vijayalekshmi Sarojini and Lisa I. Pilkington
Molecules 2020, 25(11), 2713; https://doi.org/10.3390/molecules25112713 - 11 Jun 2020
Cited by 6 | Viewed by 3139
Abstract
In an effort to gain more understanding on the structure activity relationship of pseudoceratidine 1, a di-bromo pyrrole spermidine alkaloid derived from the marine sponge Pseudoceratina purpurea that has been shown to exhibit potent biofouling, anti-fungal, antibacterial, and anti-malarial activities, a large [...] Read more.
In an effort to gain more understanding on the structure activity relationship of pseudoceratidine 1, a di-bromo pyrrole spermidine alkaloid derived from the marine sponge Pseudoceratina purpurea that has been shown to exhibit potent biofouling, anti-fungal, antibacterial, and anti-malarial activities, a large series of 65 compounds that incorporated several aspects of structural variation has been synthesised through an efficient, divergent method that allowed for a number of analogues to be generated from common precursors. Subsequently, all analogues were assessed for their antibacterial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Overall, several compounds exhibited comparable or better activity than that of pseudoceratidine 1, and it was found that this class of compounds is generally more effective against Gram-positive than Gram-negative bacteria. Furthermore, altering several structural features allowed for the establishment of a comprehensive structure activity relationship (SAR), where it was concluded that several structural features are critical for potent anti-bacterial activity, including di-halogenation (preferable bromine, but chlorine is also effective) on the pyrrole ring, two pyrrolic units in the structure and with one or more secondary amines in the chain adjoining these units, with longer chains giving rise to better activities. Full article
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20 pages, 1726 KiB  
Article
Pharmacokinetic Properties of 68Ga-labelled Folic Acid Conjugates: Improvement Using HEHE Tag
by Anton Larenkov, Marat Rakhimov, Kristina Lunyova, Olga Klementyeva, Alesya Maruk and Aleksei Machulkin
Molecules 2020, 25(11), 2712; https://doi.org/10.3390/molecules25112712 - 11 Jun 2020
Cited by 3 | Viewed by 3574
Abstract
The folate receptor (FR) is a promising cell membrane-associated target for molecular imaging and radionuclide therapy of cancer (FR-α) and potentially also inflammatory diseases (FR-β) through use of folic acid-based radioconjugate. FR is often overexpressed by cells of epithelial tumors, including tumors of [...] Read more.
The folate receptor (FR) is a promising cell membrane-associated target for molecular imaging and radionuclide therapy of cancer (FR-α) and potentially also inflammatory diseases (FR-β) through use of folic acid-based radioconjugate. FR is often overexpressed by cells of epithelial tumors, including tumors of ovary, cervix, endometrium, lungs, kidneys, etc. In healthy tissues, FR can be found in small numbers by the epithelial cells, mainly in the kidneys. Extremely high undesired accumulation of the folate radioconjugates in the renal tissue is a main drawback of FR-targeting concept. In the course of this work, we aimed to reduce the undesirable accumulation of folate radioconjugates in the kidneys by introducing a histidine/glutamic acid tag into their structure. Two folic acid based compounds were synthesized: NODAGA-1,4-butanediamine-folic acid (FA-I, as control) and NODAGA-[Lys-(HE)2]-folic acid (FA-II) which contains a (His-Glu)2 fragment. In vitro studies with FR (+) cells (KB and others) showed that both compounds have specificity for FR. Introduction of (HE)2-tag does not affect FR binding ability of the conjugates. In vivo biodistribution studies with normal laboratory animals, as well as with KB tumor bearing animals, were carried out. The results showed that introduction of the (HE)2 tag into the structure of folate radioconjugates can significantly reduce the accumulation of these compounds in non-target tissues and important organs (the accumulation in the kidneys is reduced 2–4 times), leaving the accumulation in tumor at least at the same level, and even increasing it. Full article
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11 pages, 6391 KiB  
Communication
Continuous Bioinspired Oxidation of Sulfides
by Francesca Mangiavacchi, Letizia Crociani, Luca Sancineto, Francesca Marini and Claudio Santi
Molecules 2020, 25(11), 2711; https://doi.org/10.3390/molecules25112711 - 11 Jun 2020
Cited by 17 | Viewed by 3545
Abstract
A simple, efficient, and selective oxidation under flow conditions of sulfides into their corresponding sulfoxides and sulfones is reported herein, using as a catalyst perselenic acid generated in situ by the oxidation of selenium (IV) oxide in a diluted aqueous solution of hydrogen [...] Read more.
A simple, efficient, and selective oxidation under flow conditions of sulfides into their corresponding sulfoxides and sulfones is reported herein, using as a catalyst perselenic acid generated in situ by the oxidation of selenium (IV) oxide in a diluted aqueous solution of hydrogen peroxide as the final oxidant. The scope of the proposed methodology was investigated using aryl alkyl sulfides, aryl vinyl sulfides, and dialkyl sulfides as substrates, evidencing, in general, a good applicability. The scaled-up synthesis of (methylsulfonyl)benzene was also demonstrated, leading to its gram-scale preparation. Full article
(This article belongs to the Special Issue Chalcogenides: New Developments and Cutting-Edge Applications)
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28 pages, 7089 KiB  
Article
One-Pot Multicomponent Synthesis and Bioevaluation of Tetrahydroquinoline Derivatives as Potential Antioxidants, α-Amylase Enzyme Inhibitors, Anti-Cancerous and Anti-Inflammatory Agents
by Samra Farooq, Aqsa Mazhar, Areej Ghouri, Ihsan-Ul-Haq and Naseem Ullah
Molecules 2020, 25(11), 2710; https://doi.org/10.3390/molecules25112710 - 11 Jun 2020
Cited by 12 | Viewed by 4629
Abstract
Mankind has always suffered from multiple diseases. Therefore, there has been a rigorous need in the field of medicinal chemistry for the design and discovery of new and potent molecular entities. In this work, thirteen tetrahydroquinoline derivatives were synthesized and evaluated biologically for [...] Read more.
