Molecules

11 pages, 268 KiB

Open AccessFeature PaperArticle

A Comparative Study of Black and White Allium sativum L.: Nutritional Composition and Bioactive Properties

by Joana Botas, Ângela Fernandes, Lillian Barros, Maria José Alves, Ana Maria Carvalho and Isabel C.F.R. Ferreira

Molecules 2019, 24(11), 2194; https://doi.org/10.3390/molecules24112194 - 11 Jun 2019

Cited by 35 | Viewed by 5473

Abstract

Garlic (Allium sativum L.) has been used worldwide not only for its being a subject of dietary interest, but also for medicinal purposes, in prophylaxis, and for the treatment of diverse pathologies. New processing techniques have been developed and placed on the [...] Read more.

Garlic (Allium sativum L.) has been used worldwide not only for its being a subject of dietary interest, but also for medicinal purposes, in prophylaxis, and for the treatment of diverse pathologies. New processing techniques have been developed and placed on the market in recent years to improve the organoleptic and nutritional value of food products. The present work aimed to study bulbils (cloves) of white (commercial and traditionally cultivated samples with different proveniences) and black (processed samples) garlic. All samples were compared with regard to their nutritional composition as well as their antioxidant and antimicrobial activities. Black garlic had the lowest moisture content but the highest total amount of sugars and energetic value. Black garlic also presented the highest antioxidant and antimicrobial (especially against methicillin-resistant Staphylococcus aureus) activities. Thus, black garlic, obtained by processing techniques, can be considered a promising product with high value that will be able to be exploited by the functional food/nutraceutical industry. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 2474 KiB

Open AccessArticle

Microbiological Evaluation of 5 L- and 20 L-Transparent Polypropylene Buckets for Solar Water Disinfection (SODIS)

by M. Inmaculada Polo-López, Azahara Martínez-García, Maria Jesus Abeledo-Lameiro, Hipolito H. Gómez-Couso, Elvira E. Ares-Mazás, Aurora Reboredo-Fernández, Tracy D. Morse, Lyndon Buck, Kingsley Lungu, Kevin G. McGuigan and Pilar Fernández-Ibáñez

Molecules 2019, 24(11), 2193; https://doi.org/10.3390/molecules24112193 - 11 Jun 2019

Cited by 22 | Viewed by 5175

Abstract

Background: Solar water disinfection (SODIS) is an appropriate technology for household treatment of drinking water in low-to-middle-income communities, as it is effective, low cost and easy to use. Nevertheless, uptake is low due partially to the burden of using small volume polyethylene terephthalate [...] Read more.

Background: Solar water disinfection (SODIS) is an appropriate technology for household treatment of drinking water in low-to-middle-income communities, as it is effective, low cost and easy to use. Nevertheless, uptake is low due partially to the burden of using small volume polyethylene terephthalate bottles (1.5–2 L). A major challenge is to develop a low-cost transparent container for disinfecting larger volumes of water. (2) Methods: This study examines the capability of transparent polypropylene (PP) buckets of 5 L- and 20 L- volume as SODIS containers using three waterborne pathogen indicators: Escherichia coli, MS2-phage and Cryptosporidium parvum. (3) Results: Similar inactivation kinetics were observed under natural sunlight for the inactivation of all three organisms in well water using 5 L- and 20 L-buckets compared to 1.5 L-polyethylene-terephthalate (PET) bottles. The PP materials were exposed to natural and accelerated solar ageing (ISO-16474). UV transmission of the 20 L-buckets remained stable and with physical integrity even after the longest ageing periods (9 months or 900 h of natural or artificial solar UV exposure, respectively). The 5 L-buckets were physically degraded and lost significant UV-transmission, due to the thinner wall compared to the 20 L-bucket. (4) Conclusion: This work demonstrates that the 20 L SODIS bucket technology produces excellent bacterial, viral and protozoan inactivation and is obtained using a simple transparent polypropylene bucket fabricated locally at very low cost ($2.90 USD per unit). The increased bucket volume of 20 L allows for a ten-fold increase in treatment batch volume and can thus more easily provide for the drinking water requirements of most households. The use of buckets in households across low to middle income countries is an already accepted practice. Full article

(This article belongs to the Special Issue Photochemical Processes in Sunlit Surface and Atmospheric Waters)

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15 pages, 1992 KiB

Open AccessArticle

The PPARγ Agonist Rosiglitazone Suppresses Syngeneic Mouse SCC (Squamous Cell Carcinoma) Tumor Growth through an Immune-Mediated Mechanism

by Raymond L. Konger, Ethel Derr-Yellin, Nurmukambed Ermatov, Lu Ren and Ravi P. Sahu

Molecules 2019, 24(11), 2192; https://doi.org/10.3390/molecules24112192 - 11 Jun 2019

Cited by 15 | Viewed by 3679

Abstract

Recent evidence suggests that PPARγ agonists may promote anti-tumor immunity. We show that immunogenic PDV cutaneous squamous cell carcinoma (CSCC) tumors are rejected when injected intradermally at a low cell number (1 × 10⁶) into immune competent syngeneic hosts, but not [...] Read more.

Recent evidence suggests that PPARγ agonists may promote anti-tumor immunity. We show that immunogenic PDV cutaneous squamous cell carcinoma (CSCC) tumors are rejected when injected intradermally at a low cell number (1 × 10⁶) into immune competent syngeneic hosts, but not immune deficient mice. At higher cell numbers (5 × 10⁶ PDV cells), progressively growing tumors were established in 14 of 15 vehicle treated mice while treatment of mice with the PPARγ agonist rosiglitazone resulted in increased tumor rejection (5 of 14 tumors), a significant decrease in PDV tumor size, and a significant decrease in tumor cell Ki67 labeling. Rosiglitazone treatment had no effect on tumor rejection, tumor volume or PDV tumor cell proliferation in immune deficient NOD.CB17-Prkdc^SCID/J mice. Rosiglitazone treatment also promoted an increase in tumor infiltrating CD3⁺ T-cells at both early and late time points. In contrast, rosiglitazone treatment had no significant effect on myeloid cells expressing either CD11b or Gr-1 but suppressed a late accumulation of myeloid cells expressing both CD11b and Gr-1, suggesting a potential role for CD11b⁺Gr-1⁺ myeloid cells in the late anti-tumor immune response. Overall, our data provides evidence that the PPARγ agonist rosiglitazone promotes immune-mediated anti-neoplastic activity against tumors derived from this immunogenic CSCC cell line. Full article

(This article belongs to the Special Issue Role of PPAR Receptors in Human Health and Disease)

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11 pages, 239 KiB

Open AccessArticle

In Vitro Human Metabolism and Inhibition Potency of Verbascoside for CYP Enzymes

by Anna-Mari Reid, Risto Juvonen, Pasi Huuskonen, Marko Lehtonen, Markku Pasanen and Namrita Lall

Molecules 2019, 24(11), 2191; https://doi.org/10.3390/molecules24112191 - 11 Jun 2019

Cited by 12 | Viewed by 3602

Abstract

Verbascoside is found in many medicinal plant families such as Verbenaceae. Important biological activities have been ascribed to verbascoside. Investigated in this study is the potential of verbascoside as an adjuvant during tuberculosis treatment. The present study reports on the in vitro metabolism [...] Read more.

