Molecules

16 pages, 6635 KiB

Open AccessArticle

Simultaneous Determination of Cortisol, Cortisone, and Multiple Illicit Drugs in Hair among Female Drug Addicts with LC-MS/MS

by Cailing Duan, Yan Wu, Jin Yang, Shenghuo Chen, Yun Pu and Huihua Deng

Molecules 2021, 26(2), 516; https://doi.org/10.3390/molecules26020516 - 19 Jan 2021

Cited by 7 | Viewed by 3607

Abstract

Long-term dependence of illicit drugs impairs the function of the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the secretion of endogenous steroids, cortisol, and cortisone. Thus, the present study aimed to develop a sensitive method for simultaneous determination of the multiple illicit drugs and two [...] Read more.

Long-term dependence of illicit drugs impairs the function of the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the secretion of endogenous steroids, cortisol, and cortisone. Thus, the present study aimed to develop a sensitive method for simultaneous determination of the multiple illicit drugs and two steroids in hair to monitor the status of illicit drug exposure and the physiological and psychological health of drug addicts. The target analytes were extracted from hair by incubation with 1 mL methanol for 24 h at 40 °C and then determined with LC-APCI⁺-MS/MS. The validated method showed acceptable linearity (R² > 0.99) in the range of 1.25–250 pg/mg for cortisol and cortisone, 2.5–125 pg/mg for heroin, 2.5–1250 pg/mg for ketamine, 2.5–5000 pg/mg for methamphetamine (MAM), 2.5–250 pg/mg for 3, 4-methylenedioxymethamphetamine (MDMA), morphine, and 6-monoacetylmorphine (6-AM). Limits of quantification were 1.6, 1.2, 1.6, 1.0, 1.4, 0.3, 2.1, and 1.2 pg/mg for cortisol, cortisone, heroin, ketamine, MAM, MDMA, morphine, and 6-AM, respectively. Method recoveries were from 90–115% for all analytes. Inter-day and intra-day coefficients of variation were within 10%. Finally, this method was successfully applied to detect the aforementioned analytes in hair among female drug addicts who self-reported to be MAM abuser, heroin abuser, ketamine abuser, and abuser of mixture drugs of MAM and heroin. MAM abusers with current MAM use showed significantly higher concentrations of cortisol, MAM, and MDMA than controls with drug withdrawal. Full article

(This article belongs to the Special Issue Bioanalysis and Biological Matrix Sampling)

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42 pages, 2576 KiB

Open AccessReview

The Potential of Selected Agri-Food Loss and Waste to Contribute to a Circular Economy: Applications in the Food, Cosmetic and Pharmaceutical Industries

by Lady Laura Del Rio Osorio, Edwin Flórez-López and Carlos David Grande-Tovar

Molecules 2021, 26(2), 515; https://doi.org/10.3390/molecules26020515 - 19 Jan 2021

Cited by 218 | Viewed by 22092

Abstract

The food sector includes several large industries such as canned food, pasta, flour, frozen products, and beverages. Those industries transform agricultural raw materials into added-value products. The fruit and vegetable industry is the largest and fastest-growing segment of the world agricultural production market, [...] Read more.

The food sector includes several large industries such as canned food, pasta, flour, frozen products, and beverages. Those industries transform agricultural raw materials into added-value products. The fruit and vegetable industry is the largest and fastest-growing segment of the world agricultural production market, which commercialize various products such as juices, jams, and dehydrated products, followed by the cereal industry products such as chocolate, beer, and vegetable oils are produced. Similarly, the root and tuber industry produces flours and starches essential for the daily diet due to their high carbohydrate content. However, the processing of these foods generates a large amount of waste several times improperly disposed of in landfills. Due to the increase in the world’s population, the indiscriminate use of natural resources generates waste and food supply limitations due to the scarcity of resources, increasing hunger worldwide. The circular economy offers various tools for raising awareness for the recovery of waste, one of the best alternatives to mitigate the excessive consumption of raw materials and reduce waste. The loss and waste of food as a raw material offers bioactive compounds, enzymes, and nutrients that add value to the food cosmetic and pharmaceutical industries. This paper systematically reviewed literature with different food loss and waste by-products as animal feed, cosmetic, and pharmaceutical products that strongly contribute to the paradigm shift to a circular economy. Additionally, this review compiles studies related to the integral recovery of by-products from the processing of fruits, vegetables, tubers, cereals, and legumes from the food industry, with the potential in SARS-CoV-2 disease and bacterial diseases treatment. Full article

(This article belongs to the Special Issue Circular Economy: Agri-Food Byproducts as Source of Bioactive Compounds)

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28 pages, 7424 KiB

Open AccessReview

Effects of Ionic Liquids on Metalloproteins

by Aashka Y. Patel, Keertana S. Jonnalagadda, Nicholas Paradis, Timothy D. Vaden, Chun Wu and Gregory A. Caputo

Molecules 2021, 26(2), 514; https://doi.org/10.3390/molecules26020514 - 19 Jan 2021

Cited by 16 | Viewed by 4034

Abstract

In the past decade, innovative protein therapies and bio-similar industries have grown rapidly. Additionally, ionic liquids (ILs) have been an area of great interest and rapid development in industrial processes over a similar timeline. Therefore, there is a pressing need to understand the [...] Read more.

In the past decade, innovative protein therapies and bio-similar industries have grown rapidly. Additionally, ionic liquids (ILs) have been an area of great interest and rapid development in industrial processes over a similar timeline. Therefore, there is a pressing need to understand the structure and function of proteins in novel environments with ILs. Understanding the short-term and long-term stability of protein molecules in IL formulations will be key to using ILs for protein technologies. Similarly, ILs have been investigated as part of therapeutic delivery systems and implicated in numerous studies in which ILs impact the activity and/or stability of protein molecules. Notably, many of the proteins used in industrial applications are involved in redox chemistry, and thus often contain metal ions or metal-associated cofactors. In this review article, we focus on the current understanding of protein structure-function relationship in the presence of ILs, specifically focusing on the effect of ILs on metal containing proteins. Full article

(This article belongs to the Special Issue Biomolecules in Non-aqueous Media, from Small Molecules to Macromolecules)

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16 pages, 2727 KiB

Open AccessArticle

Energetics of Electron Pairs in Electrophilic Aromatic Substitutions

by Julen Munárriz, Miguel Gallegos, Julia Contreras-García and Ángel Martín Pendás

Molecules 2021, 26(2), 513; https://doi.org/10.3390/molecules26020513 - 19 Jan 2021

Cited by 4 | Viewed by 3301

Abstract

The interacting quantum atoms approach (IQA) as applied to the electron-pair exhaustive partition of real space induced by the electron localization function (ELF) is used to examine candidate energetic descriptors to rationalize substituent effects in simple electrophilic aromatic substitutions. It is first shown [...] Read more.

