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 23, Issue 5 (May 2018)

  • 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 1-248
Export citation of selected articles as:

Research

Jump to: Review, Other

Open AccessArticle Antioxidative, Antiproliferative and Antimicrobial Activities of Phenolic Compounds from Three Myrcia Species
Molecules 2018, 23(5), 986; https://doi.org/10.3390/molecules23050986
Received: 21 February 2018 / Revised: 24 March 2018 / Accepted: 29 March 2018 / Published: 24 April 2018
PDF Full-text (2093 KB) | HTML Full-text | XML Full-text
Abstract
Myrcia bella Cambess., Myrcia fallax (Rich.) DC. and Myrcia guianensis (Aubl.) DC. (Myrtaceae) are trees found in Brazilian Cerrado. They have been widely used in folk medicine for the treatment of gastrointestinal disorders, hemorrhagic and infectious diseases. Few reports have been found in
[...] Read more.
Myrcia bella Cambess., Myrcia fallax (Rich.) DC. and Myrcia guianensis (Aubl.) DC. (Myrtaceae) are trees found in Brazilian Cerrado. They have been widely used in folk medicine for the treatment of gastrointestinal disorders, hemorrhagic and infectious diseases. Few reports have been found in the literature connecting their phenolic composition and biological activities. In this regard, we have profiled the main phenolic constituents of Myrcia spp. leaves extracts by ESI(−)Q-TOF-MS. The main constituents found were ellagic acid (M. bella), galloyl glucose isomers (M. guianensis) and hexahydroxydiphenic (HHDP) acid derivatives (M. fallax). In addition, quercetin and myricetin derivatives were also found in all Myrcia spp. extracts. The most promising antioxidant activity, measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, was found for M. fallax extracts (EC50 8.61 ± 0.22 µg·mL−1), being slightly less active than quercetin and gallic acid (EC50 2.96 ± 0.17 and 2.03 ± 0.02 µg·mL−1, respectively). For in vitro antiproliferative activity, M. guianensis showed good activity against leukemia (K562 TGI = 7.45 µg·mL−1). The best antimicrobial activity was observed for M. bella and M. fallax to Escherichia coli (300 and 250 µg·mL−1, respectively). In conclusion, the activities found are closely related to the phenolic composition of these plants. Full article
(This article belongs to the Section Natural Products Chemistry)
Figures

Figure 1

Open AccessArticle Sulforaphane Modulates Joint Inflammation in a Murine Model of Complete Freund’s Adjuvant-Induced Mono-Arthritis
Molecules 2018, 23(5), 988; https://doi.org/10.3390/molecules23050988
Received: 11 January 2018 / Revised: 20 March 2018 / Accepted: 23 March 2018 / Published: 24 April 2018
PDF Full-text (5584 KB) | HTML Full-text | XML Full-text
Abstract
Rheumatoid arthritis (RA) is characterized by inflammation of one or more joints, and affects ~1% of the adult population worldwide. Sulforaphane (SFN) is a natural compound that has been suggested as an antioxidant. Here, SFN’s effects were evaluated in a murine mono-arthritis model.
[...] Read more.
Rheumatoid arthritis (RA) is characterized by inflammation of one or more joints, and affects ~1% of the adult population worldwide. Sulforaphane (SFN) is a natural compound that has been suggested as an antioxidant. Here, SFN’s effects were evaluated in a murine mono-arthritis model. Mono-arthritis was induced in mice by a single intra-articular injection of Complete Freund’s Adjuvant (CFA-10 µg/joint, in 10 µL) into the ipsilateral joint. The contralateral joint received an equal volume of PBS. On the 4th day post-joint inflammation induction, animals received either SFN (10 mg/kg) or vehicle (3% DMSO in saline), intraperitoneally (i.p.), twice a day for 3 days. Joint swelling and secondary mechanical allodynia and hyperalgesia were evaluated over 7 days post-CFA. After this period, animals were culled and their blood and synovial fluid samples were collected for analysis of cell populations, cytokine release and thioredoxin reductase (TrxR) activity. Knee joint samples were also collected for histology. SFN reduced joint swelling and damage whilst increasing the recruitment of Ly6C+ and Ly6G+ cells to CFA-injected joints. SFN-treated animals presented down-regulation of CD11b and CD62L on synovial fluid Ly6G+ cells. Synovial fluid samples obtained from CFA-injected joints and plasma samples of SFN-treated mice presented higher levels of IL-6 and increased activity of TrxR, in comparison with controls. These results indicate that SFN reduces knee joint damage by modulating cell activation/migration to the joints, cytokine production and increasing the activity of TrxR, and therefore, may represent an alternative treatment to joint inflammation. Full article
Figures

Figure 1

Open AccessArticle Effects of UV-B Radiation on the Content of Bioactive Components and the Antioxidant Activity of Prunella vulgaris L. Spica during Development
Molecules 2018, 23(5), 989; https://doi.org/10.3390/molecules23050989
Received: 1 March 2018 / Revised: 21 March 2018 / Accepted: 5 April 2018 / Published: 24 April 2018
PDF Full-text (2936 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The effects of UV-B radiation on the content of bioactive components and the antioxidant activity of Prunella vulgaris L. spica during development were studied. The experimental design involved two levels of UV-B radiation intensity (0 and 120 μW cm−2 nm−1).
[...] Read more.
The effects of UV-B radiation on the content of bioactive components and the antioxidant activity of Prunella vulgaris L. spica during development were studied. The experimental design involved two levels of UV-B radiation intensity (0 and 120 μW cm−2 nm−1). The results showed that the contents of total flavonoids, rosmarinic acid, caffeic acid and hyperoside, as well as the antioxidant capacities (DPPH and ABTS•+ scavenging activities), in the spicas significantly decreased during spica development. The content of salviaflaside in the spicas significantly increased during development. The highest contents of total flavonoids, rosmarinic acid, and caffeic acid and the highest antioxidant activities were found in spicas in the full-flowering stage, while the highest content of hyperoside was found in spicas in the bud stage. In addition, the highest content of salviaflaside was found in spicas in the mature-fruiting stage. UV-B radiation significantly promoted the synthesis of secondary metabolites, increased the contents of the main bioactive components in the three developmental stages of isolated dried spicas, and significantly increased the DPPH and ABTS•+ scavenging activities of P. vulgaris spicas in the mature-fruiting stage. Moreover, the total flavonoids content was positively correlated with the DPPH and ABTS•+ scavenging activities, and the correlation with the DPPH scavenging activity was very strong. This result shows that the highest contents of the main bioactive components in the spicas were not all found in the same developmental stages of P. vulgaris. Our research revealed that the best stage for harvesting P. vulgaris spica was between the bud stage and the full-flowering stage since harvesting at this point provides a higher content of bioactive components and a higher antioxidant capacity, which is relevant for medicinal applications. Full article
Figures

Graphical abstract

Open AccessFeature PaperArticle Synthesis and Guest Recognition of Switchable Pt-Salphen Based Molecular Tweezers
Molecules 2018, 23(5), 990; https://doi.org/10.3390/molecules23050990
Received: 30 March 2018 / Revised: 18 April 2018 / Accepted: 20 April 2018 / Published: 24 April 2018
PDF Full-text (4360 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Molecular tweezers are artificial receptors that have an open cavity generated by two recognition units pre-organized by a spacer. Switchable molecular tweezers, using a stimuli-responsive spacer, are particularly appealing as prototypes of the molecular machines that combine mechanical motion and allosteric recognition properties.
[...] Read more.
Molecular tweezers are artificial receptors that have an open cavity generated by two recognition units pre-organized by a spacer. Switchable molecular tweezers, using a stimuli-responsive spacer, are particularly appealing as prototypes of the molecular machines that combine mechanical motion and allosteric recognition properties. In this present study, the synthesis of switchable molecular tweezers composed of a central terpyridine unit substituted in 4,4″ positions by two Pt(II)-salphen complexes is reported. The terpyridine ligand can be reversibly converted upon Zn(II) coordination from a free ‘U’-shaped closed form to a coordinated ‘W’ open form. This new substitution pattern enables a reverse control of the mechanical motion compared to the previously reported 6,6″ substituted terpyridine-based tweezers. Guest binding studies with aromatic guests showed an intercalation of coronene in the cavity created by the Pt-salphen moieties in the closed conformation. The formation of 1:1 host-guest complex was investigated by a combination of NMR studies and DFT calculations. Full article
(This article belongs to the Special Issue Interlocked Molecules, Molecular Machines, Motors and Muscles)
Figures

Graphical abstract

Open AccessArticle Isolation of High Purity Anthocyanin Monomers from Red Cabbage with Recycling Preparative Liquid Chromatography and Their Photostability
Molecules 2018, 23(5), 991; https://doi.org/10.3390/molecules23050991
Received: 23 March 2018 / Revised: 18 April 2018 / Accepted: 20 April 2018 / Published: 24 April 2018
PDF Full-text (2461 KB) | HTML Full-text | XML Full-text
Abstract
Anthocyanins from red cabbage are of great importance for their applications in the food industry as natural colorants and their beneficial effects on human wellness as natural antioxidants. This study aimed to develop an effective method for the isolation of anthocyanins with the
[...] Read more.
Anthocyanins from red cabbage are of great importance for their applications in the food industry as natural colorants and their beneficial effects on human wellness as natural antioxidants. This study aimed to develop an effective method for the isolation of anthocyanins with the help of a combination of alternate recycling and direct recycling preparative liquid chromatography. Ten major components of anthocyanins from red cabbage were isolated and their structures were identified by HPLC-MS/MS. Meanwhile, the stability of the isolated anthocyanins under various light conditions was also investigated so as to provide data for their storage. In sum, the results showed that twin column recycling preparative chromatography is an effective method for the isolation of anthocyanin monomers with similar structures. Besides, the stability of various anthocyanins from red cabbage was related to the number of acylated groups and mainly affected by illumination. Full article
(This article belongs to the Special Issue Qualitative and Quantitative Analysis of Bioactive Natural Products)
Figures

Figure 1

Open AccessArticle Design, Synthesis, and Docking Studies of New Torin2 Analogs as Potential ATR/mTOR Kinase Inhibitors
Molecules 2018, 23(5), 992; https://doi.org/10.3390/molecules23050992
Received: 20 March 2018 / Revised: 11 April 2018 / Accepted: 13 April 2018 / Published: 24 April 2018
PDF Full-text (11391 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Targeting DNA damage and response (DDR) pathway has become an attractive approach in cancer therapy. The key mediators involved in this pathway are ataxia telangiectasia-mutated kinase (ATM) and ataxia telangiectasia-mutated, Rad3-related kinase (ATR). These kinases induce cell cycle arrest in response to chemo-
[...] Read more.
Targeting DNA damage and response (DDR) pathway has become an attractive approach in cancer therapy. The key mediators involved in this pathway are ataxia telangiectasia-mutated kinase (ATM) and ataxia telangiectasia-mutated, Rad3-related kinase (ATR). These kinases induce cell cycle arrest in response to chemo- and radio-therapy and facilitate DNA repair via their major downstream targets. Targeting ATP-binding site of these kinases is currently under study. Torin2 is a second generation ATP competitive mTOR kinase inhibitor (EC50 = 250 pmol/L) with better pharmacokinetic profile. Torin2 also exhibits potent biochemical and cellular activity against ATM (EC50 = 28 nmol/L) and ATR (EC50 = 35 nmol/L) kinases. In this study, eight new Torin2 analogs were designed and synthesized through multistep synthesis. All the synthesized compounds were characterized by NMR and mass analysis. The newly synthesized analogs were evaluated for their anti-cancer activity via CellTiter-Glo® assay. Additionally, compounds 13 and 14 also showed significant inhibition for ATR and mTOR substrates, i.e., p-Chk1 Ser 317 and p70 S6K Thr 389, respectively. Compounds 13 and 14 displayed promising anti-cancer activity with HCT-116 cell lines in the preliminary study. Further, a comparative model of ATR kinase was generated using the SWISS-MODEL server and validated using PROCHECK, ProSA analysis. Synthesized compounds were docked into the ATP-binding site to understand the binding modes and for the rational design of new inhibitors. Full article
(This article belongs to the Special Issue Recent Trends on Enzymes Inhibitors and Activators in Drug Research)
Figures

Graphical abstract

Open AccessArticle Assessing the Effects of Alloxydim Phototransformation Products by QSAR Models and a Phytotoxicity Study
Molecules 2018, 23(5), 993; https://doi.org/10.3390/molecules23050993
Received: 21 March 2018 / Revised: 13 April 2018 / Accepted: 21 April 2018 / Published: 24 April 2018
PDF Full-text (554 KB) | HTML Full-text | XML Full-text
Abstract
Once applied, an herbicide first makes contact with leaves and soil. It is known that photolysis can be one of the most important processes of dissipation of herbicides in the field. However, degradation does not guarantee detoxification and can give rise to byproducts
[...] Read more.
Once applied, an herbicide first makes contact with leaves and soil. It is known that photolysis can be one of the most important processes of dissipation of herbicides in the field. However, degradation does not guarantee detoxification and can give rise to byproducts that could be more toxic and/or persistent than the active substance. In this work, the photodegradation of alloxydim herbicide in soil and leaf cuticle surrogates was studied and a detailed study on the phytotoxicity of the main byproduct on sugar beet, tomato, and rotational crops was performed. Quantitative structure–activity relationship (QSAR) models were used to obtain a first approximation of the possible ecotoxicological and environmental implications of the alloxydim and its degradation product. The results show that alloxydim is rapidly degraded on carnauba and sandy loam soil surfaces, two difficult matrices to analyze and not previously studied with alloxydim. Two transformation products that formed in both matrices were identified: alloxydim Z-isomer and imine derivative (mixture of two tautomers). The phytotoxicity of alloxydim and the major byproduct shows that tomato possesses high sensitivity to the imine byproduct, while wheat crops are inhibited by the parent compound. This paper demonstrates the need to further investigate the behavior of herbicide degradation products on target and nontarget species to determine the adequate use of herbicidal products to maximize productivity in the context of sustainable agriculture. Full article
(This article belongs to the Section Analytical Chemistry)
Figures

Graphical abstract

Open AccessArticle To Decipher the Mycoplasma hominis Proteins Targeting into the Endoplasmic Reticulum and Their Implications in Prostate Cancer Etiology Using Next-Generation Sequencing Data
Molecules 2018, 23(5), 994; https://doi.org/10.3390/molecules23050994
Received: 7 March 2018 / Revised: 16 April 2018 / Accepted: 18 April 2018 / Published: 24 April 2018
PDF Full-text (7063 KB) | HTML Full-text | XML Full-text
Abstract
Cancer was initially considered a genetic disease. However, recent studies have revealed the connection between bacterial infections and growth of different types of cancer. The enteroinvasive strain of Mycoplasma hominis alters the normal behavior of host cells that may result in the growth
[...] Read more.
Cancer was initially considered a genetic disease. However, recent studies have revealed the connection between bacterial infections and growth of different types of cancer. The enteroinvasive strain of Mycoplasma hominis alters the normal behavior of host cells that may result in the growth of prostate cancer. The role of M. hominis in the growth and development of prostate cancer still remains unclear. The infection may regulate several factors that influence prostate cancer growth in susceptible individuals. The aim of this study was to predict M. hominis proteins targeted into the endoplasmic reticulum (ER) of the host cell, and their potential role in the induction of prostate cancer. From the whole proteome of M. hominis, 19 proteins were predicted to be targeted into the ER of host cells. The results of our study predict that several proteins of M. hominis may be targeted to the host cell ER, and possibly alter the normal pattern of protein folding. These predicted proteins can modify the normal function of the host cell. Thus, the intercellular infection of M. hominis in host cells may serve as a potential factor in prostate cancer etiology. Full article
(This article belongs to the Special Issue Molecular Computing and Bioinformatics)
Figures

Figure 1

Open AccessArticle Synthesis and Acaricidal Activities of Scopoletin Phenolic Ether Derivatives: QSAR, Molecular Docking Study and in Silico ADME Predictions
Molecules 2018, 23(5), 995; https://doi.org/10.3390/molecules23050995
Received: 3 April 2018 / Revised: 15 April 2018 / Accepted: 18 April 2018 / Published: 24 April 2018
PDF Full-text (3893 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Thirty phenolic ether derivatives of scopoletin modified at the 7-hydroxy position were synthesized, and their structures were confirmed by IR, 1H-NMR, 13C-NMR, MS and elemental analysis. Preliminary acaricidal activities of these compounds against female adults of Tetranychus cinnabarinus (Boisduval) were evaluated
[...] Read more.
Thirty phenolic ether derivatives of scopoletin modified at the 7-hydroxy position were synthesized, and their structures were confirmed by IR, 1H-NMR, 13C-NMR, MS and elemental analysis. Preliminary acaricidal activities of these compounds against female adults of Tetranychus cinnabarinus (Boisduval) were evaluated using the slide-dip method. The results indicated that some of these compounds exhibit more pronounced acaricidal activity than scopoletin, especially compounds 32, 20, 28, 27 and 8 which exhibited about 8.41-, 7.32-, 7.23-, 6.76-, and 6.65-fold higher acaricidal potency. Compound 32 possessed the the most promising acaricidal activity and exhibited about 1.45-fold higher acaricidal potency against T. cinnabarinus than propargite. Statistically significant 2D-QSAR model supports the observed acaricidal activities and reveals that polarizability (HATS5p) was the most important parameter controlling bioactivity. 3D-QSAR (CoMFA: q2 = 0.802, r2 = 0.993; CoMSIA: q2 = 0.735, r2 = 0.965) results show that bulky substituents at R4, R1, R2 and R5 (C6, C3, C4, and C7) positions, electron positive groups at R5 (C7) position, hydrophobic groups at R1 (C3) and R2 (C4), H-bond donors groups at R1 (C3) and R4 (C6) will increase their acaricidal activity, which provide a good insight into the molecular features relevant to the acaricidal activity for further designing novel acaricidal agents. Molecular docking demonstrates that these selected derivatives display different bide modes with TcPMCA1 from lead compound and they interact with more key amino acid residues than scopoletin. In silico ADME properties of scopoletin and its phenolic ether derivatives were also analyzed and showed potential to develop as good acaricidal candidates. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Figure 1

