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Molecules, Volume 25, Issue 17 (September-1 2020) – 269 articles

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Cover Story (view full-size image) Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) stands out from other plasma membrane lipids as [...] Read more.
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Open AccessFeature PaperArticle
Evaluation of Self-Assembly Pathways to Control Crystallization-Driven Self-Assembly of a Semicrystalline P(VDF-co-HFP)-b-PEG-b-P(VDF-co-HFP) Triblock Copolymer
Molecules 2020, 25(17), 4033; https://doi.org/10.3390/molecules25174033 - 03 Sep 2020
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Abstract
To date, amphiphilic block copolymers (BCPs) containing poly(vinylidene fluoride-co-hexafluoropropene) (P(VDF-co-HFP)) copolymers are rare. At moderate content of HFP, this fluorocopolymer remains semicrystalline and is able to crystallize. Amphiphilic BCPs, containing a P(VDF-co-HFP) segment could, thus be appealing for the [...] Read more.
To date, amphiphilic block copolymers (BCPs) containing poly(vinylidene fluoride-co-hexafluoropropene) (P(VDF-co-HFP)) copolymers are rare. At moderate content of HFP, this fluorocopolymer remains semicrystalline and is able to crystallize. Amphiphilic BCPs, containing a P(VDF-co-HFP) segment could, thus be appealing for the preparation of self-assembled block copolymer morphologies through crystallization-driven self-assembly (CDSA) in selective solvents. Here the synthesis, characterization by 1H and 19F NMR spectroscopies, GPC, TGA, DSC, and XRD; and the self-assembly behavior of a P(VDF-co-HFP)-b-PEG-b-P(VDF-co-HFP) triblock copolymer were studied. The well-defined ABA amphiphilic fluorinated triblock copolymer was self-assembled into nano-objects by varying a series of key parameters such as the solvent and the non -solvent, the self-assembly protocols, and the temperature. A large range of morphologies such as spherical, square, rectangular, fiber-like, and platelet structures with sizes ranging from a few nanometers to micrometers was obtained depending on the self-assembly protocols and solvents systems used. The temperature-induced crystallization-driven self-assembly (TI-CDSA) protocol allowed some control over the shape and size of some of the morphologies. Full article
(This article belongs to the Special Issue Organofluorine Chemistry)
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Open AccessReview
Ethiopian Medicinal Plants Traditionally Used for the Treatment of Cancer, Part 2: A Review on Cytotoxic, Antiproliferative, and Antitumor Phytochemicals, and Future Perspective
Molecules 2020, 25(17), 4032; https://doi.org/10.3390/molecules25174032 - 03 Sep 2020
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Abstract
This review provides an overview on the active phytochemical constituents of medicinal plants that are traditionally used to manage cancer in Ethiopia. A total of 119 articles published between 1968 and 2020 have been reviewed, using scientific search engines such as ScienceDirect, PubMed, [...] Read more.
This review provides an overview on the active phytochemical constituents of medicinal plants that are traditionally used to manage cancer in Ethiopia. A total of 119 articles published between 1968 and 2020 have been reviewed, using scientific search engines such as ScienceDirect, PubMed, and Google Scholar. Twenty-seven medicinal plant species that belong to eighteen families are documented along with their botanical sources, potential active constituents, and in vitro and in vivo activities against various cancer cells. The review is compiled and discusses the potential anticancer, antiproliferative, and cytotoxic agents based on the types of secondary metabolites, such as terpenoids, phenolic compounds, alkaloids, steroids, and lignans. Among the anticancer secondary metabolites reported in this review, only few have been isolated from plants that are originated and collected in Ethiopia, and the majority of compounds are reported from plants belonging to different areas of the world. Thus, based on the available bioactivity reports, extensive and more elaborate ethnopharmacology-based bioassay-guided studies have to be conducted on selected traditionally claimed Ethiopian anticancer plants, which inherited from a unique and diverse landscape, with the aim of opening a way forward to conduct anticancer drug discovery program. Full article
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Open AccessReview
Peptidyl Fluoromethyl Ketones and Their Applications in Medicinal Chemistry
Molecules 2020, 25(17), 4031; https://doi.org/10.3390/molecules25174031 - 03 Sep 2020
Viewed by 259
Abstract
Peptidyl fluoromethyl ketones occupy a pivotal role in the current scenario of synthetic chemistry, thanks to their numerous applications as inhibitors of hydrolytic enzymes. The insertion of one or more fluorine atoms adjacent to a C-terminal ketone moiety greatly modifies the physicochemical [...] Read more.
Peptidyl fluoromethyl ketones occupy a pivotal role in the current scenario of synthetic chemistry, thanks to their numerous applications as inhibitors of hydrolytic enzymes. The insertion of one or more fluorine atoms adjacent to a C-terminal ketone moiety greatly modifies the physicochemical properties of the overall substrate, especially by increasing the reactivity of this functionalized carbonyl group toward nucleophiles. The main application of these peptidyl α-fluorinated ketones in medicinal chemistry relies in their ability to strongly and selectively inhibit serine and cysteine proteases. These compounds can be used as probes to study the proteolytic activity of the aforementioned proteases and to elucidate their role in the insurgence and progress on several diseases. Likewise, if the fluorinated methyl ketone moiety is suitably connected to a peptidic backbone, it may confer to the resulting structure an excellent substrate peculiarity and the possibility of being recognized by a specific subclass of human or pathogenic proteases. Therefore, peptidyl fluoromethyl ketones are also currently highly exploited for the target-based design of compounds for the treatment of topical diseases such as various types of cancer and viral infections. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle
Construction of Molecular Model and Adsorption of Collectors on Bulianta Coal
Molecules 2020, 25(17), 4030; https://doi.org/10.3390/molecules25174030 - 03 Sep 2020
Viewed by 228
Abstract
To study the effects of different oxygen functional groups on the quality of flotation clean low-rank coal, two kinds of collectors with different oxygen-containing functional groups, methyl laurate, and dodecanol, were selected and their flotation behaviors were investigated. The Bulianta coal was the [...] Read more.
