Previous Issue

E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Table of Contents

Molecules, Volume 22, Issue 9 (September 2017)

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-182
Export citation of selected articles as:

Editorial

Jump to: Research, Review, Other

Open AccessEditorial Strait Gate: Special Issue on Advances in Silicon Chemistry
Molecules 2017, 22(9), 1497; doi:10.3390/molecules22091497
Received: 5 September 2017 / Accepted: 6 September 2017 / Published: 7 September 2017
PDF Full-text (171 KB) | HTML Full-text | XML Full-text
Abstract
Manufacturing high-purity element silicon and organic polysilicones are two major silicon industries, supporting the basis of the modern electronic industry and our daily lives [...]
Full article
(This article belongs to the Special Issue Advances in Silicon Chemistry)
Open AccessEditorial Special Issue: Asymmetric Synthesis 2017
Molecules 2017, 22(9), 1504; doi:10.3390/molecules22091504
Received: 6 September 2017 / Accepted: 7 September 2017 / Published: 8 September 2017
PDF Full-text (175 KB) | HTML Full-text | XML Full-text
Abstract
The use of asymmetric synthetic methodologies plays a crucial role, nowadays, in the preparation of bioactive or other interesting compounds [...]
Full article
(This article belongs to the Special Issue Asymmetric Synthesis 2017)
Open AccessEditorial Special Issue: Intramolecular Hydrogen Bonding 2017
Molecules 2017, 22(9), 1521; doi:10.3390/molecules22091521
Received: 8 September 2017 / Accepted: 10 September 2017 / Published: 11 September 2017
PDF Full-text (177 KB) | HTML Full-text | XML Full-text
Abstract
Even after more than a century of study [1–6], scrutiny, and detailed examination, the H-bond continues [7–12] to evoke a level of fascination that surpasses many other phenomena [...]
Full article
(This article belongs to the Special Issue Intramolecular Hydrogen Bonding 2017)

Research

Jump to: Editorial, Review, Other

Open AccessCommunication MTLD, a Database of Multiple Target Ligands, the Updated Version
Molecules 2017, 22(9), 1375; doi:10.3390/molecules22091375
Received: 3 July 2017 / Revised: 14 August 2017 / Accepted: 16 August 2017 / Published: 6 September 2017
PDF Full-text (2424 KB) | HTML Full-text | XML Full-text
Abstract
Polypharmacology plays an important role in drug discovery and polypharmacology drug strategies provide a novel path in drug design. However, to develop a polypharmacology drug with the desired profile remains a challenge. Previously, we developed a free web-accessible database called Multiple Target Ligand
[...] Read more.
Polypharmacology plays an important role in drug discovery and polypharmacology drug strategies provide a novel path in drug design. However, to develop a polypharmacology drug with the desired profile remains a challenge. Previously, we developed a free web-accessible database called Multiple Target Ligand Database (MTLD, www.mtdcadd.com). Herein, the MTLD database has been updated, containing 2444 Multiple Target Ligands (MTLs) that bind with 21,424 binding sites from 18,231 crystal structures. Of the MTLs, 304 entries are approved drugs, and 1911 entries are drug-like compounds. Also, we added new functions such as multiple conditional search and linkage visualization. Through querying the updated database, extremely useful information for the development of polypharmacology drugs may be provided. Full article
(This article belongs to the Special Issue Polypharmacology and Multitarget Drug Discovery)
Figures

Figure 1

Open AccessCommunication Study on the Fluorescent Activity of N2-Indolyl-1,2,3-triazole
Molecules 2017, 22(9), 1380; doi:10.3390/molecules22091380
Received: 24 July 2017 / Revised: 8 August 2017 / Accepted: 15 August 2017 / Published: 5 September 2017
PDF Full-text (3269 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new type of blue emitter, N2-Indolyl-1,2,3-triazoles (NITs), with the λmax ranging from 420–480 nm and the Stokes shift from 89–143 nm, were synthesized through the coupling reaction of indoles with triazole derivatives. The influence of different substitution patterns on
[...] Read more.
A new type of blue emitter, N2-Indolyl-1,2,3-triazoles (NITs), with the λmax ranging from 420–480 nm and the Stokes shift from 89–143 nm, were synthesized through the coupling reaction of indoles with triazole derivatives. The influence of different substitution patterns on the optical properties (efficiency, excitation, and emission wavelengths) of the NITs was investigated. In addition, one palladium complex were synthesized by using NITs as the ligands, which, however, exhibited no fluorescent activity, but did show the enhanced co-planarity. Lastly, two bio-active molecule derivatives were explored for the potential use of these novel dyes in related chemical and biological applications. Full article
(This article belongs to the Section Photochemistry)
Figures

Figure 1

Open AccessArticle Chemical Composition of Pinus roxburghii Bark Volatile Oil and Validation of Its Anti-Inflammatory Activity Using Molecular Modelling and Bleomycin-Induced Inflammation in Albino Mice
Molecules 2017, 22(9), 1384; doi:10.3390/molecules22091384
Received: 5 August 2017 / Revised: 16 August 2017 / Accepted: 19 August 2017 / Published: 29 August 2017
PDF Full-text (4699 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The chemical composition of Pinus roxburghii bark essential oil (PRO) was qualitatively and quantitatively determined using GC/FID and GC/MS. The anti-inflammatory activity was assessed in vitro by evaluating the binding percentages on the cannabinoids and opioids receptors. Bleomycin (BLM)-induced pulmonary inflammation in albino
[...] Read more.
The chemical composition of Pinus roxburghii bark essential oil (PRO) was qualitatively and quantitatively determined using GC/FID and GC/MS. The anti-inflammatory activity was assessed in vitro by evaluating the binding percentages on the cannabinoids and opioids receptors. Bleomycin (BLM)-induced pulmonary inflammation in albino mice was adopted to assess PRO anti-inflammatory efficacy in vivo. In silico molecular modelling of its major components was performed on human glucocorticoids receptor (GR). Seventy-five components were identified in which longifolene (33.13%) and palmitic acid (9.34%) constituted the predominant components. No binding was observed on cannabinoid receptor type 1 (CB1), whereas mild binding was observed on cannabinoid receptor type 2 (CB2), delta, kappa, and mu receptors accounting for 2.9%, 6.9%, 10.9% and 22% binding. A significant in vivo activity was evidenced by reduction of the elevated malondialdehyde (MDA), nitric oxide (NO), myeloperoxidase (MPO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels by 55.56%, 55.66%, 64.64%, 58.85% and 77.78% with concomitant elevation of superoxide dismutase (SOD) and catalase (CAT) activities comparable to BLM-treated group at 100 mg/kg body weight. In silico studies showed that palmitic acid exerted the fittest binding. PRO could serve as a potent anti-inflammatory natural candidate that should be supported by further clinical trials. Full article
(This article belongs to the Special Issue Anti-inflammatory Agents)
Figures

Open AccessArticle One-Pot Green Regioselesctive Synthesis of γ-Lactones from Epoxides and Ketene Silyl Acetals Using 1,3-Dimethylimidazolium Fluoride as a Recoverable Metal-Free Catalyst
Molecules 2017, 22(9), 1385; doi:10.3390/molecules22091385
Received: 28 July 2017 / Revised: 18 August 2017 / Accepted: 19 August 2017 / Published: 28 August 2017
PDF Full-text (1487 KB) | HTML Full-text | XML Full-text
Abstract
In a straightforward and fast protocol, a mixture of 1,3-dimethylimidazolium fluoride ([DMIM]F) and 1-butylimidazolium tetrafluoroborate ([Hbim]BF4) efficiently catalyzed the reaction of epoxides with ketene silyl acetals (KSA) to give various γ-lactones under metal-free conditions. Diverse kinds of the desired γ-lactones were
[...] Read more.
In a straightforward and fast protocol, a mixture of 1,3-dimethylimidazolium fluoride ([DMIM]F) and 1-butylimidazolium tetrafluoroborate ([Hbim]BF4) efficiently catalyzed the reaction of epoxides with ketene silyl acetals (KSA) to give various γ-lactones under metal-free conditions. Diverse kinds of the desired γ-lactones were directly prepared with high regioselectivities and yields in a simple one-pot procedure using [DMIM]F as Si–O bond activator and [Hbim]BF4 as solvent and acidic ionic liquid catalyst. The ionic liquid mixture was recovered and reused three times and no loss in its activity was observed. Full article
Figures

Figure 1

Open AccessFeature PaperArticle Determination of Coenzyme A and Acetyl-Coenzyme A in Biological Samples Using HPLC with UV Detection
Molecules 2017, 22(9), 1388; doi:10.3390/molecules22091388
Received: 19 July 2017 / Accepted: 12 August 2017 / Published: 23 August 2017
PDF Full-text (1327 KB) | HTML Full-text | XML Full-text
Abstract
Coenzyme A (CoA) and acetyl-coenzyme A (acetyl-CoA) play essential roles in cell energy metabolism. Dysregulation of the biosynthesis and functioning of both compounds may contribute to various pathological conditions. We describe here a simple and sensitive HPLC-UV based method for simultaneous determination of
[...] Read more.
Coenzyme A (CoA) and acetyl-coenzyme A (acetyl-CoA) play essential roles in cell energy metabolism. Dysregulation of the biosynthesis and functioning of both compounds may contribute to various pathological conditions. We describe here a simple and sensitive HPLC-UV based method for simultaneous determination of CoA and acetyl-CoA in a variety of biological samples, including cells in culture, mouse cortex, and rat plasma, liver, kidney, and brain tissues. The limits of detection for CoA and acetyl-CoA are >10-fold lower than those obtained by previously described HPLC procedures, with coefficients of variation <1% for standard solutions, and 1–3% for deproteinized biological samples. Recovery is 95–97% for liver extracts spiked with Co-A and acetyl-CoA. Many factors may influence the tissue concentrations of CoA and acetyl-CoA (e.g., age, fed, or fasted state). Nevertheless, the values obtained by the present HPLC method for the concentration of CoA and acetyl-CoA in selected rodent tissues are in reasonable agreement with literature values. The concentrations of CoA and acetyl-CoA were found to be very low in rat plasma, but easily measurable by the present HPLC method. The method should be useful for studying cellular energy metabolism under normal and pathological conditions, and during targeted drug therapy treatment. Full article
(This article belongs to the Section Metabolites)
Figures

Open AccessArticle Spasmolytic Mechanism of Aqueous Licorice Extract on Oxytocin-Induced Uterine Contraction through Inhibiting the Phosphorylation of Heat Shock Protein 27
Molecules 2017, 22(9), 1392; doi:10.3390/molecules22091392
Received: 29 July 2017 / Accepted: 21 August 2017 / Published: 29 August 2017
PDF Full-text (8033 KB) | HTML Full-text | XML Full-text
Abstract
Licorice derived from the roots and rhizomes of Glycyrrhiza uralensis Fisch. (Fabaceae), is one of the most widely-used traditional herbal medicines in China. It has been reported to possess significant analgesic activity for treating spastic pain. The aim of this study is
[...] Read more.
Licorice derived from the roots and rhizomes of Glycyrrhiza uralensis Fisch. (Fabaceae), is one of the most widely-used traditional herbal medicines in China. It has been reported to possess significant analgesic activity for treating spastic pain. The aim of this study is to investigate the spasmolytic molecular mechanism of licorice on oxytocin-induced uterine contractions and predict the relevant bioactive constituents in the aqueous extract. The aqueous extraction from licorice inhibited the amplitude and frequency of uterine contraction in a concentration-dependent manner. A morphological examination showed that myometrial smooth muscle cells of oxytocin-stimulated group were oval-shaped and arranged irregularly, while those with a single centrally located nucleus of control and licorice-treated groups were fusiform and arranged orderly. The percentage of phosphorylation of HSP27 at Ser-15 residue increased up to 50.33% at 60 min after oxytocin stimulation. Furthermore, this increase was significantly suppressed by licorice treatment at the concentration of 0.2 and 0.4 mg/mL. Colocalization between HSP27 and α-SMA was observed in the myometrial tissues, especially along the actin bundles in the oxytocin-stimulated group. On the contrary, the colocalization was no longer shown after treatment with licorice. Additionally, employing ChemGPS-NP provided support for a preliminary assignment of liquiritigenin and isoliquiritigenin as protein kinase C (PKC) inhibitors in addition to liquiritigenin, isoliquiritigenin, liquiritin and isoliquiritin as MAPK-activated protein kinase 2 (MK2) inhibitors. These assigned compounds were docked with corresponding crystal structures of respective proteins with negative and low binding energy, which indicated a high affinity and tight binding capacity for the active site of the kinases. These results suggest that licorice exerts its spasmolytic effect through inhibiting the phosphorylation of HSP27 to alter the interaction between HSP27 and actin. Furthermore, our results provide support for the prediction that potential bioactive constituents from aqueous licorice extract inhibit the relevant up-stream kinases that phosphorylate HSP27. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle High Boron-loaded DNA-Oligomers as Potential Boron Neutron Capture Therapy and Antisense Oligonucleotide Dual-Action Anticancer Agents
Molecules 2017, 22(9), 1393; doi:10.3390/molecules22091393
Received: 18 July 2017 / Accepted: 14 August 2017 / Published: 23 August 2017
PDF Full-text (4665 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Boron cluster-modified therapeutic nucleic acids with improved properties are of interest in gene therapy and in cancer boron neutron capture therapy (BNCT). High metallacarborane-loaded antisense oligonucleotides (ASOs) targeting epidermal growth factor receptor (EGFR) were synthesized through post-synthetic Cu (I)-assisted “click” conjugation of alkyne-modified
[...] Read more.
Boron cluster-modified therapeutic nucleic acids with improved properties are of interest in gene therapy and in cancer boron neutron capture therapy (BNCT). High metallacarborane-loaded antisense oligonucleotides (ASOs) targeting epidermal growth factor receptor (EGFR) were synthesized through post-synthetic Cu (I)-assisted “click” conjugation of alkyne-modified DNA-oligonucleotides with a boron cluster alkyl azide component. The obtained oligomers exhibited increased lipophilicity compared to their non-modified precursors, while their binding affinity to complementary DNA and RNA strands was slightly decreased. Multiple metallacarborane residues present in the oligonucleotide chain, each containing 18 B-H groups, enabled the use of IR spectroscopy as a convenient analytical method for these oligomers based on the diagnostic B-H signal at 2400–2650 cm−1. The silencing activity of boron cluster-modified ASOs used at higher concentrations was similar to that of unmodified oligonucleotides. The screened ASOs, when used in low concentrations (up to 50 μM), exhibited pro-oxidative properties by inducing ROS production and an increase in mitochondrial activities in HeLa cells. In contrast, when used at higher concentrations, the ASOs exhibited anti-oxidative properties by lowering ROS species levels. In the HeLa cells (tested in the MTT assay) treated (without lipofectamine) or transfected with the screened compounds, the mitochondrial activity remained equal to the control level or only slightly changed (±30%). These findings may be useful in the design of dual-action boron cluster-modified therapeutic nucleic acids with combined antisense and anti-oxidant properties. Full article
(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)
Figures

Open AccessArticle Development and Validation of HPLC-DAD and UHPLC-DAD Methods for the Simultaneous Determination of Guanylhydrazone Derivatives Employing a Factorial Design
Molecules 2017, 22(9), 1394; doi:10.3390/molecules22091394
Received: 20 July 2017 / Accepted: 18 August 2017 / Published: 30 August 2017
PDF Full-text (3175 KB) | HTML Full-text | XML Full-text
Abstract
Guanylhydrazones are molecules with great pharmacological potential in various therapeutic areas, including antitumoral activity. Factorial design is an excellent tool in the optimization of a chromatographic method, because it is possible quickly change factors such as temperature, mobile phase composition, mobile phase pH,
[...] Read more.
Guanylhydrazones are molecules with great pharmacological potential in various therapeutic areas, including antitumoral activity. Factorial design is an excellent tool in the optimization of a chromatographic method, because it is possible quickly change factors such as temperature, mobile phase composition, mobile phase pH, column length, among others to establish the optimal conditions of analysis. The aim of the present work was to develop and validate a HPLC and UHPLC methods for the simultaneous determination of guanylhydrazones with anticancer activity employing experimental design. Precise, exact, linear and robust HPLC and UHPLC methods were developed and validated for the simultaneous quantification of the guanylhydrazones LQM10, LQM14, and LQM17. The UHPLC method was more economic, with a four times less solvent consumption, and 20 times less injection volume, what allowed better column performance. Comparing the empirical approach employed in the HPLC method development to the DoE approach employed in the UHPLC method development, we can conclude that the factorial design made the method development faster, more practical and rational. This resulted in methods that can be employed in the analysis, evaluation and quality control of these new synthetic guanylhydrazones. Full article
Figures

Figure 1

Open AccessArticle Chemical and Antimicrobial Analyses of Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood, an Endemic of the Western Balkan
Molecules 2017, 22(9), 1395; doi:10.3390/molecules22091395
Received: 29 July 2017 / Revised: 13 August 2017 / Accepted: 18 August 2017 / Published: 23 August 2017
PDF Full-text (775 KB) | HTML Full-text | XML Full-text
Abstract
A comprehensive study on essential oil and different solvent extracts of Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood (Lamiaceae) from Montenegro is reported. The gas chromatography-mass spectrometry analysis of the essential oil revealed a total of 43 components with bicyclogermacrene (23.8%),
[...] Read more.
A comprehensive study on essential oil and different solvent extracts of Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood (Lamiaceae) from Montenegro is reported. The gas chromatography-mass spectrometry analysis of the essential oil revealed a total of 43 components with bicyclogermacrene (23.8%), germacrene D (8%), (E)-caryophyllene (7.9%) and spathulenol (5.5%) as the major ones. Sesquiterpenoid group was found to be the most dominant one (64.8%), with 19.9% of the oxygenated forms. In the crude methanol extract of the investigated plant, obtained by Sohhlet exraction, the total phenol content was 14.7 ± 0.4 mg of GA/g, the total flavonoids were 0.29 ± 0.03% expressed as hyperoside percentage, whereas the total tannins content was 0.22 ± 0.04% expressed as pyrogallol percentage. For the antimicrobial activity determination, the following microorganisms have been used: methicillin-susceptible Staphylococcus aureus (MSSA (American Type Culture Collection (ATCC) 29213)) and methicillin-resistant S. aureus (MRSA (clinical strain)), Escherichia coli (ATCC 25922), carbapenem-susceptible Klebsiella pneumoniae (clinical strain), carbapenem-resistant K. pneumoniae (clinical strain) and Candida albicans (ATCC 14053). The essential oil showed high potency against MSSA and MRSA, both at high (~5 × 105 CFU/mL) and low (~5 × 103 CFU/mL) inoculum. With respect to MSSA, the minimal inhibitory concentration (MIC) value was 0.307 mg/mL, with bactericidal activity obtained at 0.615 mg/mL, while, in the case of MRSA, the MIC and minimal bactericidal concentration (MBC) values were 0.076 and 0.153 mg/mL, respectively. Regarding anti-Candida albicans activity, the MIC value was 2.46 mg/mL without reaching fungicidal activity. In addition to the observed essential oil efficacy, different solvent extracts were analyzed for their antimicrobial activity. Similarly to the essential oil, thehighest efficacy was observed against both MSSA and MRSA strains, at high and low inoculums, in the case of the 1,2-dichloroethane and methanol extracts. A potent fungicidal activity has been also found for the n-hexane and 1,2-dichloroethane extracts. It can be concluded that Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood provides a wide range of application in different fields such as phytochemistry, pharmacology, toxicology or pharmacognosy. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
Figures