Open AccessArticle Scale-Up Synthesis and Identification of GLYX-13, a NMDAR Glycine-Site Partial Agonist for the Treatment of Major Depressive Disorder
Molecules 2018, 23(5), 996; https://doi.org/10.3390/molecules23050996
Received: 21 March 2018 / Revised: 11 April 2018 / Accepted: 21 April 2018 / Published: 24 April 2018
PDF Full-text (3174 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
GLYX-13, a NMDAR glycine-site partial agonist, was discovered as a promising antidepressant with rapidly acting effects but no ketamine-like side effects. However, the reported synthetic process route had deficiencies of low yield and the use of unfriendly reagents. Here, we report a scaled-up
[...] Read more.
GLYX-13, a NMDAR glycine-site partial agonist, was discovered as a promising antidepressant with rapidly acting effects but no ketamine-like side effects. However, the reported synthetic process route had deficiencies of low yield and the use of unfriendly reagents. Here, we report a scaled-up synthesis of GLYX-13 with an overall yield of 30% on the hectogram scale with a column chromatography-free strategy, where the coupling and deprotection reaction conditions were systematically optimized. Meanwhile, the absolute configuration of precursor compound of GLYX-13 was identified by X-ray single crystal diffraction. Finally, the activity of GLYX-13 was verified in the cortical neurons of mice through whole-cell voltage-clamp technique. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Figure 1

Open AccessArticle Dendrimeric Antigens for Drug Allergy Diagnosis: A New Approach for Basophil Activation Tests
Molecules 2018, 23(5), 997; https://doi.org/10.3390/molecules23050997
Received: 5 March 2018 / Revised: 6 April 2018 / Accepted: 20 April 2018 / Published: 24 April 2018
PDF Full-text (1193 KB) | HTML Full-text | XML Full-text
Abstract
Dendrimeric Antigens (DeAns) consist of dendrimers decorated with multiple units of drug antigenic determinants. These conjugates have been shown to be a powerful tool for diagnosing penicillin allergy using in vitro immunoassays, in which they are recognized by specific IgE from allergic patients.
[...] Read more.
Dendrimeric Antigens (DeAns) consist of dendrimers decorated with multiple units of drug antigenic determinants. These conjugates have been shown to be a powerful tool for diagnosing penicillin allergy using in vitro immunoassays, in which they are recognized by specific IgE from allergic patients. Here we propose a new diagnostic approach using DeAns in cellular tests, in which recognition occurs through IgE bound to the basophil surface. Both IgE molecular recognition and subsequent cell activation may be influenced by the tridimensional architecture and size of the immunogens. Structural features of benzylpenicilloyl-DeAn and amoxicilloyl-DeAn (G2 and G4 PAMAM) were studied by diffusion Nuclear Magnetic Resonance (NMR) experiments and are discussed in relation to molecular dynamics simulation (MDS) observations. IgE recognition was clinically evaluated using the basophil activation test (BAT) for allergic patients and tolerant subjects. Diffusion NMR experiments, MDS and cellular studies provide evidence that the size of the DeAn, its antigen composition and tridimensional distribution play key roles in IgE-antigen recognition at the effector cell surface. These results indicate that the fourth generation DeAns induce a higher level of basophil activation in allergic patients. This approach can be considered as a potential complementary diagnostic method for evaluating penicillin allergy. Full article
Figures

Graphical abstract

Open AccessArticle The Tryptophan Decarboxylase in Solanum lycopersicum
Molecules 2018, 23(5), 998; https://doi.org/10.3390/molecules23050998
Received: 26 February 2018 / Revised: 17 April 2018 / Accepted: 17 April 2018 / Published: 24 April 2018
PDF Full-text (1610 KB) | HTML Full-text | XML Full-text
Abstract
Melatonin plays an important role in plant growth, development, and environmental stress. In this study, a systematic analysis of tomato tryptophan decarboxylase (SlTrpDC), which is the first enzyme of melatonin biosynthesis, was conducted by integrating structural features, phylogenetic relationships, an exon/intron feature, and
[...] Read more.
Melatonin plays an important role in plant growth, development, and environmental stress. In this study, a systematic analysis of tomato tryptophan decarboxylase (SlTrpDC), which is the first enzyme of melatonin biosynthesis, was conducted by integrating structural features, phylogenetic relationships, an exon/intron feature, and a divergent expression profile. The results determined that the tomato genome encoded five members (SlTrpDC1-SlTrpDC5). The phylogenetic relationships indicated that gene expansion was proposed as the major mode of evolution of the TrpDC genes from the different plant algae species to the higher plants species. The analyses of the exon/intron configurations revealed that the intron loss events occurred during the structural evolution of the TrpDCs in plants. Additionally, the RNA-seq and qRT-PCR analysis revealed that the expression of the SlTrpDC3 was high in all of the tested tissues, while the SlTrpDC4 and SlTrpDC5 were not expressed. The expression patterns of the remaining two (SlTrpDC1 and SlTrpDC2) were tissue-specific, which indicated that these genes may play important roles within the different tissues. No expression difference was observed in the tomato plants in response to the biotic stresses. This study will expand the current knowledge of the roles of the TrpDC genes in tomato growth and development. Full article
Figures

Figure 1

Open AccessArticle Dietary Polyphenol Intake and Depression: Results from the Mediterranean Healthy Eating, Lifestyle and Aging (MEAL) Study
Molecules 2018, 23(5), 999; https://doi.org/10.3390/molecules23050999
Received: 27 February 2018 / Revised: 17 April 2018 / Accepted: 20 April 2018 / Published: 24 April 2018
PDF Full-text (298 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Background: The epidemiological evidence for a relation between dietary polyphenol intake and depression is limited. Therefore, the aim of this study was to assess the association between habitual dietary intake of total polyphenols, their classes, subclasses and individual compounds and depressive symptoms
[...] Read more.
Background: The epidemiological evidence for a relation between dietary polyphenol intake and depression is limited. Therefore, the aim of this study was to assess the association between habitual dietary intake of total polyphenols, their classes, subclasses and individual compounds and depressive symptoms among the participants of the Mediterranean healthy Eating, Lifestyle and Aging (MEAL) study. Methods: Demographic and dietary characteristics of 1572 adults living in southern Italy were analyzed. Food frequency questionnaires and Phenol-Explorer were used to calculate habitual dietary intakes of polyphenols. The Center for Epidemiologic Studies Depression Scale (CES-D-10) was used as screening tool for depressive symptoms. Multivariate logistic regression analyses were used to test associations and were expressed as odds ratio (OR) and 95% confidence intervals (CI). Results: A total of 509 individuals reported having depressive symptoms. Based on multivariate logistic regression analyses, total polyphenol intake was not associated with depressive symptoms. After adjustment for potential confounding factors, dietary intake of phenolic acid (OR = 0.64, 95% CI: 0.44, 0.93), flavanones (OR = 0.54, 95% CI: 0.32, 0.91), and anthocyanins (OR = 0.61, 95% CI: 0.42, 0.89) showed significant inverse association with depressive symptoms, when comparing the highest with the lowest quartile. Moreover, flavanones and anthocyanins, were associated with depressive symptoms in a dose-response manner. Among individual compounds, inverse association was observed for quercetin (OR = 0.53, 95% CI: 0.32, 0.86) and naringenin (OR = 0.51, 95% CI: 0.30, 0.85), for the highest versus lowest quartile of intake. When taking into consideration the major sources of the polyphenols, only citrus fruits and wine consumption was inversely associated with depressive symptoms (Q4 vs. Q1: OR= 0.51, 95% CI: 0.35, 0.75; Q4 vs. Q1: OR = 0.53, 95% CI: 0.38, 0.74, respectively). Conclusions: Higher dietary intake of flavonoid may be inversely associated with depressive symptoms. Further studies are needed to definitively confirm these observed associations. Full article
Open AccessArticle Flow Injection Analysis with Direct UV Detection Following Electric Field Driven Membrane Extraction
Molecules 2018, 23(5), 1000; https://doi.org/10.3390/molecules23051000
Received: 28 March 2018 / Revised: 17 April 2018 / Accepted: 20 April 2018 / Published: 25 April 2018
PDF Full-text (996 KB) | HTML Full-text | XML Full-text
Abstract
A method for on-line matrix elimination to enable selective quantification of ultraviolet absorbing analytes by a flow-injection analysis procedure is described. Selectivity is achieved by electric field driven extraction across a polymer inclusion membrane. The method was demonstrated on the example of the
[...] Read more.
A method for on-line matrix elimination to enable selective quantification of ultraviolet absorbing analytes by a flow-injection analysis procedure is described. Selectivity is achieved by electric field driven extraction across a polymer inclusion membrane. The method was demonstrated on the example of the determination of naproxen from spiked human urine. Membranes of 10 μm thickness were employed which consisted of 7.5 mg cellulose triacetate as base polymer, 5 mg of o-nitrophenyl octyl ether as plasticizer and 7.5 mg of Aliquat 336 as cationic carrier. Ten μL of sample was introduced into a continuous stream of background solution consisting of 100 µM aqueous NaClO4 with a flow rate of 2 μL/min while applying a voltage of 150 V to the extraction cell. The target ion was electrokinetically transported across the membrane and enriched in 1.5 μL of a stagnant acceptor solution. This was subsequently pumped past a flow-through UV detector for quantification. The method showed a linear range from 5 to 200 µM with a correlation coefficient of 0.9978 and a reproducibility of typically 7% (n = 8). The detection limit of the method for naproxen was 2 µM. Full article
(This article belongs to the Special Issue Green Analytical Chemistry)
Figures

Figure 1

Open AccessArticle Rapid Determination of the Geographical Origin of Chinese Red Peppers (Zanthoxylum Bungeanum Maxim.) Based on Sensory Characteristics and Chemometric Techniques
Molecules 2018, 23(5), 1001; https://doi.org/10.3390/molecules23051001
Received: 29 March 2018 / Revised: 19 April 2018 / Accepted: 21 April 2018 / Published: 24 April 2018
PDF Full-text (1427 KB) | HTML Full-text | XML Full-text
Abstract
In this paper, principal component analysis (PCA), linear discriminant analysis (LDAp, artificial neural networks (ANN), and support vector machine (SVM) were applied to discriminate the geographical origin of Chinese red peppers (Zanthoxylum bungeanum Maxim.). The models based on color, smell and taste
[...] Read more.
In this paper, principal component analysis (PCA), linear discriminant analysis (LDAp, artificial neural networks (ANN), and support vector machine (SVM) were applied to discriminate the geographical origin of Chinese red peppers (Zanthoxylum bungeanum Maxim.). The models based on color, smell and taste may discriminate quickly and effectively the geographical origin of Chinese red peppers from different regions, but the successful identification rates may vary with different kinds of parameters and chemometric methods. Among them, all models based on taste indexes showed an excellent ability to discriminate the geographical origin of Chinese red peppers with correct classifications of 100% for the training set and the 100% for test set. The present study provided a simple, efficient, inexpensive, practical and fast method to discriminate the geographical origin of Chinese red peppers from different regions, which was of great importance for both consumers and producers. Full article
Figures

Graphical abstract

Open AccessArticle Estimation of the Toxicity of Different Substituted Aromatic Compounds to the Aquatic Ciliate Tetrahymena pyriformis by QSAR Approach
Molecules 2018, 23(5), 1002; https://doi.org/10.3390/molecules23051002
Received: 19 March 2018 / Revised: 20 April 2018 / Accepted: 21 April 2018 / Published: 24 April 2018
PDF Full-text (1604 KB) | HTML Full-text | XML Full-text
Abstract
Nowadays, quantitative structure–activity relationship (QSAR) methods have been widely performed to predict the toxicity of compounds to organisms due to their simplicity, ease of implementation, and low hazards. In this study, to estimate the toxicities of substituted aromatic compounds to Tetrahymena pyriformis,
[...] Read more.
Nowadays, quantitative structure–activity relationship (QSAR) methods have been widely performed to predict the toxicity of compounds to organisms due to their simplicity, ease of implementation, and low hazards. In this study, to estimate the toxicities of substituted aromatic compounds to Tetrahymena pyriformis, the QSAR models were established by the multiple linear regression (MLR) and radial basis function neural network (RBFNN). Unlike other QSAR studies, according to the difference of functional groups (−NO2, −X), the whole dataset was divided into three groups and further modeled separately. The statistical characteristics for the models are obtained as the following: MLR: n = 36, R2 = 0.829, RMS (root mean square) = 0.192, RBFNN: n = 36, R2 = 0.843, RMS = 0.167 for Group 1; MLR: n = 60, R2 = 0.803, RMS = 0.222, RBFNN: n = 60, R2 = 0.821, RMS = 0.193 for Group 2; MLR: n = 31 R2 = 0.852, RMS = 0.192; RBFNN: n = 31, R2 = 0.885, RMS = 0.163 for Group 3, respectively. The results were within the acceptable range, and the models were found to be statistically robust with high external predictivity. Moreover, the models also gave some insight on those characteristics of the structures that most affect the toxicity. Full article
Figures

Graphical abstract

Open AccessArticle A Metabolism-Based Synergy for Total Coumarin Extract of Radix Angelicae Dahuricae and Ligustrazine on Migraine Treatment in Rats
Molecules 2018, 23(5), 1004; https://doi.org/10.3390/molecules23051004
Received: 21 March 2018 / Revised: 19 April 2018 / Accepted: 21 April 2018 / Published: 25 April 2018
PDF Full-text (1304 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Radix Angelicae dahuricae, containing coumarins, which might affect cytochrome P450 enzyme (CYP450) activity, has been co-administered with ligustrazine, a substrate of CYP450s, for the clinical treatment of migraine. However, whether a pharmacokinetic-based synergy exists between Radix Angelicae dahuricae and ligustrazine is still
[...] Read more.
Radix Angelicae dahuricae, containing coumarins, which might affect cytochrome P450 enzyme (CYP450) activity, has been co-administered with ligustrazine, a substrate of CYP450s, for the clinical treatment of migraine. However, whether a pharmacokinetic-based synergy exists between Radix Angelicae dahuricae and ligustrazine is still unknown. In this study, the total coumarin extract (TCE) of Radix Angelicae dahuricae (50 mg/kg, orally) reinforced the anti-migraine activity of ligustrazine by declining head scratching, plasma calcitonin gene-related peptide, and serum nitric oxide, as well as increasing plasma endothelin levels in rats (p < 0.05). Moreover, the pharmacokinetic study reflected that TCE potentiated the area under the concentration–time curve of ligustrazine and prolonged its mean retention time in rats (p < 0.05). Besides, the IC50 for TCE, imperatorin and isoimperatorin inhibiting ligustrazine metabolism were 5.0 ± 1.02, 1.35 ± 0.46, 4.81 ± 1.14 µg/mL in human liver microsomes, and 13.69 ± 1.11, 1.19 ± 1.09, 1.69 ± 1.17 µg/mL in rat liver microsomes, respectively. Moreover, imperatorin and isoimperatorin were CYP450s inhibitors with IC50 < 10 µM for CYP1A2, 2C9, 2D6, and 3A4. Therefore, this study concluded that Radix Angelicae dahuricae could increase ligustrazine plasma concentration and then reinforce its pharmacological effect by inhibiting its metabolism through interference with CYP450s. This could be one mechanism for the synergy between Radix Angelicae dahuricae and ligustrazine on migraine treatment. Full article
(This article belongs to the Section Natural Products Chemistry)
Figures

Graphical abstract

Open AccessArticle The Effect of PUFA-Rich Plant Oils and Bioactive Compounds Supplementation in Pig Diet on Color Parameters and Myoglobin Status in Long-Frozen Pork Meat
Molecules 2018, 23(5), 1005; https://doi.org/10.3390/molecules23051005
Received: 14 March 2018 / Revised: 12 April 2018 / Accepted: 19 April 2018 / Published: 25 April 2018
PDF Full-text (643 KB) | HTML Full-text | XML Full-text
Abstract
The study evaluated the effect of pig diet supplementation with rapeseed or linseed oil, and vitamin E or selenium, or both vitamin E and selenium on color parameters and myoglobin content of pork Semimembranosus muscle after long-term freezing storage during nine months. The
[...] Read more.
The study evaluated the effect of pig diet supplementation with rapeseed or linseed oil, and vitamin E or selenium, or both vitamin E and selenium on color parameters and myoglobin content of pork Semimembranosus muscle after long-term freezing storage during nine months. The influence of the type of the bioactive compounds added to pig diet on the content of myoglobin or oxymyoglobin, metmyoglobin and deoksymyoglobin in Semimembranosus m. was also assessed. The results indicate that the presence of oils rich in polyunsaturated fatty acids (PUFA) in pig diet improves the color of pork meat. Supplementation of dietary plant oils or dietary oils with antioxidants tended to increase significantly the concentration of oxymyoglobin and decrease the concentration of metmyoglobin in meat compared to the control group. The highest content of oxymyoglobin was observed in meat obtained from pigs fed diets with linseed oil. The best color scores (highest a* parameter) was noted for rapeseed oil group (with no addition of antioxidants). In conclusion, the addition of antioxidants to pigs’ forage supplemented with PUFA-rich oils is not recommended in order to improve color of long-term frozen pork. Full article
(This article belongs to the Section Natural Products Chemistry)
Figures

