Molecules

16 pages, 2387 KiB

Open AccessArticle

A Metabolomics-Guided Exploration of the Phytochemical Constituents of Vernonia fastigiata with the Aid of Pressurized Hot Water Extraction and Liquid Chromatography-Mass Spectrometry

by Keabetswe Masike, Bradley S. Khoza, Paul A. Steenkamp, Elize Smit, Ian A. Dubery and Ntakadzeni E. Madala

Molecules 2017, 22(8), 1200; https://doi.org/10.3390/molecules22081200 - 27 Jul 2017

Cited by 23 | Viewed by 5545

Abstract

Vernonia fastigiata is a multi-purpose nutraceutical plant with interesting biological properties. However, very little is known about its phytochemical composition and, thus the need for its phytochemical characterization. In the current study, an environmentally friendly method, pressurized hot water extraction (PHWE), was used [...] Read more.

Vernonia fastigiata is a multi-purpose nutraceutical plant with interesting biological properties. However, very little is known about its phytochemical composition and, thus the need for its phytochemical characterization. In the current study, an environmentally friendly method, pressurized hot water extraction (PHWE), was used to extract metabolites from the leaves of V. fastigiata at various temperatures (50 °C, 100 °C, 150 °C and 200 °C). Ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-qTOF-MS) analysis in combination with chemometric methods, particularly principal component analysis (PCA) and liquid/gas chromatography mass spectrometry (XCMS) cloud plots, were used to descriptively visualize the data and identify significant metabolites extracted at various temperatures. A total of 25 different metabolites, including hydroxycinnamic acid derivatives, clovamide, deoxy-clovamide and flavonoids, were noted for the first time in this plant. Overall, an increase in extraction temperature resulted in an increase in metabolite extraction during PHWE. This study is the first scientific report on the phytochemical composition of V. fastigiata, providing insight into the components of the chemo-diversity of this important plant. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

11 pages, 1707 KiB

Open AccessArticle

Tetrabutylammonium Iodide–Promoted Thiolation of Oxindoles Using Sulfonyl Chlorides as Sulfenylation Reagents

by Xia Zhao, Aoqi Wei, Xiaoyu Lu and Kui Lu

Molecules 2017, 22(8), 1208; https://doi.org/10.3390/molecules22081208 - 1 Aug 2017

Cited by 14 | Viewed by 7124

Abstract

3-Sulfanyloxindoles were synthesised by triphenylphosphine-mediated transition-metal-free thiolation of oxindoles using sulfonyl chlorides as sulfenylation reagents. The above reaction was promoted by iodide anions, which was ascribed to the in situ conversion of sulfenyl chlorides into the more reactive sulfenyl iodides. Moreover, the thiolation [...] Read more.

3-Sulfanyloxindoles were synthesised by triphenylphosphine-mediated transition-metal-free thiolation of oxindoles using sulfonyl chlorides as sulfenylation reagents. The above reaction was promoted by iodide anions, which was ascribed to the in situ conversion of sulfenyl chlorides into the more reactive sulfenyl iodides. Moreover, the thiolation of 3-aryloxindoles was facilitated by bases. The use of a transition-metal-free protocol, readily available reagents, and mild reaction conditions make this protocol more practical for preparing 3-sulfanyloxindoles than traditional methods. Full article

(This article belongs to the Collection Heterocyclic Compounds)

► Show Figures

Graphical abstract

25 pages, 13079 KiB

Open AccessReview

Chalcone Derivatives: Promising Starting Points for Drug Design

by Marcelo N. Gomes, Eugene N. Muratov, Maristela Pereira, Josana C. Peixoto, Lucimar P. Rosseto, Pedro V. L. Cravo, Carolina H. Andrade and Bruno J. Neves

Molecules 2017, 22(8), 1210; https://doi.org/10.3390/molecules22081210 - 25 Jul 2017

Cited by 311 | Viewed by 26785

Abstract

Medicinal chemists continue to be fascinated by chalcone derivatives because of their simple chemistry, ease of hydrogen atom manipulation, straightforward synthesis, and a variety of promising biological activities. However, chalcones have still not garnered deserved attention, especially considering their high potential as chemical [...] Read more.

Medicinal chemists continue to be fascinated by chalcone derivatives because of their simple chemistry, ease of hydrogen atom manipulation, straightforward synthesis, and a variety of promising biological activities. However, chalcones have still not garnered deserved attention, especially considering their high potential as chemical sources for designing and developing new effective drugs. In this review, we summarize current methodological developments towards the design and synthesis of new chalcone derivatives and state-of-the-art medicinal chemistry strategies (bioisosterism, molecular hybridization, and pro-drug design). We also highlight the applicability of computer-assisted drug design approaches to chalcones and address how this may contribute to optimizing research outputs and lead to more successful and cost-effective drug discovery endeavors. Lastly, we present successful examples of the use of chalcones and suggest possible solutions to existing limitations. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

► Show Figures

Figure 1

19 pages, 8778 KiB

Open AccessArticle

Structure and Catalysis of Fe(III) and Cu(II) Microperoxidase-11 Interacting with the Positively Charged Interfaces of Lipids

by Tatiana Prieto, Vinicius Santana, Adrianne M. M. Britto, Juliana C. Araujo-Chaves, Otaciro R. Nascimento and Iseli L. Nantes-Cardoso

Molecules 2017, 22(8), 1212; https://doi.org/10.3390/molecules22081212 - 26 Jul 2017

Cited by 3 | Viewed by 5435

Abstract

Numerous applications have been described for microperoxidases (MPs) such as in photoreceptors, sensing, drugs, and hydrogen evolution. The last application was obtained by replacing Fe(III), the native central metal, by cobalt ion and inspired part of the present study. Here, the Fe(III) of [...] Read more.

Numerous applications have been described for microperoxidases (MPs) such as in photoreceptors, sensing, drugs, and hydrogen evolution. The last application was obtained by replacing Fe(III), the native central metal, by cobalt ion and inspired part of the present study. Here, the Fe(III) of MP-11 was replaced by Cu(II) that is also a stable redox state in aerated medium, and the structure and activity of both MPs were modulated by the interaction with the positively charged interfaces of lipids. Comparative spectroscopic characterization of Fe(III) and Cu(II)MP-11 in the studied media demonstrated the presence of high and low spin species with axial distortion. The association of the Fe(III)MP-11 with CTAB and Cu(II)MP-11 with DODAB affected the colloidal stability of the surfactants that was recovered by heating. This result is consistent with hydrophobic interactions of MPs with DODAB vesicles and CTAB micelles. The hydrophobic interactions decreased the heme accessibility to substrates and the Fe(III) MP-11catalytic efficiency. Cu(II)MP-11 challenged by peroxides exhibited a cyclic Cu(II)/Cu(I) interconversion mechanism that is suggestive of a mimetic Cu/ZnSOD (superoxide dismutase) activity against peroxides. Hydrogen peroxide-activated Cu(II)MP-11 converted Amplex Red^® to dihydroresofurin. This study opens more possibilities for technological applications of MPs. Full article

(This article belongs to the Special Issue Metallopeptides)

► Show Figures

Graphical abstract

13 pages, 1106 KiB

Open AccessArticle

Extracts Obtained from Pterocarpus angolensis DC and Ziziphus mucronata Exhibit Antiplasmodial Activity and Inhibit Heat Shock Protein 70 (Hsp70) Function

by Tawanda Zininga, Chinedu P. Anokwuru, Muendi T. Sigidi, Milingoni P. Tshisikhawe, Isaiah I. D. Ramaite, Afsatou N. Traoré, Heinrich Hoppe, Addmore Shonhai and Natasha Potgieter

Molecules 2017, 22(8), 1224; https://doi.org/10.3390/molecules22081224 - 28 Jul 2017

Cited by 16 | Viewed by 5765

Abstract

Malaria parasites are increasingly becoming resistant to currently used antimalarial therapies, therefore there is an urgent need to expand the arsenal of alternative antimalarial drugs. In addition, it is also important to identify novel antimalarial drug targets. In the current study, extracts of [...] Read more.

Malaria parasites are increasingly becoming resistant to currently used antimalarial therapies, therefore there is an urgent need to expand the arsenal of alternative antimalarial drugs. In addition, it is also important to identify novel antimalarial drug targets. In the current study, extracts of two plants, Pterocarpus angolensis and Ziziphus mucronata were obtained and their antimalarial functions were investigated. Furthermore, we explored the capability of the extracts to inhibit Plasmodium falciparum heat shock protein 70 (Hsp70) function. Heat shock protein 70 (Hsp70) are molecular chaperones whose function is to facilitate protein folding. Plasmodium falciparum the main agent of malaria, expresses two cytosol-localized Hsp70s: PfHsp70-1 and PfHsp70-z. The PfHsp70-z has been reported to be essential for parasite survival, while inhibition of PfHsp70-1 function leads to parasite death. Hence both PfHsp70-1 and PfHsp70-z are potential antimalarial drug targets. Extracts of P. angolensis and Z. mucronata inhibited the basal ATPase and chaperone functions of the two parasite Hsp70s. Furthermore, fractions of P. angolensis and Z. mucronata inhibited P. falciparum 3D7 parasite growth in vitro. The extracts obtained in the current study exhibited antiplasmodial activity as they killed P. falciparum parasites maintained in vitro. In addition, the findings further suggest that some of the compounds in P. angolensis and Z. mucronata may target parasite Hsp70 function. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

► Show Figures

Graphical abstract

13 pages, 5654 KiB

Open AccessArticle

Enhanced Uptake of Fe₃O₄ Nanoparticles by Intestinal Epithelial Cells in a State of Inflammation

by Gang Zhou, Jin Zhang, Chun Pan, Naicheng Liu, Zhenheng Wang and Junfeng Zhang

Molecules 2017, 22(8), 1240; https://doi.org/10.3390/molecules22081240 - 27 Jul 2017

Cited by 12 | Viewed by 5731

Abstract

Fe₃O₄ nanoparticles (Fe₃O₄ NPs) have been used for medical and drug applications, although the mechanisms of cellular uptake and transport need to be further evaluated under inflammatory conditions. In the present study, we investigated the uptake of [...] Read more.

Fe₃O₄ nanoparticles (Fe₃O₄ NPs) have been used for medical and drug applications, although the mechanisms of cellular uptake and transport need to be further evaluated under inflammatory conditions. In the present study, we investigated the uptake of Fe₃O₄ NPs (20, 50, 100, and 200 nm) by intestinal epithelial cells under inflammatory conditions via the light scattering of flow cytometry and inductively coupled plasma mass spectrometry (ICP-MS) techniques. The results of the correlation analysis indicated that the uptake ratios of Fe₃O₄ NPs by intestinal epithelial cells under inflammatory conditions were higher than those under the control conditions. The transportation ratios of NPs by inflammatory Caco-2 cells increased almost 0.8–1.2 fold compared to the control. The internalization of the Fe₃O₄ NPs in Caco-2 cells was mediated by clathrin-related routes in both the control and an interleukin-1β (IL-1β)-induced inflammatory condition. The level of mRNA of clathrin expressed in Caco-2 cells that were stimulated by IL-1β was almost three times more than the control. Consistently with the mRNA expression, the level of protein in the clathrin was upregulated. Additionally, it was verified for the first time that the expression of clathrin was upregulated in IL-1β-stimulated Caco-2 cells. Collectively, these results provided a further potential understanding about the mechanism of Fe₃O₄ NPs’ uptake by intestinal epithelial cells under inflammatory conditions. Full article

► Show Figures

Figure 1

24 pages, 6527 KiB

Open AccessArticle

Systems Biology Approach to Bioremediation of Nitroaromatics: Constraint-Based Analysis of 2,4,6-Trinitrotoluene Biotransformation by Escherichia coli

by Maryam Iman, Tabassom Sobati, Yunes Panahi and Meysam Mobasheri

Molecules 2017, 22(8), 1242; https://doi.org/10.3390/molecules22081242 - 14 Aug 2017

Cited by 11 | Viewed by 6212

Abstract

Microbial remediation of nitroaromatic compounds (NACs) is a promising environmentally friendly and cost-effective approach to the removal of these life-threating agents. Escherichia coli (E. coli) has shown remarkable capability for the biotransformation of 2,4,6-trinitro-toluene (TNT). Efforts to develop E. coli as [...] Read more.

Microbial remediation of nitroaromatic compounds (NACs) is a promising environmentally friendly and cost-effective approach to the removal of these life-threating agents. Escherichia coli (E. coli) has shown remarkable capability for the biotransformation of 2,4,6-trinitro-toluene (TNT). Efforts to develop E. coli as an efficient TNT degrading biocatalyst will benefit from holistic flux-level description of interactions between multiple TNT transforming pathways operating in the strain. To gain such an insight, we extended the genome-scale constraint-based model of E. coli to account for a curated version of major TNT transformation pathways known or evidently hypothesized to be active in E. coli in present of TNT. Using constraint-based analysis (CBA) methods, we then performed several series of in silico experiments to elucidate the contribution of these pathways individually or in combination to the E. coli TNT transformation capacity. Results of our analyses were validated by replicating several experimentally observed TNT degradation phenotypes in E. coli cultures. We further used the extended model to explore the influence of process parameters, including aeration regime, TNT concentration, cell density, and carbon source on TNT degradation efficiency. We also conducted an in silico metabolic engineering study to design a series of E. coli mutants capable of degrading TNT at higher yield compared with the wild-type strain. Our study, therefore, extends the application of CBA to bioremediation of nitroaromatics and demonstrates the usefulness of this approach to inform bioremediation research. Full article

► Show Figures

Figure 1

21 pages, 4206 KiB

Open AccessArticle

Structural Characterization of Cholestane Rhamnosides from Ornithogalum saundersiae Bulbs and Their Cytotoxic Activity against Cultured Tumor Cells

by Tomoki Iguchi, Minpei Kuroda, Rei Naito, Tomoyuki Watanabe, Yukiko Matsuo, Akihito Yokosuka and Yoshihiro Mimaki

Molecules 2017, 22(8), 1243; https://doi.org/10.3390/molecules22081243 - 25 Jul 2017

Cited by 18 | Viewed by 4633

Abstract

Previous phytochemical studies of the bulbs of Ornithogalum saundersiae, an ornamental perennial plant native to South Africa, resulted in the isolation of 29 new cholestane glycosides, some of which were structurally unique and showed potent cytotoxic activity against cultured tumor cell lines. [...] Read more.

Previous phytochemical studies of the bulbs of Ornithogalum saundersiae, an ornamental perennial plant native to South Africa, resulted in the isolation of 29 new cholestane glycosides, some of which were structurally unique and showed potent cytotoxic activity against cultured tumor cell lines. Therefore, we aimed to perform further phytochemical examinations of methanolic extracts obtained from Ornithogalum saundersiae bulbs, isolating 12 new cholestane rhamnosides (1–12) and seven known compounds (13–19). The structures of the new compounds (1–12) were identified via NMR-based structural characterization methods, and through a sequence of chemical transformations followed by spectroscopic and chromatographic analysis. The cytotoxic activity of the isolated compounds (1–19) and the derivatives (1a and 6a) against HL-60 human promyelocytic leukemia cells and A549 human lung adenocarcinoma cells was evaluated. Compounds 10–12, 16, and 17 showed cytotoxicity against both HL-60 and A549 cells. Compound 11 showed potent cytotoxicity with an IC₅₀ value of 0.16 µM against HL-60 cells and induced apoptotic cell death via a mitochondrion-independent pathway. Full article

► Show Figures

Figure 1

16 pages, 616 KiB

Open AccessReview

Electronic Spectroscopy of Phthalocyanine and Porphyrin Derivatives in Superfluid Helium Nanodroplets

by Alkwin Slenczka

Molecules 2017, 22(8), 1244; https://doi.org/10.3390/molecules22081244 - 25 Jul 2017

Cited by 11 | Viewed by 5828

Abstract

Phthalocyanine and porphyrin were among the first organic compounds investigated by means of electronic spectroscopy in superfluid helium nanodroplets. Superfluid helium nanodroplets serve as a very gentle host system for preparing cold and isolated molecules. The uniqueness of helium nanodroplets is with respect [...] Read more.

Phthalocyanine and porphyrin were among the first organic compounds investigated by means of electronic spectroscopy in superfluid helium nanodroplets. Superfluid helium nanodroplets serve as a very gentle host system for preparing cold and isolated molecules. The uniqueness of helium nanodroplets is with respect to the superfluid phase which warrants the vanishing viscosity and, thus, minimal perturbation of the dopant species at a temperature as low as 0.37 K. These are ideal conditions for the study of molecular spectra in order to analyze structures as well as dynamic processes. Besides the investigation of the dopant species itself, molecular spectroscopy in helium droplets provides information on the helium droplet and in particular on microsolvation. This article, as part of a special issue on phthalocyanines and porphyrins, reviews electronic spectroscopy of phthalocyanine and porphyrin compounds in superfluid helium nanodroplets. In addition to the wide variety of medical as well as technical and synthetical aspects, this article discusses electronic spectroscopy of phthalocyanines and porphyrins in helium droplets in order to learn about both the dopant and the helium environment. Full article

(This article belongs to the Special Issue Porphyrins and Phthalocyanines: Synthesis, Properties and Applications)

► Show Figures

Graphical abstract

8 pages, 1833 KiB

Open AccessArticle

Diarylethenes Display In Vitro Anti-TB Activity and Are Efficient Hits Targeting the Mycobacterium tuberculosis HU Protein

by María Angélica Suarez, Jhesua Valencia, Christian Camilo Cadena, Raktim Maiti, Chandreyee Datta, Gloria Puerto, José Hipólito Isaza, Homero San Juan, Valakunja Nagaraja and Juan David Guzman

Molecules 2017, 22(8), 1245; https://doi.org/10.3390/molecules22081245 - 25 Jul 2017

Cited by 12 | Viewed by 5687

Abstract

Tuberculosis continues to be a great source of concern in global health because of the large reservoir of humans infected with the bacilli and the appearance of clinical isolates resistant to a wide array of anti-tuberculosis drugs. New drugs with novel mechanisms of [...] Read more.

Tuberculosis continues to be a great source of concern in global health because of the large reservoir of humans infected with the bacilli and the appearance of clinical isolates resistant to a wide array of anti-tuberculosis drugs. New drugs with novel mechanisms of action on new targets are urgently required to reduce global tuberculosis burden. Mycobacterium tuberculosis nucleoid associated protein (NAP) HU has been shown to be druggable and essential for the organism’s survival. In this study, four diarylethenes were synthesized using a one-pot decarboxylated Heck-coupling of coumaric acids with iodoanisoles. The prepared compounds 1–4 were tested for their in vitro growth inhibition of M. tuberculosis H37Rv using the spot culture growth inhibition assay, displaying minimum inhibitory concentrations between 9 and 22 µM. Their cytotoxicity against BHK-21 cell line showed half inhibition at concentrations between 98 and 729 µM. The most selective hit (SI = 81), demonstrated inhibition of M. tuberculosis HU protein involved in maintaining bacterial genome architecture. Full article

(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)

► Show Figures

Graphical abstract

12 pages, 5630 KiB

Open AccessArticle

Effects of P-Glycoprotein on the Transport of DL0410, a Potential Multifunctional Anti-Alzheimer Agent

by Xiaocong Pang, Lin Wang, De Kang, Ying Zhao, Song Wu, Ai-Lin Liu and Guan-Hua Du

Molecules 2017, 22(8), 1246; https://doi.org/10.3390/molecules22081246 - 25 Jul 2017

Cited by 15 | Viewed by 6952

Abstract

In our study, we attempted to investigate the influences of P-glycoprotein (P-gp) on DL0410, a novel synthetic molecule for Alzheimer’s disease (AD) treatment, for intestinal absorption and blood-brain barrier permeability in vitro and related binding mechanisms in silico. Caco-2, MDCK, and MDCK-MDR1 cells [...] Read more.

In our study, we attempted to investigate the influences of P-glycoprotein (P-gp) on DL0410, a novel synthetic molecule for Alzheimer’s disease (AD) treatment, for intestinal absorption and blood-brain barrier permeability in vitro and related binding mechanisms in silico. Caco-2, MDCK, and MDCK-MDR1 cells were utilized for transport studies, and homology modelling of human P-gp was built for further docking study to uncover the binding mode of DL0410. The results showed that the apparent permeability (Papp) value of DL0410 was approximately 1 × 10⁻⁶ cm/s, indicating the low permeability of DL0410. With the presence of verapamil, the directional transport of DL0410 disappeared in Caco-2 and MDCK-MDR1 cells, suggesting that DL0410 should be a substrate of P-gp, which was also confirmed by P-gp ATPase assay. In addition, DL0410 could competitively inhibit the transport of Rho123, a P-gp known substrate. According to molecular docking, we also found that DL0410 could bind to the drug binding pocket (DBP), but not the nucleotide binding domain (NBD). In conclusion, DL0410 was a substrate as well as a competitive inhibitor of P-gp, and P-gp had a remarkable impact on the intestine and brain permeability of DL0410, which is of significance for drug research and development. Full article

(This article belongs to the Special Issue Neuroprotective Agents)

► Show Figures

Graphical abstract

17 pages, 2049 KiB

Open AccessArticle

Multifunctional Cinnamic Acid Derivatives

by Aikaterini Peperidou, Eleni Pontiki, Dimitra Hadjipavlou-Litina, Efstathia Voulgari and Konstantinos Avgoustakis

Molecules 2017, 22(8), 1247; https://doi.org/10.3390/molecules22081247 - 25 Jul 2017

Cited by 53 | Viewed by 10071

Abstract

Our research to discover potential new multitarget agents led to the synthesis of 10 novel derivatives of cinnamic acids and propranolol, atenolol, 1-adamantanol, naphth-1-ol, and (benzylamino) ethan-1-ol. The synthesized molecules were evaluated as trypsin, lipoxygenase and lipid peroxidation inhibitors and for their cytotoxicity. [...] Read more.

Our research to discover potential new multitarget agents led to the synthesis of 10 novel derivatives of cinnamic acids and propranolol, atenolol, 1-adamantanol, naphth-1-ol, and (benzylamino) ethan-1-ol. The synthesized molecules were evaluated as trypsin, lipoxygenase and lipid peroxidation inhibitors and for their cytotoxicity. Compound 2b derived from phenoxyphenyl cinnamic acid and propranolol showed the highest lipoxygenase (LOX) inhibition (IC₅₀ = 6 μΜ) and antiproteolytic activity (IC₅₀ = 0.425 μΜ). The conjugate 1a of simple cinnamic acid with propranolol showed the higher antiproteolytic activity (IC₅₀ = 0.315 μΜ) and good LOX inhibitory activity (IC₅₀ = 66 μΜ). Compounds 3a and 3b, derived from methoxylated caffeic acid present a promising combination of in vitro inhibitory and antioxidative activities. The S isomer of 2b also presented an interesting multitarget biological profile in vitro. Molecular docking studies point to the fact that the theoretical results for LOX-inhibitor binding are identical to those from preliminary in vitro study. Full article

(This article belongs to the Special Issue Polypharmacology and Multitarget Drug Discovery)

► Show Figures

Graphical abstract

9 pages, 776 KiB

Open AccessArticle

Rapid Mechanistic Evaluation and Parameter Estimation of Putative Inhibitors in a Single-Step Progress-Curve Analysis: The Case of Horse Butyrylcholinesterase

by Jure Stojan

Molecules 2017, 22(8), 1248; https://doi.org/10.3390/molecules22081248 - 26 Jul 2017

Cited by 7 | Viewed by 4863

Abstract

Highly efficient and rapid lead compound evaluation for estimation of inhibition parameters and type of inhibition is proposed. This is based on a single progress-curve measurement in the presence of each candidate compound, followed by the simultaneous analysis of all of these curves [...] Read more.

Highly efficient and rapid lead compound evaluation for estimation of inhibition parameters and type of inhibition is proposed. This is based on a single progress-curve measurement in the presence of each candidate compound, followed by the simultaneous analysis of all of these curves using the ENZO enzyme kinetics suite, which can be implemented as a web application. In the first step, all of the candidate ligands are tested as competitive inhibitors. Where the theoretical curves do not correspond to the experimental data, minimal additional measurements are added, with subsequent processing according to modified reaction mechanisms. Full article

(This article belongs to the Special Issue The Cholinesterases—Structure, Mechanism, Function and Drug Design: The 25th Anniversary of the Solution of the Crystal Structure of Acetylcholinesterase by Joel L. Sussman and Israel Silman)

► Show Figures

Figure 1

3 pages, 198 KiB

Open AccessEditorial

Recent Advances in Plant Phenolics

by Daniel A. Jacobo-Velázquez and Luis Cisneros-Zevallos

Molecules 2017, 22(8), 1249; https://doi.org/10.3390/molecules22081249 - 26 Jul 2017

Cited by 11 | Viewed by 4317

Abstract

The scientific interest in plant phenolics as chemopreventive and therapeutic agents against chronic and degenerative diseases has been increasing since the late 1990s, when the French paradox was associated with the high intake of phenolics present in red wine [1]. [...]
Full article

(This article belongs to the Special Issue Recent Advances in Plant Phenolics)

14 pages, 3056 KiB

Open AccessArticle

A Novel Fluoroimmunoassay for Detecting Ruscogenin with Monoclonal Antibodies Conjugated with CdSe/ZnS Quantum Dots

by Hongwei Zhang, Tao Xu, Lan Gao, Xiufeng Liu, Jihua Liu and Boyang Yu

Molecules 2017, 22(8), 1250; https://doi.org/10.3390/molecules22081250 - 26 Jul 2017

Cited by 11 | Viewed by 5484

Abstract

Ruscogenin (RUS) is a steroidal sapogenin found in Ruscus aculeatus and Ophiopogon japonicus with several pharmacological activities. In the work reported herein, a novel method termed competitive fluorescence-linked immunosorbent assay (cFLISA) based on monoclonal antibodies (mAbs) coupled with quantum dots (QDs) was developed [...] Read more.

Ruscogenin (RUS) is a steroidal sapogenin found in Ruscus aculeatus and Ophiopogon japonicus with several pharmacological activities. In the work reported herein, a novel method termed competitive fluorescence-linked immunosorbent assay (cFLISA) based on monoclonal antibodies (mAbs) coupled with quantum dots (QDs) was developed for the quick and sensitive determination of RUS in biological samples. The mAbs against RUS were conjugated with CdSe/ZnS QDs by the crossing-linking reagents and an indirect cFLISA method was developed. There was a good linear relationship between inhibition efficiency and logarithm concentration of RUS which was varied from 0.1 to 1000 ng/mL. The IC₅₀ and limit of detection (LOD) were 9.59 ng/mL and 0.016 ng/mL respectively, which much lower than the enzyme-linked immunosorbent assay (ELISA) method. The recoveries in plasma and tissues were ranged from 82.3% to 107.0% and the intra- and inter-day precision values were below 15%. The developed cFLISA has been successfully applied to the measurement of the concentrations of RUS in biological samples of rats, and showed great potential for the tissue distribution study of RUS. The cFLISA method may provide a valuable tool for the analysis of small molecules in biological samples and such an approach could be applied to other natural products. Full article

(This article belongs to the Special Issue New Methodologies in Natural Product Analytics and Structure Elucidation)

► Show Figures

Graphical abstract

7 pages, 779 KiB

Open AccessArticle

Synthesis of Compounds of the Pyrimidine Series Based on the Reactions of 3-Arylmethylidenefuran-2(3H)-ones with N,N-Binucleophilic Reagents

by Tatyana Aniskova, Vyacheslav Grinev and Alevtina Yegorova

Molecules 2017, 22(8), 1251; https://doi.org/10.3390/molecules22081251 - 28 Jul 2017

Cited by 3 | Viewed by 5899

Abstract

The arylmethylidene derivatives of furan-2(3H)-ones are important building blocks for the synthesis of various heterocyclic compounds containing pyrimidine and pyridazine structural fragments, analogues of nitrogen-containing bases of pyrimidine series. In order to continue the development of constructing of molecules containing pyridine [...] Read more.

The arylmethylidene derivatives of furan-2(3H)-ones are important building blocks for the synthesis of various heterocyclic compounds containing pyrimidine and pyridazine structural fragments, analogues of nitrogen-containing bases of pyrimidine series. In order to continue the development of constructing of molecules containing pyridine and pyridazine fragments, this article is devoted to the synthesis of new biologically active compounds with these moieties. The introduction of a heterocyclic chromenone fragment changes the previously observed 5-R-3-arylmethylidenefuran-2(3H)-ones route of reaction with guanidine carbonate and leads to 3-[(2-amino-4-(2-hydroxyphenyl)pyrimidin-5-yl)methylene]-5-phenylfuran-2(3H)-ones (2a–d). The structure of the reaction products depends on the nature of the aromatic substituent at the C-3 position of the furanone ring. The interaction of 5-aryl-3-arylmethylidenefuran-2(3H)-ones (1e–h) with thiourea in the basic medium leads to the isolation of 5-(2-oxo-2-phenylethyl)-6-aryl-2-thioxotetrahydropyrimidine-4(1H)-ones (3a–d), demonstrating pronounced plant-growth regulatory activity. Optimal conditions for all discussed processes were developed. Full article

(This article belongs to the Special Issue Nucleoside and Nucleotide Analogues)

► Show Figures

Graphical abstract

11 pages, 2056 KiB

Open AccessArticle

A Lanosteryl Triterpene from Protorhus longifolia Improves Glucose Tolerance and Pancreatic Beta Cell Ultrastructure in Type 2 Diabetic Rats

by Sihle E. Mabhida, Rebamang A. Mosa, Dambudzo Penduka, Foluso O. Osunsanmi, Phiwayinkosi V. Dludla, Tryana G. Djarova and Andy R. Opoku

Molecules 2017, 22(8), 1252; https://doi.org/10.3390/molecules22081252 - 26 Jul 2017

Cited by 15 | Viewed by 5868

Abstract

Type 2 diabetes remains one of the leading causes of death worldwide. Persistent hyperglycemia within a diabetic state is implicated in the generation of oxidative stress and aggravated inflammation that is responsible for accelerated modification of pancreatic beta cell structure. Here we investigated [...] Read more.

Type 2 diabetes remains one of the leading causes of death worldwide. Persistent hyperglycemia within a diabetic state is implicated in the generation of oxidative stress and aggravated inflammation that is responsible for accelerated modification of pancreatic beta cell structure. Here we investigated whether a lanosteryl triterpene, methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA-3), isolated from Protorhus longifolia can improve glucose tolerance and pancreatic beta cell ultrastructure by reducing oxidative stress and inflammation in high fat diet and streptozotocin-induced type 2 diabetes in rats. In addition to impaired glucose tolerance, the untreated diabetic rats showed increased fasting plasma glucose and C-peptide levels. These untreated diabetic rats further demonstrated raised cholesterol, interleukin-6 (IL-6), and lipid peroxidation levels as well as a destroyed beta cell ultrastructure. Treatment with RA-3 was as effective as metformin in improving glucose tolerance and antioxidant effect in the diabetic rats. Interestingly, RA-3 displayed a slightly more enhanced effect than metformin in reducing elevated IL-6 levels and in improving beta cell ultrastructure. Although the involved molecular mechanisms remain to be established, RA-3 demonstrates a strong potential to improve pancreatic beta cell ultrastructure by attenuating impaired glucose tolerance, reducing oxidative stress and inflammation. Full article

(This article belongs to the Special Issue Natural Products and Chronic Diseases)

► Show Figures

Figure 1

11 pages, 3583 KiB

Open AccessArticle

Synthesis, Characterization and In Vitro Evaluation of a Novel Glycol Chitosan-EDTA Conjugate to Inhibit Aminopeptidase-Mediated Degradation of Thymopoietin Oligopeptides

by Jiao Feng, Yan Chen, Feng Li, Lili Cui, Nianqiu Shi, Wei Kong and Yong Zhang

Molecules 2017, 22(8), 1253; https://doi.org/10.3390/molecules22081253 - 26 Jul 2017

Cited by 16 | Viewed by 6251

Abstract

In this study, a novel conjugate consisting of glycol chitosan (GCS) and ethylene diamine tetraacetic acid (EDTA) was synthesized and characterized in terms of conjugation and heavy metal ion chelating capacity. Moreover, its potential application as a metalloenzyme inhibitor was evaluated with three [...] Read more.

In this study, a novel conjugate consisting of glycol chitosan (GCS) and ethylene diamine tetraacetic acid (EDTA) was synthesized and characterized in terms of conjugation and heavy metal ion chelating capacity. Moreover, its potential application as a metalloenzyme inhibitor was evaluated with three thymopoietin oligopeptides in the presence of leucine aminopeptidase. The results from FTIR and NMR spectra revealed that the covalent attachment of EDTA to GCS was achieved by the formation of amide bonds between the carboxylic acid group of EDTA and amino groups of GCS. The conjugated EDTA lost part of its chelating capacity to cobalt ions compared with free EDTA as evidenced by the results of cobalt ion chelation-mediated fluorescence recovery of calcein. However, further investigation confirmed that GCS-EDTA at low concentrations significantly inhibited leucine aminopeptidase-mediated degradation of all thymopoietin oligopeptides. Full article

(This article belongs to the Special Issue Chitin and Chitosan Derivatives: Biological Activities and Application)

► Show Figures

Figure 1

16 pages, 9628 KiB

Open AccessArticle

Evaluation of Novel Dual Acetyl- and Butyrylcholinesterase Inhibitors as Potential Anti-Alzheimer’s Disease Agents Using Pharmacophore, 3D-QSAR, and Molecular Docking Approaches

by Xiaocong Pang, Hui Fu, Shilun Yang, Lin Wang, Ai-Lin Liu, Song Wu and Guan-Hua Du

Molecules 2017, 22(8), 1254; https://doi.org/10.3390/molecules22081254 - 26 Jul 2017

Cited by 23 | Viewed by 5792

Abstract

DL0410, containing biphenyl and piperidine skeletons, was identified as an acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitor through high-throughput screening assays, and further studies affirmed its efficacy and safety for Alzheimer’s disease treatment. In our study, a series of novel DL0410 derivatives were evaluated [...] Read more.

DL0410, containing biphenyl and piperidine skeletons, was identified as an acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitor through high-throughput screening assays, and further studies affirmed its efficacy and safety for Alzheimer’s disease treatment. In our study, a series of novel DL0410 derivatives were evaluated for inhibitory activities towards AChE and BuChE. Among these derivatives, compounds 6-1 and 7-6 showed stronger AChE and BuChE inhibitory activities than DL0410. Then, pharmacophore modeling and three-dimensional quantitative structure activity relationship (3D-QSAR) models were performed. The R² of AChE and BuChE 3D-QSAR models for training set were found to be 0.925 and 0.883, while that of the test set were 0.850 and 0.881, respectively. Next, molecular docking methods were utilized to explore the putative binding modes. Compounds 6-1 and 7-6 could interact with the amino acid residues in the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE/BuChE, which was similar with DL0410. Kinetics studies also suggested that the three compounds were all mixed-types of inhibitors. In addition, compound 6-1 showed better absorption and blood brain barrier permeability. These studies provide better insight into the inhibitory behaviors of DL0410 derivatives, which is beneficial for rational design of AChE and BuChE inhibitors in the future. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

13 pages, 244 KiB

Open AccessReview

Lactic Acid Bacteria and Their Bacteriocins: Classification, Biosynthesis and Applications against Uropathogens: A Mini-Review

by Mduduzi Paul Mokoena

Molecules 2017, 22(8), 1255; https://doi.org/10.3390/molecules22081255 - 26 Jul 2017

Cited by 482 | Viewed by 27828

Abstract

Several lactic acid bacteria (LAB) isolates from the Lactobacillus genera have been applied in food preservation, partly due to their antimicrobial properties. Their application in the control of human pathogens holds promise provided appropriate strains are scientifically chosen and a suitable mode of [...] Read more.