The interacting quantum atoms approach (IQA) as applied to the electron-pair exhaustive partition of real space induced by the electron localization function (ELF) is used to examine candidate energetic descriptors to rationalize substituent effects in simple electrophilic aromatic substitutions. It is first shown that inductive and mesomeric effects can be recognized from the decay mode of the aromatic valence bond basin populations with the distance to the substituent, and that the fluctuation of the population of adjacent bonds holds also regioselectivity information. With this, the kinetic energy of the electrons in these aromatic basins, as well as their mutual exchange-correlation energies are proposed as suitable energetic indices containing relevant information about substituent effects. We suggest that these descriptors could be used to build future reactive force fields. Full article

(This article belongs to the Special Issue Advances in the Theory of Chemical Bonding)

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11 pages, 4204 KiB

Open AccessArticle

Evaluation of Fluorescent Cu²⁺ Probes: Instant Sensing, Cell Permeable Recognition and Quantitative Detection

by Hao He, Zhao Cheng, Lei Zheng and Xuejiao Zhang

Molecules 2021, 26(2), 512; https://doi.org/10.3390/molecules26020512 - 19 Jan 2021

Cited by 7 | Viewed by 2557

Abstract

By incorporating a rhodamine spirolactam structure as the recognition site for Cu²⁺, two novel probes were synthesized through a connection of rhodamine 6G acylhydrazine and 5-formyl-6-hydroxyl-4-methylcoumarin/2,4-dihydroxybenzaldehyde. In the recognition process of probes towards Cu²⁺, the spirolactam ring exhibited opening [...] Read more.

By incorporating a rhodamine spirolactam structure as the recognition site for Cu²⁺, two novel probes were synthesized through a connection of rhodamine 6G acylhydrazine and 5-formyl-6-hydroxyl-4-methylcoumarin/2,4-dihydroxybenzaldehyde. In the recognition process of probes towards Cu²⁺, the spirolactam ring exhibited opening and closing, accompanying an instant and specific change in fluorescence and in color, which could also achieve a naked-eye and semiquantitative recognition of aqueous Cu²⁺ besides the fluorescent Cu²⁺ detection method. Fluorescent analyses and ECV304 cell imaging further revealed the probes’ good optical stability, instant response, low toxicity, and membrane permeability, which offers future possibilities for the probes’ instant detection and the real-time tracking of Cu²⁺ in biological systems. Full article

(This article belongs to the Special Issue Fluorescent Probes in Pharmaceutical and Drug Design Applications: Quantum Chemistry-Based Design, Synthesis, Photophysical and Chemical Properties, Biological Applications)

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16 pages, 4335 KiB

Open AccessArticle

Arginine Deiminase Induces Immunogenic Cell Death and Is Enhanced by N-acetylcysteine in Murine MC38 Colorectal Cancer Cells and MDA-MB-231 Human Breast Cancer Cells In Vitro

by Zhiying Huang and Haifeng Hu

Molecules 2021, 26(2), 511; https://doi.org/10.3390/molecules26020511 - 19 Jan 2021

Cited by 10 | Viewed by 4350

Abstract

The use of arginine deiminase (ADI) for arginine depletion therapy is an attractive anticancer approach. Combination strategies are needed to overcome the resistance of severe types of cancer cells to this monotherapy. In the current study, we report, for the first time, that [...] Read more.

The use of arginine deiminase (ADI) for arginine depletion therapy is an attractive anticancer approach. Combination strategies are needed to overcome the resistance of severe types of cancer cells to this monotherapy. In the current study, we report, for the first time, that the antioxidant N-acetylcysteine (NAC), which has been used in therapeutic practices for several decades, is a potent enhancer for targeted therapy that utilizes arginine deiminase. We demonstrated that pegylated arginine deiminase (ADI-PEG 20) induces apoptosis and G0/G1 phase arrest in murine MC38 colorectal cancer cells; ADI-PEG 20 induces Ca²⁺ overload and decreases the mitochondrial membrane potential in MC38 cells. ADI-PEG 20 induced the most important immunogenic cell death (ICD)-associated feature: cell surface exposure of calreticulin (CRT). The antioxidant NAC enhanced the antitumor activity of ADI-PEG 20 and strengthened its ICD-associated features including the secretion of high mobility group box 1 (HMGB1) and adenosine triphosphate (ATP). In addition, these regimens resulted in phagocytosis of treated MC38 cancer cells by bone marrow-derived dendritic cells (BMDCs). In conclusion, we describe, for the first time, that NAC in combination with ADI-PEG 20 not only possesses unique cytotoxic anticancer properties but also triggers the hallmarks of immunogenic cell death. Hence, ADI-PEG 20 in combination with NAC may represent a promising approach to treat ADI-sensitive tumors while preventing relapse and metastasis. Full article

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10 pages, 1711 KiB

Open AccessArticle

Heterologous Expression of Pseudouridimycin and Description of the Corresponding Minimal Biosynthetic Gene Cluster

by Nils Böhringer, Maria A. Patras and Till F. Schäberle

Molecules 2021, 26(2), 510; https://doi.org/10.3390/molecules26020510 - 19 Jan 2021

Cited by 6 | Viewed by 2864

Abstract

Pseudouridimycin (PUM) was recently discovered from Streptomyces sp. DSM26212 as a novel bacterial nucleoside analog that competes with UTP for access to the RNA polymerase (RNAP) active site, thereby inhibiting bacterial RNAP by blocking transcription. This represents a novel antibacterial mode of action [...] Read more.

Pseudouridimycin (PUM) was recently discovered from Streptomyces sp. DSM26212 as a novel bacterial nucleoside analog that competes with UTP for access to the RNA polymerase (RNAP) active site, thereby inhibiting bacterial RNAP by blocking transcription. This represents a novel antibacterial mode of action and it is known that PUM inhibits bacterial RNAP in vitro, inhibits bacterial growth in vitro, and was active in vivo in a mouse infection model of Streptococcus pyogenes peritonitis. The biosynthetic gene cluster (BGC) was previously identified and characterized by knockout experiments. However, the minimal set of genes necessary for PUM production was not proposed. To identify the minimal BGC and to create a plug-and-play production platform for PUM and its biosynthetic precursors, several versions of a redesigned PUM BGC were generated and expressed in the heterologous host Streptomyces coelicolor M1146 under control of strong promotors. Heterologous expression allowed identification of the putative serine/threonine kinase PumF as an enzyme essential for heterologous PUM production and thus corroboration of the PUM minimal BGC. Full article

(This article belongs to the Section Chemical Biology)

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18 pages, 2755 KiB

Open AccessFeature PaperArticle

Characterisation of Elastomers as Food Contact Materials–Part 1: Quantification of Extractable Compounds, Swelling of Elastomers in Food Simulants and Release of Elements

by Friederike Kühne, Maurus Biedermann, Angela Eicher, Florian Felder, Stefan Sander, Roman Schmidt, Saskia Lehmann, Gregor McCombie, Stefan Merkel, Oliver Kappenstein and Andreas Luch

Molecules 2021, 26(2), 509; https://doi.org/10.3390/molecules26020509 - 19 Jan 2021

Cited by 9 | Viewed by 4784

Abstract

Elastomers are not a uniform class of materials but comprise a broad spectrum of chemically different polymers. Sealing gaskets, gloves, teats, conveyor belts and tubing are examples of elastomers being used as food contact materials (FCMs). Ten elastomer samples were evaluated with respect [...] Read more.

