Molecules

11 pages, 2711 KiB

Open AccessArticle

The First Total Synthesis of (±)-Methyl Salvianolate A Using a Convergent Strategy

by Bo Wang, Liping Wang, Ying Peng, Yiying Pang, Hesheng Xiao, Xiaoji Wang and Shuangping Huang

Molecules 2019, 24(5), 999; https://doi.org/10.3390/molecules24050999 - 12 Mar 2019

Cited by 2 | Viewed by 3955

Abstract

Herein, a convergent, practicable and first total synthesis of the natural product, (±)-methyl salvianolate A, is reported. The key features of the approach are the use of a Horner–Wadsworth–Emmons reaction and the protection of multiple hydroxyls using silyl protecting groups. The employment of [...] Read more.

Herein, a convergent, practicable and first total synthesis of the natural product, (±)-methyl salvianolate A, is reported. The key features of the approach are the use of a Horner–Wadsworth–Emmons reaction and the protection of multiple hydroxyls using silyl protecting groups. The employment of the readily removable silyl protecting groups allows the synthesis of (±)-methyl salvianolate A and its derivatives on a reasonably large scale. Full article

(This article belongs to the Special Issue Application of Organic Synthesis to Bioactive Compounds)

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18 pages, 3061 KiB

Open AccessArticle

RNA Sequencing Analysis to Capture the Transcriptome Landscape during Tenderization in Sea Cucumber Apostichopus japonicus

by Xiufang Dong, Hang Qi, Baoyu He, Di Jiang and Beiwei Zhu

Molecules 2019, 24(5), 998; https://doi.org/10.3390/molecules24050998 - 12 Mar 2019

Cited by 5 | Viewed by 3856

Abstract

Sea cucumber (Apostichopus japonicus) is an economically significant species in China having great commercial value. It is challenging to maintain the textural properties during thermal processing due to the distinctive physiochemical structure of the A. japonicus body wall (AJBW). In this [...] Read more.

Sea cucumber (Apostichopus japonicus) is an economically significant species in China having great commercial value. It is challenging to maintain the textural properties during thermal processing due to the distinctive physiochemical structure of the A. japonicus body wall (AJBW). In this study, the gene expression profiles associated with tenderization in AJBW were determined at 0 h (CON), 1 h (T_1h), and 3 h (T_3h) after treatment at 37 °C using Illumina HiSeq™ 4000 platform. Seven-hundred-and-twenty-one and 806 differentially expressed genes (DEGs) were identified in comparisons of T_1h vs. CON and T_3h vs. CON, respectively. Among these DEGs, we found that two endogenous proteases—72 kDa type IV collagenase and matrix metalloproteinase 16 precursor—were significantly upregulated that could directly affect the tenderness of AJBW. In addition, 92 genes controlled four types of physiological and biochemical processes such as oxidative stress response (3), immune system process (55), apoptosis (4), and reorganization of the cytoskeleton and extracellular matrix (30). Further, the RT-qPCR results confirmed the accuracy of RNA-sequencing analysis. Our results showed the dynamic changes in global gene expression during tenderization and provided a series of candidate genes that contributed to tenderization in AJBW. This can help further studies on the genetics/molecular mechanisms associated with tenderization. Full article

(This article belongs to the Section Bioorganic Chemistry)

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20 pages, 995 KiB

Open AccessReview

Novel Therapeutics for Epstein–Barr Virus

by Graciela Andrei, Erika Trompet and Robert Snoeck

Molecules 2019, 24(5), 997; https://doi.org/10.3390/molecules24050997 - 12 Mar 2019

Cited by 86 | Viewed by 20347

Abstract

Epstein–Barr virus (EBV) is a human γ-herpesvirus that infects up to 95% of the adult population. Primary EBV infection usually occurs during childhood and is generally asymptomatic, though the virus can cause infectious mononucleosis in 35–50% of the cases when infection occurs later [...] Read more.

Epstein–Barr virus (EBV) is a human γ-herpesvirus that infects up to 95% of the adult population. Primary EBV infection usually occurs during childhood and is generally asymptomatic, though the virus can cause infectious mononucleosis in 35–50% of the cases when infection occurs later in life. EBV infects mainly B-cells and epithelial cells, establishing latency in resting memory B-cells and possibly also in epithelial cells. EBV is recognized as an oncogenic virus but in immunocompetent hosts, EBV reactivation is controlled by the immune response preventing transformation in vivo. Under immunosuppression, regardless of the cause, the immune system can lose control of EBV replication, which may result in the appearance of neoplasms. The primary malignancies related to EBV are B-cell lymphomas and nasopharyngeal carcinoma, which reflects the primary cell targets of viral infection in vivo. Although a number of antivirals were proven to inhibit EBV replication in vitro, they had limited success in the clinic and to date no antiviral drug has been approved for the treatment of EBV infections. We review here the antiviral drugs that have been evaluated in the clinic to treat EBV infections and discuss novel molecules with anti-EBV activity under investigation as well as new strategies to treat EBV-related diseases. Full article

(This article belongs to the Special Issue Recent Advances in the Development of Antiviral Agents)

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16 pages, 3620 KiB

Open AccessArticle

Identification of Leishmania major UDP-Sugar Pyrophosphorylase Inhibitors Using Biosensor-Based Small Molecule Fragment Library Screening

by Ohm Prakash, Jana Führing, John Post, Sharon M. Shepherd, Thomas C. Eadsforth, David Gray, Roman Fedorov and Françoise H. Routier

Molecules 2019, 24(5), 996; https://doi.org/10.3390/molecules24050996 - 12 Mar 2019

Cited by 7 | Viewed by 4923

Abstract

Leishmaniasis is a neglected disease that is caused by different species of the protozoan parasite Leishmania, and it currently affects 12 million people worldwide. The antileishmanial therapeutic arsenal remains very limited in number and efficacy, and there is no vaccine for this [...] Read more.

Leishmaniasis is a neglected disease that is caused by different species of the protozoan parasite Leishmania, and it currently affects 12 million people worldwide. The antileishmanial therapeutic arsenal remains very limited in number and efficacy, and there is no vaccine for this parasitic disease. One pathway that has been genetically validated as an antileishmanial drug target is the biosynthesis of uridine diphosphate-glucose (UDP-Glc), and its direct derivative UDP-galactose (UDP-Gal). De novo biosynthesis of these two nucleotide sugars is controlled by the specific UDP-glucose pyrophosphorylase (UGP). Leishmania parasites additionally express a UDP-sugar pyrophosphorylase (USP) responsible for monosaccharides salvage that is able to generate both UDP-Gal and UDP-Glc. The inactivation of the two parasite pyrophosphorylases UGP and USP, results in parasite death. The present study reports on the identification of structurally diverse scaffolds for the development of USP inhibitors by fragment library screening. Based on this screening, we selected a small set of commercially available compounds, and identified molecules that inhibit both Leishmania major USP and UGP, with a half-maximal inhibitory concentration in the 100 µM range. The inhibitors were predicted to bind at allosteric regulation sites, which were validated by mutagenesis studies. This study sets the stage for the development of potent USP inhibitors. Full article

(This article belongs to the Special Issue Synthesis and Biological Applications of Glycoconjugates Ⅱ)

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14 pages, 1158 KiB

Open AccessReview

Pleiotropic Pharmacological Actions of Capsazepine, a Synthetic Analogue of Capsaicin, against Various Cancers and Inflammatory Diseases

by Min Hee Yang, Sang Hoon Jung, Gautam Sethi and Kwang Seok Ahn

Molecules 2019, 24(5), 995; https://doi.org/10.3390/molecules24050995 - 12 Mar 2019

Cited by 48 | Viewed by 7639

Abstract

Capsazepine is a synthetic analogue of capsaicin that can function as an antagonist of TRPV1. Capsazepine can exhibit diverse effects on cancer (prostate cancer, breast cancer, colorectal cancer, oral cancer, and osteosarcoma) growth and survival, and can be therapeutically used against other major [...] Read more.