To study the effects of different oxygen functional groups on the quality of flotation clean low-rank coal, two kinds of collectors with different oxygen-containing functional groups, methyl laurate, and dodecanol, were selected and their flotation behaviors were investigated. The Bulianta coal was the typical sub-bituminous coal in China, and the coal molecular model of which was constructed based on proximate analysis, ultimate analysis, 13C-NMR, and XPS. The chemical structure model of the coal molecule was optimized, and the periodic boundary condition was added via the method of molecular dynamics methods. The different combined systems formed by collectors, water, and a model surface of Bulianta coal have been studied using molecular dynamics simulation. The simulation results of dodecanol and methyl laurate on the surface of Bulianta coal show that dodecanol molecules are not evenly adsorbed on the surface of coal, and have higher adsorption capacity near carboxyl and hydroxyl groups, but less adsorption capacity near carbonyl and ether bonds. Methyl laurate can completely cover the oxygen-containing functional groups on the coal surface. Compared with dodecanol, methyl laurate can effectively improve the hydrophobicity of the Bulianta coal surface, which is consistent with the results of the XPS test and the flotation test. Full article
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Open AccessArticle
On Viscous Flow in Glass-Forming Organic Liquids
Molecules 2020, 25(17), 4029; https://doi.org/10.3390/molecules25174029 - 03 Sep 2020
Viewed by 342
Abstract
The two-exponential Sheffield equation of viscosity η(T) = A1·T·[1 + A2·exp(Hm/RT)]·[1 + C·exp(Hd/RT)], where A1, A2, Hm, C, and Hm are material-specific constants, is used to analyze the [...] Read more.
The two-exponential Sheffield equation of viscosity η(T) = A1·T·[1 + A2·exp(Hm/RT)]·[1 + C·exp(Hd/RT)], where A1, A2, Hm, C, and Hm are material-specific constants, is used to analyze the viscous flows of two glass-forming organic materials—salol and α-phenyl-o-cresol. It is demonstrated that the viscosity equation can be simplified to a four-parameter version: η(T) = A·T·exp(Hm/RT)]·[1 + C·exp(Hd/RT)]. The Sheffield model gives a correct description of viscosity, with two exact Arrhenius-type asymptotes below and above the glass transition temperature, whereas near the Tg it gives practically the same results as well-known and widely used viscosity equations. It is revealed that the constants of the Sheffield equation are not universal for all temperature ranges and may need to be updated for very high temperatures, where changes occur in melt properties leading to modifications of A and Hm for both salol and α-phenyl-o-cresol. Full article
(This article belongs to the Special Issue Physical Chemistry of Aqueous Solutions and Glass Forming Systems)
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Open AccessReview
Interacting Quantum Atoms—A Review
Molecules 2020, 25(17), 4028; https://doi.org/10.3390/molecules25174028 - 03 Sep 2020
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Abstract
The aim of this review is threefold. On the one hand, we intend it to serve as a gentle introduction to the Interacting Quantum Atoms (IQA) methodology for those unfamiliar with it. Second, we expect it to act as an up-to-date reference of [...] Read more.
The aim of this review is threefold. On the one hand, we intend it to serve as a gentle introduction to the Interacting Quantum Atoms (IQA) methodology for those unfamiliar with it. Second, we expect it to act as an up-to-date reference of recent developments related to IQA. Finally, we want it to highlight a non-exhaustive, yet representative set of showcase examples about how to use IQA to shed light in different chemical problems. To accomplish this, we start by providing a brief context to justify the development of IQA as a real space alternative to other existent energy partition schemes of the non-relativistic energy of molecules. We then introduce a self-contained algebraic derivation of the methodological IQA ecosystem as well as an overview of how these formulations vary with the level of theory employed to obtain the molecular wavefunction upon which the IQA procedure relies. Finally, we review the several applications of IQA as examined by different research groups worldwide to investigate a wide variety of chemical problems. Full article
(This article belongs to the Special Issue Electron Density Analysis Tools)
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Open AccessArticle
IgY Targeting Bacterial Quorum-Sensing Molecules in Implant-Associated Infections
Molecules 2020, 25(17), 4027; https://doi.org/10.3390/molecules25174027 - 03 Sep 2020
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Abstract
Background: Implant-associated infections are still a major complication in the field of orthopedics. Bacteria can form biofilms on implant surfaces, making them more difficult to detect and treat. Since standard antibiotic therapy is often impaired in biofilm infections, particular interest is directed [...] Read more.
Background: Implant-associated infections are still a major complication in the field of orthopedics. Bacteria can form biofilms on implant surfaces, making them more difficult to detect and treat. Since standard antibiotic therapy is often impaired in biofilm infections, particular interest is directed towards finding treatment alternatives. Biofilm-formation is a well-organized process during which bacteria communicate via quorum-sensing molecules (QSM). The aim of this study was to inhibit bacterial communication by directing avian IgY against specific QSM. Methods: Chicken were immunized against the following QSM: (1) AtlE, a member of the autolysin family which mediates attachment to a surface in Staphylococcus epidermidis; (2) GroEL, the bacterial heat shock protein; (3) PIA (polysaccharide intercellular adhesion), which is essential for cell–cell adhesion in biofilms. Staphylococcus epidermidis biofilms were grown and inhibition of biofilm-formation by IgYs was evaluated. Additionally, human osteoblasts were cultivated and biocompatibility of IgYs was tested. Results: We were able to demonstrate that all IgYs reduced biofilm-formation, also without prior immunization. Therefore, the response was probably not specific with regard to the QSM. Osteoblasts were activated by all IgYs which was demonstrated by microscopy and an increased release of IL-8. Conclusions: In conclusion, avian IgY inhibits biofilm-formation, though the underlying mechanism is not yet clear. However, adverse effects on local tissue cells (osteoblasts) were also observed. Full article
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Open AccessReview
Review of Chromatographic Methods Coupled with Modern Detection Techniques Applied in the Therapeutic Drugs Monitoring (TDM)
Molecules 2020, 25(17), 4026; https://doi.org/10.3390/molecules25174026 - 03 Sep 2020
Viewed by 272
Abstract
Therapeutic drug monitoring (TDM) is a tool used to integrate pharmacokinetic and pharmacodynamics knowledge to optimize and personalize various drug therapies. The optimization of drug dosing may improve treatment outcomes, reduce toxicity, and reduce the risk of developing drug resistance. To adequately implement [...] Read more.