Several lactic acid bacteria (LAB) isolates from the Lactobacillus genera have been applied in food preservation, partly due to their antimicrobial properties. Their application in the control of human pathogens holds promise provided appropriate strains are scientifically chosen and a suitable mode of delivery is utilized. Urinary tract infection (UTI) is a global problem, affecting mainly diabetic patients and women. Many uropathogens are developing resistance to commonly used antibiotics. There is a need for more research on the ability of LAB to inhibit uropathogens, with a view to apply them in clinical settings, while adhering to strict selection guidelines in the choice of candidate LAB. While several studies have indicated the ability of LAB to elicit inhibitory activities against uropathogens in vitro, more in vivo and clinical trials are essential to validate the efficacy of LAB in the treatment and prevention of UTI. The emerging applications of LAB such as in adjuvant therapy, oral vaccine development, and as purveyors of bioprotective agents, are relevant in infection prevention and amelioration. Therefore, this review explores the potential of LAB isolates and their bacteriocins to control uropathogens, with a view to limit clinical use of antibiotics. Full article

(This article belongs to the Section Natural Products Chemistry)

18 pages, 4028 KiB

Open AccessArticle

Phenolic Compounds Contained in Little-known Wild Fruits as Antiadhesive Agents Against the Beverage-Spoiling Bacteria Asaia spp.

by Hubert Antolak, Agata Czyzowska, Marijana Sakač, Aleksandra Mišan, Olivera Đuragić and Dorota Kregiel

Molecules 2017, 22(8), 1256; https://doi.org/10.3390/molecules22081256 - 28 Jul 2017

Cited by 39 | Viewed by 6330

Abstract

The aim of the study was to evaluate antioxidant activity and total phenolic content of juice from three different types of fruits: elderberry (Sambucus nigra), lingonberry (Vaccinium vitis-idaea) and cornelian cherry (Cornus mas), and their action against [...] Read more.

The aim of the study was to evaluate antioxidant activity and total phenolic content of juice from three different types of fruits: elderberry (Sambucus nigra), lingonberry (Vaccinium vitis-idaea) and cornelian cherry (Cornus mas), and their action against adhesion of bacterial strains of Asaia lannensis and Asaia bogorensis isolated from spoiled soft drinks. The antioxidant profiles were determined by total antioxidant capacity (2,2-diphenyl-1-picrylhydrazyl, DPPH), and ferric-reducing antioxidant power (FRAP). Additionally, total polyphenol content (TPC) was investigated. Chemical compositions of juices were tested using the chromatographic techniques: high-performance liquid chromatography (HPLC) and liquid chromatography–mass spectrometry (LC-MS). Adhesion properties of Asaia spp. cells to various abiotic materials were evaluated by luminometry, plate count and fluorescence microscopy. Antioxidant activity of fruit juices expressed as inhibitory concentration (IC₅₀) ranged from 0.042 ± 0.001 (cornelian cherry) to 0.021 ± 0.001 g/mL (elderberry). TPC ranged from 8.02 ± 0.027 (elderberry) to 2.33 ± 0.013 mg/mL (cornelian cherry). Cyanidin-3-sambubioside-5-glucoside, cyanidin-3-glucoside, and cyanidin-3-sambubioside were detected as the major anthocyanins and caffeic, cinnamic, gallic, protocatechuic, and p-coumaric acids as the major phenolic acids. A significant linear correlation was noted between TPC and antioxidant capacity. In the presence of fruit juices a significant decrease of bacterial adhesion from 74% (elderberry) to 67% (lingonberry) was observed. The high phenolic content indicated that these compounds may contribute to the reduction of Asaia spp. adhesion. Full article

(This article belongs to the Special Issue Antibacterial Materials and Coatings)

► Show Figures

Figure 1

14 pages, 5407 KiB

Open AccessArticle

Synthesis and Identification of Novel Berberine Derivatives as Potent Inhibitors against TNF-α-Induced NF-κB Activation

by Yan-Xiang Wang, Lu Liu, Qing-Xuan Zeng, Tian-Yun Fan, Jian-Dong Jiang, Hong-Bin Deng and Dan-Qing Song

Molecules 2017, 22(8), 1257; https://doi.org/10.3390/molecules22081257 - 27 Jul 2017

Cited by 37 | Viewed by 7286

Abstract

Twenty-three new berberine (BBR) analogues defined on substituents of ring D were synthesized and evaluated for their activity for suppression of tumor necrosis factor (TNF)-α-induced nuclear factor (NF)-κB activation. Structure–activity relationship (SAR) analysis indicated that suitable tertiary/quaternary carbon substitutions at the 9-position or [...] Read more.

Twenty-three new berberine (BBR) analogues defined on substituents of ring D were synthesized and evaluated for their activity for suppression of tumor necrosis factor (TNF)-α-induced nuclear factor (NF)-κB activation. Structure–activity relationship (SAR) analysis indicated that suitable tertiary/quaternary carbon substitutions at the 9-position or rigid fragment at position 10 might be beneficial for enhancing their anti-inflammatory potency. Among them, compounds 2d, 2e, 2i and 2j exhibited satisfactory inhibitory potency against NF-κB activation, with an inhibitory rate of around 90% (5 μM), much better than BBR. A preliminary mechanism study revealed that all of them could inhibit TNF-α-induced NF-κB activation via impairing IκB kinase (IKK) phosphorylation as well as cytokines interleukin (IL)-6 and IL-8 induced by TNF-α. Therefore, the results provided powerful information on further structural modifications and development of BBR derivatives into a new class of anti-inflammatory candidates for the treatment of inflammatory diseases. Full article

(This article belongs to the Special Issue Anti-inflammatory Agents)

► Show Figures

Graphical abstract

10 pages, 2853 KiB

Open AccessArticle

Study of the Interactions of Bovine Serum Albumin with the New Anti-Inflammatory Agent 4-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-N′-[(4-ethoxy-phenyl)methylidene]benzohydrazide Using a Multi-Spectroscopic Approach and Molecular Docking

by Tanveer A. Wani, Ahmed H. Bakheit, Abdul-Rahman A. Al-Majed, Mashooq A. Bhat and Seema Zargar

Molecules 2017, 22(8), 1258; https://doi.org/10.3390/molecules22081258 - 27 Jul 2017

Cited by 56 | Viewed by 8076

Abstract

The lipophilic derivative of thalidomide (4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N′-[(4-ethoxyphenyl)methylidene]benzohydrazide, 6P) was synthesized to enhance its characteristics and efficacy. Earlier studies have proved the immunomodulatory and anti-inflammatory effects of 6P. In this study the interaction between bovine serum albumin (BSA) and [...] Read more.

The lipophilic derivative of thalidomide (4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N′-[(4-ethoxyphenyl)methylidene]benzohydrazide, 6P) was synthesized to enhance its characteristics and efficacy. Earlier studies have proved the immunomodulatory and anti-inflammatory effects of 6P. In this study the interaction between bovine serum albumin (BSA) and 6P was studied using a multi-spectroscopic approach which included UV spectrophotometry, spectrofluorimetry and three dimensional spectrofluorometric and molecular docking studies. Static quenching was involved in quenching the fluorescence of BSA by 6P, because a complex formation occurred between the 6P and BSA. The binding constant decreased with higher temperature and was in the range of 2.5 × 10⁵–4.8 × 10³ L mol⁻¹ suggesting an unstable complex at higher temperatures. A single binding site was observed and the the site probe experiments showed site II (sub-domain IIIA) of BSA as the binding site for 6P. The negative values of ∆G⁰, ∆H⁰ and ∆S⁰ at (298/303/308 K) indicated spontaneous binding between 6P and BSA as well as the interaction was enthalpy driven and van der Waals forces and hydrogen bonding were involved in the interaction. The docking results and the results from the experimental studies are complimentary to each other and confirm that 6P binds at site II (sub-domain IIIA) of BSA. Full article

(This article belongs to the Special Issue Anti-inflammatory Agents)

► Show Figures

Figure 1

20 pages, 1389 KiB

Open AccessReview

Advanced Growth Factor Delivery Systems in Wound Management and Skin Regeneration

by Jin Woo Park, Seung Rim Hwang and In-Soo Yoon

Molecules 2017, 22(8), 1259; https://doi.org/10.3390/molecules22081259 - 27 Jul 2017

Cited by 309 | Viewed by 22231

Abstract

Growth factors are endogenous signaling molecules that regulate cellular responses required for wound healing processes such as migration, proliferation, and differentiation. However, exogenous application of growth factors has limited effectiveness in clinical settings due to their low in vivo stability, restricted absorption through [...] Read more.

Growth factors are endogenous signaling molecules that regulate cellular responses required for wound healing processes such as migration, proliferation, and differentiation. However, exogenous application of growth factors has limited effectiveness in clinical settings due to their low in vivo stability, restricted absorption through skin around wound lesions, elimination by exudation prior to reaching the wound area, and other unwanted side effects. Sophisticated systems to control the spatio-temporal delivery of growth factors are required for the effective and safe use of growth factors as regenerative treatments in clinical practice, such as biomaterial-based drug delivery systems (DDSs). The current review describes the roles of growth factors in wound healing, their clinical applications for the treatment of chronic wounds, and advances in growth factor-loaded DDSs for enhanced wound healing, focusing on micro- and nano-particulate systems, scaffolds, hydrogels, and other miscellaneous systems. Full article

► Show Figures

Figure 1

17 pages, 1398 KiB

Open AccessArticle

Pharmacokinetic Study of Biotransformation Products from an Anxiolytic Fraction of Tilia americana

by Virgilio Alfonso Juárez Ramírez, María Isabel Jiménez-Beltrán, Alejandro Zamilpa, Maribel Herrera-Ruiz, Rodolfo Abarca-Vargas, Galia Lombardo-Earl, Jaime Tortoriello and Enrique Jiménez-Ferrer

Molecules 2017, 22(8), 1260; https://doi.org/10.3390/molecules22081260 - 27 Jul 2017

Cited by 6 | Viewed by 3944

Abstract

An anxiolytic fraction of Tilia americana standardized in tiliroside, rutin, quercitrin, quercetin glucoside, and kaempferol was obtained. After oral administration of the fraction, the above-mentioned flavonoids were not detected in plasma over 24 h. However, meta and para hydroxyphenylacetic acid and dihydroxyphenylacetic acid [...] Read more.

An anxiolytic fraction of Tilia americana standardized in tiliroside, rutin, quercitrin, quercetin glucoside, and kaempferol was obtained. After oral administration of the fraction, the above-mentioned flavonoids were not detected in plasma over 24 h. However, meta and para hydroxyphenylacetic acid and dihydroxyphenylacetic acid (m-HPAA, p-HPAA and DOPAC) were monitored. These are the biotransformation compounds of the aglycones of kaempferol and quercetin; these aglycones are products of the other flavonoids present in the anxiolytic fraction. The analytical methods (HPLC) for flavonoids and the related compounds (m-HPAA, p-HPAA and DOPAC) were validated, determining the parameters of accuracy, precision, specificity or selectivity, limit of detection, quantification range, and robustness. The pharmacokinetic assay was performed with ICR mice strains, which were given 200 mg/kg of the standardized active fraction. The results of validation of the analytical methods were obtained, allowing it to be established in a validated way that no flavonoids present in the anxiolytic fraction of T. americana were detected in plasma. However, detection and follow up was possible for the serum levels of m-HPAA, p-HPAA, and DOPAC. The three compounds follow a two-compartment model with very similar parameters between m-HPAA and p-HPAA, some being different from the ones characterized in the pharmacokinetics of DOPAC. Full article

► Show Figures

Figure 1

13 pages, 3438 KiB

Open AccessArticle

Distinct Mechanisms of Biotic and Chemical Elicitors Enable Additive Elicitation of the Anticancer Phytoalexin Glyceollin I

by Kelli Farrell, Md Asraful Jahan and Nik Kovinich

Molecules 2017, 22(8), 1261; https://doi.org/10.3390/molecules22081261 - 27 Jul 2017

Cited by 27 | Viewed by 7991

Abstract

Phytoalexins are metabolites biosynthesized in plants in response to pathogen, environmental, and chemical stresses that often have potent bioactivities, rendering them promising for use as therapeutics or scaffolds for pharmaceutical development. Glyceollin I is an isoflavonoid phytoalexin from soybean that exhibits potent anticancer [...] Read more.

Phytoalexins are metabolites biosynthesized in plants in response to pathogen, environmental, and chemical stresses that often have potent bioactivities, rendering them promising for use as therapeutics or scaffolds for pharmaceutical development. Glyceollin I is an isoflavonoid phytoalexin from soybean that exhibits potent anticancer activities and is not economical to synthesize. Here, we tested a range of source tissues from soybean, in addition to chemical and biotic elicitors, to understand how to enhance the bioproduction of glyceollin I. Combining the inorganic chemical silver nitrate (AgNO₃) with the wall glucan elicitor (WGE) from the soybean pathogen Phytophthora sojae had an additive effect on the elicitation of soybean seeds, resulting in a yield of up to 745.1 µg gt⁻¹ glyceollin I. The additive elicitation suggested that the biotic and chemical elicitors acted largely by separate mechanisms. WGE caused a major accumulation of phytoalexin gene transcripts, whereas AgNO₃ inhibited and enhanced the degradation of glyceollin I and 6″-O-malonyldaidzin, respectively. Full article

(This article belongs to the Special Issue Structure, Chemical Analysis, Biosynthesis, Metabolism, Molecular Engineering and Biological Functions of Phytoalexins)

► Show Figures

Graphical abstract

17 pages, 3844 KiB

Open AccessArticle

Evaluation of the Nutritional Quality of Chinese Kale (Brassica alboglabra Bailey) Using UHPLC-Quadrupole-Orbitrap MS/MS-Based Metabolomics

by Ya-Qin Wang, Li-Ping Hu, Guang-Min Liu, De-Shuang Zhang and Hong-Ju He

Molecules 2017, 22(8), 1262; https://doi.org/10.3390/molecules22081262 - 27 Jul 2017

Cited by 45 | Viewed by 6679

Abstract

Chinese kale (Brassica alboglabra Bailey) is a widely consumed vegetable which is rich in antioxidants and anticarcinogenic compounds. Herein, we used an untargeted ultra-high-performance liquid chromatography (UHPLC)-Quadrupole-Orbitrap MS/MS-based metabolomics strategy to study the nutrient profiles of Chinese kale. Seven Chinese kale cultivars [...] Read more.

Chinese kale (Brassica alboglabra Bailey) is a widely consumed vegetable which is rich in antioxidants and anticarcinogenic compounds. Herein, we used an untargeted ultra-high-performance liquid chromatography (UHPLC)-Quadrupole-Orbitrap MS/MS-based metabolomics strategy to study the nutrient profiles of Chinese kale. Seven Chinese kale cultivars and three different edible parts were evaluated, and amino acids, sugars, organic acids, glucosinolates and phenolic compounds were analysed simultaneously. We found that two cultivars, a purple-stem cultivar W1 and a yellow-flower cultivar Y1, had more health-promoting compounds than others. The multivariate statistical analysis results showed that gluconapin was the most important contributor for discriminating both cultivars and edible parts. The purple-stem cultivar W1 had higher levels of some phenolic acids and flavonoids than the green stem cultivars. Compared to stems and leaves, the inflorescences contained more amino acids, glucosinolates and most of the phenolic acids. Meanwhile, the stems had the least amounts of phenolic compounds among the organs tested. Metabolomics is a powerful approach for the comprehensive understanding of vegetable nutritional quality. The results provide the basis for future metabolomics-guided breeding and nutritional quality improvement. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

► Show Figures

Figure 1

20 pages, 4541 KiB

Open AccessReview

Recent Developments in the Medicinal Applications of Silver-NHC Complexes and Imidazolium Salts

by Nicholas A. Johnson, Marie R. Southerland and Wiley J. Youngs

Molecules 2017, 22(8), 1263; https://doi.org/10.3390/molecules22081263 - 27 Jul 2017

Cited by 136 | Viewed by 11164

Abstract

Because of their great structural diversity and multitude of chemical properties, N-heterocyclic carbenes (NHCs) have been utilized in a variety of capacities. Most recently, NHCs have been utilized as carrier molecules for many transition metals in medicinal chemistry. Specifically, Ag(I)-NHCs have been investigated [...] Read more.

Because of their great structural diversity and multitude of chemical properties, N-heterocyclic carbenes (NHCs) have been utilized in a variety of capacities. Most recently, NHCs have been utilized as carrier molecules for many transition metals in medicinal chemistry. Specifically, Ag(I)-NHCs have been investigated as potent antibacterial agents and chemotherapeutics and have shown great efficacy in both in vitro and in vivo studies. Ag(I)-NHC compounds have been shown to be effective against a wide range of both Gram-positive and Gram-negative bacterial strains. Many compounds have also shown great efficacy as antitumor agents demonstrating comparable or better antitumor activity than standard chemotherapeutics such as cisplatin and 5-fluorouracil. While these compounds have shown great promise, clinical use has remained an unattained goal. Current research has been focused upon synthesis of novel Ag(I)-NHC compounds and further investigations of their antibacterial and antitumor activity. This review will focus on recent advances of Ag(I)-NHCs in medicinal applications. Full article

(This article belongs to the Special Issue Group 11 Metal Complexes with N-Heterocyclic Carbene Ligands: Recent Developments)

► Show Figures

Figure 1

14 pages, 5987 KiB

Open AccessArticle

Screening Hepatotoxic Components in Euodia rutaecarpa by UHPLC-QTOF/MS Based on the Spectrum-Toxicity Relationship

by Jian Liang, Yang Chen, Gang Ren, Wei Dong, Min Shi, Li Xiong, Jiankang Li, Jiahao Dong, Fei Li and Jinbin Yuan

Molecules 2017, 22(8), 1264; https://doi.org/10.3390/molecules22081264 - 27 Jul 2017

Cited by 42 | Viewed by 5384

Abstract

Euodia rutaecarpa is a common traditional Chinese medicine (TCM) in clinical practice, having the ability to suppress pain and cease coughing; however, with the increasing reports showing that it is toxic, particularly hepatotoxic, the concerns raised by what cause its toxicity is growing. [...] Read more.

Euodia rutaecarpa is a common traditional Chinese medicine (TCM) in clinical practice, having the ability to suppress pain and cease coughing; however, with the increasing reports showing that it is toxic, particularly hepatotoxic, the concerns raised by what cause its toxicity is growing. In the current study, an analysis method based on the spectrum effect has been employed to screen the major hepatotoxic components in Euodia rutaecarpa so that the toxic material’s basis would be elucidated. A fingerprinting method of the Euodia rutaecarpa extracts (which were petroleum ether, chloroform, ethyl acetate, n-butanol, and water) using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (UHPLC-QTOF/MS) has been developed. Orthogonal partial least squares (OPLS) was used to establish the spectrum-toxicity relationship with the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice serum as evaluation indices for liver injury. The UHPLC-MS fingerprint was established and the OPLS analytical results suggested that coniferin, 1-methyl-2-undecyl-4(1H)-quinolone, 1-methyl-2-[(6Z,9Z,12E)-pentadeca triene]-4(1H)-quinolone, evocarpine, 1-methyl-2-[(Z)-7-tridecenyl]-4(1H)-quinolone, dihydroevocarpine, and 1-methyl-2-tetradecy-4-(1H)-quinolone probably associated with the hepatotoxicity of Euodia rutaecarpa. This paper offered considerable methods and insight for the fundamental research of the toxic material basis of similar toxic TCMs. Full article

► Show Figures

Graphical abstract

19 pages, 2402 KiB

Open AccessArticle

Development of 2-Methoxyhuprine as Novel Lead for Alzheimer’s Disease Therapy

by Eva Mezeiova, Jan Korabecny, Vendula Sepsova, Martina Hrabinova, Petr Jost, Lubica Muckova, Tomas Kucera, Rafael Dolezal, Jan Misik, Katarina Spilovska, Ngoc Lam Pham, Lucia Pokrievkova, Jaroslav Roh, Daniel Jun, Ondrej Soukup, Daniel Kaping and Kamil Kuca

Molecules 2017, 22(8), 1265; https://doi.org/10.3390/molecules22081265 - 28 Jul 2017

Cited by 25 | Viewed by 7512

Abstract

Tacrine (THA), the first clinically effective acetylcholinesterase (AChE) inhibitor and the first approved drug for the treatment of Alzheimer’s disease (AD), was withdrawn from the market due to its side effects, particularly its hepatotoxicity. Nowadays, THA serves as a valuable scaffold for the [...] Read more.

Tacrine (THA), the first clinically effective acetylcholinesterase (AChE) inhibitor and the first approved drug for the treatment of Alzheimer’s disease (AD), was withdrawn from the market due to its side effects, particularly its hepatotoxicity. Nowadays, THA serves as a valuable scaffold for the design of novel agents potentially applicable for AD treatment. One such compound, namely 7-methoxytacrine (7-MEOTA), exhibits an intriguing profile, having suppressed hepatotoxicity and concomitantly retaining AChE inhibition properties. Another interesting class of AChE inhibitors represents Huprines, designed by merging two fragments of the known AChE inhibitors—THA and (−)-huperzine A. Several members of this compound family are more potent human AChE inhibitors than the parent compounds. The most promising are so-called huprines X and Y. Here, we report the design, synthesis, biological evaluation, and in silico studies of 2-methoxyhuprine that amalgamates structural features of 7-MEOTA and huprine Y in one molecule. Full article

(This article belongs to the Special Issue The Cholinesterases—Structure, Mechanism, Function and Drug Design: The 25th Anniversary of the Solution of the Crystal Structure of Acetylcholinesterase by Joel L. Sussman and Israel Silman)

► Show Figures

Figure 1

14 pages, 1868 KiB

Open AccessArticle

Chemical Synthesis of Sulfated Yeast (Saccharomyces cerevisiae) Glucans and Their In Vivo Antioxidant Activity

by Hua Zhang, Jing Zhang, Ziluan Fan, Xintao Zhou, Lin Geng, Zhenyu Wang, Joe M. Regenstein and Zhiqiang Xia

Molecules 2017, 22(8), 1266; https://doi.org/10.3390/molecules22081266 - 28 Jul 2017

Cited by 8 | Viewed by 4952

Abstract

The effects of sulfation of yeast glucans was optimized using response surface methodology. The degree of sulfation was evaluated from 0.11 to 0.75 using ion-chromatography. The structural characteristics of SYG (sulfation of yeast glucans) with a DS = 0.75 were determined using high-performance [...] Read more.

The effects of sulfation of yeast glucans was optimized using response surface methodology. The degree of sulfation was evaluated from 0.11 to 0.75 using ion-chromatography. The structural characteristics of SYG (sulfation of yeast glucans) with a DS = 0.75 were determined using high-performance liquid chromatography/gel-permeation chromatography and finally by Fourier transform infrared spectrometry. The SYG had lower viscosity and greater solubility than the native yeast glucans, suggesting that the conformation of the SYG had significantly changed. The results also showed that SYG had a significantly greater antioxidant activity in vivo compared to native yeast glucans. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

► Show Figures

Figure 1

14 pages, 1296 KiB

Open AccessArticle

Development of a UPLC-MS/MS Method for Simultaneous Determination of Six Flavonoids in Rat Plasma after Administration of Maydis stigma Extract and Its Application to a Comparative Pharmacokinetic Study in Normal and Diabetic Rats

by Bin-Bin Wei, Zai-Xing Chen, Ming-Yan Liu and Min-Jie Wei

Molecules 2017, 22(8), 1267; https://doi.org/10.3390/molecules22081267 - 29 Jul 2017

Cited by 18 | Viewed by 5840

Abstract

Maydis stigma is an important medicine herb used in many parts of the world for treatment of diabetes mellitus, which main bioactive ingredients are flavonoids. This paper describes for the first time a study on the comparative pharmacokinetics of six active flavonoid ingredients [...] Read more.

Maydis stigma is an important medicine herb used in many parts of the world for treatment of diabetes mellitus, which main bioactive ingredients are flavonoids. This paper describes for the first time a study on the comparative pharmacokinetics of six active flavonoid ingredients of Maydis stigma in normal and diabetic rats orally administrated with the decoction. Therefore, an efficient and sensitive ultra high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of six anti-diabetic ingredients (cynaroside, quercetin, luteolin, isorhamnetin, rutin and formononetin) of Maydis stigma in rat plasma has been developed and validated in plasma samples, which showed good linearity over a wide concentration range (r² > 0.99), and gave a lower limit of quantification of 1.0 ng·mL⁻¹ for the analytes. The intra- and interday assay variability was less than 15% for all analytes. The mean extraction recoveries and matrix effect of analytes and IS from rats plasma were all more than 85.0%. The stability results showed the measured concentration for six analytes at three QC levels deviated within 15.0%. The results indicated that significant differences in the pharmacokinetic parameters of the analytes were observed between the two groups of animals, whereby the absorptions of these analytes in the diabetic group were all significantly higher than those in the normal group, which provides an experimental basis for the role of Maydis stigma in anti-diabetic treatment. Full article

(This article belongs to the Special Issue Plant Polyphenols as Potential Therapeutic Agents for Diabetes and Obesity)

► Show Figures

Graphical abstract

12 pages, 5262 KiB

Open AccessArticle

Molecular Cloning and Characterization of PnbHLH1 Transcription Factor in Panax notoginseng

by Xiang Zhang, Feng Ge, Bing Deng, Taif Shah, Zhuangjia Huang, Diqiu Liu and Chaoyin Chen

Molecules 2017, 22(8), 1268; https://doi.org/10.3390/molecules22081268 - 29 Jul 2017

Cited by 39 | Viewed by 7851

Abstract

Panax notoginseng has been extensively used as a traditional Chinese medicine. In the current study, molecular cloning and characterization of PnbHLH1 transcription factor were explored in Panax notoginseng. The full length of the PnbHLH1 gene obtained by splicing was 1430 bp, encoding [...] Read more.

Panax notoginseng has been extensively used as a traditional Chinese medicine. In the current study, molecular cloning and characterization of PnbHLH1 transcription factor were explored in Panax notoginseng. The full length of the PnbHLH1 gene obtained by splicing was 1430 bp, encoding 321 amino acids. Prokaryotic expression vector pET-28a-PnbHLH1 was constructed and transferred into the BL21 prokaryotic expression strain. An electrophoretic mobility shift assay of PnbHLH1 protein binding to E-box cis-acting elements verified that PnbHLH1 belonged to the bHLH class transcription factor which could interact with the promoter region of the E-box core sequence. The expression levels of key genes involved in the biosynthesis of triterpenoid saponins in PnbHLH1 transgenic cells were higher than those in the wild cells. Similarly, the total saponin contents were increased in the PnbHLH1 transgenic cell lines compared with the wild cell lines. Such results suggest that the PnbHLH1 transcription factor is a positive regulator in the biosynthesis of triterpenoid saponins in Panax notoginseng. Full article

(This article belongs to the Special Issue Current Trends in Ginseng Research)

► Show Figures

Figure 1

44 pages, 11894 KiB

Open AccessFeature PaperReview

β-Formyl- and β-Vinylporphyrins: Magic Building Blocks for Novel Porphyrin Derivatives

by Ana F. R. Cerqueira, Nuno M. M. Moura, Vanda Vaz Serra, M. Amparo F. Faustino, Augusto C. Tomé, José A. S. Cavaleiro and M. Graça P. M. S. Neves

Molecules 2017, 22(8), 1269; https://doi.org/10.3390/molecules22081269 - 29 Jul 2017

Cited by 29 | Viewed by 9808

Abstract

Porphyrins bearing formyl or vinyl groups have been explored as starting materials to prepare new compounds with adequate features for different applications. In this review it is discussed mainly synthetic strategies based on the reaction of meso-tetraarylporphyrins bearing those groups at β-pyrrolic [...] Read more.

Porphyrins bearing formyl or vinyl groups have been explored as starting materials to prepare new compounds with adequate features for different applications. In this review it is discussed mainly synthetic strategies based on the reaction of meso-tetraarylporphyrins bearing those groups at β-pyrrolic positions. The use of some of the obtained porphyrin derivatives for further transformations, namely via pericyclic reactions, is also highlighted. Full article

(This article belongs to the Special Issue Women in Organic Chemistry)

► Show Figures

Graphical abstract

27 pages, 5215 KiB

Open AccessReview

Research Progress in the Modification of Quercetin Leading to Anticancer Agents

by Alessandro Massi, Olga Bortolini, Daniele Ragno, Tatiana Bernardi, Gianni Sacchetti, Massimo Tacchini and Carmela De Risi

Molecules 2017, 22(8), 1270; https://doi.org/10.3390/molecules22081270 - 29 Jul 2017

Cited by 195 | Viewed by 14111

Abstract

The flavonoid quercetin (3,3′,4′,5,7-pentahydroxyflavone) is widely distributed in plants, foods, and beverages. This polyphenol compound exhibits varied biological actions such as antioxidant, radical-scavenging, anti-inflammatory, antibacterial, antiviral, gastroprotective, immune-modulator, and finds also application in the treatment of obesity, cardiovascular diseases and diabetes. Besides, quercetin [...] Read more.

The flavonoid quercetin (3,3′,4′,5,7-pentahydroxyflavone) is widely distributed in plants, foods, and beverages. This polyphenol compound exhibits varied biological actions such as antioxidant, radical-scavenging, anti-inflammatory, antibacterial, antiviral, gastroprotective, immune-modulator, and finds also application in the treatment of obesity, cardiovascular diseases and diabetes. Besides, quercetin can prevent neurological disorders and exerts protection against mitochondrial damages. Various in vitro studies have assessed the anticancer effects of quercetin, although there are no conclusive data regarding its mode of action. However, low bioavailability, poor aqueous solubility as well as rapid body clearance, fast metabolism and enzymatic degradation hamper the use of quercetin as therapeutic agent, so intense research efforts have been focused on the modification of the quercetin scaffold to obtain analogs with potentially improved properties for clinical applications. This review gives an overview of the developments in the synthesis and anticancer-related activities of quercetin derivatives reported from 2012 to 2016. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

► Show Figures

Graphical abstract

11 pages, 2380 KiB

Open AccessCommunication

In Vitro Evaluation of Sub-Lethal Concentrations of Plant-Derived Antifungal Compounds on FUSARIA Growth and Mycotoxin Production

by Caterina Morcia, Giorgio Tumino, Roberta Ghizzoni, Assetou Bara, Nesrine Salhi and Valeria Terzi

Molecules 2017, 22(8), 1271; https://doi.org/10.3390/molecules22081271 - 29 Jul 2017

Cited by 31 | Viewed by 5289

Abstract

Phytopathogenic fungi can lead to significant cereal yield losses, also producing mycotoxins dangerous for human and animal health. The fungal control based on the use of synthetic fungicides can be complemented by "green" methods for crop protection, based on the use of natural [...] Read more.

Phytopathogenic fungi can lead to significant cereal yield losses, also producing mycotoxins dangerous for human and animal health. The fungal control based on the use of synthetic fungicides can be complemented by "green" methods for crop protection, based on the use of natural products. In this frame, the antifungal activities of bergamot and lemon essential oils and of five natural compounds recurrent in essential oils (citronellal, citral, cinnamaldehyde, cuminaldehyde and limonene) have been evaluated against three species of mycotoxigenic fungi (Fusarium sporotrichioides, F. graminearum and F. langsethiae) responsible for Fusarium Head Blight in small-grain cereals. The natural products concentrations effective for reducing or inhibiting the in vitro fungal growth were determined for each fungal species and the following scale of potency was found: cinnamaldehyde > cuminaldehyde > citral > citronellal > bergamot oil > limonene > lemon oil. Moreover, the in vitro mycotoxin productions of the three Fusaria strains exposed to sub-lethal concentrations of the seven products was evaluated. The three fungal species showed variability in response to the treatments, both in terms of inhibition of mycelial growth and in terms of modulation of mycotoxin production that can be enhanced by sub-lethal concentrations of some natural products. This last finding must be taken into account in the frame of an open field application of some plant-derived fungicides. Full article

(This article belongs to the Special Issue Essential Oils as Antimicrobial and Anti-infectious Agents)

► Show Figures

Figure 1

15 pages, 2372 KiB

Open AccessArticle

Artesunate Activates the Intrinsic Apoptosis of HCT116 Cells through the Suppression of Fatty Acid Synthesis and the NF-κB Pathway

by Xiao Chen, Yin Kwan Wong, Teck Kwang Lim, Wei Hou Lim, Qingsong Lin, Jigang Wang and Zichun Hua

Molecules 2017, 22(8), 1272; https://doi.org/10.3390/molecules22081272 - 8 Aug 2017

Cited by 36 | Viewed by 9504

Abstract

The artemisinin compounds, which are well-known for their potent therapeutic antimalarial activity, possess in vivo and in vitro antitumor effects. Although the anticancer effect of artemisinin compounds has been extensively reported, the precise mechanisms underlying its cytotoxicity remain under intensive study. In the [...] Read more.

The artemisinin compounds, which are well-known for their potent therapeutic antimalarial activity, possess in vivo and in vitro antitumor effects. Although the anticancer effect of artemisinin compounds has been extensively reported, the precise mechanisms underlying its cytotoxicity remain under intensive study. In the present study, a high-throughput quantitative proteomics approach was applied to identify differentially expressed proteins of HCT116 colorectal cancer cell line with artesunate (ART) treatment. Through Ingenuity Pathway Analysis, we discovered that the top-ranked ART-regulated biological pathways are abrogation of fatty acid biosynthetic pathway and mitochondrial dysfunction. Subsequent assays showed that ART inhibits HCT116 cell proliferation through suppressing the fatty acid biosynthetic pathway and activating the mitochondrial apoptosis pathway. In addition, ART also regulates several proteins that are involved in NF-κB pathway, and our subsequent assays showed that ART suppresses the NF-κB pathway. These proteomic findings will contribute to improving our understanding of the underlying molecular mechanisms of ART for its therapeutic cytotoxic effect towards cancer cells. Full article

(This article belongs to the Special Issue Artemisinin: Against Malaria, Cancer and Viruses)

► Show Figures

Figure 1

8 pages, 846 KiB

Open AccessArticle

Kinetics and Energetics of Thermal Cis-Trans Isomerization of a Resonance-Activated Azobenzene in BMIM-Based Ionic Liquids for PF₆⁻/Tf₂N⁻ Comparison

by Guido Angelini, Cristina Campestre, Luca Scotti and Carla Gasbarri

Molecules 2017, 22(8), 1273; https://doi.org/10.3390/molecules22081273 - 29 Jul 2017

Cited by 9 | Viewed by 6749

Abstract

BMIM PF₆ (1-butyl-3-methylimidazolium hexafluorophosphate) and BMIM Tf₂N (1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) are two conventional room-temperature ionic liquids widely employed and investigated as reaction media. Despite the presence of the same imidazolium ring in their structure they are different in many chemical and [...] Read more.