Capsazepine is a synthetic analogue of capsaicin that can function as an antagonist of TRPV1. Capsazepine can exhibit diverse effects on cancer (prostate cancer, breast cancer, colorectal cancer, oral cancer, and osteosarcoma) growth and survival, and can be therapeutically used against other major disorders such as colitis, pancreatitis, malaria, and epilepsy. Capsazepine has been reported to exhibit pleiotropic anti-cancer effects against numerous tumor cell lines. Capsazepine can modulate Janus activated kinase (JAK)/signal transducer and activator of the transcription (STAT) pathway, intracellular Ca²⁺ concentration, and reactive oxygen species (ROS)-JNK-CCAAT/enhancer-binding protein homologous protein (CHOP) pathways. It can inhibit cell proliferation, metastasis, and induce apoptosis. Moreover, capsazepine can exert anti-inflammatory effects through the downregulation of lipopolysaccharide (LPS)-induced nuclear transcription factor-kappa B (NF-κB), as well as the blockage of activation of both transient receptor potential cation channel subfamily V member 1 (TRPV1) and transient receptor potential cation channel, subfamily A, and member 1 (TRPA1). This review briefly summarizes the diverse pharmacological actions of capsazepine against various cancers and inflammatory conditions. Full article

(This article belongs to the Special Issue Antitumoral Properties of Natural Products)

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14 pages, 2088 KiB

Open AccessArticle

Differential Proteomics Reveals miR-155 as a Novel Indicator of Liver and Spleen Pathology in the Symptomatic Niemann-Pick Disease, Type C1 Mouse Model

by Melissa R. Pergande, Antony Cougnoux, Rathnayake A. C. Rathnayake, Forbes D. Porter and Stephanie M. Cologna

Molecules 2019, 24(5), 994; https://doi.org/10.3390/molecules24050994 - 12 Mar 2019

Cited by 11 | Viewed by 4139

Abstract

Niemann-Pick disease, type C1 (NPC1) is a rare, autosomal recessive, lipid storage disorder caused by mutations in NPC1. As a result, there is accumulation of unesterified cholesterol and sphingolipids in the late endosomal/lysosomal system. Clinically, patients can present with splenomegaly and hepatomegaly. [...] Read more.

Niemann-Pick disease, type C1 (NPC1) is a rare, autosomal recessive, lipid storage disorder caused by mutations in NPC1. As a result, there is accumulation of unesterified cholesterol and sphingolipids in the late endosomal/lysosomal system. Clinically, patients can present with splenomegaly and hepatomegaly. In the current study, we analyzed the differential proteome of the spleen in symptomatic Npc1^−/− mice to complement previous studies focused on the differential proteome of the liver, and then evaluated biomolecules that may serve as tissue biomarkers. The proteomic analysis revealed altered pathways in NPC1 representing different functional categories including heme synthesis, cellular regulation and phosphoinositide metabolism in both tissues. Differential proteins included several activators of the ubiquitous and critical protein, Akt, a major kinase involved in multiple cellular processes. Evaluation of Akt revealed decreased expression in both the liver and spleen tissues of symptomatic Npc1^−/− mice. Upstream regulation analysis also suggested that miR-155 may modulate the differences of known downstream protein targets observed in our dataset. Upon evaluation of miR-155, we observed an increased expression in the liver and decreased expression in the spleen of symptomatic Npc1^−/− mice. Here, we propose that miR-155 may be a novel indicator of spleen and liver pathology in NPC1. Full article

(This article belongs to the Special Issue CZE/LC-MS-based Proteomics)

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25 pages, 4634 KiB

Open AccessArticle

Antrodin C, an NADPH Dependent Metabolism, Encourages Crosstalk between Autophagy and Apoptosis in Lung Carcinoma Cells by Use of an AMPK Inhibition-Independent Blockade of the Akt/mTOR Pathway

by Hairui Yang, Xu Bai, Henan Zhang, Jingsong Zhang, Yingying Wu, Chuanhong Tang, Yanfang Liu, Yan Yang, Zhendong Liu, Wei Jia and Wenhan Wang

Molecules 2019, 24(5), 993; https://doi.org/10.3390/molecules24050993 - 12 Mar 2019

Cited by 12 | Viewed by 4360

Abstract

The current study aims to explore the possible anti-lung carcinoma activity of ADC as well as the underlying mechanisms by which ADC exerts its actions in NSCLC. Findings showed that ADC potently inhibited the viability of SPCA-1, induced apoptosis triggered by ROS, and [...] Read more.

The current study aims to explore the possible anti-lung carcinoma activity of ADC as well as the underlying mechanisms by which ADC exerts its actions in NSCLC. Findings showed that ADC potently inhibited the viability of SPCA-1, induced apoptosis triggered by ROS, and arrested the cell cycle at the G2/M phase via a P53 signaling pathway. Interestingly, phenomena such as autophagosomes accumulation, conversion of the LC3-I to LC3-II, etc., indicated that autophagy could be activated by ADC. The blockage of autophagy-augmented ADC induced inhibition of cell proliferation, while autophagy activation restored cell death, indicating that autophagy had a protective effect against cell death which was induced by ADC treatment. Meanwhile, ADC treatment suppressed both the Akt/mTOR and AMPK signaling pathways. The joint action of both ADC and the autophagy inhibitor significantly increased the death of SPCA-1. An in vitro phase I metabolic stability assay showed that ADC was highly metabolized in SD rat liver microsomes and moderately metabolized in human liver microsomes, which will assist in predicting the outcomes of clinical pharmacokinetics and toxicity studies. These findings imply that blocking the Akt/mTOR signaling pathway, which was independent of AMPK inhibition, could activate ADC-induced protective autophagy in non-small-cell lung cancer cells. Full article

(This article belongs to the Special Issue Antitumoral Properties of Natural Products)

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12 pages, 3355 KiB

Open AccessArticle

Photo-Reduction of CO₂ by VIS Light on Polythiophene-ZSM-5 Zeolite Hybrid Photo-Catalyst

by Jana Kianička, Gabriel Čík, František Šeršeň, Ivan Špánik, Robert Sokolík and Juraj Filo

Molecules 2019, 24(5), 992; https://doi.org/10.3390/molecules24050992 - 12 Mar 2019

Cited by 7 | Viewed by 3498

Abstract

A new hybrid photo-catalyst based on ZSM-5 zeolite suitable for reduction of carbon dioxide was synthesized. The photo-catalyst was prepared by oxidative polymerization of thiophene with FeCl₃ in the presence of ZSM-5 with participation of ultrasound. The synthesized photo-catalyst strongly absorbs light [...] Read more.