Elastomers are not a uniform class of materials but comprise a broad spectrum of chemically different polymers. Sealing gaskets, gloves, teats, conveyor belts and tubing are examples of elastomers being used as food contact materials (FCMs). Ten elastomer samples were evaluated with respect to the content of extractable compounds, migration of substances into ethanolic food simulants, swelling in food simulants and release of elements in different food simulants. The number of extractable substances <1000 Da was determined by comprehensive two-dimensional gas chromatography coupled with flame ionisation detection (GC × GC–FID) analysis of tetrahydrofuran (THF) extracts. The number of signals ranged from 61 (a thermoplastic elastomer (TPE)) to 690 (a natural rubber/styrene-butadiene-rubber blend (NR/SBR)). As for risk assessment, the decisive factor is which substances reach the food. The extent of substances that migrate into ethanolic food simulants was investigated. Elastomer FCMs can be the source of food contamination with heavy metals. Notably, contamination with lead was detected in some samples investigated in this study. It was shown that food simulants harbour the potential to morphologically alter or even disintegrate elastomeric materials. The results presented here highlight the importance to carefully choose the elastomer type for the intended use as FCMs as not every application may prove safe for consumers. Full article

(This article belongs to the Special Issue Food Packaging Materials)

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21 pages, 370 KiB

Open AccessReview

Effects of Physical and Chemical Factors on the Structure of Gluten, Gliadins and Glutenins as Studied with Spectroscopic Methods

by Konrad Kłosok, Renata Welc, Emilia Fornal and Agnieszka Nawrocka

Molecules 2021, 26(2), 508; https://doi.org/10.3390/molecules26020508 - 19 Jan 2021

Cited by 44 | Viewed by 7732

Abstract

This review presents applications of spectroscopic methods, infrared and Raman spectroscopies in the studies of the structure of gluten network and gluten proteins (gliadins and glutenins). Both methods provide complimentary information on the secondary and tertiary structure of the proteins including analysis of [...] Read more.

This review presents applications of spectroscopic methods, infrared and Raman spectroscopies in the studies of the structure of gluten network and gluten proteins (gliadins and glutenins). Both methods provide complimentary information on the secondary and tertiary structure of the proteins including analysis of amide I and III bands, conformation of disulphide bridges, behaviour of tyrosine and tryptophan residues, and water populations. Changes in the gluten structure can be studied as an effect of dough mixing in different conditions (e.g., hydration level, temperature), dough freezing and frozen storage as well as addition of different compounds to the dough (e.g., dough improvers, dietary fibre preparations, polysaccharides and polyphenols). Additionally, effect of above mentioned factors can be determined in a common wheat dough, model dough (prepared from reconstituted flour containing only wheat starch and wheat gluten), gluten dough (lack of starch), and in gliadins and glutenins. The samples were studied in the hydrated state, in the form of powder, film or in solution. Analysis of the studies presented in this review indicates that an adequate amount of water is a critical factor affecting gluten structure. Full article

(This article belongs to the Special Issue Vibrational Spectroscopy as a Versatile Tool To Predict Protein Structure)

12 pages, 2288 KiB

Open AccessArticle

Micellar Casein and Whey Powder Hold a TGF-β Activity and Regulate ID Genes In Vitro

by Layla Panahipour, Selma Husejnovic, Jila Nasirzade, Stephan Semelmayer and Reinhard Gruber

Molecules 2021, 26(2), 507; https://doi.org/10.3390/molecules26020507 - 19 Jan 2021

Cited by 6 | Viewed by 3196

Abstract

Casein and whey being food supplements have been considered to be used in oral health care products. However, the response of oral cells to micellar casein and whey powder remains unclear. Considering that milk contains the growth factor TGF-β, and lactoperoxidase was recently [...] Read more.

Casein and whey being food supplements have been considered to be used in oral health care products. However, the response of oral cells to micellar casein and whey powder remains unclear. Considering that milk contains the growth factor TGF-β, and lactoperoxidase was recently reported to decrease the expression of inhibitor of DNA-binding (ID) proteins, there is a rationale to assume that casein and whey can also provoke these responses in oral cells. To examine the TGF-β activity, gingival fibroblasts were exposed to reconstituted casein and whey powder from food supplement before the expression of TGF-β target genes were analyzed by reverse transcription-quantitative polymerase chain reaction. Immunoassays were performed for interleukin11 (IL11) in the cell culture supernatant and for TGF-β in the reconstituted casein and whey. We blocked TGF-β by neutralizing the antibody and the TGF-β receptor type I kinase with the inhibitor SB431542. We also showed smad3 phosphorylation and smad2/3 nuclear translocation by Western blot and immunostaining, respectively. Moreover, with reconstituted casein and whey powder, ID1 and ID3 expression analysis was evaluated in HSC2 human oral squamous carcinoma cells. We report here that casein and whey powder caused a robust increase of TGF-β target genes interleukin11 (IL11), NADPH oxidase 4 (NOX4) and proteoglycan4 (PRG4) in gingival fibroblasts that was blocked by SB431542 and the neutralizing antibody. Moreover, casein and whey powder increased the phosphorylation of smad3 and nuclear translocation of smad2/3. No changes of proliferation markers Ki67 and cyclinD1 were observed. Furthermore, reconstituted casein and whey powder decreased ID1 and ID3 expression in the HSC2 oral squamous carcinoma cells. These findings suggest that the processing of milk into casein and whey powder maintains the TGF-β activity and its capacity to regulate ID1 and ID3 genes in oral fibroblasts and oral squamous carcinoma cells, respectively. These data increase the scientific knowledge on the biological activity of casein and whey with a special emphasis on oral health. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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29 pages, 5304 KiB

Open AccessArticle

Revealing the Potential Application of EC-Synthetic Retinoid Analogues in Anticancer Therapy

by Mohamed R. Abdelaal, Sameh H. Soror, Mohamed R. Elnagar and Hesham Haffez

Molecules 2021, 26(2), 506; https://doi.org/10.3390/molecules26020506 - 19 Jan 2021

Cited by 13 | Viewed by 4156

Abstract

(1) Background and Aim: All-trans retinoic acid (ATRA) induces differentiation and inhibits growth of many cancer cells. However, resistance develops rapidly prompting the urgent need for new synthetic and potent derivatives. EC19 and EC23 are two synthetic retinoids with potent stem cell [...] Read more.

(1) Background and Aim: All-trans retinoic acid (ATRA) induces differentiation and inhibits growth of many cancer cells. However, resistance develops rapidly prompting the urgent need for new synthetic and potent derivatives. EC19 and EC23 are two synthetic retinoids with potent stem cell neuro-differentiation activity. Here, these compounds were screened for their in vitro antiproliferative and cytotoxic activity using an array of different cancer cell lines. (2) Methods: MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, AV/PI (annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI)), cell cycle analysis, immunocytochemistry, gene expression analysis, Western blotting, measurement of glutamate and total antioxidant concentrations were recruited. (3) Results: HepG2, Caco-2, and MCF-7 were the most sensitive cell lines; HepG2 (ATRA; 36.2, EC19; 42.2 and EC23; 0.74 µM), Caco-2 (ATRA; 58.0, EC19; 10.8 and EC23; 14.7 µM) and MCF-7 (ATRA; 99.0, EC19; 9.4 and EC23; 5.56 µM). Caco-2 cells were selected for further biochemical investigations. Isobologram analysis revealed the combined synergistic effects with 5-fluorouracil with substantial reduction in IC₅₀. All retinoids induced apoptosis but EC19 had higher potency, with significant cell cycle arrest at subG₀-G₁, -S and G₂/M phases, than ATRA and EC23. Moreover, EC19 reduced cellular metastasis in a transwell invasion assay due to overexpression of E-cadherin, retinoic acid-induced 2 (RAI2) and Werner (WRN) genes. (4) Conclusion: The present study suggests that EC-synthetic retinoids, particularly EC19, can be effective, alone or in combinations, for potential anticancer activity to colorectal cancer. Further in vivo studies are recommended to pave the way for clinical applications. Full article

