Molecules

15 pages, 4164 KiB

Open AccessArticle

Substrate Profiling of the Cobalt Nitrile Hydratase from Rhodococcus rhodochrous ATCC BAA 870

by Adelaide R. Mashweu, Varsha P. Chhiba-Govindjee, Moira L. Bode and Dean Brady

Molecules 2020, 25(1), 238; https://doi.org/10.3390/molecules25010238 - 06 Jan 2020

Cited by 16 | Viewed by 6749

The aromatic substrate profile of the cobalt nitrile hydratase from Rhodococcus rhodochrous ATCC BAA 870 was evaluated against a wide range of nitrile containing compounds (>60). To determine the substrate limits of this enzyme, compounds ranging in size from small (90 Da) to [...] Read more.

The aromatic substrate profile of the cobalt nitrile hydratase from Rhodococcus rhodochrous ATCC BAA 870 was evaluated against a wide range of nitrile containing compounds (>60). To determine the substrate limits of this enzyme, compounds ranging in size from small (90 Da) to large (325 Da) were evaluated. Larger compounds included those with a bi-aryl axis, prepared by the Suzuki coupling reaction, Morita–Baylis–Hillman adducts, heteroatom-linked diarylpyridines prepared by Buchwald–Hartwig cross-coupling reactions and imidazo[1,2-a]pyridines prepared by the Groebke–Blackburn–Bienaymé multicomponent reaction. The enzyme active site was moderately accommodating, accepting almost all of the small aromatic nitriles, the diarylpyridines and most of the bi-aryl compounds and Morita–Baylis–Hillman products but not the Groebke–Blackburn–Bienaymé products. Nitrile conversion was influenced by steric hindrance around the cyano group, the presence of electron donating groups (e.g., methoxy) on the aromatic ring, and the overall size of the compound. Full article

(This article belongs to the Special Issue Nitrilases and Nitrile Hydratases)

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10 pages, 3913 KiB

Open AccessArticle

Identification and Biological Evaluation of CK2 Allosteric Fragments through Structure-Based Virtual Screening

by Chunqiong Li, Xuewen Zhang, Na Zhang, Yue Zhou, Guohui Sun, Lijiao Zhao and Rugang Zhong

Molecules 2020, 25(1), 237; https://doi.org/10.3390/molecules25010237 - 06 Jan 2020

Cited by 8 | Viewed by 4500

Abstract

Casein kinase II (CK2) is considered as an attractive cancer therapeutic target, and recent efforts have been made to develop its ATP-competitive inhibitors. However, achieving selectivity with respect to related kinases remains challenging due to the highly conserved ATP-binding pocket of kinases. Allosteric [...] Read more.

Casein kinase II (CK2) is considered as an attractive cancer therapeutic target, and recent efforts have been made to develop its ATP-competitive inhibitors. However, achieving selectivity with respect to related kinases remains challenging due to the highly conserved ATP-binding pocket of kinases. Allosteric inhibitors, by targeting the much more diversified allosteric site relative to the highly conserved ATP-binding pocket, might be a promising strategy with the enhanced selectivity and reduced toxicity than ATP-competitive inhibitors. The previous studies have highlighted the traditional serendipitousity of discovering allosteric inhibitors owing to the complicate allosteric modulation. In this current study, we identified the novel allosteric inhibitors of CK2α by combing structure-based virtual screening and biological evaluation methods. The structure-based pharmacophore model was built based on the crystal structure of CK2α-compound 15 complex. The ChemBridge fragment library was searched by evaluating the fit values of these molecules with the optimized pharmacophore model, as well as the binding affinity of the CK2α-ligand complexes predicted by Alloscore web server. Six hits forming the holistic interaction mechanism with the αD pocket were retained after pharmacophore- and Alloscore-based screening for biological test. Compound 3 was found to be the most potent non-ATP competitive CK2α inhibitor (IC₅₀ = 13.0 μM) with the anti-proliferative activity on A549 cancer cells (IC₅₀ = 23.1 μM). Our results provide new clues for further development of CK2 allosteric inhibitors as anti-cancer hits. Full article

(This article belongs to the Special Issue Fragment Based Drug Discovery)

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14 pages, 2587 KiB

Open AccessFeature PaperArticle

Tracking Extracellular Matrix Remodeling in Lungs Induced by Breast Cancer Metastasis. Fourier Transform Infrared Spectroscopic Studies

by Karolina Chrabaszcz, Katarzyna Kaminska, Karolina Augustyniak, Monika Kujdowicz, Marta Smeda, Agnieszka Jasztal, Marta Stojak, Katarzyna M. Marzec and Kamilla Malek

Molecules 2020, 25(1), 236; https://doi.org/10.3390/molecules25010236 - 06 Jan 2020

Cited by 12 | Viewed by 4842

Abstract

This work focused on a detailed assessment of lung tissue affected by metastasis of breast cancer. We used large-area chemical scanning implemented in Fourier transform infrared (FTIR) spectroscopic imaging supported with classical histological and morphological characterization. For the first time, we differentiated and [...] Read more.

This work focused on a detailed assessment of lung tissue affected by metastasis of breast cancer. We used large-area chemical scanning implemented in Fourier transform infrared (FTIR) spectroscopic imaging supported with classical histological and morphological characterization. For the first time, we differentiated and defined biochemical changes due to metastasis observed in the lung parenchyma, atelectasis, fibrous, and muscle cells, as well as bronchi ciliate cells, in a qualitative and semi-quantitative manner based on spectral features. The results suggested that systematic extracellular matrix remodeling with the progress of the metastasis process evoked a decrease in the fraction of the total protein in atelectasis, fibrous, and muscle cells, as well as an increase of fibrillar proteins in the parenchyma. We also detected alterations in the secondary conformations of proteins in parenchyma and atelectasis and changes in the level of hydroxyproline residues and carbohydrate moieties in the parenchyma. The results indicate the usability of FTIR spectroscopy as a tool for the detection of extracellular matrix remodeling, thereby enabling the prediction of pre-metastatic niche formation. Full article

(This article belongs to the Special Issue Biomedical Raman and Infrared Spectroscopy: Recent Advancement and Applications)

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18 pages, 6272 KiB

Open AccessFeature PaperArticle

Silk/Natural Rubber (NR) and 3,4-Dihydroxyphenylalanine (DOPA)-Modified Silk/NR Composites: Synthesis, Secondary Structure, and Mechanical Properties

by Hiromitsu Sogawa, Treratanakulwongs Korawit, Hiroyasu Masunaga and Keiji Numata

Molecules 2020, 25(1), 235; https://doi.org/10.3390/molecules25010235 - 06 Jan 2020

Cited by 8 | Viewed by 4559

Abstract

Silk composites with natural rubber (NR) were prepared by mixing degummed silk and NR latex solutions. A significant enhancement of the mechanical properties was confirmed for silk/NR composites compared to a NR-only product, indicating that silk can be applied as an effective reinforcement [...] Read more.