Open AccessArticle Isolation, Characterization and Bioactivities of an Extracellular Polysaccharide Produced from Streptomyces sp. MOE6
Molecules 2017, 22(9), 1396; doi:10.3390/molecules22091396
Received: 8 July 2017 / Revised: 18 August 2017 / Accepted: 20 August 2017 / Published: 24 August 2017
PDF Full-text (3164 KB) | HTML Full-text | XML Full-text
Abstract
A Streptomyces strain was isolated from soil and the sequence of 1471 nucleotides of its 16S rDNA showed 99% identity to Streptomyces sp. HV10. This newly isolated Streptomyces strain produced an extracellular polysaccharide (EPS) composed mainly of glucose and mannose in a ratio
[...] Read more.
A Streptomyces strain was isolated from soil and the sequence of 1471 nucleotides of its 16S rDNA showed 99% identity to Streptomyces sp. HV10. This newly isolated Streptomyces strain produced an extracellular polysaccharide (EPS) composed mainly of glucose and mannose in a ratio of 1:4.1, as was characterized by Fourier transform infrared spectroscopy (FTIR), HPLC and 1H-NMR. The antioxidant activities of the partially purified MOE6-EPS were determined by measuring the hydroxyl free radical scavenging activity and the scavenging of 2,2-diphenyl-2-picryl-hydrazyl (DPPH) radicals. In addition, the partially purified MOE6-EPS showed high ferrous ion (Fe2+) chelation activity which is another antioxidant activity. Interestingly, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays that were colorimetric assays for NAD(P)H-dependent cellular oxidoreductases and a proxy of the number of viable cells, showed that the partially purified MOE6-EPS inhibited the proliferation of the human breast cancer cells (MDA-MB-231). The scratch wound assay showed that MOE6-EPS reduced the migration of mouse breast cancer cells (4T1). This study reports the production of EPS from Streptomyces species with promising antioxidant, metal chelating and mammalian cell inhibitory activities. Full article
(This article belongs to the Special Issue Advances in Natural Polysaccharides Research)
Figures

Figure 1

Open AccessArticle Acceptor Side-Chain Effects on the Excited State Dynamics of Two-Dimensional-Like Conjugated Copolymers in Solution
Molecules 2017, 22(9), 1398; doi:10.3390/molecules22091398
Received: 14 June 2017 / Accepted: 18 August 2017 / Published: 25 August 2017
PDF Full-text (3028 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Excited state dynamics of two-dimensional-like conjugated copolymers PFDCN and PFSDCN based on alternating fluorene and triphenylamine main chains and malononitrile pendant acceptor groups with thiophene as π-bridge, have been investigated by using transient absorption spectroscopy. There is an additional conjugated –C=C– bond in
[...] Read more.
Excited state dynamics of two-dimensional-like conjugated copolymers PFDCN and PFSDCN based on alternating fluorene and triphenylamine main chains and malononitrile pendant acceptor groups with thiophene as π-bridge, have been investigated by using transient absorption spectroscopy. There is an additional conjugated –C=C– bond in PFDCN, which distinguishes it from PFSDCN. The lowest energy absorption band of each copolymer absorption spectrum is attributed to the π−π* transition with intramolecular charge-transfer, which has a lower fluorescence contribution than those of higher energy absorption bands. The optical excitation of either PFDCN or PFSDCN solution generates polaron pairs that then self-localize and evolve to a bound singlet exciton within a few picoseconds. Due to the additional conjugated –C=C– bond in the acceptor side-chain, PFDCN has a stronger intramolecular charge-transfer characteristic compared with PFSDCN, therefore exhibiting a longer self-localization time (7 ps vs. 3 ps for PFSDCN) and a shorter fluorescence lifetime (1.48 ns vs. 1.60 ns for PFSDCN). Full article
(This article belongs to the Special Issue Photoresponsive Polymers)
Figures

Figure 1

Open AccessArticle Covalent Porphyrin Hybrids Linked with Dipyrrin, Bidipyrrin or Thiacorrole
Molecules 2017, 22(9), 1400; doi:10.3390/molecules22091400
Received: 3 August 2017 / Revised: 19 August 2017 / Accepted: 20 August 2017 / Published: 23 August 2017
PDF Full-text (2137 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Novel meso-meso directly linked porphyrin hybrids were successfully targeted and synthesized, with porphyrin units linked with dipyrrin, bidipyrrin or thiacorrole, expanding the ranges of dipyrrin derivatives and showing diverse metal coordinations and further influencing the chemical shift of pyrrole units. The porphyrinyl dipyrrin
[...] Read more.
Novel meso-meso directly linked porphyrin hybrids were successfully targeted and synthesized, with porphyrin units linked with dipyrrin, bidipyrrin or thiacorrole, expanding the ranges of dipyrrin derivatives and showing diverse metal coordinations and further influencing the chemical shift of pyrrole units. The porphyrinyl dipyrrin nickel complex 3 was successfully obtained in a high yield by the oxidation of porphyrinyl dipyrromethane 2 and subsequent coordination. Further oxidative coupling reactions of 3 afforded por-bidipyrrin-por hybrid 4. Interestingly, an unexpected methoxy por-bidipyrrin-por hybrid 6 was generated by treating 4 with FeCl3 in CH2Cl2/MeOH and subsequent coordination. In addition to open chain hybrids, an aromatic scaffold hybrid por-thiacorrole-por 8 was synthesized by treating porphyrinyl dibromo-dipyrrin nickel complex 7 with Na2S·9H2O. A series of porphyrin hybrids offers a new approach for π-conjugated molecules. Full article
(This article belongs to the collection Heterocyclic Compounds)
Figures

Open AccessArticle Determination and Visualization of Peimine and Peiminine Content in Fritillaria thunbergii Bulbi Treated by Sulfur Fumigation Using Hyperspectral Imaging with Chemometrics
Molecules 2017, 22(9), 1402; doi:10.3390/molecules22091402
Received: 24 July 2017 / Revised: 21 August 2017 / Accepted: 21 August 2017 / Published: 23 August 2017
PDF Full-text (1195 KB) | HTML Full-text | XML Full-text
Abstract
Rapid, non-destructive, and accurate quantitative determination of the effective components in traditional Chinese medicine (TCM) is required by industries, planters, and regulators. In this study, near-infrared hyperspectral imaging was applied for determining the peimine and peiminine content in Fritillaria thunbergii bulbi under sulfur
[...] Read more.
Rapid, non-destructive, and accurate quantitative determination of the effective components in traditional Chinese medicine (TCM) is required by industries, planters, and regulators. In this study, near-infrared hyperspectral imaging was applied for determining the peimine and peiminine content in Fritillaria thunbergii bulbi under sulfur fumigation. Spectral data were extracted from the hyperspectral images. High-performance liquid chromatography (HPLC) was conducted to determine the reference peimine and peiminine content. The successive projection algorithm (SPA), weighted regression coefficient (Bw), competitive adaptive reweighted sampling (CARS), and random frog (RF) were used to select optimal wavelengths, while the partial least squares (PLS), least-square support vector machine (LS–SVM) and extreme learning machine (ELM) were used to build regression models. Regression models using the full spectra and optimal wavelengths obtained satisfactory results with the correlation coefficient of calibration (rc), cross-validation (rcv) and prediction (rp) of most models being over 0.8. Prediction maps of peimine and peiminine content in Fritillaria thunbergii bulbi were formed by applying regression models to the hyperspectral images. The overall results indicated that hyperspectral imaging combined with regression models and optimal wavelength selection methods were effective in determining peimine and peiminine content in Fritillaria thunbergii bulbi, which will help in the development of an online detection system for real-world quality control of Fritillaria thunbergii bulbi under sulfur fumigation. Full article
Figures

Figure 1

Open AccessArticle Preclinical Assessment of a 68Ga-DOTA-Functionalized Depsipeptide as a Radiodiagnostic Infection Imaging Agent
Molecules 2017, 22(9), 1403; doi:10.3390/molecules22091403
Received: 30 May 2017 / Accepted: 18 August 2017 / Published: 24 August 2017
PDF Full-text (1926 KB) | HTML Full-text | XML Full-text
Abstract
The study assessed a radiolabeled depsipeptide conjugate (68Ga-DOTA-TBIA101) for its potential as an imaging agent targeting infection or infection-associated inflammation. 68Ga-labeled DOTA-TBIA101 imaging was performed in (NZR1) healthy rabbits; (NZR2) rabbits bearing muscular sterile inflammation and Staphylococcus aureus (SA) infection;
[...] Read more.
The study assessed a radiolabeled depsipeptide conjugate (68Ga-DOTA-TBIA101) for its potential as an imaging agent targeting infection or infection-associated inflammation. 68Ga-labeled DOTA-TBIA101 imaging was performed in (NZR1) healthy rabbits; (NZR2) rabbits bearing muscular sterile inflammation and Staphylococcus aureus (SA) infection; and (NZR3) rabbits infected with Mycobacterium tuberculosis (MTB) combined with a subcutaneous scruff infection of SA in the same animal. All animals were imaged using a PET/CT scanner at 5 and 60 min post injection. Images showed elevated accumulation of 68Ga-DOTA-TBIA101 in the sterile muscular inflammation site (T/NT ratio = 2.6 ± 0.37 (5 min) and 2.8 ± 2.3 (60 min)) and muscles infected with MTB (T/NT ratio = 2.6 ± 0.35 (5 min) and 2.8 ± 0.16 (60 min)). The findings suggest that 68Ga-DOTA-TBIA101-PET/CT may detect MTB-associated inflammation, although more foundational studies need to be performed to rationalize the diagnostic value of this technique. Full article
(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)
Figures

Figure 1

Open AccessArticle The Influence of Lead on Generation of Signalling Molecules and Accumulation of Flavonoids in Pea Seedlings in Response to Pea Aphid Infestation
Molecules 2017, 22(9), 1404; doi:10.3390/molecules22091404
Received: 30 June 2017 / Revised: 14 August 2017 / Accepted: 21 August 2017 / Published: 24 August 2017
PDF Full-text (19384 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The aim of this study was to investigate the effect of an abiotic factor, i.e., lead at various concentrations (low causing a hormesis effect and causing high toxicity effects), on the generation of signalling molecules in pea (Pisum sativum L. cv. Cysterski)
[...] Read more.
The aim of this study was to investigate the effect of an abiotic factor, i.e., lead at various concentrations (low causing a hormesis effect and causing high toxicity effects), on the generation of signalling molecules in pea (Pisum sativum L. cv. Cysterski) seedlings and then during infestation by the pea aphid (Acyrthosiphon pisum Harris). The second objective was to verify whether the presence of lead in pea seedling organs and induction of signalling pathways dependent on the concentration of this metal trigger defense responses to A. pisum. Therefore, the profile of flavonoids and expression levels of genes encoding enzymes of the flavonoid biosynthesis pathway (phenylalanine ammonialyase and chalcone synthase) were determined. A significant accumulation of total salicylic acid (TSA) and abscisic acid (ABA) was recorded in the roots and leaves of pea seedlings growing on lead-supplemented medium and next during infestation by aphids. Increased generation of these phytohormones strongly enhanced the biosynthesis of flavonoids, including a phytoalexin, pisatin. This research provides insights into the cross-talk between the abiotic (lead) and biotic factor (aphid infestation) on the level of the generation of signalling molecules and their role in the induction of flavonoid biosynthesis. Full article
Figures

Open AccessArticle Homoisoflavonoids and Chalcones Isolated from Haematoxylum campechianum L., with Spasmolytic Activity
Molecules 2017, 22(9), 1405; doi:10.3390/molecules22091405
Received: 13 July 2017 / Revised: 18 August 2017 / Accepted: 18 August 2017 / Published: 24 August 2017
PDF Full-text (1449 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Haematoxylum campechianum is a medicinal plant employed as an astringent to purify the blood and to treat stomach problems such as diarrhea and dysentery. A bio-guided chemical fractionation of the methanolic extract obtained from this plant allowed for the isolation of five compounds:
[...] Read more.
Haematoxylum campechianum is a medicinal plant employed as an astringent to purify the blood and to treat stomach problems such as diarrhea and dysentery. A bio-guided chemical fractionation of the methanolic extract obtained from this plant allowed for the isolation of five compounds: two chalcones known as sappanchalcone (1); 3-deoxysappanchalcone (2); three homoisoflavonoids known as hematoxylol A (3); 4-O-methylhematoxylol (4); and, hematoxin (5). The spasmolytic activity was determined in an in vitro model (electrically induced contractions of guinea pig ileum), and allowed to demonstrate that the methanolic extract (EC50 = 62.11 ± 3.23) fractions HcF7 (EC50 = 61.75 ± 3.55) and HcF9 (EC50 = 125.5 ± 10.65) and compounds 1 (EC50 = 16.06 ± 2.15) and 2 (EC50 = 25.37 ± 3.47) of Haematoxylum campechianum present significant relaxing activity as compared to papaverine (EC50 = 20.08 ± 2.0) as a positive control. Full article
(This article belongs to the collection Bioactive Compounds)
Figures

Figure 1

Open AccessArticle Biosynthesis of Silver Nanoparticles on Orthodontic Elastomeric Modules: Evaluation of Mechanical and Antibacterial Properties
Molecules 2017, 22(9), 1407; doi:10.3390/molecules22091407
Received: 23 June 2017 / Revised: 11 August 2017 / Accepted: 21 August 2017 / Published: 25 August 2017
PDF Full-text (4494 KB) | HTML Full-text | XML Full-text
Abstract
In the present study, silver nanoparticles (AgNPs) were synthesized in situ on orthodontic elastomeric modules (OEM) using silver nitrate salts as metal-ion precursors and extract of the plant Hetheroteca inuloides (H. inuloides) as bioreductant via a simple and eco-friendly method. The
[...] Read more.
In the present study, silver nanoparticles (AgNPs) were synthesized in situ on orthodontic elastomeric modules (OEM) using silver nitrate salts as metal-ion precursors and extract of the plant Hetheroteca inuloides (H. inuloides) as bioreductant via a simple and eco-friendly method. The synthesized AgNPs were characterized by UV-visible spectroscopy; scanning electron microscopy-energy-dispersive spectroscopy (SEM-EDS) and transmission electron microscopy (TEM). The surface plasmon resonance peak found at 472 nm confirmed the formation of AgNPs. SEM and TEM images reveal that the particles are quasi-spherical. The EDS analysis of the AgNPs confirmed the presence of elemental silver. The antibacterial properties of OEM with AgNPs were evaluated against the clinical isolates Streptococcus mutans, Lactobacillus casei, Staphylococcus aureus and Escherichia coli using agar diffusion tests. The physical properties were evaluated by a universal testing machine. OEM with AgNPs had shown inhibition halos for all microorganisms in comparison with OEM control. Physical properties increased with respect to the control group. The results suggest the potential of the material to combat dental biofilm and in turn decrease the incidence of demineralization in dental enamel, ensuring their performance in patients with orthodontic treatment. Full article
(This article belongs to the Special Issue Antibacterial Materials and Coatings)
Figures

Figure 1

Open AccessArticle Purification, Preliminary Characterization and Hepatoprotective Effects of Polysaccharides from Dandelion Root
Molecules 2017, 22(9), 1409; doi:10.3390/molecules22091409
Received: 30 July 2017 / Accepted: 22 August 2017 / Published: 25 August 2017
PDF Full-text (5530 KB) | HTML Full-text | XML Full-text
Abstract
In this study, purification, preliminary characterization and hepatoprotective effects of water-soluble polysaccharides from dandelion root (DRP) were investigated. Two polysaccharides, DRP1 and DRP2, were isolated from DRP. The two polysaccharides were α-type polysaccharides and didn’t contain protein. DRP1, with a molecular weight of
[...] Read more.
In this study, purification, preliminary characterization and hepatoprotective effects of water-soluble polysaccharides from dandelion root (DRP) were investigated. Two polysaccharides, DRP1 and DRP2, were isolated from DRP. The two polysaccharides were α-type polysaccharides and didn’t contain protein. DRP1, with a molecular weight of 5695 Da, was composed of glucose, galactose and arabinose, whereas DRP2, with molecular weight of 8882 Da, was composed of rhamnose, galacturonic acid, glucose, galactose and arabinose. The backbone of DRP1 was mainly composed of (1→6)-linked-α-d-Glc and (1→3,4)-linked-α-d-Glc. DRP2 was mainly composed of (1→)-linked-α-d-Ara and (1→)-linked-α-d-Glc. A proof-of-concept study was performed to assess the therapeutic potential of DRP1 and DRP2 in a mouse model that mimics acetaminophen (APAP) -induced liver injury (AILI) in humans. The present study shows DRP1 and DRP2 could protect the liver from APAP-induced hepatic injury by activating the Nrf2-Keap1 pathway. These conclusions demonstrate that the DRP1 and DRP2 might be suitable as functional foods and natural drugs in preventing APAP-induced liver injury. Full article
(This article belongs to the Special Issue Advances in Natural Polysaccharides Research)
Figures

Open AccessArticle Enantiomeric-Enriched Ferrocenes: Synthesis, Chiral Resolution, and Mathematic Evaluation of CD-chiral Selector Energies with Ferrocene-Conjugates
Molecules 2017, 22(9), 1410; doi:10.3390/molecules22091410
Received: 14 July 2017 / Revised: 23 August 2017 / Accepted: 24 August 2017 / Published: 25 August 2017
PDF Full-text (2958 KB) | HTML Full-text | XML Full-text
Abstract
Enantiomeric-enriched ferrocene-modified pyrazoles were synthesized via the reaction of the ferrocene alcohol, (S)-FcCH(OH)CH3 (Fc = ferrocenyl), with various pyrazoles in acidic conditions at room temperature within several minutes. X-ray structural data for racemic (R,S)-1N-(3,5-dimethyl
[...] Read more.
Enantiomeric-enriched ferrocene-modified pyrazoles were synthesized via the reaction of the ferrocene alcohol, (S)-FcCH(OH)CH3 (Fc = ferrocenyl), with various pyrazoles in acidic conditions at room temperature within several minutes. X-ray structural data for racemic (R,S)-1N-(3,5-dimethyl pyrazolyl)ethyl ferrocene (1) and its (S)-enantiomer (S)-1 were determined. A series of racemic pyrazolylalkyl ferrocenes was separated into enantiomers by analytical HPLC on β- and γ-cyclodextrins (CD) chiral stationary phases. The quantum chemical calculations of interaction energies of β-CD were carried out for both (R)- and (S)-enantiomers. A high correlation between experimental HPLC data and calculated interaction energies values was obtained. Full article
(This article belongs to the Special Issue Chirality in Health and Environment: Recent developments)
Figures

Figure 1

Open AccessArticle Structure Identification and In Vitro Anticancer Activity of Lathyrol-3-phenylacetate-5,15-diacetate
Molecules 2017, 22(9), 1412; doi:10.3390/molecules22091412
Received: 7 August 2017 / Accepted: 22 August 2017 / Published: 25 August 2017
PDF Full-text (4630 KB) | HTML Full-text | XML Full-text
Abstract
Natural products from the genus Euphorbia show attention-attracting activities, such as anticancer activity. In this article, classical isolation and structure identification were used in a study on Caper Euphorbia Seed. Subsequently, MTT and wound healing assays, flow cytometry, western blotting, Hoechst 33258 staining
[...] Read more.
Natural products from the genus Euphorbia show attention-attracting activities, such as anticancer activity. In this article, classical isolation and structure identification were used in a study on Caper Euphorbia Seed. Subsequently, MTT and wound healing assays, flow cytometry, western blotting, Hoechst 33258 staining and fluorescence microscopy examination were applied to investigate the anticancer activity of the obtained compounds. In a result, lathyrol-3-phenyl- acetate-5,15-diacetate (deoxy Euphorbia factor L1, DEFL1) was isolated from Caper Euphorbia Seed. Moreover, the NMR signals were totally assigned. DEFL1 showed potent inhibition against lung cancer A549 cells, with an IC50 value of 17.51 ± 0.85 μM. Furthermore, DEFL1 suppressed wound healing of A549 cells in a concentration-dependent manner. Mechanically, DEFL1 induced apoptosis, with involvement of an increase of reactive oxygen species (ROS), decrease of mitochondrial membrane potential (ΔΨm), release of cytochrome c, activity raise of caspase-9 and 3. Characteristic features of apoptosis were observed by fluorescence microscopy. In summary, DEFL1 inhibited growth and induced apoptosis in lung cancer A549 cells via a mitochondrial pathway. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
Figures