Verbascoside is found in many medicinal plant families such as Verbenaceae. Important biological activities have been ascribed to verbascoside. Investigated in this study is the potential of verbascoside as an adjuvant during tuberculosis treatment. The present study reports on the in vitro metabolism in human hepatic microsomes and cytosol incubations as well as the presence and quantity of verbascoside within Lippia scaberrima. Additionally, studied are the inhibitory properties on human hepatic CYP enzymes together with antioxidant and cytotoxic properties. The results yielded no metabolites in the hydrolysis or cytochrome P450 (CYP) oxidation incubations. However, five different methylated conjugates of verbascoside could be found in S-adenosylmethionine incubation, three different sulphate conjugates with 3′-phosphoadenosine 5′-phosphosulfate (PAPS) incubation with human liver samples, and very low levels of glucuronide metabolites after incubation with recombinant human uridine 5’-diphospho-glucuronosyltransferase (UGT) 1A7, UGT1A8, and UGT1A10. Additionally, verbascoside showed weak inhibitory potency against CYP1A2 and CYP1B1 with IC₅₀ values of 83 µM and 86 µM, respectively. Potent antioxidant and low cytotoxic potential were observed. Based on these data, verbascoside does not possess any clinically relevant CYP-mediated interaction potential, but it has effective biological activity. Therefore, verbascoside could be considered as a lead compound for further drug development and as an adjuvant during tuberculosis treatment. Full article

(This article belongs to the Collection Bioactive Compounds)

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18 pages, 1497 KiB

Open AccessReview

The Versatile Applications of DES and Their Influence on Oxidoreductase-Mediated Transformations

by Fatima Zohra Ibn Majdoub Hassani, Saaid Amzazi and Iván Lavandera

Molecules 2019, 24(11), 2190; https://doi.org/10.3390/molecules24112190 - 11 Jun 2019

Cited by 32 | Viewed by 3794

Abstract

In the last decade, new types of solvents called deep eutectic solvents (DES) have been synthesized and commercialized. Among their main advantages, they can be eco-friendly and are easy to synthesize at different molar ratios depending on the desired solvent properties. This review [...] Read more.

In the last decade, new types of solvents called deep eutectic solvents (DES) have been synthesized and commercialized. Among their main advantages, they can be eco-friendly and are easy to synthesize at different molar ratios depending on the desired solvent properties. This review aims to show the different uses of DES in some relevant biocatalytic redox reactions. Here we analyze oxidoreductase-mediated transformations that are performed in the presence of DES and compare them with the ones that avoided those solvents. DES were found to present advantages such as the increase in the product yield and enantiomeric excess in many reactions. Full article

(This article belongs to the Special Issue Biocatalysis in Organic Synthesis)

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23 pages, 2400 KiB

Open AccessFeature PaperArticle

Spectra–Structure Correlations in Isotopomers of Ethanol (CX₃CX₂OX; X = H, D): Combined Near-Infrared and Anharmonic Computational Study

by Krzysztof B. Beć, Justyna Grabska, Christian W. Huck and Mirosław A. Czarnecki

Molecules 2019, 24(11), 2189; https://doi.org/10.3390/molecules24112189 - 11 Jun 2019

Cited by 20 | Viewed by 3649

Abstract

The effect of isotopic substitution on near-infrared (NIR) spectra has not been studied in detail. With an exception of few major bands, it is difficult to follow the spectral changes due to complexity of NIR spectra. Recent progress in anharmonic quantum mechanical calculations [...] Read more.

The effect of isotopic substitution on near-infrared (NIR) spectra has not been studied in detail. With an exception of few major bands, it is difficult to follow the spectral changes due to complexity of NIR spectra. Recent progress in anharmonic quantum mechanical calculations allows for accurate reconstruction of NIR spectra. Taking this opportunity, we carried out a systematic study of NIR spectra of six isotopomers of ethanol (CX₃CX₂OX; X = H, D). Besides, we calculated the theoretical spectra of two other isotopomers (CH₃CD₂OD and CD₃CH₂OD) for which the experimental spectra are not available. The anharmonic calculations were based on generalized vibrational second-order perturbation theory (GVPT2) at DFT and MP2 levels with several basis sets. We compared the accuracy and efficiency of various computational methods. It appears that the best results were obtained with B2PLYP-GD3BJ/def2-TZVP//CPCM approach. Our simulations included the first and second overtones, as well as binary and ternary combinations bands. This way, we reliably reproduced even minor bands in the spectra of diluted samples (0.1 M in CCl₄). On this basis, the effect of isotopic substitution on NIR spectra of ethanol was accurately reproduced and comprehensively explained. Full article

(This article belongs to the Special Issue Advances in Near Infrared Spectroscopy and Related Computational Methods)

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16 pages, 3365 KiB

Open AccessArticle

Simultaneous Profiling and Holistic Comparison of the Metabolomes among the Flower Buds of Panax ginseng, Panax quinquefolius, and Panax notoginseng by UHPLC/IM-QTOF-HDMS^E-Based Metabolomics Analysis

by Li Jia, Tiantian Zuo, Chunxia Zhang, Weiwei Li, Hongda Wang, Ying Hu, Xiaoyan Wang, Yuexin Qian, Wenzhi Yang and Heshui Yu

Molecules 2019, 24(11), 2188; https://doi.org/10.3390/molecules24112188 - 11 Jun 2019

Cited by 57 | Viewed by 5506

Abstract

The flower buds of three Panax species (PGF: flower bud of P. ginseng; PQF: flower bud of P. quinquefolius; PNF: flower bud of P. notoginseng), widely consumed as healthcare products, are easily confused particularly in the extracts or traditional Chinese [...] Read more.

The flower buds of three Panax species (PGF: flower bud of P. ginseng; PQF: flower bud of P. quinquefolius; PNF: flower bud of P. notoginseng), widely consumed as healthcare products, are easily confused particularly in the extracts or traditional Chinese medicine (TCM) formulae. We are aimed to develop an untargeted metabolomics approach, by ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS) to unveil the chemical markers diagnostic for the differentiation of PGF, PQF, and PNF. Key parameters affecting chromatographic separation and MS detection were optimized in sequence. Forty-two batches of flower bud samples were analyzed in negative high-definition MS^E (HDMS^E; enabling three-dimensional separations). Efficient metabolomics data processing was performed by Progenesis QI (Waters, Milford, MA, USA), while pattern-recognition chemometrics was applied for species classification and potential markers discovery. Reference compounds comparison, analysis of both HDMS^E and targeted MS/MS data, and retrieval of an in-house ginsenoside library, were simultaneously utilized for the identification of discovered potential markers. Satisfactory conditions for metabolite profiling were achieved on a BEH Shield RP18 column and Vion™ IMS-QTOF instrument (Waters; by setting the capillary voltage of 1.0 kV and the cone of voltage 20 V) within 37 min. A total of 32 components were identified as the potential markers, of which Rb3, Ra1, isomer of m-Rc/m-Rb2/m-Rb3, isomer of Ra1/Ra2, Rb1, and isomer of Ra3, were the most important for differentiating among PGF, PQF, and PNF. Conclusively, UHPLC/IM-QTOF-MS-based metabolomics is a powerful tool for the authentication of TCM at the metabolome level. Full article

(This article belongs to the Section Analytical Chemistry)

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15 pages, 2180 KiB

Open AccessArticle

One-Step Regioselective Synthesis of Benzofurans from Phenols and α-Haloketones

by Bingqiao Wang, Qiu Zhang, Juan Luo, Zongjie Gan, Wengao Jiang and Qiang Tang

Molecules 2019, 24(11), 2187; https://doi.org/10.3390/molecules24112187 - 11 Jun 2019

Cited by 16 | Viewed by 4011

Abstract

Reported here is the direct synthesis of naphthofurans and benzofurans from readily available phenols and α-haloketones promoted by titanium tetrachloride which combines Friedel–Crafts-like alkylation and intramolecular cyclodehydration into one step. This simple protocol allows for the formation of a variety of high [...] Read more.