Therapeutic drug monitoring (TDM) is a tool used to integrate pharmacokinetic and pharmacodynamics knowledge to optimize and personalize various drug therapies. The optimization of drug dosing may improve treatment outcomes, reduce toxicity, and reduce the risk of developing drug resistance. To adequately implement TDM, accurate and precise analytical procedures are required. In clinical practice, blood is the most commonly used matrix for TDM; however, less invasive samples, such as dried blood spots or non-invasive saliva samples, are increasingly being used. The choice of sample preparation method, type of column packing, mobile phase composition, and detection method is important to ensure accurate drug measurement and to avoid interference from matrix effects and drug metabolites. Most of the reported procedures used liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) techniques due to its high selectivity and sensitivity. High-performance chromatography with ultraviolet detection (HPLC-UV) methods are also used when a simpler and more cost-effective methodology is desired for clinical monitoring. The application of high-performance chromatography with fluorescence detection (HPLC-FLD) with and without derivatization processes and high-performance chromatography with electrochemical detection (HPLC-ED) techniques for the analysis of various drugs in biological samples for TDM have been described less often. Before chromatographic analysis, samples were pretreated by various procedures—most often by protein precipitation, liquid–liquid extraction, and solid-phase extraction, rarely by microextraction by packed sorbent, dispersive liquid–liquid microextraction. The aim of this article is to review the recent literature (2010–2020) regarding the use of liquid chromatography with various detection techniques for TDM. Full article
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Open AccessFeature PaperArticle
Mechanistic Insights into the Chaperoning of Human Lysosomal-Galactosidase Activity: Highly Functionalized Aminocyclopentanes and C-5a-Substituted Derivatives of 4-epi-Isofagomine
Molecules 2020, 25(17), 4025; https://doi.org/10.3390/molecules25174025 - 03 Sep 2020
Viewed by 241
Abstract
Glycosidase inhibitors have shown great potential as pharmacological chaperones for lysosomal storage diseases. In light of this, a series of new cyclopentanoid β-galactosidase inhibitors were prepared and their inhibitory and pharmacological chaperoning activities determined and compared with those of lipophilic analogs of the [...] Read more.
Glycosidase inhibitors have shown great potential as pharmacological chaperones for lysosomal storage diseases. In light of this, a series of new cyclopentanoid β-galactosidase inhibitors were prepared and their inhibitory and pharmacological chaperoning activities determined and compared with those of lipophilic analogs of the potent β-d-galactosidase inhibitor 4-epi-isofagomine. Structure-activity relationships were investigated by X-ray crystallography as well as by alterations in the cyclopentane moiety such as deoxygenation and replacement by fluorine of a “strategic” hydroxyl group. New compounds have revealed highly promising activities with a range of β-galactosidase-compromised human cell lines and may serve as leads towards new pharmacological chaperones for GM1-gangliosidosis and Morquio B disease. Full article
(This article belongs to the Special Issue Targeting Carbohydrate–Protein Interactions)
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Open AccessArticle
Qualitative and Quantitative Study of Glycosphingolipids in Human Milk and Bovine Milk Using High Performance Liquid Chromatography–Data-Dependent Acquisition–Mass Spectrometry
Molecules 2020, 25(17), 4024; https://doi.org/10.3390/molecules25174024 - 03 Sep 2020
Viewed by 310
Abstract
Cerebrosides (Crb; including glucosylceramide and galactosylceramide) and lactosylceramide (LacCer) are structurally complex lipids found in many eukaryotic cell membranes, where they play important roles in cell growth, apoptosis, cell recognition and signaling. They are also found in mammalian milk as part of the [...] Read more.
Cerebrosides (Crb; including glucosylceramide and galactosylceramide) and lactosylceramide (LacCer) are structurally complex lipids found in many eukaryotic cell membranes, where they play important roles in cell growth, apoptosis, cell recognition and signaling. They are also found in mammalian milk as part of the milk fat globule membrane (MFGM), making milk an important dietary component for the rapidly growing infant. This study reports the development of a robust analytical method for the identification and characterization of 44 Crb and 23 LacCer molecular species in milk, using high performance liquid chromatography–tandem mass spectrometry in data-dependent acquisition mode. For the first time, it also compares the distributions of these species in human and bovine milks, a commercial MFGM-enriched dairy ingredient (MFGM Lipid 100) and commercial standards purified from bovine milk. A method for quantifying Crb and LacCer in milk using mass spectrometry in neutral loss scan mode was developed and validated for human milk, bovine milk and MFGM Lipid 100. Human milk was found to contain approximately 9.9–17.4 µg Crb/mL and 1.3–3.0 µg LacCer/mL, whereas bovine milk (pooled milk from a Friesian herd) contained 9.8–12.0 and 14.3–16.2 µg/mL of these lipids, respectively. The process used to produce MFGM Lipid 100 was shown to have enriched these components to 448 and 1036 µg/g, respectively. No significant changes in the concentrations of both Crb and LacCer were observed during lactation. Full article
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Open AccessFeature PaperArticle
Spatial Metagenomics of Three Geothermal Sites in Pisciarelli Hot Spring Focusing on the Biochemical Resources of the Microbial Consortia
Molecules 2020, 25(17), 4023; https://doi.org/10.3390/molecules25174023 - 03 Sep 2020
Viewed by 292
Abstract
Terrestrial hot springs are of great interest to the general public and to scientists alike due to their unique and extreme conditions. These have been sought out by geochemists, astrobiologists, and microbiologists around the globe who are interested in their chemical properties, which [...] Read more.
Terrestrial hot springs are of great interest to the general public and to scientists alike due to their unique and extreme conditions. These have been sought out by geochemists, astrobiologists, and microbiologists around the globe who are interested in their chemical properties, which provide a strong selective pressure on local microorganisms. Drivers of microbial community composition in these springs include temperature, pH, in-situ chemistry, and biogeography. Microbes in these communities have evolved strategies to thrive in these conditions by converting hot spring chemicals and organic matter into cellular energy. Following our previous metagenomic analysis of Pisciarelli hot springs (Naples, Italy), we report here the comparative metagenomic study of three novel sites, formed in Pisciarelli as result of recent geothermal activity. This study adds comprehensive information about phylogenetic diversity within Pisciarelli hot springs by peeking into possible mechanisms of adaptation to biogeochemical cycles, and high applicative potential of the entire set of genes involved in the carbohydrate metabolism in this environment (CAZome). This site is an excellent model for the study of biodiversity on Earth and biosignature identification, and for the study of the origin and limits of life. Full article
(This article belongs to the Special Issue From Molecules to Origin of Life: The Astrobiology Network)
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Open AccessFeature PaperArticle
Colorimetry of Luminescent Lanthanide Complexes
Molecules 2020, 25(17), 4022; https://doi.org/10.3390/molecules25174022 - 03 Sep 2020
Viewed by 266
Abstract
Europium, terbium, dysprosium, and samarium are the main trivalent lanthanide ions emitting in the visible spectrum. In this work, the potential of these ions for colorimetric applications and colour reproduction was studied. The conversion of spectral data to colour coordinates was undertaken for [...] Read more.
