Molecules

9 pages, 1288 KiB

Open AccessArticle

Fatty Acid Ethyl Esters (FAEE): A New, Green and Renewable Solvent for the Extraction of Carotenoids from Tomato Waste Products

by Aurel Diacon, Ioan Călinescu, Mircea Vinatoru, Petre Chipurici, Alexandru Vlaicu, Aurelian Cristian Boscornea and Timothy J. Mason

Molecules 2021, 26(14), 4388; https://doi.org/10.3390/molecules26144388 - 20 Jul 2021

Cited by 14 | Viewed by 4737

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 Collection Ultrasound- and Microwave-Assisted Extraction of Bioactive Compounds)

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16 pages, 3311 KiB

Open AccessArticle

Structural, Mechanistic, and Functional Insights into an Arthrobacter nicotinovorans Molybdenum Hydroxylase Involved in Nicotine Degradation

by Lei Wang, Xia Mu, Wenjin Li, Qin Xu, Ping Xu, Liyun Zhang, Yuebin Zhang and Geng Wu

Molecules 2021, 26(14), 4387; https://doi.org/10.3390/molecules26144387 - 20 Jul 2021

Cited by 2 | Viewed by 2697

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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11 pages, 1524 KiB

Open AccessArticle

Valorization of Artichoke Industrial By-Products Using Green Extraction Technologies: Formulation of Hydrogels in Combination with Paulownia Extracts

by Gabriela Órbenes, Paula Rodríguez-Seoane, María Dolores Torres, Rolando Chamy, María Elvira Zúñiga and Herminia Domínguez

Molecules 2021, 26(14), 4386; https://doi.org/10.3390/molecules26144386 - 20 Jul 2021

Cited by 16 | Viewed by 2874

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 Collection Ultrasound- and Microwave-Assisted Extraction of Bioactive Compounds)

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19 pages, 5858 KiB

Open AccessFeature PaperReview

Direct Arylation in the Presence of Palladium Pincer Complexes

by Garazi Urgoitia, Maria Teresa Herrero, Fátima Churruca, Nerea Conde and Raul SanMartin

Molecules 2021, 26(14), 4385; https://doi.org/10.3390/molecules26144385 - 20 Jul 2021

Cited by 12 | Viewed by 4261

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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9 pages, 2274 KiB

Open AccessArticle

Lignin Quantification of Papyri by TGA—Not a Good Idea

by Florian Bausch, Dickson D. Owusu, Paul Jusner, Mario J. Rosado, Jorge Rencoret, Sabine Rosner, José C. del Río, Thomas Rosenau and Antje Potthast

Molecules 2021, 26(14), 4384; https://doi.org/10.3390/molecules26144384 - 20 Jul 2021

Cited by 11 | Viewed by 3459

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

(This article belongs to the Special Issue Polysaccharide Chemistry—a Tool for Novel, Sustainable, and Advanced Products and Materials: A Themed Issue in Honor of Prof. Dr. Thomas Heinze)

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17 pages, 2508 KiB

Open AccessArticle

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

by Irina M. Petrova, Yury I. Lyakhovetsky, Nikolai S. Ikonnikov and Nataliya N. Makarova

Molecules 2021, 26(14), 4383; https://doi.org/10.3390/molecules26144383 - 20 Jul 2021

Cited by 1 | Viewed by 2418

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 (C_HCl) 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 (C_HCl) 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-T_8,10,12,14 and uncompleted cage-like Ph-T_10,12OSi(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-T_10,12 and Ph-T_10,12OSi(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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20 pages, 2829 KiB

Open AccessArticle

Simulation of Organic Liquid Products Deoxygenation by Multistage Countercurrent Absorber/Stripping Using CO₂ as Solvent with Aspen-HYSYS: Thermodynamic Data Basis and EOS Modeling

by Elinéia Castro Costa, Welisson de Araújo Silva, Eduardo Gama Ortiz Menezes, Marcilene Paiva da Silva, Vânia Maria Borges Cunha, Andréia de Andrade Mâncio, Marcelo Costa Santos, Sílvio Alex Pereira da Mota, Marilena Emmi Araújo and Nélio Teixeira Machado

Molecules 2021, 26(14), 4382; https://doi.org/10.3390/molecules26144382 - 20 Jul 2021

