Molecules

17 pages, 7417 KiB

Open AccessArticle

QSAR Model for Predicting the Cannabinoid Receptor 1 Binding Affinity and Dependence Potential of Synthetic Cannabinoids

by Wonyoung Lee, So-Jung Park, Ji-Young Hwang, Kwang-Hyun Hur, Yong Sup Lee, Jongmin Kim, Xiaodi Zhao, Aekyung Park, Kyung Hoon Min, Choon-Gon Jang and Hyun-Ju Park

Molecules 2020, 25(24), 6057; https://doi.org/10.3390/molecules25246057 - 21 Dec 2020

Cited by 6 | Viewed by 3104

Abstract

In recent years, there have been frequent reports on the adverse effects of synthetic cannabinoid (SC) abuse. SCs cause psychoactive effects, similar to those caused by marijuana, by binding and activating cannabinoid receptor 1 (CB1R) in the central nervous system. The aim of [...] Read more.

In recent years, there have been frequent reports on the adverse effects of synthetic cannabinoid (SC) abuse. SCs cause psychoactive effects, similar to those caused by marijuana, by binding and activating cannabinoid receptor 1 (CB1R) in the central nervous system. The aim of this study was to establish a reliable quantitative structure–activity relationship (QSAR) model to correlate the structures and physicochemical properties of various SCs with their CB1R-binding affinities. We prepared tetrahydrocannabinol (THC) and 14 SCs and their derivatives (naphthoylindoles, naphthoylnaphthalenes, benzoylindoles, and cyclohexylphenols) and determined their binding affinity to CB1R, which is known as a dependence-related target. We calculated the molecular descriptors for dataset compounds using an R/CDK (R package integrated with CDK, version 3.5.0) toolkit to build QSAR regression models. These models were established, and statistical evaluations were performed using the mlr and plsr packages in R software. The most reliable QSAR model was obtained from the partial least squares regression method via Y-randomization test and external validation. This model can be applied in vivo to predict the addictive properties of illicit new SCs. Using a limited number of dataset compounds and our own experimental activity data, we built a QSAR model for SCs with good predictability. This QSAR modeling approach provides a novel strategy for establishing an efficient tool to predict the abuse potential of various SCs and to control their illicit use. Full article

(This article belongs to the Special Issue QSAR and QSPR: Recent Developments and Applications II)

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20 pages, 5800 KiB

Open AccessArticle

Protaetia brevitarsis seulensis Derived Protein Isolate with Enhanced Osteomodulatory and Antioxidative Property

by Keya Ganguly, Min-Soo Jeong, Sayan Deb Dutta, Dinesh K. Patel, Seong-Jun Cho and Ki-Taek Lim

Molecules 2020, 25(24), 6056; https://doi.org/10.3390/molecules25246056 - 21 Dec 2020

Cited by 11 | Viewed by 2504

Abstract

The osteogenic differentiation of stem cells is profoundly affected by their microenvironmental conditions. The differentiation behavior of stem cells can be tuned by changing the niche environments. The proteins or peptides that are derived by living organisms facilitate the osteogenic differentiation of stem [...] Read more.

The osteogenic differentiation of stem cells is profoundly affected by their microenvironmental conditions. The differentiation behavior of stem cells can be tuned by changing the niche environments. The proteins or peptides that are derived by living organisms facilitate the osteogenic differentiation of stem cells. Here, we have evaluated the osteoinductive and antioxidative potential of the Protaetia brevitarsis seulensis insect-derived protein for human bone marrow-derived mesenchymal stem cells (hBMSCs). The amino acid contents in the isolated protein were determined by an amino acid analyzer. Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) were used to analyze the extract’s functional groups and surface morphology. The extracted protein exhibited 51.08% β-sheet conformation. No adverse effects were observed in extract-treated cells, indicating their biocompatibility. The protein isolate showed an excellent antioxidative property. Besides this, an enhancement in the hBMSCs’ mineralization has been observed in the presence of treated protein isolates. Notably, osteogenic marker genes and proteins were effectively expressed in the treated cells. These results indicated that the P. brevitarsis-derived protein isolate can be used as a potential antioxidative biomaterial for bone tissue engineering applications. Full article

(This article belongs to the Special Issue Biomaterials for Hard Tissue Regeneration)

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9 pages, 2104 KiB

Open AccessBrief Report

Binding Interactions of Peptide Aptamers

by Roger R. C. New, Tam T. T. Bui and Michal Bogus

Molecules 2020, 25(24), 6055; https://doi.org/10.3390/molecules25246055 - 21 Dec 2020

Cited by 6 | Viewed by 2795

Abstract

Peptide aptamers are short amino acid chains that are capable of binding specifically to ligands in the same way as their much larger counterparts, antibodies. Ligands of therapeutic interest that can be targeted are other peptide chains or loops located on the surface [...] Read more.

Peptide aptamers are short amino acid chains that are capable of binding specifically to ligands in the same way as their much larger counterparts, antibodies. Ligands of therapeutic interest that can be targeted are other peptide chains or loops located on the surface of protein receptors (e.g., GCPR), which take part in cell-to-cell communications either directly or via the intermediary of hormones or signalling molecules. To confer on aptamers the same sort of conformational rigidity that characterises an antibody binding site, aptamers are often constructed in the form of cyclic peptides, on the assumption that this will encourage stronger binding interactions than would occur if the aptamers were simply linear chains. However, no formal studies have been conducted to confirm the hypothesis that linear peptides will engage in stronger binding interactions with cyclic peptides than with other linear peptides. In this study, the interaction of a model cyclic decamer with a series of linear peptide constructs was compared with that of a linear peptide with the same sequence, showing that the cyclic configuration does confer benefits by increasing the strength of binding. Full article

(This article belongs to the Special Issue Advances in Research of Short Peptides)

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18 pages, 2570 KiB

Open AccessArticle

Synthesis and Matrix Properties of α-Cyano-5-phenyl-2,4-pentadienic Acid (CPPA) for Intact Proteins Analysis by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry

by Antonio Monopoli, Angelo Nacci, Tommaso R. I. Cataldi and Cosima D. Calvano

Molecules 2020, 25(24), 6054; https://doi.org/10.3390/molecules25246054 - 21 Dec 2020

Cited by 7 | Viewed by 2888

Abstract

The effectiveness of a synthesized matrix, α-cyano-5-phenyl-2,4-pentadienic acid (CPPA), for protein analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in complex samples such as foodstuff and bacterial extracts, is demonstrated. Ultraviolet (UV) absorption along with laser desorption/ionization mass spectrometry (LDI-MS) experiments [...] Read more.