Figure 1

Open AccessArticle Synthesis and Fluorescence Properties of Structurally Characterized Heterobimetalic Cu(II)–Na(I) Bis(salamo)-Based Complex Bearing Square Planar, Square Pyramid and Triangular Prism Geometries of Metal Centers
Molecules 2018, 23(5), 1006; https://doi.org/10.3390/molecules23051006
Received: 27 March 2018 / Revised: 20 April 2018 / Accepted: 23 April 2018 / Published: 25 April 2018
PDF Full-text (2346 KB) | HTML Full-text | XML Full-text
Abstract
A novel heterotrinuclear complex [Cu2(L)Na(µ-NO3)]∙CH3OH∙CHCl3 derived from a symmetric bis(salamo)-type tetraoxime H4L having a naphthalenediol unit, was prepared and structurally characterized via means of elemental analyses, UV-Vis, FT-IR, fluorescent spectra and single-crystal
[...] Read more.
A novel heterotrinuclear complex [Cu2(L)Na(µ-NO3)]∙CH3OH∙CHCl3 derived from a symmetric bis(salamo)-type tetraoxime H4L having a naphthalenediol unit, was prepared and structurally characterized via means of elemental analyses, UV-Vis, FT-IR, fluorescent spectra and single-crystal X-ray diffraction. The heterobimetallic Cu(II)–Na(I) complex was acquired via the reaction of H4L with 2 equivalents of Cu(NO3)2·2H2O and 1 equivalent of NaOAc. Clearly, the heterotrinuclear Cu(II)–Na(I) complex has a 1:2:1 ligand-to-metal (Cu(II) and Na(I)) ratio. X-ray diffraction results exhibited the different geometric behaviors of the Na(I) and Cu(II) atoms in the heterotrinuclear complex; the both Cu(II) atoms are sited in the N2O2 coordination environments of fully deprotonated (L)4− unit. One Cu(II) atom (Cu1) is five-coordinated and possesses a geometry of slightly distorted square pyramid, while another Cu(II) atom (Cu2) is four-coordination possessing a square planar coordination geometry. Moreover, the Na(I) atom is in the O6 cavity and adopts seven-coordination with a geometry of slightly distorted single triangular prism. In addition, there are abundant supramolecular interactions in the Cu(II)–Na(I) complex. The fluorescence spectra showed the Cu(II)–Na(I) complex possesses a significant fluorescent quenching and exhibited a hypsochromic-shift compared with the ligand H4L. Full article
(This article belongs to the Special Issue Lumino and Fluorophores—Illuminating Science and Technology)
Figures

Figure 1

Open AccessArticle Poly(urethane-norbornene) Aerogels via Ring Opening Metathesis Polymerization of Dendritic Urethane-Norbornene Monomers: Structure-Property Relationships as a Function of an Aliphatic Versus an Aromatic Core and the Number of Peripheral Norbornene Moieties
Molecules 2018, 23(5), 1007; https://doi.org/10.3390/molecules23051007
Received: 2 March 2018 / Revised: 13 April 2018 / Accepted: 21 April 2018 / Published: 25 April 2018
PDF Full-text (5795 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We report the synthesis and characterization of synthetic polymer aerogels based on dendritic-type urethane-norbornene monomers. The core of those monomers is based either on an aromatic/rigid (TIPM/Desmodur RE), or an aliphatic/flexible (Desmodur N3300) triisocyanate. The terminal norbornene groups (three at the tip of
[...] Read more.
We report the synthesis and characterization of synthetic polymer aerogels based on dendritic-type urethane-norbornene monomers. The core of those monomers is based either on an aromatic/rigid (TIPM/Desmodur RE), or an aliphatic/flexible (Desmodur N3300) triisocyanate. The terminal norbornene groups (three at the tip of each of the three branches) were polymerized via ROMP using the inexpensive 1st generation Grubbs catalyst. The polymerization/gelation conditions were optimized by varying the amount of the catalyst. The resulting wet-gels were dried either from pentane under ambient pressure at 50 °C, or from t-butanol via freeze-drying, or by using supercritical fluid (SCF) CO2. Monomers were characterized with high resolution mass spectrometry (HRMS), 1H- and solid-state 13C-NMR. Aerogels were characterized with ATR-FTIR and solid-state 13C-NMR. The porous network was probed with N2-sorption and SEM. The thermal stability of monomers and aerogels was studied with TGA, which also provides evidence for the number of norbornene groups that reacted via ROMP. At low densities (<0.1 g cm−3) all aerogels were highly porous (porosity > 90%), mostly macroporous materials; aerogels based on the aliphatic/flexible core were fragile, whereas aerogels containing the aromatic/rigid core were plastic, and at even lower densities (0.03 g cm−3) foamy. At higher densities (0.2–0.7 g cm−3) all materials were stiff, strong, and hard. At low monomer concentrations all aerogels consisted of discrete primary particles that formed spherical secondary aggregates. At higher monomer concentrations the structure consisted of fused particles with the size of the previous secondary aggregates, due to the low solubility of the developing polymer, which phase-separated and formed a primary particle network. Same-size fused aggregates were observed for both aliphatic and aromatic triisocyanate-derived aerogels, leading to the conclusion that it is not the aliphatic or aromatic core that determines phase separation, but rather the solubility of the polymeric backbone (polynorbornene) that is in both cases the same. The material properties were compared to those of analogous aerogels bearing only one norbornene moiety at the tip of each branch deriving from the same cores. Full article
(This article belongs to the Special Issue Organometallic Catalysis in Organic Synthesis)
Figures

Graphical abstract

Open AccessArticle Rapid Determination of Chlorophyll and Pheophytin in Green Tea Using Fourier Transform Infrared Spectroscopy
Molecules 2018, 23(5), 1010; https://doi.org/10.3390/molecules23051010
Received: 30 March 2018 / Revised: 16 April 2018 / Accepted: 20 April 2018 / Published: 26 April 2018
PDF Full-text (3036 KB) | HTML Full-text | XML Full-text
Abstract
The chlorophyll, pheophytin, and their proportions are critical factors to evaluate the sensory quality of green tea. This research aims to establish an effective method to determine the quantification of chlorophyll and pheophytin in green tea, based on Fourier transform infrared (FT–IR) spectroscopy.
[...] Read more.
The chlorophyll, pheophytin, and their proportions are critical factors to evaluate the sensory quality of green tea. This research aims to establish an effective method to determine the quantification of chlorophyll and pheophytin in green tea, based on Fourier transform infrared (FT–IR) spectroscopy. First, five brands of tea were collected for spectral acquisition, and the chlorophyll and pheophytin were measured using the reference method. Then, a relation between these two pigments and FT–IR spectroscopy were developed based on chemometrics. Additionally, the characteristic IR wavenumbers of these pigments were extracted and proved to be effective for a quantitative determination. Successively, non-linear models were also built based on these characteristic wavenumbers, obtaining coefficients of determination of 0.87, 0.80, 0.85 and 0.89; and relative predictive deviations of 2.77, 2.62, 2.26 and 3.07 for the four pigments, respectively. These results demonstrate the feasibility of FT–IR spectroscopy for the determination of chlorophyll and pheophytin. Full article
(This article belongs to the Special Issue Green Analytical Chemistry)
Figures

Figure 1

Open AccessArticle Effects of 200 Gy 60Co-γ Radiation on the Regulation of Antioxidant Enzymes, Hsp70 Genes, and Serum Molecules of Plutella xylostella (Linnaeus)
Molecules 2018, 23(5), 1011; https://doi.org/10.3390/molecules23051011
Received: 18 March 2018 / Revised: 19 April 2018 / Accepted: 23 April 2018 / Published: 26 April 2018
PDF Full-text (1153 KB) | HTML Full-text | XML Full-text
Abstract
The diamondback moth, Plutella xylostella (Linnaeus), is one of the notorious pests causing substantial loses to many cruciferous vegetables across the nations. The effects of 60Co-γ radiation on physiology of P. xylostella were investigated and the results displayed that 200 Gy irradiation
[...] Read more.
The diamondback moth, Plutella xylostella (Linnaeus), is one of the notorious pests causing substantial loses to many cruciferous vegetables across the nations. The effects of 60Co-γ radiation on physiology of P. xylostella were investigated and the results displayed that 200 Gy irradiation significantly alters the antioxidant enzyme regulation in six-day-old male pupae of P. xylostella. First, in our research, we detected Oxidase system and stress response mechanism of irradiated pupae, the results displayed that 200 Gy irradiation significantly alters the antioxidant enzyme regulation in six-day-old male pupae of P. xylostella. The levels of superoxide dismutase (SOD) and catalase (CAT) were increased significantly in contrast the level of peroxidase (POD) and glutathione S-transferase (GST) were decreased in 12–24 h post-treatment. The heat shock proteins (Hsps) gene expression level was significant increasing, maximum > 2-folds upregulation of genes were observed in peak. However, they also had a trend of gradual recovery with development. Second, we detected the testis lactate dehydrogenase (LDH) and acid phosphatase (ACP) activity found that in male adults testis they increased significantly than control during its development. Thus the present research investigation highlights that the 60Co-γ radiation treatments alters the physiological development of diamondback moth. The results showed that 200 Gy dosage resulted in stress damage to the body and reproductive system of the diamondback moth. Full article
Figures

Figure 1

Open AccessArticle Determination of Arsenic Species in Ophiocordyceps sinensis from Major Habitats in China by HPLC-ICP-MS and the Edible Hazard Assessment
Molecules 2018, 23(5), 1012; https://doi.org/10.3390/molecules23051012
Received: 2 April 2018 / Revised: 21 April 2018 / Accepted: 24 April 2018 / Published: 26 April 2018
PDF Full-text (4285 KB) | HTML Full-text | XML Full-text
Abstract
This study sought to determine the concentration and distribution of arsenic (As) species in Ophiocordyceps sinensis (O. sinensis), and to assess its edible hazard for long term consumption. The total arsenic concentrations, measured through inductively coupled plasma mass spectrometry (ICP-MS), ranged
[...] Read more.
This study sought to determine the concentration and distribution of arsenic (As) species in Ophiocordyceps sinensis (O. sinensis), and to assess its edible hazard for long term consumption. The total arsenic concentrations, measured through inductively coupled plasma mass spectrometry (ICP-MS), ranged from 4.00 mg/kg to 5.25 mg/kg. As determined by HPLC-ICP-MS, the most concerning arsenic species—AsB, MMAV, DMAV, AsV, and AsШ—were either not detected (MMAV and DMAV) or were detected as minor As species (AsB: 1.4–2.9%; AsV: 1.3–3.2%, and AsШ: 4.1–6.0%). The major components were a cluster of unknown organic As (uAs) compounds with AsШ, which accounted for 91.7–94.0% of the As content. Based on the H2O2 test and the chromatography behavior, it can be inferred that, the uAs might not be toxic organic As. Estimated daily intake (EDI), hazard quotient (HQ), and cancer risk (CR) caused by the total As content; the sum of inorganic As (iAs) and uAs, namely i+uAs; and iAs exposure from long term O. sinensis consumption were calculated and evaluated through equations from the US Environmental Protection Agency and the uncertainties were analyzed by Monte-Carlo Simulation (MCS). EDItotal As and EDIi+uAs are approximately ten times more than EDIiAs; HQtotal As and HQi+uAs > 1 while HQiAs < 1; and CRtotal As and CRi+uAs > 1 × 10−4 while CRiAs < 1 × 10−4. Thus, if the uAs is non-toxic, there is no particular risk to local consumers and the carcinogenic risk is acceptable for consumption of O. sinensis because the concentration of toxic iAs is very low. Full article
(This article belongs to the Section Analytical Chemistry)
Figures

Figure 1

Open AccessArticle Identification of Ophiocordyceps sinensis and Its Artificially Cultured Ophiocordyceps Mycelia by Ultra-Performance Liquid Chromatography/Orbitrap Fusion Mass Spectrometry and Chemometrics
Molecules 2018, 23(5), 1013; https://doi.org/10.3390/molecules23051013
Received: 25 March 2018 / Revised: 18 April 2018 / Accepted: 19 April 2018 / Published: 26 April 2018
PDF Full-text (5143 KB) | HTML Full-text | XML Full-text
Abstract
Since the cost of Ophiocordyceps sinensis, an important fungal drug used in Chinese medicine, has increased dramatically, and the counterfeits may have adverse health effects, a rapid and precise marker using the peptide mass spectrometry identification system could significantly enhance the regulatory
[...] Read more.
Since the cost of Ophiocordyceps sinensis, an important fungal drug used in Chinese medicine, has increased dramatically, and the counterfeits may have adverse health effects, a rapid and precise marker using the peptide mass spectrometry identification system could significantly enhance the regulatory capacity. In this study, we determined the marker peptides in the digested mixtures of fungal proteins in wild O. sinensis fruiting bodies and various commercially available mycelium fermented powders using ultra-performance liquid chromatography/Orbitrap Fusion mass spectrometry coupled with chemometrics. The results indicated the following marker peptides: TLLEAIDSIEPPK (m/z 713.39) was identified in the wild O. sinensis fruiting body, AVLSDAITLVR (m/z 579.34) was detected in the fermented O. sinensis mycelium powder, FAELLEK (m/z 849.47) was found in the fermented Ophiocordyceps mycelium powder, LESVVTSFTK (m/z 555.80) was discovered in the artificial Ophiocordyceps mycelium powder, and VPSSAVLR (m/z 414.75) was observed in O. mortierella mycelium powder. In order to verify the specificity and applicability of the method, the five marker peptides were synthesized and tested on all samples. All in all, to the best of our knowledge, this is the first time that mass spectrometry has been employed to detect the marker peptides of O.sinensis and its related products. Full article
(This article belongs to the Special Issue Mass Spectrometric Proteomics)
Figures

Figure 1a

Open AccessArticle Comparison of Serum Metabolite Changes of Radiated Mice Administered with Panax quinquefolium from Different Cultivation Regions Using UPLC-Q/TOF-MS Based Metabolomic Approach
Molecules 2018, 23(5), 1014; https://doi.org/10.3390/molecules23051014
Received: 10 April 2018 / Revised: 22 April 2018 / Accepted: 24 April 2018 / Published: 26 April 2018
PDF Full-text (4065 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chemometric analysis of bioactive compounds revealed that American ginsengs (AGs) from different cultivation regions of China had a difference in quality, which indicates their possible pharmacological difference. A UPLC-Q/TOF-MS-based untargeted metabolomic approach was used to uncover serum metabolite changes in radiated mice pre-administered
[...] Read more.
Chemometric analysis of bioactive compounds revealed that American ginsengs (AGs) from different cultivation regions of China had a difference in quality, which indicates their possible pharmacological difference. A UPLC-Q/TOF-MS-based untargeted metabolomic approach was used to uncover serum metabolite changes in radiated mice pre-administered with AG root decoctions from seven cultivation regions and to further assess their quality difference. OPLS-DA revealed that 51 metabolites (ESI) and 110 (ESI+) were differentially expressed in sera between the control and the radiated model mice. Heatmap analysis further revealed that AG could not reverse most of these radiation-altered metabolites, which indicates dietary supplement of AG before cobalt radiation had the weak potential to mediate serum metabolites that were altered by the sub-lethal high dose radiation. In addition, 83 (ESI) and 244 (ESI+) AG altered metabolites were detected in radiated mice under radiation exposure. Both OPLS-DA on serum metabolomes and heatmap analysis on discriminant metabolites showed that AGs from different cultivation regions differentially influenced metabolic alterations in radiated mice, which indicates AGs from different cultivation regions showed the pharmacological difference in modulation of metabolite changes. AGs from Shandong, Shanxi, and Beijing provinces had more similar pharmacological effects than AGs from USA, Canada, Jilin, and Heilongjiang. Finally, 28 important potential biomarkers were annotated and assigned onto three metabolic pathways including lipid, amino acid, and energy metabolisms. Full article
Figures