Mankind has always suffered from multiple diseases. Therefore, there has been a rigorous need in the field of medicinal chemistry for the design and discovery of new and potent molecular entities. In this work, thirteen tetrahydroquinoline derivatives were synthesized and evaluated biologically for their antioxidant, α-amylase enzyme inhibitory, anti-proliferative and anti-inflammatory activities. SF8 showed the lowest IC50 of 29.19 ± 0.25 µg/mL by scavenging DPPH free radicals. SF5 showed significant antioxidant activity in total antioxidant capacity (TAC) and total reducing power (TRP) assays. SF5 and SF9 showed the maximum inhibition of α-amylase enzyme i.e., 97.47% and 89.93%, respectively, at 200 µg/mL concentration. Five compounds were shortlisted to determine their anti-proliferative potential against Hep-2C cells. The study was conducted for 24, 48 and 72 h. SF8 showed significant results, having an IC50 value of 11.9 ± 1.04 µM at 72 h when compared with standard cisplatin (IC50 value of 14.6 ± 1.01 µM). An in vitro nitric oxide (NO) assay was performed to select compounds for in vivo anti-inflammatory activity evaluation. SF13 scavenged the NO level to a maximum of 85% at 50 µM concentration, followed by SF1 and SF2. Based on the NO scavenging assay results, in vivo anti-inflammatory studies were also performed and the results showed significant activity compared to the standard, acetylsalicylic acid (ASA). Full article
(This article belongs to the Special Issue Synthesis and Application of Quinolines and Quinoline Derivatives)
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21 pages, 5863 KiB  
Article
Synthesis and Studies of the Inhibitory Effect of Hydroxylated Phenylpropanoids and Biphenols Derivatives on Tyrosinase and Laccase Enzymes
by Maria Antonietta Dettori, Davide Fabbri, Alessandro Dessì, Roberto Dallocchio, Paola Carta, Claudia Honisch, Paolo Ruzza, Donatella Farina, Rossana Migheli, Pier Andrea Serra, Roberto A. Pantaleoni, Xenia Fois, Gaia Rocchitta and Giovanna Delogu
Molecules 2020, 25(11), 2709; https://doi.org/10.3390/molecules25112709 - 11 Jun 2020
Cited by 12 | Viewed by 3256
Abstract
The impaired activity of tyrosinase and laccase can provoke serious concerns in the life cycles of mammals, insects and microorganisms. Investigation of inhibitors of these two enzymes may lead to the discovery of whitening agents, medicinal products, anti-browning substances and compounds for controlling [...] Read more.
The impaired activity of tyrosinase and laccase can provoke serious concerns in the life cycles of mammals, insects and microorganisms. Investigation of inhibitors of these two enzymes may lead to the discovery of whitening agents, medicinal products, anti-browning substances and compounds for controlling harmful insects and bacteria. A small collection of novel reversible tyrosinase and laccase inhibitors with a phenylpropanoid and hydroxylated biphenyl core was prepared using naturally occurring compounds and their activity was measured by spectrophotometric and electrochemical assays. Biosensors based on tyrosinase and laccase enzymes were constructed and used to detect the type of protein-ligand interaction and half maximal inhibitory concentration (IC50). Most of the inhibitors showed an IC50 in a range of 20–423 nM for tyrosinase and 23–2619 nM for laccase. Due to the safety concerns of conventional tyrosinase and laccase inhibitors, the viability of the new compounds was assayed on PC12 cells, four of which showed a viability of roughly 80% at 40 µM. In silico studies on the crystal structure of laccase enzyme identified a hydroxylated biphenyl bearing a prenylated chain as the lead structure, which activated strong and effective interactions at the active site of the enzyme. These data were confirmed by in vivo experiments performed on the insect model Tenebrio molitur. Full article
(This article belongs to the Special Issue Protein-Peptide and Protein-Small Molecule Interactions)
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11 pages, 695 KiB  
Article
Synthesis and Characterization of New Series of 1,3-5-Triazine Hydrazone Derivatives with Promising Antiproliferative Activity
by Hessa H. Al H. Al Rasheed, Azizah M. M. Malebari, Kholood A. A. Dahlous and Ayman El-Faham
Molecules 2020, 25(11), 2708; https://doi.org/10.3390/molecules25112708 - 11 Jun 2020
Cited by 10 | Viewed by 3043
Abstract
A new series of s-triazine hydrazone derivatives was prepared based on the reaction of 6-hydrazino-2,4-disubstituted-s-triazine with p-substituted benzaldehyde derivatives using a straightforward synthetic pathway. The antiproliferative activity of all synthesized compounds was evaluated against two human cancer cell lines; [...] Read more.
A new series of s-triazine hydrazone derivatives was prepared based on the reaction of 6-hydrazino-2,4-disubstituted-s-triazine with p-substituted benzaldehyde derivatives using a straightforward synthetic pathway. The antiproliferative activity of all synthesized compounds was evaluated against two human cancer cell lines; breast cancer MCF-7 and colon carcinoma HCT-116 using MTT assay. Among all, 11 compounds have shown strong to moderate antiproliferative activity with IC50 values in the range 1.01–18.20 µM in MCF-7 and 0.97–19.51 µM in HCT-116. The best results were obtained with 4,4’-(6-(2-(pyridin-2-ylmethylene)hydrazinyl)-1,3,5-triazine-2,4-diyl) dimorpholine 11 (IC50 = 1.0 µM and 0.98 µM in MCF-7 and HCT-116 cell lines, respectively). The substituents on the s-triazine core as well as the substituent at the benzylidene moiety have a great effect on the antiproliferative activity. Whereas compounds containing dimorpholino-s-triazine derivatives 8a–e showed more potent antiproliferative in MCF-7 compared to their analogs 7a–f (compounds containing two-piperidine rings), compounds containing one piperidine and one morpholine ring 9a–f showed better IC50 values in the range 10.4–22.2 µM. On the other hand, compounds containing two-piperidine rings 7a–f showed more potent antiproliferative in HCT-116 (IC50 values in the range 8.8–19.5 µM) than their analogs 8a–e and 9a–f. Full article
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10 pages, 1696 KiB  
Communication
Potential of Flavonoid-Inspired Phytomedicines against COVID-19
by Wilfred Ngwa, Rajiv Kumar, Daryl Thompson, William Lyerly, Roscoe Moore, Terry-Elinor Reid, Henry Lowe and Ngeh Toyang
Molecules 2020, 25(11), 2707; https://doi.org/10.3390/molecules25112707 - 11 Jun 2020
Cited by 112 | Viewed by 11745
Abstract
Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include: caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based [...] Read more.
Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include: caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19. Meanwhile, in vitro studies show potential of caflanone to inhibit virus entry factors including, ABL-2, cathepsin L, cytokines (IL-1β, IL-6, IL-8, Mip-1α, TNF-α), and PI4Kiiiβ as well as AXL-2, which facilitates mother-to-fetus transmission of coronavirus. The potential for the use of smart drug delivery technologies like nanoparticle drones loaded with these phytomedicines to overcome bioavailability limitations and improve therapeutic efficacy are discussed. Full article
(This article belongs to the Special Issue Flavonoids and Their Disease Prevention and Treatment Potential)
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15 pages, 1901 KiB  
Article
Effect of Addition of Pectins from Jujubes (Ziziphus jujuba Mill.) on Vitamin C Production during Heterolactic Fermentation
by Alessia Fazio, Chiara La Torre, Maria Cristina Caroleo, Paolino Caputo, Roberto Cannataro, Pierluigi Plastina and Erika Cione
Molecules 2020, 25(11), 2706; https://doi.org/10.3390/molecules25112706 - 11 Jun 2020
Cited by 11 | Viewed by 2666
Abstract
Soluble fibers, including pectins from apple and lemon, are commonly used as prebiotic and to prepare functional foods. The present study aimed to investigate the physicochemical and functional properties of pectins extracted from jujubes (Ziziphus jujuba Mill.). Pectins were extracted from jujubes [...] Read more.
Soluble fibers, including pectins from apple and lemon, are commonly used as prebiotic and to prepare functional foods. The present study aimed to investigate the physicochemical and functional properties of pectins extracted from jujubes (Ziziphus jujuba Mill.). Pectins were extracted from jujubes at three stages of harvesting and characterized by FTIR and SEM analyses. Whole milk inoculated with kefir grains was supplemented by 0.25 mg·mL−1 of pectins. The pH value and vitamin C content were evaluated after 24 and 48 h of fermentation. Pectins from jujubes at the first harvesting stage (PJ1K) showed the lowest methoxylation degree. The addition of pectins enhanced the production of vitamin C during heterolactic process. This result was found to depend on jujube harvesting stage as PJ1K stimulated the growth of yeasts in kefir grains yielding to the highest amount of vitamin C (0.83 ± 0.01 µg·mL−1) compared to other samples (0.53–0.60 µg·mL−1) at 24 h. Lactic acid bacteria diminish pH rapidly with respect to control (4.13 ± 0.05), according to the stage of maturation, reducing its initial value by 38.3% in PJ1K. Besides being an excellent prebiotic, pectins from jujubes could be used to enrich kefir with vitamin C. Full article
(This article belongs to the Special Issue New Frontiers in Fermented Products)
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20 pages, 6121 KiB  
Review
The Lisbon Supramolecular Green Story: Mechanochemistry towards New Forms of Pharmaceuticals
by João Luís Ferreira da Silva, M. Fátima Minas da Piedade, Vânia André, Sofia Domingos, Inês C. B. Martins and M. Teresa Duarte
Molecules 2020, 25(11), 2705; https://doi.org/10.3390/molecules25112705 - 11 Jun 2020
Cited by 8 | Viewed by 2640
Abstract
This short review presents and highlights the work performed by the Lisbon Group on the mechanochemical synthesis of active pharmaceutical ingredients (APIs) multicomponent compounds. Here, we show some of our most relevant contributions on the synthesis of supramolecular derivatives of well-known commercial used [...] Read more.
This short review presents and highlights the work performed by the Lisbon Group on the mechanochemical synthesis of active pharmaceutical ingredients (APIs) multicomponent compounds. Here, we show some of our most relevant contributions on the synthesis of supramolecular derivatives of well-known commercial used drugs and the corresponding improvement on their physicochemical properties. The study reflects, not only our pursuit of using crystal engineering principles for the search of supramolecular entities, but also our aim to correlate them with the desired properties. The work also covers our results on polymorphic screening and describes our proposed alternatives to induce and maintain specific polymorphic forms, and our approach to avoid polymorphism using APIs as ionic liquids. We want to stress that all the work was performed using mechanochemistry, a green advantageous synthetic technique. Full article
(This article belongs to the Special Issue 1st CQE Days Meeting: 44 Years Connecting People and Chemistry)
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16 pages, 2263 KiB  
Article
Conversion of the Propane–Butane Fraction into Arenes on MFI Zeolites Modified by Zinc Oxide and Activated by Low-Temperature Plasma
by Vladimir I. Erofeev, Sofiya N. Dzhalilova, Mikhail V. Erofeev, Vasilii S. Ripenko and Vladimir P. Reschetilowski
Molecules 2020, 25(11), 2704; https://doi.org/10.3390/molecules25112704 - 11 Jun 2020
Cited by 4 | Viewed by 2326
Abstract
The effect of modification of MFI zeolite 1–5 wt.% ZnO activated by plasma on acid and catalytic properties in the conversion of the propane–butane fraction into arenes was investigated. The high-silica zeolites with silicate module 45 were synthesized from alkaline alumina–silica gels in [...] Read more.