Reported here is the direct synthesis of naphthofurans and benzofurans from readily available phenols and α-haloketones promoted by titanium tetrachloride which combines Friedel–Crafts-like alkylation and intramolecular cyclodehydration into one step. This simple protocol allows for the formation of a variety of high value naphthofurans and benzofurans within which a series of cyclic and acyclic groups are readily incorporated. This process demonstrates the advantages of high levels of regioselectivity, broad substrate scope, and moderate to excellent yields. Full article

(This article belongs to the Section Organic Chemistry)

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16 pages, 748 KiB

Open AccessReview

Wine Fining with Plant Proteins

by Matteo Marangon, Simone Vincenzi and Andrea Curioni

Molecules 2019, 24(11), 2186; https://doi.org/10.3390/molecules24112186 - 11 Jun 2019

Cited by 48 | Viewed by 7296

Abstract

Fining treatments involve the addition of a substance or a mixture to wine, and are generally carried out in order to clarify, stabilize or modify the wine’s organoleptic characteristics. Usually these fining agents will bind the target compound(s) to form insoluble aggregates that [...] Read more.

Fining treatments involve the addition of a substance or a mixture to wine, and are generally carried out in order to clarify, stabilize or modify the wine’s organoleptic characteristics. Usually these fining agents will bind the target compound(s) to form insoluble aggregates that are subsequently removed from the wine. The main reasons to perform wine fining treatments are to carry out wine clarification, stabilization and to remove phenolic compounds imparting unwanted sensory characteristics on the wine, which is an operation that often relies on the use of animal proteins, such as casein, gelatin, egg and fish proteins. However, due to the allergenic potential of these animal proteins, there is an increasing interest in developing alternative solutions including the use of fining proteins extracted from plants (e.g., proteins from cereals, grape seeds, potatoes, legumes, etc.), and non-proteinaceous plant-based substances (e.g., cell wall polysaccharides and pomace materials). In this article, the state of the art alternative fining agents of plant origins are reviewed for the first time, including considerations of their organoleptic and technological effects on wine, and of the allergenic risks that they can pose for consumers. Full article

(This article belongs to the Special Issue Fining Agents in Wine)

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13 pages, 2417 KiB

Open AccessArticle

A Practical and Total Synthesis of Pasireotide: Synthesis of Cyclic Hexapeptide via a Three-Component Condensation

by Chunying Ma, Miao Chen, Weiming Chu, Jiayi Tao, Delong Kong, Mengmeng Zhang and Wenhua Feng

Molecules 2019, 24(11), 2185; https://doi.org/10.3390/molecules24112185 - 11 Jun 2019

Cited by 4 | Viewed by 4285

Abstract

Pasireotide is a multi-receptor ligand somatostatin analogue approved for medical treatment of Cushing’s disease and acromegaly. The liquid-phase total synthesis of pasireotide-a 18-membered cyclic hexapeptide-was achieved by the 3 + 2 + 1 strategy, and the Pro¹-Phe⁶ peptide bond was [...] Read more.

Pasireotide is a multi-receptor ligand somatostatin analogue approved for medical treatment of Cushing’s disease and acromegaly. The liquid-phase total synthesis of pasireotide-a 18-membered cyclic hexapeptide-was achieved by the 3 + 2 + 1 strategy, and the Pro¹-Phe⁶ peptide bond was selected as the final cyclization position. Two key fragments were simply synthesized using N,O-bis(trimethylsilyl)acetamide/N-hydroxysuccinimide ester (BSA/NHS) as coupling agents, and processes of the two key fragments were simple without any chromatographic purification. The current synthesis method is easily scalable and produces the target peptide with an overall yield of 15%. Full article

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14 pages, 3496 KiB

Open AccessArticle

Antidiabetic Activity and Potential Mechanism of Amentoflavone in Diabetic Mice

by Chengfu Su, Chuanbin Yang, Man Gong, Yingying Ke, Peipei Yuan, Xiaolan Wang, Min Li, Xiaoke Zheng and Weisheng Feng

Molecules 2019, 24(11), 2184; https://doi.org/10.3390/molecules24112184 - 11 Jun 2019

Cited by 40 | Viewed by 4969

Abstract

Aim: To investigate the anti-diabetic activity of amentoflavone (AME) in diabetic mice, and to explore the potential mechanisms. Methods: Diabetic mice induced by high fat diet and streptozotocin were administered with amentoflavone for 8 weeks. Biochemical indexes were tested to evaluate its anti-diabetic [...] Read more.

Aim: To investigate the anti-diabetic activity of amentoflavone (AME) in diabetic mice, and to explore the potential mechanisms. Methods: Diabetic mice induced by high fat diet and streptozotocin were administered with amentoflavone for 8 weeks. Biochemical indexes were tested to evaluate its anti-diabetic effect. Hepatic steatosis, the histopathology change of the pancreas was evaluated. The activity of glucose metabolic enzymes, the expression of Akt and pAkt, and the glucose transporter type 4 (GLUT4) immunoreactivity were detected. Results: AME decreased the level of glucose, total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and glucagon, and increased the levels of high density lipoprotein cholesterol (HDL-C) and insulin. Additionally, AME increased the activity of glucokinase (GCK), phosphofructokinase-1 (PFK-1), and pyruvate kinase (PK), and inhibited the activity of glycogen synthase kinase-3 (GSK-3), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G-6-Pase). Mechanistically, AME increased superoxide dismutase (SOD), decreased malondialdehyde (MDA), activation of several key signaling molecules including pAkt (Ser473), and increased the translocation to the sedimenting membranes of GLUT4 in skeletal muscle tissue. Conclusions: AME exerted anti-diabetic effects by regulating glucose and lipid metabolism, perhaps via anti-oxidant effects and activating the PI3K/Akt pathway. Our study provided novel insight into the role and underlying mechanisms of AME in diabetes. Full article

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20 pages, 12755 KiB

Open AccessArticle

Systematic Studies on the Protocol and Criteria for Selecting a Covalent Docking Tool

by Chang Wen, Xin Yan, Qiong Gu, Jiewen Du, Di Wu, Yutong Lu, Huihao Zhou and Jun Xu

Molecules 2019, 24(11), 2183; https://doi.org/10.3390/molecules24112183 - 10 Jun 2019

Cited by 23 | Viewed by 5010

Abstract

With the resurgence of drugs with covalent binding mechanisms, much attention has been paid to docking methods for the discovery of targeted covalent inhibitors. The existence of many available covalent docking tools has inspired development of a systematic and objective procedure and criteria [...] Read more.