Figure 1

Open AccessArticle Comparative Analysis of the Complete Chloroplast Genomes of Four Aconitum Medicinal Species
Molecules 2018, 23(5), 1015; https://doi.org/10.3390/molecules23051015
Received: 8 April 2018 / Revised: 23 April 2018 / Accepted: 24 April 2018 / Published: 26 April 2018
PDF Full-text (7913 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Aconitum (Ranunculaceae) consists of approximately 400 species distributed in the temperate regions of the northern hemisphere. Many species are well-known herbs, mainly used for analgesia and anti-inflammatory purposes. This genus is well represented in China and has gained widespread attention for its toxicity
[...] Read more.
Aconitum (Ranunculaceae) consists of approximately 400 species distributed in the temperate regions of the northern hemisphere. Many species are well-known herbs, mainly used for analgesia and anti-inflammatory purposes. This genus is well represented in China and has gained widespread attention for its toxicity and detoxification properties. In southwestern China, several Aconitum species, called ‘Dula’ in the Yi Nationality, were often used to control the poisonous effects of other Aconitum plants. In this study, the complete chloroplast (cp) genomes of these species were determined for the first time through Illumina paired-end sequencing. Our results indicate that their cp genomes ranged from 151,214 bp (A. episcopale) to 155,769 bp (A. delavayi) in length. A total of 111–112 unique genes were identified, including 85 protein-coding genes, 36–37 tRNA genes and eight ribosomal RNA genes (rRNA). We also analyzed codon usage, IR expansion or contraction and simple sequence repeats in the cp genomes. Eight variable regions were identified and these may potentially be useful as specific DNA barcodes for species identification of Aconitum. Phylogenetic analysis revealed that all five studied species formed a new clade and were resolved with 100% bootstrap support. This study will provide genomic resources and potential plastid markers for DNA barcoding, further taxonomy and germplasm exploration of Aconitum. Full article
(This article belongs to the Section Molecular Diversity)
Figures

Figure 1

Open AccessArticle Regularized Multi-View Subspace Clustering for Common Modules Across Cancer Stages
Molecules 2018, 23(5), 1016; https://doi.org/10.3390/molecules23051016
Received: 4 April 2018 / Revised: 23 April 2018 / Accepted: 23 April 2018 / Published: 26 April 2018
PDF Full-text (336 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Discovering the common modules that are co-expressed across various stages can lead to an improved understanding of the underlying molecular mechanisms of cancers. There is a shortage of efficient tools for integrative analysis of gene expression and protein interaction networks for discovering common
[...] Read more.
Discovering the common modules that are co-expressed across various stages can lead to an improved understanding of the underlying molecular mechanisms of cancers. There is a shortage of efficient tools for integrative analysis of gene expression and protein interaction networks for discovering common modules associated with cancer progression. To address this issue, we propose a novel regularized multi-view subspace clustering (rMV-spc) algorithm to obtain a representation matrix for each stage and a joint representation matrix that balances the agreement across various stages. To avoid the heterogeneity of data, the protein interaction network is incorporated into the objective of rMV-spc via regularization. Based on the interior point algorithm, we solve the optimization problem to obtain the common modules. By using artificial networks, we demonstrate that the proposed algorithm outperforms state-of-the-art methods in terms of accuracy. Furthermore, the rMV-spc discovers common modules in breast cancer networks based on the breast data, and these modules serve as biomarkers to predict stages of breast cancer. The proposed model and algorithm effectively integrate heterogeneous data for dynamic modules. Full article
(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)
Figures

Figure 1

Open AccessArticle Effect of Hydrophobic Polypeptide Length on Performances of Thermo-Sensitive Hydrogels
Molecules 2018, 23(5), 1017; https://doi.org/10.3390/molecules23051017
Received: 12 April 2018 / Revised: 19 April 2018 / Accepted: 21 April 2018 / Published: 26 April 2018
PDF Full-text (1997 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Thermosensitive gels are commonly used as drug carriers in medical fields, mainly due to their convenient processing and easy functionalization. However, their overall performance has been severely affected by their unsatisfying biocompatibility and biodegradability. To this end, we synthesized poly(l-alanine) (PLAla)-based
[...] Read more.
Thermosensitive gels are commonly used as drug carriers in medical fields, mainly due to their convenient processing and easy functionalization. However, their overall performance has been severely affected by their unsatisfying biocompatibility and biodegradability. To this end, we synthesized poly(l-alanine) (PLAla)-based thermosensitive hydrogels with different degrees of polymerization by ring-opening polymerization. The obtained mPEG45−PLAla copolymers showed distinct transition temperatures and degradation abilities. It was found that slight changes in the length of hydrophobic side groups had a decisive effect on the gelation behavior of the polypeptide hydrogel. Longer hydrophobic ends led to a lower gelation temperature of gel at the same concentration, which implied better gelation capability. The hydrogels showed rapid gelling, enhanced biocompatibility, and better degradability. Therefore, this thermosensitive hydrogel is a promising material for biomedical application. Full article
(This article belongs to the Special Issue Smart and Functional Polymers)
Figures

Figure 1

Open AccessArticle A Chemical Investigation of the Leaves of Morus alba L.
Molecules 2018, 23(5), 1018; https://doi.org/10.3390/molecules23051018
Received: 31 March 2018 / Revised: 21 April 2018 / Accepted: 24 April 2018 / Published: 26 April 2018
PDF Full-text (717 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The leaves of Morus alba L. are an important herbal medicine in Asia. The systematic isolation of the metabolites of the leaves of Morus alba L. was achieved using a combination of liquid chromatography techniques. The structures were elucidated by spectroscopic data analysis
[...] Read more.
The leaves of Morus alba L. are an important herbal medicine in Asia. The systematic isolation of the metabolites of the leaves of Morus alba L. was achieved using a combination of liquid chromatography techniques. The structures were elucidated by spectroscopic data analysis and the absolute configuration was determined based on electronic circular dichroism (ECD) spectroscopic data and hydrolysis experiments. Their biological activity was evaluated using different biological assays, such as the assessment of their capacity to inhibit the aldose reductase enzyme; the determination of their cytotoxic activity and the evaluation of their neuroprotective effects against the deprivation of serum or against the presence of nicouline. Chemical investigation of the leaves of Morus alba L. resulted in four new structures 14 and a known molecule 5. Compounds 2 and 5 inhibited aldose reductase with IC50 values of 4.33 μM and 6.0 μM compared with the potent AR inhibitor epalrestat (IC50 1.88 × 10−3 μM). Pretreatment with compound 3 decreased PC12 cell apoptosis subsequent serum deprivation condition and pretreatment with compound 5 decreased nicouline-induced PC12 cell apoptosis as compared with control cells (p < 0.001). Full article
Figures

Graphical abstract

Open AccessArticle Simultaneous Determination of Decursin, Decursinol Angelate, Nodakenin, and Decursinol of Angelica gigas Nakai in Human Plasma by UHPLC-MS/MS: Application to Pharmacokinetic Study
Molecules 2018, 23(5), 1019; https://doi.org/10.3390/molecules23051019
Received: 28 March 2018 / Revised: 20 April 2018 / Accepted: 23 April 2018 / Published: 26 April 2018
PDF Full-text (1834 KB) | HTML Full-text | XML Full-text
Abstract
Coumarins in Cham-dang-gwi, the dried root of Angelica gigas Nakai (AGN), possess pharmacological effects on anemia, pain, infection, and articular rheumatism. The AGN root containes decursin (D), decursinol angelate (DA), nodakenin, and decursinol (DOH), a major metabolite of D and DA. The aim
[...] Read more.
Coumarins in Cham-dang-gwi, the dried root of Angelica gigas Nakai (AGN), possess pharmacological effects on anemia, pain, infection, and articular rheumatism. The AGN root containes decursin (D), decursinol angelate (DA), nodakenin, and decursinol (DOH), a major metabolite of D and DA. The aim of this study was to develop a simultaneous determination method for these four coumarins in human plasma using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Chromatographic separation was performed on dual columns (Kinetex® C18 column and Capcell core C18 column) with mobile phase consisting of water and acetonitrile at a flow rate of 0.3 mL/min using gradient elution. Multiple reaction monitoring was operated in positive ion mode with precursors to product ion transition values of m/z 328.9→228.8, 328.9→228.9, 409.4→248.8, and 246.8→212.9 to measure D, DA, nodakenin, and DOH, respectively. Linear calibration curves were fitted over concentration range of 0.05–50 ng/mL for these four components, with correlation coefficient greater than 0.995. Inter- and intra-day accuracies were between 90.60% and 108.24%. These precisions were within 11.19% for all components. The established method was then applied to a pharmacokinetic study for the four coumarins after usual dosing in Korean subjects. Full article
(This article belongs to the Special Issue Qualitative and Quantitative Analysis of Bioactive Natural Products)
Figures

Figure 1

Open AccessArticle Anticancer Profiling for Coumarins and Related O-Naphthoquinones from Mansonia gagei against Solid Tumor Cells In Vitro
Molecules 2018, 23(5), 1020; https://doi.org/10.3390/molecules23051020
Received: 29 March 2018 / Revised: 17 April 2018 / Accepted: 21 April 2018 / Published: 26 April 2018
PDF Full-text (1257 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Napthoquinones and coumarins are naturally occurring compounds with potential anticancer activity. In the current study, two O-naphthoquinons (mansonone-G and mansonone-N) and six coumarins (mansorin-A, mansorin-B, mansorin-C, mansorins-I, mansorin-II, and mansorin-III) were isolated from the heartwood of Mansonia gagei family Sterculariaceae. Isolated compounds
[...] Read more.
Napthoquinones and coumarins are naturally occurring compounds with potential anticancer activity. In the current study, two O-naphthoquinons (mansonone-G and mansonone-N) and six coumarins (mansorin-A, mansorin-B, mansorin-C, mansorins-I, mansorin-II, and mansorin-III) were isolated from the heartwood of Mansonia gagei family Sterculariaceae. Isolated compounds were examined for their potential anticancer activity against breast (MCF-7), cervix (HeLa), colorectal (HCT-116) and liver (HepG2) cancer cells using Sulfarhodamine-B (SRB) assay. Mansorin-II and mansorin-III showed relatively promising cytotoxic profile in all cell lines under investigation with inhibitory concentrations (IC50s) in the range of 0.74 µM to 36 µM and 3.95 µM to 35.3 µM, respectively. In addition, mansorin-B, mansorin-C, mansorin-II and mansorin-III significantly increased cellular entrapment of the P-glycoprotein (P-gp) substrate, doxorubicin, in colorectal cancer cells expressing the P-gp pump. The inhibitory effect of the isolated compounds on P-gp pump was examined using human recombinant P-gp molecules attached to ATPase subunit. Mansorin-B and mansonone-G were found to inhibit the P-gp attached ATPase subunit. On the other hand, mansorin-C, mansorin-III and mansorin-II inhibited P-gp pump via dual action (P-gp related ATPase subunit inhibition and P-gp substrate binding site occupation). However, mansorin II was examined for its potential chemomodulatory effect to paclitaxel (PTX) against colorectal cancer cells (HCT-116 and CaCo-2). Mansorin-II significantly reduced the IC50 of PTX in HCT-116 cells from 27.9 ± 10.2 nM to 5.1 ± 1.9 nM (synergism with combination index of 0.44). Additionally, Mansorin-II significantly reduced the IC50 of PTX in CaCo-2 cells from 2.1 ± 0.8 µM to 0.13 ± 0.03 µM (synergism with combination index of 0.18). Furthermore, cell cycle analysis was studied after combination of mansorin-II with paclitaxel using DNA flow cytometry analysis. Synergism of mansorin-II and PTX was reflected in increasing apoptotic cell population in both HCT-116 and CaCo-2 cells compared to PTX treatment alone. Combination of mansorin-II with PTX in CaCo-2 cells significantly increased the cell population in G2/M phase (from 2.9 ± 0.3% to 7.7 ± 0.8%) with reciprocal decrease in G0/G1 cell fraction from 52.1 ± 1.1% to 45.5 ± 1.0%. Similarly in HCT-116 cells, mansorin-II with PTX significantly increased the cell population in G2/M phase (from 33.4 ± 2.8% to 37.6 ± 1.3%) with reciprocal decrease in the S-phase cell population from 22.8 ± 1.7% to 20.2 ± 0.8%. In conclusion, mansorin-II synergizes the anticancer effect of paclitaxel in colorectal cancer cells, which might be partially attributed to enhancing its cellular entrapment via inhibiting P-gp efflux pump. Full article
(This article belongs to the collection Bioactive Compounds)
Figures

Figure 1

Open AccessArticle Effects of Essential Oils from Zingiberaceae Plants on Root-Rot Disease of Panax notoginseng
Molecules 2018, 23(5), 1021; https://doi.org/10.3390/molecules23051021
Received: 6 April 2018 / Revised: 20 April 2018 / Accepted: 24 April 2018 / Published: 26 April 2018
PDF Full-text (2992 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Replanting obstacles of Panax notoginseng caused by complex factors, including pathogens, have received great attention. In this study, essential oils (EOs) from either Alpinia officinarum Hance or Amomum tsao-ko (Zingiberaceae) were found to inhibit the growth of P. notoginseng-associated pathogenic fungi in
[...] Read more.
Replanting obstacles of Panax notoginseng caused by complex factors, including pathogens, have received great attention. In this study, essential oils (EOs) from either Alpinia officinarum Hance or Amomum tsao-ko (Zingiberaceae) were found to inhibit the growth of P. notoginseng-associated pathogenic fungi in vitro. Subsequent GC-MS analysis revealed the chemical profiles of two plant derived EOs. Linalool and eucalyptol were found to be abundant in the EOs and tested for their antifungal activities. In addition, the synergistic effects of A. tsao-ko EOs and hymexazol were also examined. These findings suggested that Zingiberaceae EOs might be a good source for developing new green natural pesticides fighting against root-rot of P. notoginseng. Full article
Figures

Figure 1a

Open AccessArticle LiGe(SiMe3)3: A New Substituent for the Synthesis of Metalloid Tin Clusters from Metastable Sn(I) Halide Solutions
Molecules 2018, 23(5), 1022; https://doi.org/10.3390/molecules23051022
Received: 28 March 2018 / Revised: 23 April 2018 / Accepted: 23 April 2018 / Published: 26 April 2018
PDF Full-text (4300 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The most fruitful synthetic route to metalloid tin clusters applies the disproportionation reaction of metastable Sn(I) halide solutions, whereby Si(SiMe3)3 is mostly used as the stabilizing substituent. Here, we describe the synthesis and application of the slightly modified substituent Ge(SiMe
[...] Read more.
The most fruitful synthetic route to metalloid tin clusters applies the disproportionation reaction of metastable Sn(I) halide solutions, whereby Si(SiMe3)3 is mostly used as the stabilizing substituent. Here, we describe the synthesis and application of the slightly modified substituent Ge(SiMe3)3, which can be used for the synthesis of metalloid tin clusters to give the neutral cluster Sn10[Ge(SiMe3)3]6 as well as the charged clusters {Sn10[Ge(SiMe3)3]5} and {Sn10[Ge(SiMe3)3]4}2−. The obtained metalloid clusters are structurally similar to their Si(SiMe3)3 derivatives. However, differences with respect to the stability in solution are observed. Additionally, a different electronic situation for the tin atoms is realized as shown by 119mSn Mössbauer spectroscopy, giving further insight into the different kinds of tin atoms within the metalloid cluster {Sn10[Ge(SiMe3)3]4}2−. The synthesis of diverse derivatives gives the opportunity to check the influence of the substituent for further investigations of metalloid tin cluster compounds. Full article
(This article belongs to the Special Issue Main Group Elements in Synthesis)
Figures

Graphical abstract

Open AccessArticle Synthesis and Antibacterial Activity of New Thiazolidine-2,4-dione-Based Chlorophenylthiosemicarbazone Hybrids
Molecules 2018, 23(5), 1023; https://doi.org/10.3390/molecules23051023
Received: 28 March 2018 / Revised: 13 April 2018 / Accepted: 24 April 2018 / Published: 26 April 2018
PDF Full-text (1906 KB) | HTML Full-text | XML Full-text
Abstract
Series of new thiazolidine-2,4-dione-based chlorophenylthiosemicarbazone hybrids (1740) were synthesized by the reaction of condensation chlorophenylthiosemicarbazides with formylphenyl 2-(2,4-dioxothiazolidin-5-yl/ylidene)acetates. New compounds were tested on reference strains of Gram-positive and Gram-negative bacteria. The antibacterial activity of target compounds was determined by
[...] Read more.
Series of new thiazolidine-2,4-dione-based chlorophenylthiosemicarbazone hybrids (1740) were synthesized by the reaction of condensation chlorophenylthiosemicarbazides with formylphenyl 2-(2,4-dioxothiazolidin-5-yl/ylidene)acetates. New compounds were tested on reference strains of Gram-positive and Gram-negative bacteria. The antibacterial activity of target compounds was determined by broth dilution method. Most active compounds possess minimum inhibitory concentration (MIC) = 3.91 mg/L. These compounds were non-toxic at concentrations close to their antibacterial effect. The antibacterial activity of some compounds was similar to or higher than the activity of used reference drugs such as oxacillin and cefuroxime. The structure–activity relationships (SARs) analysis collectively suggests that at least two different molecular mechanisms of their antibacterial activity should be expected. Full article
(This article belongs to the Section Organic Chemistry)
Figures