The effect of modification of MFI zeolite 1–5 wt.% ZnO activated by plasma on acid and catalytic properties in the conversion of the propane–butane fraction into arenes was investigated. The high-silica zeolites with silicate module 45 were synthesized from alkaline alumina–silica gels in the presence of an ‘X-oil’ organic structure-forming additive. The modification of the zeolite with zinc was carried out by impregnating the zeolite granules in the H-form with an aqueous solution of Zn(NO3)2. The obtained zeolites were characterized by X-ray phase analysis and IR spectroscopy. It is shown that the synthesized zeolites belong to the high-silica MFI zeolites. The study of microporous zeolite-containing catalysts during the conversion of C3-C4 alkanes to aromatic hydrocarbons made it possible to establish that the highest yield of aromatic hydrocarbons is observed on zeolite catalysts modified with 1 and 3% ZnO and amount to 63.7 and 64.4% at 600 °C, respectively, which is 7.7–8.4% more than on the original zeolite. The preliminary activation of microporous zeolites modified with 1–5% ZnO and plasma leads to an increase in the yield of aromatic hydrocarbons from the propane–butane fraction; the maximum yield of arenes is observed in zeolite catalysts modified with 1 and 3% ZnO and activated by plasma, amounting to 64.9 and 65.5% at 600 °C, respectively, which is 8.9–9.5% more than on the initial zeolite. The activity of the zeolite catalysts modified by ZnO and activated by plasma show good agreement with their acid properties. Activation of the zeolites modified by 1 and 3% ZnO and plasma leads to an increase in the concentration of the weak acid sites of the catalyst to 707 and 764 mmol/g in comparison with plasma-inactivated 1 and 3% ZnO/ZKE-XM catalysts at 626 and 572 mmol/g, respectively. Full article
(This article belongs to the Special Issue Zeolitic Microporous Materials and Their Applications)
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15 pages, 1886 KiB  
Article
The Nature of Triel Bonds, a Case of B and Al Centres Bonded with Electron Rich Sites
by Sławomir J. Grabowski
Molecules 2020, 25(11), 2703; https://doi.org/10.3390/molecules25112703 - 11 Jun 2020
Cited by 34 | Viewed by 2925
Abstract
The second-order Møller–Plesset perturbation theory calculations with the aug-cc-pVTZ basis set were performed on complexes of triel species: BCl3, BH3, AlCl3, and AlH3 acting as Lewis acids through the B or Al centre with Lewis base [...] Read more.
The second-order Møller–Plesset perturbation theory calculations with the aug-cc-pVTZ basis set were performed on complexes of triel species: BCl3, BH3, AlCl3, and AlH3 acting as Lewis acids through the B or Al centre with Lewis base units: NCH, N2, NH3, and Cl anion. These complexes are linked by triel bonds: B/Al⋅⋅⋅N or B/Al⋅⋅⋅Cl. The Quantum Theory of ´Atoms in Molecules´ approach, Natural Bond Orbital method, and the decomposition of energy of interaction were applied to characterise the latter links. The majority of complexes are connected through strong interactions possessing features of covalent bonds and characterised by short intermolecular distances, often below 2 Å. The BCl3⋅⋅⋅N2 complex is linked by a weak interaction corresponding to the B⋅⋅⋅N distance of ~3 Å. For the BCl3⋅⋅⋅NCH complex, two configurations corresponding to local energetic minima are observed, one characterised by a short B⋅⋅⋅N distance and a strong interaction and another one characterised by a longer B⋅⋅⋅N distance and a weak triel bond. The tetrahedral triel structure is observed for complexes linked by strong triel bonds, while, for complexes connected by weak interactions, the structure is close to the trigonal pyramid, particularly observed for the BCl3⋅⋅⋅N2 complex. Full article
(This article belongs to the Special Issue Bonding in Inorganic and Coordination Compounds)
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25 pages, 4072 KiB  
Article
Expanding the Role of Sub-Exploited DOE-High Energy Extraction and Metabolomic Profiling towards Agro-Byproduct Valorization: The Case of Carotenoid-Rich Apricot Pulp
by Thalia Tsiaka, Charalambos Fotakis, Dimitra Z. Lantzouraki, Konstantinos Tsiantas, Eleni Siapi, Vassilia J. Sinanoglou and Panagiotis Zoumpoulakis
Molecules 2020, 25(11), 2702; https://doi.org/10.3390/molecules25112702 - 11 Jun 2020
Cited by 11 | Viewed by 2760
Abstract
Traditional extraction remains the method-of-choice for phytochemical analyses. However, the absence of an integrated analytical platform, focusing on customized, validated extraction steps, generates tendentious and non-reproducible data regarding the phytochemical profile. Such a platform would also support the exploration and exploitation of plant [...] Read more.
Traditional extraction remains the method-of-choice for phytochemical analyses. However, the absence of an integrated analytical platform, focusing on customized, validated extraction steps, generates tendentious and non-reproducible data regarding the phytochemical profile. Such a platform would also support the exploration and exploitation of plant byproducts, which are a valuable source of bioactive metabolites. This study deals with the incorporation of (a) the currently sub-exploited high energy extraction methods (ultrasound (UAE)- and microwave-assisted extraction (MAE)), (b) experimental design (DOE), and (c) metabolomics, in an integrated analytical platform for the extensive study of plant metabolomics and phytochemical profiling. The recovery of carotenoids from apricot by-products (pulp) is examined as a case study. MAE, using ethanol as solvent, achieved higher carotenoid yields compared to UAE, where 1:1 chloroform-methanol was employed, and classic extraction. Nuclear magnetic resonance (NMR)-based metabolomic profiling classified extracts according to the variations in co-extractives in relation to the extraction conditions. Extracts with a lower carotenoid content contained branched-chain amino acids as co-extractives. Medium carotenoid content extracts contained choline, unsaturated fatty acids, and sugar alcohols, while the highest carotenoid extracts were also rich in sugars. Overall, the proposed pipeline can provide different the phytochemical fractions of bioactive compounds according to the needs of different industrial sectors (cosmetics, nutraceuticals, etc.). Full article
(This article belongs to the Special Issue Bioactive Compounds with Applications in Health and Food)
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9 pages, 1357 KiB  
Article
Synthesis of Nitroxide Diradical Using a New Approach
by Pavel Fedyushin, Tatyana Rybalova, Nargiz Asanbaeva, Elena Bagryanskaya, Alexey Dmitriev, Nina Gritsan, Maxim Kazantsev and Evgeny Tretyakov
Molecules 2020, 25(11), 2701; https://doi.org/10.3390/molecules25112701 - 11 Jun 2020
Cited by 9 | Viewed by 3055
Abstract
A new synthetic pathway to diradical organic systems is proposed. The effectiveness of this approach was exemplified by the synthesis of a new nitroxide diradical. An interaction of perfluorobiphenyl with lithium tert-butylamide, followed by oxidation of the thusly formed N4,N [...] Read more.