(This article belongs to the Section Chemical Biology)

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16 pages, 4552 KiB

Open AccessArticle

Ellagic Acid–Cyclodextrin Complexes for the Treatment of Oral Candidiasis

by Aline da Graça Sampaio, Aline Vidal Lacerda Gontijo, Gabriela de Morais Gouvêa Lima, Maria Alcionéia Carvalho de Oliveira, Laura Soares Souto Lepesqueur and Cristiane Yumi Koga-Ito

Molecules 2021, 26(2), 505; https://doi.org/10.3390/molecules26020505 - 19 Jan 2021

Cited by 15 | Viewed by 3082

Abstract

The increase in the prevalence of fungal infections worldwide and the rise in the occurrence of antifungal resistance suggest that new research to discover antifungal molecules is needed. The aim of this study was to evaluate the potential use of ellagic acid–cyclodextrin complexes [...] Read more.

The increase in the prevalence of fungal infections worldwide and the rise in the occurrence of antifungal resistance suggest that new research to discover antifungal molecules is needed. The aim of this study was to evaluate the potential use of ellagic acid–cyclodextrin complexes (EA/HP-β-CD) for the treatment of oral candidiasis. First, the effect of EA/HP-β-CD on C. albicans planktonic cells and biofilms was evaluated. Then, the cytotoxicity of the effective concentration was studied to ensure safety of in vivo testing. Finally, the in vivo effectiveness was determined by using a murine model of induced oral candidiasis. Data was statistically analyzed. The minimal inhibitory concentration of EA/HP-β-CD was 25 µg/mL and a concentration of 10 times MIC (250 µg/mL) showed an inhibitory effect on C. albicans 48 h-biofilms. The complex at concentration 250 µg/mL was classified as slightly cytotoxic. In vivo experiments showed a reduction in fungal epithelial invasion after treatment with EA/HP-β-CD for 24 h and 96 h when compared to the negative control. In conclusion, the results demonstrated that EA/HP-β-CD has antifungal and anti-inflammatory effects, reducing the invasive capacity of C. albicans, which suggests that EA/HP-β-CD may be a promising alternative for the treatment of oral candidiasis. Full article

(This article belongs to the Special Issue Novel Biologically Active Molecules, Biomaterials and Nanoparticles for the Microbial Biofilm Control in Human Medicine)

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15 pages, 2920 KiB

Open AccessArticle

Identification of Organic Volatile Markers Associated with Aroma during Maturation of Strawberry Fruits

by Samuel Macario Padilla-Jiménez, María Valentina Angoa-Pérez, Hortencia Gabriela Mena-Violante, Guadalupe Oyoque-Salcedo, José Luis Montañez-Soto and Ernesto Oregel-Zamudio

Molecules 2021, 26(2), 504; https://doi.org/10.3390/molecules26020504 - 19 Jan 2021

Cited by 31 | Viewed by 3725

Abstract

In the present study, organic volatile markers of three strawberry varieties (Albion, Festival and Frontera) during the maturation process were investigated. Forty metabolites associated with aroma in fresh strawberries were monitored during seven stages of maturation using gas chromatography–mass spectrometry (GC-MS) equipped with [...] Read more.

In the present study, organic volatile markers of three strawberry varieties (Albion, Festival and Frontera) during the maturation process were investigated. Forty metabolites associated with aroma in fresh strawberries were monitored during seven stages of maturation using gas chromatography–mass spectrometry (GC-MS) equipped with headspace-solid phase microextraction (HS-SPME). The data were evaluated using multivariate analysis to observe correlations between the organic volatile compound profile and the seven phenological stages of maturation for each strawberry variety. The dynamic levels of butanoic acid methyl ester, hexanoic acid methyl ester, octylcyclohexane, cyclohexane,1,1,2-trimethyl, linalool, tetradecane, and α-muurolene underwent distinctive changes in concentration during the maturation process. The multivariate analysis also allowed the identification of these compounds as possible volatile markers to measure the maturation of strawberry fruits in all three varieties. These findings highlight the importance of the timing of harvest and maturation stage in each variety to preserve or improve the desirable aromatic characteristics of strawberry fruits. Full article

(This article belongs to the Special Issue Flavoromics for the Quality and Authenticity of Foods and Beverages)

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13 pages, 1861 KiB

Open AccessArticle

Analyzing the Carotenoid Composition of Melilot (Melilotus officinalis (L.) Pall.) Extracts and the Effects of Isolated (All-E)-lutein-5,6-epoxide on Primary Sensory Neurons and Macrophages

by Györgyi Horváth, Eszter Csikós, Eichertné Violetta Andres, Tímea Bencsik, Anikó Takátsy, Gergely Gulyás-Fekete, Erika Turcsi, József Deli, Éva Szőke, Ágnes Kemény, Maja Payrits, Lajos Szente, Marianna Kocsis, Péter Molnár and Zsuzsanna Helyes

Molecules 2021, 26(2), 503; https://doi.org/10.3390/molecules26020503 - 19 Jan 2021

Cited by 5 | Viewed by 3260

Abstract

Melilotus officinalis is known to contain several types of secondary metabolites. In contrast, the carotenoid composition of this medicinal plant has not been investigated, although it may also contribute to the biological activities of the drug, such as anti-inflammatory effects. Therefore, this study [...] Read more.

Melilotus officinalis is known to contain several types of secondary metabolites. In contrast, the carotenoid composition of this medicinal plant has not been investigated, although it may also contribute to the biological activities of the drug, such as anti-inflammatory effects. Therefore, this study focuses on the isolation and identification of carotenoids from Meliloti herba and on the effect of isolated (all-E)-lutein 5,6-epoxide on primary sensory neurons and macrophages involved in nociception, as well as neurogenic and non-neurogenic inflammatory processes. The composition of the plant extracts was analyzed by high performance liquid chromatography (HPLC). The main carotenoid was isolated by column liquid chromatography (CLC) and identified by MS and NMR. The effect of water-soluble lutein 5,6-epoxide-RAMEB (randomly methylated-β-cyclodextrin) was investigated on Ca²⁺-influx in rat primary sensory neurons induced by the activation of the transient receptor potential ankyrin 1 receptor agonist to mustard-oil and on endotoxin-induced IL-1β release from isolated mouse peritoneal macrophages. (all-E)-Lutein 5,6-epoxide significantly decreased the percent of responsive primary sensory neurons compared to the vehicle-treated stimulated control. Furthermore, endotoxin-evoked IL-1β release from macrophages was significantly decreased by 100 µM lutein 5,6-epoxide compared to the vehicle-treated control. The water-soluble form of lutein 5,6-epoxide-RAMEB decreases the activation of primary sensory neurons and macrophages, which opens perspectives for its analgesic and anti-inflammatory applications. Full article

(This article belongs to the Special Issue A Themed Issue in Honor of Professor K.Hüsnü Can Baser—Outstanding Contributions in the Fields of Pharmacognosy, Phytochemistry, Botany and Ethnopharmacology)

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23 pages, 11715 KiB

Open AccessArticle

Effect of Substitution of Hydrogen Atoms in the Molecules of Anthrone and Anthraquinone

by Małgorzata Szymańska and Irena Majerz

Molecules 2021, 26(2), 502; https://doi.org/10.3390/molecules26020502 - 19 Jan 2021

Cited by 4 | Viewed by 2520

Abstract

The geometry of anthrone and anthraquinone—natural substances of plant origin—was investigated under the substitution of hydrogen atoms in side aromatic ring and, for anthrone, also in the central ring. A significant influence of substitution on geometry expressed by the angle between the side [...] Read more.