Figure 1

Open AccessArticle Synthesis and Pharmacological Studies of Unprecedented Fused Pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b][1,3,4]thiadiazine Derivatives
Molecules 2018, 23(5), 1024; https://doi.org/10.3390/molecules23051024
Received: 22 March 2018 / Revised: 23 April 2018 / Accepted: 23 April 2018 / Published: 27 April 2018
PDF Full-text (3418 KB) | HTML Full-text | XML Full-text
Abstract
A novel fused system with three or four fused rings—pyridazino[3′,4′:5,6][1,2,4]triazino[4,3-b][1,2,4,5]tetrazine and pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b]pyrimido[4,5-e][1,3,4]thiadiazine was obtained from the starting materials 4(6H)-amino-3-hydrazino-7-(2-thienyl)pyridazino[3,4-e][1,2,4]-triazine 2 and 9-amino-3-(2-thienyl)-2H,8H-pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b][1,3,4]thiadiazine-8-carbonitrile 12. Each of the
[...] Read more.
A novel fused system with three or four fused rings—pyridazino[3′,4′:5,6][1,2,4]triazino[4,3-b][1,2,4,5]tetrazine and pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b]pyrimido[4,5-e][1,3,4]thiadiazine was obtained from the starting materials 4(6H)-amino-3-hydrazino-7-(2-thienyl)pyridazino[3,4-e][1,2,4]-triazine 2 and 9-amino-3-(2-thienyl)-2H,8H-pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b][1,3,4]thiadiazine-8-carbonitrile 12. Each of the starting compounds was subjected to a number of cyclization reactions to obtain a series of new heterocyclic fused systems, 310 and 1323, via bifunctional reagents. Some of the synthesized compounds were screened against three cell lines including HepG2, HCT-116 and MCF-7 to discover their anticancer activity. The synthesized compounds were characterized depending on their elemental analyses and spectral data. Full article
(This article belongs to the collection Heterocyclic Compounds)
Figures

Figure 1

Open AccessFeature PaperArticle Preferential and Increased Uptake of Hydroxyl-Terminated PAMAM Dendrimers by Activated Microglia in Rabbit Brain Mixed Glial Culture
Molecules 2018, 23(5), 1025; https://doi.org/10.3390/molecules23051025
Received: 20 March 2018 / Revised: 18 April 2018 / Accepted: 20 April 2018 / Published: 27 April 2018
PDF Full-text (5447 KB) | HTML Full-text | XML Full-text
Abstract
Polyamidoamine (PAMAM) dendrimers are multifunctional nanoparticles with tunable physicochemical features, making them promising candidates for targeted drug delivery in the central nervous system (CNS). Systemically administered dendrimers have been shown to localize in activated glial cells, which mediate neuroinflammation in the CNS. These
[...] Read more.
Polyamidoamine (PAMAM) dendrimers are multifunctional nanoparticles with tunable physicochemical features, making them promising candidates for targeted drug delivery in the central nervous system (CNS). Systemically administered dendrimers have been shown to localize in activated glial cells, which mediate neuroinflammation in the CNS. These dendrimers delivered drugs specifically to activated microglia, producing significant neurological improvements in multiple brain injury models, including in a neonatal rabbit model of cerebral palsy. To gain further insight into the mechanism of dendrimer cell uptake, we utilized an in vitro model of primary glial cells isolated from newborn rabbits to assess the differences in hydroxyl-terminated generation 4 PAMAM dendrimer (D4-OH) uptake by activated and non-activated glial cells. We used fluorescently-labelled D4-OH (D-Cy5) as a tool for investigating the mechanism of dendrimer uptake. D4-OH PAMAM dendrimer uptake was determined by fluorescence quantification using confocal microscopy and flow cytometry. Our results indicate that although microglial cells in the mixed cell population demonstrate early uptake of dendrimers in this in vitro system, activated microglia take up more dendrimer compared to resting microglia. Astrocytes showed delayed and limited uptake. We also illustrated the differences in mechanism of uptake between resting and activated microglia using different pathway inhibitors. Both resting and activated microglia primarily employed endocytotic pathways, which are enhanced in activated microglial cells. Additionally, we demonstrated that hydroxyl terminated dendrimers are taken up by primary microglia using other mechanisms including pinocytosis, caveolae, and aquaporin channels for dendrimer uptake. Full article
Figures

Figure 1

Open AccessArticle Tunable Polarity Carbon Fibers, a Holistic Approach to Environmental Protection
Molecules 2018, 23(5), 1026; https://doi.org/10.3390/molecules23051026
Received: 10 April 2018 / Revised: 19 April 2018 / Accepted: 24 April 2018 / Published: 27 April 2018
PDF Full-text (2373 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The pollution of environmental resources is an issue of social concern worldwide. Chemistry is essential for the design of decontamination strategies and analytical approaches to detect and monitor the contamination. Sorptive materials are usually required in both approaches and green synthesis should be
[...] Read more.
The pollution of environmental resources is an issue of social concern worldwide. Chemistry is essential for the design of decontamination strategies and analytical approaches to detect and monitor the contamination. Sorptive materials are usually required in both approaches and green synthesis should be used to minimize their own environmental impact. Carbon fibers (CFs) obtained by the pyrolysis of natural cellulose-rich materials fulfill these requirements. In this article, thirty CFs obtained under different conditions are chemically characterized and their sorption ability towards selected pollutants, covering a wide range of polarity, is evaluated. This study provides more profound knowledge related to the polarity of these materials, their interactions with chemical substances and allows the prediction of more appropriate materials (pyrolysis temperature and time) in order to remove the given pollutant. Furthermore, the use of CFs as sorptive materials for the extraction of contaminants from water samples to assist with their instrumental detection is outlined. In this sense, the use of CFs and gas chromatography with mass spectrometric detection allows the detection of selected pollutants in the low ng/mL range. Thus, this article provides an integrated approach to the potential of CFs for environmental protection. Full article
(This article belongs to the Special Issue Environmental Nanotechnology)
Figures

Graphical abstract

Open AccessArticle Profiling of Heterobranchia Sea Slugs from Portuguese Coastal Waters as Producers of Anti-Cancer and Anti-Inflammatory Agents
Molecules 2018, 23(5), 1027; https://doi.org/10.3390/molecules23051027
Received: 15 March 2018 / Revised: 24 April 2018 / Accepted: 25 April 2018 / Published: 27 April 2018
PDF Full-text (2042 KB) | HTML Full-text | XML Full-text
Abstract
Bioprospection of marine invertebrates has been predominantly biased by the biological richness of tropical regions, thus neglecting macro-organisms from temperate ecosystems. Species that were not the object of studies on their biochemical composition include the Heterobranchia gastropods Armina maculata, Armina tigrina and
[...] Read more.
Bioprospection of marine invertebrates has been predominantly biased by the biological richness of tropical regions, thus neglecting macro-organisms from temperate ecosystems. Species that were not the object of studies on their biochemical composition include the Heterobranchia gastropods Armina maculata, Armina tigrina and Aglaja tricolorata, inhabitants of the Portuguese Atlantic coastal waters. Here, we present for the first time the fatty acid profile of neutral lipids and homarine content of these three species. Qualitative and quantitative differences in the fatty acid content among species points to the existence of a fatty acid profile of neutral lipids, particularly of each genus. The results from cytotoxicity assays, using the acetonic extracts of the gastropods on human gastric adenocarcinoma (AGS) and human lung adenocarcinoma (A549) cell lines, revealed a pronounced cytotoxic effect of the A. tigrina extract on both cell lines (IC50 values of 68.75 and 69.77 μg mL−1 for AGS and A549, respectively). It is worth noting the significant reduction of NO levels in LPS-challenged RAW 264.7 macrophages exposed to A. tricolorata extract, at concentrations as low as 125 μg mL−1. Full article
Figures

Figure 1

Open AccessArticle ParaBTM: A Parallel Processing Framework for Biomedical Text Mining on Supercomputers
Molecules 2018, 23(5), 1028; https://doi.org/10.3390/molecules23051028
Received: 9 April 2018 / Revised: 22 April 2018 / Accepted: 25 April 2018 / Published: 27 April 2018
PDF Full-text (4270 KB) | HTML Full-text | XML Full-text
Abstract
A prevailing way of extracting valuable information from biomedical literature is to apply text mining methods on unstructured texts. However, the massive amount of literature that needs to be analyzed poses a big data challenge to the processing efficiency of text mining. In
[...] Read more.
A prevailing way of extracting valuable information from biomedical literature is to apply text mining methods on unstructured texts. However, the massive amount of literature that needs to be analyzed poses a big data challenge to the processing efficiency of text mining. In this paper, we address this challenge by introducing parallel processing on a supercomputer. We developed paraBTM, a runnable framework that enables parallel text mining on the Tianhe-2 supercomputer. It employs a low-cost yet effective load balancing strategy to maximize the efficiency of parallel processing. We evaluated the performance of paraBTM on several datasets, utilizing three types of named entity recognition tasks as demonstration. Results show that, in most cases, the processing efficiency can be greatly improved with parallel processing, and the proposed load balancing strategy is simple and effective. In addition, our framework can be readily applied to other tasks of biomedical text mining besides NER. Full article
(This article belongs to the Special Issue Molecular Computing and Bioinformatics)
Figures

Graphical abstract

Open AccessArticle Multi-Response Optimization of Ultrasonic Assisted Enzymatic Extraction Followed by Macroporous Resin Purification for Maximal Recovery of Flavonoids and Ginkgolides from Waste Ginkgo biloba Fallen Leaves
Molecules 2018, 23(5), 1029; https://doi.org/10.3390/molecules23051029
Received: 16 March 2018 / Revised: 12 April 2018 / Accepted: 19 April 2018 / Published: 27 April 2018
PDF Full-text (4087 KB) | HTML Full-text | XML Full-text
Abstract
In the present study, the process of ultrasonic assisted enzymatic extraction (UAEE), followed by macroporous resin purification, was successfully developed to achieve maximal recovery of flavonoids and ginkgolides from Ginkgo biloba fallen leaves (GBFL). Three effective extracted factors, including UAE power, EtOH%, and
[...] Read more.
In the present study, the process of ultrasonic assisted enzymatic extraction (UAEE), followed by macroporous resin purification, was successfully developed to achieve maximal recovery of flavonoids and ginkgolides from Ginkgo biloba fallen leaves (GBFL). Three effective extracted factors, including UAE power, EtOH%, and the amount of cellulase were screened by Plackett–Burman design (PBD). The important variables were further optimized by rotatable central composite design (RCCD). After the combination of PBD and RCCD, the resulting optimal UAEE conditions were as follows: UAE power of 218 W; EtOH% of 68%; the amount of cellulase of 8.4 mg; UAE temperature of 40 °C; UAE time of 20 min; pH of 5.0; and, sample particle size of 40 mesh. Under the optimum conditions; the yields of flavonoids were 0.74 ± 0.05% (n = 3) and ginkgolides was 0.42 ± 0.06% (n = 3), which were close to the predicted values. Moreover, the further enriching flavonoids and ginkgolides from the obtained GBFL extracts using the above optimum UAEE condition was successfully achieved by macroporous resin DA-201. After column adsorption and desorption on DA-201; the percentage of total flavonoids was (25.36 ± 1.03)%; ginkgolides was (12.43 ± 0.85)% and alkylphenols was (0.003 ± 0.0005)% from the obtained dry extracts of GBFL which were complied with Chinese pharmacopoeias. Therefore, the present study provided a convenient and efficient method for extraction and purification of flavonoids and ginkgolides from waste GBFL. Full article
(This article belongs to the Section Natural Products Chemistry)
Figures

Figure 1

Open AccessArticle Spectroscopic-Chemical Fingerprint and Biostimulant Activity of a Protein-Based Product in Solid Form
Molecules 2018, 23(5), 1031; https://doi.org/10.3390/molecules23051031
Received: 7 February 2018 / Revised: 13 April 2018 / Accepted: 23 April 2018 / Published: 27 April 2018
PDF Full-text (2678 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A solid biostimulant (AA309) obtained through thermobaric hydrolysis applied on trimmings and shavings of bovine hides tanned with wet-blue technology was chemically characterized, and its effects in maize (Zea mays L.) were evaluated. AA309 contained 13.60% total nitrogen (N), mainly in organic
[...] Read more.
A solid biostimulant (AA309) obtained through thermobaric hydrolysis applied on trimmings and shavings of bovine hides tanned with wet-blue technology was chemically characterized, and its effects in maize (Zea mays L.) were evaluated. AA309 contained 13.60% total nitrogen (N), mainly in organic forms (13.40%), and several amino acids, especially lysine, phenylalanine, glycine, aspartate, and isoleucine. AA309 was further analyzed using Fourier Transform Infrared (FT-IR) spectroscopy, which revealed the presence of amide I and amide II bands, indicative of peptide structures. When supplied to maize plants for 15 days at two N dosages (2.1 or 4.2 mg/kg), AA309 induced positive physiological responses, likely because of its content in amino acids functioning as signaling molecules. The low dosage was the most effective in improving leaf (+24%) and root (+98%) dry weight, photosynthetic activity (+70%), and accumulation of N (+80%), proteins (+65–75%) and antioxidants (+60%). Spectroscopic analyses (Solid-state Cross-Polarization Magic Angle Spinning Carbon-13 Nuclear Magnetic Resonance, CP/MAS 13C–NMR, and High resolution-magic angle spinning nuclear magnetic resonance, HR-MAS NMR) on plant tissues revealed the increase in proteins, lignin structures and cutin in AA309-treated plants compared to untreated plants. Our results indicate that AA309 could be used as a valuable biostimulant in agriculture. Full article
(This article belongs to the Section Natural Products Chemistry)
Figures

Figure 1

Open AccessArticle Anthocidins A–D, New 5-Hydroxyanthranilic Acid Related Metabolites from the Sea Urchin-Associated Actinobacterium, Streptomyces sp. HDa1
Molecules 2018, 23(5), 1032; https://doi.org/10.3390/molecules23051032
Received: 4 April 2018 / Revised: 24 April 2018 / Accepted: 25 April 2018 / Published: 27 April 2018
PDF Full-text (814 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four new 5-hydroxyanthranilic acid related compounds, named anthocidins A–D (14), two known analogues n-lauryl 5-hydroxyanthranilate (5) and isolauryl 5-hydroxyanthranilate (6), together with benzamide (7), 3-hydroxy-4-methoxycinnamamide (8), and (3S-
[...] Read more.
Four new 5-hydroxyanthranilic acid related compounds, named anthocidins A–D (14), two known analogues n-lauryl 5-hydroxyanthranilate (5) and isolauryl 5-hydroxyanthranilate (6), together with benzamide (7), 3-hydroxy-4-methoxycinnamamide (8), and (3S-cis)-hexahydro-3-[(3,4-dihydroxyphenyl)methyl]pyrrolo[1,2-a]pyrazine-1,4-dione (9), were isolated from the fermentation broth of the marine-derived actinomycete, Streptomyces sp. HDa1, which was isolated from the gut of a sea urchin, Anthocidaris crassispina, collected from Hainan Island, China. The structures of these secondary metabolites were elucidated on the basis of their 1D and 2D-NMR and mass spectroscopic data, and anthocidin A was confirmed by single-crystal X-ray diffraction with Cu Kα radiation. Anthocidins A–D (14) feature an acetyl group substitution at the amino group and varying alkyl side chains at the carboxyl group of 5-hydroxyanthranilic acid, and compound 5 was isolated as a natural product for the first time. The cytotoxic and antibacterial activity of compounds 19 were evaluated. Full article
Figures

Figure 1

Open AccessArticle Identification of Peptides in Flowers of Sambucus nigra with Antimicrobial Activity against Aquaculture Pathogens
Molecules 2018, 23(5), 1033; https://doi.org/10.3390/molecules23051033
Received: 27 March 2018 / Revised: 25 April 2018 / Accepted: 26 April 2018 / Published: 27 April 2018
PDF Full-text (1550 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The elder (Sambucus spp.) tree has a number of uses in traditional medicine. Previous studies have demonstrated the antimicrobial properties of elderberry liquid extract against human pathogenic bacteria and also influenza viruses. These properties have been mainly attributed to phenolic compounds. However,
[...] Read more.
The elder (Sambucus spp.) tree has a number of uses in traditional medicine. Previous studies have demonstrated the antimicrobial properties of elderberry liquid extract against human pathogenic bacteria and also influenza viruses. These properties have been mainly attributed to phenolic compounds. However, other plant defense molecules, such as antimicrobial peptides (AMPs), may be present. Here, we studied peptide extracts from flowers of Sambucus nigra L. The mass spectrometry analyses determined peptides of 3 to 3.6 kDa, among them, cysteine-rich peptides were identified with antimicrobial activity against various Gram-negative bacteria, including recurrent pathogens of Chilean aquaculture. In addition, membrane blebbing on the bacterial surface after exposure to the cyclotide was visualized by SEM microscopy and SYTOX Green permeabilization assay showed the ability to disrupt the bacterial membrane. We postulate that these peptides exert their action by destroying the bacterial membrane. Full article
(This article belongs to the Special Issue Cyclic Peptides)
Figures

Figure 1

Open AccessArticle Synthesis, Stability and Relaxivity of TEEPO-Met: An Organic Radical as a Potential Tumour Targeting Contrast Agent for Magnetic Resonance Imaging
Molecules 2018, 23(5), 1034; https://doi.org/10.3390/molecules23051034
Received: 9 March 2018 / Revised: 6 April 2018 / Accepted: 25 April 2018 / Published: 27 April 2018
PDF Full-text (1657 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cancer is a widespread and life-threatening disease and its early-stage diagnosis is vital. One of the most effective, non-invasive tools in medical diagnostics is magnetic resonance imaging (MRI) with the aid of contrast agents. Contrast agents that are currently in clinical use contain
[...] Read more.
Cancer is a widespread and life-threatening disease and its early-stage diagnosis is vital. One of the most effective, non-invasive tools in medical diagnostics is magnetic resonance imaging (MRI) with the aid of contrast agents. Contrast agents that are currently in clinical use contain metals, causing some restrictions in their use. Also, these contrast agents are mainly non-specific without any tissue targeting capabilities. Subsequently, the interest has notably increased in the research of organic, metal-free contrast agents. This study presents a new, stable organic radical, TEEPO-Met, where a radical moiety 2,2,6,6-tetraethylpiperidinoxide (TEEPO) is attached to an amino acid, methionine (Met), as a potentially tumour-targeting moiety. We describe the synthesis, stability assessment with electron paramagnetic resonance (EPR) spectroscopy and relaxation enhancement abilities by an in vitro nuclear magnetic resonance (NMR) and phantom MRI studies of TEEPO-Met. The new compound proved to be stable notably longer than the average imaging time in conditions mimicking a biological matrix. Also, it significantly reduced the relaxation times of water, making it a promising candidate as a novel tumour targeting contrast agent for MRI. Full article
(This article belongs to the Special Issue Molecular Imaging and Treatment Monitoring of Cancer)
Figures