With the resurgence of drugs with covalent binding mechanisms, much attention has been paid to docking methods for the discovery of targeted covalent inhibitors. The existence of many available covalent docking tools has inspired development of a systematic and objective procedure and criteria with which to evaluate these programs. In order to find a tool appropriate to studies of a covalently binding system, protocols and criteria are proposed for protein–ligand covalent docking studies. This paper consists of three sections: (1) curating a standard data set to evaluate covalent docking tools objectively; (2) establishing criteria to measure the performance of a tool applied for docking ligands into a complex system; and (3) creating a protocol to evaluate and select covalent binding tools. The protocols were applied to evaluate four covalent docking tools (MOE, GOLD, CovDock, and ICM-Pro) and parameters affecting covalent docking performance were investigated. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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20 pages, 13879 KiB

Open AccessArticle

Lycopodium Attenuates Loss of Dopaminergic Neurons by Suppressing Oxidative Stress and Neuroinflammation in a Rat Model of Parkinson’s Disease

by Richard L. Jayaraj, Rami Beiram, Sheikh Azimullah, Mohamed Fizur Nagoor Meeran, Shreesh K. Ojha, Abdu Adem and Fakhreya Yousuf Jalal

Molecules 2019, 24(11), 2182; https://doi.org/10.3390/molecules24112182 - 10 Jun 2019

Cited by 32 | Viewed by 10116

Abstract

Parkinson’s disease, a chronic, age related neurodegenerative disorder, is characterized by a progressive loss of nigrostriatal dopaminergic neurons. Several studies have proven that the activation of glial cells, presence of alpha-synuclein aggregates, and oxidative stress, fuels neurodegeneration, and currently there is no definitive [...] Read more.

Parkinson’s disease, a chronic, age related neurodegenerative disorder, is characterized by a progressive loss of nigrostriatal dopaminergic neurons. Several studies have proven that the activation of glial cells, presence of alpha-synuclein aggregates, and oxidative stress, fuels neurodegeneration, and currently there is no definitive treatment for PD. In this study, a rotenone-induced rat model of PD was used to understand the neuroprotective potential of Lycopodium (Lyc), a commonly-used potent herbal medicine. Immunohistochemcial data showed that rotenone injections significantly increased the loss of dopaminergic neurons in the substantia nigra, and decreased the striatal expression of tyrosine hydroxylase. Further, rotenone administration activated microglia and astroglia, which in turn upregulated the expression of α-synuclein, pro-inflammatory, and oxidative stress factors, resulting in PD pathology. However, rotenone-injected rats that were orally treated with lycopodium (50 mg/kg) were protected against dopaminergic neuronal loss by diminishing the expression of matrix metalloproteinase-3 (MMP-3) and MMP-9, as well as reduced activation of microglia and astrocytes. This neuroprotective mechanism not only involves reduction in pro-inflammatory response and α-synuclein expression, but also synergistically enhanced antioxidant defense system by virtue of the drug’s multimodal action. These findings suggest that Lyc has the potential to be further developed as a therapeutic candidate for PD. Full article

(This article belongs to the Special Issue Natural Products for Neurodegenerative Diseases)

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19 pages, 3658 KiB

Open AccessArticle

Rubus ulmifolius Schott as a Novel Source of Food Colorant: Extraction Optimization of Coloring Pigments and Incorporation in a Bakery Product

by Liliana Primo da Silva, Eliana Pereira, Miguel A. Prieto, Jesus Simal-Gandara, Tânia C.S.P. Pires, Maria José Alves, Ricardo Calhelha, Lillian Barros and Isabel C.F.R. Ferreira

Molecules 2019, 24(11), 2181; https://doi.org/10.3390/molecules24112181 - 10 Jun 2019

Cited by 24 | Viewed by 5049

Abstract

(1) Background: Color has been considered to be the flashiest attribute of foodstuffs and researchers have shown a great interest in the extraction of pigmented compounds from vegetal products, with the purpose to provide alternative counterparts to the food industry; (2) Methods: This [...] Read more.

(1) Background: Color has been considered to be the flashiest attribute of foodstuffs and researchers have shown a great interest in the extraction of pigmented compounds from vegetal products, with the purpose to provide alternative counterparts to the food industry; (2) Methods: This study aimed to explore Rubus ulmifolius Schott fruits as a potential source of anthocyanins, optimizing the extraction method, evaluating the bioactivity and incorporating the rich extract into a bakery food product; (3) Results: After the extraction optimization, results showed R. ulmifolius fruits to be a great source of anthocyanins, obtaining an amount of 33.58 mg AT/g E, with an extraction yield of 62.08%. The rich anthocyanin extract showed antitumor and antimicrobial potential in some tumor cell lines and strains, respectively, as well as the absence of toxicity; (4) Conclusions: The extract when incorporated in a bakery product showed a good coloring capacity, maintaining the nutritional value, revealing its use to be a great approach for replacing artificial colorants. Full article

(This article belongs to the Special Issue Secondary Metabolites in Plant Foods)

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8 pages, 780 KiB

Open AccessCommunication

A Simple HPLC Method for the Quantitative Determination of Silybin in Rat Plasma: Application to a Comparative Pharmacokinetic Study on Commercial Silymarin Products

by Eun-Sol Ha, Dong-Gyun Han, Seong-Wook Seo, Ji-Min Kim, Seon-Kwang Lee, Woo-Yong Sim, In-Soo Yoon and Min-Soo Kim

Molecules 2019, 24(11), 2180; https://doi.org/10.3390/molecules24112180 - 10 Jun 2019

Cited by 13 | Viewed by 4064

Abstract

Silybin (SBN) is a major active constituent of silymarin, a mixture of flavonoids found in fruits and seeds of milk thistle. The aim of this study was to describe a simple bioanalytical method for quantifying SBN in rat plasma. A simple protein deproteinization [...] Read more.

Silybin (SBN) is a major active constituent of silymarin, a mixture of flavonoids found in fruits and seeds of milk thistle. The aim of this study was to describe a simple bioanalytical method for quantifying SBN in rat plasma. A simple protein deproteinization procedure with acetonitrile (ACN) was employed for plasma sample preparation. A reversed column and gradient elution of a mobile phase (mixture of phosphate buffer (pH 5.0) and ACN) were used for chromatographic separation. The selectivity, linearity (50–5000 ng/mL), precision, accuracy, recovery, matrix effect, and stability for this method were validated as per the current Food and Drug Administration (FDA) guidelines. Our method for SBN was applied to a comparative pharmacokinetic study on four different commercial silymarin products. This in vivo rat study demonstrated that product #4 significantly enhanced the relative oral bioavailability of SBN, as compared to product #1–3. Therefore, the bioanalytical method proposed herein could serve as a promising alternative for preclinical pharmacokinetic studies on silymarin products and, by extension, clinical use after partial modification and validation. Full article

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

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16 pages, 1286 KiB

Open AccessFeature PaperArticle

The EFSA Health Claim on Olive Oil Polyphenols: Acid Hydrolysis Validation and Total Hydroxytyrosol and Tyrosol Determination in Italian Virgin Olive Oils

by Maria Bellumori, Lorenzo Cecchi, Marzia Innocenti, Maria Lisa Clodoveo, Filomena Corbo and Nadia Mulinacci

Molecules 2019, 24(11), 2179; https://doi.org/10.3390/molecules24112179 - 10 Jun 2019

Cited by 80 | Viewed by 7095

Abstract

The health claims of olive oil represent an important marketing lever in raising the willingness to pay for a product, but world producers of extra virgin olive oil (EVOO) do not take advantage of it because there are still obstacles to their use. [...] Read more.