The geometry of anthrone and anthraquinone—natural substances of plant origin—was investigated under the substitution of hydrogen atoms in side aromatic ring and, for anthrone, also in the central ring. A significant influence of substitution on geometry expressed by the angle between the side rings was shown. The geometry changes are connected with the changes of electron density and aromaticity of the anthrone and anthraquinone rings. The flexibility of the investigated compounds was confirmed by comparison of the optimized molecules and the molecules in the crystal state where the packing forces can influence the molecular geometry. Full article

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15 pages, 1640 KiB

Open AccessReview

Trending Topics on Coumarin and Its Derivatives in 2020

by Aitor Carneiro, Maria João Matos, Eugenio Uriarte and Lourdes Santana

Molecules 2021, 26(2), 501; https://doi.org/10.3390/molecules26020501 - 19 Jan 2021

Cited by 102 | Viewed by 8954

Abstract

Coumarins are naturally occurring molecules with a versatile range of activities. Their structural and physicochemical characteristics make them a privileged scaffold in medicinal chemistry and chemical biology. Many research articles and reviews compile information on this important family of compounds. In this overview, [...] Read more.

Coumarins are naturally occurring molecules with a versatile range of activities. Their structural and physicochemical characteristics make them a privileged scaffold in medicinal chemistry and chemical biology. Many research articles and reviews compile information on this important family of compounds. In this overview, the most recent research papers and reviews from 2020 are organized and analyzed, and a discussion on these data is included. Multiple electronic databases were scanned, including SciFinder, Mendeley, and PubMed, the latter being the main source of information. Particular attention was paid to the potential of coumarins as an important scaffold in drug design, as well as fluorescent probes for decaging of prodrugs, metal detection, and diagnostic purposes. Herein we do an analysis of the trending topics related to coumarin and its derivatives in the broad field of drug discovery. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives)

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6 pages, 241 KiB

Open AccessEditorial

CO₂ Valorization and Its Subsequent Valorization

by Juan Antonio Cecilia, Daniel Ballesteros Plata and Enrique Vilarrasa García

Molecules 2021, 26(2), 500; https://doi.org/10.3390/molecules26020500 - 19 Jan 2021

Cited by 3 | Viewed by 2579

Abstract

After the industrial revolution, the increase in the world population and the consumption of fossil fuels has led to an increase in anthropogenic CO₂ emissions [...] Full article

(This article belongs to the Special Issue CO₂ Capture Storage and Its Subsequent Valorization)

12 pages, 2196 KiB

Open AccessArticle

Antiparasitic Potential of Chromatographic Fractions of Nephrolepis biserrata and Liquid Chromatography-Quadrupole Time-of-Flight-Mass Spectrometry Analysis

by Muhammad Dawood Shah, Kazuki Tani, Yoong Soon Yong, Fui Fui Ching, Sitti Raehanah Muhamad Shaleh, Charles S. Vairappan and Balu Alagar Venmathi Maran

Molecules 2021, 26(2), 499; https://doi.org/10.3390/molecules26020499 - 19 Jan 2021

Cited by 8 | Viewed by 4297

Abstract

Marine aquaculture development is recently impeded by parasitic leech Zeylanicobdellaarugamensis (Hirudinea, Piscicolidae) in Sabah, Malaysia. The parasitic leech infests a variety of cultured fishes in aquaculture facilities. In this study, we evaluated the antiparasitic activity of the chromatographic fractions of the medicinal [...] Read more.

Marine aquaculture development is recently impeded by parasitic leech Zeylanicobdellaarugamensis (Hirudinea, Piscicolidae) in Sabah, Malaysia. The parasitic leech infests a variety of cultured fishes in aquaculture facilities. In this study, we evaluated the antiparasitic activity of the chromatographic fractions of the medicinal plant Nephrolepis biserrata methanol extract against Z.arugamensis and highlighted the potential metabolites responsible for the antiparasitic properties through liquid chromatography (LC)–quadrupole time-of-flight (QTOF)–mass spectrometry (MS) analysis. Out of seven fractions obtained through flash column chromatography techniques, three fractions demonstrated antiparasitic properties. Significant parasitic mortality was indicated by fraction 3 at a concentration of 2.50 mg/mL, all the leeches were killed in a time limit of 1.92 ± 0.59 min. followed by fraction 4 (14 mg/mL) in 34.57 ± 3.39 and fraction 5 (15.3 mg/mL) in 36.82 ± 4.53 min. LC-QTOF-MS analysis indicated the presence of secondary metabolites including phytosphingosine (6), pyrethrosin (1), haplophytine (9), ivalin (2), warburganal (3), isodomedin (4) and pheophorbide a (16), representing sphingoid, alkaloid, terpenoid, phenolic and flavonoid groups. Thus, our study indicated that the chromatographic fractions of N. biserrata demonstrated significant antiparasitic activity against the marine parasitic leeches due to the presence of potent antiparasitic bioactive compounds. Full article

(This article belongs to the Special Issue Natural Products and Their Semi-synthetic Derivatives against Bacteria, Fungi and Parasites)

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15 pages, 4070 KiB

Open AccessArticle

Functional Component Isolated from Phaseolus vulgaris Lectin Exerts In Vitro and In Vivo Anti-Tumor Activity through Potentiation of Apoptosis and Immunomodulation

by Peipei Wang, Xiaohong Leng, Jiaqi Duan, Yue Zhu, Jue Wang, Zirui Yan, Shitong Min, Dapeng Wei and Xia Wang

Molecules 2021, 26(2), 498; https://doi.org/10.3390/molecules26020498 - 18 Jan 2021

Cited by 14 | Viewed by 3364

Abstract

Phytohemagglutinin (PHA), the lectin purified from red kidney bean (Phaseolus vulgaris), is a well-known mitogen for human lymphocyte. Because it has obvious anti-proliferative and anti-tumor activity, PHA may serve as a potential antineoplastic drug in future cancer therapeutics. However, the literature is also [...] Read more.