Europium, terbium, dysprosium, and samarium are the main trivalent lanthanide ions emitting in the visible spectrum. In this work, the potential of these ions for colorimetric applications and colour reproduction was studied. The conversion of spectral data to colour coordinates was undertaken for three sets of Ln complexes composed of different ligands. We showed that Eu is the most sensitive of the visible Ln ions, regarding ligand-induced colour shifts, due to its hypersensitive transition. Further investigation on the spectral bandwidth of the emission detector, on the wavelengths’ accuracy, on the instrumental correction function, and on the use of incorrect intensity units confirm that the instrumental correction function is the most important spectrophotometric parameter to take into account in order to produce accurate colour values. Finally, we established and discussed the entire colour range (gamut) that can be generated by combining a red-emitting Eu complex with a green-emitting Tb complex and a blue fluorescent compound. The importance of choosing a proper white point is demonstrated. The potential of using different sets of complexes with different spectral fingerprints in order to obtain metameric colours suitable for anti-counterfeiting is also highlighted. This work answers many questions that could arise during a colorimetric analysis of luminescent probes. Full article
(This article belongs to the Special Issue Luminescent Lanthanide Complexes)
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Open AccessArticle
Enhancing the Performance of Dye Sensitized Solar Cells Using Silver Nanoparticles Modified Photoanode
Molecules 2020, 25(17), 4021; https://doi.org/10.3390/molecules25174021 - 03 Sep 2020
Viewed by 267
Abstract
In this study, silver nanoparticles were synthesized, characterized, and applied to a dye-sensitized solar cell (DSSC) to enhance the efficiency of solar cells. The synthesized silver nanoparticles were characterized with UV–Vis spectroscopy, dynamic light scattering, transmission electron microscopy, and field emission scanning electron [...] Read more.
In this study, silver nanoparticles were synthesized, characterized, and applied to a dye-sensitized solar cell (DSSC) to enhance the efficiency of solar cells. The synthesized silver nanoparticles were characterized with UV–Vis spectroscopy, dynamic light scattering, transmission electron microscopy, and field emission scanning electron microscopy. The silver nanoparticles infused titanium dioxide film was also characterized by Fourier transform infrared and Raman spectroscopy. The performance of DSSC fabricated with silver nanoparticle-modified photoanode was compared with that of a control group. The current and voltage characteristics of the devices as well as the electrochemical impedance measurements were also carried out to assess the performance of the fabricated solar cells. The solar-to-electric efficiency of silver nanoparticles based DSSC was 1.76%, which is quite remarkable compared to the 0.98% realized for DSSC fabricated without silver nanoparticles. Full article
(This article belongs to the Special Issue Photosensitizer: Design, Characteriazation and Application)
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Open AccessFeature PaperArticle
Unveiling the Differential Antioxidant Activity of Maslinic Acid in Murine Melanoma Cells and in Rat Embryonic Healthy Cells Following Treatment with Hydrogen Peroxide
Molecules 2020, 25(17), 4020; https://doi.org/10.3390/molecules25174020 - 03 Sep 2020
Viewed by 252
Abstract
Maslinic acid (MA) is a natural triterpene from Olea europaea L. with multiple biological properties. The aim of the present study was to examine MA’s effect on cell viability (by the MTT assay), reactive oxygen species (ROS levels, by flow cytometry) and key [...] Read more.
Maslinic acid (MA) is a natural triterpene from Olea europaea L. with multiple biological properties. The aim of the present study was to examine MA’s effect on cell viability (by the MTT assay), reactive oxygen species (ROS levels, by flow cytometry) and key antioxidant enzyme activities (by spectrophotometry) in murine skin melanoma (B16F10) cells compared to those on healthy cells (A10). MA induced cytotoxic effects in cancer cells (IC50 42 µM), whereas no effect was found in A10 cells treated with MA (up to 210 µM). In order to produce a stress situation in cells, 0.15 mM H2O2 was added. Under stressful conditions, MA protected both cell lines against oxidative damage, decreasing intracellular ROS, which were higher in B16F10 than in A10 cells. The treatment with H2O2 and without MA produced different responses in antioxidant enzyme activities depending on the cell line. In A10 cells, all the enzymes were up-regulated, but in B16F10 cells, only superoxide dismutase, glutathione S-transferase and glutathione peroxidase increased their activities. MA restored the enzyme activities to levels similar to those in the control group in both cell lines, highlighting that in A10 cells, the highest MA doses induced values lower than control. Overall, these findings demonstrate the great antioxidant capacity of MA. Full article
(This article belongs to the Special Issue Anticancer Properties of Natural and Derivative Products)
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Open AccessReview
A Review of the Ethnomedicinal Uses, Biological Activities, and Triterpenoids of Euphorbia Species
Molecules 2020, 25(17), 4019; https://doi.org/10.3390/molecules25174019 - 03 Sep 2020
Viewed by 258
Abstract
The genus Euphorbia is one of the largest genera in the spurge family, with diversity in range, distribution, and morphology. The plant species in this genus are widely used in traditional medicine for the treatment of diseases, ranging from respirational infections, body and [...] Read more.
The genus Euphorbia is one of the largest genera in the spurge family, with diversity in range, distribution, and morphology. The plant species in this genus are widely used in traditional medicine for the treatment of diseases, ranging from respirational infections, body and skin irritations, digestion complaints, inflammatory infections, body pain, microbial illness, snake or scorpion bites, pregnancy, as well as sensory disorders. Their successes have been attributed to the presence of diverse phytochemicals like polycyclic and macrocyclic diterpenes with various pharmacological properties. As a result, Euphorbia diterpenes are of interest to chemists and biochemists with regard to drug discovery from natural products due to their diverse therapeutic applications as well as their great structural diversity. Other chemical constituents such as triterpenoids have also been reported to possess various pharmacological properties, thus supporting the traditional uses of the Euphorbia species. These triterpenoids can provide potential leads that can be developed into pharmaceutical compounds for a wide range of medicinal applications. However, there are scattered scientific reports about the anticancer activities of these constituents. Harnessing such information could provide a database of bioactive pharmacopeia or targeted scaffolds for drug discovery. Therefore, this review presents an updated and comprehensive summary of the ethnomedicinal uses, phytochemistry, and the anticancer activities of the triterpenoids of Euphorbia species. Most of the reported triterpenoids in this review belong to tirucallane, cycloartanes, lupane, oleanane, ursane, and taraxane subclass. Their anticancer activities varied distinctly with the majority of them exhibiting significant cytotoxic and anticancer activities in vitro. It is, therefore, envisaged that the report on Euphorbia triterpenoids with interesting anticancer activities will form a database of potential leads or scaffolds that could be advanced into the clinical trials with regard to drug discovery. Full article
(This article belongs to the Special Issue Bioactive Compounds from Natural Sources 2020)
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Open AccessArticle
In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained from Boehmeria caudata Sw. Aerial Parts
Molecules 2020, 25(17), 4018; https://doi.org/10.3390/molecules25174018 - 03 Sep 2020
Viewed by 243
Abstract
In the context of the cancer-inflammation relationship and the use of natural products as potential antitumor and anti-inflammatory agents, the alkaloid-enriched fraction of Boehmeriacaudata (BcAEF) aerial parts was evaluated. In vitro antiproliferative studies with human tumor cell lines showed high activity at [...] Read more.