A new synthetic pathway to diradical organic systems is proposed. The effectiveness of this approach was exemplified by the synthesis of a new nitroxide diradical. An interaction of perfluorobiphenyl with lithium tert-butylamide, followed by oxidation of the thusly formed N4,N4′-di-tert-butyl-2,2′,3,3′,5,5′,6,6′-octafluorobiphenyl-4,4′-diamine with meta-chloroperoxybenzoic acid, led to the polyfluorinated nitroxide diradical, N,N′-(perfluorobiphenyl-4,4′-diyl)bis(N-tert-butyl(oxyl)amine), with a good total yield. The polyfluorinated diradical is stable and can be isolated in free form and completely characterized. The structure of the nitroxide diradical was proved by single-crystal X-ray diffraction analysis. According to the X-ray diffraction data, the diradical is considerably twisted: dihedral angles between the planes of the nitroxide groups and aromatic cycles are 65.1° and 69.5°, and between aromatic cycles 52.6°. Quantum chemical calculations predict well-balanced size of both intramolecular and intermolecular exchange interactions with J from −2.65 to −1.14 cm−1. Full article
(This article belongs to the Special Issue Stable Organic Radicals)
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13 pages, 4430 KiB  
Article
Modulation of Macrophage Polarization by Phospholipids on the Surface of Titanium
by Hongxuan Quan, Yongjoon Kim, Lele Wu, Hee-Chul Park and Hyeong-Cheol Yang
Molecules 2020, 25(11), 2700; https://doi.org/10.3390/molecules25112700 - 10 Jun 2020
Cited by 9 | Viewed by 3255
Abstract
Macrophage polarization has become increasingly important for the improvement of the biocompatibility of biomaterials. In this study, we coated Ti discs with phospholipids (phosphatidylserine/phosphatidylcholine [4:1 mole/mole]) by evaporating the solvent under vacuum, and observed the polarization of RAW 264.7 cells cultured on the [...] Read more.
Macrophage polarization has become increasingly important for the improvement of the biocompatibility of biomaterials. In this study, we coated Ti discs with phospholipids (phosphatidylserine/phosphatidylcholine [4:1 mole/mole]) by evaporating the solvent under vacuum, and observed the polarization of RAW 264.7 cells cultured on the discs. The coated discs were hydrated before cell culture was added. The shape of the hydrated phospholipids varied with the concentration of loaded phospholipids: a perforated layer (0.1 mM), tubules and spheres (1 mM), and spheres (10 mM). RAW 264.7 cells exhibited different morphologies, depending on the concentration of phospholipids. On the coated discs, the gene expression and protein release of TGF-β1, VEGF, Arg-1, and TNF-α were downregulated, especially with 10 mM phospholipids. The stimulation of mRNA expression and the protein release of those genes by IL-4 and LPS were also disturbed on the phospholipid-coated discs. In conclusion, the polarization of RAW 264.7 cells was prevented by hydrated phospholipids on Ti discs. Full article
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25 pages, 2481 KiB  
Review
Nanomaterials for Wound Dressings: An Up-to-Date Overview
by Alexandra Elena Stoica, Cristina Chircov and Alexandru Mihai Grumezescu
Molecules 2020, 25(11), 2699; https://doi.org/10.3390/molecules25112699 - 10 Jun 2020
Cited by 119 | Viewed by 9462
Abstract
As wound healing continues to be a challenge for the medical field, wound management has become an essential factor for healthcare systems. Nanotechnology is a domain that could provide different new approaches concerning regenerative medicine. It is worth mentioning the importance of nanoparticles, [...] Read more.
As wound healing continues to be a challenge for the medical field, wound management has become an essential factor for healthcare systems. Nanotechnology is a domain that could provide different new approaches concerning regenerative medicine. It is worth mentioning the importance of nanoparticles, which, when embedded in biomaterials, can induce specific properties that make them of interest in applications as materials for wound dressings. In the last years, nano research has taken steps to develop molecular engineering strategies for different self-assembling biocompatible nanoparticles. It is well-known that nanomaterials can improve burn treatment and also the delayed wound healing process. In this review, the first-line of bioactive nanomaterials-based dressing categories frequently applied in clinical practice, including semi-permeable films, semipermeable foam dressings, hydrogel dressings, hydrocolloid dressings, alginate dressings, non-adherent contact layer dressings, and multilayer dressings will be discussed. Additionally, this review will highlight the lack of high-quality evidence and the necessity for future advanced trials because current wound healing therapies generally fail to provide an excellent clinical outcome, either structurally or functionally. The use of nanomaterials in wound management represents a unique tool that can be specifically designed to closely reflect the underlying physiological processes in tissue repair. Full article
(This article belongs to the Special Issue 25th Anniversary of Molecules—Recent Advances in Nanochemistry)
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9 pages, 1330 KiB  
Article
Laser-Inscribed Diamond Waveguide Resonantly Coupled to Diamond Microsphere
by Nurperi Yavuz, Mustafa Mert Bayer, Hüseyin Ozan Ҫirkinoğlu, Ali Serpengüzel, Thien Le Phu, Argyro Giakoumaki, Vibhav Bharadwaj, Roberta Ramponi and Shane M. Eaton
Molecules 2020, 25(11), 2698; https://doi.org/10.3390/molecules25112698 - 10 Jun 2020
Cited by 3 | Viewed by 2708
Abstract
An all-diamond photonic circuit was implemented by integrating a diamond microsphere with a femtosecond-laser-written bulk diamond waveguide. The near surface waveguide was fabricated by exploiting the Type II fabrication method to achieve stress-induced waveguiding. Transverse electrically and transverse magnetically polarized light from a [...] Read more.