Silk composites with natural rubber (NR) were prepared by mixing degummed silk and NR latex solutions. A significant enhancement of the mechanical properties was confirmed for silk/NR composites compared to a NR-only product, indicating that silk can be applied as an effective reinforcement for rubber materials. Attenuated total reflection Fourier transform infrared (ATR-FTIR) and wide-angle X-ray diffraction (WAXD) analysis revealed that a β-sheet structure was formed in the NR matrix by increasing the silk content above 20 wt%. Then, 3,4-dihydroxyphenylalanine (DOPA)-modified silk was also blended with NR to give a DOPA-silk/NR composite, which showed superior mechanical properties to those of the unmodified silk-based composite. Not only the chemical structure but also the dominant secondary structure of silk in the composite was changed after DOPA modification. It was concluded that both the efficient adhesion property of DOPA residue and the secondary structure change improved the compatibility of silk and NR, resulting in the enhanced mechanical properties of the formed composite. The knowledge obtained herein should contribute to the development of the fabrication of novel silk-based elastic materials. Full article

(This article belongs to the Special Issue Silk Fibroin Materials)

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17 pages, 3180 KiB

Open AccessArticle

Can We Safely Obtain Formal Oxidation States from Centroids of Localized Orbitals?

by Martí Gimferrer, Gerard Comas-Vilà and Pedro Salvador

Molecules 2020, 25(1), 234; https://doi.org/10.3390/molecules25010234 - 06 Jan 2020

Cited by 13 | Viewed by 4806

Abstract

The use of centroids of localized orbitals as a method to derive oxidation states (OS) from first-principles is critically analyzed. We explore the performance of the closest-atom distance criterion to assign electrons for a number of challenging systems, including high-valent transition metal compounds, [...] Read more.

The use of centroids of localized orbitals as a method to derive oxidation states (OS) from first-principles is critically analyzed. We explore the performance of the closest-atom distance criterion to assign electrons for a number of challenging systems, including high-valent transition metal compounds, π-adducts, and transition metal (TM) carbenes. Here, we also introduce a mixed approach that combines the position of the centroids with Bader’s atomic basins as an alternative criterion for electron assignment. The closest-atom criterion performs reasonably well for the challenging systems, but wrongly considers O-H and N-H bonds as hydrides. The new criterion fixes this problem, but underperforms in the case of TM carbenes. Moreover, the OS assignment in dubious cases exhibit undesirable dependence on the particular choice for orbital localization. Full article

(This article belongs to the Special Issue Modern Computational Methods for Chemical Bonding and Reactivity)

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19 pages, 2183 KiB

Open AccessFeature PaperArticle

Comparative Phytochemical Characterization, Genetic Profile, and Antiproliferative Activity of Polyphenol-Rich Extracts from Pigmented Tubers of Different Solanum tuberosum Varieties

by Luigi De Masi, Paola Bontempo, Daniela Rigano, Paola Stiuso, Vincenzo Carafa, Angela Nebbioso, Sonia Piacente, Paola Montoro, Riccardo Aversano, Vincenzo D’Amelia, Domenico Carputo and Lucia Altucci

Molecules 2020, 25(1), 233; https://doi.org/10.3390/molecules25010233 - 06 Jan 2020

Cited by 31 | Viewed by 4736

Abstract

Plants produce a vast array of biomolecules with beneficial effects for human health. In this study, polyphenol and anthocyanin-rich extracts (PAE) from pigmented tubers of Solanum tuberosum L. varieties “Blue Star”, “Magenta Love”, and “Double Fun” in comparison with the more extensively studied [...] Read more.

Plants produce a vast array of biomolecules with beneficial effects for human health. In this study, polyphenol and anthocyanin-rich extracts (PAE) from pigmented tubers of Solanum tuberosum L. varieties “Blue Star”, “Magenta Love”, and “Double Fun” in comparison with the more extensively studied “Vitelotte” were evaluated and compared for antiproliferative effects in human leukemia cells, and their phytochemical and genetic profiles were determined. In U937 cells, upon treatment with PAE, it was possible to reveal the expression of specific apoptotic players, such as caspase 8, 9, 3, and poly (ADP-ribose) polymerase (PARP), as well as the induction of monocyte and granulocyte differentiation. A liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) investigation revealed the presence of polyphenolic compounds in all the varieties of potatoes analyzed, among which caffeoyl and feruloyl quinic acid derivatives were the most abundant, as well as several acylated anthocyanins. Each pigmented variety was genotyped by DNA-based molecular markers, and flavonoid-related transcription factors were profiled in tubers in order to better characterize these outstanding resources and contribute to their exploitation in breeding. Interesting biological activities were observed for “Blue Star” and “Vitelotte” varieties with respect to the minor or no effect of the “Double Fun” variety. Full article

(This article belongs to the Section Natural Products Chemistry)

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2 pages, 1886 KiB

Open AccessCorrection

Correction: Zhao, X.W., et al. Dioscin Induces the Apoptosis of Human Cervical Carcinoma HeLa and SiHa Cells Through ROS-mediated DNA Damage, Cell Cycle Arrest and Mitochondrial Signaling Pathways. Molecules 2016, 21, 730

by Xinwei Zhao, Xufeng Tao, Lina Xu, Lianhong Yin, Yan Qi, Youwei Xu, Xu Han and Jinyong Peng

Molecules 2020, 25(1), 232; https://doi.org/10.3390/molecules25010232 - 06 Jan 2020

Cited by 1 | Viewed by 2067

Abstract

During the course of a review of our publications, an error in the title paper [...] Full article

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30 pages, 6408 KiB

Open AccessArticle

Potential of Thai Herbal Extracts on Lung Cancer Treatment by Inducing Apoptosis and Synergizing Chemotherapy

by Juthathip Poofery, Patompong Khaw-on, Subhawat Subhawa, Bungorn Sripanidkulchai, Apichat Tantraworasin, Somcharoen Saeteng, Sopon Siwachat, Nirush Lertprasertsuke and Ratana Banjerdpongchai

Molecules 2020, 25(1), 231; https://doi.org/10.3390/molecules25010231 - 06 Jan 2020

Cited by 25 | Viewed by 8050

Abstract

The incidence of lung cancer has increased while the mortality rate has continued to remain high. Effective treatment of this disease is the key to survival. Therefore, this study is a necessity in continuing research into new effective treatments. In this study we [...] Read more.

The incidence of lung cancer has increased while the mortality rate has continued to remain high. Effective treatment of this disease is the key to survival. Therefore, this study is a necessity in continuing research into new effective treatments. In this study we determined the effects of three different Thai herbs on lung cancer. Bridelia ovata, Croton oblongifolius, and Erythrophleum succirubrum were extracted by ethyl acetate and 50% ethanol. The cytotoxicity was tested with A549 lung cancer cell line. We found four effective extracts that exhibited toxic effects on A549 cells. These extracts included ethyl acetate extracts of B. ovata (BEA), C. oblongifolius (CEA), and E. succirubrum (EEA), and an ethanolic extract of E. succirubrum (EE). Moreover, these effective extracts were tested in combination with chemotherapeutic drugs. An effective synergism of these treatments was found specifically through a combination of BEA with methotrexate, EE with methotrexate, and EE with etoposide. Apoptotic cell death was induced in A549 cells by these effective extracts via the mitochondria-mediated pathway. Additionally, we established primary lung cancer and normal epithelial cells from lung tissue of lung cancer patients. The cytotoxicity results showed that EE had significant potential to be used for lung cancer treatment. In conclusion, the four effective extracts possessed anticancer effects on lung cancer. The most effective extract was found to be E. succirubrum (EE). Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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13 pages, 3680 KiB

Open AccessEditor’s ChoiceArticle

Iron-Catalyzed C(sp²)–C(sp³) Cross-Coupling of Aryl Chlorobenzoates with Alkyl Grignard Reagents

by Elwira Bisz and Michal Szostak

Molecules 2020, 25(1), 230; https://doi.org/10.3390/molecules25010230 - 06 Jan 2020

Cited by 14 | Viewed by 5599

Abstract

Aryl benzoates are compounds of high importance in organic synthesis. Herein, we report the iron-catalyzed C(sp²)–C(sp³) Kumada cross-coupling of aryl chlorobenzoates with alkyl Grignard reagents. The method is characterized by the use of environmentally benign and sustainable iron salts [...] Read more.