In the context of the cancer-inflammation relationship and the use of natural products as potential antitumor and anti-inflammatory agents, the alkaloid-enriched fraction of Boehmeriacaudata (BcAEF) aerial parts was evaluated. In vitro antiproliferative studies with human tumor cell lines showed high activity at low concentrations. Further investigation on NCI-H460 cells showed an irreversible effect on cell proliferation, with cell cycle arrest at G2/M phase and programmed cell death induction. Molecular docking studies of four alkaloids identified in BcAEF with colchicine’s binding site on β-tubulin were performed, suggesting (−)-C (15R)-hydroxycryptopleurine as the main inductor of the observed mitotic death. In vivo studies showed that BcAEF was able to reduce Ehrlich tumor volume progression by 30 to 40%. Checking myeloperoxidase activity, BcAEF reduced neutrophils migration towards the tumor. The in vivo anti-inflammatory activity was evaluated by chemically induced edema models. In croton oil-induced ear edema and carrageenan (CG)-induced paw edema models, BcAEF reduced edema around 70 to 80% together with inhibition of activation and/or migration of neutrophils to the inflammatory area. All together the results presented herein show BcAEF as a potent antitumor agent combining antiproliferative and anti-inflammatory properties, which could be further explored in (pre)clinical studies. Full article
(This article belongs to the Special Issue Current Trends in the Analysis of Medicinal Plants)
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Open AccessReview
PET Radiotracers for CNS-Adrenergic Receptors: Developments and Perspectives
Molecules 2020, 25(17), 4017; https://doi.org/10.3390/molecules25174017 - 03 Sep 2020
Viewed by 287
Abstract
Epinephrine (E) and norepinephrine (NE) play diverse roles in our body’s physiology. In addition to their role in the peripheral nervous system (PNS), E/NE systems including their receptors are critical to the central nervous system (CNS) and to mental health. Various antipsychotics, antidepressants, [...] Read more.
Epinephrine (E) and norepinephrine (NE) play diverse roles in our body’s physiology. In addition to their role in the peripheral nervous system (PNS), E/NE systems including their receptors are critical to the central nervous system (CNS) and to mental health. Various antipsychotics, antidepressants, and psychostimulants exert their influence partially through different subtypes of adrenergic receptors (ARs). Despite the potential of pharmacological applications and long history of research related to E/NE systems, research efforts to identify the roles of ARs in the human brain taking advantage of imaging have been limited by the lack of subtype specific ligands for ARs and brain penetrability issues. This review provides an overview of the development of positron emission tomography (PET) radiotracers for in vivo imaging of AR system in the brain. Full article
(This article belongs to the Special Issue Radiolabeled Compounds for Diagnosis and Treatment of Cancer)
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Open AccessArticle
Targeting the Initiator Protease of the Classical Pathway of Complement Using Fragment-Based Drug Discovery
Molecules 2020, 25(17), 4016; https://doi.org/10.3390/molecules25174016 - 03 Sep 2020
Viewed by 276
Abstract
The initiating protease of the complement classical pathway, C1r, represents an upstream and pathway-specific intervention point for complement-related autoimmune and inflammatory diseases. Yet, C1r-targeted therapeutic development is currently underrepresented relative to other complement targets. In this study, we developed a fragment-based drug discovery [...] Read more.
The initiating protease of the complement classical pathway, C1r, represents an upstream and pathway-specific intervention point for complement-related autoimmune and inflammatory diseases. Yet, C1r-targeted therapeutic development is currently underrepresented relative to other complement targets. In this study, we developed a fragment-based drug discovery approach using surface plasmon resonance (SPR) and molecular modeling to identify and characterize novel C1r-binding small-molecule fragments. SPR was used to screen a 2000-compound fragment library for binding to human C1r. This led to the identification of 24 compounds that bound C1r with equilibrium dissociation constants ranging between 160–1700 µM. Two fragments, termed CMP-1611 and CMP-1696, directly inhibited classical pathway-specific complement activation in a dose-dependent manner. CMP-1611 was selective for classical pathway inhibition, while CMP-1696 also blocked the lectin pathway but not the alternative pathway. Direct binding experiments mapped the CMP-1696 binding site to the serine protease domain of C1r and molecular docking and molecular dynamics studies, combined with C1r autoactivation assays, suggest that CMP-1696 binds within the C1r active site. The group of structurally distinct fragments identified here, along with the structure–activity relationship profiling of two lead fragments, form the basis for future development of novel high-affinity C1r-binding, classical pathway-specific, small-molecule complement inhibitors. Full article
(This article belongs to the Special Issue Deep Learning for Molecular Structure Modelling)
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Open AccessArticle
Free Amino Acids in Three Pleurotus Species Cultivated on Agricultural and Agro-Industrial By-Products
Molecules 2020, 25(17), 4015; https://doi.org/10.3390/molecules25174015 - 02 Sep 2020
Viewed by 315
Abstract
Previous studies have demonstrated the feasibility of employing by-products of the olive and wine sectors for the production of Pleurotus mushrooms with enhanced functionalities. In this work we investigated the influence of endogenous and exogenous factors on free amino acids (FAAs) profile of [...] Read more.