BMIM PF₆ (1-butyl-3-methylimidazolium hexafluorophosphate) and BMIM Tf₂N (1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) are two conventional room-temperature ionic liquids widely employed and investigated as reaction media. Despite the presence of the same imidazolium ring in their structure they are different in many chemical and physical properties due to the nature of the anions. The thermal cis-trans isomerization of an electronically activated azobenzene have been used as reaction model to compare the behavior of PF₆⁻ and Tf₂N⁻. Rotation is the mechanism by which the investigated azobenzene is converted into the trans isomer spontaneously in the dark both in BMIM PF₆ and in BMIM Tf₂N. The kinetic rate constants of the process have been determined at different temperatures and the activation energies of the reaction have been calculated according to the Arrhenius and Eyring equations. The results presented herein highlight different solute-solvent interactions involving the PF₆⁻ and Tf₂N⁻ anions during the cis-trans isomerization. Full article

► Show Figures

Graphical abstract

15 pages, 1730 KiB

Open AccessArticle

Adiponectin, Leptin, and Leptin Receptor in Obese Patients with Type 2 Diabetes Treated with Insulin Detemir

by Paweł Olczyk, Robert Koprowski, Katarzyna Komosinska-Vassev, Agnieszka Jura-Półtorak, Katarzyna Winsz-Szczotka, Kornelia Kuźnik-Trocha, Łukasz Mencner, Alicja Telega, Diana Ivanova and Krystyna Olczyk

Molecules 2017, 22(8), 1274; https://doi.org/10.3390/molecules22081274 - 30 Jul 2017

Cited by 19 | Viewed by 5801

Abstract

The aim of the present study is to quantitatively assess the expression of selected regulatory molecules, such as leptin, leptin receptor, and adiponectin in the blood of obese patients with type 2 diabetes both before treatment and after six months of pharmacological therapy [...] Read more.

The aim of the present study is to quantitatively assess the expression of selected regulatory molecules, such as leptin, leptin receptor, and adiponectin in the blood of obese patients with type 2 diabetes both before treatment and after six months of pharmacological therapy with the long-lasting insulin analogue, insulin detemir. A significant decrease in the analysed regulatory molecules, i.e., leptin receptor and adiponectin, was found in blood plasma of the patients with untreated type 2 diabetes. These changes were accompanied by an increase in plasma leptin concentrations. Insulin treatment resulted in the normalization of plasma leptin receptor and adiponectin concentrations. The circulating leptin level did not change following anti-diabetic therapy with insulin detemir. Gender was a significant factor modifying the circulating level of all the analysed regulatory active compounds. Bioinformatic analysis was performed using Matlab with the Signal Processing Toolbox. The conducted discriminant analysis revealed that the leptin receptor, Δw(19), and adiponectin, Δw(21), were the parameters undergoing the most significant quantitative changes during the six-month therapy with insulin detemir. The conducted examinations indicated the contribution of adipocytokines—the biologically-active mediators of systemic metabolism, such as leptin and adiponectin in the pathomechanism of disorders being the basis for obesity which leads to development of insulin resistance, which, in turn, results in the occurrence of type 2 diabetes. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)

► Show Figures

Figure 1

7 pages, 898 KiB

Open AccessArticle

Astragalosidic Acid: A New Water-Soluble Derivative of Astragaloside IV Prepared Using Remarkably Simple TEMPO-Mediated Oxidation

by Lin-Sen Qing, Shu-Lin Peng, Jian Liang and Li-Sheng Ding

Molecules 2017, 22(8), 1275; https://doi.org/10.3390/molecules22081275 - 31 Jul 2017

Cited by 14 | Viewed by 4228

Abstract

There is an urgent need for a water-soluble derivative of astragaloside IV for drug R&D. In the present study, a remarkably simple method for the preparation of such a water-soluble derivative of astragaloside IV has been developed. This protocol involves oxidative 2,2,6,6-tetramethylpiperidine-1-oxyl free [...] Read more.

There is an urgent need for a water-soluble derivative of astragaloside IV for drug R&D. In the present study, a remarkably simple method for the preparation of such a water-soluble derivative of astragaloside IV has been developed. This protocol involves oxidative 2,2,6,6-tetramethylpiperidine-1-oxyl free radical (TEMPO)-mediated transformation of astragaloside IV to its carboxylic acid derivative, which is a new compound named astragalosidic acid. The structure of astragalosidic acid was elucidated by means of spectroscopic analysis. Its cardioprotective activity was investigated using an in vitro model of cardiomyocyte damage induced by hypoxia/reoxygenation in H9c2 cells. The oxidative TEMPO-mediated transformation proposed in the present study could be applied to other natural saponins, offering an effective and convenient way to develop a new compound with greatly improved structure-based druggability. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

13 pages, 2189 KiB

Open AccessArticle

Isolation, Purification and Structural Characterization of Two Novel Water-Soluble Polysaccharides from Anredera cordifolia

by Zhi-Peng Zhang, Can-Can Shen, Fu-Li Gao, Hui Wei, Di-Feng Ren and Jun Lu

Molecules 2017, 22(8), 1276; https://doi.org/10.3390/molecules22081276 - 3 Aug 2017

Cited by 34 | Viewed by 6312

Abstract

Anredera cordifolia, a climber and member of the Basellaceae family, has long been a traditional medicine used for the treatment of hyperglycemia in China. Two water-soluble polysaccharides, ACP1-1 and ACP2-1, were isolated from A. cordifolia seeds by hot water extraction. The two [...] Read more.

Anredera cordifolia, a climber and member of the Basellaceae family, has long been a traditional medicine used for the treatment of hyperglycemia in China. Two water-soluble polysaccharides, ACP1-1 and ACP2-1, were isolated from A. cordifolia seeds by hot water extraction. The two fractions, ACP1-1 and ACP2-1 with molecular weights of 46.78 kDa ± 0.03 and 586.8 kDa ± 0.05, respectively, were purified by chromatography. ACP1-1 contained mannose, glucose, galactose in a molar ratio of 1.08:4.65:1.75, whereas ACP2-1 contained arabinose, ribose, galactose, glucose, mannose in a molar ratio of 0.9:0.4:0.5:1.2:0.9. Based on methylation analysis, ultraviolet and Fourier transform-infrared spectroscopy, and periodate oxidation the main backbone chain of ACP1-1 contained (1→3,6)-galacturonopyranosyl residues interspersed with (1→4)-residues and (1→3)-mannopyranosyl residues. The main backbone chain of ACP2-1 contained (1→3)-galacturonopyranosyl residues interspersed with (1→4)-glucopyranosyl residues. Full article

(This article belongs to the Special Issue Advances in Natural Polysaccharides Research)

► Show Figures

Figure 1

7 pages, 6246 KiB

Open AccessCommunication

An Efficient Synthesis of Arylated Pyridines from Conjugated Acetylenes and Substituted Benzylamines Catalyzed by Base

by Mengping Guo, Bo Chen, Qiming Zhu, Hua Jin, Qiuling Peng and Yanping Kang

Molecules 2017, 22(8), 1277; https://doi.org/10.3390/molecules22081277 - 31 Jul 2017

Cited by 3 | Viewed by 3501

Abstract

An efficient base-catalyzed synthesis of arylated pyridines has been disclosed. This reaction involving conjugated acetylenes and substituted benzylamines proceeded smoothly, giving rise to tri-aryl substituted pyridines which are biologically relevant compounds in good to excellent yields in N,N-dimethylformamide (DMF) under air at 140 [...] Read more.

An efficient base-catalyzed synthesis of arylated pyridines has been disclosed. This reaction involving conjugated acetylenes and substituted benzylamines proceeded smoothly, giving rise to tri-aryl substituted pyridines which are biologically relevant compounds in good to excellent yields in N,N-dimethylformamide (DMF) under air at 140 °C with K₂CO₃ as catalyst. Full article

21 pages, 1922 KiB

Open AccessArticle

An Efficient One-Pot Catalyzed Synthesis of 2,4-Disubstituted 5-Nitroimidazoles Displaying Antiparasitic and Antibacterial Activities

by Fanny Mathias, Youssef Kabri, Liliane Okdah, Carole Di Giorgio, Jean-Marc Rolain, Cédric Spitz, Maxime D. Crozet and Patrice Vanelle

Molecules 2017, 22(8), 1278; https://doi.org/10.3390/molecules22081278 - 3 Aug 2017

Cited by 10 | Viewed by 5399

Abstract

A one-pot regioselective bis-Suzuki-Miyaura or Suzuki-Miyaura/Sonogashira reaction on 2,4-dibromo-1-methyl-5-nitro-1H-imidazole under microwave heating was developed. This method is applicable to a wide range of (hetero)arylboronic acids and terminal alkynes. Additionally, this approach provides a simple and efficient way to synthesize 2,4-disubstituted 5-nitroimidazole [...] Read more.

A one-pot regioselective bis-Suzuki-Miyaura or Suzuki-Miyaura/Sonogashira reaction on 2,4-dibromo-1-methyl-5-nitro-1H-imidazole under microwave heating was developed. This method is applicable to a wide range of (hetero)arylboronic acids and terminal alkynes. Additionally, this approach provides a simple and efficient way to synthesize 2,4-disubstituted 5-nitroimidazole derivatives with antibacterial and antiparasitic properties. Full article

(This article belongs to the Special Issue Multicomponent Reaction-Based Synthesis of Bioactive Molecules)

► Show Figures

Figure 1

16 pages, 4686 KiB

Open AccessArticle

Effect of Sunlight Radiation on the Growth and Chemical Constituents of Salvia plebeia R.Br.

by Hyun-Jae Jang, Seung-Jae Lee, Cha Young Kim, Joo Tae Hwang, Jung Ho Choi, Jee Hun Park, Seung Woong Lee and Mun-Chual Rho

Molecules 2017, 22(8), 1279; https://doi.org/10.3390/molecules22081279 - 1 Aug 2017

Cited by 16 | Viewed by 6021

Abstract

This study investigated the chemical composition changes of Salvia plebeia R.Br. cultivated under different light sources, including florescent light and sunlight. The plants were exposed to fluorescent light for four months and sunlight and then examined for the next 5–7 months. Plants were [...] Read more.

This study investigated the chemical composition changes of Salvia plebeia R.Br. cultivated under different light sources, including florescent light and sunlight. The plants were exposed to fluorescent light for four months and sunlight and then examined for the next 5–7 months. Plants were harvested monthly during the seven months, and we examined whether the difference in light source affected the phenolic and flavonoid contents and antioxidant activity. A simple and reliable HPLC method using a PAH C₁₈ column was applied for the quantitative analysis of two triterpenoids from the S. plebeia groups. Oleanolic acid (OA) and ursolic acid (UA) showed good linearity (R² > 0.9999) within the test ranges (0.005–0.05 mg/mL), and the average percentage recoveries of the OA and UA were 95.1–104.8% and 97.2–107.1%, respectively. The intra- and inter-day relative standard deviations (RSDs) were less than 2.0%. After exposure to sunlight, the phenolic contents, including rosmarinic acid, showed a reduced tendency, whereas the flavonoid contents, including homoplantaginin and luteolin 7-glucoside, were increased. The content of the triterpenoids also showed an increased tendency under sunlight irradiation, but the variance was not larger than those of the phenolic and flavonoid contents. Among experimental groups, the group harvested at six months, having been exposed to sunlight for two months, showed the most potent antioxidant activity. Therefore, these results showed that the chemical composition and antioxidant activities of S. plebeia R.Br. was affected from environmental culture conditions, such as light source. Our studies will be useful for the development of functional materials using S. plebeia R.Br. Full article

► Show Figures

Graphical abstract

16 pages, 1608 KiB

Open AccessArticle

Nontargeted Metabolomic Analysis of Four Different Parts of Platycodon grandiflorum Grown in Northeast China

by Cuizhu Wang, Nanqi Zhang, Zhenzhou Wang, Zeng Qi, Hailin Zhu, Bingzhen Zheng, Pingya Li and Jinping Liu

Molecules 2017, 22(8), 1280; https://doi.org/10.3390/molecules22081280 - 3 Aug 2017

Cited by 54 | Viewed by 6145

Abstract

Platycodonis radix is extensively used for treating cough, excessive phlegm, sore throat, bronchitis and asthma in the clinic. Meanwhile, the stems, leaves and seeds of Platycodon grandiflorum (PG) have some pharmaceutical activities such as anti-inflammation and anti-oxidation effects, etc. These effects must be [...] Read more.

Platycodonis radix is extensively used for treating cough, excessive phlegm, sore throat, bronchitis and asthma in the clinic. Meanwhile, the stems, leaves and seeds of Platycodon grandiflorum (PG) have some pharmaceutical activities such as anti-inflammation and anti-oxidation effects, etc. These effects must be caused by the different metabolites in various parts of herb. In order to profile the different parts of PG, the ultra-high performance liquid chromatography combined with quadrupole time-of- flight mass spectrometry (UPLC-QTOF-MS^E) coupled with UNIFI platform and multivariate statistical analyses was used in this study. Consequently, for the constituent screening, 73, 42, 35, 44 compounds were characterized from the root, stem, leaf and seed, respectively. The stem, leaf and seed contain more flavonoids but few saponins that can be easily discriminated in the root. For the metabolomic analysis, 15, 5, 7, 11 robust biomarkers enabling the differentiation among root, stem, leaf and seed, were discovered. These biomarkers can be used for rapid identification of four different parts of PG grown in northeast China. Full article

(This article belongs to the Section Metabolites)

► Show Figures

Figure 1

28 pages, 5500 KiB

Open AccessFeature PaperReview

Tubulin Inhibitor-Based Antibody-Drug Conjugates for Cancer Therapy

by Hao Chen, Zongtao Lin, Kinsie E. Arnst, Duane D. Miller and Wei Li

Molecules 2017, 22(8), 1281; https://doi.org/10.3390/molecules22081281 - 1 Aug 2017

Cited by 164 | Viewed by 19644

Abstract

Antibody-drug conjugates (ADCs) are a class of highly potent biopharmaceutical drugs generated by conjugating cytotoxic drugs with specific monoclonal antibodies through appropriate linkers. Specific antibodies used to guide potent warheads to tumor tissues can effectively reduce undesired side effects of the cytotoxic drugs. [...] Read more.

Antibody-drug conjugates (ADCs) are a class of highly potent biopharmaceutical drugs generated by conjugating cytotoxic drugs with specific monoclonal antibodies through appropriate linkers. Specific antibodies used to guide potent warheads to tumor tissues can effectively reduce undesired side effects of the cytotoxic drugs. An in-depth understanding of antibodies, linkers, conjugation strategies, cytotoxic drugs, and their molecular targets has led to the successful development of several approved ADCs. These ADCs are powerful therapeutics for cancer treatment, enabling wider therapeutic windows, improved pharmacokinetic/pharmacodynamic properties, and enhanced efficacy. Since tubulin inhibitors are one of the most successful cytotoxic drugs in the ADC armamentarium, this review focuses on the progress in tubulin inhibitor-based ADCs, as well as lessons learned from the unsuccessful ADCs containing tubulin inhibitors. This review should be helpful to facilitate future development of new generations of tubulin inhibitor-based ADCs for cancer therapy. Full article

(This article belongs to the Special Issue Tubulin Inhibitors)

► Show Figures

Figure 1

21 pages, 1073 KiB

Open AccessReview

New Insights in the Design of Bioactive Peptides and Chelating Agents for Imaging and Therapy in Oncology

by Anna Lucia Tornesello, Luigi Buonaguro, Maria Lina Tornesello and Franco Maria Buonaguro

Molecules 2017, 22(8), 1282; https://doi.org/10.3390/molecules22081282 - 2 Aug 2017

Cited by 71 | Viewed by 9092

Abstract

Many synthetic peptides have been developed for diagnosis and therapy of human cancers based on their ability to target specific receptors on cancer cell surface or to penetrate the cell membrane. Chemical modifications of amino acid chains have significantly improved the biological activity, [...] Read more.

Many synthetic peptides have been developed for diagnosis and therapy of human cancers based on their ability to target specific receptors on cancer cell surface or to penetrate the cell membrane. Chemical modifications of amino acid chains have significantly improved the biological activity, the stability and efficacy of peptide analogues currently employed as anticancer drugs or as molecular imaging tracers. The stability of somatostatin, integrins and bombesin analogues in the human body have been significantly increased by cyclization and/or insertion of non-natural amino acids in the peptide sequences. Moreover, the overall pharmacokinetic properties of such analogues and others (including cholecystokinin, vasoactive intestinal peptide and neurotensin analogues) have been improved by PEGylation and glycosylation. Furthermore, conjugation of those peptide analogues to new linkers and bifunctional chelators (such as AAZTA, TETA, TRAP, NOPO etc.), produced radiolabeled moieties with increased half life and higher binding affinity to the cognate receptors. This review describes the most important and recent chemical modifications introduced in the amino acid sequences as well as linkers and new bifunctional chelators which have significantly improved the specificity and sensitivity of peptides used in oncologic diagnosis and therapy. Full article

(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)

► Show Figures

Graphical abstract

7 pages, 517 KiB

Open AccessArticle

Three New Sesquiterpene Glycosides from the Rhizomes of Trillium tschonoskii

by Jie Yang, Yin-Jun Yang, Xin-Guang Sun, Jie Zhang, Yang Zhao, Bei Wang, Qian-Zhi Ding, Bao-Lin Guo and Bai-Ping Ma

Molecules 2017, 22(8), 1283; https://doi.org/10.3390/molecules22081283 - 2 Aug 2017

Viewed by 3924

Abstract

Three new sesquiterpene glycosides, possessing a rare aglycone with a sulfonyl between C-1 and C-15 positions, named 3-(3′E-7′R,8′-dihydroxy-4′,8′-dimethyl-3′-nonenyl)-2,5-dihydro-1,1-dioxo-thiophen 7′-O-β-d-glucopyranosyl-(1→4)-O-β-d-glucopyranosyl-(1→4)-O-β-d-glucopyranoside (1), 3-(3′E-7′R,8′-dihydroxy-4′,8′-dimethyl-3′-nonenyl)-2,5-dihydro-1,1-dioxo-thiophen [...] Read more.

Three new sesquiterpene glycosides, possessing a rare aglycone with a sulfonyl between C-1 and C-15 positions, named 3-(3′E-7′R,8′-dihydroxy-4′,8′-dimethyl-3′-nonenyl)-2,5-dihydro-1,1-dioxo-thiophen 7′-O-β-d-glucopyranosyl-(1→4)-O-β-d-glucopyranosyl-(1→4)-O-β-d-glucopyranoside (1), 3-(3′E-7′R,8′-dihydroxy-4′,8′-dimethyl-3′-nonenyl)-2,5-dihydro-1,1-dioxo-thiophen 7′-O-β-d-glucopyranosyl-(1→4)-O-β-d-glucopyranoside (2), and 3-(3′E-7′R,8′-dihydroxy-4′,8′-dimethyl-3′-nonenyl)-2,5-dihydro-1,1-dioxo-thiophen 7′-O-β-d-glucopyranosyl-6′-O-acetyl-(1→4)-O-β-d-glucopyranosyl-(1→4)-O-β-d-glucopyranoside (3), respectively, were isolated from the rhizomes of Trillium tschonoskii. Their structures were established on the basis of spectroscopic data, including HR-ESI-MS, IR, 1D and 2D NMR. The cytotoxic properties of the three compounds were investigated using human hepatic L02 cells. Full article

(This article belongs to the Special Issue Diversity of Terpenoids)

► Show Figures

Graphical abstract

6 pages, 2350 KiB

Open AccessCommunication

Efficient Dye-Sensitized Solar Cells Based on Nanoflower-like ZnO Photoelectrode

by Xiaobo Chen, Yu Tang and Weiwei Liu

Molecules 2017, 22(8), 1284; https://doi.org/10.3390/molecules22081284 - 3 Aug 2017

Cited by 32 | Viewed by 5397

Abstract

A photoanode material ZnO nanoflower (ZNFs) for efficient dye-sensitized solar cell (DSSC) was prepared. This unique structure can significantly increase the specific surface area and amount of light absorption, leading to a higher short-circuit current density. Furthermore, ZNFs resulted in closer spacing between [...] Read more.

A photoanode material ZnO nanoflower (ZNFs) for efficient dye-sensitized solar cell (DSSC) was prepared. This unique structure can significantly increase the specific surface area and amount of light absorption, leading to a higher short-circuit current density. Furthermore, ZNFs resulted in closer spacing between the nanorods and more direct conduction paths for electrons, leading to higher open-circuit voltage. The overall promising power conversion efficiency of 5.96% was obtained with photoanodes of 8.5 μm thickness. This work shows that ZNFs is an attractive material and has good potential for application in high efficiency ZnO-based DSSCs. Full article

(This article belongs to the Special Issue Nanocrystals: Synthesis, Characterization and Applications)

► Show Figures

Figure 1

13 pages, 2254 KiB

Open AccessArticle

Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells

by Kyoung-jin Min, Ju-Ock Nam and Taeg Kyu Kwon

Molecules 2017, 22(8), 1285; https://doi.org/10.3390/molecules22081285 - 2 Aug 2017

Cited by 31 | Viewed by 7303

Abstract

Fisetin is a natural compound found in fruits and vegetables such as strawberries, apples, cucumbers, and onions. Since fisetin can elicit anti-cancer effects, including anti-proliferation and anti-migration, we investigated whether fisetin induced apoptosis in human renal carcinoma (Caki) cells. Fisetin markedly induced sub-G1 [...] Read more.

Fisetin is a natural compound found in fruits and vegetables such as strawberries, apples, cucumbers, and onions. Since fisetin can elicit anti-cancer effects, including anti-proliferation and anti-migration, we investigated whether fisetin induced apoptosis in human renal carcinoma (Caki) cells. Fisetin markedly induced sub-G1 population and cleavage of poly (ADP-ribose) polymerase (PARP), which is a marker of apoptosis, and increased caspase activation. We found that pan-caspase inhibitor (z-VAD-fmk) inhibited fisetin-induced apoptosis. In addition, fisetin induced death receptor 5 (DR5) expression at the transcriptional level, and down-regulation of DR5 by siRNA blocked fisetin-induced apoptosis. Furthermore, fisetin induced p53 protein expression through up-regulation of protein stability, whereas down-regulation of p53 by siRNA markedly inhibited fisetin-induced DR5 expression. In contrast, fisetin induced up-regulation of CHOP expression and reactive oxygen species production, which had no effect on fisetin-induced apoptosis. Taken together, our study demonstrates that fisetin induced apoptosis through p53 mediated up-regulation of DR5 expression at the transcriptional level. Full article

(This article belongs to the Collection Natural Products: Anticancer Potential and Beyond)

► Show Figures

Figure 1

13 pages, 4073 KiB

Open AccessArticle

Optimization of the Ultrasound-Assisted Extraction of Phenolic Compounds from Brosimum alicastrum Leaves and the Evaluation of Their Radical-Scavenging Activity

by Mariel Gullian Klanian and Montserrat Terrats Preciat

Molecules 2017, 22(8), 1286; https://doi.org/10.3390/molecules22081286 - 7 Aug 2017

Cited by 16 | Viewed by 5232

Abstract

In order to maximize the yield of the total phenolic content (TPC) and total monomeric anthocyanin (TMA) from Brosimum alicastrum leaf and to study the radical-scavenging activity, a three-level three-factor Box–Behnken design (BBD) was used to determine the optimal points for ultrasound-assisted extraction [...] Read more.

In order to maximize the yield of the total phenolic content (TPC) and total monomeric anthocyanin (TMA) from Brosimum alicastrum leaf and to study the radical-scavenging activity, a three-level three-factor Box–Behnken design (BBD) was used to determine the optimal points for ultrasound-assisted extraction (UAE). In this study, we analyzed the extraction time (10, 20, and 30 min), temperature (28, 30, and 32 °C), and probe sonication power (40%, 28 W/cm²; 60%, 51 W/cm²; and 80%, 74 W/cm²). Analysis of variance (ANOVA) indicated that the sonication power plays a significant role in the extraction of phenolic compounds. An increase in time and temperature resulted in a decrease in the yield, in particular, of the TMA group. DPPH was found to be a better indicator of radical-scavenging activity than ABTS. The predicted TPC and TMA optimum levels (45.18 mg GAE/g and 15.16 mg CyE/100 g) were obtained at 28 °C, 80%, and 20–10 min. DPPH obtained a maximum value (67.27 μmol TE/g) under same optimization conditions. The RSM confirmed that TPC and TMA enhanced the antioxidant activity when subjected to low temperature (28 °C), extraction time less than 20 min, and higher sonication power (74 W/cm²), and hence achieving the better DPPH scavenging activity. Full article

(This article belongs to the Special Issue Green Extraction of Natural Product: Innovative Techniques, Alternative Solvents and Original Procedures)

► Show Figures

Figure 1

23 pages, 2375 KiB

Open AccessReview

Recent Advances in the Inhibition of p38 MAPK as a Potential Strategy for the Treatment of Alzheimer’s Disease

by Jong Kil Lee and Nam-Jung Kim

Molecules 2017, 22(8), 1287; https://doi.org/10.3390/molecules22081287 - 2 Aug 2017

Cited by 271 | Viewed by 19223

Abstract

P38 mitogen-activated protein kinase (MAPK) is a crucial target for chronic inflammatory diseases. Alzheimer’s disease (AD) is characterized by the presence of amyloid plaques and neurofibrillary tangles in the brain, as well as neurodegeneration, and there is no known cure. Recent studies on [...] Read more.

P38 mitogen-activated protein kinase (MAPK) is a crucial target for chronic inflammatory diseases. Alzheimer’s disease (AD) is characterized by the presence of amyloid plaques and neurofibrillary tangles in the brain, as well as neurodegeneration, and there is no known cure. Recent studies on the underlying biology of AD in cellular and animal models have indicated that p38 MAPK is capable of orchestrating diverse events related to AD, such as tau phosphorylation, neurotoxicity, neuroinflammation and synaptic dysfunction. Thus, the inhibition of p38 MAPK is considered a promising strategy for the treatment of AD. In this review, we summarize recent advances in the targeting of p38 MAPK as a potential strategy for the treatment of AD and envision possibilities of p38 MAPK inhibitors as a fundamental therapeutics for AD. Full article

(This article belongs to the Special Issue Kinase Inhibitors)

► Show Figures

Figure 1

23 pages, 7521 KiB

Open AccessArticle

Novel Methylselenoesters as Antiproliferative Agents

by Nuria Díaz-Argelich, Ignacio Encío, Daniel Plano, Aristi P. Fernandes, Juan Antonio Palop and Carmen Sanmartín

Molecules 2017, 22(8), 1288; https://doi.org/10.3390/molecules22081288 - 2 Aug 2017

Cited by 16 | Viewed by 6338

Abstract

Selenium (Se) compounds are potential therapeutic agents in cancer. Importantly, the biological effects of Se compounds are exerted by their metabolites, with methylselenol (CH₃SeH) being one of the key executors. In this study, we developed a new series of methylselenoesters with [...] Read more.

Selenium (Se) compounds are potential therapeutic agents in cancer. Importantly, the biological effects of Se compounds are exerted by their metabolites, with methylselenol (CH₃SeH) being one of the key executors. In this study, we developed a new series of methylselenoesters with different scaffolds aiming to modulate the release of CH₃SeH. The fifteen compounds follow Lipinski’s Rule of Five and with exception of compounds 1 and 14, present better drug-likeness values than the positive control methylseleninic acid. The compounds were evaluated to determine their radical scavenging activity. Compound 11 reduced both DPPH and ABTS radicals. The cytotoxicity of the compounds was evaluated in a panel of five cancer cell lines (prostate, colon and lung carcinoma, mammary adenocarcinoma and chronic myelogenous leukemia) and two non-malignant (lung and mammary epithelial) cell lines. Ten compounds had GI₅₀ values below 10 μM at 72 h in four cancer cell lines. Compounds 5 and 15 were chosen for further characterization of their mechanism of action in the mammary adenocarcinoma cell line due to their similarity with methylseleninic acid. Both compounds induced G₂/M arrest whereas cell death was partially executed by caspases. The reduction and metabolism were also investigated, and both compounds were shown to be substrates for redox active enzyme thioredoxin reductase. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

► Show Figures

Graphical abstract

9 pages, 698 KiB

Open AccessArticle

Capillary-Inserted Rotor Design for HRµMAS NMR-Based Metabolomics on Mass-Limited Neurospheres

by Nghia Tuan Duong, Masanori Yamato, Masayuki Nakano, Satoshi Kume, Yasuhisa Tamura, Yosky Kataoka, Alan Wong and Yusuke Nishiyama

Molecules 2017, 22(8), 1289; https://doi.org/10.3390/molecules22081289 - 3 Aug 2017

Cited by 6 | Viewed by 5349

Abstract

Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical technique and has been widely used in metabolomics. However, the intrinsic low sensitivity of NMR prevents its applications to systems with limited sample availabilities. In this study, a new experimental approach is presented to [...] Read more.

Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical technique and has been widely used in metabolomics. However, the intrinsic low sensitivity of NMR prevents its applications to systems with limited sample availabilities. In this study, a new experimental approach is presented to analyze mass-scarce samples in limited volumes of less than 300 nL with simple handling. The sample is loaded into the glass capillary, and this capillary is then inserted into a Kel-F rotor. The experimental performance of the capillary-inserted rotor (capillary-insert) is investigated on an isotropic solution of sucrose by the use of a high-resolution micro-sized magic angle spinning (HRµMAS) probe. The acquired NMR signal’s sensitivity to a given sample amount is comparable or even higher in comparison to that recorded by the standard solution NMR probe. More importantly, this capillary-insert coupled with the HRµMAS probe allows in-depth studies of heterogeneous samples as the MAS removes the line broadening caused by the heterogeneity. The NMR analyses of mass-limited cultured neurospheres have been demonstrated, resulting in high quality spectra where numerous metabolites are unambiguously identified. Full article

(This article belongs to the Special Issue Recent Advances in Biomolecular NMR Spectroscopy)

► Show Figures

Figure 1

21 pages, 3467 KiB

Open AccessReview

Essential Oils and Their Constituents: An Alternative Source for Novel Antidepressants

by Damião P. De Sousa, Rayanne H. N. Silva, Epifanio F. da Silva and Elaine C. Gavioli

Molecules 2017, 22(8), 1290; https://doi.org/10.3390/molecules22081290 - 3 Aug 2017

Cited by 35 | Viewed by 12477

Abstract

Depression is a disease that has affected a high proportion of the world’s population and people of different ages, incapacitating them from good performance at work and in social relationships, and causing emotional disorders to millions of families. Therefore, the search for new [...] Read more.

Depression is a disease that has affected a high proportion of the world’s population and people of different ages, incapacitating them from good performance at work and in social relationships, and causing emotional disorders to millions of families. Therefore, the search for new therapeutic agents is considered a priority for the discovery of more effective forms of treatment. In this review, studies of essential oils and their constituents in experimental models related to depression are discussed. The mechanisms of action of the oils and the presence of psychoactive constituents in their chemical compositions are discussed. The data in the review show the therapeutic potential of essential oils and their chemical constituents for use in depressive disorders. Advanced studies using humans are needed to confirm the antidepressant properties described in animals. Full article

(This article belongs to the Special Issue Essential Oils: Chemistry and Bioactivity)

12 pages, 5572 KiB

Open AccessArticle

Development of HA/Ag-NPs Composite Coating from Green Process for Hip Applications

by Denisse A. Lozoya-Rodríguez, Renata De Lima, Leonardo F. Fraceto, Antonio Ledezma Pérez, Mercedes Bazaldua Domínguez, Roberto Gómez Batres, Armando Reyes Rojas and Víctor Orozco Carmona

Molecules 2017, 22(8), 1291; https://doi.org/10.3390/molecules22081291 - 8 Aug 2017

Cited by 12 | Viewed by 4699

Abstract

In the present study, biological hydroxyapatite (HA) was obtained from bovine bones through a thermal process. A total of 0% and 1% of silver nanoparticles (Ag-NPs) synthesized from Opuntia ficus (nopal) were added to the biological hydroxyapatite coatings using an atmospheric plasma spray [...] Read more.

In the present study, biological hydroxyapatite (HA) was obtained from bovine bones through a thermal process. A total of 0% and 1% of silver nanoparticles (Ag-NPs) synthesized from Opuntia ficus (nopal) were added to the biological hydroxyapatite coatings using an atmospheric plasma spray (APS) on a Ti6Al4V substrate. Following this, its antimicrobial efficiency was evaluated against the following bacterial strains: Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. This was conducted according to the Japanese Industrial Standard (JIS) Z2801:2000 “Antimicrobial Product-Test for Antimicrobial Activity and Efficacy”. Scanning electron microscopy (SEM) showed that the silver nanoparticles (Ag-NPs) were evenly distributed on the coating surface. Energy dispersive X-ray spectroscopy (EDX) shows that apatite deposition occurs on a daily basis, maintaining a Ca/P rate between 2.12 and 1.45. Biocompatibility properties were evaluated with osteoblast-like cells (MC3T3-E1) by single-cell gel electrophoresis assay and Tali image cytometry. Full article

(This article belongs to the Special Issue Antibacterial Materials and Coatings)

► Show Figures

Graphical abstract

22 pages, 2716 KiB

Open AccessArticle

Apigenin Impacts the Growth of the Gut Microbiota and Alters the Gene Expression of Enterococcus

by Minqian Wang, Jenni Firrman, Liqing Zhang, Gustavo Arango-Argoty, Peggy Tomasula, LinShu Liu, Weidong Xiao and Kit Yam

Molecules 2017, 22(8), 1292; https://doi.org/10.3390/molecules22081292 - 3 Aug 2017

Cited by 52 | Viewed by 7873

Abstract

Apigenin is a major dietary flavonoid with many bioactivities, widely distributed in plants. Apigenin reaches the colon region intact and interacts there with the human gut microbiota, however there is little research on how apigenin affects the gut bacteria. This study investigated the [...] Read more.