The health claims of olive oil represent an important marketing lever in raising the willingness to pay for a product, but world producers of extra virgin olive oil (EVOO) do not take advantage of it because there are still obstacles to their use. Among these, one issue is the lack of an official method for determination of all free and linked forms derived from secoiridoidic structures of hydroxytyrosol and tyrosol. In this study, different acidic hydrolytic procedures for analyzing the linked forms were tested. The best method was validated and then applied to more than 100 EVOOs. The content of oleuropein and ligstroside derivatives in EVOOs was indirectly evaluated comparing the amount of phenols before and after hydrolysis. After acidic hydrolysis, a high content of total tyrosol was found in most of the EVOOs. The use of a suitable corrective factor for the evaluation of hydroxytyrosol allows an accurate determination only using pure tyrosol as a standard. Further knowledge on the concentration of total hydroxytyrosol will assist in forecasting the resistance of oils against aging, its antioxidant potential and to better control its quality over time. Full article

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

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10 pages, 887 KiB

Open AccessArticle

Bioactive Dimeric Abietanoid Peroxides from the Bark of Cryptomeria japonica

by Chi-I Chang, Cheng-Chi Chen, Chiy-Rong Chen, Ming-Der Wu, Ming-Jen Cheng, Ping-Jyun Sung and Yueh-Hsiung Kuo

Molecules 2019, 24(11), 2178; https://doi.org/10.3390/molecules24112178 - 10 Jun 2019

Cited by 8 | Viewed by 2852

Abstract

Three new dimeric abietane-type diterpenoids, abieta-6,8,11,13-tetraen-12-yl 12-hydroxyabieta-8,11,13-trien-7α-yl peroxide (1), abieta-6,8,11,13-tetraen-12-yl 12-hydroxyabieta-8,11,13-trien-7β-yl peroxide (2), and 12-hydroxyabieta-8,11,13-trien-7β-yl 7-oxoabieta-5,8,11,13-tetraen-12-yl peroxide (3), together with four known abietane-type diterpenoids (4–7) were isolated from the methanol extract of the [...] Read more.

Three new dimeric abietane-type diterpenoids, abieta-6,8,11,13-tetraen-12-yl 12-hydroxyabieta-8,11,13-trien-7α-yl peroxide (1), abieta-6,8,11,13-tetraen-12-yl 12-hydroxyabieta-8,11,13-trien-7β-yl peroxide (2), and 12-hydroxyabieta-8,11,13-trien-7β-yl 7-oxoabieta-5,8,11,13-tetraen-12-yl peroxide (3), together with four known abietane-type diterpenoids (4–7) were isolated from the methanol extract of the bark of Cryptomeria japonica. Their structures were elucidated on the basis of spectroscopic analysis and comparison of NMR data with those of known analogues. At a concentration of 50 μM, compounds 1, 2, and 3 showed 26.2%, 23.6%, and 35.7% inhibition towards xanthine oxidase enzyme, respectively. In addition, compound 3 also showed 24.9% inhibition toward angiotensin-converting enzyme (ACE). Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 1699 KiB

Open AccessFeature PaperArticle

Metal-Free Air Oxidation in a Convenient Cascade Approach for the Access to Isoquinoline-1,3,4(2H)-triones

by Antonia Di Mola, Consiglia Tedesco and Antonio Massa

Molecules 2019, 24(11), 2177; https://doi.org/10.3390/molecules24112177 - 10 Jun 2019

Cited by 6 | Viewed by 3388

Abstract

Herein we describe a very useful application of the readily available trifunctional aromatic ketone methyl-2-(2-bromoacetyl)benzoate in reactions with primary amines. An unexpected in situ air oxidation that follows a cascade process allowed the access to a series of isoquinoline-1,3,4(2H)-triones, a class [...] Read more.

Herein we describe a very useful application of the readily available trifunctional aromatic ketone methyl-2-(2-bromoacetyl)benzoate in reactions with primary amines. An unexpected in situ air oxidation that follows a cascade process allowed the access to a series of isoquinoline-1,3,4(2H)-triones, a class of heterocyclic compounds of great interest containing an oxygen-rich heterocyclic scaffold. A modification of the original protocol, utilizing a Staudinger reaction in the presence of trimethylphosphine, was necessary for the synthesis of Caspase inhibitor trione with free NH group. Full article

(This article belongs to the Special Issue Recent Advances in Cascade Reactions and Related One-Pot Processes)

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11 pages, 1474 KiB

Open AccessArticle

Synthesis and Biological Evaluation of NH₂-Sulfonyl Oseltamivir Analogues as Influenza Neuraminidase Inhibitors

by Yaping Hu, Binfeng Chen, Zaiqiang Lei, Hongqian Zhao, Hongxi Zhu, Peng Quan and Yongshou Tian

Molecules 2019, 24(11), 2176; https://doi.org/10.3390/molecules24112176 - 10 Jun 2019

Cited by 7 | Viewed by 3679

Abstract

A series of NH₂-sulfonyl oseltamivir analogues were designed, synthesized, and their inhibitory activities against neuraminidase from H5N1 subtype evaluated. The results indicated that the IC₅₀ value of compound 4a, an oseltamivir analogue via methyl sulfonylation of C5-NH₂ [...] Read more.

A series of NH₂-sulfonyl oseltamivir analogues were designed, synthesized, and their inhibitory activities against neuraminidase from H5N1 subtype evaluated. The results indicated that the IC₅₀ value of compound 4a, an oseltamivir analogue via methyl sulfonylation of C5-NH₂, was 3.50 μM. Molecular docking simulations suggested that 4a retained most of the interactions formed by oseltamivir carboxylate moieties and formed an additional hydrogen bond with the methylsulfonyl group. Meanwhile, 4a showed high stability towards human liver microsomes. More importantly, 4a without basic moieties is not a zwitterion as reported on the general structure of neuraminidase inhibitors. This research will provide valuable reference for the research of new types of neuraminidase inhibitors. Full article

(This article belongs to the Special Issue Antiviral Agents)

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12 pages, 1355 KiB

Open AccessArticle

Catechins Controlled Bioavailability of Benzo[a]pyrene (B[α]P) from the Gastrointestinal Tract to the Brain towards Reducing Brain Toxicity Using the In Vitro Bio-Mimic System Coupled with Sequential Co-Cultures

by Kang-Hyun Jeong, Hyun Jeong Lee, Tae-Sik Park and Soon-Mi Shim

Molecules 2019, 24(11), 2175; https://doi.org/10.3390/molecules24112175 - 10 Jun 2019

Cited by 2 | Viewed by 3962

Abstract

The aim of the current study was to examine the preventive effect of green tea catechins on the transport of Benzo[a]pyrene (B[α]P) into the brain using an in vitro bio-mimic system coupled with sequential co-cultures. When 72 μM of catechins was pre-treated, cellular [...] Read more.