The effectiveness of a synthesized matrix, α-cyano-5-phenyl-2,4-pentadienic acid (CPPA), for protein analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in complex samples such as foodstuff and bacterial extracts, is demonstrated. Ultraviolet (UV) absorption along with laser desorption/ionization mass spectrometry (LDI-MS) experiments were systematically conducted in positive ion mode under standard Nd:YLF laser excitation with the aim of characterizing the matrix in terms of wavelength absorption and proton affinity. Besides, the results for standard proteins revealed that CPPA significantly enhanced the protein signals, reduced the spot-to-spot variability and increased the spot homogeneity. The CPPA matrix was successful employed to investigate intact microorganisms, milk and seed extracts for protein profiling. Compared to conventional matrices such as sinapinic acid (SA), α-cyano-4-hydroxycinnamic acid (CHCA) and 4-chloro-α-cyanocinnamic acid (CClCA), CPPA exhibited better signal-to-noise (S/N) ratios and a uniform response for most examined proteins occurring in milk, hazelnut and in intact bacterial cells of E. coli. These findings not only provide a reactive proton transfer MALDI matrix with excellent reproducibility and sensitivity, but also contribute to extending the battery of useful matrices for intact protein analysis. Full article

(This article belongs to the Special Issue Advancements in Analytical Techniques for Proteomics)

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20 pages, 2402 KiB

Open AccessReview

Effervescence-Assisted Microextraction—One Decade of Developments

by Guillermo Lasarte-Aragonés, Rafael Lucena and Soledad Cárdenas

Molecules 2020, 25(24), 6053; https://doi.org/10.3390/molecules25246053 - 21 Dec 2020

Cited by 22 | Viewed by 3752

Abstract

Dispersive microextraction techniques are key in the analytical sample treatment context as they combine a favored thermodynamics and kinetics isolation of the target analytes from the sample matrix. The dispersion of the extractant in the form of tiny particles or drops, depending on [...] Read more.

Dispersive microextraction techniques are key in the analytical sample treatment context as they combine a favored thermodynamics and kinetics isolation of the target analytes from the sample matrix. The dispersion of the extractant in the form of tiny particles or drops, depending on the technique, into the sample enlarges the contact surface area between phases, thus enhancing the mass transference. This dispersion can be achieved by applying external energy sources, the use of chemicals, or the combination of both strategies. Effervescence-assisted microextraction emerged in 2011 as a new alternative in this context. The technique uses in situ-generated carbon dioxide as the disperser, and it has been successfully applied in the solid-phase and liquid-phase microextraction fields. This minireview explains the main fundamentals of the technique, its potential and the main developments reported. Full article

(This article belongs to the Special Issue Advances towards Green Analytical Chemistry)

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33 pages, 12836 KiB

Open AccessReview

Phytochemicals with Added Value from Morella and Myrica Species

by Gonçalo P. Rosa, Bruno J. C. Silva, Ana M. L. Seca, Laila M. Moujir and Maria Carmo Barreto

Molecules 2020, 25(24), 6052; https://doi.org/10.3390/molecules25246052 - 21 Dec 2020

Cited by 5 | Viewed by 2998

Abstract

Terrestrial plants, due to their sessile nature, are highly exposed to environmental pressure and therefore need to produce very effective molecules that enable them to survive all the threats. Myrica and Morella (Myricaceae) are taxonomically close genera, which include species of trees or [...] Read more.

Terrestrial plants, due to their sessile nature, are highly exposed to environmental pressure and therefore need to produce very effective molecules that enable them to survive all the threats. Myrica and Morella (Myricaceae) are taxonomically close genera, which include species of trees or shrubs with edible fruits that exhibit relevant uses in traditional medicine. For instance, in Chinese or Japanese folk medicine, they are used to treat diarrhea, digestive problems, headache, burns, and skin diseases. A wide array of compounds isolated from different parts of Myrica and/or Morella species possess several biological activities, like anticancer, antidiabetic, anti-obesity, and cardio-/neuro-/hepatoprotective activities, both in vitro and in vivo, with myricanol, myricitrin, quercitrin, and betulin being the most promising. There are still many other compounds isolated from both genera whose biological activities have not been evaluated, which represents an excellent opportunity to discover new applications for those compounds and valorize Morella/Myrica species. Full article

(This article belongs to the Special Issue Discovering New Natural Compounds with Pharmacological or Biotechnological Applications)

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12 pages, 2368 KiB

Open AccessArticle

FT-IR/ATR Solid Film Formation: Qualitative and Quantitative Analysis of a Piperacillin-Tazobactam Formulation

by Ioanna Chrisikou, Malvina Orkoula and Christos Kontoyannis

Molecules 2020, 25(24), 6051; https://doi.org/10.3390/molecules25246051 - 21 Dec 2020

Cited by 5 | Viewed by 2741

Abstract

FT-IR/ATR analytical technique is one of the most applicable techniques worldwide. It is closely associated with easy-to-use equipment, rapid analysis, and reliable results. This study reports the simultaneous qualitative and quantitative analysis of two active pharmaceutical ingredients (APIs), of a piperacillin and tazobactam [...] Read more.

FT-IR/ATR analytical technique is one of the most applicable techniques worldwide. It is closely associated with easy-to-use equipment, rapid analysis, and reliable results. This study reports the simultaneous qualitative and quantitative analysis of two active pharmaceutical ingredients (APIs), of a piperacillin and tazobactam formulation using a film formation method. This method requires film formation on the ATR crystal, resulting from solvent evaporation of a small amount of liquid sample. Good contact between the film and the crystal led to the identification of both APIs, although tazobactam was of low content in the formulation mixture. The quantification of the APIs in the commercial mixture was also achieved, using a single calibration line with a correlation coefficient equal to 0.999, not only after film formation but also in the initial dry formulation before reconstitution. The present spectroscopic technique combined with the proposed relatively simple sample treatment outweighs chromatographic protocols already applied, which require specialized staff and are costly, time-consuming, and not environmentally friendly. Taking all the above into consideration, it turns out that such an approach has the potential to be used for off-line quality control procedures in manufacture or, in terms of portable equipment and automated software, anywhere for on-site analysis, even in a hospital workflow. Full article

(This article belongs to the Special Issue Sample Preparation-Quo Vadis: Current Status of Sample Preparation Approaches)

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16 pages, 2928 KiB

Open AccessArticle

Identification of Aroma Composition and Key Odorants Contributing to Aroma Characteristics of White Teas

by Qin-Cao Chen, Yin Zhu, Han Yan, Mei Chen, Dong-Chao Xie, Meng-Qi Wang, De-Jiang Ni and Zhi Lin

Molecules 2020, 25(24), 6050; https://doi.org/10.3390/molecules25246050 - 21 Dec 2020

Cited by 46 | Viewed by 3762

Abstract

The identification of aroma composition and key odorants contributing to aroma characteristics of white tea is urgently needed, owing to white tea’s charming flavors and significant health benefits. In this study, a total of 238 volatile components were identified in the three subtypes [...] Read more.