Open AccessArticle Interactions Controlling the Slow Dynamic Conformational Motions of Ubiquitin
Molecules 2017, 22(9), 1414; doi:10.3390/molecules22091414
Received: 11 August 2017 / Revised: 20 August 2017 / Accepted: 20 August 2017 / Published: 28 August 2017
PDF Full-text (5778 KB) | HTML Full-text | XML Full-text
Abstract
Rational mutation of proteins based on their structural and dynamic characteristics is a useful strategy for amplifying specific fluctuations in proteins. Here, we show the effects of mutation on the conformational fluctuations and thermodynamic stability of ubiquitin. In particular, we focus on the
[...] Read more.
Rational mutation of proteins based on their structural and dynamic characteristics is a useful strategy for amplifying specific fluctuations in proteins. Here, we show the effects of mutation on the conformational fluctuations and thermodynamic stability of ubiquitin. In particular, we focus on the salt bridge between K11 and E34 and the hydrogen bond between I36 and Q41, which are predicted to control the fluctuation between the basic folded state, N1, and the alternatively folded state, N2, of the protein, using high-pressure NMR spectroscopy. The E34A mutation, which disrupts the salt bridge, did not alter picosecond–to–nanosecond, microsecond–to–millisecond dynamic motions, and stability of the protein, while the Q41N mutation, which destabilizes the hydrogen bond, specifically amplified the N1–N2 conformational fluctuation and decreased stability. Based on the observed thermodynamic stabilities of the various conformational states, we showed that in the Q41N mutant, the N1 state is more significantly destabilized than the N2 state, resulting in an increase in the relative population of N2. Identifying the interactions controlling specific motions of a protein will facilitate molecular design to achieve functional dynamics beyond native state dynamics. Full article
(This article belongs to the Special Issue Recent Advances in Biomolecular NMR Spectroscopy)
Figures

Open AccessArticle Bis(1-pyrenylmethyl)-2-benzyl-2-methyl-malonate as a Cu2+ Ion-Selective Fluoroionophore
Molecules 2017, 22(9), 1415; doi:10.3390/molecules22091415
Received: 3 August 2017 / Revised: 22 August 2017 / Accepted: 23 August 2017 / Published: 25 August 2017
PDF Full-text (2528 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new malonate possessing two pyrene moieties was synthesized as a fluoroionophore, and its structure and fluorescence spectroscopic properties were investigated. When excited at 344 nm in acetonitrile/chloroform (9:1, v/v), the synthesized bispyrenyl malonate has the fluorescence of intramolecular excimer
[...] Read more.
A new malonate possessing two pyrene moieties was synthesized as a fluoroionophore, and its structure and fluorescence spectroscopic properties were investigated. When excited at 344 nm in acetonitrile/chloroform (9:1, v/v), the synthesized bispyrenyl malonate has the fluorescence of intramolecular excimer (λem = 467 nm) emissions and not a pyrene monomer emission (λem = 394 nm). A large absolute fluorescence quantum yield was obtained in the solid state (ΦPL = 0.65) rather than in solution (ΦPL = 0.13). X-ray crystallography analysis clarified the molecular structure and alignment of the bispyrenyl malonate in the crystal phase, elucidating its fluorescence spectroscopic properties. Such analysis also suggests there are intramolecular C–H···π interactions and intermolecular π···π interactions between the pyrenyl rings. Interestingly, the synthesized bispyrenyl malonate exhibits excellent fluorescence sensing for the Cu2+ ion. Remarkable fluorescence intensity enhancement was only observed with the addition of the Cu2+ ion. Full article
Figures

Open AccessArticle Identification of Optically Active Pyrimidine Derivatives as Selective 5-HT2C Modulators
Molecules 2017, 22(9), 1416; doi:10.3390/molecules22091416
Received: 31 July 2017 / Revised: 22 August 2017 / Accepted: 23 August 2017 / Published: 26 August 2017
PDF Full-text (993 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of pyrimidine derivatives 4ai were synthesized and evaluated for their binding affinities towards 5-HT2C receptors. With regard to designed molecules 4ai, the influence of the size of alkyl ether and the absolute configuration of a
[...] Read more.
A series of pyrimidine derivatives 4ai were synthesized and evaluated for their binding affinities towards 5-HT2C receptors. With regard to designed molecules 4ai, the influence of the size of alkyl ether and the absolute configuration of a stereogenic center on the 5-HT2C binding affinity and selectivity was studied. The most promising diasteromeric mixtures 4d and 4e were selected in the initial radioligand binding assay and they were further synthesized as optically active forms starting from optically active alcohols 5d and 5e, prepared by an enzymatic kinetic resolution. Pyrimidine analogue (R,R)-4e displayed an excellent 5-HT2C binding affinity with good selectivity values against a broad range of other 5-HT receptor subtypes. Full article
(This article belongs to the Special Issue Nucleoside and Nucleotide Analogues)
Figures

Figure 1

Open AccessArticle Pyrene-Phosphonate Conjugate: Aggregation-Induced Enhanced Emission, and Selective Fe3+ Ions Sensing Properties
Molecules 2017, 22(9), 1417; doi:10.3390/molecules22091417
Received: 19 July 2017 / Revised: 17 August 2017 / Accepted: 21 August 2017 / Published: 29 August 2017
PDF Full-text (3540 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new pyrene-phosphonate colorimetric receptor 1 has been designed and synthesized in a one-step process via amide bond formation between pyrene butyric acid chloride and phosphonate-appended aniline. The pyrene-phosphonate receptor 1 showed aggregation-induced enhanced emission (AIEE) properties in water/acetonitrile (ACN) solutions. Dynamic light
[...] Read more.
A new pyrene-phosphonate colorimetric receptor 1 has been designed and synthesized in a one-step process via amide bond formation between pyrene butyric acid chloride and phosphonate-appended aniline. The pyrene-phosphonate receptor 1 showed aggregation-induced enhanced emission (AIEE) properties in water/acetonitrile (ACN) solutions. Dynamic light scattering (DLS) characterization revealed that the aggregates of receptor 1 at 80% water fraction have an average size of ≈142 nm. Field emission scanning electron microscopy (FE-SEM) analysis confirmed the formation of spherical aggregates upon solvent evaporation. The sensing properties of receptor 1 were investigated by UV-vis, fluorescence emission spectroscopy, and other optical methods. Among the tested metal ions, receptor 1 is capable of recognizing the Fe3+ ion selectively. The changes in spectral measurements were explained on the basis of complex formation. The composition of receptor 1 and Fe3+ ions was determined by using Job’s plot and found to be 1:1. The receptor 1–Fe3+ complex showed a reversible UV-vis response in the presence of EDTA. Full article
(This article belongs to the collection Heterocyclic Compounds)
Figures

Open AccessArticle Acetylation of Microcrystalline Cellulose by Transesterification in AmimCl/DMSO Cosolvent System
Molecules 2017, 22(9), 1419; doi:10.3390/molecules22091419
Received: 3 July 2017 / Revised: 21 August 2017 / Accepted: 24 August 2017 / Published: 27 August 2017
PDF Full-text (1765 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Recently, IL/cosolvent systems have generated a lot of interest as cellulose-dissolving solvents and reaction media for various kinds of cellulose modification. In the present study, both 1-allyl-3-methylimidazolium chloride (AmimCl)/dimethyl sulfoxide (DMSO) and AmimCl/N,N-dimethylformamide (DMF) systems were employed to synthesize
[...] Read more.
Recently, IL/cosolvent systems have generated a lot of interest as cellulose-dissolving solvents and reaction media for various kinds of cellulose modification. In the present study, both 1-allyl-3-methylimidazolium chloride (AmimCl)/dimethyl sulfoxide (DMSO) and AmimCl/N,N-dimethylformamide (DMF) systems were employed to synthesize cellulose acetate by transesterification. Microcrystalline cellulose, 1,8-diazabicyclo[5.4.0]undec-7-ene and isopropenyl acetate were chosen as the raw material, catalyst and acetylation reagent, respectively. The results revealed that DMSO was a suitable cosolvent for the transesterification in the homogeneous solution. Moreover, DMSO had a positive effect on the reaction as the cosolvent under the given conditions and the degree of the substitution of cellulose acetate could be significantly enhanced through increasing the molar ratio of DMSO. The synthesized products were characterized by Fourier transform infrared (FT-IR) spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopy (1H-NMR and 13C-NMR), correlation spectroscopy (COSY), heteronuclear single quantum correlation (HSQC) spectroscopy, and X-ray diffraction (XRD) to confirm the chemical and physical structure of the cellulose acetate generated. The thermal properties were also evaluated using thermogravimetric analysis (TGA)/derivative thermogravimetry (DTG). Full article
(This article belongs to the Special Issue Cellulose Chemical Modifications—Towards Sustainable Materials)
Figures

Figure 1

Open AccessArticle Sensitive and Selective Detection of Oxo-Form Organophosphorus Pesticides Based on CdSe/ZnS Quantum Dots
Molecules 2017, 22(9), 1421; doi:10.3390/molecules22091421
Received: 9 August 2017 / Revised: 25 August 2017 / Accepted: 25 August 2017 / Published: 28 August 2017
PDF Full-text (2026 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A rapid, sensitive and enzyme-based optical biosensor was applied for the determination of seven organophosphorus pesticides (OPPs), including the oxo forms (malaoxon, paraoxon, dibrom, and dichlorvos), the thio forms (malathion and parathion) and the mixed form (demeton) in Panax ginseng. The principal
[...] Read more.
A rapid, sensitive and enzyme-based optical biosensor was applied for the determination of seven organophosphorus pesticides (OPPs), including the oxo forms (malaoxon, paraoxon, dibrom, and dichlorvos), the thio forms (malathion and parathion) and the mixed form (demeton) in Panax ginseng. The principal of the proposed method is that the fluorescence quenching effect of quantum dots (QDs) can be observed by enzyme-generated H2O2. The active centers of acetylcholinesterase (AChE) could be inhibited in the presence of pesticides, which caused decrease of the generated H2O2. Then, the inhibition efficiency of pesticide to AChE activity could be evaluated by measuring the fluorescence changes. Different from biosensors based on immobilized enzyme or self-assembling technique, the proposed biosensor demonstrated a good selectivity for the detection of oxo forms of OPPs. In the present study, the important experimental conditions of the proposed biosensor were investigated. Under the optimized conditions (incubation temperature, 35 °C; incubation time, 20 min; pH value, 8.0; detection time, 30 min; AChE concentration, 40.9 U/L; and choline oxidase (ChOx) concentration, 637.5 U/L), the limit of detection for the investigated oxo-form OPPs was no more than 0.05 μM, which suggested that the proposed method could be used for sensitive and selective determination of trace amounts of OPPs residues in real samples with complex matrices. Full article
Figures

Open AccessArticle Multienzyme Biosynthesis of Dihydroartemisinic Acid
Molecules 2017, 22(9), 1422; doi:10.3390/molecules22091422
Received: 13 August 2017 / Revised: 27 August 2017 / Accepted: 27 August 2017 / Published: 28 August 2017
PDF Full-text (2463 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
One-pot multienzyme biosynthesis is an attractive method for producing complex, chiral bioactive compounds. It is advantageous over step-by-step synthesis, as it simplifies the process, reduces costs and often leads to higher yield due to the synergistic effects of enzymatic reactions. In this study,
[...] Read more.
One-pot multienzyme biosynthesis is an attractive method for producing complex, chiral bioactive compounds. It is advantageous over step-by-step synthesis, as it simplifies the process, reduces costs and often leads to higher yield due to the synergistic effects of enzymatic reactions. In this study, dihydroartemisinic acid (DHAA) pathway enzymes were overexpressed in Saccharomyces cerevisiae, and whole-cell biotransformation of amorpha-4,11-diene (AD) to DHAA was demonstrated. The first oxidation step by cytochrome P450 (CYP71AV1) is the main rate-limiting step, and a series of N-terminal truncation and transcriptional tuning improved the enzymatic activity. With the co-expression of artemisinic aldehyde dehydrogenase (ALDH1), which recycles NADPH, a significant 8-fold enhancement of DHAA production was observed. Subsequently, abiotic conditions were optimized to further enhance the productivity of the whole-cell biocatalysts. Collectively, approximately 230 mg/L DHAA was produced by the multi-step whole-cell reaction, a ~50% conversion from AD. This study illustrates the feasibility of producing bioactive compounds by in vitro one-pot multienzyme reactions. Full article
(This article belongs to the Special Issue Multicomponent Reaction-Based Synthesis of Bioactive Molecules)
Figures

Figure 1a

Open AccessCommunication Enhancement of Glucose Uptake by Meso-Dihydroguaiaretic Acid through GLUT4 Up-Regulation in 3T3-L1 Adipocytes
Molecules 2017, 22(9), 1423; doi:10.3390/molecules22091423
Received: 2 August 2017 / Revised: 22 August 2017 / Accepted: 25 August 2017 / Published: 28 August 2017
PDF Full-text (2586 KB) | HTML Full-text | XML Full-text
Abstract
Type 2 diabetes is characterized by insulin resistance, which leads to increased blood glucose levels. Adipocytes are involved in the development of insulin resistance, resulting from the dysfunction of the insulin signaling pathway. In this study, we investigated whether meso-dihydroguaiaretic acid (MDGA)
[...] Read more.
Type 2 diabetes is characterized by insulin resistance, which leads to increased blood glucose levels. Adipocytes are involved in the development of insulin resistance, resulting from the dysfunction of the insulin signaling pathway. In this study, we investigated whether meso-dihydroguaiaretic acid (MDGA) may modulate glucose uptake in adipocytes, and examined its mechanism of action. MDGA enhanced adipogenesis through up-regulation of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α in 3T3-L1 adipocytes partially differentiated with sub-optimal concentrations of insulin. MDGA also increased glucose uptake by stimulating expression and translocation of glucose transporter 4 (GLUT4) in adipocytes. These results suggest that MDGA may increase GLUT4 expression and its translocation by promoting insulin sensitivity, leading to enhanced glucose uptake. Full article
(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)
Figures

Open AccessArticle The Effect of Pressure and Solvent on the Supercritical Fluid Chromatography Separation of Tocol Analogs in Palm Oil
Molecules 2017, 22(9), 1424; doi:10.3390/molecules22091424
Received: 21 June 2017 / Revised: 15 August 2017 / Accepted: 16 August 2017 / Published: 29 August 2017
PDF Full-text (3790 KB) | HTML Full-text | XML Full-text
Abstract
There are six tocol analogs present in palm oil, namely α-tocopherol (α-T), α-tocomonoenol (α-T1), α-tocotrienol (α-T3), γ-tocotrienol (γ-T3), β-tocotrioenol (β-T3) and δ-tocotrienol (δ-T3). These analogs were difficult to separate chromatographically due to their
[...] Read more.
There are six tocol analogs present in palm oil, namely α-tocopherol (α-T), α-tocomonoenol (α-T1), α-tocotrienol (α-T3), γ-tocotrienol (γ-T3), β-tocotrioenol (β-T3) and δ-tocotrienol (δ-T3). These analogs were difficult to separate chromatographically due to their similar structures, physical and chemical properties. This paper reports on the effect of pressure and injection solvent on the separation of the tocol analogs in palm oil. Supercritical CO2 modified with ethanol was used as the mobile phase. Both total elution time and resolution of the tocol analogs decreased with increased pressure. Ethanol as an injection solvent resulted in peak broadening of the analogs within the entire pressure range studied. Solvents with an eluent strength of 3.4 or less were more suitable for use as injecting solvents. Full article
(This article belongs to the Special Issue Sub- and Supercritical Fluids and Green Chemistry)
Figures

Figure 1

Open AccessArticle Identification and Analysis of Amygdalin, Neoamygdalin and Amygdalin Amide in Different Processed Bitter Almonds by HPLC-ESI-MS/MS and HPLC-DAD
Molecules 2017, 22(9), 1425; doi:10.3390/molecules22091425
Received: 27 June 2017 / Accepted: 25 August 2017 / Published: 30 August 2017
PDF Full-text (1438 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Processing is a traditional pharmacy technology based on traditional Chinese medicine theory. The traditional Chinese medicine (TCM) ingredients should be processed before being used as a medicine. Processed bitter almonds are widely used in the clinic in TCM for the treatment of cough
[...] Read more.
Processing is a traditional pharmacy technology based on traditional Chinese medicine theory. The traditional Chinese medicine (TCM) ingredients should be processed before being used as a medicine. Processed bitter almonds are widely used in the clinic in TCM for the treatment of cough and asthma. In this work the amygdalin profile of three producing areas in China was determined, with respect to three differently processed bitter almond products: raw, stir-fried and scalded. Identification of the compounds was done by using high performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC-ESI-MS/MS). Results indicated that amygdalin, neoamygdalin and amygdalin amide were identified in the different processed bitter almonds. Meanwhile, amygdalin was used as a standard to calculate the quantification of amygdalin and the concentration ratio of neoamygdalin and total amygdalin by HPLC-DAD. The data suggested that composition of amygdalin isomers in bitter almonds was influenced by the processing method. It also gives a new understanding of the processing principle of bitter almonds. Moreover, the classification of different processed bitter almonds can be achieved on the basis of amygdalin isomers levels. Full article
Figures

Figure 1

Open AccessArticle NO-Donor Iron Nitrosyl Complex with N-Ethylthiourea Ligand Exhibits Selective Toxicity to Glioma A172 Cells
Molecules 2017, 22(9), 1426; doi:10.3390/molecules22091426
Received: 10 July 2017 / Accepted: 22 August 2017 / Published: 29 August 2017
PDF Full-text (2205 KB) | HTML Full-text | XML Full-text
Abstract
We studied effects of NO-donor iron nitrosyl complex with N-ethylthiourea ligand (ETM) on normal or tumor-derived cell lines. ETM was mildly toxic to most cell lines studied except the human glioma cell line A172 that proved to be highly sensitive to the
[...] Read more.
We studied effects of NO-donor iron nitrosyl complex with N-ethylthiourea ligand (ETM) on normal or tumor-derived cell lines. ETM was mildly toxic to most cell lines studied except the human glioma cell line A172 that proved to be highly sensitive to the complex and underwent cell death after ETM exposure. The high susceptibility of A172 cells to ETM was attributed to its NO-donor properties since no toxicity was detected for the N-ethylthiourea ligand. Full article
(This article belongs to the Special Issue Metal Based Drugs: Opportunities and Challenges)
Figures

Open AccessArticle Stringent Nucleotide Recognition by the Ribosome at the Middle Codon Position
Molecules 2017, 22(9), 1427; doi:10.3390/molecules22091427
Received: 25 July 2017 / Revised: 15 August 2017 / Accepted: 22 August 2017 / Published: 29 August 2017
PDF Full-text (1664 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Accurate translation of the genetic code depends on mRNA:tRNA codon:anticodon base pairing. Here we exploit an emissive, isosteric adenosine surrogate that allows direct measurement of the kinetics of codon:anticodon University of California base formation during protein synthesis. Our results suggest that codon:anticodon base
[...] Read more.
Accurate translation of the genetic code depends on mRNA:tRNA codon:anticodon base pairing. Here we exploit an emissive, isosteric adenosine surrogate that allows direct measurement of the kinetics of codon:anticodon University of California base formation during protein synthesis. Our results suggest that codon:anticodon base pairing is subject to tighter constraints at the middle position than at the 5′- and 3′-positions, and further suggest a sequential mechanism of formation of the three base pairs in the codon:anticodon helix. Full article
(This article belongs to the Special Issue Nucleoside and Nucleotide Analogues)
Figures