Phytohemagglutinin (PHA), the lectin purified from red kidney bean (Phaseolus vulgaris), is a well-known mitogen for human lymphocyte. Because it has obvious anti-proliferative and anti-tumor activity, PHA may serve as a potential antineoplastic drug in future cancer therapeutics. However, the literature is also replete with data on detrimental effects of PHA including oral toxicity, hemagglutinating activity, and immunogenicity. There is a critical need to evaluate the functional as well as the toxic components of PHAs to assist the rational designs of treatment with it. In this report, we performed SDS-PAGE to identify components of PHA-L, the tetrameric isomer of PHA with four identical L-type subunits, and then characterized biological function or toxicity of the major protein bands through in vitro experiments. It was found that the protein appearing as a 130 kD band in SDS-PAGE gel run under the condition of removal of β-mercaptoethanol from the sample buffer together with omission of a heating step could inhibit tumor cell growth and stimulate lymphocyte proliferation, while most of the 35 kD proteins are likely non-functional impurity proteins and 15 kD protein may be related to hemolytic effect. Importantly, the 130 kD functional protein exhibits promising in vivo anti-tumor activity in B16-F10 melanoma C57 BL/6 mouse models, which may be achieved through potentiation of apoptosis and immunomodulation. Altogether, our results suggest that PHA-L prepared from crude extracts of red kidney bean by standard strategies is a mixture of many ingredients, and a 130 kD protein of PHA-L was purified and identified as the major functional component. Our study may pave the way for PHA-L as a potential anticancer drug. Full article

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15 pages, 2483 KiB

Open AccessArticle

Modulation of Oxidative Stress and Hemostasis by Flavonoids from Lentil Aerial Parts

by Jerzy Żuchowski, Agata Rolnik, Weronika Adach, Anna Stochmal and Beata Olas

Molecules 2021, 26(2), 497; https://doi.org/10.3390/molecules26020497 - 18 Jan 2021

Cited by 8 | Viewed by 2591

Abstract

While specific metabolites of lentil (Lens culinaris L.) seeds and their biological activity have been well described, other organs of this plant have attracted little scientific attention. In recent years, green parts of lentils have been shown to contain diverse acylated flavonoids. [...] Read more.

While specific metabolites of lentil (Lens culinaris L.) seeds and their biological activity have been well described, other organs of this plant have attracted little scientific attention. In recent years, green parts of lentils have been shown to contain diverse acylated flavonoids. This work presents the results of the research on the effect of the crude extract, the phenolic fraction, and seven flavonoids obtained from aerial parts of lentils on oxidative damage induced by H₂O₂/Fe to lipid and protein constituents of human plasma. Another goal was to determine their effect on hemostasis parameters of human plasma in vitro. Most of the purified lentil flavonoids had antioxidant and anticoagulant properties. The crude extract and the phenolic fraction of lentil aerial parts showed antioxidant activity, only at the highest tested concentration (50 μg/mL). Our results indicate that aerial parts of lentils may be recommended as a source of bioactive substances. Full article

(This article belongs to the Special Issue Flavonoids and Their Disease Prevention and Treatment Potential 2021)

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18 pages, 5018 KiB

Open AccessArticle

Synthesis, Physical Properties and Application of a Series of New Polyoxometalate-Based Ionic Liquids

by Yohan Martinetto, Salomé Basset, Bruce Pégot, Catherine Roch-Marchal, Franck Camerel, Jelena Jeftic, Betty Cottyn-Boitte, Emmanuel Magnier and Sébastien Floquet

Molecules 2021, 26(2), 496; https://doi.org/10.3390/molecules26020496 - 18 Jan 2021

Cited by 4 | Viewed by 3415

Abstract

This paper deals with the preparation and the characterization of four new ionic liquids resulting from the pairing of various polyoxotungstates or polyoxomolybdates with the cation trihexyltetradecylphosphonium. The physical properties measured by different techniques evidence that the viscosity and the rheological behaviors of [...] Read more.

This paper deals with the preparation and the characterization of four new ionic liquids resulting from the pairing of various polyoxotungstates or polyoxomolybdates with the cation trihexyltetradecylphosphonium. The physical properties measured by different techniques evidence that the viscosity and the rheological behaviors of such POM-based ionic liquids, POM-ILs, strongly depend on the nature of the POM, especially its charge. Playing on the nature of the POM, we can indeed obtain Newtonian liquids or some much more viscous materials exhibiting characteristics of resins or pseudo-plastics. In a second part of this study, the potentialities of using such materials both as solvent and catalyst for the oxidation of a series of alcohols are presented as proof of concept. This part highlights great differences in strength and selectivity as a function of the POM-IL used. Furthermore, a very simple way to recycle the catalyst is also presented. Full article

(This article belongs to the Special Issue Polyoxometalates)

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31 pages, 2299 KiB

Open AccessReview

Plant Secondary Metabolites: An Opportunity for Circular Economy

by Ilaria Chiocchio, Manuela Mandrone, Paola Tomasi, Lorenzo Marincich and Ferruccio Poli

Molecules 2021, 26(2), 495; https://doi.org/10.3390/molecules26020495 - 18 Jan 2021

Cited by 113 | Viewed by 13186

Abstract

Moving toward a more sustainable development, a pivotal role is played by circular economy and a smarter waste management. Industrial wastes from plants offer a wide spectrum of possibilities for their valorization, still being enriched in high added-value molecules, such as secondary metabolites [...] Read more.

Moving toward a more sustainable development, a pivotal role is played by circular economy and a smarter waste management. Industrial wastes from plants offer a wide spectrum of possibilities for their valorization, still being enriched in high added-value molecules, such as secondary metabolites (SMs). The current review provides an overview of the most common SM classes (chemical structures, classification, biological activities) present in different plant waste/by-products and their potential use in various fields. A bibliographic survey was carried out, taking into account 99 research articles (from 2006 to 2020), summarizing all the information about waste type, its plant source, industrial sector of provenience, contained SMs, reported bioactivities, and proposals for its valorization. This survey highlighted that a great deal of the current publications are focused on the exploitation of plant wastes in human healthcare and food (including cosmetic, pharmaceutical, nutraceutical and food additives). However, as summarized in this review, plant SMs also possess an enormous potential for further uses. Accordingly, an increasing number of investigations on neglected plant matrices and their use in areas such as veterinary science or agriculture are expected, considering also the need to implement “greener” practices in the latter sector. Full article

(This article belongs to the Special Issue Circular Economy: Agri-Food Byproducts as Source of Bioactive Compounds)

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15 pages, 3112 KiB

Open AccessArticle

Flavonoid Glycosides in Brassica Species Respond to UV-B Depending on Exposure Time and Adaptation Time

by Susanne Neugart and Christiane Bumke-Vogt

Molecules 2021, 26(2), 494; https://doi.org/10.3390/molecules26020494 - 18 Jan 2021

Cited by 18 | Viewed by 3581

Abstract

Recently, there have been efforts to use ultraviolet-B radiation (UV-B) as a biotechnological tool in greenhouses. Leafy Brassica species are mainly considered for their ability to synthesize glucosinolates and are valued as baby salads. They also have a remarkable concentration of chemically diverse [...] Read more.