Aryl benzoates are compounds of high importance in organic synthesis. Herein, we report the iron-catalyzed C(sp²)–C(sp³) Kumada cross-coupling of aryl chlorobenzoates with alkyl Grignard reagents. The method is characterized by the use of environmentally benign and sustainable iron salts for cross-coupling in the catalytic system, employing benign urea ligands in the place of reprotoxic NMP (NMP = N-methyl-2-pyrrolidone). It is notable that high selectivity for the cross-coupling is achieved in the presence of hydrolytically-labile and prone to nucleophilic addition phenolic ester C(acyl)–O bonds. The reaction provides access to alkyl-functionalized aryl benzoates. The examination of various O-coordinating ligands demonstrates the high activity of urea ligands in promoting the cross-coupling versus nucleophilic addition to the ester C(acyl)–O bond. The method showcases the functional group tolerance of iron-catalyzed Kumada cross-couplings. Full article

(This article belongs to the Special Issue Recent Advances in Iron Catalysis)

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21 pages, 4028 KiB

Open AccessArticle

Biocompatible Organic Coatings Based on Bisphosphonic Acid RGD-Derivatives for PEO-Modified Titanium Implants

by Lyudmila V. Parfenova, Elena S. Lukina, Zulfia R. Galimshina, Guzel U. Gil’fanova, Veta R. Mukaeva, Ruzil G. Farrakhov, Ksenia V. Danilko, Grigory S. Dyakonov and Evgeny V. Parfenov

Molecules 2020, 25(1), 229; https://doi.org/10.3390/molecules25010229 - 06 Jan 2020

Cited by 17 | Viewed by 4247

Abstract

Currently, significant attention is attracted to the problem of the development of the specific architecture and composition of the surface layer in order to control the biocompatibility of implants made of titanium and its alloys. The titanium surface properties can be tuned both [...] Read more.

Currently, significant attention is attracted to the problem of the development of the specific architecture and composition of the surface layer in order to control the biocompatibility of implants made of titanium and its alloys. The titanium surface properties can be tuned both by creating an inorganic sublayer with the desired morphology and by organic top coating contributing to bioactivity. In this work, we developed a composite biologically active coatings based on hybrid molecules obtained by chemical cross-linking of amino acid bisphosphonates with a linear tripeptide RGD, in combination with inorganic porous sublayer created on titanium by plasma electrolytic oxidation (PEO). After the addition of organic molecules, the PEO coated surface gets nobler, but corrosion currents increase. In vitro studies on proliferation and viability of fibroblasts, mesenchymal stem cells and osteoblast-like cells showed the significant dependence of the molecule bioactivity on the structure of bisphosphonate anchor and the linker. Several RGD-modified bisphosphonates of β-alanine, γ-aminobutyric and ε-aminocaproic acids with BMPS or SMCC linkers can be recommended as promising candidates for further in vivo research. Full article

(This article belongs to the Section Materials Chemistry)

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15 pages, 4170 KiB

Open AccessArticle

Pterostilbene Suppresses both Cancer Cells and Cancer Stem-Like Cells in Cervical Cancer with Superior Bioavailability to Resveratrol

by Hee Jeong Shin, Jang Mi Han, Ye Seul Choi and Hye Jin Jung

Molecules 2020, 25(1), 228; https://doi.org/10.3390/molecules25010228 - 06 Jan 2020

Cited by 48 | Viewed by 5337

Abstract

Increasing studies have reported that cancer stem cells (CSCs) play critical roles in therapeutic resistance, recurrence, and metastasis of tumors, including cervical cancer. Pterostilbene, a dimethylated derivative of resveratrol, is a plant polyphenol compound with potential chemopreventive activity. However, the therapeutic effect of [...] Read more.

Increasing studies have reported that cancer stem cells (CSCs) play critical roles in therapeutic resistance, recurrence, and metastasis of tumors, including cervical cancer. Pterostilbene, a dimethylated derivative of resveratrol, is a plant polyphenol compound with potential chemopreventive activity. However, the therapeutic effect of pterostilbene against cervical CSCs remains unclear. In this study, we compared the anticancer effects of resveratrol and pterostilbene using both HeLa cervical cancer adherent and stem-like cells. Pterostilbene more effectively inhibited the growth and clonogenic survival, as well as metastatic ability of HeLa adherent cells than those of resveratrol. Moreover, the superior inhibitory effects of pterostilbene compared to resveratrol were associated with the enhanced activation of multiple mechanisms, including cell cycle arrest at S and G2/M phases, induction of ROS-mediated caspase-dependent apoptosis, and inhibition of matrix metalloproteinase (MMP)-2/-9 expression. Notably, pterostilbene exhibited a greater inhibitory effect on the tumorsphere-forming and migration abilities of HeLa cancer stem-like cells compared to resveratrol. This greater effect was achieved through more potent inhibition of the expression levels of stemness markers, such as CD133, Oct4, Sox2, and Nanog, as well as signal transducer and activator of transcription 3 signaling. These results suggest that pterostilbene might be a potential anticancer agent targeting both cancer cells and cancer stem-like cells of cervical cancer via the superior bioavailability to resveratrol. Full article

(This article belongs to the Special Issue Antitumor and Anti-HIV Agents from Natural Products)

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9 pages, 3201 KiB

Open AccessArticle

Screening of Nanocellulose from Different Biomass Resources and Its Integration for Hydrophobic Transparent Nanopaper

by Yanran Qi, Hao Zhang, Dandan Xu, Zaixin He, Xiya Pan, Shihan Gui, Xiaohan Dai, Jilong Fan, Xiaoying Dong and Yongfeng Li

Molecules 2020, 25(1), 227; https://doi.org/10.3390/molecules25010227 - 06 Jan 2020

Cited by 21 | Viewed by 4268

Abstract

Petroleum-based plastics, such as PP, PE, PVC, etc., have become an important source of environmental pollution due to their hard degradation, posing a serious threat to the human health. Isolating nanocellulose from abundant biomass waste resources and further integrating the nanocellulose into hydrophobic [...] Read more.