Apigenin is a major dietary flavonoid with many bioactivities, widely distributed in plants. Apigenin reaches the colon region intact and interacts there with the human gut microbiota, however there is little research on how apigenin affects the gut bacteria. This study investigated the effect of pure apigenin on human gut bacteria, at both the single strain and community levels. The effect of apigenin on the single gut bacteria strains Bacteroides galacturonicus, Bifidobacterium catenulatum, Lactobacillus rhamnosus GG, and Enterococcus caccae, was examined by measuring their anaerobic growth profiles. The effect of apigenin on a gut microbiota community was studied by culturing a fecal inoculum under in vitro conditions simulating the human ascending colon. 16S rRNA gene sequencing and GC-MS analysis quantified changes in the community structure. Single molecule RNA sequencing was used to reveal the response of Enterococcus caccae to apigenin. Enterococcus caccae was effectively inhibited by apigenin when cultured alone, however, the genus Enterococcus was enhanced when tested in a community setting. Single molecule RNA sequencing found that Enterococcus caccae responded to apigenin by up-regulating genes involved in DNA repair, stress response, cell wall synthesis, and protein folding. Taken together, these results demonstrate that apigenin affects both the growth and gene expression of Enterococcus caccae. Full article

► Show Figures

Figure 1

12 pages, 2670 KiB

Open AccessArticle

Trehalose Inhibits A53T Mutant α-Synuclein Overexpression and Neurotoxicity in Transduced PC12 Cells

by Juan Zhao, Xiuling Zhi, Luanfeng Pan and Ping Zhou

Molecules 2017, 22(8), 1293; https://doi.org/10.3390/molecules22081293 - 8 Aug 2017

Cited by 16 | Viewed by 7183

Abstract

Fibrillar accumulation of A53T mutant α-synuclein (A53T-AS) in Lewy bodies is a symptom of Parkinsonism. Inhibitions of the overexpression and fibrillar aggregation of α-synuclein (AS) in vivo could be a promising strategy for treating Parkinson’s disease (PD). In this study, at concentrations lower [...] Read more.

Fibrillar accumulation of A53T mutant α-synuclein (A53T-AS) in Lewy bodies is a symptom of Parkinsonism. Inhibitions of the overexpression and fibrillar aggregation of α-synuclein (AS) in vivo could be a promising strategy for treating Parkinson’s disease (PD). In this study, at concentrations lower than 1 mM, trehalose decreased the A53T-AS expression level in transduced PC12 cells. Although H₂O₂ and aluminum ions increased the expression level and neurotoxicity of A53T-AS in cells, proper trehalose concentrations inhibited the event. These studies adequately prove that trehalose at an appropriate dose would be potentially useful for PD treatment. Full article

(This article belongs to the Special Issue Neuroprotective Agents)

► Show Figures

Graphical abstract

21 pages, 5114 KiB

Open AccessArticle

Intramolecular Hydrogen Bonding and Conformational Preferences of Arzanol—An Antioxidant Acylphloroglucinol

by Liliana Mammino

Molecules 2017, 22(8), 1294; https://doi.org/10.3390/molecules22081294 - 3 Aug 2017

Cited by 27 | Viewed by 5747

Abstract

Arzanol is a naturally-occurring prenylated acylphloroglucinol isolated from Helichrysum italicum and exhibiting anti-oxidant, antibiotic and antiviral activities. The molecule contains an α-pyrone moiety attached to the phloroglucinol moiety through a methylene bridge. The presence of several hydrogen bond donor or acceptor sites makes [...] Read more.

Arzanol is a naturally-occurring prenylated acylphloroglucinol isolated from Helichrysum italicum and exhibiting anti-oxidant, antibiotic and antiviral activities. The molecule contains an α-pyrone moiety attached to the phloroglucinol moiety through a methylene bridge. The presence of several hydrogen bond donor or acceptor sites makes intramolecular hydrogen bonding patterns the dominant stabilising factor. Conformers with all the possible different hydrogen bonding patterns were calculated at the HF/6-31G(d,p) and DFT/B3LYP/6-31+G(d,p) levels with fully relaxed geometry in vacuo and in three solvents—chloroform, acetonitrile and water (these levels being chosen to enable comparisons with previous studies on acylphloroglucinols). Calculations in solution were performed with the Polarisable Continuum Model. The results show that the lowest energy conformers have the highest number of stronger intramolecular hydrogen bonds. The influence of intramolecular hydrogen bonding patterns on the other molecular properties is also analysed. Full article

(This article belongs to the Special Issue Intramolecular Hydrogen Bonding 2017)

► Show Figures

Figure 1

7 pages, 570 KiB

Open AccessArticle

An Efficient Synthesis of Spiro[indoline-3,9′-xanthene]trione Derivatives Catalyzed by Magnesium Perchlorate

by Chunfeng Chen, Chunlei Lv, Jianfeng Liang, Jianqing Jin, Lijun Wang, Chunlei Wu and Runpu Shen

Molecules 2017, 22(8), 1295; https://doi.org/10.3390/molecules22081295 - 4 Aug 2017

Cited by 14 | Viewed by 5142

Abstract

A simple and efficient method for the synthesis of spiro[indoline-3,9′-xanthene]trione derivatives by means of condensation between isatins and 1,3-cyclohexanedione in the presence of a catalytic amount of magnesium perchlorate at 80 °C in 50% aqueous ethanol medium has been described. Notably, the present [...] Read more.

A simple and efficient method for the synthesis of spiro[indoline-3,9′-xanthene]trione derivatives by means of condensation between isatins and 1,3-cyclohexanedione in the presence of a catalytic amount of magnesium perchlorate at 80 °C in 50% aqueous ethanol medium has been described. Notably, the present method offers desirable advantages of good yields, simplicity of workup procedure, easy purification, and reduced reaction times. Full article

(This article belongs to the Special Issue Advances in Spiro Compounds)

► Show Figures

Graphical abstract

7 pages, 722 KiB

Open AccessArticle

A New Approach to Synthesize of 4-Phenacylideneflavene Derivatives and to Evaluate Their Cytotoxic Effects on HepG2 Cell Line

by Hongbin Chen, Yang Xu, Yinan Zhang and Zongping Zheng

Molecules 2017, 22(8), 1296; https://doi.org/10.3390/molecules22081296 - 9 Aug 2017

Cited by 2 | Viewed by 4398

Abstract

In this study, a convenient approach and green procedure for the synthesis of 4-phenacylideneflavenes has been developed from the reaction between 2,4-dihydroxybenzaldehyde and substituted acetophenones using boric acid as a catalyst in polyethylene glycol 400. Seven 4-phenacylideneflavenes were synthetized and their structures were [...] Read more.

In this study, a convenient approach and green procedure for the synthesis of 4-phenacylideneflavenes has been developed from the reaction between 2,4-dihydroxybenzaldehyde and substituted acetophenones using boric acid as a catalyst in polyethylene glycol 400. Seven 4-phenacylideneflavenes were synthetized and their structures were confirmed by NMR and mass spectral analyses. Meanwhile, their possible mechanism of formation was also discussed. These products were found to have potential cytotoxic effect on HepG2 cell line with IC₅₀ values from 12.5 to 50 µM. Full article

(This article belongs to the Special Issue Multicomponent Reaction-Based Synthesis of Bioactive Molecules)

► Show Figures

Graphical abstract

12 pages, 251 KiB

Open AccessReview

Immuno-Stimulatory Peptides as a Potential Adjunct Therapy against Intra-Macrophagic Pathogens

by Tânia Silva and Maria Salomé Gomes

Molecules 2017, 22(8), 1297; https://doi.org/10.3390/molecules22081297 - 4 Aug 2017

Cited by 18 | Viewed by 5625

Abstract

The treatment of infectious diseases is increasingly prone to failure due to the rapid spread of antibiotic-resistant pathogens. Antimicrobial peptides (AMPs) are natural components of the innate immune system of most living organisms. Their capacity to kill microbes through multiple mechanisms makes the [...] Read more.

The treatment of infectious diseases is increasingly prone to failure due to the rapid spread of antibiotic-resistant pathogens. Antimicrobial peptides (AMPs) are natural components of the innate immune system of most living organisms. Their capacity to kill microbes through multiple mechanisms makes the development of bacterial resistance less likely. Additionally, AMPs have important immunomodulatory effects, which critically contribute to their role in host defense. In this paper, we review the most recent evidence for the importance of AMPs in host defense against intracellular pathogens, particularly intra-macrophagic pathogens, such as mycobacteria. Cathelicidins and defensins are reviewed in more detail, due to the abundance of studies on these molecules. The cell-intrinsic as well as the systemic immune-related effects of the different AMPs are discussed. In the face of the strong potential emerging from the reviewed studies, the prospects for future use of AMPs as part of the therapeutic armamentarium against infectious diseases are presented. Full article

(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)

16 pages, 2799 KiB

Open AccessArticle

Time- and NADPH-Dependent Inhibition on CYP3A by Gomisin A and the Pharmacokinetic Interactions between Gomisin A and Cyclophosphamide in Rats

by Jianxiu Zhai, Feng Zhang, Shouhong Gao, Li Chen, Ge Feng, Jun Yin and Wansheng Chen

Molecules 2017, 22(8), 1298; https://doi.org/10.3390/molecules22081298 - 8 Aug 2017

Cited by 11 | Viewed by 4904

Abstract

The traditional Chinese medicine Schisandra chinensis has remarkable protective effects against chemical-induced toxicity. Cyclophosphamide (CTX), in spite advances in chemotherapy and immunosuppressive regimes, is prone to cause severe toxicity due to its chloroacetaldehyde (CAA) metabolite produced by CYP3A. Our previous study identified that [...] Read more.

The traditional Chinese medicine Schisandra chinensis has remarkable protective effects against chemical-induced toxicity. Cyclophosphamide (CTX), in spite advances in chemotherapy and immunosuppressive regimes, is prone to cause severe toxicity due to its chloroacetaldehyde (CAA) metabolite produced by CYP3A. Our previous study identified that S. chinensis extract (SCE) co-administration potently decreased CAA production and attenuated liver, kidney and brain injuries in CTX-treated rats. Gomisin A (Gom A) is proved to be one of the most abundant bioactive lignans in S. chinensis with a significant CYP3A inhibitory effect. To find out whether and how Gom A participated in the chemoprevention of SCE against CTX toxicity, the Gom A-caused CYP3A inhibition in vitro as well as the pharmacokinetic interactions between Gom A and CTX in vivo were examined in this study. Using human liver microsomes, a reversible inhibition assay revealed that Gom A was a competitive inhibitor with a K_I value of 1.10 µM, and the time- and NADPH-dependent CYP3A inhibition of Gom A was observed in a time-dependent inhibition assay (K_I = 0.35 µM, k_inact = 1.96 min⁻¹). Hepatic CYP3A mRNA expression experienced a significant increase in our rat model with Gom A administration. This explained why CAA production decreased in the 0.5 h- and 6 h-pretreatment rat groups while it increased in the 24 h- and 72 h-pretreatment groups, indicating a bidirectional effect of Gom A on CYP3A-mediated CTX metabolism. The present study suggested that Gom A participates like SCE in the pharmacokinetic intervention of CTX by blocking CYP3A-mediated metabolism and reducing CAA production, and thus plays an important role in the chemopreventive activity of S. chinensis against CTX toxicity, in addition to the previously recognized protective effects. Also, the combined use of S. chinensis preparation or other drugs containing Gom A as the main component with CTX needed to be addressed for better clinical intervention. Full article

(This article belongs to the Collection Herbal Medicine Research)

► Show Figures

Graphical abstract

15 pages, 5063 KiB

Open AccessArticle

γ-Tocotrienol Inhibits Proliferation and Induces Apoptosis via the Mitochondrial Pathway in Human Cervical Cancer HeLa Cells

by Weili Xu, Yaqing Mi, Pan He, Shenghua He and Lingling Niu

Molecules 2017, 22(8), 1299; https://doi.org/10.3390/molecules22081299 - 4 Aug 2017

Cited by 31 | Viewed by 7117

Abstract

γ-Tocotrienol, a kind of isoprenoid phytochemical, has antitumor activity. However, there is limited evidence that it has an effect on cervical cancer. In this study, the capacity to inhibit proliferation and induce apoptosis in human cervical cancer HeLa cells and the mechanism underlying [...] Read more.

γ-Tocotrienol, a kind of isoprenoid phytochemical, has antitumor activity. However, there is limited evidence that it has an effect on cervical cancer. In this study, the capacity to inhibit proliferation and induce apoptosis in human cervical cancer HeLa cells and the mechanism underlying these effects were examined. The results indicated that a γ-tocotrienol concentration over 30 μM inhibited the growth of HeLa cells with a 50% inhibitory concentration (IC₅₀) of 46.90 ± 3.50 μM at 24 h, and significantly down-regulated the expression of proliferative cell nuclear antigen (PCNA) and Ki-67. DNA flow cytometric analysis indicated that γ-tocotrienol arrested the cell cycle at G0/G1 phase and reduced the S phase in HeLa cells. γ-tocotrienol induced apoptosis of HeLa cells in a time- and dose-dependent manner. γ-tocotrienol-induced apoptosis in HeLa cells was accompanied by down-regulation of Bcl-2, up-regulation of Bax, release of cytochrome from mitochondria, activation of caspase-9 and caspase-3, and subsequent poly (ADP-ribose) polymerase (PARP) cleavage. These results suggested that γ-tocotrienol could significantly inhibit cell proliferation through G0/G1 cell cycle arrest, and induce apoptosis via the mitochondrial apoptotic pathway in human cervical cancer HeLa cells. Thus, our findings revealed that γ-tocotrienol may be considered as a potential agent for cervical cancer therapy. Full article

(This article belongs to the Collection Natural Products: Anticancer Potential and Beyond)

► Show Figures

Graphical abstract

15 pages, 4062 KiB

Open AccessReview

Ultrafast and Slow Cholinergic Transmission. Different Involvement of Acetylcholinesterase Molecular Forms

by Yves Dunant and Victor Gisiger

Molecules 2017, 22(8), 1300; https://doi.org/10.3390/molecules22081300 - 4 Aug 2017

Cited by 19 | Viewed by 6001

Abstract

Acetylcholine (ACh), an ubiquitous mediator substance broadly expressed in nature, acts as neurotransmitter in cholinergic synapses, generating specific communications with different time-courses. (1) Ultrafast transmission. Vertebrate neuromuscular junctions (NMJs) and nerve-electroplaque junctions (NEJs) are the fastest cholinergic synapses; able to transmit brief [...] Read more.

Acetylcholine (ACh), an ubiquitous mediator substance broadly expressed in nature, acts as neurotransmitter in cholinergic synapses, generating specific communications with different time-courses. (1) Ultrafast transmission. Vertebrate neuromuscular junctions (NMJs) and nerve-electroplaque junctions (NEJs) are the fastest cholinergic synapses; able to transmit brief impulses (1–4 ms) at high frequencies. The collagen-tailed A12 acetylcholinesterase is concentrated in the synaptic cleft of NMJs and NEJs, were it curtails the postsynaptic response by ultrafast ACh hydrolysis. Here, additional processes contribute to make transmission so rapid. (2) Rapid transmission. At peripheral and central cholinergic neuro-neuronal synapses, transmission involves an initial, relatively rapid (10–50 ms) nicotinic response, followed by various muscarinic or nicotinic effects. Acetylcholinesterase (AChE) being not concentrated within these synapses, it does not curtail the initial rapid response. In contrast, the late responses are controlled by a globular form of AChE (mainly G4-AChE), which is membrane-bound and/or secreted. (3) Slow ACh signalling. In non-neuronal systems, in muscarinic domains, and in most regions of the central nervous system (CNS), many ACh-releasing structures (cells, axon terminals, varicosities, boutons) do not form true synaptic contacts, most muscarinic and also part of nicotinic receptors are extra-synaptic, often situated relatively far from ACh releasing spots. A12-AChE being virtually absent in CNS, G4-AChE is the most abundant form, whose function appears to modulate the “volume” transmission, keeping ACh concentration within limits in time and space. Full article

(This article belongs to the Special Issue The Cholinesterases—Structure, Mechanism, Function and Drug Design: The 25th Anniversary of the Solution of the Crystal Structure of Acetylcholinesterase by Joel L. Sussman and Israel Silman)

► Show Figures

Figure 1

8 pages, 2111 KiB

Open AccessArticle

Five New Phenolic Compounds with Antioxidant Activities from the Medicinal Insect Blaps rynchopetera

by Huai Xiao, Tian-Peng Yin, Jian-Wei Dong, Xiu-Mei Wu, Qing Luo, Jian-Rong Luo, Le Cai and Zhong-Tao Ding

Molecules 2017, 22(8), 1301; https://doi.org/10.3390/molecules22081301 - 4 Aug 2017

Cited by 32 | Viewed by 5477

Abstract

Five new phenolic compounds rynchopeterines A–E (1–5), in addition to thirteen known phenolics, were isolated from Blaps rynchopetera Fairmaire, a kind of medicinal insect utilized by the Yi Nationality in Yunnan Province of China. Their structures were established on [...] Read more.

Five new phenolic compounds rynchopeterines A–E (1–5), in addition to thirteen known phenolics, were isolated from Blaps rynchopetera Fairmaire, a kind of medicinal insect utilized by the Yi Nationality in Yunnan Province of China. Their structures were established on the basis of extensive spectroscopic analyses (1D and 2D NMR, HR-MS, IR) along with calculated electronic circular dichroism method. Rynchopeterines A–E (1–4) exhibited significant antioxidant activities with IC₅₀ values of 7.67–12.3 μg/mL measured by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Besides, rynchopeterines B (2) and C (3) showed mild cytotoxicity against tumor cell Caco-2 and A549. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

► Show Figures

Figure 1

9 pages, 898 KiB

Open AccessArticle

Identification and Biological Evaluation of Secondary Metabolites from Marine Derived Fungi-Aspergillus sp. SCSIOW3, Cultivated in the Presence of Epigenetic Modifying Agents

by Xiaofan Li, Zhenyao Xia, Jianqiang Tang, Jiahui Wu, Jing Tong, Mengjie Li, Jianhua Ju, Huirong Chen and Liyan Wang

Molecules 2017, 22(8), 1302; https://doi.org/10.3390/molecules22081302 - 4 Aug 2017

Cited by 45 | Viewed by 6322

Abstract

Chemical epigenetic manipulation was applied to a deep marine-derived fungus, Aspergillus sp. SCSIOW3, resulting in significant changes of the secondary metabolites. One new diphenylether-O-glycoside (diorcinol 3-O-α-D-ribofuranoside), along with seven known compounds, were isolated from the culture treated with a [...] Read more.

Chemical epigenetic manipulation was applied to a deep marine-derived fungus, Aspergillus sp. SCSIOW3, resulting in significant changes of the secondary metabolites. One new diphenylether-O-glycoside (diorcinol 3-O-α-D-ribofuranoside), along with seven known compounds, were isolated from the culture treated with a combination of histone deacetylase inhibitor (suberohydroxamic acid) and DNA methyltransferase inhibitor (5-azacytidine). Compounds 2 and 4 exhibited significant biomembrane protective effect of erythrocytes. 2 also showed algicidal activity against Chattonella marina, a bloom forming alga responsible for large scale fish deaths. Full article

(This article belongs to the Collection Bioactive Compounds)

► Show Figures

Graphical abstract

28 pages, 11249 KiB

Open AccessReview

Upregulation of Melanogenesis and Tyrosinase Activity: Potential Agents for Vitiligo

by Chao Niu and Haji A. Aisa

Molecules 2017, 22(8), 1303; https://doi.org/10.3390/molecules22081303 - 4 Aug 2017

Cited by 147 | Viewed by 19142

Abstract

Melanin, the compound primarily responsible in humans for hair, eye and skin pigmentation, is produced by melanocytes through a complicated process called melanogenesis that is catalyzed by tyrosinase and other tyrosinase-related proteins. The abnormal loss of melanin causes dermatological problems such as vitiligo. [...] Read more.

Melanin, the compound primarily responsible in humans for hair, eye and skin pigmentation, is produced by melanocytes through a complicated process called melanogenesis that is catalyzed by tyrosinase and other tyrosinase-related proteins. The abnormal loss of melanin causes dermatological problems such as vitiligo. Hence the regulation of melanogenesis and tyrosinase activity is very important for treating hypopigmentary disorders. Many melanogenesis stimulators have been discovered during the past decade. This article reviews recent advances in research on extracts and active ingredients of plants, synthesized compounds with stimulating effect on melanin synthesis and tyrosinase activity, as well as their influence on the expression of related proteins and possible signaling pathways for the design and development of novel anti-vitiligo agents. Full article

► Show Figures

Graphical abstract

7 pages, 1890 KiB

Open AccessCommunication

High Solid Fluorescence of a Pyrazoline Derivative through Hydrogen Bonding

by Liang Zhang, Jie Liu, Junkuo Gao, Feng Zhang and Liang Ding

Molecules 2017, 22(8), 1304; https://doi.org/10.3390/molecules22081304 - 4 Aug 2017

Cited by 14 | Viewed by 4353

Abstract

Pyrazoline and its derivatives often exhibit strong emissions in dilute solutions, but their emission intensity is often dramatically reduced in the solid state due to strong intermolecular interactions between neighboring molecules. In this report, we successfully synthesized a new pyrazoline 4-(3-(4-(decyloxy)phenyl)-1-(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl)-4,5-dihydro-1H-pyrazol-5-yl)-N,N-diethylaniline (PPDPD), into [...] Read more.

Pyrazoline and its derivatives often exhibit strong emissions in dilute solutions, but their emission intensity is often dramatically reduced in the solid state due to strong intermolecular interactions between neighboring molecules. In this report, we successfully synthesized a new pyrazoline 4-(3-(4-(decyloxy)phenyl)-1-(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl)-4,5-dihydro-1H-pyrazol-5-yl)-N,N-diethylaniline (PPDPD), into which seven fluorine (F) atoms were incorporated. In the solid state, PPDPD emits a strong blue light at λ_max 430 nm with a fluorescence quantum yield of up to 41.3%. Single-crystal analysis showed the presence of intra/intermolecular C-H···F bonds that may impede molecular motion and block the non-radiative decay channel. Compound PPDPD therefore shows high emission efficiency in the solid state. Full article

(This article belongs to the Section Photochemistry)

► Show Figures

Graphical abstract

11 pages, 1422 KiB

Open AccessReview

Structures and Functions of Snake Venom Metalloproteinases (SVMP) from Protobothrops venom Collected in Japan

by Etsuko Oyama and Hidenobu Takahashi

Molecules 2017, 22(8), 1305; https://doi.org/10.3390/molecules22081305 - 4 Aug 2017

Cited by 17 | Viewed by 7606

Abstract

Snake venom metalloproteinases (SVMP) are widely distributed among the venoms of Crotalinae and Viperidae, and are organized into three classes (P-I, P-II and P-III) according to their size and domain structure. P-I SVMP are the smallest SVMP, as they only have a metalloproteinase [...] Read more.

Snake venom metalloproteinases (SVMP) are widely distributed among the venoms of Crotalinae and Viperidae, and are organized into three classes (P-I, P-II and P-III) according to their size and domain structure. P-I SVMP are the smallest SVMP, as they only have a metalloproteinase (M) domain. P-II SVMP contain a disintegrin-like (D) domain, which is connected by a short spacer region to the carboxyl terminus of the M domain. P-III SVMP contain a cysteine-rich (C) domain, which is attached to the carboxyl terminus of the D domain. Some SVMP exhibit hemorrhagic activity, whereas others do not. In addition, SVMP display fibrinolytic/fibrinogenolytic (FL) activity, and the physiological functions of SVMP are controlled by their structures. Furthermore, these proteinases also demonstrate fibrinogenolytic and proteolytic activity against synthetic substrates for matrix metalloproteinases and ADAM (a disintegrin and metalloproteinase). This article describes the structures and FL, hemorrhagic, and platelet aggregation-inhibiting activity of SVMP derived from Protobothrops snake venom that was collected in Japan. Full article

(This article belongs to the Section Bioorganic Chemistry)

► Show Figures

Figure 1

15 pages, 4174 KiB

Open AccessArticle

Fluorescent Polystyrene Films for the Detection of Volatile Organic Compounds Using the Twisted Intramolecular Charge Transfer Mechanism

by Mirko Borelli, Giuseppe Iasilli, Pierpaolo Minei and Andrea Pucci

Molecules 2017, 22(8), 1306; https://doi.org/10.3390/molecules22081306 - 6 Aug 2017

Cited by 42 | Viewed by 8500

Abstract

Thin films of styrene copolymers containing fluorescent molecular rotors were demonstrated to be strongly sensitive to volatile organic compounds (VOCs). Styrene copolymers of 2-[4-vinyl(1,1′-biphenyl)-4′-yl]-cyanovinyljulolidine (JCBF) were prepared with different P(STY-co-JCBF)(m) compositions (m% = 0.10–1.00) and molecular weights of about 12,000 g/mol. [...] Read more.

Thin films of styrene copolymers containing fluorescent molecular rotors were demonstrated to be strongly sensitive to volatile organic compounds (VOCs). Styrene copolymers of 2-[4-vinyl(1,1′-biphenyl)-4′-yl]-cyanovinyljulolidine (JCBF) were prepared with different P(STY-co-JCBF)(m) compositions (m% = 0.10–1.00) and molecular weights of about 12,000 g/mol. Methanol solutions of JCBF were not emissive due to the formation of the typical twisted intramolecular charge transfer (TICT) state at low viscosity regime, which formation was effectively hampered by adding progressive amounts of glycerol. The sensing performances of the spin-coated copolymer films (thickness of about 4 µm) demonstrated significant vapochromism when exposed to VOCs characterized by high vapour pressure and favourable interaction with the polymer matrix such as THF, CHCl₃ and CH₂Cl₂. The vapochromic response was also reversible and reproducible after successive exposure cycles, whereas the fluorescence variation scaled linearly with VOC concentration, thus suggesting future applications as VOC optical sensors. Full article

(This article belongs to the Special Issue Aggregation-Induced Emission: Commemorative Issue in Honor of Professor Ben Zhong Tang’s Research Achievements on the Occasion of His 60th Birthday)

► Show Figures

Figure 1

19 pages, 20360 KiB

Open AccessReview

An Introduction to Zeolite Synthesis Using Imidazolium-Based Cations as Organic Structure-Directing Agents

by Paloma Vinaches, Katia Bernardo-Gusmão and Sibele B. C. Pergher

Molecules 2017, 22(8), 1307; https://doi.org/10.3390/molecules22081307 - 6 Aug 2017

Cited by 35 | Viewed by 11090

Abstract

Zeolite synthesis is a wide area of study with increasing popularity. Several general reviews have already been published, but they did not summarize the study of imidazolium species in zeolite synthesis. Imidazolium derivatives are promising compounds in the search for new zeolites and [...] Read more.

Zeolite synthesis is a wide area of study with increasing popularity. Several general reviews have already been published, but they did not summarize the study of imidazolium species in zeolite synthesis. Imidazolium derivatives are promising compounds in the search for new zeolites and can be used to help understand the structure-directing role. Nearly 50 different imidazolium cations have already been used, resulting in a variety of zeolitic types, but there are still many derivatives to be studied. In this context, the purpose of this short review is to help researchers starting in this area by summarizing the most important concepts related to imidazolium-based zeolite studies and by presenting a table of recent imidazolium derivatives that have been recently studied to facilitate filling in the knowledge gaps. Full article

(This article belongs to the Special Issue Zeolites and Related Nanoporous Materials: Synthesis, Characterization and Applications in Catalysis and Green Chemistry)

► Show Figures

Graphical abstract

18 pages, 8684 KiB

Open AccessArticle

Characterization of Proanthocyanidin Oligomers of Ephedra sinica

by Joanna Orejola, Yosuke Matsuo, Yoshinori Saito and Takashi Tanaka

Molecules 2017, 22(8), 1308; https://doi.org/10.3390/molecules22081308 - 6 Aug 2017

Cited by 16 | Viewed by 7330

Abstract

Ephedra sinica, an important plant in Chinese traditional medicine, contains a complex mixture of proanthocyanidin oligomers as major constituents; however, only the minor components have been chemically characterized. In this study, oligomers with relatively large molecular weights, which form the main body [...] Read more.

Ephedra sinica, an important plant in Chinese traditional medicine, contains a complex mixture of proanthocyanidin oligomers as major constituents; however, only the minor components have been chemically characterized. In this study, oligomers with relatively large molecular weights, which form the main body of the proanthocyanidin fractions, were separated by adsorption and size-exclusion chromatography. Acid-catalyzed degradation in the presence of mercaptoethanol or phloroglucinol led to the isolation of 18 fragments, the structures of which were elucidated from their experimental and TDDFT-calculated ECD spectra. The results indicated that (−)-epigallocatechin was the main extension unit, while catechin, the A-type epigallocatechin–gallocatechin dimer, and the A-type epigallocatechin homodimer, were identified as the terminal units. Among the degradation products, thioethers of gallocatechin with 3,4-cis configurations, a B-type prodelphinidin dimer, a prodelphinidin trimer with both A- and B-type linkages, and a prodelphinidin dimer with an α-substituted A-type linkage were new compounds. In addition, a phloroglucinol adduct of an A-type prodelphinidin dimer, a doubly-linked phloroglucinol adduct of epigallocatechin, and a unique product with a flavan-3-ol skeleton generated by the rearrangement of the aromatic rings were also isolated. Full article

(This article belongs to the Special Issue Special Issue Dedicated to Late Professor Takuo Okuda, “Tannins and Related Polyphenols Revisited: Chemistry, Biochemistry and Biological Activities”)

► Show Figures

Figure 1

13 pages, 2694 KiB

Open AccessArticle

Bioactive Constituents from the Whole Plants of Gentianella acuta (Michx.) Hulten

by Zhijuan Ding, Yanxia Liu, Jingya Ruan, Shengcai Yang, Haiyang Yu, Meiling Chen, Yi Zhang and Tao Wang

Molecules 2017, 22(8), 1309; https://doi.org/10.3390/molecules22081309 - 6 Aug 2017

Cited by 11 | Viewed by 4391

Abstract

As a Mongolian native medicine and Ewenki folk medicinal plant, Gentianella acuta has been widely used for the treatment of diarrhea, hepatitis, arrhythmia, and coronary heart disease. In the course of investigating efficacy compounds to treat diarrhea using a mouse isolated intestine tissue [...] Read more.

As a Mongolian native medicine and Ewenki folk medicinal plant, Gentianella acuta has been widely used for the treatment of diarrhea, hepatitis, arrhythmia, and coronary heart disease. In the course of investigating efficacy compounds to treat diarrhea using a mouse isolated intestine tissue model, we found 70% EtOH extract of G. acuta whole plants had an inhibitory effect on intestine contraction tension. Here, nineteen constituents, including five new compounds, named as gentiiridosides A (1), B (2), gentilignanoside A (3), (1R)-2,2,3-trimethyl-4-hydroxymethylcyclopent-3-ene-1-methyl-O-β-d-glucopyranoside (4), and (3Z)-3-hexene-1,5-diol 1-O-α-l-arabinopyranosyl(1→6)-β-d-glucopyranoside (5) were obtained from it. The structures of them were elucidated by chemical and spectroscopic methods. Furthermore, the inhibitory effects on motility of mouse isolated intestine tissue of the above mentioned compounds and other thirteen iridoid- and secoiridoid-type monoterpenes (7–10, 13–16, 18, 19, 21, 22, and 25) previously obtained in the plant were analyzed. As results, new compound 5, some secoiridoid-type monoterpenes 7, 10, 12–14, 16, and 17, as well as 7-O-9′-type lignans 31 and 32 displayed significant inhibitory effect on contraction tension at 40 μM. Full article

► Show Figures

Figure 1

7 pages, 956 KiB

Open AccessArticle

Isolation and Purification of Three Ecdysteroids from the Stems of Diploclisia glaucescens by High-Speed Countercurrent Chromatography and Their Anti-Inflammatory Activities In Vitro

by Lei Fang, Jialian Li, Jie Zhou, Xiao Wang and Lanping Guo

Molecules 2017, 22(8), 1310; https://doi.org/10.3390/molecules22081310 - 7 Aug 2017

Cited by 13 | Viewed by 4564

Abstract

High-speed counter-current chromatography was used to separate and purify ecdysteroids for the first time from the stems of Diploclisia glaucescens using a two-phase solvent system composed of ethyl acetate–n-butanol–ethanol–water (3:0.2:0.8:3, v/v). Three ecdysteroids were obtained from 260 mg [...] Read more.

High-speed counter-current chromatography was used to separate and purify ecdysteroids for the first time from the stems of Diploclisia glaucescens using a two-phase solvent system composed of ethyl acetate–n-butanol–ethanol–water (3:0.2:0.8:3, v/v). Three ecdysteroids were obtained from 260 mg of ethyl acetate extract of the residue obtained after evaporation of the crude ethanolicextractof D. glaucescens in one-step separation, which were identified as paristerone (I, 30.5 mg), ecdysterone (II, 7.2 mg), and capitasterone (III, 8.1 mg) by electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR). Their anti-inflammatory activities were evaluated by measuring the inhibitory ratios of β-glucuronidase release in rat polymorphonuclear leukocytes (PMNs) induced by platelet-activating factor. Compounds I–III showed significant anti-inflammatory activities with IC₅₀-values ranging from 1.51 to 11.68 μM, respectively. Full article

(This article belongs to the Special Issue Anti-inflammatory Agents)

► Show Figures

Figure 1

15 pages, 2084 KiB

Open AccessReview

Carbohydrate-Based Host-Guest Complexation of Hydrophobic Antibiotics for the Enhancement of Antibacterial Activity

by Daham Jeong, Sang-Woo Joo, Vijay Vilas Shinde, Eunae Cho and Seunho Jung

Molecules 2017, 22(8), 1311; https://doi.org/10.3390/molecules22081311 - 8 Aug 2017

Cited by 19 | Viewed by 7506

Abstract

Host-guest complexation with various hydrophobic drugs has been used to enhance the solubility, permeability, and stability of guest drugs. Physical changes in hydrophobic drugs by complexation have been related to corresponding increases in the bioavailability of these drugs. Carbohydrates, including various derivatives of [...] Read more.

Host-guest complexation with various hydrophobic drugs has been used to enhance the solubility, permeability, and stability of guest drugs. Physical changes in hydrophobic drugs by complexation have been related to corresponding increases in the bioavailability of these drugs. Carbohydrates, including various derivatives of cyclodextrins, cyclosophoraoses, and some linear oligosaccharides, are generally used as host complexation agents in drug delivery systems. Many antibiotics with low bioavailability have some limitations to their clinical use due to their intrinsically poor aqueous solubility. Bioavailability enhancement is therefore an important step to achieve the desired concentration of antibiotics in the treatment of bacterial infections. Antibiotics encapsulated in a complexation-based drug delivery system will display improved antibacterial activity making it possible to reduce dosages and overcome the serious global problem of antibiotic resistance. Here, we review the present research trends in carbohydrate-based host-guest complexation of various hydrophobic antibiotics as an efficient delivery system to improve solubility, permeability, stability, and controlled release. Full article

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

► Show Figures

Graphical abstract

20 pages, 3476 KiB

Open AccessArticle

The Role of Solvent-Accessible Leu-208 of Cold-Active Pseudomonas fluorescens Strain AMS8 Lipase in Interfacial Activation, Substrate Accessibility and Low-Molecular Weight Esterification in the Presence of Toluene

by Norhayati Yaacob, Nor Hafizah Ahmad Kamarudin, Adam Thean Chor Leow, Abu Bakar Salleh, Raja Noor Zaliha Raja Abd Rahman and Mohd Shukuri Mohamad Ali

Molecules 2017, 22(8), 1312; https://doi.org/10.3390/molecules22081312 - 12 Aug 2017

Cited by 31 | Viewed by 5518

Abstract

The alkaline cold-active lipase from Pseudomonas fluorescens AMS8 undergoes major structural changes when reacted with hydrophobic organic solvents. In toluene, the AMS8 lipase catalytic region is exposed by the moving hydrophobic lid 2 (Glu-148 to Gly-167). Solvent-accessible surface area analysis revealed that Leu-208, [...] Read more.

