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Molecules, Volume 26, Issue 14 (July-2 2021) – 282 articles

Cover Story (view full-size image): Harnessing solar energy and converting it into renewable fuels by chemical processes represent a highly promising, yet challenging, strategy to mitigate the effects arising from the global energy crisis and environmental concerns. In recent years, covalent organic framework (COF)-based materials have gained substantial research interest because of their diversified architecture, tunable composition and high thermal and chemical stability. In this feature article, we have highlighted the latest progress in the synthetic methodologies of COFs for their application in photocatalytic hydrogen evolution and CO2 utilization reactions. The novelty aspect and the photocatalytic performances have been summarized along with a discussion of mechanistic pathways under visible light irradiation conditions. View this paper.
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Article
Fatty Acid Ethyl Esters (FAEE): A New, Green and Renewable Solvent for the Extraction of Carotenoids from Tomato Waste Products
Molecules 2021, 26(14), 4388; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144388 - 20 Jul 2021
Viewed by 868
Abstract
Currently there is a drive towards the minimisation and reclamation of valuable materials from the waste products of the food and beverage industry. This can be achieved through the extraction of residual nutraceuticals from such materials. Tomato pomace contains carotenoids and other chemicals [...] Read more.
Currently there is a drive towards the minimisation and reclamation of valuable materials from the waste products of the food and beverage industry. This can be achieved through the extraction of residual nutraceuticals from such materials. Tomato pomace contains carotenoids and other chemicals which can be extracted directly into edible oils to improve the health-giving properties of such oils. We report here a novel green solvent, fatty acid ethyl esters (FAEE), which is significantly more effective than sunflower oil and hexane for the extraction of lycopene and beta-carotene from tomato skin waste. FAEE are a non-toxic renewable resource that is environmentally friendly and to our knowledge has never been used as a vegetal extraction fluid. The efficiency of FAEE extraction was significantly improved relative to both sunflower oil and hexane under ultrasound-assisted extraction (UAE) conditions. In addition, FAEE have the additional and significant advantage that once enriched with the extracted nutraceuticals can be used directly as a food additive. Full article
(This article belongs to the Special Issue Ultrasound- and Microwave-Assisted Extraction of Bioactive Compounds)
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Article
Structural, Mechanistic, and Functional Insights into an Arthrobacter nicotinovorans Molybdenum Hydroxylase Involved in Nicotine Degradation
Molecules 2021, 26(14), 4387; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144387 - 20 Jul 2021
Viewed by 507
Abstract
Arthrobacter nicotinovorans decomposes nicotine through the pyridine pathway. 6-hydroxypseudooxynicotine 2-oxidoreductase (also named ketone dehydrogenase, Kdh) is an important enzyme in nicotine degradation pathway of A. nicotinovorans, and is responsible for the second hydroxylation of nicotine. Kdh belongs to the molybdenum hydroxylase family, [...] Read more.
Arthrobacter nicotinovorans decomposes nicotine through the pyridine pathway. 6-hydroxypseudooxynicotine 2-oxidoreductase (also named ketone dehydrogenase, Kdh) is an important enzyme in nicotine degradation pathway of A. nicotinovorans, and is responsible for the second hydroxylation of nicotine. Kdh belongs to the molybdenum hydroxylase family, and catalyzes the oxidation of 6-hydroxy-pseudooxynicotine (6-HPON) to 2,6-dihydroxy-pseudooxynicotine (2,6-DHPON). We determined the crystal structure of the Kdh holoenzyme from A. nicotinovorans, with its three subunits KdhL, KdhM, and KdhS, and their associated cofactors molybdopterin cytosine dinucleotide (MCD), two iron-sulfur clusters (Fe2S2), and flavin adenine dinucleotide (FAD), respectively. In addition, we obtained a structural model of the substrate 6-HPON-bound Kdh through molecular docking, and performed molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations to unveil the catalytic mechanism of Kdh. The residues Glu345, Try551, and Glu748 of KdhL were found to participate in substrate binding, and Phe269 and Arg383 of KdhL were found to contribute to stabilize the MCD conformation. Furthermore, site-directed mutagenesis and enzymatic activity assays were performed to support our structural and computational results, which also revealed a trend of increasing catalytic efficiency with the increase in the buffer pH. Lastly, our electrochemical results demonstrated electron transfer among the various cofactors of Kdh. Therefore, our work provides a comprehensive structural, mechanistic, and functional study on the molybdenum hydroxylase Kdh in the nicotine degradation pathway of A. nicotinovorans. Full article
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Article
Valorization of Artichoke Industrial By-Products Using Green Extraction Technologies: Formulation of Hydrogels in Combination with Paulownia Extracts
Molecules 2021, 26(14), 4386; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144386 - 20 Jul 2021
Viewed by 362
Abstract
The integral valorization of artichoke bracts generated during industrial canning of artichoke was assessed. The extraction of bioactive compounds was addressed with pressurized hot water under subcritical conditions. The performance of this stage on the extraction of phenolics with antioxidant properties and the [...] Read more.
The integral valorization of artichoke bracts generated during industrial canning of artichoke was assessed. The extraction of bioactive compounds was addressed with pressurized hot water under subcritical conditions. The performance of this stage on the extraction of phenolics with antioxidant properties and the saccharidic fraction using conventional and microwave heating was compared. The microwave assisted process was more efficient than the conventional one regarding extraction yields of total solubles, and glucose and fructose oligomers and phenolics, because lower operational temperatures and shorter times were needed. Degradation of fructose oligomers was observed at temperatures higher than 160 °C, whereas the maximal phenolic content occurred at 220 °C. Both the extracts and the residual solids, obtained at conditions leading to maximum phenolics yields, were evaluated for the production of starch-based hydrogels, supplemented with Paulownia leaves’ aqueous extracts. Full article
(This article belongs to the Special Issue Ultrasound- and Microwave-Assisted Extraction of Bioactive Compounds)
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Review
Direct Arylation in the Presence of Palladium Pincer Complexes
Molecules 2021, 26(14), 4385; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144385 - 20 Jul 2021
Viewed by 583
Abstract
Direct arylation is an atom-economical alternative to more established procedures such as Stille, Suzuki or Negishi arylation reactions. In comparison with other palladium sources and ligands, the use of palladium pincer complexes as catalysts or pre-catalysts for direct arylation has resulted in improved [...] Read more.