Petroleum-based plastics, such as PP, PE, PVC, etc., have become an important source of environmental pollution due to their hard degradation, posing a serious threat to the human health. Isolating nanocellulose from abundant biomass waste resources and further integrating the nanocellulose into hydrophobic transparent film (i.e., nanopaper), to replace the traditional nondegradable plastic film, is of great significance for solving the problem of environmental pollution and achieving sustainable development of society. This study respectively extracted nanocellulose from the branches of Amorpha fruticosa Linn., wheat straw, and poplar residues via combined mechanical treatments of grinding and high-pressure homogenization. Among them, the nanocellulose derived from the Amorpha fruticosa has a finer structure, with diameter of about 10 nm and an aspect ratio of more than 500. With the nanocellulose as building block, we constructed hydrophilic nanopaper with high light transmittance (up to 90%) and high mechanical strength (tensile strength up to 110 MPa). After further hybridization by incorporating nano-silica into the nanopaper, followed by hydrophobic treatment, we built hydrophobic nanopaper with transmittance over 82% and a water contact angle of about 102° that could potentially replace transparent plastic film and has wide applications in food packaging, agricultural film, electronic device, and other fields. Full article

(This article belongs to the Special Issue Emerging Trends in Nanocelluloses)

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13 pages, 3041 KiB

Open AccessArticle

Chitosan-Based Bio-Composite Modified with Thiocarbamate Moiety for Decontamination of Cations from the Aqueous Media

by Nisar Ali, Adnan Khan, Muhammad Bilal, Sumeet Malik, Syed Badshah and Hafiz M. N. Iqbal

Molecules 2020, 25(1), 226; https://doi.org/10.3390/molecules25010226 - 06 Jan 2020

Cited by 68 | Viewed by 3368

Abstract

Herein, we report the development of chitosan (CH)-based bio-composite modified with acrylonitrile (AN) in the presence of carbon disulfide. The current work aimed to increase the Lewis basic centers on the polymeric backbone using single-step three-components (chitosan, carbon disulfide, and acrylonitrile) reaction. For [...] Read more.

Herein, we report the development of chitosan (CH)-based bio-composite modified with acrylonitrile (AN) in the presence of carbon disulfide. The current work aimed to increase the Lewis basic centers on the polymeric backbone using single-step three-components (chitosan, carbon disulfide, and acrylonitrile) reaction. For a said purpose, the thiocarbamate moiety was attached to the pendant functional amine (NH₂) of chitosan. Both the pristine CH and modified CH-AN bio-composites were first characterized using numerous analytical and imaging techniques, including ¹³C-NMR (solid-form), Fourier-transform infrared spectroscopy (FTIR), elemental investigation, thermogravimetric analysis, and scanning electron microscopy (SEM). Finally, the modified bio-composite (CH-AN) was deployed for the decontamination of cations from the aqueous media. The sorption ability of the CH-AN bio-composite was evaluated by applying it to lead and copper-containing aqueous solution. The chitosan-based CH-AN bio-composite exhibited greater sorption capacity for lead (2.54 mmol g⁻¹) and copper (2.02 mmol g⁻¹) than precursor chitosan from aqueous solution based on Langmuir sorption isotherm. The experimental findings fitted better to Langmuir model than Temkin and Freundlich isotherms using linear regression method. Different linearization of Langmuir model showed different error functions and isothermal parameters. The nonlinear regression analysis showed lower values of error functions as compared with linear regression analysis. The chitosan with thiocarbamate group is an outstanding material for the decontamination of toxic elements from the aqueous environment. Full article

(This article belongs to the Special Issue Biocomposites – A Path Towards Circular Economy)

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21 pages, 2987 KiB

Open AccessArticle

The Link between Polyphenol Structure, Antioxidant Capacity and Shelf-Life Stability in the Presence of Fructose and Ascorbic Acid

by Inbal Hanuka Katz, Eden Eran Nagar, Zoya Okun and Avi Shpigelman

Molecules 2020, 25(1), 225; https://doi.org/10.3390/molecules25010225 - 06 Jan 2020

Cited by 31 | Viewed by 5639

Abstract

Polyphenols play an important role in the sensorial and health-promoting properties of fruits and vegetables and display varying structure-dependent stability during processing and shelf-life. The current work aimed to increase the fundamental understanding of the link between the stability of polyphenols as a [...] Read more.

Polyphenols play an important role in the sensorial and health-promoting properties of fruits and vegetables and display varying structure-dependent stability during processing and shelf-life. The current work aimed to increase the fundamental understanding of the link between the stability of polyphenols as a function of their structure, presence of ascorbic acid and fructose and total antioxidant capacity (TAC), using a multi-component model system. Polyphenol extract, used as the multi-component model system, was obtained from freeze-dried, high polyphenol content strawberry (Fragaria × ananassa ‘Nerina’) and twenty-one compounds were identified using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The TAC and the first-order degradation kinetics were obtained, linking the polyphenol stability to its chemical structure, with and without the presence of fructose and ascorbic acid. The TAC (measured by oxygen radical absorption capacity (ORAC) and ferric reducing antioxidant potential (FRAP) assays) was not dramatically affected by storage temperatures and formulation, while polyphenol stability was significantly and structure dependently affected by temperature and the presence of ascorbic acid and fructose. Anthocyanins and phenolic acids were more unstable in the presence of ascorbic acid, while flavonol stability was enhanced by its presence. Shelf life study performed at 37 °C revealed significantly higher stability of purified polyphenols vs. the stability of the same polyphenols in the strawberry extract (multi-component system). Full article

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15 pages, 2778 KiB

Open AccessArticle

Chelerythrine Chloride Downregulates β-Catenin and Inhibits Stem Cell Properties of Non-Small Cell Lung Carcinoma

by Win Sen Heng and Shiau-Chuen Cheah

Molecules 2020, 25(1), 224; https://doi.org/10.3390/molecules25010224 - 06 Jan 2020

Cited by 30 | Viewed by 3837

Abstract

Plant secondary metabolites have been seen as alternatives to seeking new medicines for treating various diseases. Phytochemical scientists remain hopeful that compounds isolated from natural sources could help alleviate the leading problem in oncology—the lung malignancy that kills an estimated two million people [...] Read more.

Plant secondary metabolites have been seen as alternatives to seeking new medicines for treating various diseases. Phytochemical scientists remain hopeful that compounds isolated from natural sources could help alleviate the leading problem in oncology—the lung malignancy that kills an estimated two million people annually. In the present study, we characterized a medicinal compound benzophenanthridine alkaloid, called chelerythrine chloride for its anti-tumorigenic activities. Cell viability assays confirmed its cytotoxicity and anti-proliferative activity in non-small cell lung carcinoma (NSCLC) cell lines. Immunofluorescence staining of β-catenin revealed that there was a reduction of nuclear content as well as overall cellular content of β-catenin after treating NCI-H1703 with chelerythrine chloride. In functional characterizations, we observed favorable inhibitory activities of chelerythrine chloride in cancer stem cell (CSC) properties, which include soft agar colony-forming, migration, invasion, and spheroid forming abilities. Interesting observations in chelerythrine chloride treatment noted that its action abides to certain concentration-specific-targeting behavior in modulating β-catenin expression and apoptotic cell death. The downregulation of β-catenin implicates the downregulation of CSC transcription factors like SOX2 and MYC. In conclusion, chelerythrine chloride has the potential to mitigate cancer growth due to inhibitory actions toward the tumorigenic activity of CSC in lung cancer and it can be flexibly adjusted according to concentration to modulate specific targeting in different cell lines. Full article

(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)

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19 pages, 24009 KiB

Open AccessArticle

Hierarchical Structure of the Cocos nucifera (Coconut) Endocarp: Functional Morphology and its Influence on Fracture Toughness

by Stefanie Schmier, Naoe Hosoda and Thomas Speck

Molecules 2020, 25(1), 223; https://doi.org/10.3390/molecules25010223 - 06 Jan 2020

Cited by 26 | Viewed by 7956

Abstract

In recent years, the biomimetic potential of lignified or partially lignified fruit pericarps has moved into focus. For the transfer of functional principles into biomimetic applications, a profound understanding of the structural composition of the role models is important. The aim of this [...] Read more.