Graphical abstract

Open AccessArticle Solid-Phase Synthesis of Azole-Comprising Peptidomimetics and Coordination of a Designed Analog to Zn2+
Molecules 2018, 23(5), 1035; https://doi.org/10.3390/molecules23051035
Received: 6 April 2018 / Revised: 23 April 2018 / Accepted: 26 April 2018 / Published: 28 April 2018
PDF Full-text (6522 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Peptidomimetics that can coordinate transition metals have a variety of potential applications as catalysts, sensors, or materials. A new modular peptidomimetic scaffold, the “azole peptoid”, is introduced here. We report methods for the solid-phase synthesis of eleven examples of trimeric N-substituted oligoamides
[...] Read more.
Peptidomimetics that can coordinate transition metals have a variety of potential applications as catalysts, sensors, or materials. A new modular peptidomimetic scaffold, the “azole peptoid”, is introduced here. We report methods for the solid-phase synthesis of eleven examples of trimeric N-substituted oligoamides that include oxazole- or thiazole-functionalized backbones. The products prepared comprise a diversity of functionality, including a metal-coordinating terpyridine group. The modular synthetic approach enables ready preparation of analogs for specific applications. To highlight a potential use of this new synthetic scaffold, a trimeric azole peptoid functionalized with a terpyridine residue was prepared and studied. The characteristic 2:1 ligand:metal binding of this terpyridine-functionalized azole peptoid to Zn2+ in aqueous solution was observed. These studies introduce azole peptoids as a useful class of biomimetic molecules for further study and application. Full article
(This article belongs to the Special Issue Solid Phase Synthesis)
Figures

Graphical abstract

Open AccessArticle Discovery of Pyrazolo[4,3-c]quinolines Derivatives as Potential Anti-Inflammatory Agents through Inhibiting of NO Production
Molecules 2018, 23(5), 1036; https://doi.org/10.3390/molecules23051036
Received: 16 April 2018 / Revised: 25 April 2018 / Accepted: 27 April 2018 / Published: 28 April 2018
PDF Full-text (3058 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The synthesis and anti-inflammatory effects of certain pyrazolo[4,3-c]quinoline derivatives 2a2r are described. The anti-inflammatory activities of these derivatives were evaluated by means of inhibiting nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among them, 3-amino-4-(4-hydroxyphenylamino)-1H-pyrazolo[4,3-
[...] Read more.
The synthesis and anti-inflammatory effects of certain pyrazolo[4,3-c]quinoline derivatives 2a2r are described. The anti-inflammatory activities of these derivatives were evaluated by means of inhibiting nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among them, 3-amino-4-(4-hydroxyphenylamino)-1H-pyrazolo[4,3-c]-quinoline (2i) and 4-(3-amino-1H-pyrazolo[4,3-c]quinolin-4-ylamino)benzoic acid (2m) exhibited significant inhibition of LPS-stimulated NO production with a potency approximately equal to that of the positive control, 1400 W. Important structure features were analyzed by quantitative structure–activity relationship (QSAR) analysis to give better insights into the structure determinants for predicting the inhibitory effects on the accumulation of nitric oxide for RAW 264.7 cells in response to LPS. In addition, our results indicated that their anti-inflammatory effects involve the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expression. Further studies on the structural optimization are ongoing. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Figure 1

Open AccessFeature PaperArticle Phenolic Composition and Bioactivity of Lavandula pedunculata (Mill.) Cav. Samples from Different Geographical Origin
Molecules 2018, 23(5), 1037; https://doi.org/10.3390/molecules23051037
Received: 9 April 2018 / Revised: 24 April 2018 / Accepted: 27 April 2018 / Published: 28 April 2018
PDF Full-text (892 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to characterize the phenolic composition and evaluate the bioactivity of several samples of Lavandula pedunculata (Mill.) Cav, and to compare aqueous and hydroethanolic extracts. Plant materials were obtained by growing some accessions (seed samples) of various wild
[...] Read more.
The aim of this study was to characterize the phenolic composition and evaluate the bioactivity of several samples of Lavandula pedunculata (Mill.) Cav, and to compare aqueous and hydroethanolic extracts. Plant materials were obtained by growing some accessions (seed samples) of various wild populations from different regions of Portugal conserved at the Portuguese Genebank in Braga. Phenolic compounds were analised by HPLC-DAD-ESI/MSn, antioxidant potential through in vitro assays (DPPH radical scavenging activity, reducing power and inhibition of lipid peroxidation), cytotoxicity on tumor cells (MCF-7, NCI-H460, HeLa and HepG2) and non-tumor (PLP2) cells, anti-inflammatory activity in rat RAW 264.7 macrophages, by the ability to inhibit NO production and antimicrobial potential by the microdilution method with INT dye (iodonitrotetrazolium chloride). Thirteen compounds were identified, being salvianolic acid B, rosmarinic acid and luteolin-7-O-glucuronide, the main compounds present, with values ranging between 44.3–582, 50.9–550, and 24.36–101.5 mg/g extract, respectively. L. pedunculata aqueous extract revealed a higher antioxidant potential (EC50 values between 14 to 530 μg/mL), which could be related to its higher concentration in phenolic compounds; however, the hydroethanolic extract showed a higher anti-inflammatory (lower EC50 values than 124 μg/mL) potential and antiproliferative capacity (lower GI50 values than 34 μg/mL). Thus, this study highlights the bioactive effects of this species and opens up possibilities of uses in food and pharmaceutical formulations. However, there are potential differences in such properties according to geographical origin of plant material, as in general, the samples from Alentejo presented higher results in all the bioactivities, compared with Trás-os-Montes samples. Full article
(This article belongs to the collection Bioactive Compounds)
Figures

Graphical abstract

Open AccessArticle Is It Reliable to Take the Molecular Docking Top Scoring Position as the Best Solution without Considering Available Structural Data?
Molecules 2018, 23(5), 1038; https://doi.org/10.3390/molecules23051038
Received: 11 March 2018 / Revised: 21 April 2018 / Accepted: 26 April 2018 / Published: 28 April 2018
PDF Full-text (1992 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Molecular docking is the most frequently used computational method for studying the interactions between organic molecules and biological macromolecules. In this context, docking allows predicting the preferred pose of a ligand inside a receptor binding site. However, the selection of the “best” solution
[...] Read more.
Molecular docking is the most frequently used computational method for studying the interactions between organic molecules and biological macromolecules. In this context, docking allows predicting the preferred pose of a ligand inside a receptor binding site. However, the selection of the “best” solution is not a trivial task, despite the widely accepted selection criterion that the best pose corresponds to the best energy score. Here, several rigid-target docking methods were evaluated on the same dataset with respect to their ability to reproduce crystallographic binding orientations, to test if the best energy score is a reliable criterion for selecting the best solution. For this, two experiments were performed: (A) to reconstruct the ligand-receptor complex by performing docking of the ligand in its own crystal structure receptor (defined as self-docking), and (B) to reconstruct the ligand-receptor complex by performing docking of the ligand in a crystal structure receptor that contains other ligand (defined as cross-docking). Root-mean square deviation (RMSD) was used to evaluate how different the obtained docking orientation is from the corresponding co-crystallized pose of the same ligand molecule. We found that docking score function is capable of predicting crystallographic binding orientations, but the best ranked solution according to the docking energy is not always the pose that reproduces the experimental binding orientation. This happened when self-docking was achieved, but it was critical in cross-docking. Taking into account that docking is typically used with predictive purposes, during cross-docking experiments, our results indicate that the best energy score is not a reliable criterion to select the best solution in common docking applications. It is strongly recommended to choose the best docking solution according to the scoring function along with additional structural criteria described for analogue ligands to assure the selection of a correct docking solution. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Graphical abstract

Open AccessArticle Discovery of Potential Inhibitors of Squalene Synthase from Traditional Chinese Medicine Based on Virtual Screening and In Vitro Evaluation of Lipid-Lowering Effect
Molecules 2018, 23(5), 1040; https://doi.org/10.3390/molecules23051040
Received: 19 March 2018 / Revised: 19 April 2018 / Accepted: 25 April 2018 / Published: 28 April 2018
PDF Full-text (4702 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Squalene synthase (SQS), a key downstream enzyme involved in the cholesterol biosynthetic pathway, plays an important role in treating hyperlipidemia. Compared to statins, SQS inhibitors have shown a very significant lipid-lowering effect and do not cause myotoxicity. Thus, the paper aims to discover
[...] Read more.
Squalene synthase (SQS), a key downstream enzyme involved in the cholesterol biosynthetic pathway, plays an important role in treating hyperlipidemia. Compared to statins, SQS inhibitors have shown a very significant lipid-lowering effect and do not cause myotoxicity. Thus, the paper aims to discover potential SQS inhibitors from Traditional Chinese Medicine (TCM) by the combination of molecular modeling methods and biological assays. In this study, cynarin was selected as a potential SQS inhibitor candidate compound based on its pharmacophoric properties, molecular docking studies and molecular dynamics (MD) simulations. Cynarin could form hydrophobic interactions with PHE54, LEU211, LEU183 and PRO292, which are regarded as important interactions for the SQS inhibitors. In addition, the lipid-lowering effect of cynarin was tested in sodium oleate-induced HepG2 cells by decreasing the lipidemic parameter triglyceride (TG) level by 22.50%. Finally. cynarin was reversely screened against other anti-hyperlipidemia targets which existed in HepG2 cells and cynarin was unable to map with the pharmacophore of these targets, which indicated that the lipid-lowering effects of cynarin might be due to the inhibition of SQS. This study discovered cynarin is a potential SQS inhibitor from TCM, which could be further clinically explored for the treatment of hyperlipidemia. Full article
(This article belongs to the Special Issue Molecular Modeling in Drug Design)
Figures

Figure 1a

Open AccessArticle Synthesis of a Novel Series of Amino Acid Prodrugs Based on Thienopyridine Scaffolds and Evaluation of Their Antiplatelet Activity
Molecules 2018, 23(5), 1041; https://doi.org/10.3390/molecules23051041
Received: 15 March 2018 / Revised: 26 April 2018 / Accepted: 26 April 2018 / Published: 28 April 2018
PDF Full-text (9790 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The thienopyridines class of drugs used as P2Y12 receptor antagonists plays a vital role in antiplatelet therapy. To further optimized this compound class, we designed and synthesized a series of amino acid prodrugs of 2-hydroxytetrahydrothienopyridine. All compounds were then evaluated for their
[...] Read more.
The thienopyridines class of drugs used as P2Y12 receptor antagonists plays a vital role in antiplatelet therapy. To further optimized this compound class, we designed and synthesized a series of amino acid prodrugs of 2-hydroxytetrahydrothienopyridine. All compounds were then evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats and then ED50 and bleeding time of the most potent compounds were compared with commercial drugs. The results showed compound 5c could be a potent and safe candidate for further research. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Figure 1

Open AccessArticle Antidiabetic Effect of Cyclocarya paliurus Leaves Depends on the Contents of Antihyperglycemic Flavonoids and Antihyperlipidemic Triterpenoids
Molecules 2018, 23(5), 1042; https://doi.org/10.3390/molecules23051042
Received: 16 April 2018 / Revised: 24 April 2018 / Accepted: 29 April 2018 / Published: 29 April 2018
PDF Full-text (749 KB) | HTML Full-text | XML Full-text
Abstract
Cyclocarya paliurus has been used commonly to treat diabetes in China. However, the effective components and the effect of plant origin remain unclear. In this study, C. paliurus leaves with different chemical compositions were selected from five geographical locations, and their effects on
[...] Read more.
Cyclocarya paliurus has been used commonly to treat diabetes in China. However, the effective components and the effect of plant origin remain unclear. In this study, C. paliurus leaves with different chemical compositions were selected from five geographical locations, and their effects on streptozotocin (STZ)-induced diabetic mice were evaluated with both ethanol and aqueous extracts. Glucose levels, lipid levels, and biomarkers of liver and kidney function were measured. The principal components of both C. paliurus ethanol and aqueous extracts from different geographical locations differed quantitatively and qualitatively. Results showed that C. paliurus extracts with better antihyperglycemic effects were characterized by higher contents of total flavonoids, especially quercetin-3-O-glucuronide and kaempferol-3-O-glucuronide. Furthermore, significantly negative correlations were found between triterpenoids contents and lipid levels. These results revealed the potential antihyperglycemic capacity of C. paliurus flavonoids and the antihyperlipidemic effect of C. paliurus triterpenoids. Thus, we suggest that the composition of C. paliurus compounds might help to design therapeutic alternatives for the treatment of diabetes mellitus. However, geographic origins and the extraction solvents can also affect the effectiveness of the treatment as these factors influence the chemical compositions and thereby the biological activities. Full article
(This article belongs to the Special Issue Medicinal Plants and Diabetes)
Figures

Graphical abstract

Open AccessArticle Synthesis, Spectroscopic Identification and Molecular Docking of Certain N-(2-{[2-(1H-Indol-2-ylcarbonyl)hydrazinyl](oxo)acetyl}phenyl)acetamides and N-[2-(2-{[2-(Acetylamino)phenyl](oxo)acetyl}hydrazinyl)-2-oxoethyl]-1H-indole-2-carboxamides: New Antimicrobial Agents
Molecules 2018, 23(5), 1043; https://doi.org/10.3390/molecules23051043
Received: 25 March 2018 / Revised: 25 April 2018 / Accepted: 27 April 2018 / Published: 29 April 2018
PDF Full-text (1253 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
N-(2-{[2-(1H-Indol-2-ylcarbonyl)hydrazinyl](oxo)acetyl}phenyl)acetamides (5a–h) and N-[2-(2-{[2-(acetylamino)phenyl](oxo)acetyl}hydrazinyl)-2-oxoethyl]-1H-indole-2-carboxamides (5i–l) were synthesized and characterized with different analytical tools. N-Acetylisatines 4a–d were subjected to ring opening at their C2 carbons with the aid of different indole-bearing hydrazides 3a,b
[...] Read more.
N-(2-{[2-(1H-Indol-2-ylcarbonyl)hydrazinyl](oxo)acetyl}phenyl)acetamides (5a–h) and N-[2-(2-{[2-(acetylamino)phenyl](oxo)acetyl}hydrazinyl)-2-oxoethyl]-1H-indole-2-carboxamides (5i–l) were synthesized and characterized with different analytical tools. N-Acetylisatines 4a–d were subjected to ring opening at their C2 carbons with the aid of different indole-bearing hydrazides 3a,b and 7 to afford the respective glyoxylamides 5a–l. The antimicrobial activity of the target compounds 5a–l was assessed with the aid of Diameter of the Inhibition Zone (DIZ) and Minimum Inhibitory Concentration (MIC) assays against a panel of Gram-positive and Gram-negative bacteria and certain fungal strains. The antimicrobial screening revealed that Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans are the most sensitive microorganisms towards the synthesized compounds 5a–l. In addition, compounds 5c and 5h emerged as the most active congeners towards Staphylococcus aureus and Candida albicans, respectively. Molecular docking studies revealed the possible binding mode of compounds 5c and 5h to their target proteins. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Figure 1

Open AccessArticle Anti-Proliferative Activity of HPOB against Multiple Myeloma Cells via p21 Transcriptional Activation
Molecules 2018, 23(5), 1044; https://doi.org/10.3390/molecules23051044
Received: 5 April 2018 / Revised: 25 April 2018 / Accepted: 27 April 2018 / Published: 30 April 2018
PDF Full-text (2349 KB) | HTML Full-text | XML Full-text
Abstract
Histone acetylation or deacetylation is closely associated with the progression of multiple myeloma (MM). Currently, many histone deacetylase (HDAC) inhibitors have been approved for being used in clinical trials, but theirtherapeutic effectsarestill not ideal. As a novel HDAC inhibitor, hydroxamicacid-based small-moleculeN-hydroxy-4-(2-[(2-hydroxyethyl)(phenyl)amino]-2-oxoethyl)benzamide
[...] Read more.
Histone acetylation or deacetylation is closely associated with the progression of multiple myeloma (MM). Currently, many histone deacetylase (HDAC) inhibitors have been approved for being used in clinical trials, but theirtherapeutic effectsarestill not ideal. As a novel HDAC inhibitor, hydroxamicacid-based small-moleculeN-hydroxy-4-(2-[(2-hydroxyethyl)(phenyl)amino]-2-oxoethyl)benzamide (HPOB)’s possible roles in MM have not been studied. In this present study, the effect of HPOB as a potential anti-tumor agent in preventingproliferation and inducing apoptosis of MM cells had been investigated in detail. Our results showed that HPOB decreased the survival of MM cells in dose- and time-dependent manner. In addition, HPOB caused the accumulation of MM cells in G1 phase compared with the dimethylsulfoxide (DMSO) control group. Interestingly, we found that HPOB could overcome bortezomib (BTZ) resistance inMM cells and combining HPOB with BTZ could further sensitize MM cells. Certainly, our data illuminated that HPOB-mediated cell death occurs via transcriptional activation of p21, which was associated with an elevated level of global histone 3 acetylation (H3Ac) modification. Therefore, HPOB could be a potential candidate for MM treatment and the combination of HPOB and bortezomibcould bea possible therapeutic strategy for relapsed and refractory MM. Full article
Figures