Previous studies have demonstrated the feasibility of employing by-products of the olive and wine sectors for the production of Pleurotus mushrooms with enhanced functionalities. In this work we investigated the influence of endogenous and exogenous factors on free amino acids (FAAs) profile of Pleurotus ostreatus, P. eryngii and P. nebrodensis mushrooms produced on wheat straw (WS), alone or mixed with grape marc (GM), and on by-products of the olive industry (OL). Overall, 22 FAAs were determined in substrates and mushrooms, including all the essential amino acids, the neurotransmitter γ-aminobutyric acid (GABA) and ornithine. On a dry weight (dw) basis, total FAAs ranged from 17.37 mg/g in P. nebrodensis to 130.12 mg/g in P. ostreatus samples, with alanine, leucine, glutamine, valine and serine predominating. Similar distribution patterns were followed by the monosodium glutamate (MSG)-like, sweet and bitter FAAs. Significant differences in FAAs level were observed among the species examined and among the cultivation substrates used. Principal Component Analysis (PCA) performed on the entire FAAs profile of six Pleurotus strains, clearly separated P. ostreatus from P. eryngii and P. nebrodensis, in accordance to their phylogenetic affinity. This is the first report of FAAs in P. nebrodensis. Full article
(This article belongs to the Special Issue Mushrooms:The Versatile Roles)
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Open AccessFeature PaperReview
Methods of Purification and Application Procedures of Alpha1 Antitrypsin: A Long-Lasting History
Molecules 2020, 25(17), 4014; https://doi.org/10.3390/molecules25174014 - 02 Sep 2020
Viewed by 336
Abstract
The aim of the present report is to review the literature addressing the methods developed for the purification of alpha1-antitrypsin (AAT) from the 1950s to the present. AAT is a glycoprotein whose main function is to protect tissues from human neutrophil elastase (HNE) [...] Read more.
The aim of the present report is to review the literature addressing the methods developed for the purification of alpha1-antitrypsin (AAT) from the 1950s to the present. AAT is a glycoprotein whose main function is to protect tissues from human neutrophil elastase (HNE) and other proteases released by neutrophils during an inflammatory state. The lack of this inhibitor in human serum is responsible for the onset of alpha1-antitrypsin deficiency (AATD), which is a severe genetic disorder that affects lungs in adults and for which there is currently no cure. Being used, under special circumstances, as a medical treatment of AATD in the so-called “replacement” therapy (consisting in the intravenous infusion of the missing protein), AAT is a molecule with a lot of therapeutic importance. For this reason, interest in AAT purification from human plasma or its production in a recombinant version has grown considerably in recent years. This article retraces all technological advances that allowed the manufacturers to move from a few micrograms of partially purified AAT to several grams of highly purified protein. Moreover, the chronic augmentation and maintenance therapy in individuals with emphysema due to congenital AAT deficiency (current applications in the clinical setting) is also presented. Full article
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Open AccessCommunication
Proteinoid Nanocapsules as Drug Delivery System for Improving Antipsychotic Activity of Risperidone
Molecules 2020, 25(17), 4013; https://doi.org/10.3390/molecules25174013 - 02 Sep 2020
Viewed by 469
Abstract
Risperidone (RSP) is an atypical antipsychotic drug widely used to treat schizophrenia and bipolar disorder. Nanoparticles (NPs) are being developed as in vivo targeted drug delivery systems, which cross the blood-brain barrier and improve pharmacokinetics and drug effectiveness. Here, biodegradable proteinoids were synthesized [...] Read more.
Risperidone (RSP) is an atypical antipsychotic drug widely used to treat schizophrenia and bipolar disorder. Nanoparticles (NPs) are being developed as in vivo targeted drug delivery systems, which cross the blood-brain barrier and improve pharmacokinetics and drug effectiveness. Here, biodegradable proteinoids were synthesized by thermal step-growth polymerization from the amino acids l-glutamic acid, l-phenylalanine and l-histidine and poly (l-lactic acid). Proteinoid NPs containing RSP were then formed by self-assembly, overcoming the insolubility of the drug in water, followed by PEGylation (poly ethylene glycol (PEG) conjugation to increase the stability of the NPs in the aqueous continuous phase. These NPs are biodegradable owing to their peptide and ester moieties. They were characterized in terms of diameter, size distribution, drug loading, and long-term storage. Behavioral studies on mice found enhanced antipsychotic activity compared to free RSP. Full article
(This article belongs to the Special Issue Nanotechnology-Drug Delivery Systems)
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Open AccessReview
Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy
Molecules 2020, 25(17), 4012; https://doi.org/10.3390/molecules25174012 - 02 Sep 2020
Viewed by 337
Abstract
Identified in 1973, somatostatin (SST) is a cyclic hormone peptide with a short biological half-life. Somatostatin receptors (SSTRs) are widely expressed in the whole body, with five subtypes described. The interaction between SST and its receptors leads to the internalization of the ligand–receptor [...] Read more.
Identified in 1973, somatostatin (SST) is a cyclic hormone peptide with a short biological half-life. Somatostatin receptors (SSTRs) are widely expressed in the whole body, with five subtypes described. The interaction between SST and its receptors leads to the internalization of the ligand–receptor complex and triggers different cellular signaling pathways. Interestingly, the expression of SSTRs is significantly enhanced in many solid tumors, especially gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). Thus, somatostatin analogs (SSAs) have been developed to improve the stability of the endogenous ligand and so extend its half-life. Radiolabeled analogs have been developed with several radioelements such as indium-111, technetium-99 m, and recently gallium-68, fluorine-18, and copper-64, to visualize the distribution of receptor overexpression in tumors. Internal metabolic radiotherapy is also used as a therapeutic strategy (e.g., using yttrium-90, lutetium-177, and actinium-225). With some radiopharmaceuticals now used in clinical practice, somatostatin analogs developed for imaging and therapy are an example of the concept of personalized medicine with a theranostic approach. Here, we review the development of these analogs, from the well-established and authorized ones to the most recently developed radiotracers, which have better pharmacokinetic properties and demonstrate increased efficacy and safety, as well as the search for new clinical indications. Full article
(This article belongs to the Special Issue Radiolabeled Compounds for Diagnosis and Treatment of Cancer)
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Open AccessArticle
Development of a Molecular Snail Xenomonitoring Assay to Detect Schistosoma haematobium and Schistosoma bovis Infections in their Bulinus Snail Hosts
Molecules 2020, 25(17), 4011; https://doi.org/10.3390/molecules25174011 - 02 Sep 2020
Viewed by 414
Abstract
Schistosomiasis, a neglected tropical disease of medical and veterinary importance, transmitted through specific freshwater snail intermediate hosts, is targeted for elimination in several endemic regions in sub-Saharan Africa. Multi-disciplinary methods are required for both human and environmental diagnostics to certify schistosomiasis elimination when [...] Read more.