In recent years, the biomimetic potential of lignified or partially lignified fruit pericarps has moved into focus. For the transfer of functional principles into biomimetic applications, a profound understanding of the structural composition of the role models is important. The aim of this study was to qualitatively analyze and visualize the functional morphology of the coconut endocarp on several hierarchical levels, and to use these findings for a more precise evaluation of the toughening mechanisms in the endocarp. Eight hierarchical levels of the ripe coconut fruit were identified using different imaging techniques, including light and scanning electron microscopy as well as micro-computer-tomography. These range from the organ level of the fruit (H0) to the molecular composition (H7) of the endocarp components. A special focus was laid on the hierarchical levels of the endocarp (H3–H6). This investigation confirmed that all hierarchical levels influence the crack development in different ways and thus contribute to the pronounced fracture toughness of the coconut endocarp. By providing relevant morphological parameters at each hierarchical level with the associated toughening mechanisms, this lays the basis for transferring those properties into biomimetic technical applications. Full article

(This article belongs to the Special Issue Biological and Bio-inspired Materials)

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29 pages, 2709 KiB

Open AccessReview

Bioplatform Fabrication Approaches Affecting Chitosan-Based Interpolymer Complex Properties and Performance as Wound Dressings

by Hillary Mndlovu, Lisa C. du Toit, Pradeep Kumar, Yahya E. Choonara, Thashree Marimuthu, Pierre P. D. Kondiah and Viness Pillay

Molecules 2020, 25(1), 222; https://doi.org/10.3390/molecules25010222 - 06 Jan 2020

Cited by 20 | Viewed by 4500

Abstract

Chitosan can form interpolymer complexes (IPCs) with anionic polymers to form biomedical platforms (BMPs) for wound dressing/healing applications. This has resulted in its application in various BMPs such as gauze, nano/microparticles, hydrogels, scaffolds, and films. Notably, wound healing has been highlighted as a [...] Read more.

Chitosan can form interpolymer complexes (IPCs) with anionic polymers to form biomedical platforms (BMPs) for wound dressing/healing applications. This has resulted in its application in various BMPs such as gauze, nano/microparticles, hydrogels, scaffolds, and films. Notably, wound healing has been highlighted as a noteworthy application due to the remarkable physical, chemical, and mechanical properties enabled though the interaction of these polyelectrolytes. The interaction of chitosan and anionic polymers can improve the properties and performance of BMPs. To this end, the approaches employed in fabricating wound dressings was evaluated for their effect on the property–performance factors contributing to BMP suitability in wound dressing. The use of chitosan in wound dressing applications has had much attention due to its compatible biological properties. Recent advancement includes the control of the degree of crosslinking and incorporation of bioactives in an attempt to enhance the physicochemical and physicomechanical properties of wound dressing BMPs. A critical issue with polyelectrolyte-based BMPs is that their effective translation to wound dressing platforms has yet to be realised due to the unmet challenges faced when mimicking the complex and dynamic wound environment. Novel BMPs stemming from the IPCs of chitosan are discussed in this review to offer new insight into the tailoring of physical, chemical, and mechanical properties via fabrication approaches to develop effective wound dressing candidates. These BMPs may pave the way to new therapeutic developments for improved patient outcomes. Full article

(This article belongs to the Special Issue The Progresses on Polyelectrolytes and Polyelectrolyte Complexes)

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17 pages, 2827 KiB

Open AccessArticle

Synthesis, Structural Characterization, and Biological Activity of New Pyrazolo[4,3-e][1,2,4]triazine Acyclonucleosides

by Mariusz Mojzych, Zofia Bernat, Zbigniew Karczmarzyk, Joanna Matysiak and Andrzej Fruziński

Molecules 2020, 25(1), 221; https://doi.org/10.3390/molecules25010221 - 05 Jan 2020

Cited by 7 | Viewed by 3503

Abstract

A series of new pyrazolo[4,3-e][1,2,4]triazine acyclonucleosides 2–5 and 8 were prepared and evaluated for their anticancer activity against human cancer cell lines (MCF-7, K-562) and CDK2/E, as well as Abl protein kinases inhibitors. Lipophilicity of the compounds was determined [...] Read more.

A series of new pyrazolo[4,3-e][1,2,4]triazine acyclonucleosides 2–5 and 8 were prepared and evaluated for their anticancer activity against human cancer cell lines (MCF-7, K-562) and CDK2/E, as well as Abl protein kinases inhibitors. Lipophilicity of the compounds was determined using C-18 and immobilized artificial membrane (IAM) chromatography. In order to confirm the molecular structures and synthesis pathway of new acyclonucleosides, X-ray analysis was performed for model compound 3. Theoretical calculations at the DFT/B3LYP/6-311++G(d,p) level were used for the characterization of electronic structures of 1–8. The potential antiviral activity of acyclonucleosides 2–8 was tested in silico using molecular docking method. Full article

(This article belongs to the Section Medicinal Chemistry)

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25 pages, 1293 KiB

Open AccessArticle

Synthesis of Novel Benzodifuranyl; 1,3,5-Triazines; 1,3,5-Oxadiazepines; and Thiazolopyrimidines Derived from Visnaginone and Khellinone as Anti-Inflammatory and Analgesic Agents

by Ameen Ali Abu-Hashem, Sami A Al-Hussain and Magdi E. A. Zaki

Molecules 2020, 25(1), 220; https://doi.org/10.3390/molecules25010220 - 05 Jan 2020

Cited by 34 | Viewed by 4324

Abstract

Novel (4-methoxy or 4,8-dimethoxy)-3-methyl-N-(6-oxo-2-thioxo-1,2,3, 6-tetrahydro- pyrimidin-4-yl) benzo [1,2-b: 5, 4-b’] difuran-2-carboxamide (5a–b) has been synthesized by the reaction of visnagenone–ethylacetate (2a) or khellinone–ethylacetate (2b) with 6-aminothiouracil in dimethylformamide or refluxing of benzofuran-oxy-N [...] Read more.

Novel (4-methoxy or 4,8-dimethoxy)-3-methyl-N-(6-oxo-2-thioxo-1,2,3, 6-tetrahydro- pyrimidin-4-yl) benzo [1,2-b: 5, 4-b’] difuran-2-carboxamide (5a–b) has been synthesized by the reaction of visnagenone–ethylacetate (2a) or khellinone–ethylacetate (2b) with 6-aminothiouracil in dimethylformamide or refluxing of benzofuran-oxy-N-(2-thioxopyrimidine) acetamide (4a–b) in sodium ethoxide to give the same products (5a,b) in good yields. Thus, compounds 5a–b are used as an initiative to prepare many new heterocyclic compounds such as 2-(4-(3-methylbenzodifuran- 2-carbox-amido) pyrimidine) acetic acid (6a–b), N-(thiazolo[3, 2-a]pyrimidine)-3-methylbenzo- difuran-2-carboxamide (7a–b), N-(2-thioxopyrimidine)-methylbenzodifuran-2-carbimidoylchloride (8a–b), N-(2-(methyl-thio) pyrimidine)-3-methylbenzodifuran-2-carbimidoylchloride (9a–b), N-(2, 6 -di(piperazine or morpholine)pyrimidine)-1-(3-methylbenzodifuran)-1-(piperazine or morpholine) methanimine(10a–d), 8-(methylbenzodifuran)-thiazolopyrimido[1,6-a][1,3,5]triazine-3,5-dione (11a –b), 8-(3-methyl benzodifuran)-thiazolopyrimido[6,1-d][1,3,5]oxadiazepine-trione (12a–b), and 2,10 -di(sub-benzylidene)-8-(3-methylbenzodifuran)-thiazolopyrimido[6,1-d][1,3,5]oxadiazepine-3,5,11- trione (13a–f). All new chemical structures were illustrated on the basis of elemental and spectral analysis (IR, NMR, and MS). The new compounds were screened as cyclooxygenase-1/ cyclooxygenase-2 (COX-1/COX-2) inhibitors and had analgesic and anti-inflammatory activities. The compounds 10a–d and 13a–f had the highest inhibitory activity on COX-2 selectivity, with indices of 99–90, analgesic activity of 51–42% protection, and anti-inflammatory activity of 68%–59%. The inhibition of edema for the same compounds, 10a–d and 13a–f, was compared with sodium diclofenac as a standard drug. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 2084 KiB