A new hybrid photo-catalyst based on ZSM-5 zeolite suitable for reduction of carbon dioxide was synthesized. The photo-catalyst was prepared by oxidative polymerization of thiophene with FeCl₃ in the presence of ZSM-5 with participation of ultrasound. The synthesized photo-catalyst strongly absorbs light radiation up to approx. 650 nm, with the absorption edge in the NIR region. Reactive radicals were generated by VIS light irradiation in an aqueous suspension consisting of the photo-catalyst with CO₂. Formic acid and acetic acid were generated as the main products of the CO₂ reduction. EPR spin trapping technique was applied to identify the reactive radical intermediates. In this work, the mechanism of product formation is also discussed. Full article

(This article belongs to the Section Green Chemistry)

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10 pages, 1990 KiB

Open AccessArticle

Dietary Fiber from Chickpea (Cicer arietinum) and Soybean (Glycine max) Husk Byproducts as Baking Additives: Functional and Nutritional Properties

by Guillermo Niño-Medina, Dolores Muy-Rangel, Ana Laura de la Garza, Werner Rubio-Carrasco, Briceida Pérez-Meza, Ana P. Araujo-Chapa, Kelsy A. Gutiérrez-Álvarez and Vania Urías-Orona

Molecules 2019, 24(5), 991; https://doi.org/10.3390/molecules24050991 - 12 Mar 2019

Cited by 37 | Viewed by 4955

Abstract

Dietary fiber extracted from soybean and chickpea husks was used in the formulation of white bread. Treatments at different concentrations of dietary fiber (DF): bread + 0.15%, 0.3%, 1.5%, 2% soybean dietary fiber (SDF); bread + 0.15%, 0.3%, 1.5%, 2% chickpea dietary fiber [...] Read more.

Dietary fiber extracted from soybean and chickpea husks was used in the formulation of white bread. Treatments at different concentrations of dietary fiber (DF): bread + 0.15%, 0.3%, 1.5%, 2% soybean dietary fiber (SDF); bread + 0.15%, 0.3%, 1.5%, 2% chickpea dietary fiber (CDF), and a control treatment (Bread 0% DF) were used initially. However, the treatments that showed the greatest improvement effects were: bread + 2% SDF and bread + 2% CDF. The functionality and the nutritional contribution in the treatments were evaluated during four days of storage. The weight loss on the third day of storage was 30% higher in the control treatment than the products with 2% SDF and 2% CDF, while for the evaluation of firmness, the control obtained a hardness of 86 N, and treatments with 2% SDF and 2% CDF 60 N and 45 N, respectively. The presence of phenolic compounds and their antioxidant activity was evident, mainly in the 2% SDF treatment, which had a total phenolic content of 1036, while in the Bread 0% DF it was 232 mgEAC/kg. The antioxidant activity for 2% SDF by DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (3-ethyl-benzothiazoline-6-sulfonic acid), and FRAP (ferric reducing antioxidant power) was 1096, 2567, and 1800 µmolTE/kg, respectively. Dietary fiber addition favored the reduction of weight loss and firmness of white bread during storage. In addition, color was not affected and the content calcium, phenolics, as well as antioxidant capacity were slightly improved. Full article

(This article belongs to the Special Issue Extraction of Bioactive Molecules from Food By-Products and Their Utilization as Functional Ingredients)

11 pages, 1853 KiB

Open AccessArticle

Oligonucleotide Binding to Non-B-DNA in MYC

by Tea Umek, Karin Sollander, Helen Bergquist, Jesper Wengel, Karin E. Lundin, C.I. Edvard Smith and Rula Zain

Molecules 2019, 24(5), 1000; https://doi.org/10.3390/molecules24051000 - 12 Mar 2019

Cited by 4 | Viewed by 4557

Abstract

MYC, originally named c-myc, is an oncogene deregulated in many different forms of cancer. Translocation of the MYC gene to an immunoglobulin gene leads to an overexpression and the development of Burkitt’s lymphoma (BL). Sporadic BL constitutes one subgroup where [...] Read more.

MYC, originally named c-myc, is an oncogene deregulated in many different forms of cancer. Translocation of the MYC gene to an immunoglobulin gene leads to an overexpression and the development of Burkitt’s lymphoma (BL). Sporadic BL constitutes one subgroup where one of the translocation sites is located at the 5’-vicinity of the two major MYC promoters P₁ and P₂. A non-B-DNA forming sequence within this region has been reported with the ability to form an intramolecular triplex (H-DNA) or a G-quadruplex. We have examined triplex formation at this site first by using a 17 bp triplex-forming oligonucleotide (TFO) and a double strand DNA (dsDNA) target corresponding to the MYC sequence. An antiparallel purine-motif triplex was detected using electrophoretic mobility shift assay. Furthermore, we probed for H-DNA formation using the BQQ-OP based triplex-specific cleavage assay, which indicated the formation of the structure in the supercoiled plasmid containing the corresponding region of the MYC promoter. Targeting non-B-DNA structures has therapeutic potential; therefore, we investigated their influence on strand-invasion of anti-gene oligonucleotides (ON)s. We show that in vitro, non-B-DNA formation at the vicinity of the ON target site facilitates dsDNA strand-invasion of the anti-gene ONs. Full article

(This article belongs to the Special Issue Molecular Tools for Nucleic Acid Manipulation for Biological Intervention)

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13 pages, 2778 KiB

Open AccessFeature PaperArticle

Synthesis of New Indanyl Nucleoside Analogues and their Biological Evaluation on Hepatitis C Virus (HCV) Replicon

by Matías E. Gómez, Emiliano A. Gentile, M. Florencia Martini, María L. Cuestas, Verónica L. Mathet, Graciela Y. Moltrasio and Albertina G. Moglioni

Molecules 2019, 24(5), 990; https://doi.org/10.3390/molecules24050990 - 11 Mar 2019

Cited by 2 | Viewed by 2936

Abstract

Here, we report a convenient synthetic procedure for the preparation of four novel indanyl carbanucleoside derivatives in the racemic form. The action of these compounds against hepatitis C virus was evaluated in vitro using the replicon cell line, Huh7.5 SG. Contrary to our [...] Read more.

Here, we report a convenient synthetic procedure for the preparation of four novel indanyl carbanucleoside derivatives in the racemic form. The action of these compounds against hepatitis C virus was evaluated in vitro using the replicon cell line, Huh7.5 SG. Contrary to our expectations, all these compounds did not inhibit, but rather promoted HCV genotype 1b (HCVg1b) replication. Similar effects have been reported for morphine in the replicon cell lines, Huh7 and Huh8. Several biological experiments and computational studies were performed to elucidate the effect of these compounds on HCVg1b replication. Based on all the experiments performed, we propose that the increase in HCVg1b replication could be mediated, at least in part, by a similar mechanism to that of morphine on the enhancement of this replication. The presence of opioid receptors in Huh7.5 SG cells was indirectly determined for the first time in this work. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 3025 KiB

Open AccessArticle

Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS

by Roberta Ottria, Alessandro Ravelli, Matteo Miceli, Sara Casati, Marica Orioli and Pierangela Ciuffreda

Molecules 2019, 24(5), 989; https://doi.org/10.3390/molecules24050989 - 11 Mar 2019

Cited by 10 | Viewed by 4790 | Correction

Abstract

Olaparib, an orally active inhibitor of poly(ADP-ribose)polymerase(PARP), is the drug of choice in the treatment of gBRCA1/2+ metastatic breast cancers. Unfortunately, Olaparib is poorly soluble with low bioavailability and tumor accumulation; nano-delivery could be a good choice to overcome these disadvantages. Here, a [...] Read more.

Olaparib, an orally active inhibitor of poly(ADP-ribose)polymerase(PARP), is the drug of choice in the treatment of gBRCA1/2+ metastatic breast cancers. Unfortunately, Olaparib is poorly soluble with low bioavailability and tumor accumulation; nano-delivery could be a good choice to overcome these disadvantages. Here, a rapid and robust HPLC-ESI–MS/MS method for the quantification of Olaparib in ferritin nano-carriers led to the development of cells compartments, different tissues, plasma and urines and were validated to assess the effects of nano-delivery on cell compartment distribution of the drug. This method allows the quantification of Olaparib within the linear range of 0.1–10ng/mL in cells culture medium and cell cytoplasm, of 0.5–10ng/mL in nuclei, of 0.5–100ng/mL in plasma and urine and of 10–500ng/mL in tissue samples (kidney and liver). The limit of quantification was found to be 1.54 ng/mL for liver, 2.87 ng/mL for kidney, and lower than 0.48 ng/mL for all matrices. The method has been applied to quantify Ola encapsulated in ferritin-nano-carriers during the nano-drug development. The application of the method to human BRCA-mutated cell model to quantify the Olaparib distribution after incubation of free or ferritin-encapsulated Olaparib is also reported. This sensitive method allows the quantification of low concentrations of Olaparib released from nano-carriers in different cell compartments, leading to the determination of the drug release and kinetic profile of an essential parameter to validate nano-carriers. Full article

(This article belongs to the Special Issue Biological Sample Analysis by Liquid Chromatography)

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30 pages, 2098 KiB

Open AccessArticle

Green and Facile Assembly of Diverse Fused N-Heterocycles Using Gold-Catalyzed Cascade Reactions in Water

by Xiuwen Jia, Pinyi Li, Xiaoyan Liu, Jiafu Lin, Yiwen Chu, Jinhai Yu, Jiang Wang, Hong Liu and Fei Zhao

Molecules 2019, 24(5), 988; https://doi.org/10.3390/molecules24050988 - 11 Mar 2019

Cited by 23 | Viewed by 4767

Abstract

The present study describes an AuPPh₃Cl/AgSbF₆-catalyzed cascade reaction between amine nucleophiles and alkynoic acids in water. This process proceeds in high step economy with water as the sole coproduct, and leads to the generation of two rings, together with [...] Read more.

The present study describes an AuPPh₃Cl/AgSbF₆-catalyzed cascade reaction between amine nucleophiles and alkynoic acids in water. This process proceeds in high step economy with water as the sole coproduct, and leads to the generation of two rings, together with the formation of three new bonds in a single operation. This green cascade process exhibits valuable features such as low catalyst loading, good to excellent yields, high efficiency in bond formation, excellent selectivity, great tolerance of functional groups, and extraordinarily broad substrate scope. In addition, this is the first example of the generation of an indole/thiophene/pyrrole/pyridine/naphthalene/benzene-fused N-heterocycle library through gold catalysis in water from readily available materials. Notably, the discovery of antibacterial molecules from this library demonstrates its high quality and potential for the identification of active pharmaceutical ingredients. Full article

(This article belongs to the Special Issue Modern Strategies for Heterocycle Synthesis)

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21 pages, 3589 KiB

Open AccessArticle

Vasodilation Elicited by Isoxsuprine, Identified by High-Throughput Virtual Screening of Compound Libraries, Involves Activation of the NO/cGMP and H₂S/K_ATP Pathways and Blockade of α₁-Adrenoceptors and Calcium Channels

by Daniella Medina-Ruiz, Berenice Erreguin-Luna, Francisco J. Luna-Vázquez, Antonio Romo-Mancillas, Alejandra Rojas-Molina and César Ibarra-Alvarado

Molecules 2019, 24(5), 987; https://doi.org/10.3390/molecules24050987 - 11 Mar 2019

Cited by 10 | Viewed by 4617

Abstract

Recently, our research group demonstrated that uvaol and ursolic acid increase NO and H₂S production in aortic tissue. Molecular docking studies showed that both compounds bind with high affinity to endothelial NO synthase (eNOS) and cystathionine gamma-lyase (CSE). The aim of [...] Read more.

Recently, our research group demonstrated that uvaol and ursolic acid increase NO and H₂S production in aortic tissue. Molecular docking studies showed that both compounds bind with high affinity to endothelial NO synthase (eNOS) and cystathionine gamma-lyase (CSE). The aim of this study was to identify hits with high binding affinity for the triterpene binding-allosteric sites of eNOS and CSE and to evaluate their vasodilator effect. Additionally, the mechanism of action of the most potent compound was explored. A high-throughput virtual screening (HTVS) of 107,373 compounds, obtained from four ZINC database libraries, was performed employing the crystallographic structures of eNOS and CSE. Among the nine top-scoring ligands, isoxsuprine showed the most potent vasodilator effect. Pharmacological evaluation, employing the rat aorta model, indicated that the vasodilation produced by this compound involved activation of the NO/cGMP and H₂S/K_ATP signaling pathways and blockade of α₁-adrenoceptors and L-type voltage-dependent Ca²⁺ channels. Incubation of aorta homogenates in the presence of isoxsuprine caused 2-fold greater levels of H₂S, which supported our preliminary in silico data. This study provides evidence to propose that the vasodilator effect of isoxsuprine involves various mechanisms, which highlights its potential to treat a wide variety of cardiovascular diseases. Full article

(This article belongs to the Section Medicinal Chemistry)

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17 pages, 2271 KiB

Open AccessArticle

Hydrodistillation Extraction Kinetics Regression Models for Essential Oil Yield and Composition in Juniperus virginiana, J. excelsa, and J. sabina

by Ivanka B. Semerdjieva, Santosh Shiwakoti, Charles L. Cantrell, Valtcho D. Zheljazkov, Tess Astatkie, Vicki Schlegel and Tzenka Radoukova

Molecules 2019, 24(5), 986; https://doi.org/10.3390/molecules24050986 - 11 Mar 2019

Cited by 24 | Viewed by 5349

Abstract

The chemical profile and antioxidant capacity of Juniperus virginiana, J. excelsa, and J. sabina essential oil (EO) fractions as a function of time was the subject of this study. The hypothesis was that, capturing EO in sequential timeframes during hydrodistillation would [...] Read more.

The chemical profile and antioxidant capacity of Juniperus virginiana, J. excelsa, and J. sabina essential oil (EO) fractions as a function of time was the subject of this study. The hypothesis was that, capturing EO in sequential timeframes during hydrodistillation would generate fractions containing unique compositions and antioxidant capacity. In J. virginiana, the highest limonene (43%) was found in the 0–5 min oil fraction, with safrole (37%) being highest in the 10–20 and 20–40 min fractions, and elemol (34%) being highest in the 160–240 min fraction. In J. excelsa, α-pinene (34-36%) was the highest in the 0–5 min fraction and in the control (non-stop 0–240 min distillation) oil, limonene (39%) was the highest in the 0–10 min fractions and cedrol (50-53%) was the highest in the 40–240 min fractions. In J. sabina, sabinene (80%) was highest in the 0–3 min fraction. The highest antioxidant capacity of J. virginiana was demonstrated by the 5–10 min fraction; the one in J. sabina by the 3–10 min fraction; and, the one in J. excelsa, by the control. The kinetics regression models that were developed can predict EO composition of the three juniper species eluted at different timeframes. Various industries could benefit from the results from this study. Full article

(This article belongs to the Special Issue Recent Research Advances in Essential Oils: From Green Extraction and Synthesis to Sustainable Applications and Utilization)

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14 pages, 3672 KiB

Open AccessArticle

Synthesis and Broad Antiviral Activity of Novel 2-aryl-isoindolin-1-ones towards Diverse Enterovirus A71 Clinical Isolates

by Yixuan Wang, Huiqiang Wang, Xinbei Jiang, Zhi Jiang, Tingting Guo, Xingyue Ji, Yanping Li, Yuhuan Li and Zhuorong Li

Molecules 2019, 24(5), 985; https://doi.org/10.3390/molecules24050985 - 11 Mar 2019

Cited by 10 | Viewed by 4060

Abstract

Enterovirus 71 (EV-A71) is the main causative pathogen of childhood hand, foot and mouth disease. Effective medicine is currently unavailable for the treatment of this viral disease. Using the fragment-hopping strategy, a series of 2-aryl-isoindolin-1-one compounds were designed, synthesized and investigated for their [...] Read more.

Enterovirus 71 (EV-A71) is the main causative pathogen of childhood hand, foot and mouth disease. Effective medicine is currently unavailable for the treatment of this viral disease. Using the fragment-hopping strategy, a series of 2-aryl-isoindolin-1-one compounds were designed, synthesized and investigated for their in vitro antiviral activity towards multiple EV-A71 clinical isolates (H, BrCr, Shenzhen98, Jiangsu52) in Vero cell culture in this study. The structure–activity relationship (SAR) studies identified 2-phenyl-isoindolin-1-ones as a new potent chemotype with potent antiviral activity against EV-A71. Ten out of the 24 tested compounds showed significant antiviral activity (EC₅₀ < 10 µM) towards four EV-A71 strains. Compounds A3 and A4 exhibited broad and potent antiviral activity with the 50% effective concentration (EC₅₀) values in the range of 1.23–1.76 μM. Moreover, the selectivity indices of A3 and A4 were significantly higher than those of the reference compound, pirodavir. The western blotting experiment indicated that the viral VP1 was significantly decreased at both the protein and RNA level in a dose-dependent manner following treatment with compound A3. Moreover, compound A3 inhibited the viral replication by acting on the virus entry stage. In summary, this study led to the discovery of 2-aryl-isoindolin-1-ones as a promising scaffold with potent anti-EV-A71 activities, which deserves further in-depth studies. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 1767 KiB

Open AccessArticle

Evolution and Antibacterial Evaluation of 8-Hydroxy-cycloberberine Derivatives as a Novel Family of Antibacterial Agents Against MRSA

by Yuan-Shuai Yang, Wei Wei, Xin-Xin Hu, Sheng Tang, Jing Pang, Xue-Fu You, Tian-Yun Fan, Yan-Xiang Wang and Dan-Qing Song

Molecules 2019, 24(5), 984; https://doi.org/10.3390/molecules24050984 - 11 Mar 2019

Cited by 12 | Viewed by 4504

Abstract

Twenty-five new derivatives of 8-hydroxycycloberberine (1) were synthesized and evaluated for their activities against Gram-positive bacteria, taking 1 as the lead. Part of them displayed satisfactory antibacterial activities against methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), as well as [...] Read more.

Twenty-five new derivatives of 8-hydroxycycloberberine (1) were synthesized and evaluated for their activities against Gram-positive bacteria, taking 1 as the lead. Part of them displayed satisfactory antibacterial activities against methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), as well as vancomycin-intermediate Staphylococcus aureus (VISA). Especially, compound 15a displayed an excellent anti-MRSA activity with MICs (minimum inhibitory concentrations) of 0.25–0.5 μg/mL, better than that of 1. It also displayed high stability in liver microsomes and whole blood, and the LD₅₀ value of over 65.6 mg·kg⁻¹ in mice via intravenous route, suggesting a good druglike feature. The mode of action showed that 15a could effectively suppress topo IV-mediated decatenation activity at the concentration of 7.5 μg/mL, through binding a different active pocket of bacterial topo IV from quinolones. Taken together, the derivatives of 1 constituted a promising kind of anti-MRSA agents with a unique chemical scaffold and a specific biological mechanism, and compound 15a has been chosen for the next investigation. Full article

(This article belongs to the Collection Antibiotics & Superbugs: New Strategies to Combat Antimicrobial Resistance)

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18 pages, 2397 KiB

Open AccessArticle

Investigation of 8-Aza-7-Deaza Purine Nucleoside Derivatives

by Hang Ren, Haoyun An and Jingchao Tao

Molecules 2019, 24(5), 983; https://doi.org/10.3390/molecules24050983 - 11 Mar 2019

Cited by 6 | Viewed by 4054

Abstract

Glycosylation of 6-amino-4-methoxy-1H-pyrazolo[3,4-d]pyrimidine and its iodo- and bromo- analogues with the protected ribofuranose and 2′-deoxyribofuranose under different conditions resulted in the synthesis of N⁹- and N⁸-glycosylated purine nucleosides. Five key intermediate nucleosides, having 6-methoxy, 7-iodo, and 2-bromo [...] Read more.

Glycosylation of 6-amino-4-methoxy-1H-pyrazolo[3,4-d]pyrimidine and its iodo- and bromo- analogues with the protected ribofuranose and 2′-deoxyribofuranose under different conditions resulted in the synthesis of N⁹- and N⁸-glycosylated purine nucleosides. Five key intermediate nucleosides, having 6-methoxy, 7-iodo, and 2-bromo groups, were further derivatized to 23 final 8-aza-7-deazapurine nucleoside derivatives. The structures of N⁹- and N⁸-glycosylated products were assigned based on UV and NMR spectra. HMBC analysis of 2D NMR spectra and X-ray crystallographic studies of the representative compounds unambiguously verified the connection of ribose ring to N⁹- or N⁸-position of the purine ring. The anticancer activity of these new compounds was evaluated. Full article

(This article belongs to the Section Organic Chemistry)

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14 pages, 446 KiB

Open AccessArticle

Determination of Antioxidant Capacity, Phenolics and Volatile Maillard Reaction Products in Rye-Buckwheat Biscuits Supplemented with 3β-d-Rutinoside

by Małgorzata Starowicz, Georgios Koutsidis and Henryk Zieliński

Molecules 2019, 24(5), 982; https://doi.org/10.3390/molecules24050982 - 11 Mar 2019

Cited by 30 | Viewed by 4480

Abstract

The Maillard reaction (MR) is responsible for the development of color, taste and aroma in bakery products though the formation of numerous aroma compounds such as pyrazines, pyrroles and aldehydes, nonvolatile taste active compounds and melanoidins. In this article, we investigate the effect [...] Read more.

The Maillard reaction (MR) is responsible for the development of color, taste and aroma in bakery products though the formation of numerous aroma compounds such as pyrazines, pyrroles and aldehydes, nonvolatile taste active compounds and melanoidins. In this article, we investigate the effect of quercetin 3β-D-rutinoside (rutin) supplementation, at the level of 5–50 mg per 100 g, of rye-buckwheat biscuits on the formation of phenolics and volatile Maillard reaction products (MRPs) such as pyrazines, furfuryl alcohol and furfural, determined by headspace solid phase microextraction followed by gas chromatography–mass spectrometry (HS-SPME/GC–MS), in addition to the effect on the antioxidant capacity. The study confirmed that rutin was stable under baking conditions as showed by its content in rye-buckwheat biscuits. Supplementation of biscuits with increasing amounts of rutin resulted in the progressive increase of total phenolics and antioxidant capacity measured by DPPH and OxHLIA assays, but it had no effect on their sensory quality. From the eighteen compounds identified by HS-SPME/GC–MS in the volatile fraction of biscuits were quantitated as a compounds-of-interest: methylpyrazine, ethylpyrazine, 2,3-; 2,5- and 2,6-dimethylpyrazines, as well as furfural, furfuryl alcohol and hexanal. The rutin supplementation of biscuits might be one of the factors to influence the formation of both desirable volatile compounds and undesirable toxic compounds. In conclusion, this study indicates for the significant role of polyphenols on the formation of volatile compounds in biscuits with possible future application in the development of healthy bakery products with high antioxidant capacity. Full article

(This article belongs to the Special Issue Recent Advances in Studies of Food and Beverages)

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13 pages, 1656 KiB

Open AccessArticle

Multi-year Quantitative Evaluation of Stilbenoids Levels Among Selected Muscadine Grape Cultivars

by Devaiah M. Kambiranda, Sheikh M. Basha, Stephen J. Stringer, James O. Obuya and Janana J. Snowden

Molecules 2019, 24(5), 981; https://doi.org/10.3390/molecules24050981 - 11 Mar 2019

Cited by 13 | Viewed by 3104

Abstract

Stilbenoids such as t-piceid, t-resveratrol, ε-viniferins, and t-pterostilbene can differ significantly among grape cultivars and years due to variation in environmental conditions and subsequent stressors encountered during a year. This study evaluated diverse muscadine grape cultivars for their ability to [...] Read more.

Stilbenoids such as t-piceid, t-resveratrol, ε-viniferins, and t-pterostilbene can differ significantly among grape cultivars and years due to variation in environmental conditions and subsequent stressors encountered during a year. This study evaluated diverse muscadine grape cultivars for their ability to consistently produce four major stilbenoids such as t-piceid, t-resveratrol, ε-viniferins, and t-pterostilbene irrespective of environmental changes that can impact their production. Berries from forty-two muscadine grape cultivars were collected for three years (2013, 2014, and 2015) to measure stilbenoids. Results showed significant differences in the composition of four stilbenoids among the muscadine cultivars. The highest level of stilbenoids was observed in ‘Fry Seedless’ (270.20 µg/g fresh weight) in each of the three consecutive years tested followed by ‘Pride’ (46.18 µg/g fresh weight) while ‘Doreen’ produced the lowest level of stilbenoids (1.73 µg/g fresh weight). Results demonstrated that certain muscadine grape cultivars consistently produced varied levels of the four major stilbenoids year after year. Based on the total content of stilbenoids, the 42 muscadine cultivars studied were grouped into three categories such as High, Medium and Low stilbenoid-containing cultivars. This information will help establish new vineyards with cultivars that are less prone to variations in environmental conditions and can consistently produce stilbenoid-rich muscadine grape berries with enhanced market value to promote consumer health. Full article

(This article belongs to the Collection Wine Chemistry)

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15 pages, 3433 KiB

Open AccessArticle

Tea Seed Oil Prevents Obesity, Reduces Physical Fatigue, and Improves Exercise Performance in High-Fat-Diet-Induced Obese Ovariectomized Mice

by Yu-Tang Tung, Yi-Ju Hsu, Yi-Wen Chien, Chi-Chang Huang, Wen-Ching Huang and Wan-Chun Chiu

Molecules 2019, 24(5), 980; https://doi.org/10.3390/molecules24050980 - 11 Mar 2019

Cited by 22 | Viewed by 5486

Abstract

Menopause is associated with changes in body composition (a decline in lean body mass and an increase in total fat mass), leading to an increased risk of metabolic syndrome, nonalcoholic fatty liver disease, and heart disease. A healthy diet to control body weight [...] Read more.

Menopause is associated with changes in body composition (a decline in lean body mass and an increase in total fat mass), leading to an increased risk of metabolic syndrome, nonalcoholic fatty liver disease, and heart disease. A healthy diet to control body weight is an effective strategy for preventing and treating menopause-related metabolic syndromes. In the present study, we investigated the effect of long-term feeding of edible oils (soybean oil (SO), tea seed oil (TO), and lard oil (LO)) on female ovariectomized (OVX) mice. SO, TO, and LO comprise mainly polyunsaturated fatty acids (PUFA), monounsaturated fatty acids (MUFA), and saturated fatty acids (SFA), respectively. However, there have been quite limited studies to investigate the effects of different fatty acids (PUFA, MUFA, and SFA) on physiological adaption and metabolic homeostasis in a menopausal population. In this study, 7-week-old female Institute of Cancer Research (ICR) mice underwent either bilateral laparotomy (sham group, n = 8) or bilateral oophorectomy (OVX groups, n = 24). The OVX mice given a high-fat diet (HFD) were randomly divided into three groups: OVX+SO, OVX+TO, and OVX+LO. An HFD rich in SO, TO, or LO was given to the OVX mice for 12 weeks. Our findings revealed that the body weight and relative tissues of UFP (uterus fatty peripheral) and total fat (TF) were significantly decreased in the OVX+TO group compared with those in the OVX+SO and OVX+LO groups. However, no significant difference in body weight or in the relative tissues of UFP and TF was noted among the OVX+SO and OVX+LO groups. Furthermore, mice given an HFD rich in TO exhibited significantly decreased accumulation of liver lipid droplets and adipocyte sizes of UFP and brown adipose tissue (BAT) compared with those given an HFD rich in SO or LO. Moreover, replacing SO or LO with TO significantly increased oral glucose tolerance. Additionally, TO improved endurance performance and exhibited antifatigue activity by lowering ammonia, blood urea nitrogen, and creatine kinase levels. Thus, tea seed oil (TO) rich in MUFA could prevent obesity, reduce physical fatigue, and improve exercise performance compared with either SO (PUFA)- or LO(SFA)-rich diets in this HFD-induced obese OVX mice model. Full article

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

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11 pages, 1989 KiB

Open AccessArticle

Sulfonylimino Group Transfer Reaction Using Imino-λ³-iodanes with I₂ as Catalyst Under Metal-free Conditions

by Akira Yoshimura, Cody L. Makitalo, Melissa E. Jarvi, Michael T. Shea, Pavel S. Postnikov, Gregory T. Rohde, Viktor V. Zhdankin, Akio Saito and Mekhman S. Yusubov

Molecules 2019, 24(5), 979; https://doi.org/10.3390/molecules24050979 - 11 Mar 2019

Cited by 12 | Viewed by 4910

Abstract

A new practical procedure of imination for sulfide has been developed. The treatment of (N-tosylimino)-phenyl-λ³-iodane, PhINTs, with various sulfides in the presence of a catalytic amount of I₂ under metal-free conditions affords the corresponding N-tosylsulfilimine compounds with [...] Read more.

A new practical procedure of imination for sulfide has been developed. The treatment of (N-tosylimino)-phenyl-λ³-iodane, PhINTs, with various sulfides in the presence of a catalytic amount of I₂ under metal-free conditions affords the corresponding N-tosylsulfilimine compounds with moderate to good yields. This facile transfer procedure of the sulfonylimino group can also be applied to triphenylphosphine to produce the respective iminotriphenylphosphoranes in high yields. According to the reaction mechanism studies, the process of imination from (N-tosylimino)-phenyl-λ³-iodane to sulfide under the conditions may involve radical steps within the reaction mechanism. Full article

(This article belongs to the Special Issue Advances in the Chemistry of Hypervalent Iodine Compounds)

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4 pages, 159 KiB

Open AccessEditorial

Chemicals from Food Supply Chain By-Products and Waste Streams

by Marta Coma and Afroditi Chatzifragkou

Molecules 2019, 24(5), 978; https://doi.org/10.3390/molecules24050978 - 11 Mar 2019

Cited by 7 | Viewed by 2944

Abstract

Circular economy and bioeconomy concepts have been introduced within an EU framework to sustainably overcome the dominant development model of “take, make, and dispose”, which has contributed to current economic, environmental, and societal burdens [...] Full article

(This article belongs to the Special Issue Chemicals from Food Supply Chain By-Products and Waste Streams)

21 pages, 11944 KiB

Open AccessArticle

Identification and Characterization of the Caspase-Mediated Apoptotic Activity of Teucrium mascatense and an Isolated Compound in Human Cancer Cells

by Neena Gopinathan Panicker, Sameera Omar Mohammed Saeed Balhamar, Shaima Akhlaq, Mohammed Mansour Qureshi, Tania Shamim Rizvi, Ahmed Al-Harrasi, Javid Hussain and Farah Mustafa

Molecules 2019, 24(5), 977; https://doi.org/10.3390/molecules24050977 - 11 Mar 2019

Cited by 11 | Viewed by 4210

Abstract

Plants of the genus Teucrium (Lamiaceae or Labiatae family) are known historically for their medicinal value. Here, we identify and characterize the anticancer potential of T. mascatense and its active compound, IM60, in human cancer cells. The anti-proliferative effect of a T. mascatense [...] Read more.

Plants of the genus Teucrium (Lamiaceae or Labiatae family) are known historically for their medicinal value. Here, we identify and characterize the anticancer potential of T. mascatense and its active compound, IM60, in human cancer cells. The anti-proliferative effect of a T. mascatense methanol extract and its various fractions were analyzed in MCF-7 and HeLa cells in a dose- and time dependent manner. The dichloromethane fraction (TMDF) was observed to be the most effective with cytotoxicity against a more expanded series of cell lines, including MDA-MB-231. A time and dose-dependent toxicity profile was also observed for IM60; it could induce rapid cell death (within 3 h) in MCF-7 cells. Activation of caspases and PARP, hallmarks of apoptotic cell death pathways, following treatment with TMDF was demonstrated using western blot analysis. Inversion of the phosphatidylserine phospholipid from the inner to the outer membrane was confirmed by annexin V staining that was inhibited by the classical apoptosis inhibitor, Z-VAK-FMK. Changes in cell rounding, shrinkage, and detachment from other cells following treatment with TMDF and IM60 also supported these findings. Finally, the potential of TMDF and IM60 to induce enzymatic activity of caspases was also demonstrated in MCF-7 cells. This study, thus, not only characterizes the anticancer potential of T. mascatense, but also identifies a lead terpenoid, IM60, with the potential to activate anticancer cell death pathways in human cancer cells. Full article

(This article belongs to the Special Issue Natural Products and Derivatives in Human Disorders)

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18 pages, 7629 KiB

Open AccessArticle

Enhanced Supercapacitor Performance Based on CoAl Layered Double Hydroxide-Polyaniline Hybrid Electrodes Manufactured Using Hydrothermal-Electrodeposition Technology

by Guoshen Yang, Takahiro Takei, Sayaka Yanagida and Nobuhiro Kumada

Molecules 2019, 24(5), 976; https://doi.org/10.3390/molecules24050976 - 10 Mar 2019

Cited by 24 | Viewed by 5324

Abstract

Electrodes with nanosheet architectures can offer the possibility to achieve enhanced energy storage performance. Herein, we have designed and synthesized novel nanosheet structures of CoAl layered double hydroxide (LDH)-polyaniline (PANI) nanocomposite thin films by a hydrothermal-electrodeposition method. The molecular structure, crystal structure, morphology [...] Read more.

Electrodes with nanosheet architectures can offer the possibility to achieve enhanced energy storage performance. Herein, we have designed and synthesized novel nanosheet structures of CoAl layered double hydroxide (LDH)-polyaniline (PANI) nanocomposite thin films by a hydrothermal-electrodeposition method. The molecular structure, crystal structure, morphology and chemical composition of the composites were characterized by FT-IR, XRD (SXRD), FESEM, and XPS, whereas their electrochemical properties were evaluated by cyclic voltammetry, electrochemical impedance spectroscopy and galvanostatic charge-discharge tests. Compared with the unmodified CoAl LDH, the CoAl LDH-PANI exhibits significantly improved the specific capacitance and cyclic stability. The composite exhibits a high specific capacitance of 528 F/g at a current density of 10 A/g and excellent cyclic stability with an increase of the specific capacitance of 42.7% after 6000 cycle tests. We revealed the degradation behavior of PANI in 1 M KOH/KCl electrolyte, and the active degradation products also further increased the total specific capacitance of the composite. The enhanced electrochemical performance of the nanocomposite can be attributed to its well-designed nanostructure and the synergistic effects of each component. By analyzing the band structure and density of states of CoAl LDH and PANI, we proposed the possible mechanism of synergistic effect in a new perspective. Full article

(This article belongs to the Section Materials Chemistry)

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10 pages, 1446 KiB

Open AccessFeature PaperArticle

Hemi-Synthesis of Chiral Imine, Benzimidazole and Benzodiazepines from Essential Oil of Ammodaucus leucotrichus subsp. leucotrichus

by Farid Chebrouk, Khodir Madani, Brahim Cherfaoui, Leila Boukenna, Mónica Válega, Ricardo F. Mendes, Filipe A. A. Paz, Khaldoun Bachari, Oualid Talhi and Artur M. S. Silva

Molecules 2019, 24(5), 975; https://doi.org/10.3390/molecules24050975 - 10 Mar 2019

Cited by 10 | Viewed by 4599

Abstract

The hemi-synthesis of chiral imine, benzimidazole and benzodiazepine structures is reported by the condensation of (S)-(−)-perillaldehyde, the major phytochemical of Ammodaucus leucotrichus subsp. leucotrichus essential oil, with different amine derivatives of 2,3-diaminomaleonitrile, o-phenylenediamine and 3-[(2-aminoaryl)amino]dimedone. The reaction proceeds in situ [...] Read more.