Recently, there have been efforts to use ultraviolet-B radiation (UV-B) as a biotechnological tool in greenhouses. Leafy Brassica species are mainly considered for their ability to synthesize glucosinolates and are valued as baby salads. They also have a remarkable concentration of chemically diverse flavonoid glycosides. In this study, the effect of short-term UV-B radiation at the end of the production cycle was investigated without affecting plant growth. The aim was to verify which exposure and adaptation time was suitable and needs to be further investigated to use UV as a biotechnological tool in greenhouse production of Brassica species. It is possible to modify the flavonoid glycoside profile of leafy Brassica species by increasing compounds that appear to have potentially high antioxidant activity. Exemplarily, the present experiment shows that kaempferol glycosides may be preferred over quercetin glycosides in response to UV-B in Brassica rapa ssp. chinensis, for example, whereas other species appear to prefer quercetin glycosides over kaempferol glycosides, such as Brassica oleracea var. sabellica or Brassica carinata. However, the response to short-term UV-B treatment is species-specific and conclusions on exposure and adaptation time cannot be unified but must be drawn separately for each species. Full article

(This article belongs to the Special Issue Assessment of Food Quality and Nutrition)

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16 pages, 4963 KiB

Open AccessArticle

Achiral Molecular Recognition of Substituted Aniline Position Isomers by Crown Ether Type Chiral Stationary Phase

by Atsushi Ohnishi, Tohru Shibata, Tatsuya Imase, Satoshi Shinkura and Kanji Nagai

Molecules 2021, 26(2), 493; https://doi.org/10.3390/molecules26020493 - 18 Jan 2021

Cited by 11 | Viewed by 2878

Abstract

To understand the selectivity of the crown ether type chiral stationary phase (CSP), the retention selectivity for aniline and the positional isomers of substituted anilines were studied. In various substituted isomers, except nitroaniline, a remarkable decrease of retention due to steric hindrance was [...] Read more.

To understand the selectivity of the crown ether type chiral stationary phase (CSP), the retention selectivity for aniline and the positional isomers of substituted anilines were studied. In various substituted isomers, except nitroaniline, a remarkable decrease of retention due to steric hindrance was observed for the 2-substituted isomer. To determine the detailed molecular recognition mechanism, quantum chemical calculations were performed for the aggregates between the crown ether and the anilines. The results suggested that the 20-Crown-6, which includes a phenyl-substituted 1,1′-binaphthyl moiety, interacts with alkyl and aryl amines in an unconventional form different from the proposed one for 18-Crown-6. Full article

(This article belongs to the Special Issue Molecular Recognition and Self-Assembly in Chemistry and Medicine)

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13 pages, 2636 KiB

Open AccessFeature PaperArticle

Virtual Screening of Natural Compounds as Potential PI₃K-AKT1 Signaling Pathway Inhibitors and Experimental Validation

by Serena Dotolo, Carmen Cervellera, Maria Russo, Gian Luigi Russo and Angelo Facchiano

Molecules 2021, 26(2), 492; https://doi.org/10.3390/molecules26020492 - 18 Jan 2021

Cited by 18 | Viewed by 3361

Abstract

A computational screening for natural compounds suitable to bind the AKT protein has been performed after the generation of a pharmacophore model based on the experimental structure of AKT1 complexed with IQO, a well-known inhibitor. The compounds resulted as being most suitable from [...] Read more.

A computational screening for natural compounds suitable to bind the AKT protein has been performed after the generation of a pharmacophore model based on the experimental structure of AKT1 complexed with IQO, a well-known inhibitor. The compounds resulted as being most suitable from the screening have been further investigated by molecular docking, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis and toxicity profiles. Two compounds selected at the end of the computational analysis, i.e., ZINC2429155 (also named STL1) and ZINC1447881 (also named AC1), have been tested in an experimental assay, together with IQO as a positive control and quercetin as a negative control. Only STL1 clearly inhibited AKT activation negatively modulating the PI₃K/AKT pathway. Full article

(This article belongs to the Special Issue Molecular Simulations Applications in Biochemistry and Molecular Biology)

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16 pages, 2967 KiB

Open AccessArticle

Zn^II and Cu^II-Based Coordination Polymers and Metal Organic Frameworks by the of Use of 2-Pyridyl Oximes and 1,3,5-Benzenetricarboxylic Acid

by Ioannis Mylonas-Margaritis, Julia Mayans, Patrick McArdle and Constantina Papatriantafyllopoulou

Molecules 2021, 26(2), 491; https://doi.org/10.3390/molecules26020491 - 18 Jan 2021

Cited by 11 | Viewed by 3880

Abstract

The simultaneous use of 2-pyridyl oximes (pyridine-2 amidoxime, H₂pyaox; 2-methyl pyridyl ketoxime, Hmpko) and 1,3,5-benzenetricarboxylic acid (H₃btc) provided access to five new compounds, namely [Zn(H₂btc)₂(H₂pyaox)₂]•2H₂O (1•2H₂ [...] Read more.

The simultaneous use of 2-pyridyl oximes (pyridine-2 amidoxime, H₂pyaox; 2-methyl pyridyl ketoxime, Hmpko) and 1,3,5-benzenetricarboxylic acid (H₃btc) provided access to five new compounds, namely [Zn(H₂btc)₂(H₂pyaox)₂]•2H₂O (1•2H₂O), [Zn(Hbtc)(H₂pyaox)₂]_n (2), [Cu(Hbtc)(H₂pyaox)]_n (3), [Cu(Hbtc)(HmpKo)]_n (4) and [Cu₂(Hbtc)₂(Hmpko)₂(H₂O)₂]•4H₂O (5•4H₂O). Among them, 3 is the first example of a metal-organic framework (MOF) containing H₂pyaox. Its framework can be described as a 3-c uninodal net of hcb topology with the layers being parallel to the (1,0,1) plane. Furthermore, 3 is the third reported MOF based on a 2-pyridyl oxime in general. 2 and 4 are new members of a small family of coordination polymers containing an oximic ligand. 1–5 form 3D networks through strong intermolecular interactions. Dc magnetic susceptibility studies were carried out in a crystalline sample of 3 and revealed the presence of weak exchange interactions between the metal centres; the experimental data were fitted to a theoretical model with the fitting parameters being J = −0.16(1) cm⁻¹ and g = 2.085(1). The isotropic g value was also confirmed by electronic paramagnetic resonance (EPR) spectroscopy. Reactivity studies were performed for 3 in the presence of metal ions; the reaction progress was studied and discussed for Fe(NO₃)₃ by the use of several characterization techniques, including single crystal X-ray crystallography and IR spectroscopy. Full article

(This article belongs to the Special Issue Exclusive Feature Papers in Inorganic Chemistry)

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11 pages, 1686 KiB

Open AccessCommunication

Expanding the Scope of the Cleavable N-(Methoxy)oxazolidine Linker for the Synthesis of Oligonucleotide Conjugates

by Aapo Aho, Antti Äärelä, Heidi Korhonen and Pasi Virta

Molecules 2021, 26(2), 490; https://doi.org/10.3390/molecules26020490 - 18 Jan 2021

Cited by 4 | Viewed by 3259

Abstract

Oligonucleotides modified by a 2′-deoxy-2′-(N-methoxyamino) ribonucleotide react readily with aldehydes in slightly acidic conditions to yield the corresponding N-(methoxy)oxazolidine-linked oligonucleotide-conjugates. The reaction is reversible and dynamic in slightly acidic conditions, while the products are virtually stable above pH 7, where [...] Read more.