Open AccessArticle

Improving the High-Frequency Response of PEI-Based Earphone with Sodium Copper Chlorophyllin

by Hao-Zhi Li, Jun-Jie Wu, Wei-Jen Lee and Chien-Sheng Chen

Molecules 2020, 25(1), 219; https://doi.org/10.3390/molecules25010219 - 05 Jan 2020

Cited by 1 | Viewed by 3337

Abstract

The polyetherimide diaphragm, sodium copper chlorophyllin (SCC), and copper ion coating composite used on earphones were observed to improve the high-frequency (10k–14k Hz) performance. This reinforcement phenomenon was expected to make the sound experience brighter and more diverse. By SEM observation, the mixed [...] Read more.

The polyetherimide diaphragm, sodium copper chlorophyllin (SCC), and copper ion coating composite used on earphones were observed to improve the high-frequency (10k–14k Hz) performance. This reinforcement phenomenon was expected to make the sound experience brighter and more diverse. By SEM observation, the mixed coating of SCC/Cu²⁺ on the polyethylenimine (PEI) diaphragm exhibited a planar blocky structure and was tightly bonded to the surface of the PEI polymer without the aid of colloids. The endothermic process of SCC and metal ion complexation was analyzed by isothermal titration calorimetry. The association ratios of SCC/Cu²⁺ and SCC/Ni²⁺ were 4/1 and 6/1, respectively, and the SCC/Cu²⁺ association yielded a stronger binding constant and more free energy. It was expected that the SCC/Cu²⁺(4/1) mixed liquid would be immobilized on the PEI polymer by multivalent interaction, including hydrogen-bonding networks between carboxyl groups of SCC and amine groups of PEI, and cross-linking of bridging copper ions. We used dimethylethylenediamine (DME) monomer instead of PEI polymer to analyze this multivalent interaction and observed a two-stage exothermic association of SCC/Cu²⁺(4/1) and DME with a total Gibbs free energy of 15.15 kcal/mol. We observed that the binding energy could be used to explain that the SCC/Cu²⁺ mixed formulation could be fixed on the surface of the PEI polymer and could enhance the strength of the PEI film. Compared with graphene films, which can continuously improve the performance of high and ultrasonic frequencies, this study was devoted to and was initiated for the purpose of applying porphyrin compounds to improve music performance. Full article

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14 pages, 1931 KiB

Open AccessArticle

Convergent Synthesis of Thioether Containing Peptides

by Spyridon Mourtas, Christina Katakalou, Dimitrios Gatos and Kleomenis Barlos

Molecules 2020, 25(1), 218; https://doi.org/10.3390/molecules25010218 - 05 Jan 2020

Cited by 4 | Viewed by 5059

Abstract

Thioether containing peptides were obtained following three synthetic routes. In route A, halo acids esterified on 2-chlorotrityl(Cltr) resin were reacted with N-fluorenylmethoxycarbonyl (Fmoc) aminothiols. These were either cleaved from the resin to the corresponding (Fmoc-aminothiol)carboxylic acids, which were used as key building [...] Read more.

Thioether containing peptides were obtained following three synthetic routes. In route A, halo acids esterified on 2-chlorotrityl(Cltr) resin were reacted with N-fluorenylmethoxycarbonyl (Fmoc) aminothiols. These were either cleaved from the resin to the corresponding (Fmoc-aminothiol)carboxylic acids, which were used as key building blocks in solid phase peptide synthesis (SPPS), or the N-Fmoc group was deprotected and peptide chains were elongated by standard SPPS. The obtained N-Fmoc protected thioether containing peptides were then condensed either in solution, or on solid support, with the appropriate amino components of peptides. In route B, the thioether containing peptides were obtained by the reaction of N-Fmoc aminothiols with bromoacetylated peptides, which were synthesized on Cltr-resin, followed by removal of the N-Fmoc group and subsequent peptide elongation by standard SPPS. In route C, the thioether containing peptides were obtained by the condensation of a haloacylated peptide synthesized on Cltr-resin and a thiol-peptide synthesized either on 4-methoxytrityl(Mmt) or trityl(Trt) resin. Full article

(This article belongs to the Special Issue Cyclic Peptide Analogues and Non-peptide Mimetics)

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12 pages, 669 KiB

Open AccessArticle

Chemical Composition, Antimicrobial, Antioxidant, and Antiproliferative Properties of Grapefruit Essential Oil Prepared by Molecular Distillation

by Weihui Deng, Ke Liu, Shan Cao, Jingyu Sun, Balian Zhong and Jiong Chun

Molecules 2020, 25(1), 217; https://doi.org/10.3390/molecules25010217 - 05 Jan 2020

Cited by 98 | Viewed by 8490

Abstract

Grapefruit essential oil has been proven to have wide range of bioactivities. However, bioactivity of its molecular distillate has not been well studied. In this study, a light phase oil was obtained by molecular distillation from cold-pressed grapefruit essential oil and GC-MS was [...] Read more.

Grapefruit essential oil has been proven to have wide range of bioactivities. However, bioactivity of its molecular distillate has not been well studied. In this study, a light phase oil was obtained by molecular distillation from cold-pressed grapefruit essential oil and GC-MS was used to identify its chemical composition. The antimicrobial activity of the light phase oil was tested by filter paper diffusion method, and the anticancer activity was determined by the Cell Counting Kit-8 (CCK-8) assay. Twenty-four components were detected with a total relative content of 99.74%, including 97.48% of terpenes and 1.66% of oxygenated terpenes. The light phase oil had the best antimicrobial effect on Bacillus subtilis, followed by Escherichia coli, Staphylococcus aureus and Salmonellaty phimurium. DPPH and ABTS assays demonstrated that the light phase oil had good antioxidant activity. The CCK-8 assay of cell proliferation showed that the light phase oil had a good inhibitory effect on the proliferation of HepG2 liver cancer cells and HCT116 colon cancer cells. Full article

(This article belongs to the Special Issue Plant Extracts: Biological and Pharmacological Activity)

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16 pages, 3119 KiB

Open AccessArticle

Two Natural Alkaloids Synergistically Induce Apoptosis in Breast Cancer Cells by Inhibiting STAT3 Activation

by Di Chen, Yangmin Ma, Zhiyu Guo, Li Liu, Yaru Yang, Yuru Wang, Bonan Pan, Luyang Wu, Yuyu Hui and Wenjuan Yang

Molecules 2020, 25(1), 216; https://doi.org/10.3390/molecules25010216 - 05 Jan 2020

Cited by 21 | Viewed by 4176

Abstract

Breast cancer has become a worldwide threat, and chemotherapy remains a routine treatment. Patients are forced to receive continuous chemotherapy and suffer from severe side effects and poor prognosis. Natural alkaloids, such as piperine (PP) and piperlongumine (PL), are expected to become a [...] Read more.