Schistosomiasis, a neglected tropical disease of medical and veterinary importance, transmitted through specific freshwater snail intermediate hosts, is targeted for elimination in several endemic regions in sub-Saharan Africa. Multi-disciplinary methods are required for both human and environmental diagnostics to certify schistosomiasis elimination when eventually reached. Molecular xenomonitoring protocols, a DNA-based detection method for screening disease vectors, have been developed and trialed for parasites transmitted by hematophagous insects, such as filarial worms and trypanosomes, yet few have been extensively trialed or proven reliable for the intermediate host snails transmitting schistosomes. Here, previously published universal and Schistosoma-specific internal transcribed spacer (ITS) rDNA primers were adapted into a triplex PCR primer assay that allowed for simple, robust, and rapid detection of Schistosoma haematobium and Schistosoma bovis in Bulinus snails. We showed this two-step protocol could sensitively detect DNA of a single larval schistosome from experimentally infected snails and demonstrate its functionality for detecting S. haematobium infections in wild-caught snails from Zanzibar. Such surveillance tools are a necessity for succeeding in and certifying the 2030 control and elimination goals set by the World Health Organization. Full article
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Open AccessArticle
A Lanosteryl Triterpene (RA-3) Exhibits Antihyperuricemic and Nephroprotective Effects in Rats
Molecules 2020, 25(17), 4010; https://doi.org/10.3390/molecules25174010 - 02 Sep 2020
Viewed by 265
Abstract
Considering the global health threat posed by kidney disease burden, a search for new nephroprotective drugs from our local flora could prove a powerful strategy to respond to this health threat. In this study we investigated the antihyperuricemic and nephroprotective potential of RA-3, [...] Read more.
Considering the global health threat posed by kidney disease burden, a search for new nephroprotective drugs from our local flora could prove a powerful strategy to respond to this health threat. In this study we investigated the antihyperuricemic and nephroprotective potential of RA-3, a plant-derived lanosteryl triterpene. The antihyperuricemic and nephroprotective effect of RA-3 was investigated using the adenine and gentamicin induced hyperuricemic and nephrotoxicity rat model. Following the induction of hyperuricemia and nephrotoxicity, the experimental model rats (Sprague Dawley) were orally administered with RA-3 at 50 and 100 mg/kg body weight, respectively, daily for 14 days. Treatment of the experimental rats with RA-3, especially at 100 mg/kg, effectively lowered the serum renal dysfunction (blood urea nitrogen and creatinine) and hyperuricemic (uric acid and xanthine oxidase) biomarkers. These were accompanied by increased antioxidant status with decrease in malondialdehyde content. A much improved histomorphological structure of the kidney tissues was also observed in the triterpene treated groups when compared to the model control group. It is evident that RA-3 possesses the antihyperuricemic and nephroprotective properties, which could be vital for prevention and amelioration of kidney disease. Full article
(This article belongs to the Special Issue Biological and Pharmacological Activity of Plant Natural Compounds)
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Open AccessArticle
Synthesis of Potential Haptens with Morphine Skeleton and Determination of Protonation Constants
Molecules 2020, 25(17), 4009; https://doi.org/10.3390/molecules25174009 - 02 Sep 2020
Viewed by 329
Abstract
Vaccination could be a promising alternative warfare against drug addiction and abuse. For this purpose, so-called haptens can be used. These molecules alone do not induce the activation of the immune system, this occurs only when they are attached to an immunogenic carrier [...] Read more.
Vaccination could be a promising alternative warfare against drug addiction and abuse. For this purpose, so-called haptens can be used. These molecules alone do not induce the activation of the immune system, this occurs only when they are attached to an immunogenic carrier protein. Hence obtaining a free amino or carboxylic group during the structural transformation is an important part of the synthesis. Namely, these groups can be used to form the requisite peptide bond between the hapten and the carrier protein. Focusing on this basic principle, six nor-morphine compounds were treated with ethyl acrylate and ethyl bromoacetate, while the prepared esters were hydrolyzed to obtain the N-carboxymethyl- and N-carboxyethyl-normorphine derivatives which are considered as potential haptens. The next step was the coupling phase with glycine ethyl ester, but the reactions did not work or the work-up process was not accomplishable. As an alternative route, the normorphine-compounds were N-alkylated with N-(chloroacetyl)glycine ethyl ester. These products were hydrolyzed in alkaline media and after the work-up process all of the derivatives contained the free carboxylic group of the glycine side chain. The acid-base properties of these molecules are characterized in detail. In the N-carboxyalkyl derivatives, the basicity of the amino and phenolate site is within an order of magnitude. In the glycine derivatives the basicity of the amino group is significantly decreased compared to the parent compounds (i.e., morphine, oxymorphone) because of the electron withdrawing amide group. The protonation state of the carboxylate group significantly influences the basicity of the amino group. All of the glycine ester and the glycine carboxylic acid derivatives are currently under biological tests. Full article
(This article belongs to the Special Issue ECSOC-23)
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Open AccessReview
Sunlight-Operated TiO2-Based Photocatalysts
Molecules 2020, 25(17), 4008; https://doi.org/10.3390/molecules25174008 - 02 Sep 2020
Viewed by 290
Abstract
Photo-catalysis is a research field with broad applications in terms of potential technological applications related to energy production and managing, environmental protection, and chemical synthesis fields. A global goal, common to all of these fields, is to generate photo-catalytic materials able to use [...] Read more.
Photo-catalysis is a research field with broad applications in terms of potential technological applications related to energy production and managing, environmental protection, and chemical synthesis fields. A global goal, common to all of these fields, is to generate photo-catalytic materials able to use a renewable energy source such as the sun. As most active photocatalysts such as titanium oxides are essentially UV absorbers, they need to be upgraded in order to achieve the fruitful use of the whole solar spectrum, from UV to infrared wavelengths. A lot of different strategies have been pursued to reach this goal. Here, we selected representative examples of the most successful ones. We mainly highlighted doping and composite systems as those with higher potential in this quest. For each of these two approaches, we highlight the different possibilities explored in the literature. For doping of the main photocatalysts, we consider the use of metal and non-metals oriented to modify the band gap energy as well as to create specific localized electronic states. We also described selected cases of using up-conversion doping cations. For composite systems, we described the use of binary and ternary systems. In addition to a main photo-catalyst, these systems contain low band gap, up-conversion or plasmonic semiconductors, plasmonic and non-plasmonic metals and polymers. Full article
(This article belongs to the Section Inorganic Chemistry)
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Open AccessArticle
Semi-Synthetic Approach Leading to 8-Prenylnaringenin and 6-Prenylnaringenin: Optimization of the Microwave-Assisted Demethylation of Xanthohumol Using Design of Experiments
Molecules 2020, 25(17), 4007; https://doi.org/10.3390/molecules25174007 - 02 Sep 2020
Viewed by 313
Abstract
The isomers 8-prenylnaringenin and 6-prenylnaringenin, both secondary metabolites occurring in hops, show interesting biological effects, like estrogen-like, cytotoxic, or neuro regenerative activities. Accordingly, abundant sources for this special flavonoids are needed. Extraction is not recommended due to the very low amounts present in [...] Read more.