The alkaline cold-active lipase from Pseudomonas fluorescens AMS8 undergoes major structural changes when reacted with hydrophobic organic solvents. In toluene, the AMS8 lipase catalytic region is exposed by the moving hydrophobic lid 2 (Glu-148 to Gly-167). Solvent-accessible surface area analysis revealed that Leu-208, which is located next to the nucleophilic Ser-207 has a focal function in influencing substrate accessibility and flexibility of the catalytic pocket. Based on molecular dynamic simulations, it was found that Leu-208 strongly facilitates the lid 2 opening via its side-chain. The K_M and K_cat/K_M of L208A mutant were substrate dependent as it preferred a smaller-chain ester (pNP-caprylate) as compared to medium (pNP-laurate) or long-chain (pNP-palmitate) esters. In esterification of ethyl hexanoate, L208A promotes a higher ester conversion rate at 20 °C but not at 30 °C, as a 27% decline was observed. Interestingly, the wild-type (WT) lipase’s conversion rate was found to increase with a higher temperature. WT lipase AMS8 esterification was higher in toluene as compared to L208A. Hence, the results showed that Leu-208 of AMS8 lipase plays an important role in steering a broad range of substrates into its active site region by regulating the flexibility of this region. Leu-208 is therefore predicted to be crucial for its role in interfacial activation and catalysis in toluene. Full article

(This article belongs to the Special Issue Lipases and Lipases Modification)

► Show Figures

Figure 1

16 pages, 1661 KiB

Open AccessArticle

Semi-Continuous Fermentation of Onion Vinegar and Its Functional Properties

by Sulhee Lee, Jin-A Lee, Gwi-Gun Park, Jae-Kweon Jang and Young-Seo Park

Molecules 2017, 22(8), 1313; https://doi.org/10.3390/molecules22081313 - 8 Aug 2017

Cited by 29 | Viewed by 7762

Abstract

For the fermentation of vinegar using onion, acetic acid bacteria and yeast strains with high fermentation ability were screened. Among them, Saccharomyces cerevisiae 1026 was selected as a starter for ethanol production and Acetobacter orientalis MAK88 was selected as a vinegar producer. When [...] Read more.

For the fermentation of vinegar using onion, acetic acid bacteria and yeast strains with high fermentation ability were screened. Among them, Saccharomyces cerevisiae 1026 was selected as a starter for ethanol production and Acetobacter orientalis MAK88 was selected as a vinegar producer. When the two-stage fermentation of onion vinegar was performed at 28 °C, the titratable acidity reached 4.80% at 24 h of fermentation. When semi-continuous fermentation proceeded to charge-discharge consisting of three cycles, the acetic acid content reached 4.35% at 48 h of fermentation. At this stage, the fermentation efficiency, acetic acid productivity, and specific product formation rate were 76.71%, 17.73 g/(L·d), and 20.58 g/(g·h), respectively. The process in this study significantly reduced the fermentation time and simplified the vinegar production process. The content of total flavonoids and total polyphenols in onion vinegar were 104.36 and 455.41 μg/mL, respectively. The antioxidant activities of onion vinegar in terms of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic) acid (ABTS⁺) radical scavenging activity, and reducing power were 75.33%, 98.88%, and 1.28, respectively. The nitrite scavenging abilities of onion vinegar were 95.38 at pH 1.2. The onion vinegar produced in this study showed higher organoleptic acceptability than commercial onion vinegar. Full article

► Show Figures

Figure 1

22 pages, 5088 KiB

Open AccessArticle

Antitumoural Sulphur and Selenium Heteroaryl Compounds: Thermal Characterization and Stability Evaluation

by Verónica Alcolea, Pablo Garnica, Juan A. Palop, Carmen Sanmartín, Elena González-Peñas, Adrián Durán and Elena Lizarraga

Molecules 2017, 22(8), 1314; https://doi.org/10.3390/molecules22081314 - 8 Aug 2017

Cited by 6 | Viewed by 5335

Abstract

The physicochemical properties of a compound play a crucial role in the cancer development process. In this context, polymorphism can become an important obstacle for the pharmaceutical industry because it frequently leads to the loss of therapeutic effectiveness of some drugs. Stability under [...] Read more.

The physicochemical properties of a compound play a crucial role in the cancer development process. In this context, polymorphism can become an important obstacle for the pharmaceutical industry because it frequently leads to the loss of therapeutic effectiveness of some drugs. Stability under manufacturing conditions is also critical to ensure no undesired degradations or transformations occur. In this study, the thermal behaviour of 40 derivatives of a series of sulphur and selenium heteroaryl compounds with potential antitumoural activity were studied. In addition, the most promising cytotoxic derivatives were analysed by a combination of differential scanning calorimetry, X-ray diffraction and thermogravimetric techniques in order to investigate their polymorphism and thermal stability. Moreover, stability under acid, alkaline and oxidative media was tested. Degradation under stress conditions as well as the presence of polymorphism was found for the compounds VA6E and VA7J, which might present a hurdle to carrying on with formulation. On the contrary, these obstacles were not found for derivative VA4J. Full article

► Show Figures

Figure 1

16 pages, 3391 KiB

Open AccessArticle

The Inhibitory Effects of Purple Sweet Potato Color on Hepatic Inflammation Is Associated with Restoration of NAD⁺ Levels and Attenuation of NLRP3 Inflammasome Activation in High-Fat-Diet-Treated Mice

by Xin Wang, Zi-Feng Zhang, Gui-Hong Zheng, Ai-Min Wang, Chun-Hui Sun, Su-Ping Qin, Juan Zhuang, Jun Lu, Dai-Fu Ma and Yuan-Lin Zheng

Molecules 2017, 22(8), 1315; https://doi.org/10.3390/molecules22081315 - 8 Aug 2017

Cited by 52 | Viewed by 9273

Abstract

Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, exhibits beneficial effects on metabolic syndrome. Sustained inflammation plays a crucial role in the pathogenesis of metabolic syndrome. Here we explored the effects of PSPC on high-fat diet (HFD)-induced hepatic inflammation and [...] Read more.

Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, exhibits beneficial effects on metabolic syndrome. Sustained inflammation plays a crucial role in the pathogenesis of metabolic syndrome. Here we explored the effects of PSPC on high-fat diet (HFD)-induced hepatic inflammation and the mechanisms underlying these effects. Mice were divided into four groups: Control group, HFD group, HFD + PSPC group, and PSPC group. PSPC was administered by daily oral gavage at doses of 700 mg/kg/day for 20 weeks. Nicotinamide riboside (NR) was used to increase NAD⁺ levels. Our results showed that PSPC effectively ameliorated obesity and liver injuries in HFD-fed mice. Moreover, PSPC notably blocked hepatic oxidative stress in HFD-treated mice. Furthermore, PSPC dramatically restored NAD⁺ level to abate endoplasmic reticulum stress (ER stress) in HFD-treated mouse livers, which was confirmed by NR treatment. Consequently, PSPC remarkably suppressed the nuclear factor-κB (NF-κB) p65 nuclear translocation and nucleotide oligomerization domain protein1/2 (NOD1/2) signaling in HFD-treated mouse livers. Thereby, PSPC markedly diminished the NLR family, pyrin domain containing 3 (NLRP3) inflammasome activation, ultimately lowering the expressions of inflammation-related genes in HFD-treated mouse livers. In summary, PSPC protected against HFD-induced hepatic inflammation by boosting NAD⁺ level to inhibit NLRP3 inflammasome activation. Full article

► Show Figures

Figure 1

15 pages, 3139 KiB

Open AccessArticle

Genetic Structure and Eco-Geographical Differentiation of Wild Sheep Fescue (Festuca ovina L.) in Xinjiang, Northwest China

by Chenglin Zhang, Jianbo Zhang, Yan Fan, Ming Sun, Wendan Wu, Wenda Zhao, Xiaopeng Yang, Linkai Huang, Yan Peng, Xiao Ma and Xinquan Zhang

Molecules 2017, 22(8), 1316; https://doi.org/10.3390/molecules22081316 - 9 Aug 2017

Cited by 12 | Viewed by 5410

Abstract

Glaciation and mountain orogeny have generated new ecologic opportunities for plants, favoring an increase in the speciation rate. Moreover, they also act as corridors or barriers for plant lineages and populations. High genetic diversity ensures that species are able to survive and adapt. [...] Read more.

Glaciation and mountain orogeny have generated new ecologic opportunities for plants, favoring an increase in the speciation rate. Moreover, they also act as corridors or barriers for plant lineages and populations. High genetic diversity ensures that species are able to survive and adapt. Gene flow is one of the most important determinants of the genetic diversity and structure of out-crossed species, and it is easily affected by biotic and abiotic factors. The aim of this study was to characterize the genetic diversity and structure of an alpine species, Festuca ovina L., in Xinjiang, China. A total of 100 individuals from 10 populations were analyzed using six amplified fragment length polymorphism (AFLP) primer pairs. A total of 583 clear bands were generated, of which 392 were polymorphic; thus, the percentage of polymorphic bands (PPB) was 67.24%. The total and average genetic diversities were 0.2722 and 0.2006 (0.1686–0.2225), respectively. The unweighted group method with arithmetic mean (UPGMA) tree, principal coordinates analysis (PCoA) and Structure analyses revealed that these populations or individuals could be clustered into two groups. The analysis of molecular variance analysis (AMOVA) suggested that most of the genetic variance existed within a population, and the genetic differentiation (Fst) among populations was 20.71%. The Shannon differentiation coefficient (G’st) among populations was 0.2350. Limited gene flow (Nm = 0.9571) was detected across all sampling sites. The Fst and Nm presented at different levels under the genetic barriers due to fragmentation. The population genetic diversity was significant relative to environmental factors such as temperature, altitude and precipitation. Full article

(This article belongs to the Section Molecular Diversity)

► Show Figures

Figure 1

19 pages, 5414 KiB

Open AccessArticle

Interaction of Flavonoids from Woodwardia unigemmata with Bovine Serum Albumin (BSA): Application of Spectroscopic Techniques and Molecular Modeling Methods

by Rui Ma, Hong Pan, Tao Shen, Peng Li, Yanan Chen, Zhenyu Li, Xiaxia Di and Shuqi Wang

Molecules 2017, 22(8), 1317; https://doi.org/10.3390/molecules22081317 - 9 Aug 2017

Cited by 16 | Viewed by 7516

Abstract

Phytochemical investigation on the methanol extract of Woodwardia unigemmata resulted in the isolation of seven flavonoids, including one new flavonol acylglycoside (1). The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis and comparison of literature data. [...] Read more.

Phytochemical investigation on the methanol extract of Woodwardia unigemmata resulted in the isolation of seven flavonoids, including one new flavonol acylglycoside (1). The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis and comparison of literature data. The multidrug resistance (MDR) reversing activity was evaluated for the isolated compounds using doxorubicin-resistant K562/A02 cells model. Compound 6 showed comparable MDR reversing effect to verapamil. Furthermore, the interaction between compounds and bovine serum albumin (BSA) was investigated by spectroscopic methods, including steady-state fluorescence, synchronous fluorescence, circular dichroism (CD) spectroscopies, and molecular docking approach. The experimental results indicated that the seven flavonoids bind to BSA by static quenching mechanisms. The negative ΔH and ΔS values indicated that van der Waals interactions and hydrogen bonds contributed in the binding of compounds 2–6 to BSA. In the case of compounds 1 and 7 systems, the hydrophobic interactions play a major role. The binding of compounds to BSA causes slight changes in the secondary structure of BSA. There are two binding sites of compound 6 on BSA and site I is the main site according to the molecular docking studies and the site marker competitive binding assay. Full article

(This article belongs to the Collection Natural Products: Anticancer Potential and Beyond)

► Show Figures

Graphical abstract

21 pages, 3821 KiB

Open AccessArticle

Transcriptional Responses of Creeping Bentgrass to 2,3-Butanediol, a Bacterial Volatile Compound (BVC) Analogue

by Yi Shi, Kuiju Niu, Bingru Huang, Wenhui Liu and Huiling Ma

Molecules 2017, 22(8), 1318; https://doi.org/10.3390/molecules22081318 - 16 Aug 2017

Cited by 23 | Viewed by 6160

Abstract

Bacterial volatile compounds (BVCs) have been reported to enhance plant growth and elicit plant defenses against fungal infection and insect damage. The objective of this study was to determine transcriptomic changes in response to synthetic BVC that could be associated with plant resistance [...] Read more.

Bacterial volatile compounds (BVCs) have been reported to enhance plant growth and elicit plant defenses against fungal infection and insect damage. The objective of this study was to determine transcriptomic changes in response to synthetic BVC that could be associated with plant resistance to Rhizoctonia solani in creeping bentgrass. The 2,3-butanediol (BD) (250 µM) was sprayed on creeping bentgrass leaves grown in jam jars. The result showed that synthetic BD induced plant defense against R. solani for creeping bentgrass. Transcriptomic analysis demonstrated that more genes were repressed by BD while less showed up-regulation. BD suppressed the expression of some regular stress-related genes in creeping bentgrass, such as pheromone activity, calcium channel activity, photosystem II oxygen evolving complex, and hydrolase activity, while up-regulated defense related transcription factors (TFs), such as basic helix-loop-helix (bHLH) TFs, cysteine2-cysteine2-contans-like (C2C2-CO) and no apical meristem TFs (NAC). Other genes related to disease resistance, such as jasmonic acid (JA) signaling, leucine rich repeats (LRR)-transmembrane protein kinase, pathogen-related (PR) gene 5 receptor kinase and nucleotide binding site-leucine rich repeats (NBS-LRR) domain containing plant resistance gene (R-gene) were also significantly up-regulated. These results suggest that BD may induce changes to the plant transcriptome in induced systemic resistance (ISR) pathways. Full article

► Show Figures

Figure 1

11 pages, 839 KiB

Open AccessArticle

Cytotoxic and Antiviral Triterpenoids from the Mangrove Plant Sonneratia paracaseolaris

by Kai-Kai Gong, Ping-Lin Li, Dan Qiao, Xing-Wang Zhang, Mei-Jun Chu, Guo-Fei Qin, Xu-Li Tang and Guo-Qiang Li

Molecules 2017, 22(8), 1319; https://doi.org/10.3390/molecules22081319 - 9 Aug 2017

Cited by 28 | Viewed by 4589

Abstract

A chemical investigation was conducted on the aerial parts of the mangrove plant Sonneratia paracaseolaris, yielding five new triterpenoid paracaseolins A–E (1–4, and 11) together with twelve known analogues (5–10, 12– [...] Read more.

A chemical investigation was conducted on the aerial parts of the mangrove plant Sonneratia paracaseolaris, yielding five new triterpenoid paracaseolins A–E (1–4, and 11) together with twelve known analogues (5–10, 12–17). Their structures were established by extensive spectroscopic methods and comparisons their spectroscopic data with those of the known related compounds. The cytotoxicities against P388, HeLa, A549, and K562 tumor cell lines and anti-H1N1 (Influenza A virus) activities for the isolates were evaluated. Compound 4 showed potent cytotoxicity against the A549 cell line with an IC₅₀ value of 1.89 µM, and compound 1 exhibited significant anti-H1N1 virus activity with an IC₅₀ value of 28.4 µg/mL. A preliminary structure activity relationship was discussed. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

15 pages, 2327 KiB

Open AccessFeature PaperArticle

Enzymatic Synthesis of N-Acetyllactosamine (LacNAc) Type 1 Oligomers and Characterization as Multivalent Galectin Ligands

by Thomas Fischöder, Dominic Laaf, Carina Dey and Lothar Elling

Molecules 2017, 22(8), 1320; https://doi.org/10.3390/molecules22081320 - 10 Aug 2017

Cited by 34 | Viewed by 11174

Abstract

Repeats of the disaccharide unit N-acetyllactosamine (LacNAc) occur as type 1 (Galβ1, 3GlcNAc) and type 2 (Galβ1, 4GlcNAc) glycosylation motifs on glycoproteins and glycolipids. The LacNAc motif acts as binding ligand for lectins and is involved in many biological recognition events. To [...] Read more.

Repeats of the disaccharide unit N-acetyllactosamine (LacNAc) occur as type 1 (Galβ1, 3GlcNAc) and type 2 (Galβ1, 4GlcNAc) glycosylation motifs on glycoproteins and glycolipids. The LacNAc motif acts as binding ligand for lectins and is involved in many biological recognition events. To the best of our knowledge, we present, for the first time, the synthesis of LacNAc type 1 oligomers using recombinant β1,3-galactosyltransferase from Escherichia coli and β1,3-N-acetylglucosaminyltranferase from Helicobacter pylori. Tetrasaccharide glycans presenting LacNAc type 1 repeats or LacNAc type 1 at the reducing or non-reducing end, respectively, were conjugated to bovine serum albumin as a protein scaffold by squarate linker chemistry. The resulting multivalent LacNAc type 1 presenting neo-glycoproteins were further studied for specific binding of the tumor-associated human galectin 3 (Gal-3) and its truncated counterpart Gal-3∆ in an enzyme-linked lectin assay (ELLA). We observed a significantly increased affinity of Gal-3∆ towards the multivalent neo-glycoprotein presenting LacNAc type 1 repeating units. This is the first evidence for differences in glycan selectivity of Gal-3∆ and Gal-3 and may be further utilized for tracing Gal-3∆ during tumor progression and therapy. Full article

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

► Show Figures

Graphical abstract

16 pages, 583 KiB

Open AccessArticle

Potential Development of Tumor-Targeted Oral Anti-Cancer Prodrugs: Amino Acid and Dipeptide Monoester Prodrugs of Gemcitabine

by Yasuhiro Tsume, Adam J. Drelich, David E. Smith and Gordon L. Amidon

Molecules 2017, 22(8), 1322; https://doi.org/10.3390/molecules22081322 - 10 Aug 2017

Cited by 16 | Viewed by 5985

Abstract

One of the main obstacles for cancer therapies is to deliver medicines effectively to target sites. Since stroma cells are developed around tumors, chemotherapeutic agents have to go through stroma cells in order to reach tumors. As a method to improve drug delivery [...] Read more.

One of the main obstacles for cancer therapies is to deliver medicines effectively to target sites. Since stroma cells are developed around tumors, chemotherapeutic agents have to go through stroma cells in order to reach tumors. As a method to improve drug delivery to the tumor site, a prodrug approach for gemcitabine was adopted. Amino acid and dipeptide monoester prodrugs of gemcitabine were synthesized and their chemical stability in buffers, resistance to thymidine phosphorylase and cytidine deaminase, antiproliferative activity, and uptake/permeability in HFF cells as a surrogate to stroma cells were determined and compared to their parent drug, gemcitabine. The activation of all gemcitabine prodrugs was faster in pancreatic cell homogenates than their hydrolysis in buffer, suggesting enzymatic action. All prodrugs exhibited great stability in HFF cell homogenate, enhanced resistance to glycosidic bond metabolism by thymidine phosphorylase, and deamination by cytidine deaminase compared to their parent drug. All gemcitabine prodrugs exhibited higher uptake in HFF cells and better permeability across HFF monolayers than gemcitabine, suggesting a better delivery to tumor sites. Cell antiproliferative assays in Panc-1 and Capan-2 pancreatic ductal cell lines indicated that the gemcitabine prodrugs were more potent than their parent drug gemcitabine. The transport and enzymatic profiles of gemcitabine prodrugs suggest their potential for delayed enzymatic bioconversion and enhanced resistance to metabolic enzymes, as well as for enhanced drug delivery to tumor sites, and cytotoxic activity in cancer cells. These attributes would facilitate the prolonged systemic circulation and improved therapeutic efficacy of gemcitabine prodrugs. Full article

(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)

► Show Figures

Figure 1

18 pages, 3469 KiB

Open AccessArticle

Phosphate-Linked Silibinin Dimers (PLSd): New Promising Modified Metabolites

by Valeria Romanucci, Raffaele Gravante, Martina Cimafonte, Cinzia Di Marino, Gilles Mailhot, Marcello Brigante, Armando Zarrelli and Giovanni Di Fabio

Molecules 2017, 22(8), 1323; https://doi.org/10.3390/molecules22081323 - 11 Aug 2017

Cited by 23 | Viewed by 5134

Abstract

By exploiting the regioselective protection of the hydroxyl groups of silibinin along with the well-known phosphoramidite chemistry, we have developed an efficient strategy for the synthesis of new silibinin-modified species, which we have named Phosphate-Linked Silibinin Dimers (PLSd), in which the monomer units [...] Read more.

By exploiting the regioselective protection of the hydroxyl groups of silibinin along with the well-known phosphoramidite chemistry, we have developed an efficient strategy for the synthesis of new silibinin-modified species, which we have named Phosphate-Linked Silibinin Dimers (PLSd), in which the monomer units are linked by phosphodiester bonds. The antioxidant abilities of the new PLSd were estimated on HepG2 cells using DPPH free radical scavenging and xanthine/xanthine oxidase assays. The new phosphate-metabolites showed a higher anti-oxidant activity than the silibinin, as well as very low toxicity. The ability to scavenge reactive oxygen species (ROS) such as singlet oxygen () and hydroxyl radical () reveals that the two dimers are able to scavenge about two times more effectively than silibinin. Finally, solubility studies have shown that the PLSd present good water solubility (more than 20 mg·L⁻¹) under circumneutral pH values, whereas the silibinin was found to be very poorly soluble (less than 0.4 mg·L⁻¹) and not stable under alkaline conditions. Together, the above promising results warrant further investigation of the future potential of the PLSd as anti-oxidant metabolites within the large synthetic polyphenols field. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

► Show Figures

Figure 1

20 pages, 2209 KiB

Open AccessFeature PaperReview

Computational Studies on Acetylcholinesterases

by Yechun Xu, Shanmei Cheng, Joel L. Sussman, Israel Silman and Hualiang Jiang

Molecules 2017, 22(8), 1324; https://doi.org/10.3390/molecules22081324 - 10 Aug 2017

Cited by 49 | Viewed by 10190

Abstract

Functions of biomolecules, in particular enzymes, are usually modulated by structural fluctuations. This is especially the case in a gated diffusion-controlled reaction catalyzed by an enzyme such as acetylcholinesterase. The catalytic triad of acetylcholinesterase is located at the bottom of a long and [...] Read more.

Functions of biomolecules, in particular enzymes, are usually modulated by structural fluctuations. This is especially the case in a gated diffusion-controlled reaction catalyzed by an enzyme such as acetylcholinesterase. The catalytic triad of acetylcholinesterase is located at the bottom of a long and narrow gorge, but it catalyzes the extremely rapid hydrolysis of the neurotransmitter, acetylcholine, with a reaction rate close to the diffusion-controlled limit. Computational modeling and simulation have produced considerable advances in exploring the dynamical and conformational properties of biomolecules, not only aiding in interpreting the experimental data, but also providing insights into the internal motions of the biomolecule at the atomic level. Given the remarkably high catalytic efficiency and the importance of acetylcholinesterase in drug development, great efforts have been made to understand the dynamics associated with its functions by use of various computational methods. Here, we present a comprehensive overview of recent computational studies on acetylcholinesterase, expanding our views of the enzyme from a microstate of a single structure to conformational ensembles, strengthening our understanding of the integration of structure, dynamics and function associated with the enzyme, and promoting the structure-based and/or mechanism-based design of new inhibitors for it. Full article

(This article belongs to the Special Issue The Cholinesterases—Structure, Mechanism, Function and Drug Design: The 25th Anniversary of the Solution of the Crystal Structure of Acetylcholinesterase by Joel L. Sussman and Israel Silman)

► Show Figures

Figure 1

15 pages, 2192 KiB

Open AccessArticle

Research on a Nonwoven Fabric Made from Multi-Block Biodegradable Copolymer Based on l-Lactide, Glycolide, and Trimethylene Carbonate with Shape Memory

by Joanna Walczak, Michał Chrzanowski and Izabella Krucińska

Molecules 2017, 22(8), 1325; https://doi.org/10.3390/molecules22081325 - 10 Aug 2017

Cited by 8 | Viewed by 5592

Abstract

The presented paper concerns scientific research on processing a poly(lactide-co-glycolide-co-trimethylene carbonate) copolymer (PLLAGLTMC) with thermally induced shape memory and a transition temperature around human body temperature. The material in the literature called terpolymer was used to produce smart, nonwoven [...] Read more.

The presented paper concerns scientific research on processing a poly(lactide-co-glycolide-co-trimethylene carbonate) copolymer (PLLAGLTMC) with thermally induced shape memory and a transition temperature around human body temperature. The material in the literature called terpolymer was used to produce smart, nonwoven fabric with the melt blowing technique. Bioresorbable and biocompatible terpolymers with shape memory have been investigated for its medical applications, such as cardiovascular stents. There are several research studies on shape memory in polymers, but this phenomenon has not been widely studied in textile products made from shape memory polymers (SMPs). The current research aims to explore the characteristics of the PLLAGLTMC nonwoven fabric in detail and the mechanism of its shape memory behavior. In this study, the nonwoven fabric was subjected to thermo-mechanical, morphological, and shape memory analysis. The thermo-mechanical and structural properties were investigated by means of differential scanning calorimetry, dynamic mechanical analysis, scanning electron microscopic examination, and mercury porosimetry measurements. Eventually, the gathered results confirmed that the nonwoven fabric possessed characteristics that classified it as a smart material with potential applications in medicine. Full article

(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

► Show Figures

Figure 1

12 pages, 4477 KiB

Open AccessArticle

Sequestration Effect on the Open-Cyclic Switchable Property of Warfarin Induced by Cyclodextrin: Time-Resolved Fluorescence Study

by Naji Al-Dubaili and Na’il Saleh

Molecules 2017, 22(8), 1326; https://doi.org/10.3390/molecules22081326 - 11 Aug 2017

Cited by 7 | Viewed by 4599

Abstract

The excited-state lifetimes of the anticoagulant drug warfarin (W) in water and in the absence and presence of methyl-β-cyclodextrins (Me-β-CD) were recorded using time-resolved fluorescence measurements. Selective excitation of the open and cyclic protonated isomers of W were acquired with laser emitting diodes [...] Read more.

The excited-state lifetimes of the anticoagulant drug warfarin (W) in water and in the absence and presence of methyl-β-cyclodextrins (Me-β-CD) were recorded using time-resolved fluorescence measurements. Selective excitation of the open and cyclic protonated isomers of W were acquired with laser emitting diodes (LED) producing 320 and 280 nm excitation pulses, respectively. Formation of the inclusion complex was checked by UV-visible absorption spectroscopy, and the values of binding constants (2.9 × 10³ M^–1 and 4.2 × 10² M⁻¹ for protonated and deprotonated forms, respectively) were extracted from the spectrophotometric data. Both absorption and time-resolved fluorescence results established that the interior of the macromolecular host binds preferentially the open protonated form, red shifts the maximum of its absorption of light at ~305 nm, extends its excited-state lifetime, and decreases its emission quantum yield (Ф_F). Collectively, sequestration of the open guest molecules decreases markedly their radiative rate constants (k_r), likely due to formation of hydrogen-bonded complexes in both the ground and excited states. Due to lack of interactions, no change was observed in the excited-state lifetime of the cyclic form in the presence of Me-β-CD. The host also increases the excited-state lifetime and Ф_F of the drug deprotonated form (W⁻). These later findings could be attributed to the increased rigidity inside the cavity of Me-β-CD. The pK_a values extracted from the variations of the UV-visible absorption spectra of W versus the pH of aqueous solution showed that the open isomer is more acidic in both ground and excited states. The positive shifts in pK_a values induced by three derivatives of cyclodextrins: HE-β-CD, Ac-β-CD, and Me-β-CD supported the preferential binding of these hosts to open isomers over cyclic. Full article

(This article belongs to the Section Photochemistry)

► Show Figures

Graphical abstract

12 pages, 2281 KiB

Open AccessArticle

UPLC-QTOF-MS Identification of the Chemical Constituents in Rat Plasma and Urine after Oral Administration of Rubia cordifolia L. Extract

by Zuoliang Zheng, Shengqing Li, Yuping Zhong, Ruoting Zhan, Yan Yan, Huafeng Pan and Ping Yan

Molecules 2017, 22(8), 1327; https://doi.org/10.3390/molecules22081327 - 11 Aug 2017

Cited by 13 | Viewed by 5335

Abstract

An effective ultra-performance liquid chromatography coupled with the quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF/MS) method was developed for analysing the chemical constituents in rat plasma and urine after the oral administration of Rubia cordifolia L. extract. Under the optimized conditions, nine of 11 [...] Read more.

An effective ultra-performance liquid chromatography coupled with the quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF/MS) method was developed for analysing the chemical constituents in rat plasma and urine after the oral administration of Rubia cordifolia L. extract. Under the optimized conditions, nine of 11 prototypes in rat plasma and four prototypes in urine were identified or characterized by comparing the retention time, accurate mass, fragmentation patterns, reference compounds, and literature data. In total, six metabolites, including alizarin-1-O-β-glucuronide, alizarin-2-O-β-glucuronide, alizarin-1-O-sulfation, alizarin-2-O-sulfation, purpurin-1-O-β-glucuronide, and purpurin-3-O-β-glucuronide, were identified in rat plasma, which were confirmed by lavaging standard solutions. Purpurin was found to be able to be transformed into alizarin based on the results in which alizarin was detected in rat plasma after the oral administration of a purpurin solution. In total, four metabolites were found in rat urine, but their chemical structures were not confirmed. The results indicate that the metabolic pathway of alizarin involves glucuronidation and sulfation, with the purpurins having undergone glucuronidation. The components absorbed into the blood, and the metabolites have the opportunity to become bioactive constituents. The experimental results would supply a helpful chemical basis for further research on the mechanism of actions of Rubia cordifolia L. Full article

► Show Figures

Figure 1

14 pages, 2524 KiB

Open AccessFeature PaperArticle

Asymmetric Michael Addition Organocatalyzed by α,β-Dipeptides under Solvent-Free Reaction Conditions

by C. Gabriela Avila-Ortiz, Lenin Díaz-Corona, Erika Jiménez-González and Eusebio Juaristi

Molecules 2017, 22(8), 1328; https://doi.org/10.3390/molecules22081328 - 10 Aug 2017

Cited by 27 | Viewed by 7516

Abstract

The application of six novel α,β-dipeptides as chiral organocatalysts in the asymmetric Michael addition reaction between enolizable aldehydes and N-arylmaleimides or nitroolefins is described. With N-arylmaleimides as substrates, the best results were achieved with dipeptide 2 as a catalyst in the [...] Read more.

The application of six novel α,β-dipeptides as chiral organocatalysts in the asymmetric Michael addition reaction between enolizable aldehydes and N-arylmaleimides or nitroolefins is described. With N-arylmaleimides as substrates, the best results were achieved with dipeptide 2 as a catalyst in the presence of aq. NaOH. Whereas dipeptides 4 and 6 in conjunction with 4-dimethylaminopyridine (DMAP) and thiourea as a hydrogen bond donor proved to be highly efficient organocatalytic systems in the enantioselective reaction between isobutyraldehyde and various nitroolefins. Full article

(This article belongs to the Collection Recent Advances in Organocatalysis)

► Show Figures

Figure 1

19 pages, 986 KiB

Open AccessReview

Significance of Resveratrol in Clinical Management of Chronic Diseases

by Awais Wahab, Kuo Gao, Caixia Jia, Feilong Zhang, Guihua Tian, Ghulam Murtaza and Jianxin Chen

Molecules 2017, 22(8), 1329; https://doi.org/10.3390/molecules22081329 - 18 Aug 2017

Cited by 92 | Viewed by 9200

Abstract

Resveratrol could be beneficial to health and provides protection against a wide array of pathologies and age-associated problems, as evident from preclinical studies. However, a comparison of animal and human studies reveals that this dietary polyphenol cannot protect against metabolic diseases and their [...] Read more.

Resveratrol could be beneficial to health and provides protection against a wide array of pathologies and age-associated problems, as evident from preclinical studies. However, a comparison of animal and human studies reveals that this dietary polyphenol cannot protect against metabolic diseases and their associated complications. The clinical outcomes are affected by many factors such as sample size. This article not only presents a comprehensive review of the current advances concerning the dose, the extent of absorption, interaction and toxicity of resveratrol in human studies, but also describes its therapeutic effects against several chronic diseases such as diabetes mellitus, obesity, cardiovascular diseases, cancer and aging and the related diseases. Full article

(This article belongs to the Special Issue Improvements for Resveratrol Efficacy)

► Show Figures

Figure 1

14 pages, 6080 KiB

Open AccessArticle

Complete Chloroplast Genome Sequence and Phylogenetic Analysis of the Medicinal Plant Artemisia annua

by Xiaofeng Shen, Mingli Wu, Baosheng Liao, Zhixiang Liu, Rui Bai, Shuiming Xiao, Xiwen Li, Boli Zhang, Jiang Xu and Shilin Chen

Molecules 2017, 22(8), 1330; https://doi.org/10.3390/molecules22081330 - 11 Aug 2017

Cited by 138 | Viewed by 9849

Abstract

The complete chloroplast genome of Artemisia annua (Asteraceae), the primary source of artemisinin, was sequenced and analyzed. The A. annua cp genome is 150,995 bp, and harbors a pair of inverted repeat regions (IRa and IRb), of 24,850 bp each that separate large [...] Read more.