The identification of aroma composition and key odorants contributing to aroma characteristics of white tea is urgently needed, owing to white tea’s charming flavors and significant health benefits. In this study, a total of 238 volatile components were identified in the three subtypes of white teas using headspace solid-phase microextraction (HS-SPME) combined with comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry (GC × GC–TOFMS). The multivariate statistical analysis demonstrated that the contents of 103 volatile compounds showed extremely significant differences, of which 44 compounds presented higher contents in Baihaoyinzhen and Baimudan, while the other 59 compounds exhibited higher contents in Shoumei. The sensory evaluation experiment carried out by gas chromatography–olfactometry/mass spectrometry (GC–O/MS) revealed 44 aroma-active compounds, of which 25 compounds were identified, including 9 alcohols, 6 aldehydes, 5 ketones, and 5 other compounds. These odorants mostly presented green, fresh, floral, fruity, or sweet odors. Multivariate analyses of chemical characterization and sensory evaluation results showed that high proportions of alcohols and aldehydes form the basis of green and fresh aroma characteristic of white teas, and phenylethyl alcohol, γ-Nonalactone, trans-β-ionone, trans-linalool oxide (furanoid), α-ionone, and cis-3-hexenyl butyrate were considered as the key odorants accounting for the different aroma characteristics of the three subtypes of white tea. The results will contribute to in-depth understand chemical and sensory markers associated with different subtypes of white tea, and provide a solid foundation for tea aroma quality control and improvement. Full article

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18 pages, 5294 KiB

Open AccessArticle

Methotrexate Gold Nanocarriers: Loading and Release Study: Its Activity in Colon and Lung Cancer Cells

by Beatriz Álvarez-González, Marisa Rozalen, María Fernández-Perales, Miguel A. Álvarez and Manuel Sánchez-Polo

Molecules 2020, 25(24), 6049; https://doi.org/10.3390/molecules25246049 - 21 Dec 2020

Cited by 18 | Viewed by 3101

Abstract

In the present study, the synthesis of gold nanoparticles (AuNPs) loaded with methotrexate (MTX) has been carried out in order to obtain controlled size and monodispersed nanocarriers of around 20 nm. The characterization study shows metallic AuNPs with MTX polydispersed on the surface. [...] Read more.

In the present study, the synthesis of gold nanoparticles (AuNPs) loaded with methotrexate (MTX) has been carried out in order to obtain controlled size and monodispersed nanocarriers of around 20 nm. The characterization study shows metallic AuNPs with MTX polydispersed on the surface. MTX is linked by the replacement of citrate by the MTX carboxyl group. The drug release profiles show faster MTX release when it is conjugated, which leads to the best control of plasma concentration. Moreover, the enhanced release observed at pH 5 could take advantage of the pH gradients that exist in tumor microenvironments to achieve high local drug concentrations. AuNP–MTX conjugates were tested by flow cytometry against lung (A-549) and colon (HTC-116) cancer cell lines. Results for A-549 showed a weaker dose–response effect than for colon cancer ones. This could be related to the presence of folate receptors in line HTC-116 in comparison to line A-549, supporting the specific uptake of folate-conjugated AuNP–MTX by folate receptor positive tumor cells. Conjugates exhibited considerably higher cytotoxic effects compared with the effects of equal doses of free MTX. Annexin V-PI tests sustained the cell death mechanism of apoptosis, which is normally disabled in cancer cells. Full article

(This article belongs to the Special Issue Metallodrugs, Metallopharmaceuticals and Bio-Inspired Metal-organic Frameworks)

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12 pages, 3424 KiB

Open AccessCommunication

Mapping the Chiroptical Properties of Local Domains in Thin Films of Chiral Silicon Phthalocyanines by CD Imaging

by Dora-M. Răsădean, Tiberiu-M. Gianga, Tamás Jávorfi, Rohanah Hussain, Giuliano Siligardi and G. Dan Pantoș

Molecules 2020, 25(24), 6048; https://doi.org/10.3390/molecules25246048 - 21 Dec 2020

Cited by 5 | Viewed by 2193

Abstract

The first example of uniformly chiral thin films of silicon phthalocyanines (SiPcs) are reported. The local domains of the films are mapped using circular dichroism (CD) imaging (CDi) technique available at the Diamond B23 beamline. The CDi allowed us to [...] Read more.

The first example of uniformly chiral thin films of silicon phthalocyanines (SiPcs) are reported. The local domains of the films are mapped using circular dichroism (CD) imaging (CDi) technique available at the Diamond B23 beamline. The CDi allowed us to increase the spatial resolution up to 525× when compared with benchtop spectrometers. The results indicate formation on-surface of chiral and stable supramolecular assemblies with homogenous distribution. Chemical functionalization and solvent choice for deposition allow controllable chiroptical properties to be obtained. The method and technique reported in this work could be applied to prepare and characterize a wide variety of chiral thin films. Full article

(This article belongs to the Special Issue Phthalocyanines and Porphyrins)

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26 pages, 5422 KiB

Open AccessArticle

Structural Analysis of Oxidized Cerebrosides from the Extract of Deep-Sea Sponge Aulosaccus sp.: Occurrence of Amide-Linked Allylically Oxygenated Fatty Acids

by Elena A. Santalova, Vladimir A. Denisenko and Pavel S. Dmitrenok

Molecules 2020, 25(24), 6047; https://doi.org/10.3390/molecules25246047 - 21 Dec 2020

Cited by 4 | Viewed by 2241

Abstract

The structural elucidation of primary and secondary peroxidation products, formed from complex lipids, is a challenge in lipid analysis. In the present study, rare minor oxidized cerebrosides, isolated from the extract of a far eastern deep-sea glass sponge, Aulosaccus sp., were analyzed as [...] Read more.

The structural elucidation of primary and secondary peroxidation products, formed from complex lipids, is a challenge in lipid analysis. In the present study, rare minor oxidized cerebrosides, isolated from the extract of a far eastern deep-sea glass sponge, Aulosaccus sp., were analyzed as constituents of a multi-component RP-HPLC (high-performance liquid chromatography on reversed-phase column) fraction using NMR (nuclear magnetic resonance) spectroscopy, mass spectrometry, GC (gas chromatography), and chemical transformations (including hydrogenation or derivatization with dimethyl disulfide before hydrolysis). Eighteen previously unknown β-D-glucopyranosyl-(1→1)-ceramides (1a–a^//, 1b–b^//, 2a–a^//, 2b–b^//, 3c–c^//, 3d–d^//) were shown to contain phytosphingosine-type backbones (2S,3S,4R,11Z)-2-aminoeicos-11-ene-1,3,4-triol (in 1), (2S,3S,4R,13Z)-2-aminoeicos-13-ene-1,3,4-triol (in 2), and (13S*,14R*)-2-amino-13,14-methylene-eicosane-1,3,4-triol (in 3). These backbones were N-acylated with straight-chain monoenoic (2R)-2-hydroxy acids that had allylic hydroperoxy/hydroxy/keto groups on C-17^/ in the 15^/E-23:1 chain (a–a^//), C-16^/ in the 17^/E-23:1 (b–b^//) and 14^/E-22:1 (c–c^//) chains, and C-15^/ in the 16^/E-22:1 chain (d–d^//). Utilizing complementary instrumental and chemical methods allowed for the first detailed structural analysis of a complex mixture of glycosphingolipids, containing allylically oxygenated monoenoic acyl chains. Full article

(This article belongs to the Special Issue Dedicated to the 55th Anniversary of G.B. Elyakov Pacific Institute of Bioorganic Chemistry of the Far Eastern Branch of the Russian Academy of Sciences)

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16 pages, 2971 KiB

Open AccessArticle

Diesel Exhaust Particulates Induce Neutrophilic Lung Inflammation by Modulating Endoplasmic Reticulum Stress-Mediated CXCL1/KC Expression in Alveolar Macrophages

by Dong Im Kim, Mi-Kyung Song, Hye-In Kim, Kang Min Han and Kyuhong Lee

Molecules 2020, 25(24), 6046; https://doi.org/10.3390/molecules25246046 - 21 Dec 2020

Cited by 20 | Viewed by 2231

Abstract

Diesel exhaust particulates (DEP) have adverse effects on the respiratory system. Endoplasmic reticulum (ER) abnormalities contribute to lung inflammation. However, the relationship between DEP exposure and ER stress in the respiratory immune system and especially the alveolar macrophages (AM) is poorly understood. Here, [...] Read more.