Breast cancer has become a worldwide threat, and chemotherapy remains a routine treatment. Patients are forced to receive continuous chemotherapy and suffer from severe side effects and poor prognosis. Natural alkaloids, such as piperine (PP) and piperlongumine (PL), are expected to become a new strategy against breast cancer due to their reliable anticancer potential. In the present study, cell viability, flow cytometry, and Western blot assays were performed to evaluate the suppression effect of PP and PL, alone or in combination. Data showed that PP and PL synergistically inhibited breast cancer cells proliferation at lower doses, while only weak killing effect was observed in normal breast cells, indicating a good selectivity. Furthermore, apoptosis and STAT3 signaling pathway-associated protein levels were analyzed. We demonstrated that PP and PL in combination inhibit STAT3 phosphorylation and regulate downstream molecules to induce apoptosis in breast cancer cells. Taken together, these results revealed that inactivation of STAT3 was a novel mechanism with treatment of PP and PL, suggesting that combination application of natural alkaloids may be a potential strategy for prevention and therapy of breast cancer. Full article

(This article belongs to the Section Chemical Biology)

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11 pages, 885 KiB

Open AccessArticle

Optimization of Microwave-Assisted Extraction of Antioxidants from Bamboo Shoots of Phyllostachys pubescens

by Gualtiero Milani, Francesca Curci, Maria Maddalena Cavalluzzi, Pasquale Crupi, Isabella Pisano, Giovanni Lentini, Maria Lisa Clodoveo, Carlo Franchini and Filomena Corbo

Molecules 2020, 25(1), 215; https://doi.org/10.3390/molecules25010215 - 05 Jan 2020

Cited by 24 | Viewed by 4229

Abstract

Bamboo is a well-known medicinal plant in Southeast Asia that recently has attracted attention for its high polyphenol content and its medical and nutraceutical applications. In this work, polyphenols have been recovered for the first time by microwave-assisted extraction (MAE) from an unusual [...] Read more.

Bamboo is a well-known medicinal plant in Southeast Asia that recently has attracted attention for its high polyphenol content and its medical and nutraceutical applications. In this work, polyphenols have been recovered for the first time by microwave-assisted extraction (MAE) from an unusual Italian cultivar of Phyllostachys pubescens bamboo shoots. The effects of three independent variables, such as extraction time, temperature, and solid/liquid ratio, on polyphenol recovery yield were investigated and successfully optimized through the response surface methodology. We demonstrated that MAE is an excellent polyphenols extraction technique from bamboo shoots because the total phenolic content obtained under microwave irradiation optimal conditions (4 min at 105 °C with 6.25 mg/mL ratio) was about eight-fold higher than that obtained with the conventional extraction method. Furthermore, higher total flavonoid content was also obtained under MAE. Consistent with these results, MAE enhanced the extract antioxidant properties with significant improved DPPH, ABTS, and FRAP scavenging ability. Therefore, this innovative extraction process enhances the recovery of biologically active compounds from Phyllostachys pubescens bamboo shoots with a dramatic reduction of time and energy consumption, which paves the way for its industrial application in functional food production. Full article

(This article belongs to the Special Issue Green Extraction of Natural Products)

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17 pages, 4149 KiB

Open AccessArticle

Astaxanthin Protects PC12 Cells against Homocysteine- and Glutamate-Induced Neurotoxicity

by Chi-Huang Chang, Kuan-Chou Chen, Kuo-Chun Liaw, Chiung-Chi Peng and Robert Y. Peng

Molecules 2020, 25(1), 214; https://doi.org/10.3390/molecules25010214 - 05 Jan 2020

Cited by 17 | Viewed by 3904

Abstract

Memory impairment has been shown to be associated with glutamate (Glu) excitotoxicity, homocysteine (Hcy) accumulation, and oxidative stress. We hypothesize that Glu and Hcy could damage neuronal cells, while astaxanthin (ATX) could be beneficial to alleviate the adverse effects. Using PC12 cell model, [...] Read more.

Memory impairment has been shown to be associated with glutamate (Glu) excitotoxicity, homocysteine (Hcy) accumulation, and oxidative stress. We hypothesize that Glu and Hcy could damage neuronal cells, while astaxanthin (ATX) could be beneficial to alleviate the adverse effects. Using PC12 cell model, we showed that Glu and Hcy provoked a huge amount of reactive oxygen species (ROS) production, causing mitochondrial damage at EC₅₀ 20 and 10 mm, respectively. The mechanisms of action include: (1) increasing calcium influx; (2) producing ROS; (3) initiating lipid peroxidation; (4) causing imbalance of the Bcl-2/Bax homeostasis; and (5) activating cascade of caspases involving caspases 12 and 3. Conclusively, the damages caused by Glu and Hcy to PC12 cells can be alleviated by the potent antioxidant ATX. Full article

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18 pages, 3058 KiB

Open AccessArticle

Assessing Amphiphilic ABAB Zn(II) Phthalocyanines with Enhanced Photosensitization Abilities in In Vitro Photodynamic Therapy Studies Against Cancer

by Miguel Á. Revuelta-Maza, Marta Mascaraque, Patricia González-Jiménez, Arturo González-Camuñas, Santi Nonell, Ángeles Juarranz, Gema de la Torre and Tomás Torres

Molecules 2020, 25(1), 213; https://doi.org/10.3390/molecules25010213 - 04 Jan 2020

Cited by 11 | Viewed by 3236

Abstract

We have previously demonstrated that singlet oxygen photosensitization abilities of Zn(II) phthalocyanines (Zn(II)Pcs) are enhanced through α-functionalization with bulky fluorinated substituents (i.e., bis(trifluoromethyl)phenyl units) at facing positions of ABAB Zn(II)Pcs, where A and B refer to differently functionalized isoindoles. In this work, we [...] Read more.

We have previously demonstrated that singlet oxygen photosensitization abilities of Zn(II) phthalocyanines (Zn(II)Pcs) are enhanced through α-functionalization with bulky fluorinated substituents (i.e., bis(trifluoromethyl)phenyl units) at facing positions of ABAB Zn(II)Pcs, where A and B refer to differently functionalized isoindoles. In this work, we have prepared the Zn(II)Pc ABAB 1 endowed with hydrophilic triethylene glycol monomethyl ether (i.e., at the A isoindoles) to provide solubility in aqueous media, together with its A₃B and A₄ counterparts, and compared their ability to behave as photosensitizers for photodynamic therapy. All photophysical data, aggregation studies and preliminary in vitro biological assays in cell cultures of SCC-13 (squamous cell carcinoma) and HeLa (cervical cancer cells), have proved ABAB 1 as the best photosensitizer of the series. Full article

(This article belongs to the Special Issue Porphyrinoid Derivatives: Synthesis and Biological Applications)

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14 pages, 3424 KiB

Open AccessArticle

Anti-Tumor Activity of Atractylenolide I in Human Colon Adenocarcinoma In Vitro

by Ka Woon Karen Chan, Hau Yin Chung and Wing Shing Ho

Molecules 2020, 25(1), 212; https://doi.org/10.3390/molecules25010212 - 04 Jan 2020

Cited by 12 | Viewed by 4609

Abstract

Atractylodes macrocephala is known to exhibit multi-arrays of biologic activity in vitro. However, detail of its anti-tumor activity is lacking. In this study, the effects of atractylenolide I (AT-I), a bio-active compound present in Atractylodes macrocephala rhizome was studied in the human colorectal [...] Read more.