The aim of the current study was to examine the preventive effect of green tea catechins on the transport of Benzo[a]pyrene (B[α]P) into the brain using an in vitro bio-mimic system coupled with sequential co-cultures. When 72 μM of catechins was pre-treated, cellular cytotoxicity induced by IC₅₀ of B[α]P in human liver hepatocellular carcinoma (HepG2) and human brain microvascular endothelial cells (HBMECs) was reduced by 27% and 26%, respectively. The cellular integrity measured in HBMECs, which was exposed to IC₅₀ of B[α]P, slowly decreased. However, the pre-treatment of catechins retained cellular integrity that was 1.14 times higher than with the absence of catechins. Co-consumption of catechins reduced not only the bio-accessibility of B[α]P in digestive fluid, but it also decreased absorption of B[α]P in human intestinal epithelial cells (Caco-2) with a HepG2 co-culture system. It was found that approximately a two times lower amount of B[α]P was transported via the blood-brain barrier (BBB) compared to only the B[α]P intake. These results are taken in conjunction with each other support that catechins could be able to prevent brain toxicity induced by B[α]P in the human body by limiting the bio-availability of B[α]P. Full article

(This article belongs to the Special Issue Bioactives and Functional Ingredients in Foods and Beverages)

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16 pages, 5912 KiB

Open AccessArticle

Pressure-Induced Polymorphism of Caprolactam: A Neutron Diffraction Study

by Ian B. Hutchison, Craig L. Bull, William G. Marshall, Andrew J. Urquhart and Iain D.H. Oswald

Molecules 2019, 24(11), 2174; https://doi.org/10.3390/molecules24112174 - 10 Jun 2019

Cited by 4 | Viewed by 4509

Abstract

Caprolactam, a precursor to nylon-6 has been investigated as part of our studies into the polymerization of materials at high pressure. Single-crystal X-ray and neutron powder diffraction data have been used to explore the high-pressure phase behavior of caprolactam; two new high pressure [...] Read more.

Caprolactam, a precursor to nylon-6 has been investigated as part of our studies into the polymerization of materials at high pressure. Single-crystal X-ray and neutron powder diffraction data have been used to explore the high-pressure phase behavior of caprolactam; two new high pressure solid forms were observed. The transition between each of the forms requires a substantial rearrangement of the molecules and we observe that the kinetic barrier to the conversion can aid retention of phases beyond their region of stability. Form II of caprolactam shows a small pressure region of stability between 0.5 GPa and 0.9 GPa with Form III being stable from 0.9 GPa to 5.4 GPa. The two high-pressure forms have a catemeric hydrogen-bonding pattern compared with the dimer interaction observed in ambient pressure Form I. The interaction between the chains has a marked effect on the directions of maximal compressibility in the structure. Neither of the high-pressure forms can be recovered to ambient pressure and there is no evidence of any polymerization occurring. Full article

(This article belongs to the Special Issue High–Pressure Behaviour of Solids: From Molecular Species to 3D-Framework Materials)

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23 pages, 4484 KiB

Open AccessArticle

Synthesis and Cytostatic Effect of 3’-deoxy-3’-C-Sulfanylmethyl Nucleoside Derivatives with d-xylo Configuration

by Miklós Bege, Alexandra Kiss, Máté Kicsák, Ilona Bereczki, Viktória Baksa, Gábor Király, Gábor Szemán-Nagy, M. Zsuzsa Szigeti, Pál Herczegh and Anikó Borbás

Molecules 2019, 24(11), 2173; https://doi.org/10.3390/molecules24112173 - 10 Jun 2019

Cited by 8 | Viewed by 3880

Abstract

A small library of 3’-deoxy-C3’-substituted xylofuranosyl-pyrimidine nucleoside analogues were prepared by photoinduced thiol-ene addition of various thiols, including normal and branched alkyl-, 2-hydroxyethyl, benzyl-, and sugar thiols, to 3’-exomethylene derivatives of 2’,5’-di-O-tert-butyldimethylsilyl-protected ribothymidine and uridine. The bioactivity of these [...] Read more.

A small library of 3’-deoxy-C3’-substituted xylofuranosyl-pyrimidine nucleoside analogues were prepared by photoinduced thiol-ene addition of various thiols, including normal and branched alkyl-, 2-hydroxyethyl, benzyl-, and sugar thiols, to 3’-exomethylene derivatives of 2’,5’-di-O-tert-butyldimethylsilyl-protected ribothymidine and uridine. The bioactivity of these derivatives was studied on tumorous SCC (mouse squamous carcinoma cell) and immortalized control HaCaT (human keratinocyte) cell lines. Several alkyl-substituted analogues elicited promising cytostatic activity in low micromolar concentrations with a slight selectivity toward tumor cells. Near-infrared live-cell imaging revealed SCC tumor cell-specific mitotic blockade via genotoxicity of analogue 10, bearing an n-butyl side chain. This analogue essentially affects the chromatin structure of SCC tumor cells, inducing a condensed nuclear material and micronuclei as also supported by fluorescent microscopy. The results highlight that thiol-ene chemistry represents an efficient strategy to discover novel nucleoside analogues with non-natural sugar structures as anticancer agents. Full article

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21 pages, 715 KiB

Open AccessReview

Avocado Oil: Characteristics, Properties, and Applications

by Marcos Flores, Carolina Saravia, Claudia E. Vergara, Felipe Avila, Hugo Valdés and Jaime Ortiz-Viedma

Molecules 2019, 24(11), 2172; https://doi.org/10.3390/molecules24112172 - 10 Jun 2019

Cited by 107 | Viewed by 35564

Abstract

Avocado oil has generated growing interest among consumers due to its nutritional and technological characteristics, which is evidenced by an increase in the number of scientific articles that have been published on it. The purpose of the present research was to discuss the [...] Read more.

Avocado oil has generated growing interest among consumers due to its nutritional and technological characteristics, which is evidenced by an increase in the number of scientific articles that have been published on it. The purpose of the present research was to discuss the extraction methods, chemical composition, and various applications of avocado oil in the food and medicine industries. Our research was carried out through a systematic search in scientific databases. Even though there are no international regulations concerning the quality of avocado oil, some authors refer to the parameters used for olive oil, as stated by the Codex Alimentarius or the International Olive Oil Council. They indicate that the quality of avocado oil will depend on the quality and maturity of the fruit and the extraction technique in relation to temperature, solvents, and conservation. While the avocado fruit has been widely studied, there is a lack of knowledge about avocado oil and the potential health effects of consuming it. On the basis of the available data, avocado oil has established itself as an oil that has a very good nutritional value at low and high temperatures, with multiple technological applications that can be exploited for the benefit of its producers. Full article

(This article belongs to the Special Issue Analytical Technology in Nutrition Analysis)

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10 pages, 1761 KiB

Open AccessArticle

Kynurenic Acid and Its Analogs Are Beneficial Physiologic Attenuators in Bdelloid Rotifers

by Zsolt Datki, Zita Galik-Olah, Zsuzsanna Bohar, Denes Zadori, Ferenc Fulop, Istvan Szatmari, Bence Galik, Janos Kalman and Laszlo Vecsei

Molecules 2019, 24(11), 2171; https://doi.org/10.3390/molecules24112171 - 10 Jun 2019

Cited by 10 | Viewed by 3835

Abstract

The in vivo investigation of kynurenic acid (KYNA) and its analogs is one of the recent exciting topics in pharmacology. In the current study we assessed the biological effects of these molecules on bdelloid rotifers (Philodina acuticornis and Adineta vaga) by [...] Read more.