Direct arylation is an atom-economical alternative to more established procedures such as Stille, Suzuki or Negishi arylation reactions. In comparison with other palladium sources and ligands, the use of palladium pincer complexes as catalysts or pre-catalysts for direct arylation has resulted in improved efficiency, higher reaction yields, and advantageous reaction conditions. In addition to a revision of the literature concerning intra- and intermolecular direct arylation reactions performed in the presence of palladium pincer complexes, the role of these remarkably active catalysts will also be discussed. Full article
(This article belongs to the Special Issue Organic Synthesis via Transition Metal-Catalysis)
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Article
Lignin Quantification of Papyri by TGA—Not a Good Idea
Molecules 2021, 26(14), 4384; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144384 - 20 Jul 2021
Viewed by 495
Abstract
Papyri belong to the oldest writing grounds in history. Their conservation is of the highest importance in preserving our cultural heritage, which is best achieved based on an extensive knowledge of the materials’ constituents to choose a tailored conservation approach. Thermogravimetric Analysis (TGA) [...] Read more.
Papyri belong to the oldest writing grounds in history. Their conservation is of the highest importance in preserving our cultural heritage, which is best achieved based on an extensive knowledge of the materials’ constituents to choose a tailored conservation approach. Thermogravimetric Analysis (TGA) has been widely employed to quantify cellulose and lignin in papyrus sheets, yielding reported lignin contents of 25% to 40%. In this work, the TGA method conventionally used for papyrus samples was repeated and compared to other lignin determination approaches (Klason-lignin and acetyl bromide-soluble lignin). TGA can lead to a large overestimation of the lignin content of commercial papyrus sheets (~27%) compared to the other methods (~5%). A similar overestimation of the lignin content was found for the pith and rind of the native papyrus plant. We concluded that the TGA method should, therefore, not be used for lignin quantification. Full article
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Article
The Influence of HCl Concentration on the Rate of the Hydrolysis–Condensation Reaction of Phenyltrichlorosilane and the Yield of (Tetrahydroxy)(Tetraphenyl)Cyclotetrasiloxanes, Synthesis of All Its Geometrical Isomers and Thermal Self-Condensation of Them under “Pseudo”-Equilibrium Conditions
Molecules 2021, 26(14), 4383; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144383 - 20 Jul 2021
Viewed by 376
Abstract
The rate of hydrolysis–condensation reaction of phenyltrichlorosilane in water-acetone solutions and the product yields were shown to significantly depend on the concentration of HCl (CHCl) in the solutions. The main product of the reaction was all-cis-(tetrahydroxy)(tetraphenyl)cyclotetrasiloxane. This was different [...] Read more.
The rate of hydrolysis–condensation reaction of phenyltrichlorosilane in water-acetone solutions and the product yields were shown to significantly depend on the concentration of HCl (CHCl) in the solutions. The main product of the reaction was all-cis-(tetrahydroxy)(tetraphenyl)cyclotetrasiloxane. This was different from the earlier published results of analogous reactions of m-tolylSiCl3, m-ClPhSiCl3, and α-naphtylSiCl, in which some products of other types were formed. For example, trans-1,1,3,3-tetrahydroxy-1,3-di-α-naphtyldisiloxane was obtained in the case of α-naphtylSiCl3. All-cis-(tetrahydroxy)(tetraphenyl)cyclotetrasiloxane was treated in acetone with HCl to give the other three geometric isomers (cis-cis-trans-, cis-trans-, and all-trans-). The thermal self-condensation of these four isomers under “pseudo”-equilibrium conditions (under atmospheric pressure) was investigated in different solvents, in quartz or molybdenum glass flasks. The compositions of the products were monitored by APCI-MS and 29Si NMR spectroscopy. It was shown that all-cis- and cis-cis-trans-isomers in toluene or anisole mostly gave the cage-like Ph-T8,10,12,14 and uncompleted cage-like Ph-T10,12OSi(HO)Ph compounds. In contrast to these two isomers, the cis-trans–isomer in toluene mainly formed dimers with the loss of one or two molecules of water. However, in acetonitrile, significant amounts of Ph-T10,12 and Ph-T10,12OSi(HO)Ph species were formed along with the dimers. All-trans-isomer did not enter into the reaction at all. Full article
(This article belongs to the Special Issue Synthesis of Functional Silicon Compounds)
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Article
Simulation of Organic Liquid Products Deoxygenation by Multistage Countercurrent Absorber/Stripping Using CO2 as Solvent with Aspen-HYSYS: Thermodynamic Data Basis and EOS Modeling
Molecules 2021, 26(14), 4382; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144382 - 20 Jul 2021
Viewed by 506
Abstract
In this work, the thermodynamic data basis and equation of state (EOS) modeling necessary to simulate the fractionation of organic liquid products (OLP), a liquid reaction product obtained by thermal catalytic cracking of palm oil at 450 °C, 1.0 atmosphere, with 10% (wt.) [...] Read more.
In this work, the thermodynamic data basis and equation of state (EOS) modeling necessary to simulate the fractionation of organic liquid products (OLP), a liquid reaction product obtained by thermal catalytic cracking of palm oil at 450 °C, 1.0 atmosphere, with 10% (wt.) Na2CO3 as catalyst, in multistage countercurrent absorber/stripping columns using supercritical carbon dioxide (SC-CO2) as solvent, with Aspen-HYSYS was systematically investigated. The chemical composition of OLP was used to predict the density (ρ), boiling temperature (Tb), critical temperature (Tc), critical pressure (Pc), critical volume (Vc), and acentric factor (ω) of all the compounds present in OLP by applying the group contribution methods of Marrero-Gani, Han-Peng, Marrero-Pardillo, Constantinou-Gani, Joback and Reid, and Vetere. The RK-Aspen EOS used as thermodynamic fluid package, applied to correlate the experimental phase equilibrium data of binary systems OLP-i/CO2 available in the literature. The group contribution methods selected based on the lowest relative average deviation by computing Tb, Tc, Pc, Vc, and ω. For n-alkanes, the method of Marrero-Gani selected for the prediction of Tc, Pc and Vc, and that of Han-Peng for ω. For alkenes, the method of Marrero-Gani selected for the prediction of Tb and Tc, Marrero-Pardillo for Pc and Vc, and Han-Peng for ω. For unsubstituted cyclic hydrocarbons, the method of Constantinou-Gani selected for the prediction of Tb, Marrero-Gani for Tc, Joback for Pc and Vc, and the undirected method of Vetere for ω. For substituted cyclic hydrocarbons, the method of Constantinou-Gani selected for the prediction of Tb and Pc, Marrero-Gani for Tc and Vc, and the undirected method of Vetere for ω. For aromatic hydrocarbon, the method of Joback selected for the prediction of Tb, Constantinou-Gani for Tc and Vc, Marrero-Gani for Pc, and the undirected method of Vetere for ω. The regressions show that RK-Aspen EOS was able to describe the experimental phase equilibrium data for all the binary pairs undecane-CO2, tetradecane-CO2, pentadecane-CO2, hexadecane-CO2, octadecane-CO2, palmitic acid-CO2, and oleic acid-CO2, showing average absolute deviation for the liquid phase (AADx) between 0.8% and 1.25% and average absolute deviation for the gaseous phase (AADy) between 0.01% to 0.66%. Full article
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Article
Chemical Profile, Antioxidant Capacity, and Antimicrobial Activity of Essential Oils Extracted from Three Different Varieties (Moldoveanca 4, Vis Magic 10, and Alba 7) of Lavandula angustifolia
Molecules 2021, 26(14), 4381; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144381 - 20 Jul 2021
Viewed by 611
Abstract
Chemical composition, antioxidant capacity, and antimicrobial activity of lavender essential oils (LEOs) extracted from three different varieties of Lavandula angustifolia Mill. (1-Moldoveanca 4, 2-Vis magic 10, and 3-Alba 7) have been determined. These plants previously patented in the Republic of Moldova were cultivated [...] Read more.