Oligonucleotides modified by a 2′-deoxy-2′-(N-methoxyamino) ribonucleotide react readily with aldehydes in slightly acidic conditions to yield the corresponding N-(methoxy)oxazolidine-linked oligonucleotide-conjugates. The reaction is reversible and dynamic in slightly acidic conditions, while the products are virtually stable above pH 7, where the reaction is in a ‘‘switched off-state’’. Small molecular examinations have demonstrated that aldehyde constituents affect the cleavage rate of the N-(methoxy)oxazolidine-linkage. This can be utilized to adjust the stability of this pH-responsive cleavable linker for drug delivery applications. In the present study, Fmoc-β-Ala-H was immobilized to a serine-modified ChemMatrix resin and used for the automated assembly of two peptidealdehydes and one aldehyde-modified peptide nucleic acid (PNA). In addition, a triantennary N-acetyl-d-galactosamine-cluster with a β-Ala-H unit has been synthesized. These aldehydes were conjugated via N-(methoxy)oxazolidine-linkage to therapeutically relevant oligonucleotide phosphorothioates and one DNA-aptamer in 19–47% isolated yields. The cleavage rates of the conjugates were studied in slightly acidic conditions. In addition to the diverse set of conjugates synthesized, these experiments and a comparison to published data demonstrate that the simple conversion of Gly-H to β-Ala-H residue resulted in a faster cleavage of the N-(methoxy)oxazolidine-linker at pH 5, being comparable (T_0.5 ca 7 h) to hydrazone-based structures. Full article

(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugate II)

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11 pages, 2780 KiB

Open AccessCommunication

Chiral Tertiary Amine Catalyzed Asymmetric [4 + 2] Cyclization of 3-Aroylcoumarines with 2,3-Butadienoate

by Jun-Lin Li, Xiao-Hui Wang, Jun-Chao Sun, Yi-Yuan Peng, Cong-Bin Ji and Xing-Ping Zeng

Molecules 2021, 26(2), 489; https://doi.org/10.3390/molecules26020489 - 18 Jan 2021

Cited by 5 | Viewed by 2468

Abstract

Coumarins and 2H-pyran derivatives are among the most commonly found structural units in natural products. Therefore, the introduction of 2H-pyran moiety into the coumarin structural unit, i.e., dihydrocoumarin-fused dihydropyranones, is a potentially successful route for the identification of novel [...] Read more.

Coumarins and 2H-pyran derivatives are among the most commonly found structural units in natural products. Therefore, the introduction of 2H-pyran moiety into the coumarin structural unit, i.e., dihydrocoumarin-fused dihydropyranones, is a potentially successful route for the identification of novel bioactive structures, and the synthesis of these structures has attracted continuing research interest. Herein, a chiral tertiary amine catalyzed [4 + 2] cyclization of 3-aroylcoumarines with benzyl 2,3-butadienoate was reported. In the presence of Kumar’s 6’-(4-biphenyl)-β-iso-cinchonine, the desired dihydrocoumarin-fused dihydropyranone products could be obtained in up to 97% yield and 90% ee values. Full article

(This article belongs to the Special Issue Coumarin and Its Derivatives)

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67 pages, 21847 KiB

Open AccessReview

Chemical Diversity and Bioactivities of Monoterpene Indole Alkaloids (MIAs) from Six Apocynaceae Genera

by Afrah E. Mohammed, Zainab H. Abdul-Hameed, Modhi O. Alotaibi, Nahed O. Bawakid, Tariq R. Sobahi, Ahmed Abdel-Lateff and Walied M. Alarif

Molecules 2021, 26(2), 488; https://doi.org/10.3390/molecules26020488 - 18 Jan 2021

Cited by 67 | Viewed by 7146

Abstract

By the end of the twentieth century, the interest in natural compounds as probable sources of drugs has declined and was replaced by other strategies such as molecular target-based drug discovery. However, in the recent times, natural compounds regained their position as extremely [...] Read more.

By the end of the twentieth century, the interest in natural compounds as probable sources of drugs has declined and was replaced by other strategies such as molecular target-based drug discovery. However, in the recent times, natural compounds regained their position as extremely important source drug leads. Indole-containing compounds are under clinical use which includes vinblastine and vincristine (anticancer), atevirdine (anti-HIV), yohimbine (erectile dysfunction), reserpine (antihypertension), ajmalicine (vascular disorders), ajmaline (anti-arrhythmic), vincamine (vasodilator), etc. Monoterpene Indole Alkaloids (MIAs) deserve the curiosity and attention of researchers due to their chemical diversity and biological activities. These compounds were considered as an impending source of drug-lead. In this review 444 compounds, were identified from six genera belonging to the family Apocynaceae, will be discussed. These genera (Alstonia, Rauvolfia, Kopsia, Ervatamia, and Tabernaemontana, and Rhazya) consist of 400 members and represent 20% of Apocynaceae species. Only 30 (7.5%) species were investigated, whereas the rest are promising to be investigated. Eleven bioactivities, including antibacterial, antifungal, anti-inflammatory and immunosuppressant activities, were reported. Whereas cytotoxic effect represents 47% of the reported activities. Convincingly, the genera selected in this review are a wealthy source for future anticancer drug lead. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 1944 KiB

Open AccessArticle

Antioxidant, Anti-Inflammatory and Antidiabetic Proprieties of LC-MS/MS Identified Polyphenols from Coriander Seeds

by Hamza Mechchate, Imane Es-safi, Amal Amaghnouje, Smahane Boukhira, Amal A. Alotaibi, Mohammed Al-zharani, Fahd A. Nasr, Omar M. Noman, Raffaele Conte, El Hamsas El Youbi Amal, Hicham Bekkari and Dalila Bousta

Molecules 2021, 26(2), 487; https://doi.org/10.3390/molecules26020487 - 18 Jan 2021

Cited by 56 | Viewed by 11455

Abstract

Coriandrum sativum L. seeds are traditionally used to treat diabetes and its complications (inflammation and formation of reactive oxygen species) around the world. The present study investigates the antidiabetic, anti-inflammatory, and antioxidant effects of the polyphenol fraction of Coriandrum sativum seeds (PCS). Diabetic [...] Read more.

Coriandrum sativum L. seeds are traditionally used to treat diabetes and its complications (inflammation and formation of reactive oxygen species) around the world. The present study investigates the antidiabetic, anti-inflammatory, and antioxidant effects of the polyphenol fraction of Coriandrum sativum seeds (PCS). Diabetic mice were orally administered with PCS (25 and 50 mg/kg b.w.) for 28 days. Oral glucose tolerance (OGTT) was also evaluated along with the anti-inflammatory effect, assessed by measuring paw edema development induced with carrageenan in Wistar rat and the antioxidant activity assessed using two tests (β-carotene discoloration and DPPH). Treatment of diabetic mice with PCS for four weeks managed their high fasting blood glucose levels, improved their overall health, also revealed an excellent antihyperlipidemic activity. The OGTT result showed a potent antihyperglycemic activity, and following the anti-inflammatory and antioxidant effects, the PCS exhibited a perfect activity. LC-MS/MS result revealed the presence of 9 polyphenols. This modest work indicates that the PCS have an important antidiabetic, antihyperglycemic, antihyperlipidemic, anti-inflammatory, and antioxidant effect that can be well established treatment of diabetes and its complications. Full article

(This article belongs to the Special Issue Antioxidant Activity of Food Constituents)

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