The in vivo investigation of kynurenic acid (KYNA) and its analogs is one of the recent exciting topics in pharmacology. In the current study we assessed the biological effects of these molecules on bdelloid rotifers (Philodina acuticornis and Adineta vaga) by monitoring changes in their survival and phenotypical characteristics. In addition to longitudinal (slowly changing) markers (survival, number of rotifers alive and body size index), some dynamic (quickly responding) ones (cellular reduction capacity and mastax contraction frequency) were measured as well. KYNA and its analogs increased longevity, reproduction and growth, whereas reduction capacity and energy-dependent muscular activity decreased conversely. We found that spermidine, a calorie restriction mimetic, exerted similar changes in the applied micro-invertebrates. This characterized systemic profile evoked by the above-mentioned compounds was named beneficial physiologic attenuation. In reference experiments, using a stimulator (cyclic adenosine monophosphate) and a toxin (sodium azide), all parameters changed in the same direction (positively or negatively, respectively), as expected. The currently described adaptive phenomenon in bdelloid rotifers may provide holistic perspectives in translational research. Full article

(This article belongs to the Section Chemical Biology)

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12 pages, 2316 KiB

Open AccessArticle

para-Menthane as a Stable Terpene Derived from Orange By-Products as a Novel Solvent for Green Extraction and Solubilization of Natural Substances

by Sara Madji, Soukaina Hilali, Anne-Sylvie Fabiano-Tixier, Mathieu Tenon, Antoine Bily, Mickaël Laguerre and Farid Chemat

Molecules 2019, 24(11), 2170; https://doi.org/10.3390/molecules24112170 - 9 Jun 2019

Cited by 11 | Viewed by 6098

Abstract

This study aims at investigating p-menthane, a novel bio-based solvent resulting from the hydrogenation of d-limonene, as a green alternative to n-hexane or toluene for the extraction and solubilization of natural substances. First, conductor-like combination of quantum chemistry (COSMO) coupled [...] Read more.

This study aims at investigating p-menthane, a novel bio-based solvent resulting from the hydrogenation of d-limonene, as a green alternative to n-hexane or toluene for the extraction and solubilization of natural substances. First, conductor-like combination of quantum chemistry (COSMO) coupled with statistical thermodynamics (RS) calculations show a comparable solubilization profile of p-menthane and n-hexane for carotene, volatile monoterpenes such as carvone and limonene, and model triglycerides. Other data obtained experimentally in solid/liquid extraction conditions further indicate that p-menthane showed similar performances to n-hexane for extracting carotenes from carrots, aromas from caraway seeds, and oils from rapeseeds, as these products showed a comparable composition. p-Menthane was also tested using common analytical extraction procedures such as Soxhlet for determination of oil content via multiple extraction stages, and Dean–Stark for determination of water content via azeotropic distillation. For both systems, yields were comparable, but for Dean–Stark, the distillation curve slope was higher when using p-menthane, and the time needed to attain 100% water recovery was 55% shorter than for toluene. Taken together, these results reveal the potential of p-menthane as a green replacer for petroleum-based solvents such as n-hexane or toluene. Full article

(This article belongs to the Special Issue Green Extraction, Separation and Purification Processes)

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13 pages, 2878 KiB

Open AccessArticle

Peppermint Essential Oil-Doped Hydroxyapatite Nanoparticles with Antimicrobial Properties

by Monica Luminita Badea, Simona Liliana Iconaru, Andreea Groza, Mariana Carmen Chifiriuc, Mircea Beuran and Daniela Predoi

Molecules 2019, 24(11), 2169; https://doi.org/10.3390/molecules24112169 - 9 Jun 2019

Cited by 41 | Viewed by 6507

Abstract

This study aimed at developing an antimicrobial material based on hydroxyapatite (HAp) and peppermint essential oil (P-EO) in order to stimulate the antimicrobial activity of hydroxyapatite. The molecular spectral features and morphology of the P-EO, HAp and hydroxyapatite coated with peppermint essential oil [...] Read more.

This study aimed at developing an antimicrobial material based on hydroxyapatite (HAp) and peppermint essential oil (P-EO) in order to stimulate the antimicrobial activity of hydroxyapatite. The molecular spectral features and morphology of the P-EO, HAp and hydroxyapatite coated with peppermint essential oil (HAp-P) were analyzed using Fourier-transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The coating of the HAp with the P-EO did not affect the ellipsoidal shape of the nanoparticles. The overlapping of IR bands of P-EO and HAp in the HAp-P spectrum determined the formation of the broad molecular bands that were observed in the spectral regions of 400–1000 cm⁻¹ and 1000–1200 cm⁻¹. The antibacterial activity of the P-EO, HAp and HAp-P were also tested against different Gram-positive bacteria (methicillin-resistant Staphylococcus aureus (MRSA) 388, S. aureus ATCC 25923, S. aureus ATCC 6538, E. faecium DSM 13590), Gram-negative bacteria (Escherichia coli ATCC 25922, E. coli C5, P. aeruginosa ATCC 27853, P. aeruginosa ATCC 9027) and a fungal strain of Candida parapsilosis. The results of the present study revealed that the antimicrobial activity of HAp-P increased significantly over that of HAp. Full article

(This article belongs to the Special Issue Biological Activities of Essential Oils)

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16 pages, 8688 KiB

Open AccessArticle

Structural and Conformational Studies on Carboxamides of 5,6-Diaminouracils—Precursors of Biologically Active Xanthine Derivatives

by Daniel Marx, Gregor Schnakenburg, Stefan Grimme and Christa E. Müller

Molecules 2019, 24(11), 2168; https://doi.org/10.3390/molecules24112168 - 9 Jun 2019

Cited by 1 | Viewed by 4383

Abstract

8-Arylethynylxanthine derivatives are potent, selective adenosine A_2A receptor antagonists, which represent (potential) therapeutics for Parkinson’s disease, Alzheimer’s dementia, and the immunotherapy of cancer. 6-Amino-5-amidouracil derivatives are important precursors for the synthesis of such xanthines. We noticed an unexpected duplication of NMR signals [...] Read more.

8-Arylethynylxanthine derivatives are potent, selective adenosine A_2A receptor antagonists, which represent (potential) therapeutics for Parkinson’s disease, Alzheimer’s dementia, and the immunotherapy of cancer. 6-Amino-5-amidouracil derivatives are important precursors for the synthesis of such xanthines. We noticed an unexpected duplication of NMR signals in many of these uracil derivatives. Here, we present a detailed analytical study of structurally diverse 6-amino-5-carboxamidouracils employing dynamic and two-dimensional NMR spectroscopy, density functional theory calculations, and X-ray analysis to explain the unexpected properties of these valuable drug intermediates. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 677 KiB

Open AccessArticle

Four New Flavonoids Isolated from the Aerial Parts of Cadaba rotundifolia Forssk. (Qadab)

by Gadah Abdulaziz Al-Hamoud, Raha Saud Orfali, Sachiko Sugimoto, Yoshi Yamano, Nafee Alothyqi, Ali Mohammed Alzahrani and Katsuyoshi Matsunami

Molecules 2019, 24(11), 2167; https://doi.org/10.3390/molecules24112167 - 9 Jun 2019

Cited by 8 | Viewed by 3855

Abstract

Cadaba rotundifolia (Forssk.) (family: Capparaceae; common name: Qadab) is one of four species that grow in the Red Sea costal region in the Kingdom of Saudi Arabia. The roots and leaves of C. rotundifolia is traditionally used to treat tumors and abscesses in [...] Read more.