Open AccessArticle Discovery of Phylloseptins that Defense against Gram-Positive Bacteria and Inhibit the Proliferation of the Non-Small Cell Lung Cancer Cell Line, from the Skin Secretions of Phyllomedusa Frogs
Molecules 2017, 22(9), 1428; doi:10.3390/molecules22091428
Received: 3 August 2017 / Accepted: 26 August 2017 / Published: 29 August 2017
PDF Full-text (5543 KB) | HTML Full-text | XML Full-text
Abstract
The growing occurrence of bacterial resistance to conventional antibiotics has called for the development of new classes of antimicrobial agents. Antimicrobial peptides (AMPs) with broad antimicrobial spectrum derived from frog skin secretions have been demonstrated to be promising candidates for new antibiotic development.
[...] Read more.
The growing occurrence of bacterial resistance to conventional antibiotics has called for the development of new classes of antimicrobial agents. Antimicrobial peptides (AMPs) with broad antimicrobial spectrum derived from frog skin secretions have been demonstrated to be promising candidates for new antibiotic development. A proven rich source of these compounds are the skin secretions of the frogs in the Phyllomedusa genus. In this study, two novel phylloseptin peptides—phylloseptin-PTa and phylloseptin-PHa—were isolated from the skin secretions of the South American frogs, Phyllomedusa tarsius (P. tarsius) and Phyllomedusa hypochondrialis (P. hypochondrialis) through parallel transcriptomic and peptidomic studies. Replicates obtained by chemical synthesis were structurally analysed and shown to adopt an α-helix configuration in an amphiphilic environment. Both peptides demonstrated antimicrobial activities against planktonic Gram-positive bacteria strains, including Staphylococcus aureus, Enterococcus faecalis and methicillin-resistant Staphylococcus aureus , biofilms, as well as cytostatic effects on the non-small cell lung cancer cell line, NCI-H157, with relatively low haemolysis on horse erythrocytes and low cytotoxicity on the human microvascular endothelial cell line, HMEC-1. The discovery of phylloseptin peptides may further inspire the development of new types of antibiotics. Full article
(This article belongs to the Special Issue Bioactive Natural Peptides As A Pipeline For Therapeutics)
Figures

Open AccessArticle New Antifeedant Grayanane Diterpenoids from the Flowers of Pieris formosa
Molecules 2017, 22(9), 1431; doi:10.3390/molecules22091431
Received: 8 August 2017 / Accepted: 24 August 2017 / Published: 31 August 2017
PDF Full-text (1316 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three new grayanane diterpenoids, pierisoids C‒E (13), as well as 10 known ones (413), were evaluated from the flowers of Pieris formosa, which is used as an insecticide in rural areas of China. Their
[...] Read more.
Three new grayanane diterpenoids, pierisoids C‒E (13), as well as 10 known ones (413), were evaluated from the flowers of Pieris formosa, which is used as an insecticide in rural areas of China. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analyses. Significant antifeedant activity of 1, 3 and 10 against the beet armyworm (Spodoptera exigua) was found, indicating that these diterpenoids might also be involved in the plant defense against insect herbivores. Full article
Figures

Figure 1

Open AccessArticle Soluble Epoxide Hydrolase Inhibitory Activity of Components Isolated from Apios americana Medik
Molecules 2017, 22(9), 1432; doi:10.3390/molecules22091432
Received: 13 July 2017 / Revised: 22 August 2017 / Accepted: 28 August 2017 / Published: 30 August 2017
PDF Full-text (1672 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new compound 1, 5-methoxy-2,5,7,4′-tetrahydroxy-coumaronochromone, along with seven known compounds (28), were isolated from Apios americana using open column chromatography. Their structures were established based on an analysis of 1D and 2D NMR, and MS spectra. Among these,
[...] Read more.
A new compound 1, 5-methoxy-2,5,7,4′-tetrahydroxy-coumaronochromone, along with seven known compounds (28), were isolated from Apios americana using open column chromatography. Their structures were established based on an analysis of 1D and 2D NMR, and MS spectra. Among these, two compounds 1 and 2 showed inhibitory activity on soluble epoxide hydrolase (sEH) at a concentration below 50 μM. The respective competitive (1) and mixed (2) inhibitors were revealed to have Ki values of 21.0 ± 0.8 and 14.5 ± 1.5 μM, based on the Dixon plot. The potential inhibitor (2) was visually presented in a predicted binding pose in the receptor by molecular docking. Additionally, molecular dynamics were performed for a detailed understanding of their complex by Gromacs 4.6.5 package. Full article
(This article belongs to the collection Bioactive Compounds)
Figures

Open AccessFeature PaperArticle An Unusual Dimeric Inhibitor of Acetylcholinesterase: Cooperative Binding of Crystal Violet
Molecules 2017, 22(9), 1433; doi:10.3390/molecules22091433
Received: 30 June 2017 / Accepted: 16 August 2017 / Published: 30 August 2017
PDF Full-text (3070 KB) | HTML Full-text | XML Full-text
Abstract
Acetylcholinesterase (AChE) is an essential enzyme that terminates cholinergic transmission by a rapid hydrolysis of the neurotransmitter acetylcholine. AChE is an important target for treatment of various cholinergic deficiencies, including Alzheimer’s disease and myasthenia gravis. In a previous high throughput screening campaign, we
[...] Read more.
Acetylcholinesterase (AChE) is an essential enzyme that terminates cholinergic transmission by a rapid hydrolysis of the neurotransmitter acetylcholine. AChE is an important target for treatment of various cholinergic deficiencies, including Alzheimer’s disease and myasthenia gravis. In a previous high throughput screening campaign, we identified the dye crystal violet (CV) as an inhibitor of AChE. Herein, we show that CV displays a significant cooperativity for binding to AChE, and the molecular basis for this observation has been investigated by X-ray crystallography. Two monomers of CV bind to residues at the entrance of the active site gorge of the enzyme. Notably, the two CV molecules have extensive intermolecular contacts with each other and with AChE. Computational analyses show that the observed CV dimer is not stable in solution, suggesting the sequential binding of two monomers. Guided by the structural analysis, we designed a set of single site substitutions, and investigated their effect on the binding of CV. Only moderate effects on the binding and the cooperativity were observed, suggesting a robustness in the interaction between CV and AChE. Taken together, we propose that the dimeric cooperative binding is due to a rare combination of chemical and structural properties of both CV and the AChE molecule itself. Full article
Figures

Figure 1

Open AccessArticle Cytotoxic Activity of Origanum Vulgare L. on Hepatocellular Carcinoma cell Line HepG2 and Evaluation of its Biological Activity
Molecules 2017, 22(9), 1435; doi:10.3390/molecules22091435
Received: 1 August 2017 / Revised: 22 August 2017 / Accepted: 29 August 2017 / Published: 30 August 2017
PDF Full-text (2657 KB) | HTML Full-text | XML Full-text
Abstract
The potential of plant essential oils (EOs) in anticancer treatment has recently received many research efforts to overcome the development of multidrug resistance and their negative side effects. The aims of the current research are to study (i) the cytotoxic effect of the
[...] Read more.
The potential of plant essential oils (EOs) in anticancer treatment has recently received many research efforts to overcome the development of multidrug resistance and their negative side effects. The aims of the current research are to study (i) the cytotoxic effect of the crude EO extracted from Origanum vulgare subsp hirtum and its main constituents (carvacrol, thymol, citral and limonene) on hepatocarcinoma HepG2 and healthy human renal cells HEK293; (ii) the antibacterial and phytotoxic activities of the above EO and its main constituents. Results showed that cell viability percentage of treated HepG2 by EO and its main constituents was significantly decreased when compared to untreated cells. The calculated inhibition concentration (IC50) values for HepG2 were lower than healthy renal cells, indicating the sort of selectivity of the studied substances. Citral is not potentially recommended as an anticancer therapeutic agent, since there are no significant differences between IC50 values against both tested cell lines. Results showed also that oregano EO and its main constituents have a significant antibacterial activity and a moderate phytotoxic effect. The current research verified that oregano EO and its main constituents could be potentially utilized as anticancer therapeutic agents. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
Figures

Figure 1

Open AccessArticle Molecular Dynamic Analysis of Hyaluronic Acid and Phospholipid Interaction in Tribological Surgical Adjuvant Design for Osteoarthritis
Molecules 2017, 22(9), 1436; doi:10.3390/molecules22091436
Received: 13 July 2017 / Accepted: 25 August 2017 / Published: 4 September 2017
PDF Full-text (10122 KB) | HTML Full-text | XML Full-text
Abstract
Tribological surgical adjuvants constitute a therapeutic discipline made possible by surgical advances in the treatment of damaged articular cartilage beyond palliative care. The purpose of this study is to analyze interactions between hyaluronic acid and phospholipid molecules, and the formation of geometric forms,
[...] Read more.
Tribological surgical adjuvants constitute a therapeutic discipline made possible by surgical advances in the treatment of damaged articular cartilage beyond palliative care. The purpose of this study is to analyze interactions between hyaluronic acid and phospholipid molecules, and the formation of geometric forms, that play a role in the facilitated lubrication of synovial joint organ systems. The analysis includes an evaluation of the pathologic state to detail conditions that may be encountered by adjuvants during surgical convalescence. The synovial fluid changes in pH, hyaluronic acid polydispersity, and phospholipid concentration associated with osteoarthritis are presented as features that influence the lubricating properties of adjuvant candidates. Molecular dynamic simulation studies are presented, and the Rouse model is deployed, to rationalize low molecular weight hyaluronic acid behavior in an osteoarthritic environment of increased pH and phospholipid concentration. The results indicate that the hyaluronic acid radius of gyration time evolution is both pH- and phospholipid concentration-dependent. Specifically, dipalmitoylphosphatidylcholine induces hydrophobic interactions in the system, causing low molecular weight hyaluronic acid to shrink and at high concentration be absorbed into phospholipid vesicles. Low molecular weight hyaluronic acid appears to be insufficient for use as a tribological surgical adjuvant because an increased pH and phospholipid concentration induces decreased crosslinking that prevents the formation of supramolecular lubricating forms. Dipalmitoylphosphatidylcholine remains an adjuvant candidate for certain clinical situations. The need to reconcile osteoarthritic phenotypes is a prerequisite that should serve as a framework for future adjuvant design and subsequent tribological testing. Full article
(This article belongs to the Special Issue Hyaluronic Acid and its Derivatives for Biomedical Applications)
Figures

Figure 1

Open AccessArticle Alkaloid Constituents of the Amaryllidaceae Plant Amaryllis belladonna L
Molecules 2017, 22(9), 1437; doi:10.3390/molecules22091437
Received: 19 July 2017 / Accepted: 26 August 2017 / Published: 31 August 2017
PDF Full-text (1003 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The plant family Amaryllidaceae is well-known for its unique alkaloid constituents, which exhibit a wide range of biological activities. Its representative, Amaryllis belladonna, has a geographical distribution covering mainly southern Africa, where it has significant usage in the traditional medicine of the
[...] Read more.
The plant family Amaryllidaceae is well-known for its unique alkaloid constituents, which exhibit a wide range of biological activities. Its representative, Amaryllis belladonna, has a geographical distribution covering mainly southern Africa, where it has significant usage in the traditional medicine of the native people. In this study, A. belladonna samples collected in Brazil were examined for alkaloid content. Alkaloid profiles of A. belladonna bulbs were generated by a combination of chromatographic, spectroscopic and spectrometric methods, including GC–MS and 2D NMR. In vitro screening against four different parasitic protozoa (Trypanosoma cruzi, T. brucei rhodesiense, Leishmania donovani and Plasmodium falciparum) was carried out using the A. belladonna crude methanol extract, as well as three of its alkaloid isolates. Twenty-six different Amaryllidaceae alkaloids were identified in the A. belladonna bulb samples, and three of them were isolated. Evidence for their respective biosynthetic pathways was afforded via their mass-spectral fragmentation data. Improved data for 1-O-acetylcaranine was provided by 2D NMR experiments, together with new 1H-NMR data for buphanamine. The crude extract and 3-O-acetylhamayne exhibited good antiprotozoal activity in vitro, although both with a high cytotoxic index. Full article
(This article belongs to the collection Herbal Medicine Research)
Figures

Figure 1

Open AccessArticle Preparation and Characterization of Novel Cationic Chitosan Derivatives Bearing Quaternary Ammonium and Phosphonium Salts and Assessment of Their Antifungal Properties
Molecules 2017, 22(9), 1438; doi:10.3390/molecules22091438
Received: 14 August 2017 / Accepted: 29 August 2017 / Published: 31 August 2017
PDF Full-text (2943 KB) | HTML Full-text | XML Full-text
Abstract
Chitosan is an abundant and renewable polysaccharide, its derivatives exhibit attractive bioactivities and the wide applications in various biomedical fields. In this paper, two novel cationic chitosan derivatives modified with quaternary phosphonium salts were successfully synthesized via trimethylation, chloride acetylation, and quaternization with
[...] Read more.
Chitosan is an abundant and renewable polysaccharide, its derivatives exhibit attractive bioactivities and the wide applications in various biomedical fields. In this paper, two novel cationic chitosan derivatives modified with quaternary phosphonium salts were successfully synthesized via trimethylation, chloride acetylation, and quaternization with tricyclohexylphosphine and triphenylphosphine. The structures and properties of synthesized products in the reactions were characterized by FTIR spectroscopy, 1H-NMR, 31P-NMR, elemental and thermogravimetric analysis. The antifungal activities of chitosan derivatives against four kinds of phytopathogens, including Phomopsis asparagi, Watermelon fusarium, Colletotrichum lagenarium, and Fusarium oxysporum were tested using the radial growth assay in vitro. The results revealed that the synthesized cationic chitosan derivatives showed significantly improved antifungal efficiency compared to chitosan. It was reasonably suggested that quaternary phosphonium groups enabled the obviously stronger antifungal activity of the synthesized chitosans. Especially, the triphenylphosphonium-functionalized chitosan derivative inhibited the growth of Phomopsis asparagi most effectively, with inhibitory indices of about 80% at 0.5 mg/mL. Moreover, the data demonstrated that the substituted groups with stronger electron-withdrawing ability relatively possessed greater antifungal activity. The results suggest the possibility that cationic chitosan derivatives bearing quaternary phosphonium salts could be effectively employed as novel antifungal biomaterials for application in the field of agriculture. Full article
Figures

Open AccessArticle Novel Selective Estrogen Receptor Ligand Conjugates Incorporating Endoxifen-Combretastatin and Cyclofenil-Combretastatin Hybrid Scaffolds: Synthesis and Biochemical Evaluation
Molecules 2017, 22(9), 1440; doi:10.3390/molecules22091440
Received: 9 July 2017 / Revised: 9 August 2017 / Accepted: 17 August 2017 / Published: 31 August 2017
PDF Full-text (2820 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nuclear receptors such as the estrogen receptors (ERα and ERβ) modulate the effects of the estrogen hormones and are important targets for design of innovative chemotherapeutic agents for diseases such as breast cancer and osteoporosis. Conjugate and bifunctional compounds which incorporate an ER
[...] Read more.
Nuclear receptors such as the estrogen receptors (ERα and ERβ) modulate the effects of the estrogen hormones and are important targets for design of innovative chemotherapeutic agents for diseases such as breast cancer and osteoporosis. Conjugate and bifunctional compounds which incorporate an ER ligand offer a useful method of delivering cytotoxic drugs to tissue sites such as breast cancers which express ERs. A series of novel conjugate molecules incorporating both the ER ligands endoxifen and cyclofenil-endoxifen hybrids covalently linked to the antimitotic and tubulin targeting agent combretastatin A-4 were synthesised and evaluated as ER ligands. A number of these compounds demonstrated pro-apoptotic effects, with potent antiproliferative activity in ER-positive MCF-7 breast cancer cell lines and low cytotoxicity. These conjugates displayed binding affinity towards ERα and ERβ isoforms at nanomolar concentrations e.g., the cyclofenil-amide compound 13e is a promising lead compound of a clinically relevant ER conjugate with IC50 in MCF-7 cells of 187 nM, and binding affinity to ERα (IC50 = 19 nM) and ERβ (IC50 = 229 nM) while the endoxifen conjugate 16b demonstrates antiproliferative activity in MCF-7 cells (IC50 = 5.7 nM) and binding affinity to ERα (IC50 = 15 nM) and ERβ (IC50 = 115 nM). The ER binding effects are rationalised in a molecular modelling study in which the disruption of the ER helix-12 in the presence of compounds 11e, 13e and 16b is presented These conjugate compounds have potential application for further development as antineoplastic agents in the treatment of ER positive breast cancers. Full article
(This article belongs to the Special Issue Polypharmacology and Multitarget Drug Discovery)
Figures

Open AccessArticle Evaluation of Rhamnetin as an Inhibitor of the Pharmacological Effect of Secretory Phospholipase A2
Molecules 2017, 22(9), 1441; doi:10.3390/molecules22091441
Received: 25 July 2017 / Revised: 28 August 2017 / Accepted: 29 August 2017 / Published: 31 August 2017
PDF Full-text (1174 KB) | HTML Full-text | XML Full-text
Abstract
Rhamnetin (Rhm), 3-O-methylquercetin (3MQ), and Rhamnazin (Rhz) are methylated derivatives of quercetin commonly found in fruits and vegetables that possess antioxidant and anti-inflammatory properties. Phospholipase A2 (PLA2) displays several important roles during acute inflammation; therefore, this study aimed at investigating new
[...] Read more.
Rhamnetin (Rhm), 3-O-methylquercetin (3MQ), and Rhamnazin (Rhz) are methylated derivatives of quercetin commonly found in fruits and vegetables that possess antioxidant and anti-inflammatory properties. Phospholipase A2 (PLA2) displays several important roles during acute inflammation; therefore, this study aimed at investigating new compounds able to inhibit this enzyme, besides evaluating creatine kinase (CK) levels and citotoxicity. Methylated quercetins were compared with quercetin (Q) and were incubated with secretory PLA2 (sPLA2) from Bothrops jararacussu to determine their inhibitory activity. Cytotoxic studies were performed by using the J774 cell lineage incubated with quercertins. In vivo tests were performed with Swiss female mice to evaluate decreasing paw edema potential and compounds’ CK levels. Structural modifications on sPLA2 were made with circular dichroism (CD). Despite Q and Rhz showing greater enzymatic inhibitory potential, high CK was observed. Rhm exhibited sPLA2 inhibitory potential, no toxicity and, remarkably, it decreased CK levels. The presence of 3OH on the C-ring of Rhm may contribute to both its anti-inflammatory and enzymatic inhibition of sPLA2, and the methylation of ring A may provide the increase in cell viability and low CK level induced by sPLA2. These results showed that Rhm can be a candidate as a natural compound for the development of new anti-inflammatory drugs. Full article
(This article belongs to the Special Issue Phospholipases and Lipases: Targets for Drug Development)
Figures

Open AccessArticle Voltammetric Study of Some 3-Aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide Derivatives with Anti-Tumor Activities
Molecules 2017, 22(9), 1442; doi:10.3390/molecules22091442
Received: 9 August 2017 / Revised: 28 August 2017 / Accepted: 29 August 2017 / Published: 31 August 2017
PDF Full-text (3960 KB) | HTML Full-text | XML Full-text
Abstract
The electrochemical properties of twenty 3-aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives with varying degrees of cytotoxic activity were investigated in dimethylformamide (DMF) using cyclic voltammetry and first derivative cyclic voltammetry. With one exception, the first reduction of these compounds was found to be reversible
[...] Read more.
The electrochemical properties of twenty 3-aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives with varying degrees of cytotoxic activity were investigated in dimethylformamide (DMF) using cyclic voltammetry and first derivative cyclic voltammetry. With one exception, the first reduction of these compounds was found to be reversible or quasireversible and is attributed to reduction of the N-oxide moiety to form a radical anion. The second reduction of the diazine ring was found to be irreversible. Compounds containing a nitro group on the 3-phenyl ring also exhibited a reduction process that may be attributed to that group. There was good correlation between molecular structure and reduction potential, with reduction being facilitated by an enhanced net positive charge at the electroactive site created by electron withdrawing substituents. Additionally, the reduction potential was calculated using two common basis sets, 6-31g and lanl2dz, for five of the test molecules. There was a strong correlation between the computational data and the experimental data, with the exception of the derivative containing the nitro functionality. No relationship between the experimentally measured reduction potentials and reported cytotoxic activities was evident upon comparison of the data. Full article
(This article belongs to the collection Heterocyclic Compounds)
Figures

Open AccessArticle Identification of a Quality Marker (Q-Marker) of Danhong Injection by the Zebrafish Thrombosis Model
Molecules 2017, 22(9), 1443; doi:10.3390/molecules22091443
Received: 1 August 2017 / Revised: 24 August 2017 / Accepted: 25 August 2017 / Published: 31 August 2017
PDF Full-text (3266 KB) | HTML Full-text | XML Full-text
Abstract
Quality-marker (Q-marker) is an emerging concept to ensure the quality and batch-to-batch consistency of Chinese medicine (CM). However, significant difficulties remain in the identification of Q-markers due to the unclear relationship between complex chemical compositions and the pharmacological efficacy of CM. In the
[...] Read more.
Quality-marker (Q-marker) is an emerging concept to ensure the quality and batch-to-batch consistency of Chinese medicine (CM). However, significant difficulties remain in the identification of Q-markers due to the unclear relationship between complex chemical compositions and the pharmacological efficacy of CM. In the present study, we proposed a novel strategy to identify the potential Q-marker of danhong injection (DHI) by an in vivo zebrafish thrombosis model. The anti-thrombotic effects of DHI and its major constituents were evaluated by the zebrafish model of arachidonic acid (AA)-induced thrombosis. The results indicated that DHI can attenuate tail venous thrombus and recover the decrease of heart red blood cell (RBC) intensity in a dose-dependent manner. The result that DHI prevented the formulation of thrombosis in zebrafish was also validated in the zebrafish thrombosis model with green fluorescence protein (GFP)-labeled hemoglobin. The major components of DHI, namely danshen (DS) and honghua (HH), as well as the major chemical constituents of DHI, also exerted anti-thrombotic effects, among which rosmarinic acid (RA) and p-coumaric acid (pCA) showed moderate anti-thrombotic effects. This is the first time that pCA from HH has been found as an active compound exerting an anti-thrombotic effect in a dose-dependent manner, whose IC50 value is approximately 147 μg/mL. By analyzing 10 batches of normal DHI samples and five abnormal samples by high-performance liquid chromatography (HPLC), we found the contents of pCA and RA can be positively correlated to the anti-thrombotic effect of DHI, suggesting that pCA and RA could be potential Q-markers of DHI to ensure batch-to-batch consistency. Our findings illustrated that discovering major active compounds from CM by in vivo pharmacological models can be a useful approach to identifying Q-markers of CM, and in vivo pharmacological models can be a potential tool to evaluate batch-to-batch consistency of CMs. Full article
(This article belongs to the collection Herbal Medicine Research)
Figures

Figure 1

Open AccessArticle Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake
Molecules 2017, 22(9), 1444; doi:10.3390/molecules22091444
Received: 3 August 2017 / Revised: 28 August 2017 / Accepted: 29 August 2017 / Published: 31 August 2017
PDF Full-text (6034 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Background: Andrographolide (ADR), the main active component of Andrographis paniculata, displays anticancer activity in various cancer cell lines, among which leukemia cell lines exhibit the highest sensitivity to ADR. In particular, ADR was also reported to have reduced drug resistance in
[...] Read more.
Background: Andrographolide (ADR), the main active component of Andrographis paniculata, displays anticancer activity in various cancer cell lines, among which leukemia cell lines exhibit the highest sensitivity to ADR. In particular, ADR was also reported to have reduced drug resistance in multidrug resistant cell lines. However, the mechanism of action (MOA) of ADR’s anticancer and anti-drug-resistance activities remain elusive. Methods: In this study, we used the MV4-11 cell line, a FLT3 positive acute myeloid leukemia (AML) cell line that displays multidrug resistance, as our experimental system. We first evaluated the effect of ADR on MV4-11 cell proliferation. Then, a quantitative proteomics approach was applied to identify differentially expressed proteins in ADR-treated MV4-11 cells. Finally, cellular processes and signal pathways affected by ADR in MV4-11 cell were predicted with proteomic analysis and validated with in vitro assays. Results: ADR inhibits MV4-11 cell proliferation in a dose- and time-dependent manner. With a proteomic approach, we discovered that ADR inhibited fatty acid synthesis, cellular iron uptake and FLT3 signaling pathway in MV4-11 cells. Conclusions: ADR inhibits MV4-11 cell proliferation through inhibition of fatty acid synthesis, iron uptake and protein synthesis. Furthermore, ADR reduces drug resistance by blocking FLT3 signaling. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
Figures

Open AccessArticle Comparison of Chemical Profiles, Anti-Inflammatory Activity, and UPLC-Q-TOF/MS-Based Metabolomics in Endotoxic Fever Rats between Synthetic Borneol and Natural Borneol
Molecules 2017, 22(9), 1446; doi:10.3390/molecules22091446
Received: 31 July 2017 / Revised: 25 August 2017 / Accepted: 28 August 2017 / Published: 31 August 2017
PDF Full-text (4422 KB) | HTML Full-text | XML Full-text
Abstract
Natural borneol (NB, called “Bingpian”) is an important traditional Chinese medicine to restore consciousness, remove heat and relieve pain, all of which are inflammation-related diseases. Recently, due to the limited source of NB, synthetic borneol (SB) is widely used as a substitute for
[...] Read more.
Natural borneol (NB, called “Bingpian”) is an important traditional Chinese medicine to restore consciousness, remove heat and relieve pain, all of which are inflammation-related diseases. Recently, due to the limited source of NB, synthetic borneol (SB) is widely used as a substitute for NB in clinics. However, little is known about the effects of SB instead of NB. Herein, the aim of the present study was to compare NB and SB on chemical profiles by gas chromatography-mass spectrometer (GC-MS) analysis, anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomic approaches in endotoxic fever induced in rats. Results showed that, in total, 13 volatile components could be identified in NB and SB by GC-MS analysis, in which a significant difference between them still existed. The main constituents in SB were iso-borneol and borneol, while borneol contributes to 98.96% of the amount in NB. Additionally, both NB and SB exhibited remarkable anti-inflammatory effects to reduce the level of inflammatory factors including NO, TNF-α and IL-6 in LPS-induced RAW 264.7 macrophages, and lower the high body temperature in rats with endotoxic fever induced by LPS. Moreover, it seems that NB exhibited higher efficacy than SB. The unequal bioactive efficiency between NB and SB was also indicated by means of non-targeting metabolomics. Based on UPLC-Q-TOF/MS technology, 12 biomarkers in the serum of fever rats were identified. Pathway analysis revealed that the anti-fever effect of NB and SB was related to regulating the abnormal glycerophospholipid, linoleic acid and alpha-linoleic acid metabolism pathways in the fever model. Results indicated that there was still a great difference between NB and SB involving chemical constituents, anti-inflammation activity and the ability to regulate the abnormal metabolism pathways of the fever model. Certainly, further studies are warranted to better understand the replacement rationale in medicinal application. Full article
Figures

Figure 1

Open AccessArticle Different Covalent Immobilizations Modulate Lipase Activities of Hypocrea pseudokoningii
Molecules 2017, 22(9), 1448; doi:10.3390/molecules22091448
Received: 3 August 2017 / Accepted: 29 August 2017 / Published: 4 September 2017
PDF Full-text (1525 KB) | HTML Full-text | XML Full-text
Abstract
Enzyme immobilization can promote several advantages for their industrial application. In this work, a lipase from Hypocrea pseudokoningii was efficiently linked to four chemical supports: agarose activated with cyanogen bromide (CNBr), glyoxyl-agarose (GX), MANAE-agarose activated with glutaraldehyde (GA) and GA-crosslinked with glutaraldehyde. Results
[...] Read more.
Enzyme immobilization can promote several advantages for their industrial application. In this work, a lipase from Hypocrea pseudokoningii was efficiently linked to four chemical supports: agarose activated with cyanogen bromide (CNBr), glyoxyl-agarose (GX), MANAE-agarose activated with glutaraldehyde (GA) and GA-crosslinked with glutaraldehyde. Results showed a more stable lipase with both the GA-crosslinked and GA derivatives, compared to the control (CNBr), at 50 °C, 60 °C and 70 °C. Moreover, all derivatives were stabilized when incubated with organic solvents at 50%, such as ethanol, methanol, n-propanol and cyclohexane. Furthermore, lipase was highly activated (4-fold) in the presence of cyclohexane. GA-crosslinked and GA derivatives were more stable than the CNBr one in the presence of organic solvents. All derivatives were able to hydrolyze sardine, açaí (Euterpe oleracea), cotton seed and grape seed oils. However, during the hydrolysis of sardine oil, GX derivative showed to be 2.3-fold more selectivity (eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) ratio) than the control. Additionally, the types of immobilization interfered with the lipase enantiomeric preference. Unlike the control, the other three derivatives preferably hydrolyzed the R-isomer of 2-hydroxy-4-phenylbutanoic acid ethyl ester and the S-isomer of 1-phenylethanol acetate racemic mixtures. On the other hand, GX and CNBr derivatives preferably hydrolyzed the S-isomer of butyryl-2-phenylacetic acid racemic mixture while the GA and GA-crosslink derivatives preferably hydrolyzed the R-isomer. However, all derivatives, including the control, preferably hydrolyzed the methyl mandelate S-isomer. Moreover, the derivatives could be used for eight consecutive cycles retaining more than 50% of their residual activity. This work shows the importance of immobilization as a tool to increase the lipase stability to temperature and organic solvents, thus enabling the possibility of their application at large scale processes. Full article
(This article belongs to the Special Issue Lipases and Lipases Modification)
Figures

Open AccessArticle Molecular Cloning and Characterization of Carotenoid Pathway Genes and Carotenoid Content in Ixeris dentata var. albiflora
Molecules 2017, 22(9), 1449; doi:10.3390/molecules22091449
Received: 14 August 2017 / Revised: 26 August 2017 / Accepted: 30 August 2017 / Published: 31 August 2017
PDF Full-text (3881 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ixeris dentata var. albiflora is considered as a potential therapeutic agent against mithridatism, calculous, indigestion, pneumonia, hepatitis, and tumors as well as good seasoned vegetable in Far East countries. Phytoene synthase (PSY), phytoene desaturase (PDS) ξ-carotene desaturase (ZDS), lycopene β-cyclase (LCYB), lycopene ε-cyclase
[...] Read more.
Ixeris dentata var. albiflora is considered as a potential therapeutic agent against mithridatism, calculous, indigestion, pneumonia, hepatitis, and tumors as well as good seasoned vegetable in Far East countries. Phytoene synthase (PSY), phytoene desaturase (PDS) ξ-carotene desaturase (ZDS), lycopene β-cyclase (LCYB), lycopene ε-cyclase (LCYE), ε-ring carotene hydroxylase (CHXB), and zeaxanthin epoxidase (ZDS) are vital enzymes in the carotenoid biosynthesis pathway. We have examined these seven genes from I. dentata that are participated in carotenoid biosynthesis utilizing an Illumina/Solexa HiSeq 2000 platform. In silico analysis of the seven deduced amino acid sequences were revealed its closest homology with other Asteracea plants. Further, we explored transcript levels and carotenoid accumulation in various organs of I. dentata using quantitative real time PCR and high-performance liquid chromatography, respectively. The highest transcript levels were noticed in the leaf for all the genes while minimal levels were noticed in the root. The maximal carotenoid accumulation was also detected in the leaf. We proposed that these genes expressions are associated with the accumulation of carotenoids. Our findings may suggest the fundamental clues to unravel the molecular insights of carotenoid biosynthesis in various organs of I. dentata. Full article
(This article belongs to the Section Natural Products)
Figures

Figure 1

Open AccessArticle Synthesis and Detailed Examination of Spectral Properties of (S) and (R)-Higenamine 4′-O-β-d-Glucoside and HPLC Analytical Conditions to Distinguish the Diastereomers
Molecules 2017, 22(9), 1450; doi:10.3390/molecules22091450
Received: 17 August 2017 / Revised: 30 August 2017 / Accepted: 31 August 2017 / Published: 31 August 2017
PDF Full-text (874 KB) | HTML Full-text | XML Full-text
Abstract
Higenamine is a tetrahydroisoquinoline present in several plants that has β-adrenergic receptor agonist activity. Study of the biosynthesis of higenamine has shown the participation of norcoclaurine synthase, which controls the stereochemistry to construct the (S)-isomer. However, when isolated from nature, higenamine
[...] Read more.
Higenamine is a tetrahydroisoquinoline present in several plants that has β-adrenergic receptor agonist activity. Study of the biosynthesis of higenamine has shown the participation of norcoclaurine synthase, which controls the stereochemistry to construct the (S)-isomer. However, when isolated from nature, higenamine is found as the racemate, or even the (R)-isomer. We recently reported the isolation of higenamine 4′-O-β-d-glucoside. Herein, its (R)- and (S)-isomers were synthesized and compared to precisely determine the stereochemistry of the isolate. Owing to their similar spectral properties, determination of the stereochemistry based on NMR data was considered inappropriate. Therefore, a high-performance liquid chromatography method was established to separate the isomers, and natural higenamine 4′-O-β-d-glucoside was determined to be a mixture of isomers. Full article
Figures

Figure 1

Open AccessArticle Coordination Mechanism and Bio-Evidence: Reactive γ-Ketoenal Intermediated Hepatotoxicity of Psoralen and Isopsoralen Based on Computer Approach and Bioassay
Molecules 2017, 22(9), 1451; doi:10.3390/molecules22091451
Received: 30 July 2017 / Revised: 23 August 2017 / Accepted: 29 August 2017 / Published: 4 September 2017
PDF Full-text (23194 KB) | HTML Full-text | XML Full-text
Abstract
Psoralen and isopsoralen are secondary plant metabolites found in many fruits, vegetables, and medicinal herbs. Psoralen-containing plants (Psoralea corylifolia L.) have been reported to cause hepatotoxicity. Herein, we found that psoralen and isopsoralen were oxidized by CYP450s to reactive furanoepoxide or γ-ketoenal
[...] Read more.
Psoralen and isopsoralen are secondary plant metabolites found in many fruits, vegetables, and medicinal herbs. Psoralen-containing plants (Psoralea corylifolia L.) have been reported to cause hepatotoxicity. Herein, we found that psoralen and isopsoralen were oxidized by CYP450s to reactive furanoepoxide or γ-ketoenal intermediates, causing a mechanism-based inhibition of CYP3A4. Furthermore, in GSH-depleted mice, the hepatotoxicity of these reactive metabolites has been demonstrated by pre-treatment with a well-known GSH synthesis inhibitor, L-buthionine-S, Rsulfoxinine (BSO). Moreover, a molecular docking simulation of the present study was undertaken to understand the coordination reaction that plays a significant role in the combination of unstable intermediates and CYP3A4. These results suggested that psoralen and isopsoralen are modest hepatotoxic agents, as their reactive metabolites could be deactivated by H2O and GSH in the liver, which partly contributes to the ingestion of psoralen-containing fruits and vegetables being safe. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Figure 1a

Open AccessArticle Identification of Polar Constituents in the Decoction of Juglans mandshurica and in the Medicated Egg Prepared with the Decoction by HPLC-Q-TOF MS2
Molecules 2017, 22(9), 1452; doi:10.3390/molecules22091452
Received: 25 July 2017 / Accepted: 30 August 2017 / Published: 1 September 2017
PDF Full-text (1241 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
As a folk medicinal plant, Juglans mandshurica has been used for the treatment of cancer in China and Korea. Traditionally, J. mandshurica is decocted together with chicken eggs. Both the decoction and medicated eggs possess anti-tumor properties. Clarifying the constituents of the decoction
[...] Read more.
As a folk medicinal plant, Juglans mandshurica has been used for the treatment of cancer in China and Korea. Traditionally, J. mandshurica is decocted together with chicken eggs. Both the decoction and medicated eggs possess anti-tumor properties. Clarifying the constituents of the decoction and absorbed by the medicated eggs is essential for the investigation of the active principles of J. mandshurica. Herein, the medicated eggs were prepared by decocting raw chicken eggs, having unbroken shells, with the decoction of J. mandshurica. A systematic investigation of the chemical profile of the J. mandshurica decoction and the medicated egg extraction was conducted by HPLC-Q-TOF-MS2. In total, 93 peaks, including 45 tannins, 14 naphthalene derivatives, 17 organic acids, 3 diarylheptanoids, 4 lignans, 3 anthraquinones, 1 flavonoid glycoside, 3 amino acids, and 3 nitrogenous compounds, were tentatively identified in the decoction. In the medicated egg extraction, 44 peaks including 11 organic acids, 3 amino acids, 3 nitrogenous compounds, 8 naphthalene derivatives, 3 diarylheptanoids, 15 tannins, and 1 lignan were tentatively identified. The chemical profile presented provided a detailed overview of the polar chemical constituents in J. mandshurica and useful information for the research of bioactive compounds of this plant. Full article
(This article belongs to the Section Natural Products)
Figures

Figure 1

Open AccessArticle Changes in Tannin Composition of Syrah Grape Skins and Seeds during Fruit Ripening under Contrasting Water Conditions
Molecules 2017, 22(9), 1453; doi:10.3390/molecules22091453
Received: 28 July 2017 / Revised: 28 August 2017 / Accepted: 30 August 2017 / Published: 1 September 2017
PDF Full-text (1604 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Tannin accumulation and composition were determined in skins and seeds isolated from Vitis vinifera cv. Syrah grapes submitted to contrasting water regimes under semiarid climatic conditions. Three irrigation treatments were conducted, starting at berry set through harvest of two growing seasons, 2011 and
[...] Read more.
Tannin accumulation and composition were determined in skins and seeds isolated from Vitis vinifera cv. Syrah grapes submitted to contrasting water regimes under semiarid climatic conditions. Three irrigation treatments were conducted, starting at berry set through harvest of two growing seasons, 2011 and 2012: irrigation at 100% of crop evapotranspiration ETc (FI), irrigation at 50% of ETc (DI) and non-irrigated (NI). Seed total tannins did not vary with maturity but those of skins underwent a progressive decline (especially in 2011), expressed both on a fresh weight and on a per berry basis. Skin total tannin concentration and content per berry were increased under NI and DI conditions, mainly in 2012. In contrast, seed total tannins (in 2012) and flavan-3-ol monomers and tannin oligomers (both years) were higher in the fully irrigated vines (FI). Skin polymer size increased during ripening, NI and DI skins showing higher mean degree of polymerization (mDP) compared to FI at harvest. NI was also associated with a lower percentage of galloylation (%G) in skin oligomeric fraction (in 2012) and a lower percentage of prodelphinidins in the skin polymeric fraction (both years) at harvest. The mDP and %G of seed extracts did not vary during ripening and were higher in NI but only in 2012. According to the results, management of vine water status was shown to influence tannin amount and composition of Syrah grapes grown under semiarid conditions. Full article
(This article belongs to the collection Wine Chemistry)
Figures

Open AccessArticle Constituents of the Fruits of Citrus medica L. var. sarcodactylis and the Effect of 6,7-Dimethoxy-coumarin on Superoxide Anion Formation and Elastase Release
Molecules 2017, 22(9), 1454; doi:10.3390/molecules22091454
Received: 3 August 2017 / Revised: 30 August 2017 / Accepted: 30 August 2017 / Published: 1 September 2017
PDF Full-text (719 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Investigation of the chemical constituents from the fruits of Citrus medica L. var. sarcodactylis Swingle has led to the characterization of a new sesquiterpene 1 along with thirty-two known compounds. The structure of 1 was established on the basis of 2D NMR spectroscopic
[...] Read more.
Investigation of the chemical constituents from the fruits of Citrus medica L. var. sarcodactylis Swingle has led to the characterization of a new sesquiterpene 1 along with thirty-two known compounds. The structure of 1 was established on the basis of 2D NMR spectroscopic and mass spectrometric analyses, and the known compounds were identified by comparison of their physical and spectroscopic data with those reported in the literature. In addition, most of the isolated compounds were evaluated for the activity assayed by the in vitro inhibition of superoxide anion generation and elastase release by human neutrophils. The results showed that only 6,7-dimethoxycoumarin (5) exhibited significant inhibition of superoxide anion generation, with IC50 value of 3.8 ± 1.4 μM. Full article
(This article belongs to the Section Natural Products)
Figures

Figure 1

Open AccessArticle Zeamide, a Glycosylinositol Phosphorylceramide with the Novel Core Arap(1β→6)Ins Motif from the Marine Sponge Svenzea zeai
Molecules 2017, 22(9), 1455; doi:10.3390/molecules22091455
Received: 19 August 2017 / Revised: 30 August 2017 / Accepted: 1 September 2017 / Published: 1 September 2017
PDF Full-text (1415 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Glycosylinositol phosphorylceramides (GIPCs) show a great structural diversity, but all share a small number of core structures, with a glucosamine, a mannose, or a glucuronic acid as the first sugar linked to the inositol. The Caribbean sponge Svenzea zeai was shown to consistently
[...] Read more.
Glycosylinositol phosphorylceramides (GIPCs) show a great structural diversity, but all share a small number of core structures, with a glucosamine, a mannose, or a glucuronic acid as the first sugar linked to the inositol. The Caribbean sponge Svenzea zeai was shown to consistently contain zeamide (1), the first example of a new class of GIPCs, in which the inositol is glycosylated by a d-arabinose. The structure of zeamide was determined by spectroscopic analysis (NMR, MS, ECD) and microscale chemical degradation. The 6-O-β-d-arabinopyranosyl-myo-inositol (d-Arap(1β→6)Ins) core motif of zeamide is unprecedented not only among GIPCs, but also in any natural glycoconjugate. Full article
(This article belongs to the Section Metabolites)
Figures

Open AccessArticle Origin and Formation Mechanism Investigation of Compound Precipitation from the Traditional Chinese Prescription Huang-Lian-Jie-Du-Tang by Isothermal Titration Calorimetry
Molecules 2017, 22(9), 1456; doi:10.3390/molecules22091456
Received: 7 August 2017 / Revised: 30 August 2017 / Accepted: 31 August 2017 / Published: 1 September 2017
PDF Full-text (2360 KB) | HTML Full-text | XML Full-text
Abstract
Previous studies have shown that compounds in the form of precipitate (CFP) from Huang-Lian-Jie-Du-Tang (HLJDT) were stable, and the CFP content reached 2.63% of the whole decoction and had good neuroprotective effects. However, there has been no research on their specific source. In
[...] Read more.
Previous studies have shown that compounds in the form of precipitate (CFP) from Huang-Lian-Jie-Du-Tang (HLJDT) were stable, and the CFP content reached 2.63% of the whole decoction and had good neuroprotective effects. However, there has been no research on their specific source. In this study, it was found that HLJDT CFP mainly came from the reaction of Scutellaria baicalensis and Coptis chinensis by studying the separated prescription components (accounting for 81.33% of HLJDT CFP). Unlike previous studies on HLJDT CFP, in this research the chemical composition of Scutellaria baicalensis–Coptis chinensis (SB–CC) CFP was identified by high performance liquid chromatography coupled with mass spectrometry (HPLC-MSn), which further proved that the main source of HLJDT CFP was Scutellaria baicalensis–Coptis chinensis CFP compared with previous HLJDT CFP studies. To explain the reaction mechanism between the decoctions of Scutellaria baicalensis and Coptis chinensis, isothermal titration calorimetry (ITC) was used to analyze their binding heat and the thermodynamic parameters (ΔH, ΔS, ΔG, n, Ka) of the reaction between baicalin and berberine, which are the main components of Scutellaria baicalensis and Coptis chinensis, respectively. The results showed that the reaction between decoctions of Scutellaria baicalensis and Coptis chinensis was exothermic and the reaction between baicalin and berberine was a spontaneous and enthalpy-driven chemical reaction, the binding ratio being 1:1. In addition, HLJDT CFP (EC50 = 14.71 ± 0.91 µg/mL) and SB-CC CFP (EC50 = 6.11 ± 0.12 µg/mL) showed similar protective activities on PC12 cells injured by cobalt chloride (CoCl2). This study provided a new angle to research on the main chemical components and therapeutic values of CFP in Traditional Chinese Medicine compounds. Full article
Figures

Figure 1

Open AccessArticle Mechanochemical Synthesis and Biological Evaluation of Novel Isoniazid Derivatives with Potent Antitubercular Activity
Molecules 2017, 22(9), 1457; doi:10.3390/molecules22091457
Received: 2 July 2017 / Revised: 19 July 2017 / Accepted: 24 July 2017 / Published: 1 September 2017
PDF Full-text (9621 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of isoniazid derivatives bearing a phenolic or heteroaromatic coupled frame were obtained by mechanochemical means. Their pH stability and their structural (conformer/isomer) analysis were checked. The activity of prepared derivatives against Mycobacterium tuberculosis cell growth was evaluated. Some compounds such as
[...] Read more.
A series of isoniazid derivatives bearing a phenolic or heteroaromatic coupled frame were obtained by mechanochemical means. Their pH stability and their structural (conformer/isomer) analysis were checked. The activity of prepared derivatives against Mycobacterium tuberculosis cell growth was evaluated. Some compounds such as phenolic hydrazine 1a and almost all heteroaromatic ones, especially 2, 5 and 7, are more active than isoniazid, and their activity against some M. tuberculosis MDR clinical isolates was determined. Compounds 1a and 7 present a selectivity index >1400 evaluated on MRC5 human fibroblast cells. The mechanism of action of selected hydrazones was demonstrated to block mycolic acid synthesis due to InhA inhibition inside the mycobacterial cell. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Open AccessArticle Dramatic Influence of Ionic Liquid and Ultrasound Irradiation on the Electrophilic Sulfinylation of Aromatic Compounds by Sulfinic Esters
Molecules 2017, 22(9), 1458; doi:10.3390/molecules22091458
Received: 12 August 2017 / Revised: 28 August 2017 / Accepted: 28 August 2017 / Published: 4 September 2017
PDF Full-text (7072 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The sulfinylation reaction of aromatic and hetero-aromatic compounds with sulfinic esters as electrophiles has been investigated in different ionic liquids and by means of different Lewis acid salts in order to get moderate to good yields of asymmetrical sulfoxides. Mixtures of 1-butyl-3-methylimidazolium chloride
[...] Read more.
The sulfinylation reaction of aromatic and hetero-aromatic compounds with sulfinic esters as electrophiles has been investigated in different ionic liquids and by means of different Lewis acid salts in order to get moderate to good yields of asymmetrical sulfoxides. Mixtures of 1-butyl-3-methylimidazolium chloride and aluminum chloride were found to be the most efficient and recyclable reaction framework. Ultrasound sonication appeared to be the most useful and green activation method to afford the sulfoxides in yields better than or equivalent to those obtained under the longer-lasting conventional stirring conditions. Full article
(This article belongs to the Section Organic Synthesis)
Figures

Figure 1

Open AccessArticle Diuretic Activity of Compatible Triterpene Components of Alismatis rhizoma
Molecules 2017, 22(9), 1459; doi:10.3390/molecules22091459
Received: 15 August 2017 / Revised: 31 August 2017 / Accepted: 31 August 2017 / Published: 6 September 2017
PDF Full-text (1368 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Alismatis rhizoma (AR), the dried rhizoma of Alisma orientale Juzepzuk (Alismataceae), is a traditional Chinese medicine. AR is an important part of many prescriptions and is commonly used as a diuretic agent in Asia. This study aimed to evaluate the diuretic effects of
[...] Read more.
Alismatis rhizoma (AR), the dried rhizoma of Alisma orientale Juzepzuk (Alismataceae), is a traditional Chinese medicine. AR is an important part of many prescriptions and is commonly used as a diuretic agent in Asia. This study aimed to evaluate the diuretic effects of total triterpene extract (TTE) and triterpene component compatibility (TCC, the mixture of alisol B 23-acetate, alisol B, alisol A 24-acetate, alisol A, and alisol C 23-acetate) of AR in saline-loaded rats. The optimal diuretic TCC of AR was optimized using a uniform design. Different doses (5, 20, and 40 mg/kg) of TTE and TCC groups (N1–N8) were orally administered to rats. Urinary excretion rate, pH, and electrolyte excretion were measured in the urine of saline-loaded rats. Results showed that TTE doses increased urine volume and electrolyte excretion compared with the control group. All uniformly designed groups of TCC also increased urine excretion. In addition, optimal diuretic TCC was calculated (alisol B 23-acetate: alisol B: alisol A 24-acetate: alisol A: alisol C 23-acetate 7.2:0.6:2.8:3.0:6.4) and further validated by saline-loaded rats. This study demonstrated that TTE presented a notable diuretic effect by increasing Na+, K+, and Cl displacements. The most suitable TTC compatible proportion of alisol B 23-acetate: alisol B: alisol A 24-acetate: alisol A: alisol C 23-acetate for diuretic activity was validated, and triterpenes were the material basis for the diuretic activity of AR. Full article
(This article belongs to the collection Herbal Medicine Research)
Figures

Open AccessArticle Statistical Methodologies for the Optimization of Lipase and Biosurfactant by Ochrobactrum intermedium Strain MZV101 in an Identical Medium for Detergent Applications
Molecules 2017, 22(9), 1460; doi:10.3390/molecules22091460
Received: 22 July 2017 / Revised: 25 August 2017 / Accepted: 31 August 2017 / Published: 11 September 2017
PDF Full-text (1374 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The Plackett–Burman design and the Box–Behnken design, statistical methodologies, were employed for the optimization lipase and biosurfactant production by Ochrobactrum intermedium strain MZV101 in an identical broth medium for detergent applications. Environmental factor pH determined to be most mutual significant variables on production.
[...] Read more.
The Plackett–Burman design and the Box–Behnken design, statistical methodologies, were employed for the optimization lipase and biosurfactant production by Ochrobactrum intermedium strain MZV101 in an identical broth medium for detergent applications. Environmental factor pH determined to be most mutual significant variables on production. A high concentration of molasses at high temperature and pH has a negative effect on lipase and biosurfactant production by O. intermedium strain MZV101. The chosen mathematical method of medium optimization was sufficient for improving the industrial production of lipase and biosurfactant by bacteria, which were respectively increased 3.46- and 1.89-fold. The duration of maximum production became 24 h shorter, so it was fast and cost-saving. In conclusion, lipase and biosurfactant production by O. intermedium strain MZV101 in an identical culture medium at pH 10.5–11 and 50–60 °C, with 1 g/L of molasses, seemed to be economical, fast, and effective for the enhancement of yield percentage for use in detergent applications. Full article
(This article belongs to the Special Issue Lipases and Lipases Modification)
Figures

Figure 1

Open AccessArticle Persimmon Fruit Powder May Substitute Indolbi, a Synthetic Growth Regulator, in Soybean Sprout Cultivation
Molecules 2017, 22(9), 1462; doi:10.3390/molecules22091462
Received: 30 July 2017 / Revised: 1 September 2017 / Accepted: 3 September 2017 / Published: 3 September 2017
PDF Full-text (259 KB) | HTML Full-text | XML Full-text
Abstract
Soybean sprouts are a major food item in Korea. Various studies have been carried out to enhance their yield and nutritional values. The objective of the present study was to examine the influence of persimmon fruit powder and Indolbi, a synthetic plant growth
[...] Read more.
Soybean sprouts are a major food item in Korea. Various studies have been carried out to enhance their yield and nutritional values. The objective of the present study was to examine the influence of persimmon fruit powder and Indolbi, a synthetic plant growth regulator, on the yield and nutritional value of soybean sprouts. Seeds were soaked in tap water containing 0.5%, 1.0%, 2.5% and 5.0% (w/v) persimmon fruit powder and the samples were named as PT-1, PT-2, PT-3, and PT-4, respectively. The yield increment was almost doubled in PT-3 and PT-4 than in the Indolbi treated sprouts on basis of the control. Vitamin C, isoflavones, and total phenolic contents as well as antioxidant potentials (determined by 1,1-diphenyl-2-picrylhydrazyl and superoxide anion radical scavenging assays) were also significantly (p < 0.05) higher in PT-3 compared to the Indolbi treatment and the control. However, total free amino acid and magnesium contents of Indolbi- applied sprouts were higher than in the fruit powder treatments. The overall results of the present study showed that persimmon fruit powder can be an option to enhance the yield and nutritional value of soybean sprouts since, due to potential health hazards, the use of synthetic chemicals like Indolbi is less preferred than the natural products. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle EPuL: An Enhanced Positive-Unlabeled Learning Algorithm for the Prediction of Pupylation Sites
Molecules 2017, 22(9), 1463; doi:10.3390/molecules22091463
Received: 23 July 2017 / Revised: 29 August 2017 / Accepted: 30 August 2017 / Published: 5 September 2017
PDF Full-text (665 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Protein pupylation is a type of post-translation modification, which plays a crucial role in cellular function of bacterial organisms in prokaryotes. To have a better insight of the mechanisms underlying pupylation an initial, but important, step is to identify pupylation sites. To date,
[...] Read more.
Protein pupylation is a type of post-translation modification, which plays a crucial role in cellular function of bacterial organisms in prokaryotes. To have a better insight of the mechanisms underlying pupylation an initial, but important, step is to identify pupylation sites. To date, several computational methods have been established for the prediction of pupylation sites which usually artificially design the negative samples using the verified pupylation proteins to train the classifiers. However, if this process is not properly done it can affect the performance of the final predictor dramatically. In this work, different from previous computational methods, we proposed an enhanced positive-unlabeled learning algorithm (EPuL) to the pupylation site prediction problem, which uses only positive and unlabeled samples. Firstly, we separate the training dataset into the positive dataset and the unlabeled dataset which contains the remaining non-annotated lysine residues. Then, the EPuL algorithm is utilized to select the reliably negative initial dataset and then iteratively pick out the non-pupylation sites. The performance of the proposed method was measured with an accuracy of 90.24%, an Area Under Curve (AUC) of 0.93 and an MCC of 0.81 by 10-fold cross-validation. A user-friendly web server for predicting pupylation sites was developed and was freely available at http://59.73.198.144:8080/EPuL Full article
(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)
Figures

Figure 1

Open AccessArticle Synergic Anti-Pruritus Mechanisms of Action for the Radix Sophorae Flavescentis and Fructus Cnidii Herbal Pair
Molecules 2017, 22(9), 1465; doi:10.3390/molecules22091465
Received: 22 July 2017 / Revised: 24 August 2017 / Accepted: 31 August 2017 / Published: 4 September 2017
PDF Full-text (3008 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Radix Sophorae Flavescentis (RSF) and Fructus Cnidii (FC) compose a typical herbal synergic pair in traditional Chinese medicine (TCM) for pruritus symptom treatments. The mechanisms of action for the synergy are not understood. This paper aims at predicting the anti-pruritus targets and the
[...] Read more.
Radix Sophorae Flavescentis (RSF) and Fructus Cnidii (FC) compose a typical herbal synergic pair in traditional Chinese medicine (TCM) for pruritus symptom treatments. The mechanisms of action for the synergy are not understood. This paper aims at predicting the anti-pruritus targets and the main active ingredients for the RSF and FC herbal pair. We demonstrate that the RSF–FC herbal pair can be elucidated by mining the chemical structures of compounds derived from RSF and FC. Based on chemical structure data, the putative targets for RSF and FC were predicted. Additional putative targets that interact with the anti-pruritus targets were derived by mapping the putative targets onto a PPI network. By examining the annotations of these proteins, we conclude that (1) RSF’s active compounds are mainly alkaloids and flavonoids. The representative putative targets of the alkaloids are inflammation-related proteins (MAPK14, PTGS2, PTGS2, and F2) and pruritus-related proteins (HRH1, TRPA1, HTR3A, and HTR6). The representative putative targets of the flavonoids are inflammation-related proteins (TNF, NF-κB, F2, PTGS2, and PTGS2) and pruritus-related proteins (NR3C1 and IL2). (2) FC’s active compounds are mainly coumarins. Their representative putative targets are CNS-related proteins (AChE and OPRK1) and inflammation-related proteins (PDE4D, TLR9, and NF-κB). (3) Both RSF and FC display anti-inflammatory effects, though they exhibit their anti-pruritus effects in different ways. Their synergy shows that RSF regulates inflammation-related pruritus and FC regulates CNS-related pruritus. Full article
Figures

Figure 1

Open AccessArticle Phenolics Isolated from Aframomum meleguta Enhance Proliferation and Ossification Markers in Bone Cells
Molecules 2017, 22(9), 1467; doi:10.3390/molecules22091467
Received: 13 August 2017 / Revised: 30 August 2017 / Accepted: 2 September 2017 / Published: 4 September 2017
PDF Full-text (1276 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Osteoporosis is a serious health problem characterized by decreased bone mineral density and deterioration of bone microarchitecture. Current antiosteoporotic agents exhibit a wide range of adverse effects; meanwhile, phytochemicals are effective and safer alternatives. In the current work, nine compounds belonging to hydroxyphenylalkane
[...] Read more.
Osteoporosis is a serious health problem characterized by decreased bone mineral density and deterioration of bone microarchitecture. Current antiosteoporotic agents exhibit a wide range of adverse effects; meanwhile, phytochemicals are effective and safer alternatives. In the current work, nine compounds belonging to hydroxyphenylalkane and diarylheptanoid groups were isolated from Aframomum meleguea seeds and identified as 6-gingerol (1), 6-paradol (2), 8-dehydrogingerdione (3), 8-gingerol (4), dihydro-6-paradol (5), dihydrogingerenone A (6), dihydrogingerenone C (7), 1,7-bis(3,4-dihydroxy-5-methoxyphenyl)heptane-3,5-diyl diacetate (8), and 1-(3,4-dihydroxy-5-methoxyphenyl)-7-(3,4-dihydroxyphenyl)heptane-3,5-diyl diacetate (9). The structures of isolated compounds were established by NMR and mass spectral data, in addition to referring to literature data. Exposure of MCF-7, MG-63, and SAOS-2 cells to subcytotoxic concentrations of the compounds under investigation resulted in accelerated proliferation. Among them, paradol was selected for further detailed biochemical analysis in SAOS-2 cells. DNA flowcytometric analysis of cell cycle distribution revealed that paradol did not induce any significant change in the proliferation index of SAOS-2 cells. Assessment of osteogenic gene expression revealed that paradol enhanced the expression of osteocyte and osteoblast-related genes and inhibited osteoclast and RUNX suppressor genes. Biochemically, paradol enhanced alkaline phosphatase activity and vitamin D content and decreased the osteoporotic marker acid phosphatase. In conclusion, paradol, which is a major constituents of A. melegueta seeds, exhibited potent proliferative and ossification characteristics in bone cells. Full article
(This article belongs to the collection Bioactive Compounds)
Figures

Figure 1

Open AccessArticle The Variation of Oncidium Rosy Sunset Flower Volatiles with Daily Rhythm, Flowering Period, and Flower Parts
Molecules 2017, 22(9), 1468; doi:10.3390/molecules22091468
Received: 1 August 2017 / Revised: 31 August 2017 / Accepted: 1 September 2017 / Published: 4 September 2017
PDF Full-text (2428 KB) | HTML Full-text | XML Full-text
Abstract
Oncidium is an important ornamental crop worldwide, and in recent years, the characteristics of the flower aroma have become a concern for breeders. This study used headspace solid-phase microextraction (HS-SPME) and gas chromatography/mass spectrometry (GC-MS) analysis of the volatile compounds to study the
[...] Read more.
Oncidium is an important ornamental crop worldwide, and in recent years, the characteristics of the flower aroma have become a concern for breeders. This study used headspace solid-phase microextraction (HS-SPME) and gas chromatography/mass spectrometry (GC-MS) analysis of the volatile compounds to study the aroma characteristics of Onc. Rosy Sunset. A total of 45 compounds were identified, with the major compound being linalool. Onc. Rosy Sunset had the highest odor concentration from 10:00 to 12:00 and lowest from 20:00 to 24:00. The inflorescence emitted the highest quantities of volatile compounds during stages 3–6, which then decreased with the aging of the flowers. In Onc. Rosy Sunset, the sepals and petals were the major parts for the floral fragrance emission, in which linalool content was the highest, whereas the lip and column had a different composition of major volatile compounds, of which benzaldehyde, β-myrcene, and β-caryophyllene dominated. Full article
Figures