Chemical composition, antioxidant capacity, and antimicrobial activity of lavender essential oils (LEOs) extracted from three different varieties of Lavandula angustifolia Mill. (1-Moldoveanca 4, 2-Vis magic 10, and 3-Alba 7) have been determined. These plants previously patented in the Republic of Moldova were cultivated in an organic agriculture system in the northeastern part of Romania and then harvested in 3 consecutive years (2017–2019) to obtain the essential oils. From the inflorescences in the complete flowering stage, the LEOs were extracted by hydrodistillation. Then, their composition was analyzed by gas chromatography coupled with mass spectrometry (GC-MS) and by Fourier Transformed Infrared spectroscopy (FT-IR). The major identified constituents are as follows: linalool (1: 32.19–46.83%; 2: 29.93–30.97%; 3: 31.97–33.77%), linalyl acetate (1: 17.70–35.18%; 2: 27.55–37.13%; 3: 28.03–35.32%), and terpinen-4-ol (1: 3.63–7.70%; 2: 3.06–7.16%; 3: 3.10–6.53%). The antioxidant capacity as determined by ABTS and DPPH assays indicates inhibition, with the highest activity obtained for LEO var. Alba 7 from 2019. The in vitro antimicrobial activities of the LEOs and combinations were investigated as well, by using the disk diffusion method and minimum inhibitory concentration (MIC) against the Gram-positive bacterial strain Staphylococcus aureus (ATCC 6538), Gram-negative Pseudomonas aeruginosa (ATCC 27858), Escherichia coli (ATCC 25922), the yeast Candida albicans (ATCC 10231), and clinical isolates. Our results have shown that LEOs obtained from the three studied varieties of L. angustifolia manifest significant bactericidal effects against tested microorganisms (Staphylococcus aureus and Escherichia coli), and antifungal effects against Candida albicans. The mixture of LEOs (Var. Alba 7) and geranium, respectively, in tea tree EOs, in different ratios, showed a significant enhancement of the antibacterial effect against all the studied strains, except Pseudomonas aeruginosa. Full article
(This article belongs to the Special Issue Plant Extracts: Technologies, Characterizations and Applications)
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Review
Targeting Inflammation by Anthocyanins as the Novel Therapeutic Potential for Chronic Diseases: An Update
Molecules 2021, 26(14), 4380; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144380 - 20 Jul 2021
Viewed by 610
Abstract
Low-grade chronic inflammation (LGCI) and oxidative stress act as cooperative and synergistic partners in the pathogenesis of a wide variety of diseases. Polyphenols, including anthocyanins, are involved in regulating the inflammatory state and activating the endogenous antioxidant defenses. Anthocyanins’ effects on inflammatory markers [...] Read more.
Low-grade chronic inflammation (LGCI) and oxidative stress act as cooperative and synergistic partners in the pathogenesis of a wide variety of diseases. Polyphenols, including anthocyanins, are involved in regulating the inflammatory state and activating the endogenous antioxidant defenses. Anthocyanins’ effects on inflammatory markers are promising and may have the potential to exert an anti-inflammatory effect in vitro and in vivo. Therefore, translating these research findings into clinical practice would effectively contribute to the prevention and treatment of chronic disease. The present narrative review summarizes the results of clinical studies from the last 5 years in the context of the anti-inflammatory and anti-oxidative role of anthocyanins in both health and disease. There is evidence to indicate that anthocyanins supplementation in the regulation of pro-inflammatory markers among the healthy and chronic disease population. Although the inconsistencies between the result of randomized control trials (RCTs) and meta-analyses were also observed. Regarding anthocyanins’ effects on inflammatory markers, there is a need for long-term clinical trials allowing for the quantifiable progression of inflammation. The present review can help clinicians and other health care professionals understand the importance of anthocyanins use in patients with chronic diseases. Full article
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Article
Synthesis, Biological and In Silico Studies of a Tripodal Schiff Base Derived from 2,4,6-Triamino-1,3,5-triazine and Its Trinuclear Dy(III), Er(III), and Gd(III) Salen Capped Complexes
Molecules 2021, 26(14), 4379; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144379 - 20 Jul 2021
Viewed by 979
Abstract
A tripodal Schiff base ligand, 2,4,6-Tris(4-carboxybenzimino)-1,3,5-triazine (MT) and its trinuclear Dy(III), Er(III), and Gd(III) complexes were synthesized. These were characterized using UV-visible, IR, 1H, and 13C NMR spectroscopies, elemental analysis, and molar conductivity measurements. The spectral studies indicate that the ligand [...] Read more.
A tripodal Schiff base ligand, 2,4,6-Tris(4-carboxybenzimino)-1,3,5-triazine (MT) and its trinuclear Dy(III), Er(III), and Gd(III) complexes were synthesized. These were characterized using UV-visible, IR, 1H, and 13C NMR spectroscopies, elemental analysis, and molar conductivity measurements. The spectral studies indicate that the ligand is hexadentate and coordinates to the Ln(III) ions through the oxygen atoms of the carboxylic group. The trinuclear complexes were characterized as being bridged by carboxylate anions to the Dy(III), Er(III), and Gd(III) salen centers and displaying a coordination number of six. Biological studies revealed that MT is more active against the test micro-organisms relative to the trinuclear complexes. Acute toxicity studies revealed that MT is safe and has a wide range of effective doses (ED50). In vivo antimalarial studies indicate that MT could serve as an effective antimalarial agent since it has parasitemia inhibition of 84.02% at 50 mg/kg and 65.81% at 25 mg/kg, close to the value (87.22%) of the standard drug—Artesunate. Molecular docking simulation studies on the compounds against SARS-CoV-2 (6Y84) and E. coli DNA gyrase (5MMN) revealed effective binding interactions through multiple bonding modes. The binding energy calculated for Er(III)MT-6Y84 and Er(III)MT-5MMN complexes showed active molecules with the ability to inhibit SARS-CoV-2 and E. coli DNA gyrase. Full article
(This article belongs to the Section Inorganic Chemistry)
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Article
Development of Chitosan-Based Surfaces to Prevent Single- and Dual-Species Biofilms of Staphylococcus aureus and Pseudomonas aeruginosa
Molecules 2021, 26(14), 4378; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144378 - 20 Jul 2021
Cited by 1 | Viewed by 691
Abstract
Implantable medical devices (IMDs) are susceptible to microbial adhesion and biofilm formation, which lead to several clinical complications, including the occurrence of implant-associated infections. Polylactic acid (PLA) and its composites are currently used for the construction of IMDs. In addition, chitosan (CS) is [...] Read more.
Implantable medical devices (IMDs) are susceptible to microbial adhesion and biofilm formation, which lead to several clinical complications, including the occurrence of implant-associated infections. Polylactic acid (PLA) and its composites are currently used for the construction of IMDs. In addition, chitosan (CS) is a natural polymer that has been widely used in the medical field due to its antimicrobial and antibiofilm properties, which can be dependent on molecular weight (Mw). The present study aims to evaluate the performance of CS-based surfaces of different Mw to inhibit bacterial biofilm formation. For this purpose, CS-based surfaces were produced by dip-coating and the presence of CS and its derivatives onto PLA films, as well surface homogeneity were confirmed by contact angle measurements, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The antimicrobial activity of the functionalized surfaces was evaluated against single- and dual-species biofilms of Staphylococcus aureus and Pseudomonas aeruginosa. Chitosan-based surfaces were able to inhibit the development of single- and dual-species biofilms by reducing the number of total, viable, culturable, and viable but nonculturable cells up to 79%, 90%, 81%, and 96%, respectively, being their activity dependent on chitosan Mw. The effect of CS-based surfaces on the inhibition of biofilm formation was corroborated by biofilm structure analysis using confocal laser scanning microscopy (CLSM), which revealed a decrease in the biovolume and thickness of the biofilm formed on CS-based surfaces compared to PLA. Overall, these results support the potential of low Mw CS for coating polymeric devices such as IMDs where the two bacteria tested are common colonizers and reduce their biofilm formation. Full article
(This article belongs to the Collection Early-Career Researchers in Chemistry)
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Article
Multicomponent Crystal of Metformin and Barbital: Design, Crystal Structure Analysis and Characterization
Molecules 2021, 26(14), 4377; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144377 - 20 Jul 2021
Viewed by 442
Abstract
The formation of most multicomponent crystals relies on the interaction of hydrogen bonds between the components, so rational crystal design based on the expected hydrogen-bonded supramolecular synthons was employed to establish supramolecular compounds with desirable properties. This theory was put into practice for [...] Read more.
The formation of most multicomponent crystals relies on the interaction of hydrogen bonds between the components, so rational crystal design based on the expected hydrogen-bonded supramolecular synthons was employed to establish supramolecular compounds with desirable properties. This theory was put into practice for metformin to participate in more therapeutic fields to search for a fast and simple approach for the screening of candidate crystal co-formers. The prediction of intermolecular synthons facilitated the successful synthesis of a new multicomponent crystal of metformin (Met) and barbital (Bar) through an anion exchange reaction and cooling crystallization method. The single crystal X-ray diffraction analysis demonstrated the hydrogen bond-based ureide/ureide and guanidine/ureide synthons were responsible for the self-assembly of the primary structural motif and extended into infinite supramolecular heterocatemeric structures. Full article
(This article belongs to the Section Medicinal Chemistry)
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Article
Bio-Guided Fractionation of Stem Bark Extracts from Phyllanthus muellarianus: Identification of Phytocomponents with Anti-Cholinesterase Activity
Molecules 2021, 26(14), 4376; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144376 - 20 Jul 2021
Viewed by 536
Abstract
A combination of flash chromatography, solid phase extraction, high-performance liquid chromatography, and in vitro bioassays was used to isolate phytocomponents endowed with anticholinesterase activity in extract from Phyllanthus muellarianus. Phytocomponents responsible for the anti-cholinesterase activity of subfractions PMF1 and PMF4 were identified and [...] Read more.
A combination of flash chromatography, solid phase extraction, high-performance liquid chromatography, and in vitro bioassays was used to isolate phytocomponents endowed with anticholinesterase activity in extract from Phyllanthus muellarianus. Phytocomponents responsible for the anti-cholinesterase activity of subfractions PMF1 and PMF4 were identified and re-assayed to confirm their activity. Magnoflorine was identified as an active phytocomponent from PMF1 while nitidine was isolated from PMF4. Magnoflorine was shown to be a selective inhibitor of human butyrylcholinesterase—hBChE (IC50 = 131 ± 9 μM and IC50 = 1120 ± 83 μM, for hBuChE and human acetylcholinesterase—hAChE, respectively), while nitidine showed comparable inhibitory potencies against both enzymes (IC50 = 6.68 ± 0.13 μM and IC50 = 5.31 ± 0.50 μM, for hBChE and hAChE, respectively). When compared with the commercial anti-Alzheimer drug galanthamine, nitidine was as potent as galanthamine against hAChE and one order of magnitude more potent against hBuChE. Furthermore, nitidine also showed significant, although weak, antiaggregating activity towards amyloid-β self-aggregation. Full article
(This article belongs to the Special Issue Plant Derived Natural Products and Age-Related Diseases)
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Article
Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies
Molecules 2021, 26(14), 4375; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144375 - 20 Jul 2021
Viewed by 610
Abstract
Regulating insulin and leptin levels using a protein tyrosine phosphatase 1B (PTP1B) inhibitor is an attractive strategy to treat diabetes and obesity. Glycyrrhetinic acid (GA), a triterpenoid, may weakly inhibit this enzyme. Nonetheless, semisynthetic derivatives of GA have not been developed as PTP1B [...] Read more.