Cadaba rotundifolia (Forssk.) (family: Capparaceae; common name: Qadab) is one of four species that grow in the Red Sea costal region in the Kingdom of Saudi Arabia. The roots and leaves of C. rotundifolia is traditionally used to treat tumors and abscesses in Sudan. A previous phytochemical study of the roots yielded a quaternary alkaloid, but no report on chemical constituents of the aerial parts of the C. rotundifolia growing in Saudi Arabia has been issued so far. Oxidative stress and advanced glycation end products (AGEs) are thought as causal factors in many degenerative diseases, such as Alzheimer’s disease, diabetes, atherosclerosis and aging. In this study, a total of twenty compounds, including four previously undescribed acylated kaempferol glucosides, were isolated from the aerial parts of C. rotundifolia collected in Saudi Arabia. These new compounds were identified as kaempferol 3-O-[2-O-(trans-feruloyl)-3-O-β-d-glucopyranosyl]-β-d-glucopyranoside (1), kaempferol 3-O-β-neohesperidoside-7-O-[2-O-(cis-p-coumaroyl)-3-O-β-d-glucopyranosyl]-β-d-glucopyranoside (2), kaempferol 3-O-[2,6-di-O-α-l-rhamnopyranosyl]-β-d-glucopyranoside-7-O-[6-O-(trans-feruloyl)]-β-d-glucopyranoside (3) and kaempferol 3-O-[2,6-di-O-α-l-rhamnopyranosyl]-β-d-glucopyranoside-7-O-[6-O-(trans-p-coumaroyl)]-β-d-glucopyranoside (4). Their structures were established based on UV-visible, 1D, 2D NMR, and HR-ESI-MS analyses. Of the assayed compounds, 17 and 18 showed potent radical scavenging activity with IC₅₀ values of 14.5 and 11.7 µM, respectively, and inhibitory activity toward AGEs together with compound 7 with IC₅₀ values 96.5, 34.9 and 85.5 µM, respectively. Full article

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

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27 pages, 8540 KiB

Open AccessArticle

A Candidate for Multitopic Probes for Ligand Discovery in Dynamic Combinatorial Chemistry

by Keiko Yoneyama, Rina Suzuki, Yusuke Kuramochi and Akiharu Satake

Molecules 2019, 24(11), 2166; https://doi.org/10.3390/molecules24112166 - 8 Jun 2019

Cited by 5 | Viewed by 3412

Abstract

Multifunctionalized materials are expected to be versatile probes to find specific interactions between a ligand and a target biomaterial. Thus, efficient methods to prepare possible combinations of the functionalities is desired. The concept of dynamic combinatorial chemistry (DCC) is ideal for the generation [...] Read more.

Multifunctionalized materials are expected to be versatile probes to find specific interactions between a ligand and a target biomaterial. Thus, efficient methods to prepare possible combinations of the functionalities is desired. The concept of dynamic combinatorial chemistry (DCC) is ideal for the generation of any possible combination, as well as screening for target biomaterials. Here, we propose a new molecular design of multitopic probes for ligand discovery in DCC. We synthesized a new Gable Porphyrin, GP1, having prop-2-yne groups as a scaffold to introduce various functional groups. GP1 is a bis(imidazolylporphyrinatozinc) compound connected through a 1,3-phenylene moiety, and it gives macrocycles spontaneously and quantitatively by strong imidazole-to-zinc complementary coordination. Some different types of functional groups were introduced into GP1 in high yields. Formation of heterogeneous macrocycles composed of GP1 derivatives having different types of substituents was accomplished under equilibrium conditions. These results promise that enormous numbers of macrocycles having various functional groups can be provided when the kinds of GP components increase. These features are desirable for DCC, and the present system using GP1 is a potential candidate to provide a dynamic combinatorial library of multitopic probes to discover specific interactions between a ligand and a biomaterial. Full article

(This article belongs to the Special Issue Macrocycles in Drug Discovery)

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12 pages, 2628 KiB

Open AccessArticle

A Ferulic Acid Derivative FXS-3 Inhibits Proliferation and Metastasis of Human Lung Cancer A549 Cells via Positive JNK Signaling Pathway and Negative ERK/p38, AKT/mTOR and MEK/ERK Signaling Pathways

by Shi-Jun Yue, Peng-Xuan Zhang, Yue Zhu, Nian-Guang Li, Yan-Yan Chen, Jia-Jia Li, Sai Zhang, Ru-Yi Jin, Hao Yan, Xu-Qin Shi, Yu-Ping Tang and Jin-Ao Duan

Molecules 2019, 24(11), 2165; https://doi.org/10.3390/molecules24112165 - 8 Jun 2019

Cited by 39 | Viewed by 4555

Abstract

Lung cancer is one of the most common malignancies and is an increasing cause of cancer-related deaths. In our previous study, a series of ferulic acid (FA) derivatives were designed and synthesized; they exhibited positive anti-cancer activities, especially for a compound labelled FXS-3. [...] Read more.

Lung cancer is one of the most common malignancies and is an increasing cause of cancer-related deaths. In our previous study, a series of ferulic acid (FA) derivatives were designed and synthesized; they exhibited positive anti-cancer activities, especially for a compound labelled FXS-3. In this study, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed, wherein it revealed the inhibitory effect of FXS-3 on the proliferation and metastasis of human lung cancer A549 cells. The further flow cytometry assay showed that FXS-3 induced apoptosis of A549 cells induced cell cycle arrest at the G0/G1 phase. The trans-well migration and Matrigel invasion assays revealed that FXS-3 inhibited the migration and invasion of A549 cells. By the western blotting analysis, FXS-3 increased the expression of B-cell lymphoma-2 (Bcl-2) associated X protein (Bax)/Bcl-2 ratio, inhibited matrix metalloproteinase (MMP)-2 and MMP-9, and regulated the extracellular signal-regulated kinase (ERK)/p38, c-Jun N-terminal kinase (JNK), protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), as well as mitogen-activated protein kinase (MEK)/ERK signaling pathways. The subsequent A549 xenograft-bearing mouse model and tail vein injection of A549 cells induced pulmonary tumor metastasis model showed that FXS-3 significantly restrained the tumor growth and metastasis. In conclusion, FXS-3 might inhibit proliferation and metastasis of human lung cancer A549 cells by positively regulating JNK signaling pathway and negativly regulating ERK/p38, AKT/mTOR, and MEK/ERK signaling pathways, which provides important scientific basis for the development of anti-cancer drugs about FA derivatives. Full article

(This article belongs to the Section Medicinal Chemistry)

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