Diesel exhaust particulates (DEP) have adverse effects on the respiratory system. Endoplasmic reticulum (ER) abnormalities contribute to lung inflammation. However, the relationship between DEP exposure and ER stress in the respiratory immune system and especially the alveolar macrophages (AM) is poorly understood. Here, we examined ER stress and inflammatory responses using both in vivo and in vitro study. For in vivo study, mice were intratracheally instilled with 25, 50, and 100 μg DEP and in vitro AM were stimulated with DEP at 1, 2, and 3 mg/mL. DEP increased lung weight and the number of inflammatory cells, especially neutrophils, and inflammatory cytokines in bronchoalveolar lavage fluid of mice. DEP also increased the number of DEP-pigmented AM and ER stress markers including bound immunoglobulin protein (BiP) and CCAAT/enhancer binding protein-homologous protein (CHOP) were upregulated in the lungs of DEP-treated mice. In an in vitro study, DEP caused cell damage, increased intracellular reactive oxygen species, and upregulated inflammatory genes and ER stress-related BiP, CHOP, splicing X-box binding protein 1, and activating transcription factor 4 expressions in AM. Furthermore, DEP released the C-X-C Motif Chemokine Ligand 1 (CXCL1/KC) in AM. In conclusion, DEP may contribute to neutrophilic lung inflammation pathogenesis by modulating ER stress-mediated CXCL1/KC expression in AM. Full article

(This article belongs to the Section Chemical Biology)

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12 pages, 3284 KiB

Open AccessArticle

Therapeutic Potential of Rhododendron arboreum Polysaccharides in an Animal Model of Lipopolysaccharide-Inflicted Oxidative Stress and Systemic Inflammation

by Ajaz Ahmad, Adil Farooq Wali, Muneeb U. Rehman, Andleeb Khan, Mohammad Raish, Mohsin Kazi, Osamah Alnemer and Padma G. M. Rao

Molecules 2020, 25(24), 6045; https://doi.org/10.3390/molecules25246045 - 21 Dec 2020

Cited by 10 | Viewed by 2375

Abstract

Systemic inflammation results in physiological changes, largely mediated by inflammatory cytokines. The present investigation was performed to determine the effect of Rhododendron arboreum (RAP) on inflammatory parameters in the animal model. The RAP (100 and 200 mg/kg) were pre-treated for animals, given orally [...] Read more.

Systemic inflammation results in physiological changes, largely mediated by inflammatory cytokines. The present investigation was performed to determine the effect of Rhododendron arboreum (RAP) on inflammatory parameters in the animal model. The RAP (100 and 200 mg/kg) were pre-treated for animals, given orally for one week, followed by lipopolysaccharide (LPS) injection. Body temperature, burrowing, and open field behavioral changes were assessed. Biochemical parameters (AST, ALT, LDH, BIL, CK, Cr, BUN, and albumin) were done in the plasma after 6 h of LPS challenge. Oxidative stress markers SOD, CAT, and MDA were measured in different organs. Levels of inflammatory markers like tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β) and, interleukin-6 (IL-6) as well as VEGF, a specific sepsis marker in plasma, were quantified. The plasma enzymes, antioxidant markers and plasma pro-inflammatory cytokines were significantly restored (p < 0.5) by RAP treatment, thus preventing the multi-organ and tissue damage in LPS induced rats. The protective effect of RAP may be due to its potent antioxidant potential. Thus, RAP can prevent LPS induced oxidative stress, as well as inflammatory and multi-organ damage as reported in histopathological studies in rats when administered to the LPS treated animals. These findings indicate that RAP can benefit in the management of systemic inflammation from LPS and may have implications for a new treatment or preventive therapeutic strategies with an inflammatory component. Full article

(This article belongs to the Special Issue Plant Natural Products: Isolation, Identification and Biological Activity)

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17 pages, 1924 KiB

Open AccessArticle

Effect of CO₂ Flow Rate on the Extraction of Astaxanthin and Fatty Acids from Haematococcus pluvialis Using Supercritical Fluid Technology

by Carolina Espinosa Álvarez, Renata Vardanega, Francisca Salinas-Fuentes, Jenifer Palma Ramírez, Waldo Bugueño Muñoz, Diana Jiménez-Rondón, M. Angela A. Meireles, Pedro Cerezal Mezquita and Mari Carmen Ruiz-Domínguez

Molecules 2020, 25(24), 6044; https://doi.org/10.3390/molecules25246044 - 21 Dec 2020

Cited by 20 | Viewed by 3353

Abstract

Haematococcus pluvialis is the largest producer of natural astaxanthin in the world. Astaxanthin is a bioactive compound used in food, feed, nutraceutics, and cosmetics. In this study, astaxanthin extraction from H. pluvialis by supercritical fluid extraction was evaluated. The effects of temperature (40 [...] Read more.

Haematococcus pluvialis is the largest producer of natural astaxanthin in the world. Astaxanthin is a bioactive compound used in food, feed, nutraceutics, and cosmetics. In this study, astaxanthin extraction from H. pluvialis by supercritical fluid extraction was evaluated. The effects of temperature (40 and 50 °C), pressure (40 and 50 MPa), and CO₂ flow rate (2 and 4 L/min) were investigated. The results showed that the highest astaxanthin recovery was obtained at 50 °C/50 MPa and the CO₂ flow rates evaluated had no significant effect. It was possible to achieve astaxanthin recoveries of 95% after 175 min for a CO₂ flow rate of 2 L/min, and 95 min for CO₂ flow rate of 4 L/min. The ω-6/ω-3 ratios obtained were similar in all conditions, reaching 0.87, demonstrating that the extracts from H. pluvialis by SFE are rich in unsaturated fatty acids (UFA) which increases their positive effects when used as a functional ingredient in food. Full article

(This article belongs to the Special Issue Chemical Applications of Supercritical Fluids)

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10 pages, 2745 KiB

Open AccessArticle

Chitosan Oligosaccharides Coupling Inhibits Bacterial Biofilm-Related Antibiotic Resistance against Florfenicol

by Xianghua Yuan, Jing Liu, Ruilian Li, Junlin Zhou, Jinhua Wei, Siming Jiao, Zhuo A. Wang and Yuguang Du

Molecules 2020, 25(24), 6043; https://doi.org/10.3390/molecules25246043 - 21 Dec 2020

Cited by 9 | Viewed by 2120

Abstract

The formation of bacterial biofilms has increased the resistance of bacteria to various environmental factors and is tightly associated with many persistent and chronic bacterial infections. Herein we design a strategy conjugating florfenicol, an antibiotic commonly used in the treatment of streptococcus, [...] Read more.