Figure 1

Open AccessArticle Design and Antiproliferative Evaluation of Novel Sulfanilamide Derivatives as Potential Tubulin Polymerization Inhibitors
Molecules 2017, 22(9), 1470; doi:10.3390/molecules22091470
Received: 21 July 2017 / Revised: 21 August 2017 / Accepted: 31 August 2017 / Published: 5 September 2017
PDF Full-text (1823 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of sulfanilamide-1,2,3-triazole hybrids were designed by a molecular hybridization strategy and evaluated for antiproliferative activity against three selected cancer cell lines (MGC-803, MCF-7 and PC-3). The detailed structure-activity relationships for these sulfanilamide-1,2,3-triazole hybrids were investigated. All these sulfanilamide-1,2,3-triazole hybrids exhibited moderate
[...] Read more.
A series of sulfanilamide-1,2,3-triazole hybrids were designed by a molecular hybridization strategy and evaluated for antiproliferative activity against three selected cancer cell lines (MGC-803, MCF-7 and PC-3). The detailed structure-activity relationships for these sulfanilamide-1,2,3-triazole hybrids were investigated. All these sulfanilamide-1,2,3-triazole hybrids exhibited moderate to potent activity against all cell lines. In particular 4-methyl-N-((1-(3-phenoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)benzenesulfonamide (11f) showed the most potent inhibitory effect against PC-3 cells, with an IC50 value of 4.08 μM. Furthermore, the tubulin polymerization inhibitory activity in vitro of compound 11f was 2.41 μM. These sulfanilamide hybrids might serve as bioactive fragments for developing more potent antiproliferative agents. Full article
Figures

Open AccessCommunication A New Monoterpene from the Leaves of a Radiation Mutant Cultivar of Perilla frutescens var. crispa with Inhibitory Activity on LPS-Induced NO Production
Molecules 2017, 22(9), 1471; doi:10.3390/molecules22091471
Received: 17 August 2017 / Revised: 31 August 2017 / Accepted: 3 September 2017 / Published: 4 September 2017
PDF Full-text (3764 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The leaves of Perilla frutescens var. crispa (Lamiaceae)—known as ‘Jureum-soyeop’ or ‘Cha-jo-ki’ in Korean, ‘ZI SU YE’ in Chinese, and ‘Shiso’ in Japan—has been used as a medicinal herb. Recent gamma irradiated mutation breeding on P. frutescens var. crispa in our research group
[...] Read more.
The leaves of Perilla frutescens var. crispa (Lamiaceae)—known as ‘Jureum-soyeop’ or ‘Cha-jo-ki’ in Korean, ‘ZI SU YE’ in Chinese, and ‘Shiso’ in Japan—has been used as a medicinal herb. Recent gamma irradiated mutation breeding on P. frutescens var. crispa in our research group resulted in the development of a new perilla cultivar, P. frutescens var. crispa (cv. Antisperill; PFCA), which has a higher content of isoegomaketone. The leaves of PFCA were extracted by supercritical carbon dioxide (SC-CO2) extraction, and phytochemical investigation on this extract led to the isolation and identification of a new compound, 9-hydroxy-isoegomaketone [(2E)-1-(3-furanyl)-4-hydroxy-4-methyl-2-penten-1-one; 1]. Compound 1 exhibited inhibitory activity on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 cells with an IC50 value of 14.4 μM. The compounds in the SC-CO2 extracts of the radiation mutant cultivar and the original plant were quantified by high-performance liquid chromatography with diode array detection. Full article
(This article belongs to the collection Bioactive Compounds)
Figures

Figure 1

Open AccessArticle Targeting PDE10A GAF Domain with Small Molecules: A Way for Allosteric Modulation with Anti-Inflammatory Effects
Molecules 2017, 22(9), 1472; doi:10.3390/molecules22091472
Received: 8 August 2017 / Revised: 1 September 2017 / Accepted: 1 September 2017 / Published: 4 September 2017
PDF Full-text (1224 KB) | HTML Full-text | XML Full-text
Abstract
Phosphodiesterase (PDE) enzymes regulate the levels of cyclic nucleotides, cAMP, and/or cGMP, being attractive therapeutic targets. In order to modulate PDE activity in a selective way, we focused our efforts on the search of allosteric modulators. Based on the crystal structure of the
[...] Read more.
Phosphodiesterase (PDE) enzymes regulate the levels of cyclic nucleotides, cAMP, and/or cGMP, being attractive therapeutic targets. In order to modulate PDE activity in a selective way, we focused our efforts on the search of allosteric modulators. Based on the crystal structure of the PDE10A GAF-B domain, a virtual screening study allowed the discovery of new hits that were also tested experimentally, showing inhibitory activities in the micromolar range. Moreover, these new PDE10A inhibitors were able to decrease the nitrite production in LPS-stimulated cells, thus demonstrating their potential as anti-inflammatory agents. Full article
(This article belongs to the Special Issue Anti-inflammatory Agents)
Figures

Open AccessArticle Medicinal Plants Based Products Tested on Pathogens Isolated from Mastitis Milk
Molecules 2017, 22(9), 1473; doi:10.3390/molecules22091473
Received: 4 August 2017 / Revised: 31 August 2017 / Accepted: 2 September 2017 / Published: 4 September 2017
PDF Full-text (703 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Bovine mastitis a major disease that is commonly associated with bacterial infection. The common treatment is with antibiotics administered intramammary into infected quarters of the udder. The excessive use of antibiotics leads to multidrug resistance and associated risks for human health. In this
[...] Read more.
Bovine mastitis a major disease that is commonly associated with bacterial infection. The common treatment is with antibiotics administered intramammary into infected quarters of the udder. The excessive use of antibiotics leads to multidrug resistance and associated risks for human health. In this context, the search for alternative drugs based on plants has become a priority in livestock medicine. These products have a low manufacturing cost and no reports of antimicrobial resistance to these have been documented. In this context, the main objective of this study was to determine the antimicrobial effect of extracts and products of several indigenous, or acclimatized plants on pathogens isolated from bovine mastitis. A total of eleven plant alcoholic extracts and eight plant-derived products were tested against 32 microorganisms isolated from milk. The obtained results have shown an inhibition of bacterial growth for all tested plants, with better results for Evernia prunastri, Artemisia absinthium, and Lavandula angustifolia. Moreover, E. prunastri, Populus nigra, and L. angustifolia presented small averages of minimum inhibitory and bactericidal concentrations. Among the plant-derived products, three out of eight have shown a strong anti-microbial effect comparable with the effect of florfenicol and enrofloxacin, and better than individual plant extracts possibly due to synergism. These results suggest an important anti-microbial effect of these products on pathogens isolated from bovine mastitis with a possible applicability in this disease. Full article
Figures

Figure 1

Open AccessArticle Synthesis and DFT Calculations of Novel Vanillin-Chalcones and Their 3-Aryl-5-(4-(2-(dimethylamino)-ethoxy)-3-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehyde Derivatives as Antifungal Agents
Molecules 2017, 22(9), 1476; doi:10.3390/molecules22091476
Received: 8 August 2017 / Revised: 31 August 2017 / Accepted: 31 August 2017 / Published: 5 September 2017
PDF Full-text (4634 KB) | HTML Full-text | XML Full-text
Abstract
Novel (E)-1-(aryl)-3-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl) prop-2-en-1-ones 4 were synthesized by a Claisen-Schmidt reaction of 4-(2-(dimethylamino)ethoxy)-3-methoxy-benzaldehyde (2) with several acetophenone derivatives 3. Subsequently, cyclocondensation reactions of chalcones 4 with hydrazine hydrate afforded the new racemic 3-aryl-5-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehydes 5 when the reaction
[...] Read more.
Novel (E)-1-(aryl)-3-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl) prop-2-en-1-ones 4 were synthesized by a Claisen-Schmidt reaction of 4-(2-(dimethylamino)ethoxy)-3-methoxy-benzaldehyde (2) with several acetophenone derivatives 3. Subsequently, cyclocondensation reactions of chalcones 4 with hydrazine hydrate afforded the new racemic 3-aryl-5-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehydes 5 when the reaction was carried out in formic acid. The antifungal activity of both series of compounds against eight fungal species was determined. In general, chalcone derivatives 4 showed better activities than pyrazolines 5 against all tested fungi. None of the compounds 4ag and 5ag showed activity against the three Aspergillus spp. In contrast, most of the compounds 4 showed moderate to high activities against three dermatophytes (MICs 31.25–62.5 µg/mL), being 4a followed by 4c the most active structures. Interestingly, 4a and 4c possess fungicidal rather than fungistatic activities, with MFC values between 31.25 and 62.5 μg/mL. The comparison of the percentages of inhibition of C. neoformans by the most active compounds 4, allowed us to know the role played by the different substituents of the chalcones’ A-ring. Also the most anti-cryptococcal compounds 4ac and 4g, were tested in a second panel of five clinical C. neoformans strains in order to have an overview of their inhibition capacity not only of standardized but also of clinical C. neoformans strains. DFT calculations showed that the electrophilicity is the main electronic property to explain the differences in antifungal activities for the synthesized chalcones and pyrazolines compounds. Furthermore, a quantitative reactivity analysis showed that electron-withdrawing substituted chalcones presented the higher electrophilic character and hence, the greater antifungal activities among compounds of series 4. Full article
(This article belongs to the collection Heterocyclic Compounds)
Figures

Open AccessArticle Ginger Phytochemicals Inhibit Cell Growth and Modulate Drug Resistance Factors in Docetaxel Resistant Prostate Cancer Cell
Molecules 2017, 22(9), 1477; doi:10.3390/molecules22091477
Received: 1 August 2017 / Accepted: 2 September 2017 / Published: 5 September 2017
PDF Full-text (1250 KB) | HTML Full-text | XML Full-text
Abstract
Ginger has many bioactive compounds with pharmacological activities. However, few studies are known about these bioactive compounds activity in chemoresistant cells. The aim of the present study was to investigate the anticancer properties of ginger phytochemicals in docetaxel-resistant human prostate cancer cells in
[...] Read more.
Ginger has many bioactive compounds with pharmacological activities. However, few studies are known about these bioactive compounds activity in chemoresistant cells. The aim of the present study was to investigate the anticancer properties of ginger phytochemicals in docetaxel-resistant human prostate cancer cells in vitro. In this study, we isolated 6-gingerol, 10-gingerol, 4-shogaol, 6-shogaol, 10-shogaol, and 6-dehydrogingerdione from ginger. Further, the antiproliferation activity of these compounds was examined in docetaxel-resistant (PC3R) and sensitive (PC3) human prostate cancer cell lines. 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol at the concentration of 100 μM significantly inhibited the proliferation in PC3R but 6-gingerol, 6-shogaol, and 10-shogaol displayed similar activity in PC3. The protein expression of multidrug resistance associated protein 1 (MRP1) and glutathione-S-transferase (GSTπ) is higher in PC3R than in PC3. In summary, we isolated the bioactive compounds from ginger. Our results showed that 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol inhibit the proliferation of PC3R cells through the downregulation of MRP1 and GSTπ protein expression. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
Figures

Figure 1

Open AccessArticle Non-Polar Natural Products from Bromelia laciniosa, Neoglaziovia variegata and Encholirium spectabile (Bromeliaceae)
Molecules 2017, 22(9), 1478; doi:10.3390/molecules22091478
Received: 30 June 2017 / Revised: 29 August 2017 / Accepted: 2 September 2017 / Published: 6 September 2017
PDF Full-text (2043 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Extensive regional droughts are already a major problem on all inhabited continents and severe regional droughts are expected to become an increasing and extended problem in the future. Consequently, extended use of available drought resistant food plants should be encouraged. Bromelia laciniosa,
[...] Read more.
Extensive regional droughts are already a major problem on all inhabited continents and severe regional droughts are expected to become an increasing and extended problem in the future. Consequently, extended use of available drought resistant food plants should be encouraged. Bromelia laciniosa, Neoglaziovia variegata and Encholirium spectabile are excellent candidates in that respect because they are established drought resistant edible plants from the semi-arid Caatinga region. From a food safety perspective, increased utilization of these plants would necessitate detailed knowledge about their chemical constituents. However, their chemical compositions have previously not been determined. For the first time, the non-polar constituents of B. laciniosa, N. variegata and E. spectabile have been identified. This is the first thorough report on natural products from N. variegata, E. spectabile, and B. laciniosa. Altogether, 20 non-polar natural products were characterized. The identifications were based on hyphenated gas chromatography-high resolution mass spectrometry (GC-HRMS) and supported by 1D and 2D Nuclear Magnetic Resonance (NMR) plant metabolomics. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Masticadienonic and 3α-OH Masticadienoic Acids Induce Apoptosis and Inhibit Cell Proliferation and Tumor Growth in Prostate Cancer Xenografts in Vivo
Molecules 2017, 22(9), 1479; doi:10.3390/molecules22091479
Received: 5 July 2017 / Revised: 29 August 2017 / Accepted: 30 August 2017 / Published: 6 September 2017
PDF Full-text (4896 KB) | HTML Full-text | XML Full-text
Abstract
The triterpenes have been constituted as a group of interesting molecules as possible antitumor agents. Despite several of them not presenting a potent cytotoxic activity in vitro against cancer cells, in vivo in xenotransplant tumors studies, they show promising results. Based on the
[...] Read more.
The triterpenes have been constituted as a group of interesting molecules as possible antitumor agents. Despite several of them not presenting a potent cytotoxic activity in vitro against cancer cells, in vivo in xenotransplant tumors studies, they show promising results. Based on the above considerations, we investigated the antitumor activity of both masticadienonic (MDA) and 3α-OH masticadienoic (3α-OH MDA) acids in a mouse prostate cancer xenograft model. Immunohistochemical assays were used to evaluate the decrease in the expression of the Proliferating Cell Nuclear Antigen (PCNA) and the Ki-67 induced by MDA and 3α-OH MDA. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to demonstrate the fragmentation of DNA. Our results showed that the two triterpenes inhibited tumor growth, had anti-proliferative effect in vivo and induced cell death by apoptosis. Collectively, our data suggested that the antitumor mechanism of MDA and 3α-OH MDA involves several molecular targets related to cell proliferation and apoptosis. Full article
(This article belongs to the Section Natural Products)
Figures

Open AccessArticle Anti-Melanogenic Effects of Flavonoid Glycosides from Limonium tetragonum (Thunb.) Bullock via Inhibition of Tyrosinase and Tyrosinase-Related Proteins
Molecules 2017, 22(9), 1480; doi:10.3390/molecules22091480
Received: 20 July 2017 / Revised: 30 August 2017 / Accepted: 2 September 2017 / Published: 5 September 2017
PDF Full-text (1593 KB) | HTML Full-text | XML Full-text
Abstract
Overproduction and stimulation of tyrosinase result in increased melanogenesis of which several skin disorders such as freckles, spots, and hyperpigmentation appear as complications. Limonium tetragonum is a halophyte well-known for its antioxidative properties. This study investigated the anti-melanogenic effects of solvent-partitioned L. tetragonum
[...] Read more.
Overproduction and stimulation of tyrosinase result in increased melanogenesis of which several skin disorders such as freckles, spots, and hyperpigmentation appear as complications. Limonium tetragonum is a halophyte well-known for its antioxidative properties. This study investigated the anti-melanogenic effects of solvent-partitioned L. tetragonum extracts (LTEs) and its bioactive constituents, two isolated flavonoid glycosides. Current study followed a set of experiments on B16-F10 mouse melanoma cell model with a focus on tyrosinase activity and production. The anti-melanogenic capacity of LTEs was confirmed by their tyrosinase inhibitory effects, prevention of DOPA oxidation, and suppression of melanin production. The inhibition of tyrosinase and DOPA oxidation by LTEs was suggested to be related with the downregulation of microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2, verified with mRNA and protein expression levels. Among all tested LTEs, 85% aq. MeOH and n-BuOH were found to be the most active fractions which later yielded the two known compounds, myricetin 3-galactoside and quercetin 3-O-β-galactopyronaside. The anti-melanogenic potential of the compounds were confirmed by their tyrosinase inhibitory effects. These results suggested that L. tetragonum may serve as a potential source of bioactive substances with effective anti-melanogenesis properties. Full article
(This article belongs to the Special Issue Metalloenzyme Inhibitors and Activators)
Figures

Figure 1

Open AccessArticle Microwave-Assisted Extraction of Natural Antioxidants from the Exotic Gordonia axillaris Fruit: Optimization and Identification of Phenolic Compounds
Molecules 2017, 22(9), 1481; doi:10.3390/molecules22091481
Received: 12 August 2017 / Revised: 30 August 2017 / Accepted: 3 September 2017 / Published: 6 September 2017
PDF Full-text (3037 KB) | HTML Full-text | XML Full-text
Abstract
Our previous study reported that the fruit of Gordonia axillaris, an edible wild fruit, possessed strong antioxidant activity. In this study, a microwave-assisted extraction (MAE) method was established to extract antioxidants from the fruit of Gordonia axillaris. The influence of five
[...] Read more.
Our previous study reported that the fruit of Gordonia axillaris, an edible wild fruit, possessed strong antioxidant activity. In this study, a microwave-assisted extraction (MAE) method was established to extract antioxidants from the fruit of Gordonia axillaris. The influence of five parameters, including ethanol concentration, solvent/material ratio, extraction time, extraction temperature and microwave power, was investigated by single-factor experiments. Three factors, namely ethanol concentration, solvent/material ratio, extraction time, were found to exert a major influence on extraction efficacy, and were further studied by response surface methodology to investigate their interactions. Ethanol concentration of 36.89%, solvent/material ratio of 29.56 mL/g, extraction time of 71.04 min, temperature of 40 °C, and microwave power of 400 W were found to be the optimal condition. The TEAC value was 198.16 ± 5.47 µmol Trolox/g DW under the optimal conditions, which was in conformity to the predicted value (200.28 µmol Trolox/g DW). In addition, the MAE method was compared with two conventional methods (Soxhlet extraction and maceration extraction). Results showed that the antioxidant capacity of the extract obtained by MAE method was stronger than that obtained by maceration (168.67 ± 3.88 µmol Trolox/g DW) or Soxhlet extraction (114.09 ± 2.01 µmol Trolox/g DW). Finally, several phenolic compounds in the extract were identified and quantified by UPLC-MS/MS, which were rutin, gallic acid, protocatechuic acid, epicatechin, epicatechin gallate, 2-hydrocinnamic acid, p-coumaric acid, quercetin, chlorogenic acid and ferulic acid. Full article
Figures

Figure 1

Open AccessArticle Deep Eutectic Solvents as Convenient Media for Synthesis of Novel Coumarinyl Schiff Bases and Their QSAR Studies
Molecules 2017, 22(9), 1482; doi:10.3390/molecules22091482
Received: 8 August 2017 / Revised: 29 August 2017 / Accepted: 2 September 2017 / Published: 5 September 2017
PDF Full-text (2687 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Deep eutectic solvents, as green and environmentally friendly media, were utilized in the synthesis of novel coumarinyl Schiff bases. Novel derivatives were synthesized from 2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)acetohydrazide and corresponding aldehyde in choline chloride:malonic acid (1:1) based deep eutectic solvent. In these reactions, deep
[...] Read more.
Deep eutectic solvents, as green and environmentally friendly media, were utilized in the synthesis of novel coumarinyl Schiff bases. Novel derivatives were synthesized from 2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)acetohydrazide and corresponding aldehyde in choline chloride:malonic acid (1:1) based deep eutectic solvent. In these reactions, deep eutectic solvent acted as a solvent and catalyst as well. Novel Schiff bases were synthesized in high yields (65–75%) with no need for further purification, and their structures were confirmed by mass spectra, 1H and 13C NMR. Furthermore, their antioxidant activity was determined and compared to antioxidant activity of previously synthesized derivatives, thus investigating their structure–activity relationship utilizing quantitative structure-activity relationship QSAR studies. Calculation of molecular descriptors has been performed by DRAGON software. The best QSAR model (Rtr = 0.636; Rext = 0.709) obtained with three descriptors (MATS3m, Mor22u, Hy) implies that the pairs of atoms higher mass at the path length 3, three-dimensional arrangement of atoms at scattering parameter s = 21 Å1, and higher number of hydrophilic groups (-OH, -NH) enhanced antioxidant activity. Electrostatic potential surface of the most active compounds showed possible regions for donation of electrons to 1,1-diphenyl-2-picryhydrazyl (DPPH) radicals. Full article
(This article belongs to the Special Issue Versatile Coumarins)
Figures