An all-diamond photonic circuit was implemented by integrating a diamond microsphere with a femtosecond-laser-written bulk diamond waveguide. The near surface waveguide was fabricated by exploiting the Type II fabrication method to achieve stress-induced waveguiding. Transverse electrically and transverse magnetically polarized light from a tunable laser operating in the near-infrared region was injected into the diamond waveguide, which when coupled to the diamond microsphere showed whispering-gallery modes with a spacing of 0.33 nm and high-quality factors of 105. By carefully engineering these high-quality factor resonances, and further exploiting the properties of existing nitrogen-vacancy centers in diamond microspheres and diamond waveguides in such configurations, it should be possible to realize filtering, sensing and nonlinear optical applications in integrated diamond photonics. Full article
(This article belongs to the Special Issue Crystallography and Crystal Chemistry)
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20 pages, 4675 KiB  
Article
Phenylacetonitrile (C6H5CH2CN) Ionic Liquid Blends as Alternative Electrolytes for Safe and High-Performance Supercapacitors
by Flavien Ivol, Marina Porcher, Arunabh Ghosh, Johan Jacquemin and Fouad Ghamouss
Molecules 2020, 25(11), 2697; https://doi.org/10.3390/molecules25112697 - 10 Jun 2020
Cited by 10 | Viewed by 4106
Abstract
The increasing need in the development of storage devices is calling for the formulation of alternative electrolytes, electrochemically stable and safe over a wide range of conditions. To achieve this goal, electrolyte chemistry must be explored to propose alternative solvents and salts to [...] Read more.
The increasing need in the development of storage devices is calling for the formulation of alternative electrolytes, electrochemically stable and safe over a wide range of conditions. To achieve this goal, electrolyte chemistry must be explored to propose alternative solvents and salts to the current acetonitrile (ACN) and tetraethylammonium tetrafluoroborate (Et4NBF4) benchmarks, respectively. Herein, phenylacetonitrile (Ph-ACN) has been proposed as a novel alternative solvent to ACN in supercapacitors. To establish the main advantages and drawbacks of such a substitution, Ph-ACN + Et4NBF4 blends were formulated and characterized prior to being compared with the benchmark electrolyte and another alternative electrolyte based on adiponitrile (ADN). While promising results were obtained, the low Et4NBF4 solubility in Ph-ACN seems to be the main limiting factor. To solve such an issue, an ionic liquid (IL), namely 1-ethyl-3-methylimidazolium bis [(trifluoromethyl)sulfonyl] imide (EmimTFSI), was proposed to replace Et4NBF4. Unsurprisingly, the Ph-ACN + EmimTFSI blend was found to be fully miscible over the whole range of composition giving thus the flexibility to optimize the electrolyte formulation over a large range of IL concentrations up to 4.0 M. The electrolyte containing 2.7 M of EmimTFSI in Ph-ACN was identified as the optimized blend thanks to its interesting transport properties. Furthermore, this blend possesses also the prerequisites of a safe electrolyte, with an operating liquid range from at least −60 °C to +130 °C, and operating window of 3.0 V and more importantly, a flash point of 125 °C. Finally, excellent electrochemical performances were observed by using this electrolyte in a symmetric supercapacitor configuration, showing another advantage of mixing an ionic liquid with Ph-ACN. We also supported key structural descriptors by density functional theory (DFT) and COnductor-like Screening Model for Real Solvents (COSMO-RS) calculations, which can be associated to physical and electrochemical properties of the resultant electrolytes. Full article
(This article belongs to the Special Issue Ionic Liquids, from Their Synthesis to Their Applications)
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16 pages, 2879 KiB  
Article
Plant Extracts Containing Saponins Affects the Stability and Biological Activity of Hempseed Oil Emulsion System
by Maciej Jarzębski, Przemysław Siejak, Wojciech Smułek, Farahnaz Fathordoobady, Yigong Guo, Jarosław Pawlicz, Tomasz Trzeciak, Przemysław Łukasz Kowalczewski, David D. Kitts, Anika Singh and Anubhav Pratap Singh
Molecules 2020, 25(11), 2696; https://doi.org/10.3390/molecules25112696 - 10 Jun 2020
Cited by 25 | Viewed by 4441
Abstract
In this study, two saponins-rich plant extracts, viz. Saponaria officinalis and Quillaja saponaria, were used as surfactants in an oil-in-water (O/W) emulsion based on hempseed oil (HSO). This study focused on a low oil phase content of 2% v/v HSO [...] Read more.