Figure 1

Open AccessArticle Hypoglycemic Effects in Alloxan-Induced Diabetic Rats of the Phenolic Extract from Mongolian Oak Cups Enriched in Ellagic Acid, Kaempferol and Their Derivatives
Molecules 2018, 23(5), 1046; https://doi.org/10.3390/molecules23051046
Received: 4 April 2018 / Revised: 25 April 2018 / Accepted: 28 April 2018 / Published: 30 April 2018
PDF Full-text (1792 KB) | HTML Full-text | XML Full-text
Abstract
Our previous reports showed that crude extract prepared with 50% ethanol (ethanol crude extract, ECE) from Mongolian oak cups possessed excellent in vitro antioxidant capacities as well as inhibitory activities against α-glucosidase, α-amylase and protein glycation caused by its enrichment in phenolics, including
[...] Read more.
Our previous reports showed that crude extract prepared with 50% ethanol (ethanol crude extract, ECE) from Mongolian oak cups possessed excellent in vitro antioxidant capacities as well as inhibitory activities against α-glucosidase, α-amylase and protein glycation caused by its enrichment in phenolics, including mainly ellagic acid, kaempferol and their derivatives. Nevertheless, few in vivo studies on antidiabetic activities of these phenolics were conducted. The present study investigated hypoglycemic effects with normal and diabetic rats being administrated orally without or with ECE at 200 and 800 mg/kg for 15 days. In normal rats, no significant differences were exhibited after ECE administration in body weight, fasting blood glucose level, levels of cholesterol, triglyceride, LDL and AST in serum, organ indexes, and levels of GSH and MDA in organs. In diabetic rats, the fasting blood glucose level, indexes of heart and liver, and levels of cholesterol and triglyceride in serum and MDA in heart tissue were significantly decreased. Moreover, HDL levels in serum and SOD activities in the four organs of diabetic rats were significantly improved after ECE administration at 800 mg/kg. Thus, in addition to inhibiting α-glucosidase, α-amylase and protein glycation reported previously, oak cups might contain novel dietary phytonutrients in preventing abnormal changes in blood glucose and lipid profile and attenuating oxidant stress in vivo. The results also implied that it is ellagic acid, kaempferol and their derivatives enriched in ECE that might play vital roles in managing type 1 as well as type 2 diabetes. Full article
(This article belongs to the Section Natural Products Chemistry)
Figures

Graphical abstract

Open AccessArticle Screening and Identification for Immunological Active Components from Andrographis Herba Using Macrophage Biospecific Extraction Coupled with UPLC/Q-TOF-MS
Molecules 2018, 23(5), 1047; https://doi.org/10.3390/molecules23051047
Received: 27 March 2018 / Revised: 21 April 2018 / Accepted: 27 April 2018 / Published: 30 April 2018
PDF Full-text (2764 KB) | HTML Full-text | XML Full-text
Abstract
The method of cell biospecific extraction coupled with UPLC/Q-TOF-MS has been developed as a tool for the screening and identification of potential immunological active components from Andrographis Herba (AH). In our study, a macrophage cell line (RAW264.7) was used to extract cell-combining compounds
[...] Read more.
The method of cell biospecific extraction coupled with UPLC/Q-TOF-MS has been developed as a tool for the screening and identification of potential immunological active components from Andrographis Herba (AH). In our study, a macrophage cell line (RAW264.7) was used to extract cell-combining compounds from the ethanol extract of AH. The cell binding system was then analyzed and identified by UPLC/Q-TOF-MS analysis. Finally, nine compounds, which could combine with macrophages, in an ethanol extract of AH were detected by comparing basic peak intensity (BPI) profiles of macrophages before and after treatment with AH. Then they were identified as Andrographidine E (1), Andrographidine D (2), Neoandrographolide (3), Dehydroandrographolide (4), 5, 7, 2′, 3′-tetramethoxyflavone (5), β-sitosterol (7), 5-hydroxy-7, 2′, 3′-trimethoxyflavone (8) and 5-hydroxy-7, 8, 2′, 3′-tetramethoxyflavone (9), which could classified into five flavonoids, three diterpene lactones, and one sterol. Their structures were recognized by their characteristic fragment ions and fragmentations pattern of diterpene lactones and flavonoids. Additionally, the activity of compounds 3, 4, and 7 was tested in vitro. Results showed that these three compounds could decrease the release of NO (p < 0.01) in macrophages remarkably. Moreover, 3, 4, and 7 showed satisfactory dose-effect relationships and their IC50 values were 9.03, 18.18, and 13.76 μg/mL, respectively. This study is the first reported work on the screening of immunological active components from AH. The potential immunological activity of flavonoids from AH has not been reported previously. Full article
(This article belongs to the Special Issue Green Analytical Chemistry)
Figures

Figure 1

Open AccessArticle Molecular Sex Identification in Dioecious Hippophae rhamnoides L. via RAPD and SCAR Markers
Molecules 2018, 23(5), 1048; https://doi.org/10.3390/molecules23051048
Received: 7 April 2018 / Revised: 24 April 2018 / Accepted: 27 April 2018 / Published: 1 May 2018
PDF Full-text (3294 KB) | HTML Full-text | XML Full-text
Abstract
The dioecious property of the sea buckthorn (Hippophae rhamnoides L.) prevents sex recognition via traditional observation at the juvenile stage, thus impeding breeding and economic cropping; A random amplified polymorphic DNA (RAPD) and a sequence characterized amplified region (SCAR) markers were used
[...] Read more.
The dioecious property of the sea buckthorn (Hippophae rhamnoides L.) prevents sex recognition via traditional observation at the juvenile stage, thus impeding breeding and economic cropping; A random amplified polymorphic DNA (RAPD) and a sequence characterized amplified region (SCAR) markers were used to identify the sexes. A total of 45 random decamer primers were used to screen genomic DNA pools of staminate and pistillate genotypes for genetic polymorphisms. One female sex-linked marker was identified. D15 (5′-CATCCGTGCT-3′) amplified a particular band of 885 bp, which showed polymorphism among staminate and pistillate genotype plants. The SCAR marker Hrcx-15 was obtained by sequencing the fragment. The alleles of 140 pistillate genotypes were examined but not of the 140 staminate genotypes discerned via taxonomy. Staminate and pistillate genotypes of sea buckthorn plants can be distinguished, using Hrcx-15 as a genetic marker for sex identification and for expediting cultivation for commercial applications. Full article
Figures

Figure 1

Open AccessArticle Effective Saccharification of Corn Stover Using Low-Liquid Aqueous Ammonia Pretreatment and Enzymatic Hydrolysis
Molecules 2018, 23(5), 1050; https://doi.org/10.3390/molecules23051050
Received: 27 March 2018 / Revised: 22 April 2018 / Accepted: 28 April 2018 / Published: 1 May 2018
PDF Full-text (1593 KB) | HTML Full-text | XML Full-text
Abstract
Low-liquid aqueous ammonia (LLAA) pretreatment using aqueous ammonia was investigated to enhance enzymatic saccharification of corn stover. In this method, ground corn stover was simply contacted with aqueous ammonia mist (ammoniation step), followed by pretreatment at elevated temperature (90–150 °C) for an extended
[...] Read more.
Low-liquid aqueous ammonia (LLAA) pretreatment using aqueous ammonia was investigated to enhance enzymatic saccharification of corn stover. In this method, ground corn stover was simply contacted with aqueous ammonia mist (ammoniation step), followed by pretreatment at elevated temperature (90–150 °C) for an extended period (24–120 h) at different solid/liquid (S/L) ratios (0.29, 0.47 or 0.67), termed a pretreatment step. After that, excess (unreacted) ammonia was removed by evaporation, and the pretreated material was immediately saccharified by an enzyme without a washing step. The effects of key reaction parameters on both glucan digestibility and XMG digestibility were evaluated by analysis of variance (ANOVA). Under the best pretreatment conditions [S/L = 0.47, 0.16 (g NH3)/(g biomass), 90 °C, 24 h], LLAA pretreatment enhanced enzymatic digestibility from 23.1% for glucan and 11.3% for XMG (xylan + galactan + mannan) of untreated corn stover to 91.8% for glucan and 72.6% for XMG in pretreated solid. Full article
(This article belongs to the Special Issue Efficient Technology for the Pretreatment of Biomass)
Figures

Graphical abstract

Open AccessArticle Comparative Targeted Proteomics of the Central Metabolism and Photosystems in SigE Mutant Strains of Synechocystis sp. PCC 6803
Molecules 2018, 23(5), 1051; https://doi.org/10.3390/molecules23051051
Received: 9 April 2018 / Revised: 27 April 2018 / Accepted: 27 April 2018 / Published: 1 May 2018
PDF Full-text (2793 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A targeted proteome analysis was conducted to investigate the SigE dependent-regulation of central metabolism in Synechocystis sp. PCC 6803 by directly comparing the protein abundance profiles among the wild type, a sigE deletion mutant (ΔsigE), and a sigE over-expression (sigE
[...] Read more.
A targeted proteome analysis was conducted to investigate the SigE dependent-regulation of central metabolism in Synechocystis sp. PCC 6803 by directly comparing the protein abundance profiles among the wild type, a sigE deletion mutant (ΔsigE), and a sigE over-expression (sigEox) strains. Expression levels of 112 target proteins, including the central metabolism related-enzymes and the subunits of the photosystems, were determined by quantifying the tryptic peptides in the multiple reaction monitoring (MRM) mode of liquid-chromatography–triple quadrupole mass spectrometry (LC–MS/MS). Comparison with gene-expression data showed that although the abundance of Gnd protein was closely correlated with that of gnd mRNA, there were poor correlations for GdhA/gdhA and glycogen degradation-related genes such as GlgX/glgX and GlgP/glgP pairs. These results suggested that the regulation of protein translation and degradation played a role in regulating protein abundance. The protein abundance profile suggested that SigE overexpression reduced the proteins involved in photosynthesis and increased GdhA abundance, which is involved in the nitrogen assimilation pathway using NADPH. The results obtained in this study successfully demonstrated that targeted proteome analysis enables direct comparison of the abundance of central metabolism- and photosystem-related proteins. Full article
(This article belongs to the Special Issue Mass Spectrometric Proteomics)
Figures

Figure 1

Open AccessArticle Porphyrin Co(III)-Nitrene Radical Mediated Pathway for Synthesis of o-Aminoazobenzenes
Molecules 2018, 23(5), 1052; https://doi.org/10.3390/molecules23051052
Received: 3 April 2018 / Revised: 25 April 2018 / Accepted: 26 April 2018 / Published: 1 May 2018
PDF Full-text (3565 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Azobenzenes are versatile compounds with a range of applications, including dyes and pigments, food additives, indicators, radical reaction initiators, molecular switches, etc. In this context, we report a general method for synthesizing o-aminoazobenzenes using the commercially available cobalt(II) tetraphenyl porphyrin [CoII
[...] Read more.
Azobenzenes are versatile compounds with a range of applications, including dyes and pigments, food additives, indicators, radical reaction initiators, molecular switches, etc. In this context, we report a general method for synthesizing o-aminoazobenzenes using the commercially available cobalt(II) tetraphenyl porphyrin [CoII(TPP)]. The net reaction is a formal dimerization of two phenyl azides with concomitant loss of two molecules of dinitrogen. The most commonly used methodology to synthesize azobenzenes is based on the initial diazotization of an aromatic primary amine at low temperatures, which then reacts with an electron rich aromatic nucleophile. As such, this limits the synthesis of azobenzenes with an amine functionality. In contrast, the method we report here relies heavily on the o-amine moiety and retains it in the product. The reaction is metal catalyzed and proceeds through a porphyrin Co(III)-nitrene radical intermediate, which is known to form on activation of organic azides at the cobalt center. The synthesized o-aminoazobenzenes are bathochromatically shifted, as compared to azobenzenes without amine substituents. Based on the crystal structure of one of the products, strong H-bonding between the N-atom of the azo functionality and the H of the NH2 substituent is shown to stabilize the trans isomeric form of the product. The NH2 substituents offers possibilities for further functionalization of the synthesized azo compounds. Full article
(This article belongs to the Special Issue Radical Chemistry)
Figures

Graphical abstract

Open AccessArticle Triorganotin Derivatives Induce Cell Death Effects on L1210 Leukemia Cells at Submicromolar Concentrations Independently of P-glycoprotein Expression
Molecules 2018, 23(5), 1053; https://doi.org/10.3390/molecules23051053
Received: 12 April 2018 / Revised: 25 April 2018 / Accepted: 26 April 2018 / Published: 1 May 2018
PDF Full-text (2574 KB) | HTML Full-text | XML Full-text
Abstract
The acceleration of drug efflux activity realized by plasma membrane transporters in neoplastic cells, particularly by P-glycoprotein (P-gp, ABCB1 member of the ABC transporter family), represents a frequently observed molecular cause of multidrug resistance (MDR). This multiple resistance represents a real obstacle in
[...] Read more.
The acceleration of drug efflux activity realized by plasma membrane transporters in neoplastic cells, particularly by P-glycoprotein (P-gp, ABCB1 member of the ABC transporter family), represents a frequently observed molecular cause of multidrug resistance (MDR). This multiple resistance represents a real obstacle in the effective chemotherapy of neoplastic diseases. Therefore, identifying cytotoxic substances that are also effective in P-gp overexpressing cells may be useful for the rational design of substances for the treatment of malignancies with developed MDR. Here, we showed that triorganotin derivatives—tributyltin-chloride (TBT-Cl), tributyltin-bromide (TBT-Br), tributyltin-iodide (TBT-I) and tributyltin-isothiocyanate (TBT-NCS) or triphenyltin-chloride (TPT-Cl) and triphenyltin-isothiocyanate (TPT-NCS)—could induce the death of L1210 mice leukemia cells at a submicromolar concentration independently of P-gp overexpression. The median lethal concentration obtained for triorganotin derivatives did not exceed 0.5 µM in the induction of cell death of either P-gp negative or P-gp positive L1210 cells. Apoptosis related to regulatory pathway of Bcl-2 family proteins seems to be the predominant mode of cell death in either P-gp negative or P-gp positive L1210 cells. TBT-Cl and TBT-Br were more efficient with L1210 cells overexpressing P-gp than with their counterpart P-gp negative cells. In contrast, TBT-I and TPT-NCS induced a more pronounced cell death effect on P-gp negative cells than on P-gp positive cells. Triorganotin derivatives did not affect P-gp efflux in native cells measured by calcein retention within the cells. Taken together, we assumed that triorganotin derivatives represent substances suitable for suppressing the viability of P-gp positive malignant cells. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Graphical abstract

Open AccessArticle Synthesis of New Benzothiazole Acylhydrazones as Anticancer Agents
Molecules 2018, 23(5), 1054; https://doi.org/10.3390/molecules23051054
Received: 22 March 2018 / Revised: 27 April 2018 / Accepted: 27 April 2018 / Published: 1 May 2018
PDF Full-text (2290 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
During the last five decades, a large number of BT (Benzothiazole) derivatives formed one of the eligible structures in medicinal chemistry as anticancer agents. Most of the studies reveal that various substitutions at specific positions on BT scaffold modulate the antitumor property. The
[...] Read more.
During the last five decades, a large number of BT (Benzothiazole) derivatives formed one of the eligible structures in medicinal chemistry as anticancer agents. Most of the studies reveal that various substitutions at specific positions on BT scaffold modulate the antitumor property. The potential of BTs encouraged us to synthesize a number of new 2-((5-substitutedbenzothiazol-2-yl)thio)-N’-(2-(4-(substitutedphenyl)ethylidene)acetohydrazide derivatives and investigate their probable anticancer activity. 4-Substitued benzaldehyde derivatives (1a1e) were afforded by the reaction of appropriate secondary amine and 4-fluorobenzaldehyde in DMF. Equimolar quantitates of 5-substitutedbenzothiazole-2-thiol, ethyl chloroacetate and K2CO3 were refluxed in acetone to obtain 2-((5-substitutedbenzothiazol-2-yl)thio)acetate derivatives (2a,2b), which reacted with excess of hydrazine hydrate to get 2-((5-substitutebenzothiazol-2-yl)thio)acetohydrazides (3a,3b). In the last step, 2-((5-substitutedbenzothiazol-2-yl)thio)-N’-(4-substitutedbenzylidene)acetohydrazide derivatives (4a4j) were synthesized by the reaction of 1a1e and 3a3b in EtOH. The anticancer activity of target compounds was evaluated in three steps. First, an MTT test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was performed to observe cytotoxic activity of the compounds against carcinogenic C6 (Rat brain glioma cell line), A549 (Human lung adenocarcinoma epithelial cell line), MCF-7 (Human breast adenocarcinoma cell line), and HT-29 (Human colorectal adenocarcinoma cell line) cancer cell lines. Healthy NIH3T3 (Mouse embryo fibroblast cell line) cells were also subjected to MTT assay to determine selectivity of the compounds towards carcinogenic cell lines. Secondly, inhibitory effects of selected compounds 4d, 4e, and 4h on DNA synthesis of C6 cells were investigated. Finally, flow cytometric analysis were performed to identify the death pathway of the carcinogenic cells. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Figure 1