Open AccessArticle Ultrasonic Assisted Extraction of Paclitaxel from Taxus x media Using Ionic Liquids as Adjuvants: Optimization of the Process by Response Surface Methodology
Molecules 2017, 22(9), 1483; doi:10.3390/molecules22091483
Received: 1 August 2017 / Revised: 25 August 2017 / Accepted: 4 September 2017 / Published: 11 September 2017
PDF Full-text (3713 KB) | HTML Full-text | XML Full-text
Abstract
(1) Background: Ionic liquids (ILs) are considered “green” solvents and have been widely used in the extraction and separation field in recent years; (2) Methods: In this study, some common ILs and functionalized magnetic ionic liquids (MILs) were used as adjuvants for the
[...] Read more.
(1) Background: Ionic liquids (ILs) are considered “green” solvents and have been widely used in the extraction and separation field in recent years; (2) Methods: In this study, some common ILs and functionalized magnetic ionic liquids (MILs) were used as adjuvants for the solvent extraction of paclitaxel from Taxus x media (T. x media) using methanol solution. The extraction conditions of methanol concentration, IL type and amount, solid–liquid ratio, extraction temperature, and ultrasonic irradiation time were investigated in single factor experiments. Then, three factors of IL amount, solid–liquid ratio, and ultrasonic irradiation time were optimized by response surface methodology (RSM); (3) Results: The MIL [C4MIM]FeCl3Br was screened as the optimal adjuvant. Under the optimization conditions of 1.2% IL amount, 1:10.5 solid–liquid ratio, and 30 min ultrasonic irradiation time, the extraction yield reached 0.224 mg/g; and (4) Conclusions: Compared with the conventional solvent extraction, this ultrasonic assisted extraction (UAE) using methanol and MIL as adjuvants can significantly improve the extraction yield, reduce the use of methanol, and shorten the extraction time, which has the potentiality of being used in the extraction of some other important bioactive compounds from natural plant resources. Full article
Figures

Open AccessArticle Synthesis and Biological Activity of Novel O-Alkyl Derivatives of Naringenin and Their Oximes
Molecules 2017, 22(9), 1485; doi:10.3390/molecules22091485
Received: 13 August 2017 / Revised: 1 September 2017 / Accepted: 2 September 2017 / Published: 6 September 2017
PDF Full-text (1098 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
O-Alkyl derivatives of naringenin (1a10a) were prepared from naringenin using the corresponding alkyl iodides and anhydrous potassium carbonate. The resulting products were used to obtain oximes (1b10b). All compounds were tested for antimicrobial activity
[...] Read more.
O-Alkyl derivatives of naringenin (1a10a) were prepared from naringenin using the corresponding alkyl iodides and anhydrous potassium carbonate. The resulting products were used to obtain oximes (1b10b). All compounds were tested for antimicrobial activity against Escherichia coli ATCC10536, Staphylococcus aureus DSM799, Candida albicans DSM1386, Alternaria alternata CBS1526, Fusarium linii KB-F1, and Aspergillus niger DSM1957. The resulting biological activity was expressed as the increase in optical density (ΔOD). The highest inhibitory effect against E. coli ATCC10536 was observed for 7,4′-di-O-pentylnaringenin (8a), 7-O-dodecylnaringenin (9a), naringenin oxime (NG-OX), 7,4′-di-O-pentylnaringenin oxime (8b), and 7-O-dodecylnaringenin oxime (9b) (ΔOD = 0). 7-O-dodecylnaringenin oxime (9b) also inhibited the growth of S. aureus DSM799 (ΔOD = 0.35) and C. albicans DSM1386 (ΔOD = 0.22). The growth of A. alternata CBS1526 was inhibited as a result of the action of 7,4′-di-O-methylnaringenin (2a), 7-O-ethylnaringenin (4a), 7,4′-di-O-ethylnaringenin (5a), 5,7,4′-tri-O-ethylnaringenin (6a), 7,4′-di-O-pentylnaringenin (8a), and 7-O-dodecylnaringenin (9a) (ΔOD in the range of 0.49–0.42) in comparison to that of the control culture (ΔOD = 1.87). In the case of F. linii KB-F1, naringenin (NG), 7,4′-di-O-dodecylnaringenin (10a), 7-O-dodecylnaringenin oxime (9b), and 7,4′-di-O-dodecylnaringenin oxime (10b) showed the strongest effect (ΔOD = 0). 7,4′-Di-O-pentylnaringenin (8a) and naringenin oxime (NG-OX) hindered the growth of A. niger DSM1957 (ΔOD = 0). Full article
(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)
Figures

Figure 1

Open AccessArticle Silver Oxide Coatings with High Silver-Ion Elution Rates and Characterization of Bactericidal Activity
Molecules 2017, 22(9), 1487; doi:10.3390/molecules22091487
Received: 7 August 2017 / Revised: 29 August 2017 / Accepted: 30 August 2017 / Published: 7 September 2017
PDF Full-text (4495 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This paper reports the synthesis and characterization of silver oxide films for use as bactericidal coatings. Synthesis parameters, dissolution/elution rate, and bactericidal efficacy are reported. Synthesis conditions were developed to create AgO, Ag2O, or mixtures of AgO and Ag2O
[...] Read more.
This paper reports the synthesis and characterization of silver oxide films for use as bactericidal coatings. Synthesis parameters, dissolution/elution rate, and bactericidal efficacy are reported. Synthesis conditions were developed to create AgO, Ag2O, or mixtures of AgO and Ag2O on surfaces by reactive magnetron sputtering. The coatings demonstrate strong adhesion to many substrate materials and impede the growth of all bacterial strains tested. The coatings are effective in killing Escherichia coli and Staphylococcus aureus, demonstrating a clear zone-of-inhibition against bacteria growing on solid media and the ability to rapidly inhibit bacterial growth in planktonic culture. Additionally, the coatings exhibit very high elution of silver ions under conditions that mimic dynamic fluid flow ranging between 0.003 and 0.07 ppm/min depending on the media conditions. The elution of silver ions from the AgO/Ag2O surfaces was directly impacted by the complexity of the elution media, with a reduction in elution rate when examined in complex cell culture media. Both E. coli and S. aureus were shown to bind ~1 ppm Ag+/mL culture. The elution of Ag+ resulted in no increases in mammalian cell apoptosis after 24 h exposure compared to control, but apoptotic cells increased to ~35% by 48 and 72 h of exposure. Taken together, the AgO/Ag2O coatings described are effective in eliciting antibacterial activity and have potential for application on a wide variety of surfaces and devices. Full article
(This article belongs to the Special Issue Antibacterial Materials and Coatings)
Figures

Open AccessArticle Effect of Sipjeondaebo-Tang on the Pharmacokinetics of S-1, an Anticancer Agent, in Rats Evaluated by Population Pharmacokinetic Modeling
Molecules 2017, 22(9), 1488; doi:10.3390/molecules22091488
Received: 9 July 2017 / Revised: 31 August 2017 / Accepted: 5 September 2017 / Published: 7 September 2017
PDF Full-text (1295 KB) | HTML Full-text | XML Full-text
Abstract
S-1 (TS-1®) is an oral fluoropyrimidine anticancer agent containing tegafur, oteracil, and gimeracil. Sipjeondaebo-tang (SDT) is a traditional oriental herbal medicine that has potential to alleviate chemotherapy-related adverse effects. The aim of the present study was to evaluate the effect of
[...] Read more.
S-1 (TS-1®) is an oral fluoropyrimidine anticancer agent containing tegafur, oteracil, and gimeracil. Sipjeondaebo-tang (SDT) is a traditional oriental herbal medicine that has potential to alleviate chemotherapy-related adverse effects. The aim of the present study was to evaluate the effect of SDT on the pharmacokinetics of S-1. Sprague-Dawley rats were pretreated with a single dose or repeated doses of SDT for seven consecutive days (1200 mg/kg/day). After the completion of pretreatment with SDT, S-1 was orally administered and plasma concentrations of tegafur, its active metabolite 5-FU, and gimeracil were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS). A population pharmacokinetic model was developed to evaluate the effect of SDT on pharmacokinetics of tegafur and 5-FU. Although a single dose of SDT did not have any significant effect, the absorption rate of tegafur decreased, and the plasma levels of 5-FU reduced significantly in rats pretreated with SDT for seven days in parallel to the decreased gimeracil concentrations. Population pharmacokinetic modeling also showed the enhanced elimination of 5-FU in the SDT-pretreated group. Repeated doses of SDT may inhibit the absorption of gimeracil, an inhibitor of 5-FU metabolism, resulting in enhanced elimination of 5-FU and decrease its plasma level. Full article
Figures

Figure 1

Open AccessArticle Quantitative Analysis, Extraction Optimization, and Biological Evaluation of Cudrania tricuspidata Leaf and Fruit Extracts
Molecules 2017, 22(9), 1489; doi:10.3390/molecules22091489
Received: 22 August 2017 / Accepted: 5 September 2017 / Published: 7 September 2017
PDF Full-text (1765 KB) | HTML Full-text | XML Full-text
Abstract
Cudrania tricuspidata Bureau (Moraceae) shows numerous pharmacological effects and has been used in traditional herbal remedies for inflammation, gastritis, tumors, and liver diseases. However, no validated analytical method for the standardization and optimization of the biological properties of C. tricuspidata preparations has been
[...] Read more.
Cudrania tricuspidata Bureau (Moraceae) shows numerous pharmacological effects and has been used in traditional herbal remedies for inflammation, gastritis, tumors, and liver diseases. However, no validated analytical method for the standardization and optimization of the biological properties of C. tricuspidata preparations has been reported. We developed and validated a reverse-phase high-performance liquid chromatography (HPLC) method for the separation and quantification of active markers. Ethanolic extracts of C. tricuspidata leaves were prepared and evaluated for chemical profiles and biological activities. The 80% ethanolic extract demonstrated the greatest antioxidant activity and phenolic content, while the 100% ethanolic extract had the greatest total flavonoid content and xanthine oxidase (XO) inhibitory activity. The validated HPLC method confirmed that chlorogenic acid, rutin, and kaempferol were present in C. tricuspidata leaf extracts. We postulated that the antioxidant and anti-hyperuricemic/gout effects of C. tricuspidata extract could be attributed to these marker compounds. Our results suggested that the flavonoid-rich fraction of the leaf extract may be utilized for the treatment and prevention of hyperuricemia-related diseases, and the validated method and marker compounds could be applied for the quality control of C. tricuspidata preparations. Full article
(This article belongs to the Section Natural Products)
Figures

Figure 1a

Open AccessArticle Synthesis and Antidepressant Activity Profile of Some Novel Benzothiazole Derivatives
Molecules 2017, 22(9), 1490; doi:10.3390/molecules22091490
Received: 9 August 2017 / Revised: 4 September 2017 / Accepted: 5 September 2017 / Published: 7 September 2017
PDF Full-text (1429 KB) | HTML Full-text | XML Full-text
Abstract
Within the scope of our new antidepressant drug development efforts, in this study, we synthesized eight novel benzothiazole derivatives 3a3h. The chemical structures of the synthesized compounds were elucidated by spectroscopic methods. Test compounds were administered orally at a dose
[...] Read more.
Within the scope of our new antidepressant drug development efforts, in this study, we synthesized eight novel benzothiazole derivatives 3a3h. The chemical structures of the synthesized compounds were elucidated by spectroscopic methods. Test compounds were administered orally at a dose of 40 mg/kg to mice 24, 5 and 1 h before performing tail suspension, modified forced swimming, and activity cage tests. The obtained results showed that compounds 3c, 3d, 3f3h reduced the immobility time of mice as assessed in the tail suspension test. Moreover, in the modified forced swimming tests, the same compounds significantly decreased the immobility, but increased the swimming frequencies of mice, without any alteration in the climbing frequencies. These results, similar to the results induced by the reference drug fluoxetine (20 mg/kg, po), indicated the antidepressant-like activities of the compounds 3c, 3d, 3f3h. Owing to the fact that test compounds did not induce any significant alteration in the total number of spontaneous locomotor activities, the antidepressant-like effects of these derivatives seemed to be specific. In order to predict ADME parameters of the synthesized compounds 3a3h, some physicochemical parameters were calculated. The ADME prediction study revealed that all synthesized compounds may possess good pharmacokinetic profiles. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Figure 1

Open AccessArticle Design, Synthesis, Antimycobacterial Evaluation, and In Silico Studies of 3-(Phenylcarbamoyl)-pyrazine-2-carboxylic Acids
Molecules 2017, 22(9), 1491; doi:10.3390/molecules22091491
Received: 15 August 2017 / Accepted: 5 September 2017 / Published: 7 September 2017
PDF Full-text (775 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Pyrazinamide, the first-line antitubercular drug, has been regarded the basic component of tuberculosis treatment for over sixty years. Researchers have investigated its effect on Mycobacterium tuberculosis for this long time, and as a result, new potential targets of pyrazinamide or its active form,
[...] Read more.
Pyrazinamide, the first-line antitubercular drug, has been regarded the basic component of tuberculosis treatment for over sixty years. Researchers have investigated its effect on Mycobacterium tuberculosis for this long time, and as a result, new potential targets of pyrazinamide or its active form, pyrazinoic acid, have been found. We have designed and prepared 3-(phenyl-carbamoyl)pyrazine-2-carboxylic acids as more lipophilic derivatives of pyrazinoic acid. We also prepared methyl and propyl derivatives as prodrugs with further increased lipophilicity. Antimycobacterial, antibacterial and antifungal growth inhibiting activity was investigated in all prepared compounds. 3-[(4-Nitrophenyl)carbamoyl]pyrazine-2-carboxylic acid (16) exerted high antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MIC = 1.56 μg·mL−1 (5 μM). Propyl 3-{[4-(trifluoromethyl)phenyl]carbamoyl}pyrazine-2-carboxylate (18a) showed also high antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MIC = 3.13 μg·mL−1. In vitro cytotoxicity of the active compounds was investigated and no significant cytotoxic effect was observed. Based to structural similarity to known inhibitors of decaprenylphosphoryl-β-d-ribose oxidase, DprE1, we performed molecular docking of the prepared acids to DprE1. These in silico experiments indicate that modification of the linker connecting aromatic parts of molecule does not have any negative influence on the binding. Full article
(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)
Figures

Figure 1

Open AccessCommunication Forbidden Coherence Transfer of 19F Nuclei to Quantitatively Measure the Dynamics of a CF3-Containing Ligand in Receptor-Bound States
Molecules 2017, 22(9), 1492; doi:10.3390/molecules22091492
Received: 10 August 2017 / Revised: 4 September 2017 / Accepted: 4 September 2017 / Published: 7 September 2017
PDF Full-text (1573 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The dynamic property of a ligand in the receptor-bound state is an important metric to characterize the interactions in the ligand–receptor interface, and the development of an experimental strategy to quantify the amplitude of motions in the bound state is of importance to
[...] Read more.
The dynamic property of a ligand in the receptor-bound state is an important metric to characterize the interactions in the ligand–receptor interface, and the development of an experimental strategy to quantify the amplitude of motions in the bound state is of importance to introduce the dynamic aspect into structure-guided drug development (SGDD). Fluorine modifications are frequently introduced at the hit-to-lead optimization stage to enhance the binding potency and other characteristics of a ligand. However, the effects of fluorine modifications are generally difficult to predict, owing to the pleiotropic nature of the interactions. In this study, we report an NMR-based approach to experimentally evaluate the local dynamics of trifluoromethyl (CF3)-containing ligands in the receptor-bound states. For this purpose, the forbidden coherence transfer (FCT) analysis, which has been used to study the dynamics of methyl moieties in proteins, was extended to the 19F nuclei of CF3-containing ligands. By applying this CF3–FCT analysis to a model interaction system consisting of a ligand, AST-487, and a receptor, p38α, we successfully quantified the amplitude of the CF3 dynamics in the p38α-bound state. The strategy would bring the CF3-containing ligands within the scope of dynamic SGDD to improve the affinity and specificity for the drug-target receptors. Full article
(This article belongs to the Special Issue Recent Advances in Biomolecular NMR Spectroscopy)
Figures

Open AccessArticle Simultaneous Determination of Seven Phenolic Acids in Rat Plasma Using UHPLC-ESI-MS/MS after Oral Administration of Echinacea purpurea Extract
Molecules 2017, 22(9), 1494; doi:10.3390/molecules22091494
Received: 15 August 2017 / Accepted: 4 September 2017 / Published: 7 September 2017
PDF Full-text (3471 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A rapid and sensitive Ultra High Performance Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (UHPLC-ESI-MS/MS) method was developed and validated to simultaneously determine the concentration of seven phenolic acids (syringic acid, ferulic acid, caffeic acid, vanillic acid, p-coumaric acid, 3,4-dihydroxybenzoic acid and
[...] Read more.
A rapid and sensitive Ultra High Performance Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (UHPLC-ESI-MS/MS) method was developed and validated to simultaneously determine the concentration of seven phenolic acids (syringic acid, ferulic acid, caffeic acid, vanillic acid, p-coumaric acid, 3,4-dihydroxybenzoic acid and 4-hydroxybenzoic acid) in rat plasma after oral administration of Echinacea purpurea extract. After mixing with the internal standard (IS), butylparaben, plasma samples were prepared by liquid–liquid extraction with ethyl acetate. The separation was performed using the Agilent Eclipse Plus C18 column (1.8 μm, 2.1 mm × 50 mm) with a gradient system consisting of solution A (0.1% acetic acid in water) and solution B (methanol) at a flow rate of 0.3 mL/min. The detection was accomplished by a multiple reaction monitoring (MRM) mode with electrospray ionization (ESI). The method was validated in terms of linearity, precision, accuracy, extraction recovery, matrix effect and stability. This method was successfully applied to study the pharmacokinetic properties of the seven compounds after oral administration of Echinacea purpurea extract in rats. Full article
Figures

Figure 1

Open AccessArticle The Small Glutathione Peroxidase Mimic 5P May Represent a New Strategy for the Treatment of Liver Cancer
Molecules 2017, 22(9), 1495; doi:10.3390/molecules22091495
Received: 19 July 2017 / Revised: 4 September 2017 / Accepted: 5 September 2017 / Published: 8 September 2017
PDF Full-text (4752 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Glutathione peroxidase (GPx) is an antioxidant protein containing selenium. Owing to the limitations of native GPx, considerable efforts have been made to develop GPx mimics. Here, a short 5-mer peptides (5P) was synthesized and characterized using matrix-assisted laser desorption ionization time-of-flight mass spectrometry.
[...] Read more.
Glutathione peroxidase (GPx) is an antioxidant protein containing selenium. Owing to the limitations of native GPx, considerable efforts have been made to develop GPx mimics. Here, a short 5-mer peptides (5P) was synthesized and characterized using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Enzyme coupled assays were used to evaluate GPx activity. The cell viability and apoptosis of H22 cells were tested, and mice bearing H22 cell-derived tumors were used to determine the effects of 5P on tumor inhibition. In comparison with other enzyme models, 5P provided a suitable substrate with proper catalytic site positions, resulting in enhanced catalytic activity. In our mouse model, 5P showed excellent inhibition of tumor growth and improved immunity. In summary, our findings demonstrated the design and synthesis of the small 5P molecule, which inhibited tumor growth and improved immunity. Notably, 5P could inhibit tumor growth without affecting normal growth. Based on these advantages, the novel mimic may have several clinical applications. Full article
(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)
Figures

Figure 1

Open AccessArticle Topological Characterization of Carbon Graphite and Crystal Cubic Carbon Structures
Molecules 2017, 22(9), 1496; doi:10.3390/molecules22091496
Received: 2 August 2017 / Revised: 30 August 2017 / Accepted: 1 September 2017 / Published: 7 September 2017
PDF Full-text (1458 KB) | HTML Full-text | XML Full-text
Abstract
Graph theory is used for modeling, designing, analysis and understanding chemical structures or chemical networks and their properties. The molecular graph is a graph consisting of atoms called vertices and the chemical bond between atoms called edges. In this article, we study the
[...] Read more.
Graph theory is used for modeling, designing, analysis and understanding chemical structures or chemical networks and their properties. The molecular graph is a graph consisting of atoms called vertices and the chemical bond between atoms called edges. In this article, we study the chemical graphs of carbon graphite and crystal structure of cubic carbon. Moreover, we compute and give closed formulas of degree based additive topological indices, namely hyper-Zagreb index, first multiple and second multiple Zagreb indices, and first and second Zagreb polynomials. Full article
Figures

Figure 1