Atractylodes macrocephala is known to exhibit multi-arrays of biologic activity in vitro. However, detail of its anti-tumor activity is lacking. In this study, the effects of atractylenolide I (AT-I), a bio-active compound present in Atractylodes macrocephala rhizome was studied in the human colorectal adenocarcinoma cell line HT-29. The results showed that AT-I induced apoptosis of human colon cancer cells through activation of the mitochondria-dependent pathway. The IC₅₀ of AT-I was 277.6 μM, 95.7 μM and 57.4 μM, after 24, 48 and 72 h of incubation with HT-29, respectively. TUNEL and Annexin V-FITC/PI double stain assays showed HT-29 DNA fragmentation after cell treatment with various AT-I concentrations. Western blotting analysis revealed activation of both initiator and executioner caspases, including caspase 3, caspase 7, and caspase 9, as well as PARP, after HT-29 treatment with AT-I via downregulation of pro-survival Bcl-2, and upregulation of anti-survival Bcl-2 family proteins, including Bax, Bak, Bad, Bim, Bid and Puma. The studies show for the first time that AT-I is an effective drug candidate towards the HT-29 cell. Full article

(This article belongs to the Special Issue Anti-Cancer Drug: Discovery, Development and Combination)

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15 pages, 2008 KiB

Open AccessFeature PaperArticle

Interactions of Paraoxonase-1 with Pharmacologically Relevant Carbamates

by Anita Bosak, Aljoša Bavec, Tilen Konte, Goran Šinko, Zrinka Kovarik and Marko Goličnik

Molecules 2020, 25(1), 211; https://doi.org/10.3390/molecules25010211 - 04 Jan 2020

Cited by 9 | Viewed by 2992

Abstract

Mammalian paraoxonase-1 hydrolyses a very broad spectrum of esters such as certain drugs and xenobiotics. The aim of this study was to determine whether carbamates influence the activity of recombinant PON1 (rePON1). Carbamates were selected having a variety of applications: bambuterol and physostigmine [...] Read more.

Mammalian paraoxonase-1 hydrolyses a very broad spectrum of esters such as certain drugs and xenobiotics. The aim of this study was to determine whether carbamates influence the activity of recombinant PON1 (rePON1). Carbamates were selected having a variety of applications: bambuterol and physostigmine are drugs, carbofuran is used as a pesticide, while Ro 02-0683 is diagnostic reagent. All the selected carbamates reduced the arylesterase activity of rePON1 towards the substrate S-phenyl thioacetate (PTA). Inhibition dissociation constants (K_i), evaluated by both discontinuous and continuous inhibition measurements (progress curves), were similar and in the mM range. The rePON1 displayed almost the same values of K_i constants for Ro 02-0683 and physostigmine while, for carbofuran and bambuterol, the values were approximately ten times lower and two times higher, respectively. The affinity of rePON1 towards the tested carbamates was about 3–40 times lower than that of PTA. Molecular modelling of rePON1-carbamate complexes suggested non-covalent interactions with residues of the rePON1 active site that could lead to competitive inhibition of its arylesterase activity. In conclusion, carbamates can reduce the level of PON1 activity, which should be kept in mind, especially in medical conditions characterized by reduced PON1 levels. Full article

(This article belongs to the Special Issue Enzymes Reacting with Organophosphorus Compounds)

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11 pages, 1396 KiB

Open AccessArticle

Extraction of High Value Triterpenic Acids from Eucalyptus globulus Biomass Using Hydrophobic Deep Eutectic Solvents

by Nuno H. C. S. Silva, Eduarda S. Morais, Carmen S. R. Freire, Mara G. Freire and Armando J. D. Silvestre

Molecules 2020, 25(1), 210; https://doi.org/10.3390/molecules25010210 - 04 Jan 2020

Cited by 36 | Viewed by 4602

Abstract

Triterpenic acids (TTAs), known for their promising biological properties, can be found in different biomass sources and related by-products, such as Eucalyptus globulus bark, and have been extracted using organic volatile solvents such as dichloromethane. Recently, deep eutectic solvents (DES) have been identified [...] Read more.

Triterpenic acids (TTAs), known for their promising biological properties, can be found in different biomass sources and related by-products, such as Eucalyptus globulus bark, and have been extracted using organic volatile solvents such as dichloromethane. Recently, deep eutectic solvents (DES) have been identified as promising alternatives for the extraction of value-added compounds from biomass. In the present work, several hydrophobic DES were tested for the extraction of TTAs from E. globulus bark. Initial solubility studies revealed that DES based on menthol and thymol as the most promising solvents for these compounds given the highest solubilities obtained for ursolic acid (UA) at temperatures ranging from room temperature up to 90 °C. Accordingly, an eutectic mixture of menthol:thymol (1:2) was confirmed as the best candidate for the TTAs extraction from E. globulus outer bark, leading to extraction yields (weight of TTA per weight of biomass) at room temperature of 1.8 wt% for ursolic acid, 0.84 wt% for oleanolic acid and 0.30 wt% for betulinic acid. These values are significantly higher than those obtained with conventional organic solvents under similar conditions. The results obtained using these DES are promising for the recovery of TTAs for nutraceutical and pharmacological applications, while reinforcing the potential of DES as promising solvents to be applied in biorefinery processes. Full article

(This article belongs to the Special Issue Deep Eutectic Solvents)

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20 pages, 2693 KiB

Open AccessArticle

Pharmacokinetic Comparison of Epinastine Using Developed Human Plasma Assays

by Seung-Hyun Jeong, Ji-Hun Jang, Hea-Young Cho and Yong-Bok Lee

Molecules 2020, 25(1), 209; https://doi.org/10.3390/molecules25010209 - 03 Jan 2020

Cited by 3 | Viewed by 3716

Abstract

The purpose of the study was to develop two new methods, HPLC-UV and UPLC-MS/MS, for quantifying epinastine in human plasma and to compare pharmacokinetic (PK) parameters obtained using them. Even in the same sample, there may be a difference in the quantitative value [...] Read more.

The purpose of the study was to develop two new methods, HPLC-UV and UPLC-MS/MS, for quantifying epinastine in human plasma and to compare pharmacokinetic (PK) parameters obtained using them. Even in the same sample, there may be a difference in the quantitative value of drug depending on the assay, so that minor changes in PK parameter values may affect drug dose and usage settings. Therefore, selection and establishment of analytical methods are very important in PK studies of drugs, and a comparison of PK parameters according to analytical methods will be vital. For this study of PK parameter change, we newly developed two methods, HPLC-UV and UPLC-MS/MS, which are most commonly used to quantify epinastine concentrations in human plasma. All developed methods satisfied the international guidelines and criteria for successful application to PK study of 20 mg epinastine hydrochloride tablets after oral administration to twenty-six humans. A comparison of these two methods for in vivo analysis of epinastine was performed for the first time. This comparison study confirmed that different dose and usage settings might be possible based on PK parameters calculated using other analyses. Such changes in calculated PK parameters according to analytical methods would be crucial in the clinic. Full article

(This article belongs to the Special Issue Method Development and Validation in Food and Pharmaceutical Analysis)

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