The complete chloroplast genome of Artemisia annua (Asteraceae), the primary source of artemisinin, was sequenced and analyzed. The A. annua cp genome is 150,995 bp, and harbors a pair of inverted repeat regions (IRa and IRb), of 24,850 bp each that separate large (LSC, 82,988 bp) and small (SSC, 18,267 bp) single-copy regions. Our annotation revealed that the A. annua cp genome contains 113 genes and 18 duplicated genes. The gene order in the SSC region of A. annua is inverted; this fact is consistent with the sequences of chloroplast genomes from three other Artemisia species. Fifteen (15) forward and seventeen (17) inverted repeats were detected in the genome. The existence of rich SSR loci in the genome suggests opportunities for future population genetics work on this anti-malarial medicinal plant. In A. annua cpDNA, the rps19 gene was found in the LSC region rather than the IR region, and the rps19 pseudogene was absent in the IR region. Sequence divergence analysis of five Asteraceae species indicated that the most highly divergent regions were found in the intergenic spacers, and that the differences between A. annua and A. fukudo were very slight. A phylogenetic analysis revealed a sister relationship between A. annua and A. fukudo. This study identified the unique characteristics of the A. annua cp genome. These results offer valuable information for future research on Artemisia species identification and for the selective breeding of A. annua with high pharmaceutical efficacy. Full article

► Show Figures

Figure 1

12 pages, 1458 KiB

Open AccessArticle

Anti-Anxiety Effect of (−)-Syringaresnol-4-O-β-d-apiofuranosyl-(1→2)-β-d-glucopyranoside from Albizzia julibrissin Durazz (Leguminosae)

by Jie Liu, Yue-Wei Lv, Jin-Li Shi, Xiao-Jie Ma, Yi Chen, Zhi-Quan Zheng, Sheng-Nan Wang and Jian-You Guo

Molecules 2017, 22(8), 1331; https://doi.org/10.3390/molecules22081331 - 11 Aug 2017

Cited by 19 | Viewed by 5522

Abstract

Albizzia julibrissin Durazz, a Chinese Medicine, is commonly used for its anti-anxiety effects. (−)-syringaresnol-4-O-β-d-apiofuranosyl-(1→2)-β-d-glucopyranoside (SAG) is the main ingredient of Albizzia julibrissin Durazz. The present study investigated the anxiolytic effect and potential mechanisms on the HPA axis [...] Read more.

Albizzia julibrissin Durazz, a Chinese Medicine, is commonly used for its anti-anxiety effects. (−)-syringaresnol-4-O-β-d-apiofuranosyl-(1→2)-β-d-glucopyranoside (SAG) is the main ingredient of Albizzia julibrissin Durazz. The present study investigated the anxiolytic effect and potential mechanisms on the HPA axis and monoaminergic systems of SAG on acute restraint-stressed rats. The anxiolytic effect of SAG was examined through an open field test and an elevated plus maze test. The concentration of CRF, ACTH, and CORT in plasma was examined by an enzyme-linked immune sorbent assay (ELISA) kit while neurotransmitters in the cerebral cortex and hippocampus of the brain were examined by High Performance Liquid Chromatography (HPLC). We show that repeated treatment with SAG (3.6 mg/kg, p.o.) significantly increased the number and time spent on the central entries in the open-field test when compared to the vehicle/stressed group. In the elevated plus maze test, 3.6 mg/kg SAG could increase the percentage of entries into and time spent on the open arms of the elevated plus maze. In addition, the concentration of CRF, ACTH, and CORT in plasma and neurotransmitters (NE, 5-HT, DA and their metabolites 5-HIAA, DOPAC, and HVA) in the cerebral cortex and hippocampus of the brain were decreased after SAG treatment, as compared to the repeated acute restraint-stressed rats. These results suggest that SAG is a potential anti-anxiety drug candidate. Full article

(This article belongs to the Collection Herbal Medicine Research)

► Show Figures

Figure 1

17 pages, 5644 KiB

Open AccessArticle

Effect of 2,6-Bis-(1-hydroxy-1,1-diphenyl-methyl) Pyridine as Organic Additive in Sulfide NiMoP/γ-Al₂O₃ Catalyst for Hydrodesulfurization of Straight-Run Gas Oil

by Carlos Eduardo Santolalla-Vargas, Victor Santes, Erick Meneses-Domínguez, Vicente Escamilla, Agileo Hernández-Gordillo, Elizabeth Gómez, Felipe Sánchez-Minero, José Escobar, Leonardo Díaz and Oscar Goiz

Molecules 2017, 22(8), 1332; https://doi.org/10.3390/molecules22081332 - 15 Aug 2017

Cited by 4 | Viewed by 5389

Abstract

The effect of 2,6-bis-(1-hydroxy-1,1-diphenyl-methyl) pyridine (BDPHP) in the preparation of NiMoP/γ-Al₂O₃ catalysts have been investigated in the hydrodesulfurization (HDS) of straight-run gas oil. The γ-Al₂O₃ support was modified by surface impregnation of a solution of BDPHP to [...] Read more.

The effect of 2,6-bis-(1-hydroxy-1,1-diphenyl-methyl) pyridine (BDPHP) in the preparation of NiMoP/γ-Al₂O₃ catalysts have been investigated in the hydrodesulfurization (HDS) of straight-run gas oil. The γ-Al₂O₃ support was modified by surface impregnation of a solution of BDPHP to afford BDPHP/Ni molar ratios (0.5 and 1.0) in the final composition. The highest activity for NiMoP materials was found when the molar ratio of BDPHP/Ni was of 0.5. X-ray diffraction (XRD) results revealed that NiMoP (0.5) showed better dispersion of MoO₃ than the NiMoP (1.0). Fourier transform infrared spectroscopy (FT-IR) results indicated that the organic additive interacts with the γ-Al₂O₃ surface and therefore discards the presence of Mo or Ni complexes. Raman spectroscopy suggested a high Raman ratio for the NiMoP (0.5) sample. The increment of the Mo=O species is related to a major availability of Mo species in the formation of MoS₂. The temperature programmed reduction (TPR) results showed that the NiMoP (0.5) displayed moderate metal–support interaction. Likewise, X-ray photoelectron spectroscopy (XPS) exhibited higher sulfurization degree for NiMoP (0.5) compared with NiMoP (1.0). The increment of the MoO₃ dispersion, the moderate metal–support interaction, the increase of sulfurization degree and the increment of Mo=O species provoked by the BDPHP incorporation resulted in a higher gas oil HDS activity. Full article

(This article belongs to the Special Issue Bimetallic Catalysis)

► Show Figures

Figure 1

11 pages, 1145 KiB

Open AccessArticle

Readily Available Chiral Benzimidazoles-Derived Guanidines as Organocatalysts in the Asymmetric α-Amination of 1,3-Dicarbonyl Compounds

by Llorenç Benavent, Francesco Puccetti, Alejandro Baeza and Melania Gómez-Martínez

Molecules 2017, 22(8), 1333; https://doi.org/10.3390/molecules22081333 - 11 Aug 2017

Cited by 16 | Viewed by 6405

Abstract

The synthesis and the evaluation as organocatalysts of new chiral guanidines derived from benzimidazoles in the enantioselective α-amination of 1,3-dicarbonyl compounds using di-t-butylazodicarboxylate as aminating agent is herein disclosed. The catalysts are readily synthesized through the reaction of 2-chlorobezimidazole and a [...] Read more.

The synthesis and the evaluation as organocatalysts of new chiral guanidines derived from benzimidazoles in the enantioselective α-amination of 1,3-dicarbonyl compounds using di-t-butylazodicarboxylate as aminating agent is herein disclosed. The catalysts are readily synthesized through the reaction of 2-chlorobezimidazole and a chiral amine in moderate-to-good yields. Among all of them, those derived from (R)-1-phenylethan-1-amine (1) and (S)-1-(2-naphthyl)ethan-1-amine (3) turned out to be the most efficient for such asymmetric transformation, rendering good-to-high yields and moderate-to-good enantioselectivities for the amination products. Full article

(This article belongs to the Collection Recent Advances in Organocatalysis)

► Show Figures

Figure 1

11 pages, 1816 KiB

Open AccessReview

H₂S-Mediated Protein S-Sulfhydration: A Prediction for Its Formation and Regulation

by Youngjun Ju, Ming Fu, Eric Stokes, Lingyun Wu and Guangdong Yang

Molecules 2017, 22(8), 1334; https://doi.org/10.3390/molecules22081334 - 11 Aug 2017

Cited by 52 | Viewed by 9140

Abstract

Protein S-sulfhydration is a newly discovered post-translational modification of specific cysteine residue(s) in target proteins, which is involved in a broad range of cellular functions and metabolic pathways. By changing local conformation and the final activity of target proteins, S-sulfhydration is [...] Read more.

Protein S-sulfhydration is a newly discovered post-translational modification of specific cysteine residue(s) in target proteins, which is involved in a broad range of cellular functions and metabolic pathways. By changing local conformation and the final activity of target proteins, S-sulfhydration is believed to mediate most cellular responses initiated by H₂S, a novel gasotransmitter. In comparison to protein S-sulfhydration, nitric oxide-mediated protein S-nitrosylation has been extensively investigated, including its formation, regulation, transfer and metabolism. Although the investigation on the regulatory mechanisms associated with protein S-sulfhydration is still in its infancy, accumulated evidence suggested that protein S-sulfhydration may share similar chemical features with protein S-nitrosylation. Glutathione persulfide acts as a major donor for protein S-sulfhydration. Here, we review the present knowledge on protein S-sulfhydration, and also predict its formation and regulation mechanisms based on the knowledge from protein S-nitrosylation. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

12 pages, 846 KiB

Open AccessArticle

Phytochemicals of Euphorbia lathyris L. and Their Antioxidant Activities

by Lizhen Zhang, Chu Wang, Qiuxia Meng, Qin Tian, Yu Niu and Wei Niu

Molecules 2017, 22(8), 1335; https://doi.org/10.3390/molecules22081335 - 18 Aug 2017

Cited by 21 | Viewed by 5539

Abstract

The objectives of this study were to characterize the antioxidant capacities and phytochemicals such as phenolics and flavonoids in four parts of Euphorbia lathyris L. HPLC was employed to detect the type and content of phenolic acids and flavonoids in the root, stem, [...] Read more.

The objectives of this study were to characterize the antioxidant capacities and phytochemicals such as phenolics and flavonoids in four parts of Euphorbia lathyris L. HPLC was employed to detect the type and content of phenolic acids and flavonoids in the root, stem, seed, and testa of the plant. The total phenolic content (TPC) and total flavonoid content (TFC) were different among various parts of E. lathyris. The highest TPC were found in the testa (290.46 ± 15.09 mg of gallic acid equiv/100 g dry weight (DW)). However, the root contained the highest TFC (215.68 ± 3.10 mg of rutin equiv/g DW). Of the different antioxidant activities detected, DPPH free radical scavenging activity was highest in the testa (61.29 ± 0.29 mmol Trolox/100 g DW), but the highest FRAP antioxidant activity was found in the seed (1131.25 ± 58.68 mg FeSO₄/100 g DW of free compounds and 1927.43 ± 52.13 mg FeSO₄/100 g DW of bound compounds). There was a positive correlation between the total phenolic contents and DPPH free radical scavenging activity in different parts of E. lathyris. Full article

(This article belongs to the Special Issue Selected Papers from the 6th International Conference on Biotechnology and Bioengineering (6-ICBB 2017))

► Show Figures

Figure 1

20 pages, 2821 KiB

Open AccessArticle

Human Adenocarcinoma Cell Line Sensitivity to Essential Oil Phytocomplexes from Pistacia Species: a Multivariate Approach

by Alessandro Buriani, Stefano Fortinguerra, Vincenzo Sorrenti, Stefano Dall’Acqua, Gabbriella Innocenti, Monica Montopoli, Daniela Gabbia and Maria Carrara

Molecules 2017, 22(8), 1336; https://doi.org/10.3390/molecules22081336 - 11 Aug 2017

Cited by 31 | Viewed by 5807

Abstract

Principal component analysis (PCA) multivariate analysis was applied to study the cytotoxic activity of essential oils from various species of the Pistacia genus on human tumor cell lines. In particular, the cytotoxic activity of essential oils obtained from P. lentiscus, P. lentiscus [...] Read more.

Principal component analysis (PCA) multivariate analysis was applied to study the cytotoxic activity of essential oils from various species of the Pistacia genus on human tumor cell lines. In particular, the cytotoxic activity of essential oils obtained from P. lentiscus, P. lentiscus var. chia (mastic gum), P. terebinthus, P. vera, and P. integerrima, was screened on three human adenocarcinoma cell lines: MCF-7 (breast), 2008 (ovarian), and LoVo (colon). The results indicate that all the Pistacia phytocomplexes, with the exception of mastic gum oil, induce cytotoxic effects on one or more of the three cell lines. PCA highlighted the presence of different cooperating clusters of bioactive molecules. Cluster variability among species, and even within the same species, could explain some of the differences seen among samples suggesting the presence of both common and species-specific mechanisms. Single molecules from one of the most significant clusters were tested, but only bornyl-acetate presented cytotoxic activity, although at much higher concentrations (IC₅₀ = 138.5 µg/mL) than those present in the essential oils, indicating that understanding of the full biological effect requires a holistic vision of the phytocomplexes with all its constituents. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Graphical abstract

18 pages, 1304 KiB

Open AccessReview

A Review of the Antiviral Role of Green Tea Catechins

by Jun Xu, Zhao Xu and Wenming Zheng

Molecules 2017, 22(8), 1337; https://doi.org/10.3390/molecules22081337 - 12 Aug 2017

Cited by 175 | Viewed by 19921

Abstract

Over the centuries, infectious diseases caused by viruses have seriously threatened human health globally. Viruses are responsible not only for acute infections but also many chronic infectious diseases. To prevent diseases caused by viruses, the discovery of effective antiviral drugs, in addition to [...] Read more.

Over the centuries, infectious diseases caused by viruses have seriously threatened human health globally. Viruses are responsible not only for acute infections but also many chronic infectious diseases. To prevent diseases caused by viruses, the discovery of effective antiviral drugs, in addition to vaccine development, is important. Green tea catechins (GTCs) are polyphenolic compounds from the leaves of Camellia sinensis. In recent decades, GTCs have been reported to provide various health benefits against numerous diseases. Studies have shown that GTCs, especially epigallocatechin-3-gallate (EGCG), have antiviral effects against diverse viruses. The aim of this review is to summarize the developments regarding the antiviral activities of GTCs, to discuss the mechanisms underlying these effects and to offer suggestions for future research directions and perspectives on the antiviral effects of EGCG. Full article

(This article belongs to the Special Issue Natural Products and Chronic Diseases)

► Show Figures

Figure 1

15 pages, 906 KiB

Open AccessArticle

Portuguese Honeys from Different Geographical and Botanical Origins: A 4-Year Stability Study Regarding Quality Parameters and Antioxidant Activity

by Sonia Soares, Diana Pinto, Francisca Rodrigues, Rita C. Alves and M. Beatriz P.P. Oliveira

Molecules 2017, 22(8), 1338; https://doi.org/10.3390/molecules22081338 - 11 Aug 2017

Cited by 36 | Viewed by 5511

Abstract

Portuguese honeys (n = 15) from different botanical and geographical origins were analysed regarding their quality parameters (diastase activity, hydroxymethylfurfural content, moisture and pH), colour (L*, a*, b*) and antioxidant profile (total phenolics content, total flavonoids content, DPPH• scavenging activity, and ferric reducing [...] Read more.

Portuguese honeys (n = 15) from different botanical and geographical origins were analysed regarding their quality parameters (diastase activity, hydroxymethylfurfural content, moisture and pH), colour (L*, a*, b*) and antioxidant profile (total phenolics content, total flavonoids content, DPPH• scavenging activity, and ferric reducing power). The samples were analysed fresh and after 4-years of storage (at 25 °C and protected from light). The hydroxymethylfurfural content and diastase activity of the fresh samples were in accordance with the recommended values described in the legislation. In general, the antioxidant activity of the samples correlated more with the bioactive compounds content than with colour. The storage affected differently each individual sample, especially regarding the antioxidant profile. Nevertheless, although in general the lightness of the samples decreased (and the redness increased), after 4 years, 11 samples still presented acceptable diastase activity and hydroxymethylfurfural values. Full article

(This article belongs to the Collection Bioactive Compounds)

► Show Figures

Graphical abstract

12 pages, 1130 KiB

Open AccessArticle

Chemometric Analysis of Lavender Essential Oils Using Targeted and Untargeted GC-MS Acquired Data for the Rapid Identification and Characterization of Oil Quality

by David J. Beale, Paul D. Morrison, Avinash V. Karpe and Michael S. Dunn

Molecules 2017, 22(8), 1339; https://doi.org/10.3390/molecules22081339 - 11 Aug 2017

Cited by 59 | Viewed by 8943

Abstract

Standard raw material test methods such as the ISO Standard 11024 are focused on the identification of lavender oil and not the actual class/quality of the oil. However, the quality of the oil has a significant effect on its price at market. As [...] Read more.

Standard raw material test methods such as the ISO Standard 11024 are focused on the identification of lavender oil and not the actual class/quality of the oil. However, the quality of the oil has a significant effect on its price at market. As such, there is a need for raw material tests to identify not only the type of oil but its quality. This paper describes two approaches to rapidly identifying and classifying lavender oil. First, the ISO Standard 11024 test method was evaluated in order to determine its suitability to assess lavender oil quality but due to its targeted and simplistic approach, it has the potential to miss classify oil quality. Second, utilizing the data generated by the ISO Standard 11024 test methodology, an untargeted chemometric predicative model was developed in order to rapidly assess and characterize lavender oils (Lavandula angustifolia L.) for geographical/environmental adulteration that impact quality. Of the 170 compounds identified as per the ISO Standard 11024 test method utilizing GC-MS analyses, 15 unique compounds that greatly differentiate between the two classes of lavender were identified. Using these 15 compounds, a predicative multivariate chemometric model was developed that enabled lavender oil samples to be reliably differentiated based on quality. A misclassification analysis was performed and it was found that the predictions were sound (100% matching rate). Such an approach will enable producers, distributers, suppliers and manufactures to rapidly screen lavender essential oil. The authors concede that the validation and implementation of such an approach is more difficult than a conventional chromatographic assay. However, the rapid, reliable and less problematic screening is vastly superior and easily justifies any early implementation validation difficulties and costs. Full article

► Show Figures

Figure 1

14 pages, 3517 KiB

Open AccessArticle

7-Dialkylaminocoumarin Oximates: Small Molecule Fluorescent “Turn-On” Chemosensors for Low-Level Water Content in Aprotic Organic Solvents

by Marek Cigáň, Miroslav Horváth, Juraj Filo, Klaudia Jakusová, Jana Donovalová, Vladimír Garaj and Anton Gáplovský

Molecules 2017, 22(8), 1340; https://doi.org/10.3390/molecules22081340 - 12 Aug 2017

Cited by 18 | Viewed by 6010

Abstract

The water sensing properties of two efficient two-component fluorescent “turn-on” chemo-sensors based on the 7-dialkylaminocoumarin oxime acid-base equilibrium were investigated. Interestingly, although simple frontier orbital analysis predicts an intramolecular photoinduced electron transfer quenching pathway in conjugated oximates, TD-DFT (Time-dependent density functional theory) quantum [...] Read more.

The water sensing properties of two efficient two-component fluorescent “turn-on” chemo-sensors based on the 7-dialkylaminocoumarin oxime acid-base equilibrium were investigated. Interestingly, although simple frontier orbital analysis predicts an intramolecular photoinduced electron transfer quenching pathway in conjugated oximates, TD-DFT (Time-dependent density functional theory) quantum chemical calculations support non-radiative dark S₁ excited state deactivation as a fluorescence quenching mechanism. Due to the acid-base sensing mechanism and sensitive “turn-on” fluorescent response, both studied coumarin aldoxime chemosensors exhibit rapid response to low-level water content in polar aprotic solvents, with detection limits comparable to chemodosimeters or chemosensors based on interpolymer π-stacking aggregation. Full article

(This article belongs to the Section Photochemistry)

► Show Figures

Graphical abstract

12 pages, 1432 KiB

Open AccessArticle

A Pectic Polysaccharide from Sijunzi Decoction Promotes the Antioxidant Defenses of SW480 Cells

by Chao Huang, Zhongkai Zhu, Xiyue Cao, Xingfu Chen, Yuping Fu, Zhengli Chen, Lixia Li, Xu Song, Renyong Jia, Zhongqiong Yin, Gang Ye, Bin Feng and Yuanfeng Zou

Molecules 2017, 22(8), 1341; https://doi.org/10.3390/molecules22081341 - 12 Aug 2017

Cited by 12 | Viewed by 5251

Abstract

Sijunzi Decoction (SJZD) is a formula used for the treatment of spleen deficiency and gastrointestinal diseases in Traditional Chinese Medicine. Polysaccharides are reported to be the main components of SJZD responsible for its bio-functions. However, highly purified and clearly characterized polysaccharides from SJZD [...] Read more.

Sijunzi Decoction (SJZD) is a formula used for the treatment of spleen deficiency and gastrointestinal diseases in Traditional Chinese Medicine. Polysaccharides are reported to be the main components of SJZD responsible for its bio-functions. However, highly purified and clearly characterized polysaccharides from SJZD are not well described. Here we obtained a purified polysaccharide (SJZDP-II-I) from SJZD using ion exchange chromatography and gel filtration. Structure analysis by FT-IR and NMR identified SJZDP-II-I as a typical pectic polysaccharide with homogalacturonan and rhamnogalacturonan type I regions and arabinogalactan type I and II as side chains. In vitro studies indicated that SJZDP-II-I treatment could significantly enhance the total antioxidant capacity of SW480 cells, resulting from the promoted expressions of antioxidant enzymes and their master regulator PGC-1α, which would be valuable for further research and applications. Full article

(This article belongs to the Special Issue Advances in Natural Polysaccharides Research)

► Show Figures

Figure 1

16 pages, 4254 KiB

Open AccessArticle

Predicting and Interpreting the Structure of Type IV Pilus of Electricigens by Molecular Dynamics Simulations

by Chuanjun Shu, Ke Xiao, Changchang Cao, Dewu Ding and Xiao Sun

Molecules 2017, 22(8), 1342; https://doi.org/10.3390/molecules22081342 - 12 Aug 2017

Cited by 7 | Viewed by 5149

Abstract

Nanowires that transfer electrons to extracellular acceptors are important in organic matter degradation and nutrient cycling in the environment. Geobacter pili of the group of Type IV pilus are regarded as nanowire-like biological structures. However, determination of the structure of pili remains challenging [...] Read more.

Nanowires that transfer electrons to extracellular acceptors are important in organic matter degradation and nutrient cycling in the environment. Geobacter pili of the group of Type IV pilus are regarded as nanowire-like biological structures. However, determination of the structure of pili remains challenging due to the insolubility of monomers, presence of surface appendages, heterogeneity of the assembly, and low-resolution of electron microscopy techniques. Our previous study provided a method to predict structures for Type IV pili. In this work, we improved on our previous method using molecular dynamics simulations to optimize structures of Neisseria gonorrhoeae (GC), Neisseria meningitidis and Geobacter uraniireducens pilus. Comparison between the predicted structures for GC and Neisseria meningitidis pilus and their native structures revealed that proposed method could predict Type IV pilus successfully. According to the predicted structures, the structural basis for conductivity in G.uraniireducens pili was attributed to the three N-terminal aromatic amino acids. The aromatics were interspersed within the regions of charged amino acids, which may influence the configuration of the aromatic contacts and the rate of electron transfer. These results will supplement experimental research into the mechanism of long-rang electron transport along pili of electricigens. Full article

(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)

► Show Figures

Figure 1

11 pages, 1661 KiB

Open AccessFeature PaperArticle

BILP-19—An Ultramicroporous Organic Network with Exceptional Carbon Dioxide Uptake

by Christoph Klumpen, Florian Radakovitsch, Andreas Jess and Jürgen Senker

Molecules 2017, 22(8), 1343; https://doi.org/10.3390/molecules22081343 - 12 Aug 2017

Cited by 14 | Viewed by 7263

Abstract

Porous benzimidazole-based polymers (BILPs) have proven to be promising for carbon dioxide capture and storage. The polarity of their chemical structure in combination with an inherent porosity allows for adsorbing large amounts of carbon dioxide in combination with high selectivities over unpolar guest [...] Read more.

Porous benzimidazole-based polymers (BILPs) have proven to be promising for carbon dioxide capture and storage. The polarity of their chemical structure in combination with an inherent porosity allows for adsorbing large amounts of carbon dioxide in combination with high selectivities over unpolar guest molecules such as methane and nitrogen. For this reason, among purely organic polymers, BILPs contain some of the most effective networks to date. Nevertheless, they are still outperformed by competitive materials such as metal-organic frameworks (MOFs) or metal doped porous polymers. Here, we report the synthesis of BILP-19 and its exceptional carbon dioxide uptake of up to 6 mmol•g−1 at 273 K, making the network comparable to state-of-the-art materials. BILP-19 precipitates in a particulate structure with a strongly anisotropic growth into platelets, indicating a sheet-like structure for the network. It exhibits only a small microporous but a remarkable ultra-microporous surface area of 144 m2•g−1 and 1325 m2•g−1, respectively. We attribute the exceptional uptake of small guest molecules such as carbon dioxide and water to the distinct ultra-microporosity. Additionally, a pronounced hysteresis for both guests is observed, which in combination with the platelet character is probably caused by an expansion of the interparticle space, creating additional accessible ultra-microporous pore volume. For nitrogen and methane, this effect does not occur which explains their low affinity. In consequence, Henry selectivities of 123 for CO2/N2 at 298 K and 12 for CO2/CH4 at 273 K were determined. The network was carefully characterized with solid-state nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy, thermal gravimetry (TG) and elemental analyses as well as physisorption experiments with Ar, N2, CO2, CH4 and water. Full article

(This article belongs to the Special Issue Covalent Organic Frameworks and Related Porous Organic Materials)

► Show Figures

Figure 1

10 pages, 1220 KiB

Open AccessCommunication

Fenton Discoloration of Ultrasonicated Purple Cactus Pear Juice

by Isidro Reyes-Hernández, Nelly Del S. Cruz-Cansino, Ingrid Renata Santander-Martínez, Ernesto Alanís-García, Luis Delgado-Olivares, Esther Ramírez-Moreno, José A. Ariza-Ortega, Ariana Omaña-Covarrubias, Jesús Martín Torres-Valencia and José De Jesús Manríquez-Torres

Molecules 2017, 22(8), 1344; https://doi.org/10.3390/molecules22081344 - 15 Aug 2017

Cited by 3 | Viewed by 4653

Abstract

The aim of this study was to evaluate the stability of color, betaxanthin, and betacyanin pigments in the presence of Cu(II)-dependent hydroxyl radicals (HO•) from ultrasonicated purple cactus pear juice at amplitudes of 40%, 60%, and 80%, in comparison to untreated sample. L* [...] Read more.

The aim of this study was to evaluate the stability of color, betaxanthin, and betacyanin pigments in the presence of Cu(II)-dependent hydroxyl radicals (HO•) from ultrasonicated purple cactus pear juice at amplitudes of 40%, 60%, and 80%, in comparison to untreated sample. L* parameter of juice treated at 40% and 80% amplitude for 25 and 15 min, respectively (11.3 and 9.3, respectively), were significantly higher compared to the control; b* and hue parameters of juice treated at 80%, 25 min showed values of 1.7 and 0.1, respectively. Color differences (ΔE) were lower (<3) for juices treated at high amplitude (80%) and short times (3–5 min). Juice treated at 40% 15 min, 60% 25 min, 80% 15 and 25 min presented high values of betacyanins (281.7 mg·L⁻¹, 255.9 mg·L⁻¹, 294.4 mg·L⁻¹, and 276.7 mg·L⁻¹, respectively). Betaxanthin values were higher in the juices treated at 40% 5 min and 80% 15 and 25 min (154.2 mg·L⁻¹, 135.2 mg·L⁻¹, and 128.5 mg·L⁻¹, respectively). Purple cactus pear juice exhibited significant chelating activity of copper ions and great stability when exposed to HO•. Full article

(This article belongs to the Special Issue Dietary Antioxidants: Evidence of Protective Effects against Chronic Disease)

► Show Figures

Figure 1

15 pages, 2546 KiB

Open AccessArticle

Inhibitors of the Detoxifying Enzyme of the Phytoalexin Brassinin Based on Quinoline and Isoquinoline Scaffolds

by M. Soledade C. Pedras, Abbas Abdoli and Vijay K. Sarma-Mamillapalle

Molecules 2017, 22(8), 1345; https://doi.org/10.3390/molecules22081345 - 14 Aug 2017

Cited by 19 | Viewed by 7026

Abstract

The detoxification of the phytoalexin brassinin to indole-3-carboxaldehyde and S-methyl dithiocarbamate is catalyzed by brassinin oxidase (BOLm), an inducible fungal enzyme produced by the plant pathogen Leptosphaeria maculans. Twenty-six substituted quinolines and isoquinolines are synthesized and evaluated for antifungal activity against [...] Read more.

The detoxification of the phytoalexin brassinin to indole-3-carboxaldehyde and S-methyl dithiocarbamate is catalyzed by brassinin oxidase (BOLm), an inducible fungal enzyme produced by the plant pathogen Leptosphaeria maculans. Twenty-six substituted quinolines and isoquinolines are synthesized and evaluated for antifungal activity against L. maculans and inhibition of BOLm. Eleven compounds that inhibit BOLm activity are reported, of which 3-ethyl-6-phenylquinoline displays the highest inhibitory effect. In general, substituted 3-phenylquinolines show significantly higher inhibitory activities than the corresponding 2-phenylquinolines. Overall, these results indicate that the quinoline scaffold is a good lead to design paldoxins (phytoalexin detoxification inhibitors) that inhibit the detoxification of brassinin by L. maculans. Full article

(This article belongs to the Special Issue Structure, Chemical Analysis, Biosynthesis, Metabolism, Molecular Engineering and Biological Functions of Phytoalexins)

► Show Figures

Figure 1

10 pages, 1243 KiB

Open AccessArticle

ADP-ribosyl-N₃: A Versatile Precursor for Divergent Syntheses of ADP-ribosylated Compounds

by Lingjun Li, Qianqian Li, Shengqiang Ding, Pengyang Xin, Yuqin Zhang, Shenlong Huang and Guisheng Zhang

Molecules 2017, 22(8), 1346; https://doi.org/10.3390/molecules22081346 - 14 Aug 2017

Cited by 10 | Viewed by 5958

Abstract

Adenosine diphosphate-ribose (ADP-ribose) and its derivatives play important roles in a series of complex physiological procedures. The design and synthesis of artificial ADP-ribosylated compounds is an efficient way to develop valuable chemical biology tools and discover new drug candidates. However, the synthesis of [...] Read more.

Adenosine diphosphate-ribose (ADP-ribose) and its derivatives play important roles in a series of complex physiological procedures. The design and synthesis of artificial ADP-ribosylated compounds is an efficient way to develop valuable chemical biology tools and discover new drug candidates. However, the synthesis of ADP-ribosylated compounds is currently difficult due to structural complexity, easily broken pyrophosphate bond and high hydrophilicity. In this paper, ADP-ribosyl-N₃ was designed and synthesized for the first time. With ADP-ribosyl-N₃ as the key precursor, a divergent post-modification strategy was developed to prepare structurally diverse ADP-ribosylated compounds including novel nucleotides and peptides bearing ADP-ribosyl moieties. Full article

(This article belongs to the Special Issue Nucleic Acid Chemistry and Nucleic Acid Drugs: A Themed Issue in Honor of Professor Lihe Zhang on the Occasion of His 80th Birthday)

► Show Figures

Figure 1

21 pages, 4547 KiB

Open AccessReview

Application of Solution NMR to Structural Studies on α-Helical Integral Membrane Proteins

by Dae-Won Sim, Zhenwei Lu, Hyung-Sik Won, Seu-Na Lee, Min-Duk Seo, Bong-Jin Lee and Ji-Hun Kim

Molecules 2017, 22(8), 1347; https://doi.org/10.3390/molecules22081347 - 15 Aug 2017

Cited by 12 | Viewed by 7926

Abstract

A large portion of proteins in living organisms are membrane proteins which play critical roles in the biology of the cell, from maintenance of the biological membrane integrity to communication of cells with their surroundings. To understand their mechanism of action, structural information [...] Read more.

A large portion of proteins in living organisms are membrane proteins which play critical roles in the biology of the cell, from maintenance of the biological membrane integrity to communication of cells with their surroundings. To understand their mechanism of action, structural information is essential. Nevertheless, structure determination of transmembrane proteins is still a challenging area, even though recently the number of deposited structures of membrane proteins in the PDB has rapidly increased thanks to the efforts using X-ray crystallography, electron microscopy, and solid and solution nuclear magnetic resonance (NMR) technology. Among these technologies, solution NMR is a powerful tool for studying protein-protein, protein-ligand interactions and protein dynamics at a wide range of time scales as well as structure determination of membrane proteins. This review provides general and useful guideline for membrane protein sample preparation and the choice of membrane-mimetic media, which are the key step for successful structural analysis. Furthermore, this review provides an opportunity to look at recent applications of solution NMR to structural studies on α-helical membrane proteins through some success stories. Full article

(This article belongs to the Special Issue Recent Advances in Biomolecular NMR Spectroscopy)

► Show Figures

Figure 1

12 pages, 1249 KiB

Open AccessArticle

Synthesis and Evaluation of Novel Benzofuran Derivatives as Selective SIRT2 Inhibitors

by Yumei Zhou, Huaqing Cui, Xiaoming Yu, Tao Peng, Gang Wang, Xiaoxue Wen, Yunbo Sun, Shuchen Liu, Shouguo Zhang, Liming Hu and Lin Wang

Molecules 2017, 22(8), 1348; https://doi.org/10.3390/molecules22081348 - 14 Aug 2017

Cited by 9 | Viewed by 4930

Abstract

A series of benzofuran derivatives were designed and synthesized, and their inhibitory activites were measured against the SIRT1–3. The enzymatic assay showed that all the compounds showed certain anti-SIRT2 activity and selective over SIRT1 and SIRT3 with IC₅₀ (half maximal inhibitory concentration) [...] Read more.

A series of benzofuran derivatives were designed and synthesized, and their inhibitory activites were measured against the SIRT1–3. The enzymatic assay showed that all the compounds showed certain anti-SIRT2 activity and selective over SIRT1 and SIRT3 with IC₅₀ (half maximal inhibitory concentration) values at the micromolar level. The preliminary structure–activity relationships were analyzed and the binding features of compound 7e (IC₅₀ 3.81 µM) was predicted using the CDOCKER program. The results of this research could provide informative guidance for further optimizing benzofuran derivatives as potent SIRT2 inhibitors. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Graphical abstract

8 pages, 1051 KiB

Open AccessArticle

Inositol Derivatives and Phenolic Compounds from the Roots of Taraxacum coreanum

by Eun Jin Mo, Jong Hoon Ahn, Yang Hee Jo, Seon Beom Kim, Bang Yeon Hwang and Mi Kyeong Lee

Molecules 2017, 22(8), 1349; https://doi.org/10.3390/molecules22081349 - 14 Aug 2017

Cited by 32 | Viewed by 5069

Abstract

In this study, the characterization of chemical constituents and biological activity of the roots of Taraxacum coreanum (Asteraceae) was attempted. Phytochemical investigation of the roots of T. coreanum led to the isolation of two new inositol derivatives, taraxinositols A (1) and [...] Read more.