The isomers 8-prenylnaringenin and 6-prenylnaringenin, both secondary metabolites occurring in hops, show interesting biological effects, like estrogen-like, cytotoxic, or neuro regenerative activities. Accordingly, abundant sources for this special flavonoids are needed. Extraction is not recommended due to the very low amounts present in plants and different synthesis approaches are characterized by modest yields, multiple steps, the use of expensive chemicals, or an elaborate synthesis. An easy synthesis strategy is the demethylation of xanthohumol, which is available due to hop extraction industry, using lithium chloride and dimethylformamide, but byproducts and low yield did not make this feasible until now. In this study, the demethylation of xanthohumol to 8-prenylnaringenin and 6-prenylnaringenin is described the first time and this reaction was optimized using Design of Experiment and microwave irradiation. With the optimized conditions—temperature 198 °C, 55 eq. lithium chloride, and a reaction time of 9 min, a final yield of 76% of both prenylated flavonoids is reached. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle
Comprehensive Metabolome Analysis of Fermented Aqueous Extracts of Viscum album L. by Liquid Chromatography−High Resolution Tandem Mass Spectrometry
Molecules 2020, 25(17), 4006; https://doi.org/10.3390/molecules25174006 - 02 Sep 2020
Viewed by 316
Abstract
Fermented aqueous extracts of Viscum album L. are widely used for cancer treatment in complementary medicine. The high molecular weight compounds viscotoxins and lectins are considered to be the main active substances in the extracts. However, a vast number of small molecules (≤1500 [...] Read more.
Fermented aqueous extracts of Viscum album L. are widely used for cancer treatment in complementary medicine. The high molecular weight compounds viscotoxins and lectins are considered to be the main active substances in the extracts. However, a vast number of small molecules (≤1500 Da) is also expected to be present, and few studies have investigated their identities. In this study, a comprehensive metabolome analysis of samples of fermented aqueous extracts of V. album from two host tree species (Malus domestica and Pinus sylvestris), both prepared by two pharmaceutical manufacturing processes, was performed by liquid chromatography−high resolution tandem mass spectrometry (LC-HRMS/MS). A total of 212 metabolites were putatively annotated, including primary metabolites (e.g., amino acids, organic acids, etc.) and secondary metabolites (mostly phenolic compounds). A clear separation between V. album samples according to the host tree species, but not due to manufacturing processes, was observed by principal component analysis. The biomarkers responsible for this discrimination were assessed by partial least squares−discriminant analysis. Because V. album extracts from different host trees have different clinical applications, the present work highlights the possibility of characterizing the metabolome for identification and traceability of V. album fermented aqueous extracts. Full article
(This article belongs to the Special Issue Current Trends in the Analysis of Medicinal Plants)
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Open AccessReview
Memantine Derivatives as Multitarget Agents in Alzheimer’s Disease
Molecules 2020, 25(17), 4005; https://doi.org/10.3390/molecules25174005 - 02 Sep 2020
Viewed by 409
Abstract
Memantine (3,5-dimethyladamantan-1-amine) is an orally active, noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist approved for treatment of moderate-to-severe Alzheimer’s disease (AD), a neurodegenerative condition characterized by a progressive cognitive decline. Unfortunately, memantine as well as the other class of drugs licensed for AD treatment acting [...] Read more.
Memantine (3,5-dimethyladamantan-1-amine) is an orally active, noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist approved for treatment of moderate-to-severe Alzheimer’s disease (AD), a neurodegenerative condition characterized by a progressive cognitive decline. Unfortunately, memantine as well as the other class of drugs licensed for AD treatment acting as acetylcholinesterase inhibitors (AChEIs), provide only symptomatic relief. Thus, the urgent need in AD drug development is for disease-modifying therapies that may require approaching targets from more than one path at once or multiple targets simultaneously. Indeed, increasing evidence suggests that the modulation of a single neurotransmitter system represents a reductive approach to face the complexity of AD. Memantine is viewed as a privileged NMDAR-directed structure, and therefore, represents the driving motif in the design of a variety of multi-target directed ligands (MTDLs). In this review, we present selected examples of small molecules recently designed as MTDLs to contrast AD, by combining in a single entity the amantadine core of memantine with the pharmacophoric features of known neuroprotectants, such as antioxidant agents, AChEIs and Aβ-aggregation inhibitors. Full article
(This article belongs to the Special Issue Multitarget Ligands)
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Open AccessArticle
Quercitrin Stimulates Hair Growth with Enhanced Expression of Growth Factors via Activation of MAPK/CREB Signaling Pathway
Molecules 2020, 25(17), 4004; https://doi.org/10.3390/molecules25174004 - 02 Sep 2020
Viewed by 302
Abstract
The present study aimed to investigate the molecular mechanism of quercitrin, a major constituent of Hottuynia cordata extract, for its hair growth stimulating activities in cultured human dermal papilla cells (hDPCs). Quercitrin enhanced the cell viability and cellular energy metabolism in cultured hDPCs [...] Read more.
The present study aimed to investigate the molecular mechanism of quercitrin, a major constituent of Hottuynia cordata extract, for its hair growth stimulating activities in cultured human dermal papilla cells (hDPCs). Quercitrin enhanced the cell viability and cellular energy metabolism in cultured hDPCs by stimulating the production of NAD(P)H and mitochondrial membrane potential (ΔΨ). The expression of Bcl2, an essential marker for anagen hair follicle and cell survival, was increased by quercitrin treatment. Quercitrin also increased the cell proliferation marker Ki67. The expression of growth factors—such as bFGF, KGF, PDGF-AA, and VEGF—were increased by quercitrin both in mRNA and protein levels. In addition, quercitrin was found to increase the phosphorylation of Akt, Erk, and CREB in cultured hDPCs, while inhibitors of MAPKs reversed the effects of quercitrin. Finally, quercitrin stimulated hair shaft growth in cultured human hair follicles. Our data obtained from present study are in line with those previously reported and demonstrate that quercitrin is (one of) the active compound(s) of Hottuynia cordata extract which showed hair growth promoting effects. It is strongly suggested that the hair growth stimulating activity of quercitrin was exerted by enhancing the cellular energy metabolism, increasing the production of growth factors via activation of MAPK/CREB signaling pathway. Full article
(This article belongs to the Section Medicinal Chemistry)
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