In this study, two saponins-rich plant extracts, viz. Saponaria officinalis and Quillaja saponaria, were used as surfactants in an oil-in-water (O/W) emulsion based on hempseed oil (HSO). This study focused on a low oil phase content of 2% v/v HSO to investigate stable emulsion systems under minimum oil phase conditions. Emulsion stability was characterized by the emulsification index (EI), centrifugation tests, droplet size distribution as well as microscopic imaging. The smallest droplets recorded by dynamic light scattering (droplets size v. number), one day after the preparation of the emulsion, were around 50–120 nm depending the on use of Saponaria and Quillaja as a surfactant and corresponding to critical micelle concentration (CMC) in the range 0–2 g/L. The surface and interfacial tension of the emulsion components were studied as well. The effect of emulsions on environmental bacteria strains was also investigated. It was observed that emulsions with Saponaria officinalis extract exhibited slight toxic activity (the cell metabolic activity reduced to 80%), in contrast to Quillaja emulsion, which induced Pseudomonas fluorescens ATCC 17400 growth. The highest-stability samples were those with doubled CMC concentration. The presented results demonstrate a possible use of oil emulsions based on plant extract rich in saponins for the food industry, biomedical and cosmetics applications, and nanoemulsion preparations. Full article
(This article belongs to the Special Issue Bioactive Compounds of Fruits, Vegetables and Mushrooms)
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17 pages, 5298 KiB  
Article
In Vivo Wound Healing and In Vitro Anti-Inflammatory Activity Evaluation of Phlomis russeliana Extract Gel Formulations
by Mehmet Evren Okur, Ayşe Esra Karadağ, Neslihan Üstündağ Okur, Yağmur Özhan, Hande Sipahi, Şule Ayla, Benay Daylan, Betül Demirci and Fatih Demirci
Molecules 2020, 25(11), 2695; https://doi.org/10.3390/molecules25112695 - 10 Jun 2020
Cited by 26 | Viewed by 4522
Abstract
The air-dried aerial parts of Phlomis russeliana (Sims) Lag. Ex Benth. was extracted by methanol and fractionated by n-hexane, dichloromethane, and ethyl acetate, respectively. The wound healing properties of P. russeliana extract gel was evaluated using the in vivo excisional wound model [...] Read more.
The air-dried aerial parts of Phlomis russeliana (Sims) Lag. Ex Benth. was extracted by methanol and fractionated by n-hexane, dichloromethane, and ethyl acetate, respectively. The wound healing properties of P. russeliana extract gel was evaluated using the in vivo excisional wound model using Balb-c mice. Initially, the P. russeliana methanol extract showed LOX inhibitory activity at IC50 = 23.2 µg/mL, whereas the DPPH assay showed IC50 = 0.89 mg/mL, and the ABTS assay showed IC50 = 0.99 mg/mL, respectively. In addition, a remarkable anti-inflammatory activity was observed in the cell culture assay. Thereafter, activity-guided fractionation was performed by LOX enzyme inhibition assays, and the structures of the two most active fractions were revealed by both GC–FID and GC/MS analyses, simultaneously. Phytol and 1-heptadecanoic acid were characterized as the active constituents. Moreover, the P. russeliana extract gel formulation was applied for in vivo tests, where the new gel formulation supported the in vitro anti-inflammatory activity findings. As a conclusion, this experimental results support the wound healing evidence based on the ethnobotanical application of Phlomis species with further potential. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry II)
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21 pages, 2536 KiB  
Article
Computational Study of the Coupled Mechanism of Thermophoretic Transportation and Mixed Convection Flow around the Surface of a Sphere
by Amir Abbas, Muhammad Ashraf, Yu-Ming Chu, Saqib Zia, Ilyas Khan and Kottakkaran Sooppy Nisar
Molecules 2020, 25(11), 2694; https://doi.org/10.3390/molecules25112694 - 10 Jun 2020
Cited by 23 | Viewed by 2556
Abstract
The main goal of the current work was to study the coupled mechanism of thermophoretic transportation and mixed convection flow around the surface of the sphere. To analyze the characteristics of heat and fluid flow in the presence of thermophoretic transportation, a mathematical [...] Read more.
The main goal of the current work was to study the coupled mechanism of thermophoretic transportation and mixed convection flow around the surface of the sphere. To analyze the characteristics of heat and fluid flow in the presence of thermophoretic transportation, a mathematical model in terms of non-linear coupled partial differential equations obeying the laws of conservation was formulated. Moreover, the mathematical model of the proposed phenomena was approximated by implementing the finite difference scheme and boundary value problem of fourth order code BVP4C built-in scheme. The novelty point of this paper is that the primitive variable formulation is introduced to transform the system of partial differential equations into a primitive form to make the line of the algorithm smooth. Secondly, the term thermophoretic transportation in the mass equation is introduced in the mass equation and thus the effect of thermophoretic transportation can be calculated at different positions of the sphere. Basically, in this study, some favorite positions around the sphere were located, where the velocity field, temperature distribution, mass concentration, skin friction, and rate of heat transfer can be calculated simultaneously without any separation in flow around the surface of the sphere. Full article
(This article belongs to the Special Issue Applications of Computational Fluid Dynamics)
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18 pages, 3008 KiB  
Article
Effect of Supplementation with Hydroethanolic Extract of Campomanesia xanthocarpa (Berg.) Leaves and Two Isolated Substances from the Extract on Metabolic Parameters of Mice Fed a High-Fat Diet
by Carla Maiara Lopes Cardozo, Aline Carla Inada, Claudia Andrea Lima Cardoso, Wander Fernando de Oliveira Filiú, Bernardo Barcelar de Farias, Flávio Macedo Alves, Mariana Bento Tatara, Júlio Henrique Rosa Croda, Rita de Cássia Avellaneda Guimarães, Priscila Aiko Hiane and Karine de Cássia Freitas
Molecules 2020, 25(11), 2693; https://doi.org/10.3390/molecules25112693 - 10 Jun 2020
Cited by 5 | Viewed by 2861
Abstract
There are still controversies regarding the correlation between the beneficial effects for health and the administration of isolated compounds or crude extracts in therapeutic applications. Campomanesia xanthocarpa, found in the Brazilian Cerrado, demonstrated beneficial effects in metabolic disorders associated with obesity. We [...] Read more.
There are still controversies regarding the correlation between the beneficial effects for health and the administration of isolated compounds or crude extracts in therapeutic applications. Campomanesia xanthocarpa, found in the Brazilian Cerrado, demonstrated beneficial effects in metabolic disorders associated with obesity. We investigated the effects of Campomanesia xanthocarpa hydroethanolic extract and two isolated substances from the extract (S1 and S2) in a diet-induced obesity (DIO) model. Male Swiss mice were divided into five groups: (1) American Institute of Nutrition (AIN-93M) diet, (2) high-fat diet (HF), (3) HF supplemented with C. xanthocarpa hydroethanolic leaf extract at 100 mg/kg (HFE), (4) HF supplemented with S1 at 1 mg/kg (HFS1) and (5) HF supplemented with S2 at 1 mg/kg (HFS2). The HFS1, HFS2 and HFE groups did not present decreasing body weight or visceral adiposity gain. No differences in glycemic and lipid parameters, or in the expression of protein content in two cytokines, interleukin-6 (IL-6) and anti-inflammatory (IL-10), were observed. Only the HFS1 group displayed decreased food intake. Even though substantial effects such as an improvement in obesity features or the metabolic and histological parameters promoted by S1, S2 and the extract were not observed, further investigations are necessary to evaluate the principal genes and protein expressions involved in regulating food behavior promoted by S1. Full article
(This article belongs to the Special Issue Biological Activities of Medicinal Plants)
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18 pages, 900 KiB  
Review
Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy
by Francesco Mainini and Michael R. Eccles
Molecules 2020, 25(11), 2692; https://doi.org/10.3390/molecules25112692 - 10 Jun 2020
Cited by 98 | Viewed by 9905
Abstract
RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor [...] Read more.
RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor and/or host cells in the tumor micro-environment (TME). Consequently, lipid and polymer-based nanoparticle siRNA delivery systems have been developed to surmount these physiological barriers. In this article, we review the strategies that have been developed to facilitate siRNA survival in the circulatory system, siRNA movement from the blood into tissues and the TME, targeted siRNA delivery to the tumor or specific cell types, cellular uptake, and escape from endosomal degradation. We also discuss the use of various types of lipid and polymer-based carriers for cancer therapy, including a section on anti-tumor nanovaccines enhanced by siRNAs. Finally, we review current and recent clinical trials using NPs loaded with siRNAs for cancer therapy. The siRNA cancer therapeutics field is rapidly evolving, and it is conceivable that precision cancer therapy could, in the relatively near future, benefit from the combined use of cancer therapies, for example immune checkpoint blockade together with gene-targeting siRNAs, personalized for enhancing and fine-tuning a patient’s therapeutic response. Full article
(This article belongs to the Special Issue Advances in Therapeutic RNA Design and Delivery)
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20 pages, 4055 KiB  
Article
Developing an Improved UHPLC Method for Efficient Determination of European Pharmacopeia Process-Related Impurities in Ropinirole Hydrochloride Using Analytical Quality by Design Principles
by Tim Tome, Aleš Obreza and Zdenko Časar
Molecules 2020, 25(11), 2691; https://doi.org/10.3390/molecules25112691 - 10 Jun 2020
Cited by 6 | Viewed by 3146
Abstract
This article presents the development of a reversed-phase ultra-high-performance liquid chromatographic method for determining process-related impurities in ropinirole hydrochloride drug substance applying the analytical quality by design approach. The current pharmacopeial method suffers from selectivity issues due to two coelutions of two pairs [...] Read more.
This article presents the development of a reversed-phase ultra-high-performance liquid chromatographic method for determining process-related impurities in ropinirole hydrochloride drug substance applying the analytical quality by design approach. The current pharmacopeial method suffers from selectivity issues due to two coelutions of two pairs of impurities. The development of a new method began with preliminary experiments, based on which the Acquity UPLC BEH C8 was selected as the most appropriate column. The effects of six different critical method parameters (CMPs) were then investigated using a fractional factorial screening design. Column temperature, the ratio of methanol in mobile phase B, and gradient slope turned out to be highly significant CMPs in achieving critical resolutions, and they were further evaluated using a central composite face-centered response-surface design. Mathematical models were created by applying a multiple linear regression method. Based on the elution order of an unknown degradation impurity and impurity C, two design spaces were established, and for each design space an optimal combination of CMPs was determined. The method developed was validated for precision, accuracy, linearity, and sensitivity, and it was proven suitable for determining nine process-related impurities of ropinirole. Full article
(This article belongs to the Special Issue Drug Analysis in Pharmaceutical Development and Drug Manufacturing)
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11 pages, 440 KiB  
Communication
In Vitro Metabolic Transformation of Pharmaceuticals by Hepatic S9 Fractions from Common Carp (Cyprinus carpio)
by Viktoriia Burkina, Sidika Sakalli, Pham Thai Giang, Kateřina Grabicová, Andrea Vojs Staňová, Galia Zamaratskaia and Vladimir Zlabek
Molecules 2020, 25(11), 2690; https://doi.org/10.3390/molecules25112690 - 10 Jun 2020
Cited by 2 | Viewed by 3316
Abstract
Water from wastewater treatment plants contains concentrations of pharmaceutically active compounds as high as micrograms per liter, which can adversely affect fish health and behavior, and contaminate the food chain. Here, we tested the ability of the common carp hepatic S9 fraction to [...] Read more.
Water from wastewater treatment plants contains concentrations of pharmaceutically active compounds as high as micrograms per liter, which can adversely affect fish health and behavior, and contaminate the food chain. Here, we tested the ability of the common carp hepatic S9 fraction to produce the main metabolites from citalopram, metoprolol, sertraline, and venlafaxine. Metabolism in fish S9 fractions was compared to that in sheep. The metabolism of citalopram was further studied in fish. Our results suggest a large difference in the rate of metabolites formation between fish and sheep. Fish hepatic S9 fractions do not show an ability to form metabolites from venlafaxine, which was also the case for sheep. Citalopram, metoprolol, and sertraline were metabolized by both fish and sheep S9. Citalopram showed concentration-dependent N-desmethylcitalopram formation with Vmax = 1781 pmol/min/mg and Km = 29.7 μM. The presence of ellipticine, a specific CYP1A inhibitor, in the incubations reduced the formation of N-desmethylcitalopram by 30–100% depending on the applied concentration. These findings suggest that CYP1A is the major enzyme contributing to the formation of N-desmethylcitalopram. In summary, the results from the present in vitro study suggest that common carp can form the major metabolites of citalopram, metoprolol, and sertraline. Full article
(This article belongs to the Special Issue Drugs in the Environment—Risks and Solutions)
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