In this study, the characterization of chemical constituents and biological activity of the roots of Taraxacum coreanum (Asteraceae) was attempted. Phytochemical investigation of the roots of T. coreanum led to the isolation of two new inositol derivatives, taraxinositols A (1) and B (2), and a new phenolic compound, taraxinol (16), together with twenty known compounds including four inositol derivatives, neo-inositol-1,4-bis (4-hydroxybenzeneacetate) (3), chiro-inositol-1,5-bis(4- hydroxybenzeneacetate) (4), chiro-inositol-2,3-bis (4-hydroxybenzeneacetate) (5) and chiro-inositol- 1,2,3-tris (4-hydroxybenzeneacetate) (6), nine phenolic compounds: p-hydroxybenzaldehyde (7), vanillin (8), syringaldehyde (9), vanillic acid (10), 4-methoxyphenylacetic acid (11), 4-hydroxy- phenylacetic acid methyl ester (12), optivanin (13), isoferulic acid (14) and dihydroconiferyl alcohol (15), four coumarins: nodakenetin (17), decursinol (18), prangol (19) and isobyakangelicin (20), and three lignans: syringaresinol-4′-O-β-d-glucoside (21), syringaresinol (22), and pinoresinol (23). The structures of isolated compounds were determined on the basis of spectroscopic analysis. Among the isolated compounds, vanillic acid, isoferulic acid and syringaresinol showed radical scavenging activity with IC₅₀ values ranging from 30.4 to 75.2 μM. Full article

► Show Figures

Figure 1

14 pages, 5284 KiB

Open AccessArticle

Two New Tetravacant Organometallic Keggin-Type Heteropolyoxomolybdates-Supported Manganese Carbonyl Derivatives

by Vikram Singh, Yujiao Zhang, Linping Yang, Pengtao Ma, Dongdi Zhang, Chao Zhang, Li Yu, Jingyang Niu and Jingping Wang

Molecules 2017, 22(8), 1351; https://doi.org/10.3390/molecules22081351 - 14 Aug 2017

Cited by 7 | Viewed by 4759

Abstract

Two novel heteropolyoxomolybdate [XMo₈O₃₁]ⁿ⁻ (X = Ge(1) or P(2)) manganese carbonyl derivatives [(CH₃)₄N]₆H₆{Mn^II(GeMo₈O₃₁)[Mn^I(CO)₃]₂}₂ [...] Read more.

Two novel heteropolyoxomolybdate [XMo₈O₃₁]ⁿ⁻ (X = Ge(1) or P(2)) manganese carbonyl derivatives [(CH₃)₄N]₆H₆{Mn^II(GeMo₈O₃₁)[Mn^I(CO)₃]₂}₂·12H₂O (1) and [(CH₃)₄N]₄H₆{Mn^II(PMo₈O₃₁)[Mn^I(CO)₃]₂}₂·14H₂O (2), have been successfully synthesized and characterized in the solid state by single crystal X-ray diffraction, IR and thermogravimetric analysis, and in solution by UV-Vis spectroscopy and electrochemistry. The two polyoxomolybdate-based organometallic compounds 1 and 2 represent rare examples of transition metal sandwich-based polyoxometalate metal carbonyl derivatives (PMCDs), in which the organic-inorganic hybrids are composed of four Mn(CO)₃⁺ groups symmetrically occupied the tetravacant sites of dimeric heteropolyoxomolybdate {Mn₂(XMo₈O₃₁)₂}ⁿ⁻ through Mn^I-O-Mo bonds. The carbonyl functionalized Mn atoms are octahedrally coordinated via three μ₂-oxygens of the [XMo₈O₃₁]ⁿ⁻ unit and three carbonyl carbon atoms. Interestingly, 1 and 2 form a psedocuboidal ring Mn(CO)₃Mo₃O₁₂ with {Mn(CO)₃}⁺ occupying the three fold axis of the Mo₃O₁₂ octahedral triad. Beside this, the two centrally placed adjacent Mn^II atoms show intramolecular Mn∙∙∙Mn interactions of 3.11 and 3.16 Å in 1 and 2, respectively. Significant n→π* and O···O intermolecular interactions between the orthogonally aligned adjacent carbonyl groups through the overlap of lone-pair electrons on oxygen atoms with the antibonding orbital (π*) of the adjacent carbony carbon atom of the subsequent units in 1 and 2 were observed. The electrochemical properties of the two compounds were also been investigated. Full article

(This article belongs to the Section Organometallic Chemistry)

► Show Figures

Figure 1

20 pages, 2023 KiB

Open AccessArticle

Sulfonamide-Linked Ciprofloxacin, Sulfadiazine and Amantadine Derivatives as a Novel Class of Inhibitors of Jack Bean Urease; Synthesis, Kinetic Mechanism and Molecular Docking

by Pervaiz Ali Channar, Aamer Saeed, Fernando Albericio, Fayaz Ali Larik, Qamar Abbas, Mubashir Hassan, Hussain Raza and Sung-Yum Seo

Molecules 2017, 22(8), 1352; https://doi.org/10.3390/molecules22081352 - 16 Aug 2017

Cited by 52 | Viewed by 10432

Abstract

Sulfonamide derivatives serve as an important building blocks in the drug design discovery and development (4D) process. Ciprofloxacin-, sulfadiazine- and amantadine-based sulfonamides were synthesized as potent inhibitors of jack bean urease and free radical scavengers. Molecular diversity was explored and electronic factors were [...] Read more.

Sulfonamide derivatives serve as an important building blocks in the drug design discovery and development (4D) process. Ciprofloxacin-, sulfadiazine- and amantadine-based sulfonamides were synthesized as potent inhibitors of jack bean urease and free radical scavengers. Molecular diversity was explored and electronic factors were also examined. All 24 synthesized compounds exhibited excellent potential against urease enzyme. Compound 3e (IC₅₀ = 0.081 ± 0.003 µM), 6a (IC₅₀ = 0.0022 ± 0.0002 µM), 9e (IC₅₀ = 0.0250 ± 0.0007 µM) and 12d (IC₅₀ = 0.0266 ± 0.0021 µM) were found to be the lead compounds compared to standard (thiourea, IC₅₀ = 17.814 ± 0.096 µM). Molecular docking studies were performed to delineate the binding affinity of the molecules and a kinetic mechanism of enzyme inhibition was propounded. Compounds 3e, 6a and 12d exhibited a mixed type of inhibition, while derivative 9e revealed a non-competitive mode of inhibition. Compounds 12a, 12b, 12d, 12e and 12f showed excellent radical scavenging potency in comparison to the reference drug vitamin C. Full article

(This article belongs to the Special Issue Sulfonamides)

► Show Figures

Figure 1

14 pages, 5737 KiB

Open AccessArticle

Molecular Mechanisms Underlying Inhibitory Binding of Alkylimidazolium Ionic Liquids to Laccase

by Jianliang Sun, Hao Liu, Wenping Yang, Shicheng Chen and Shiyu Fu

Molecules 2017, 22(8), 1353; https://doi.org/10.3390/molecules22081353 - 15 Aug 2017

Cited by 13 | Viewed by 5952

Abstract

Water-miscible alkylimidazolium ionic liquids (ILs) are “green” co-solvents for laccase catalysis, but generally inhibit enzyme activity. Here, we present novel insights into inhibition mechanisms by a combination of enzyme kinetics analysis and molecular simulation. Alkylimidazolium cations competitively bound to the T_I Cu [...] Read more.

Water-miscible alkylimidazolium ionic liquids (ILs) are “green” co-solvents for laccase catalysis, but generally inhibit enzyme activity. Here, we present novel insights into inhibition mechanisms by a combination of enzyme kinetics analysis and molecular simulation. Alkylimidazolium cations competitively bound to the T_I Cu active pocket in the laccase through hydrophobic interactions. Cations with shorter alkyl chains (C₂~C₆) entered the channel inside the pocket, exhibiting a high compatibility with laccase (competitive inhibition constant K_ic = 3.36~3.83 mM). Under the same conditions, [Omim]Cl (K_ic = 2.15 mM) and [Dmim]Cl (K_ic = 0.18 mM) with longer alkyl chains bound with Leu296 or Leu297 near the pocket edge and Leu429 around T_I Cu, which resulted in stronger inhibition. Complexation with alkylimidazolium cations shifted the pH optima of laccase to the right by 0.5 unit, and might, thereby, lead to invalidation of the Hofmeister series of anions. EtSO₄⁻ showed higher biocompatibility than did Ac⁻ or Cl⁻, probably due to its binding near the T_I Cu and its hindering the entry of alkylimidazolium cations. In addition, all tested ILs accelerated the scavenging of 2, 2′-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals, which, however, did not play a determining role in the inhibition of laccase. Full article

► Show Figures

Figure 1

26 pages, 6941 KiB

Open AccessArticle

Synthesis and Physicochemical Characterization of the Process-Related Impurities of Eplerenone, an Antihypertensive Drug

by Iwona Dams, Agata Białońska, Piotr Cmoch, Małgorzata Krupa, Anita Pietraszek, Anna Ostaszewska and Michał Chodyński

Molecules 2017, 22(8), 1354; https://doi.org/10.3390/molecules22081354 - 15 Aug 2017

Cited by 6 | Viewed by 9823

Abstract

Two unknown impurities were observed during the process development for multigram-scale synthesis of eplerenone (Inspra^®). The new process-related impurities were identified and fully characterized as the corresponding (7β,11α,17α)-11-hydroxy- and (7α,11β,17α)-9,11-dichloroeplerenone derivatives 12a and 13. Seven other known but poorly described [...] Read more.

Two unknown impurities were observed during the process development for multigram-scale synthesis of eplerenone (Inspra^®). The new process-related impurities were identified and fully characterized as the corresponding (7β,11α,17α)-11-hydroxy- and (7α,11β,17α)-9,11-dichloroeplerenone derivatives 12a and 13. Seven other known but poorly described in the literature eplerenone impurities, including four impurities A, B, C and E listed in the European Pharmacopoeia 8.4 were also detected, identified and fully characterized. All these contaminants result from side reactions taking place on the steroid ring C of the starting 11α-hydroxy-7α-(methoxycarbonyl)-3-oxo-17α-pregn-4-ene-21,17-carbolactone (12) and the key intermediate (7α,17α)-9(11)-enester 7, including epimerization of the C-7 asymmetric center, oxidation, dehydration, chlorination and lactonization. The impurities were isolated and/or synthesized and fully characterized by infrared spectroscopy (IR), nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrometry/electrospray ionization (HRMS/ESI). Their ¹H- and ¹³C-NMR signals were fully assigned. The molecular structures of the eight impurities, including the new (7β,11α,17α)-11-hydroxy- and (7α,11β,17α)-9,11-dichloroeplerenone related substances 12a and 13, were solved and refined using single-crystal X-ray diffraction (SCXRD). The full identification and characterization of these impurities should be useful for the quality control and the validation of the analytical methods in the manufacture of eplerenone. Full article

(This article belongs to the Special Issue Medicinal Chemistry in Europe)

► Show Figures

Figure 1

10 pages, 1137 KiB

Open AccessArticle

A Unique and Simple Approach to Improve Sensitivity in ¹⁵N-NMR Relaxation Measurements for NH₃⁺ Groups: Application to a Protein-DNA Complex

by Dan Nguyen, Ganesh L. R. Lokesh, David E. Volk and Junji Iwahara

Molecules 2017, 22(8), 1355; https://doi.org/10.3390/molecules22081355 - 15 Aug 2017

Cited by 5 | Viewed by 5673

Abstract

NMR spectroscopy is a powerful tool for research on protein dynamics. In the past decade, there has been significant progress in the development of NMR methods for studying charged side chains. In particular, NMR methods for lysine side-chain NH₃⁺ groups have [...] Read more.

NMR spectroscopy is a powerful tool for research on protein dynamics. In the past decade, there has been significant progress in the development of NMR methods for studying charged side chains. In particular, NMR methods for lysine side-chain NH₃⁺ groups have been proven to be powerful for investigating the dynamics of hydrogen bonds or ion pairs that play important roles in biological processes. However, relatively low sensitivity has been a major practical issue in NMR experiments on NH₃⁺ groups. In this paper, we present a unique and simple approach to improve sensitivity in ¹⁵N relaxation measurements for NH₃⁺ groups. In this approach, the efficiency of coherence transfers for the desired components are maximized, whereas undesired anti-phase or multi-spin order components are purged through pulse schemes and rapid relaxation. For lysine side-chain NH₃⁺ groups of a protein-DNA complex, we compared the data obtained with the previous and new pulse sequences under the same conditions and confirmed that the ¹⁵N relaxation parameters were consistent for these datasets. While retaining accuracy in measuring ¹⁵N relaxation, our new pulse sequences for NH₃⁺ groups allowed an 82% increase in detection sensitivity of ¹⁵N longitudinal and transverse relaxation measurements. Full article

(This article belongs to the Special Issue Recent Advances in Biomolecular NMR Spectroscopy)

► Show Figures

Figure 1

12 pages, 1842 KiB

Open AccessCommunication

Synthesis of 5′-GalNAc-Conjugated Oligonucleotides: A Comparison of Solid and Solution-Phase Conjugation Strategies

by Isaiah Cedillo, Dana Chreng, Elyse Engle, Lijian Chen, Andrew K. McPherson and Andrew A. Rodriguez

Molecules 2017, 22(8), 1356; https://doi.org/10.3390/molecules22081356 - 15 Aug 2017

Cited by 24 | Viewed by 13191

Abstract

Antisense oligonucleotides (ASOs) conjugated to triantennary N-acetyl galactosamine (GalNAc) ligands represent an emerging approach to antisense therapy. Our current generation of GalNAc-ASO conjugates link the GalNAc to the 5′-terminus of the ASO. The conjugation reaction can be accomplished using solution-phase or solid-phase [...] Read more.

Antisense oligonucleotides (ASOs) conjugated to triantennary N-acetyl galactosamine (GalNAc) ligands represent an emerging approach to antisense therapy. Our current generation of GalNAc-ASO conjugates link the GalNAc to the 5′-terminus of the ASO. The conjugation reaction can be accomplished using solution-phase or solid-phase techniques. Here we show a direct comparison of a solution-phase and a solid-phase conjugation strategy. The solution-phase approach, using amine-pentafluorophenyl (PFP) ester coupling, is higher yielding and gives material of slightly higher purity, but requires several additional unit operations and longer production time. The solid-phase approach, using a protected GalNAc ligand phosphoramidite, is more expedient, but results in lower yield and purity. Both strategies efficiently deliver conjugated material in excellent purity. Full article

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

► Show Figures

Figure 1

15 pages, 3688 KiB

Open AccessFeature PaperArticle

Lactose Binding Induces Opposing Dynamics Changes in Human Galectins Revealed by NMR-Based Hydrogen–Deuterium Exchange

by Chih-Ta Henry Chien, Meng-Ru Ho, Chung-Hung Lin and Shang-Te Danny Hsu

Molecules 2017, 22(8), 1357; https://doi.org/10.3390/molecules22081357 - 16 Aug 2017

Cited by 15 | Viewed by 6875

Abstract

Galectins are β-galactoside-binding proteins implicated in a myriad of biological functions. Despite their highly conserved carbohydrate binding motifs with essentially identical structures, their affinities for lactose, a common galectin inhibitor, vary significantly. Here, we aimed to examine the molecular basis of differential lactose [...] Read more.

Galectins are β-galactoside-binding proteins implicated in a myriad of biological functions. Despite their highly conserved carbohydrate binding motifs with essentially identical structures, their affinities for lactose, a common galectin inhibitor, vary significantly. Here, we aimed to examine the molecular basis of differential lactose affinities amongst galectins using solution-based techniques. Consistent dissociation constants of lactose binding were derived from nuclear magnetic resonance (NMR) spectroscopy, intrinsic tryptophan fluorescence, isothermal titration calorimetry and bio-layer interferometry for human galectin-1 (hGal1), galectin-7 (hGal7), and the N-terminal and C-terminal domains of galectin-8 (hGal8^NTD and hGal8^CTD, respectively). Furthermore, the dissociation rates of lactose binding were extracted from NMR lineshape analyses. Structural mapping of chemical shift perturbations revealed long-range perturbations upon lactose binding for hGal1 and hGal8^NTD. We further demonstrated using the NMR-based hydrogen–deuterium exchange (HDX) that lactose binding increases the exchange rates of residues located on the opposite side of the ligand-binding pocket for hGal1 and hGal8^NTD, indicative of allostery. Additionally, lactose binding induces significant stabilisation of hGal8^CTD across the entire domain. Our results suggested that lactose binding reduced the internal dynamics of hGal8^CTD on a very slow timescale (minutes and slower) at the expense of reduced binding affinity due to the unfavourable loss of conformational entropy. Full article

(This article belongs to the Special Issue Recent Advances in Biomolecular NMR Spectroscopy)

► Show Figures

Figure 1

17 pages, 2800 KiB

Open AccessArticle

Insights into the Effect of the G245S Single Point Mutation on the Structure of p53 and the Binding of the Protein to DNA

by Marco Gaetano Lepre, Sara Ibrahim Omar, Gianvito Grasso, Umberto Morbiducci, Marco Agostino Deriu and Jack A. Tuszynski

Molecules 2017, 22(8), 1358; https://doi.org/10.3390/molecules22081358 - 16 Aug 2017

Cited by 23 | Viewed by 6091

Abstract

The transcription factor p53 is a potent tumor suppressor dubbed as the “guardian of the genome” because of its ability to orchestrate protective biological outputs in response to a variety of oncogenic stresses. Mutation and thus inactivation of p53 can be found in [...] Read more.

The transcription factor p53 is a potent tumor suppressor dubbed as the “guardian of the genome” because of its ability to orchestrate protective biological outputs in response to a variety of oncogenic stresses. Mutation and thus inactivation of p53 can be found in 50% of human tumors. The majority are missense mutations located in the DNA binding region. Among them, G245S is known to be a structural hotspot mutation. To understand the behaviors and differences between the wild-type and mutant, both a dimer of the wild type p53 (wt-p53) and its G245S mutant (G245S-mp53), complexed with DNA, were simulated using molecular dynamics for more than 1 μs. wt-p53 and G245S-mp53 apo monomers were simulated for 1 μs as well. Conformational analyses and binding energy evaluations performed underline important differences and therefore provide insights to understand the G245S-mp53 loss of function. Our results indicate that the G245S mutation destabilizes several structural regions in the protein that are crucial for DNA binding when found in its apo form and highlight differences in the mutant-DNA complex structure compared to the wt protein. These findings not only provide means that can be applied to other p53 mutants but also serve as structural basis for further studies aimed at the development of cancer therapies based on restoring the function of p53. Full article

(This article belongs to the Special Issue Frontiers in Computational Chemistry for Drug Discovery)

► Show Figures

Figure 1

13 pages, 1188 KiB

Open AccessArticle

Tissue-Specific Accumulation of Sulfur Compounds and Saponins in Different Parts of Garlic Cloves from Purple and White Ecotypes

by Gianfranco Diretto, Angela Rubio-Moraga, Javier Argandoña, Purificación Castillo, Lourdes Gómez-Gómez and Oussama Ahrazem

Molecules 2017, 22(8), 1359; https://doi.org/10.3390/molecules22081359 - 20 Aug 2017

Cited by 76 | Viewed by 6676

Abstract

This study set out to determine the distribution of sulfur compounds and saponin metabolites in different parts of garlic cloves. Three fractions from purple and white garlic ecotypes were obtained: the tunic (SS), internal (IS) and external (ES) parts of the clove. Liquid [...] Read more.

This study set out to determine the distribution of sulfur compounds and saponin metabolites in different parts of garlic cloves. Three fractions from purple and white garlic ecotypes were obtained: the tunic (SS), internal (IS) and external (ES) parts of the clove. Liquid Chromatography coupled to High Resolution Mass spectrometry (LC-HRMS), together with bioinformatics including Principal Component Analysis (PCA), Hierarchical Clustering (HCL) and correlation network analyses were carried out. Results showed that the distribution of these metabolites in the different parts of garlic bulbs was different for the purple and the white ecotypes, with the main difference being a slightly higher number of sulfur compounds in purple garlic. The SS fraction in purple garlic had a higher content of sulfur metabolites, while the ES in white garlic was more enriched by these compounds. The correlation network indicated that diallyl disulfide was the most relevant metabolite with regards to sulfur compound metabolism in garlic. The total number of saponins was almost 40-fold higher in purple garlic than in the white variety, with ES having the highest content. Interestingly, five saponins including desgalactotigonin-rhamnose, proto-desgalactotigonin, proto-desgalactotigonin-rhamnose, voghieroside D1, sativoside B1-rhamnose and sativoside R1 were exclusive to the purple variety. Data obtained from saponin analyses revealed a very different network between white and purple garlic, thus suggesting a very robust and tight coregulation of saponin metabolism in garlic. Findings in this study point to the possibility of using tunics from purple garlic in the food and medical industries, since it contains many functional compounds which can be exploited as ingredients. Full article

(This article belongs to the Section Molecular Diversity)

► Show Figures

Figure 1

32 pages, 1511 KiB

Open AccessReview

Bioactive Compounds from Mexican Varieties of the Common Bean (Phaseolus vulgaris): Implications for Health

by Celia Chávez-Mendoza and Esteban Sánchez

Molecules 2017, 22(8), 1360; https://doi.org/10.3390/molecules22081360 - 17 Aug 2017

Cited by 113 | Viewed by 15279

Abstract

As Mexico is located within Mesoamerica, it is considered the site where the bean plant originated and where it was domesticated. Beans have been an integral part of the Mexican diet for thousands of years. Within the country, there are a number of [...] Read more.

As Mexico is located within Mesoamerica, it is considered the site where the bean plant originated and where it was domesticated. Beans have been an integral part of the Mexican diet for thousands of years. Within the country, there are a number of genotypes possessing highly diverse physical and chemical properties. This review describes the major bioactive compounds contained on the Mexican varieties of the common bean. A brief analysis is carried out regarding the benefits they have on health. The effect of seed coat color on the nutraceutical compounds content is distinguished, where black bean stands out because it is high content of anthocyanins, polyphenols and flavonoids such as quercetin. This confers black bean with an elevated antioxidant capacity. The most prominent genotypes within this group are the “Negro San Luis”, “Negro 8025” and “Negro Jamapa” varieties. Conversely, the analyzed evidence shows that more studies are needed in order to expand our knowledge on the nutraceutical quality of the Mexican bean genotypes, either grown or wild-type, as well as their impact on health in order to be used in genetic improvement programs or as a strategy to encourage their consumption. The latter is based on the high potential it has for health preservation and disease prevention. Full article

(This article belongs to the Special Issue Plant Polyphenols as Potential Therapeutic Agents for Diabetes and Obesity)

► Show Figures

Figure 1

12 pages, 6744 KiB

Open AccessArticle

Anticancer Activity of Ramalin, a Secondary Metabolite from the Antarctic Lichen Ramalina terebrata, against Colorectal Cancer Cells

by Sung-Suk Suh, Tai Kyoung Kim, Jung Eun Kim, Ju-Mi Hong, Trang Thu Thi Nguyen, Se Jong Han, Ui Joung Youn, Joung Han Yim and Il-Chan Kim

Molecules 2017, 22(8), 1361; https://doi.org/10.3390/molecules22081361 - 17 Aug 2017

Cited by 28 | Viewed by 7676

Abstract

Colorectal cancer is a leading cause of death worldwide and occurs through the highly complex coordination of multiple cellular pathways, resulting in carcinogenesis. Recent studies have increasingly revealed that constituents of lichen extracts exhibit potent pharmaceutical activities, including anticancer activity against various cancer [...] Read more.

Colorectal cancer is a leading cause of death worldwide and occurs through the highly complex coordination of multiple cellular pathways, resulting in carcinogenesis. Recent studies have increasingly revealed that constituents of lichen extracts exhibit potent pharmaceutical activities, including anticancer activity against various cancer cells, making them promising candidates for new anticancer therapeutic drugs. The main objective of this study was to evaluate the anticancer capacities of ramalin, a secondary metabolite from the Antarctic lichen Ramalina terebrata, in the human colorectal cancer cell line HCT116. In this study, ramalin displayed concentration-dependent anticancer activity against HCT116 cells, significantly suppressing proliferation and inducing apoptosis. Furthermore, ramalin induced cell cycle arrest in the gap 2/mitosis (G2/M) phase through the modulation of hallmark genes involved in the G2/M phase transition, such as tumour protein p53 (TP53), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin-dependent kinase 1 (CDK1) and cyclin B1 (CCNB1). At both the transcriptional and translational level, ramalin caused a gradual increase in the expression of TP53 and its downstream gene CDKN1A, while decreasing the expression of CDK1 and CCNB1 in a concentration-dependent manner. In addition, ramalin significantly inhibited the migration and invasion of colorectal cancer cells in a concentration-dependent manner. Taken together, these data suggest that ramalin may be a therapeutic candidate for the targeted therapy of colorectal cancer. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

► Show Figures

Figure 1

14 pages, 3161 KiB

Open AccessArticle

Extended Physicochemical Characterization of the Synthetic Anticoagulant Pentasaccharide Fondaparinux Sodium by Quantitative NMR and Single Crystal X-ray Analysis

by William de Wildt, Huub Kooijman, Carel Funke, Bülent Üstün, Afranina Leika, Maarten Lunenburg, Frans Kaspersen and Edwin Kellenbach

Molecules 2017, 22(8), 1362; https://doi.org/10.3390/molecules22081362 - 17 Aug 2017

Cited by 8 | Viewed by 6349

Abstract

Fondaparinux sodium is a synthetic pentasaccharide representing the high affinity antithrombin III binding site in heparin. It is the active pharmaceutical ingredient of the anticoagulant drug Arixtra^®. The single crystal X-ray structure of Fondaparinux sodium is reported, unequivocally confirming both structure [...] Read more.

Fondaparinux sodium is a synthetic pentasaccharide representing the high affinity antithrombin III binding site in heparin. It is the active pharmaceutical ingredient of the anticoagulant drug Arixtra^®. The single crystal X-ray structure of Fondaparinux sodium is reported, unequivocally confirming both structure and absolute configuration. The iduronic acid adopts a somewhat distorted chair conformation. Due to the presence of many sulfur atoms in the highly sulfated pentasaccharide, anomalous dispersion could be applied to determine the absolute configuration. A comparison with the conformation of Fondaparinux in solution, as well as complexed with proteins is presented. The content of the solution reference standard was determined by quantitative NMR using an internal standard both in 1999 and in 2016. A comparison of the results allows the conclusion that this method shows remarkable precision over time, instrumentation and analysts. Full article

(This article belongs to the Special Issue Looking Forward to the Future of Heparin: New Sources, Developments and Applications)

► Show Figures

Figure 1

10 pages, 1897 KiB

Open AccessArticle

Spirulina maxima Extract Prevents Neurotoxicity via Promoting Activation of BDNF/CREB Signaling Pathways in Neuronal Cells and Mice

by Eun-Jeong Koh, Young-Jin Seo, Jia Choi, Hyeon Yong Lee, Do-Hyung Kang, Kui-Jin Kim and Boo-Yong Lee

Molecules 2017, 22(8), 1363; https://doi.org/10.3390/molecules22081363 - 17 Aug 2017

Cited by 38 | Viewed by 8254

Abstract

Spirulina maxima is a microalgae which contains flavonoids and other polyphenols. Although Spirulina maxima 70% ethanol extract (SM70EE) has diverse beneficial effects, its effects on neurotoxicity have not been fully understood. In this study, we investigated the neuroprotective effects of SM70EE against trimethyltin [...] Read more.

Spirulina maxima is a microalgae which contains flavonoids and other polyphenols. Although Spirulina maxima 70% ethanol extract (SM70EE) has diverse beneficial effects, its effects on neurotoxicity have not been fully understood. In this study, we investigated the neuroprotective effects of SM70EE against trimethyltin (TMT)-induced neurotoxicity in HT-22 cells. SM70EE inhibited the cleavage of poly-ADP ribose polymerase (PARP). Besides, ROS production was decreased by down-regulating oxidative stress-associated enzymes. SM70EE increased the factors of brain-derived neurotrophic factor (BDNF)/cyclic AMPresponsive elementbinding protein (CREB) signalling pathways. Additionally, acetylcholinesterase (AChE) was suppressed by SM70EE. Furthermore, we investigated whether SM70EE prevents cognitive deficits against scopolamine-induced neurotoxicity in mice by applying behavioral tests. SM70EE increased step-through latency time and decreased the escape latency time. Therefore, our data suggest that SM70EE may prevent TMT neurotoxicity through promoting activation of BDNF/CREB neuroprotective signaling pathways in neuronal cells. In vivo study, SM70EE would prevent cognitive deficits against scopolamine-induced neurotoxicity in mice. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

► Show Figures

Figure 1

19 pages, 17205 KiB

Open AccessArticle

Biochemical and Comparative Transcriptomic Analyses Identify Candidate Genes Related to Variegation Formation in Paeonia rockii

by Qianqian Shi, Long Li, Xiaoxiao Zhang, Jianrang Luo, Xiang Li, Lijuan Zhai, Lixia He and Yanlong Zhang

Molecules 2017, 22(8), 1364; https://doi.org/10.3390/molecules22081364 - 17 Aug 2017

Cited by 23 | Viewed by 5653

Abstract

Paeonia rockii is a wild tree peony species with large and dark purple variegations at the base of its petals. It is the genetic resource for various variegation patterns in tree peony cultivars, which is in contrast to the pure white petals of [...] Read more.

Paeonia rockii is a wild tree peony species with large and dark purple variegations at the base of its petals. It is the genetic resource for various variegation patterns in tree peony cultivars, which is in contrast to the pure white petals of Paeonia ostii. However, the molecular mechanism underlying the formation of variegation in this plant is still unknown. Here, we conducted Illumina transcriptome sequencing for P. rockii, P. ostii (with pure white petals) and their F1 individuals (with purple-red variegation). A total of 181,866 unigenes were generated, including a variety of unigenes involved in anthocyanin biosynthesis and sequestration and the regulation of anthocyanin biosynthesis. The dark purple or purple-red variegation patterns mainly occurred due to the proportions of cyanidin (Cy)- and peonidin (Pn)-based anthocyanins. The variegations of P. rockii exhibited a “Cy > Pn” phenotype, whereas the F1 progeny showed a “Pn > Cy” phenotype. The CHS, DFR, ANS, and GST genes might play key roles in variegation pigmentation in P. rockii according to gene expression and interaction network analysis. Two R2R3-MYB transcription factors (c131300.graph_c0 and c133735.graph_c0) regulated variegation formation by controlling CHS, ANS and GST genes. Our results indicated that the various variegation patterns were caused by transcriptional regulation of anthocyanin biosynthesis genes, and the transcription profiles of the R2R3-MYBs provided clues to elucidate the mechanisms underlying this trait. The petal transcriptome data produced in this study will provide a valuable resource for future association investigations of the genetic regulation of various variegation patterns in tree peonies. Full article

► Show Figures

Figure 1

13 pages, 1814 KiB

Open AccessArticle

Biosynthesis of S-Adenosylmethionine by Magnetically Immobilized Escherichia coli Cells Highly Expressing a Methionine Adenosyltransferase Variant

by Chunli Yin, Tao Zheng and Xin Chang

Molecules 2017, 22(8), 1365; https://doi.org/10.3390/molecules22081365 - 18 Aug 2017

Cited by 15 | Viewed by 5674

Abstract

S-Adenosylmethionine (SAM) is a natural metabolite having important uses in the treatment of various diseases. To develop a simple and effective way to produce SAM, immobilized Escherichia coli cells highly expressing an engineered variant of methionine adenosyltransferase (MAT) were employed to synthesize SAM. [...] Read more.

S-Adenosylmethionine (SAM) is a natural metabolite having important uses in the treatment of various diseases. To develop a simple and effective way to produce SAM, immobilized Escherichia coli cells highly expressing an engineered variant of methionine adenosyltransferase (MAT) were employed to synthesize SAM. The recombinant I303V MAT variant was successfully produced at approximately 900 mg/L in a 10-L bioreactor and exhibited significantly less product inhibition and had a four-fold higher specific activity (14.2 U/mg) than the wild-type MAT (3.6 U/mg). To reduce the mass transfer resistance, the free whole-cells were permeabilized and immobilized using gellan gum gel as support in the presence of 100 mg/L Fe₃O₄ nanoparticles, and the highest activity (4152.4 U/L support) was obtained, with 78.2% of the activity recovery. The immobilized cells were more stable than the free cells under non-reactive conditions, with a half-life of 9.1 h at 50 °C. Furthermore, the magnetically immobilized cells were employed to produce SAM at a 40-mM scale. The residual activity of the immobilized cells was 67% of its initial activity after 10 reuses, and the conversion rate of ATP was ≥95% in all 10 batches. These results indicated that magnetically immobilized cells should be a promising biocatalyst for the biosynthesis of SAM. Full article

(This article belongs to the Section Green Chemistry)

► Show Figures

Figure 1

13 pages, 978 KiB

Open AccessArticle

Detection of Interactions between Proteins by Using Legendre Moments Descriptor to Extract Discriminatory Information Embedded in PSSM

by Yan-Bin Wang, Zhu-Hong You, Li-Ping Li, Yu-An Huang and Hai-Cheng Yi

Molecules 2017, 22(8), 1366; https://doi.org/10.3390/molecules22081366 - 18 Aug 2017

Cited by 28 | Viewed by 5109

Abstract

Protein-protein interactions (PPIs) play a very large part in most cellular processes. Although a great deal of research has been devoted to detecting PPIs through high-throughput technologies, these methods are clearly expensive and cumbersome. Compared with the traditional experimental methods, computational methods have [...] Read more.

Protein-protein interactions (PPIs) play a very large part in most cellular processes. Although a great deal of research has been devoted to detecting PPIs through high-throughput technologies, these methods are clearly expensive and cumbersome. Compared with the traditional experimental methods, computational methods have attracted much attention because of their good performance in detecting PPIs. In our work, a novel computational method named as PCVM-LM is proposed which combines the probabilistic classification vector machine (PCVM) model and Legendre moments (LMs) to predict PPIs from amino acid sequences. The improvement mainly comes from using the LMs to extract discriminatory information embedded in the position-specific scoring matrix (PSSM) combined with the PCVM classifier to implement prediction. The proposed method was evaluated on Yeast and Helicobacter pylori datasets with five-fold cross-validation experiments. The experimental results show that the proposed method achieves high average accuracies of 96.37% and 93.48%, respectively, which are much better than other well-known methods. To further evaluate the proposed method, we also compared the proposed method with the state-of-the-art support vector machine (SVM) classifier and other existing methods on the same datasets. The comparison results clearly show that our method is better than the SVM-based method and other existing methods. The promising experimental results show the reliability and effectiveness of the proposed method, which can be a useful decision support tool for protein research. Full article

(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)

► Show Figures

Figure 1

13 pages, 1526 KiB

Open AccessFeature PaperArticle

Copper-Catalyzed Synthesis of Unsymmetrical Diorganyl Chalcogenides (Te/Se/S) from Boronic Acids under Solvent-Free Conditions

by Sumbal Saba, Giancarlo Vaccari Botteselle, Marcelo Godoi, Tiago Elias Allievi Frizon, Fábio Zazyki Galetto, Jamal Rafique and Antonio L. Braga

Molecules 2017, 22(8), 1367; https://doi.org/10.3390/molecules22081367 - 18 Aug 2017

Cited by 46 | Viewed by 7679

Abstract

The efficient and mild copper-catalyzed synthesis of unsymmetrical diorganyl chalcogenides under ligand- and solvent-free conditions is described. The cross-coupling reaction was performed using aryl boric acids and 0.5 equiv. of diorganyl dichalcogenides (Te/Se/S) in the presence of 3 mol % of CuI and [...] Read more.