Cited by 1 | Viewed by 3236

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 (T_b), critical temperature (T_c), critical pressure (P_c), critical volume (V_c), 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 T_b, T_c, P_c, V_c, and ω. For n-alkanes, the method of Marrero-Gani selected for the prediction of T_c, P_c and V_c, and that of Han-Peng for ω. For alkenes, the method of Marrero-Gani selected for the prediction of T_b and T_c, Marrero-Pardillo for P_c and V_c, and Han-Peng for ω. For unsubstituted cyclic hydrocarbons, the method of Constantinou-Gani selected for the prediction of T_b, Marrero-Gani for T_c, Joback for P_c and V_c, and the undirected method of Vetere for ω. For substituted cyclic hydrocarbons, the method of Constantinou-Gani selected for the prediction of T_b and P_c, Marrero-Gani for T_c and V_c, and the undirected method of Vetere for ω. For aromatic hydrocarbon, the method of Joback selected for the prediction of T_b, Constantinou-Gani for T_c and V_c, Marrero-Gani for P_c, 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 (

A A D_{x}

) between 0.8% and 1.25% and average absolute deviation for the gaseous phase (

A A D_{y}

) between 0.01% to 0.66%. Full article

(This article belongs to the Special Issue A Themed Issue in Honor of Professor Ernesto Reverchon: The Top 20 in Chemical Engineering)

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20 pages, 2028 KiB

Open AccessArticle

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

by Mihaela Alexandra Bogdan, Simona Bungau, Delia Mirela Tit, Dana Carmen Zaha, Aurelia Cristina Nechifor, Tapan Behl, Dorina Chambre, Andreea Ioana Lupitu, Lucian Copolovici and Dana Maria Copolovici

Molecules 2021, 26(14), 4381; https://doi.org/10.3390/molecules26144381 - 20 Jul 2021

Cited by 28 | Viewed by 3735

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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17 pages, 601 KiB

Open AccessReview

Targeting Inflammation by Anthocyanins as the Novel Therapeutic Potential for Chronic Diseases: An Update

by Aleksandra Kozłowska and Tomasz Dzierżanowski

Molecules 2021, 26(14), 4380; https://doi.org/10.3390/molecules26144380 - 20 Jul 2021

Cited by 34 | Viewed by 4600

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

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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15 pages, 2826 KiB

Open AccessArticle

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

by Uchechukwu Susan Oruma, Pius Oziri Ukoha, Chiamaka Peace Uzoewulu, Joseph Chinedum Ndefo, Sabastine Chinweike Ugwuoke, Nkechinyere Nwanneka Ukwueze, Tochukwu Emmanuella Eze, Lilian Chinenye Ekowo, Florence Uchenna Eze, Uchenna Vivian Chinaegbomkpa, Sunday Nwankwo Okafor and Chigozie Julius Ezeorah

Molecules 2021, 26(14), 4379; https://doi.org/10.3390/molecules26144379 - 20 Jul 2021

Cited by 14 | Viewed by 3492

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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17 pages, 4297 KiB

Open AccessArticle

Development of Chitosan-Based Surfaces to Prevent Single- and Dual-Species Biofilms of Staphylococcus aureus and Pseudomonas aeruginosa

by Marta Lima, Rita Teixeira-Santos, Luciana C. Gomes, Sara I. Faria, Jesus Valcarcel, José Antonio Vázquez, Miguel A. Cerqueira, Lorenzo Pastrana, Ana I. Bourbon and Filipe J. Mergulhão

Molecules 2021, 26(14), 4378; https://doi.org/10.3390/molecules26144378 - 20 Jul 2021

Cited by 15 | Viewed by 5342

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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13 pages, 3828 KiB

Open AccessArticle

Multicomponent Crystal of Metformin and Barbital: Design, Crystal Structure Analysis and Characterization

by Linhong Cai, Lan Jiang, Cong Li, Xiaoshu Guan, Li Zhang and Xiangnan Hu

Molecules 2021, 26(14), 4377; https://doi.org/10.3390/molecules26144377 - 20 Jul 2021

Cited by 2 | Viewed by 2732

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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14 pages, 1250 KiB

Open AccessArticle

Bio-Guided Fractionation of Stem Bark Extracts from Phyllanthus muellarianus: Identification of Phytocomponents with Anti-Cholinesterase Activity

by Marina Naldi, Gloria Brusotti, Gabriella Massolini, Vincenza Andrisano, Caterina Temporini and Manuela Bartolini

Molecules 2021, 26(14), 4376; https://doi.org/10.3390/molecules26144376 - 20 Jul 2021

Cited by 2 | Viewed by 2676

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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21 pages, 2531 KiB

Open AccessArticle

Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies

by Ledy De-la-Cruz-Martínez, Constanza Duran-Becerra, Martin González-Andrade, José C. Páez-Franco, Juan Manuel Germán-Acacio, Julio Espinosa-Chávez, J. Martin Torres-Valencia, Jaime Pérez-Villanueva, Juan Francisco Palacios-Espinosa, Olivia Soria-Arteche and Francisco Cortés-Benítez

Molecules 2021, 26(14), 4375; https://doi.org/10.3390/molecules26144375 - 20 Jul 2021

Cited by 17 | Viewed by 4144

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 (4a–f and 5a–f). 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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15 pages, 4163 KiB

Open AccessFeature PaperArticle

Electrosprayed Shrimp and Mushroom Nanochitins on Cellulose Tissue for Skin Contact Application

by Bahareh Azimi, Claudio Ricci, Alessandra Fusco, Lorenzo Zavagna, Stefano Linari, Giovanna Donnarumma, Ahdi Hadrich, Patrizia Cinelli, Maria-Beatrice Coltelli, Serena Danti and Andrea Lazzeri

Molecules 2021, 26(14), 4374; https://doi.org/10.3390/molecules26144374 - 20 Jul 2021

Cited by 15 | Viewed by 4348

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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23 pages, 7476 KiB

Open AccessFeature PaperArticle

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

by Hans-Heinrich Limbach, Simone Baumgärtner, Roland Franke, Ferdinand Männle, Gerd Scherer and Gleb S. Denisov

Molecules 2021, 26(14), 4373; https://doi.org/10.3390/molecules26144373 - 20 Jul 2021

Cited by 5 | Viewed by 2511

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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13 pages, 980 KiB

Open AccessFeature PaperArticle

Incorporation of Molecular Reorientation into Modeling Surface Pressure-Area Isotherms of Langmuir Monolayers

by José Agudelo, Guilherme Volpe Bossa and Sylvio May

Molecules 2021, 26(14), 4372; https://doi.org/10.3390/molecules26144372 - 20 Jul 2021

Cited by 2 | Viewed by 2034

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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16 pages, 1063 KiB

Open AccessArticle

Energy Properties and Biomass Yield of Miscanthus x Giganteus Fertilized by Municipal Sewage Sludge

by Neven Voća, Josip Leto, Tomislav Karažija, Nikola Bilandžija, Anamarija Peter, Hrvoje Kutnjak, Jona Šurić and Milan Poljak

Molecules 2021, 26(14), 4371; https://doi.org/10.3390/molecules26144371 - 20 Jul 2021

Cited by 23 | Viewed by 3335

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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14 pages, 7170 KiB

Open AccessArticle

Development of a Water Matrix Certified Reference Material for Volatile Organic Compounds Analysis in Water

by Liping Fang, Linyan Huang, Gang Yang, Yang Jiang, Haiping Liu, Bingwen Lu, Yaxian Zhao and Wen Tian

Molecules 2021, 26(14), 4370; https://doi.org/10.3390/molecules26144370 - 20 Jul 2021

Viewed by 2473

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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15 pages, 3355 KiB

Open AccessArticle

Evaluation of Antiproliferative Palladium(II) Complexes of Synthetic Bisdemethoxycurcumin towards In Vitro Cytotoxicity and Molecular Docking on DNA Sequence

by Natalia Miklášová, Peter Herich, Juan Carlos Dávila-Becerril, Joaquín Barroso-Flores, Eva Fischer-Fodor, Jindra Valentová, Janka Leskovská, Jozef Kožíšek, Peter Takáč and Ján Mojžiš

Molecules 2021, 26(14), 4369; https://doi.org/10.3390/molecules26144369 - 20 Jul 2021

Cited by 8 | Viewed by 4629

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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15 pages, 314 KiB

Open AccessArticle

Identification of Rotundone as an Important Contributor to the Flavor of Oak-Aged Spirits

by Elizabeth Genthner-Kreger and Keith R. Cadwallader

Molecules 2021, 26(14), 4368; https://doi.org/10.3390/molecules26144368 - 20 Jul 2021

Cited by 10 | Viewed by 3413

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

(This article belongs to the Special Issue Flavor Chemistry and Technology: A Themed Issue in Honor of Professor Gary A. Reineccius)

8 pages, 724 KiB

Open AccessReview

A Brief Updated Review of Advances to Enhance Resveratrol’s Bioavailability

by Konrad de Vries, Morné Strydom and Vanessa Steenkamp

Molecules 2021, 26(14), 4367; https://doi.org/10.3390/molecules26144367 - 20 Jul 2021

Cited by 19 | Viewed by 3999

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

(This article belongs to the Special Issue Resveratrol 2021: Recent Advances in the Application of Resveratrol to Improve Health)

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10 pages, 1349 KiB

Open AccessArticle

Syntheses and Study of a Pyrroline Nitroxide Condensed Phospholene Oxide and a Pyrroline Nitroxide Attached Diphenylphosphine

by Mostafa Isbera, Balázs Bognár, Ferenc Gallyas, Attila Bényei, József Jekő and Tamás Kálai

Molecules 2021, 26(14), 4366; https://doi.org/10.3390/molecules26144366 - 19 Jul 2021

Cited by 5 | Viewed by 2883

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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17 pages, 2015 KiB

Open AccessArticle

Base-Mediated Claisen Rearrangement of CF₃-Containing Bisallyl Ethers

by Yoko Hamada, Rio Matsunaga, Tomoko Kawasaki-Takasuka and Takashi Yamazaki

Molecules 2021, 26(14), 4365; https://doi.org/10.3390/molecules26144365 - 19 Jul 2021

Viewed by 2372

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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19 pages, 2478 KiB

Open AccessArticle

Cyclohumulanoid Sesquiterpenes from the Culture Broth of the Basidiomycetous Fungus Daedaleopsis tricolor

by Ryuhi Kanehara, Akio Tonouchi, Katsuhiro Konno and Masaru Hashimoto

Molecules 2021, 26(14), 4364; https://doi.org/10.3390/molecules26144364 - 19 Jul 2021

Cited by 6 | Viewed by 3158

Abstract

A series of cyclohumulanoids, i.e., tricocerapicanols A–C (1a–1c), tricoprotoilludenes A (2a) and B (3), tricosterpurol (4), and tricoilludins A–C (5–7) were isolated along with known violascensol (2b) [...] Read more.

A series of cyclohumulanoids, i.e., tricocerapicanols A–C (1a–1c), tricoprotoilludenes A (2a) and B (3), tricosterpurol (4), and tricoilludins A–C (5–7) 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 1–5 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 1–7 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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14 pages, 5713 KiB

Open AccessFeature PaperArticle

Optimization of MAE for the Separation of Nicotine and Phenolics from Tobacco Waste by Using the Response Surface Methodology Approach

by Marija Banožić, Ines Banjari, Ivana Flanjak, Mate Paštar, Jelena Vladić and Stela Jokić

Molecules 2021, 26(14), 4363; https://doi.org/10.3390/molecules26144363 - 19 Jul 2021

Cited by 9 | Viewed by 4286

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 Collection Ultrasound- and Microwave-Assisted Extraction of Bioactive Compounds)

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16 pages, 1447 KiB

Open AccessReview

Current Status of Endoplasmic Reticulum Stress in Type II Diabetes

by Sagir Mustapha, Mustapha Mohammed, Ahmad Khusairi Azemi, Abubakar Ibrahim Jatau, Aishatu Shehu, Lukman Mustapha, Ibrahim Muazzamu Aliyu, Rabi’u Nuhu Danraka, Abdulbasit Amin, Auwal Adam Bala, Wan Amir Nizam Wan Ahmad, Aida Hanum Ghulam Rasool, Mohd Rais Mustafa and Siti Safiah Mokhtar

Molecules 2021, 26(14), 4362; https://doi.org/10.3390/molecules26144362 - 19 Jul 2021

Cited by 29 | Viewed by 5393

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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13 pages, 28715 KiB

Open AccessArticle

Novel Perbutyrylated Glucose Derivatives of (–)-Epigallocatechin-3-Gallate Inhibit Cancer Cells Proliferation by Decreasing Phosphorylation of the EGFR: Synthesis, Cytotoxicity, and Molecular Docking

by Ya Wang, Xiao-Jing Shen, Fa-Wu Su, Yin-Rong Xie, Li-Xia Wang, Ning Zhang, Yi-Long Wu, Yun Niu, Dong-Ying Zhang, Cheng-Ting Zi, Xuan-Jun Wang and Jun Sheng

Molecules 2021, 26(14), 4361; https://doi.org/10.3390/molecules26144361 - 19 Jul 2021

Cited by 8 | Viewed by 2512

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 (7–12) 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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12 pages, 4284 KiB

Open AccessArticle

Aromatic Amines in Organic Synthesis. Part II. p-Aminocinnamaldehydes

by Marek Pietrzak and Beata Jędrzejewska

Molecules 2021, 26(14), 4360; https://doi.org/10.3390/molecules26144360 - 19 Jul 2021

Cited by 4 | Viewed by 2850

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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19 pages, 4669 KiB

Open AccessArticle

The HDAC/HSP90 Inhibitor G570 Attenuated Blue Light-Induced Cell Migration in RPE Cells and Neovascularization in Mice through Decreased VEGF Production

by Tai-Ju Hsu, Kunal Nepali, Chi-Hao Tsai, Zuha Imtiyaz, Fan-Li Lin, George Hsiao, Mei-Jung Lai and Yu-Wen Cheng

Molecules 2021, 26(14), 4359; https://doi.org/10.3390/molecules26144359 - 19 Jul 2021

Cited by 6 | Viewed by 2999

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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