Regulating insulin and leptin levels using a protein tyrosine phosphatase 1B (PTP1B) inhibitor is an attractive strategy to treat diabetes and obesity. Glycyrrhetinic acid (GA), a triterpenoid, may weakly inhibit this enzyme. Nonetheless, semisynthetic derivatives of GA have not been developed as PTP1B inhibitors to date. Herein we describe the synthesis and evaluation of two series of indole- and N-phenylpyrazole-GA derivatives (4af and 5af). We measured their inhibitory activity and enzyme kinetics against PTP1B using p-nitrophenylphosphate (pNPP) assay. GA derivatives bearing substituted indoles or N-phenylpyrazoles fused to their A-ring showed a 50% inhibitory concentration for PTP1B in a range from 2.5 to 10.1 µM. The trifluoromethyl derivative of indole-GA (4f) exhibited non-competitive inhibition of PTP1B as well as higher potency (IC50 = 2.5 µM) than that of positive controls ursolic acid (IC50 = 5.6 µM), claramine (IC50 = 13.7 µM) and suramin (IC50 = 4.1 µM). Finally, docking and molecular dynamics simulations provided the theoretical basis for the favorable activity of the designed compounds. Full article
(This article belongs to the Special Issue Discovery of Enzyme Inhibitors from Natural Products)
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Article
Electrosprayed Shrimp and Mushroom Nanochitins on Cellulose Tissue for Skin Contact Application
Molecules 2021, 26(14), 4374; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144374 - 20 Jul 2021
Cited by 1 | Viewed by 826
Abstract
Cosmetics has recently focused on biobased skin-compatible materials. Materials from natural sources can be used to produce more sustainable skin contact products with enhanced bioactivity. Surface functionalization using natural-based nano/microparticles is thus a subject of study, aimed at better understanding the skin compatibility [...] Read more.
Cosmetics has recently focused on biobased skin-compatible materials. Materials from natural sources can be used to produce more sustainable skin contact products with enhanced bioactivity. Surface functionalization using natural-based nano/microparticles is thus a subject of study, aimed at better understanding the skin compatibility of many biopolymers also deriving from biowaste. This research investigated electrospray as a method for surface modification of cellulose tissues with chitin nanofibrils (CNs) using two different sources—namely, vegetable (i.e., from fungi), and animal (from crustaceans)—and different solvent systems to obtain a biobased and skin-compatible product. The surface of cellulose tissues was uniformly decorated with electrosprayed CNs. Biological analysis revealed that all treated samples were suitable for skin applications since human dermal keratinocytes (i.e., HaCaT cells) successfully adhered to the processed tissues and were viable after being in contact with released substances in culture media. These results indicate that the use of solvents did not affect the final cytocompatibility due to their effective evaporation during the electrospray process. Such treatments did not also affect the characteristics of cellulose; in addition, they showed promising anti-inflammatory and indirect antimicrobial activity toward dermal keratinocytes in vitro. Specifically, cellulosic substrates decorated with nanochitins from shrimp showed strong immunomodulatory activity by first upregulating then downregulating the pro-inflammatory cytokines, whereas nanochitins from mushrooms displayed an overall anti-inflammatory activity via a slight decrement of the pro-inflammatory cytokines and increment of the anti-inflammatory marker. Electrospray could represent a green method for surface modification of sustainable and biofunctional skincare products. Full article
(This article belongs to the Special Issue New Trends in Skin Care: Topical Delivery of Cosmeceutical Molecules)
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Article
Double Proton Tautomerism via Intra- or Intermolecular Pathways? The Case of Tetramethyl Reductic Acid Studied by Dynamic NMR: Hydrogen Bond Association, Solvent and Kinetic H/D Isotope Effects
Molecules 2021, 26(14), 4373; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144373 - 20 Jul 2021
Viewed by 490
Abstract
Using dynamic liquid-state NMR spectroscopy a degenerate double proton tautomerism was detected in tetramethyl reductic acid (TMRA) dissolved in toluene-d8 and in CD2Cl2. Similar to vitamin C, TMRA belongs to the class of reductones of biologically important [...] Read more.
Using dynamic liquid-state NMR spectroscopy a degenerate double proton tautomerism was detected in tetramethyl reductic acid (TMRA) dissolved in toluene-d8 and in CD2Cl2. Similar to vitamin C, TMRA belongs to the class of reductones of biologically important compounds. The tautomerism involves an intramolecular HH transfer that interconverts the peripheric and the central positions of the two OH groups. It is slow in the NMR time scale around 200 K and fast at room temperature. Pseudo-first-order rate constants of the HH transfer and of the HD transfer after suitable deuteration were obtained by line shape analyses. Interestingly, the chemical shifts were found to be temperature dependent carrying information about an equilibrium between a hydrogen bonded dimer and a monomer forming two weak intramolecular hydrogen bonds. The structures of the monomer and the dimer are discussed. The latter may consist of several rapidly interconverting hydrogen-bonded associates. A way was found to obtain the enthalpies and entropies of dissociation, which allowed us to convert the pseudo-first-order rate constants of the reaction mixture into first-order rate constants of the tautomerization of the monomer. Surprisingly, these intrinsic rate constants were the same for toluene-d8 and CD2Cl2, but in the latter solvent more monomer is formed. This finding is attributed to the dipole moment of the TMRA monomer, compensated in the dimer, and to the larger dielectric constant of CD2Cl2. Within the margin of error, the kinetic HH/HD isotope effects were found to be of the order of 3 but independent of temperature. That finding indicates a stepwise HH transfer involving a tunnel mechanism along a double barrier pathway. The Arrhenius curves were described in terms of the Bell–Limbach tunneling model. Full article
(This article belongs to the Special Issue Tautomerism and Proton Transfer Related Phenomena)
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Article
Incorporation of Molecular Reorientation into Modeling Surface Pressure-Area Isotherms of Langmuir Monolayers
Molecules 2021, 26(14), 4372; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144372 - 20 Jul 2021
Viewed by 410
Abstract
Langmuir monolayers can be assembled from molecules that change from a low-energy orientation occupying a large cross-sectional area to a high-energy orientation of small cross-sectional area as the lateral pressure grows. Examples include cyclosporin A, amphotericin B, nystatin, certain alpha-helical peptides, cholesterol oxydation [...] Read more.
Langmuir monolayers can be assembled from molecules that change from a low-energy orientation occupying a large cross-sectional area to a high-energy orientation of small cross-sectional area as the lateral pressure grows. Examples include cyclosporin A, amphotericin B, nystatin, certain alpha-helical peptides, cholesterol oxydation products, dumbbell-shaped amphiphiles, organic–inorganic nanoparticles and hybrid molecular films. The transition between the two orientations leads to a shoulder in the surface pressure-area isotherm. We propose a theoretical model that describes the shoulder and can be used to extract the energy cost per molecule for the reorientation. Our two-state model is based on a lattice–sublattice approximation that hosts the two orientations and a corresponding free energy expression which we minimize with respect to the orientational distribution. Inter-molecular interactions other than steric repulsion are ignored. We provide an analysis of the model, including an analytic solution for one specific lateral pressure near a point of inflection in the surface pressure-area isotherm, and an approximate solution for the entire range of the lateral pressures. We also use our model to estimate energy costs associated with orientational transitions from previously reported experimental surface pressure-area isotherms. Full article
(This article belongs to the Special Issue 25th Anniversary of Molecules—Recent Advances in Physical Chemistry)
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Article
Energy Properties and Biomass Yield of Miscanthus x Giganteus Fertilized by Municipal Sewage Sludge
Molecules 2021, 26(14), 4371; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144371 - 20 Jul 2021
Cited by 1 | Viewed by 446
Abstract
The application of municipal sewage sludge as fertilizer in the production of non-food energy crops is an environmentally and economically sustainable approach to sewage sludge management. In addition, the application of municipal sewage sludge to energy crops such as Miscanthus x giganteus is [...] Read more.