The formation of bacterial biofilms has increased the resistance of bacteria to various environmental factors and is tightly associated with many persistent and chronic bacterial infections. Herein we design a strategy conjugating florfenicol, an antibiotic commonly used in the treatment of streptococcus, with the antimicrobial biomaterial, chitosan oligosaccharides. The results demonstrated that the florfenicol-COS conjugate (F-COS) efficiently eradicated the mature Streptococcus hyovaginalis biofilm, apparently inhibiting drug resistance to florfenicol. A quantity of 250 μg/mL F-COS showed effective inhibitory activity against planktonic cells and biofilm of the bacteria, and a 4-fold improvement of the F-COS compared to unmodified florfenicol was observed. Furthermore, the conjugate showed a broad-spectrum activity against both Gram-positive and Gram-negative bacteria. It suggested that F-COS might have a potential for application in the treatment of biofilm-related infections. Full article

(This article belongs to the Special Issue Antibiofilm Efficacy of Natural and Natural-Based Products)

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24 pages, 2869 KiB

Open AccessFeature PaperReview

Fluorine-18-Labeled Fluorescent Dyes for Dual-Mode Molecular Imaging

by Maxime Munch, Benjamin H. Rotstein and Gilles Ulrich

Molecules 2020, 25(24), 6042; https://doi.org/10.3390/molecules25246042 - 21 Dec 2020

Cited by 10 | Viewed by 4101

Abstract

Recent progress realized in the development of optical imaging (OPI) probes and devices has made this technique more and more affordable for imaging studies and fluorescence-guided surgery procedures. However, this imaging modality still suffers from a low depth of penetration, thus limiting its [...] Read more.

Recent progress realized in the development of optical imaging (OPI) probes and devices has made this technique more and more affordable for imaging studies and fluorescence-guided surgery procedures. However, this imaging modality still suffers from a low depth of penetration, thus limiting its use to shallow tissues or endoscopy-based procedures. In contrast, positron emission tomography (PET) presents a high depth of penetration and the resulting signal is less attenuated, allowing for imaging in-depth tissues. Thus, association of these imaging techniques has the potential to push back the limits of each single modality. Recently, several research groups have been involved in the development of radiolabeled fluorophores with the aim of affording dual-mode PET/OPI probes used in preclinical imaging studies of diverse pathological conditions such as cancer, Alzheimer’s disease, or cardiovascular diseases. Among all the available PET-active radionuclides, ¹⁸F stands out as the most widely used for clinical imaging thanks to its advantageous characteristics (t_1/2 = 109.77 min; 97% β⁺ emitter). This review focuses on the recent efforts in the synthesis and radiofluorination of fluorescent scaffolds such as 4,4-difluoro-4-bora-diazaindacenes (BODIPYs), cyanines, and xanthene derivatives and their use in preclinical imaging studies using both PET and OPI technologies. Full article

(This article belongs to the Special Issue Fluorine in Imaging toward Biological and Medical Applications)

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20 pages, 15143 KiB

Open AccessArticle

An Analysis of Exhaust Emission of the Internal Combustion Engine Treated by the Non-Thermal Plasma

by Ming-Hsien Hsueh, Chia-Nan Wang, Meng-Chang Hsieh, Chao-Jung Lai, Shi-Hao Wang, Chia-Hsin Hsieh, Tsung-Liang Wu and Jo-Hung Yu

Molecules 2020, 25(24), 6041; https://doi.org/10.3390/molecules25246041 - 21 Dec 2020

Cited by 6 | Viewed by 2561

Abstract

Industries’ air pollution causes serious challenges to modern society, among them exhaust gases from internal combustion engines, which are currently one of the main sources. This study proposes a non-thermal plasma (NTP) system for placement in the exhaust system of internal combustion engines [...] Read more.

Industries’ air pollution causes serious challenges to modern society, among them exhaust gases from internal combustion engines, which are currently one of the main sources. This study proposes a non-thermal plasma (NTP) system for placement in the exhaust system of internal combustion engines to reduce the toxic contaminants (HC, CO, and NO_x) of exhaust gases. This NTP system generates a high-voltage discharge that not only responds to the ion chemical reaction to eliminate NO_x and CO, but that also generates a combustion reaction at the local high temperature of plasma to reduce HC. The NTP system was designed on both the front and rear of the exhaust pipe to analyze the difference of different exhaust flow rates under the specified frequency. The results indicate that the NTP system can greatly reduce toxic contaminants. The NTP reactor placed in the front of exhaust pipe gave HC and CO removal efficiency of about 34.5% and 16.0%, respectively, while the NTP reactor placed in the rear of exhaust pipe gave NO_x removal efficiency of about 41.3%. In addition, the voltage and material directly affect the exhaust gases obviously. In conclusion, the proposed NTP system installed in the exhaust system can significantly reduce air pollutants. These results suggest that applying NTP to the combustion engine should be a useful tool to simultaneously reduce both emissions of NO_x and CO. Full article

(This article belongs to the Special Issue Innovative Materials and Methods for the Removal of Pollutants from the Environment)

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10 pages, 888 KiB

Open AccessCommentary

John B. Goodenough’s Role in Solid State Chemistry Community: A Thrilling Scientific Tale Told by a French Chemist

by Michel Pouchard

Molecules 2020, 25(24), 6040; https://doi.org/10.3390/molecules25246040 - 21 Dec 2020

Cited by 5 | Viewed by 2949

Abstract

In this tribute to John B. Goodenough I will describe how John’s talk on the metal-to-nonmetal transition of vanadium oxide VO₂, presented at the Bordeaux Conference (September 1964) attended by inorganic chemists, metallurgists, crystallographers, thermodynamicists and physicists, provided a pioneering vision [...] Read more.

In this tribute to John B. Goodenough I will describe how John’s talk on the metal-to-nonmetal transition of vanadium oxide VO₂, presented at the Bordeaux Conference (September 1964) attended by inorganic chemists, metallurgists, crystallographers, thermodynamicists and physicists, provided a pioneering vision of interdisciplinary research to come. John gave a complete description of the paradigm on how the physical properties of a solid depend on its structure and bonding, by employing the chemical notions as local distortions and interatomic distances as well as the physics notions such as band width and the Hubbard on-site repulsion U. I will illustrate how inspiring John’s ideas were, by discussing the research examples of my own research group in the sixties-seventies. The fundamental approach of John B. Goodenough to Solid State Chemistry, leading particularly to lithium battery applications, is at the heart of the 2019 Nobel Prize awarded to John. Full article

(This article belongs to the Special Issue A Themed Issue Dedicated to Professor John B. Goodenough on the Occasion of His 100th Birthday Anniversary)

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9 pages, 1623 KiB

Open AccessFeature PaperArticle

Multicomponent Synthesis of Luminescent Iminoboronates

by Samuel Guieu, Cátia I. C. Esteves, João Rocha and Artur M. S. Silva

Molecules 2020, 25(24), 6039; https://doi.org/10.3390/molecules25246039 - 21 Dec 2020

Cited by 4 | Viewed by 2337

Abstract

A family of iminoboronates was prepared through a one-pot multicomponent reaction, starting from boronic acid, anthranilic acid, and different salicylaldehydes. Their synthesis was straightforward and the complexes were obtained in good to excellent yields. Their photophysical properties were assessed in a diluted solution, [...] Read more.

A family of iminoboronates was prepared through a one-pot multicomponent reaction, starting from boronic acid, anthranilic acid, and different salicylaldehydes. Their synthesis was straightforward and the complexes were obtained in good to excellent yields. Their photophysical properties were assessed in a diluted solution, and the complexes proved to be faintly luminescent. These chelates demonstrated remarkable Aggregation-Induced Emission Enhancement, which was rationalized using crystal structures. Full article

(This article belongs to the Special Issue New Synthetic Methods for Organic Compounds)

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11 pages, 1481 KiB

Open AccessArticle

Effects of Deacidification on Composition of Schisandra chinensis Ethanolic Extract and Studies on Acute Toxicity in Mice

by Gaosheng Hu, Zhuangbo Qi, Anhua Wang and Jingming Jia

Molecules 2020, 25(24), 6038; https://doi.org/10.3390/molecules25246038 - 21 Dec 2020

Cited by 4 | Viewed by 2119

Abstract

Schisandra chinensis Fructus (SCF), a well-known traditional medicinal material, is a rich source of dibenzocyclooctene type lignans and polyphenols, which are important ingredients in SCF and show various activities. SCF also contains about 18% organic acids, mainly citric acid, which makes the fruit [...] Read more.

Schisandra chinensis Fructus (SCF), a well-known traditional medicinal material, is a rich source of dibenzocyclooctene type lignans and polyphenols, which are important ingredients in SCF and show various activities. SCF also contains about 18% organic acids, mainly citric acid, which makes the fruit and extract taste extremely sour and limited its application in beverages or food industries. In the present study, a chemical deacidification method was applied to defatted and non-defatted ethanol extract of SCF, and the effects on organic acid, lignans, and phenolic compounds were evaluated. Free radical scavenging activity and acute toxicity in mice before and after deacidification were also compared. Our results demonstrated that chemical deacidification significantly decreased the contents of organic acid and lignan compounds and markedly improves the safety of the ethanol extract of SCF, which will facilitate the comprehensive utilization of SCF extract in food and beverage industries. Full article

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25 pages, 8158 KiB

Open AccessReview

Revisiting the Self-Assembly of Highly Aromatic Phenylalanine Homopeptides

by Enric Mayans and Carlos Alemán

Molecules 2020, 25(24), 6037; https://doi.org/10.3390/molecules25246037 - 20 Dec 2020

Cited by 22 | Viewed by 2817

Abstract

Diphenylalanine peptide (FF), which self-assembles into rigid tubular nanostructures, is a very short core recognition motif in Alzheimer’s disease β-amyloid (Aβ) polypeptide. Moreover, the ability of the phenylalanine (F or Phe)-homopeptides to self-assemble into ordered nanostructures has been proved. Within this context it [...] Read more.

Diphenylalanine peptide (FF), which self-assembles into rigid tubular nanostructures, is a very short core recognition motif in Alzheimer’s disease β-amyloid (Aβ) polypeptide. Moreover, the ability of the phenylalanine (F or Phe)-homopeptides to self-assemble into ordered nanostructures has been proved. Within this context it was shown that the assembly preferences of this family of compounds is altered by capping both the N- and C-termini using highly aromatic fluorenyl groups (i.e., fluorenyl-9-methoxycarbonyl and 9-fluorenylmethyl ester, named Fmoc and OFm, respectively). In this article the work performed in the field of the effect of the structure and incubation conditions on the morphology and polymorphism of short (from two to four amino acid residues) Phe-homopeptides is reviewed and accompanied by introducing some new results for completing the comparison. Special attention has been paid to the influence of solvent: co-solvent mixture used to solubilize the peptide, the peptide concentration and, in some cases, the temperature. More specifically, uncapped (FF, FFF, and FFFF), N-capped with Fmoc (Fmoc-FF, Fmoc-FFF, and Fmoc-FFFF), C-capped with OFm (FF-OFm), and doubly capped (Fmoc-FF-OFm, Fmoc-FFF-OFm, and Fmoc-FFFF-OFm) Phe-homopeptides have been re-measured. Although many of the experienced assembly conditions have been only revisited as they were previously reported, other experimental conditions have been examined by the first time in this work. In any case, pooling the effect of highly aromatic blocking groups in a single study, using a wide variety of experimental conditions, allows a perspective of how the disappearance of head-to-tail electrostatic interactions and the gradual increase in the amount of π–π stacking interactions, affects the morphology of the assemblies. Future technological applications of Phe-homopeptides can be envisaged by choosing the most appropriate self-assemble structure, defining not only the length of the peptide but also the amount and the position of fluorenyl capping groups. Full article

(This article belongs to the Special Issue Peptides and Peptidomimetics: From Synthesis to Applications)

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8 pages, 2885 KiB

Open AccessArticle

Correlation between Ferromagnetic Layer Easy Axis and the Tilt Angle of Self Assembled Chiral Molecules

by Nir Sukenik, Francesco Tassinari, Shira Yochelis, Oded Millo, Lech Tomasz Baczewski and Yossi Paltiel

Molecules 2020, 25(24), 6036; https://doi.org/10.3390/molecules25246036 - 20 Dec 2020

Cited by 19 | Viewed by 2882

Abstract

The spin–spin interactions between chiral molecules and ferromagnetic metals were found to be strongly affected by the chiral induced spin selectivity effect. Previous works unraveled two complementary phenomena: magnetization reorientation of ferromagnetic thin film upon adsorption of chiral molecules and different interaction rate [...] Read more.

The spin–spin interactions between chiral molecules and ferromagnetic metals were found to be strongly affected by the chiral induced spin selectivity effect. Previous works unraveled two complementary phenomena: magnetization reorientation of ferromagnetic thin film upon adsorption of chiral molecules and different interaction rate of opposite enantiomers with a magnetic substrate. These phenomena were all observed when the easy axis of the ferromagnet was out of plane. In this work, the effects of the ferromagnetic easy axis direction, on both the chiral molecular monolayer tilt angle and the magnetization reorientation of the magnetic substrate, are studied using magnetic force microscopy. We have also studied the effect of an applied external magnetic field during the adsorption process. Our results show a clear correlation between the ferromagnetic layer easy axis direction and the tilt angle of the bonded molecules. This tilt angle was found to be larger for an in plane easy axis as compared to an out of plane easy axis. Adsorption under external magnetic field shows that magnetization reorientation occurs also after the adsorption event. These findings show that the interaction between chiral molecules and ferromagnetic layers stabilizes the magnetic reorientation, even after the adsorption, and strongly depends on the anisotropy of the magnetic substrate. This unique behavior is important for developing enantiomer separation techniques using magnetic substrates. Full article

(This article belongs to the Special Issue Advances of Magnetic Materials)

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4 pages, 7679 KiB

Open AccessEditorial

The “Materials Chemistry” Section of Molecules: A Multidisciplinary Environment for Materials-Based Researches

by Giuseppe Cirillo

Molecules 2020, 25(24), 6035; https://doi.org/10.3390/molecules25246035 - 20 Dec 2020

Viewed by 1589

Abstract

The “Materials Chemistry” Section of Molecules is an open access place for the dissemination of theoretical and experimental studies related to the chemical approaches to materials-based problems [...] Full article

(This article belongs to the Section Materials Chemistry)

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9 pages, 1152 KiB

Open AccessArticle

New Cyclic Diarylheptanoids from Platycarya strobilacea

by Wen-bing Ding, Rui-yuan Zhao, Guan-hua Li, Bing-lei Liu, Hua-liang He, Lin Qiu, Jin Xue and You-zhi Li

Molecules 2020, 25(24), 6034; https://doi.org/10.3390/molecules25246034 - 20 Dec 2020

Cited by 8 | Viewed by 1946

Abstract

Five new cyclic diarylheptanoids (platycary A–E, compounds 1–5) and three previously identified analogues (i.e., phttyearynol (compound 6), myricatomentogenin (compound 7), and juglanin D (compound 8)) were isolated from the stem bark of Platycarya strobilacea. The structures [...] Read more.

Five new cyclic diarylheptanoids (platycary A–E, compounds 1–5) and three previously identified analogues (i.e., phttyearynol (compound 6), myricatomentogenin (compound 7), and juglanin D (compound 8)) were isolated from the stem bark of Platycarya strobilacea. The structures of these compounds were determined using NMR, HRESIMS, and electronic circular dichroism (ECD) data. The cytotoxicity of compounds 1–5 and their ability to inhibit nitric oxide (NO) production, as well as protect against the corticosterone-induced apoptosis of Pheochromocytoma (PC12) cells, were evaluated in vitro using the appropriate bioassays. Compounds 1 and 2 significantly inhibited the corticosterone-induced apoptosis of PC12 cells at a concentration of 20 μΜ. Full article

(This article belongs to the Section Natural Products Chemistry)

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18 pages, 2573 KiB

Open AccessArticle

New Application of 1,2,4-Triazole Derivatives as Antitubercular Agents. Structure, In Vitro Screening and Docking Studies

by Zbigniew Karczmarzyk, Marta Swatko-Ossor, Waldemar Wysocki, Monika Drozd, Grazyna Ginalska, Anna Pachuta-Stec and Monika Pitucha

Molecules 2020, 25(24), 6033; https://doi.org/10.3390/molecules25246033 - 19 Dec 2020

Cited by 31 | Viewed by 3338

Abstract

A series of 1,2,4-triazole derivatives were synthesized and assigned as potential anti-tuberculosis substances. The molecular and crystal structures for the model compounds C1, C12, and C13 were determined using X-ray analysis. The X-ray investigation confirmed the synthesis pathway and the assumed molecular structures [...] Read more.

A series of 1,2,4-triazole derivatives were synthesized and assigned as potential anti-tuberculosis substances. The molecular and crystal structures for the model compounds C1, C12, and C13 were determined using X-ray analysis. The X-ray investigation confirmed the synthesis pathway and the assumed molecular structures for analyzed 1,2,4-triazol-5-thione derivatives. The conformational preferences resulting from rotational degrees of freedom of the 1,2,4-triazole ring substituents were characterized. The lipophilicity (logP) and electronic parameters as the energy of frontier orbitals, dipole moments, NBO net charge distribution on the atoms, and electrostatic potential distribution for all structures were calculated at AM1 and DFT/B3LYP/6-311++G(d,p) level. The in vitro test was done against M. tuberculosis H₃₇Ra, M. phlei, M. smegmatis, and M. timereck. The obtained results clearly confirmed the antituberculosis potential of compound C4, which turned out to be the most active against Mycobacterium H₃₇Ra (MIC = 0.976 μg/mL), Mycobaterium pheli (MIC = 7.81 μg/mL) and Mycobacerium timereck (62.6 μg/mL). Satisfactory results were obtained with compounds C8, C11, C14 versus Myc. H₃₇Ra, Myc. pheli, Myc. timereck (MIC = 31.25−62.5 μg/mL). The molecular docking studies were carried out for all investigated compounds using the Mycobacterium tuberculosis cytochrome P450 CYP121 enzyme as molecular a target connected with antimycobacterial activity. Full article

(This article belongs to the Special Issue Design, Synthesis, and Analysis of Potential Drugs)

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15 pages, 2791 KiB

Open AccessArticle

Sample Preparation of Posaconazole Oral Suspensions for Identification of the Crystal Form of the Active Pharmaceutical Ingredient

by Michail Lykouras, Stefani Fertaki, Malvina Orkoula and Christos Kontoyannis

Molecules 2020, 25(24), 6032; https://doi.org/10.3390/molecules25246032 - 19 Dec 2020

Cited by 2 | Viewed by 3321

Abstract

Determination of the polymorphic form of an active pharmaceutical ingredient (API) in a suspension could be really challenging because of the water phase and the low concentration of the API in this formulation. Posaconazole is an antifungal drug available also as an oral [...] Read more.

Determination of the polymorphic form of an active pharmaceutical ingredient (API) in a suspension could be really challenging because of the water phase and the low concentration of the API in this formulation. Posaconazole is an antifungal drug available also as an oral suspension. The aim of this study was to develop a sample-preparation method for polymorphic identification of the dispersed API by increasing the concentration of the API but with no compromise of polymorph stability. For this purpose, filtration, drying and centrifugation were tested for separating the API from the suspending medium. Centrifugation was selected because it succeeded in separating Posaconazole API with no polymorph transformation during the process. During this study, it was found that Posaconazole in oral suspensions is Form-S. However, when slower scanning rates were used for acquiring an XRPD pattern with better signal/noise ratio, Posaconazole was converted to Form I due to water loss. In order to protect the sample from conversion, different approaches were tested to secure an airtight sample including a commercially available XRPD sample holder with a dome-like transparent cap, standard polymethylmethacrylate (PMMA) sample holders covered with Mylar film, transparent pressure-sensitive tape and a transparent food membrane. Only usage of the transparent food membrane was found to protect the API from conversion for a period of at least two weeks and resulted in a Posaconazole Form-S XRPD pattern with no artificial peaks. Full article

(This article belongs to the Special Issue Sample Preparation-Quo Vadis: Current Status of Sample Preparation Approaches)

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19 pages, 3079 KiB

Open AccessArticle

Extraction of Vanillin Following Bioconversion of Rice Straw and Its Optimization by Response Surface Methodology

by Irnia Nurika, Sri Suhartini, Nurul Azizah and Guy C. Barker

Molecules 2020, 25(24), 6031; https://doi.org/10.3390/molecules25246031 - 19 Dec 2020

Cited by 12 | Viewed by 4496

Abstract

Value-added chemicals, including phenolic compounds, can be generated through lignocellulosic biomass conversion via either biological or chemical pretreatment. Currently vanillin is one of the most valuable of these products that has been shown to be extractable on an industrial scale. This study demonstrates [...] Read more.