Open AccessFeature PaperArticle KOtBu as a Single Electron Donor? Revisiting the Halogenation of Alkanes with CBr4 and CCl4
Molecules 2018, 23(5), 1055; https://doi.org/10.3390/molecules23051055
Received: 8 April 2018 / Revised: 24 April 2018 / Accepted: 26 April 2018 / Published: 1 May 2018
PDF Full-text (5040 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The search for reactions where KOtBu and other tert-alkoxides might behave as single electron donors led us to explore their reactions with tetrahalomethanes, CX4, in the presence of adamantane. We recently reported the halogenation of adamantane under these
[...] Read more.
The search for reactions where KOtBu and other tert-alkoxides might behave as single electron donors led us to explore their reactions with tetrahalomethanes, CX4, in the presence of adamantane. We recently reported the halogenation of adamantane under these conditions. These reactions appeared to mirror the analogous known reaction of NaOH with CBr4 under phase-transfer conditions, where initiation features single electron transfer from a hydroxide ion to CBr4. We now report evidence from experimental and computational studies that KOtBu and other alkoxide reagents do not go through an analogous electron transfer. Rather, the alkoxides form hypohalites upon reacting with CBr4 or CCl4, and homolytic decomposition of appropriate hypohalites initiates the halogenation of adamantane. Full article
(This article belongs to the Special Issue Radical Chemistry)
Figures

Graphical abstract

Open AccessArticle Analysis of Menaquinone-7 Content and Impurities in Oil and Non-Oil Dietary Supplements
Molecules 2018, 23(5), 1056; https://doi.org/10.3390/molecules23051056
Received: 17 March 2018 / Revised: 24 April 2018 / Accepted: 28 April 2018 / Published: 1 May 2018
PDF Full-text (1930 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Rapid, global technological development has caused the food industry to use concentrated food component sources like dietary supplements ever more commonly as part of the human diet. This study analysed the menaquinone-7 (MK-7) content of dietary supplements in oil capsule and hard tablet
[...] Read more.
Rapid, global technological development has caused the food industry to use concentrated food component sources like dietary supplements ever more commonly as part of the human diet. This study analysed the menaquinone-7 (MK-7) content of dietary supplements in oil capsule and hard tablet forms. A novel method for separating and measuring geometric isomers of MK-7 in dietary supplements was developed and validated. Eleven different isomers of cis/trans- menaquinone-7 were identified. Identification of cis/trans isomers was performed by combination of HPLC, UPLC and HRMS-QTOF detection, whereas their quantities were determined by DAD detection. The content of menaquinone impurities was ascertained, including cis/trans- menaquinone-6 isomers (5.5–16.9 µg per tablet/capsule) and cis/trans-menaquinone-7 isomers (70.9–218.7 µg tablet/capsule), which were most likely formed during the chemical synthesis of the menaquinone-7. The all-trans MK-7 content was lower than the isomeric form and often lower than what the labels declared. A new method of quantification, developed and validated for menaquinones in oil capsules, provided on average 90% recovery and a limit of quantification (LOQ) of approximately 1 µg mL−1. Full article
(This article belongs to the Section Analytical Chemistry)
Figures

Figure 1

Open AccessArticle An Improved Weighted Partial Least Squares Method Coupled with Near Infrared Spectroscopy for Rapid Determination of Multiple Components and Anti-Oxidant Activity of Pu-Erh Tea
Molecules 2018, 23(5), 1058; https://doi.org/10.3390/molecules23051058
Received: 8 March 2018 / Revised: 24 April 2018 / Accepted: 25 April 2018 / Published: 2 May 2018
PDF Full-text (822 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Background: Pu-erh tea is a unique microbially fermented tea, which distinctive chemical constituents and activities are worthy of systematic study. Near infrared spectroscopy (NIR) coupled with suitable chemometrics approaches can rapidly and accurately quantitatively analyze multiple compounds in samples. Methods: In this study,
[...] Read more.
Background: Pu-erh tea is a unique microbially fermented tea, which distinctive chemical constituents and activities are worthy of systematic study. Near infrared spectroscopy (NIR) coupled with suitable chemometrics approaches can rapidly and accurately quantitatively analyze multiple compounds in samples. Methods: In this study, an improved weighted partial least squares (PLS) algorithm combined with near infrared spectroscopy (NIR) was used to construct a fast calibration model for determining four main components, i.e., tea polyphenols, tea polysaccharide, total flavonoids, theanine content, and further determine the total antioxidant capacity of pu-erh tea. Results: The final correlation coefficients R square for tea polyphenols, tea polysaccharide, total flavonoids content, theanine content, and total antioxidant capacity were 0.8288, 0.8403, 0.8415, 0.8537 and 0.8682, respectively. Conclusions: The current study provided a comprehensive study of four main ingredients and activity of pu-erh tea, and demonstrated that NIR spectroscopy technology coupled with multivariate calibration analysis could be successfully applied to pu-erh tea quality assessment. Full article
(This article belongs to the Section Analytical Chemistry)
Figures

Figure 1

Open AccessArticle Green Extraction of Natural Antioxidants from the Sterculia nobilis Fruit Waste and Analysis of Phenolic Profile
Molecules 2018, 23(5), 1059; https://doi.org/10.3390/molecules23051059
Received: 10 April 2018 / Revised: 24 April 2018 / Accepted: 27 April 2018 / Published: 2 May 2018
PDF Full-text (1679 KB) | HTML Full-text | XML Full-text
Abstract
The waste of Sterculia nobilis fruit was massively produced during food processing, which contains lots of natural antioxidants. In this study, antioxidants in the Sterculia nobilis fruit waste were extracted using the green microwave-assisted extraction (MAE) technique. The effects of five independent variables
[...] Read more.
The waste of Sterculia nobilis fruit was massively produced during food processing, which contains lots of natural antioxidants. In this study, antioxidants in the Sterculia nobilis fruit waste were extracted using the green microwave-assisted extraction (MAE) technique. The effects of five independent variables (ethanol concentration, solvent/material ratio, extraction time, temperature, and microwave power) on extraction efficiency were explored, and three major factors (ethanol concentration, extraction time, and temperature) showing great influences were chosen to study their interactions by response surface methodology. The optimal conditions were as follows: 40.96% ethanol concentration, 30 mL/g solvent/material ratio, 37.37 min extraction time at 66.76 °C, and 700 W microwave power. The Trolox equivalent antioxidant capacity value obtained in optimal conditions was in agreement with the predicted value. Besides, MAE improved the extraction efficiency compared with maceration and Soxhlet extraction methods. Additionally, the phenolic profile in the extract was analyzed by UPLC-MS/MS, and eight kinds of phenolic compounds were identified and quantified, including epicatechin, protocatechuic acid, ferulic acid, gallic acid, p-coumaric acid, caffeic acid, quercetin, and p-hydroxycinnamic acid. This study could contribute to the value-added utilization of the waste from Sterculia nobilis fruit, and the extract could be developed as food additive or functional food. Full article
(This article belongs to the Special Issue Antioxidants Chemistry and Applications)
Figures

Figure 1

Open AccessArticle Residue and Dietary Risk Assessment of Chiral Cyflumetofen in Apple
Molecules 2018, 23(5), 1060; https://doi.org/10.3390/molecules23051060
Received: 3 April 2018 / Revised: 20 April 2018 / Accepted: 29 April 2018 / Published: 2 May 2018
PDF Full-text (2448 KB) | HTML Full-text | XML Full-text
Abstract
Ultra-performance convergence chromatography is an environmentally-friendly analytical method that uses dramatically reduced amounts of organic solvents. In addition, a robust and highly sensitive chiral separation method was developed for the novel chiral acaricide cyflumetofen by using ultra-performance convergence chromatography coupled with tandem mass
[...] Read more.
Ultra-performance convergence chromatography is an environmentally-friendly analytical method that uses dramatically reduced amounts of organic solvents. In addition, a robust and highly sensitive chiral separation method was developed for the novel chiral acaricide cyflumetofen by using ultra-performance convergence chromatography coupled with tandem mass spectrometry, which shows that stereoisomer recoveries determined for various apple parts ranged from 78.3% to 119.9%, with the relative standard deviations being lower than 14.0%. The half-lives of (−)-cyflumetofen and (+)-cyflumetofen obtained under 5-fold applied dosage equal to 22.13 and 22.23 days, respectively. For 1.5-fold applied dosage, the respective values were determined as 22.42 and 23.64 days, i.e., the degradation of (−)-cyflumetofen was insignificantly favored over that of its enantiomer. Importantly, cyflumetofen was unevenly distributed in apples, with its relative contents in apple peel, peduncle, and pomace equal to 50%, 22%, and 16%, respectively. The proposed method can be used to efficiently separate and quantify chiral pesticide with advantages of a shorter analysis time, greater sensitivity, and better environmental compatibility. Additionally, the consumption of apples with residue of cyflumetofen did not pose a health risk to the population if the cyflumetofen applied under satisfactory agricultural practices after the long-term dietary risk assessment. Full article
(This article belongs to the Special Issue Recent Advances in Studies of Food and Beverages)
Figures

Figure 1

Open AccessArticle Tryptanthrin Protects Mice against Dextran Sulfate Sodium-Induced Colitis through Inhibition of TNF-α/NF-κB and IL-6/STAT3 Pathways
Molecules 2018, 23(5), 1062; https://doi.org/10.3390/molecules23051062
Received: 17 April 2018 / Revised: 27 April 2018 / Accepted: 27 April 2018 / Published: 2 May 2018
PDF Full-text (51835 KB) | HTML Full-text | XML Full-text
Abstract
Inflammatory bowel disease (IBD) is a notable health problem and may considerably affect the quality of human life. Previously, the protective roles of tryptanthrin (TRYP) against dextran sulfate sodium (DSS) induced colitis has been proved, but the concrete mechanism remained elusive. It has
[...] Read more.
Inflammatory bowel disease (IBD) is a notable health problem and may considerably affect the quality of human life. Previously, the protective roles of tryptanthrin (TRYP) against dextran sulfate sodium (DSS) induced colitis has been proved, but the concrete mechanism remained elusive. It has been suggested that TRYP could diminish the weight loss and improve the health conditions of mice with DSS induced colitis. Hematoxylin and eosin staining revealed that TRYP could improve the histopathological structure of the colon tissue. Two signaling pathways (TNF-α/NF-κBp65 and IL-6/STAT3) were investigated using immunochemistry and western blot. The detected concentrations of the two cytokines TNF-α and IL-6 showed that their levels decreased after TRYP treatment of the colitis. The protein expression level of NF-κBp65 in cytoplasm increased after TRYP treatment of the induced colitis. However, the protein level of NF-κBp65 in the nucleus decreased after administration of TRYP. The expression level of IκBα, the inhibitory protein of NF-κBp65, was tested and the results suggested that TRYP could inhibit the degradation of IκBα. The phosphorylation level of STAT3 was inhibited by TRYP and the expression level of STAT3 and p-STAT3 decreased after administration of TRYP. We conclude that TRYP improves the health condition of mice with DSS induced colitis by regulating the TNF-α/NF-κBp65 and IL-6/STAT3 signaling pathways via inhibiting the degradation of IκBα and the phosphorylation of STAT3. Full article
(This article belongs to the Section Natural Products Chemistry)
Figures

Figure 1

Open AccessArticle Exploration of the Fluorescent Properties and the Modulated Activities against Sirtuin Fluorogenic Assays of Chromenone-Derived Natural Products
Molecules 2018, 23(5), 1063; https://doi.org/10.3390/molecules23051063
Received: 18 March 2018 / Revised: 20 April 2018 / Accepted: 27 April 2018 / Published: 2 May 2018
PDF Full-text (8402 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chromenone-derived natural products include chromones (flavone, isoflavone) and coumarins. Chromenone compounds not only exhibit impressive biological activities, but also are an important resource of experimentally used fluorophores, such as, 7-amino-4-methylcoumarin (AMC). Various chromenone compounds have reported to have weak fluorescence, and this has
[...] Read more.
Chromenone-derived natural products include chromones (flavone, isoflavone) and coumarins. Chromenone compounds not only exhibit impressive biological activities, but also are an important resource of experimentally used fluorophores, such as, 7-amino-4-methylcoumarin (AMC). Various chromenone compounds have reported to have weak fluorescence, and this has the potential to interfere with the measurements during AMC fluorogenic assays and result in non-robust assay readouts. Several flavones and isoflavones were found as SIRT1 activators, while fluorogenic sirtuin assays utilized AMC labelled peptides as the substrates. In this study we investigated whether the fluorescent properties of chromenone-derived natural products interrupt the measurement of SIRT1/2 modulated activities. We found that the reported SIRT1 activators: flavones were detected with the SIRT1 activation activity, but isoflavones were not detected with SIRT1 activation activity, and instead that they were found to be fluorogenic compounds. Another chromenone compound, osthole, exhibited a moderate SIRT2 inhibitory activity with an IC50 of 10 μM. In conclusion, the fluorescent properties of these chromenone compounds do affect the measurement of the sirtuin activities of both inhibitors and activators. However, if the possible fluorescence properties are mitigated in the assay readout, these fluorogenic assays enable the screening of activity modulators. Full article
(This article belongs to the Section Natural Products Chemistry)
Figures

Graphical abstract

Open AccessArticle Determination of Critical Micellar Concentration of Homologous 2-Alkoxyphenylcarbamoyloxyethyl-Morpholinium Chlorides
Molecules 2018, 23(5), 1064; https://doi.org/10.3390/molecules23051064
Received: 16 March 2018 / Revised: 23 April 2018 / Accepted: 23 April 2018 / Published: 2 May 2018
PDF Full-text (2611 KB) | HTML Full-text | XML Full-text
Abstract
The critical micellar concentrations of selected alkyloxy homologues of local anesthetic 4-(2-{[(2-alkoxyphenyl)carbamoyl]oxy}ethyl)morpholin-4-ium chloride with nc = 2, 4, 5, 6, 7, 8, and 9 carbons in alkyloxy tail were determined by absorption spectroscopy in the UV–vis spectral region with the use of
[...] Read more.
The critical micellar concentrations of selected alkyloxy homologues of local anesthetic 4-(2-{[(2-alkoxyphenyl)carbamoyl]oxy}ethyl)morpholin-4-ium chloride with nc = 2, 4, 5, 6, 7, 8, and 9 carbons in alkyloxy tail were determined by absorption spectroscopy in the UV–vis spectral region with the use of a pyrene probe. Within the homologous series of the studied amphiphilic compounds, the ln(cmc) was observed to be dependent linearly on the number of carbon atoms nc in the hydrophobic tail: ln(cmc) = 0.705–0.966 nc. The Gibbs free energy, necessary for the transfer of the methylene group of the alkoxy chain from the water phase into the inner part of the micelle at the temperature of 25 °C and pH ≈ 4.5–5.0, was found to be −2.39 kJ/mol. The experimentally determined cmc values showed good correlations with the predicted values of the bulkiness of the alkoxy tail expressed as the molar volume of substituent R, as well as with the surface tension of the compounds. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Figure 1

Open AccessArticle Preparation and Antioxidant Activity of Ethyl-Linked Anthocyanin-Flavanol Pigments from Model Wine Solutions
Molecules 2018, 23(5), 1066; https://doi.org/10.3390/molecules23051066
Received: 2 March 2018 / Revised: 18 April 2018 / Accepted: 24 April 2018 / Published: 3 May 2018
PDF Full-text (3317 KB) | HTML Full-text | XML Full-text
Abstract
Anthocyanin-flavanol pigments, formed during red wine fermentation and storage by condensation reactions between anthocyanins and flavanols (monomers, oligomers, and polymers), are one of the major groups of polyphenols in aged red wine. However, knowledge of their biological activities is lacking. This is probably
[...] Read more.
Anthocyanin-flavanol pigments, formed during red wine fermentation and storage by condensation reactions between anthocyanins and flavanols (monomers, oligomers, and polymers), are one of the major groups of polyphenols in aged red wine. However, knowledge of their biological activities is lacking. This is probably due to the structural diversity and complexity of these molecules, which makes the large-scale separation and isolation of the individual compounds very difficult, thus restricting their further study. In this study, anthocyanins (i.e., malvidin-3-glucoside, cyanidin-3-glucoside, and peonidin-3-glucoside) and (–)-epicatechin were first isolated at a preparative scale by high-speed counter-current chromatography. The condensation reaction between each of the isolated anthocyanins and (–)-epicatechin, mediated by acetaldehyde, was conducted in model wine solutions to obtain ethyl-linked anthocyanin-flavanol pigments. The effects of pH, molar ratio, and temperature on the reaction rate were investigated, and the reaction conditions of pH 1.7, molar ratio 1:6:10 (anthocyanin/(–)-epicatechin/acetaldehyde), and reaction temperature of 35 °C were identified as optimal for conversion of anthocyanins to ethyl-linked anthocyanin-flavanol pigments. Six ethyl-linked anthocyanin-flavanol pigments were isolated in larger quantities and collected under optimal reaction conditions, and their chemical structures were identified by HPLC-QTOF-MS and ECD analyses. Furthermore, DPPH, ABTS, and FRAP assays indicate that ethyl-linked anthocyanin-flavanol pigments show stronger antioxidant activities than their precursor anthocyanins. Full article
(This article belongs to the collection Wine Chemistry)
Figures

Figure 1