The application of municipal sewage sludge as fertilizer in the production of non-food energy crops is an environmentally and economically sustainable approach to sewage sludge management. In addition, the application of municipal sewage sludge to energy crops such as Miscanthus x giganteus is an alternative form of recycling nutrients and organic material from waste. Municipal sewage sludge is a potential source of heavy metals in the soil, some of which can be removed by growing energy crops that are also remediation agents. Therefore, the objective of the research was to investigate the effect of municipal sewage sludge applied at three different rates of 1.66, 3.22 and 6.44 t/ha on the production of Miscanthus. Based on the analyses conducted on the biomass of Miscanthus fertilized with sludge from the wastewater treatment plant in three fertilization treatments, it can be concluded that the biomass of Miscanthus is a good feedstock for the process of direct combustion. Moreover, the application of the largest amount of municipal sewage sludge during cultivation had no negative effect on the properties of Miscanthus biomass. Moreover, the cellulose and hemicellulose content of Miscanthus is ideal for the production of second-generation liquid biofuels. Fertilizer treatments had no effect on the content of cellulose and lignin, while a significant statistical difference was found for hemicellulose. Full article
(This article belongs to the Special Issue Residues of Organic Pollutants in Environmental Samples)
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Article
Development of a Water Matrix Certified Reference Material for Volatile Organic Compounds Analysis in Water
Molecules 2021, 26(14), 4370; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144370 - 20 Jul 2021
Viewed by 423
Abstract
Water matrix certified reference material (MCRM) of volatile organic compounds (VOCs) is used to provide quality assurance and quality control (QA/QC) during the analysis of VOCs in water. In this research, a water MCRM of 28 VOCs was developed using a “reconstitution” approach [...] Read more.
Water matrix certified reference material (MCRM) of volatile organic compounds (VOCs) is used to provide quality assurance and quality control (QA/QC) during the analysis of VOCs in water. In this research, a water MCRM of 28 VOCs was developed using a “reconstitution” approach by adding VOCs spiking, methanol solution into pure water immediately prior to analysis. The VOCs spiking solution was prepared gravimetrically by dividing 28 VOCs into seven groups, then based on ISO Guide 35, using gas chromatography-mass spectrometry (GC-MS) to investigate the homogeneity and long-term stability. The studies of homogeneity and long-term stability indicated that the batch of VOCs spiking solution was homogeneous and stable at room temperature for at least 15 months. Moreover, the water MCRM of 28 VOCs was certified by a network of nine competent laboratories, and the certified values and expanded uncertainties of 28 VOCs ranged from 6.2 to 17 μg/L and 0.5 to 5.3 μg/L, respectively. Full article
(This article belongs to the Special Issue Environmental Analysis of Organic Pollutants)
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Article
Evaluation of Antiproliferative Palladium(II) Complexes of Synthetic Bisdemethoxycurcumin towards In Vitro Cytotoxicity and Molecular Docking on DNA Sequence
Molecules 2021, 26(14), 4369; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144369 - 20 Jul 2021
Viewed by 1077
Abstract
Metallodrugs form a large family of therapeutic agents against cancer, among which is cisplatin, a paradigmatic member. Therapeutic resistance and undesired side effects to Pt(II) related drugs, prompts research on different metal–ligand combinations with potentially enhanced biological activity. We present the synthesis and [...] Read more.
Metallodrugs form a large family of therapeutic agents against cancer, among which is cisplatin, a paradigmatic member. Therapeutic resistance and undesired side effects to Pt(II) related drugs, prompts research on different metal–ligand combinations with potentially enhanced biological activity. We present the synthesis and biological tests of novel palladium(II) complexes containing bisdemethoxycurcumin (BDMC) 1 and 2. Complexes were fully characterized and their structures were determined by X-ray diffraction. Their biological activity was assessed for several selected human tumor cell lines: Jurkat (human leukaemic T-cell lymphoma), HCT-116 (human colorectal carcinoma), HeLa (human cervix epitheloid carcinoma), MCF-7 (human breast adenocarcinoma), MDA-MB-231 (human mammary gland adenocarcinoma), A549 (human alveolar adenocarcinoma), Caco-2 (human colorectal carcinoma), and for non-cancerous 3T3 cells (murine fibroblasts). The cytotoxicity of 1 is comparable to that of cisplatin, and superior to that of 2 in all cell lines. It is a correlation between IC50 values of 1 and 2 in the eight studied cell types, promising a potential use as anti-proliferative drugs. Moreover, for Jurkat cell line, complexes 1 and 2, show an enhanced activity. DFT and docking calculations on the NF-κB protein, Human Serum Albumin (HSA), and DNA were performed for 1 and 2 to correlate with their biological activities. Full article
(This article belongs to the Special Issue Coordination Chemistry in Cancer Therapy)
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Article
Identification of Rotundone as an Important Contributor to the Flavor of Oak-Aged Spirits
Molecules 2021, 26(14), 4368; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144368 - 20 Jul 2021
Viewed by 622
Abstract
Experiments were conducted to identify a compound responsible for a spicy, woody, incense-like odor note in oak-aged spirits. The target compound was extracted from oak wood and various oak-aged spirits and analyzed by multidimensional (heart-cut) gas chromatography–mass spectrometry–olfactometry (MD–GC–MS–O), and was [...] Read more.