Value-added chemicals, including phenolic compounds, can be generated through lignocellulosic biomass conversion via either biological or chemical pretreatment. Currently vanillin is one of the most valuable of these products that has been shown to be extractable on an industrial scale. This study demonstrates the potential of using rice straw inoculated with Serpula lacrymans, which produced a mixture of high value bio-based compounds including vanillin. Key extraction conditions were identified to be the volume of solvent used and extraction time, which were optimized using response surface methodology (RSM). The vanillin compounds extracted from rice straw solid state fermentation (SSF) was confirmed through LC-ESI MS/MS in selective ion mode. The optimum concentration and yield differed depending on the solvent, which was predicted using 60 mL ethyl acetate for 160 min were 0.408% and 3.957 μg g⁻¹ respectively. In comparison, when ethanol was used, the highest concentration and yields of vanillin were 0.165% and 2.596 μg g⁻¹. These were achieved using 40 mL of solvent, and extraction time increased to 248 min. The results confirm that fungal conversion of rice straw to vanillin could consequently offer a cost-effect alternative to other modes of production. Full article

(This article belongs to the Special Issue Biobased Chemicals: Environmentally Friendly Solutions for Sustainable Development)

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18 pages, 5110 KiB

Open AccessArticle

Dendrons and Dendritic Terpolymers: Synthesis, Characterization and Self-Assembly Comparison

by Sofia Rangou, Dimitrios Moschovas, Ioannis Moutsios, Gkreti-Maria Manesi, Konstantina Tsitoni, Polina V. Bovsunovskaya, Dimitri A. Ivanov, Edwin L. Thomas and Apostolos Avgeropoulos

Molecules 2020, 25(24), 6030; https://doi.org/10.3390/molecules25246030 - 19 Dec 2020

Cited by 4 | Viewed by 2249

Abstract

To the best of our knowledge, this is the very first time that a thorough study of the synthetic procedures, molecular and thermal characterization, followed by structure/properties relationship for symmetric and non-symmetric second generation (2-G) dendritic terpolymers is reported. Actually, the synthesis of [...] Read more.

To the best of our knowledge, this is the very first time that a thorough study of the synthetic procedures, molecular and thermal characterization, followed by structure/properties relationship for symmetric and non-symmetric second generation (2-G) dendritic terpolymers is reported. Actually, the synthesis of the non-symmetric materials is reported for the first time in the literature. Anionic polymerization enables the synthesis of well-defined polymers that, despite the architecture complexity, absolute control over the average molecular weight, as well as block composition, is achieved. The dendritic type macromolecular architecture affects the microphase separation, because different morphologies are obtained, which do not exhibit long range order, and various defects or dislocations are evident attributed to the increased number of junction points of the final material despite the satisfactory thermal annealing at temperatures above the highest glass transition temperature of all blocks. For comparison reasons, the initial dendrons (miktoarm star terpolymer precursors) which are connected to each other in order to synthesize the final dendritic terpolymers are characterized in solution and in bulk and their self-assembly is also studied. A major conclusion is that specific structures are adopted which depend on the type of the core connection between the ligand and the active sites of the dendrons. Full article

(This article belongs to the Special Issue Exclusive Contributions by the Editorial Board Members (EBMs) of the Macromolecular Chemistry Section of Molecules)

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14 pages, 2391 KiB

Open AccessArticle

PARP Theranostic Auger Emitters Are Cytotoxic in BRCA Mutant Ovarian Cancer and Viable Tumors from Ovarian Cancer Patients Enable Ex-Vivo Screening of Tumor Response

by Aladdin Riad, Sarah B. Gitto, Hwan Lee, Harrison D. Winters, Paul M. Martorano, Chia-Ju Hsieh, Kuiying Xu, Dalia K. Omran, Daniel J. Powell, Jr., Robert H. Mach and Mehran Makvandi

Molecules 2020, 25(24), 6029; https://doi.org/10.3390/molecules25246029 - 19 Dec 2020

Cited by 20 | Viewed by 3600

Abstract

Theranostics are emerging as a pillar of cancer therapy that enable the use of single molecule constructs for diagnostic and therapeutic application. As poly adenosine diphosphate (ADP)-ribose polymerase 1 (PARP-1) is overexpressed in various cancer types, and is localized to the nucleus, PARP-1 [...] Read more.

Theranostics are emerging as a pillar of cancer therapy that enable the use of single molecule constructs for diagnostic and therapeutic application. As poly adenosine diphosphate (ADP)-ribose polymerase 1 (PARP-1) is overexpressed in various cancer types, and is localized to the nucleus, PARP-1 can be safely targeted with Auger emitters to induce DNA damage in tumors. Here, we investigated a radioiodinated PARP inhibitor, [¹²⁵I]KX1, and show drug target specific DNA damage and subsequent killing of BRCA1 and non-BRCA mutant ovarian cancer cells at sub-pharmacological concentrations several orders of magnitude lower than traditional PARP inhibitors. Furthermore, we demonstrated that viable tumor tissue from ovarian cancer patients can be used to screen tumor radiosensitivity ex-vivo, enabling the direct assessment of therapeutic efficacy. Finally, we showed tumors can be imaged by single-photon computed tomography (SPECT) with PARP theranostic, [¹²³I]KX1, in a human ovarian cancer xenograft mouse model. These data support the utility of PARP-1 targeted radiopharmaceutical therapy as a theranostic option for PARP-1 overexpressing ovarian cancers. Full article

(This article belongs to the Special Issue Recent Advances in Techniques with Radionuclide for Theranostic Drugs)

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15 pages, 3464 KiB

Open AccessArticle

The Antiasthma Medication Ciclesonide Suppresses Breast Cancer Stem Cells through Inhibition of the Glucocorticoid Receptor Signaling-Dependent YAP Pathway

by Su-Lim Kim, Hack Sun Choi, Ji-Hyang Kim and Dong-Sun Lee

Molecules 2020, 25(24), 6028; https://doi.org/10.3390/molecules25246028 - 19 Dec 2020

Cited by 9 | Viewed by 2439

Abstract

Ciclesonide is an FDA-approved glucocorticoid used to treat asthma and allergic rhinitis. However, whether it has anticancer and anti-cancer stem cell (CSC) effects is unknown. This study focused on investigating the effect of ciclesonide on breast cancer and CSCs and determining its underlying [...] Read more.

Ciclesonide is an FDA-approved glucocorticoid used to treat asthma and allergic rhinitis. However, whether it has anticancer and anti-cancer stem cell (CSC) effects is unknown. This study focused on investigating the effect of ciclesonide on breast cancer and CSCs and determining its underlying mechanism. Here, we showed that ciclesonide inhibits breast cancer and CSC formation. Similar glucocorticoids—dexamethasone and prednisone—did not inhibit CSC formation. Ciclesonide-induced glucocorticoid receptor (GR) degradation was dependent on ubiquitination. We showed via GR small interfering RNA (siRNA) that GR plays an important role in CSC formation. We showed via western blot and immunofluorescence assays that ciclesonide reduces the nuclear level of GR. The GR antagonist RU-486 also inhibited CSC formation. Ciclesonide reduced the protein level of the Hippo transducer Yes-associated protein (YAP). GR siRNA induced a decrease in YAP protein expression and inhibited mammosphere formation. The YAP inhibitor verteporfin inhibited CSC formation and transcription of the connective tissue growth factor and cysteine-rich protein 61 genes. The GR/YAP1 pathway regulated breast CSC formation. We showed that the GR/YAP signaling pathway regulates breast CSC formation and revealed a new approach for targeting GR and YAP to inhibit CSC formation. Full article

(This article belongs to the Special Issue Recent Advances in Anticancer Drugs II)

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