The hemi-synthesis of chiral imine, benzimidazole and benzodiazepine structures is reported by the condensation of (S)-(−)-perillaldehyde, the major phytochemical of Ammodaucus leucotrichus subsp. leucotrichus essential oil, with different amine derivatives of 2,3-diaminomaleonitrile, o-phenylenediamine and 3-[(2-aminoaryl)amino]dimedone. The reaction proceeds in situ at ambient temperature without prior isolation of the natural (S)-(−)-perillaldehyde. Final products precipitate in the ethanolic reaction medium. 2D NMR and single-crystal X-ray diffraction studies were used to unequivocally characterize the structures in solution and in the solid state, respectively. Chiral HPLC analysis confirms the formation of unique enantiomers and diastereomeric mixtures. Full article

(This article belongs to the Special Issue Enantioselective Synthesis, Enantiomeric Separations and Chiral Recognition)

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20 pages, 2117 KiB

Open AccessArticle

Differentiation of Fresh and Processed Fruit Juices Using Volatile Composition

by Rosa Perestrelo, Catarina Silva, Pedro Silva, Sonia Medina and José S. Câmara

Molecules 2019, 24(5), 974; https://doi.org/10.3390/molecules24050974 - 10 Mar 2019

Cited by 21 | Viewed by 5826

Abstract

In the current study, a comprehensive approach based on headspace solid-phase microextraction (HS-SPME), combined with gas chromatography-quadrupole mass spectrometry (GC-qMS), was used to establish the volatile signature of fresh and processed fruit juices, obtained from the same batch of grapes, red fruits, orange, [...] Read more.

In the current study, a comprehensive approach based on headspace solid-phase microextraction (HS-SPME), combined with gas chromatography-quadrupole mass spectrometry (GC-qMS), was used to establish the volatile signature of fresh and processed fruit juices, obtained from the same batch of grapes, red fruits, orange, pear, and apple. This is a powerful tool for evaluating the impact of the production process on the volatomic pattern of fruit juice. A total of 169 volatile organic compounds (VOCs) belonging to different chemical groups were identified. Esters, carbonyl compounds, terpenoids, and alcohols are the major chemical groups in the investigated fruit juices. However, their contribution to the total volatile profile varied. Special attention should be paid to processed fruit juices to avoid the possible deleterious effects associated with the formation of furanic compounds (e.g., heat treatment), since their furanic content was significantly higher in comparison to that of fresh fruit juices. The knowledge obtained in the current study will allow for the introduction of modifications to the process involved in processing juice, which will improve the organoleptic characteristics of processed juices, contributing to a better acceptance by consumers. Furthermore, more assays should be performed to assess the effect of harvests, geography, and agronomy on the volatile profile of juices. Full article

(This article belongs to the Section Analytical Chemistry)

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12 pages, 775 KiB

Open AccessArticle

Green Methodologies for Copper(I)-Catalyzed Azide-Alkyne Cycloadditions: A Comparative Study

by Marissa Trujillo, Clayton Hull-Crew, Andrew Outlaw, Kevin Stewart, Loren Taylor, Laura George, Allison Duensing, Breanna Tracey and Allen Schoffstall

Molecules 2019, 24(5), 973; https://doi.org/10.3390/molecules24050973 - 10 Mar 2019

Cited by 15 | Viewed by 4207

Abstract

Successful copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions may be achieved by several methods. In this paper, four synthetic protocols were performed for direct comparison of time required for the synthesis, yield, and purity of the 1H-1,2,3-triazole products. The methods with Cu(I) catalysts [...] Read more.

Successful copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions may be achieved by several methods. In this paper, four synthetic protocols were performed for direct comparison of time required for the synthesis, yield, and purity of the 1H-1,2,3-triazole products. The methods with Cu(I) catalysts were conventional, microwave heating, solvent-free, and a method using glycerol solvent. The compounds synthesized in this paper were known non-fluorinated triazoles and new fluorinated triazoles. The results lead to the conclusion that the microwave method should be strongly considered for CuAAC syntheses. Full article

(This article belongs to the Special Issue Microwave-Mediated Chemistry)

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14 pages, 1626 KiB

Open AccessArticle

Effects of a Lysine-Involved Maillard Reaction on the Structure and In Vitro Activities of Polysaccharides from Longan Pulp

by Yang Yi, Miao-Miao Han, Fei Huang, Li-Mei Wang, Ting Min and Hong-Xun Wang

Molecules 2019, 24(5), 972; https://doi.org/10.3390/molecules24050972 - 10 Mar 2019

Cited by 22 | Viewed by 3930

Abstract

The effects of amino acid-involved Maillard reactions (MRs) on the structure and activities of longan pulp polysaccharides (LPs), which were heteropolysaccharides mainly composed of glucose, galactose, mannose, rhamnose, glucuronic acid, ribose, and galacturonic acid, were investigated. The changes of browning degree and molecular [...] Read more.

The effects of amino acid-involved Maillard reactions (MRs) on the structure and activities of longan pulp polysaccharides (LPs), which were heteropolysaccharides mainly composed of glucose, galactose, mannose, rhamnose, glucuronic acid, ribose, and galacturonic acid, were investigated. The changes of browning degree and molecular weight (M_w) distribution in the MR systems containing LPs and amino acids (lysine, proline, or glycine) indicated that lysine was more active in conjugating with LPs. The MR-modified LPs (MLPs) obtained via a 4 h MR between LPs and lysine showed obvious structural differences from LPs. Specifically, particle-like LPs contained 94% fractions with a M_w less than 7.07 kDa, by contrast, network-like MLPs contained 45% fractions with a M_w larger than 264.1 kDa. Moreover, MLPs showed stronger radical scavenging abilities and macrophage immunostimulating effects, but weaker cancer cell growth-inhibitory abilities. The results indicate that the amino acid-involved MR is a promising method to modify native polysaccharides for better biological properties. Full article

(This article belongs to the Special Issue The Fascinating Story of Natural Polysaccharides in Glycosciences: From Extraction to Applications)

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15 pages, 1247 KiB

Open AccessArticle

Synthesis of 1-(5-Chloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic Acid Derivatives and Their Antioxidant Activity

by Ingrida Tumosienė, Kristina Kantminienė, Ilona Jonuškienė, Artūras Peleckis, Sergey Belyakov and Vytautas Mickevičius

Molecules 2019, 24(5), 971; https://doi.org/10.3390/molecules24050971 - 9 Mar 2019

Cited by 11 | Viewed by 4888

Abstract

A series of novel 1-(5-chloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid derivatives containing chloro, hydroxyl, isopropyl, nitro, nitroso, and amino substituents at benzene ring and 1-(5-chloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carbohydrazide derivatives bearing heterocyclic moieties were synthesized. Antioxidant activity of the synthesized compounds was screened by DPPH radical scavenging method and reducing power [...] Read more.

A series of novel 1-(5-chloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid derivatives containing chloro, hydroxyl, isopropyl, nitro, nitroso, and amino substituents at benzene ring and 1-(5-chloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carbohydrazide derivatives bearing heterocyclic moieties were synthesized. Antioxidant activity of the synthesized compounds was screened by DPPH radical scavenging method and reducing power assay. A number of compounds were identified as potent antioxidants. Antioxidant activity of 1-(5-chloro-2-hydroxyphenyl)-4-(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one has been tested to be 1.5 times higher than that of a well-known antioxidant ascorbic acid. 1-(5-Chloro-2-hydroxyphenyl)-4-(4-methyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)pyrrolidin-2-one has shown 1.35 times higher antioxidant activity than that of vitamin C by DPPH radical scavenging method and optical density value of 1.149 in reducing power assay. The structure of 1-(5-chloro-2-hydroxyphenyl)-N-(1,3-dioxoisoindolin-2-yl)-5-oxopyrrolidine-3-carboxamide was unambiguously assigned by means of X-ray diffraction analysis data. Full article

(This article belongs to the Special Issue Synthesis and Characterization of Heterocyclic Compounds)

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