Experiments were conducted to identify a compound responsible for a spicy, woody, incense-like odor note in oak-aged spirits. The target compound was extracted from oak wood and various oak-aged spirits and analyzed by multidimensional (heart-cut) gas chromatography–mass spectrometry–olfactometry (MD–GC–MS–O), and was unambiguously identified as the sesquiterpene ketone, 5-isopropenyl-3,8-dimethyl-3,4,5,6,7,8-hexadydro-1(2H)-azulenone (rotundone). Quantitation of the trace-level target compound was done by stable isotope dilution analysis (SIDA) in a variety of oak-aged spirits, including bourbon, rye, Tennessee whiskey, scotch, rum, and tequila. The content of rotundone was found to increase as a function of years of barrel aging for 4-, 8-, and 12-year-old bourbons obtained from the same manufacturer, thus confirming its origin to be from oak. In addition, odor-activity values (OAVs) were compared for selected potent odorants, including rotundone, in the same 4-, 8-, and 12-year-old bourbons, which indicated the relative importance of rotundone in the overall flavor of oak-aged spirits. Full article
Review
A Brief Updated Review of Advances to Enhance Resveratrol’s Bioavailability
Molecules 2021, 26(14), 4367; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144367 - 20 Jul 2021
Viewed by 745
Abstract
Resveratrol (RES) has a low bioavailability. This limitation was addressed in an earlier review and several recommendations were offered. A literature search was conducted in order to determine the extent of the research that was conducted in line with these recommendations, along with [...] Read more.
Resveratrol (RES) has a low bioavailability. This limitation was addressed in an earlier review and several recommendations were offered. A literature search was conducted in order to determine the extent of the research that was conducted in line with these recommendations, along with new developments in this field. Most of the identified studies were pre-clinical and confirmed the heightened activity of RES analogues compared to their parent compound. Although this has provided additional scientific kudos for these compounds and has strengthened their potential to be developed into phytopharmaceutical products, clinical trials designed to confirm this increased activity remain lacking and are warranted. Full article
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Article
Syntheses and Study of a Pyrroline Nitroxide Condensed Phospholene Oxide and a Pyrroline Nitroxide Attached Diphenylphosphine
Molecules 2021, 26(14), 4366; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144366 - 19 Jul 2021
Cited by 1 | Viewed by 537
Abstract
The reaction of a diene nitroxide precursor with dichlorophenylphosphine in a McCormac procedure afforded 1,1,3,3-tetramethyl-5-phenyl-1,2,3,4,5,6-hexahydrophospholo[3,4-c]pyrrole-5-oxide-2-oxyl. Lithiation of the protected 3-iodo-pyrroline nitroxide followed by treatment with chlorodiphenylphosphine after deprotection afforded (1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)diphenylphosphine oxide, and after reduction, (1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)diphenylphosphine was realized, which was [...] Read more.
The reaction of a diene nitroxide precursor with dichlorophenylphosphine in a McCormac procedure afforded 1,1,3,3-tetramethyl-5-phenyl-1,2,3,4,5,6-hexahydrophospholo[3,4-c]pyrrole-5-oxide-2-oxyl. Lithiation of the protected 3-iodo-pyrroline nitroxide followed by treatment with chlorodiphenylphosphine after deprotection afforded (1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)diphenylphosphine oxide, and after reduction, (1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)diphenylphosphine was realized, which was also supported by X-ray single crystal diffraction measurements. This pyrroline diphenylphosphine derivative was converted to hexadecylphosphonium salt, which is an analogue of antineoplastic agent, MITO-CP. Full article
(This article belongs to the Special Issue Stable Organic Radicals)
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Article
Base-Mediated Claisen Rearrangement of CF3-Containing Bisallyl Ethers
Molecules 2021, 26(14), 4365; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144365 - 19 Jul 2021
Viewed by 466
Abstract
We have previously clarified that the strongly electron-withdrawing CF3 group nicely affected the base-mediated proton shift of CF3-containing propargylic or allylic alcohols to afford the corresponding α,β-unsaturated or saturated ketones, respectively, which was applied this time to the Claisen rearrangement [...] Read more.
We have previously clarified that the strongly electron-withdrawing CF3 group nicely affected the base-mediated proton shift of CF3-containing propargylic or allylic alcohols to afford the corresponding α,β-unsaturated or saturated ketones, respectively, which was applied this time to the Claisen rearrangement after O-allylation of the allylic alcohols with a CF3 group, followed by isomerization to the corresponding allyl vinyl ethers via the proton shift, enabling the desired rearrangement in a tandem fashion, or in a stepwise manner, the latter of which was proved to have attained an excellent diastereoselectivity with the aid of a palladium catalyst. Full article
(This article belongs to the Special Issue Organofluorine Chemistry and Beyond)
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Article
Cyclohumulanoid Sesquiterpenes from the Culture Broth of the Basidiomycetous Fungus Daedaleopsis tricolor
Molecules 2021, 26(14), 4364; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144364 - 19 Jul 2021
Viewed by 539
Abstract
A series of cyclohumulanoids, i.e., tricocerapicanols A–C (1a1c), tricoprotoilludenes A (2a) and B (3), tricosterpurol (4), and tricoilludins A–C (57) were isolated along with known violascensol (2b) [...] Read more.
A series of cyclohumulanoids, i.e., tricocerapicanols A–C (1a1c), tricoprotoilludenes A (2a) and B (3), tricosterpurol (4), and tricoilludins A–C (57) were isolated along with known violascensol (2b) and omphadiol (8) from the culture broth of Daedaleopsis tricolor, an inedible but not toxic mushroom. The structures were fully elucidated on the basis of NMR spectroscopic analysis, and the suggested relative structures were confirmed via density functional theory (DFT)-based chemical shift calculations involving a DP4 probability analysis. In the present study, the 1H chemical shifts were more informative than the 13C chemical shifts to distinguish the diastereomers at C-11. The absolute configurations of 15 were determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectra. For 6 and 7, the same chirality was assigned according to their biosynthetic similarities with the other compounds. The successful assignment of some Cotton effects was achieved by utilizing DFT calculations using simple model compounds. The plausible biosynthesis of 17 was also discussed on the basis of the structural commonality and general cyclohumulanoid biosynthesis. Compounds 2a and 5 were found to simultaneously induce hyphal swelling and branching at 5.0 μg/mL against a test fungus Cochliobolus miyabeanus. Full article
(This article belongs to the Special Issue Recent Advances on Natural Product Research)
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Article
Optimization of MAE for the Separation of Nicotine and Phenolics from Tobacco Waste by Using the Response Surface Methodology Approach
Molecules 2021, 26(14), 4363; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144363 - 19 Jul 2021
Viewed by 456
Abstract
This study intends to valorize by-products of the industrial processing of tobacco to obtain nicotine and phenolics as value-added compounds. Three influential parameters of the microwave-assisted extraction-MAE (temperature, treatment time, and solvent/solid ratio) were studied for the optimization of the extraction protocol for [...] Read more.
This study intends to valorize by-products of the industrial processing of tobacco to obtain nicotine and phenolics as value-added compounds. Three influential parameters of the microwave-assisted extraction-MAE (temperature, treatment time, and solvent/solid ratio) were studied for the optimization of the extraction protocol for tobacco leaves and three types of waste—scrap, dust, and midrib, respectively. Nicotine was the dominant bioactive compound in all extracts, ranging from 1.512 to 5.480% in leaves, 1.886 to 3.709% in scrap, 2.628 to 4.840% dust, and 0.867 to 1.783% in midrib extracts. Five phenolic compounds were identified and quantified, predominated by chlorogenic acid and rutin. Additionally, total phenol content and antioxidant activity were determined using spectrophotometric assays. Optimization was performed in two aspects: to obtain a maximum extraction yield with minimum nicotine content and to obtain a maximum extraction yield with maximum nicotine content. These findings demonstrate that tobacco waste is a valuable source of bioactive compounds and MAE can be a promising alternative technique to obtain extracts rich in targeted bioactive compounds, especially nicotine. Full article
(This article belongs to the Special Issue Ultrasound- and Microwave-Assisted Extraction of Bioactive Compounds)
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Review
Current Status of Endoplasmic Reticulum Stress in Type II Diabetes
Molecules 2021, 26(14), 4362; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144362 - 19 Jul 2021
Viewed by 728
Abstract
The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis is essential for cellular functions. Several pathophysiological conditions and pharmacological agents are known to disrupt ER homeostasis, thereby, causing ER stress. The [...] Read more.
The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis is essential for cellular functions. Several pathophysiological conditions and pharmacological agents are known to disrupt ER homeostasis, thereby, causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways when ER stress persists. ER stress is linked to several diseases, such as cancer, obesity, and diabetes. Thus, its regulation can provide possible therapeutic targets for these. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, thereby, resulting in irreversible UPR activation and cell death. Despite progress in understanding the pathophysiology of the UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provides up-to-date information regarding the UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways. Full article
(This article belongs to the Special Issue Oxidative Stress as a Pharmacological Target for Medicinal Chemistry)
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Article
Novel Perbutyrylated Glucose Derivatives of (–)-Epigallocatechin-3-Gallate Inhibit Cancer Cells Proliferation by Decreasing Phosphorylation of the EGFR: Synthesis, Cytotoxicity, and Molecular Docking
Molecules 2021, 26(14), 4361; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144361 - 19 Jul 2021
Viewed by 447
Abstract
Lung cancer is one of the most commonly occurring cancer mortality worldwide. The epidermal growth factor receptor (EGFR) plays an important role in cellular functions and has become the new promising target. Natural products and their derivatives with various structures, unique biological activities, [...] Read more.
Lung cancer is one of the most commonly occurring cancer mortality worldwide. The epidermal growth factor receptor (EGFR) plays an important role in cellular functions and has become the new promising target. Natural products and their derivatives with various structures, unique biological activities, and specific selectivity have served as lead compounds for EGFR. D-glucose and EGCG were used as starting materials. A series of glucoside derivatives of EGCG (712) were synthesized and evaluated for their in vitro anticancer activity against five human cancer cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW480. In addition, we investigated the structure-activity relationship and physicochemical property–activity relationship of EGCG derivatives. Compounds 11 and 12 showed better growth inhibition than others in four cancer cell lines (HL-60, SMMC-7721, A-549, and MCF), with IC50 values in the range of 22.90–37.87 μM. Compounds 11 and 12 decreased phosphorylation of EGFR and downstream signaling protein, which also have more hydrophobic interactions than EGCG by docking study. The most active compounds 11 and 12, both having perbutyrylated glucose residue, we found that perbutyrylation of the glucose residue leads to increased cytotoxic activity and suggested that their potential as anticancer agents for further development. Full article
(This article belongs to the Section Medicinal Chemistry)
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Article
Aromatic Amines in Organic Synthesis. Part II. p-Aminocinnamaldehydes
Molecules 2021, 26(14), 4360; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144360 - 19 Jul 2021
Viewed by 473
Abstract
Ten derivatives of p-aminocinnamic aldehydes were prepared from the reaction of either aromatic amines with dimethylaminoacrolein or benzaldehydes with acetaldehyde. Their chemical structure and purity were verified by 1H NMR, 13C NMR and IR spectroscopic methods. We found that the [...] Read more.
Ten derivatives of p-aminocinnamic aldehydes were prepared from the reaction of either aromatic amines with dimethylaminoacrolein or benzaldehydes with acetaldehyde. Their chemical structure and purity were verified by 1H NMR, 13C NMR and IR spectroscopic methods. We found that the synthesis applying dimethylaminoacrolein as the reagent gets better yields than the one based on the reaction with acetaldehyde. The yields of the cinnamic aldehydes varied according to the type of the amino group and the number and position of the substituents. The basic spectroscopic properties of the p-aminocinnamic aldehydes are also described since the compounds may be a precursor for the synthesis of dyes for diverse applications, e.g., in medicine and optoelectronics. Full article
(This article belongs to the Section Organic Chemistry)
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Article
The HDAC/HSP90 Inhibitor G570 Attenuated Blue Light-Induced Cell Migration in RPE Cells and Neovascularization in Mice through Decreased VEGF Production
Molecules 2021, 26(14), 4359; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144359 - 19 Jul 2021
Viewed by 550
Abstract
Age-related macular degeneration (AMD) occurs due to an abnormality of retinal pigment epithelium (RPE) cells that leads to gradual degeneration of the macula. Currently, AMD drug pipelines are endowed with limited options, and anti-VEGF agents stand as the dominantly employed therapy. Despite the [...] Read more.
Age-related macular degeneration (AMD) occurs due to an abnormality of retinal pigment epithelium (RPE) cells that leads to gradual degeneration of the macula. Currently, AMD drug pipelines are endowed with limited options, and anti-VEGF agents stand as the dominantly employed therapy. Despite the proven efficacy of such agents, the evidenced side effects associated with their use underscore the need to elucidate other mechanisms involved and identify additional molecular targets for the sake of therapy improvement. The previous literature provided us with a solid rationale to preliminarily explore the potential of selective HDAC6 and HSP90 inhibitors to treat wet AMD. Rather than furnishing single-target agents (either HDAC6 or HSP90 inhibitor), this study recruited scaffolds endowed with the ability to concomitantly modulate both targets (HDAC6 and HSP90) for exploration. This plan was anticipated to accomplish the important goal of extracting amplified benefits via dual inhibition (HDAC6/HSP90) in wet AMD. As a result, G570 (indoline-based hydroxamate), a dual selective HDAC6-HSP90 inhibitor exerting its effects at micromolar concentrations, was pinpointed in the present endeavor to attenuate blue light-induced cell migration and retinal neovascularization by inhibiting VEGF production. In addition to the identification of a potential chemical tool (G570), the outcome of this study validates the candidate HDAC6-HSP90 as a compelling target for the development of futuristic therapeutics for wet AMD. Full article
(This article belongs to the Section Medicinal Chemistry)
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