The efficient and mild copper-catalyzed synthesis of unsymmetrical diorganyl chalcogenides under ligand- and solvent-free conditions is described. The cross-coupling reaction was performed using aryl boric acids and 0.5 equiv. of diorganyl dichalcogenides (Te/Se/S) in the presence of 3 mol % of CuI and 3 equiv. of DMSO, under microwave irradiation. This new protocol allowed the preparation of several unsymmetrical diorganyl chalcogenides in good to excellent yields. Full article

(This article belongs to the Special Issue Celebrating Two Centuries of Research in Selenium Chemistry: State of the Art and New Prospectives)

► Show Figures

Graphical abstract

17 pages, 6335 KiB

Open AccessArticle

Phase Behaviour and Miscibility Studies of Collagen/Silk Fibroin Macromolecular System in Dilute Solutions and Solid State

by Ima Ghaeli, Mariana A. De Moraes, Marisa M. Beppu, Katarzyna Lewandowska, Alina Sionkowska, Frederico Ferreira-da-Silva, Maria P. Ferraz and Fernando J. Monteiro

Molecules 2017, 22(8), 1368; https://doi.org/10.3390/molecules22081368 - 18 Aug 2017

Cited by 26 | Viewed by 6941

Abstract

Miscibility is an important issue in biopolymer blends for analysis of the behavior of polymer pairs through the detection of phase separation and improvement of the mechanical and physical properties of the blend. This study presents the formulation of a stable and one-phase [...] Read more.

Miscibility is an important issue in biopolymer blends for analysis of the behavior of polymer pairs through the detection of phase separation and improvement of the mechanical and physical properties of the blend. This study presents the formulation of a stable and one-phase mixture of collagen and regenerated silk fibroin (RSF), with the highest miscibility ratio between these two macromolecules, through inducing electrostatic interactions, using salt ions. For this aim, a ternary phase diagram was experimentally built for the mixtures, based on observations of phase behavior of blend solutions with various ratios. The miscibility behavior of the blend solutions in the miscible zones of the phase diagram was confirmed quantitatively by viscosimetric measurements. Assessing the effects of biopolymer mixing ratio and salt ions, before and after dialysis of blend solutions, revealed the importance of ion-specific interactions in the formation of coacervate-based materials containing collagen and RSF blends that can be used in pharmaceutical, drug delivery, and biomedical applications. Moreover, the conformational change of silk fibroin from random coil to beta sheet, in solution and in the final solid films, was detected by circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR), respectively. Scanning electron microscopy (SEM) exhibited alterations of surface morphology for the biocomposite films with different ratios. Surface contact angle measurement illustrated different hydrophobic properties for the blended film surfaces. Differential scanning calorimetry (DSC) showed that the formation of the beta sheet structure of silk fibroin enhances the thermal stability of the final blend films. Therefore, the novel method presented in this study resulted in the formation of biocomposite films whose physico-chemical properties can be tuned by silk fibroin conformational changes by applying different component mixing ratios. Full article

(This article belongs to the Special Issue Natural Polymers and Biopolymers)

► Show Figures

Graphical abstract

34 pages, 1711 KiB

Open AccessReview

Anesthetic Agents of Plant Origin: A Review of Phytochemicals with Anesthetic Activity

by Hironori Tsuchiya

Molecules 2017, 22(8), 1369; https://doi.org/10.3390/molecules22081369 - 18 Aug 2017

Cited by 93 | Viewed by 16679

Abstract

The majority of currently used anesthetic agents are derived from or associated with natural products, especially plants, as evidenced by cocaine that was isolated from coca (Erythroxylum coca, Erythroxylaceae) and became a prototype of modern local anesthetics and by thymol and [...] Read more.

The majority of currently used anesthetic agents are derived from or associated with natural products, especially plants, as evidenced by cocaine that was isolated from coca (Erythroxylum coca, Erythroxylaceae) and became a prototype of modern local anesthetics and by thymol and eugenol contained in thyme (Thymus vulgaris, Lamiaceae) and clove (Syzygium aromaticum, Myrtaceae), respectively, both of which are structurally and mechanistically similar to intravenous phenolic anesthetics. This paper reviews different classes of phytochemicals with the anesthetic activity and their characteristic molecular structures that could be lead compounds for anesthetics and anesthesia-related drugs. Phytochemicals in research papers published between 1996 and 2016 were retrieved from the point of view of well-known modes of anesthetic action, that is, the mechanistic interactions with Na⁺ channels, γ-aminobutyric acid type A receptors, N-methyl-d-aspartate receptors and lipid membranes. The searched phytochemicals include terpenoids, alkaloids and flavonoids because they have been frequently reported to possess local anesthetic, general anesthetic, antinociceptive, analgesic or sedative property. Clinical applicability of phytochemicals to local and general anesthesia is discussed by referring to animal in vivo experiments and human pre-clinical trials. This review will give structural suggestions for novel anesthetic agents of plant origin. Full article

(This article belongs to the Special Issue Polypharmacology and Multitarget Drug Discovery)

► Show Figures

Figure 1

37 pages, 4598 KiB

Open AccessReview

Metal-Based Nanoparticles for the Treatment of Infectious Diseases

by Blessing Atim Aderibigbe

Molecules 2017, 22(8), 1370; https://doi.org/10.3390/molecules22081370 - 18 Aug 2017

Cited by 215 | Viewed by 15330

Abstract

Infectious diseases can be transmitted and they cause a significant burden on public health globally. They are the greatest world killers and it is estimated that they are responsible for the demise of over 17 million people annually. The impact of these diseases [...] Read more.

Infectious diseases can be transmitted and they cause a significant burden on public health globally. They are the greatest world killers and it is estimated that they are responsible for the demise of over 17 million people annually. The impact of these diseases is greater in the developing countries. People with compromised immune systems and children are the most affected. Infectious diseases may be caused by bacteria, viruses, and protozoa. The treatment of infectious diseases is hampered by simultaneous resistance to multiple drugs, indicating that there is a serious and pressing need to develop new therapeutics that can overcome drug resistance. This review will focus on the recent reports of metal-based nanoparticles that are potential therapeutics for the treatment of infectious diseases and their biological efficacy (in vitro and in vivo). Full article

(This article belongs to the Special Issue Metal Based Drugs: Opportunities and Challenges)

► Show Figures

Figure 1

14 pages, 3480 KiB

Open AccessFeature PaperArticle

BET & ELF Quantum Topological Analysis of Neutral 2-Aza-Cope Rearrangement of γ-Alkenyl Nitrones

by Pedro Merino, Maria A. Chiacchio, Laura Legnani and Tomás Tejero

Molecules 2017, 22(8), 1371; https://doi.org/10.3390/molecules22081371 - 19 Aug 2017

Cited by 5 | Viewed by 5979

Abstract

The 2-Aza-Cope rearrangement of γ-alkenyl nitrones is a rare example of the neutral thermal 2-aza-Cope process that usually takes place with cationic species. During the rearrangement, a redistribution of bonds and electronic density occurs in one kinetic step. However, the introduction of substituents [...] Read more.

The 2-Aza-Cope rearrangement of γ-alkenyl nitrones is a rare example of the neutral thermal 2-aza-Cope process that usually takes place with cationic species. During the rearrangement, a redistribution of bonds and electronic density occurs in one kinetic step. However, the introduction of substituents with different steric requirements and electronic features might alter the activation energies and the synchronicity of the reaction. The electron localization function (ELF) analysis and its application to Bonding Evolution Theory (BET) analysis within the context of Molecular Electron Density Theory (MEDT) is an excellent tool to monitor the electron density along the reaction coordinate and thus investigate in detail bond breaking and formation and the corresponding energy barriers. By analyzing topological ELF calculations of seventeen 2-aza-Cope nitrone rearrangements with selected substituents, the main factors influencing the synchronicity of the process were investigated. This MEDT study results revealed that the rearrangement is a non-polar process mostly influenced by steric factors rather than by electronic ones, and confirms the pseudoradical character of the process rather than any pericyclic electron-reorganization. Full article

(This article belongs to the Special Issue The Molecular Electron Density Theory: A Modern View of Molecular Reactivity in Organic Chemistry)

► Show Figures

Graphical abstract

10 pages, 647 KiB

Open AccessArticle

Synthesis and Antimicrobial Studies of New Antibacterial Azo-Compounds Active against Staphylococcus aureus and Listeria monocytogenes

by Stefano Piotto, Simona Concilio, Lucia Sessa, Rosita Diana, Gabriel Torrens, Carlos Juan, Ugo Caruso and Pio Iannelli

Molecules 2017, 22(8), 1372; https://doi.org/10.3390/molecules22081372 - 19 Aug 2017

Cited by 52 | Viewed by 7410

Abstract

Some novel (phenyl-diazenyl)phenols (4a–m) were designed and synthesized to be evaluated for their antibacterial activity. Starting from an active previously-synthesized azobenzene chosen as lead compound, we introduced some modifications and optimization of the structure, in order to improve solubility [...] Read more.

Some novel (phenyl-diazenyl)phenols (4a–m) were designed and synthesized to be evaluated for their antibacterial activity. Starting from an active previously-synthesized azobenzene chosen as lead compound, we introduced some modifications and optimization of the structure, in order to improve solubility and drug conveyance. Structures of all newly-synthesized compounds were confirmed by ¹H nuclear magnetic resonance (NMR), mass spectrometry, and UV-Vis spectroscopy. Antibacterial activity of the new compounds was tested with the dilution method against the bacteria strains Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa PAO1. All the compounds were selectively active against Gram-positive bacteria. In particular, compounds 4d, 4h, and 4i showed the highest activity against S. aureus and Listeria monocytogenes, reaching remarkable MIC₁₀₀ values of 4 μg/mL and 8 μg/mL. The relationship between antimicrobial activity and compound structure has suggested that the presence of hydroxyl groups seems to be essential for antimicrobial activity of phenolic compounds. Full article

(This article belongs to the Special Issue Antibacterial Materials and Coatings)

► Show Figures

Figure 1

12 pages, 2068 KiB

Open AccessArticle

Inhibitory Effect of Bovine Lactoferrin on Catechol-O-Methyltransferase

by Masayuki Ikeda, Hiroshi Iijima, Ichizo Shinoda, Hiroshi Iwamoto and Yasuhiro Takeda

Molecules 2017, 22(8), 1373; https://doi.org/10.3390/molecules22081373 - 19 Aug 2017

Cited by 8 | Viewed by 7697

Abstract

Lactoferrin (LF) is a well-known multifunctional protein. In this study, we report the inhibitory potency of bovine LF (bLF) on catechol-O-methyltransferase (COMT), which catalyzes methylation of catechol substrates. We found that bLF binds to and inhibits COMT using its N-terminal [...] Read more.

Lactoferrin (LF) is a well-known multifunctional protein. In this study, we report the inhibitory potency of bovine LF (bLF) on catechol-O-methyltransferase (COMT), which catalyzes methylation of catechol substrates. We found that bLF binds to and inhibits COMT using its N-terminal region. An N-terminal peptide fragment obtained from bLF by trypsin digestion showed a higher inhibitory activity than intact bLF. A synthetic fragment of the bLF N-terminal residues 6–50, with two pairs of disulfide bonds, also showed higher inhibitory activity than intact bLF. Enzyme kinetic studies proved that bLF did not compete with S-adenosylmethionine (the methyl donor substrate) as well as methyl acceptor substrates such as dihydroxybenzoic acid, (−)-epicatechin, norepinephrine, or l-3,4-dihydroxyphenylalanine. The inhibitory potency of bLF decreased against a COMT preparation pretreated with dithiothreitol, suggesting that the oxidation status of COMT is relevant to interaction with bLF. We further confirmed that COMT activity in the cell extracts form Caco-2 and HepG2 cells was inhibited by bLF and by the synthesized fragment. Enzyme kinetic study indicated that bLF functions as a non-competitive inhibitor by binding to an allosteric surface of COMT. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Graphical abstract

20 pages, 1605 KiB

Open AccessArticle

Pharmacological and Toxicological Screening of Novel Benzimidazole-Morpholine Derivatives as Dual-Acting Inhibitors

by Nafiz Öncü Can, Ulviye Acar Çevik, Begüm Nurpelin Sağlık, Yusuf Özkay, Özlem Atlı, Merve Baysal, Ümide Demir Özkay and Özgür Devrim Can

Molecules 2017, 22(8), 1374; https://doi.org/10.3390/molecules22081374 - 19 Aug 2017

Cited by 22 | Viewed by 6710

Abstract

The aim of this study was to investigate acetylcholinesterase (AChE), monoamine oxidase A (MAO-A), monoamine oxidase B (MAO-B), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme inhibitory, and antimicrobial activities of a new series of 2-(4-substituted phenyl)-1-[2-(morpholin-4-yl)ethyl]-1H-benzimidazole derivatives, for their possible use as [...] Read more.

The aim of this study was to investigate acetylcholinesterase (AChE), monoamine oxidase A (MAO-A), monoamine oxidase B (MAO-B), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme inhibitory, and antimicrobial activities of a new series of 2-(4-substituted phenyl)-1-[2-(morpholin-4-yl)ethyl]-1H-benzimidazole derivatives, for their possible use as multi-action therapeutic agents. Target compounds (n = 15) were synthesized under microwave irradiation conditions in two steps, and their structures were elucidated by FT-IR, ¹H-NMR, ¹³C-NMR and high resolution mass spectroscopic analyses. Pharmacological screening studies revealed that two of the compounds (2b and 2j) have inhibitory potential on both COX-1 and COX-2 enzymes. In addition, cytotoxic and genotoxic properties of the compounds 2b, 2j and 2m were investigated via the well-known MTT and Ames tests, which revealed that the mentioned compounds are non-cytotoxic and non-genotoxic. As a concise conclusion, two novel compounds were characterized as potential candidates for treatment of frequently encountered inflammatory diseases. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

17 pages, 1689 KiB

Open AccessArticle

Impact of Xanthylium Derivatives on the Color of White Wine

by Franziska Bührle, Anita Gohl and Fabian Weber

Molecules 2017, 22(8), 1376; https://doi.org/10.3390/molecules22081376 - 19 Aug 2017

Cited by 17 | Viewed by 6960

Abstract

Xanthylium derivatives are yellow to orange pigments with a glyoxylic acid bridge formed by dimerization of flavanols, which are built by oxidative cleavage of tartaric acid. Although their structure and formation under wine-like conditions are well established, knowledge about their color properties and [...] Read more.

Xanthylium derivatives are yellow to orange pigments with a glyoxylic acid bridge formed by dimerization of flavanols, which are built by oxidative cleavage of tartaric acid. Although their structure and formation under wine-like conditions are well established, knowledge about their color properties and their occurrence and importance in wine is deficient. Xanthylium cations and their corresponding esters were synthesized in a model wine solution and isolated via high-performance countercurrent chromatography (HPCCC) and solid phase extraction (SPE). A Three-Alternative-Forced-Choice (3-AFC) test was applied to reveal the color perception threshold of the isolated compounds in white wine. Their presence and color impact was assessed in 70 different wines (58 white and 12 rosé wines) by UHPLC-DAD-ESI-MSⁿ and the storage stability in wine was determined. The thresholds in young Riesling wine were 0.57 mg/L (cations), 1.04 mg/L (esters) and 0.67 mg/L (1:1 (w/w) mixture), respectively. The low thresholds suggest a possible impact on white wine color, but concentrations in wines were below the threshold. The stability study showed the degradation of the compounds during storage under several conditions. Despite the low perception threshold, xanthylium derivatives might have no direct impact on white wine color, but might play a role in color formation as intermediate products in polymerization and browning. Full article

(This article belongs to the Collection Wine Chemistry)

► Show Figures

Figure 1

13 pages, 2510 KiB

Open AccessArticle

Germination under Moderate Salinity Increases Phenolic Content and Antioxidant Activity in Rapeseed (Brassica napus var oleifera Del.) Sprouts

by Beatrice Falcinelli, Valeria Sileoni, Ombretta Marconi, Giuseppe Perretti, Muriel Quinet, Stanley Lutts and Paolo Benincasa

Molecules 2017, 22(8), 1377; https://doi.org/10.3390/molecules22081377 - 19 Aug 2017

Cited by 54 | Viewed by 6380

Abstract

The use of sprouts in the human diet is becoming more and more widespread because they are tasty and high in bioactive compounds and antioxidants, with related health benefits. In this work, we sprouted rapeseed under increasing salinity to investigate the effect on [...] Read more.

The use of sprouts in the human diet is becoming more and more widespread because they are tasty and high in bioactive compounds and antioxidants, with related health benefits. In this work, we sprouted rapeseed under increasing salinity to investigate the effect on free and bound total phenolics (TP), non-flavonoids (NF), tannins (TAN), phenolic acids (PAs), and antioxidant activity. Seeds were incubated at 0, 25, 50, 100, 200 mM NaCl until early or late sprout stage, i.e., before or after cotyledon expansion, respectively. Sprouting and increasing salinity slightly decreased the bound fractions of TP, NF, TAN, PAs, while it increased markedly the free ones and their antioxidant activity. Further increases were observed in late sprouts. Moderate salinity (25–50 mM NaCl) caused the highest relative increase in phenolic concentration while it slightly affected sprout growth. On the contrary, at higher NaCl concentrations, sprouts grew slowly (100 mM NaCl) or even died before reaching the late sprout stage (200 mM). Overall, moderate salinity was the best compromise to increase phenolic content of rapeseed sprouts. The technique may be evaluated for transfer to other species as a cheap and feasible way to increase the nutritional value of sprouts. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

► Show Figures

Figure 1

7 pages, 711 KiB

Open AccessArticle

Cryochemical Synthesis of Polymorphous Nanostructures of a Steroid Neurohormone

by Yurii Morozov, Dmitry Chistyakov, Vladimir Chernyshev and Gleb Sergeev

Molecules 2017, 22(8), 1378; https://doi.org/10.3390/molecules22081378 - 21 Aug 2017

Cited by 4 | Viewed by 4042

Abstract

A new cryochemical strategy of producing nanoparticles and polymorphous nanostructures of drugs is used, which is based on the dynamic combination of high and low temperatures, gas and solid phases, and inert carrier gases. This technology is applied to the synthesis of nanoparticles [...] Read more.

A new cryochemical strategy of producing nanoparticles and polymorphous nanostructures of drugs is used, which is based on the dynamic combination of high and low temperatures, gas and solid phases, and inert carrier gases. This technology is applied to the synthesis of nanoparticles of steroid neurohormone dehydroepiandrosterone (DHEA). We have optimized the conditions of synthesis of the new polymorphous DHEA structure, FVII. The molecules of DHEA in FVII structure are bound by hydrogen bonds via oxygen atoms. The grain size is 100 nm. It is shown that the yield and ratio of the resulting nanoforms of this hormone are determined by the nature and properties of the inert carrier gas. The highest yield and selectivity of FVII are observed when carbon dioxide is used as the carrier gas. In the case of helium, the FVII content decreases from 85 to 30% and other structures are formed. In experiments without carrier gas, nanoparticles are formed but no FVII is produced. The selectivity and the effect of carrier gas are considered on the basis of homogeneous and heterogeneous formation of nanoparticles and the relationship between particle selectivity and its activity. The synthesis of various polymorphous structures on the nanoscale is assumed to be the manifestation of the size effect in the synthesis of drugs. Full article

(This article belongs to the Section Molecular Diversity)

► Show Figures

Figure 1

11 pages, 789 KiB

Open AccessArticle

Chemical Constituents of Murraya tetramera Huang and Their Repellent Activity against Tribolium castaneum

by Chun-Xue You, Shan-Shan Guo, Wen-Juan Zhang, Zhu-Feng Geng, Jun-Yu Liang, Ning Lei, Shu-Shan Du and Zhi-Wei Deng

Molecules 2017, 22(8), 1379; https://doi.org/10.3390/molecules22081379 - 20 Aug 2017

Cited by 13 | Viewed by 5286

Abstract

Sixteen compounds were isolated from the leaves and stems of Murraya tetramera Huang. Based on the NMR and MS spectral results, the structures were determined. It was confirmed that the isolated compounds included three new compounds (9, 10 and 13) [...] Read more.

Sixteen compounds were isolated from the leaves and stems of Murraya tetramera Huang. Based on the NMR and MS spectral results, the structures were determined. It was confirmed that the isolated compounds included three new compounds (9, 10 and 13) and one new natural product (8), which were identified asmurratetra A (9), murratetra B (10), murratetra C (13) and [2-(7-methoxy-2-oxochromen-8-yl)-3-methylbut-2-enyl]3-methylbut-2-enoate (8), respectively. Meanwhile, the repellent activity against Tribolium castaneum was investigated for 13 of these isolated compounds. The results showed that the tested compounds had various levels of repellent activity against T. castaneum. Among them, compounds 1 (4(15)-eudesmene-1β,6α-diol), 11 (isoferulic acid) and 16 (2,3-dihydroxypropyl hexadecanoate) showed fair repellent activity against T. castaneum. They might be considered as potential leading compounds for the development of natural repellents. Full article

(This article belongs to the Collection Bioactive Compounds)

► Show Figures

Figure 1

19 pages, 3283 KiB

Open AccessArticle

Synthesis of New Hydrazone Derivatives for MAO Enzymes Inhibitory Activity

by Nafiz Öncü Can, Derya Osmaniye, Serkan Levent, Begüm Nurpelin Sağlık, Beril İnci, Sinem Ilgın, Yusuf Özkay and Zafer Asım Kaplancıklı

Molecules 2017, 22(8), 1381; https://doi.org/10.3390/molecules22081381 - 20 Aug 2017

Cited by 55 | Viewed by 8997

Abstract

In the present work, 14 new 1-substituted-2-phenylhydrazone derivatives were synthesized to evaluate their inhibitory activity against hMAO enzymes. The structures of the newly synthesized hydrazones 2a–2n were characterized by IR, 1H-NMR, 13C-NMR, HR-MS spectroscopic methods. The inhibitory activity of compounds 2a–2n against hMAO-A [...] Read more.

In the present work, 14 new 1-substituted-2-phenylhydrazone derivatives were synthesized to evaluate their inhibitory activity against hMAO enzymes. The structures of the newly synthesized hydrazones 2a–2n were characterized by IR, 1H-NMR, 13C-NMR, HR-MS spectroscopic methods. The inhibitory activity of compounds 2a–2n against hMAO-A and hMAO-B enzymes was elucidated by using an in-vitro Amplex Red® reagent assay based on fluorometric methods. According to the activity studies, 2a and 2b were found to be the most active compounds against hMAO-A enzyme, with IC50 values of 0.342 µM and 0.028 µM, respectively. The most active compounds 2a–2b were evaluated by means of enzyme kinetics and docking studies. Moreover, these compounds were subjected to cytotoxicity and genotoxicity tests to establish their preliminary toxicological profiles and were found to be non-cytotoxic and non-genotoxic. Consequently, the findings of this study display the biological importance of compounds 2a, 2b as selective, irreversible and competitive inhibitors of hMAO-A. Docking studies revealed that there is a strong interaction between hMAO-A and the most active compound 2b. Full article

(This article belongs to the Collection Molecular Docking)

► Show Figures

Figure 1

17 pages, 1330 KiB

Open AccessArticle

Composition and Antioxidant, Antienzymatic and Antimicrobial Activities of Volatile Molecules from Spanish Salvia lavandulifolia (Vahl) Essential Oils

by Ana-Belen Cutillas, Alejandro Carrasco, Ramiro Martinez-Gutierrez, Virginia Tomas and Jose Tudela

Molecules 2017, 22(8), 1382; https://doi.org/10.3390/molecules22081382 - 21 Aug 2017

Cited by 27 | Viewed by 6339

Abstract

The current study describes the composition of Salvia lavandulifolia (Vahl) essential oils (SlEOs) obtained from plants cultivated in Murcia (Spain), as determined by gas chromatography. Relative and absolute concentrations, the enantiomeric ratios of chiral compounds and the in vitro antioxidant, antienzymatic and antimicrobial [...] Read more.

The current study describes the composition of Salvia lavandulifolia (Vahl) essential oils (SlEOs) obtained from plants cultivated in Murcia (Spain), as determined by gas chromatography. Relative and absolute concentrations, the enantiomeric ratios of chiral compounds and the in vitro antioxidant, antienzymatic and antimicrobial activities are described. The main components of the SlEOs were camphor, 1,8-cineole, camphene and α-pinene, and the main enantiomers were (+)-camphor and (−)-camphene. The activities against free radicals and the capacity to reduce and chelate metallic ions were measured. SlEO-3 showed the highest activity in ORAC, DPPH, ABTS and reducing power methods, while SlEO-1 exhibited the highest chelating power. The activity of lipoxygenase and acetylcholinesterase could be inhibited by all the SlEOs, being bornyl acetate and limonene the most active individual compounds against lipoxygenase and 1,8-cineole against acetylcholinesterase. SlEOs and some individual compounds inhibited Escherichia coli, Staphylococcus aureus and Candida albicans. These results increase our knowledge of SlEOs and, particularly, provide for the first time a complete characterization of SlEOs from Murcia, Spain, while proposing possible biotechnological uses for them. Full article

(This article belongs to the Special Issue Essential Oils: Chemistry and Bioactivity)

► Show Figures

Graphical abstract

40 pages, 5591 KiB

Open AccessReview

The Genus Alnus, A Comprehensive Outline of Its Chemical Constituents and Biological Activities

by Xueyang Ren, Ting He, Yanli Chang, Yicheng Zhao, Xiaoyi Chen, Shaojuan Bai, Le Wang, Meng Shen and Gaimei She

Molecules 2017, 22(8), 1383; https://doi.org/10.3390/molecules22081383 - 21 Aug 2017

Cited by 42 | Viewed by 8184

Abstract

The genus Alnus (Betulaceae) is comprised of more than 40 species. Many species of this genus have a long history of use in folk medicines. Phytochemical investigations have revealed the presence of diarylheptanoids, polyphenols, flavonoids, terpenoids, steroids and other compounds. Diarylheptanoids, natural products [...] Read more.

The genus Alnus (Betulaceae) is comprised of more than 40 species. Many species of this genus have a long history of use in folk medicines. Phytochemical investigations have revealed the presence of diarylheptanoids, polyphenols, flavonoids, terpenoids, steroids and other compounds. Diarylheptanoids, natural products with a 1,7-diphenylheptane structural skeleton, are the dominant constituents in the genus, whose anticancer effect has been brought into focus. Pure compounds and crude extracts from the genus exhibit a wide spectrum of pharmacological activities both in vitro and in vivo. This paper compiles 273 naturally occurring compounds from the genus Alnus along with their structures and pharmacological activities, as reported in 138 references. Full article

► Show Figures

Figure 1

12 pages, 2748 KiB

Open AccessArticle

Effects of Refined Xiaoyaosan on Depressive-Like Behaviors in Rats with Chronic Unpredictable Mild Stress through Neurosteroids, Their Synthesis and Metabolic Enzymes

by Xiaoling Guo, Wenqi Qiu, Yueyun Liu, Yifang Zhang, Hongbo Zhao and Jiaxu Chen

Molecules 2017, 22(8), 1386; https://doi.org/10.3390/molecules22081386 - 21 Aug 2017

Cited by 28 | Viewed by 5384

Abstract

Abstract: To observe the effects of refined Xiaoyaosan (XYS) on the depressive-like behaviors in rats with chronic unpredictable mild stress (CUMS), and to explore the relationship between the changes of neurosteroids and mRNA expressions of their synthesis and metabolic enzymes, and [...] Read more.

Abstract: To observe the effects of refined Xiaoyaosan (XYS) on the depressive-like behaviors in rats with chronic unpredictable mild stress (CUMS), and to explore the relationship between the changes of neurosteroids and mRNA expressions of their synthesis and metabolic enzymes, and the mechanism of XYS in the treatment of depression. Methods: Eighty-four healthy male Sprague-Dawley rats were randomly divided into normal group, model group, XYS group and fluoxetine group. The latter three groups were subjected to 21 days of CUMS to prepare the stress depression model. Rats in the XYS group, and fluoxetine group were given intragastric administration with refined XYS and fluoxetine, respectively. The behavioral changes of the rats were observed after 21 days. The contents of pregnenolone (PREG), progesterone (PROG) and alloprognanolone (ALLO) in the plasma of rats were measured by ELISA. The levels of PREG, PROG and ALLO in the hippocampus and amygdala tissues were measured by LC-MS/MS. The mRNA expressions of 3α-hydroxysteroid dehydrogenase (3α-HSD), 3β-hydroxysteroid dehydrogenase (3β-HSD), cholesterol side-chain cleavage enzyme (P450scc) and 5α-reductase (5a-R) in the hippocampus and amygdala were detected by RT-qPCR methods. Results: There were changes in the model rats. The contents of PREG, PROG and ALLO changed similarly, which reflected in the decrease of PROG and ALLO, and the increase of PREG. The mRNA expression of P450scc was increased, and the mRNA expressions of 3α-HSD, 3β-HSD and 5a-R were decreased. Refined XYS could improve the behaviors of rats and the biological indicators. Conclusions: There is a neurosteroid dysfunction in the brain region of depression rat model animals, and the mechanism of refined XYS depression treatment may be related to the regulation of the control of mRNA expression of related synthesis and metabolic enzymes in the hippocampus and amygdala, further affecting the contents of neurosteroids. Full article

(This article belongs to the Special Issue Herbal Remedies Meet Modern Day Medicine: Challenges and Opportunities)

► Show Figures

Figure 1

14 pages, 9573 KiB

Open AccessArticle

Cloning and Characterization of Two Iridoid Synthase Homologs from Swertia Mussotii

by Beibei Xiang, Xiaoxue Li, Yan Wang, Xiaoxuan Tian, Zhen Yang, Lin Ma, Xia Liu and Yong Wang

Molecules 2017, 22(8), 1387; https://doi.org/10.3390/molecules22081387 - 22 Aug 2017

Cited by 17 | Viewed by 5994

Abstract

Swertia mussotii is an important medicinal plant found on the Qinghai Tibetan Plateau that has great economic and medicinal value. This plant has enjoyed a long history of use as a curative for hepatitis. The biological activity of secoiridoids, including gentiopicroside and swertiamarin, [...] Read more.

Swertia mussotii is an important medicinal plant found on the Qinghai Tibetan Plateau that has great economic and medicinal value. This plant has enjoyed a long history of use as a curative for hepatitis. The biological activity of secoiridoids, including gentiopicroside and swertiamarin, has been mainly tested for its anti-hepatitis effects. Here, we identify two candidate genes (SmIS1 and SmIS2) that are homologues of iridoid synthase and that are components of the secoiridoid pathway in S. mussotii. Using sequencing and phylogenetic analyses, we confirm that SmIS1 and SmIS2 contain six conserved short-chain dehydrogenases/reductase (SDR) motifs and thus belong to the P5βRs group. The two purified Escherichia coli-expressed proteins reduced 8-oxogeranial to both nepetalactol and iridodials. A comparison of the kinetic parameters of SmIS1 and SmIS2 recombinant proteins revealed that SmIS2 has a lower affinity than SmIS1 for 8-oxogeranial. Transcript levels of the two genes were analysed in three different tissues of S. mussotii using semi-quantitative RT-PCR and RT-qPCR. SmIS1 and SmIS2 expression levels were more abundant in leaves and stems. This investigation adds to our knowledge of P5βRs genes in the secoiridoid synthesis pathway and provides candidate genes for genetically improving S. mussotii by enhancing secondary metabolite production. Full article

► Show Figures

Figure 1

8 pages, 1274 KiB

Open AccessArticle

Base-Mediated One-Pot Synthesis of Aliphatic Diazirines for Photoaffinity Labeling

by Lei Wang, Zetryana Puteri Tachrim, Natsumi Kurokawa, Fumina Ohashi, Yasuko Sakihama, Yasuyuki Hashidoko and Makoto Hashimoto

Molecules 2017, 22(8), 1389; https://doi.org/10.3390/molecules22081389 - 22 Aug 2017

Cited by 17 | Viewed by 11820

Abstract

Aliphatic diazirines have been widely used as prominent photophores for photoaffinity labeling owing to their relatively small size which can reduce the steric effect on the natural interaction between ligands and proteins. Based on our continuous efforts to develop efficient methods for the [...] Read more.

Aliphatic diazirines have been widely used as prominent photophores for photoaffinity labeling owing to their relatively small size which can reduce the steric effect on the natural interaction between ligands and proteins. Based on our continuous efforts to develop efficient methods for the synthesis of aliphatic diazirines, we present here a comprehensive study about base-mediated one-pot synthesis of aliphatic diazirines. It was found that potassium hydroxide (KOH) can also promote the construction of aliphatic diazirine with good efficiency. Importantly, KOH is cheaper, highly available, and easily handled and stored compared with the previously used base, potassium tert-butoxide (t-BuOK). Gram-scale study showed that it owned great advantages in being used for the large-scale production of aliphatic diazirines. This protocol is highly neat and the desired products can be easily isolated and purified. As the first comprehensive study of the base-mediated one-pot synthesis of aliphatic diazirines, this work provided good insight into the preparation and utilization of diazirine-based photoaffinity labeling probes. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Scheme 1

11 pages, 1160 KiB

Open AccessArticle

The Potential of α-Spinasterol to Mimic the Membrane Properties of Natural Cholesterol

by Ivan Haralampiev, Holger A. Scheidt, Daniel Huster and Peter Müller

Molecules 2017, 22(8), 1390; https://doi.org/10.3390/molecules22081390 - 22 Aug 2017

Cited by 5 | Viewed by 5765

Abstract

Sterols play a unique role for the structural and dynamical organization of membranes. The current study reports data on the membrane properties of the phytosterol (3β,5α,22E)-stigmasta-7,22-dien-3-β-ol (α-spinasterol), which represents an important component of argan oil and have not been investigated so far in [...] Read more.

Sterols play a unique role for the structural and dynamical organization of membranes. The current study reports data on the membrane properties of the phytosterol (3β,5α,22E)-stigmasta-7,22-dien-3-β-ol (α-spinasterol), which represents an important component of argan oil and have not been investigated so far in molecular detail. In particular, the impact of α-spinasterol on the structure and organization of lipid membranes was investigated and compared with those of cholesterol. Various membrane parameters such as the molecular packing of the phospholipid fatty acyl chains, the membrane permeability toward polar molecules, and the formation of lateral membrane domains were studied. The experiments were performed on lipid vesicles using methods of NMR spectroscopy and fluorescence spectroscopy and microscopy. The results show that α-spinasterol resembles the membrane behavior of cholesterol to some degree. Full article

(This article belongs to the Special Issue New Methodologies in Natural Product Analytics and Structure Elucidation)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Molecules, Volume 22, Issue 8 (August 2017) – 149 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI